Association between long working hours and metabolic dysfunction-associated steatotic liver disease: a nationwide population-based study in Korea.

OBJECTIVES: Long working hour is a known risk factor for metabolic diseases. We explored the association between working hours and metabolic dysfunction-associated steatotic liver disease (MASLD). STUDY DESIGN: Data on working hours among 22,818 workers (11,999 females) from the Korea National Health and Nutrition Examination Survey (2013-2021) were used for this study. METHODS: MASLD was defined as a combination of hepatic steatosis combined with one or more of cardiometabolic risk factors (overweight/obesity, prediabetes/diabetes, raised blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol). Hepatic steatosis was assessed using the hepatic steatosis index. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The overall prevalence of MASLD was 30.4% in men and 18.1% in women. Among male workers, 20.2% worked ≥55 h/week, whereas among female workers, 10.1% worked ≥55 h/week. Compared with working 35-40 h/week, working ≥55 h/week was positively associated with overweight/obesity (OR: 1.21; 95% CI: 1.05-1.40), pre-diabetes mellitus (pre-DM)/DM (OR: 1.20; 95% CI: 1.04-1.38), raised blood pressure (OR: 1.17; 95% CI: 1.02-1.35), and presence of any cardiometabolic risk factors (OR: 1.56; 95% CI: 1.21-2.02). The adjusted OR (95% CI) of the association between working hours and MASLD was 1.27 (1.09-1.47) for ≥55 h/week compared with working 35-40 h/week in male workers. In female workers, long working hours were not clearly associated with cardiometabolic risk factors and MASLD. CONCLUSION: Long working hours are positively associated with MASLD among Korean male workers. Policy interventions are needed to mitigate the adverse metabolic effects of prolonged working hours.

Anchoring device to prevent membrane detachment and preterm prelabor rupture of membranes after fetal intervention.

OBJECTIVE: To assess the feasibility of using a novel device designed for minimally invasive suturing to anchor fetal membranes to the uterine wall and to close surgical defects after fetoscopy. METHODS: We tested the WestStitch™ suturing device both ex vivo and in vivo. In the ex-vivo studies, 12-Fr trocar defects were created with a fetoscope in five specimens of human uterine tissue with fetal membranes attached. Specimens were examined for integrity of the anchoring stitch. For the in-vivo studies, trocar defects were created in the two uterine horns of three pregnant ewes, each carrying twins at approximately 79-90 days' gestation. One trocar defect in each ewe was repaired using the suture device, and the other was left unrepaired as a control. The repair sites were examined for membrane-anchoring integrity when the defect was created and at delivery. RESULTS: Fetal membranes were anchored successfully to the uterine myometrium using the suture-delivery device in all five experiments performed ex vivo. The in-vivo experiments also revealed successful membrane anchoring compared with controls, both at the time of device deployment and 1-9 weeks after the procedure. CONCLUSIONS: We successfully anchored amniotic membranes to the underlying myometrium using a suturing device, both ex vivo and in vivo. Further studies are needed to evaluate the efficacy of the device and to determine whether it can successfully anchor fetal membranes percutaneously in human patients. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial.

We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial.

Correlations between H2 Permeation and Physical/Mechanical Properties in Ethylene Propylene Diene Monomer Polymers Blended with Carbon Black and Silica Fillers.

H2 permeation in peroxide-crosslinked EPDM blended with carbon black (CB) and silica fillers was studied at pressures ranging from 1.2 MPa to 90 MPa via the volumetric analysis technique. H2 uptake in the CB-filled EPDM revealed dual-sorption behaviors via Henry's law and the Langmuir model, which were attributed to H2 absorption by the polymer chains and H2 adsorption at the filler interfaces, respectively. Additionally, single-sorption mechanisms were observed for neat EPDM and silica-blended EPDM according to Henry's law, indicating H2 absorption by the polymer chain. The linear decreases in the diffusivity with filler content for the silica-blended EPDMs were attributed to increases in the diffusion paths caused by the filler. Exponential decreases in the diffusivity with increasing filler content and in the permeation with the physical/mechanical properties for CB-filled EPDMs were caused by decreases in the fractional free volume due to increased densities for the EPDM composites. Moreover, good filler-dependent correlations between permeability and density, hardness, and tensile strength were demonstrated for EPDMs used as sealing materials for O-rings. From the resulting equation, we predicted the permeation value without further measurements. Thus, we can select EPDM candidates satisfying the permeation guidelines used in hydrogen infrastructure for the future hydrogen economy.

PurUUpurU: An Oligonucleotide Virulence Factor in RNA Viruses.

Background The copy number of the oligonucleotide 5'-purine-uridine-uridine-purine-uridine-3' (purUUpurU) motif in a viral genome was previously shown to correlate with the severity of acute illness. This study aimed to determine whether purUUpurU content correlates with virulence in other single-strand RNA (ssRNA) viruses that vary in clinical severity. Methodology We determined the copy number of purUUpurU in the genomes of two subtypes of human respiratory syncytial virus (RSV), respiratory syncytial virus A (RSV-A), and respiratory syncytial virus B (RSV-B), which vary in clinical severity. In addition, we determined the purUUpurU content of the four ebolaviruses that cause human disease, dengue virus, rabies virus, human rhinovirus-A, poliovirus type 1, astrovirus, rubella, yellow fever virus, and measles virus. Viral nucleotide sequence files were downloaded from the National Center for Biotechnology Information (NCBI)/National Institutes of Health website. In addition, we determined the cumulative case fatality rate of 20 epidemics of the Ebola virus and compared it with that of the other human ebolaviruses. Results The genomic purUUpurU content correlated with the severity of acute illness caused by both subtypes of RSV and human ebolaviruses. The lowest purUUpurU content was in the genome of the rubella virus, which causes mild disease. Conclusions The quantity of genomic purUUpurU is a virulence factor in ssRNA viruses. Blood hyperviscosity is one mechanism by which purUUpurU causes pathology. Comparative quantitative genomic analysis for purUUpurU will be helpful in estimating the risk posed by emergent ssRNA viruses.

Cluster Analysis of DSC MRI, Dynamic Contrast-Enhanced MRI, and DWI Parameters Associated with Prognosis in Patients with Glioblastoma after Removal of the Contrast-Enhancing Component: A Preliminary Study.

BACKGROUND AND PURPOSE: No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering. MATERIALS AND METHODS: A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors. RESULTS: The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (P = .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04; P = .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival. CONCLUSIONS: Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.

Evaluation of Kinesiophobia in Survivors of Major Burn Injury.

Kinesiophobia, the fear of movement and reinjury, has not been described in burn injury survivors. Physical activity is a key component of burn rehabilitation programs. Yet, not all burn survivors exercise at the recommended level. This is an exploratory study examining the association of the demographics and injury characteristics of burn survivors with a fear of movement. The subjective fear of movement was measured using the Tampa Scale for Kinesiophobia (TSK). The TSK score was compared between several demographics and injury characteristics by performing the independent sample t-test. Sixty-six percent of subjects in our study (n = 35), reported high levels of kinesiophobia (score 37 or above). The mean scores of the TSK were greater in males (40.7), non-white (43.0), Hispanic/Latino (41.1), age greater than 50 years (42.3), and TBSA burn of >15% compared to females (36.9), white (38.5), non-Hispanic/Latino (39.3), age 50 years or less (38.1), and TBSA 15% or less (39.4), respectively. However, with the exception of time postinjury, none of the mean differences were statistically significant. Subjects who had sustained a burn injury more than 12 months ago showed higher levels of kinesiophobia than the subjects who were injured within 12 months with a mean difference of 7.35 (P = .01). Thus, this study highlights the importance of 1) continued, long-term follow-up for burn survivors, and 2) appropriate educational and treatment interventions to address any underlying existing, new, or emerging medical issues that may contribute to the fear or avoidance of movement.

Improved Water and Waste Management Practices Reduce Diarrhea Risk in Children under Age Five in Rural Tanzania: A Community-Based, Cross-Sectional Analysis.

Diarrhea remains a significant cause of morbidity and mortality among children in developing countries. Water, sanitation, and hygiene practices (WASH) have demonstrated improved diarrhea-related outcomes but may have limited implementation in certain communities. This study analyzes the adoption and effect of WASH-based practices on diarrhea in children under age five in the rural Busiya chiefdom in northwestern Tanzania. In a cross-sectional analysis spanning July-September 2019, 779 households representing 1338 under-five children were surveyed. Among households, 250 (32.1%) reported at least one child with diarrhea over a two-week interval. Diarrhea prevalence in under-five children was 25.6%. In per-household and per-child analyses, the strongest protective factors against childhood diarrhea included dedicated drinking water storage (OR 0.25, 95% CI 0.18−0.36; p < 0.001), improved waste management (OR 0.37, 95% CI 0.27−0.51; p < 0.001), and separation of drinking water (OR 0.38, 95% CI 0.24−0.59; p < 0.001). Improved water sources were associated with decreased risk of childhood diarrhea in per-household analysis (OR 0.72, 95% CI 0.52−0.99, p = 0.04), but not per-child analysis (OR 0.83, 95% CI 0.65−1.05, p = 0.13). Diarrhea was widely treated (87.5%), mostly with antibiotics (44.0%) and oral rehydration solution (27.3%). Targeting water transportation, storage, and sanitation is key to reducing diarrhea in rural populations with limited water access.

Effects of military life on changes in body mass index of enlisted men: a cross-sectional study.

BACKGROUND: Obesity is a serious health problem with an incidence that is increasing rapidly. Enlisted men are a distinctive group characterised by 24-hour community-living and are likely to experience changes in body weight as a result of regular diet and exercise during enlistment. METHODS: This study reviewed data from the Second Military Health Survey. Changes in body mass index (BMI) before and during military service were analysed using paired t-test. We calculated OR and 95% CI for factors affecting weight improvement during military service through logistic regression. RESULTS: The mean BMI in the underweight group increased by 5.87 kg/m2 during service, while that in the normal weight group increased by 1.18 kg/m2. In contrast, the mean BMI in the overweight group decreased by 5.47 kg/m2 during service. The OR for an improved BMI in the subjective good health group compared with the subjective poor health group was statistically significant (OR=1.71, 95% CI 1.02 to 2.87). The OR for an improved BMI was significantly higher in the group with three or more times per week of strength training than in the group with one to two times per week of strength training, and was higher among the marines compared with the Army soldiers (OR=1.48, 95% CI 1.03 to 2.12 and OR=2.15, 95% CI 1.07 to 4.32, respectively). CONCLUSIONS: Strength training showed a statistically significant increase in BMI during military service. Furthermore, the BMI of men who were underweight before their service increased, while it decreased among those who were overweight.

Time-resolved Rayleigh scattering measurements of methane clusters for laser-cluster fusion experiments.

We present a time-resolved analysis of Rayleigh scattering measurements to determine the average size of methane clusters and find the optimum timing for laser-cluster fusion experiments. We measure Rayleigh scattering and determine the average size of methane clusters varying the backing pressure (P0) from 11 bar to 69 bar. Regarding the onset of clustering, we estimate that the average size of methane clusters at the onset of clustering is Nc0≅20 at 11 bar. According to our measurements, the average cluster radius r follows the power law of r∝P01.86. Our ion time-of-flight measurements indicate that we have produced energetic deuterium ions with kT = 52±2 keV after laser-cluster interaction using CD4 gas at 50 bar. We find that this ion temperature agrees with the predicted temperature from CD4 clusters at 50 bar with r = 14 nm assuming the Coulomb explosion model.

From bench to bedside: Single-cell analysis for cancer immunotherapy.

Single-cell technologies are emerging as powerful tools for cancer research. These technologies characterize the molecular state of each cell within a tumor, enabling new exploration of tumor heterogeneity, microenvironment cell-type composition, and cell state transitions that affect therapeutic response, particularly in the context of immunotherapy. Analyzing clinical samples has great promise for precision medicine but is technically challenging. Successfully identifying predictors of response requires well-coordinated, multi-disciplinary teams to ensure adequate sample processing for high-quality data generation and computational analysis for data interpretation. Here, we review current approaches to sample processing and computational analysis regarding their application to translational cancer immunotherapy research.

Constraint-induced intervention as an emergent phenomenon from synaptic competition in biological systems.

The principle of constraint-induced therapy is widely practiced in rehabilitation. In hemiplegic cerebral palsy (CP) with impaired contralateral corticospinal projection due to unilateral injury, function improves after imposing a temporary constraint on limbs from the less affected hemisphere. This type of partially-reversible impairment in motor control by early brain injury bears a resemblance to the experience-dependent plastic acquisition and modification of neuronal response selectivity in the visual cortex. Previously, such mechanism was modeled within the framework of BCM (Bienenstock-Cooper-Munro) theory, a rate-based synaptic modification theory. Here, we demonstrate a minimally complex yet sufficient neural network model which provides a fundamental explanation for inter-hemispheric competition using a simplified spike-based model of information transmission and plasticity. We emulate the restoration of function in hemiplegic CP by simulating the competition between cells of the ipsilateral and contralateral corticospinal tracts. We use a high-speed hardware neural simulation to provide realistic numbers of spikes and realistic magnitudes of synaptic modification. We demonstrate that the phenomenon of constraint-induced partial reversal of hemiplegia can be modeled by simplified neural descending tracts with 2 layers of spiking neurons and synapses with spike-timing-dependent plasticity (STDP). We further demonstrate that persistent hemiplegia following unilateral cortical inactivation or deprivation is predicted by the STDP-based model but is inconsistent with BCM model. Although our model is a highly simplified and limited representation of the corticospinal system, it offers an explanation of how constraint as an intervention can help the system to escape from a suboptimal solution. This is a display of an emergent phenomenon from the synaptic competition.

A Prototype of a Fully-Implantable Charge-Balanced Artificial Sensory Stimulator for Bi-directional Brain-Computer-Interface (BD-BCI).

Bi-directional brain-computer interfaces (BD-BCI) to restore movement and sensation must achieve concurrent operation of recording and decoding of motor commands from the brain and stimulating the brain with somatosensory feedback. Previously we developed and validated a benchtop prototype of a fully implantable BCI system for motor decoding. Here, a prototype artificial sensory stimulator was integrated into the benchtop system to develop a prototype of a fully-implantable BD-BCI. The artificial sensory stimulator incorporates an active charge balancing mechanism based on pulse-width modulation to ensure safe stimulation for chronically interfaced electrodes to prevent damage to brain tissue and electrodes. The feasibility of the BD-BCI system's active charge balancing was tested in phantom brain tissue. With the charge-balancing, the removal of the residual charges on an electrode was evident. This is a critical milestone toward fully-implantable BD-BCI systems.

NITROGEN RESPONSE DEFICIENCY 1-mediated CHL1 induction contributes to optimized growth performance during altered nitrate availability in Arabidopsis.

Plants cannot fix nitrogen directly; they must absorb it from the soil through their roots, or in rare cases, form associations with nitrogen-fixing bacteria. The efficiency of nitrogen use in most domesticated crops is low, and more than half of the available nitrogen in the soil can leach into the environment. Understanding the nitrogen signaling pathways is essential for maximizing the efficiency of nitrogen use in crops. In the present study, we characterized the Myeloblastosis (Myb)-like gene NITROGEN RESPONSE DEFICIENCY 1 (NID1). We observed that the growth performance of nid1 knockout (KO) mutant Arabidopsis plants was better than that of wild-type Col-0 plants under very low-nitrate conditions, leading to improved growth performance in the nid1 KO plants. The results of chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that NID1 binds to the promoter of the NITRATE TRANSPORTER (NRT)1.1 gene. Furthermore, nid1 KO plants exhibited similar growth performance to the nid1 KO/chl1-5 (nrt1.1 KO) double mutant and chl1-5 (nrt1.1 KO) plants in response to low-nitrate conditions. We suggest that NID1 plays a crucial role as a transcription factor in optimizing plant growth by modulating the transcript abundance of the nitrate transceptor CHL1, leading to enhanced ABA accumulation in low-nitrate conditions.

Disruption in murine Eml1 perturbs retinal lamination during early development.

During mammalian development, establishing functional neural networks in stratified tissues of the mammalian central nervous system depends upon the proper migration and positioning of neurons, a process known as lamination. In particular, the pseudostratified neuroepithelia of the retina and cerebrocortical ventricular zones provide a platform for progenitor cell proliferation and migration. Lamination defects in these tissues lead to mispositioned neurons, disrupted neuronal connections, and abnormal function. The molecular mechanisms necessary for proper lamination in these tissues are incompletely understood. Here, we identified a nonsense mutation in the Eml1 gene in a novel murine model, tvrm360, displaying subcortical heterotopia, hydrocephalus and disorganization of retinal architecture. In the retina, Eml1 disruption caused abnormal positioning of photoreceptor cell nuclei early in development. Upon maturation, these ectopic photoreceptors possessed cilia and formed synapses but failed to produce robust outer segments, implying a late defect in photoreceptor differentiation secondary to mislocalization. In addition, abnormal positioning of Müller cell bodies and bipolar cells was evident throughout the inner neuroblastic layer. Basal displacement of mitotic nuclei in the retinal neuroepithelium was observed in tvrm360 mice at postnatal day 0. The abnormal positioning of retinal progenitor cells at birth and ectopic presence of photoreceptors and secondary neurons upon maturation suggest that EML1 functions early in eye development and is crucial for proper retinal lamination during cellular proliferation and development.

Dynamic Contrast-Enhanced MR Imaging of Nonenhancing T2 High-Signal-Intensity Lesions in Baseline and Posttreatment Glioblastoma: Temporal Change and Prognostic Value.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma has not been thoroughly elucidated to date. We evaluated the temporal change and prognostic value for progression-free survival of dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma before and after standard treatment, including gross total surgical resection. MATERIALS AND METHODS: This retrospective study included 33 patients who were newly diagnosed with glioblastoma and treated with gross total surgical resection followed by concurrent chemoradiation therapy and adjuvant chemotherapy with temozolomide in a single institution. All patients underwent dynamic contrast-enhanced MR imaging before surgery as a baseline and after completion of maximal surgical resection and concurrent chemoradiation therapy. On the whole nonenhancing T2 high-signal-intensity lesion, dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters (volume transfer constant [K trans], volume of extravascular extracellular space [v e], and blood plasma volume [vp ]) were calculated. The Cox proportional hazards regression model analysis was performed to determine the histogram features or percentage changes of pharmacokinetic parameters related to progression-free survival. RESULTS: Baseline median K trans, baseline first quartile K trans, and posttreatment median K trans were significant independent variables, as determined by univariate analysis (P < .05). By multivariate Cox regression analysis including methylation status of O6-methylguanine-DNA methyltransferase, baseline median K trans was determined to be the significant independent variable and was negatively related to progression-free survival (hazard ratio = 1.48, P = .003). CONCLUSIONS: Baseline median K trans from nonenhancing T2 high-signal-intensity lesions could be a potential prognostic imaging biomarker in patients undergoing gross total surgical resection followed by standard therapy for glioblastoma.

Prognostic Predictions for Patients with Glioblastoma after Standard Treatment: Application of Contrast Leakage Information from DSC-MRI within Nonenhancing FLAIR High-Signal-Intensity Lesions.

BACKGROUND AND PURPOSE: Attempts have been made to quantify the microvascular leakiness of glioblastomas and use it as an imaging biomarker to predict the prognosis of the tumor. The purpose of our study was to evaluate whether the extraction fraction value from DSC-MR imaging within nonenhancing FLAIR hyperintense lesions was a better prognostic imaging biomarker than dynamic contrast-enhanced MR imaging parameters for patients with glioblastoma. MATERIALS AND METHODS: A total of 102 patients with glioblastoma who received a preoperative dynamic contrast-enhanced MR imaging and DSC-MR imaging were included in this retrospective study. Patients were classified into the progression (n = 87) or nonprogression (n = 15) groups at 24 months after surgery. We extracted the means and 95th percentile values for the contrast leakage information parameters from both modalities within the nonenhancing FLAIR high-signal-intensity lesions. RESULTS: The extraction fraction 95th percentile value was higher in the progression-free survival group of >24 months than at ≤24 months. The median progression-free survival of the group with an extraction fraction 95th percentile value of >13.32 was 17 months, whereas that of the group of ≤13.32 was 12 months. In addition, it was an independent predictor variable for progression-free survival in the patients regardless of their ages and genetic information. CONCLUSIONS: The extraction fraction 95th percentile value was the only independent parameter for prognostic prediction in patients with glioblastoma among the contrast leakage information, which has no statistically significant correlations with the DCE-MR imaging parameters.

Impact of stringent response in proteinuria on long-term renal outcomes in proliferative lupus nephritis.

OBJECTIVES: Favourable long-term prognosis in proliferative lupus nephritis (LN) is associated with the achievement of complete renal response (CR), which is defined as a urine protein/creatinine ratio (UPCR) of < 0.5. However, it is unclear whether a more stringent cut-off for proteinuria (normal value of proteinuria; UPCR < 0.15) is better than CR. We aimed to evaluate the effect of stringent CR, defined as a UPCR of <0.15, on long-term renal outcomes in proliferative LN. METHODS: We included 87 patients with class III or IV LN who achieved CR at one year after induction therapy. Clinical and laboratory data were compared between the stringent and non-stringent CR groups. Logistic regression analysis was performed to identify factors associated with achievement of stringent CR. Cox analysis was performed to analyse the risk factors for renal flare and development of chronic kidney disease (CKD). RESULTS: The stringent and non-stringent CR groups included 58 and 29 patients, respectively. The two groups showed no significant baseline differences in terms of the clinical, laboratory and pathological classification. The sustained CR rates during five years were 91.3% and 50.0% (p = 0.014) in the stringent and non-stringent CR groups, respectively. In Cox analyses, the achievement of stringent CR was associated with a lower risk of five-year renal flare rate (hazard ratio (HR) = 0.161, 95% confidence interval (CI) 0.063-0.411, p < 0.01) and development of CKD (HR = 0.189, 95% CI 0.047-0.752, p = 0.018). Mycophenolate mofetil induction therapy was associated with achievement of stringent CR at a borderline level of significance (HR = 7.268, 95% CI 0.894-59.089, p = 0.064). CONCLUSION: Achievement of stringent CR predicted lower risk of renal flare and development of CKD in proliferative LN. These findings suggest that stringent CR is a valuable treatment target in proliferative LN.

Interventions to improve hand hygiene compliance in emergency departments: a systematic review.

The emergency department (ED) is where hand hygiene problems are significant as the procedures in the ED are often high risk and invasive. To date, there have been no comprehensive reviews on hand hygiene in EDs. The aim of this study was to investigate hand hygiene compliance (HHC) rate, factors affecting the HHC rate, and intervention strategies to improve HHC in EDs. Electronic databases were used to search for research published from 1948 to January 2018. The databases included ovidMEDLINE, ovidEMBASE, the Cochrane Library, CINAHL, Koreamed, and Kmbase. All study designs were included. Two reviewers independently extracted the data and assessed the bias risk using reliable and validated tools. A narrative synthesis was performed. Twenty-four studies, including 12 cross-sectional surveys and 12 interventional studies, were included. Of the 12 interventional studies reviewed, only 33% (N = 4) reported HHC rates of more than 50%. Factors that influenced HHC included types of healthcare worker, hand hygiene indication, ED crowding, positive attitudes towards HHC, patient location, auditing hand hygiene, and type of shift. Almost all of the studies (83.3%) applied multimodal or dual interventions to improve HHC. A range of strategies, including education, monitoring and providing feedback, campaigns, and cues, effectively improved HHC. The review findings indicate that there is a room for improvement in HHC in EDs. Future randomized controlled trials are necessary to determine which intervention modalities are most effective and sustainable for HHC improvement.

Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes.

The Gram-negative human pathogen N. gonorrhoeae (Ngo) quickly attaches to epithelial cells, and large numbers of the bacteria remain on the cell surface for prolonged periods. Ngo invades cells but few viable intracellular bacteria are recovered until later stages of infection, leading to the assumption that Ngo is a weak invader. On the cell surface, Ngo quickly recruits CD46-cyt1 to the epithelial cell cortex directly beneath the bacteria and causes its cleavage by metalloproteinases and Presenilin/γSecretease; how these interactions affect the Ngo lifecycle is unknown. Here, we show Ngo induces an autophagic response in the epithelial cell through CD46-cyt1/GOPC, and this response kills early invaders. Throughout infection, the pathogen slowly downregulates CD46-cyt1 and remodeling of lysosomes, another key autophagy component, and these activities ultimately promote intracellular survival. We present a model on the dynamics of Ngo infection and describe how this dual interference with the autophagic pathway allows late invaders to survive within the cell.