Refining Field Cancerization: An Institutional Cohort Analysis of Patient Characteristics in a Validation Cohort.

BACKGROUND: Field cancerization is poorly defined in dermatology. The author group previously proposed and applied a classification system in an original cohort to risk-stratify patients with field cancerization. OBJECTIVE: Apply the authors' classification system within a validation cohort. METHODS: Patients with keratinocyte carcinoma history completed a survey regarding demographic information, medical history, and chemoprevention use. Patients were assigned a field cancerization class, and differences between validation and original cohorts were assessed. RESULTS: A total of 363 patients were enrolled (mean age 67.4; 61.7% male). After comparing validation and original cohorts, there were differences in age between class II (p = .02) and class IVb (p = .047), and differences in chemoprevention use in class III (p = .04). Similar to the original cohort, the validation cohort was associated with increases in total number of skin cancers in the last year (p < .001), 5 years (p < .001), lifetime (p < .001), years since first skin cancer (p < .001), and chemoprevention use (p < .001). In the validation cohort, there were increases in age (p = .03) and immunocompromised status (p = .04) with increasing class, which were not observed in the original cohort. CONCLUSION: Differences among field cancerization classes were similar in a validation cohort, further highlighting the importance of class-specific treatment and management.

An insight into the therapeutic effects of isoliquiritigenin in breast cancer.

Breast cancer ranks as the most widespread malignant condition in women, emerging as a primary contributor to mortality. The primary challenges in cancer treatments involve undesirable side effects. Therefore, exploring natural compounds as additional therapy could provide valuable insights. Isoliquiritigenin (ILN), an isoflavonoid featuring a chalcone moiety primarily sourced from Glycyrrhiza species, has garnered increasing interest in breast cancer research. This review aims to provide a comprehensive understanding of ILN's mechanisms of action in breast cancer, drawing from a range of in vitro and in vivo studies. ILN primarily acts by inhibiting angiogenesis, aromatase, inflammation, and cell proliferation, and preventing invasion and metastasis. Mechanistically, it downregulates miR-374a, phosphoinositide-3-kinase-protein kinase B/Akt, maternal embryonic leucine zipper kinase, vascular endothelial growth factor, and estrogen receptor protein levels, and causes enhancement of Wnt inhibitory factor-1, and Unc-51-like kinase 1 expression to treat breast cancer. ILN emerges as a promising natural option, offering therapeutic advantages with minimal side effects. However, it is important to note that current research on ILN is primarily limited to preclinical models, underscoring the need for further investigation to validate its potential efficacy.

Validation of a novel NGS based BCR::ABL1 kinase domain mutation detection assay in Indian cohort.

The efficacy and treatment outcome of a CML patient are heavily dependent on BCR::ABL1 kinase domain (KD) mutation status. Next-generation sequencing technology is a bright alternative to the previously used sanger sequencing method due to its global presence in diagnostic setups, massive parallel sequencing ability, and far better sensitivity. In the present study, we have demonstrated a new protocol for kinase domain mutation analysis using the next-generation sequencing (NGS) method using the ion torrent sequencing platform. This protocol uses RNA as the starting material, followed by nested PCR to amplify the fusion transcript, which is subsequently used as a template for NGS. Initial validation and comparison of this assay with the sanger sequencing (SS) method yielded 95.23% agreement. CML samples (n = 121) with a failure to TKI response were subjected to this newly developed NGS-based assay to detect KD mutations, from which samples were found to have mutations with a sensitivity ranging from 2.32 to 93.41%. A total of 34.71% of samples (n = 42) were found to be positive for one or more KD mutations, whereas 65.29% of samples (n = 81) were found to be negative. Nine samples out of 42 positive samples, i.e., 21.42%, were found to have compound mutations. This is one of the first studies from India, which includes more than 160 samples and is analyzed by the NGS approach for KD mutation analysis.

Exploring the genetic architecture of powdery mildew resistance in wheat through QTL meta-analysis.

Powdery mildew (PM), caused by Blumeria graminis f. sp. tritici, poses a significant threat to wheat production, necessitating the development of genetically resistant varieties for long-term control. Therefore, exploring genetic architecture of PM in wheat to uncover important genomic regions is an important area of wheat research. In recent years, the utilization of meta-QTL (MQTL) analysis has gained prominence as an essential tool for unraveling the complex genetic architecture underlying complex quantitative traits. The aim of this research was to conduct a QTL meta-analysis to pinpoint the specific genomic regions in wheat responsible for governing PM resistance. This study integrated 222 QTLs from 33 linkage-based studies using a consensus map with 54,672 markers. The analysis revealed 39 MQTLs, refined to 9 high-confidence MQTLs (hcMQTLs) with confidence intervals of 0.49 to 12.94 cM. The MQTLs had an average physical interval of 41.00 Mb, ranging from 0.000048 Mb to 380.71 Mb per MQTL. Importantly, 18 MQTLs co-localized with known resistance genes like Pm2, Pm3, Pm8, Pm21, Pm38, and Pm41. The study identified 256 gene models within hcMQTLs, providing potential targets for marker-assisted breeding and genomic prediction programs to enhance PM resistance. These MQTLs would serve as a foundation for fine mapping, gene isolation, and functional genomics studies, facilitating a deeper understanding of molecular mechanisms. The identification of candidate genes opens up exciting possibilities for the development of PM-resistant wheat varieties after validation.

Husband's involvement in utilization of maternal health services by their spouse in district Rohtak, Haryana.

Introduction: Husband and wife as a couple are fully responsible for their current and future. In our society, the husband is mostly responsible for making the decision regarding any expenses. In India, there is a need to reduce the maternal mortality rate, and Husband's involvement in antenatal care could be a key to success as it will enable them to support their partner in adequate preparation for birth and to utilize emergency obstetric care early if complications arise. Aim and Objectives: To find out about male involvement in the utilization of maternal healthcare services by their spouse and various factors affecting male involvement in the utilization of maternal healthcare services. Methods: This study was conducted in urban and rural field practice areas attached to the Department of Community Medicine, PGIMS, Rohtak. The study included 400 couples where 200 each were recruited from rural and urban areas. Out of 17 subcenters under CHC Chiri eight, subcenters were selected randomly by lottery method. A line list of these couples was prepared at each subcenter using ANC and birth register. Couples were enrolled from this line list till a sample size of 25 was reached at each of these eight subcenters. In this way, a total of 200 couples were enrolled from rural areas in which women delivered and availed maternal health services in the last 6 months. In urban areas, an equal number of couples were enrolled from each of these three urban health posts till the sample size of 200 was reached in an urban area. Results: The majority of the husbands (73%) reported that they participated in their wives' utilization of maternal health services. Twenty-seven percent did not participate in their wives' utilization of maternal health services. It also showed that 71.0% of the husbands did not know about the investigations that needed to be performed during a woman's pregnancy. Only 29% were aware of it. On analysis, it was observed that 73% of the husbands had good participation in their spouses' maternal and child health (MCH) care, while the rest had poor participation (27%). It also showed that as the education level of the participants' husbands increased, their participation in their spouses' MCH care increased, with the highest being observed among graduates (91.3%) and the lowest among those with primary schooling level education (66.7%) which were statistically significant.

Evaluation of the Tolerability of Hedgehog Pathway Inhibitors in the Treatment of Advanced Basal Cell Carcinoma: A Narrative Review of Treatment Strategies.

Hedgehog pathway inhibitors (HHIs) have broadened the treatment options available for patients with advanced basal cell carcinoma (BCC) for whom traditional therapeutic approaches are not feasible or effective. Sonidegib and vismodegib are oral HHIs that were approved for treatment of patients with advanced BCC after demonstrating promising efficacy in the pivotal Phase II BOLT (NCT01327053) and ERIVANCE (NCT00833417) trials, respectively. However, the incidence and types of treatment-emergent adverse events (AEs) observed with these agents may limit continuous use of HHIs and ultimately impact clinical outcomes. In this review, we summarize the safety and tolerability profiles of sonidegib and vismodegib and discuss potential management strategies for HHI class-effect AEs, including muscle spasms, creatine phosphokinase increase, alopecia, and dysgeusia. These AEs primarily occur early in treatment and can lead to treatment discontinuation. Differences in the pharmacokinetic profiles of sonidegib and vismodegib may contribute to the variability noted in times to onset and resolution of these and other AEs. Evidence suggests that protocol modifications, such as treatment interruptions and dose reductions, are effective ways to manage AEs while maintaining disease control. Nonpharmacologic and pharmacologic interventions may also be considered as part of an AE management strategy. Overall, healthcare providers and patients with advanced BCC should be aware of the HHI class-effect AEs and plan effective management strategies to avoid treatment discontinuation and optimize therapeutic response.

Noma in the WHO's list of neglected tropical diseases: A review of its impact on undeveloped and developing tropical regions.

Background: Noma is a neglected tropical disease and a global health concern. Objectives: To elucidate the epidemiology, management, prevention, and public health implications of Noma. Methods: PubMed, Scopus, and Web of Science, supplemented by Google Scholar and World Health Organization databases, were searched using keywords to gather both published and grey literature from 1970 to 2023 in English. Results: Approximately 30,000-40,000 cases occur annually, with varying incidences across various African countries, such as Nigeria, Niger, and Chad. Incidence in Nigerian and Ethiopian states range from 0.6 to 3300 and 1.64 to 13.4 per 100,000 population, respectively. Mortality is approximately 8.5% in Niger. Risk factors include malnutrition, immunocompromised status, poor dental hygiene, inadequate sanitation, gingival lesions, low socioeconomic status, chronic and infectious diseases, low birth weight, high parity, diarrhoea, and fever. Diagnosis is primarily made based on clinical signs/symptoms and accordingly staging of disease is done. Stage I, II and II presents with acute necrotizing gingivitis, facial edema with halitosis, and necrotizing stomatitis, respectively. If the patient survives acute stages, the progress to Stage IV and Stage V manifests as trismus, difficulty in deglutition and phonation, and facial disfigurement, with increased severity in last stage. Treatment encompasses antibiotic therapy (amoxicillin, metronidazole, chlorhexidine, ampicillin, gentamicin), surgical interventions, wound management (honey dressing, ketamine), and nutritional support. Prevention strategies include oral hygiene, vaccination, health education, and community-based interventions. Conclusion: Noma's recent inclusion in WHO list of neglected tropical diseases is a milestone in recognizing the importance of prevention and early intervention to globally enhance health outcomes.

Adequate Levels of Zinc and Copper on Turkey Poult Performance, Immunological Response, and Skeletal Health.

In this study, the impact of varying dietary zinc (Zn) and copper (Cu) levels on the growth, immunological response, and skeletal health of developing turkey poults was investigated. For 0-4 and 5-8 weeks of age, respectively, three Zn levels of 50, 70, and 90 mg/kg and 45, 65, and 85 mg/kg were employed. Three Cu levels, namely 8, 12, and 16 mg/kg for 0-8 weeks of age, were also utilized. There were 288 (9 × 4 × 8) day-old turkey poults with equal body weight that were randomly assigned to 9 treatments, each consisting of 4 replicates and 8 poults per replicate. In comparison to other dietary combinations, there was a significant (P ≤ 0.05) increase in body weight gain observed in the 90 and 85 mg Zn/kg with 16 mg Cu/kg diet during 0-4 and 0-8 weeks of age, respectively, and the 70 and 65 mg Zn with 16 mg Cu /kg diet during 0-4 and 0-8 weeks of age, respectively. When compared to low levels of zinc in the diet at 5-8 and 0-8 weeks of age, respectively, feed conversion ratio was shown to be significantly (P ≤ 0.01) better with 90 and 85 mg Zn/kg diet. In a similar pattern, feed utilization efficiency was considerably (P ≤ 0.01) higher at 16 mg Cu/kg diet than it was at lower Cu levels in the diets given to the animals over the 0-4 week period. Compared to other dietary combinations, there was a substantial (P ≤ 0.01) improvement in cell-mediated immune response (foot web index to PHAP) and humoral immune response (HA titer to SRBC) when 85 mg zinc and 16 mg copper/kg diet was consumed at 0-4 and 5-8 weeks of age. At greater dietary Zn and Cu levels than its lower values, the weight of the spleen and thymus was considerably (P ≤ 0.05) higher. In a dietary combination of 90 mg Zn with 16 mg Cu/kg during 0-4 and 85 mg Zn with 16 mg Cu/kg diet during 5-8 weeks of age, respectively, there were significantly (P ≤ 0.05) greater bone width (proximal and distal), tibia bone ash, calcium, and phosphorus detected respectively. Significantly (P ≤ 0.01) greater Zn and Fe contents were found in the tibia bone at 90 and 85 mg Zn/kg diet, respectively, compared to values obtained at other Zn levels in the diet throughout 0-4 and 5-8 weeks of age. During the first 8 weeks of life, a diet containing 12 mg of copper per kilogram was shown to have a significantly (P ≤ 0.05) increased Zn and Fe content in the tibia bone compared to other levels. It is possible to draw the conclusion from the data that, for growing turkey poults, dietary combinations of 90 mg Zn/kg with 16 mg Cu/kg diet and 85 mg Zn with 16 mg Cu/kg diet between 0 and 4 and 5-8 weeks of age, respectively, were sufficient for optimum development, immunity, and skeletal health indices.