NRF2 is a spatiotemporal metabolic hub essential for the polyfunctionality of Th2 cells.

Upon encountering allergens, CD4+ T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.

Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder.

BACKGROUND: Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD. METHODS: A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci. RESULTS: In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E). CONCLUSION: Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.

Effects of changes in daily life attributed to COVID-19 on allergic diseases among Korean adolescents.

OBJECTIVE: The daily lives of adolescents have changed significantly because of COVID-19 pandemic. We investigated the effects of changes in daily life attributed to COVID-19 on allergic diseases among Korean adolescents. METHODS: Data from the 2021 Korea Youth Risk Behavior Survey were used. In total, 54,848 survey participants were included in the analysis. Allergic diseases included allergic rhinitis, atopic dermatitis, and asthma. Changes attributed to COVID-19 included family economic difficulties, physical activity, breakfast skipping frequency, alcohol consumption, smoking, and depressive moods. Chi-square tests and multiple logistic regression analyses were conducted to examine the impact of changes in daily life attributed to COVID-19 on allergic diseases. RESULTS: Among the Korean adolescents surveyed, 29.8% experienced a deterioration in their economic status due to COVID-19, 49.1% reported decreased physical activity, 2.8% reported increased alcohol consumption, 1.0% reported an increase in their smoking behavior, and 36.9% reported an increase in depressive moods. Those diagnosed with atopic dermatitis, allergic rhinitis, or asthma within the previous 12 months accounted for 17.1%, 6.2%, and 1.0% of the population, respectively. Adolescents who were significantly affected by COVID-19 in their daily lives were frequently diagnosed with allergic diseases within the last 12 months. CONCLUSION: Changes in daily life due to COVID-19, including decreased physical activity and increased depressive mood, were common in adolescents and were associated with an increased prevalence of allergic diseases. Since changes in daily life due to the pandemic may increase the burden of allergic disease, additional interventions for disease management should be considered.

Helmet wearing and related factors among electric personal mobility device users in Korea.

Using data from the 2022 Korea Community Health Survey (n = 13 320), this study investigated helmet use and related factors among Korean adults using personal mobility devices, without distinguishing between private and hired users. Among mobility device users, 32.1% responded that they always wore a helmet. The proportion of helmet use was 35.2% among men, 25.8% among women, 29.2% among those aged 19-44 years, 42.3% among those aged 45-64 years and 26.6% among those aged 65 years or older. Furthermore, those who drank less frequently and were physically active were more likely to wear helmets. Moreover, people who always wore a seat belt when driving a car or sitting in the rear seat and people who always wore a helmet when riding a motorcycle were more likely to wear a helmet while using electric personal mobility devices. Approximately one-third of users always wore a helmet. The helmet-wearing rate was related to general characteristics such as gender and education level, and to safety behaviors such as wearing a seat belt when driving a car, sitting in the rear seat of a car, or when riding a motorcycle. In addition to considering personal characteristics investigated in this study, the helmet-wearing rate should be improved through policies or systems at the national or regional levels.

Changes in Daily life due to the COVID-19 Pandemic and Mental Health Status in Korean Adolescents.

This study assessed the relationship between daily life changes and mental health in Korean adolescents during the COVID-19 pandemic. Data from middle and high school students who responded to the relevant survey items the 2021 Korea Youth Risk Behavior Survey were analyzed (n = 53,868). The survey assessed changes in economic status, physical activity, skipping breakfast, drinking, smoking, and mental health, including stress, depression, generalized anxiety disorder, and suicidal ideation, due to the COVID-19 pandemic. The overall prevalence of perceived stress, depression, generalized anxiety disorder, and suicidal ideation was 38.6%, 26.4%, 12.2%, and 12.4%. Adolescents whose economic status worsened due to COVID-19 had a higher risk of perceived stress, depression, generalized anxiety disorder, and suicidal ideation. Changes in physical activity and breakfast consumption due to the COVID-19 pandemic were significantly associated with increases in perceived stress, depression, generalized anxiety disorder, and suicidal ideation. Adolescents who increased their alcohol consumption had the highest risk of perceived stress, depression, generalized anxiety disorder, and suicidal ideation. Changes in economic status and health behaviors caused by the COVID-19 pandemic had a negative effect on the mental health of Korean adolescents. These results can be used to identify adolescents at high risk of developing mental health problems.

Comparison of Lower Extremity Alignment among Taekwondo Athletes of Various Subdisciplines.

Background and Objectives: Studies analyzing lower extremity alignment (LEA) LEA among taekwondo subdisciplines athletes are lacking. This study compared LEA in the dominant and nondominant legs intaekwondo athletes. Materials and Methods: Twelve measurements of LEA were analyzed for 157 athletes (63 sparring, 50 demonstration, and 44 poomsae athletes) registered with the Korea Taekwondo Association. LEA was measured in the standing, supine, and prone positions using alignment application, a goniometer, a bubble inclinometer, a height gage, and a palpation meter. Results: The analysis revealed that the dominant leg of poomsae athletes showed greater genu valgum alignment than that of sparring athletes (p < 0.01), whereas the dominant leg of sparring athletes showed greater rearfoot varum alignment than that of demonstration athletes (p < 0.01). Furthermore, the nondominant leg of poomsae athletes showed greater genu valgum alignment than that of sparring and demonstration athletes (p < 0.01), whereas the nondominant leg of sparring athletes showed greater rearfoot varum alignment than that of demonstration athletes (p < 0.01). In addition, demonstration athletes had better forefoot varus alignment than poomsae athletes (p < 0.01). Conclusions: This study revealed that LEA characteristics vary among taekwondo athletes according to their subdiscipline. The results of this study would help in designing training programs tailored to each subdiscipline that would best address their LEA characteristics and help to prevent injuries.

MRI-based breast cancer radiogenomics using RNA profiling: association with subtypes in a single-center prospective study.

BACKGROUND: There are few prospective studies on the correlations between MRI features and whole RNA-sequencing data in breast cancer according to molecular subtypes. The purpose of our study was to explore the association between genetic profiles and MRI phenotypes of breast cancer and to identify imaging markers that influences the prognosis and treatment according to subtypes. METHODS: From June 2017 to August 2018, MRIs of 95 women with invasive breast cancer were prospectively analyzed, using the breast imaging-reporting and data system and texture analysis. Whole RNA obtained from surgical specimens was analyzed using next-generation sequencing. The association between MRI features and gene expression profiles was analyzed in the entire tumor and subtypes. Gene networks, enriched functions, and canonical pathways were analyzed using Ingenuity Pathway Analysis. The P value for differential expression was obtained using a parametric F test comparing nested linear models and adjusted for multiple testing by reporting Q value. RESULTS: In 95 participants (mean age, 53 years ± 11 [standard deviation]), mass lesion type was associated with upregulation of CCL3L1 (sevenfold) and irregular mass shape was associated with downregulation of MIR421 (sixfold). In estrogen receptor-positive cancer with mass lesion type, CCL3L1 (21-fold), SNHG12 (11-fold), and MIR206 (sevenfold) were upregulated, and MIR597 (265-fold), MIR126 (12-fold), and SOX17 (fivefold) were downregulated. In triple-negative breast cancer with increased standard deviation of texture analysis on precontrast T1-weighted imaging, CLEC3A (23-fold), SRGN (13-fold), HSPG2 (sevenfold), KMT2D (fivefold), and VMP1 (fivefold) were upregulated, and IGLC2 (73-fold) and PRDX4 (sevenfold) were downregulated (all, P < 0.05 and Q < 0.1). Gene network and functional analysis showed that mass type estrogen receptor-positive cancers were associated with cell growth, anti-estrogen resistance, and poor survival. CONCLUSION: MRI characteristics are associated with the different expressions of genes related to metastasis, anti-drug resistance, and prognosis, depending on the molecular subtypes of breast cancer.

Dissecting the PRSS37 interactome and potential mechanisms leading to ADAM3 loss in PRSS37-null sperm.

A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein critical for sperm migration from the uterus into the oviduct and sperm-egg binding in mice. Disruption of PRSS37 results in male infertility concurrent with the absence of mature ADAM3 from cauda epididymal sperm. However, how PRSS37 modulates ADAM3 maturation remains largely unclear. Here, we determine the PRSS37 interactome by GFP immunoprecipitation coupled with mass spectrometry in PRSS37-EGFP knock-in mice. Three molecular chaperones (CLGN, CALR3 and PDILT) and three ADAM proteins (ADAM2, ADAM6B and ADAM4) were identified to be interacting with PRSS37. Coincidently, five of them (except ADAM4) have been reported to interact with ADAM3 precursor and regulate its maturation. We further demonstrated that PRSS37 also interacts directly with ADAM3 precursor and its deficiency impedes the association between PDILT and ADAM3. This could contribute to improper translocation of ADAM3 to the germ cell surface, leading to ADAM3 loss in PRSS37-null mature sperm. The understanding of the maturation mechanisms of pivotal sperm plasma membrane proteins will pave the way toward novel strategies for contraception and the treatment of unexplained male infertility.

GRADE Reporting in Systematic Reviews Published in the Urological Literature (2009-2021).

PURPOSE: We evaluate the reporting of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to rating the certainty of evidence in systematic reviews published in the urological literature. MATERIALS AND METHODS: Based on a predefined protocol, we identified all systematic reviews published in 5 major urological journals from 1998 to 2021 that reported the use of GRADE. Two authors performed study selection and data abstraction independently to assess reporting in accordance with established criteria for applying GRADE. RESULTS: We included 68 of 522 (13.0%) systematic reviews that reported the use of GRADE; the first was published in 2009. Approximately half were published between 2009-2018 (n=36) and the other half between 2019-2021 (n=32). Oncology (24; 35.3%) was the most common clinical topic, and the authors were mostly based in Europe (34; 50%). In their abstract, less than half of all systematic reviews (32; 47.1%) provided any certainty of evidence rating. Only 41 (60.3%) included a tabular result summary in the format of a summary of findings table (24; 35.3%) or evidence profile (17; 25.0%). Few (35.3%) addressed the GRADE certainty of evidence rating in the discussion section. Reporting did not improve over time when comparing the 2 time periods. CONCLUSIONS: Whereas GRADE is increasingly being applied for rating the certainty of evidence, systematic reviews published in the urological literature frequently have not followed established criteria for applying or using GRADE. There is a need for better training of authors and editors, as well as for a GRADE reporting checklist for systematic review authors.

Construction of a CCL20-centered circadian-signature based prognostic model in cervical cancer.

BACKGROUND: Rather low vaccination rates for Human papillomavirus (HPV) and pre-existing cervical cancer patients with limited therapeutic strategies ask for more precise prognostic model development. On the other side, the clinical significance of circadian clock signatures in cervical cancer lacks investigation. METHODS: Subtypes classification based upon eight circadian clock core genes were implemented in TCGA-CESC through k-means clustering methods. Afterwards, KEGG, GO and GSEA analysis were conducted upon differentially expressed genes (DEGs) between high and low-risk groups, and tumor microenvironment (TME) investigation by CIBERSORT and ESTIMATE. Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis. Lastly, FISH and IHC were used for validation of CCL20 expression in patients' specimens and U14 subcutaneous tumor models were built for TME composition. RESULTS: We successfully classified cervical patients into high-risk and low-risk groups based upon circadian-oscillation-signatures. Afterwards, we built a prognostic risk model composed of GJB2, CCL20 and KRT24 with excellent predictive value on patients' overall survival (OS). We then proposed metabolism unbalance, especially for glycolysis, and immune related pathways to be major enriched signatures between the high-risk and low-risk groups. Then, we proposed an 'immune-desert'-like suppressive myeloid cells infiltration pattern in high-risk group TME and verified its resistance to immunotherapies. Finally, CCL20 was proved positively correlated with real-world patients' stages and induced significant less CD8+ T cells and more M2 macrophages infiltration in mouse model. CONCLUSIONS: We unraveled a prognostic risk model based upon circadian oscillation and verified its solidity. Specifically, we unveiled distinct TME immune signatures in high-risk groups.

Efficacy of online cognitive behavioral therapy for nonorganic erectile dysfunction in reproductive-age males during the COVID-19 pandemic: a randomized wait list-controlled trial.

BACKGROUND: Previous research has documented the impact of the COVID-19 pandemic on male sexual and mental health. However, no prior study has evaluated the efficacy of online cognitive behavioral therapy (CBT) during the COVID-19 pandemic for treating nonorganic erectile dysfunction (ED) by improving negative emotions and self-esteem. AIM: To test the efficacy of online CBT for nonorganic ED during the COVID-19 pandemic in Shanghai, China. METHODS: A randomized controlled trial was conducted during the COVID-19 pandemic. Paired t-tests and 1-way analysis of variance were used to analyze and compare erectile functioning, self-esteem, and emotional state between and within groups. OUTCOMES: The main outcome measures included scores on the 5-item International Index of Erectile Function, Rosenberg Self-esteem Scale, 9-item Patient Health Questionnaire, and 7-item Generalized Anxiety Disorder scale to evaluate erectile functioning, self-esteem, depression, and anxiety, respectively. RESULTS: In the CBT group, erectile functioning, intercourse satisfaction, orgasmic functioning, sexual desire, and overall satisfaction were significantly improved at posttreatment as compared with pretreatment (P < .05). After treatment, group differences in emotional state and self-esteem were observed between the CBT group and the control group. Results revealed that the CBT group had significantly better scores than the control group at posttreatment on the Rosenberg Self-esteem Scale (mean ± SD, 30.43 ± 6.51 vs 22.67 ± 10.74), Patient Health Questionnaire (7.07 ± 2.74 vs 11.07 ± 4.41), and Generalized Anxiety Disorder scale (8.36 ± 1.97 vs 11.13 ± 3.94; P < .05). CLINICAL IMPLICATIONS: This study represents an important advance in understanding of the efficacy of online CBT for treating nonorganic ED in reproductive-age males during the COVID-19 pandemic. STRENGTHS AND LIMITATIONS: The study participants, treatment modality, and COVID-19 pandemic background of this study are innovative and therefore strengths. However, our study has several limitations-namely, its sample size and use of self-report data to measure erectile functioning due to the pandemic. Further studies should incorporate sexual functioning-monitoring instruments as well as self-report data to measure erectile function. CONCLUSION: Online CBT clearly improved the emotional state and self-esteem of patients with ED during the COVID-19 pandemic.

Vascular and metabolic effects of ipragliflozin versus sitagliptin (IVS) in type 2 diabetes treated with sulphonylurea and metformin: IVS study.

OBJECTIVE: In patients with type 2 diabetes who were inadequately controlled with metformin and sulphonylurea, we compared the glucose-lowering efficacy, cardiometabolic parameters and safety of two drugs, ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, and sitagliptin, a dipeptidyl peptidase-4 inhibitor. MATERIALS AND METHODS: Patients with 7.5%-9.0% glycated haemoglobin treated with metformin and sulphonylurea were randomly assigned to ipragliflozin (50 mg, n = 70) or sitagliptin (100 mg, n = 70) therapy for 24 weeks. Measures of glycaemic control, fatty liver indices, other metabolic parameters and subclinical atherosclerosis were compared by a paired t-test before and after 24 weeks of treatment. RESULTS: Mean glycated haemoglobin levels decreased from 8.5% to 7.5% in the ipragliflozin group and from 8.5% to 7.8% in the sitagliptin group, resulting in a 0.34% between-group difference (95% confidence interval, 0.10%-0.43%, p = .088). Fasting and postprandial 2-h glucose levels also showed a similar trend, with a greater reduction with ipragliflozin therapy. An increase of over 70% in ketone levels and a decrease in whole body and abdominal fat masses were observed with ipragliflozin treatment. Fatty liver indices also improved with ipragliflozin treatment. Despite no difference in carotid intima-media thickness and ankle-brachial index, ipragliflozin therapy improved flow-mediated vasodilation, reflecting endothelial function, while sitagliptin did not. The safety profile did not differ between the two groups. CONCLUSIONS: Ipragliflozin add-on therapy can be a viable option for better glycaemic control with multiple vascular and metabolic benefits in patients with type 2 diabetes who are inadequately controlled with metformin and sulphonylurea.

Etiology and Clinical Characteristics of Community-Acquired Pneumonia in Korean Children During the Pre-COVID-19 Period, 2015-2020.

BACKGROUND: There have been many epidemiologic studies on community-acquired pneumonia (CAP) among children, most of which had substantial limitations. This study investigated the etiologic distribution and clinical characteristics of CAP in Korean children for 5 years before the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective analysis of children hospitalized for CAP at 4 referral hospitals during 2015-2020 was performed. Cases in which bronchiolitis was suspected or pulmonary infiltration was not evident on chest radiography (CXR) were excluded. Viruses and atypical bacteria were defined as detected when positive in the polymerase chain reaction test performed for respiratory specimens. Serologic testing result for Mycoplasma pneumoniae was incorporated with strict interpretation. Pyogenic bacteria were included only when cultured in blood, pleural fluid, or bronchoalveolar lavage, but those cultured in endotracheal aspirate or sputum when the case was clinically evident bacterial pneumonia were also included. RESULTS: A total of 2,864 cases of suspected pneumonia were selected by diagnosis code and CXR findings. Medical chart and CXR review excluded nosocomial pneumonia and cases without evident infiltration, resulting in 517 (18.1%) CAP cases among 489 children. Regarding clinical symptoms, high fever was present in 59.4% and dyspnea in 19.9% of cases. Respiratory support was required for 29.2% of patients, including mechanical ventilation for 3.9%. Pathogens were detected in 49.9% of cases, with viruses in 32.3%, atypical bacteria in 17.8%, and pyogenic bacteria in 2.3% of cases. As single pathogens, M. pneumoniae (16.8%) and respiratory syncytial virus (RSV, 13.7%) were the most common. Parenteral ß-lactam and macrolide antibiotics were administered in 81.6% and 50.7% of cases, respectively. A total of 12 (2.3%) cases resulted in poor outcomes, including 3 deaths. CONCLUSION: M. pneumoniae and RSV were the most commonly detected pathogens of pediatric CAP, which was selected by strict clinical and radiologic criteria. It is necessary to carefully decide whether to use parenteral antibiotics based on the epidemiology and clinical features of CAP in children.

Health behaviors according to the ability to understand health information in Korean adults.

This study aimed to verify the relationship between the level of understanding of health information and health behaviors among Korean adults. In total, 228 984 adults who participated in the 2021 Korea Community Health Survey were included. Participants were divided into three groups according to age (19-44, 45-64 and 65+). The ability to understand verbal and written health information was included, and its association with health behaviors, including smoking, alcohol consumption and preventive health service uptake, was assessed. Associations between the ability to understand health information and health behaviors were analyzed using chi-squared tests and multiple logistic regression analyses. Approximately 22.7% and 20% of the participants responded that verbal and written health information were easy to understand, respectively, with significant differences by age group. Compared to those with easy-to-understand verbal health information, those with difficulty in understanding had a higher risk of current cigarette smoking and monthly drinking and were less likely to engage in more than moderate physical activity, walking, influenza vaccination in 1 year, cancer examination in 2 years and medical examination in 2 years. Difficulty in understanding or no interest in written health information was also associated with unhealthy behaviors. A strong ability to understand health information is related to positive health behaviors. However, there are differences in the associations by age group, which should be considered when establishing a health literacy improvement strategy. These findings could promote health literacy and ultimately contribute to helping individuals make better choices for positive health behaviors.

Whole Transcriptome Analysis of Hypothalamus in Mice during Short-Term Starvation.

Molecular profiling of the hypothalamus in response to metabolic shifts is a critical cue to better understand the principle of the central control of whole-body energy metabolism. The transcriptional responses of the rodent hypothalamus to short-term calorie restriction have been documented. However, studies on the identification of hypothalamic secretory factors that potentially contribute to the control of appetite are lacking. In this study, we analyzed the differential expression of hypothalamic genes and compared the selected secretory factors from the fasted mice with those of fed control mice using bulk RNA-sequencing. We verified seven secretory genes that were significantly altered in the hypothalamus of fasted mice. In addition, we determined the response of secretory genes in cultured hypothalamic cells to treatment with ghrelin and leptin. The current study provides further insights into the neuronal response to food restriction at the molecular level and may be useful for understanding the hypothalamic control of appetite.

Fosfomycin for Antibiotic Prophylaxis in Men Undergoing a Transrectal Prostate Biopsy: A Systematic Review and Meta-Analysis.

Background and Objectives: To assess the effects of fosfomycin compared with other antibiotics as a prophylaxis for urinary tract infections (UTIs) in men undergoing transrectal prostate biopsies. Materials and Methods: We searched multiple databases and trial registries without publication language or status restrictions until 4 January 2022. Parallel-group randomized controlled trials (RCTs) and non-randomized studies (NRS) were included. The primary outcomes were febrile UTI, afebrile UTI, and overall UTI. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs. The protocol was registered with PROSPERO (CRD42022302743). Results: We found data on five comparisons; however, this abstract focuses on the primary outcomes of the two most clinically relevant comparisons. Regarding fosfomycin versus fluoroquinolone, five RCTs and four NRSs with a one-month follow-up were included. Based on the RCT evidence, fosfomycin likely resulted in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to four fewer febrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in afebrile UTIs compared with fluoroquinolone. This difference corresponded to 29 fewer afebrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in overall UTIs compared with fluoroquinolone. This difference corresponded to 35 fewer overall UTIs per 1000 patients. Regarding fosfomycin and fluoroquinolone combined versus fluoroquinolone, two NRSs with a one- to three-month follow-up were included. Based on the NRS evidence, fosfomycin and fluoroquinolone combined may result in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to 16 fewer febrile UTIs per 1000 patients. Conclusions: Compared with fluoroquinolone, fosfomycin or fosfomycin and fluoroquinolone combined may have a similar prophylactic effect on UTIs after a transrectal prostate biopsy. Given the increasing fluoroquinolone resistance and its ease to use, fosfomycin may be a good option for antibiotic prophylaxis.

Decreased CD44v3 expression impairs endometrial stromal cell proliferation and decidualization in women with recurrent implantation failure.

BACKGROUND: The precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) remains unclear. This study was aimed at exploring the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF. METHODS: Mid-secretory phase endometrial tissue samples were obtained from the following two groups of women who had undergone IVF: (a) 24 patients with RIF and (b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed using immunohistochemistry, qPCR, and western blotting. Effects of overexpression and knockdown of CD44v3 on proliferation and decidualization of immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and western blot analysis. A heterologous coculture system of embryo implantation was constructed to mimic the process of trophoblast invasion during implantation. RESULTS: The expression of CD44v3 was significantly higher in the mid-secretory phase of endometrial stromal cells than in the proliferation phase, but was notably lower in RIF patients. Knockdown of CD44v3 significantly downregulated cell proliferation both in T-HESCs and HESCs. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following the knockdown of CD44v3, whereas the expression of both PRL and IGFBP1 increased after its overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed significant deficiency in supporting trophoblast outgrowth in a coculture system of embryo implantation; however, overexpression of CD44v3 in HESCs promoted trophoblast outgrowth. CONCLUSION: The reduced expression of CD44v3 suppresses the proliferation and decidualization of HESCs, which might play a pivotal role in poor endometrial receptivity in women with RIF.

Shikonin N-benzyl matrinic acid ester derivatives as novel telomerase inhibitors with potent activity against lung cancer cell lines.

In this study, a series of novel shikonin N-benzyl matrinic acid ester derivatives (PMMB-299-PMMB-310) were synthesized and tested for their ability to inhibit the proliferation of cancer cells. Compared with shikonin and matrine, some of the ester derivatives were found to exhibit better anti-proliferative activity against seven different cancer cell lines, with less cytotoxicity toward non-cancerous cells. The strongest anti-proliferative activity was exhibited by PMMB-302, which had an IC50 value of 2.71 µM against A549 cells. The compound caused cell cycle arrest in the G2/M phase and induced apoptosis. Effects on the expression of apoptosis-related molecules such as Bcl2, Bcl-XL, caspase-3, caspase-9 and FADD suggested that PMMB-302 has tumor suppressive roles in lung cancer cells. In addition, PMMB-302 inhibited expression of telomerase core proteins, dyskerin and NHP2, and telomerase reverse transcriptase RNA. Moreover, molecular docking of PMMB-302 was subsequently conducted to determine the probable binding mode with telomerase. Taken together, the results indicate that PMMB-302 acts as a tumor suppressor in lung cancer cells by negatively regulating telomerase expression.

Increased expression of HMGB1 in the implantation phase endometrium is related to recurrent implantation failure.

BACKGROUND: Impaired endometrial receptivity was the main cause of recurrent implantation failure (RIF); however, its underlying mechanisms had not been elucidated. This study aimed to determine the expression level of high-mobility group box protein 1 (HMGB1) in the endometrium with RIF and its effect on endometrial receptivity. METHODS AND RESULTS: Genome-wide expression profiling, real-time reverse transcription PCR, immunohistochemical staining, western blot, and in vitro assays were performed in this study. We found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility and successfully achieve conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to that in the control group (P = 0.001), consistent with the results of the genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells dramatically displayed a marked deficiency in supporting blastocysts and human embryonic JAR cells adhesion, which mimic the process of embryo adhesion. CONCLUSION: These findings strongly indicated that increased HMGB1 levels suppressed the epithelial cell adhesion capability, therefore contributing to impaired endometrial receptivity in patients with recurrent implantation failure, which can be used as a target for the recognition and treatment of recurrent implantation failure in clinical practice.

Croup as a Manifestation of SARS-CoV-2 Omicron Variant Infection in Young Children.

Croup is an acute upper respiratory disease primarily caused by the parainfluenza virus. Owing to inflammation and edema of the upper airways, children present with barky cough and stridor, and some may experience respiratory distress. We investigated children aged < 5 years with coronavirus disease 2019 (COVID-19) admitted to two hospitals in Seoul, South Korea, and observed a spike in croup cases during the omicron surge. Among the 569 children admitted from March 1, 2021 to February 25, 2022, 21 children (3.7%) had croup, and the proportion of croup cases was significantly higher during the omicron wave than that during the delta wave (12.4% vs. 1.2%, P < 0.001). With the immediate administration of corticosteroids and epinephrine via nebulizer, the symptoms improved rapidly. During the current omicron surge, careful monitoring of the symptoms of croup in young children is needed for the diagnosis of COVID-19 and its timely management.