Capacity building to address antimicrobial resistance in remote Australia: The inaugural HOT NORTH Antimicrobial Academy.

BACKGROUND: Rates of antimicrobial resistance (AMR) for some pathogens in Australia are considerably higher in rural and remote compared to urban regions. The inaugural Hot North Antimicrobial Academy was a 9-month educational programme aimed to build workforce knowledge and capacity in antimicrobial use, audit, stewardship, surveillance and drug resistance in remote primary health care. METHODS: The Academy was advertised to Aboriginal and Torres Strait Islander, regional and remote healthcare workers. Participants were Aboriginal health practitioners, nurses, pharmacists and doctors from Queensland, Northern Territory, South Australia and Western Australia working in remote primary health care with a focus on Indigenous health. Due to COVID-19 restrictions, the Academy ran virtually from February-November 2021 using Microsoft Teams. The Academy was evaluated using surveys and yarning circles to assess impact and knowledge gain. RESULTS: Participants and faculty from across Australia attended 19 lectures and mentorship sessions. Eleven participants commenced and eight (73%) completed the Academy. The Academy raised participants awareness of AMR guidelines, governance and generating change; built confidence in advocacy; grew knowledge about drug resistant infections; and created a community of AMR champions in Indigenous health. CONCLUSION: The evaluation confirmed the Academy met the needs of participants, provided opportunities to move stewardship from tertiary hospitals into Indigenous and remote clinics and developed skills in research, audit, stewardship and advocacy for all involved. All sessions were recorded for future use, with facilitation by the National Aboriginal Community Controlled Health Organisation (NACCHO) in future years.

Designing Calcium Silicate Cements with On-Demand Properties for Precision Endodontics.

Calcium silicate (C3S) cements are available in kits that do not account for patients' specific needs or clinicians' preferences regarding setting time, radiopacity, mechanical, and handling properties. Moreover, slight variations in powder components and liquid content affect cement's properties and bioactivity. Unfortunately, it is virtually impossible to optimize several cement properties simultaneously via the traditional "one variable at a time" strategy, as inputs often induce trade-offs in properties (e.g., a higher water-to-powder ratio [W/P] increases flowability but decreases mechanical properties). Herein, we used Taguchi's methods and genetic algorithms (GAs) to simultaneously analyze the effect of multiple inputs (e.g., powder composition, radiopacifier concentration, and W/P) on setting time, pH, flowability, diametral tensile strength, and radiopacity, as well as prescribe recipes to produce cements with predicted properties. The properties of cements designed with GAs were experimentally tested, and the results matched the predictions. Finally, we show that the cements increased the genetic expression of odonto/osteogenic genes, alkaline phosphatase activity, and mineralization potential of dental pulp stem cells. Hence, GAs can produce cements with tailor-made properties and differentiation potential for personalized endodontic treatment.

[Dihydromyricetin alleviates pyroptosis and necroptosis in mice with MPTP-induced chronic Parkinson's disease by inducing autophagy].

OBJECTIVE: To investigate the effect of 8-week dihydromyricetin (DHM) treatment on motor ability of mice with MPTP/probenecid-induced Parkinson's disease (PD) and explore the molecular mechanism. METHODS: Sixty C57BL/6 mice were randomized into the control group, PD model group, PD+DHM group and PD+NEC-1 group (n=15). In the latter 3 groups, the mice were treated with 25 mg·kg-1·d-1 MPTP and 250 mg·kg-1·d-1 probenecid twice a week for 5 weeks to establish PD models; DHM (100 mg·kg-1·d-1) was administered 5 times a week via gavage for 8 weeks and NEC-1 (6.25 mg·kg-1·d-1, twice a week) via intraperitoneal injection for 5 weeks. The changes in motor function of the mice were assessed, and the expressions of TH, GFAP and Iba-1 in the substantia nigra were detected with immunofluorescence assay; serum levels of IL-1ß and LDH were detected using ELISA. The mRNA expressions of TNF-α and IL-6 were determined with RT-PCR, and the expressions of TH and proteins associated with pyroptosis, neuroinflammation, necroptosis and autophagy in the striatum were detected using Western blotting. MPP +-activated Bv-2 cells were treated with different concentrations of DHM or 3-MA, and the expressions of proteins associated with autophagy and NLRP3 were detected using Western blotting; PI staining was used to detect cell necroptosis. RESULTS: The PD mouse models showed significantly reduced TH-positive cells and TH protein expression (P < 0.001). DHM obviously ameliorated motor deficits and TH loss in PD mice, increased TH expression (P=0.0023), decreased α-syn levels (P < 0.001), lowered the protein expressions of GFAP (P=0.045) and Iba-1 (P < 0.001) and the mRNA and protein levels of TNF-α (P=0.0015) and IL-6 (P < 0.001), and increased IL-4 level (P < 0.001). The 8-week DHM treatment significantly suppressed pyroptosis and necroptosis and activated autophagy in the striatum of the PD mice. In MPP +-induced Bv-2 cells, DHM treatment effectively reversed autophagy impairment and inhibited NLRP3 and TNF-α, IL-6 and IL-1ß release, and the anti--inflammatory effects of DHM was obviously blunted by 3-MA. CONCLUSION: DHM can improve motor function of PD mice probably by activating autophagy to inhibit pyroptosis and necroptosis and reduce neuroinflammation.

Impact of fetal growth restriction on pregnancy outcome in women undergoing expectant management for preterm pre-eclampsia.

OBJECTIVES: To assess whether coexisting fetal growth restriction (FGR) influences pregnancy latency among women with preterm pre-eclampsia undergoing expectant management. Secondary outcomes assessed were indication for delivery, mode of delivery and rate of serious adverse maternal and perinatal outcomes. METHODS: We conducted a secondary analysis of the Pre-eclampsia Intervention (PIE) and the Pre-eclampsia Intervention 2 (PI2) trial data. These randomized controlled trials evaluated whether esomeprazole and metformin could prolong gestation of women diagnosed with pre-eclampsia between 26 and 32 weeks of gestation undergoing expectant management. Delivery indications were deteriorating maternal or fetal status, or reaching 34 weeks' gestation. FGR (defined by Delphi consensus) at the time of pre-eclampsia diagnosis was examined as a predictor of outcome. Only placebo data from PI2 were included, as the trial showed that metformin use was associated with prolonged gestation. All outcome data were collected prospectively from diagnosis of pre-eclampsia to 6 weeks after the expected due date. RESULTS: Of the 202 women included, 92 (45.5%) had FGR at the time of pre-eclampsia diagnosis. Median pregnancy latency was 6.8 days in the FGR group and 15.3 days in the control group (difference 8.5 days; adjusted 0.49-fold change (95% CI, 0.33-0.74); P < 0.001). FGR pregnancies were less likely to reach 34 weeks' gestation (12.0% vs 30.9%; adjusted relative risk (aRR), 0.44 (95% CI, 0.23-0.83)) and more likely to be delivered for suspected fetal compromise (64.1% vs 36.4%; aRR, 1.84 (95% CI, 1.36-2.47)). More women with FGR underwent a prelabor emergency Cesarean section (66.3% vs 43.6%; aRR, 1.56 (95% CI, 1.20-2.03)) and were less likely to have a successful induction of labor (4.3% vs 14.5%; aRR, 0.32 (95% CI, 0.10-1.00)), compared to those without FGR. The rate of maternal complications did not differ significantly between the two groups. FGR was associated with a higher rate of infant death (14.1% vs 4.5%; aRR, 3.26 (95% CI, 1.08-9.81)) and need for intubation and mechanical ventilation (15.2% vs 5.5%; aRR, 2.97 (95% CI, 1.11-7.90)). CONCLUSION: FGR is commonly present in women with early preterm pre-eclampsia and outcome is poorer. FGR is associated with shorter pregnancy latency, more emergency Cesarean deliveries, fewer successful inductions and increased rates of neonatal morbidity and mortality. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Current status and influencing factors for physicians in different departments prescribing novel hypoglycemic agent with cardiovascular benefits].

Objective: To investigate the knowledge, use and barriers when prescribing GLP-1RA and SGLT2i among cardiologists, endocrinologists and general practitioners, and explore the influencing factors that hinder the use of these medications. Methods: A questionnaire was conducted among physicians in the above departments in Peking University Third Hospital and health service institutions at all levels in its medical consortium. A total of 342 physicians were involved. Among them, 40.6% (139) were cardiologists, 28.9% (99) were endocrinologists and 30.4% (104) were general practitioners; 66.7% (270) came from Beijing while 33.3% (72) from other provinces. The survey included clinicians' knowledge and current use of GLP-1RA and SGLT2i, and the possible reasons that influenced the prescription of these medications. Medical therapies of physicians were investigated by simulating different clinical scenarios. The difference of measures among physicians in different departments was compared. Results: A total of 342 physicians were involved, with the average age of 40 (35, 46) years old and the average working time of 13 (7, 20) years. Among them, 40.6% (139) were male. 77.5% (265) physicians had comprehensive knowledge of SGLT2i and prescribed it, which was higher than that for GLP-1RA (70.5%, 241) (P<0.001). 21.1% (72) physicians prescribed SGLT2i more than 20 times per month, which was higher than that for GLP-1RA (8.2%, 28) (P<0.001). Endocrinologists had more knowledge and prescribed more GLP-1RA and SGLT2i compared with other physicians (both P values<0.001). 38.1% (53) cardiologists, 22.2% (22) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust GLP-1RA, which was the primary barrier for the use of medications (P=0.042). 27.4% (38) cardiologists, 14.1% (14) endocrinologists, and 30.8% (32) general practitioners believed patients needed an endocrinologist to evaluate and adjust SGLT2i, which was the primary barrier for the use of medications (P=0.018). 21.6% (30) cardiologists, 45.5% (45) endocrinologists, and 31.7% (33) general practitioners believed side effects of SGLT2i was the primary barrier for the use of medications (P<0.001). For patients with unqualified glycemic control and cardiovascular complications, 65.4% (75) cardiologists, 69.7% (69) endocrinologists, and 43.3% (45) general practitioners chose the above medications (P<0.001). For patients with qualified glycemic control, combined with cardiovascular complications and diabetic organ damage, 35.3% (49) cardiologists, 52.5% (52) endocrinologists, and 25.0% (26) general practitioners chose the above medications (P<0.001). Conclusions: Physicians had more knowledge and prescription of SGLT2i than that of GLP-1RA. Endocrinologists had more knowledge and prescription of the above medications than other physicians. The side effect of medications was potential primary barrier for the use of the novel hypoglycemic agent with cardiovascular benefits. In clinical practice, most of physicians considered that high-risk patients with cardiovascular comorbidities need to be referred to cardiologist or endocrinologist to adjust clinical therapies.

Plant-based milk: unravel the changes of the antioxidant index during processing and storage - a review.

As a nutrient rich emulsion extracted from plant materials, plant-based milk (PBM) has been the latest trend and hot topic in the food industry due to the growing awareness of consumers toward plant-based products in managing the environmental (carbon footprint and land utility), ethical (animal well-fare) and societal (health-conscious) issues. There have been extensive studies and reviews done to discuss the distinct perspective of PBM including its production, health effects and market acceptance. However, not much has been emphasized on the valuable antioxidants present in PBM which is one of the attributes making them stand apart from dairy milk. The amounts of antioxidants in PBM are important. They offered tremendous health benefits in maintaining optimum health and reducing the risk of various health disorders. Therefore, enhancing the extraction of antioxidants and preserving their activity during production and storage is important. However, there is a lack of a comprehensive review of how these antioxidants changes in response to different processing steps involved in PBM production. Presumably, antioxidants in PBM could be potentially lost due to thermal degradation, oxidation or leaching into processing water. Hence, this paper aims to fill the gaps by addressing an extensive review of how different production steps (germination, roasting, soaking, blanching, grinding and filtration, and microbial inactivation) affect the antioxidant content in PBM. In addition, the effect of different microbial inactivation treatments (thermal or non-thermal processing) on the alteration of antioxidant in PBM was also highlighted. This paper can provide useful insight for the industry that aims in selecting suitable processing steps to produce PBM products that carry with them a health declaration.

Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)-an open-labelled pilot randomized controlled trial.

BACKGROUND: Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs). OBJECTIVES: This pilot RCT aimed to determine the feasibility of conducting a clinical trial to examine if adjunctive clindamycin with standard therapy has greater efficacy than standard therapy alone for S. aureus infections. METHODS: We performed an investigator-initiated, open-label, multicentre, pilot RCT (ACTRN12617001416381p) in adults and children with severe S. aureus infections, randomized to standard antibiotic therapy with or without clindamycin for 7 days. RESULTS: Over 28 months, across nine sites, 127 individuals were screened and 34 randomized, including 11 children (32%). The primary outcome-number of days alive and free of systemic inflammatory response syndrome ≤14 days-was similar between groups: clindamycin (3 days [IQR 1-6]) versus standard therapy (4 days [IQR 0-8]). The 90 day mortality was 0% (0/17) in the clindamycin group versus 24% (4/17) in the standard therapy group. Secondary outcomes-microbiological relapse, treatment failure or diarrhoea-were similar between groups. CONCLUSIONS: As the first clinical trial assessing adjunctive clindamycin for S. aureus infections, this study indicates feasibility and that adults and children can be incorporated into one trial using harmonized endpoints, and there were no safety concerns. The CASSETTE trial will inform the definitive S. aureus Network Adaptive Platform (SNAP) trial, which includes an adjunctive clindamycin domain and participants with non-severe disease.

The burden of heat-related mortality attributable to recent human-induced climate change.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Study on effects of miR-141-3p in proliferation, migration, invasion and apoptosis of colon cancer cells by inhibiting Bcl2.

PURPOSE: This study aimed to investigate the relationship between miR-141-3p and B lymphocyte-2 gene (Bcl2) gene and its biological behavior on colon cancer cell line SW480. METHODS: qRT-PCR was used to detect the expression level of miR-141-3p in colon cancer tissues and adjacent tissues, as well as in colon cancer cell line and normal human colonic epithelial cell line FHC. MTT assay, wound assay, and Transwell demonstrated the effects of miR-141-3p on colon cancer proliferation, migration and invasion. Targetscan7.1 predictive software and dual luciferase reporter assays were used to detect the targeted regulation of miR-141-3p on the apoptosis-related gene Bcl2. MTT assay, wound assay, Transwell and flow cytometry were used to detect the effect of Bcl2 on miR-141-3p on colon cancer proliferation, migration, invasion and apoptosis. RESULTS: Compared with adjacent tissues, the expression of miR-141-3p in colon cancer tissues was significantly down-regulated. Colon cancer patients with low expression of miR-141-3p had poorer prognosis. Compared with normal colonic epithelial cells, miR-141-3p expression was significantly down-regulated in colon cancer cell lines, and overexpression of miR-141-3p significantly attenuated the proliferation, migration and invasion of colon cancer cells. Knockdown of miR-141-3p significantly promoted the proliferation, migration and invasion of colon cancer cells. miR-141-3p targets the negative regulation of Bcl2. Knockdown of Bcl2 significantly attenuated the promotion of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells and inhibition of apoptosis. Knockdown of Bcl2 significantly enhanced the inhibition effect of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells. CONCLUSIONS: In conclusion, miR-141-3p can inhibit the cancer by regulating Bcl2, and miR-141-3p has the potential to become a potential therapeutic target for colon cancer.

Influences of Hypothermia on the Cortical Blood Supply by Laser Speckle Imaging.

Induced hypothermia has been broadly applied in neurological intensive care unit (NICU). Meanwhile, accidental hypothermia is also a threatening condition in daily life. It is meaningful to investigate the influences of temperature change on the cerebral blood flow (CBF). In the present study, temporal laser speckle image contrast analysis (tLASCA) was implemented to study the relative CBF change in cerebral artery, vein and capillary level under mild (35$\circ$C) and moderate (32$\circ$C) hypothermia. Twelve male Sprague-Dawley rats (300±50g) were anesthetized with sodium pentobarbital and randomly assigned to mild and moderate hypothermia groups (n=9 each). Laser speckle imaging trials were acquired from baseline (37$\circ$C), hypothermia (35$\circ$C or 32$\circ$C) and post-rewarming (37$\circ$C) phases. In the mild group, mean CBF in different vessels all increased throughout the hypothermic and post-rewarming phases. On the contrary, mean CBF reduced by 10% to 20% at 32$\circ$C and returned to ~95% of the baseline level during the post-rewarming session in the moderate group. Besides, in the moderate group, a CBF rebound in vein was found in the post-rewarming phase. Our results suggested that the CBF changed differently between mild and moderate hypothermia, which may worth for further study in clinical. And we demonstrated LSI as a promising method to achieve high spatiotemporal resolution CBF change with minimal invasion.

Intention to seek professional help for depression and its associated factors among elderly patients in Tenkera Health Clinic, Melaka, Malaysia.

BACKGROUND: Prevalence of mental disorders such as depression in the elderly is rising with the ageing population. This study is aimed to determine the prevalence of depression, their intention to seek help and the factors associated to seek professional help among elderly patients in a primary care clinic. METHODS: This was a cross-sectional with systematic sampling conducted from June to December 2019 in Tengkera Health Clinic (THC). Patient Health Questionnaire- 9 (PHQ-9), socioeconomic data and a dichotomous yes-no response for intention to seek help was collected from 273 elderly patients attending the outpatient clinic. RESULTS: The prevalence of elderly depression at THC was 10.3% and the prevalence of intention to seek professional help for depression among elderly patients at Tengkera Health Clinic was 27.5%. Factors that were associated with intention to seek professional help for depression were prior experience of seeking professional help, adjusted OR 3.45[95%CI (1.41-8.48)] and education level of the respondents- secondary education, adjusted OR 3.10 [95%CI (1.01-9.53)] comparing with no formal education; tertiary education, adjusted OR 4.66 [95%CI (1.08-20.04)] comparing with no formal education. CONCLUSION: The prevalence of elderly depression was high while the prevalence of intention to seek professional help for depression in the sample population was low. Primary care physicians play a vital role in identifying elderly patients with low education level for screening and treatment as well as promoting awareness and breaking down barriers and stigma towards mental illness.

Analysis of associations of FBXL19-AS1 with occurrence, development and prognosis of acute pancreatitis.

OBJECTIVE: The aim of the study was to explore the association between F-box and leucine-rich repeat protein 19-antisense ribonucleic acid 1 (FBXL19-AS1) and acute pancreatitis (AP) and its role in prognostic evaluation. PATIENTS AND METHODS: According to the severity of AP, the patients were classified into mild group, moderate-severe group, and severe group, and the expression of FBXL19-AS1 was compared among the three groups. The associations of FBXL19-AS1 with Atlanta classification, computed tomography severity index (CTSI), acute physiology and chronic health evaluation (APACHE) II score, bedside index for severity in acute pancreatitis (BISAP) and Ranson score were analyzed. The optimal cut-off point of severe hyperlipidemia-induced AP was predicted by the receiver operating characteristic (ROC) curves. Then, the incidence rates of local and systemic complications were compared among AP patients with different levels of FBXL19-AS1. After overexpression of FBXL19-AS1 in AP cells, the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) results showed that significantly upregulated the mRNA level of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6. The opposite results were obtained after the knockdown of FBXL19-AS1 in cells. RESULTS: There were no statistical differences in the basic data among the three groups. The FBXL19-AS1 level was increased in severe group than the moderate-severe group and mild group. The area under the curve (AUC) of FBXL19-AS1 in predicting severe AP was 0.9177 (p<0.001). According to the Spearman correlation analysis, the FBXL19-AS1 level had significant positive correlations with the predictive scores of AP severity. The incidence rate of shock, liver dysfunction, and pancreatic necrotic tissue infection was significantly higher in FBXL19-AS1 high-expression group than that in FBXL19-AS1 low-expression group. FBXL19-AS1 could promote the upregulation of inflammatory indexes. CONCLUSIONS: FBXL19-AS1 is highly expressed in the serum of AP patients, and it is positively correlated with the severity of AP. FBXL19-AS1 mediates the inflammatory response and promotes the occurrence and development of pancreatitis, harming the prognosis of patients.

Geospatial epidemiology of Staphylococcus aureus in a tropical setting: an enabling digital surveillance platform.

Delivery of information to clinicians on evolving antimicrobial susceptibility needs to be accurate for the local needs, up-to-date and readily available at point of care. In northern Australia, bacterial infection rates are high but resistance to first- and second-line antibiotics is poorly described and currently-available datasets exclude primary healthcare data. We aimed to develop an online geospatial and interactive platform for aggregating, analysing and disseminating data on regional bacterial pathogen susceptibility. We report the epidemiology of Staphylococcus aureus as an example of the power of digital platforms to tackle the growing spread of antimicrobial resistance in a high-burden, geographically-sparse region and beyond. We developed an online geospatial platform called HOTspots that visualises antimicrobial susceptibility patterns and temporal trends. Data on clinically-important bacteria and their antibiotic susceptibility profiles were sought from retrospectively identified clinical specimens submitted to three participating pathology providers (96 unique tertiary and primary healthcare centres, n = 1,006,238 tests) between January 2008 and December 2017. Here we present data on S. aureus only. Data were available on specimen type, date and location of collection. Regions from the Australian Bureau of Statistics were used to provide spatial localisation. The online platform provides an engaging visual representation of spatial heterogeneity, demonstrating striking geographical variation in S. aureus susceptibility across northern Australia. Methicillin resistance rates vary from 46% in the west to 26% in the east. Plots generated by the platform show temporal trends in proportions of S. aureus resistant to methicillin and other antimicrobials across the three jurisdictions of northern Australia. A quarter of all, and up to 35% of methicillin-resistant S. aureus (MRSA) blood isolates in parts of the northern Australia were resistant to inducible-clindamycin. Clindamycin resistance rates in MRSA are worryingly high in regions of northern Australia and are a local impediment to empirical use of this agent for community MRSA. Visualising routinely collected laboratory data with digital platforms, allows clinicians, public health physicians and guideline developers to monitor and respond to antimicrobial resistance in a timely manner. Deployment of this platform into clinical practice supports national and global efforts to innovate traditional disease surveillance systems with the use of digital technology and to provide practical solutions to reducing the threat of antimicrobial resistance.

Impact of climate variability on length of stay in hospital for childhood pneumonia in rural Bangladesh.

OBJECTIVES: Pneumonia is a significant contributor to mortality and morbidity in children aged <5 years, and it is also one of the leading causes of hospitalisation for children in this age group. This study assessed the association between climate variability, patient characteristics (i.e. age, sex, weight, parental education, socio-economic status) and length of stay (LOS) in hospital for childhood pneumonia and its economic impact on rural Bangladesh. STUDY DESIGN: An ecological study design was used. METHODS: Data on daily hospitalisation for pneumonia in children aged <5 years (including patient characteristics) and daily climate data (temperature and relative humidity) between 1st January 2012 and 31st December 2016 were obtained from the Matlab Hospital (the International Centre for Diarrhoeal Disease Research, Bangladesh) and the Bangladesh Meteorological Department, respectively. A generalised linear model with Poisson link was used to quantify the association between climate factors, patient characteristics and LOS in hospital. RESULTS: The study showed that average temperature, temperature variation and humidity variation were positively associated with the LOS in hospital for pneumonia. A 1°C rise in average temperature and temperature variation during hospital stay increased the LOS in hospital by 1% (relative risk [RR]: 1.010, 95% confidence interval [CI]: 1.001-1.018) and 9.3% (RR: 1.093, 95% CI: 1.051-1.138), respectively. A 1% increase in humidity variation increased the LOS in hospital for pneumonia by 2.2% (RR: 1.022, 95% CI: 1.004-1.039). In terms of economic impact, for every 1° C temperature variation during the period of hospital stay, there is an addition of 0.81 USD/day/patient as a result of direct costs and 1.8 USD/day/patient for total costs. Annually, this results in an additional 443 USD for direct and 985 USD for total costs. CONCLUSIONS: Climate variation appears to significantly contribute to the LOS in hospital for childhood pneumonia. These findings may help policymakers to develop effective disease management and prevention strategies.

TCF19 aggravates the malignant progression of colorectal cancer by negatively regulating WWC1.

OBJECTIVE: The aim of this study was to clarify the role of TCF19 in influencing the malignant progression of colorectal cancer (CRC) by negatively regulating WWC1. PATIENTS AND METHODS: Relative expression levels of TCF19 and WWC1 in CRC tissues and cells were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The prognosis of CRC patients was assessed by the Kaplan-Meier method. Meanwhile, the correlation between TCF19 and pathological indexes of CRC patients was evaluated. Regulatory effects of TCF19/WWC1 on viability, colony formation ability, and migration in HT29 and HCT-8 cells were evaluated. Finally, rescue experiments were conducted to elucidate a negative feedback loop of TCF19/WWC1 in influencing the progression of CRC. RESULTS: TCF19 was significantly up-regulated in CRC, while WWC1 was down-regulated. High-level TCF19 or low-level WWC1 indicated worse survival of CRC patients. Besides, TCF19 expression level was positively correlated with the occurrence of distant metastasis in CRC. Silence of TCF19 significantly attenuated proliferative and migratory capacities of HT29 cells. However, overexpression of TCF19 yielded the opposite trends in HCT-8 cells. WWC1 expression was negatively regulated by TCF19 in CRC tissues. In addition, knockdown of WWC1 abolished the regulatory effect of TCF19 on CRC cells. CONCLUSIONS: TCF19 is closely correlated with the occurrence of distant metastasis and poor prognosis of CRC. Furthermore, it aggravates the malignant progression of CRC via negatively regulating WWC1.

Use of acidified versus non-acidified liquid human milk fortifier in very low birth weight infants: A retrospective comparison of clinical outcomes.

BACKGROUND: Use of human milk is recommended for low birth weight (VLBW) infants, but must be safety fortified with sterile liquid fortifiers to be nutritionally sufficient. Due to clinical concern for a high incidence of metabolic acidosis among VLBW infants fed human milk fortified with acidified liquid human milk fortifier (ALHMF), we aimed to retrospectively compare the outcomes of infants fed ALHMF to those fortified with non-acidified liquid HMF (NLHMF). METHODS: Medical records of VLBW neonates admitted to our institution's neonatal intensive care unit from July 1st, 2013 to June 30th, 2014 were reviewed. 129 patients were included in the study, 61 of which received ALHMF and 68 received NLHMF. Metabolic, nutritional and clinical outcomes, including growth, were compared between the two cohorts. RESULTS: Of the infants who received ALHMF, 70.5% developed metabolic acidosis compared to only 11.8% in the NLHMF group (p < 0.001). In addition, infants who received NLHMF had a 10% greater growth velocity during the period of fortification (p = 0.01). During the full course of hospitalization, no difference in growth velocity was seen between the groups and greater length gains were found in the ALHMF group. CONCLUSIONS: The use of human milk fortified with ALHMF was associated with an increased incidence of metabolic acidosis and poorer growth during the period of fortification when compared to NLHMF-fortified feedings. These growth effects were not apparent when the duration of hospitalization was considered, suggesting a need for further study to better characterize the advantages and disadvantages of each fortifier.

[Efficiency analysis on functional protection of nerve plane-oriented laparoscopic total mesorectal excision].

Objective: Using previous total mesorectal excision with pelvic autonomic nerve preservation (PANP+TME) and simple total mesorectal excision (TME) without emphasis on retained nerves as control, we explore the advantages of nerve plane-oriented laparoscopic total mesorectal excision (NPO+LTME) on urinary and sexual function. Methods: A retrospective cohort study was carried out. Case inclusion criteria: (1) male patients with pathologically confirmed middle and low rectal adenocarcinoma (4 to 11 cm from the anus); (2) stage T1-2tumor; (3) normal sexual life before operation. Exclusion criteria: (1) no pathological diagnosis before surgery; (2) local recurrence or distant metastasis; (3) preoperative neoadjuvant chemoradiotherapy; (4) opensurgery and laparoscopic surgery conversionto open; (5) no follow-up data. According to the above criteria, clinical data of 173 male patients with low and middle rectal adenocarcinoma who underwent radical operation for laparoscopic rectal cancer from July 2003 to July 2018 at the Department of Gastrointestinal Surgery, Wuhan University People's Hospital were collected. According to different surgical methods, patients were divided into TME group (58 cases), PANP+TME group (63 cases) and NPO+LTME group (52 cases). There were no significant differences in the baseline data including age, body mass index and pathological examination between the 3 groups (all P>0.05). The nerve plane referred to the nerve, the adipose tissue, the extremely finecapillaries around the nerve with overlying fine membranous tissue. NPO+LTME referred to the process of laparoscopic TME guided by the nerve plane, performing in the loose connective tissue between the nerve plane and the rectal properfascia, in order to ensure the integrity of the nerve plane, and maximally protect the patient's urinary and reproductive functions. The operation time, intraoperative blood loss, urinary catheter removal time, urinary function grading, postoperative first erection time, and erectile function and ejaculation function were observed and compared among the 3 groups at 3- and 6-month after operation. Results: In the NPO+LTME group, the PANP+TME group and the TME group, the operation time was (181.9±24.5) minutes, (176.7±29.2) minutes and (137.7±16.2) minutes, respectively (F=54.868, P<0.001); the intraoperative blood lost was (6.0±1.4) ml, (6.5±1.8) ml and (12.8±4.6) ml, respectively (F=95.016, P<0.001); the time to postoperative removal of the catheter was (2.4±1.1) days, (3.7 ±1.7) days and (6.5±2.4) days, respectively (F=79.409, P<0.001); the first postoperative erection time was (1.6±0.6) days, (8.9±2.7) days and (15.9±6.8) days (F=177.677, P<0.001), respectively, whose differences were all statistically significant (all P<0.01). In comparison of urinary function grading, the proportion of grade I (normal function, no urinary dysfunction) in the NPO+LTME, the ANP+TME group and the TME group was 84.1% (53/63), 39.7% (23/58) and 19.2% (10/52), respectively, and the difference was statistically significant (H=52.915, P<0.001). At postoperative 3- and 6-month, proportion of patients with grade I erectile function (normal erectile function) was 77.8% (49/63) and 85.7% (54/63), 44.8% (26/58) and 53.4% (31/58), 28.8% (15/52) and 48.1% (25/52) in the NPO+LTME group, the PANP+TME group, and the TME group, respectively. The differences were statistically significant (H=91.709, P<0.001; H=79.692, P<0.001). The proportion of patients with grade I ejaculation function (with ejaculation, no abnormalities in routine semen examination before and after surgery) at 3- and 6-month after surgery in the NPO+LTME group, the PANP+TME group and the TME group was 82.5% (52/63) and 87.3% (55/63), 53.4% (31/58) and 60.3% (35/58), 28.8% (15/52) and 46.1% (24/52), respectively. The differences were statistically significant as well (H=86.543, P<0.001; H=78.667, P<0.001). Patients in the NPO+LTME group had no grade III erections and ejaculation disorders. Conclusion: The surgical procedure of NPO+LTME can promote the recovery of postoperative neurological function and preserve urination and sexual function better.

Challenging immunodominance of influenza-specific CD8+ T cell responses restricted by the risk-associated HLA-A*68:01 allomorph.

Although influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease are largely unknown. As the HLA-A*68:01 allele can be linked to severe pandemic 2009-H1N1 disease, we investigate a potential impairment of HLA-A*68:01-restricted CD8+ T cells to mount robust responses. We elucidate the HLA-A*68:01+CD8+ T cell response directed toward an extended influenza-derived nucleoprotein (NP) peptide and show that only ~35% individuals have immunodominant A68/NP145+CD8+ T cell responses. Dissecting A68/NP145+CD8+ T cells in low vs. medium/high responders reveals that high responding donors have A68/NP145+CD8+ memory T cells with clonally expanded TCRαßs, while low-responders display A68/NP145+CD8+ T cells with predominantly naïve phenotypes and non-expanded TCRαßs. Single-cell index sorting and TCRαß analyses link expansion of A68/NP145+CD8+ T cells to their memory potential. Our study demonstrates the immunodominance potential of influenza-specific CD8+ T cells presented by a risk HLA-A*68:01 molecule and advocates for priming CD8+ T cell compartments in HLA-A*68:01-expressing individuals for establishment of pre-existing protective memory T cell pools.