Efficacy and Safety of Bempedoic Acid in Patients With Hyperlipidemia and Non-alcoholic Fatty Liver Disease.

Hyperlipidemia and its association with cardiovascular diseases have been significant public health concerns for many decades. Statins have long been the primary therapeutic option for lowering cholesterol levels and reducing cardiovascular mortality. However, a substantial number of patients either do not achieve optimal lipid goals with maximally tolerated statin doses or experience statin intolerance. In recent years, there have been remarkable developments in the field of hyperlipidemia management, leading to the approval of novel hypolipidemic drugs in North America and Europe. This article reviews the clinical development of bempedoic acid, a promising new drug, alone and in combination with ezetimibe, as an alternative approach to managing hyperlipidemia. The Phase I trials established the safety and tolerability of bempedoic acid, paving the way for further investigation in Phase II and Phase III trials. Multiple phase II studies evaluated the lipid-lowering efficacy of bempedoic acid as monotherapy or in combination with other hypolipidemic agents, showing significant improvements in lipid levels and inflammatory markers. The recently approved fixed drug combination of bempedoic acid and ezetimibe presents a viable option for patients who need additional LDL-C lowering alongside dietary modifications and maximally tolerated statin therapy.

Renal epithelioid angiomyolipomas overexpress TFE3 and the TFE3-regulated gene TRIM63 in the absence of TFE3 rearrangement.

Angiomyolipoma (AML) is a neoplasm within the perivascular epithelioid cell tumor family that occurs somewhat frequently in the kidney. Most are indolent and discovered incidentally, with rare tumors demonstrating malignant clinical behavior. A small subset of renal AMLs with epithelioid features are associated with aggressive behavior, and may demonstrate morphologic overlap with renal cell carcinomas (e.g., clear cell renal cell carcinoma (RCC), TFE3-rearranged RCC). Prior studies of spindle cell and epithelioid AMLs have identified rare examples with underlying TFE3 gene fusions. TFE3 protein expression (demonstrated by immunohistochemistry) with no evidence of concurrent TFE3 rearrangements has been reported previously in 4/24 AMLs (17%) (Argani et al. Am J Surg Pathol 34:1395-1406, 2010). Currently, the relationship between TFE3 protein expression, TFE3 fusions, and expression of TFE3-mediated genes remains incompletely understood in renal epithelioid AMLs. We sought to explore these relationships using TFE3 break-apart fluorescence in situ hybridization (FISH) and TRIM63 RNA in situ hybridization (ISH) on epithelioid AMLs with moderate to strong TFE3 expression by immunohistochemistry. RNA sequencing (fusion panel) was performed on two cases with negative FISH results to assess for FISH-cryptic gene fusions. The series comprised five epithelioid AMLs from four patients (three women, one man) aged 13 to 76 years. All were considered positive for TFE3 by immunohistochemistry (2 + /3 + expression). TRIM63 ISH was performed on four specimens from three patients, yielding positive results in 3/3 tumors (100%) that were successfully analyzed. TFE3 break-apart FISH was performed on all samples, demonstrating a TFE3 rearrangement in only 1/4 tumors (25%). RNA sequencing demonstrated the absence of productive TFE3 gene fusions in three tumors with negative break-apart TFE3 FISH results. This study demonstrates that renal epithelioid AMLs overexpress TFE3 and TFE3-mediated genes (TRIM63) even in the absence of TFE3 rearrangements. This finding could be explained by functional upregulation of TFE3 secondary to activation of the mammalian target of rapamycin complex 1 (mTORC1). Expression of TFE3 and TRIM63 in this tumor type represents a potential pitfall, given the morphologic and immunophenotypic overlap between epithelioid AML and TFE3-altered renal cell carcinoma.

Comparison of Efficacy of Autologous Platelet Rich Plasma Therapy With 5% Topical Minoxidil Spray in Treating Alopecia Areata: A Head-to-Head Assessment of Novel Approaches.

BACKGROUND: Alopecia areata (AA) remains one of the most challenging afflictions encountered in dermatology clinics. It is characterized by an autoimmune-mediated inflammatory process of and around hair follicles, causing reversible, non-scarring hair loss. With the ongoing search for optimal treatment strategies, the potentially positive role of autologous platelet-rich plasma (PRP) therapy as well as minoxidil has been reported in various studies; however, the comparison of the two treatment modalities is largely underexplored. This research aims to compare and assess the effectiveness of intralesional PRP with topical minoxidil therapy in AA to identify efficacious management options amongst the newly described treatment modalities. METHODOLOGY: The research work was conducted over four months and included 40 (31 males and 9 females) patients suffering from alopecia areata. They were divided into Group A, which was administered monthly autologous PRP injections, while Group B was given daily topical 5% minoxidil therapy. In group A, four treatments of PRP were given, each one month apart. While in group B, daily topical minoxidil spray was administered for the same duration. The alopecia areata severity grade was recorded by employing the "Severity of Alopecia Tool" (SALT) scoring system. The pre- and post-treatment SALT scores were noted and compared at each monthly visit. RESULTS: The study comprised nine (22.5%) female and 31 (77.5%) male patients. At the beginning of the study and after one month of treatment, the difference in the SALT score was not statistically significant between the two groups, suggesting that both interventions had similar effects during the early stages of the treatment. At two months, a statistically significant difference emerged (p-value 0.037), indicating that a more significant fall in the SALT score was observed with autologous PRP treatment compared to topical minoxidil. After four months, a highly significant difference was noted between the two groups (p-value <0.0001), implying that intralesional PRP therapy led to a far more significant decrease in the SALT score compared to topical minoxidil therapy. CONCLUSION: Monthly intralesional autologous PRP therapy for four months manifests better outcomes in alopecia areata than daily 5% topical minoxidil therapy.

Spiral ganglion neuron degeneration in aminoglycoside-deafened rats involves innate and adaptive immune responses not requiring complement.

Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for effective functioning of cochlear implants, which stimulate SGNs when hair cells are missing. SGNs slowly degenerate following aminoglycoside-induced hair cell loss, a process thought to involve an immune response. However, the specific immune response pathways involved remain unknown. We used RNAseq to gain a deeper understanding immune-related and other transcriptomic changes that occur in the rat spiral ganglion after kanamycin-induced deafening. Among the immune and inflammatory genes that were selectively upregulated in deafened spiral ganglia, the complement cascade genes were prominent. We then assessed SGN survival, as well as immune cell numbers and activation, in the spiral ganglia of rats with a CRISPR-Cas9-mediated knockout of complement component 3 (C3). Similar to previous findings in our lab and other deafened rodent models, we observed an increase in macrophage number and increased expression of CD68, a marker of phagocytic activity and cell activation, in macrophages in the deafened ganglia. Moreover, we found an increase in MHCII expression on spiral ganglion macrophages and an increase in lymphocyte number in the deafened ganglia, suggestive of an adaptive immune response. However, C3 knockout did not affect SGN survival or increase in macrophage number/activation, implying that complement activation does not play a role in SGN death after deafening. Together, these data suggest that both innate and adaptive immune responses are activated in the deafened spiral ganglion, with the adaptive response directly contributing to cochlear neurodegeneration.

Electrocardiographic changes in pneumothorax: an updated review.

ECG changes in pneumothorax have gained recognition as important indicators of cardiopulmonary interactions. This narrative review examines the existing literature to provide insights into the various ECG abnormalities observed in patients with pneumothorax, their underlying mechanisms, and clinical implications. The review highlights the commonly reported changes, including alterations in the electrical axis, ST segment deviations, T-wave abnormalities, and arrhythmias. The rightward shift of the electrical axis is attributed to cardiac displacement caused by increased intrathoracic pressure. ST segment deviations may reflect the influence of altered intrathoracic pressure on myocardial oxygen supply and demand. T-wave abnormalities may result from altered myocardial repolarization and hypoxemia. Arrhythmias, although varying in incidence and type, have been associated with pneumothorax. The clinical implications of these ECG changes are discussed, emphasizing their role in diagnosis, risk stratification, treatment optimization, and prognostication. Additionally, future research directions are outlined, including prospective studies, mechanistic investigations, and the integration of artificial intelligence. Enhancing our understanding of ECG changes in pneumothorax can lead to improved patient care, better management strategies, and the development of evidence-based guidelines. The objective of this review is to demonstrate the presence of various ECG abnormalities in patients with pneumothorax.

Beta-Catenin Alterations in Postchemotherapy Yolk Sac Tumor, Postpubertal-Type With Enteroblastic Features.

Postchemotherapy postpubertal-type yolk sac tumors (YST) with glandular and solid phenotypes are aggressive and commonly resistant to systemic chemotherapy. These neoplasms show morphologic features that significantly overlap with those of somatic carcinomas with "enteroblastic" or "fetal" phenotype (the preferred terminology depends on the site of origin). They often present as late or very late recurrences, and their diagnosis is challenging because they frequently affect patients in an age group at risk for carcinomas of somatic origin. Recently, we incidentally identified examples of postchemotherapy glandular and solid YST with "enteroblastic" phenotypes and nuclear expression of beta-catenin, prompting us to further evaluate the prevalence of this phenomenon. We found nuclear expression of beta-catenin in 10 (29%) of 34 such tumors. A subset of cases with nuclear beta-catenin expression was further analyzed with a DNA sequencing panel (n = 6) and fluorescence in situ hybridization for isochromosome 12p [i(12p); n = 5]. Sequencing identified exon 3 CTNNB1 variants in 3 (50%) of 6 analyzed cases, and fluorescence in situ hybridization was positive for i(12p) in 5 of 5 cases. In conclusion, a significant subset of postchemotherapy YST with glandular or solid architecture and "enteroblastic" phenotype demonstrates beta-catenin alterations, suggesting that activation of Wnt signaling may play a role in the progression of these neoplasms. Moreover, nuclear beta-catenin expression in these tumors represents a potential diagnostic pitfall given that carcinomas of true somatic origin with overlapping morphology may also be positive for this marker.

Cross-lagged relationships between exposure to intimate partner violence, depressive symptoms and suicidal thoughts among adolescent and young married women.

BACKGROUND: High rates of depression and suicidal ideation are found in women experiencing intimate partner violence (IPV), but their temporal relationship is unclear. This study explores the bidirectional causality between IPV victimization, depressive symptoms, and suicidal thoughts among adolescent and young married women in India. METHODS: Data sourced from the UDAYA longitudinal survey in India, comprising 3,965 women aged 15-22. Employing Pearson's correlation coefficient, we analyzed the relationship between variables. Additionally, a two-wave cross-lagged autoregressive panel model explored the bidirectional link between IPV, depressive symptoms, and suicidal ideation. RESULTS: Approximately 25 % and 45 % of the participants reported some form of partner violence at baseline and at follow-up after three years, respectively. Exposure to IPV at baseline was significantly associated with depressive symptoms at follow-up [ß = 0.10, p < 0.001], and the association between depressive symptoms at baseline and IPV at follow-up was statistically not significant [ß = -0.02, 95 % CI: -0.06-0.02]. Similarly, exposure to IPV at baseline was significantly associated with suicidal thoughts at follow-up [ß = 0.24, p < 0.001], and the association between suicidal thoughts at baseline and IPV at follow-up was statistically not significant [ß = 0.003, 95 % CI: -0.001-006]. CONCLUSIONS: The findings suggest that exposure to IPV is consistently and strongly associated with depressive symptoms and suicidal thoughts in adolescent and young married women. However, the reciprocal relationships did not hold true in this study, implying that reducing IPV during adolescence could potentially minimize the prevalence of depressive symptoms and suicidal thoughts during young adulthood.

Unveiling the dynamics of social engagement and subjective health in older adults: A gendered perspective.

OBJECTIVES: As populations age globally, understanding the dynamics that influence the well-being of older individuals become increasingly crucial. The research employs a comprehensive approach to unravel the multifaceted interplay between social engagements and subjective health perceptions of older Indians, with a special focus on gender differences. SUBJECTS AND METHODS: This study used data from the Longitudinal Aging Study in India (LASI) wave 1, 2017-18 with a total sample of 30,533 older adults aged 60 years and above. Bivariate analysis, chi-square tests and unadjusted and adjusted average marginal effects from logistic regression models were used to assess the relationship between social engagements and subjective health among older adults, stratified by gender. RESULTS: The prevalence of poor health status decreased with higher frequency of social networks among both men (pp. (percentage point) = 6.1; CI (Confidence Interval): 10.6, 1.6) and women (pp. = 9.2; CI: 14.9, 3.4). The adjusted average marginal effects demonstrate that with an increase in the overall score of social engagement, the likelihood of poor health is almost reduced by half. For men, the prevalence of poor health was 9.8 pp. (95 % CI: 13.7, 5.8), while for women, it was 9.3 pp. (95 % CI: 15.2, 3.1). CONCLUSION: Gendered perspectives unveil unique patterns, highlighting how societal expectations and roles assigned to each gender may influence the subjective health perceptions of older individuals. This study adds to the expanding knowledge base to enhance the well-being and fulfillment of aging populations, considering the complex interplay of social dynamics and gendered perspectives.

Isotope-Edited Variable Temperature Infrared Spectroscopy for Measuring Transition Temperatures of Single A-T Watson-Crick Base Pairs in DNA Duplexes.

Experimental methods to determine transition temperatures for individual base pair melting events in DNA duplexes are lacking despite intense interest in these thermodynamic parameters. Here, we determine the dimensions of the thymine (T) C2═O stretching vibration when it is within the DNA duplex via isotopic substitutions at other atomic positions in the structure. First, we determined that this stretching state was localized enough to specific atoms in the molecule to make submolecular scale measurements of local structure and stability in high molecular weight complexes. Next, we develop a new isotope-edited variable temperature infrared method to measure melting transitions at various locations in a DNA structure. As an initial test of this "sub-molecular scale thermometer", we applied our T13C2 difference infrared signal to measure location-dependent melting temperatures (TmL) in a DNA duplex via variable temperature attenuated total reflectance Fourier transform infrared (VT-ATR-FTIR) spectroscopy. We report that the TmL of a single Watson-Crick A-T base pair near the end of an A-T rich sequence (poly T) is ∼34.9 ± 0.7°C. This is slightly lower than the TmL of a single base pair near the middle position of the poly T sequence (TmL ∼35.6±0.2°C). In addition, we also report that the TmL of a single Watson-Crick A-T base pair near the end of a 50% G-C sequence (12-mer) is ∼52.5 ± 0.3°C, which is slightly lower than the global melting Tm of the 12-mer sequence (TmL ∼54.0±0.9°C). Our results provide direct physical evidence for end fraying in DNA sequences with our novel spectroscopic methods.

Corrigendum to "Moderating role of functional/mobility limitations in the association between sleep problems and hypertension among middle-aged and older adults in India" [Prev. Med. Rep. 38 (2024) 102589].

[This corrects the article DOI: 10.1016/j.pmedr.2024.102589.].

Thyroid Dysfunction Risk After Iodinated Contrast Media Administration: A Prospective Longitudinal Cohort Analysis.

CONTEXT: Iodinated contrast media (ICM) is a common source of excess iodine in medical settings, given the common use of iodinated radiologic procedures. OBJECTIVE: To determine the long-term risks of thyroid dysfunction following iodinated contrast administration in a prospective study. DESIGN, SETTING, PARTICIPANTS: A longitudinal cohort study was conducted of patients in the U.S. Veterans Affairs medical system who received ICM. MAIN OUTCOME MEASURES: Serum thyroid function, thyroid antibody, and inflammatory markers were measured at baseline. Thyroid function tests were repeated at 1 month, 3 months, and every 6 months thereafter until 36 months. Risk of thyroid dysfunction and longitudinal changes in thyroid hormone levels were assessed using mixed effect models. RESULTS: There were 122 participants (median age, 70.0 [IQR 62.2-74.0] years; 98.4% male). At baseline, six subjects had subclinical thyroid dysfunction prior to ICM receipt. During median follow-up of 18 months, iodine-induced thyroid dysfunction was observed in 11.5% (14/122); six (4.9%) developed hyperthyroidism (including one with overt hyperthyroidism) and eight (6.6%) subclinical hypothyroidism. At last follow-up, ten of 20 subjects with thyroid dysfunction (14 new-onset cases and six with preexisting thyroid dysfunction) had persistent subclinical hyperthyroidism or hypothyroidism. There were also subtle changes in thyroid hormones observed longitudinally within the reference ranges in the overall cohort. CONCLUSIONS: There is a rare long-term risk of an excess iodine load on thyroid dysfunction even among individuals from an overall iodine-sufficient region, supporting the need for targeted monitoring following iodinated contrast administration.

Vertical transmission of SARS-CoV-2 delta-variant in a preterm infant.

BACKGROUND: As SARS-CoV-2 continues to be relevant and cause illnesses, the effect of emerging virus variants on perinatal health remains to be elucidated. It was demonstrated that vertical transmission of SARS-CoV-2 is a relatively rare event in the original SARS-CoV-2 strain. However, very few reports describe vertical transmission related to the delta-variant. CASE PRESENTATION: We report a case of a preterm male neonate born to a mother with positive SARS-CoV-2 and mild respiratory complications. The neonate was born by cesarean section due to fetal distress. The rupture of the amniotic membrane was at delivery. The neonate had expected prematurity-related complications. His nasopharyngeal swabs for RT-PCR were positive from birth till three weeks of age. RT-ddPCR of the Placenta showed a high load of the SARS-CoV-2 virus with subgenomic viral RNA. RNAscope technique demonstrated both the positive strand of the S gene and the orf1ab negative strand. Detection of subgenomic RNA and the orf1ab negative strand indicats active viral replication in the placenta. CONCLUSIONS: Our report demonstrates active viral replication of the SARS-CoV-2 delta-variant in the placenta associated with vertical transmission in a preterm infant.

Associations between neighbourhood safety, social cohesion, sleep quality and sleep duration among older adults in India: Findings from the Study on Global Aging and Adult Health (WHO-SAGE), 2015.

BACKGROUND: Most studies on later-life health in India focus on families, with far less attention given to the health repercussions of neighbourhood conditions among older Indians. We address this limitation in existing research by examining the associations between perceptions of neighbourhood safety and social cohesion and sleep duration and sleep quality among older adults in India. METHODS: Data come from the Study on Global Aging and Adult Health (WHO-SAGE), India 2015 wave 2, with a sample of 7118 adults aged 50 years and above. Sleep quality and duration were assessed using subjective responses. Multivariable logistic and linear regression analyses were employed to test the research hypotheses. RESULTS: Prevalence of poor sleep quality was higher among older adults living in unsafe neighbourhoods (4.46%) than peers residing in safe neighbourhoods (3.52%), and it was also higher among those living in neighbourhoods with poor social cohesion (5.31%) than counterparts who lived in socially cohesive communities (3.10%). Older adults in neighbourhoods with poor social cohesion had higher odds of reporting compromised sleep quality (adjusted odds ratio 1.75, CI: 1.22-2.51) than those living in socially cohesive neighbourhoods. Moreover, compared to those who perceived they were living in safe neighbourhoods, their peers who perceived their neighbourhoods as unsafe reported shorter sleep duration, with a negative beta coefficient of -0.27 (CI: -0.45 to -0.085). CONCLUSION: That perceived unsafety and poor social cohesion within one's neighbourhood are associated with compromised sleep reflects the significance of making neighbourhoods safer and more integrated for later-life sleep health. In addition to micro-level strategies (e.g., balanced nutrition and physical activity), efforts to improve sleep health should optimise macro-level opportunities, such as rehabilitating and revitalising neighbourhoods, which may alleviate sleep disturbances and improve sleep outcomes among older adults.

Carcinoma arising in ileal conduit or orthotopic ileal neobladder reconstruction: A 20-year single institute experience.

CONTEXT: Carcinomas found in urinary diversion specimens are uncommon, particularly new primary tumours. New primary tumours primarily occur when the large intestine is utilised, whereas the occurrence is infrequent with the use of the ileum. These tumours include both the recurrence of primary malignancy or the development of a new primary malignancy originating from the small intestine. DESIGN: A search was performed within the pathology laboratory system to identify cases of malignancies involving ileal conduit/reconstruction from 2002 to 2022. Data on demographics, clinical details, pathology and management was recorded. RESULTS: A total of 13 male patients, with a mean age of 67 years (range = 49-81 years) were included in the study. The initial procedure performed included cystoprostatectomy (n = 10, including one case with right nephroureterectomy) and cystectomy (n = 3, including one case for bladder exstrophy) for initial diagnoses including urothelial carcinoma (n = 11; conventional, 6; sarcomatoid, 1; glandular 1; plasmacytoid, 1; micropapillary, 2) and adenocarcinoma (n = 1). The initial management included radical surgery with neoadjuvant chemotherapy/immunotherapy (n = 1), adjuvant chemotherapy (n = 3), intravesical adjuvant BCG (n = 2) and intravesical adjuvant chemotherapy (n = 1). Malignancies in ileal conduit or orthotopic ileal neobladder included recurrent urothelial carcinoma (n = 10) and new secondary adenocarcinomas (n = 3), which developed as early as 3 months (usually recurrence) and up to 13, 33 and 45 years (new primary malignancy) following primary resection. CONCLUSIONS: Utilising the ileum as conduit/neobladder presents a viable alternative for urinary diversion with a reduced malignancy risk compared to using a segment of the large intestine. However, there remains a potential for malignancy, either tumour recurrence or a new primary malignancy. In our study, tumour recurrence occurred up to 4 years following the initial diagnosis and the development of a new primary malignancy occurred up to 45 years after the initial diagnosis. Consequently, it is crucial to prioritise long-term follow-up for these patients undergoing this procedure.

Uncovering the Cardioprotective Potential of Diacerein in Doxorubicin Cardiotoxicity: Mitigating Ferritinophagy-Mediated Ferroptosis via Upregulating NRF2/SLC7A11/GPX4 Axis.

Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a life-threatening clinical issue with limited preventive approaches, posing a substantial challenge to cancer survivors. The anthraquinone diacerein (DCN) exhibits significant anti-inflammatory, anti-proliferative, and antioxidant actions. Its beneficial effects on DIC have yet to be clarified. Therefore, this study investigated DCN's cardioprotective potency and its conceivable molecular targets against DIC. Twenty-eight Wister rats were assigned to CON, DOX, DCN-L/DOX, and DCN-H/DOX groups. Serum cardiac damage indices, iron assay, oxidative stress, inflammation, endoplasmic reticulum (ER) stress, apoptosis, ferritinophagy, and ferroptosis-related biomarkers were estimated. Nuclear factor E2-related factor 2 (NRF2) DNA-binding activity and phospho-p53 immunoreactivity were assessed. DCN administration effectively ameliorated DOX-induced cardiac cytomorphological abnormalities. Additionally, DCN profoundly combated the DOX-induced labile iron pool expansion alongside its consequent lethal lipid peroxide overproduction, whereas it counteracted ferritinophagy and enhanced iron storage. Indeed, DCN valuably reinforced the cardiomyocytes' resistance to ferroptosis, mainly by restoring the NRF2/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling axis. Furthermore, DCN abrogated the cardiac oxidative damage, inflammatory response, ER stress, and cardiomyocyte apoptosis elicited by DOX. In conclusion, for the first time, our findings validated DCN's cardioprotective potency against DIC based on its antioxidant, anti-inflammatory, anti-ferroptotic, and anti-apoptotic imprint, chiefly mediated by the NRF2/SLC7A11/GPX4 axis. Accordingly, DCN could represent a promising therapeutic avenue for patients under DOX-dependent chemotherapy.

Antenatal Psychiatric Hospitalization: Factors Associated With Newborns' Custody Under Child Protective Services (CPS).

BACKGROUND: Psychiatric illness during pregnancy is associated with adverse obstetric outcomes, but investigations into its impact on parenting capacity are limited. Child Protective Services (CPS) contact disproportionately impacts families marginalized by poverty, mental health disorders, and substance use disorders. Recently, there have been investigations into the significance of psychiatric illness and nonmental health-related factors that predict CPS custody arrangements. OBJECTIVE: To identify clinical factors associated with newborns' custody under CPS for mothers with antenatal psychiatric hospitalization. METHODS: We conducted a retrospective review of electronic medical records over a 10-year period (2012-2021) for patients who were pregnant during their inpatient psychiatric hospitalizations. We followed 81 patients (18 to 43 years old) who delivered within the hospital. The study endpoint was whether the newborn was placed under CPS custody. For the purposes of this study, psychiatric illness was categorized by the presence or absence of psychotic symptoms. We utilized logistic regressions to investigate the associations of these demographic and clinical factors with the study outcome of CPS custody. RESULTS: For the entire study population, 64.2% of newborns had CPS custody arrangements. In multivariate analysis, after adjusting for potential confounders, patients with psychotic symptoms were at increased odds of having CPS custody arrangements (odds ratio = 8.43; 95% confidence interval 2.16-32.85) compared with patients without psychotic symptoms. Furthermore, multivariate analyses revealed that patients with a history of homelessness also had a higher risk (odds ratio = 6.59; 95% confidence interval: 1.24-35.13) of CPS custody arrangements for their newborns than those without a history of homelessness. CONCLUSIONS: The results of this study suggest that among pregnant and psychiatrically hospitalized patients, those with psychotic symptoms are significantly more likely to have CPS custody arrangements compared to those without psychotic symptoms. However, it is important to note that psychotic symptoms were not definitive for the inability to parent appropriately. In fact, nearly 25% of the study population who had psychotic symptoms were able to successfully transition home with their newborns as mothers. This emphasizes the importance of optimizing the management of psychotic symptoms, particularly among those who have children or plan to have children. The findings of this study also highlight the chronic impacts that those who have struggled with homelessness may experience, including parenting capacity after homelessness resolves.

ß-Catenin alterations in testicular Leydig cell tumour: a immunohistochemical and molecular analysis.

BACKGROUND: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord-stromal tumour in men, representing 1%-3% of all testicular neoplasms. Among testicular sex cord-stromal tumours, CTNNB1 mutations and nuclear expression of ß-catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of ß-catenin alterations remain incompletely understood in this tumour type. METHODS: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using ß-catenin immunohistochemistry and DNA sequencing. RESULTS: Immunohistochemistry revealed focal or multifocal nuclear ß-catenin expression in 47% of the tumours. Diffuse nuclear ß-catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of ß-catenin-positive and ß-catenin-negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional ß-catenin-positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively. CONCLUSION: These results demonstrate that ß-catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of ß-catenin in this tumour type.

Evolution of Testicular Germ Cell Tumors in the Molecular Era With Histogenetic Implications.

The current WHO classification of testicular germ cell tumors is based on the pathogenesis of the tumors driven by different genomic events. The germ cell neoplasia in situ is the precursor lesion for all malignant germ cell tumors. The current understanding of pathogenesis is that the developmental and environmental factors with the erasure of parental genomic imprinting lead to the development of abnormal gonocytes that settle in the "spermatogonial Niche" in seminiferous tubules. The abnormal primordial germ cells in the seminiferous tubules give rise to pre-GCNIS cells under the influence of TPSY and OCT4 genes. The whole genome duplication events give rise to germ cell neoplasia in situ, which further acquires alterations in 12p along with NRAS and KRAS mutations to produce seminoma. A subset of seminomas acquires KIT mutation and does not differentiate further. The remaining KIT-stable seminomas differentiate to nonseminomatous GCTs after obtaining recurrent chromosomal losses, epigenetic modification, and posttranscriptional regulation by multiple genes. Nonseminomatous germ cell tumors also develop directly from differentiated germ cell neoplasia in situ. TP53 pathway with downstream drivers may give rise to somatic-type malignancies of GCT. The GCTs are remarkably sensitive to cisplatin-based combination chemotherapy; however, resistance to cisplatin develops in up to 8% of tumors and appears to be driven by TP53/MDM2 gene mutations. Serum and Plasma miRNAs show promise in diagnosing, managing, and following up on these tumors. The mechanisms underlying the development of most tumors have been elucidated; however, additional studies are required to pinpoint the events directing specific characteristics. Advances in identifying specific molecular markers have been seen recently and may be adopted as gold standards in the future.

Examining the factors contributing to a reduction in hardship financing among inpatient households in India.

In India, the rising double burden of diseases and the low fiscal capacity of the government forces people to resort to hardship financing. This study aimed to examine the factors contributing to the reduction in hardship financing among inpatient households in India. The study relies on two rounds of National Sample Surveys with a sample of 34,478 households from the 71st round (2014) and 56,681 households from the 75th round (2018). We employed multivariable logistic regression and multivariate decomposition analyses to explore the factors associated with hardship financing in Indian households with hospitalized member(s) and assess the contributing factors to the reduction in hardship financing between 2014 and 2018. Notably, though hardship financing for inpatient households has decreased between 2014 and 2018, households with catastrophic health expenditure (CHE) had higher odds of hardship financing than those without CHE. While factors such as CHE, prolonged hospitalization, and private hospitals had impoverishing effects on hardship financing in 2014 and 2018, the decomposition model showed the potential of CHE (32%), length of hospitalization (32%), and private hospitals (24%) to slow down this negative impact over time. The findings showed the potential for further improvements in financial health protection for inpatient care over time, and underscore the need for continuing efforts to strengthen the implementation of public programs and schemes in India such as Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (PMJAY).