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Background: The fetal origins hypothesis suggests that an adverse prenatal environment, indexed by low birthweight (LBW), may increase the risk of developing later disease. Recently the hypothesis has been extended to psychological outcomes, especially depression. The aim of this analysis was to test, for the first time in a developing country setting, the association between LBW and psychological symptoms, in Soweto, South Africa.Methods: A sample of 1029 children was drawn from Birth to Twenty, a longitudinal cohort followed from pregnancy to young adulthood. This sample completed the Youth Self Report at age 12 years, a validated psychological measure of behavioural and emotional adjustment. Scores were compared between LBW (<2500 g) and normal birthweight children using multivariate analysis with adjustment for potential birth and life events confounding factors.Results: No associations were found between LBW and total [adjusted odds ratio (OR) 1.09, 95% confidence interval (CI) 0.69-1.74], internalizing (adjusted OR 0.81, 95% CI 0.52-1.28) or externalizing profiles (adjusted OR 0.81, 95% CI 0.49-1.36). The only difference detected was for the internalizing sub-profile of Somatic Complaints (adjusted OR 2.02, 95% CI 1.21-3.38), which on subgroup analysis was greatest among females.Conclusions: We found no convincing evidence of an association between LBW and emotional and behavioural outcomes in 12-year olds in this sample in urban South Africa. To our knowledge, this is the first published assessment of this association in a developing world context. [ABSTRACT FROM AUTHOR]

The article presents the research study "Epitonium dendrophylliae (Gastropoda: Epitoniidae) feeding on Astroides calycularis (Anthozoa, Scleractinia)." The study mentions that the gastropod is a rare, thin shelled marine invertebrates that inhabits on the deep shelf of the eastern Atlantic and western Mediterranean epitoniid. It is also mentioned that the organism's mantle and visceral mass are golden yellow in color and it feeds at the polyp of Astroides calycularis using its proboscis.

Objective The role of inspiratory muscle performance in functional performance in patients with coronavirus disease 2019 (COVID-19) is poorly understood. The purpose of this study was to perform a longitudinal examination of inspiratory and functional performance from intensive care unit (ICU) discharge (ICUD) to hospital discharge (HD) and symptoms at HD and 1 month after HD in patients with COVID-19. Methods Thirty patients (19 men, 11 women) with COVID-19 were included. Examination of inspiratory muscle performance at ICUD and HD was performed with an electronic manometer, which provided the maximal inspiratory pressure (MIP) and several other inspiratory measures. Examination of dyspnea and functional performance was performed at ICUD and HD with the Modified Borg Dyspnea Scale and the 1-minute sit-to-stand test (1MSST), respectively. Results The mean age was 71 (SD = 11) years, the mean length of ICU stay was 9 (SD = 6) days, and the mean length of hospital stay was 26 (SD = 16) days. Most of the patients were diagnosed with severe COVID-19 (76.7%) and had a mean Charlson Comorbidity Index of 4.4 (SD = 1.9), reflecting high comorbidity. The mean MIP of the entire cohort increased minimally from ICUD to HD (from 36 [SD = 21] to 40 [SD = 20] cm H2O), reflecting predicted values for men and women at ICUD and HD of 46 (25%) to 51 (23%) and 37 (24%) to 37 (20%), respectively. The 1MSTS score increased significantly from ICUD to HD (9.9 [SD = 7.1] vs 17.7 [SD = 11.1]) for the entire cohort but remained far below population-based reference values (2.5th percentile) for the majority of patients at ICUD and HD. At ICUD, MIP was found to be a significant predictor of a favorable change in 1MSTS performance (β = 0.308; odds ratio = 1.36) at HD. Conclusion A significant reduction in inspiratory and functional performance exists in patients with COVID-19 at both ICUD and HD, with a greater MIP at ICUD being a significant predictor of a greater 1MSTS score at HD. Impact This study shows that inspiratory muscle training may be an important adjunct after COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Government and health organizations in the United States and the United Kingdom have taken different stances on e-cigarettes policy. To explore the potential effects of these policies, we describe e-cigarette user characteristics, intentions to quit, and perceived attitudes toward vaping.Methods: We used the online crowdsourcing platform Prolific to conduct a cross-sectional survey of current vapers in both countries. Measures were drawn from international surveys.Results: The sample included 1044 vapers (524 United Kingdom; 520 United States) with a mean age of 34. Samples differed by gender (United States: 57% male vs 45% in United Kingdom), race (United States: 79% White vs 90% in United Kingdom) and employment (United States: 73% employed vs 79% in United Kingdom). UK respondents were more likely than US respondents to be ever smokers (89% vs 71%, p < .0001); be daily vapers (69% vs 53%, p < .0001) and to use e-cigarettes to quit smoking (75% vs 65%, p < .0007). Most vapers in the United Kingdom and the United States want to stop vaping (62% vs 61%; p < .9493), but US respondents plan to quit significantly sooner (odds ratio 0.47, p < .0004). Attitudes differed as well. Over half (56%) of UK respondents reported their government-approved e-cigarette use, and 24% felt health care providers had positive views on e-cigarettes versus 29% and 13% from the United States, respectively (p < .0004 for both).Conclusions: Plans for quitting and perceptions regarding e-cigarettes differ markedly between demographically similar groups of vapers in the two countries. Future research should determine whether e-cigarette cessation for adults should be a public health goal, and if so, identify effective ways to stop.Implications: The contribution of this study is that it describes differences in behaviors and attitudes of vapers recruited through the same research platform and adjusted to account for minor demographic differences across country samples. For clinicians, these findings suggest that most vapers would welcome assistance in quitting. For researchers and policymakers, findings suggest that government policy regarding nicotine devices might influence behaviors and attitudes related to use and also that future research is needed to determine effective ways to quit. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the tolerability, effectiveness and utilization of tocilizumab for the treatment of RA in a usual care setting. Methods. ROUTINE was a prospective, non-interventional, observational 52-week study performed at 174 sites throughout Germany. RA patients were selected and treated according to label. Study objectives included the targeted documentation of infections, other adverse events, and various effectiveness out-comes (e.g. DAS28, clinical disease activity). Statistical analyses were performed primarily based on the data as observed. Results. A total of 850 patients (75% women, mean age: 56 ±13 years, mean RA duration: 10.3 ±8.6 years) were enrolled. Most patients (79%) were pretreated with TNF-inhibitors, whereas 21% were pre-treated with conventional DMARDs only. Most common DMARD pretreatments were MTX (79%), LEF (68%), adalimumab (53%) and etanercept (50%). At baseline, 60.5% of patients received tocilizumab in combination with any other RA drugs, while 39.5% were treated in monotherapy. Mean baseline DAS28 was 5.5 ±1.3, and this decreased to 2.6 ±1.6 at week 52. At week 52, good EULAR response was achieved in 62.3%, low disease activity state in 66.4%, and DAS28 remission in 55.1 % of patients (ad-justed relative frequencies). 35.3% of patients discontinued the study prematurely; common reasons were lack of effectiveness (10.5%) and intolerability (7.3%). Any infections and severe infections occurred in 37.6% and 7.2% of patients, respectively (N = 836); serious infections were seen in 5.3% (N = 850). Event rates of any, severe and serious infections were 70.3, 9.8 and 4.4 events/100 patient-years, respectively. Conclusion. Tocilizumab administered in a real-life setting showed clinically meaningful improvements and a safety profile that was consistent with data reported from pre-approval Phase III studies. [ABSTRACT FROM AUTHOR]

Introduction: Smoking is a key determinant of mortality among people living with HIV (PLWH).Methods: To better understand the effects of smoking cessation interventions in PLWH, we conducted a pooled analysis of four randomized controlled trials of hospital-initiated smoking interventions conducted through the Consortium of Hospitals Advancing Research on Tobacco (CHART). In each study, cigarette smokers were randomly assigned to usual care or a smoking cessation intervention. The primary outcome was self-reported past 30-day tobacco abstinence at 6-month follow-up. Abstinence rates were compared between PLWH and participants without HIV and by treatment arm, using both complete-case and intention-to-treat analyses. Multivariable logistic regression was used to determine the effect of HIV status on 6-month tobacco abstinence and to determine predictors of smoking cessation within PLWH.Results: Among 5550 hospitalized smokers, there were 202 (3.6%) PLWH. PLWH smoked fewer cigarettes per day and were less likely to be planning to quit than smokers without HIV. At 6 months, cessation rates did not differ between intervention and control groups among PLWH (28.9% vs. 30.5%) or smokers without HIV (36.1% vs. 34.1%). In multivariable regression analysis, HIV status was not significantly associated with smoking cessation at 6 months. Among PLWH, confidence in quitting was the only clinical factor independently associated with smoking cessation (OR 2.0, 95% CI = 1.4 to 2.8, p < .01).Conclusions: HIV status did not alter likelihood of quitting smoking after hospital discharge, whether or not the smoker was offered a tobacco cessation intervention, but power was limited to identify potentially important differences.Implications: PLWH had similar quit rates to participants without HIV following a hospital-initiated smoking cessation intervention. The findings suggest that factors specific to HIV infection may not influence response to smoking cessation interventions and that all PLWH would benefit from efforts to assist in quitting smoking.Trial Registration: (1) Using "warm handoffs" to link hospitalized smokers with tobacco treatment after discharge: study protocol of a randomized controlled trial: NCT01305928. (2) Web-based smoking cessation intervention that transitions from inpatient to outpatient: NCT01277250. (3) Effectiveness of smoking-cessation interventions for urban hospital patients: NCT01363245. (4) Effectiveness of Post-Discharge Strategies for Hospitalized Smokers (HelpingHAND2): NCT01714323. [ABSTRACT FROM AUTHOR]

Although the CNS is immune privileged, continuous search for pathogens and tumours by immune cells within the CNS is indispensable. Thus, distinct immune-cell populations also cross the blood-brain barrier independently of inflammation/under homeostatic conditions. It was previously shown that effector memory T cells populate healthy CNS parenchyma in humans and, independently, that CCR5-expressing lymphocytes as well as CCR5 ligands are enriched in the CNS of patients with multiple sclerosis. Apart from the recently described CD8+ CNS tissue-resident memory T cells, we identified a population of CD4+CCR5high effector memory cells as brain parenchyma-surveilling cells. These cells used their high levels of VLA-4 to arrest on scattered VCAM1, their open-conformation LFA-1 to crawl preferentially against the flow in search for sites permissive for extravasation, and their stored granzyme K (GZMK) to induce local ICAM1 aggregation and perform trans-, rather than paracellular diapedesis through unstimulated primary brain microvascular endothelial cells. This study included peripheral blood mononuclear cell samples from 175 healthy donors, 29 patients infected with HIV, with neurological symptoms in terms of cognitive impairment, 73 patients with relapsing-remitting multiple sclerosis in remission, either 1-4 weeks before (n = 29), or 18-60 months after the initiation of natalizumab therapy (n = 44), as well as white matter brain tissue of three patients suffering from epilepsy. We here provide ex vivo evidence that CCR5highGZMK+CD4+ effector memory T cells are involved in CNS immune surveillance during homeostasis, but could also play a role in CNS pathology. Among CD4+ T cells, this subset was found to dominate the CNS of patients without neurological inflammation ex vivo. The reduction in peripheral blood of HIV-positive patients with neurological symptoms correlated to their CD4 count as a measure of disease progression. Their peripheral enrichment in multiple sclerosis patients and specific peripheral entrapment through the CNS infiltration inhibiting drug natalizumab additionally suggests a contribution to CNS autoimmune pathology. Our transcriptome analysis revealed a migratory phenotype sharing many features with tissue-resident memory and Th17.1 cells, most notably the transcription factor eomesodermin. Knowledge on this cell subset should enable future studies to find ways to strengthen the host defence against CNS-resident pathogens and brain tumours or to prevent CNS autoimmunity. [ABSTRACT FROM AUTHOR]

Charcot-Marie-Tooth disease type 4C is the most common recessively inherited demyelinating neuropathy that results from loss of function mutations in the SH3TC2 gene. Sh3tc2-/- mice represent a well characterized disease model developing early onset progressive peripheral neuropathy with hypo- and demyelination, slowing of nerve conduction velocities and disturbed nodal architecture. The aim of this project was to develop a gene replacement therapy for treating Charcot-Marie-Tooth disease type 4C to rescue the phenotype of the Sh3tc2-/- mouse model. We generated a lentiviral vector LV-Mpz.SH3TC2.myc to drive expression of the human SH3TC2 cDNA under the control of the Mpz promoter specifically in myelinating Schwann cells. The vector was delivered into 3-week-old Sh3tc2-/- mice by lumbar intrathecal injection and gene expression was assessed 4-8 weeks after injection. Immunofluorescence analysis showed presence of myc-tagged human SH3TC2 in sciatic nerves and lumbar roots in the perinuclear cytoplasm of a subset of Schwann cells, in a dotted pattern co-localizing with physiologically interacting protein Rab11. Quantitative PCR analysis confirmed SH3TC2 mRNA expression in different peripheral nervous system tissues. A treatment trial was initiated in 3 weeks old randomized Sh3tc2-/- littermate mice which received either the full or mock (LV-Mpz.Egfp) vector. Behavioural analysis 8 weeks after injection showed improved motor performance in rotarod and foot grip tests in treated Sh3tc2-/- mice compared to mock vector-treated animals. Moreover, motor nerve conduction velocities were increased in treated Sh3tc2-/- mice. On a structural level, morphological analysis revealed significant improvement in g-ratios, myelin thickness, and ratios of demyelinated fibres in lumbar roots and sciatic nerves of treated Sh3tc2-/- mice. Finally, treated mice also showed improved nodal molecular architecture and reduction of blood neurofilament light levels, a clinically relevant biomarker for axonal injury/degeneration. This study provides a proof of principle for viral gene replacement therapy targeted to Schwann cells to treat Charcot-Marie-Tooth disease type 4C and potentially other similar demyelinating inherited neuropathies. [ABSTRACT FROM AUTHOR]

Objectives: The features of a newly established, web-based surveillance system for hospital antibiotic consumption are described and data on broad-spectrum antibiotic use in German acute care hospitals are presented.Methods: The watch- and reserve-group antibiotics, two categories of antibiotics derived from the WHO Essential Medicines List comprising key agents for antimicrobial stewardship, were used as a framework for data analysis. The median antibiotic consumption densities (ACDs; DDD/100 patient days) for the years 2015/16 based on data from 137 acute care hospitals have been calculated for whole facilities, ICUs and medical and surgical departments, stratified by type of care.Results: The new web-based system provides real-time surveillance at unit and facility levels, accessible to all relevant stakeholders. User-defined reports are available via an interactive database, various report types support different approaches to analysis, and different complementing quantification measures of antimicrobial consumption are available. Watch- and reserve-group antibiotics accounted for 42% and 2% of total antibiotic use, respectively. Surgical services presented with considerably lower median ACDs of the watch-group antibiotics compared with medical services. Tertiary care hospitals exhibited higher ACDs of the reserve-group antibiotics and carbapenems than primary/secondary care hospitals, while the ACDs of the watch-group antibiotics as a whole did not differ significantly. Comparing the proportional use with other European countries revealed a relatively high use of the watch-group, ranking beyond the 75th percentile.Conclusions: Because of its particular features the new web-based surveillance system is a valuable tool for antimicrobial stewardship. The WHO categories of watch- and reserve-group antibiotics proved to be a useful framework for the analysis of hospital antibiotic consumption data. [ABSTRACT FROM AUTHOR]

Madagascar reports few measles cases annually and high vaccination campaign coverage. However, the underlying age profile of immunity and risk of a measles outbreak is unknown. We conducted a nested serological survey, testing 1,005 serum samples (collected between November 2013 and December 2015 via Madagascar's febrile rash surveillance system) for measles immunoglobulin G antibody titers. We directly estimated the age profile of immunity and compared these estimates with indirect estimates based on a birth cohort model of vaccination coverage and natural infection. Combining these estimates of the age profile of immunity in the population with an age-structured model of transmission, we further predicted the risk of a measles outbreak and the impact of mitigation strategies designed around supplementary immunization activities. The direct and indirect estimates of age-specific seroprevalence show that current measles susceptibility is over 10%, and modeling suggests that Madagascar may be at risk of a major measles epidemic. [ABSTRACT FROM AUTHOR]

Objectives: To examine whether nursing home residents with concurrent vision and hearing impairment, dual sensory impairment (DSI), have a greater cognitive decline over time than do those without sensory impairment and whether social engagement modifies this association.Methods: Based on the Services and Health for Elderly in Long TERm Care study, 1,989 nursing home residents who were assessed using the interRAI LTCF at 6-month intervals over 1 year were included. Multivariate linear regression models with time-variant exposure variables of sensory impairment and social engagement using generalized estimating equations were performed to predict cognitive function measured by the Cognitive Performance Scale (range 0-6).Results: Residents with DSI had a greater cognitive decline [changes in Cognitive Performance Scale over 1 year = 1.12 (95% confidence interval = 0.81:1.42)] compared to those with either vision or hearing impairment [0.67 (0.53:0.64)] and those without sensory impairment [0.56 (0.48:0.64)]. A lower level of social engagement was also associated with a greater cognitive decline. The combined exposure variable of sensory impairment and social engagement revealed the greatest cognitive decline for socially disengaged residents with DSI [1.87 (1.24:2.51)] and the potential effect modification of social engagement on the association between DSI and cognitive decline; DSI was not associated with a greater cognitive decline among socially engaged residents, while it was associated among socially disengaged residentsDiscussion: Cognitive function declines faster in nursing home residents with DSI only when residents were not socially engaged. Therefore, residents with DSI might cognitively benefit from interventions to improve involvement in social life at nursing homes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify if psychological distress may contribute to treatment outcome in alcohol-addicted patients during a follow-up period of 5 months after detoxification. Methods: As part of a prospective, multicenter, randomized study in relapse prevention, patients' levels of psychological distress were assessed using the Symptome Checklist (SCL-90-R). At study inclusion, all patients were detoxified and showed no more withdrawal symptoms. The patients who relapsed during the 5-month follow-up period were compared with those who remained abstinent. Predictors for relapse were investigated in a logistic regression. Results: First, a significant difference in initial psychological distress between patients who stayed abstinent and patients who relapsed was found: following detoxification, patients who relapsed scored significantly higher on the SCL-90-R at study inclusion. In addition, psychological distress differed over time in both groups. Second, patients without relapse showed a larger decrease in some SCL-90-R scales between the beginning and the end of the observation period than patients who relapsed. Third, the logistic regression analyses showed that high scores on the overall score GSI (Global Severity Index) of the SCL-90-R can be seen as a predictor for future relapse. Conclusion: The SCL-90-R may be a useful instrument to predict relapse. As our study indicates that high levels of psychological distress increases the risk of relapse, specific interventions may be targeted at this risk factor. [ABSTRACT FROM AUTHOR]

Background: Studies carried out over the past 10 years have suggested that hydrosalpinges reduce the pregnancy rate in IVF. Here we report our observations of spontaneous pregnancies in patients who underwent salpingectomy (n = 18) or proximal tubal occlusion (n = 7) following diagnoses of unilateral hydrosalpinges and patent contralateral tubes.Methods: This multi-centre, retrospective study included 25 infertility patients with known unilateral hydrosalpinges with a patent contralateral Fallopian tube. Laparoscopic treatment of unilateral hydrosalpinges by either salpingectomy or tubal occlusion was performed in each patient. Rates of subsequently observed spontaneous pregnancy, and time to pregnancy, are reported.Results: The average duration of infertility in these patients was 3 years with a range of 1-10 years. Following laparoscopic surgical treatment, a total of 22 patients (88%) achieved intrauterine pregnancies, all without IVF treatment. Pregnancies occurred in an average of 5.6 months with a range of 1-21 months. There were no ectopic pregnancies in the study population.Conclusions: Selected patients with unilateral hydrosalpinges and a patent contralateral Fallopian tube may exhibit increased cycle fecundity after salpingectomy or proximal tubal occlusion of the affected tube and conceive without the need for IVF. [ABSTRACT FROM AUTHOR]

Background: Human embryonic stem (hES) cell lines were first cultured using fetal mouse fibroblasts as feeder cells. To avoid feeders and to reduce the amount of xeno-components, Matrigel- and laminin-coated dishes, and conditioned mouse feeder cell medium have been used, and hES cells have also been cultured on human fetal muscle and skin, and adult Fallopian tube epithelial cells.Methods: We used post-natal, commercially available human foreskin fibroblasts as feeder cells. Inner cell masses (ICM) were isolated from five supernumerary blastocysts, obtained as donations from couples undergoing IVF treatment.Results: Two ICM showed continuous growth. One line, HS181, has been in culture for 41 weeks with a doubling time of 24-36 h. It continues to express stem cell markers alkaline phosphatase, Oct-4, stage-specific embryonic antigen (SSEA)-4 and tumour-related antigen (TRA)-1-60. The karyotype is 46,XX. Pluripotency was demonstrated by teratoma formation in immunodeficient mice. In high-density cultures, spontaneous differentiation to beating cells and neuron-like cells was seen. The second line, HS207, was cultured for 9 weeks and cryopreserved, as were samples of line HS181. Both lines began to grow after thawing.Conclusions: We used successfully human foreskin fibroblasts as feeder cells for derivation and continued undifferentiated growth of hES cells. These feeder cells are convenient for IVF units, because no fetal human tissues or tissue from operations are needed. [ABSTRACT FROM AUTHOR]

Tobacco-specific nitrosamines (TSNAs) are one of the major classes of carcinogens found in tobacco products. As part of collaborative efforts to reduce tobacco use and resulting disease, the U.S. Centers for Disease Control and Prevention (CDC) carried out a two-phase investigation into the worldwide variation of the levels of TSNAs in cigarette tobacco. In the first phase, representatives of the World Health Organization (WHO) purchased cigarettes; scientists from the CDC subsequently measured the levels of TSNAs in tobacco from 21 different countries. Although the data collected from this initial survey suggested that globally marketed U.S.-brand cigarettes typically had higher TSNA levels than locally popular non-U.S. cigarettes in many countries, the number of samples limited the statistical power of the study. To improve statistical power and to ensure adequate sampling, the CDC conducted a second survey of 14 countries. In addition to the United States, the CDC selected the world's 10 most populous countries and three additional countries, so that at least two countries from each of the six WHO regions were represented. For each country, the CDC compared 15 packs of Marlboro cigarettes, which is the world's most popular brand of cigarettes, with 15 packs of a locally popular non-U.S. brand in the study country. Marlboro cigarettes purchased in 11/13 foreign countries had significantly higher tobacco TSNA levels than the locally popular non-U.S. brands purchased in the same country. The findings suggest that TSNA levels in tobacco can be substantially reduced in some cigarettes. [ABSTRACT FROM AUTHOR]