Assay Interference Causing Persistently Elevated Vancomycin Levels Leading to Treatment Failure and Fatal Outcome.

In patients receiving vancomycin therapy, serum drug levels are routinely monitored to ensure therapeutic dosing and minimize toxicity. In rare cases, vancomycin levels may be falsely or persistently elevated without any apparent cause. In this case report, we explore a rare case of persistently elevated vancomycin levels despite discontinuation of the drug for days.  This is a case of a 69-year-old female admitted for altered mental status secondary to sepsis from leg cellulitis. Antibiotic therapy included vancomycin. To ensure proper dosing, vancomycin trough levels were collected before the fourth dose, and the result showed a high value of 39 ug/ml. Vancomycin doses were adjusted as per the Bayesian dosing software, and the same remained to be in supratherapeutic levels. The patient eventually deteriorated, and due to persistently high vancomycin levels, the antibiotic regimen was switched to a different antibiotic. Despite normal renal functions, the vancomycin levels remained high, between 27 ug/ml and 32 ug/ml, even in the absence of any further doses. Subsequently, vancomycin serum concentration was determined by another method using high-performance liquid chromatography (HPLC). Blood cultures grew both coagulase-negative Staphylococcus aureus and Achromobacter xylosoxidans. Vancomycin levels remained high a week after discontinuation of the drug. Vancomycin by HPLC assay eventually showed that vancomycin was undetectable in the blood, but, unfortunately, the results came at a time when the patient had already expired. In conclusion, clinicians should maintain a high level of suspicion if persistently higher vancomycin levels cannot be accounted for by renal function or other causes. In patients with persistently high vancomycin levels who continue to clinically deteriorate, it is crucial to consider that assay interference can result in inaccurately elevated vancomycin levels.

Association between protein-to-energy ratio and overweight/obesity in children and adolescents in the United States: a cross-sectional study based on NHANES.

Background: The dietary protein proportion may be crucial in triggering overweight and obesity among children and adolescents. Methods: Cross-sectional data from 4,336 children and adolescents who participated in the National Health and Nutrition Survey (NHANES) between 2011 and March 2020 were analyzed. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI). Restricted cubic splines assessed the nonlinear relationships between dietary protein intake and the prevalence of overweight and obesity. Results: Adjusted logistic regression models showed that each 1% increase in dietary protein proportion was associated with a 4% higher risk of overweight and obesity (OR = 1.04, 95% CI: 1.01-1.07). A nonlinear relationship was noted in children aged 6-11 years (P < 0.05), as demonstrated by restricted cubic spline analysis. After dividing dietary protein intake into quartiles, the highest quartile had an adjusted OR of 2.07 (95% CI: 1.35, 3.16, P = 0.001) compared to the lowest, among children aged 6-11 years. Conclusion: Dietary protein intake is positively linked to overweight and obesity in American children, irrespective of individual characteristics and total energy consumption.

Impact of index admission cholecystectomy vs interval cholecystectomy on readmission rate in acute cholangitis: National Readmission Database survey.

BACKGROUND: Elective cholecystectomy (CCY) is recommended for patients with gallstone-related acute cholangitis (AC) following endoscopic decompression to prevent recurrent biliary events. However, the optimal timing and implications of CCY remain unclear. AIM: To examine the impact of same-admission CCY compared to interval CCY on patients with gallstone-related AC using the National Readmission Database (NRD). METHODS: We queried the NRD to identify all gallstone-related AC hospitalizations in adult patients with and without the same admission CCY between 2016 and 2020. Our primary outcome was all-cause 30-d readmission rates, and secondary outcomes included in-hospital mortality, length of stay (LOS), and hospitalization cost. RESULTS: Among the 124964 gallstone-related AC hospitalizations, only 14.67% underwent the same admission CCY. The all-cause 30-d readmissions in the same admission CCY group were almost half that of the non-CCY group (5.56% vs 11.50%). Patients in the same admission CCY group had a longer mean LOS and higher hospitalization costs attributable to surgery. Although the most common reason for readmission was sepsis in both groups, the second most common reason was AC in the interval CCY group. CONCLUSION: Our study suggests that patients with gallstone-related AC who do not undergo the same admission CCY have twice the risk of readmission compared to those who undergo CCY during the same admission. These readmissions can potentially be prevented by performing same-admission CCY in appropriate patients, which may reduce subsequent hospitalization costs secondary to readmissions.

Biophysical modeling and diffusion kurtosis imaging reveal microstructural alterations in normal-appearing white-matter regions of the brain in obstructive sleep apnea.

Study Objectives: Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA. Methods: Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers. Results: OSA was diagnosed when the patient's apnea-hypopnea index was ≥ 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort. Conclusions: Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia.

Antiviral Shrimp lncRNA06 Possesses Anti-Tumor Activity by Inducing Apoptosis of Human Gastric Cancer Stem Cells in a Cross-Species Manner.

Virus infection causes the metabolic disorder of host cells, whereas the metabolic disorder of cells is one of the major causes of tumorigenesis, suggesting that antiviral molecules might possess anti-tumor activities by regulating cell metabolism. As the key regulators of gene expression, long non-coding RNAs (lncRNAs) play vital roles in the regulation of cell metabolism. However, the influence of antiviral lncRNAs on tumorigenesis has not been explored. To address this issue, the antiviral and anti-tumor capacities of shrimp lncRNAs were characterized in this study. The results revealed that shrimp lncRNA06, having antiviral activity in shrimp, could suppress the tumorigenesis of human gastric cancer stem cells (GCSCs) via triggering apoptosis of GCSCs in a cross-species manner. Shrimp lncRNA06 could sponge human miR-17-5p to suppress the stemness of GCSCs via the miR-17-5p-p21 axis. At the same time, shrimp lncRNA06 could bind to ATP synthase subunit beta (ATP5F1B) to enhance the stability of the ATP5F1B protein in GCSCs, thus suppressing the tumorigenesis of GCSCs. The in vivo data demonstrated that shrimp lncRNA06 promoted apoptosis and inhibited the stemness of GCSCs through interactions with ATP5F1B and miR-17-5p, leading to the suppression of the tumorigenesis of GCSCs. Therefore, our findings highlighted that antiviral lncRNAs possessed anti-tumor capacities and that antiviral lncRNAs could be the anti-tumor reservoir for the treatment of human cancers.

Pain and Wound Management in Fungating Merkel Cell Carcinoma within a Palliative Setting: The First Case Report of this Predicament.

Merkel cell carcinoma (MCC) is a rare type of skin cancer of the neuroendocrine Merkel mechanoreceptors. These cells are closely associated with nerve terminals and, given their proximity to cutaneous tissue, have the propensity to develop into deeply ulcerated, fungating malignancies. These friable wounds are easily irritated, and can cause significant pain for patients. We report a palliative case of severe, fungating MCC of the left scalp where the main contributor to the patient's illness burden is pain. Having been referred to palliative care by the Tissue Viability team, this 90-year-old gentleman was complaining of episodic burning pain during dressing changes, which was associated with radiation to the forehead, nausea, and significant trait anxiety. It was theorised that this pain could be in part due to tension headache, not just nociception, and anticipatory lorazepam was prescribed to relieve trait anxiety. All symptoms were majorly relieved following this administration. A specialist dressing was implemented to absorb exudate and balance moisture, which we believe may have stopped further deterioration of pain. Overall, this report emphasises the need to consider alternative pain aetiologies other than nociception in a presentation that is not found in the literature.

Elucidating the modulatory effect of melatonin on enzyme activity and oxidative stress in wheat: a global meta-analysis.

In our comprehensive meta-analysis, we initially collected 177 publications focusing on the impact of melatonin on wheat. After meticulous screening, 40 published studies were selected, encompassing 558 observations for antioxidant enzymes, 312 for reactive oxygen species (ROS), and 92 for soluble biomolecules (soluble sugar and protein). This analysis revealed significant heterogeneity across studies (I2 > 99% for enzymes, ROS, and soluble biomolecules) and notable publication bias, indicating the complexity and variability in the research field. Melatonin application generally increased antioxidant enzyme activities [superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX)] in wheat, particularly under stress conditions, such as high temperature and heavy-metal exposure. Compared to control, melatonin application increased SOD, POD, CAT, and APX activities by 29.5, 16.96, 35.98, and 171.64%, respectively. Moreover, oxidative stress markers like hydrogen peroxide (H2O2), superoxide anion (O2), and malondialdehyde (MDA) decreased with melatonin by 23.73, 13.64, and 21.91%, respectively, suggesting a reduction in oxidative stress. The analysis also highlighted melatonin's role in improving carbohydrate metabolism and antioxidant defenses. Melatonin showed an overall increase of 12.77% in soluble sugar content, and 22.76% in glutathione peroxidase (GPX) activity compared to the control. However, the effects varied across different wheat varieties, environmental conditions, and application methods. Our study also uncovered complex relationships between antioxidant enzyme activities and H2O2 levels, indicating a nuanced regulatory role of melatonin in oxidative stress responses. Our meta-analysis demonstrates the significant role of melatonin in increasing wheat resilience to abiotic stressors, potentially through its regulatory impact on antioxidant defense systems and stress response.

Exploring the path to polio eradication: insights from consecutive seroprevalence surveys among Pakistani children.

Introduction: After trivalent oral poliovirus vaccine (tOPV) cessation, Pakistan has maintained immunity to type 2 poliovirus by administering inactivated polio vaccine (IPV) in routine immunization, alongside monovalent OPV type 2 (mOPV2) and IPV in supplementary immunization activities (SIAs). This study assesses the change in poliovirus type 2 immunity after tOPV withdrawal and due to SIAs with mOPV2 and IPV among children aged 6-11 months. Methods: Three cross-sectional sequential serological surveys were conducted in 12 polio high-risk areas of Pakistan. 25 clusters from each geographical stratum were selected utilizing probability proportional to size. Results: Seroprevalence of type 2 poliovirus was 49%, with significant variation observed among surveyed areas; <30% in Pishin, >80% in Killa Abdullah, Mardan & Swabi, and Rawalpindi. SIAs with IPV improved immunity from 38 to 57% in Karachi and 60 to 88% in Khyber. SIAs with IPV following mOPV2 improved immunity from 62 to 65% in Killa Abdullah, and combined mOPV2 and IPV SIAs in Pishin improved immunity from 28 to 89%. Results also reflected that immunity rates for serotypes 1 and 3 were consistently above 90% during all three phases and across all geographical areas. Conclusion: The study findings highlight the importance of implementing effective vaccination strategies to prevent the re-emergence of poliovirus. Moreover, the results provide crucial information for policymakers working toward achieving global polio eradication.

Plastic Surgery Teaching to United Kingdom Undergraduate Medical Students: A Systematic Review.

Background There are varying reports about United Kingdom medical students' exposure and teaching methods regarding plastic and reconstructive surgery. To date, no systematic review has been done looking at this topic. Methods Three databases (PubMed, Embase, and Medline) were searched from January 1, 2011 to July 20, 2023 for studies that assessed United Kingdom medical students' exposure to plastic surgery and suggested recommendations to improve teaching. Three authors performed data extraction and screening, as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Fifteen studies were included. Medical students' average current exposure to plastic surgery was 29.44%, but this was highly variable across the studies. The most common method of currently teaching plastic surgery was through lectures (34% of studies), and the most common suggested method of teaching was through courses (40% of studies). Many of the studies (12/15) were deemed as being at high risk of bias. Conclusion More recent studies need to be performed to assess current levels of teaching of plastic surgery in the United Kingdom medical school curriculum. Greater exposure to plastic surgery through lectures and integrated clinical placements is needed to ensure equitable access for all medical students to plastic surgery as a profession.

Integrating of analytical techniques with enzyme-mimicking nanomaterials for the fabrication of microfluidic systems for biomedical analysis.

Bioanalysis faces challenges in achieving fast, reliable, and point-of-care (POC) determination methods for timely diagnosis and prognosis of diseases. POC devices often display lower sensitivity compared to laboratory-based methods, limiting their ability to quantify low concentrations of target analytes. To enhance sensitivity, the synthesis of new materials and improvement of the efficiency of the analytical strategies are necessary. Enzyme-mimicking materials have revolutionized the field of the fabrication of new high-throughput sensing devices. The integration of microfluidic chips with analytical techniques offers several benefits, such as easy miniaturization, need for low biological sample volume, etc., while also enhancing the sensitivity of the probe. The use enzyme-like nanomaterials in microfluidic systems can offer portable strategies for real-time and reliable detection of biological agents. Colorimetry and electrochemical methods are commonly utilized in the fabrication of nanozyme-based microfluidic systems. The review summarizes recent developments in enzyme-mimicking materials-integrated microfluidic analytical methods in biomedical analysis and discusses the current challenges, advantages, and potential future directions.

Oxidized alginate-gelatin (ADA-GEL)/silk fibroin/Cu-Ag doped mesoporous bioactive glass nanoparticle-based hydrogels for potential wound care treatments.

The present work focuses on developing 5% w/v oxidized alginate (alginate di aldehyde, ADA)-7.5% w/v gelatin (GEL) hydrogels incorporating 0.25% w/v silk fibroin (SF) and loaded with 0.3% w/v Cu-Ag doped mesoporous bioactive glass nanoparticles (Cu-Ag MBGNs). The microstructural, mechanical, and biological properties of the composite hydrogels were characterized in detail. The porous microstructure of the developed ADA-GEL based hydrogels was confirmed by scanning electron microscopy, while the presence of Cu-Ag MBGNs in the synthesized hydrogels was determined using energy dispersive x-ray spectroscopy. The incorporation of 0.3% w/v Cu-Ag MBGNs reduced the mechanical properties of the synthesized hydrogels, as investigated using micro-tensile testing. The synthesized ADA-GEL loaded with 0.25% w/v SF and 0.3% w/v Cu-Ag MBGNs showed a potent antibacterial effect againstEscherichia coliandStaphylococcus aureus. Cellular studies using the NIH3T3-E1 fibroblast cell line confirmed that ADA-GEL films incorporated with 0.3% w/v Cu-Ag MBGNs exhibited promising cellular viability as compared to pure ADA-GEL (determined by WST-8 assay). The addition of SF improved the biocompatibility, degradation rate, moisturizing effects, and stretchability of the developed hydrogels, as determinedin vitro. Such multimaterial hydrogels can stimulate angiogenesis and exhibit desirable antibacterial properties. Therefore further (in vivo) tests are justified to assess the hydrogels' potential for wound dressing and skin tissue healing applications.

Prevalence of Misconceptions and Myths Regarding Oral Health Among Medical and Dental Students in Peshawar, Pakistan.

Background The aim of study is to assess the prevalence of dental myths and misconceptions among the students of medicine and dentistry in Peshawar, Pakistan, and to gauge the quality of dental education, knowledge, and awareness. Methods A cross-sectional descriptive study was conducted on the current students of medicine and dentistry at Rehman Medical College, Rehman College of Dentistry, Gandhara University, Khyber Medical College, and Khyber College of Dentistry. They were questioned regarding their beliefs in dental misconceptions and myths prevalent in Peshawar, Pakistan. Results The sample comprised 400 undergraduate students, of whom 47.5% (190) were males and 52.5% (210) were females. The most held beliefs were that eating sugar does not affect teeth as long as one brushes twice a day (46%), brushing right after a meal is better for teeth (70%), and the extraction of baby teeth does not matter as they are going to be replaced by the permanent teeth in any case (38%). Most of these misconceptions had a significant association with the field of study. Conclusion The issue of myths and misconceptions regarding dental health and care is widespread, even in the academic community. This should be of significant concern to the relevant authorities, and adequate measures must be taken to dispel such false information.

Breaking barriers to climate finance: Asymmetric nexus between green investment and energy innovation in Europe.

Growing concerns regarding climate change and the necessity to shift towards a low-carbon economy have resulted in a significant rise in the worth of green finance for developing energy technology. This growing emphasis on green finance underscores the urgency for a nuanced exploration of the asymmetric nexus between green investment and energy innovation in Europe. The present article investigates the asymmetric relationship between green investment and energy innovation in the top ten European nations with the highest green investment (France, Netherlands, Germany, Italy, Spain, Denmark, Austria, Finland, the UK, and Sweden). Formerly, panel data methodologies were employed to observe the link between green investment and energy innovation despite the absence of an exclusive connection in certain economies. On the other hand, this study uses 'Quantile-on-Quantile' approach for econometric estimation using the annual data from 2007 to 2022. This unique methodology enables a detailed and specific analysis of time-series interdependence in every economy, providing valuable perceptions of the nuanced relationship between these variables. Investment in renewable energy is employed as a proxy for green investment, while energy-related patents represent energy innovation. The study employs a quantile cointegration test to assess the variables long-run relationship. The results indicate a positive correlation between green investment and energy innovation in many countries at certain data points. Additionally, the analysis demonstrates that the extent of asymmetry between these variables varies across countries, stressing policymakers' need to closely monitor fluctuations in green investment and energy innovation.

Advances in nanotechnology-assisted photodynamic therapy for neurological disorders: a comprehensive review.

Neurological disorders such as neurodegenerative diseases and nervous system tumours affect more than one billion people throughout the globe. The physiological sensitivity of the nervous tissue limits the application of invasive therapies and leads to poor treatment and prognosis. One promising solution that has generated attention is Photodynamic therapy (PDT), which can potentially revolutionise the treatment landscape for neurological disorders. PDT attracted substantial recognition for anticancer efficacy and drug conjugation for targeted drug delivery. This review thoroughly explained the basic principles of PDT, scientific interventions and advances in PDT, and their complicated mechanism in treating brain-related pathologies. Furthermore, the merits and demerits of PDT in the context of neurological disorders offer a well-rounded perspective on its feasibility and challenges. In conclusion, this review encapsulates the significant potential of PDT in transforming the treatment landscape for neurological disorders, emphasising its role as a non-invasive, targeted therapeutic approach with multifaceted applications.

Photodynamic therapy is a promising tool to revolutionise the treatment landscape for neurological disorders.The nexus between photodynamic therapy and biological drug conjugation is best suited for non-invasive neurological disorder treatment.

Determinants of immunization in polio super high-risk union councils of Pakistan.

BACKGROUND: The current polio epidemiology in Pakistan poses a unique challenge for global eradication as the country is affected by ongoing endemic poliovirus transmission. Across the country, 40 union councils (UCs) which serve as core reservoirs for poliovirus with continuous incidences of polio cases are categorized as super-high-risk union councils (SHRUCs). METHODOLOGY: A cross-sectional survey was conducted in 39 SHRUCs using a two-stage stratified cluster sampling technique. 6,976 children aged 12-23 months were covered. A structured questionnaire was used for data collection. Data were analyzed using STATA version 17. RESULTS: Based on both vaccination records and recall, 48.3% of children were fully-, 35.4 % were partially-, and 16.3% were non-vaccinated in the SHRUC districts. A child is considered fully vaccinated when h/she completed vaccination for BCG, OPV0, OPV 1-3, Penta 1-3, PCV 1-3, IPV, and MCV1. Vaccination cards were seen for over half of the children in the SHRUC districts of Khyber Pakhtunkhwa (KP) and the majority of the SHRUC districts in Sindh, except for the SHRUC district of Malir the districts of Balochistan. Results for polio vacancies show that 60.9% of children from the SHRUC districts were vaccinated with at least three doses of OPV and one dose of IPV, while 20.4% were vaccinated with any OPV doses or IPV and 18.7% of children did not receive any polio vaccines. The dropout rate between vaccine visits was higher than the WHO-recommended cutoff point of 10% for all vaccine doses in the SHRUC districts. The likelihood of being fully vaccinated was higher among the children of educated parents. Full vaccination was found significant among the children of any SHRUC districts compared to district Killa Abdullah. CONCLUSION: Context-specific strategies with more focus on community engagement and targeted mobilization, along with robust monitoring mechanisms, would help address the underlying challenges of under-immunization in the SHRUCs.

Synthesis and characterization of mesoporous bioactive glass nanoparticles loaded with peganum harmala for bone tissue engineering.

Globally, there is an increase in a number of bone disorders including osteoarthritis (OA), osteomyelitis, bone cancer, and etc., which has led to a demand for bone tissue regeneration. In order to take use of the osteogenic potential of natural herbs, mesoporous bioactive glass nanoparticles (MBGNs) have the ability to deliver therapeutically active chemicals locally. MBGNs influence bioactivity and osteointegration of materials making them suitable for bone tissue engineering (BTE). In the present study, we developed Peganum Harmala (P. harmala) loaded MBGNs (PH-MBGNs) synthesized via modified Stöber process. The MBGNs were analyzed in terms of surface morphology, chemical make-up, amorphous nature, chemical interaction, pore size, and surface area before and after loading with P. harmala. A burst release of drug from PH-MBGNs was observed within 8 h immersion in phosphate buffer saline (PBS). PH-MBGNs effectively prevented Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) from spreading. Furthermore, PH-MBGNs developed a hydroxyapatite (HA) layer in the presence of simulated body fluid (SBF) after 21 days, which confirmed the in-vitro bioactivity of MBGNs. In conclusion, PH-MBGNs synthesized in this work are potential candidate for scaffolding or a constituent in the coatings for BTE applications.

Congenital erythropoietic porphyria presenting with recurrent epistaxis: a case report.

BACKGROUND: Congenital erythropoietic porphyria (CEP), also known as pink tooth or Gunther disease, is a rare hereditary disorder caused by an enzyme mutation in the heme biosynthesis pathway, which leads to the accumulation of immature and non-physiological protoporphyrin rings in various tissues. CEP is characterized by sun-exposed bullous skin lesions, hemolytic anemia, red/brown urine, and teeth staining. CASE PRESENTATION: We present a unique case of a 10-year-old Asian boy with CEP who presented with recurrent epistaxis, an unusual presentation for this condition. Based on clinical presentation and laboratory findings, including elevated urine uroporphyrin and coproporphyrin I and III levels, microcytic anemia, a higher red cell distribution width (RDW), and a lower platelet count, a thorough assessment and detailed workup resulted in a diagnosis of CEP. The patient underwent a successful splenectomy and recovered without any complications. CONCLUSION: This case report aims to raise awareness among healthcare professionals about the uncommon and atypical presentation of CEP and its management options.

The Promising Frontier of Cardiometabolic Syndrome: A New Paradigm in Cardiology.

Cardiometabolic syndrome (CMS) is a complex interplay of metabolic dysregulation, cardiovascular disease (CVD), and diabetes risk factors. It encompasses obesity, insulin resistance, dyslipidemia, hyperuricemia, and hypertension, with obesity triggering metabolic disturbances. The global prevalence of CMS, driven by rising obesity rates and sedentary lifestyles, varies across regions. Underlying CMS mechanisms intertwine genetics, sedentary behaviors, poor diets, and hormonal imbalances. Genetic predisposition interacts with environmental factors, while sedentary lifestyles and poor diets amplify obesity and insulin resistance. Hormonal disruptions further complicate the syndrome's development. CMS has far-reaching clinical implications, extending beyond CVD and diabetes to conditions such as non-alcoholic fatty liver disease, cancer, and sleep apnea. Innovative CMS approaches revolve around biomarkers, personalized medicine, lifestyle interventions, and pharmacological breakthroughs. Emerging biomarkers offer early insights, while personalized medicine tailors interventions based on genetic profiles. Lifestyle modifications, encompassing dietary changes and tailored exercise, foster metabolic recalibration. The pharmaceutical frontier targets CMS facets, promising more precise treatments.