Search Results (679)

Background: Gastrointestinal (GI) involvement is increasingly recognised in paediatric SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C), but severe GI bleeding remains rare. Its pathogenesis in this setting is multifactorial: direct viral injury, hyperinflammatory microvascular damage, treatment-related mucosal injury, and coagulopathy may all contribute, and the relative role of each is often difficult to disentangle. Case Presentation: A previously healthy 12-year-old boy underwent appendectomy for perforated appendicitis with peritonitis. On postoperative Day 1, he developed high fever and was found to be SARS-CoV-2 PCR-positive; SARS-CoV-2 IgM and IgG were also positive. He met the positive clinical elements of the CDC 2023 case definition for MIS-C (persistent fever, multisystem involvement—gastrointestinal, hepatic, haematological, and markedly elevated inflammatory markers), although perforated appendicitis with peritonitis is a sufficient alternative explanation and the diagnosis cannot be regarded as secure (see Discussion). Treatment included broad-spectrum antibiotics (meropenem, amikacin, metronidazole), methylprednisolone 2 mg/kg/day, and intravenous immunoglobulin (IVIG) 2 g/kg. On Day 4 in the paediatric intensive care unit (PICU), the patient developed sudden haematemesis with fresh blood through the nasogastric tube and haemodynamic collapse. Coagulation studies revealed prolonged INR (1.6) and reduced prothrombin activity (42%). The patient was stabilised with packed red blood cells, fresh frozen plasma, and intravenous vitamin K. Fibrogastroscopy demonstrated diffuse mucosal bleeding without ulcers or anatomical defects; histology showed mucosal hyperaemia, mixed basal inflammation with intraepithelial lymphocytes, and small erosions. Melena persisted for several days. The child recovered fully and was discharged after 20 days with substantially improved but not fully normalised laboratory values (residual mild anaemia, Hb 110 g/L, and elevated CRP 32.7 mg/L and D-dimer 5.88 mg/L). Conclusions: Severe upper GI bleeding is a rare but life-threatening event in children with severe SARS-CoV-2 infection and MIS-C. In our case, several mechanisms may have acted in combination, although none could be confirmed individually: possible direct viral enterocyte injury via ACE-2 receptors, hyperinflammatory microangiopathy, high-dose corticosteroid-related mucosal injury, possible broad-spectrum antibiotic-associated vitamin K deficiency, and postoperative critical-illness stress. Their relative contributions cannot be determined from a single retrospective case. Bleeding occurred despite continuous PPI prophylaxis, suggesting that PPI cover alone is insufficient when multiple risk factors coexist; the clinical implication is that risk-factor-based (rather than universal) PPI prophylaxis, together with monitoring of vitamin K-dependent coagulation, should be considered in critically ill children receiving high-dose corticosteroids and prolonged broad-spectrum antibiotics. Full article

Background/Objectives: Obesity is a chronic, progressive, and relapsing disease that requires long-term, multidisciplinary management rather than episodic weight-loss treatment. Although novel incretin-based anti-obesity pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have markedly improved the clinical management of obesity, weight reduction alone does not fully capture treatment success. Body composition, lean mass preservation, physical function, nutritional adequacy, psychological well-being, adherence, and long-term weight-loss maintenance are increasingly recognized as essential therapeutic outcomes. This narrative review critically examines the role of lifestyle medicine as a co-therapeutic strategy during modern anti-obesity pharmacotherapy, with particular attention to physical activity, nutrition, behavioral support, and individualized monitoring. Methods: A narrative literature search was conducted in PubMed up to June 2026. The review included studies addressing adults with overweight or obesity and evidence related to anti-obesity pharmacotherapy, physical activity, nutrition, body composition, functional outcomes, eating behavior, quality of life, treatment tolerability, adherence, weight regain, and long-term maintenance. Results: Current evidence indicates that incretin-based therapies produce substantial and clinically meaningful weight loss, but pharmacological efficacy may be limited by reductions in lean mass, gastrointestinal adverse events, inadequate nutritional intake, treatment discontinuation, and weight regain after drug withdrawal. Physical activity should be considered a therapeutic component rather than only a tool for increasing energy expenditure, as aerobic exercise supports cardiometabolic health and cardiorespiratory fitness, while resistance training helps preserve muscle strength, bone health, and functional capacity. Nutritional strategies are equally important, particularly during appetite suppression, to maintain adequate protein, fiber, fluids, micronutrients, and diet quality. Behavioral factors, including sleep, stress, mood, stigma, self-regulation, and the food environment, may influence adherence and long-term outcomes. Conclusions: Novel anti-obesity drugs should not be viewed as replacements for lifestyle medicine but as powerful tools within an integrated chronic-care model. The goal of treatment should move beyond maximal body-weight reduction to durable improvements in body composition, metabolic health, physical function, nutritional status, quality of life, and weight-loss maintenance. Full article

Background: Subjective cognitive complaints (SCCs) are common in middle-aged and older adults and may reflect early cognitive changes, alongside alterations in stress, mood, sleep, and quality of life. N-PEP-12 is a peptide-based nutritional supplement with potential neuroprotective effects, but evidence of its benefits in healthy adults with SCCs remains limited. Objective: To evaluate the effects of N-PEP-12 supplementation on attention, cognitive function, and mental wellbeing in healthy middle-aged and older adults with SCCs. Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 276 participants aged 50–75 years with SCCs and no clinically significant cognitive impairment were randomized to placebo, N-PEP-12 45 mg, or N-PEP-12 90 mg. Assessments were performed at baseline and after 30, 90, and 180 days. Primary outcomes included Test of Attentional Performance measures. Secondary outcomes included WAIS-IV Digit Span Forward and Backward, perceived stress, mood, sleep quality, and EQ-5D-5L visual analog scale. Results: Across the three primary attention outcomes analyzed jointly in a multivariate repeated-measures model, there was a significant group-by-visit interaction (p = 0.003) and a significant effect of visit (p < 0.001), without a significant main effect of treatment arm (p = 0.133), indicating a time-dependent treatment effect. This result was obtained in a sensitivity analysis population in which missing values were imputed under assumptions least favorable to the active arms. In exploratory endpoint-specific comparisons at 90 days, both N-PEP-12 groups showed greater improvements than placebo in alertness, attention omissions and memory omissions, and Digit Span Forward and Backward scores also improved. In a subsequent uncontrolled extension phase, in which all participants received active treatment, participants initially assigned to placebo showed comparable improvements after switching to N-PEP-12 90 mg. These observations are exploratory. Adverse events were infrequent and similarly distributed across groups. Conclusions: N-PEP-12 supplementation was associated with improvements in attention, working memory, and mental wellbeing in healthy middle-aged and older adults with subjective cognitive complaints. These findings support further investigation of N-PEP-12 as a nutritional intervention for early subjective cognitive changes associated with aging. Full article

Background: Oxidative stress is an important contributor to brain abnormalities in Down syndrome (DS), but the status of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway during early postnatal development remains poorly understood. The current study aimed to investigate whether an impairment of the NRF2 pathway is already present in the Ts65Dn mouse model of trisomy 21 at neonatal life stages and whether early treatment with astaxanthin-loaded stealth solid lipid nanoparticles (AST-SSLNs) positively impacts NRF2 signaling and reduces oxidative stress. Methods: Hippocampal NRF2 pathway components and oxidative stress markers were analyzed in neonate Ts65Dn and euploid mice. From postnatal day (P)3 to P15, mice received daily subcutaneous injections of AST-SSLNs or unloaded nanoparticles. NRF2 pathway activation, reactive oxygen species (ROS), lipid peroxidation, protein carbonylation, and safety parameters were evaluated. Results: Untreated Ts65Dn mice exhibited early impairment of the NRF2 pathway, characterized by increased BACH1, reduced NRF2 activation, and decreased HO-1 expression. Neonatal AST-SSLN treatment enhanced NRF2 activation, improved HO-1 levels, and normalized ROS accumulation, lipid peroxidation, and protein carbonylation in the hippocampus, a brain region critically impaired in DS. Treatment had no adverse effects on survival, body weight, or brain weight. Conclusions: These findings demonstrate that NRF2 pathway dysfunction is an early event in trisomy 21 and identify the neonatal period as a potential therapeutic window to counteract oxidative stress. AST-SSLNs represent a promising nanomedicine-based strategy to activate the impaired NRF2 pathway and reduce early hippocampal oxidative damage in DS. Full article

Considered a global public health priority, sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. Its heterogeneous clinical presentation arises, in part, from pre-existing chronic conditions such as hypertension, metabolic syndrome, diabetes, alcohol exposure, psychosocial stress, and periodontitis, which induce persistent systemic changes even before the infectious event. This narrative review synthesizes evidence from experimental models and clinical studies to clarify the molecular and immunological mechanisms by which chronic conditions influence the septic state. We discuss how these conditions converge on common pathophysiological mechanisms, including low-grade chronic inflammation, oxidative stress, endothelial and mitochondrial dysfunction, and changes in the microbiota and neuroimmune regulation. Pathways such as TLR-NF-κB signaling and the NLRP3 inflammasome are maintained in a basal state of activation, lowering the threshold for hyperinflammatory responses and increasing the risk of multiple organ dysfunction syndrome. In conclusion, understanding these phenotypes can guide the identification of biomarkers and the development of personalized therapeutic strategies, thereby moving beyond one-size-fits-all approaches to the management of sepsis and septic shock. Full article

Background: Psychological distress has been frequently reported in individual autoimmune diseases, but evidence regarding shared psychological characteristics across heterogeneous autoimmune conditions remains limited. Objective: This study compared stress vulnerability, exposure to major life events, state and trait anxiety, and Type A behavioral characteristics between adults with autoimmune diseases and controls. Methods: This cross-sectional case–control study included 389 adults: 204 patients with autoimmune diseases and 185 controls. Participants completed the Stress Vulnerability Scale, Holmes–Rahe Life Stress Inventory, State–Trait Anxiety Inventory, and Jenkins Activity Survey. Between-group differences, effect sizes, and correlations among psychometric variables were examined. Results: Patients with autoimmune diseases had significantly higher stress vulnerability scores (Cohen’s d = 0.39) and Holmes–Rahe life-event burden (d = 0.54) than controls. State anxiety (d = 0.52) and trait anxiety (d = 0.68) were also higher (all p < 0.001). Type A behavioral characteristics did not differ significantly between groups. State and trait anxiety showed the strongest correlation (r = 0.755, p < 0.001). Disease duration was positively associated with Holmes–Rahe scores but not with stress vulnerability or anxiety. Conclusions: Adults with autoimmune diseases showed a higher psychological burden across several complementary psychometric dimensions. These findings support consideration of psychological screening within multidisciplinary autoimmune disease care. Longitudinal and disease-specific studies integrating biological, psychological, and social factors are required to clarify temporal and potentially bidirectional relationships. Full article

Cardiovascular disease remains the leading cause of death among women, yet female cardiovascular risk continues to be underrecognized, and women remain underrepresented in many cardiovascular trials. Sex-related differences in hormonal exposure, immune regulation, vascular function, pregnancy-related conditions, and clinical presentation contribute to heterogeneity in cardiovascular disease across the life course. Statins reduce atherosclerotic cardiovascular events in women and men, with no consistent evidence of treatment-effect heterogeneity by sex. In addition to lowering low-density lipoprotein cholesterol, statins influence inflammatory signaling, endothelial nitric oxide bioavailability, oxidative stress, thrombosis, and plaque biology. These effects are biologically relevant to atherosclerosis; however, current clinical evidence does not establish that LDL-independent statin effects confer a uniquely greater benefit in women. Historical pathological studies suggested that plaque erosion may contribute relatively more often to acute coronary thrombosis in selected younger women, whereas contemporary optical coherence tomography studies show similar overall frequencies of plaque rupture and erosion between sexes and important age-related variation. Evidence for a female-specific effect of statins on post-myocardial infarction remodeling, cognition, or pharmacogenomic susceptibility is also insufficient. This narrative review distinguishes established clinical evidence from mechanistic plausibility and unresolved sex-specific hypotheses. It emphasizes equitable implementation of guideline-directed lipid-lowering therapy, careful evaluation of statin-associated symptoms, and the need for adequately powered studies reporting sex-stratified estimates and formal treatment-by-sex interactions. Full article

Background: Over the past decades, the global onset of menarche has progressively advanced, driven by complex interactions between metabolic, psychosocial, and environmental factors. Beyond its reproductive significance, menarche represents a critical developmental milestone that coincides with increased vulnerability to mental health difficulties. Contemporary determinants such as childhood obesity, early-life adversity, and exposure to endocrine-disrupting chemicals (EDCs) may accelerate pubertal timing while simultaneously shaping adverse psychological trajectories during adolescence. Objectives: This review aims to provide a translational and clinically oriented synthesis of modern determinants of earlier menarche and their associations with mental health outcomes in girls and adolescents, highlighting implications for early identification, prevention, and integrated clinical care. Methods: We conducted a narrative review mapping a scoping literature search conducted using PubMed/Medline, Scopus, and PsycINFO, focusing on literature from the last decade (2016–2026), with emphasis on systematic reviews, meta-analyses, and longitudinal cohort studies. Evidence was synthesized across biological, psychosocial, and environmental domains. Results: Accumulating evidence indicates that higher childhood adiposity, psychosocial stress, and EDC exposure are consistently associated with advanced pubertal timing. Earlier menarche correlates with an elevated risk of depressive symptoms, anxiety, self-harm, and body image-related distress, although effect sizes vary across populations. Emerging longitudinal data suggest that the peri-menarcheal period represents a critical window for symptom exacerbation. These associations appear to be mediated by biological mechanisms (e.g., hormonal shifts, hypothalamic–pituitary–adrenal (HPA) axis reactivity) and social processes including peer-comparison dynamics and premature sexualization. Conclusions: Earlier menarche acts as a biopsychosocial sentinel event rather than an isolated gynecological milestone. Integrating mental health screening and anticipatory guidance into pediatric and gynecological care is essential for early risk detection. A multidisciplinary, equity-oriented approach is required to address both individual vulnerability and broader environmental determinants. Full article

Background: Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are widely prescribed for type 2 diabetes mellitus (T2DM) because of their cardiovascular and renoprotective benefits. However, their use is associated with euglycemic diabetic ketoacidosis (EDKA), a rare but potentially life-threatening complication characterized by severe ketoacidosis despite relatively normal blood glucose levels. Failure to discontinue SGLT-2 inhibitors before surgery, as recommended in current guidelines, together with perioperative fasting and surgical stress, increases the risk of EDKA. Diagnostic complexity is compounded when concurrent postoperative surgical complications provide an alternative explanation for persistent metabolic acidosis. Methods: A 71-year-old man with T2DM receiving uninterrupted empagliflozin underwent direct lateral interbody fusion under general anesthesia. On postoperative day 2, he developed severe high anion-gap metabolic acidosis (pH 7.204, HCO₃⁻ 10.1 mEq/L) with near-normal blood glucose levels (178 mg/dL). Pneumoperitoneum identified on imaging was attributed to Hemovac drain-related peritoneal injury, and emergent laparoscopic exploration was performed under a working diagnosis of surgical sepsis. Although surgical source control was successfully achieved, severe metabolic acidosis persisted postoperatively (pH 7.275). Euglycemic diabetic ketoacidosis is an uncommon diabetic complication associated with several perioperative risk factors, including prolonged fasting and surgical stress. Subsequent serum ketone analysis demonstrated markedly elevated beta-hydroxybutyrate levels (4.8 mmol/L), confirming co-existing EDKA. Results: Following empagliflozin discontinuation, targeted treatment with concurrent insulin–dextrose infusion resulted in complete resolution of acid-base imbalance within five days. Conclusions: A concurrent surgical complication appeared to mask EDKA and contributed to a delay in its recognition. In patients receiving SGLT-2 inhibitors, metabolic acidosis that persists after an apparent surgical cause has been addressed should prompt measurement of serum ketones, irrespective of the blood glucose concentration. Structured perioperative protocols for SGLT-2 inhibitor management and postoperative ketone surveillance may help to prevent similar events. Full article

Background: Police and security professionals are routinely exposed to potentially traumatic events as part of occupational duties, placing them at increased risk for post-traumatic stress and broader psychological difficulties. This study aimed to identify latent classes of proximal traumatic exposure among Portuguese police/security professionals and examine their associations with PTSD symptoms and general psychological distress. Methods: A cross-sectional online survey was conducted with Portuguese police/security professionals (N = 644). Latent class analysis (LCA) was applied to 17 indicators of potentially traumatic events coded as directly experienced or witnessed, derived from the Life Events Checklist for DSM-5. PTSD symptoms were assessed using the PTSD Checklist for DSM-5, and general psychological distress was assessed using the Brief Symptom Inventory. Exploratory receiver operating characteristic (ROC) analyses examined whether counts of proximal traumatic events could approximate the LCA-derived classes. Results: A three-class solution was identified, comprising low proximal exposure (37.3%), moderate proximal exposure (40.7%), and high proximal/cumulative exposure (22.0%) classes. The classes reflected a graded cumulative pattern of exposure across traumatic event categories, rather than clearly distinct qualitative configurations defined by specific event types. Higher exposure classes were associated with progressively higher PTSD symptoms and psychological distress, and these associations remained significant after adjustment for sociodemographic and occupational variables. Exploratory receiver operating characteristic (ROC) analyses showed that a simple count of proximal traumatic event categories closely approximated the empirically derived class structure within the present sample. However, the resulting thresholds are sample-specific, exploratory, and should not be interpreted as validated screening cutoffs. Conclusions: Proximal traumatic exposure among police/security professionals appears to follow a graded cumulative structure associated with increased PTSD symptoms and psychological distress. The person-centered analysis provided an empirical test of whether exposure was organized according to qualitatively distinct event configurations or primarily along a cumulative gradient. In this sample, cumulative exposure burden emerged as the dominant organizing dimension. The count-based approximation requires external validation before any screening or decision-making application can be considered. Full article

Endocrine-disrupting pesticides (EDPs) are environmental toxicants capable of perturbing hormonal homeostasis through multiple molecular and cellular mechanisms. Growing evidence indicates that these compounds contribute to a broad spectrum of adverse health outcomes extending beyond classical endocrine dysfunction. This review critically synthesizes current knowledge on the toxicological mechanisms of EDPs and evaluates epidemiological evidence linking exposure to human disease. Mechanistically, EDPs act through modulation of nuclear hormone receptors, disruption of membrane-associated signaling pathways, interference with hormone synthesis, metabolism, and transport, induction of oxidative stress and mitochondrial dysfunction, and epigenetic reprogramming. These molecular events converge on shared biological pathways that affect multiple organ systems and life stages. Human and experimental evidence associates EDP exposure with reproductive dysfunction, endocrine-related cancers, metabolic disorders, thyroid abnormalities, and neurodevelopmental impairments. Particular concern surrounds exposure during critical windows of susceptibility, especially prenatal development and early childhood, when endocrine systems are highly vulnerable to disruption and developmental programming. Across disease endpoints, recurring mechanisms, including endocrine receptor perturbation, oxidative stress, inflammation, and epigenetic alterations, support a unifying toxicological framework linking diverse adverse outcomes. Despite substantial progress, important uncertainties remain regarding chronic low-dose exposure, non-monotonic dose–response relationships, cumulative effects of pesticide mixtures, and the translation of mechanistic findings into human risk assessment. Future research should integrate repeated biomonitoring, advanced mixture modeling, mechanistic biomarkers, and multi-omics approaches within longitudinal life-course studies. Improved integration of toxicological and epidemiological evidence will strengthen causal inference, refine hazard characterization, and support more protective regulatory strategies for reducing the human health burden associated with endocrine-disrupting pesticides worldwide. Full article

Background/Objectives: Long COVID is characterised by persistent symptoms such as fatigue, pain, cognitive impairment, sleep disturbances, and reduced quality of life (QoL) following SARS-CoV-2 infection. Proposed mechanisms include persistent immune activation, chronic inflammation, oxidative stress, endothelial dysfunction, mitochondrial disturbances, and virus-induced cellular senescence. Current management is largely supportive, highlighting the need for complementary strategies targeting these pathways. Natural polyphenols such as quercetin and curcumin possess anti-inflammatory, antioxidant, immunomodulatory, and potential senolytic properties that may modulate multiple pathways implicated in Long COVID. This study aimed to explore the potential complementary effects of oral quercetin–curcumin co-supplementation, administered alongside usual symptomatic management, in adults with persistent Long COVID symptoms. Methods: This single-centre, open-label, single-arm, pragmatic exploratory study enrolled 15 adults with Long COVID in an outpatient real-life clinical practice setting. Participants received a nutraceutical formulation containing quercetin (65 mg) and Curcuma longa extract standardised to provide 42 mg curcumin (Nasafytol^®), administered as two capsules twice daily for 8 weeks in addition to standard care. The primary endpoint was change in overall symptom burden assessed using the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS). Secondary outcomes included fatigue (Fatigue Severity Scale, FSS), pain (Brief Pain Inventory—Short Form, BPI-SF), cognitive function (Patient-Reported Outcomes Measurement Information System Cognitive Function Short Form 8a, PROMIS-CF-8a), mood (Hospital Anxiety and Depression Scale, HADS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), autonomic symptoms (Composite Autonomic Symptom Score-31, COMPASS-31), and health-related QoL (Medical Outcomes Study 36-Item Short-Form Health Survey, SF-36). Results: After 8 weeks, overall symptom burden significantly decreased (C19-YRS median 50 to 32; q = 0.018). Significant reductions were observed in patient-reported fatigue (q = 0.006), pain severity and interference (q = 0.006), and improved physical health-related QoL (SF-36 PCS; q = 0.025). Numerically favourable changes were also observed in cognitive function, anxiety, sleep quality, and autonomic symptoms, although these did not reach statistical significance. The supplementation was generally well tolerated with no serious adverse events. Conclusions: Quercetin–curcumin co-supplementation was associated with lower patient-reported symptom burden, fatigue, and pain and better physical health-related QoL after 8 weeks of supplementation in adults with Long COVID. These observed findings represent treatment-associated changes within this uncontrolled exploratory study and should be interpreted cautiously. Further evaluation in adequately powered randomised placebo-controlled trials is warranted. Trial registration: ClinicalTrials.gov (ID NCT06974058). Full article

Background/Objectives: After menopause, hormonal, age-related, and lifestyle factors may adversely affect physical functioning and psychological well-being. This study compared immediate changes in physical function, psychological health, and health-related quality of life following a five-day Combined Marine Treatment Program (CMTP) with those observed under a usual-routine control condition. Methods: A parallel-group randomized controlled trial was conducted with 62 postmenopausal women allocated equally to the CMTP and control groups. The CMTP included coastal walking, resistance exercises, mindfulness meditation, and visits to local natural attractions. Participants in the control group continued their customary daily activities. The co-primary outcomes were the Timed Up and Go test and the Short Form-36. Secondary outcomes were grip strength, pinch strength, static balance, the 10-item Perceived Stress Scale, and the Beck Depression Inventory-II. Mixed repeated-measures analysis of variance was used to test whether temporal changes differed between groups. Trial registration was completed through the Clinical Research Information Service of the Republic of Korea (KCT0009741). Results: Changes over time differed significantly between groups for the Timed Up and Go test, grip strength, pinch strength, eyes-open sway area, eyes-closed sway area, eyes-closed sway velocity, and all self-reported outcomes. Post-intervention values differed significantly between groups for the Timed Up and Go test, pinch strength, both eyes-closed balance measures, and all self-reported outcomes. No adverse events were reported during the trial. Conclusions: Relative to the usual-routine condition, the five-day CMTP was associated with immediate changes in selected performance-based physical outcomes and broader changes across self-reported psychological and health-related quality-of-life outcomes. Brief multicomponent coastal health programs therefore warrant further study in postmenopausal women. Full article

Bias Temperature Instability (BTI) remains one of the principal reliability challenges limiting advanced CMOS technologies. Although degradation is commonly described by an empirical power–law relationship, the power–law exponent is generally regarded only as a fitting parameter used for lifetime extrapolation. This Perspective reexamines a previously published Multiple-Temperature Operational Life (MTOL) dataset to investigate whether the measured exponent contains previously overlooked physical information. Individual ring oscillators stressed under identical voltage and temperature conditions exhibit substantially different, yet reproducible, power–law exponents. When these measurements are analyzed over a broader temperature range, the apparent statistical scatter reveals a systematic kinetic dependence that produces a remarkably consistent lifetime relationship after incorporating the experimentally measured exponent into the Arrhenius analysis. The resulting intrinsic activation energy is significantly smaller than values obtained using conventional extrapolation methods, suggesting that part of the apparent activation energy arises from neglecting the temperature dependence of the degradation exponent. A recently proposed thermodynamic formulation based on Gibbs free energy and correlation entropy is presented as one possible physical interpretation of these observations, in which the power–law exponent reflects the correlation between successive degradation events rather than merely an empirical fitting constant. More generally, this Perspective suggests that the power–law exponent should be regarded as a measurable kinetic quantity whose systematic variation may provide additional insight into degradation mechanisms in BTI and other reliability phenomena. Full article

Background/Objectives: Perinatal loss is a profoundly distressing life event associated with grief, depression, anxiety, post-traumatic stress symptoms, and long-term psychosocial challenges among bereaved parents who experience miscarriage, stillbirth, or neonatal death. Although psychotherapeutic interventions are increasingly used to address these adverse outcomes, there is limited synthesis on how characteristics consistent with a patient-centered care perspective are reflected in such interventions and how they may relate to psychosocial well-being. This umbrella review aimed to synthesize evidence on psychotherapeutic interventions following perinatal loss and to examine patient-centered care–related dimensions reported across the included reviews, including therapeutic communication, patient engagement, therapeutic relationships, emotional validation, and meaning-making processes. Methods: An umbrella review was conducted in accordance with the Joanna Briggs Institute methodological guidance. Systematic reviews and meta-analyses published between 2019 and 2025 were identified through searches of PubMed, CINAHL, PsycINFO, and the Cochrane Library from database inception to 31 May 2026. Eligible reviews examined psychotherapeutic, psychosocial, and psychological support interventions designed to improve grief, depression, anxiety, post-traumatic stress symptoms, psychological distress, coping, and psychosocial well-being among bereaved parents following perinatal loss. In accordance with the predefined secondary exploratory objective, a secondary interpretive synthesis examined patient-centered care–related dimensions described within the included reviews. Results: Five systematic reviews and meta-analyses met the inclusion criteria. Interventions included cognitive behavioral therapy, mindfulness-based approaches, bereavement counseling, psychosocial support programs, narrative interventions, supportive counseling, and digitally delivered psychological therapies. Across reviews, psychotherapeutic interventions were generally associated with beneficial effects on grief, depression, anxiety, post-traumatic stress symptoms, and broader indicators of psychosocial well-being. Communication-, support-, and engagement-related characteristics consistent with a patient-centered care perspective, including empathy, therapeutic alliance, individualized support, emotional validation, and continuity of communication, were identified through secondary interpretive synthesis as recurring features of beneficial interventions. Digital modalities, such as internet-based cognitive behavioral therapy and telephone-delivered counseling, were consistently described as supporting accessibility, engagement, and continuity of care. Conclusions: Psychotherapeutic interventions following perinatal loss appear to improve a range of psychosocial outcomes. A patient-centered care perspective may help interpret how communication, emotional validation, patient engagement, and supportive therapeutic relationships are described in relation to psychological adaptation after loss. These dimensions should be understood as interpretive characteristics identified across the included reviews rather than as directly measured mechanisms of intervention effectiveness. Future research should examine communication processes, therapeutic alliance, and patient engagement using validated measures, assess how these factors relate to intervention effectiveness, and support the development of integrated, patient-centered models of perinatal bereavement care. Full article