Medicine and Pharmacology

Abstract: Background/Objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors share a renal mechanism but differ in SGLT1 selectivity, off-target activity and licensed indications. We compared exposure-adjusted reporting of suspected adverse reactions for canagliflozin, dapagliflozin, empagliflozin and ertugliflozin and examined whether differences between them are consistent with molecule-specific pharmacology. Methods: UK Yellow Card reaction entries for 2021–2025 were related to English NHS general practice and estimated hospital prescribed items for the same 60 months. Rates were calculated with exact Poisson intervals, reporting rate ratios (RRRs) versus dapagliflozin with Poisson regression and Holm adjustment, and annual trends with quasi-Poisson regression; within-class disproportionality was also calculated without a prescribing denominator. Results: The analysis included 8789 reaction entries and 52.19 million items. Total reporting rates were 125.47, 188.83, 143.53 and 213.64 per million items, respectively. Ketoacidosis and ketosis reporting was higher for canagliflozin (RRR 2.45, 95% CI 2.02–2.95) and empagliflozin (1.93, 1.69–2.19), as was euglycaemic ketoacidosis reporting, and peripheral tissue injury reporting was higher for canagliflozin (2.80, 1.63–4.64). Amputation reporting was higher for canagliflozin (3.69, 1.14–10.61) but not after adjustment, and 2.68 for lower-limb terms. Within the class, the entry-level ketoacidosis reporting odds ratio for canagliflozin was 3.10 (2.53–3.80). Ketoacidosis reporting declined by 32.0% per year for dapagliflozin and by 24.4% for empagliflozin. Conclusions: Higher ketoacidosis and peripheral tissue injury reporting for canagliflozin is compatible with its lower SGLT2 selectivity, but equally with population or reporting differences, which these data cannot separate. Empagliflozin does not fit a selectivity explanation. These are reporting rates, not incidence estimates.

Abstract: The DiAL Health Pilot Trial is a well-designed study that measures body mass, fat mass, fat-free mass, and food intake using state-of-the-art methods. Yet its analysis converts these mass measurements into energy equivalents and uses energy as the primary variable. This commentary identifies three loci of energy derivation in the protocol: the weight-loss nomograms, the CR adherence quantification (Equation 1), and the calorie prescription itself. A concrete numerical example shows that energy-based and mass-based analyses can produce divergent results for the same participant. The energy balance equation is mathematically underdetermined with respect to growth composition: one equation, two unknowns. The mass measurements are not. The TRE arm of the trial is not affected by the same issue, because its adherence metric is time-based rather than energy-based. This makes the CR analysis an isolated case rather than a general problem with the trial. A mass-balance analysis would preserve the information that the energy conversion discards, and would produce adherence metrics directly interpretable in the units actually measured. The argument is not that the DiAL Health trial is flawed. It is that the analytical framework it inherited contains a detour that is no longer necessary given the measurements the trial already performs.

Abstract: Behavioral and sensory research on food intake has long treated energy content as if it were a directly perceptible property of food. Organisms are said to “detect,” “evaluate,” or “compensate for” calories. This language imports an energy-centric ontology into a sensory system that has no access to energy as such. There are no receptors for the joule or the kilocalorie. Taste, smell, texture, oral processing, and gastric distension respond to molecular identity, physical mass, volume, and structure. Post-ingestive signals report molecular identity and concentration, not energy content. Energy is a derived quantity that can be associated with sensory patterns through learning, but it is not sensed directly. The present commentary argues that this category error – a derived property treated as a perceptible one – has shaped experimental design, interpretation, and vocabulary in the behavioral literature, and that restoring mass to primacy brings the psychology of appetite into register with the physics and physiology of mass balance.

Abstract: Worldwide, consumption of ultra-processed foods (UPFs) is increasing in parallel with a rising incidence of obesity, type 2 diabetes, cardiovascular disease, kidney disease, and related cardiometabolic complications. Among the many features of UPFs that may drive these outcomes, industrial thermal processing is a defining characteristic that promotes the formation of advanced glycation end products (AGEs) and other food neo-contaminants, including acrylamide, furan, 5-hydroxymethylfurfural, heterocyclic amines, polycyclic aromatic hydrocarbons, 3-monochloropropane-1,2-diol, and glycidol. This review evaluates the hypothesis that AGEs and thermally generated neo-contaminants contribute significantly to the metabolic and toxicological effects of UPFs. After formation in food, these compounds may be partially absorbed in the gastrointestinal tract and act systemically, promoting tissue injury through protein cross-linking, oxidative stress, inflammation, endothelial dysfunction, and activation of the receptor for advanced glycation end products (RAGE). Several high-temperature neo-contaminants are linked to carcinogenicity, hepatotoxicity, neurotoxicity, and reproductive toxicity, while emerging evidence also implicates them in insulin resistance, adipogenesis, β-cell dysfunction, and cardiovascular risk. Overall, the evidence supports a biologically plausible link between thermal processing, AGE and neo-contaminant burden, and cardiometabolic disease, although the strength of evidence varies by compound. Improved exposure assessment, standardized analytical methods, mechanistic studies, and intervention trials are needed to define dose–response relationships and to determine whether reformulation and lower-temperature, moisture-rich cooking can reduce risk while maintaining food safety and acceptability.

Abstract:

Background/Objectives: Betanidin glycosides (betacyanins) are plant dietary pigments with reported significant benefits on human health. Betacyanin research has largely focused on betanin common in some plant foods like beets, amaranth, quinoa, cacti fruits , whereas the biological properties of structurally diverse gomphrenin derivatives remain insufficiently characterized. Gomphrenin-type betacyanins dietary source is predominantly Malabar spinach (Basella alba L.) but its health-promoting and disease preventing properties remain understudied. This study investigated whether differences in the composition of gomphrenin-rich preparations influence their effects on inflammatory and oxidative cellular responses. Methods: Betacyanin-rich preparations were obtained from Basella alba f. rubra fruits and Gomphrena globosa L. flowers using chromatographic purification. Their betacyanin profiles were characterized by LC-DAD-ESI-MS and total betacyanin contents were determined spectrophotometrically. The biological effects of crude and purified preparations (1–100 μg/mL) were evaluated in Caco-2 intestinal epithelial cells and human polymorphonuclear neutrophils (PMN). IL-8 secretion in Caco-2 cells, TNF-α, IL-8, and IL-1β secretion in LPS-stimulated PMN, ROS generation in f-MLP-stimulated PMN, and cell viability were assessed. Results: Purification resulted in preparations with markedly different betacyanin profiles. The gomphrenin-enriched BE₂ contained 312 ± 83 mg/g total betacyanins, whereas the acylated-betacyanin-enriched BE₃ contained 188 ± 12 mg/g and was dominated by globosin and other hydroxycinnamoyl derivatives. Despite its lower total betacyanin content, BE₃ displayed stronger inhibition of TNF-α, IL-8, and IL-1β secretion than BE₂; at 100 μg/mL, these cytokine levels were 39.17%, 44.61%, and 58.93% of the LPS control, respectively. All preparations reduced IL-8 secretion in Caco-2 cells by more than 50% at the highest concentration and the Basella preparations effectively suppressed neutrophil ROS generation. No significant cytotoxicity was observed. Conclusions: The biological activity of betalain-rich preparations was not determined by total betacyanin content alone but was associated with their qualitative pigment composition and broader chemical matrix. The stronger anti-inflammatory activity of the acylated-betacyanin-enriched preparation highlights hydroxycinnamoylated gomphrenins as candidates for further investigation, while the complex nature of the preparations warrants further studies to determine the contribution of individual pigments to the observed biological effects.

Abstract: Nutraceuticals are evaluated as though efficacy were a stable ingredient property, although net value may vary with exercise stimulus, exposure schedule, recovery pressure, athlete state, and prioritized outcome. This structured narrative review integrates exercise-adaptation biology, pe-riodized sports nutrition, training-load and recovery models, precision nutrition, and human evi-dence for sport-relevant interventions. Searches of PubMed/MEDLINE, Web of Science, and Scopus were updated through August 2026 and supplemented by citation tracking. General efficacy was separated from direct evidence of timing, context, or state modification. Nutraceutical Periodiza-tion for eXercise (NPX) is an allocation layer applied only after safety, legality, product quality, and plausible efficacy are established. It defines four non-sequential functional win-dows—performance exploitation, adaptation-permissive signaling, restoration, and resili-ence—and separates intervention strategy, training context, athlete state, and outcome hierarchy. Four falsifiable propositions test context modification, temporal allocation, bottleneck/state de-pendence, and whole-policy utility. Despite limited direct evidence for most allocation rules, NPX converts compound-specific efficacy into prospectively testable decisions. Targeted allocation may improve athlete-centered outcomes or preserve them with fewer exposures, lower burden, or less harm than standardized evidence-based use. Prospective interaction and policy trials are needed to establish the value and boundaries of these rules.

Abstract: Type 2 diabetes mellitus (T2DM), a global metabolic disease, is fundamentally characterized by a vicious cycle of chronic low-grade inflammation and metabolic dysregulation. The complement system, a key effector of innate immunity, has recently been recognized as deeply involved in initiating and amplifying metabolic inflammation. Although current studies have revealed critical roles of complement components in pancreatic β-cell damage, insulin resistance, and adipose tissue inflammation, the interactive network between complement and metabolic inflammation in T2DM microvascular and macrovascular complications remains incompletely understood, and complement-targeted therapies still face specificity and safety challenges. This review systematically summarizes the molecular crosstalk between complement components and metabolic inflammation in T2DM and its complications, focusing on complement-mediated β-cell apoptosis, suppression of insulin signaling, adipose tissue macrophage polarization, and renal and vascular endothelial injury. We also discuss the prospects of complement-targeted drug development and barriers to clinical translation, aiming to offer new insights for precision treatment of T2DM and its complications.

Abstract: Most existing reviews treat endoplasmic reticulum (ER) stress as one mechanism among several in leptin resistance. This review advances a different claim: ER proteostasis may act as a central convergence node, translating metabolic, inflammatory, developmental, and nutrient-derived signals into a shared effector signature. In common obesity, leptin responsiveness is blunted despite hyperleptinaemia—the principal obstacle to leptin-based therapy. Leptin resistance is examined at the intersection of intracellular signalling networks (JAK2/STAT3, PI3K/Akt, MAPK, AMPK, mTOR, FoxO1, SOCS3, PTP1B) and hypothalamic ER stress and the unfolded protein response (UPR). This narrative synthesis incorporates 22 primary studies, with PRISMA 2020 principles used to document study selection transparently. The ER shapes leptin signalling at three levels: receptor biogenesis (SEL1L–HRD1 ERAD), receptor bioavailability (CHOP-mediated soluble receptor), and post-receptor inhibition (SOCS3/PTP1B). Distinct stressors converge on a narrow effector set (CHOP, SOCS3, PTP1B), and receptor quality control can operate independently of ER stress, demonstrating that the ER's role is not confined to a stress response. The framework yields three testable hypotheses with an explicit falsification criterion, and proposes that leptin resistance comprises phenotypically distinct subtypes. The evidence base is entirely preclinical (17 rodent in vivo; 5 in vitro studies); translation to humans remains untested.

Abstract: Objective: to evaluate the feasibility, safety, and preliminary effectiveness of an integrated nutritional strategy combining a low-protein diet with structured micronutrient supplementation in patients with advanced CKD. Methods: A retrospective observational study was conducted in routine nephrology practice across two centers between January 2021 and June 2022. Seventeen adults aged 40–85 years with CKD stages III–V were included. Participants followed an individualized low-protein diet emphasizing plant-based foods and received a structured supplementation protocol containing vitamins, minerals, essential amino acids, and omega-3 fatty acids. Primary outcomes were feasibility, adherence, retention, safety, and tolerability. Secondary exploratory outcomes included changes in estimated glomerular filtration rate (eGFR), serum creatinine, and KDIGO stage classification. Results: The retention rate was 94% and the adherence rate was 100%. No serious adverse events or clinically significant electrolyte disturbances were reported. After a mean follow-up of 4.88 months, mean eGFR increased significantly from 43.3 to 59.8 mL/min/1.73 m² (p < 0.001), while serum creatinine decreased significantly from 1.70 to 1.25 mg/dL (p < 0.001). All patients demonstrated directional improvement, and 94.1% improved by at least one KDIGO stage. Conclusions: Integrated nutritional guidelines were feasible, well tolerated, and associated with significant short-term improvements in renal function among patients with advanced CKD. These findings support the need for a randomized controlled trial to confirm efficacy and assess long-term clinical benefits.

Abstract: The recently proposed Bedside-to-Outside model aims to bridge inpatient efficacy and free-living effectiveness trials in human nutrition research. Its translational ambition is laudable, yet its core premise – that changes in body mass can be used to calculate energy intake with sufficient precision – rests on problematic assumptions. First, the cited correlation between mass change and energy intake is tautological, not independently validating. Second, reliance on the Wishnofsky rule ignores diet-dependent variation in tissue composition, glycogen, and water. Third, recent analytical work has exposed internal logical inconsistencies in the energy balance model (EBM), while the mass balance model (MBM) delivers superior predictive accuracy by tracking macronutrient mass directly. Finally, omission of hormonal data that reportedly track mass intake more closely than energy intake further weakens the evidentiary foundation. True triangulation requires independent anchors; the present formulation risks circularity by relying solely on EBM assumptions. Six concrete modifications are proposed: (1) inclusion of mass-based metrics as co-primary outcomes; (2) pre-specification and competitive testing of both EBM and MBM predictions; (3) routine quantification of uncertainty propagation; (4) mandatory reporting of hormonal and appetite data; (5) use of MBM predictions as independent validation anchors; and (6) transparent reporting standards for all measured variables. Implemented, these changes would convert the Bedside-to-Outside model from a framework that assumes the EBM into a rigorous test of competing paradigms.

Abstract: Background: Nutritional deficiencies are common during the first postoperative year after mini gastric bypass (OAGB/MGB). This retrospective study evaluated the adequacy of a Food for Special Medical Purposes formulated for bariatric patients in maintaining mineral and vitamin status after OAGB/MGB. Methods: Patients who underwent laparoscopic OAGB/MGB at the Nutrition Clinic of Koelliker Hospital (Turin, Italy) between January 2023 and March 2024, aged 18–65 years and taking the product at 2 sachets/day for 12 consecutive months within a structured postoperative nutritional program, were retrospectively analyzed. Anthropometric and biochemical parameters were assessed at baseline (T0), 6 months (T6), and 12 months (T12) and compared using nonparametric repeated-measures tests. Results: Twenty-five patients were included (9 males, 36%; 16 females, 64%; mean age 52.8±7.2 years; preoperative BMI 46.4±5.8 kg/m²). At 12 months, mean weight loss was 34% and excess weight loss 74%. Vitamin D deficiency (<30 ng/mL) declined significantly from 79% at baseline to 28% at T6 and 16% at T12 (p<0.001). Vitamin B12 increased significantly within the first 6 months and then stabilized (p=0.0056), with only one residual deficiency at T6. Folate levels did not change significantly (p=0.099), though deficient/borderline values fell from 40% to 4%. Hemoglobin and mean corpuscular volume remained stable. Serum iron improved significantly only at 12 months (p<0.001), while ferritin declined significantly, mainly between T0 and T6 (p=0.046), remaining above the deficiency threshold on average. Conclusions: In this real-world series, the tested product combined with structured nutritional follow-up was associated with maintenance or improvement of most micronutrient parameters during the first year after OAGB/MGB, although ferritin remained a critical parameter requiring continued surveillance.

Abstract: Background: Overweight and obesity are burgeoning health epidemics. Diets including alternate-day fasting (ADF) promote weight loss but risk significant muscle loss, posing health implications to seniors at risk of sarcopenia. Leucine, the key muscle protein synthesis (MPS) driver, effectively stimulates MPS with lower calorie intake than protein. However, the effects of body-mass-scaled protein and leucine intakes are unclear. Objectives: To evaluate body-mass-scaled leucine or protein supplementation on body composition, sarcopenic and cardiometabolic markers in older men during ADF. Methods: Sixty-one older men (BMI ≥ 23.0 kg/m²) underwent 28 days of ADF, randomized across three calorie-matched supplement groups: Control (C: 0.0 g/kg protein, 0.0 g/kg leucine), Leucine (L: 0.0 g/kg protein, 0.08 g/kg leucine), or Protein (P: 0.4 g/kg protein, 0.04 g/kg leucine), consuming three doses on feeding days and one on fasting days. Dual-energy X-ray absorptiometry, sarcopenic metrics, and blood markers (blood pressure, lipid panels, diabetic profiles) were measured. Results: There were no significant interactions (p > 0.05) in body composition, sarcopenic or health outcomes, except diastolic blood pressure (p = 0.016) and HDL cholesterol (p = 0.013). There were significant main effects of time (p £ 0.05) with reductions in all body composition measures (excluding bone mineral density, p = 0.274), systolic blood pressure and lipid profiles (total and LDL cholesterol, total/HDL cholesterol ratio, triglycerides), and improvements in all muscle strength and functional sarcopenic outcomes. Conclusions: Dietary interventions alone that increase leucine and/or protein intake do not further improve body composition, sarcopenic and cardiometabolic outcomes during weight loss.

Abstract: Next-generation plant-based foods are designed to reproduce the technological, sensory, and culinary functions of animal-derived products, yet their development entails trade-offs among functionality, nutritional quality, degree of processing, acceptance, sustainability, and scalability. This critical narrative review integrated 63 publications retrieved through a structured search of five databases, with emphasis on protein ingredients, high-moisture extrusion, shear-based technologies, fermentation, lipid structuring, and 3D printing. The evidence indicated that high-moisture extrusion is the most mature platform for generating anisotropic structures, whereas fermentation, enzymatic treatments, and lipid systems broaden the control of aroma, digestibility, and juiciness. Nevertheless, a closer resemblance to animal foods frequently requires refined ingredients, hydrocolloids, and intensive processing, which may increase costs, labeling complexity, and nutritional heterogeneity. Environmental advantages likewise depended on the raw material, the energy mix, the functional unit, packaging, and logistics. We propose an integrated framework in which composition and processing determine microstructure, which in turn links technological, nutritional, sensory, and environmental performance. Advancing the field requires comparable metrics, validation in final matrices, and the simultaneous assessment of performance, cost, and impact. The central contribution of this review lies not in identifying a superior technology, but in proposing a decision-making model grounded in the interaction among product function, ingredient selection, processing, and multidimensional validation.

Abstract: Chronic metabolic diseases, including Type 2 Diabetes, hypertension, non-alcoholic fatty liver disease (NAFLD), prostate enlargement, musculoskeletal joint friction, cardiac arrhythmias, neurodegenerative waste accumulation (Alzheimer's), and elevated intraocular hydraulic pressure (glaucoma), are frequently treated as distinct, unavoidable consequences of chronological aging. However, from a systems engineering and thermodynamic perspective, the human body is an open system whose homeostatic equilibrium is dictated entirely by its input parameters. This article analyses the mechanical and biochemical pathways of human nutrition, specifically examining how dietary choices past the age of 50 modulate our master hormonal control valve: insulin. By evaluating comparative gastrointestinal architecture, this paper establishes that our physiology is evolutionarily optimized for nutrient-dense, low-entropy structural proteins and stable lipids, rather than volatile carbohydrate loads. Chronic carbohydrate influx triggers signal attenuation (insulin resistance), initiating a destructive positive feedback loop. Our liver acts as an emergency overflow reservoir, converting excess glucose into triglycerides, leading to visceral adiposity, which systematically suffocates our pancreas and gallbladder. This metabolic backlog degrades cardiovascular fluid dynamics via the suppression of endothelial nitric oxide and the permanent activation of epithelial sodium channels (ENaC) in the kidneys, causing chronic hypertension. Furthermore, this systemic signal failure acts as a potent growth accelerator in the prostate matrix, starves chondrocytes and spinal discs of nutrients to trigger musculoskeletal wear, generates disruptive electrophysiological noise in the cardiac grid, induces central nervous system energy failure (metabolic crisis) by overwhelming amyloid-clearing enzymes (amyloid is an abnormal misfolded protein), and clogs the ocular trabecular filtration sieve (optic nerve damage in glaucoma). To reverse this systemic decay, this paper outlines a practical framework utilizing the physics of gastric emptying, circadian chrononutrition, and zero-input windows (16:8 intermittent fasting). These targeted interventions leverage hormetic stress and mitophagy to flush out accumulated oxidized lipids, eliminate senescent cells, and restore high-yield mitochondrial efficiency, providing a hypothesis-driven framework for senior metabolic rejuvenation.

Abstract: Pneumonia and malnutrition are major contributors to mortality among older adults, yet their combined population-level burden remains poorly defined. We examined national trends and sociodemographic disparities in pneumonia and malnutrition-associated mortality among adults aged 65 years and older in the United States by analyzing data from the CDC WONDER Multiple Cause of Death database from 1999 to 2020. Age-adjusted mortality rates (AAMR) per 100,000 population were calculated, and temporal trends were assessed using Joinpoint regression. Between 1999 and 2020, 81,753 deaths involving both conditions occurred. The overall AAMR declined from 13.82 to 11.90 per 100,000, though a sharp increase occurred from 2017 to 2020. Mortality rates were higher among males, adults aged 85 and older, American Indian/Alaska Native and Black individuals, nonmetropolitan populations, and residents in the South, with Texas exhibiting the highest state-level rate. Pneumonia and malnutrition-associated mortality among older U.S. adults declined over much of the study period but increased substantially in recent years. Persistent demographic and geographic disparities suggest that vulnerable older adults remain at elevated risk, highlighting the need for integrated pneumonia prevention, nutritional screening, and targeted early interventions.

Abstract: Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure in adults, arising when the residual small bowel can no longer absorb the macronutrients, water and electrolytes needed to sustain health without intravenous supplementation. Its management is, at its core, a nutritional problem. This review synthesises current evidence and guideline recommendations on the two pillars of that management: dietary (oral/enteral) therapy and parenteral nutritional support. We frame both around the two variables that dominate clinical behaviour, namely residual intestinal anatomy and the phase of intestinal adaptation, and translate them into anatomy-tailored dietary strategies, rational fluid and electrolyte replacement, micronutrient surveillance, and the composition, delivery and complications of (home) parenteral nutrition. We also position the pharmacological adjuncts, culminating in glucagon-like peptide-2 (GLP-2) analogues, within a stepwise strategy to reduce parenteral-support dependence. The goal throughout is a practical, physiology-anchored approach that maximises enteral autonomy and quality of life while preventing the metabolic, hepatic and catheter-related complications of long-term intravenous feeding.

Abstract: Indonesia faces a persistent double burden of malnutrition in which undernutrition coexists with obesity, diabetes, hypertension, and other diet-related noncommunicable disease risks. This Viewpoint proposes NutriAgent+, a testable conceptual architecture for precision nutrition that combines multimodal wearable sensing, smartphone-derived behavioral context, contextual dietary data, bounded agentic artificial intelligence (AI), and a staged pathway toward national health-system interoperability. Rather than treating all wearable signals as equivalent, the framework specifies an evidence hierarchy spanning photoplethysmography and accelerometry, smartphone digital phenotyping, interstitial glucose sensing, experimental sweat and microneedle biomarkers, image- and log-based dietary capture grounded in Indonesian food-composition databases, and consented clinical context. The architecture separates sensing from interpretation, requires quality gating and uncertainty representation before AI reasoning, and constrains agent autonomy according to risk. A translational validation ladder is proposed from bench performance and analytical agreement through human-factors testing, model calibration, agent safety, prospective evaluation, interoperability, and controlled implementation. NutriAgent+ is presented as a research program rather than a clinically validated device. Its value therefore depends on demonstrating that each proposed input stream is measurable, physiologically or behaviorally interpretable, and useful for decisions before multimodal fusion or autonomous actions are attempted.

Abstract: Background: Lipedema is a chronic, progressive adipose tissue disorder that almost exclusively affects women,characterized by bilateral, disproportionate subcutaneous fat accumulation in the limbs, pain, easy bruising, andresistance to conventional weight-loss interventions. Because its appearance is frequently mistaken for obesity,women with lipedema are exposed to prolonged misdiagnosis, weight stigma, and inadequate healthcareresponses. The psychological, psychosocial, and behavioral burden of the condition is increasingly recognized,but the evidence is fragmented across clinical, psychological, and eating-related research. Objective: To synthesize the available evidence on the psychological, psychosocial, and behavioralconsequences of lipedema in adult women — including psychological distress, anxiety and depression, pain andfunctional impact, delayed diagnosis, weight stigma, body image, shame, emotion regulation, quality of life, andeating-related outcomes — and to organize this evidence within an explicit biopsychosocial framework. Methods: A structured narrative review following SANRA principles and incorporating applicable PRISMA2020 elements was conducted. Databases targeted included PubMed/MEDLINE, Embase, Scopus, Web of Science, PsycINFO, and the Cochrane Library; a complete PubMed search strategy is reported. Observational,qualitative, mixed-methods, longitudinal, and relevant intervention studies and reviews of adult women withclinically diagnosed lipedema and separately identifiable lipedema data were eligible. Data were extracted intostandardized tables, appraised for methodological quality, and synthesized thematically by domain. Each findingwas classified as direct evidence (lipedema populations), indirect evidence (related populations such as obesity,chronic pain, lymphedema, or weight-stigma research), or hypothesis (theoretical mechanisms not directlydemonstrated). Results: Thirty-six sources formed the evidence base. Direct evidence documents substantially reducedhealth-related quality of life across physical, emotional, and social domains, elevated prevalence of depressivesymptoms, and frequent experiences of weight stigma, shame, and body-image disturbance. Pain and functionallimitations are nearly universal and are associated with disability, kinesiophobia, and reduced activity. Emotionregulation difficulties and coping styles characterized by depressive processing are reported. Eating-disorderscreening indicators are elevated in preliminary samples, and clinically diagnosed binge-eating disorder waspresent in 14.7% of patients in one specialist pilot cohort. Direct evidence for compensatory behaviors andcompulsive exercise in lipedema was not identified. Conclusions: Distress, stigma, body image concerns, and impaired quality of life are the relativelybetter-documented psychological consequences of lipedema. Emotion regulation, eating-disorder risk, anddysfunctional eating behaviors remain less studied and methodologically heterogeneous. A biopsychosocialmodel — in which pain, functional limitation, delayed diagnosis, and stigma converge on body image, emotionregulation, eating behavior, and quality of life — is supported by converging direct and indirect evidence,although most links remain associative rather than causal. Multidisciplinary, non-stigmatizing, individualizedcare is warranted.

Abstract: Live-cell imaging can generate misleading readouts when physically complex multicomponent matrices alter light transmission, fluorescence, sedimentation, focusing, or segmentation. We retrospectively reconstructed a sequential fit-for-purpose qualification workflow using six coded phospholipoproteomic nutraceutical matrices (M1–M6) and two predefined pools. Records included U87 optical-compatibility screens at nominal 25%, 10%, 1%, and 0.1% inputs, one 47.5 h quantitative U87 imaging run at a laboratory-designated working input, and qualitative observations in T98G, SiHa, A375, and HMC3 stocks under complete and serum-free basal conditions. High-input conditions impaired microscopy, and a software-derived death-associated signal reached 78.85% at time zero but fell below 3.89% by 6 h, indicating early analytical instability. After lower-interference conditions were established, M4 showed the lowest sustained complete-medium image-derived trajectory, with an area under the curve (AUC) 31.3% below control and a 47.5 h endpoint of 0.910 ± 0.100 versus 1.630 ± 0.265. In basal medium, M2 showed the lowest cumulative trajectory, with an AUC 25.0% below control. The patterns were context dependent and were not supported by independent biological replication or orthogonal endpoints. Sequential qualification therefore provides a practical framework for separating matrix-related analytical interference from image-derived signals requiring biological confirmation.

Abstract: Background/Objectives: Autonomous motivation is theorized to support healthy eating, whereas body-shape concerns may fuel controlled forms of eating regulation. Their joint relations with Mediterranean diet adherence remain unexamined, particularly outside Mediterranean regions. We tested whether body-shape concerns relate differently to eating-regulation styles than to dietary behavior, and which styles are independently associated with adherence. Methods: In this cross-sectional online study, 224 Romanian adults (87.1% women; 40.7 ± 10.0 years) completed the Body Shape Questionnaire-16B (BSQ-16B), the Regulation of Eating Behaviors Scale, and the 14-item Mediterranean Diet Adherence Screener (MEDAS). Analyses included Spearman correlations with false-discovery-rate control and hierarchical regression with HC3-robust standard errors. Results: BSQ-16B scores were associated with introjected (β = 0.65) and overall controlled regulation (β = 0.54), but with none of the autonomous styles (composite β = −0.004). BSQ-16B was unrelated to MEDAS (ρ = −0.03; ΔR² < 0.001), whereas autonomous motivation was independently associated with adherence (b = 0.63 points per SD; 95% CI 0.32–0.94); integrated regulation was the only independently associated subscale (secondary analysis). Results were robust across sensitivity analyses. Conclusions: Body-shape concerns were coupled with internal pressure but decoupled from dietary behavior; only autonomous regulation was associated with adherence, consistent with autonomy-supportive counseling approaches.