Sulfamethoxazole-Trimethoprim Prophylaxis in Pediatric Oncology Patients With Glucose-6-Phosphate Dehydrogenase Deficiency.

We sought to determine whether Pneumocystis jirovecii pneumonia prophylaxis with sulfamethoxazole-trimethoprim (SMX-TMP) is associated with an increased frequency of acute hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency versus non-G6PD-deficient controls in a pediatric oncology population. There was no statistically significant difference in change in hemoglobin or transfusion requirements after starting SMX-TMP between groups. These findings suggest no increased risk of acute hemolytic anemia with SMX-TMP administered at prophylaxis doses in patients with G6PD deficiency.

Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia.

PURPOSE: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear. METHODS: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes. RESULTS: Seven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within CRLF2-, DUX4-, and KMT2A-rearranged ALL that were linked to age and cytotoxic drug resistance. In particular, a subset of children had adult-like ALL on the basis of leukemia gene expression patterns across subtypes, despite their chronological age. Resistant to cytotoxic drugs, children with adult-like ALL exhibited poor prognosis in pediatric ALL trials, even after adjusting for age and minimal residual diseases. CONCLUSION: Our results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.

Variations in Benefits of Intergenerational Tutoring in the "New Normal".

This study investigated the benefits and challenges of intergenerational tutoring in a post-pandemic context. We explored how the benefits of intergenerational tutoring vary among subgroups of volunteers-first-time tutors, male tutors, tutors who are caregivers, and tutors with moderate or severe loneliness. Older adult tutors (N = 319) were surveyed before and after the 2021-2022 school year, and the data were analyzed with structural equation multivariate regression and thematic analysis. Results indicated that while public health measures like mask-wearing posed challenges for some tutors, there were positive outcomes for tutors, especially first-time tutors, who experienced more health and well-being benefits, and tutors who are caregivers, who experienced improved civic attitudes towards public education. These results can help programs attract subgroups of volunteers who are likely to benefit the most, as well as attend to the unique challenges of pandemic-related policies.

Primary Mucinous Adenocarcinoma of the Renal Pelvis: A Case Report.

Mucinous adenocarcinomas of the upper urinary tract are extremely rare, and the majority of information available comes from case reports or short case series. Intestinal metaplasia is considered a premalignant condition in carcinogenesis. Here we present a case of a 55-year-old male who presented with a left flank mass extending to the left hemiabdomen and macroscopic hematuria. Pathologic findings revealed that the kidney was transformed into a multiloculated cystic mass measuring 18 × 12 × 11 cm, with a dilated pelvicalyceal system obstructed by a stone at the renal hilus and filled with a gray, soft, gelatinous material. Histopathologic sections showed glandular metaplasia of the proximal ureter ascending to the renal pelvis, lined by intestinal-type columnar epithelium containing goblet cells admixed with malignant glands floating in abundant extracellular mucin, along with poorly differentiated areas composed of signet ring cells. Immunohistochemistry studies showed positive periodic acid Schiff (PAS)/periodic acid Schiff-diastase (PAS-D), consistent with the mucinous nature of the intracellular and extracellular materials. Positive immunohistochemical staining for CK7, CK20, and CDX2 (CK7+/CK20+/CDX2+) highlighted the intestinal differentiation of this neoplasm. This offers evidence for the intestinal metaplasia-dysplasia-carcinoma sequence rather than a teratomatous or coelomic epithelial origin in mucinous ovarian-like cystadenocarcinoma involving the renal pelvis.

Young people in foster care and substance use.

Adolescents are at high risk for using substances and for young people in foster care, substance use rates are estimated to be as high as 49 %. Adolescence is an important period for preventing substance use and SUD. Universal screening, brief interventions, and substance use treatment can be used to decrease substance use and substance use disorders among adolescents. Brief interventions often used with adolescents include motivational interviewing and contingency management. Of the many types of outpatient therapies utilized to treat adolescents with substance use disorder, some of the most established include cognitive behavioral therapy, family-based therapy, and a combination of different types of interventions. Medication treatment is less frequently offered to adolescents due to buprenorphine being the only drug FDA approved for youth under the age of 18. Residential treatment is also an option if lower levels of care are not adequate to safely support youth. Lastly, limited research has looked at the effectiveness of continuing care options to support youth in maintaining treatment results.

Gender Disparity in Authorship Among Orthopaedic Surgery Residents.

Background: Gender disparity remains pervasive in orthopaedic surgery, which affects the research pursuits of orthopaedic surgeons. The purpose of this study was to characterize gender-related authorship trends of orthopaedic surgery residents, including evaluation of gender-concordant publication rates. Methods: An observational cross-sectional analysis of US orthopaedic surgery residency programs was performed. Information on residency programs and demographics of each cohort was collected. Publication metrics consisting of number of first and non-first author publications and H-indices were manually obtained for PGY-3 to PGY-5 residents attending the 25 programs ranked the highest for research output by Doximity. Gender of each resident and senior author was determined from institutional websites using photos, biographies, and preferred pronouns when available. Results: A total of 532 residents, 169 (31.8%) female and 363 (68.2%) male, were included for authorship analysis. Of them, 415 (78%) had at least one first author publication, which did not vary significantly by gender. Female residents had disproportionately fewer first author publications compared with their representation (22% vs. 31.8%, p < 0.00001). Female residents averaged fewer first and non-first author publications compared with male residents (2.8 vs. 4.6, p = 0.0003; 6.4 vs. 10, p = 0.0001 respectively). Despite fewer publications overall, a greater subset of publications by female residents were written in collaboration with a female senior author compared with publications by male residents (p < 0.0001). Male residents had a higher average H-index of 5.4 vs. 3.9 among female residents (p = 0.00007). Conclusion: Despite similar rates of first author publication among male and female residents, female residents had fewer publications overall, lower H-indices, and disproportionately fewer first author publications than would be expected given their representation. Findings from this study suggest that gender disparity in orthopaedic surgery extends to differences in research productivity as early as in residency. This may have negative implications on the career advancement of female orthopaedic surgeons. Additional work is needed to identify and understand biases in research productivity and career advancement, to promote more equitable strategies for academic achievement. Level of Evidence: IV.

Any better? A follow-up content analysis of adolescent sexual and reproductive health inclusion in Global Financing Facility country planning documents.

BACKGROUND: The Global Financing Facility (GFF) supports national reproductive, maternal, newborn, child, adolescent health, and nutrition needs. Previous analysis examined how adolescent sexual and reproductive health was represented in GFF national planning documents for 11 GFF partner countries. OBJECTIVES: This paper furthers that analysis for 16 GFF partner countries as part of a Special Series. METHODS: Content analysis was conducted on publicly available GFF planning documents for Afghanistan, Burkina Faso, Cambodia, CAR, Côte d'Ivoire, Guinea, Haiti, Indonesia, Madagascar, Malawi, Mali, Rwanda, Senegal, Sierra Leone, Tajikistan, Vietnam. Analysis considered adolescent health content (mindset), indicators (measure) and funding (money) relative to adolescent sexual and reproductive health needs, using a tracer indicator. RESULTS: Countries with higher rates of adolescent pregnancy had more content relating to adolescent reproductive health, with exceptions in fragile contexts. Investment cases had more adolescent content than project appraisal documents. Content gradually weakened from mindset to measures to money. Related conditions, such as fistula, abortion, and mental health, were insufficiently addressed. Documents from Burkina Faso and Malawi demonstrated it is possible to include adolescent programming even within a context of shifting or selective priorities. CONCLUSION: Tracing prioritisation and translation of commitments into plans provides a foundation for discussing global funding for adolescents. We highlight positive aspects of programming and areas for strengthening and suggest broadening the perspective of adolescent health beyond the reproductive health to encompass issues, such as mental health. This paper forms part of a growing body of accountability literature, supporting advocacy work for adolescent programming and funding.

Main findings: Adolescent health content is inconsistently included in the Global Financing Facility country documents, and despite strong or positive examples, the content is stronger in investment cases than project appraisal documents, and diminishes when comparing content, indicators and financing.Added knowledge: Although adolescent health content is generally strongest in countries with the highest proportion of births before age 18, there are exceptions in fragile contexts and gaps in addressing important issues related to adolescent health.Global health impact for policy and action: Adolescent health programming supported by the Global Financing Facility should build on examples of strong country plans, be more consistent in addressing adolescent health, and be accompanied by public transparency to facilitate accountability work such as this.

An Umbrella Review and a Meta-analysis of Meta-analyses of Disordered Eating Among Medical Students.

Objective: To prevent eating disorders in future physicians, this umbrella review and meta-analysis of previous meta-analyses estimates the prevalence of disordered eating (DE) among medical students worldwide and identifies key risk factors. Methods: Four databases were searched electronically between their inception and February 1, 2023. The search was later updated to December 31, 2023. Results: The search yielded prevalence rates for medical students who scored above established cutoffs on validated assessment measures for DE. These were computed to provide an overall pooled estimate. The data was taken from 2 previous reviews. Both these systematic reviews found a 15.1% (95% confidence interval [CI]: 14.7%-15.6%) prevalence rate of DE among medical students. The equivalent Hedges' G = 0.30 (95% CI: 0.29-0.31), the equivalent odds ratio = 1.74 (95% CI: 1.71-1.77), I2 = 97.6%, and the excess of statistical significance is P = .001. The trim and fill adjusted effect size was 16.0% (95% CI: 14.0%-20.0%). Conclusion: Because eating disorders put students' safety and well-being at risk and because the health of early-stage physicians is vital to the welfare of a country, early signs of disordered eating must become a priority of medical schools and a signal for effective prevention and intervention. The recommendation is to ensure supportive environments, provide easy access to effective care, and hold clear expectations for student eating behavior.

Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children.

BACKGROUND: Inorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth. METHODS: A total of 240 participants (8-11 years, 53 % female) drinking from wells with arsenic concentrations > 50 µg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 µg FA + 5 µg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine. RESULTS: At baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 µg/L and 91.2 ± 89.5 µg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and -1.10% (95% CI: -1.73, -0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline. CONCLUSION: This RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status.

Hypothalamic transcriptome response to simulated diel earthen pond hypoxia cycles in channel catfish (Ictalurus punctatus).

Commercial culture of channel catfish (Ictalurus punctatus) occurs in earthen ponds that are characterized by diel swings in dissolved oxygen concentration that can fall to severe levels of hypoxia, which can suppress appetite and lead to suboptimal growth. Given the significance of the hypothalamus in regulating these processes in other fishes, an investigation into the hypothalamus transcriptome was conducted to identify specific genes and expression patterns responding to hypoxia. Channel catfish in normoxic water were compared with catfish subjected to 12 h of hypoxia (20% oxygen saturation; 1.8 mg O2/L; 27°C) followed by 12 h of recovery in normoxia to mimic 24 h in a catfish aquaculture pond. Fish were sampled at 0-, 6-, 12-, 18-, and 24-h timepoints, with the 6- and 12-h samplings occurring during hypoxia. A total of 190 genes were differentially expressed during the experiment, with most occurring during hypoxia and returning to baseline values within 6 h of normoxia. Differentially expressed genes were sorted by function into Gene Ontology biological processes and revealed that most were categorized as "response to hypoxia," "sprouting angiogenesis," and "cellular response to xenobiotic stimulus." The patterns of gene expression reported here suggest that transcriptome responses to hypoxia are broad and quickly reversibly with the onset of normoxia. Although no genes commonly reported to modulate appetite were found to be differentially expressed in this experiment, several candidates were identified for future studies investigating the interplay between hypoxia and appetite in channel catfish, including adm, igfbp1a, igfbp7, and stc2b.NEW & NOTEWORTHY Channel catfish are an economically important species that experience diel episodic periods of hypoxia that can reduce appetite. This is the first study to investigate their transcriptome from the hypothalamus in a simulated 24-h span in a commercial catfish pond, with 12 h of hypoxia and 12 h of normoxia. The research revealed functional groups of genes relating to hypoxia, angiogenesis, and glycolysis as well as individual target genes possibly involved in appetite regulation.

Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment.

Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively. We identify 54 variants with transcriptional effects and high-confidence gene connectivity. Additionally, functional interrogation of the top variant, rs1247117, reveals changes in chromatin accessibility, PU.1 binding affinity and gene expression, and deletion of the genomic interval containing rs1247117 sensitizes cells to vincristine. Together, these data demonstrate that noncoding regulatory variants associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to antileukemic agents.

Dental hygiene students' and recent graduates' intentions, attitudes, and perceptions of academic careers.

PURPOSE: The purpose of this study was to explore dental hygiene students' and recent graduates' awareness, attitudes, perceived barriers, motivators, and intentions to pursue a career in academia as a dental hygiene educator. METHODS: Cross-sectional survey research was conducted with a non-probability sample of dental hygiene students and recent graduates (n = 451). The survey included sections for familiarity regarding academic careers for dental hygienists, attitudes toward academic careers, barriers and motivating factors for this career path, and future academic career intentions. Analysis included descriptive, correlations, and regression. RESULTS: Of 451 surveys started, 296 were at least 80% complete for a completion rate of 66%. The most reported barrier to a career in academia was the cost to obtain the required degree to become an educator (67.6%, n = 200), and for motivating factors was a sense of accomplishment (62.8%, n = 186). Regression analysis of likelihood to pursue a higher education degree showed two main predictors; belief that higher education would advance the dental hygiene profession (ß = 0.35, p < 0.001) and willingness to take a pay cut to become an educator (ß = 0.24, p < 0.001). CONCLUSIONS: Overall dental hygiene students and recent graduates were familiar with and had a positive view of careers in academia. However, barriers included cost and time for obtaining a higher degree, as well as the pay differential between academia and private practice. The educator shortage in dental hygiene may be alleviated by providing educators with loan forgiveness and offering salaries comparable to clinical practice.

The psychometric properties of the Arabic version of the dieting beliefs scale (DBS).

Background: There are relatively few data about the association between locus of control and weight loss in Arabic populations. A tool does exist, the Dieting Belief Scale (DBS), that was designed to measure individuals' beliefs regarding their ability to control their body weight. The aim of this study was to translate this tool into Arabic and to evaluate its psychometric properties. Methods: The forward translation of the DBS from English to Arabic was completed by two professional bilingual translators, while the back translation from Arabic to English was independently performed by another two different professional bilingual translators. An online survey using the tool was then completed by 245 participants, fully aware of the study's purpose. Psychometric analyses were subsequently conducted to assess the reliability and validity of the Arabic DBS.Internal consistency was examined using Cronbach's α and McDonald's ω coefficients. Test-retest reliability was also assessed. Confirmatory factor analysis was employed to evaluate the fit of a three-factor model, with indices including Comparative Fit Index (CFI), Tucker Lewis Index (TLI), Root Mean Square Error of Approximation (RMSEA), and Standardized Root Mean Square Residual (SRMR). Convergent validity was assessed by examining the correlation between the Arabic DBS and the Eating Attitude Test (EAT-26) previously translated into Arabic, the latter identifying attitudes, feelings and behaviors related to eating. Results: The Arabic translated DBS scale demonstrated high translation accuracy and content validity estimates. Cronbach's α and McDonald's ω reliability coefficients for the translated scale were approximately 0.91. Test-retest reliability was 0.96. The three-factor model showed an acceptable fit (CFI = 0.93, TLI = 0.92, RMSE = 0.08, SRMR = 0.06). The Arabic version of the DBS was found to have good convergent validity, as evidenced by the significant correlation between the EAT-26 and DBS questionnaires (r = 0.53, p < 0.01). Conclusion: The Arabic version of the DBS is highly reliable and has sufficient content validity to measure belief about personal ability to control one's weight.

Development and Validation of a Food Frequency Questionnaire for Evaluating the Nutritional Status of Patients with Serious Mental Illnesses (DIETQ-SMI) in Bahrain.

General food frequency questionnaires (FFQs) have not been tailored for or validated in individuals with psychiatric disorders. Given the unique eating behaviors of patients with serious mental illnesses (SMIs), custom-made tools are needed. Therefore, we developed and validated an FFQ customized to individuals with SMIs. A total of 150 adults with SMIs (schizophrenia, bipolar disorder, or major depression) were recruited from Bahrain. The participants completed the 50-item Dietary Intake Evaluation Questionnaire for Serious Mental Illness (DIETQ-SMI) FFQ and a 3-day food record (FR). The validity of the FFQ was assessed by comparing nutrient intake to FR intake using correlation and reliability statistics. The DIETQ-SMI demonstrated a good ranking validity compared to the FR based on correlation coefficients (rho 0.33 to 0.92) for energy and macro- and micronutrients. The FFQ had high internal consistency (McDonald's omega = 0.84; Cronbach's alpha = 0.91) and test-retest reliability (ICC > 0.90). The FFQ tended to estimate higher absolute intakes than the FR but adequately ranked the intakes. The FFQ value was correlated with the FR for all the items (p < 0.001). The DIETQ-SMI is a valid and reliable FFQ for ranking dietary intake in individuals with an SMI. It can help assess nutritional status and, subsequently, guide interventions in high-risk psychiatric populations.

The Translation and Preliminary Psychometric Validation of the Ghosting Questionnaire in Urdu.

BACKGROUND: "Ghosting" refers to the practice of abruptly cutting off all contact with a person with whom you have been in constant correspondence. The break comes without warning and without understandable provocation. The term most commonly applies to online romantic relationships. The motives for and effects of ghosting have been studied, and validated research questionnaires have been developed; however, there are no such questionnaires available for Urdu speakers. The purpose of this study was to adapt the "Ghosting Questionnaire (GQ)" for use in Pakistan and India, two of the world's most populous countries-a process that involves translation, adaptation, and validation. METHODS: The study's methodology involved translating the GQ into Urdu using both forward and backward translation techniques. Convergent validity, test-retest reliability, internal consistency, confirmatory factor analysis, and goodness of fit were all components of the psychometric analyses. CONCLUSIONS: The Urdu version of the GQ demonstrated a good internal consistency, with the Cronbach's alpha and McDonald's omega both exceeding 0.90. It also showed a high test-retest reliability-(0.96). The one-factor structure was confirmed by the confirmatory factor analysis, which agreed with the original English version of the GQ.

'Suspension Palatoplasty' - A method of surgical correction of VPI post Cleft Palate repair.

OBJECTIVE: To design the technique of 'Suspension Palatoplasty' for Velopharyngeal Insufficiency (VPI) post Cleft Palate (CP) based on optimal spatial positioning of palate at the time of VPI correction, by using a non-obstructive, high, midline pharyngeal flap for predictable velopharyngeal closure and normal speech. To evaluate the results of CP patients with VPI operated using the technique of 'Suspension palatoplasty'. DESIGN: An ambi-spective longitudinal clinical study. SETTING: Comprehensive cleft care clinic in a private trust hospital. PATIENTS, PARTICIPANTS: Patients operated using the 'Suspension Palatoplasty' technique for VPI post CP repair between 2014 and 2018 with a minimum follow-up period of 5 years. INTERVENTIONS: 'Suspension Palatoplasty' - Double Opposing Z (DOZ) plasty with palatal myoplasty is used to revise soft palate and a narrow superiorly based pharyngeal flap is used to suspend it for a dynamic velopharyngeal closure. MAIN OUTCOME MEASURE: Speech outcome and surgical complications. RESULTS: 70 out of 119 studied were found to have normal speech (59%), and another 25 patients (21%) had acceptable speech. Thus 95 out of 119 patients (80%) had normal or near-normal speech and did not require any further speech therapy or surgeries. 12 patients had snoring without difficulty in breathing. One patient had symptoms suggestive of obstructive sleep apnea. Younger patients had a higher percentage of normal speech outcomes. Many of our adult patients also attained normal speech. CONCLUSION: 'Suspension Palatoplasty' aims to achieve normal speech with little effort. It has minimal side effects. The author has performed 403 cases to date.