When outbreaks of emerging and reemerging zoonotic diseases are discussed, little attention is paid to differential gender impacts, or to gender involvement and roles in different settings during the outbreak. Gender roles shape how individuals' interactions with animals, wildlife, other people and the environment, which influences exposure to zoonotic pathogens. For example, in some rural communities, men may face risks of exposure to emerging pathogens during hunting whilst women who primarily take care of domestic animals may face prolonged exposure to other zoonotic diseases. In some settings, women (and men) lack access to health protection, education or communication with health officials (medical doctors or veterinarians). In some cultures, women are not allowed to speak directly with male service providers, further limiting their access to critical information and services. One Health is a holistic, inclusive approach which should be incorporating a gender lens when considering zoonoses. This includes thinking about the need to create appropriate gender sensitive policies that address disparities in surveillance, response, prevention, detection, and control of the disease (or health issue) being addressed. In this paper, we highlight these issues through several case studies that demonstrate the importance of including gender in zoonotic disease response and, ideally, when implementing prevention measures.
Age-related hearing loss is linked to loneliness and poorer cognitive health, but it remains unclear whether loneliness helps explain associations between hearing difficulties and cognitive performance or dementia, and whether these patterns reflect causal pathways or shared underlying liability. In this preregistered study, we triangulated analyses across multiple data sources spanning approximately 18 years of observational data with 8 sources of molecular genetic information to examine whether loneliness helps explain the association between hearing difficulty and cognitive performance, Alzheimer's disease dementia, and all-cause dementia, and whether hearing-aid use may buffer this association. In longitudinal parallel-process latent growth curve models ( N = 10,375) using nine waves of longitudinal data from the Survey of Health, Ageing and Retirement in Europe (SHARE), poorer hearing was associated with greater loneliness, and greater loneliness was associated with poorer cognitive performance, consistent with partial mediation. In contrast, worsening hearing over time was not clearly associated with increasing loneliness over time. Cumulative hearing-aid use did not appear to alter long-term loneliness trajectories, although current hearing-aid use weakened the concurrent association between poorer hearing and greater loneliness. In genetic analyses, we found little evidence that hearing phenotypes or loneliness had clear total or indirect effects on Alzheimer's disease dementia or all-cause dementia. Analyses accounting for shared genetic liability with neuroticism provided some evidence linking loneliness with poorer cognitive performance, and colocalization analyses further suggested shared genetic architecture across hearing, loneliness, cognition, and neuroticism-related traits. Overall, the findings support a robust cross-domain association between poorer hearing, greater loneliness, and poorer cognitive performance, while suggesting that long-term change and genetic evidence are more consistent with shared liability than with a single causal pathway.
BackgroundTo reduce avoidable Special Newborn Care Unit (SNCU) admissions by 15% over a 4-month period through focused quality improvement (QI) interventions at a high-volume tertiary care hospital in Kolkata, India.MethodsThis QI study was conducted from August to November 2024. Baseline data revealed that 25% of weekly SNCU admissions were avoidable. A multidisciplinary team implemented evidence-based admission criteria, enhanced perinatal care practices, and strengthened postnatal monitoring. Key interventions included improved delivery room practices (respiratory support with CPAP, delayed cord clamping, early skin-to-skin contact, and early initiation of breastfeeding) and standardized triage protocols. Feeding support, prefeeding oromotor stimulation, antibiotic stewardship, and reverse transport to nearby SNCUs were also integrated. Four Plan-Do-Study-Act (PDSA) cycles supported infrastructure planning, staff training, protocol implementation, and sustainability.ResultsAvoidable admissions declined from 25% to 10% over 4-months. Bed occupancy dropped from a peak of 125% to 102%. Process indicators improved significantly: delayed cord clamping increased from 30% to 88%, early initiation of breastfeeding from 40% to 90%, and exclusive breastfeeding at discharge from 67% to 81%. Admissions for neonatal jaundice decreased following the implementation of updated AAP guidelines, with 21% of cases managed without phototherapy. Only five re-admissions (0.59%) and one emergency NICU transfer (0.13%) occurred.ConclusionsNeonatal care should extend beyond SNCU optimization to include strengthened delivery point and postnatal-ward practices. When integrated with protocol based SNCU management, this continuum helps reduce morbidity, ease overcrowding, enhance efficiency, and optimize resource utilization in high-burden, resource-limited settings.
The atherogenic index of plasma (AIP) and estimated glucose disposal rate (eGDR) are two composite indices derived from routine metabolic measurements and are associated with cardiocerebrovascular disease risk. In individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome stages 0-3, however, it remains unclear whether joint stratification by these markers helps summarize gradients of cardiovascular disease, heart disease, and stroke risk beyond single-marker assessment. Using data from the China Health and Retirement Longitudinal Study (CHARLS), 5,925 participants without CVD at the start and in CKM stages 0-3 were analyzed. Participants were grouped by median AIP and/or eGDR values. Kaplan-Meier curves and Cox models assessed the link between these indicators and new CVD, heart disease, and stroke cases. Furthermore, both multiplicative and additive interactions between AIP and eGDR were assessed. The predictive value was assessed using the time-dependent Harrell's C index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). A cohort of 5,925 participants aged 45 years and older (mean age: 57.92 ± 8.52 years) was analyzed, with 54.65% of the cohort being female. During the nine-year follow-up period, 1,467 (24.76%) participants developed incident CVD, including 1,106 (18.67%) with heart disease and 525 (8.86%) with stroke. The high AIP and low eGDR group had the highest risk, with CVD hazard ratios (HRs) of 1.35 (95% CI 1.14-1.59), heart disease HRs of 1.32 (95% CI 1.08-1.62), and stroke HRs of 1.59 (95% CI 1.19-2.12), using the low AIP and high eGDR group as the reference. Neither multiplicative nor additive interaction was statistically significant. The combined application of AIP and eGDR provided a modest improvement in predictive capability for cardiovascular disease, heart disease, and stroke. In individuals with CKM stages 0-3, combined AIP and eGDR stratification captured gradients of cardiovascular risk. The combined application of these indicators may provide modest incremental value for risk stratification within CKM stages, thereby aiding in the identification of high-risk individuals during the early stages of CKM.
Chronic otitis media (COM) is an inflammatory process in the middle-ear space that results in long-standing or permanent changes in the tympanic membrane. Platelet-rich fibrin (PRF) is a unique platelet concentrate that is being used in various fields due to its capability to augment healing. Our study aimed to assess whether the use of PRF facilitated graft uptake when compared to the traditional practice of using gel foam to augment graft uptake. A prospective and interventional randomized comparative study was conducted with 100 patients, who all underwent type 1 tympanoplasty using the temporalis fascia as the graft material through the underlay technique performed via a post-aural approach with PRF in one group (Group A) and without PRF in the other (Group B). Postoperative follow-up was done at the end of the first, second, and third months after surgery for the assessment of graft uptake, postoperative infection, and hearing status. The graft uptake rate in the two groups was 98% (Group A) and 88% (Group B) but was not statistically significant (p=0.11). The infection rate in the postoperative period was low in both groups, being 2% and 12% in Groups A and B, respectively. However, there was an improvement in the air-bone gap of 24.8 dB in the PRF group, while it was only 19 dB in the control group (p=0.008), which was statistically significant. It was concluded from our study that PRF helps in better graft uptake and less postoperative infection rate and contributes to a marked enhancement in hearing.
While Anti-Müllerian hormone (AMH) helps personalise In Vitro Fertilization (IVF) stimulation protocols, a significant number of women still do not achieve an optimal ovarian response. To address this, we explore the utility of a polygenic score for age at natural menopause (ANM) as a predictor for ovarian response during IVF. This cohort study included 435 women who underwent standardised IVF stimulation, and they were genotyped to calculate a polygenic score (PGS) for ANM. Linear regression and ANCOVA models were used to assess the associations between the PGS and ovarian response, oocyte and embryo quality and pregnancy rates, adjusting for genomic components and age. A one standard deviation increase in the PGS for ANM was associated with 0.950 (p < 0.001) additional follicles two days before ovum pick-up. While the PGS did not significantly associate with the overall diminished ovarian response (DOR), a mean difference of -0.33 (p < 0.01) in PGS was observed when comparing individuals with fewer than 8 follicles retrieved to those with an optimal ovarian response. No association was found between the PGS and ongoing pregnancy. Causal mediation revealed that the effect of the PGS onto the number of follicles was partly mediated by AMH levels (proportion mediated = 31%, p = 0.002). A lower PGS for ANM, indicative for earlier menopause, is independently associated with a reduced ovarian response during IVF stimulation, specifically fewer follicles retrieved and mostly independent of AMH levels. This highlights the potential of ANM-related genetic variants to inform personalised IVF protocols by predicting ovarian responsiveness. This study was supported by Ferring Pharmaceuticals.
Highway multilevel interchanges present unique challenges, characterized by complex road conditions, ambiguous routes and short intervals. Multiple ramps necessitate swift and continuous direction changes, significantly jeopardizing pathfinding safety. Guide signs play a crucial role in improving information recognition and driving safety. This study replaces accident conflicts with risk behaviors and constructs a risk prevention research framework: Firstly, through subjective demand analysis, the cognitive preferences and functional expectations of drivers were analyzed to clarify design orientation. Secondly, the influence of pathfinding process under traffic facility intervention and potential risk relationship was captured in a driving simulation experiment. Furthermore, focus on coupled collaborative analysis, the correlation between longitudinal stability and lateral maneuvering behavior was quantified, and collaborative effectiveness evaluation was conducted. Ultimately, the optimized sign served as a guide for improving behaviors. Results show that: 1) At different ramp decision points, setting "destination separation for different directions" and "lane guidance" information represent drivers'core demands; 2) Under the influence of 4 sign schemes, there are indeed differences in the pathfinding behavior of longitudinal and lateral dimensions, which should be improved in a coordinated manner. 3) Approaching the ramp exit, setting different directions information can help drivers make decisions more quickly, reach the target speed earlier, and reduce conflict time with mainstream traffic. Approaching the ramp for the first diversion, setting both information helps drivers tend to accelerate smoothly, and conduct lane change adjustments before making decisions. Approaching the ramp for the second diversion, simplify setting lane guide information can improve lateral maneuvering and enable faster path selection. 4) Providing information prompts in the form of navigation can offer continuous direction guidance, timely lane changing, with higher longitudinal safety margin and lateral stability. The proposed suggestions for risk prevention can achieve a coordinated improvement in traffic safety across multiple dimensions.
Relied on three-dimensional metamaterial-based particulate-fluid system, an acoustic weave platform increases the sound pressure amplitude by frequency bandgap peak gain (Q-factor 4.5) in acoustically regular air media system with ways that a conventional method cannot. The interesting morphology alternations of the aggregation, fluidization, and trapping for numerous expanded-polystyrene particles (1-7.5 mm) were experimentally observed by engineering acoustic field in the low-frequency range of <0.8 kHz, improving the weak phenomenon in the absence of acoustic-metamaterial design. With vertical square-waveguide arrayed uniformly 12 of Helmholtz sound sources, the platform modulates the acoustic wave-packet movement and amplifies resonantly the time-spatial Y-shape-bifurcated-aggregation 54.7°-long-short-range-attraction wave phenomenon of complex macro soft-matter particles. Through experiment coinciding with simulation and theory, the main behaviors' phenomena were accurately explained by acoustic radiation force and secondary radiation force joint with the modulated three-dimensional acoustic field. The particle fluidization and trapping occur on contrary acoustic gradient fields at 220 and 250 Hz, respectively. There exist several vertically parallel "chiral" layer thin-film-aggregation stripes of millimeter-scale particles also obviously appearing at 220 Hz, more intuitively displaying the quasi-waves' constructive and destructive interferences of mm-scale particles themselves for wave-particle duality theory. The macro wavelike character helps to conveniently modulate collectively the environmental behaviors of fly-ash.
BACKGROUND Kennedy disease, also known as spinal and bulbar muscular atrophy (SBMA), is a rare and incurable X-linked neuromuscular disorder mainly affecting men aged 30 to 60 years. Polymyositis can present similarly, but can be excluded by measuring muscle enzymes, performing muscle imaging, and electromyography. This report describes the case of a 52-year-old man with a 10-year history of progressive limb weakness due to Kennedy disease, established by genetic testing. CASE REPORT A 52-year-old man presented with a 10-year history of gradually progressive proximal limb weakness and persistently elevated creatine kinase levels ranging from 808-2300 U/L (normal 39-308 U/L). One year prior to this admission, the limb weakness had worsened, but initial electromyography, neuroimaging, and muscle biopsy showed no specific abnormalities. Despite a trial of immunosuppressive therapy due to suspected polymyositis, there was no clinical improvement. Neurological examination later revealed gynecomastia, proximal muscle atrophy, and bilateral tongue atrophy with tremor. Electromyography showed chronic neurogenic changes and reduced sensory nerve action potentials. Repeat expansion analysis identified a hemizygous pathogenic CAG repeat expansion in exon 1 of the androgen receptor gene using a short-read next-generation sequencing-based repeat detection algorithm (ExpansionHunter), with an estimated repeat number of 51 (range 50-53). At 6-month follow-up, the patient demonstrated mild progression of motor symptoms but remained functionally stable. CONCLUSIONS This report presents a rare case of Kennedy disease, initially diagnosed as polymyositis, and highlights the importance of follow-up with genetic testing when neurological and electromyography investigations are not typical for polymyositis. Early identification of Kennedy disease helps avoid unnecessary immunosuppressive treatments.
Functional/Secondary tricuspid regurgitation (STR) accounts for over 85% of clinically significant tricuspid regurgitation (TR) and is associated with adverse prognosis and impaired quality of life. Advances in percutaneous tricuspid valve (TV) interventions underscore the need to differentiate TR aetiologies, mechanisms, and phenotypes. STR is subdivided into atrial (A-STR), caused by right atrial dilation and tricuspid annular enlargement without significant leaflet tethering, and ventricular (V-STR), resulting from right ventricular dilation/dysfunction with leaflet tethering. A-STR, increasingly prevalent with ageing and atrial fibrillation, typically presents with preserved right ventricular function, whereas V-STR reflects more advanced disease, is associated with RV dysfunction and, often, left ventricular systolic dysfunction and remodelling and/or left-sided valve disease, carrying higher mortality, compared with A-STR. Cardiac implantable electronic device (CIED) related TR is emerging as a distinct entity, while organic-TR arises from intrinsic structural abnormalities of the valve apparatus. Echocardiography, particularly three-dimensional imaging, is essential for accurate phenotyping and helps in procedural planning. Medical therapy remains primarily symptomatic, with diuretics as first-line therapy and targeted treatment of underlying cardiac pathology. In A-STR, rhythm control strategies, including catheter ablation for atrial fibrillation, may reverse annular remodelling. Surgical repair, preferably annuloplasty, is recommended in selected patients, often when concomitant left-sided surgery is needed. Transcatheter edge-to-edge repair offers a safe and increasingly used alternative, providing symptomatic improvement. The effects on outcomes are likely dependent on the time of intervention and the STR phenotype.
Trichoscopy enhances diagnostic accuracy in primary cicatricial alopecias (PCA), yet comparative data on its application across diverse skin phototypes remain limited. The aim of this study was to characterize trichoscopic features across various forms of PCAs and compare findings between fair and dark phototypes. This is a descriptive, multicenter international study analyzing trichoscopic patterns in 1102 patients with PCAs across a range of ethnic backgrounds and skin phototypes. The absence of follicular openings was the most consistent trichoscopic finding across all phototypes. Notable variations in trichoscopic patterns were observed based on skin color. In both fair and dark phototypes, signs of clinical and trichoscopic activity were predominantly observed within the first five years of disease duration, when inflammation is typically more pronounced. Clinicians should be aware of trichoscopic variations both between and within the same PCA according to the phototype. Such awareness enhances the recognition and interpretation of trichoscopic features, particularly during the early and active stages of the disease, and helps guide the selection of optimal biopsy sites across PCA subtypes in both fair and dark skin. This approach can ultimately facilitate histopathological confirmation and support clinical decision-making.
Megahertz-rate optical coherence tomography (MHz-OCT) is an optical imaging technology that has attracted considerable attention in clinical practice. Its advantages, such as ultra-high speed, noninvasiveness, and high resolution, endow it with broad application prospects in various clinical fields. However, MHz-OCT systems place high demands on the sampling rate and bandwidth of acquisition and data transmission systems, greatly increasing the system cost. Based on a high-speed k-linear swept laser with the acousto-optic deflector (AOD), this paper proposes a hardware-based down-sampling method. Sweeping a narrowband spectrum and utilizing the linear wavenumber characteristic of the laser enables an equivalent down-sampling of the original interference signal. Deep learning is employed to recover high-resolution images from the down-sampled signals. High-quality imaging results have been successfully achieved at a high sweep speed of 1 MHz while using acquisition and data transmission systems with lower bandwidth and sampling rate. The novel down-sampled OCT system proposed in this paper helps to reduce the cost of MHz-OCT systems in clinical settings and promotes their popularization and application.
RNA has long provided a plausible route by which heredity and catalysis could become linked in early evolution, and the same chemical versatility helps explain why RNA remains central to origin-of-life research, modern cell biology, and biotechnology. This review adopts a plural framing of RNA worlds to connect three regimes: a primordial RNA world constrained by geochemistry, a contemporary RNA world in which RNAs contribute to catalysis and regulation in cells, and an applied RNA world in which RNA is engineered as a programmable tool. Across these regimes, a common logic emerges from the mapping of sequence to structure to function under explicit constraints. In early evolution, cycling, interfaces, and confinement can generate heterogeneous oligomer pools and bias their persistence, whereas the transition toward Darwinian dynamics depends on copying fidelity, strand dynamics, and compartment coupled population structure. In cells and applications, noncoding RNA networks, RNA modifications, and RNA-guided targeting implement specificity in chemically complex environments, while laboratory selection and design must also confront constraints imposed by stability, delivery, and immune sensing. Across contexts, fitness landscapes and tradeoffs between peak performance and robustness provide experimental benchmarks and practical design principles for RNA function.
Diabetes mellitus (DM) is known to be associated with cardiovascular disease. This study aims to determine the level of knowledge about cardiovascular diseases among DM patients in the Kingdom of Saudi Arabia. This online cross-sectional survey study was conducted between March 2024 and April 2025 in Saudi Arabia. The study population comprised patients diagnosed with DM and aged at least 18 years who were currently residents in Saudi Arabia. The questionnaire for this study was adopted from a previous study by Wagner et al, named the Heart Disease Fact Questionnaire. Logistic regression analysis was conducted to predict significant factors influencing the knowledge of heart disease. Most participants had good knowledge of heart disease risk factors. For example, 210 (94.2%) knew that smoking is a risk factor, and 202 (94.2%) agreed that quitting smoking reduces the risk. In addition, 199 (91.7%) recognized high blood pressure as a risk factor, and 204 (93.4%) knew that controlling it reduces heart disease risk. A total of 200 (94.8%) understood that high blood sugar over time increases cholesterol and heart disease risk, and 194 (92.4%) believed that good blood sugar control helps reduce this risk. Furthermore, some misconceptions were observed: 185 (78.4%) incorrectly believed a person always knows when they have heart disease, and 118 (57.3%) thought people with diabetes rarely have high cholesterol. Smokers had significantly lower odds of good knowledge compared with nonsmokers (odds ratio = 0.32, 95% confidence interval: 0.11-0.90, P = .031). Conversely, participants who adhered to their treatment were significantly more likely to have good knowledge (odds ratio = 4.63, 95% confidence interval: 1.09-19.67, P = .038). The majority of the participants had a high level of understanding of the risk factors for heart disease. There were significant misconceptions regarding diabetes-related cholesterol risk and the symptoms of heart disease. Compliant patients had a higher level of awareness, and smokers had a significantly lower level of knowledge. These findings point to the necessity for educational interventions that are specifically designed to address particular deficiencies.
Ventriculoperitoneal shunting (VPS) helps reduce intracranial pressure and alleviate clinical symptoms caused by hydrocephalus in hemorrhagic Moyamoya disease (MMD). To date, no literature describes the occurrence of subdural fluid collection (SDFC) in hemorrhagic MMD patients undergoing VPS prior to cerebral revascularization. This report aims to explore the potential pathological mechanisms underlying SDFC following cerebral revascularization after prior VPS, and to provide effective strategies for future prevention. Clinical data of hemorrhagic MMD patients undergoing VPS prior to bypass admitted to our hospital from 2021 January and 2024 December were selected. Medical records were reviewed to analyze patient characteristics and the entire disease course. Among the 7 patients (9 cases), postoperative SDFC occurred in 7 cases (7/9, 77.8%), located contralateral to the shunt in 6 cases (6/7, 85.7%) and ipsilateral to the surgical side in 1 case (1/7, 14.3%), with onset mostly within 1 day after surgery. Among these 7 patients, 2 underwent subdural drilling and drainage due to significant mass effect caused by the effusion. One of these patients developed herniation with decreased consciousness and notable midline shift, and symptoms gradually improved after subdural drainage. Durin-g short-term clinical follow-up (postoperative period < 12 months), recurrent hemorrhage occurred in 1 out of 9 cases, while no cases of cerebral infarction or seizures were observed. CT angiography (CTA) revealed occlusion of the bypass graft in 2 out of 6 direct bypass cases. Through the findings of this study and literature review, we observe that cerebral revascularization performed during the late phase of VPS may induce SDFC complications through multiple mechanisms. Future implementation of early intervention may effectively reduce the risk of adverse events and improve surgical outcomes.
Accurate staging is critical in gastric cancer, as the presence of peritoneal metastasis directly influences treatment strategy and prognosis. Despite advances in cross-sectional imaging, occult peritoneal disease may remain undetected. Staging laparoscopy has been increasingly utilized to improve diagnostic accuracy; however, its true impact on clinical decision-making and the predictive factors for occult metastasis remain areas of ongoing investigation. This retrospective study included patients with biopsy-proven gastric adenocarcinoma who underwent staging laparoscopy between March 2019 and April 2025 at a high-volume tertiary center. Patients with radiologically metastatic disease or incomplete clinical data were excluded. All patients had clinically M0 disease on preoperative imaging. The primary outcome was the detection rate of occult stage IV disease and its impact on treatment strategy. Secondary outcomes included concordance between frozen and final cytology, postoperative outcomes, and identification of predictors for peritoneal metastasis. Multivariable logistic regression analysis was performed to determine independent risk factors. A total of 301 patients were included in the final analysis. Staging laparoscopy identified occult metastatic disease in 65 patients, corresponding to an upstaging rate of 21.6% (95% CI: 16.9-26.3%). Malignant cytology and peritoneal implants were detected in 13.9% and 17.3% of patients, respectively. Frozen cytology demonstrated high specificity (95%) but limited sensitivity (67%) compared to final cytology. Treatment strategy was altered in all patients with newly detected metastatic disease, avoiding non-beneficial surgical intervention. Multivariable analysis revealed that only clinical nodal stage was independently associated with positive peritoneal cytology and/or peritoneal involvement (OR 2.42, 95% CI: 1.4-4.2, p = 0.001). The procedure was associated with low morbidity (0.66%) and minimal mortality (0.33%). Staging laparoscopy provides substantial diagnostic value in detecting radiologically occult metastatic disease in gastric cancer and significantly influences treatment planning. Its routine use in appropriately selected patients improves staging accuracy and helps prevent unnecessary surgical interventions. Clinical nodal status appears to be the strongest independent predictor of occult peritoneal disease.
Cardiovascular diseases is the most common cause of mortality in the world. B vitamins (B₁-B₁₂) control how mitochondria make energy, how nitric oxide is made, how one-carbon is used, and how genes work. A deficiency leads to hyperhomocysteinemia, oxidative stress, and endothelial dysfunction, all of which are important to vascular disease. Observational studies consistently associate low B-vitamin levels with an elevated risk of cardiovascular diseases; nevertheless, randomized supplementation trials have demonstrated only modest reductions in significant events. This narrative review summarizes molecular, epidemiological, and clinical evidence on the role of B vitamins in cardiovascular health. Special focus was paid to functional biomarkers and gene-nutrient interactions that affect how well a therapy works. The literature was identified through targeted searches of PubMed, Scopus, and Google Scholar. Priority was given to high-quality evidence, including mechanistic studies, observational cohorts, randomized controlled trials, meta-analyses, and major review articles relevant to cardiovascular outcomes. Functional indicators, such as methylmalonic acid and holotranscobalamin, offer superior accuracy compared to blood levels in assessing vitamin status. Nutrigenetic interactions, particularly the effects of folate and riboflavin on methylenetetrahydrofolate reductase polymorphisms, exhibit blood pressure-lowering and stroke-preventive advantages. The clinical efficacy of B-vitamin supplementation is highly dependent on baseline nutritional status and regional food fortification policies. For example, folic acid supplementation significantly reduces stroke incidence in populations who lack mandatory folate fortification, whereas trials conducted in folate-sufficient cohorts generally demonstrated no added cardiovascular benefit. Recognizing this population-specific variability helps explain the historical discrepancy between the strong mechanistic potential of B-vitamins and the mixed results observed in large-scale clinical trials. While adequate B-vitamin status remains mechanistically essential for cardiovascular homeostasis, the clinical benefits of routine supplementation are nuanced and highly population-dependent. Consequently, ubiquitous supplementation is unlikely to produce extensive advantages. A precision strategy that combines biomarkers, genotype stratification, and population context can help find their therapeutic potential. Future methods should integrate diet with precision cardiology to enhance vascular prevention.
Pain is a hallmark of inflammation and tissue injury, particularly following major surgical procedures. Despite its prevalence and clinical impact, pathological pain, defined as persistent pain that impairs function, remains a major unmet medical need. Human birth tissue, including the amniotic membrane and umbilical cord, has long been recognized for its regenerative properties and its ability to support wound healing. Recent studies have identified heavy chain 1 (HC)-hyaluronic acid (HA)/pentraxin 3 (HC-HA/PTX3) as a key matrix component within these tissues. This complex exhibits anti-inflammatory and anti-scarring activities and helps maintain stem cell quiescence. Emerging evidence, including our own findings, indicates that human birth tissue-derived products may also modulate pain responses in certain settings, such as post-surgical pain, potentially through mechanisms involving neuronal inhibition and regenerative healing. We summarize the molecular and cellular mechanisms by which human birth tissue-derived products and HC-HA/PTX3 may exert anti-inflammatory and analgesic effects. We then highlight preclinical and clinical studies evaluating their potential roles in wound healing and pathological pain. Finally, we discuss translational opportunities, current challenges, and future directions for advancing these biologics within the emerging field of regenerative pain medicine. This review outlines a framework for potential regenerative pain management using birth tissue-derived products, which may serve as a foundation for developing new therapies for certain pathological pain conditions.
Myocardial ischemia-reperfusion (I/R) injury remains a major determinant of outcome after acute myocardial infarction (AMI) despite timely primary percutaneous coronary intervention (PPCI). Although epicardial patency is routinely restored, incomplete tissue reperfusion, microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and maladaptive inflammation often limit myocardial salvage and promote adverse remodeling. In this narrative review, I/R injury is synthesized as a spatiotemporal, multicompartment network in which dominant mechanisms and actionable nodes shift from seconds to weeks and across cardiomyocytes, the coronary microvasculature, and systemic immune-metabolic programs. This framework helps explain why many single-target, single-window cardioprotective strategies have shown robust preclinical benefit yet failed to improve outcomes in contemporary ST-segment elevation myocardial infarction (STEMI) trials, where heterogeneity in ischemic time, comorbidities, microvascular injury patterns, and background pharmacotherapy reshapes injury topology and dilutes target-dominant subgroups. We propose an endpoint-anchored approach that distinguishes cardiomyocyte-vulnerability, microvascular-bottleneck, and resolution-deficient endotypes and matches interventions to phase-specific objectives using compartment-aligned endpoint stacks and target-engagement biomarkers. Within this rationale, defined bioactive compounds derived from traditional Chinese medicine (TCM) and selected standardized preparations are evaluated as potential network modulators with plausible actions on mitochondrial vulnerability, immunothrombosis, endothelial integrity, and inflammatory resolution. Translational priorities include stringent standardization, pharmacokinetic/pharmacodynamic (PK/PD)-informed dosing, PCI-compatible safety and drug-drug interaction assessment, and biomarker-guided trial designs enriched for mechanistically matched endotypes.
Nicotinamide N-methyltransferase (NNMT) is an enzyme that helps regulate how cells balance energy and methylation potential; however, its abnormal activation can disrupt this balance, fueling diseases such as diabetes, obesity, fibrosis, and cancer. As a result, small-molecule inhibitors targeting NNMT have been developed to reduce this elevated activity, but insufficient target engagement, reduced bioavailability, and unknown safety profiles have led to limited preclinical success across diseases. Advances in NNMT small-molecule inhibitor development have yielded a number of compounds that address these concerns, resulting in drug-like compounds with high affinities for cellular NNMT and promising safety profiles. In this review, we assess the growing therapeutic potential of NNMT inhibitors by highlighting recent developments in NNMT pathophysiology and inhibitor medicinal chemistry.