Deyu Zuo, Yuce Peng, Guozhi Zhao, et al. · (2025) · "Hypoglycemia Induces Diabetic Macrovascular Endothelial Dysfunction via Endothelial Cell PANoptosis, Macrophage Polarization, and VSMC Fibrosis" · Advanced Science · doi: 10.1002/advs.202414530 · PMCID: PMC12499442 · PMID: 40650639

Question: What is the published background on "Hypoglycemia Induces Diabetic Macrovascular Endothelial Dysfunction via Endothelial Cell PANoptosis, Macrophage Polarization, and VSMC…"? Cite a peer-reviewed source.

Answer:
With the global increase of the aging population, there has been a surge in the number of elderly diabetic patients, with 127 million people worldwide. [ 1 , 2 ] Elderly patients with diabetes are more likely to develop hypoglycemia than younger patients, which can lead to short‐ and long‐term adverse events and increased mortality. [ 3 , 4 ] The International Hypoglycaemia Study Group (IHSG) level 2 (glucose < 3.0 mmol L −1 ) and level 3 (severe) are associated with increased risks of cardiovascular events in type 2 diabetes mellitus (T2DM), such as myocardial ischemia and infarction, heart failure, and arrhythmias. [ 4 ] Although hypoglycemia‐induced cardiovascular events have been intensively studied, [ 5 , 6 ] the underlying mechanisms are unclear.

Hypoglycemia increases circulating inflammatory mediators and atherogenic markers, which are related to endothelial cell dysfunction, manifested as a disorder of endothelium‐dependent vasodilation and cardiovascular diseases in diabetic patients. [ 7 , 8 , 9 ] A previous study revealed that proinflammatory programmed cell death (PCD) caused by hypoglycemia is one of the important reasons for endothelial dysfunction and the source of cytokine release. [ 10 ] The pattern of proinflammatory PCD includes pyroptosis, necroptosis, and PANoptosis. [ 11 ] Pyroptosis has been reported in hypoglycemia‐induced endothelial dysfunction. [ 10 ] An in‐depth elucidation of the role of other types of proinflammatory PCD in endothelial dysfunction in diabetic patients associated with hypoglycemia is fundamental for developing novel therapies to effectively avoid or alleviate hypoglycemia‐induced cardiovascular diseases .

Besides endothelial cells (ECs), macrophages and vascular smooth muscle cells (VSMCs) are also associated with hypoglycemia‐induced cardiovascular events. Macrophages are local immune cells that exist across organs and perform various crucial tasks for tissue homeostasis. [ 12 ] They facilitate vascular inflammation, which is the main factor of global mortality and morbidity. [ 13 , 14 ] However, vascular macrophage polarization in the process of hypoglycemia is poorly understood. VSMCs are closely associated with endothelial dysfunction in vascular inflammation, [ 15 ] which is detected in hypoglycemia through increased levels of proinflammatory cytokines in blood circulation, particularly interleukin (IL)‐6. [ 16 ] IL‐6 produced by VSMCs within vessel walls is highly correlated with cardiovascular risks. [ 17 ] The role of VSMCs in diabetes with hypoglycemia remains to be explored.

Previous studies have applied molecular biology to examine pathophysiological alterations in vascular function during hypoglycemia at the tissue level. [ 8 , 10 , 16 ] However, cell type‐specific variations could not be detected from bulk data. This limitation can be solved by single‐cell RNA sequencing (scRNA‐seq) or single‐nucleus RNA‐seq (snRNA‐seq), which allow for unbiased dissection of cellular alterations at remarkable resolution. snRNA‐seq has been effectively applied to compare diabetic and nondiabetic ECs in adults. [ 18 ] However, a lack of research exists on the pathophysiology of macrophages and VSMCs under hypoglycemia in the thoracic aorta of diabetic animal models. Integrated analysis of snRNA‐seq combined with molecular biology data could improve knowledge of cellular and molecular changes of hypoglycemia.

This study aimed to assess the impact of hypoglycemia on the cardiovascular system, focusing on ECs, macrophages, and VSMCs of the thoracic aorta in db/db and hypoglycemia db/db mice. Single‐nucleus RNA‐seq and comparative analyses were applied to delineate lineage‐specific variations in gene expression, subpopulation composition, and intercellular communication in thoracic aorta tissues. This study prioritized potential key genes during the transition toward the proinflammatory PCD status of ECs, macrophage proinflammatory polarization, and VSMC fibrosis, which were validated with functional and molecular biology experiments. Activation of human VSMC fibrosis could be suppressed by an in vitro silencing of ANGPTL4, suggesting that ANGPTL4 may function as a transcription repressor in vascular fibrosis. This research is expected to help mitigate hypoglycemia progression in aging diabetic patients and lessening hypoglycemia‐induced cardiovascular events.

— Source (introduction, peer-reviewed): Deyu Zuo, Yuce Peng, Guozhi Zhao, et al. · (2025) · "Hypoglycemia Induces Diabetic Macrovascular Endothelial Dysfunction via Endothelial Cell PANoptosis, Macrophage Polarization, and VSMC Fibrosis" · Advanced Science · doi: 10.1002/advs.202414530 · PMCID: PMC12499442 · PMID: 40650639
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

CGMacros-035

Question: What did subject CGMacros-035's BG do after a lunch of 16g carbs at 12:04 on 2024-12-14?

Answer:
Subject CGMacros-035 logged a lunch at 12:04 on 2024-12-14 of 16g carb / 66g protein / 14g fat / 4g fiber (435 kcal). Pre-meal Libre BG was 147.9 mg/dL. Peak in the next 150 minutes was 143.6 mg/dL (a rise of -4.3 mg/dL from baseline). At the 2-hour mark BG was 112.3 mg/dL.

Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

This describes one logged meal from one subject in a published research dataset. It is not advice. Your individual BG responses, and what they mean for you, are a conversation with your healthcare provider.


Giovanni Leuzzi, Elisa Meacci, Giacomo Cusumano, et al. · (2014) · "Thymectomy in myasthenia gravis: proposal for a predictive score of postoperative myasthenic crisis" · European Journal of Cardio-Thoracic Surgery · https://doi.org/10.1093/ejcts/ezt641 · cited 80 times

Question: Summarize the published evidence on "Thymectomy in myasthenia gravis: proposal for a predictive score of postoperative myasthenic crisis" with a citation.

Answer:
OBJECTIVES: Thymectomy plays an important role in patients with myasthenia gravis (MG). This study aimed to explore predictors of postoperative myasthenic crisis (POMC) after thymectomy and to define a predictive score of respiratory failure. METHODS: The clinical data of 177 patients with MG undergoing thymectomy from January 1995 to December 2011 were retrospectively reviewed. The following factors were analysed in relation to the occurrence of myasthenic crisis: gender, age, body mass index (BMI), anti-acetylcholine receptor-antibody level, bulbar symptoms, comorbidities, duration of symptoms, Osserman-stage, Myasthenia Gravis Foundation of America (MGFA) stage, history of myasthenic crisis, use of immoglobulins or plasmapheresis, kind of therapy, spirometric and blood gas parameters, histology, kind of surgery, non-myasthenic complications and duration of intubation. RESULTS: Twenty-two patients experienced postoperative respiratory failure after thymectomy. Univariate analysis revealed a correlation with age >60 years (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.04-6.78; P = 0.040); Osserman-stage (IIB- OR = 5.16, 95% CI = 1.10-24.18; P = 0.037, III-IV- OR = 8.75, 95% CI = 1.53-50.05; P = 0.015); bulbar symptoms (OR = 7.42, 95% CI = 1.67-32.84; P = 0.008); BMI >28 (OR = 3.99, 95% CI = 1.58-10.03; P = 0.003); preoperative plasmapheresis (OR = 2.97, 95% CI = 1.18-14.04; P = 0.021); duration of symptoms >2 years (OR = 4.00, 95% CI = 1.09-14.762; P = 0.036); extended surgery (OR = 2.52, 95% CI = 1.02-6.22; P = 0.045); lung (OR = 4.05, 95% CI = 1.44-11.42; P = 0.008), pericardial (OR = 3.78, 95% CI = 1.45-9.82; P = 0.006) or pleural resection (OR = 3.23, 95% CI = 1.30-8.03; P = 0.012); Vital Capacity % <80% (OR = 0.20, 95% CI = 0.05-0.82; P = 0.025) and PaCO2 >40 mmHg (OR = 3.76, 95% CI = 1.12-12.68; P = 0.032). Multivariate logistic regression analysis showed that Osserman-stage (IIB- OR = 5.69, 95% CI = 1.09-29.69; P = 0.039 (III-IV- OR = 11.33, 95% CI = 1.67-76.72; P = 0.013), BMI >28 (OR = 3.65, 95% CI = 1.10-12.15; P = 0.035), history of myasthenic crisis (OR = 24.10, 95% CI = 2.34-248.04; P = 0.007), duration of symptoms >2 years (OR = 5.94, 95% CI = 1.12-31.48; P = 0.036) and lung resection (OR = 8.48, 95% CI = 2.18-32.97; P = 0.002) independently predict POMC. Excluding history of preoperative myasthenic crisis (statistically associated with Osserman-stage), we built a scoring system according to the OR of Osserman-stage (I-IIA, IIB, III-IV), BMI (<28, ≥ 28), duration of symptoms (<1, 1-2, >2 years) and association with a pulmonary resection. This model helped in creating four classes with increasing risk of respiratory failure (Group I, 6%; Group II, 10%; Group III, 25%; Group IV, 50%). CONCLUSIONS: Our model facilitates the stratification of patient risk and prediction of the occurrence of POMC. Moreover, it could help to guide the anaesthesiologist's decision on the duration of intubation. Further studies based on larger series are needed to confirm these preliminary data.

— Source (peer-reviewed): Giovanni Leuzzi, Elisa Meacci, Giacomo Cusumano, et al. · (2014) · "Thymectomy in myasthenia gravis: proposal for a predictive score of postoperative myasthenic crisis" · European Journal of Cardio-Thoracic Surgery · https://doi.org/10.1093/ejcts/ezt641 · cited 80 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Duncan M. MacGillivray, Tobias R. Kollmann · (2014) · "The Role of Environmental Factors in Modulating Immune Responses in Early Life" · Frontiers in Immunology · https://doi.org/10.3389/fimmu.2014.00434 · cited 220 times

Question: Summarize the published evidence on "The Role of Environmental Factors in Modulating Immune Responses in Early Life" with a citation.

Answer:
The concept of immunological memory stipulates that past exposures shape present immune function. These exposures include not only specific antigens impacting adaptive immune memory but also conserved pathogen or danger associated molecular patterns that mold innate immune responses for prolonged periods of time. It should thus not come as a surprise that there is a vast range of external or environmental factors that impact immunity. The importance of environmental factors modulating immunity is most readily recognized in early life, a period of rapidly changing environments. We here summarize available data on the role of environment shaping immune development and from it derive an overarching hypothesis relating the underlying molecular mechanisms and evolutionary principles involved.

— Source (peer-reviewed): Duncan M. MacGillivray, Tobias R. Kollmann · (2014) · "The Role of Environmental Factors in Modulating Immune Responses in Early Life" · Frontiers in Immunology · https://doi.org/10.3389/fimmu.2014.00434 · cited 220 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Simeon I. Taylor, Zhinous Shahidzadeh Yazdi, Amber L. Beitelshees · (2021) · "Pharmacological treatment of hyperglycemia in type 2 diabetes" · Journal of Clinical Investigation · https://doi.org/10.1172/jci142243 · cited 239 times

Question: Summarize the published evidence on "Pharmacological treatment of hyperglycemia in type 2 diabetes" with a citation.

Answer:
Diabetes mellitus is a major public health problem, affecting about 10% of the population. Pharmacotherapy aims to protect against microvascular complications, including blindness, end-stage kidney disease, and amputations. Landmark clinical trials have demonstrated that intensive glycemic control slows progression of microvascular complications (retinopathy, nephropathy, and neuropathy). Long-term follow-up has demonstrated that intensive glycemic control also decreases risk of macrovascular disease, albeit rigorous evidence of macrovascular benefit did not emerge for over a decade. The US FDA's recent requirement for dedicated cardiovascular outcome trials ushered in a golden age for understanding the clinical profiles of new type 2 diabetes drugs. Some clinical trials with sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP1) receptor agonists reported data demonstrating cardiovascular benefit (decreased risk of major adverse cardiovascular events and hospitalization for heart failure) and slower progression of diabetic kidney disease. This Review discusses current guidelines for use of the 12 classes of drugs approved to promote glycemic control in patients with type 2 diabetes. The Review also anticipates future developments with potential to improve the standard of care: availability of generic dipeptidylpeptidase-4 (DPP4) inhibitors and SGLT2 inhibitors; precision medicine to identify the best drugs for individual patients; and new therapies to protect against chronic complications of diabetes.

— Source (peer-reviewed): Simeon I. Taylor, Zhinous Shahidzadeh Yazdi, Amber L. Beitelshees · (2021) · "Pharmacological treatment of hyperglycemia in type 2 diabetes" · Journal of Clinical Investigation · https://doi.org/10.1172/jci142243 · cited 239 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Diabetes UK, registered charity, patient education content

Question: Per Diabetes UK patient guidance on What causes steroid-induced diabetes, what is the summary?

Answer:
Steroids can increase your blood sugar level in different ways. They can:

cause the liver to release more glucose stop glucose being absorbed from the blood by the muscle and fat cells reduce the body’s sensitivity to insulin .

All these things can mean too much glucose stays in your blood. This can lead to diabetes.

— Source: www.diabetes.org.uk/about-diabetes/other-types-of-diabetes/steroid-induced-diabetes
  Publisher: Diabetes UK
  Page: "Steroid-induced diabetes"
  Section: "What causes steroid-induced diabetes?"
  License: Diabetes UK, registered charity, patient education content
  Retrieved: 2026-05-14

Note: This is public-health information from an authoritative international body. It reflects population-level guidance, not individualized medical advice. For decisions about your own health, please discuss with your healthcare provider.


Jenni Kinnunen, Hilkka Nikkinen, Elina Keikkala, et al. · (2025) · "Gestational diabetes mellitus and offspring health: A 12‐year register‐based analysis of specialized health care utilization in Finland" · Acta Obstetricia et Gynecologica Scandinavica · doi: 10.1111/aogs.70077 · PMCID: PMC12746197 · PMID: 41077759

Question: What does the published research conclude about "Gestational diabetes mellitus and offspring health: A 12‐year register‐based analysis of specialized health care utilization in Finland"? Cite a peer-reviewed source.

Answer:
Exposure to GDM is associated with increased morbidity in children up to 12 years of age, defined by specialized health care utilization. The difference in morbidity between exposed and unexposed children was not limited to a certain age period but was, in fact, present from early childhood to school age.

— Source (conclusions, peer-reviewed): Jenni Kinnunen, Hilkka Nikkinen, Elina Keikkala, et al. · (2025) · "Gestational diabetes mellitus and offspring health: A 12‐year register‐based analysis of specialized health care utilization in Finland" · Acta Obstetricia et Gynecologica Scandinavica · doi: 10.1111/aogs.70077 · PMCID: PMC12746197 · PMID: 41077759
License: CC-BY-NC. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Katrin Lättman, Margareta Friman, Lars E. Olsson · (2016) · "Perceived Accessibility of Public Transport as a Potential Indicator of Social Inclusion" · Social Inclusion · https://doi.org/10.17645/si.v4i3.481 · cited 171 times

Question: Summarize the published evidence on "Perceived Accessibility of Public Transport as a Potential Indicator of Social Inclusion" with a citation.

Answer:
Perceived accessibility has been acknowledged as an important aspect of transport policy since the 70s. Nevertheless, very few empirical studies have been conducted in this field. When aiming to improve social inclusion, by making sustainable transport modes accessible to all, it is important to understand the factors driving perceived accessibility. Unlike conventional accessibility measures, perceived accessibility focuses on the perceived possibilities and ease of engaging in preferred activities using different transport modes. We define perceived accessibility in terms of how easy it is to live a satisfactory life with the help of the transport system, which is not necessarily the same thing as the objective standard of the system. According to previous research, perceived accessibility varies with the subjectively-rated quality of the mode of transport. Thus, improvements in quality (e.g. trip planning, comfort, or safety) increase the perceived accessibility and make life easier to live using the chosen mode of transport. This study (n=750) focuses on the perceived accessibility of public transport, captured using the <em>Perceived Accessibility Scale </em>PAC (Lättman, Olsson, &amp; Friman, 2015). More specifically, this study aims to determine how level of quality affects the perceived accessibility in public transport. A Conditional Process Model shows that, in addition to quality, feeling safe and frequency of travel are important predictors of perceived accessibility. Furthermore, elderly and those in their thirties report a lower level of perceived accessibility to their day-to-day activities using public transport. The basic premise of this study is that subjective experiences may be as important as objective indicators when planning and designing for socially inclusive transport systems.

— Source (peer-reviewed): Katrin Lättman, Margareta Friman, Lars E. Olsson · (2016) · "Perceived Accessibility of Public Transport as a Potential Indicator of Social Inclusion" · Social Inclusion · https://doi.org/10.17645/si.v4i3.481 · cited 171 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


João Felício, Ester Chambouleyron, Valéria Nascimento, et al. · (2026) · "Vitamin D and cardiovascular autonomic neuropathy in type 2 diabetes mellitus according to diabetic kidney disease stage" · Frontiers in Endocrinology · doi: 10.3389/fendo.2026.1810159 · PMCID: PMC13124521 · PMID: 42064771

Question: What is the published background on "Vitamin D and cardiovascular autonomic neuropathy in type 2 diabetes mellitus according to diabetic kidney disease stage"? Cite a peer-reviewed source.

Answer:
Diabetic neuropathy is the most prevalent and underdiagnosed chronic complication in individuals with type 2 diabetes mellitus (T2DM) ( 1 , 2 ). Among these, cardiovascular autonomic neuropathy (CAN) is of particular clinical relevance, due to alterations in heart rate variability (HRV) and its association with higher morbidity and mortality in T2DM individuals, particularly when associated with diabetic kidney disease (DKD) ( 3 – 6 ). In individuals with T2DM, the prevalence of cardiovascular autonomic neuropathy (CAN) ranges from 12% to 73% ( 7 ), while vitamin D deficiency affects approximately 64.2% of this group ( 8 ). Both complications have been associated with reduced vitamin D (VD) concentrations in cross-sectional studies ( 9 – 14 ). There is also evidence suggesting that DKD and CAN may improve after VD supplementation ( 15 – 19 ).

Vitamin D deficiency has been associated with increased inflammation, oxidative stress, and reduced neurotrophin availability, mechanisms that may contribute to the development of CAN ( 20 – 22 ). Considering DKD, a progressive renal dysfunction characterized by worsening albuminuria and impaired VD activation, this condition may coexist with and intensify these pathophysiological pathways, in parallel with greater autonomic dysfunction across more advanced stages of kidney disease ( 23 , 24 ).

Recently, our research group demonstrated improvements in HRV (in both frequency and time domain) after vitamin D supplementation in patients with type 1 diabetes mellitus (T1DM) ( 18 ). We have also found an improvement in morning systolic blood pressure and CAN parameters after vitamin D supplementation ( 19 ). Furthermore, loss of nocturnal systolic blood pressure (NSBP) dipping is a condition that increases cardiovascular risk and is associated with both CAN and DKD ( 19 , 25 ). Although these findings provide an important conceptual basis, differences in pathophysiology require specific investigation in T2DM ( 26 , 27 ). Finally, to our knowledge, no study has evaluated a possible association between lower VD concentrations and CAN in all DKD stages in the same T2DM population.

— Source (introduction, peer-reviewed): João Felício, Ester Chambouleyron, Valéria Nascimento, et al. · (2026) · "Vitamin D and cardiovascular autonomic neuropathy in type 2 diabetes mellitus according to diabetic kidney disease stage" · Frontiers in Endocrinology · doi: 10.3389/fendo.2026.1810159 · PMCID: PMC13124521 · PMID: 42064771
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Changhyun Lim, Everson Araújo Nunes, Brad S. Currier, et al. · (2022) · "An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise–Induced Human Skeletal Muscle Hypertrophy" · Medicine & Science in Sports & Exercise · https://doi.org/10.1249/mss.0000000000002929 · cited 118 times

Question: What does the peer-reviewed literature show about "An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise–Induced Human Skeletal Muscle Hypertrophy"? Cite a published source.

Answer:
Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise (RE; loading) by hypertrophying, or during muscle disuse, RE mitigates muscle loss. Resistance exercise training (RET)-induced skeletal muscle hypertrophy is a product of external (e.g., RE programming, diet, some supplements) and internal variables (e.g., mechanotransduction, ribosomes, gene expression, satellite cells activity). RE is undeniably the most potent nonpharmacological external variable to stimulate the activation/suppression of internal variables linked to muscular hypertrophy or countering disuse-induced muscle loss. Here, we posit that despite considerable research on the impact of external variables on RET and hypertrophy, internal variables (i.e., inherent skeletal muscle biology) are dominant in regulating the extent of hypertrophy in response to external stimuli. Thus, identifying the key internal skeletal muscle-derived variables that mediate the translation of external RE variables will be pivotal to determining the most effective strategies for skeletal muscle hypertrophy in healthy persons. Such work will aid in enhancing function in clinical populations, slowing functional decline, and promoting physical mobility. We provide up-to-date, evidence-based perspectives of the mechanisms regulating RET-induced skeletal muscle hypertrophy.

— Source (peer-reviewed): Changhyun Lim, Everson Araújo Nunes, Brad S. Currier, et al. · (2022) · "An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise–Induced Human Skeletal Muscle Hypertrophy" · Medicine & Science in Sports & Exercise · https://doi.org/10.1249/mss.0000000000002929 · cited 118 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Kunihiro Matsushita, Ning Ding, Esther D. Kim, et al. · (2018) · "Cardio‐ankle vascular index and cardiovascular disease: Systematic review and meta‐analysis of prospective and cross‐sectional studies" · Journal of Clinical Hypertension · https://doi.org/10.1111/jch.13425 · cited 140 times

Question: Summarize the published evidence on "Cardio‐ankle vascular index and cardiovascular disease: Systematic review and meta‐analysis of prospective and cross‐sectional studies" with a citation.

Answer:
The cardio-ankle vascular index (CAVI) is a new measure of arterial stiffness that reflects the stiffness from the ascending aorta to the ankle arteries, and demonstrates little dependence on blood pressure during the evaluation. However, a comprehensive assessment of the association of CAVI with cardiovascular disease (CVD) has not been reported. We performed a systematic review to assess the association between CAVI and CVD. We searched for both prospective and cross-sectional studies using MEDLINE, Embase, and Cochrane from inception until April 11, 2017. We pooled the results using random-effects models. Among 1519 records, we identified nine prospective studies (n = 5214) and 17 cross-sectional eligible studies (n = 7309), with most enrolling high CVD risk populations in Asia. All nine prospective studies investigated composite CVD events as an outcome (498 cases including coronary events and stroke) but modeled CAVI inconsistently. The pooled adjusted hazard ratio for CVD events per 1 standard deviation increment of CAVI in four studies was 1.20 (95% CI: 1.05-1.36, P = 0.006). Of the 17 cross-sectional studies, 13 studies compared CAVI values between patients with and without CVD and all reported significantly higher values in those with CVD (pooled mean difference in CAVI values 1.28 [0.86-1.70], P < 0.001). This systematic review suggests a modest association between CAVI and incident CVD risk, and highlights the need for studies assessing CAVI as a predictor of CVD in the general population and non-Asian countries.

— Source (peer-reviewed): Kunihiro Matsushita, Ning Ding, Esther D. Kim, et al. · (2018) · "Cardio‐ankle vascular index and cardiovascular disease: Systematic review and meta‐analysis of prospective and cross‐sectional studies" · Journal of Clinical Hypertension · https://doi.org/10.1111/jch.13425 · cited 140 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

CGMacros-046

Question: Show me a CGMacros meal where carbs were 47g, protein was 55g, fat was 25g, and report the BG response.

Answer:
Subject CGMacros-046 logged a dinner at 14:28 on 2025-05-10 of 47g carb / 55g protein / 25g fat / 3g fiber (633 kcal). Pre-meal Libre BG was 135.8 mg/dL. Peak in the next 150 minutes was 181.0 mg/dL (a rise of 45.2 mg/dL from baseline). At the 2-hour mark BG was 178.6 mg/dL.

Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

This describes one logged meal from one subject in a published research dataset. It is not advice. Your individual BG responses, and what they mean for you, are a conversation with your healthcare provider.


Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

CGMacros-044

Question: What did subject CGMacros-044's BG do after a dinner of 24g carbs at 16:55 on 2022-10-19?

Answer:
Subject CGMacros-044 logged a dinner at 16:55 on 2022-10-19 of 24g carb / 2g protein / 6g fat / 2g fiber (155 kcal). Pre-meal Libre BG was 117.4 mg/dL. Peak in the next 150 minutes was 151.0 mg/dL (a rise of 33.6 mg/dL from baseline). At the 2-hour mark BG was 138.9 mg/dL.

Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

This describes one logged meal from one subject in a published research dataset. It is not advice. Your individual BG responses, and what they mean for you, are a conversation with your healthcare provider.


Xiaoli Huang, Jiajia Yu, Wenjun Zou, et al. · (2026) · "Clinical Significance of Conjunctival Microvascular Density in Diabetic Retinopathy: A Multimodal Correlation Study Based on Swept‐Source Optical Coherence Tomography Angiography" · Journal of Diabetes Research · doi: 10.1155/jdr/9076881 · PMCID: PMC12831052 · PMID: 41584408

Question: What did the discussion section of the paper "Clinical Significance of Conjunctival Microvascular Density in Diabetic Retinopathy: A Multimodal Correlation Study Based on Swept‐Source Optical Coherence Tomography Angiography" cover?

Answer:
Our study revealed a progressive decline in conjunctival VD with advancing DR, with the temporal conjunctival region showing the most significant changes. Conjunctival VD correlates with both retinal vascular parameters and structural alterations in the neural retina. These findings suggest that SS‐OCTA assessment of conjunctival VD, particularly in the temporal quadrant, could serve as a valuable alternative for evaluating the retinal microvascular status in DR patients with poor fundus visibility.

Owing to its superficial location, excellent optical accessibility, and high‐resolution imaging potential, the conjunctival microcirculation provides an ideal window for assessing systemic microvascular pathology. Unlike fundus examination, conjunctival vessel imaging does not require pupil dilation and is unaffected by refractive media opacities. Previous studies utilizing imaging techniques, including AS cameras, computer‐assisted in vivo microscopy, and functional slit‐lamp biomicroscopy, have demonstrated that bulbar conjunctival vascular width and tortuosity increase with DR severity, whereas overall vascular density decreases in patients with diabetes [ 4 , 14 , 15 ]. SS‐OCTA provides higher vascular density quantification than slit‐lamp examination across all quadrants, with its depth‐resolved imaging capability, allowing targeted vascular assessment of the conjunctiva [ 4 , 5 , 16 ].

Our findings align with those reported by Schuerch et al. [ 12 ], although the absolute values of conjunctival VD differed between the studies. This discrepancy may be attributed to the differences in imaging systems and analytical protocols. Specifically, we defined the conjunctival vascular measurement boundary as extending from the superficial conjunctival layer to the anterior border of the scleral stroma, with the final measurements representing the average values across this region. In contrast, Schuerch et al. utilized Heidelberg Spectralis spectral‐domain OCT in the OCTA mode, adapted for AS imaging by coupling a 25D lens with a standard 30° fundus lens. Their acquisition protocol involved 10 ° × 5 ° cube scans centered at the limbus in both the temporal and nasal conjunctival quadrants, with subsequent binarization and analysis using ImageJ (Fiji Version 2.0) to determine the average relative conjunctival VD [ 12 ]. However, they did not perform subgroup analyses stratified by DR. To investigate disease stage dependency, we systematically grouped participants according to clinically validated DR severity scales, which revealed progressive microvascular changes with advancing retinopathy.

Temporal conjunctival VD showed a progressive reduction from the control (70.67%) to PDR (55.61%). No significant conjunctival VD differences existed between controls and patients with diabetes without DR, suggesting a specificity for retinopathic changes rather than systemic diabetes. Temporal conjunctival VD demonstrated stronger correlations with DR severity ( r = −0.588) than did nasal assessments ( r = −0.438), indicating regional diagnostic utility. Comprehensive correlation analysis revealed significant positive associations between temporal conjunctival VD and both retinal VD ( r = 0.21–0.26) and GCC thickness ( r = 0.22) and inverse correlations with clinical DR stage ( r = −0.59) and BCVA ( r = −0.43). Compared to the nasal conjunctival VD, the temporal conjunctival VD showed the most robust correlations with DR severity, retinal VD, and mini‐GCC thickness, suggesting that this region may be particularly vulnerable to diabetic microangiopathy. A previous OCTA study demonstrated good repeatability and interobserver agreement in assessing limbal vascularization among healthy individuals. While significant differences in vascular density between the temporal and nasal quadrants were reported in that study [ 17 ], our findings did not replicate this spatial variation, which is consistent with the findings of Schuerch et al. [ 12 ]. This discrepancy may be attributed to methodological differences, particularly in the selection of the region of interest and the anatomical site of measurement (limbus vs. conjunctiva). Nonetheless, our analysis maintained a quadrant‐specific approach to evaluate the nasal and temporal regions independently to ensure a comprehensive assessment.

Diabetes progression induces vasoconstriction in the bulbar conjunctival microvasculature, resulting in decreased total vascular area relative to that in nondiabetic individuals [ 6 , 18 ]. However, our data do not corroborate this observation. Notably, no significant differences in conjunctival VD were found between healthy controls and diabetic patients without DR, implying that these conjunctival microvascular changes are specific to retinopathic progression rather than to systemic diabetes alone. This specificity enhances the clinical utility of conjunctival VD as a potential biomarker of DR.

Retinal OCTA revealed distinct spatial patterns of vascular compromise. The 1–3 mm parafoveal region exhibited the most marked vascular attenuation, particularly in the nasal quadrant (63.79% in controls vs. 42.07% in patients with PDR). Early temporal quadrant involvement was observed in patients with NPDR (46.91% vs. 57.99% in controls), suggesting that this region may serve as a sentinel marker of initial microvascular damage. The central 1 mm zone showed significant VD reduction across all diabetic groups, indicating early foveal microcirculation compromise, regardless of retinopathy status.

GCC thickness measurements demonstrated nonlinear neurodegenerative changes. Average GCC thickness was most pronounced in PDR (72.73 vs. 79.51 μ m in controls). Sectoral analysis identified the superonasal GCC as particularly vulnerable (85.36 μ m in NPDR vs. 74.41 μ m in PDR), with 12.8% relative thinning. The minimum GCC thickness showed a dramatic reduction in PDR (15.62 vs. 39.70 μ m in controls), highlighting focal neurodegeneration in advanced disease.

Our study demonstrated that microvascular impairment in diabetes is a systemic process that affects multiple vascular beds. Conjunctival microvascular assessments provide a unique window for monitoring diabetic microvascular health. Importantly, our data revealed a progressive reduction in conjunctival VD, which significantly correlated with decreased retinal vascular density and thinning of the GCC. These findings provide compelling evidence for the pathophysiological continuity between the anterior and posterior ocular segment microvascular alterations in DR.

The application of SS‐OCTA to quantify bulbar conjunctival vascular density offers an objective, efficient, and safe approach for evaluating microvascular changes in patients with diabetes. This innovative methodology may establish a more accessible and safer monitoring strategy for patients with DR who cannot undergo conventional fundus examination. Compared to conventional OCTA and fundus examinations, SS‐OCTA‐based conjunctival microvascular density assessment provides several key clinical benefits for diabetic patients. The nonmydriatic and rapid imaging features enhance patient compliance and broaden applicability, particularly in individuals with cataracts or poor fixation. The conjunctival microvascular alterations may precede detectable retinal changes, offering a potential window for earlier intervention in diabetic microvascular complications. Additionally, the high‐resolution quantitative nature of this technology enables precise dynamic monitoring of therapeutic responses while potentially serving as a holistic biomarker for systemic microvascular status. These combined advantages optimize diagnostic workflows and patient management, with the potential to reduce long‐term visual disability and associated healthcare costs through timely intervention.

However, our study had certain limitations. While our sample size was sufficient for initial observations, the cross‐sectional design prevented us from determining causality or predicting progression, and future multicenter longitudinal studies with larger sample sizes are needed. Investigating whether conjunctival changes precede clinically detectable retinopathy would greatly increase the value of screening for conjunctival VD changes.

— Source (discussion, peer-reviewed): Xiaoli Huang, Jiajia Yu, Wenjun Zou, et al. · (2026) · "Clinical Significance of Conjunctival Microvascular Density in Diabetic Retinopathy: A Multimodal Correlation Study Based on Swept‐Source Optical Coherence Tomography Angiography" · Journal of Diabetes Research · doi: 10.1155/jdr/9076881 · PMCID: PMC12831052 · PMID: 41584408
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Julio Rosenstock, Jan Marquard, Lori M. Laffel, et al. · (2018) · "Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials" · Diabetes Care · https://doi.org/10.2337/dc18-1749 · cited 351 times

Question: What does the peer-reviewed literature show about "Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials"? Cite a published source.

Answer:
OBJECTIVE: To evaluate the safety and efficacy of empagliflozin 10- and 25-mg doses plus a unique lower dose (2.5 mg) as adjunct to intensified insulin in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: = 241), 26-week treatment. Together they evaluated empagliflozin 10 mg and 25 mg, doses currently approved in treatment of type 2 diabetes, and additionally 2.5 mg on 26-week change in glycated hemoglobin (primary end point) and weight, glucose time-in-range (>70 to ≤180 mg/dL), insulin dose, blood pressure, and hypoglycemia. RESULTS: < 0.05). Genital infections occurred more frequently on empagliflozin. Adjudicated diabetic ketoacidosis occurred more with empagliflozin 10 mg (4.3%) and 25 mg (3.3%) but was comparable between empagliflozin 2.5 mg (0.8%) and placebo (1.2%). Severe hypoglycemia was rare and frequency was similar between empagliflozin and placebo. CONCLUSIONS: Empagliflozin improved glycemic control and weight in T1D without increasing hypoglycemia. Ketoacidosis rate was comparable between empagliflozin 2.5 mg and placebo but increased with 10 mg and 25 mg. Ketone monitoring for early ketoacidosis detection and intervention and lower empagliflozin doses may help to reduce this risk.

— Source (peer-reviewed): Julio Rosenstock, Jan Marquard, Lori M. Laffel, et al. · (2018) · "Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials" · Diabetes Care · https://doi.org/10.2337/dc18-1749 · cited 351 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Ignazio Vecchio, Cristina Tornali, Nicola Luigi Bragazzi, et al. · (2018) · "The Discovery of Insulin: An Important Milestone in the History of Medicine" · Frontiers in Endocrinology · https://doi.org/10.3389/fendo.2018.00613 · cited 252 times

Question: What does the peer-reviewed literature show about "The Discovery of Insulin: An Important Milestone in the History of Medicine"? Cite a published source.

Answer:
The discovery of insulin represents an authentic breakthrough, characterized, at the same time, by contrasts, controversies and disputes among scholars, as well as by great disappointments, failures and hopes. It is the story of famous, almost famous and little known people, of serendipities, discoveries and re-discoveries. The discovery of insulin has been a milestone and has truly revolutionized both the therapy and the prognosis of the diabetes, one of the diseases most studied in the history of medicine, whose first mentions trace back to a collection of ancient Egyptian, Indian and Chinese textbooks. As stated by Colwell, the introduction of insulin has heralded the end of the so-called "pre-insulin era" or "frustration era", paving the way for a new era and clinical advancements. The current review offers a broad, comprehensive overview of main steps culminating into insulin discovery, including recent advancements such as personalized and individualized insulin therapy.

— Source (peer-reviewed): Ignazio Vecchio, Cristina Tornali, Nicola Luigi Bragazzi, et al. · (2018) · "The Discovery of Insulin: An Important Milestone in the History of Medicine" · Frontiers in Endocrinology · https://doi.org/10.3389/fendo.2018.00613 · cited 252 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Sietse M. Rispens, Kimberley S. van Schooten, Mirjam Pijnappels, et al. · (2014) · "Identification of Fall Risk Predictors in Daily Life Measurements" · Neurorehabilitation and neural repair · https://doi.org/10.1177/1545968314532031 · cited 146 times

Question: What does the peer-reviewed literature show about "Identification of Fall Risk Predictors in Daily Life Measurements"? Cite a published source.

Answer:
Background. Gait characteristics extracted from trunk accelerations during daily life locomotion are complementary to questionnaire- or laboratory-based gait and balance assessments and may help to improve fall risk prediction. Objective. The aim of this study was to identify gait characteristics that are associated with self-reported fall history and that can be reliably assessed based on ambulatory data collected during a single week. Methods. We analyzed 2 weeks of trunk acceleration data (DynaPort MoveMonitor, McRoberts) collected among 113 older adults (age range, 65-97 years). During episodes of locomotion, various gait characteristics were determined, including local dynamic stability, interstride variability, and several spectral features. For each characteristic, we performed a negative binomial regression analysis with the participants' self-reported number of falls in the preceding year as outcome. Reliability of gait characteristics was assessed in terms of intraclass correlations between both measurement weeks. Results. The percentages of spectral power below 0.7 Hz along the vertical and anteroposterior axes and below 10 Hz along the mediolateral axis, as well as local dynamic stability, local dynamic stability per stride, gait smoothness, and the amplitude and slope of the dominant frequency along the vertical axis, were associated with the number of falls in the preceding year and could be reliably assessed (all P < .05, intraclass correlation > 0.75). Conclusions. Daily life gait characteristics are associated with fall history in older adults and can be reliably estimated from a week of ambulatory trunk acceleration measurements.

— Source (peer-reviewed): Sietse M. Rispens, Kimberley S. van Schooten, Mirjam Pijnappels, et al. · (2014) · "Identification of Fall Risk Predictors in Daily Life Measurements" · Neurorehabilitation and neural repair · https://doi.org/10.1177/1545968314532031 · cited 146 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

CGMacros-038

Question: Show me a CGMacros meal where carbs were 76g, protein was 22g, fat was 18.5g, and report the BG response.

Answer:
Subject CGMacros-038 logged a lunch at 11:30 on 2022-01-31 of 76g carb / 22g protein / 18.5g fat / 11g fiber (575 kcal). Pre-meal Libre BG was 80.3 mg/dL. Peak in the next 150 minutes was 113.0 mg/dL (a rise of 32.7 mg/dL from baseline). At the 2-hour mark BG was 106.7 mg/dL.

Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

This describes one logged meal from one subject in a published research dataset. It is not advice. Your individual BG responses, and what they mean for you, are a conversation with your healthcare provider.


Space and time in the brain

György Buzsáki, Rodolfo Llinás · (2017) · "Space and time in the brain" · Science · https://doi.org/10.1126/science.aan8869 · cited 183 times

Question: What does the peer-reviewed literature show about "Space and time in the brain"? Cite a published source.

Answer:
Nothing is more intuitive, yet more complex, than the concepts of space and time. In contrast to spacetime in physics, space and time in neuroscience remain separate coordinates to which we attach our observations. Investigators of navigation and memory relate neuronal activity to position, distance, time point, and duration and compare these parameters to units of measuring instruments. Although spatial-temporal sequences of brain activity often correlate with distance and duration measures, these correlations may not correspond to neuronal representations of space or time. Neither instruments nor brains sense space or time. Neuronal activity can be described as a succession of events without resorting to the concepts of space or time. Instead of searching for brain representations of our preconceived ideas, we suggest investigating how brain mechanisms give rise to inferential, model-building explanations.

— Source (peer-reviewed): György Buzsáki, Rodolfo Llinás · (2017) · "Space and time in the brain" · Science · https://doi.org/10.1126/science.aan8869 · cited 183 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Eva M. del Amo, Anna‐Kaisa Rimpelä, Emma M. Heikkinen, et al. · (2016) · "Pharmacokinetic aspects of retinal drug delivery" · Progress in Retinal and Eye Research · https://doi.org/10.1016/j.preteyeres.2016.12.001 · cited 659 times

Question: Summarize the published evidence on "Pharmacokinetic aspects of retinal drug delivery" with a citation.

Answer:
Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.

— Source (peer-reviewed): Eva M. del Amo, Anna‐Kaisa Rimpelä, Emma M. Heikkinen, et al. · (2016) · "Pharmacokinetic aspects of retinal drug delivery" · Progress in Retinal and Eye Research · https://doi.org/10.1016/j.preteyeres.2016.12.001 · cited 659 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Phi‐Yen Nguyen, Thomas Astell‐Burt, Hania Rahimi‐Ardabili, et al. · (2023) · "Effect of nature prescriptions on cardiometabolic and mental health, and physical activity: a systematic review" · The Lancet Planetary Health · https://doi.org/10.1016/s2542-5196(23)00025-6 · cited 184 times

Question: Summarize the published evidence on "Effect of nature prescriptions on cardiometabolic and mental health, and physical activity: a systematic review" with a citation.

Answer:
Nature prescriptions are gaining popularity as a form of social prescribing in support of sustainable health care. This systematic review and meta-analysis aims to synthesise evidence on the effectiveness of nature prescriptions and determine the factors important for their success. We searched five databases from inception up to July 25, 2021. Randomised and non-randomised controlled studies featuring a nature prescription (ie, a referral or an organised programme, by a health or social professional, to encourage spending time in nature) were included. Two reviewers independently conducted all steps of study selection; one reviewer collected summary data from published reports and conducted the risk of bias assessment. Random-effect DerSimonian-Laird meta-analyses were conducted for five key outcomes. We identified 92 unique studies (122 reports), of which 28 studies contributed data to meta-analyses. Compared with control conditions, nature prescription programmes resulted in a greater reduction in systolic blood pressure (mean difference -4·82 mm Hg [-8·92 to -0·72]) and diastolic blood pressure (mean difference -3·82 mm Hg [-6·47 to -1·16). Nature prescriptions also had a moderate to large effect on depression scores (post-intervention standardised mean difference -0·50 [-0·84 to -0·16]; change from baseline standardised mean difference -0·42 [-0·82 to -0·03]) and anxiety scores (post-intervention standardised mean difference -0·57 [-1·12 to -0·03]; change from baseline standardised mean difference -1·27 [-2·20 to -0·33]). Nature prescriptions resulted in a greater increase in daily step counts than control conditions (mean difference 900 steps [790 to 1010]) but did not improve weekly time of moderate physical activity (mean difference 25·90 min [-10·26 to 62·06]). A subgroup analysis restricted to studies featuring a referring institution showed stronger effects on depression scores, daily step counts, and weekly time of moderate physical activity than the general analysis. Beneficial effects on anxiety and depression scores were mainly provided by interventions involving social professionals whereas beneficial effects on blood pressures and daily step counts were provided mainly by interventions involving health professionals. Most studies have a moderate to high risk of bias. Nature prescription programmes showed evidence of cardiometabolic and mental health benefits and increases in walking. Effective nature prescription programmes can involve a range of natural settings and activities and can be implemented via social and community channels, in addition to health professionals.

— Source (peer-reviewed): Phi‐Yen Nguyen, Thomas Astell‐Burt, Hania Rahimi‐Ardabili, et al. · (2023) · "Effect of nature prescriptions on cardiometabolic and mental health, and physical activity: a systematic review" · The Lancet Planetary Health · https://doi.org/10.1016/s2542-5196(23)00025-6 · cited 184 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Dongwha Sohn, Katie Shpanskaya, Joseph E. Lucas, et al. · (2018) · "Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer’s disease" · Scientific Reports · https://doi.org/10.1038/s41598-018-25377-w · cited 163 times

Question: What does the peer-reviewed literature show about "Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer’s disease"? Cite a published source.

Answer:
Sex differences in Alzheimer's disease (AD) biology and progression are not yet fully characterized. The goal of this study is to examine the effect of sex on cognitive progression in subjects with high likelihood of mild cognitive impairment (MCI) due to Alzheimer's and followed up to 10 years in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cerebrospinal fluid total-tau and amyloid-beta (Aβ42) ratio values were used to sub-classify 559 MCI subjects (216 females, 343 males) as having "high" or "low" likelihood for MCI due to Alzheimer's. Data were analyzed using mixed-effects models incorporating all follow-ups. The worsening from baseline in Alzheimer's Disease Assessment Scale-Cognitive score (mean, SD) (9 ± 12) in subjects with high likelihood of MCI due to Alzheimer's was markedly greater than that in subjects with low likelihood (1 ± 6, p < 0.0001). Among MCI due to AD subjects, the mean worsening in cognitive score was significantly greater in females (11.58 ± 14) than in males (6.87 ± 11, p = 0.006). Our findings highlight the need to further investigate these findings in other populations and develop sex specific timelines for Alzheimer's disease progression.

— Source (peer-reviewed): Dongwha Sohn, Katie Shpanskaya, Joseph E. Lucas, et al. · (2018) · "Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer’s disease" · Scientific Reports · https://doi.org/10.1038/s41598-018-25377-w · cited 163 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Julio Rosenstock, Lars Hansen, Pamela Zee, et al. · (2014) · "Dual Add-on Therapy in Type 2 Diabetes Poorly Controlled With Metformin Monotherapy: A Randomized Double-Blind Trial of Saxagliptin Plus Dapagliflozin Addition Versus Single Addition of Saxagliptin or Dapagliflozin to Metformin" · Diabetes Care · https://doi.org/10.2337/dc14-1142 · cited 286 times

Question: What does the peer-reviewed literature show about "Dual Add-on Therapy in Type 2 Diabetes Poorly Controlled With Metformin Monotherapy: A Randomized Double-Blind Trial of Saxagliptin Plus…"? Cite a published source.

Answer:
OBJECTIVE: This study compared the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone in patients with type 2 diabetes poorly controlled with metformin. RESEARCH DESIGN AND METHODS: This was a double-blind trial in adults with HbA1c ≥8.0% and ≤12.0% (64-108 mmol/mol), randomized to saxagliptin (SAXA) (5 mg/day) plus dapagliflozin (DAPA) (10 mg/day; n = 179), or SAXA (5 mg/day) and placebo (n = 176), or DAPA (10 mg/day) and placebo (n = 179) on background metformin extended release (MET) ≥1,500 mg/day. Primary objective compared changes from baseline in HbA1c with SAXA+DAPA+MET versus SAXA+MET and DAPA+MET. RESULTS: Patients had a mean baseline HbA1c of 8.9% (74 mmol/mol), diabetes duration of 7.6 years, and a BMI of 32 kg/m(2). At week 24, the adjusted mean change from the baseline HbA1c was -1.5% (-16.1 mmol/mol) with SAXA+DAPA+MET versus -0.9% (-9.6 mmol/mol) with SAXA+MET (difference -0.59% [-6.4 mmol/mol], P < 0.0001) and -1.2% (-13.1 mmol/mol) with DAPA+MET (difference -0.27% [3.0 mmol/mol], P < 0.02). The proportion of patients achieving HbA1c <7% (53 mmol/mol) was 41% with SAXA+DAPA+MET versus 18% with SAXA+MET and 22% with DAPA+MET. Urinary and genital infections occurred in ≤1% of patients receiving SAXA+DAPA+MET. Hypoglycemia was infrequent, with no episodes of major hypoglycemia. CONCLUSIONS: In this first report of adding a well-tolerated combination of saxagliptin plus dapagliflozin to background metformin therapy in patients poorly controlled with metformin, greater improvements in glycemic control were obtained with triple therapy by the dual addition of saxagliptin and dapagliflozin than dual therapy with the addition of saxagliptin or dapagliflozin alone.

— Source (peer-reviewed): Julio Rosenstock, Lars Hansen, Pamela Zee, et al. · (2014) · "Dual Add-on Therapy in Type 2 Diabetes Poorly Controlled With Metformin Monotherapy: A Randomized Double-Blind Trial of Saxagliptin Plus Dapagliflozin Addition Versus Single Addition of Saxagliptin or Dapagliflozin to Metformin" · Diabetes Care · https://doi.org/10.2337/dc14-1142 · cited 286 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Byron J. Smith, Richard A. Miller, Aaron C. Ericsson, et al. · (2019) · "Changes in the gut microbiome and fermentation products concurrent with enhanced longevity in acarbose-treated mice" · BMC Microbiology · https://doi.org/10.1186/s12866-019-1494-7 · cited 366 times

Question: Summarize the published evidence on "Changes in the gut microbiome and fermentation products concurrent with enhanced longevity in acarbose-treated mice" with a citation.

Answer:
BACKGROUND: Treatment with the α-glucosidase inhibitor acarbose increases median lifespan by approximately 20% in male mice and 5% in females. This longevity extension differs from dietary restriction based on a number of features, including the relatively small effects on weight and the sex-specificity of the lifespan effect. By inhibiting host digestion, acarbose increases the flux of starch to the lower digestive system, resulting in changes to the gut microbiota and their fermentation products. Given the documented health benefits of short-chain fatty acids (SCFAs), the dominant products of starch fermentation by gut bacteria, this secondary effect of acarbose could contribute to increased longevity in mice. To explore this hypothesis, we compared the fecal microbiome of mice treated with acarbose to control mice at three independent study sites. RESULTS: Microbial communities and the concentrations of SCFAs in the feces of mice treated with acarbose were notably different from those of control mice. At all three study sites, the bloom of a single bacterial taxon was the most obvious response to acarbose treatment. The blooming populations were classified to the largely uncultured Bacteroidales family Muribaculaceae and were the same taxonomic unit at two of the three sites. Propionate concentrations in feces were consistently elevated in treated mice, while the concentrations of acetate and butyrate reflected a dependence on study site. Across all samples, Muribaculaceae abundance was strongly correlated with propionate and community composition was an important predictor of SCFA concentrations. Cox proportional hazards regression showed that the fecal concentrations of acetate, butyrate, and propionate were, together, predictive of mouse longevity even while controlling for sex, site, and acarbose. CONCLUSION: We observed a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in the longevity-enhancing properties of acarbose. Treatment modulated the taxonomic composition and fermentation products of the gut microbiome, while the site-dependence of the responses illustrate the challenges facing reproducibility and interpretation in microbiome studies. These results motivate future studies exploring manipulation of the gut microbial community and its fermentation products for increased longevity, testing causal roles of SCFAs in the observed effects of acarbose.

— Source (peer-reviewed): Byron J. Smith, Richard A. Miller, Aaron C. Ericsson, et al. · (2019) · "Changes in the gut microbiome and fermentation products concurrent with enhanced longevity in acarbose-treated mice" · BMC Microbiology · https://doi.org/10.1186/s12866-019-1494-7 · cited 366 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.

FDA disclaimer: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.


Metabolic Effects of Exercise

Paolo Moghetti, Elisabetta Bacchi, Corinna Brangani, et al. · (2016) · "Metabolic Effects of Exercise" · Frontiers of hormone research · https://doi.org/10.1159/000445156 · cited 130 times

Question: Summarize the published evidence on "Metabolic Effects of Exercise" with a citation.

Answer:
Exercise has a powerful action on metabolism, and adaptation of the body to changes induced by exercise is fundamental to be able to provide the energy required for muscle contraction and physiological functions of vital tissues. Depending on the intensity and duration of exercise, different mechanisms are called on to make energy available, and under homeostatic control, this is guaranteed by rapid and coordinated changes in the secretion of several hormones. Molecular mechanisms controlling muscle function and fiber phenotype are related to the specific mode of muscle activation. We can distinguish between two fundamental types of physical activity, endurance exercise and strength exercise, although there is a continuum between these exercise modalities. Besides the acute changes induced by a single exercise session, regular exercise may induce chronic adaptations, improving exercise capacity and affecting energy metabolism. Notably, although acute metabolic effects of exercise are mostly due to insulin-independent effects, exercise training may improve muscle insulin sensitivity and is considered a key tool in the prevention and treatment of metabolic disorders. This chapter focuses on the biochemistry of energy supply to the exercising muscle, on molecular mechanisms involved and on the physiology of energy metabolism during exercise in healthy subjects and patients with insulin resistance and/or diabetes.

— Source (peer-reviewed): Paolo Moghetti, Elisabetta Bacchi, Corinna Brangani, et al. · (2016) · "Metabolic Effects of Exercise" · Frontiers of hormone research · https://doi.org/10.1159/000445156 · cited 130 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Lucas Bouys, Anna Vaczlavik, Anne Jouinot, et al. · (2022) · "Identification of predictive criteria for pathogenic variants of primary bilateral macronodular adrenal hyperplasia (PBMAH) gene <i>ARMC5</i> in 352 unselected patients" · European Journal of Endocrinology · https://doi.org/10.1530/eje-21-1032 · cited 61 times

Question: What does the peer-reviewed literature show about "Identification of predictive criteria for pathogenic variants of primary bilateral macronodular adrenal hyperplasia (PBMAH) gene…"? Cite a published source.

Answer:
Objective: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a heterogeneous disease characterized by adrenal macronodules and variable levels of cortisol excess, with not clearly established clinical diagnostic criteria. It can be caused by ARMC5 germline pathogenic variants. In this study, we aimed to identify predictive criteria for ARMC5 variants. Methods: We included 352 consecutive index patients from 12 European centers, sequenced for germline ARMC5 alteration. Clinical, biological and imaging data were collected retrospectively. Results: 52 patients (14.8%) carried ARMC5 germline pathogenic variants and showed a more distinct phenotype than non-mutated patients for cortisol excess (24-h urinary free cortisol 2.32 vs 1.11-fold ULN, respectively, P < 0.001) and adrenal morphology (maximal adrenal diameter 104 vs 83 mm, respectively, P < 0.001) and were more often surgically or medically treated (67.9 vs 36.8%, respectively, P < 0.001). ARMC5-mutated patients showed a constant, bilateral adrenal involvement and at least a possible autonomous cortisol secretion (defined by a plasma cortisol after 1 mg dexamethasone suppression above 50 nmol/L), while these criteria were not systematic in WT patients (78.3%). The association of these two criteria holds a 100% sensitivity and a 100% negative predictive value for ARMC5 pathogenic variant. Conclusion: We report the largest series of index patients investigated for ARMC5 and confirm that ARMC5 pathogenic variants are associated with a more severe phenotype in most cases. To minimize negative ARMC5 screening, genotyping should be limited to clear bilateral adrenal involvement and autonomous cortisol secretion, with an optimum sensitivity for routine clinical practice. These findings will also help to better define PBMAH diagnostic criteria.

— Source (peer-reviewed): Lucas Bouys, Anna Vaczlavik, Anne Jouinot, et al. · (2022) · "Identification of predictive criteria for pathogenic variants of primary bilateral macronodular adrenal hyperplasia (PBMAH) gene <i>ARMC5</i> in 352 unselected patients" · European Journal of Endocrinology · https://doi.org/10.1530/eje-21-1032 · cited 61 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

CGMacros-008

Question: What did subject CGMacros-008's BG do after a breakfast of 24g carbs at 09:26 on 2023-02-04?

Answer:
Subject CGMacros-008 logged a breakfast at 09:26 on 2023-02-04 of 24g carb / 22g protein / 10.5g fat / 0g fiber (268 kcal). Pre-meal Libre BG was 96.2 mg/dL. Peak in the next 150 minutes was 128.0 mg/dL (a rise of 31.8 mg/dL from baseline). At the 2-hour mark BG was 123.3 mg/dL.

Data from the CGMacros dataset (PhysioNet). Khoo et al. (2024), CGMacros: A Continuous Glucose Monitoring and Macronutrient Dataset, PhysioNet.

This describes one logged meal from one subject in a published research dataset. It is not advice. Your individual BG responses, and what they mean for you, are a conversation with your healthcare provider.


UK National Health Service (NHS) — Medicines A-Z

About empagliflozin - Brand name: Jardiance

NHS website medicines A-Z, Open Government Licence v3.0 (Crown copyright)

Question: How does the NHS describe Key facts? Provide the verbatim source.

Answer:
You'll usually take empagliflozin once a day. Empagliflozin starts to work after about 1 to 2 hours to reduce your blood sugar levels, but it may take up to a week for it to work fully. If you're taking empagliflozin with other diabetes medicines, it can sometimes cause low blood sugar (hypoglycaemia) . It's a good idea to carry some sweets or fruit juice with you in case this happens. Unlike some diabetes medicines, empagliflozin does not make you put on weight. In fact, some people find they lose weight. If you have diabetes, you're entitled to free prescriptions for all your medicines, not just your diabetes ones.

— Source: www.nhs.uk/medicines/empagliflozin/about-empagliflozin/
  Publisher: UK National Health Service (NHS) — Medicines A-Z
  Page: "About empagliflozin - Brand name: Jardiance"
  Section: "Key facts"
  License: NHS website medicines A-Z, Open Government Licence v3.0 (Crown copyright)
  Retrieved: 2026-05-14

Note: This is public-health information from an authoritative international body. It reflects population-level guidance, not individualized medical advice. For decisions about your own health, please discuss with your healthcare provider.


Richard J. Glassock, Pierre Delanaye, Meguid El Nahas · (2015) · "An Age-Calibrated Classification of Chronic Kidney Disease" · JAMA · https://doi.org/10.1001/jama.2015.6731 · cited 134 times

Question: Summarize the published evidence on "An Age-Calibrated Classification of Chronic Kidney Disease" with a citation.

Answer:
This Viewpoint discusses the ramifications of using a glomerular filtration rate of less than 60 mL/min/1.73 m2 for patients of all ages and proteinuria (albuminuria) for chronic kidney disease classification.

— Source (peer-reviewed): Richard J. Glassock, Pierre Delanaye, Meguid El Nahas · (2015) · "An Age-Calibrated Classification of Chronic Kidney Disease" · JAMA · https://doi.org/10.1001/jama.2015.6731 · cited 134 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Mohammed S. Ellulu, Ismail Patimah, Huzwah Khaza’ai, et al. · (2016) · "Obesity and inflammation: the linking mechanism and the complications" · Archives of Medical Science · https://doi.org/10.5114/aoms.2016.58928 · cited 1,917 times

Question: What does the peer-reviewed literature show about "Obesity and inflammation: the linking mechanism and the complications"? Cite a published source.

Answer:
Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.

— Source (peer-reviewed): Mohammed S. Ellulu, Ismail Patimah, Huzwah Khaza’ai, et al. · (2016) · "Obesity and inflammation: the linking mechanism and the complications" · Archives of Medical Science · https://doi.org/10.5114/aoms.2016.58928 · cited 1,917 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Charles D. Kassardjian, Jessica Widdifield, J. Michael Paterson, et al. · (2020) · "Serious infections in patients with myasthenia gravis: population‐based cohort study" · European Journal of Neurology · https://doi.org/10.1111/ene.14153 · cited 62 times

Question: What does the peer-reviewed literature show about "Serious infections in patients with myasthenia gravis: population‐based cohort study"? Cite a published source.

Answer:
BACKGROUND AND PURPOSE: To characterize the frequency and risk of serious infections in patients with myasthenia gravis (MG) relative to age/sex/area-matched comparators. METHODS: This was a population-based cohort study in Ontario, Canada of patients with newly-diagnosed MG and 1:4 age/sex/area-matched general population comparators accrued from 1 April 2002 to 31 December 2015. The main outcome was a serious infection, defined by a primary diagnosis code on a hospitalization or emergency department record. We computed crude overall and sex-specific rates of infection among patients with MG and comparators, and the frequency of specific types of infection. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox regression. RESULTS: Among 3823 patients with MG, 1275 (33.4%) experienced a serious infection compared with 2973/15 292 (19.4%) of comparators over a mean follow-up of over 5 years. Crude infection rates among patients with MG were twice those in comparators (72.5 vs. 35.0 per 1000 person-years, respectively). The most common infection types were respiratory infections, particularly bacterial pneumonia. After adjustment for potential confounders, MG was associated with a 39% increased infection risk (adjusted hazard ratio, 1.39; 95% confidence intervals, 1.28-1.51). CONCLUSIONS: Patients with MG are at a significantly higher absolute and relative risk of serious infections compared with age/sex/area-matched comparators. This needs to be considered when selecting MG treatments and when planning vaccination/prophylaxis. Determining whether this risk is due to the use of immunosuppressive medications (vs. MG itself) is an important area for future research.

— Source (peer-reviewed): Charles D. Kassardjian, Jessica Widdifield, J. Michael Paterson, et al. · (2020) · "Serious infections in patients with myasthenia gravis: population‐based cohort study" · European Journal of Neurology · https://doi.org/10.1111/ene.14153 · cited 62 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


NHS website content, Open Government Licence v3.0 (Crown copyright)

Question: According to the NHS, on the topic of "check for signs of a stroke"

Answer:
The main symptoms of a stroke can happen suddenly. They may include:

face weakness – one side of your face may droop (fall) and it might be hard to smile arm weakness – you may not be able to fully lift both arms and keep them there because of weakness or numbness in 1 arm speech problems – you may slur your words or sound confused

The easiest way to remember these symptoms is the word FAST. This stands for: face, arms, speech and time to call 999.

There are other signs that you or someone else is having a stroke. These include:

weakness or numbness down 1 side of your body blurred vision or loss of sight in 1 or both eyes finding it difficult to speak or think of words confusion and memory loss feeling dizzy or falling over a severe headache feeling or being sick (nausea or vomiting)

Symptoms of a stroke can sometimes stop after a short time, so you may think you're OK. Even if this happens, get medical help straight away.

A stroke is more likely to happen if you're older, but it can happen at any age.

— Source: www.nhs.uk/conditions/stroke/symptoms/
  Publisher: UK National Health Service (NHS)
  Page: "Symptoms of a stroke"
  Section: "Check for signs of a stroke"
  License: NHS website content, Open Government Licence v3.0 (Crown copyright)
  Retrieved: 2026-05-14

Note: This is public-health information from an authoritative international body. It reflects population-level guidance, not individualized medical advice. For decisions about your own health, please discuss with your healthcare provider.


W. R. C. Rowley, Clement Bezold, Yasemin Arikan, et al. · (2016) · "Diabetes 2030: Insights from Yesterday, Today, and Future Trends" · Population Health Management · https://doi.org/10.1089/pop.2015.0181 · cited 653 times

Question: What does the peer-reviewed literature show about "Diabetes 2030: Insights from Yesterday, Today, and Future Trends"? Cite a published source.

Answer:
To forecast future trends in diabetes prevalence, morbidity, and costs in the United States, the Institute for Alternative Futures has updated its diabetes forecasting model and extended its projections to 2030 for the nation, all states, and several metropolitan areas. This paper describes the methodology and data sources for these diabetes forecasts and discusses key implications. In short, diabetes will remain a major health crisis in America, in spite of medical advances and prevention efforts. The prevalence of diabetes (type 2 diabetes and type 1 diabetes) will increase by 54% to more than 54.9 million Americans between 2015 and 2030; annual deaths attributed to diabetes will climb by 38% to 385,800; and total annual medical and societal costs related to diabetes will increase 53% to more than $622 billion by 2030. Improvements in management reducing the annual incidence of morbidities and premature deaths related to diabetes over this time period will result in diabetes patients living longer, but requiring many years of comprehensive management of multiple chronic diseases, resulting in dramatically increased costs. Aggressive population health measures, including increased availability of diabetes prevention programs, could help millions of adults prevent or delay the progression to type 2 diabetes, thereby helping turn around these dire projections.

— Source (peer-reviewed): W. R. C. Rowley, Clement Bezold, Yasemin Arikan, et al. · (2016) · "Diabetes 2030: Insights from Yesterday, Today, and Future Trends" · Population Health Management · https://doi.org/10.1089/pop.2015.0181 · cited 653 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Amanda S. MacLeod, Jonathan Mansbridge · (2015) · "The Innate Immune System in Acute and Chronic Wounds" · Advances in Wound Care · https://doi.org/10.1089/wound.2014.0608 · cited 281 times

Question: Summarize the published evidence on "The Innate Immune System in Acute and Chronic Wounds" with a citation.

Answer:
The review highlights processes that may be useful targets for further investigation, particularly the switch from M1 to M2 macrophages that appears to be critical as dysregulation of this switch occurs during defective wound healing.

— Source (peer-reviewed): Amanda S. MacLeod, Jonathan Mansbridge · (2015) · "The Innate Immune System in Acute and Chronic Wounds" · Advances in Wound Care · https://doi.org/10.1089/wound.2014.0608 · cited 281 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Sasitorn Kerdsuknirund, Pakanit Kupittayanant, Pattama Tongdee, et al. · (2026) · "Pandanus amaryllifolius and Tectona grandis Extracts Improve Fetal Outcomes in Streptozotocin-Induced Gestational Diabetes in Rats" · International Journal of Molecular Sciences · doi: 10.3390/ijms27020857 · PMCID: PMC12840670 · PMID: 41596503

Question: Summarize the abstract of the paper titled "Pandanus amaryllifolius and Tectona grandis Extracts Improve Fetal Outcomes in Streptozotocin-Induced Gestational Diabetes in Rats".

Answer:
Gestational diabetes mellitus (GDM) causes adverse effects on both mothers and offspring. This study investigated the effects of a polyherbal formulation combining Pandanus amaryllifolius root and Tectona grandis leaf extracts on maternal and fetal outcomes in streptozotocin (STZ)-induced GDM rats, compared with metformin. Pregnant rats were assigned to a non-diabetic reference group and diabetic groups, including an untreated diabetic group (negative control), a metformin-treated group (positive control), and diabetic groups treated with low, medium, or high doses of the pandan–teak formulation from gestation day 7 to 21. Medium and high doses significantly increased maternal body weight and pancreatic mass index ( p < 0.05) without altering maternal glycemia or insulin levels. Fetal weight increased at medium and high doses, whereas crown–rump length increased only at the high dose. Placental index and fetal glucose levels decreased in a dose-dependent manner ( p < 0.05), with no significant change in implantation loss. These findings suggest that the pandan–teak formulation may exert complementary actions that support placental–fetal glucose regulation and fetal growth while maintaining maternal glycemic stability, indicating its potential as a plant-based adjunct approach for gestational diabetes focused on fetal protection.

— Source (abstract, peer-reviewed): Sasitorn Kerdsuknirund, Pakanit Kupittayanant, Pattama Tongdee, et al. · (2026) · "Pandanus amaryllifolius and Tectona grandis Extracts Improve Fetal Outcomes in Streptozotocin-Induced Gestational Diabetes in Rats" · International Journal of Molecular Sciences · doi: 10.3390/ijms27020857 · PMCID: PMC12840670 · PMID: 41596503
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Xiaomin Xian, Jingfeng Chen, Ziqiang Li, et al. · (2026) · "Factors associated with diabetic retinopathy among patients with diabetes in rural Guangxi, China: a multicenter cross-sectional study" · Frontiers in Endocrinology · doi: 10.3389/fendo.2026.1683063 · PMCID: PMC12961075 · PMID: 41798192

Question: What does the published research conclude about "Factors associated with diabetic retinopathy among patients with diabetes in rural Guangxi, China: a multicenter cross-sectional study"? Cite a peer-reviewed source.

Answer:
This study examined diabetes in the rural population of Guangxi. The prevalence of DR among people living with diabetes was 22.36%, with age, elevated triglyceride levels, and HbA1c identified as variables independently associated with DR. These findings highlight the need for targeted interventions, including community-based screening, diabetes education, accessible healthcare services, and strengthened local healthcare infrastructure, to reduce the burden of DR and related complications.

— Source (conclusions, peer-reviewed): Xiaomin Xian, Jingfeng Chen, Ziqiang Li, et al. · (2026) · "Factors associated with diabetic retinopathy among patients with diabetes in rural Guangxi, China: a multicenter cross-sectional study" · Frontiers in Endocrinology · doi: 10.3389/fendo.2026.1683063 · PMCID: PMC12961075 · PMID: 41798192
License: CC-BY. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Santosh Shelke, Sadhana Shahi, Sunil Jalalpure, et al. · (2016) · "Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan-loaded nanoethosomes: formulation, optimization, evaluation and permeation studies" · Journal of Liposome Research · https://doi.org/10.3109/08982104.2015.1132232 · cited 95 times

Question: What does the peer-reviewed literature show about "Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan-loaded nanoethosomes: formulation, optimization, evaluation and…"? Cite a published source.

Answer:
Zolmitriptan is the drug of choice for migraine, but low oral bioavailability (<50%) and recurrence of migraine lead to frequent dosing and increase in associated side effects. Increase in the residence time of drug at the site of drug absorption along with direct nose to brain targeting of zolmitriptan can be a solution to the existing problems. Hence, in the present investigation, thermoreversible intranasal gel of zolmitriptan-loaded nanoethosomes was formulated by using mucoadhesive polymers to increase the residence of the drug into the nasal cavity. The preparation of ethosomes was optimized by using 3(2) factorial design for percent drug entrapment efficiency, vesicle size, zeta potential, and polydispersity index. Optimized formulation E6 showed the vesicle size (171.67 nm) and entrapment efficiency (66%) when compared with the other formulations. Thermoreversible gels prepared by using poloxamer 407 showed the phase transition temperature at 32-33 °C which was in line with the nasal physiological temperature. The optimized ethosomes were loaded into the thermoreversible mucoadhesive gel optimized by varying concentrations of poloxamer 407, carbopol 934, HPMC K100, and evaluated for gel strength, gelation temperature, mucoadhesive strength, in vitro drug release, and ex vivo drug permeation, where G3 and G6 were found to be optimized formulations. In vitro drug release was studied by different kinetic models suggested that G3 (n = 0.582) and G6 (n = 0.648) showed Korsemeyer-Peppas (KKP) model indicating non-Fickian release profiles. A permeation coefficient of 5.92 and 5.9 µg/cm(2) for G3 and G6, respectively, revealed very little difference in release rate after 24 h between both the formulations. Non-toxic nature of the gels on columnar epithelial cells was confirmed by histopathological evaluation.

— Source (peer-reviewed): Santosh Shelke, Sadhana Shahi, Sunil Jalalpure, et al. · (2016) · "Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan-loaded nanoethosomes: formulation, optimization, evaluation and permeation studies" · Journal of Liposome Research · https://doi.org/10.3109/08982104.2015.1132232 · cited 95 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Jorge Ruiz-Medrano, Patricia Udaondo Mirete, Marina Fernández-Jiménez, et al. · (2025) · "Biomarkers of risk of switching to dexamethasone implant for the treatment of diabetic macular oedema in real clinical practice: a multicentric study" · The British Journal of Ophthalmology · doi: 10.1136/bjo-2024-325665 · PMCID: PMC12505042 · PMID: 40379451

Question: Summarize the abstract of the paper titled "Biomarkers of risk of switching to dexamethasone implant for the treatment of diabetic macular oedema in real clinical practice: a multicentric study".

Answer:
To establish the influence of different optical coherence tomography (OCT) biomarkers at baseline treatment on the potential response to anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular oedema (DME).

Multicentric, retrospective, case-series study in patients with DME switched to dexamethasone implant injections (DEX-i) after anti-VEGF in real clinical practice. Biomarkers analysed on OCT images at baseline included intraretinal fluid (IRF), subretinal fluid (SRF), disorganisation of retinal inner layers (DRIL), disorganisation of retinal outer layers (DROL), hyperreflective foci (HRF), hyperreflective cystoid walls (HCW), dense intraretinal cyst (DIR) and vitreomacular interface (VMI) abnormalities. DME was classified according to the European School for Advanced Studies in Ophthalmology classification. Patients who were treated with anti-VEGF injections with an adequate response were selected as the control group.

275 eyes were analysed in this study; 209 eyes (76.0%) switched from anti-VEGF to DEX-i were compared with 66 control eyes (24.0%). Patients who required switching were statistically older, showed worse initial BCVA and higher CRT. Logistic regression analyses showed that female gender, age, central retinal thickness, type of diabetes, SRF, HCW, DIR and VMI increase the likelihood of switching. The OR regarding the need to switch generated by the presence of two of these three factors (SRF, HCW, VMI) was 48.95. Having all three multiplies it by 4.56×10 16 .

If baseline OCT shows two of SRF, HCW and VMI biomarkers at baseline, the risk of failure of anti-VEGF therapy is close to 50%. In the presence at baseline of all three biomarkers, failure of anti-VEGF therapy is almost certain.

— Source (abstract, peer-reviewed): Jorge Ruiz-Medrano, Patricia Udaondo Mirete, Marina Fernández-Jiménez, et al. · (2025) · "Biomarkers of risk of switching to dexamethasone implant for the treatment of diabetic macular oedema in real clinical practice: a multicentric study" · The British Journal of Ophthalmology · doi: 10.1136/bjo-2024-325665 · PMCID: PMC12505042 · PMID: 40379451
License: CC-BY-NC. Retrieved from PubMed Central full text.

Note: This reproduces published research findings. It is not individualized medical advice. Please discuss your situation with your healthcare provider or care team.


Stilianos Louca, Michael Doebeli, Laura Wegener Parfrey · (2018) · "Correcting for 16S rRNA gene copy numbers in microbiome surveys remains an unsolved problem" · Microbiome · https://doi.org/10.1186/s40168-018-0420-9 · cited 766 times

Question: Summarize the published evidence on "Correcting for 16S rRNA gene copy numbers in microbiome surveys remains an unsolved problem" with a citation.

Answer:
<0.5) for the majority of tested microbial communities. The nearest sequenced taxon index (NSTI) of microbial communities, i.e., the average distance to a sequenced genome, was a strong predictor for the agreement between GCN prediction tools on non-animal-associated samples, but only a moderate predictor for animal-associated samples. We recommend against correcting for 16S GCNs in microbiome surveys by default, unless OTUs are sufficiently closely related to sequenced genomes or unless a need for true OTU proportions warrants the additional noise introduced, so that community profiles remain interpretable and comparable between studies.

— Source (peer-reviewed): Stilianos Louca, Michael Doebeli, Laura Wegener Parfrey · (2018) · "Correcting for 16S rRNA gene copy numbers in microbiome surveys remains an unsolved problem" · Microbiome · https://doi.org/10.1186/s40168-018-0420-9 · cited 766 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Suk‐Yu Yau, Ang Li, Ruby L.C. Hoo, et al. · (2014) · "Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin" · Proceedings of the National Academy of Sciences · https://doi.org/10.1073/pnas.1415219111 · cited 317 times

Question: Summarize the published evidence on "Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin" with a citation.

Answer:
Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.

— Source (peer-reviewed): Suk‐Yu Yau, Ang Li, Ruby L.C. Hoo, et al. · (2014) · "Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin" · Proceedings of the National Academy of Sciences · https://doi.org/10.1073/pnas.1415219111 · cited 317 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Bedilu Deribe · (2014) · "Prevalence and Factors Influencing Diabetic Foot Ulcer among Diabetic Patients Attending Arbaminch Hospital, South Ethiopia" · Journal of Diabetes & Metabolism · https://doi.org/10.4172/2155-6156.1000322 · cited 92 times

Question: What does the peer-reviewed literature show about "Prevalence and Factors Influencing Diabetic Foot Ulcer among Diabetic Patients Attending Arbaminch Hospital, South Ethiopia"? Cite a published source.

Answer:
Background: Diabetic foot ulcer is one of the long standing complications of diabetic mellitus with the life time risk up to 25%. In Africa in general, particularly in Ethiopia, there are limited epidemiological studies related to diabetic foot ulcer.

— Source (peer-reviewed): Bedilu Deribe · (2014) · "Prevalence and Factors Influencing Diabetic Foot Ulcer among Diabetic Patients Attending Arbaminch Hospital, South Ethiopia" · Journal of Diabetes & Metabolism · https://doi.org/10.4172/2155-6156.1000322 · cited 92 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.


Data from the Big IDEAs Lab Glycemic Variability Database (PhysioNet). Cho et al., Big IDEAs Lab Glycemic Variability Database, PhysioNet.

012

Question: What is the glycemic variability (CV%) for subject 012 in the Big IDEAs dataset over day 2020-05-08?

Answer:
Window: day 2020-05-08 (2020-05-08 00:02 to 2020-05-08 23:57, 288 EGV readings spanning 23.9 hours). Coefficient of variation (CV%) was 11.51%, computed as standard deviation / mean x 100. SD = 13.7 mg/dL, mean = 119.1 mg/dL.

Data from the Big IDEAs Lab Glycemic Variability Database (PhysioNet). Cho et al., Big IDEAs Lab Glycemic Variability Database, PhysioNet.

This describes computed metrics from one subject in a published research dataset. It is not advice. Your individual CGM metrics, and what they mean for you, are a conversation with your healthcare provider.


M.A. Leslie, Daniel J. Cohen, Danyelle M. Liddle, et al. · (2015) · "A review of the effect of omega-3 polyunsaturated fatty acids on blood triacylglycerol levels in normolipidemic and borderline hyperlipidemic individuals" · Lipids in Health and Disease · https://doi.org/10.1186/s12944-015-0049-7 · cited 143 times

Question: What does the peer-reviewed literature show about "A review of the effect of omega-3 polyunsaturated fatty acids on blood triacylglycerol levels in normolipidemic and borderline…"? Cite a published source.

Answer:
Circulating levels of triacylglycerol (TG) is a recognized risk factor for developing cardiovascular disease, a leading cause of death worldwide. The Institute of Medicine and the American Heart Association both recommend the consumption of n-3 polyunsaturated fatty acids (PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to reduce serum TG in hyperlipidemic individuals. Additionally, a number of systematic reviews have shown that individuals with any degree of dyslipidemia, elevated serum TG and/or cholesterol, may benefit from a 20-30% reduction in serum TG after consuming n-3 PUFA derived from marine sources. Given that individuals with serum lipid levels ranging from healthy to borderline dyslipidemic constitute a large portion of the population, the focus of this review was to assess the potential for n-3 PUFA consumption to reduce serum TG in such individuals. A total of 1341 studies were retrieved and 38 clinical intervention studies, assessing 2270 individuals, were identified for inclusion in the current review. In summary, a 9-26% reduction in circulating TG was demonstrated in studies where ≥ 4 g/day of n-3 PUFA were consumed from either marine or EPA/DHA-enriched food sources, while a 4-51% reduction was found in studies where 1-5 g/day of EPA and/or DHA was consumed through supplements. Overall, this review summarizes the current evidence with regards to the beneficial effect of n-3 PUFA on circulating TG levels in normolipidemic to borderline hyperlipidemic, otherwise healthy, individuals. Thus demonstrating that n-3 PUFA may play an important role in the maintenance of cardiovascular health and disease prevention.

— Source (peer-reviewed): M.A. Leslie, Daniel J. Cohen, Danyelle M. Liddle, et al. · (2015) · "A review of the effect of omega-3 polyunsaturated fatty acids on blood triacylglycerol levels in normolipidemic and borderline hyperlipidemic individuals" · Lipids in Health and Disease · https://doi.org/10.1186/s12944-015-0049-7 · cited 143 times

Note: This summarizes published research findings. It is not individualized medical advice. For your situation, please discuss with your healthcare provider.

FDA disclaimer: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.