Strategic combination of bacteriophages with highly susceptible cells for enhanced intestinal settlement and resistant cell killing.

Avian pathogenic Escherichia coli (APEC) causes enormous economic losses and is a primary contributor to the emergence of multidrug resistance (MDR)-related problems in the poultry industry. Bacteriophage (phage) therapy has been successful in controlling MDR, but phage-resistant variants have rapidly emerged through the horizontal transmission of diverse phage defense systems carried on mobile genetic elements. Consequently, while multiple phage cocktails are recommended for phage therapy, there is a growing need to explore simpler and more cost-effective phage treatment alternatives. In this study, we characterized two novel O78-specific APEC phages, φWAO78-1 and φHAO78-1, in terms of their morphology, genome, physicochemical stability and growth kinetics. Additionally, we assessed the susceptibility of thirty-two O78 APEC strains to these phages. We analyzed the roles of highly susceptible cells in intestinal settlement and fecal shedding (susceptible cell-assisted intestinal settlement and shedding, SAIS) of phages in chickens via coinoculation with phages. Furthermore, we evaluated a new strategy, susceptible cell-assisted resistant cell killing (SARK), by comparing phage susceptibility between resistant cells alone and a mixture of resistant and highly susceptible cells in vitro. As expected, high proportions of O78 APEC strains had already acquired multiple phage defense systems, exhibiting considerable resistance to φWAO78-1 and φHAO78-1. Coinoculation of highly susceptible cells with phages prolonged phage shedding in feces, and the coexistence of susceptible cells markedly increased the phage susceptibility of resistant cells. Therefore, the SAIS and SARK strategies were demonstrated to be promising both in vivo and in vitro.

Epidemiology and Disease Burden of Respiratory Syncytial Virus Infection in Adults.

Respiratory syncytial virus (RSV) constitutes a significant cause of respiratory illness and mortality among older adults, a demographic that is expanding with considerable impact on healthcare systems worldwide. The actual burden of RSV in this population may still be underestimated, owing to factors such as low awareness and suboptimal diagnostic sensitivity in adults, the lack of robust RSV surveillance systems, and the infrequent use of diagnostic testing. Recent advancements in respiratory virus detection have spurred further exploration into appropriate preventive and therapeutic strategies. The recent approval of two vaccines highlights the critical need for the precise estimation of the RSV disease burden to optimize the effectiveness and cost-efficiency of immunization programs. This narrative review aimed to summarize the existing knowledge of the RSV burden in adults with a particular focus on older adults, incorporating data from Korea. Overall, current estimates indicate that the annual RSV attack rate in the general adult population ranges from 1 - 7%, increasing to approximately 4 - 10% among elderly and high-risk groups. The in-hospital mortality rate can be estimated to be around 7 - 10%, rising up to 40% among intensive care unit-admitted patients. To elucidate RSV's disease burden, further continuing research, including population-based studies, is necessary.

Long-term Results after Bilateral Implantation of Extended Depth of Focus Intraocular Lenses with Mini-Monovision.

PURPOSE: To assess long-term clinical results following bilateral Tecnis Symfony ZXR00 intraocular lens implantation with mini-monovision. METHODS: The medical records of cataract patients who underwent bilateral implantation of ZXR00 with intended mini-monovision (target refraction of -0.3 diopters [D] in dominant eye and -0.6 D in nondominant eye) between April 2019 and March 2021 were assessed. Postoperative uncorrected distance visual acuity (UDVA), corrected distance VA (CDVA), uncorrected intermediate VA (UIVA), uncorrected near VA (UNVA), and rate of spectacle dependence for near distance were investigated at 3 months and 2 years after surgery. RESULTS: This study included 61 patients (122 eyes) with average age of 61.8 ± 7.7 years. At 2 years postoperatively, binocular logarithm of the minimum angle of resolution UDVA, UIVA, UNVA, and CDVA were 0.086 ± 0.094, 0.056 ± 0.041, 0.140 ± 0.045, and 0.012 ± 0.024, respectively. The monocular manifest refraction spherical equivalent was -0.31 ± 0.38 in the dominant eye and -0.53 ± 0.47 in the nondominant eye at 3 months postoperatively, and -0.38 ± 0.43 in the dominant eye and -0.61 ± 0.54 in the nondominant eye at 2 years postoperatively. Eight out of 61 patients (13.1%) needed glasses 3 months after surgery, and nine out of 61 patients (14.8%) needed glasses 2 years after surgery. CONCLUSIONS: The bilateral implantation of ZXR00s with mini-monovision allows for a good VA at wide range of distance from far to near, thereby resulting in high rate of spectacle independence. These results have held up well even after 2 years after surgery.

Comprehensive Molecular Genetic Analysis in Glioma Patients by Next Generation Sequencing.

BACKGROUND: Glioma is caused by multiple genomic alterations. The evolving classification of gliomas emphasizes the significance of molecular testing. Next generation sequencing (NGS) offers the assessment of parallel combinations of multiple genetic alterations and identifying actionable mutations that guide treatment. This study comprehensively analyzed glioma patients using multi-gene NGS panels, providing powerful insights to inform diagnostic classification and targeted therapies. METHODS: We conducted a targeted panel-based NGS analysis on formalin-fixed and paraffin-embedded nucleic acids extracted from a total of 147 glioma patients. These samples underwent amplicon capture-based library preparation and sequenced using the Oncomine Comprehensive Assay platform. The resulting sequencing data were then analyzed using the bioinformatics tools. RESULTS: A total of 301 mutations, were found in 132 out of 147 tumors (89.8%). These mutations were in 68 different genes. In 62 tumor samples (42.2%), copy number variations (CNVs) with gene amplifications occurred in 25 genes. Moreover, 25 tumor samples (17.0%) showed gene fusions in 6 genes and intragenic deletion in a gene. Our analysis identified actionable targets in several genes, including 11 with mutations, 8 with CNVs, and 3 with gene fusions and intragenic deletion. These findings could impact FDA-approved therapies, NCCN guideline-based treatments, and clinical trials. CONCLUSION: We analyzed precisely diagnosing the classification of gliomas, detailing the frequency and co-occurrence of genetic alterations and identifying genetic alterations with potential therapeutic targets by NGS-based molecular analysis. The high-throughput NGS analysis is an efficient and powerful tool to comprehensively support molecular testing in neurooncology.

Validation of a new risk stratification system-based management for methicillin-resistant Staphylococcus aureus bacteraemia: analysis of a multicentre prospective study.

PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.

Synaptotagmin-4 induces anhedonic responses to chronic stress via BDNF signaling in the medial prefrontal cortex.

Stressful circumstances are significant contributors to mental illnesses such as major depressive disorder. Anhedonia, defined as loss of the ability to enjoy pleasure in pleasurable situations, including rewarding activities or social contexts, is considered a key symptom of depression. Although stress-induced depression is associated with anhedonia in humans and animals, the underlying molecular mechanisms of anhedonic responses remain poorly understood. In this study, we demonstrated that synaptotagmin-4 (SYT4), which is involved in the release of neurotransmitters and neurotrophic factors, is implicated in chronic stress-induced anhedonia. Employing chronic unpredictable stress (CUS), we evaluated two subpopulations of mice, susceptible (SUS, anhedonic) and resilient (RES, nonanhedonic), based on sucrose preference, which was strongly correlated with social reward. The FosTRAP (targeted recombination in active populations) system and optogenetic approach revealed that neural activity in the medial prefrontal cortex (mPFC) was significantly associated with CUS-induced anhedonic behavioral phenotypes. By conducting weighted gene coexpression network analysis of RNA sequencing data from the mPFC of SUS and RES mice, we identified Syt4 as a hub gene in a gene network that was unique to anhedonia. We also confirmed that Syt4 overexpression in the mPFC was pro-susceptible, while Syt4 knockdown was pro-resilient; the pro-susceptible effects of SYT4 were mediated through a reduction in brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the mPFC. These findings suggest that SYT4-BDNF interactions in the mPFC represent a crucial regulatory mechanism of anhedonic susceptibility to chronic stress.

Exploration of the effects of Yang's pricking-cupping therapy on eczema-induced pruritus based on rs-fMRI. / 基于rs-fMRI探讨杨氏絮刺火罐对湿疹瘙痒的影响.

OBJECTIVES: To explore the clinical effect of Yang's pricking-cupping therapy and its central mechanism in treatment of eczema-induced pruritus using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Fifty patients with eczema-induced pruritus were enrolled in the observation group, and 50 healthy subjects were enrolled in the control group. No any intervention was delivered in the control group. Yang's pricking-cupping therapy was operated at Dazhui (GV 14) and bilateral Quchi (LI 11), Xuehai (SP 10) and Sanyinjiao (SP 6), once a week, lasting 6 weeks in the observation group. The scores of the 12-item pruritus severity scale (12-PSS), the eczema area and severity index (EASI), the dermatology life quality index (DLQI), the Pittsburgh sleep quality index (PSQI), and the self-rating anxiety scale (SAS) were compared before and after treatment in the observation group. The rs-fMRI scanning was conducted and the regional homogeneity (ReHo) analysis performed in all of the participants before and after treatment in the observation group, as well as at the time of subject enrollment in the control group. The correlation was analyzed between ReHo values in the different areas of the brain and the scores of the above scales. RESULTS: Compared with those before treatment, the scores of 12-PSS, EASI, DLQI, PSQI, and SAS were reduced after treatment in the observation group (P<0.01, P<0.05). ReHo values were increased in the right caudate nucleus, the right middle temporal gyrus, the right orbitofrontal gyrus, the right thalamus and the left angular gyrus before treatment in the observation group when compared with those in the control group (P<0.001); and ReHo values in the above areas of the brain were decreased after treatment when compared with those before treatment in the observation group (P<0.001). In comparison with the control group, ReHo values were reduced in the left middle temporal gyrus, the left superior parietal lobule and the left supplementary motor area in the observation group before treatment (P<0.001); while when compared with those before treatment, ReHo values in the above areas of the brain were elevated after treatment in the observation group (P<0.001). Before treatment, ReHo value in the left supplementary motor area was positively correlated with 12-PSS score (r=0.432, P=0.004), and the value in the right orbitofrontal gyrus was negatively correlated with PSQI score (r=-0.318, P=0.04) in the observation group. After treatment, ReHo value in the left superior parietal lobule was positively correlated with 12-PSS score (r=0.384, P=0.012) in the observation group. CONCLUSIONS: The abnormal cerebral functional activities are exhibited in multiple areas of the brain involved in stimulus response, emotional regulation, behavior control and attention in the patients with eczema-induced pruritus. Yang's pricking-cupping therapy can effectively relieve the pruritus symptoms and skin lesions of the patients, which may be related to reversing the abnormal cerebral functional activities induced by pruritus.

Different Impact of Metabolic Syndrome on the Risk of Incidence of the Peripheral Artery Disease and the Venous Thromboembolism: A Nationwide Longitudinal Cohort Study in South Korea.

Background: Limited data is available between metabolic syndrome (MetS) and the development of peripheral arterial disease (PAD) or venous thromboembolism (VTE) in the Asian population. We investigated the incidence of PAD and VTE according to the prevalence of MetS and evaluated the impact of individual components in MetS on the development of PAD and VTE using Korean national data. Methods: Data obtained from national health screening examinations of the Korean National Health Insurance Service from January 1, to December 31, 2009. In total, 9,927,538 participants, 7,830,602 participants were included in this study and the incidence rate of PAD and VTE was investigated retrospectively during a 7-year follow-up. Using the National Cholesterol Education Program Adult Treatment Panel III criteria, patients were placed into one of three groups depending on MetS component numbers: 0 (normal), 1-2 (Pre-MetS), or 3-5 (MetS). Results: The incidence rates of PAD and VTE in MetS were 2.25% and 0.71%, respectively. After multivariable adjustment, the risk of PAD was significantly associated with MetS (hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.42-1.49), the risk of VTE was not associated with MetS (HR 1.01, 95% CI 0.96-1.05). When subgroup analyses were conducted according to MetS components, elevated fasting glucose (HR 1.26, 95% CI 1.23-1.27), abdominal obesity (HR 1.15, 95% CI 1.12-1.17), and elevated blood pressure (HR 1.13, 95% CI 1.12-1.15) were the most related to PAD. Abdominal obesity (HR 1.104, 95% CI 1.064-1.146) was associated with an increased risk of VTE. Conclusions: MetS was significantly associated with an increased incidence rate of PAD among the general Korean population. On the other hand, MetS was not associated with the VTE incidence rate. Of the MetS components, only abdominal obesity was a significant predictor of VTE.