Nevin Manimala

J Med Toxicol. 2023 Aug 28. doi: 10.1007/s13181-023-00965-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Medical toxicology is a small but growing specialty. To ensure that the specialty continues to grow and attract strong candidates, it is important to understand what influences physicians to pursue medical toxicology training. This would allow for targeted interventions to recruit strong candidates to the field.

METHODS: A cross-sectional survey was sent via email to current medical toxicology fellows and to medical toxicologists who completed fellowship in the last 5 years. ACMT listservs were utilized to target recipients. The survey was created through an iterative writing process among the study authors. Responses to the survey were recorded in REDCap. Descriptive statistics were obtained and analyzed.

RESULTS: A total of 126 participants responded to the survey request (46 fellows and 80 recent graduates). Most were primarily trained in emergency medicine. Interest in medical toxicology usually started during residency when exposure to the field was highest. Most respondents cite a mentor as a primary influence in pursuing medical toxicology training.

CONCLUSIONS: Among current fellows and recent graduates of medical toxicology, having a mentor in the field of medical toxicology, having exposure to medical toxicology during residency, and participating in a clinical rotation in medical toxicology were common shared experiences that led to the decision to subspecialize in the field. These results may guide targeted intervention to continue to recruit strong candidates to medical toxicology.

PMID:37639079 | DOI:10.1007/s13181-023-00965-z

AAPS PharmSciTech. 2023 Aug 28;24(7):177. doi: 10.1208/s12249-023-02632-6.

ABSTRACT

Antimicrobial peptides have appeared to be promising candidates for therapeutic purposes due to their broad antimicrobial activity and non-toxicity. Histatin-5 (Hst-5) is a notable salivary antimicrobial peptide that exhibited therapeutic properties in the oral cavity. Oral mucositis is an acute inflammation of the oral cavity, following cancer therapy. The current treatment methods of oral mucositis have low effectiveness. The aim of this study was to design, formulate and characterize a mucoadhesive gel delivery system for Hst-5 usage in the treatment of oral mucositis. Carbopol 934 and hydroxypropyl methylcellulose (HPMC) have been used in the development of a Hst-5 mucoadhesive gel that was optimized by using Box-Behnken design. The optimized formulation was evaluated in-vitro, based on mucoadhesive strength, viscoelasticity, spreadability, release rate, peptide secondary structure analysis, antimicrobial activity, and storage stability. The efficacy of Hst-5 gel was assessed in vivo in a chemotherapy-induced mucositis model. The results showed a sustained release of Hst-5 from the new formulation. Hst-5 gel exerted antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The histopathological, immunohistochemical and statistical analysis showed that the Hst-5 gel had wound healing activity in vivo. The findings of this study indicate that the mentioned compound possesses promising potential as a novel and efficient therapeutic agent in managing oral mucositis. Moreover, the results suggest that the compound is commercially feasible for further development and utilization.

PMID:37639072 | DOI:10.1208/s12249-023-02632-6

Lasers Med Sci. 2023 Aug 28;38(1):195. doi: 10.1007/s10103-023-03851-w.

ABSTRACT

Fractional carbon dioxide (CO₂) laser combined with subcision has been widely used for the clinical treatment, but the efficacy of the combined therapy on three types of atrophic acne scars remains unreported. This retrospective study analyzed the clinical data of 413 patients with atrophic acne scars, treated with fractional CO₂ laser combined with subcision in the combined group and with fractional CO₂ laser in the control group. The treatment efficacy was evaluated by the Investigator’s Global Assessment (IGA) and the Échelle d’évaluation clinique des cicatrices d’acné (ECCA). We reported adverse reactions such as erythema, lump, skin sensitivity, acne recurrence, and hyperpigmentation that occurred in both treatment groups. The treatment efficiency of the combined group was significantly higher than that of the control group (P < 0.001). Among the three subtypes of atrophic acne scars, the ECCA scores in the combined group of boxcar-type and rolling-type scars after treatment were lower than those in the control group (P = 0.041, P < 0.001, respectively), and no statistical difference in scores between the two groups for icepick-type scars was seen (P = 0.062). There was no statistical difference in adverse reactions between the two groups (P = 0.361). Fractional CO₂ laser combined with subcision is more effective than fractional CO₂ laser in the treatment of boxcar-type and rolling-type scars, but there is no significant difference in the treatment of icepick-type scars.

PMID:37639055 | DOI:10.1007/s10103-023-03851-w

Neurol Sci. 2023 Aug 28. doi: 10.1007/s10072-023-07038-7. Online ahead of print.

ABSTRACT

PURPOSE: The relationship between varicella zoster virus (VZV) infection and the risk of dementia has not been previously studied specifically. Therefore, this study sought to determine the relationship between studying VZV infection and dementia occurring in the general population by conducting an extensive meta-analysis of published cases.

METHOD: A systematic literature search was conducted in seven online databases by October 31, 2022. Heterogeneity was tested by the I² index. Pooled HR and 95% CI were used to estimate the effect of VZV infection on dementia. Sensitivity analyses and publication bias were also performed.

RESULT: Nine studies involving 3,326,673 subjects were included. VZV infection was associated with an increased risk of dementia (HR = 1.11, 95% CI: 1.02-1.21). The risk of dementia was reduced in those who received antiviral therapy compared to those who did not (HR = 0.84, 95% CI: 0.71-0.99). In addition, VZV infection was found to be associated with an increased risk of developing dementia in the pooled results of the moderate quality study (HR = 1.81,95% CI: 1.27-2.59), and this association persisted when subgroup analyses were performed based on region (Asia: HR = 1.18,95% CI: 1.04-1.33).

CONCLUSIONS: Our results suggest that VZV infection might increase the risk of developing dementia, but there is no clear mechanism about the true relationship, and since there is no effective treatment for dementia, and our results suggest that some populations can benefit from antiviral therapy, it is at least arguable that patients who develop VZV infection should be treated with appropriate antiviral medications.

PMID:37639023 | DOI:10.1007/s10072-023-07038-7

Eur J Pediatr. 2023 Aug 28. doi: 10.1007/s00431-023-05169-9. Online ahead of print.

ABSTRACT

This is the first meta-analysis of the available literature about the efficacy of metformin exclusively in pediatric patients with non-alcoholic fatty liver disease (NAFLD). We conducted a systematic literature search through major electronic databases till March 12, 2023, investigating the efficacy and safety of metformin in pediatric NAFLD. Weighted mean difference (WD) and standard deviation (SD) were used for continuous outcomes. In total, 4 randomized controlled trials (RCTs) with 309 pediatric patients with NAFLD were included in the meta-analysis. Metformin could not reach a statistically significant improvement in alanine aminotransferase (ALT) levels [(ALT: WMD = – 1.55 IU/L, 95% CI: – 5.38 to 2.28, I² = 16%, p = 0.43), but had a statistically significant impact (p < 0.05) in insulin and HOMA-IR regulation, triglycerides, and high-density lipoprotein level improvement. Conclusion: According to the data of this meta-analysis, treatment with metformin failed to statistically improve liver enzymes but may be beneficial in the improvement of lipid parameters and insulin metabolism regulation in pediatric patients with NAFLD. As there are not enough available studies in the literature, the influence of metformin on liver ultrasonography or histology in pediatric NAFLD should be further analyzed in future studies. What is Known: • Lifestyle modification with weight loss through physical activity and dietary modification is the recommended treatment option for pediatric NAFLD. • Metformin may reduce steatosis on ultrasound and may have a beneficial role in liver histology collated with insulin resistance improvement. What is New: • Metformin may improve insulin sensitivity and lipid parameters in children with obesity and NAFLD. • Metformin does not have a significant effect on transaminase levels in children with obesity and NAFLD.

PMID:37639015 | DOI:10.1007/s00431-023-05169-9

J Cancer Res Clin Oncol. 2023 Aug 28. doi: 10.1007/s00432-023-05318-5. Online ahead of print.

ABSTRACT

PURPOSE: The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome.

METHODS: Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant.

RESULTS: We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021).

CONCLUSIONS: Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC.

PMID:37639007 | DOI:10.1007/s00432-023-05318-5

Genet Med. 2023 Aug 24:100967. doi: 10.1016/j.gim.2023.100967. Online ahead of print.

ABSTRACT

PURPOSE: The genetic etiology of amyotrophic lateral sclerosis (ALS) includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both.

METHODS: 335 ALS cases and 356 controls from Québec, Canada were concurrently tested by SNP-chip genotyping and targeted sequencing of ALS genes known at the time of study inception. ALS GWAS summary statistics were used to estimate an ALS polygenic risk score (PRS). Cases and controls were subdivided into rare variant heterozygotes and non-heterozygotes.

RESULTS: Risk for ALS was significantly associated with PRS and rare variants independently in a logistic regression model. While ALS PRS predicted a small amount of ALS risk overall, the effect was most pronounced between ALS cases and controls that were not heterozygous for a rare variant in the ALS genes surveyed.

CONCLUSION: Both PRS and rare variants in ALS genes impact risk for ALS. PRS for ALS is most informative when rare variants are not observed in ALS genes.

PMID:37638500 | DOI:10.1016/j.gim.2023.100967

Brain Behav. 2023 Aug 28:e3239. doi: 10.1002/brb3.3239. Online ahead of print.

ABSTRACT

BACKGROUND: Observational studies have suggested an association between coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG). Here, we aimed to estimate the genetic correlation and causal relationship between COVID-19 susceptibility, hospitalization, severity, and MG phenotypes using linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) approach.

METHODS: Summary statistics of COVID-19 susceptibility, hospitalization, and severity were used as instrumental variables for exposure traits. Large-scale genome-wide association study (GWAS) data for MG were used as outcome traits. The inverse variance weighted approach was used for the main MR analysis, complemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analysis was implemented using Cochran’s Q test, MR-PRESSO method, and MR-Egger intercept test.

RESULTS: LDSC analysis did not reveal any genetic correlation among COVID-19 susceptibility, hospitalization, severity, and MG phenotypes, including MG, early-onset MG, and late-onset MG (p > .05). Our MR analysis did not provide evidence supporting a causal effect of COVID-19 susceptibility, hospitalization, or severity on MG phenotypes (p > .05). Extensive sensitivity analysis strengthened the robustness and consistency of the MR estimates.

CONCLUSION: Our study did not find evidence of a genetic correlation or causal relationship among COVID-19 susceptibility, hospitalization, severity, and MG. Future studies with more GWAS data are needed to evaluate the association between COVID-19 phenotypes and MG and its subgroups.

PMID:37638499 | DOI:10.1002/brb3.3239

J Sci Food Agric. 2023 Aug 28. doi: 10.1002/jsfa.12943. Online ahead of print.

ABSTRACT

BACKGROUND: Wheat (Triticum aestivum L.) is the second most consumed food in the world. One way to meet this demand is the expansion of wheat cultivation to the Brazilian Cerrado in the southeastern region. However, one of the major limitations is that there are few studies related to wheat climate risk zoning. Thus, this study aimed to determine the agroclimatic zoning of wheat by estimating the water needs satisfaction index (ISNA) in the southeastern region of Brazil. For this purpose, a 60-year historical series of meteorological data was used to calculate the potential evapotranspiration, crop evapotranspiration and climatological water balance values. To define the agroclimatic zones of wheat and sowing date, the ISNA method was used. The data were analyzed using descriptive statistics to determine the variations. To obtain the agroclimatic zoning of wheat, the geostatistical method of kriging interpolation was used.

RESULTS: The regions with the highest rainfall are the south of Minas Gerais and the coast of São Paulo. The sowing period directly impacts the development of the crop, the available water capacity (CAD) and the ISNA values indicated the spring and summer had better cultivation conditions, and the best window for wheat cultivation is concentrated in the fall due to the limitation of biotic factors.

CONCLUSION: Although in terms of altitude (>700 m) Minas Gerais has 39.4% of the area suitable for wheat cultivation. So, climatic variations within and between the states of the southeastern region should be considered for the positioning of wheat cultivars in these regions to obtain the maximum yield. This article is protected by copyright. All rights reserved.

PMID:37638491 | DOI:10.1002/jsfa.12943

New Phytol. 2023 Aug 28. doi: 10.1111/nph.19206. Online ahead of print.

ABSTRACT

The geographic distribution of plant diversity matches the gradient of habitat heterogeneity from lowlands to mountain regions. However, little is known about how much this relationship is conserved across scales. Using the World Checklist of Vascular Plants and high-resolution biodiversity maps developed by species distribution models, we investigated the associations between species richness and habitat heterogeneity at the scales of Eurasia and the Hengduan Mountains (HDM) in China. Habitat heterogeneity explains seed plant species richness across Eurasia, but the plant species richness of 41/97 HDM families is even higher than expected from fitted statistical relationships. A habitat heterogeneity index combining growing degree days, site water balance, and bedrock type performs better than heterogeneity based on single variables in explaining species richness. In the HDM, the association between heterogeneity and species richness is stronger at larger scales. Our findings suggest that high environmental heterogeneity provides suitable conditions for the diversification of lineages in the HDM. Nevertheless, habitat heterogeneity alone cannot fully explain the distribution of species richness in the HDM, especially in the western HDM, and complementary mechanisms, such as the complex geological history of the region, may have contributed to shaping this exceptional biodiversity hotspot.

PMID:37638474 | DOI:10.1111/nph.19206