Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans

Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.OAIID:RECH_ACHV_DSTSH_NO:T201615370RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A003535CITE_RATE:11.329FILENAME:4. ncomms12766.pdfDEPT_NM:농생명공학부EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/fce63c4a-7de7-4741-996f-d8d24af38905/linkCONFIRM:

The Efficacy and Safety of Laparoscopy for Blunt Abdominal Trauma: A Systematic Review and Meta-Analysis

The efficacy and safety of laparoscopy for blunt trauma remain controversial. This systemic review and meta-analysis aimed to evaluate the usefulness of laparoscopy in blunt trauma. The PubMed, EMBASE, and Cochrane databases were searched up to 23 February 2021. Meta-analyses were performed using odds ratios (ORs), standardized mean differences (SMDs), and overall proportions. Overall, 19 studies with a total of 1520 patients were included. All patients were hemodynamically stable. In the laparoscopy group, meta-analysis showed lesser blood loss (SMD −0.28, 95% confidence interval (CI) −0.51 to −0.05, I2 = 62%) and shorter hospital stay (SMD −0.67, 95% CI −0.90 to −0.43, I2 = 47%) compared with the laparotomy group. Pooled prevalence of missed injury (0.003 (95% CI 0 to 0.023), I2 = 0%), nontherapeutic laparotomy (0.004 (95% CI 0.001 to 0.026), I2 = 0%), and mortality (0.021 (95% CI 0.010 to 0.043), I2 = 0%) were very low in blunt trauma. In subgroup analysis, recently published studies (2011–present) showed lesser conversion rate (0.115 (95% CI 0.067 to 0.190) vs. 0.391 (95% CI 0.247 to 0.556), test for subgroup difference: p < 0.01). This meta-analysis suggests that laparoscopy is a safe and feasible option in hemodynamic stable patients with blunt abdominal trauma

Efficacy and Safety of Laparoscopy for Mild and Moderate Pediatric Abdominal Trauma: A Systematic Review and Meta-Analysis

In this systematic review and meta-analysis, we aimed to investigate the efficacy and safety of laparoscopy for pediatric patients with abdominal trauma. Relevant articles were obtained by searching the MEDLINE PubMed, EMBASE, and Cochrane databases until 7 December 2021. Meta-analyses were performed using odds ratio (OR) for binary outcomes, standardized mean differences (SMDs) for continuous outcome measures, and overall proportion for single proportional outcomes. Nine studies examining 12,492 patients were included in our meta-analysis. Our meta-analysis showed younger age (SMD −0.47, 95% confidence interval (CI) −0.52 to −0.42), lower injury severity score (SMD −0.62, 95% CI −0.67 to −0.57), shorter hospital stay (SMD −0.55, 95% CI −0.60 to −0.50), less complications (OR 0.375, 95% CI 0.309 to 0.455), and lower mortality rate (OR 0.055, 95% CI 0.0.28 to 0.109) in the laparoscopy group compared to the laparotomy group. The majority of patients were able to avoid laparotomy (0.816, 95% CI 0.800 to 0.833). There were no missed injuries during the laparoscopic procedures in seven eligible studies. Laparoscopy for stable pediatric patients showed favorable outcomes in terms of morbidity and mortality. There were no missed injuries, and laparotomy could be avoided for the majority of patients

Feeding Period Restriction Alters the Expression of Peripheral Circadian Rhythm Genes without Changing Body Weight in Mice

<div><p>Accumulating evidence suggests that the circadian clock is closely associated with metabolic regulation. However, whether an impaired circadian clock is a direct cause of metabolic dysregulation such as body weight gain is not clearly understood. In this study, we demonstrate that body weight gain in mice is not significantly changed by restricting feeding period to daytime or nighttime. The expression of peripheral circadian clock genes was altered by feeding period restriction, while the expression of light-regulated hypothalamic circadian clock genes was unaffected by either a normal chow diet (NCD) or a high-fat diet (HFD). In the liver, the expression pattern of circadian clock genes, including Bmal1, Clock, and Per2, was changed by different feeding period restrictions. Moreover, the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation-related genes in the liver was also altered by feeding period restriction. Given that feeding period restriction does not affect body weight gain with a NCD or HFD, it is likely that the amount of food consumed might be a crucial factor in determining body weight. Collectively, these data suggest that feeding period restriction modulates the expression of peripheral circadian clock genes, which is uncoupled from light-sensitive hypothalamic circadian clock genes.</p> </div

Time from Injury to Initial Operation May Be the Sole Risk Factor for Postoperative Leakage in AAST-OIS 2 and 3 Traumatic Duodenal Injury: A Retrospective Cohort Study

Background and Objectives: Traumatic duodenal injury is a rare disease with limited evidence. We aimed to evaluate the risk factors for postoperative leakage and outcomes of pyloric exclusion after duodenal grade 2 and 3 injury. Materials and Methods: We reviewed a prospectively collected trauma database for the period January 2004–December 2020. Patients with grade 2 and 3 traumatic duodenal injury were included. To identify the risk factors for postoperative leakage, we used a stepwise multivariable logistic regression model and a least absolute shrinkage and selection operator (LASSO) logistic model. We constructed a receiver operator characteristic (ROC) curve to predict risk factors for postoperative leakage. Results: During the 17-year period, 179,887 trauma patients were admitted to a regional trauma center in Korea. Of these patients, 74 (0.04%) had duodenal injuries. A total of 49 consecutive patients had grade 2 and 3 traumatic duodenal injuries and underwent laparotomy. The incidence of postoperative leakage was 32.6% (16/49). Overall mortality was 18.4% (9/49). A stepwise multivariable logistic regression and LASSO logistic regression model showed that time from injury to initial operation was the sole statistically significant risk factor. The ROC curve at the optimal threshold of 15.77 h showed the following: area under ROC curve, 0.782; sensitivity, 68.8%; specificity, 87.9%; positive predictive value, 73.3%; and negative predictive value, 85.3%. There was no significant difference in outcomes between primary repair alone and pyloric exclusion. Conclusions: Time from injury to initial operation may be the sole significant risk factor for postoperative duodenal leakage. Pyloric exclusion may not be able to prevent postoperative leakage

Delayed Severe Hemobilia after Endoscopic Biliary Plastic Stent Insertion

Hemobilia is a rare gastrointestinal bleeding, usually caused by injury to the bile duct. Hemobilia after endoscopic retrograde cholangiopancreatography (ERCP) is generally self-limiting and patients will spontaneously recover, but some severe and fatal hemorrhages have been reported. ERCP-related bowel or bile duct perforation should be managed promptly, according to the type of injury and the status of the patient. We recently experienced a case of late-onset severe hemobilia in which the patient recovered after endoscopic biliary stent insertion. The problem was attributable to ERCP-related bile duct perforation during stone removal, approximately 5 weeks prior to the hemorrhagic episode. The removal of the stent was performed 10 days before the onset of hemobilia. The bleeding was successfully treated by two sessions of transarterial coil embolization

Pancreatic tuberculosis masquerading as pancreatic serous cystadenoma

Solitary pancreatic involvement of tuberculosis is rare, especially in an immunocompetent individual, and it may be misdiagnosed as pancreatic cystic neoplasms. Pancreatic cystic neoplasms are being identified in increasing numbers, probably because of the frequent use of radiology and advances in endoscopic techniques. However, they are composed of a variety of neoplasms with a wide range of malignant potential, and it is often difficult to differentiate pancreatic tuberculosis mimicking cystic neoplasms from benign or malignant pancreatic cystic neoplasms. Non-surgical diagnosis of pancreatic tuberculosis is inconclusive and continues to be a challenge in many cases. If so, then laparotomy should be employed to establish the diagnosis. Therefore, pancreatic tuberculosis should be kept in mind during the differential diagnosis of solitary cystic masses in the pancreas. We report a patient who had solitary pancreatic tuberculosis masquerading as pancreatic serous cystadenoma