The study sheds light on dissimilarities in the purpose assigned to ADs’ procedure in the different facilities. Discrepancies in end-of-life care practices reveal more the influence of structural and organisational devices specific to each setting than conflicting views on end-of-life care principles. We analyse the interpretation of the Law and its implementation in the participating NHs as compromises that could be accounted for as a form of social regulation. CONCLUSION Dementia accentuates the uncertainty inherent to end-of-life trajectories. The implementation of standardised procedures aimed at collecting the wishes of the person deprived of his or her discernment is source of dissonances with regard to the multiple interests involved in these care situations. In this context, the drafting of ADs during end-of-life care in NH correspond to new normative constraints requiring new collective regulation actions.BACKGROUND Influenza is a major cause of respiratory illness resulting in 3-5 million severe cases and 291,243-645,832 deaths annually. Substantial health and financial burden may be averted by annual influenza vaccine application, especially for high risk groups. METHODS We used an active facility-based surveillance platform for acute respiratory diseases in three hospitals in Guatemala, Central America, to estimate the incidence of laboratory-confirmed hospitalized influenza cases and identify risk factors associated with severe disease (defined as admission to the intensive care unit (ICU) or death). We enrolled patients presenting with signs and symptoms of acute respiratory infection (ARI) and obtained naso- and oropharyngeal samples for real-time reverse transcriptase polymerase chain reaction (RT-PCR). We used multivariable logistic regression to identify risk factors for ICU admission or death, adjusted for age and sex. RESULTS From May 2008 to July 2012, among 6326 hospitalized ARI cases, 446 (7%) we0,000 for those ≥ 65 years. CONCLUSIONS Influenza is a major contributor of hospitalization and death due to respiratory diseases in Guatemala. Further application of proven influenza prevention and treatment strategies is warranted.We review the current state of quality assurance in laboratories of the five Central Asia Republics (CARs), focusing on laboratory equipment, and compare quality assurance approaches with CLSI standards. The laboratories of the CARs faced exceptional challenges including highly-structured laboratory systems that retain centralized and outmoded Soviet-era approaches to quality assurance, considerably jeopardizing the validity of laboratory tests. The relative isolation of the CARs, based on geography and almost exclusive use of the Russian language, further hamper change. CARs must make high-level government decisions to widely implement quality assurance programs within their laboratory systems, within which approaches to the management of laboratory equipment will be a prominent part.BACKGROUND Patients with bronchiectasis have a higher cardiovascular risk than their matched controls. However, the effect of cardiovascular (CV) disease on bronchiectasis remains unclear. Thus, we aimed to investigate the clinical impacts of cardiovascular disease on adult patients with bronchiectasis. METHODS The study cohort comprised 603 consecutive inpatients diagnosed with bronchiectasis in the Affiliated Yancheng Hospital of Southeast University Medical College (Jiangsu, China) from January 2014 to December 2017. Symptoms, bacterial cultures, blood biochemical indicator levels, and chest high-resolution computed tomography scans were assessed during their initial hospitalization for bronchiectasis. Three hundred and thirty five subjects finished 1 year follow-up after their hospital discharge. RESULTS Three hundred thirty five patients had at least one bronchiectasis exacerbation during the 1-year follow-up period. Patients with CV comorbidities were more likely to present with symptoms of wheezing (65.3%) and had a higher levels of brain natriuretic peptide (P  less then  0.001) and D-dimer (P  less then  0.001) than those without CV comorbidities. Independent risk factors associated with bronchiectasis exacerbations were the presence of comorbidities of cardiovascular diseases (odds ratio [OR] 2.503, 95% confidence interval [CI] 1.298-4.823; P = 0.006), the isolation of Pseudomonas aeruginosa (OR 2.076, 95% CI 1.100-3.919; P = 0.024), and extension to more than two lobes (OR 2.485, 95% CI 1.195-5.168; P = 0.015). CONCLUSION The existence of cardiovascular disease was independently associated with increased bronchiectasis exacerbation.BACKGROUND Patellar sleeve avulsion (PSA) fractures are rare injuries that occur in in skeletally immature patients. Initial diagnosis is key to a successful outcome, as these injuries are easily overlooked on plain radiographs with poor results well documented from delayed management. High index of suspicion from the mechanism of injury, thorough clinical examination and Magnetic Resonance Imaging (MRI) help to avoid misdiagnosis. CASE PRESENTATION The case of a 12-year-old male athlete with an acute PSA after a conservative treatment of a SLJ syndrome is described. The patient was referred to our clinic due to severe pain and loss of function after performing a high jump. Plain radiographs (X-ray) and MRI confirmed an inferior pole PSA which was fixed with double trans osseous ultra-high strength tapes. At the 3-month follow- up visit the patient was able to ambulate brace free. At 2-years follow up the patient was able to play soccer and ice hockey. To our knowledge, there are no case reports of inferior pole PSA with prior SLJ syndrome described in literature. CONCLUSIONS Early clinical suspicion and distinguishing this PSA from other enchondral ossification disorders around the knee is critical to avoid misdiagnosis. Whether SLJ syndrome increases the risk of sustaining a PSA is still not clear. Trans osseous fixation with suture tapes leads to good functional results in a young athlete with inferior pole PSA.BACKGROUND We describe the epidemiology and antimicrobial susceptibility patterns of culture-confirmed Shigella infections in facility-based surveillance sites in Guatemala. Current studies using quantitative molecular diagnostics suggest Shigella may contribute most to the global diarrheal disease burden. Since identification of Shigella requires culturing techniques using stool specimens and few laboratories in Guatemala routinely culture for this pathogen, little is known about the true burden of Shigella in Guatemala or, importantly, the antimicrobial resistance patterns. METHODS Clinical, epidemiological, and laboratory data were collected on 5399 patients with acute diarrhea (≥3 loose stools in 24 h) from June 2007-August 2012. Multidrug resistance (MDR) was defined as resistance to ampicillin and trimethoprim/sulfamethoxazole. RESULTS Five percent (261) of stool specimens yielded Shigella spp. The annual incidence of laboratory-confirmed infections ranged from 5.0 to 24.1 per 100,000 persons in Santa Rosa and 0.3 to 6.2 per 100,000 in Quetzaltenango; 58% of cases occurred in children less then  5 years of age. Thirty patients were hospitalized; one patient died. Oral rehydration or intravenous solution was used to treat 72% of hospitalized and 15% of ambulatory cases. Fifty-nine percent of cases were S. flexneri and 51% of cases were MDR. CONCLUSIONS Shigella is an important cause of bacterial diarrhea in children and prevalence of MDR highlights the importance of appropriate treatment regimens. This study demonstrates that strengthening laboratory capacity in Guatemala can help determine causes which can lead to prevention of diarrheal diseases, particularly in children. Such capacity building is also critical for rapid detection and control of public health threats at their source and therefore for global health security.BACKGROUND Inequalities in access to health care result in systematic health differences between social groups. Interventions to improve health do not always consider these inequalities. To examine access to reproductive health care services in Ghana and Nigeria, the patterns of use of family planning and maternal care by women in these countries are explored. METHODS We used population-level data from the Ghana and Nigeria Demographic Health Surveys of 2014 and 2013 respectively. We applied a two-step cluster analysis followed by multinomial logistic regression analysis. RESULTS The initial two-step cluster analyses related to family planning identified three clusters of women in Ghana and Nigeria women with high, medium and poor access to family planning services. The subsequent two-step cluster analyses related to maternal care identified five distinct clusters higher, high, medium, low and poor access to maternal health services in Ghana and Nigeria. Multinomial logistic regression showed that compared toe focused on the categorization of services and population groups into priority classes based on needs assessment. In this way, they can help expand coverage of quality services bottom up to improve access among these vulnerable groups.BACKGROUND Cutaneous anthrax in humans is associated with exposure to infected animals or animal products and has a case fatality rate of up to 20% if untreated. During May to June 2015, an outbreak of cutaneous anthrax was reported in Koraput district of Odisha, India, an area endemic for anthrax. We investigated the outbreak to identify risk factors and recommend control measures. METHOD We defined a cutaneous anthrax case as skin lesions (e.g., papule, vesicle or eschar) in a person residing in Koraput district with illness onset between February 1 and July 15, 2015. We established active surveillance through a house to house survey to ascertain additional cases and conducted a 12 unmatched case control study to identify modifiable risk factors. In case control study, we included cases with illness onset between May 1 and July 15, 2015. We defined controls as neighbours of case without skin lesions since last 3 months. Ulcer exudates and rolled over swabs from wounds were processed in Gram stain in the Koraput district headquarter hospital laboratory. RESULT We identified 81 cases (89% male; median age 38 years [range 5-75 years]) including 3 deaths (case fatality rate = 4%). Among 37 cases and 74 controls, illness was significantly associated with eating meat of ill cattle (OR 14.5, 95% CI 1.4-85.7) and with close handling of carcasses of ill animals such as burying, skinning, or chopping (OR 342, 95% CI 40.5-1901.8). Among 20 wound specimens collected, seven showed spore-forming, gram positive bacilli, with bamboo stick appearance suggestive of Bacillus anthracis. CONCLUSION Our investigation revealed significant associations between eating and handling of ill animals and presence of anthrax-like organisms in lesions. We immediately initiated livestock vaccination in the area, educated the community on safe handling practices and recommended continued regular anthrax animal vaccinations to prevent future outbreaks.BACKGROUND Symptoms of depression and anxiety experienced by undergraduate medical students have become a prominent concern. Evidence about students’ depression and anxiety including prevalence, trajectory during medical education, gender differences and comparisons with age-matched peers is conflicting. However few studies of medical students’ mental health specify the precise time of assessment. Proximity to examinations may be relevant. Precise identification of the time of data collection might help explain contradictory findings and facilitate provision of more timely support. METHODS This study addressed whether 1)Proximity of final examinations affected students’ depression and anxiety symptoms2)Males and females differed in this respect. We analysed data provided by 446 final year students from 6 UK medical schools. These students were a subset of data provided by 14 UK medical schools which participated in an online survey comparing first and final year students and in which final year response ratesoth male and female final year students. The study suggests that there may be times in the undergraduate medical curriculum when additional or targeted support is needed. It also highlights the need for research to provide a greater specificity of context when investigating medical students’ mental health.BACKGROUND To investigate the development of pain intensity and pressure pain thresholds during and 24 h after a light dynamic physical load among patients with chronic neck-shoulder pain. METHODS Twenty-six patients with chronic neck-shoulder pain and 12 healthy controls were included. The participants arm-cycled on an ergometer. Effort was rated with the Borg Rating of Perceived Exertion scale (RPE), and pain intensity with an numeric rating scale (NRS). Pressure pain thresholds were measured by an algometer. Participants started a pain diary 1 week before the physical exercise and continued until 1 week after. Pain intensity was assessed before, during and the following two evenings after arm-cycling. Pressure pain thresholds were assessed before, 15 min after, 105 min after and 24 h after. RESULTS The chronic pain group showed increased pain intensity during, and the following two evenings after the arm cycling, and decreased pain thresholds immediately after the arm cycling involving painful regions. In the patient group there were no impact on pain thresholds in the neck the following day. CONCLUSIONS Patients with chronic neck-shoulder pain reported increased pain intensity during and in the evenings after a light dynamic load involving painful regions. In addition, they showed decreased pain thresholds close to the exercise, indicating mechanical hyperalgesia.BACKGROUND Chronic obstructive pulmonary disease (COPD) patients with different phenotypes show different clinical characteristics. Therefore, we conducted a meta-analysis to explore the clinical characteristics between the non-exacerbator (NE) phenotype and the frequent exacerbator with chronic bronchitis (FE-CB) phenotype among patients with COPD. METHODS CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases were searched from the times of their inception to April 30, 2019. All studies that reported the clinical characteristics of the COPD phenotypes and which met the inclusion criteria were included. The quality assessment was analyzed by Cross-Sectional/Prevalence Study Quality recommendations. The meta-analysis was carried out using RevMan5.3. RESULTS Ten cross-sectional observation studies (n = 8848) were included. Compared with the NE phenotype, patients with the FE-CB phenotype showed significantly lower forced expiratory volume in 1 s percent prediy higher in patients with FE-CB phenotype. No significant between-group difference was observed with respect to BMI (MD-0.14, 95% CI -0.70-0.42, P = 0.62, I2 = 75%). CONCLUSION COPD patients with the FE-CB phenotype had worse pulmonary function and higher CAT score, mMRC scores, frequency of acute exacerbations, and the quantity of cigarettes smoked (pack-years) than those with the NE phenotype.BACKGROUND Risk factors affecting the prognosis of acute respiratory distress syndrome (ARDS) in adults were investigated. The aim was to identify new predictors for ARDS patient prognosis, including those with clinical, pathophysiological, and atypical immunodeficiency. METHODS ARDS patients were retrospectively included. The patients were grouped and analysed according to different oxygenation index grades and prognosis, and factors influencing prognosis and survival were examined. Adolescent patients, patients with typical immunodeficiency and patients who died within 24 h after being diagnosed with ARDS were excluded. The predictive value for mortality was determined by Cox proportional hazard analysis. RESULTS In total, 201 patients who fulfilled the Berlin definition of ARDS were included. The severity of critical illness on the day of enrolment, as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.016), Sequential Organ Failure Assessment (SOFA) score (P = 0.027), . Old age affected both 28-day and 100-day mortality rates (P = 0.0064,0.0057). CONCLUSIONS Age (per log10 years), BMI  less then  24, SOFA score, lymphocytes, and the lymphocyte/neutrophil ratio were independent predictors of 100-day mortality in patients with ARDS. The lymphocyte/neutrophil ratio may represent a potential molecular marker to evaluate atypical immunosuppression or impairment in patients with ARDS.BACKGROUND We explore the social network characteristics associated with depressive symptoms and social support among HIV-infected women of color (WOC). METHODS Network data were collected from 87 HIV-infected WOC at an academic Infectious Disease clinic in the United States (US) south. With validated instruments, interviewers also asked about depressive symptoms, social support, and treatment-specific social support. Linear regression models resulted in beta coefficients and 95% confidence intervals for the relationships among network characteristics, depression, and support provision. RESULTS Financial support provision was associated with lower reported depressive symptoms while emotional support provision was associated with increased reported social support. Talking less than daily to the first person named in her network, the primary alter, was associated with a nearly 3-point decrease in reported social support for respondents. Having people in their social network who knew their HIV status was also important. CONCLUSIONS We found that both functional and structural social network characteristics contributed to perceptions of support by HIV-infected WOC.The emergence of severe acute respiratory syndrome (SARS) underscored the importance of influenza detection and response in China. From 2004, the Chinese National Influenza Center (CNIC) and the United States Centers for Disease Control and Prevention (USCDC) initiated Cooperative Agreements to build capacity in influenza surveillance in China.From 2004 to 2014, CNIC and USCDC collaborated on the following activities 1) developing human technical expertise in virology and epidemiology in China; 2) developing a comprehensive influenza surveillance system by enhancing influenza-like illness (ILI) reporting and virological characterization; 3) strengthening analysis, utilization and dissemination of surveillance data; and 4) improving early response to influenza viruses with pandemic potential.Since 2004, CNIC expanded its national influenza surveillance and response system which, as of 2014, included 408 laboratories and 554 sentinel hospitals. With support from USCDC, more than 2500 public health staff from Chemphasis on long-term capacity development and sustainability, and leadership commitment.BACKGROUND Following the SARS outbreak, the World Health Organization revised the International Health Regulations to include risk communication as one of the core capacity areas. In 2006, the U.S. Centers for Disease Control and Prevention’s Global Disease Detection [GDD] program began collaborating with China to enhance China’s risk communication capacity to address gaps in the SARS communication response. This article describes tangible improvements in China’s public health emergency risk communication capacity between the SARS and H7N9 outbreaks; documents U.S. CDC GDD cooperative technical assistance during 2006-2017; and shares lessons learnt to benefit other countries and contribute to enhance global health security. METHOD A questionnaire based on the WHO Joint External Evaluation tool [Risk Communication section] was developed. A key communications official from the China National Health Commission [NHC] completed the questionnaire retrospectively to reflect China’s capacity to manage communication r outbreak of 2003 and the H7N9 outbreak of 2013. Long-term risk communication capacity building efforts in bilateral collaborations are uncommon. The U.S. CDC GDD project was one of the first such collaborations worldwide. The lessons learned from this project may benefit lower and middle-income countries as they build their national emergency risk communication capacity.BACKGROUND Antibiotic overuse is the most important modifiable factor contributing to antibiotic resistance. We conducted an educational campaign in Minya, Egypt targeting prescribers and the public through communications focused on appropriate antibiotic use for acute respiratory infections (ARIs). METHODS The entire population of Minya was targeted by the campaign. Physicians and pharmacists were invited to participate in the pre-intervention assessments. Acute care hospitals and a sample of primary healthcare centers in Minya were randomly selected for a pre-intervention survey and all patients exiting outpatient clinics on the day of the survey were invited to participate. The same survey methodology was conducted for the post-intervention assessments. Descriptive comparisons were made through three assessments conducted pre- and post-intervention. We quantitated antibiotic prescribing through a survey administered to patients with an ARI exiting outpatient clinics. Additionally, physicians, pharmacists, nts are needed to decrease antibiotic misuse and reduce the spread of antibiotic resistance in Egypt.BACKGROUND Hepatitis-E Virus (HEV) infection is endemic in Punjab, India. On 4th April 2013, public officials of Labour Colony, Amritsar reported > 20 jaundice cases occurring within several days. METHODS We performed a case-control study to identify the cause and prevent additional cases of jaundice cases in Amritsar, Punjab, India in 2013. RESULTS A total of 159 cases (attack rate 3.6%) and 1 death were identified in Labour and 5 adjoining colonies from January 1 to June 5, 2013. Persons with jaundice were more likely to report foul-smelling piped water (adjusted odds ratio [AOR], 4.0, 95% confidence interval [CI], 2.2-7.2) and used piped water for drinking (AOR, 5.1; 95% CI, 2.2-11.4) than persons without jaundice. Among 14 cases tested, all had anti-hepatitis E virus IgM, and none had anti-hepatitis A virus IgM. Additionally, 21/23 tap water samples from affected households had detectable fecal coliforms. An environmental investigation found that water pipelines were damaged during sewer construction and likely led to contamination of drinking water with hepatitis E virus. CONCLUSIONS Hepatitis E outbreaks are common in India, to curb future outbreaks of hepatitis E; measures to ensure safe drinking water are urgently needed.Since 1979, multiple CDC Kenya programs have supported the development of diagnostic expertise and laboratory capacity in Kenya. In 2004, CDC’s Global Disease Detection (GDD) program within the Division of Global Health Protection in Kenya (DGHP-Kenya) initiated close collaboration with Kenya Medical Research Institute (KEMRI) and developed a laboratory partnership called the Diagnostic and Laboratory Systems Program (DLSP). DLSP built onto previous efforts by malaria, human immunodeficiency virus (HIV) and tuberculosis (TB) programs and supported the expansion of the diagnostic expertise and capacity in KEMRI and the Ministry of Health. First, DLSP developed laboratory capacity for surveillance of diarrheal, respiratory, zoonotic and febrile illnesses to understand the etiology burden of these common illnesses and support evidenced-based decisions on vaccine introductions and recommendations in Kenya. Second, we have evaluated and implemented new diagnostic technologies such as TaqMan Array Cards (TAC) to deng global health security.BACKGROUND The UK mental health system is stretched to breaking point. Individuals presenting with mental health problems wait longer at the ED than those presenting with physical concerns and finding a bed when needed is difficult – 91% of psychiatric wards are operating at above the recommended occupancy rate. To address the pressure, a new type of facility – psychiatric decision units (also known as mental health decision units) – have been introduced in some areas. These are short-stay facilities, available upon referral, targeted to help individuals who may be able to avoid an inpatient admission or lengthy ED visit. To advance knowledge about the effectiveness of this service for this purpose, we will examine the effect of the service on the mental health crisis care pathway over a 4-year time period; the 2 years proceeding and following the introduction of the service. We use aggregate service level data of key indicators of the performance of this pathway. METHODS Data from four mental health Trusts ir of important service use indicators, providing much-needed information for those designing service pathways. TRIAL REGISTRATION primary registry isrctn.com Identifying number ISRCTN77588384 Link Date of registration in primary registry 27/02/2020. PRIMARY SPONSOR St George’s, University of London, Cramner Road, Tooting, SW17 ORE. Primary contact Joe Montebello.In 2007, South Africa (SA) launched a field epidemiology training program (SAFETP) to enhance its capacity to prevent, detect, and respond to public health threats through training in field epidemiology. The SAFETP began as a collaboration between the SA National Department of Health (NDOH), National Institute for Communicable Diseases (NICD), and the University of Pretoria (UP), with technical and financial support from the U.S. Centers for Disease Control and Prevention (CDC). In 2010, the CDC in collaboration with the NICD, established a Global Disease Detection (GDD) Center in SA, and the SAFETP became a core activity of the GDD center. Similar to other FETPs globally, the SAFETP is a 2-year, competency-based, applied epidemiology training program, following an apprenticeship model of 'learn by doing’. SAFETP residents spend approximately 25% of the training in classroom-based didactic learning activities, and 75% in field activities to attain core competencies in epidemiology, biostatistics, outbreak invwed scientific journals. The SAFETP is having an impact in building epidemiology capacity for public health in South Africa. Developing methods to directly link and measure the impact of the program is planned for the future.BACKGROUND The country of Georgia launched the world’s first Hepatitis C Virus (HCV) Elimination Program in 2015 and set a 90% prevalence reduction goal for 2020. We conducted a nationally representative HCV seroprevalence survey to establish baseline prevalence to measure progress toward elimination over time. METHODS A cross-sectional seroprevalence survey was conducted in 2015 among adults aged ≥18 years using a stratified, multi-stage cluster design (n = 7000). Questionnaire variables included demographic, medical, and behavioral risk characteristics and HCV-related knowledge. Blood specimens were tested for antibodies to HCV (anti-HCV) and HCV RNA. Frequencies were computed for HCV prevalence, risk factors, and HCV-related knowledge. Associations between anti-HCV status and potential risk factors were calculated using logistic regression. RESULTS National anti-HCV seroprevalence in Georgia was 7.7% (95% confidence interval (CI) = 6.7, 8.9); HCV RNA prevalence was 5.4% (95% CI = 4.6, 6.4). Testing anti-HCV+ was significantly associated with male sex, unemployment, urban residence, history of injection drug use (IDU), incarceration, blood transfusion, tattoos, frequent dental cleanings, medical injections, dialysis, and multiple lifetime sexual partners. History of IDU (adjusted odds ratio (AOR) = 21.4, 95% CI = 12.3, 37.4) and blood transfusion (AOR = 4.5, 95% CI = 2.8, 7.2) were independently, significantly associated with testing anti-HCV+ after controlling for sex, age, urban vs. rural residence, and history of incarceration. Among anti-HCV+ participants, 64.0% were unaware of their HCV status, and 46.7% did not report IDU or blood transfusion as a risk factor. CONCLUSIONS Georgia has a high HCV burden, and a majority of infected persons are unaware of their status. Ensuring a safe blood supply, implementing innovative screening strategies beyond a risk-based approach, and intensifying prevention efforts among persons who inject drugs are necessary steps to reach Georgia’s HCV elimination goal.BACKGROUND Non-communicable diseases (NCDs), mainly cardiovascular diseases, are a substantial cause of mortality in the country of Georgia, accounting for approximately 93% of all deaths (standardized mortality rate 630.7 deaths per 100,000 persons per year) and an important threat to health security. We conducted a nationally representative survey examining the prevalence of NCDs and their risk factors as part of a 2015 Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) serosurvey. METHODS We conducted a cross-sectional serosurvey among adults aged ≥18 years using a stratified, multi-stage cluster design (n = 7000). We asked participants standardized questions from the Global Adult Tobacco Survey and the WHO STEPwise approach to Surveillance (STEPS) Survey. We also measured blood pressure and Body Mass Index for each participant. Weighted frequencies were computed for NCD and risk factor prevalence and compared to 2010 STEPS results. RESULTS Georgians reported high rates of smoking, alcohol use, elevated bof other major NCDs have remained near levels reported in the 2010 STEPs survey. Comprehensive public health interventions are needed to control the heath security threats of major NCDs and their risk factors in the future.BACKGROUND The aim of this study was to evaluate the effect of vaginal repair in patients with cesarean section diverticulum (CSD) who had one or two previous cesarean sections (CSs). METHODS From January 2012 to December 2014, 248 women with CSD underwent vaginal repair surgery in Shanghai First Maternity and Infant Hospital. These included 193 women with one previous cesarean section and 55 women with two previous cesarean sections. Excision and suture of CSD was performed through a vaginal approach. The duration of menstruation, the length, width and depth of the CSD and thickness of the remaining muscular layer (TRM) were evaluated before and after surgery by transvaginal three-dimensional (3D) color Doppler ultrasound. RESULTS A total of 221 (89.11%) women were followed-up for more than 3 months, and 168 (67.74%) women were followed-up for more than 6 months. There were significant differences in the average duration of menstruation (7.77 ± 2.05 and 8.02 ± 2.06 days VS 13.99 ± 3.71 days), the average size of CSD (5.54*9.19*5.60 and 5.75*9.04*6.18 mm VS 7.99*12.43*6.62 mm) and the TRM (7.61 ± 2.52 and 7.60 ± 3.00 mm VS 2.51 ± 1.02 mm) after surgery compared with those figures before surgery. The results of this study reveal that vaginal repair could shorten the duration of menstruation and improve anatomical defects (P  0.05). CONCLUSION In CSD patients, the clinical effectiveness of vaginal repair was equivalent between women with one or two previous cesarean sections.BACKGROUND Intracranial hypotension is a disorder characterized by low cerebrospinal fluid (CSF) pressure typically caused by loss of CSF. Although some mechanisms account for the CSF leakage have been elucidated, spinal canal stenosis has never been reported as a pathological cause of intracranial hypotension. C1-C2 sign is a characteristic imaging feature, which indicates CSF collection between the spinous processes of C1 and C2, occasionally observed on magnetic resonance imaging (MRI) in patients with intracranial hypotension. CASE PRESENTATION A 58-year-old man was presented to our institute with complaints of posterior cervical pain persisting for 3 months, along with numbness and muscle weakness of extremities. A fat suppression T2-weighted image of MRI illustrated fluid collection in the retrospinal region at C1-C2 level, and an 111In-DTPA cisternoscintigram clearly revealed the presence of CSF leakage into the same region. The MRI also showed stenosis in spinal canal at C3/4 level, and a computed tome retrospinal region at C1-C2 level. Thus, our theory supports the mechanisms of previously reported CSF dynamics associated to C1-C2 sign, and also, we suggest spinal canal stenosis as a novel etiology of intracranial hypotension.BACKGROUND The gene encoding fibroblast growth factor receptor 1 (FGFR1) is emerging as a therapeutic and prognostic biomarker in various cancer types, including head and neck squamous cell carcinoma (SCC). Here, we investigated the clinicopathologic implication of FGFR1 gene amplification and protein overexpression in hypopharyngeal and laryngeal SCC. METHODS Fluorescence in situ hybridization and immunohistochemistry were performed to determine FGFR1 gene amplification and protein overexpression in 209 surgically resected cases. RESULTS FGFR1 amplification observed in 8 (8/66, 12.1%; 6 hypopharynx and 2 larynx) patients and high FGFR1 expression in 21 (21/199, 10.6%) patients significantly correlated with lymph node metastasis and advanced pathological stages. FGFR1 amplification was also associated with worse disease-free survival in multivariate analysis (hazard ratio = 4.527, P = 0.032). High FGFR1 expression was more frequently observed, consistent with the worsening of the degree of histologic differentiation. CONCLUSIONS FGFR1 amplification may serve as an independent prognostic factor for disease-free survival in hypopharyngeal and laryngeal SCC. Aberrant FGFR signaling caused by FGFR1 gene amplification or protein overexpression may play a crucial role in the malignant evolution and progression of hypopharyngeal and laryngeal SCC, and offer novel therapeutic opportunities in patients with hypopharyngeal and laryngeal SCC that usually lack specific therapeutic targets.BACKGROUND Early identification of congenital heart disease (CHD) allows detection of the pulmonary arteriopathy in an early stage, and timely shunt closure can permanently reverse pulmonary arterial hypertension (PAH). However, surgical correction is not recommended in patients with irreversible PAH. Herein we report our experience about Eisenmenger’s syndrome in simple CHD. CASE PRESENTATION From January 2017 to November 2018, a total of 8 CHD patients (3 ventricular septal defects (VSD), 2 atrial septal defects (ASD), and 3 patent ductus arteriosus (PDA), median age, 15.5 years [range, 3-18 years]) with PAH were detected by chest X-ray, electrocardiogram, transthoracic echocardiography (TTE), computed tomographic angiography (CTA) and cardiac catheterization. The median defect diameter, pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) were 16.5 mm (range, 3-30 mm), 75 mmHg (range, 60-86 mmHg), and 16 Woods units (range, 12-19 Woods units), respectively. Here, we report the representative cases of three types of simple CHD with irreversible PAH. The surgical correction was not performed in all patients who had fixed PAH and were referred to medical treatment. CONCLUSIONS PAH in CHD can be reversed by early shunt closure, but this potential is lost beyond a certain point of no return. This article highlights the essence of enhancing the level of healthcare and services in Chinese rural areas. Failure to accurately and timely assess PAH will delay effective treatment past optimal treatment time, and even lead to death.BACKGROUND Ashbya gossypii naturally overproduces riboflavin and has been utilized for industrial riboflavin production. To improve riboflavin production, various approaches have been developed. In this study, to investigate the change in metabolism of a riboflavin-overproducing mutant, namely, the W122032 strain (MT strain) that was isolated by disparity mutagenesis, genomic analysis was carried out. RESULTS In the genomic analysis, 33 homozygous and 1377 heterozygous mutations in the coding sequences of the genome of MT strain were detected. Among these heterozygous mutations, the proportion of mutated reads in each gene was different, ranging from 21 to 75%. These results suggest that the MT strain may contain multiple nuclei containing different mutations. We tried to isolate haploid spores from the MT strain to prove its ploidy, but this strain did not sporulate under the conditions tested. Heterozygous mutations detected in genes which are important for sporulation likely contribute to the sporulation deficiency of the MT strain. Homozygous and heterozygous mutations were found in genes encoding enzymes involved in amino acid metabolism, the TCA cycle, purine and pyrimidine nucleotide metabolism and the DNA mismatch repair system. One homozygous mutation in AgILV2 gene encoding acetohydroxyacid synthase, which is also a flavoprotein in mitochondria, was found. Gene ontology (GO) enrichment analysis showed heterozygous mutations in all 22 DNA helicase genes and genes involved in oxidation-reduction process. CONCLUSION This study suggests that oxidative stress and the aging of cells were involved in the riboflavin over-production in A. gossypii riboflavin over-producing mutant and provides new insights into riboflavin production in A. gossypii and the usefulness of disparity mutagenesis for the creation of new types of mutants for metabolic engineering.BACKGROUND Development of wheat cultivars with multiple disease resistance and high quality are major objectives in modern wheat breeding programs. Gene stacking is an efficient approach to achieve this target. In this study, we pyramided yellow rust resistance gene (Yr26), powdery mildew resistance gene (ML91260) and high-molecular-weight glutenin subunits Dx5 + Dy10 into the dwarf mutant of an elite wheat cultivar, Xiaoyan22. RESULTS Six pyramided wheat lines were obtained by molecular marker-assisted selection (MAS) and field evaluation of disease resistance. The desirable agronomic traits of pyramided lines, their identity with the original cultivar Xiaoyan22 except for plant height, tiller number and disease resistance, was achieved in this study. Meanwhile, the yield of pyramided lines is higher than Xiaoyan22 in the field test. In addition, analysis of flour quality indicated that the dough stability time of pyramided lines was longer than that of Xiaoyan22. CONCLUSIONS Six pyramided wheat lines with two disease resistance and high quality were achieved in this study. It is feasible to improve multiple agronomic traits simultaneously by rational application of MAS.BACKGROUND Strong artificial and natural selection causes the formation of highly conserved haplotypes that harbor agronomically important genes. GWAS combination with haplotype analysis has evolved as an effective method to dissect the genetic architecture of complex traits in crop species. RESULTS We used the 60 K Brassica Infinium SNP array to perform a genome-wide analysis of haplotype blocks associated with oleic acid (C181) in rapeseed. Six haplotype regions were identified as significantly associated with oleic acid (C181) that mapped to chromosomes A02, A07, A08, C01, C02, and C03. Additionally, whole-genome sequencing of 50 rapeseed accessions revealed three genes (BnmtACP2-A02, BnABCI13-A02 and BnECI1-A02) in the A02 chromosome haplotype region and two genes (BnFAD8-C02 and BnSDP1-C02) in the C02 chromosome haplotype region that were closely linked to oleic acid content phenotypic variation. Moreover, the co-expression network analysis uncovered candidate genes from these two different haplotype regions with potential regulatory interrelationships with oleic acid content accumulation. CONCLUSIONS Our results suggest that several candidate genes are closely linked, which provides us with an opportunity to develop functional haplotype markers for the improvement of the oleic acid content in rapeseed.BACKGROUND Maternal antibodies are key components of the protective responses of infants who are unable to produce their own IgG until 6 months of life. There is evidence that HIV-exposed uninfected children (HEU) have IgG levels abnormalities, that can be partially responsible for the higher vulnerability to infections in the first 2 years of the life of this population. This retrospective study aimed to characterize the dynamics in plasma levels of total IgG and their isotypes during the first 2 years of life in HEU infants exclusively breastfed through 6 months of age. METHODS Total IgG, IgG1, IgG2, IgG3 and IgG4 isotypes, and IgM and IgA plasma concentrations were determined by nephelometric methods in 30 Malawian infants born to HIV-positive women at month 1, 6 and 24 of life. RESULTS At 1-month infants had a median concentration of total IgG of 8.48 g/l, (IQR 7.57-9.15), with an overrepresentation of the IgG1 isotype (89.0% of total) and low levels of IgG2 (0.52 g/l, IQR, 0.46-0.65). Total IgG and IgG1 concentrations were lower at 6 months (- 2.1 and - 1.12 g/dl, respectively) reflecting disappearance of maternal antibodies, but at 24 months their levels were higher with respect to the reported reference values for age-matched pairs. Abnormal isotype distribution was still present at 24 months with IgG2 remaining strongly underrepresented (0.87 g/l, 7.5% of total IgG). CONCLUSION HIV exposure during pregnancy and breastfeeding seems to influence the IgG maturation and isotype distribution that persist in 2-year old infants.BACKGROUND We assessed the effects of a nurse mentoring program on neonatal mortality in eight districts in India. METHODS From 2012 to 2015, nurse mentors supported improvements in critical MNCH-related practices among health providers at primary health centres (PHCs) in northern Karnataka, South India. Baseline (n = 5240) and endline (n = 5154) surveys of randomly selected ever-married women were conducted. Neonatal mortality rates (NMR) among the last live-born children in the three years prior to each survey delivered in NM and non-NM-supported facilities were calculated and compared using survival analysis and cumulative hazard function. Mortality rates on days 1, 2-7 and 8-28 post-partum were compared. Cox survival regression analysis measured the adjusted effect on neonatal mortality of delivering in a nurse mentor supported facility. RESULTS Overall, neonatal mortality rate in the three years preceding the baseline and endline surveys was 30.5 (95% CI 24.3-38.4) and 21.6 (95% CI 16.3-28.7) respectively. There was a substantial decline in neonatal mortality between the survey rounds among children delivered in PHCs supported by NM 29.4 (95% CI 18.1-47.5) vs. 9.3 (95% CI 3.9-22.3) (p = 0.09). No significant declines in neonatal mortality rate were observed among children delivered in other facilities or at home. In regression analysis, among children born in nurse mentor supported facilities, the estimated hazard ratio at endline was significantly lower compared with baseline (HR 0.23, 95% CI 0.06-0.82, p = 0.02). CONCLUSION The nurse mentoring program was associated with a substantial reduction in neonatal mortality. Further research is warranted to delineate whether this may be an effective strategy for reducing NMR in resource-poor settings.BACKGROUND CRISPR/Cas has recently become a widely used genome editing tool in various organisms, including plants. Applying CRISPR/Cas often requires delivering multiple expression units into plant and hence there is a need for a quick and easy cloning procedure. The modular cloning (MoClo), based on the Golden Gate (GG) method, has enabled development of cloning systems with standardised genetic parts, e.g. promoters, coding sequences or terminators, that can be easily interchanged and assembled into expression units, which in their own turn can be further assembled into higher order multigene constructs. RESULTS Here we present an expanded cloning toolkit that contains 103 modules encoding a variety of CRISPR/Cas-based nucleases and their corresponding guide RNA backbones. Among other components, the toolkit includes a number of promoters that allow expression of CRISPR/Cas nucleases (or any other coding sequences) and their guide RNAs in monocots and dicots. As part of the toolkit, we present a set of modules that enable quick and facile assembly of tRNA-sgRNA polycistronic units without a PCR step involved. We also demonstrate that our tRNA-sgRNA system is functional in wheat protoplasts. CONCLUSIONS We believe the presented CRISPR/Cas toolkit is a great resource that will contribute towards wider adoption of the CRISPR/Cas genome editing technology and modular cloning by researchers across the plant science community.BACKGROUND Severe respiratory distress is a leading cause of mortality among neonates in Malawi. Despite evidence on the safety, cost effectiveness and efficacy of bubble continuous positive airway pressure (CPAP) in managing the condition, its use in Malawian health facilities is limited and little is known about caregivers’ engagement with perspectives of bubble CPAP. The purpose of this study was to explore caregiver perspectives for bubble CPAP at both central and district hospitals and key factors that enable effective caregiver engagement in Malawi. METHODS This was a descriptive qualitative study employing secondary analysis of 46 health care worker in-depth interviews. We interviewed the health workers about their thoughts on caregiver perspectives regarding use of bubble CPAP. We implemented the study at a tertiary facility and three district hospitals in southern Malawi. This was a part of a larger study to understand barriers and facilitators to implementing neonatal innovations in resource-constraate, up-to-date information on the intervention as per caregivers’ level of understanding. Notably, contextualised comprehensible information will help alleviate caregivers’ fear and anxieties about bubble CPAP.BACKGROUND Testicular germ cell tumours (TGCTs) are characterised by an overall high cisplatin-sensitivity which has been linked to their continued expression of pluripotency factors. Recently, the Nodal signalling pathway has been implicated in the regulation of pluripotency factor expression in fetal germ cells, and the pathway could therefore also be involved in regulating expression of pluripotency factors in malignant germ cells, and hence cisplatin-sensitivity in TGCTs. METHODS We used in vitro culture of the TGCT-derived cell line NTera2, ex vivo tissue culture of primary TGCT specimens and xenografting of NTera2 cells into nude mice in order to investigate the consequences of manipulating Nodal and Activin signalling on pluripotency factor expression, apoptosis, proliferation and cisplatin-sensitivity. RESULTS The Nodal signalling factors were markedly expressed concomitantly with the pluripotency factor OCT4 in GCNIS cells, seminomas and embryonal carcinomas. Despite this, inhibition of Nodal and Activin signalling either alone or simultaneously did not affect proliferation or apoptosis in malignant germ cells in vitro or ex vivo. Interestingly, inhibition of Nodal signalling in vitro reduced the expression of pluripotency factors and Nodal pathway genes, while stimulation of the pathway increased their expression. However, cisplatin-sensitivity was not affected following pharmacological inhibition of Nodal/Activin signalling or siRNA-mediated knockdown of the obligate co-receptor CRIPTO in NTera2 cells in vitro or in a xenograft model. CONCLUSION Our findings suggest that the Nodal signalling pathway may be involved in regulating pluripotency factor expression in malignant germ cells, but manipulation of the pathway does not appear to affect cisplatin-sensitivity or tumour cell proliferation.BACKGROUND Light chain proximal tubulopathy (LCPT) is a rare paraproteinemic renal disease that has been mostly reported in Western patients. LCPT is characterized by the accumulation of immunoglobulin (Ig)-light chain (LC) in the proximal tubule. Immunohistochemical staining for Ig-LC has not been investigated in the context of LCPT. We reported the clinicopathological characteristics and Ig-LC immunoexpression of patients with LCPT for the first time in Korea. METHODS We reviewed the clinicopathological findings of 5 Korean patients diagnosed with LCPT between 2016 and 2018. In addition, immunohistochemical staining for κ-LC and λ-LC was conducted on paraffin-embedded tissues. RESULTS The median age was 63 years, and the male-to-female ratio was 32. The primary renal manifestations were either azotemia or tubular proteinuria. All patients were diagnosed with multiple myeloma with monoclonal κ-LC (#1-2) or λ-LC (#3-5) in the serum and urine. Kidney biopsies revealed diverse and subtle alterations of the proximal tubule, including crystallization, vacuolization, and/or swelling. Electron microscopy revealed crystals in patients #1-2 and non-crystalline particles within numerous/large/dysmorphic lysosomes in patients #3-5. Ig-LC restriction was demonstrated in the proximal tubule as κ-type in patients #1-2 and as λ-type in patients #3-5 by immunohistochemistry and immunofluorescence. Immunohistochemical staining showed diffuse positivity to κ- and λ-LC, although immunofluorescent staining for κ-LC was focal and weak. LCPT has diverse clinicopathological characteristics and subtle morphological alterations, which necessitate ancillary tests for diagnosis. CONCLUSIONS We introduced immunohistochemical staining for Ig-LC as a useful tool for the diagnosis of LCPT, especially in the case of κ-type crystals.INTRODUCTION The relationships among PIK3CA mutations, medication use and tumor progression remains poorly understood. Aspirin use post-diagnosis may modify components of the PI3K pathway, including AKT and mTOR, and has been associated with lower risk of breast cancer recurrence and mortality. We assessed time to metastasis (TTM) and survival with respect to aspirin use and tumor PIK3CA mutations among women with metastatic breast cancer. METHODS Patients with hormone receptor positive, HER2 negative (HR+/HER2-) metastatic breast cancer treated in 2009-2016 who received tumor genotyping were included. Aspirin use between primary and metastatic diagnosis was extracted from electronic medical records. TTM and survival were estimated using Cox proportional hazards regression. RESULTS Among 267 women with metastatic breast cancer, women with PIK3CA mutated tumors had longer TTM than women with PIK3CA wildtype tumors (7.1 vs. 4.7 years, p = 0.008). There was a significant interaction between PIK3CA mutations and aspirin use on TTM (p = 0.006) and survival (p = 0.026). PIK3CA mutations were associated with longer TTM among aspirin non-users (HR = 0.60 95% CI0.44-0.82 p = 0.001) but not among aspirin users (HR = 1.57 0.86-2.84 p = 0.139). Similarly, PIK3CA mutations were associated with reduced mortality among aspirin non-users (HR = 0.70 95% CI0.48-1.02 p = 0.066) but not among aspirin users (HR = 1.75 95% CI0.88-3.49 p = 0.110). CONCLUSIONS Among women who develop metastatic breast cancer, tumor PIK3CA mutations are associated with slower time to progression and mortality only among aspirin non-users. Larger studies are needed to confirm this finding and examine the relationship among aspirin use, tumor mutation profile, and the overall risk of breast cancer progression.