Employing a Toxic Aging Coin approach to assess hexavalent chromium (Cr[VI])-induced neurotoxic effects on behavior: Heads for age differences.

We are facing a rapidly growing geriatric population (65+) that will live for multiple decades and are challenged with environmental pollution far exceeding that of previous generations. Consequently, we currently have a poor understanding of how environmental pollution will impact geriatric health distinctly from younger populations. Few toxicology studies have considered age differences with geriatric individuals. Critically, all top ten most prevalent age-related diseases are linked to metal exposures. Hexavalent chromium [Cr(VI)] is a metal of major environmental health concern that can induce aging phenotypes and neurotoxicity. However, there are many knowledge gaps for Cr(VI) neurotoxicity, including how Cr(VI) impacts behavior. To address this, we exposed male rats across three ages (3-, 7-, and 18-months old) to Cr(VI) in drinking water (0, 0.05, 0.1 mg/L) for 90 days. These levels reflect the maximum contaminant levels determined by the World Health Organization (WHO) and the U.S. Environmental Protection Agency (US EPA). Here, we report how these Cr(VI) drinking water levels impacted rat behaviors using a battery of behavior tests, including grip strength, open field assay, elevated plus maze, Y-maze, and 3-chamber assay. We observed adult rats were the most affected age group and memory assays (spatial and social) exhibited the most significant effects. Critically, the significant effects were surprising as rats should be particularly resistant to these Cr(VI) drinking water levels due to the adjustments applied in risk assessment from rodent studies to human safety, and because rats endogenously synthesize vitamin C in their livers (vitamin C is a primary reducer of Cr[VI] to Cr[III]). Our results emphasize the need to broaden the scope of toxicology research to consider multiple life stages and suggest the current regulations for Cr(VI) in drinking water need to be revisited.

Emerging green synthetic routes for thiazole and its derivatives: Current perspectives.

This review article provides an overview of the green synthesis of thiazole derivatives, emphasizing sustainable and environmentally friendly methodologies. Thiazole derivatives possess significant value and find diverse applications across various fields. However, conventional synthesis methods often involve hazardous reagents and generate substantial waste, posing environmental concerns. The green synthesis of thiazole derivatives employs renewable starting materials, nontoxic catalysts, and mild reaction conditions to minimize environmental impact. Innovative techniques such as microwave irradiation, ultrasound synthesis, green solvents, a green catalyst-based approach, and mechanochemistry-mediated synthesis are employed, offering advantages in terms of scalability, cost-effectiveness, and purification simplicity. The resulting thiazole derivatives exhibit comparable or enhanced biological activities, showcasing the feasibility and practicality of green synthesis in drug discovery. This review paper underscores the importance of sustainable approaches in functional molecular synthesis and encourages further research in this domain.

Postoperative Evaluation and Management of Portomesenteric Venous Thrombosis in Patients With IBD.

CASE SUMMARY: A 22-year-old woman with medically refractory ulcerative pancolitis underwent laparoscopic total proctocolectomy with IPAA and diverting ileostomy. She was discharged on postoperative day 4 feeling well. Because of the lack of risk factors for venous thromboembolism (including no family history or use of oral contraceptives), she was not discharged with prophylactic low-molecular-weight heparin, but she received low-molecular-weight heparin while in the hospital. The following day, she developed abdominal pain, nausea/vomiting, and decreased ostomy output. An abdominopelvic CT scan demonstrated a small amount of intraperitoneal free air felt to be postoperative in nature, small-bowel dilation consistent with ileus, and extensive portal and superior mesenteric vein thrombosis. She was started on low-molecular-weight heparin that resulted in rapid improvement. A subsequent repeat CT scan a few days later showed decreased clot burden.

Adalimumab-Adbm: The First Interchangeable Biosimilar for the Treatment of Inflammatory Diseases.

OBJECTIVE: The objective of the study was to review the pharmacologic and clinical profile of adalimumab-adbm (BI 695501), the first interchangeable biosimilar for treatment of inflammatory diseases. DATA SOURCES: A PubMed search was conducted from inception to December 2021 using the keywords BI 695501 and adalimumab-adbm. Information was also obtained from published abstracts and package inserts. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2 and 3 studies plus relevant literature on adalimumab-adbm pharmacologic and clinical profile were reviewed. DATA SYNTHESIS: Adalimumab-adbm approval was based on a series of phase 3 VOLTAIRE trials, which evaluated the biosimilar's efficacy and safety in the treatment of moderate to severe Crohn's disease, rheumatoid arthritis, and psoriasis. Interchangeability status was granted based on data from the VOLTAIRE-X trial. The VOLTAIRE and VOLTAIRE-X studies demonstrated comparable efficacy and safety between adalimumab-adbm and reference adalimumab. Common adverse events included infections and injection site reactions. Similar to reference adalimumab, adalimumab-adbm contains black box warnings related to serious infections and malignancy. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Adalimumab-adbm is the first interchangeable biosimilar to be approved for inflammatory diseases and has the potential to improve patient access to treatment while decreasing medication-related costs. However, it will not be commercially available for patient use until 2023 and its adoption into clinical practice may face potential barriers seen with other biosimilars. CONCLUSION: As an interchangeable biosimilar with comparable efficacy and safety to reference adalimumab, adalimumab-adbm is an important advance toward cost-effective management of inflammatory diseases.

Analyzing color imaging failure on consumer-grade cameras.

There are many efforts to employ consumer-grade cameras for home-based health and wellness monitoring. Such applications rely on users to capture images for analysis using their personal cameras in a home environment. When color is a primary feature for diagnostic algorithms, the camera requires calibration to ensure accurate color measurements. Given the importance of these diagnostic tests for the users' health and well-being, it is important to understand the conditions in which color calibration may fail. To this end, we analyzed a wide range of camera sensors and environmental lighting to determine (1) how often color calibration failure is likely to occur and (2) the underlying reasons for failure. Our analysis shows that it is rare to encounter a camera sensor and lighting condition combination that results in color imaging failure. Moreover, when color imaging does fail, the cause is almost always attributed to spectral poor environmental lighting and not the camera sensor. We believe this finding is useful for scientists and engineers developing color-based applications for use with consumer-grade cameras.

Trade-offs with stability modulate innate and mutationally acquired drug resistance in bacterial dihydrofolate reductase enzymes.

Structural stability is a major constraint on the evolution of protein sequences. However, under strong directional selection, mutations that confer novel phenotypes but compromise structural stability of proteins may be permissible. During the evolution of antibiotic resistance, mutations that confer drug resistance often have pleiotropic effects on the structure and function of antibiotic-target proteins, usually essential metabolic enzymes. In the present study, we show that trimethoprim (TMP)-resistant alleles of dihydrofolate reductase from Escherichia coli (EcDHFR) harboring the Trp30Gly, Trp30Arg or Trp30Cys mutations are significantly less stable than the wild-type, making them prone to aggregation and proteolysis. This destabilization is associated with a lower expression level, resulting in a fitness cost and negative epistasis with other TMP-resistant mutations in EcDHFR. Using structure-based mutational analysis, we show that perturbation of critical stabilizing hydrophobic interactions in wild-type EcDHFR enzyme explains the phenotypes of Trp30 mutants. Surprisingly, though crucial for the stability of EcDHFR, significant sequence variation is found at this site among bacterial dihydrofolate reductases (DHFRs). Mutational and computational analyses in EcDHFR and in DHFR enzymes from Staphylococcus aureus and Mycobacterium tuberculosis demonstrate that natural variation at this site and its interacting hydrophobic residues modulates TMP resistance in other bacterial DHFRs as well, and may explain the different susceptibilities of bacterial pathogens to TMP. Our study demonstrates that trade-offs between structural stability and function can influence innate drug resistance as well as the potential for mutationally acquired drug resistance of an enzyme.

Neck circumference as a predictor of all-cause mortality in middle-aged and older adults in rural Ecuador.

BACKGROUND: Neck circumference (NC) has been associated with mortality secondary to cardiovascular diseases and other conditions. However, information on this association in the population at large is limited. We aimed to assess this association in community dwellers living in rural Ecuador. METHODS: Individuals aged ≥40 y who were enrolled in the population-based Three Villages Study cohort were prospectively followed to estimate mortality risk according to baseline measurements of NC, after adjusting for relevant confounders. RESULTS: Analysis included 1521 individuals followed for a mean of 6.4±3.4 y. Mean NC was 36.2±3.7 cm, with 509 (33%) individuals allocated to the first (25-34 cm), 319 (21%) to the second (36-37 cm), 417 (27%) to the third (37-39 cm) and 276 (18%) to the fourth (40-50 cm) quartile. A total of 211 (14%) individuals died during the follow-up. Overall, the crude mortality rate was 2.3 per 100 person-years, which increased to 5.63 for those in the fourth NC quartile. An adjusted Cox-proportional hazards model showed that individuals in the fourth quartile of NC had higher mortality risk compared with the first quartile (HR: 2.98; 95% CI 1.77 to 5.02). CONCLUSION: Larger NC increases mortality risk in middle-aged and older adults of indigenous ancestry living in rural Ecuador.

A sodium ion conducting gel polymer electrolyte with counterbalance between 1-ethyl-3-methylimidazolium tetrafluoroborate and tetra ethylene glycol dimethyl ether for electrochemical applications.

For sodium batteries, the development of gel polymer electrolytes (GPEs) with remarkable electrochemical properties is in its early stage and persists to be a challenge. In this report we have synthesized a series of GPEs containing a poly(vinyllidene fluoride-co-hexafluoropropylene) (PVdF-HFP) and poly (methyl methacrylate) (PMMA) as blend polymer, sodium perchlorate (NaClO4) as ion-conducting salt and 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF4) and tetra ethylene glycol dimethyl ether (TEGDME) as molecular solvents. The counter balance between EMIM-BF4 and TEGDME is maintained by the electrolyte, which is formed through the optimal weight ratio of 2 : 1. GPEs have an advantageous set of properties, including stability window of 5 V, Na+ transference number of 0.20, and a room-temperature ionic conductivity of 5.8 × 10-3 S cm-1. According to enthalpy and entropy calculations, optimized GPE yields the highest amount of disorder or amorphicity and contributes to greatest conductivity. XRD analysis supports this argument. Thermal investigations show that optimized GPE may preserve gel phase up to 125 °C. The prototype sodium cell fabricated with optimize GPE has a specific capacity of 281 mA h g-1 and open circuit voltage of 2.5 V. The optimized GPE exhibits potential for future electrochemical applications.

Cognitive performance and all-cause mortality in community dwellers of Amerindian ancestry living in rural Ecuador: A population-based, longitudinal prospective study.

OBJECTIVE: There is limited information on mortality risk in individuals with cognitive impairment living in rural Latin America. In this study, we assess the association between cognitive impairment and all-cause mortality in adults of Amerindian ancestry living in rural Ecuador. PATIENTS AND METHODS: Middle-aged and older adults enrolled in the population-based Three Villages Study cohort were followed prospectively in order to estimate mortality risk according to their baseline cognitive performance as determined by the Montreal Cognitive Assessment (MoCA). Results were adjusted for demographics, level of education, traditional cardiovascular risk factors, symptoms of depression, severe tooth loss, and oily fish intake (factors previously associated with mortality in the study population). RESULTS: Analysis included 1022 individuals followed for an average of 7.8 ± 3.4 years. Mean MoCA score was 21.2 ± 5.4 points (median: 22 points), with 334 (32.7%) individuals showing cognitive impairment, as evidenced by a MoCA score ≤ 19 points (the cutoff for poor cognitive performance based on previous studies in the same population). A total of 150 (14.7%) individuals died during the follow-up. Crude mortality rate was 2.87 per 100 person-years (95% C.I.: 2.08 - 3.96). For individuals with normal cognition, the mortality rate was 1.21 (95% C.I.: 0.92 - 1.50) while for those with cognitive impairment the rate increased to 3.48 (95% C.I.: 2.73 - 4.23). A multivariate Cox-proportional hazards model, confirmed that individuals with cognitive impairment had a significantly higher mortality risk than those without cognitive impairment (HR: 1.52; 95% C.I.: 1.05 - 2.18). CONCLUSIONS: Cognitive impairment is associated with mortality in the study population.

Early onset of nasopharyngeal cancer in Asian/Pacific Islander Americans revealed by age-specific analysis.

PURPOSE: Incidence of nasopharyngeal cancer is substantially higher in Asian/Pacific Islanders (APIs) than other racial groups. Examining age-specific incidence patterns by racial group and histology could inform disease etiology. METHODS: We analyzed data from 2000 through 2019 from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program to compare age-specific incidence rates of nasopharyngeal cancer in non-Hispanic (NH) Blacks, NH APIs, and Hispanics to NH Whites using incidence rate ratios with 95% confidence intervals (CIs). RESULTS: NH APIs showed the highest incidence of nasopharyngeal cancer across all histologic subtypes and almost all age groups. The racial differences were most pronounced in the age 30-39 group; relative to NH Whites, NH APIs were 15.24 (95% CI: 11.69-20.05), 17.26 (95% CI: 12.56-24.07), and 8.91 (95% CI: 6.79-11.48) times as likely to have differentiated non-keratinizing, undifferentiated non-keratinizing, and keratinizing squamous cell tumors, respectively. CONCLUSIONS: These findings suggest an earlier onset of nasopharyngeal cancer among NH APIs, which highlight unique early life exposure to critical nasopharyngeal cancer risk factors as well as genetic predisposition in this high-risk population.

Assessing and Addressing the Determinants of Appalachian Population Health: A Scoping Review.

Introduction: Residents of Appalachia experience elevated rates of morbidity and mortality compared to national averages, and these disparities are associated with inequitable exposures to various determinants of population health. Social and environmental determinants of health are a useful lens through which to develop and evaluate programs to mitigate regional health disparities. Methods: This 2023 scoping review was conducted of studies linking determinants of Appalachian health with leading causes of regional mortality and morbidity. The search strategy employed a keyword search that included geographic terms for the Appalachian Region and the primary adverse health outcomes in that region. Studies meeting the following inclusion criteria were reviewed: original article, published in the last five years, involving an Appalachian population, and includes a rigorous assessment of an association between a population health determinant and one or more leading causes of Appalachian morbidity and mortality. Results: The search returned 221 research articles, including 30 interventional studies. The top three health outcomes included cancer (43.59%), diseases of despair (23.08%), and diabetes (12.82). Access to care (27.3%), rurality (18.9%), and education (14.8%) were the most common population health determinants identified. Interventional studies were categorized by program types: education, technology, partnerships, and multilevel interventions. Due to the heterogeneity of study types, the studies were combined using a narrative synthesis. Implications: The results of this work can inform the development and evaluation of additional programs to promote Appalachian population health. Our study team will use these results to inform community-based discussions that develop strategic plans to mitigate health disparities in Central and Southcentral Appalachian Virginia.

Persistent Diarrhea and Eosinophilic Esophagitis Resulting From Chronic Cannabidiol Usage for Refractory Epilepsy.

Cannabidiol is used in the care of treatment-resistant epilepsy. It has been associated with varying side effects, ranging from somnolence to diarrhea and weight loss. We present a patient on chronic cannabidiol therapy who had persistent diarrhea, abdominal pain, weight loss, and esophageal eosinophilia that improved with cannabidiol dose adjustment.

Diagnostic Value of Dynamic High-frequency Ultrasound for the Slipping Rib and Twelfth Rib Syndrome: A Case Series with Review.

BACKGROUND: High-frequency ultrasound (HFUS) is a mobile, radiation-free imaging tool for the diagnosis of musculoskeletal disorders. We aim to demonstrate the diagnostic value of dynamic HFUS for undiagnosed lower chest, upper abdomen, and loin pain with this case series. CASE SERIES: A cricketer presented with long-standing left-sided dull ache lower chest and upper abdominal pain, aggravated on exertion and leaning forward. His previous laboratory and previous imaging tests were unrevealing. Dynamic HFUS of his left ribs during hooking maneuver demonstrated slipping of the eighth rib over the seventh rib associated with clicking. He also reported tenderness over this region. He was diagnosed with slipping rib syndrome (SRS), and was treated with the eighth nerve block under the HFUS guidance. The second and third cases presented with chronic undiagnosed waxing and waning loin pain despite extensive laboratory and radiological workup. Both patients demonstrated twelfth rib HFUS probe tenderness in a sitting position with a specific movement that reproduced the pain during the dynamic HFUS study. The diagnosis of twelfth rib syndrome (TRS) was confirmed and treated successfully with a local intercostal nerve block. REVIEW OF THE LITERATURE: HFUS is the most underutilized imaging tool for the diagnosis of unexplained upper abdominal and lower chest pain syndromes. We identified only a few such reported cases managed with the help of HFUS. CONCLUSION: The dynamic HFUS is a valuable imaging modality for the undiagnosed lower chest, upper abdominal, or loin pain.

Adrenocortical Crisis Triggered by Levothyroxine in an Unrecognized Autoimmune Polyglandular Syndrome Type-2: A Case Report with Review of the Literature.

BACKGROUND: Autoimmune polyglandular syndrometype-2 (APS-2) is an uncommon endocrine disorder of Addison's disease with an autoimmune thyroid disorder and/or type 1 diabetes mellitus. The diagnosis is more challenging when a patient presents with nonspecific neuropsychiatric features with hypothyroidism in the setting of unrecognized Addison's disease. CASE REPORT: We report a case of subclinical autoimmune hypothyroidism presented with nonspecific neuropsychiatric symptoms precipitated by stress. Despite levothyroxine treatment, her symptoms deteriorated and she was admitted with persistent vomiting and hypovolemic shock. Clinical features and laboratory parameters were suggestive of underlying adrenocortical insufficiency. Preexisting autoimmune hypothyroidism combined with Addison's disease confirmed the diagnosis of unrecognized APS-2. She remarkably improved and her thyroid function tests also normalized with the treatment of corticosteroids only. REVIEW OF THE LITERATURE: We identified only five published case reports of our title by searching the database. Neufeld and Betterle have reported their data of APS-2 and concluded that a full- blown clinical picture of two or more components of the syndrome is like the tip of the iceberg. CONCLUSION: The patients of one major component of APS-2 should be screened for other components of the disease to pick up latent cases. Addison's disease should be ruled out in patients of hypothyroidism who are intolerant to levothyroxine.

Negative Impact of Vestibular Suppressant Drugs on Provocative Positional Tests of BPPV: A Study from the Western Part of India.

AIMS: To study the impact of vestibular suppressant drugs (VSD) on provocative positional tests (PPT) in patients with benign paroxysmal positional vertigo (BPPV). SETTINGS AND DESIGN: A prospective case-control observational study. MATERIALS AND METHODS: Patients with a history suggestive of BPPV were tested for PPT. Patients with vertiginous symptoms and with nystagmus on PPT were classified as objective BPPV (O-BPPV, control group), while those without nystagmus with no alternate diagnosis were classified as subjective BPPV (S-BPPV, case group). Details of VSD treatment were noted in all the patients. In both groups, patients were instructed to discontinue VSD and were further assigned as the VSD and non-VSD subgroups. Patients were followed for 2 months with PPT every week. PPT positive patients were treated by vestibular rehabilitation maneuvers. STATISTICS: Student t-test with two-tailed, unpaired, was used for continuous scale and Chi-square test for categorical differences between the two groups. RESULTS: 295 consecutive BPPV patients were enrolled in the study, 55 in the S-BPPV group and 240 in the O-BPPV group. Significantly higher proportion of patients in the S-BPPV group were on VSD at presentation, 80.00% vs. 53.75% (OR 2.52; 95% CI: 1.30-4.86), P = 0.006. In an unadjusted analysis of the S-BPPV group following discontinuation of VSD, PPT became positive in 79.54% of patients as compared to 18.19% in the non-VSD group (OR 35.0; 95% CI: 6.2-197.3), P < 0.001. CONCLUSION: A higher proportion of S-BPPV patients were receiving VSD in comparison to O-BPPV at the initial visit. The PPT converted positive four times higher after ceasing the VSD in S-BPPV patients. STUDY DESIGN: Prospective case-control observational study.

Association between socioeconomic status and influenza-like illness: A study from Western part of India.

OBJECTIVES: Health status is associated with socioeconomic status (SES) of the individuals. The aim of this study was to identify any link between the SES and influenza-like illness (ILI). MATERIALS AND METHODS: This observational case-control study was done on 18-70 years old patients presented with ILI (cases) at tertiary care hospital of western India. Controls were selected from demographically matched elective surgery patients except the SES. SES was evaluated as per the Modified B G Prasad 2017 scale and participants were further classified in lower SES (per capita income <2000 INR) and non-lower SES groups. RESULTS: 810 cases and 830 controls were compared. Many cases were from lower SES, had poor hand hygiene, and were using soil, mud, ash (SMA) for hand cleaning as compared to the control. Among the cases significant numbers were from lower SES (543/810[67%], P < 0.02), many were alcoholics, smokers, had poor hand hygiene, were using SMA for hand cleaning, and had preexisting chronic obstructive pulmonary disease (COPD), while few were having diabetes in the lower SES group as compared to the non-lower SES group. ILI was more common among lower SES class in unadjusted analysis (odds ratio [OR] 1.58, 95% CI 0.89-2.76) and the results were significant even after the adjustment of covariates (OR 1.62, 95% CI, 0.94-2.85). CONCLUSION: Lower SES people were 2.8 times more prone to ILI as compared to the age- and sex-matched control in western part of India.

Non-uremic Calciphylaxis: A Rare and Late Adverse Reaction of Warfarin.

BACKGROUND: Calciphylaxis is a complex dermatological lesion of micro vascular calcification that is typically presented as panniculitis with gangrenous painful lesions having uremic and non-uremic causes. CASE REPORT: We present a case of a 48-year old male with a history of paroxysmal atrial fibrillation and hypertension taking amlodipine 5 mg and warfarin 5 mg daily for the last 26 months. The patient had a 6- months history of painful swelling followed by necrotic skin ulcer over the right leg. His remarkable examination findings were right leg tender ulcer with surrounding erythema and secondary sepsis. His hemogram, metabolic profile and connective tissue diseases work up were unremarkable except leucocytosis and raised inflammatory markers. His local part radiological and skin biopsy findings were suggestive of calciphylaxis. RESULTS AND CONCLUSION: In our case, warfarin and amlodipine were culprit drugs for the lesion, but Naranjo score (warfarin 7and amlodipine 1) speculate warfarin as a probable adverse reaction of warfarin. The lesion was cured with local wound treatment after discontinuation of warfarin. The physician should be aware of this rare cutaneous disorder of systemic origin for proper management.

Medicated adhesive dressing is a safe and non-inferior cutaneous seal as compared to compound tincture benzoin dermal seal for percutaneous interventions.

BACKGROUND: Compound tincture benzoin (CTB) is used as a post-procedure skin seal antiseptic agent since ancient times; but this drug is reported to cause allergic contact dermatitis and other unwanted side effects. Our aim of the present study was to compare alternative agent like Medicated Adhesive dressing (MAD) with CTB as a post-procedure skin seal dressing. DESIGN: This prospective randomized controlled experimental study included an equal number of patients in MAD and CTB as a post-operative seal dressing material for percutaneous interventions. Both the groups were graded for various efficacy parameters like comfort, applicability, dressing material, and immediate post-operative complications by operating doctor and attending nurse with a maximum 10 points in each group. RESULTS: 120 patients were studied in each MAD and CTB group. Out of total patients 31.25% were males and the mean age of the patient was 33.56 ± 11.10. Allergic contact dermatitis developed in 9 (7.49%) of CTB group and in 1 (0.83%) of MAD group (P < 0.002), while local site skin infections were noted in 8 (6.67%) of CTB group and in 1 (0.83%) of MAD (P < 0.002). Operating doctor graded MAD and CTB to 7.60 ± 0.49 and 3.62 ± 0.48 (P < 0.003); and attending nurse 7.40 ± 0.49 and 3.41 ± 0.49 (P < 0.003) respectively. CONCLUSION: MAD is a safe, efficient and non-inferior alternative dressing material for post-procedure skin incision seal in comparison to CTB.