Leprosy in Post-elimination Era: A Study Conducted in Rural Tertiary Settings in North India.

Background Leprosy is an age-old disease caused by Mycobacterium leprae. The disease was declared eradicated in India in 2005. Many new cases are still being identified in the outdoor patient department. This study was undertaken to understand the epidemiological, clinical, and social aspects of leprosy among new patients, and assess the current situation regarding caseload and presentation. Material and methods This study was designed as an observational study. It was carried out in people newly diagnosed with leprosy attending the outpatient department of Dermatology, Venereology, and Leprology in the tertiary care hospital in Uttar Pradesh University of Medical Sciences from July 2022 to January 2024. A total of 231 people afflicted with leprosy were included in the study. The data collected was statistically analyzed to identify demographic and social patterns, clinical presentations, and features associated with leprosy. Result Out of these 231 patients, 139 (60.17%) were male and 92 (39.83%) were female. Most cases belonged to the age group 40-59 years 87 (37.66%). History of close contact with an afflicted person was present in 34 (14.71%). Clinically, most patients belong to the borderline tuberculoid (BT) type. Only 24 (10.4%) patients were found positive for M. leprae by slit-skin smear examination. The ulnar nerve was the most common nerve involved in 63 (27.27%) cases. Trophic ulcers were the predominant deformity in 34 (14.7%), followed by foot drop in 13 (5.62 %). Conclusion The present study provides an overview of the prevailing trends of Leprosy within a specific region in the post-elimination era. The findings underscore the significance of the ongoing National Leprosy Eradication Program (NLEP) program and stress the importance of aligning them with the common goal of eliminating the burden and stigma of Leprosy from society.

HCV Activates Somatic L1 Retrotransposition-A Potential Hepatocarcinogenesis Pathway.

Hepatitis C virus (HCV) is a common cause of hepatocellular carcinoma (HCC). The activation and mutagenic consequences of L1 retrotransposons in virus-associated-HCC have been documented. However, the direct influence of HCV upon L1 elements is unclear, and is the focus of the present study. L1 transcript expression was evaluated in a publicly available liver tissue RNA-seq dataset from patients with chronic HCV hepatitis (CHC), as well as healthy controls. L1 transcript expression was significantly higher in CHC than in controls. L1orf1p (a L1 encoded protein) expression was observed in six out of 11 CHC livers by immunohistochemistry. To evaluate the influence of HCV on retrotransposition efficiency, in vitro engineered-L1 retrotransposition assays were employed in Huh7 cells in the presence and absence of an HCV replicon. An increased retrotransposition rate was observed in the presence of replicating HCV RNA, and persisted in cells after viral clearance due to sofosbuvir (PSI7977) treatment. Increased retrotransposition could be due to dysregulation of the DNA-damage repair response, including homologous recombination, due to HCV infection. Altogether these data suggest that L1 expression can be activated before oncogenic transformation in CHC patients, with HCV-upregulated retrotransposition potentially contributing to HCC genomic instability and a risk of transformation that persists post-viral clearance.

The Effects of Anti-obesity Pharmacotherapy Interventions on Psychosocial Factors Among Adolescents with Obesity: a Scoping Review.

PURPOSE OF REVIEW: The purpose of this review was to investigate and synthesize psychosocial outcomes from pharmacotherapy experimental trials for weight loss among adolescents with obesity. RECENT FINDINGS: There is a paucity of research regarding pharmacological interventions for adolescents with obesity. These studies have typically reported reductions in weight, and side effects have been inconsistently described. Overall, medication seems to be a safe and effective obesity treatment modality for adolescents with obesity. Six articles were included in this review. Studies varied in medication type, medication dosing, lifestyle components, psychosocial measures, measurement intervals, and psychosocial outcomes. All studies found a reduction in weight and/or BMI. Studies were often underpowered to detect differences in psychosocial variables, which were always considered secondary or exploratory outcomes. Future research should include psychosocial outcomes as a primary endpoint of pharmacological interventions for adolescent obesity. Ultimately, the treatment of the complex disease of obesity deserves to be assessed through multiple health domains extending beyond weight reduction.

An Open-Label Prospective Study to Compare the Efficacy and Safety of Topical Fluticasone Versus Tacrolimus in the Proactive Treatment of Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD), a chronic, recurrent inflammatory skin condition primarily affects children. Topical treatment, systemic treatment, and phototherapy are mainstays of treatment. Topical corticosteroids (TCS) are first-line therapy for AD but are associated with various adverse effects. Topical calcineurin inhibitors (TCI) can be used as an alternative to TCS. OBJECTIVE: The aim of the study is to compare the efficacy of topical preparations of fluticasone and tacrolimus in reducing the severity of disease and, to assess the quality of life (QoL), and to estimate if any association exists between severity of disease and QoL. METHODS: Thirty-seven children with AD randomly received one of the 2 topical treatments, with daily application for the first 4 weeks in the acute phase and twice weekly for next 4 weeks in the maintenance phase. The severity of disease was assessed using SCORing Atopic Dermatitis (SCORAD), and QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI). RESULTS: At the end of the acute phase, there was a reduction in SCORAD score of 69.29% in the fluticasone group and 64.2% in the tacrolimus group (P < 0.001). In the maintenance phase, the score had risen in the fluticasone group by a mean difference of 0.81, while in the tacrolimus group it decreased by 0.99. Both fluticasone and tacrolimus groups improved in children's QoL (P < 0.001). Positive correlation (r = 0.4668) exists between SCORAD and QoL. The most common adverse skin reaction noted was skin burning with tacrolimus. CONCLUSIONS: Fluticasone and tacrolimus are equally efficacious in the treatment of AD and have similar benefits with children's QoL. Tacrolimus is better than fluticasone at reducing the extent of lesions.

A Tie2-Notch1 signaling axis regulates regeneration of the endothelial bone marrow niche.

Loss-of-function studies have determined that Notch signaling is essential for hematopoietic and endothelial development. By deleting a single allele of the Notch1 transcriptional activation domain we generated viable, post-natal mice exhibiting hypomorphic Notch signaling. These heterozygous mice, which lack only one copy of the transcriptional activation domain, appear normal and have no endothelial or hematopoietic phenotype, apart from an inherent, cell-autonomous defect in T-cell lineage development. Following chemotherapy, these hypomorphs exhibited severe pancytopenia, weight loss and morbidity. This phenotype was confirmed in an endothelial-specific, loss-of-function Notch1 model system. Ang1, secreted by hematopoietic progenitors after damage, activated endothelial Tie2 signaling, which in turn enhanced expression of Notch ligands and potentiated Notch1 receptor activation. In our heterozygous, hypomorphic model system, the mutant protein that lacks the Notch1 transcriptional activation domain accumulated in endothelial cells and interfered with optimal activity of the wildtype Notch1 transcriptional complex. Failure of the hypomorphic mutant to efficiently drive transcription of key gene targets such as Hes1 and Myc prolonged apoptosis and limited regeneration of the bone marrow niche. Thus, basal Notch1 signaling is sufficient for niche development, but robust Notch activity is required for regeneration of the bone marrow endothelial niche and hematopoietic recovery.

Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia.

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN). RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders (N = 8; 74% and 104% higher geometric mean Cmax and AUC0-28d, respectively) with persistence measurable beyond 2 years in responding patients. Cmax increased with occurrence and severity of cytokine release syndrome (CRS). Tisagenlecleucel continued to expand and persist following tocilizumab, used to manage CRS. Patients with B-cell recovery within 6 months had earlier loss of the transgene compared with patients with sustained clinical response. Clinical responses were seen across the entire dose range evaluated (patients ≤50 kg: 0.2 to 5.0 × 106/kg; patients >50 kg: 0.1 to 2.5 × 108 CAR-positive viable T cells) with no relationship between dose and safety. Neither preexisting nor treatment-induced antimurine CAR19 antibodies affected the persistence or clinical response. CONCLUSIONS: Response to tisagenlecleucel was associated with increased expansion across a wide dose range. These results highlight the importance of cellular kinetics in understanding determinants of response to chimeric antigen receptor T-cell therapy.

Comparative Study of Diagnostic Nasal Endoscopy and CT Paranasal Sinuses in Diagnosing Chronic Rhinosinusitis.

Evaluation of the accuracy of objective diagnostic modalities for chronic rhinosinusitis and their comparison to each other to reach the correct diagnosis with minimum cost and highest accuracy. Prospective diagnostic cohort study. Academic medical center. Subjects more than 10 years of age presenting for evaluation of chronic rhinosinusitis, not responding to 12 weeks of medical treatment, suffering from at least 2 or more of the following symptoms- nasal obstruction, anterior and or posterior nasal discharge, headache or facial pains, and abnormalities of smell were prospectively studied. All selected patients were subjected to nasal endoscopy and CT paranasal sinuses. Endoscopic findings were scored according to Lund Kennedy scoring system. Sinus CT scans were scored with the Lund Mackay scoring system. The clinical diagnosis of CRS was determined on the basis of the published adult sinusitis guideline criteria and nasal endoscopic findings were compared with the diagnostic gold standard CT. A total of 100 patients were studied. Endoscopy was able to diagnose 87 % as CRS based on Lund-Kennedy score ≥2. 93 % patients could be labeled as CRS based on Lund-Mackey score ≥4. On correlating endoscopy and CT PNS it was found that sensitivity was 88.04 %, specificity was 28.57 %, PPV was 94.19 %, NPV was 15.38 %. Positive likelihood ratio of 1.23 and negative likelihood ratio of 0.42 was found p value was found to be 0.10565, thereby confirming that there is no significant difference in diagnosing CRS by either modality. The addition of nasal endoscopy helps reduce the use of CT, reducing costs and radiation exposure.

Full-length trimeric influenza virus hemagglutinin II membrane fusion protein and shorter constructs lacking the fusion peptide or transmembrane domain: Hyperthermostability of the full-length protein and the soluble ectodomain and fusion peptide make significant contributions to fusion of membrane vesicles.

Influenza virus is a class I enveloped virus which is initially endocytosed into a host respiratory epithelial cell. Subsequent reduction of the pH to the 5-6 range triggers a structural change of the viral hemagglutinin II (HA2) protein, fusion of the viral and endosomal membranes, and release of the viral nucleocapsid into the cytoplasm. HA2 contains fusion peptide (FP), soluble ectodomain (SE), transmembrane (TM), and intraviral domains with respective lengths of ∼ 25, ∼ 160, ∼ 25, and ∼ 10 residues. The present work provides a straightforward protocol for producing and purifying mg quantities of full-length HA2 from expression in bacteria. Biophysical and structural comparisons are made between full-length HA2 and shorter constructs including SHA2 ≡ SE, FHA2 ≡ FP+SE, and SHA2-TM ≡ SE+TM constructs. The constructs are helical in detergent at pH 7.4 and the dominant trimer species. The proteins are highly thermostable in decylmaltoside detergent with Tm>90 °C for HA2 with stabilization provided by the SE, FP, and TM domains. The proteins are likely in a trimer-of-hairpins structure, the final protein state during fusion. All constructs induce fusion of negatively-charged vesicles at pH 5.0 with much less fusion at pH 7.4. Attractive protein/vesicle electrostatics play a role in fusion, as the proteins are positively-charged at pH 5.0 and negatively-charged at pH 7.4 and the pH-dependence of fusion is reversed for positively-charged vesicles. Comparison of fusion between constructs supports significant contributions to fusion from the SE and the FP with little effect from the TM.

Hair casts.

Hair casts or pseudonits are circumferential concretions, which cover the hair shaft in such a way that, it could be easily removed. They are thin, cylindrical, and elongated in length. We present an unusual case of an 8-year-old girl presenting with hair casts. Occurrence of these is unusual, and they may have varied associations. This patient was suffering from developmental delay. It is commonly misdiagnosed as and very important to differentiate from pediculosis capitis.

Disparity in the availability of injectable epinephrine in a large, diverse US school district.

BACKGROUND: Food allergies affect 2.5% of the US population. Results of studies show that minorities have the highest prevalence of food allergies. The Houston Independent School District (HISD) has an urban, socioeconomically diverse population and the role of ethnicity and socioeconomic status (SES) with availability of epinephrine has not been explored in this population. OBJECTIVE: This study sought to understand the association of SES and the presence of epinephrine in urban schools. METHODS: A 6-item questionnaire about food allergy characteristics was sent by e-mail to one nurse per elementary school in the HISD to identify the number, characteristics and treatment of food allergic reactions, and the presence of epinephrine injectors. The reactions and presence of injectors were assessed for the previous school year. Schools were categorized by socioeconomic variables as "low" or "non-low" based on National School Lunch Program student participation. Poisson, logistic, and linear regression analyses were used for group comparisons. RESULTS: One or more children with food allergies were reported in 97% of responding schools, but only 43% of schools reported having epinephrine injectors. A larger number of injectors in schools were associated with students of higher SES (r(2) = 0.701; P < .001). There were 6 times more injectors in non-low SES schools than in low SES schools (P < .03). Low SES and limited English proficiency were associated with decreased epinephrine injectors in schools. CONCLUSION: In the HISD, epinephrine injectors were more likely to be found in non-low SES schools versus low SES schools. Because minority students are disproportionately highly represented in low SES schools, there appears to be a disparity in the availability of injectable epinephrine for minority students in HISD schools.

Improvement of teacher food allergy knowledge in socioeconomically diverse schools after educational intervention.

BACKGROUND: Increasingly, teachers are the first respondents to food allergic reactions in schools. Studies of food allergy in school settings have identified deficiencies in teacher recognition and treatment of reactions. We sought to determine the effect of a didactic session on teacher knowledge of the causative foods, symptoms, and treatment of reactions in diverse elementary schools. METHODS: An educational intervention project using a pretest-posttest control group design was performed. Teacher knowledge about food allergy causes, symptoms, and treatment of food allergic reactions was assessed. RESULTS: The average percentage of correctly answered questions by teachers at baseline for each school ranged from 60% to 68%. After education, teachers at the intervention schools answered 24.6% to 34.6% (confidence interval = 21.5-74.1 and 32.1-103.9, respectively) more questions correctly compared with 4.0% to 4.3% (confidence interval = 2.5-21.6 and 0.9-31.0, respectively) in control schools. CONCLUSIONS: Education significantly increased teacher knowledge of food allergy causes, symptoms, and treatment of food allergic reactions in diverse schools.

Stain removal efficacy of a novel dentifrice containing papain and Bromelain extracts--an in vitro study.

OBJECTIVE: To assess the in vitro stain removal efficacy of a novel commercially available dentifrice. MATERIALS AND METHODS: Twenty four human molar teeth (12 in test and 12 in control group) were cut to obtain enamel specimens approximately 9 mm(2) and placed on a microscopic slide using mounting adhesive. They were cycled in human saliva, staining model and dried for brushing regimen using a customized brushing apparatus. Lightness values were recorded at baseline, after staining and after brushing regimen using Adobe Photoshop software. Stain removal efficacy was tested using the either of the two dentifrice slurries for 2 one minute brushing cycles. RESULTS: The mean lightness increment for test and control after brushing regimen was 13.7 ± 6.35 and 3.16 ± 1.29 respectively. There was statistically significant difference in percentage removal of stains for test and control groups (66.99 ± 9.57 and 25.89 ± 16.2 P < 0.001). CONCLUSION: There was significant stain removal with new whitening dentifrice when compared with control. Further clinical trials are recommended to evaluate this significant difference.