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IntroductionStaphylococcus aureus, is a pathogen commonly encountered in both community and hospital settings. Patients receiving hemodialysis treatment face an elevated risk of vascular access infections (VAIs) particularly Staphylococcus aureus, infection. This heightened risk is attributed to the characteristics of Staphylococcus aureus, , enabling it to adhere to suitable surfaces and form biofilms, thereby rendering it resistant to external interventions and complicating treatment efforts.MethodsTherefore this study utilized PCR and microtiter dish biofilm formation assay to determine the difference in the virulence genes and biofilm formation among in our study collected of 103 Staphylococcus aureus, isolates from hemodialysis patients utilizing arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs) during November 2013 to December 2021.ResultsOur findings revealed that both MRSA and MSSA isolates exhibited strong biofilm production capabilities. Additionally, we confirmed the presence of agr types and virulence genes through PCR analysis. The majority of the collected isolates were identified as agr type I. However, agr type II isolates displayed a higher average number of virulence genes, with MRSA isolates exhibiting a variety of virulence genes. Notably, combinations of biofilm-associated genes, such as eno−clfA−clfB−fib−icaA−icaD and eno−clfA−clfB−fib−fnbB−icaA−icaD, were prevalent among Staphylococcus aureus, isolates obtained from vascular access infections.DiscussionThese insights contribute to a better understanding of the molecular characteristics associated with Staphylococcus aureus, infections in hemodialysis patients and provided more targeted and effective treatment approaches.

Abstract Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability.

Abstract Since venous reflux is difficult to quantify, triggered angiography non-contrast-enhanced (TRANCE)-magnetic resonance imaging (MRI) is a novel tool for objectively evaluating venous diseases in the lower extremities without using contrast media. This study included 26 pre-intervention patients with superficial venous reflux in the lower extremities and 15 healthy volunteers. The quantitative flow (QFlow) analyzed the phase shift information from the pixels within the region of interest from MRI. The fast and simple radial basis function neural network (RBFNN) learning model is constructed by determining the parameters of the radial basis function and the weights of the neural network. The input parameters were the variables generated through QFlow, while the output variables were morbid limbs with venous reflux and normal limb classification. The stroke volume, forward flow volume, absolute stroke volume, mean flux, stroke distance, and mean velocity of greater saphenous veins from QFlow analysis could be used to discriminate the morbid limbs of pre-intervention patients and normal limbs of healthy controls. The neural network successfully classified the morbid and normal limbs with an accuracy of 90.24% in the training stage. The classification of venous reflux using the RBFNN model may assist physicians in clinical settings.

Objective: Shewanella algae is a zoonotic marine bacterium that causes a variety of infections in immunocompromised patients or those who have been exposed to seawater. The development of trimethoprim/sulfamethoxazole (TMP/SMX) resistance in S. algae are found in human and environment isolates during the past ten years, and thus the treatment options are decreasing. Methodology: In the study, we conduct a comparative genomic study to identify the resistant mechanism of TMP/SMX-resistance in S. algae. Results: We found the resistance of TMP/SMX in S. algae is associated with the existence of sul1 and dfrA12 within the class 1 integron. The gene cassette dfra12-aadA2-qacEΔ1/sul1 within the class 1 integron is highly conserved. In addition, the class 1 integron and encapsulated sul1 are significantly enriched in Enterobacteriaceae in NCBI and UniProt databases. Conclusion: Our study suggests that the horizontal transfer of TMP/SMX resistance via class 1 integron is most frequently occurred within Enterobacteriaceae and has spread to a wide range of sources including soil, poultry, and marine water.

Summary: Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role of network excitability during the repair phase for stroke recovery. Here, we show that β-hydroxybutyrate (β-HB), an essential ketone body (KB) component, is positively correlated with improved outcomes in patients with stroke and promotes functional recovery in rodents with stroke during the repair phase. These beneficial effects of β-HB depend on HDAC2/HDAC3-GABA transporter 1 (GAT-1) signaling-mediated enhancement of excitability and phasic GABA inhibition in the peri-infarct cortex and structural and functional plasticity in the ipsilateral cortex, the contralateral cortex, and the corticospinal tract. Together with available clinical approaches to elevate KB levels, our results offer a clinically translatable means to promote stroke recovery. Furthermore, GAT-1 can serve as a pharmacological target for developing drugs to promote functional recovery after stroke.

Background: Shewanella algae is a zoonotic pathogen that poses a serious health threat to immunocompromised hosts. Treatment of S. algae infections is challenging due to the pathogen's intrinsic resistance to a variety of β-lactam antibiotics. Therapeutic options have become further limited by the emergence of quinolone-resistant strains. Currently, there are few studies concerning the genetic and molecular mechanisms underlying acquired quinolones resistance in S. algae. qnrA was once proposed as the candidate gene related to quinolones resistance in S. algae. However, recent studies demonstrated qnrA are highly conservative and does not confer resistance to quinolones in S. algae. Methods: A total of 27 non-duplicated isolates of S. algae strains were examined. MICs of ciprofloxacin were determined using Vitek 2. Whole genome sequencing was performed using MiSeq platform. Comprehensive Antibiotic Resistance Database and ResFinder were used for annotation of quinolones resistance genes. Multiple sequence alignment by EMBOSS Clustal Omega were used to identified mutation in quinolone resistance-determining regions. To investigation of the alteration of protein structure induced by mutation, in silico molecular docking studies was conducted using Accryl Discovery studio visualizer. Results: All S. algae harbored the quinolone-resistance associated genes (qnrA, gyrA, gyrB, parC, and parE) regardless its resistance to ciprofloxacin. Comparison of these genomes identified a nonsynonymous mutation (S83V) in chromosome-encoded gyrase subunits (GyrA) in quinolone-resistant strain. We found this mutation disrupts the water-metal ion bridge, reduces the affinity of the quinolone-enzyme complex for the metal ions and therefore decrease the capability of quinolones to stabilize cleavage complexes. Conclusions: The study provides insight into the quinolone resistance mechanisms in S. algae, which would be helpful for the evolution of antibiotic resistance in this bacterium.

Chronic pain usually induces anxiety. Here, the authors report that vmPFC nNOS-expressing neurons are activated by excitatory inputs from pPVT during chronic pain and subsequently induce anxiety-like behaviors in mice through promoting AMPAR trafficking.

Persons who inject drugs (PWID) and their risk-related behaviors (e.g., unprotected sex and sharing needles/syringes/other injection equipment) have caused severe public health problems, especially in the rapid spread of HIV-1 and HCV. Here, we reconstructed the epidemic history of HIV-1 circulating recombinant form (CRF) 01_AE, CRF07_BC, and HCV subtype-6w among Taiwanese PWID. The timescales were estimated using phylogenetic and Bayesian coalescent analyses. The results revealed that CRF01_AE started to circulate in the Taiwanese PWID population in central Taiwan at 1992.5 (95% credible region: 1988.8–1995.9) and spread to other regions of Taiwan, while CRF07_BC was first identified in southern Taiwan at 2000.0 (95% CR: 1997.8–2002.2) and then spread northward to central-northern Taiwan. All HCV-6 strains were from Asia (that is, China, Myanmar, Taiwan, and Vietnam) and originated in 1928.1 (95% CR: 1890.2–1966.0). Furthermore, subtype-6w isolates from different regions of Taiwan appeared to share a common source that existed in the mid-1990s (95% CR: 1985.0–2001.8) or thereabouts. The routes of drug trafficking and the resulting high prevalence of HIV-1/HCV co-infections among PWID might have contributed to the virus transmission and promoted its spread worldwide. Long-term monitoring and policy implementation in at-risk populations would be useful for disease control.

The effects of superficial venous intervention on hemodynamics can be quantified using two-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI). Twelve patients received pre- and postintervention 2D PC-MRI analysis using quantitative hemodynamic parameters. Fifteen healthy volunteers served as controls. The 2D PC-MRI results of the target limbs (limbs scheduled for intervention for venous reflux) differed from those of the controls in terms of stroke volume (SV), forward flow volume (FFV), absolute stroke volume (ASV), and mean flux (MF) in all venous segments. The velocity time integral (VTI) and mean velocity (MV) of the popliteal vein (PV) segments were similar between the target limbs and controls preoperatively. After intervention, the target limbs exhibited an increase in VTI and MV in the femoral vein (FV) and PV segments. We compared the target and nontreated limbs of the individual patients preoperatively and postoperatively to minimalize individual bias. All QFlow parameter ratios in the FV segment increased after venous intervention (VTI, p = 0.025; MV, p = 0.024). In the PV segment, FFV and ASV increased significantly (p = 0.035 and 0.024, respectively). After interventions, the volume (FFV and ASV) of the PV segment and the efficiency (VTI and MV) of the FV segment significantly increased.

Background: Letermovir prophylaxis is currently the standard of care for the prevention of cytomegalovirus (CMV) infections in allogeneic hematopoietic stem-cell transplantation (allo-HSCT). However, drug–drug interactions between letermovir and azoles or calcineurin inhibitors and the high financial burden of letermovir remain problematic, especially in resource-limited countries. It has not been clarified whether a lower dose of valganciclovir would constitute an effective strategy for CMV prevention in patients with acute leukemia undergoing allo-HSCT. Methods: We retrospectively assessed 84 consecutive adult patients with acute leukemia who underwent allo-HSCT. These 84 patients were stratified into a valganciclovir prophylaxis group ( n = 20) and a non-valganciclovir prophylaxis group ( n = 64). Results: Patients in the valganciclovir prophylaxis group had a lower possibility of CMV DNAemia at week 14 after allo-HSCT than those in the non-valganciclovir prophylaxis group (15.0% versus 50.0%; p = 0.012). The cumulative incidence of CMV DNAemia at week 14 was also lower in patients with valganciclovir CMV prophylaxis than in those without (15.0% versus 50.4%; p = 0.006). Multivariate analysis validated these data, showing that a low dose of valganciclovir significantly reduced the risk of CMV DNAemia at week 14 by 88% (hazard ratio: 0.12; 95% confidence interval: 0.04–0.42; p = 0.001). However, these two groups had similar overall survival rates at week 48 (75.0% versus 76.6%; p = 0.805). Four of 20 (20%) patients discontinued valganciclovir prophylaxis because of adverse events. Conclusion: Low-dose valganciclovir prophylaxis could be an alternative to letermovir to prevent CMV infection in allo-HSCT, especially in resource-limited countries.

Background: Posaconazole prophylaxis during remission induction chemotherapy not only decreases the incidence of invasive aspergillosis (IA) but also improves the overall survival rate among patients with acute myeloid leukemia (AML). However, it remains debatable whether this result applies to patients in a real-world setting. Methods: We retrospectively assessed 208 adult patients with newly diagnosed AML who underwent remission induction therapy. These 208 patients were stratified into the posaconazole prophylaxis group ( n = 58) and no antifungal prophylaxis group ( n = 150). Results: Multivariate analyses showed that induction failure significantly increased the risk of proven or probable IA during the first induction chemotherapy [hazard ratio (HR), 10.47; 95% confidence interval (CI), 1.73–63.45; p = 0.011] and the entire course of AML treatment (HR, 4.48; 95% CI, 1.71–11.75; p = 0.002). However, posaconazole prophylaxis did not reduce the risk of IA during the first induction chemotherapy (HR, 1.47; 95% CI, 0.14–15.04; p = 0.746) and during the entire course of AML treatment (HR, 1.09; 95% CI, 0.29–4.09; p = 0.896). Furthermore, there was no significant difference in overall survival between these two groups of patients (514 versus 689 days; p = 0.454). Conclusion: Successful induction remains fundamental to reducing the risk of IA among AML patients undergoing remission induction chemotherapy.

The progression of clinical manifestations of lower-limb varicose veins remains unclear. This study investigated changes in lower-limb venous blood flow using phase-contrast magnetic resonance angiography. Data were collected on veins from 141 legs. We compared legs with and without varicose veins and related symptoms and examined varying levels of varicose vein symptom severity. Legs without varicose veins exhibited a lower absolute stroke volume (ASV, p < 0.01) and mean flux (MF, p = 0.03) for the great saphenous vein (GSV) compared with legs with symptomatic varicose veins. Legs with asymptomatic varicose veins exhibited lower MF for the GSV (p = 0.02) compared with legs with symptomatic varicose veins. Among legs with varicose veins, asymptomatic legs exhibited lower ASV (p = 0.03) and MF (p = 0.046) for the GSV compared with legs that exhibited skin changes or ulcers; however, no significant differences were observed between legs presenting with discomfort or edema and legs with skin changes or ulcers, and between legs presenting with discomfort or edema and asymptomatic legs. In conclusion, in the supine position, increased blood flow rate and blood flow volume in the GSV were associated with symptomatic varicose veins and increased symptom severity.

(1) Background: We used four-dimensional phase-contrast magnetic resonance imaging (4D PC-MRI) to evaluate the impact of an endovascular aortic repair (TEVAR) on aortic dissection. (2) Methods: A total of 10 patients received 4D PC-MRI on a 1.5-T MR both before and after TEVAR. (3) Results: The aortas were repaired with either a GORE TAG Stent (Gore Medical; n = 7) or Zenith Dissection Endovascular Stent (Cook Medical; n = 3). TEVAR increased the forward flow volume of the true lumen (TL) (at the abdominal aorta, p = 0.047). TEVAR also reduced the regurgitant fraction in the TL at the descending aorta but increased it in the false lumen (FL). After TEVAR, the stroke distance increased in the TL (at descending and abdominal aorta, p = 0.018 and 0.015), indicating more effective blood transport per heartbeat. Post-stenting quantitative flow revealed that the reductions in stroke volume, backward flow volume, and absolute stroke volume were greater when covered stents were used than when bare stents were used in the FL of the descending aorta. Bare stents had a higher backward flow volume than covered stents did. (4) Conclusions: TEVAR increased the stroke volume in the TL and increased the regurgitant fraction in the FL in patients with aortic dissection.

Background and Objectives: Compression of the common iliac veins (CIV) is not always associated with lower extremity symptoms. This study analyzed this issue from the perspective of patient venous blood flow changes using quantitative flow magnetic resonance imaging. Materials and Methods: After we excluded patients with active deep vein thrombosis, the mean flux (MF) and mean velocity (MV) of the popliteal vein, femoral vein, and external iliac vein (EIV) were compared between the left and right sides. Results: Overall, 26 of the patients had unilateral CIV compression, of which 16 patients had symptoms. No significant differences were noted in the MF or MV of the veins between the two sides. However, for the 10 patients without symptoms, the EIV MF of the compression side was significantly lower than the EIV MF of the non-compression side (p = 0.04). The receiver operating characteristic curve and chi-squared analyses showed that when the percentage difference of EIV MF between the compression and non-compression sides was ≤−18.5%, the relative risk of associated lower extremity symptoms was 0.44 (p = 0.016). Conclusions: If a person has compression of the CIV, a decrease in EIV blood flow rate on the compression side reduces the rate of symptom occurrence.

Imaging characteristics of stasis leg ulcers (SLUs) are not easily demonstrated through existing diagnostic tools. Early diagnosis and treatment are crucial. This pilot study was conducted to assess the quantitative flow (QFlow) in triggered angiography noncontrast enhanced (TRANCE) magnetic resonance imaging (MRI) to identify the hemodynamics of victims with stasis leg ulcers (SLUs). This study included 33 patients with SLUs and 14 healthy controls (HC). The 33 patients with SLUs were divided into a reflux (15 patients) and a nonreflux group (18 patients). QFlow was done in the reflux, the nonreflux, and the HC. The stroke volume (SV), forward flow volume (FFV), absolute flow volume (AFV), mean flow (MF), and mean velocity (MV) were higher in the reflux than in the HC group in most segments, namely the external iliac vein (EIV), popliteal vein (PV), and great saphenous vein (GSV) (SV, p = 0.008; FFV, p = 0.008; absolute stroke volume (ASV), p = 0.008; MF, p = 0.002; MV, p = 0.009). No differences in the QFlow patterns were found in the GSV segment between the nonreflux group and the HC. Excellent performance in discriminating SLU with superficial venous reflux was reported for SV in the EIV and the PV (area under the curve (AUC) = 0.851 and 0.872), FFV in the EIV and PV (AUC = 0.854 and 0.869), ASV in the EIV and PV (AUC = 0.848 and 0.881), and MF in the EIV and PV (AUC = 0.866 and 0.868). The cutoff levels of SV/FFV/ASV/MF in the EIV/FV/PV/GSV for discriminating the SLU with superficial venous reflux were identified (p < 0.005). In conclusion, SLUs present different QFlow patterns by different etiology. The QFlow parameters of all vessel segments were higher in the morbid limbs of the reflux group than HC. The GSV segment of the nonreflux group displayed a pattern like the HC.

The adverse effect of cisplatin administration causes acute kidney injury (AKI) following renal inflammation and nephrotoxicity, characterized by proximal tubular cell apoptosis and necrosis. Pro-apoptotic and pro-inflammatory roles of glycogen synthase kinase (GSK)-3β have been reported. This study investigated the therapeutic blockade of GSK-3β in cisplatin-induced AKI. A renal cisplatin nephrotoxicity model showed activation of GSK-3β in vivo, particularly in proximal tubular epithelial cells. Pharmacologically inhibiting GSK-3β abolished cisplatin nephrotoxicity, including proximal tubular injury, cell cytotoxicity, and biochemical dysfunction. Additionally, GSK-3β inhibitor treatment ameliorated renal inflammation by reducing immune cell infiltration, cell adhesion molecule expression, and pro-inflammatory cytokine/chemokine production. Cisplatin treatment caused GSK-3β activation in vitro in the human renal proximal tubular epithelial cell line HK-2, whereas either pharmacological administration of GSK-3β inhibitors or genetic transduction of GSK-3β short-hairpin RNA impeded cisplatin-induced cytotoxicity. These results indicate that cisplatin activates GSK-3β followed by GSK-3β-mediated renal inflammation and nephrotoxicity, contributing to AKI.

(1) Background: To assess the effectiveness of triggered angiography non-contrast-enhanced (TRANCE)-magnetic resonance imaging (MRI) in superficial venous reflux and its difference from health controls. (2) Methods: Thirty patients underwent TRANCE MRI before surgical intervention of their superficial venous reflux of the legs. Ten healthy volunteers were included as a control. (3) Results: TRANCE MRI involves the major tributaries, thus enhances the additional ablations in 20% of patients. QFlow pattern of superficial venous reflux (QFlow GSV/PV MF ratio > 1) was compared with the duplex scan (SFJ reflux) using Cohen’s kappa coefficient at 0.967. The 30 morbid legs undergoing TRANCE MRI-guide interventions and the healthy volunteers’ legs on the same side were compared. The stroke volumes (SV) are higher in EIV (p = 0.021) in the left-leg-intervention group. The mean flux (MF) is higher in the EIV (p = 0.012) and trend of increasing in GSV segment (p = 0.087) in the left-leg-intervention group. The QFlow of 10 patients with right leg intervention are higher in GSV in the right-leg-intervention group (SV p = 0.002; FFV p = 0.001; MF p = 0.001). QFlow data is shown for all legs for superficial venous intervention with GSV/PV (MF) ratio > 1. (4) Conclusions: Typical figures in QFlow (GSV/PV MF ratio > 1) could be observed in the morbid limbs but not in the controls.

Background: Venous interventions of the legs are less predictable owing to a lock of objective tools. Methods: One hundred and twenty patients with lower extremity venous disease were evaluated anatomically using TRANCE MRI. Then, a QFlow analysis was performed in 53 patients with only one leg affected for hemodynamic evaluation. Those patients with complete QFlow were classified into obstructive and nonobstructive. Results: The QFlow—namely, stroke volume, forward flow volume, mean flux, stroke distance (SD), and mean velocity (MV) in the external iliac vein (EIV), femoral vein (FV), popliteal vein (PV), and great saphenous vein (GSV). The obstructed group had a shorter SD and lower MV in the EIV, EIV/FV, and GSV/PV (SD: p-values of 0.025, 0.05, and 0.043, respectively; MV: p-values of 0.02, 0.05, and 0.048, respectively). A good performance in discriminating obstructive venous disease was reported for SD in the EIV (area under the curve (AUC) = 67.9%, 95% confidence interval (CI) = 53.2–82.7%), EIV/FV (AUC = 72.4%, 95% CI = 58.2–86.5%), and GSV/PV (AUC = 67.9%, 95% CI = 51.7–84.1%). The SD in the EIV, EIV/FV, and GSV/PV had the ability to discriminate between obstructive and nonobstructive diseases (p-values of 0.025, 0.005, and 0.043). The MV in the EIV, EIV/FV, and GSV/PV had ability to discriminate between obstructive and nonobstructive venous diseases (p-values of 0.02, 0.005, and 0.048). Conclusions: The SD and MV were lower for obstructive than nonobstructive disease in the EIV.

Summary: The molecular mechanism of memory formation remains a mystery. Here, we show that TERT, the catalytic subunit of telomerase, gene knockout (Tert−/−) causes extremely poor ability in spatial memory formation. Knockdown of TERT in the dentate gyrus of adult hippocampus impairs spatial memory processes, while overexpression facilitates it. We find that TERT plays a critical role in neural development including dendritic development and neuritogenesis of hippocampal newborn neurons. A monosynaptic pseudotyped rabies virus retrograde tracing method shows that TERT is required for neural circuit integration of hippocampal newborn neurons. Interestingly, TERT regulated neural development and spatial memory formation in a reverse transcription activity-independent manner. Using X-ray irradiation, we find that hippocampal newborn neurons mediate the modulation of spatial memory processes by TERT. These observations reveal an important function of TERT through a non-canonical pathway and encourage the development of a TERT-based strategy to treat neurological disease-associated memory impairment. : In this article, Qi-Gang Zhou and colleagues show that spatial memory formation, neural development including dendritic development and neuritogenesis, and neural circuit integration are impaired in Tert gene knockout mice. Hippocampal TERT accounts for these phenotypes in a reverse transcription activity-independent manner. Keywords: telomerase, neural progenitor cells, hippocampus, neural development, circuit integration

We report a case with retained products of conception (RPOC) managed by hysteroscopic resection. A 45-year-old woman, G5P3SA1AA1, experienced spontaneous abortion on March 8, 2017, and had persistent vaginal bleeding since then. On May 12, 2017, she came to emergency room where endometrium biopsy was done and revealed degenerative gestational tissue with acute inflammation. On May 23, 2017, she followed up at outpatient department where ultrasonography showed no obvious intrauterine abnormalities with endometrial thickness of 6.5 mm. Office hysteroscopy was arranged and RPOC at the posterior uterine wall was suspected. She received hysteroscopic transcervical resection (TCR) of RPOC on May 26, 2017. After TCR, the vaginal bleeding discontinued. The pathology showed degenerative gestational products with acute inflammation. In conclusion, hysteroscopic TCR might be safe and feasible for RPOC.

BackgroundStroke is a leading cause of long‐term disability worldwide. However, current therapies that promote functional recovery from stroke are limited to physical rehabilitation. No pharmacological therapy is available. Thus, understanding the role of histone deacetylase 2 (HDAC2) in the pathophysiological process of stroke‐induced functional loss may provide a novel strategy for stroke recovery. Methods and ResultsFocal stroke was induced by photothrombosis. LV‐HDAC2‐shRNA‐GFP, LV‐GFP, Ad‐HDAC2‐Flag, or Ad‐inactive‐HDAC2‐Flag was microinjected into the peri‐infarct area immediately after stroke. HDAC inhibitors were microinjected into the peri‐infarct area 4 to 10 days after stroke. Grid‐walking task and cylinder task were conducted to assess motor function. Golgi‐Cox staining, chromatin immunoprecipitation, and electrophysiology were used to reveal the mechanisms underlying stroke recovery. Knockdown or knockout of HDAC2 promoted stroke recovery, whereas overexpression of HDAC2 worsened stroke‐induced functional impairment. More importantly, trichostatin A, a pan‐HDAC inhibitor, promoted functional recovery from stroke in WT mice when used in the delayed phase, but it was ineffective in Hdac2 conditional knockout (Hdac2 CKO) mice. Treatment with suberoylanilide hydroxamic acid, a selective HDAC1 and HDAC2 inhibitor, in the delayed phase of stroke produced sustained functional recovery in mice via epigenetically enhancing neuroplasticity of surviving neurons in the peri‐infarct zone. ConclusionsOur novel findings provide evidence that HDAC2 is a crucial target for functional recovery from stroke. As there are clinically available HDAC inhibitors, our findings could be directly translated into clinical research of stroke.

One dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited.We prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3-6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%.Between 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4-72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3-79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17-3.09), RPR titer ≥32 (AOR, 1.93; 95% CI, 1.38-2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20-2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively.Single-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.

BACKGROUND: Among members of Cryptococcus neoformans- Cryptococcus gattii species complex, C. neoformans is distributed worldwide whereas C. gattii is considered to be more prevalent in the subtropics and tropics including Taiwan. This nationwide study was undertaken to determine the distribution of genotypes, clinical characteristics and outcomes of 219 patients with proven cryptococcosis at 20 hospitals representative of all geographic areas in Taiwan during 1997-2010. METHODS AND FINDINGS: Of 219 isolates analyzed, C. neoformans accounted for 210 isolates (95.9%); nine isolates were C. gattii (4.1%). The predominant genotype was VNI (206 isolates). The other genotypes included VNII (4 isolates), VGI (3 isolates) and VGII (6 isolates). Antifungal minimal inhibition concentrations higher than epidemiologic cutoff values (ECVs) were found in nine VNI isolates (7 for amphotericin B). HIV infection was the most common underlying condition (54/219, 24.6%). Among HIV-negative patients, liver diseases (HBV carrier or cirrhosis) were common (30.2%) and 15.4% did not have any underlying condition. Meningoencephalitis was the most common presentation (58.9%), followed by pulmonary infection (19.6%) and "others" (predominantly cryptococcemia) (18.7%). The independent risk factors for 10-week mortality, by multivariate analysis, were cirrhosis of liver (P = 0.014) and CSF cryptococcal antigen titer ≥ 512 (P = 0.020). All except one of 54 HIV-infected patients were infected by VNI genotype (98.1%). Of the 13 isolates of genotypes other than VNI, 12 (92.3%) were isolated from HIV-negative patients. HIV-infected patients compared to HIV-negative patients were more likely to have meningoencephalitis and serum cryptococcal antigen ≥ 1:512. Patients infected with C. gattii compared to C. neoformans were younger, more likely to have meningoencephalitis (100% vs. 57%), reside in Central Taiwan (56% vs. 31%), and higher 10-week crude mortality (44.4% vs. 22.2%). CONCLUSIONS: Cryptococcus neoformans in Taiwan, more prevalent than C. gatii, has a predominant VNI genotype. Isolates with antifungal MIC higher than ECVs were rare.

The parasite Cryptosporidium parvum has three 14-3-3 proteins: Cp14ε, Cp14a and Cp14b, with only Cp14ε similar to human 14-3-3 proteins in sequence, peptide-binding properties and structure. Structurally, Cp14a features the classical 14-3-3 dimer but with a uniquely wide pocket and a disoriented RRY triad potentially incapable of binding phosphopeptides. The Cp14b protein deviates from the norm significantly: (i) In one subunit, the phosphorylated C-terminal tail is bound in the binding groove like a phosphopeptide. This supports our binding study indicating this protein was stabilized by a peptide mimicking its last six residues. (ii) The other subunit has eight helices instead of nine, with αA and αB forming a single helix and occluding the peptide-binding cleft. (iii) The protein forms a degenerate dimer with the two binding grooves divided and facing opposite directions. These features conspire to block and disrupt the bicameral substrate-binding pocket, suggesting a possible tripartite auto-regulation mechanism that has not been observed previously.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

Introduction: Staphylococcus aureus, is a pathogen commonly encountered in both community and hospital settings. Patients receiving hemodialysis treatment face an elevated risk of vascular access infections (VAIs) particularly Staphylococcus aureus, infection. This heightened risk is attributed to the characteristics of Staphylococcus aureus,, enabling it to adhere to suitable surfaces and form biofilms, thereby rendering it resistant to external interventions and complicating treatment efforts. Methods: Therefore this study utilized PCR and microtiter dish biofilm formation assay to determine the difference in the virulence genes and biofilm formation among in our study collected of 103 Staphylococcus aureus, isolates from hemodialysis patients utilizing arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs) during November 2013 to December 2021. Results: Our findings revealed that both MRSA and MSSA isolates exhibited strong biofilm production capabilities. Additionally, we confirmed the presence of agr types and virulence genes through PCR analysis. The majority of the collected isolates were identified as agr type I. However, agr type II isolates displayed a higher average number of virulence genes, with MRSA isolates exhibiting a variety of virulence genes. Notably, combinations of biofilmassociated genes, such as eno-clfA-clfB-fib-icaA-icaD and eno-clfA-clfB-fib -fnbB-icaA-icaD, were prevalent among Staphylococcus aureus, isolates obtained from vascular access infections. Discussion: These insights contribute to a better understanding of the molecular characteristics associated with Staphylococcus aureus, infections in hemodialysis patients and provided more targeted and effective treatment approaches. [ABSTRACT FROM AUTHOR]