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PurposeTo assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM).MethodsIn this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality.ResultsAmong eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality.ConclusionsPatients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

BACKGRUOUND: Phospholipase C-γ (PLC-γ) plays a crucial role in immune responses and is related to the pathogenesis of various inflammatory disorders. In this study, we investigated the role of PLC-γ and the therapeutic effect of the PLC-specific inhibitor U73122 using orbital fibroblasts from patients with Graves orbitopathy (GO). METHODS: The expression of phospholipase C gamma 1 (PLCG1) and phospholipase C gamma 2 (PLCG2) was evaluated using polymerase chain reaction in GO and normal orbital tissues/fibroblasts. The primary cultures of orbital fibroblasts were treated with non-toxic concentrations of U73122 with or without interleukin (IL)-1β to determine its therapeutic efficacy. The proinflammatory cytokine levels and activation of downstream signaling molecules were determined using Western blotting. RESULTS: PLCG1 and PLCG2 mRNA expression was significantly higher in GO orbital tissues than in controls (P

PurposeTo explore if orbital fat-to-muscle ratio (FMR) is predictive of whether surgical decompression or teprotumumab leads to greater proptosis reduction in thyroid eye disease (TED).MethodsA single-center retrospective cohort study comparing surgical decompression with teprotumumab according to FMR. All TED patients completing an 8-dose course of teprotumumab between January 2020 and September 2022 and all patients undergoing bony orbital decompression from January 2017 to December 2019 were included. Subjects were excluded if they were

PURPOSE: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens. METHODS: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls. RESULTS: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048). CONCLUSIONS: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more intense inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease.

This paper examines the cyclicality of remittance inflows to economies in Asia and the Pacific, aiming to identify major factors associated with remittances using gravity models of bilateral remittances. An analysis that assesses correlation coefficients between the cyclical factors of remittances and gross domestic product suggests that remittances tend to be countercyclical, or acyclical, against the business cycle of the remittance-receiving economy relative to the sending economy. This observation is confirmed by the gravity models of bilateral remittances. Furthermore, the estimation results suggest that migrant stock is one of the most significant factors affecting bilateral remittances. The study also shows that an increase in bilateral remittances can be attributed to a higher occurrence of disasters triggered by natural hazards in receiving economies, an appreciation of the receiving economy’s currency value against the sending economy’s, a lower interest rate differential (receiver–sender), greater capital account openness, more political instability, and lower costs of remittances.

Abstract Thermoelectric effects refer to the voltage generation from temperature gradients in condensed matter. Although various power generators are made from them, all the known effects, such as Seebeck effect, require macroscopic temperature gradients; since the sign of the generated voltage is reversed by reversing the temperature gradient, the net voltage disappears when the temperature distribution fluctuates temporarily or spatially with a macroscopic temperature gradient of zero. It is impossible to utilize such temperature fluctuations in the conventional thermoelectric effects, a situation which limits their application. Here we report the observation of a second-order nonlinear thermoelectric effect; we develop a method to measure nonlinear thermoelectricity and observe that a superconducting MoGe film on Y3Fe5O12 generates a voltage proportional to the square of the applied temperature gradient. The nonlinear thermoelectric generation demonstrated here provides a way for making power generators that produce electric power from temperature fluctuations.

Yunosuke Usui,1 Miki Ono,1 Rintaro Nibuya,1 Masayuki Kikkawa,1 Shunichiro Ito,1 Chihiro Morishita,1 Mina Honyashiki,1 Yu Tamada,1,2 Takeshi Inoue,1 Jiro Masuya1 1Department of Psychiatry, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan; 2Department of Psychiatry, Tokyo Medical University Hachioji Medical Center, Hachioji-shi, Tokyo, JapanCorrespondence: Jiro Masuya, Department of Psychiatry, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan, Tel +81-(0)3-3342-6111, Email j-masuya@tokyo-med.ac.jpBackground: Prior research has shown that inappropriate childhood nurturing experiences (low care and high overprotection), trait anxiety, and depressive rumination are risk factors for depression. However, no studies to date have analyzed the overall association between these factors and depressive symptoms. In the present study, we hypothesized that depressive rumination mediates the impacts of inappropriate childhood nurturing experiences on depressive symptoms, and that these mediating effects are moderated by trait anxiety, and tested these hypotheses in adult volunteers.Methods: The subjects were adult volunteers who were investigated between April 2017 and April 2018. A self-report questionnaire on demographic data, childhood nurturing experiences, trait anxiety, depressive rumination, and depressive symptoms was distributed to conduct the survey, and written informed consent and valid responses were obtained from 585 subjects. Mediation and moderated-mediation analyses were performed by SPSS 28 and macro PROCESS 4.0 software. This study was approved by the Ethics Committee of Tokyo Medical University.Results: Parental care showed a significant negative indirect effect on depressive symptoms via its effect on depressive rumination (p < 0.01), whereas parental overprotection showed the opposite effect (p < 0.01). Furthermore, the mediation effect of depressive rumination on depressive symptoms was increased by trait anxiety (p < 0.05).Conclusion: Our present study demonstrated that the main factor affecting depressive symptoms is inappropriate childhood nurturing experiences, which indirectly enhance depression by intensifying depressive rumination, and that depressive rumination and trait anxiety mutually reinforce each other to enhance depressive symptoms. These findings may be useful for the prevention of depressive symptoms. Large-scale prospective studies are needed to confirm the causal associations among these factors in the future.Keywords: childhood parenting experiences, depressive rumination, trait anxiety, depressive symptoms, moderated-mediation analysis

Abstract Background The human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate source of stem cells for regenerative medicine. The major challenge of allogeneic hiPSC-derived cell products is their immunogenicity. The hypoimmunogenic cell strategy is allogenic cell therapy without using immune suppressants. Advances in gene engineering technology now permit the generation of hypoimmunogenic cells to avoid allogeneic immune rejection. In this study, we generated a hypoimmunogenic hiPSC (HyPSC) clone that had diminished expression of human leukocyte antigen (HLA) class Ia and class II and expressed immune checkpoint molecules and a safety switch. Methods First, we generated HLA class Ia and class II double knockout (HLA class Ia/II DKO) hiPSCs. Then, a HyPSC clone was generated by introducing exogenous β-2-microglobulin (B2M), HLA-G, PD-L1, and PD-L2 genes, and the Rapamycin-activated Caspase 9 (RapaCasp9)-based suicide gene as a safety switch into the HLA class Ia/II DKO hiPSCs. The characteristics and immunogenicity of the HyPSCs and their derivatives were analyzed. Results We found that the expression of HLA-G on the cell surface can be enhanced by introducing the exogenous HLA-G gene along with B2M gene into HLA class Ia/II DKO hiPSCs. The HyPSCs retained a normal karyotype and had the characteristics of pluripotent stem cells. Moreover, the HyPSCs could differentiate into cells of all three germ layer lineages including CD45+ hematopoietic progenitor cells (HPCs), functional endothelial cells, and hepatocytes. The HyPSCs-derived HPCs exhibited the ability to evade innate and adaptive immunity. Further, we demonstrated that RapaCasp9 could be used as a safety switch in vitro and in vivo. Conclusion The HLA class Ia/II DKO hiPSCs armed with HLA-G, PD-L1, PD-L2, and RapaCasp9 molecules are a potential source of stem cells for allogeneic transplantation.

OBJECTIVE: COVID-19 would kill fewer people if health programmes can predict who is at higher risk of mortality because resources can be targeted to protect those people from infection. We predict mortality in a very large population in Mexico with machine learning using demographic variables and pre-existing conditions. DESIGN: Cohort study. SETTING: March 2020 to November 2021 in Mexico, nationally represented. PARTICIPANTS: 1.4 million laboratory-confirmed patients with COVID-19 in Mexico at or over 20 years of age. PRIMARY AND SECONDARY OUTCOME MEASURES: Analysis is performed on data from March 2020 to November 2021 and over three phases: (1) from March to October in 2020, (2) from November 2020 to March 2021 and (3) from April to November 2021. We predict mortality using an ensemble machine learning method, super learner, and independently estimate the adjusted mortality relative risk of each pre-existing condition using targeted maximum likelihood estimation. RESULTS: Super learner fit has a high predictive performance (C-statistic: 0.907), where age is the most predictive factor for mortality. After adjusting for demographic factors, renal disease, hypertension, diabetes and obesity are the most impactful pre-existing conditions. Phase analysis shows that the adjusted mortality risk decreased over time while relative risk increased for each pre-existing condition. CONCLUSIONS: While age is the most important predictor of mortality, younger individuals with hypertension, diabetes and obesity are at comparable mortality risk as individuals who are 20 years older without any of the three conditions. Our model can be continuously updated to identify individuals who should most be protected against infection as the pandemic evolves.

PURPOSE: Graves orbitopathy (GO) is an orbital manifestation of autoimmune Graves disease, and orbital fibroblast is considered a target cell, producing pro-inflammatory cytokines and/or differentiating into adipocytes. Adipose tissue has been focused on as an endocrine and inflammatory organ secreting adipokines. We investigated the pathogenic role of a specific adipokine, adipsin, known as complement factor D in Graves orbital fibroblasts. METHODS: The messenger RNA (mRNA) expression of multiple adipokines was investigated in adipose tissues harvested from GO and healthy subjects. Adipsin protein production was analyzed in primary cultured orbital fibroblasts under insulin growth factor (IGF)-1, CD40 ligand (CD40L) stimulation, and adipogenesis. The effect of blocking adipsin with small interfering RNA (siRNA) on pro-inflammatory cytokine production and adipogenesis was evaluated using quantitative real-time PCR, Western blot, and ELISA. Adipogenic differentiation was identified using Oil Red O staining. RESULTS: Adipsin gene expression was significantly elevated in GO tissue and increased after the stimulation of IGF-1 and CD40L, as well as adipocyte differentiation in GO cells. Silencing of adipsin suppressed IGF-1-induced IL-6, IL-8, COX2, ICAM-1, CCL2 gene expression, and IL-6 protein secretion. Adipsin suppression also attenuated adipocyte differentiation. Exogenous treatment of recombinant adipsin resulted in the activation of the Akt, ERK, p-38, and JNK signaling pathways. CONCLUSIONS: Adipsin, secreted by orbital fibroblasts, may play a distinct role in the pathogenesis of GO. Inhibition of adipsin ameliorated the production of pro-inflammatory cytokines and adipogenesis in orbital fibroblasts. Our study provides an in vitro basis suggesting adipsin as a potential therapeutic target for GO treatment.

PurposeTo assess the association between thyroid eye disease (TED) and glaucoma.MethodsPatients 18 years of age and over enrolled in the NIH All of Us Research Program, a nationwide cohort, were extracted. Those with conditions relating to TED were identified and compared with 2020 US Census-matched controls without a diagnosis of TED in a 1:4 ratio. The authors used Pearson's χ 2 tests to study demographics by TED status, and logistic regression to generate odds ratios and 95% confidence intervals to evaluate the association between TED and glaucoma (any type, including glaucoma suspect), using those without TED as the reference group. Multivariable models were adjusted for age, gender, race/ethnicity, eye doctor visits, and smoking status.ResultsA total of 393 cases of TED and 1,572 US Census-matched controls were identified. The median age of the cohort was 63 years (interquartile range: 48-73 years). Age, gender, and race/ethnicity varied by TED status ( p < 0.001). Overall, 114 (29.0%) of TED cases had a diagnosis of glaucoma, compared with 94 (6.0%) of non-TED controls. On bivariate logistic regression models, those diagnosed with TED were significantly more likely to be diagnosed with glaucoma compared with controls (odds ratio: 6.42; 95% confidence interval: 4.76-8.70; p < 0.001). This trend persisted on multivariable logistic regression controlling for confounding factors (odds ratio: 3.37; 95% confidence interval: 1.85-6.20 p < 0.001).ConclusionsIndividuals with TED were significantly more likely to be diagnosed with glaucoma. Clinicians caring for patients with TED should be aware of this elevated risk and arrange glaucoma evaluation, accordingly.

Eiji Kose,1 Taesong An,2 Akihiko Kikkawa,2 Yoshiaki Matsumoto,3 Hiroyuki Hayashi1 1Department of Pharmacotherapy, School of Pharmacy, Nihon University, Funabashi, 2Yokosuka Kyousai Hospital, Yokosuka, 3Department of Clinical Pharmacokinetics, School of Pharmacy, Nihon University, Funabashi, Japan Background: Chronic kidney disease (CKD) is associated with a high risk of cardiovascular disease complications. Therefore, medical institutions conduct educational hospitalization for early treatment and education of CKD patients. However, patients who have been discharged after achieving educational targets can end up showing poor symptoms at home. There also have been several cases of rehospitalization or disease aggravation. In this study, we analyzed rehospitalized patients who were discharged from the hospital after CKD educational hospitalization and investigated the purpose of analyzing rehospitalization factors. Materials and methods: This was an observational case-control study conducted at Yokosuka Kyousai Hospital. We performed univariate analysis using patient background features and laboratory data between a rehospitalization group and a no-rehospitalization group. Next, we performed multiple logistic regression analysis using the results of the univariate analysis. Results: From the results of this study, we identified independent risk factors, such as serum albumin level, heart-failure complications, and estimated glomerular filtration rate (eGFR). Moreover, the serum Alb level was identified as the most important risk factor for rehospitalization. Therefore, we considered that it is important to live a life that makes it possible to maintain CKD stage G3b for a long time after discharge, because the cutoff level of eGFR is 31 mL/minute/1.73 m2. Conclusion: We believe that it is important to educate patients, their families, and medical staff on the importance of early detection and treatment, and we consider that this approach is important to inclusively protect the kidney. Keywords: albumin, glomerular filtration rate, cardiovascular disease, stages of chronic kidney disease

Abstract. Background. We investigated potential disparities in health-related quality of life, particularly concerning urinary function, between patients with preserved and those with impaired sexual function after robot-assisted radical prostatectomy (RARP). Materials and methods. Between December 2012 and April 2020, 704 men underwent RARP in our hospital. This study included 155 patients with a preoperative 5-item International Index of Erectile Function (IIEF-5) of ≥12 points and an assessable IIEF-5 at 12 months postoperatively. Health-related quality of life was assessed using the 8-item Short-Form Health Survey and Expanded Prostate Cancer Index Composite (EPIC) preoperatively and at 3, 6, and 12 months postoperatively. A logistic regression analysis and Wilcoxon rank sum tests were performed. Results. Patients were grouped according to the median IIEF-5 score 12 months after surgery: those with preserved sexual function (n = 71) and those with impaired sexual function (n = 84). The mental component summary of the 8-item Short-Form Health Survey was better in the group with preserved sexual function at 6 months postoperatively than in the group with impaired sexual function (p < 0.01). In the EPIC, the group with preserved sexual function performed better not only in the sexual domain but also in the urinary domain at all time points compared with the group with impaired sexual function (p < 0.01). In the comparison of the urinary subdomains of the EPIC, there were no significant differences in urinary function or incontinence, but there were significant differences in urinary distress and irritative/obstructive scores (p < 0.01). Conclusions. Patients with preserved postoperative sexual function after RARP showed better urinary function than those with impaired sexual function. Hence, preserved sexual function is closely associated with urinary function.

Abstract Background Emphysematous pyelonephritis represents an acute and necrotizing infection characterized by the accumulation of gas within the kidney. This condition poses a swift progression toward sepsis, leading to a poor prognosis. We experienced a rare case of emphysematous pyelonephritis in a nonfunctioning renal allograft attributed to antibody‐mediated rejection after kidney transplantation. Case presentation A 71-year-old man with diabetes had undergone living-donor renal transplantation from his wife. Unfortunately, the transplanted kidney’s function declined due to antibody-mediated rejection, necessitating the introduction of hemodialysis 12 months post-transplantation. Subsequently, 4 months after initiating hemodialysis, the patient presented with pain and swelling in the right lower abdomen. A computed tomography scan revealed the enlargement of the transplanted kidney and gas formation. This constellation of symptoms led to the diagnosis of emphysematous pyelonephritis, resulting in his hospitalization. Further contrast-enhanced computed tomography scans demonstrated an absence of arterial flow and ischemia within the renal allograft. Despite antibiotic treatment and percutaneous drainage, both the gas and fluid in the renal parenchyma and surrounding tissue displayed minimal reduction. Given these compelling findings, an allograft nephrectomy was performed 20 days into his hospital stay. Pathological examination confirmed complete allograft necrosis, revealing nonviable renal parenchyma. The patient’s postoperative recovery progressed favorably. Conclusions Instances of emphysematous pyelonephritis within transplanted kidneys are infrequently documented. Among these cases, emphysematous pyelonephritis in a nonfunctioning renal allograft is very rare and may be associated with graft ischemia and the presence of injured tissue. The determination of an immediate diagnosis and surgery is important.

Abstract Sex bias is known in the prevalence/pathology of neurodevelopmental disorders. Sex-dependent differences of the certain brain areas are known to emerge perinatally through the exposure to sex hormones, while gene expression patterns in the rodent embryonic brain does not seem to be completely the same between male and female. To investigate potential sex differences in gene expression and cortical organization during the embryonic period in mice, we conducted a comprehensive analysis of gene expression for the telencephalon at embryonic day (E) 11.5 (a peak of neural stem cell expansion) and E14.5 (a peak of neurogenesis) using bulk RNA-seq data. As a result, our data showed the existence of notable sex differences in gene expression patterns not obviously at E11.5, but clearly at E14.5 when neurogenesis has become its peak. These data can be useful for exploring potential contribution of genes exhibiting sex differences to the divergence in brain development. Additionally, our data underscore the significance of studying the embryonic period to gain a deeper understanding of sex differences in brain development.

Yoshio Iwata,1 Miki Ono,1 Yoshitaka Ishii,1 Shunichiro Ito,1 Masayuki Kikkawa,1 Chihiro Morishita,1 Yu Tamada,1,2 Mina Honyashiki,1 Takeshi Inoue,1 Jiro Masuya1 1Department of Psychiatry, Tokyo Medical University, Tokyo, Japan; 2Department of Psychiatry, Tokyo Medical University Hachioji Medical Center, Tokyo, JapanCorrespondence: Jiro Masuya, Department of Psychiatry, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan, Tel +81-3-3342-6111, Email j-masuya@tokyo-med.ac.jpBackground: The experience of peer victimization in childhood increases the risk of developing anxiety disorders and depression, risk of suicide, as well as sensitivity to stress, in adulthood. Various personality traits are known to be associated with these effects. However, the influence of trait anxiety on job stress has not yet been reported. In the present study, we tested the hypothesis that the experience of peer victimization in childhood and trait anxiety influence job stress in adulthood.Methods: A questionnaire survey, including State-Trait Anxiety Inventory, Childhood Victimization Rating Scale, and Brief Job Stress Questionnaire, was administered to 566 adult workers. The interrelationship between multiple variables was analyzed by multiple regression analysis and path analysis.Results: In the path model, childhood peer victimization had a positive direct effect on trait anxiety and the psychological and physical stress response (PPSR). Trait anxiety had a positive direct effect on job stressors and PPSR, and job stressors had a positive direct effect on PPSR. Regarding indirect effects, childhood peer victimization had a significant adverse effect on job stressors and PPSR via trait anxiety.Conclusion: Our results showed that childhood peer victimization has a negative impact on job stress in adulthood, which is influenced by trait anxiety. Interventions to address peer victimization in childhood and trait anxiety may reduce job stress in adulthood, and thus contribute to improved occupational mental health and productivity in the workplace.Keywords: job stress, peer victimization, trait anxiety, path analysis, mediation effect

Abstract Background Recent studies have shown that prenatal BPA exposure altered the transcriptome profiles of autism-related genes in the offspring’s hippocampus, disrupting hippocampal neuritogenesis and causing male-specific deficits in learning. However, the sex differences in the effects of prenatal BPA exposure on the developing prefrontal cortex, which is another brain region highly implicated in autism spectrum disorder (ASD), have not been investigated. Methods We obtained transcriptome data from RNA sequencing analysis of the prefrontal cortex of male and female rat pups prenatally exposed to BPA or control and reanalyzed. BPA-responsive genes associated with cortical development and social behaviors were selected for confirmation by qRT-PCR analysis. Neuritogenesis of primary cells from the prefrontal cortex of pups prenatally exposed to BPA or control was examined. The social behaviors of the pups were assessed using the two-trial and three-chamber tests. The male-specific impact of the downregulation of a selected BPA-responsive gene (i.e., Sema5a) on cortical development in vivo was interrogated using siRNA-mediated knockdown by an in utero electroporation technique. Results Genes disrupted by prenatal BPA exposure were associated with ASD and showed sex-specific dysregulation. Sema5a and Slc9a9, which were involved in neuritogenesis and social behaviors, were downregulated only in males, while Anxa2 and Junb, which were also linked to neuritogenesis and social behaviors, were suppressed only in females. Neuritogenesis was increased in males and showed a strong inverse correlation with Sema5a and Slc9a9 expression levels, whereas, in the females, neuritogenesis was decreased and correlated with Anxa2 and Junb levels. The siRNA-mediated knockdown of Sema5a in males also impaired cortical development in utero. Consistent with Anxa2 and Junb downregulations, deficits in social novelty were observed only in female offspring but not in males. Conclusion This is the first study to show that prenatal BPA exposure dysregulated the expression of ASD-related genes and functions, including cortical neuritogenesis and development and social behaviors, in a sex-dependent manner. Our findings suggest that, besides the hippocampus, BPA could also exert its adverse effects through sex-specific molecular mechanisms in the offspring’s prefrontal cortex, which in turn would lead to sex differences in ASD-related neuropathology and clinical manifestations, which deserves further investigation.

Introduction Fournier's gangrene refers to a necrotizing fasciitis that mainly affects the perineal region and a condition that requires immediate debridement. This case involved elective debridement of Fournier's gangrene after the general condition was improved through antibiotic treatment instead of requesting an emergency debridement. Case presentation The patient was an 85‐year‐old man with a performance status of 4 admitted to a nursing home. He was transferred by ambulance with a fever. Blood tests showed a markedly elevated inflammatory response, and computed tomography revealed widespread aerodermectasia around the right testis to the lower abdomen. The patient was diagnosed with Fournier's gangrene. However, his family declined emergency surgical debridement. The patient's general condition was improved with antibiotics, and debridement was eventually performed. After 52 days of hospitalization, the patient was transferred to another hospital. Conclusion This study describes the successful treatment of Fournier's gangrene through conservative treatment followed by elective debridement.