Contributions of side effects to contraceptive discontinuation and method switch among Kenyan women: a prospective cohort study.

OBJECTIVE: To determine the contribution of specific contraceptive side effects to method switch and modern-method discontinuation among Kenyan women. DESIGN: A prospective cohort study. SETTING: Five counties in Western Kenya. PARTICIPANTS: Women aged ≥18 years old and emancipated female minors ≥14 years old using modern, reversible contraception were recruited while attending 10 public health facilities. METHODS: Patient-reported adverse effect symptoms, method switch and discontinuation were reported through weekly text message-based surveys for 24 weeks. MAIN OUTCOME MEASUREMENTS: Prevalence, hazards ratio (HR). RESULTS: Among 825 women, 44% were using implants, 43% injectables, 7% an intrauterine device and 6% oral contraceptive pills at enrolment. Most (61%) women were continuing a method used in the previous month. During the 24-week follow up, incidence of contraceptive switch was 61.3 per 100 person-years (95% confidence interval [CI] 52.4-71.8) and incidence of discontinuation was 38.5 per 100 person-years (95% CI 31.6-47.0). On average, one-quarter (prevalence [Pr] 0.24, 95% CI 0.22-0.26) of participants reported side effects or method problems weekly, with sexual side effects the most prevalent symptom (Pr 0.15, 95% CI 0.13-0.16). Lack of expected bleeding was associated with higher risk of method switch (adjusted hazard ratio [aHR] 2.36, 95% CI 1.22-4.57). Risk of all-modern method discontinuation was higher among women experiencing irregular bleeding (aHR 2.39, 95% CI 1.20-4.77), weight changes (aHR 2.72, 95% CI 1.47-4.68) and sexual side effects (aHR 2.42, 95% CI 1.40-4.20). CONCLUSIONS: Addressing irregular bleeding, weight changes and sexual side effects through development of new products that minimise these specific side effects and anticipatory counseling may reduce method-related discontinuation. TWEETABLE ABSTRACT: Bleeding, weight changes, sexual problems associated with discontinuation of #contraception, but many continue despite side effects.

Mechanisms of GABAergic and cholinergic neurotransmission in auditory thalamus: Impact of aging.

Age-related hearing loss is a complex disorder affecting a majority of the elderly population. As people age, speech understanding becomes a challenge especially in complex acoustic settings and negatively impacts the ability to accurately analyze the auditory scene. This is in part due to an inability to focus auditory attention on a particular stimulus source while simultaneously filtering out other sound stimuli. The present review examines the impact of aging on two neurotransmitter systems involved in accurate temporal processing and auditory gating in auditory thalamus (medial geniculate body; MGB), a critical brain region involved in the coding and filtering of auditory information. The inhibitory neurotransmitter GABA and its synaptic receptors (GABAARs) are key to maintaining accurate temporal coding of complex sounds, such as speech, throughout the central auditory system. In the MGB, synaptic and extrasynaptic GABAARs mediate fast phasic and slow tonic inhibition respectively, which in turn regulate MGB neuron excitability, firing modes, and engage thalamocortical oscillations that shape coding and gating of acoustic content. Acoustic coding properties of MGB neurons are further modulated through activation of tegmental cholinergic afferents that project to MGB to potentially modulate attention and help to disambiguate difficult to understand or novel sounds. Acetylcholine is released onto MGB neurons and presynaptic terminals in MGB activating neuronal nicotinic and muscarinic acetylcholine receptors (nAChRs, mAChRs) at a subset of MGB afferents to optimize top-down and bottom-up information flow. Both GABAergic and cholinergic neurotransmission is significantly altered with aging and this review will detail how age-related changes in these circuits within the MGB may impact coding of acoustic stimuli.

Standardised patient encounters to improve quality of counselling for pre-exposure prophylaxis (PrEP) in adolescent girls and young women (AGYW) in Kenya: study protocol of a cluster randomised controlled trial.

INTRODUCTION: Adolescent girls and young women (AGYW) in sub-Saharan Africa are at high risk of HIV acquisition. Pre-exposure prophylaxis (PrEP) demonstration projects observe that AGYW uptake and adherence to PrEP during risk periods is suboptimal. Judgemental interactions with healthcare workers (HCW) and inadequate counselling can be barriers to PrEP use among AGYW. Improving HCW competency and communication to support PrEP delivery to AGYW requires new strategies. METHODS AND ANALYSIS: PrEP Implementation for Young Women and Adolescents Program-standardised patient (PrIYA-SP) is a cluster randomised trial of a standardised patient actor (SP) training intervention designed to improve HCW adherence to PrEP guidelines and communication skills. We purposively selected 24 clinics offering PrEP services under fully programmatic conditions in Kisumu County, Kenya. At baseline, unannounced SP 'mystery shoppers' present to clinics portraying AGYW in common PrEP scenarios for a cross-sectional assessment of PrEP delivery. Twelve facilities will be randomised to receive a 2-day training intervention, consisting of lectures, role-playing with SPs and group debriefing. Unannounced SPs will repeat the assessment in all 24 sites following the intervention. The primary outcome is quality of PrEP counselling, including adherence to national guidelines and communication skills, scored on a checklist by SPs blinded to intervention assignment. An intention-to-treat (ITT) analysis will evaluate whether the intervention resulted in higher scores within intervention compared with control facilities, adjusted for baseline SP scores and accounting for clustering by facility. We hypothesise that the intervention will improve quality of PrEP counselling compared with standard of care. Results from this study will inform guidelines for PrEP delivery to AGYW in low-resource settings and offer a potentially scalable strategy to improve service delivery for this high-risk group. ETHICS AND DISSEMINATION: The protocol was approved by institutional review boards at Kenyatta National Hospital and University of Washington. An external advisory committee monitors social harms. Results will be disseminated through peer-reviewed journals and presentations. TRIAL REGISTRATION NUMBER: NCT03875950.

Oxidative T Cell Modifications in Lupus and Sjogren's Syndrome.

OBJECTIVES: Lupus flares are triggered by environmental agents that cause oxidative stress, but the mechanisms involved are unclear. The flares are characterized by oxidative modifications of proteins by 4-hydroxynonenals, malondialdehydes, carbonyls and nitration. These modifications have been proposed to induce and perpetuate lupus flares by "altered self" mechanisms. An epigenetically altered CD4+CD28+ T cell subset, caused at least in part by nitration of T cell signaling molecules, is found in patients with active lupus, and nitrated T cells are sufficient to cause lupus-like autoimmunity in animal models. The relation of protein 4-hydroxynonenals, malondialdehydes, carbonyls and nitration to lupus flares though, is unknown. We tested if the size of the epigenetically altered subset is related to disease activity and one or more of these oxidative modifications in lupus patients. We also tested the relationship between subset size, disease activity and the same oxidative modifications in Sjogren's syndrome, another autoimmune disease also associated with oxidative stress and characterized by anti-nuclear antibodies and the presence of the subset. METHODS: Lupus flare severity was quantitated using the Systemic Lupus Erythematosus Disease Activity Index, and Sjogren's flare severity using the European Sjogren's Syndrome Disease Activity Index. Subset size was determined by flow cytometry. Protein modifications were determined by ELISA. RESULTS: Only protein nitration correlated with the size of the subset in lupus and Sjogren's syndrome. CONCLUSIONS: These results support a role for protein nitration in subset size and lupus flare severity. Protein nitration may also contribute to autoantibody formation in Sjogren's syndrome.

Mycobacterium tuberculosis bacteremia in adults and children: a systematic review and meta-analysis.

UNLABELLED: SETTINGp: Among human immunodeficiency virus (HIV) infected adults living in tuberculosis (TB) endemic settings, Mycobacterium tuberculosis is a common cause of bloodstream infections. Although young children have an increased propensity for M. tuberculosis dissemination, M. tuberculosis bacteremia is infrequently described in children. OBJECTIVE: To determine the prevalence of M. tuberculosis bacteremia in adult and pediatric patients and to examine sources of heterogeneity between estimates. DESIGN: Systematic review and meta-analysis. RESULTS: Of 1077 reviewed abstracts, 27 publications met the inclusion criteria, yielding 29 independent M. tuberculosis bacteremia prevalence estimates: 22 in adults, 6 in children, and 1 not stratified by age group. The random effects pooled M. tuberculosis bacteremia prevalence in adults was 13.5% (95%CI 10.8-16.2) and 0.4% (95%CI 0-0.9) in children (P for difference = 0.004). Restricting analyses to HIV-infected participants, pooled M. tuberculosis bacteremia prevalence from 21 adult studies was 15.5% (95%CI 12.5-18.5) and 0.8% (95%CI 0-1.8) in three pediatric studies (P = 0.001). Inclusion of pre-determined study-level confounders did not account for observed differences in M. tuberculosis bacteremia prevalence between age groups. CONCLUSION: While M. tuberculosis bacteremia appears relatively common in adults, particularly those with HIV infection, bloodstream M. tuberculosis appears to be rare in children.

Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?

BACKGROUND: Neuroinflammation in utero may contribute to brain injury resulting in life-long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation, e.g., by inhibiting the HMGB1 release, via the macrophages' α7 nicotinic acetylcholine receptor (α7nAChR) has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via the anatomically predominant afferent component of the vagus nerve. METHODS: We measured microglial activation in the ovine fetal brain near term 24 h after the umbilical cord occlusions mimicking human labor versus controls (no occlusions) by quantifying HMGB1 nucleus-to-cytosol translocation in the Iba1+ and α7nAChR+ microglia. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measure RMSSD that reflects fluctuations in vagus nerve activity. RESULTS: RMSSD correlated to corresponding plasma IL-1ß levels at R = 0.57 (p = 0.02, n = 17) and to white matter microglia cell counts at R = -0.89 (p = 0.03). The insult increased the HMGB1 translocation in α7nAChR+ microglia in a brain region-dependent manner (p < 0.001). In parallel, RMSSD at 1 h post insult correlated with cytosolic HMGB1 of thalamic microglia (R = -0.94, p = 0.005), and RMSSD at pH nadir correlated with microglial α7nAChR in the white matter (R = 0.83, p = 0.04). Overall, higher RMSSD values correlated with lower HMGB1 translocation and higher α7nAChR intensity per area in a brain region-specific manner. CONCLUSIONS: Afferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labor. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.

Protein Phosphatase 5 Contributes to the Overexpression of Epigenetically Regulated T-Lymphocyte Genes in Patients with Lupus.

OBJECTIVE: Lupus develops when genetically predisposed people encounter certain drugs or environmental agents causing oxidative stress such as infections and sun exposure, and then typically follows a chronic relapsing course with flares triggered by the exogenous stressors. Current evidence indicates that these environmental agents can trigger lupus flares by inhibiting the replication of DNA methylation patterns during mitosis in CD4+ T cells, altering the expression of genes suppressed by this mechanism that convert normal "helper" cells into auto reactive cells which promote lupus flares. How environmental stressors inhibit T cell DNA methylation though is incompletely understood. Protein phosphatase 5 (PP5) is a stress induced inhibitor of T cell ERK and JNK signaling in "senescent" CD4+CD28- T cells, also characterized by DNA demethylation and altered expression of genes that promote atherosclerosis. We tested if PP5 is increased in CD4+CD28+ T cells by oxidative stress, if PP5 transfection causes overexpression of methylation sensitive genes in T cells, and if PP5 is overexpressed in lupus T cells. RESULTS: PP5 was found to be overexpressed in CD4+CD28+ T cells treated with H2O2 and ONOO- and in T cells from lupus patients. CONCLUSION: The results indicate that PP5 increases expression of methylation sensitive T cell genes, and may contribute to the aberrant gene expression in CD4+CD28+ T cells that characterize lupus flares as well as the aberrant gene expression in CD4+CD28- T cells that promote atherosclerosis.

Postweaning nutritional programming of ovarian development in beef heifers.

Peripubertal caloric restriction increases primordial follicle numbers at breeding, which may improve reproductive potential. Our hypothesis was that feed restriction was changing primordial follicle number through stimulation of follicle formation via leptin, roundabout axon guidance receptor, homolog 4 (), or or through inhibition of follicle activation via anti-Müllerian hormone (). Heifers ( = 30) were fed a ration consisting of 30% alfalfa hay, 69.8% corn silage, and 0.2% salt as DM. Heifers received the control diet for 42 d before an initial 6 heifers were ovariectomized at 8 mo of age. The remaining 24 heifers were divided into 2 treatment groups. Controls were offered 97.9 g DM/kg BW over the entire feeding period. Stair-step heifers received 67.4 g DM/kg BW for 84 d. Following the 84-d restriction, heifers were stepped up to receive 118.9 g DM/kg BW over a 15-d period and were held at this feeding level 68 d. At the end of the feed restriction (11 mo of age), ovaries were collected from 6 heifers per treatment, and at the end of the refeeding period (13 mo of age), ovaries were collected from 6 heifers per treatment. Plasma leptin concentrations were greater in control heifers than in stair-step heifers at 11 mo of age ( < 0.0001). In histological sections, stair-step heifers had more primordial follicles ( = 0.03) than control heifers at 13 mo of age. There was no difference in secondary or antral follicle numbers between dietary treatment groups or ages. Relative abundance of mRNA in ovarian cortex of control heifers was greater at 13 mo than at 11 mo or before feed restriction (8 mo; = 0.01). Relative abundance of mRNA in stair-step heifers at 13 mo was greater than before feed restriction ( = 0.02) and at 11 mo did not differ from 8 or 13 mo ( = 0.70). Relative abundance of mRNA in the ovarian cortex followed a similar pattern, being greater in stair-step heifers at 11 mo compared with control heifers ( = 0.001). At 13 mo, mRNA did not differ between treatments ( = 0.30). Abundance of mRNA in the ovarian cortex did not change due to dietary treatment or age ( > 0.10). In conclusion, developing heifers on a stair-step compensatory growth scheme resulted in larger ovarian reserve before the onset of breeding, which may have beneficial effects on increasing reproductive lifespan.

Non-electrophilic modulators of the canonical Keap1/Nrf2 pathway.

Nrf2 is the major transcription factor that regulates many of the cytoprotective enzymes involved in the adaptive stress response. Modulation of Nrf2 could be therapeutically useful in a number of disease states. Activation can occur through either an electrophilic or non-electrophilic mechanism. To date, most of the research has focused on electrophilic Nrf2 activators, but there is increasing interest in non-electrophilic modulators of Nrf2. This Digest examines the current selection of small molecules that modulate Nrf2 through non-electrophilic mechanisms, and it highlights new opportunities for this important therapeutic target.

Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya.

Infants exposed to maternal HIV-1 provide an opportunity to assess correlates of HIV-1-specific interferon (IFN)-γ responses and may be informative in the development of HIV-1 vaccines. HIV-1-infected women with CD4 counts 200-500 cells/mm(3) were randomized to short-course zidovudine/nevirapine (ZDV/NVP) or highly active anti-retroviral therapy (HAART) between 2003 and 2005. Maternal plasma and breastmilk HIV-1 RNA and DNA were quantified during the first 6-12 months postpartum. HIV-1 gag peptide-stimulated enzyme-linked immunospot (ELISPOT) assays were conducted in HIV-1-exposed, uninfected infants (EU), and correlates were determined using regression and generalized estimating equations. Among 47 EU infants, 21 (45%) had ≥1 positive ELISPOT result during follow-up. Infants had a median response magnitude of 177 HIV-1-specific spot-forming units (SFU)/106 peripheral blood mononuclear cells (PBMC) [interquartile range (IQR)=117-287] directed against 2 (IQR = 1-3) gag peptide pools. The prevalence and magnitude of responses did not differ by maternal anti-retroviral (ARV) randomization arm. Maternal plasma HIV-1 RNA levels during pregnancy (P=0.009) and breastmilk HIV-1 DNA levels at 1 month (P=0.02) were associated with a higher magnitude of infant HIV-1-specific ELISPOT responses at 1 month postpartum. During follow-up, concurrent breastmilk HIV-1 RNA and DNA (cell-free virus and cell-associated virus, respectively) each were associated positively with magnitude of infant HIV-1-specific responses (P=0.01). Our data demonstrate the importance of antigenic exposure on the induction of infant HIV-1-specific cellular immune responses in the absence of infection.

Relative efficiencies of the 7 rheumatoid arthritis Core Data Set measures to distinguish active from control treatments in 9 comparisons from clinical trials of 5 agents.

The 7 Core Data Set measures to assess rheumatoid arthritis (RA) were analysed for their relative efficiencies to distinguish active from control treatments in 9 comparisons of 5 agents, methotrexate, leflunomide, infliximab, adalimumab, and abatacept, in 8 clinical trials. Among the 7 measures, levels of relative efficiencies were in a similar range, highest for the physician global estimate, followed by, in order, patient global estimate, physical function on a health assessment questionnaire (HAQ), pain, swollen joint count (SJC), an acute phase reactant laboratory test - erythrocyte sedimentation (ESR) or C-reactive protein (CRP), and tender joint count (TJC). Comparisons of only 3 measures, SJC and ESR/CRP (regarded as optimal indicators of inflammation) and HAQ function (regarded as most likely to be affected by joint damage and therefore least reversible) indicated relative efficiencies for HAQ function at least as great as for SJC or ESR/CRP, although 8 of the nine comparisons involved patients with disease duration > 6.9 years. The findings indicate a strong rationale for a Core Data Set of 7 measures, as no single measure was clearly superior in relative efficiency in all clinical trials. At the same time, 'objective' laboratory ESR/CRP, TJC and SJC were not superior to 'subjective' global estimates of the physician or patient or patient self-report measures of physical function or pain, to differentiate active from control treatments. The findings challenge a traditional view that laboratory and clinical examination findings are more robust than patient self-report scores and physician global estimates to assess and monitor RA patients.

Evaluating a federated medical search engine: tailoring the methodology and reporting the evaluation outcomes.

BACKGROUND: Federated medical search engines are health information systems that provide a single access point to different types of information. Their efficiency as clinical decision support tools has been demonstrated through numerous evaluations. Despite their rigor, very few of these studies report holistic evaluations of medical search engines and even fewer base their evaluations on existing evaluation frameworks. OBJECTIVES: To evaluate a federated medical search engine, MedSocket, for its potential net benefits in an established clinical setting. METHODS: This study applied the Human, Organization, and Technology (HOT-fit) evaluation framework in order to evaluate MedSocket. The hierarchical structure of the HOT-factors allowed for identification of a combination of efficiency metrics. Human fit was evaluated through user satisfaction and patterns of system use; technology fit was evaluated through the measurements of time-on-task and the accuracy of the found answers; and organization fit was evaluated from the perspective of system fit to the existing organizational structure. RESULTS: Evaluations produced mixed results and suggested several opportunities for system improvement. On average, participants were satisfied with MedSocket searches and confident in the accuracy of retrieved answers. However, MedSocket did not meet participants' expectations in terms of download speed, access to information, and relevance of the search results. These mixed results made it necessary to conclude that in the case of MedSocket, technology fit had a significant influence on the human and organization fit. Hence, improving technological capabilities of the system is critical before its net benefits can become noticeable. CONCLUSIONS: The HOT-fit evaluation framework was instrumental in tailoring the methodology for conducting a comprehensive evaluation of the search engine. Such multidimensional evaluation of the search engine resulted in recommendations for system improvement.

Clinical and pathologic differences in interstitial lung disease based on antisynthetase antibody type.

BACKGROUND: Interstitial lung disease (ILD) is a common extramuscular manifestation of the idiopathic inflammatory myopathies (IIMs), dermatomyositis (DM) and polymyositis (PM). Patients with antisynthetase antibodies (ASA) demonstrate some or all of the features of the antisynthetase syndrome including IIM and ILD. It has been hypothesized that the clinical expression of antisynthetase syndrome varies between specific ASAs. OBJECTIVE: We sought to determine whether the myositis-associated ILD (MA-ILD) phenotype differs based on the presence of ASAs and by ASA subtype. METHODS: A cross-sectional and longitudinal analysis of consecutive patients enrolled at the Johns Hopkins Myositis Center with ILD in the setting of clinically diagnosed autoimmune myositis was conducted. RESULTS: Seventy-seven subjects were included; 36 were ASA negative, 28 were anti-Jo1 positive, and 13 were non-Jo1 ASA positive (5 anti-PL-12, 4 anti-PL-7, 2 anti-EJ, and 2 anti-OJ). Non-Jo1 ASA positive participants were more likely to be African-American than Caucasian as compared to both the anti-Jo1 positive (p = 0.01) and ASA negative groups (p < 0.01). ASA negative participants had better mean forced vital capacity percent predicted (FVC%) and total computed tomography scores over time compared to those with anti-Jo1 after controlling for potential confounders. CONCLUSIONS: ASA status was significantly different by race. Those with anti-Jo1 antibodies had worse lung function and CT scores over time compared to those without detectable antisynthetase antibodies. Further prospective study in a larger cohort is needed to determine whether these apparent antibody-specific differences in demographics and manifestations of disease translate into meaningful disparities in clinical outcomes.

Environmental exposures, epigenetic changes and the risk of lupus.

A dose-dependent combination of environmental exposures, estrogenic hormones and genetic predisposition is thought to be required for lupus to develop and flare, but how the environment modifies the immune system in genetically predisposed people is unclear. Current evidence indicates that environmental agents that inhibit DNA methylation can convert normal antigen-specific CD4+ T lymphocytes into autoreactive, cytotoxic, pro-inflammatory cells that are sufficient to cause lupus-like autoimmunity in animal models, and that the same changes in DNA methylation characterize CD4+ T cells from patients with active lupus. Environmental agents implicated in inhibiting T-cell DNA methylation include the lupus-inducing drugs procainamide and hydralazine, as well as diet, and agents causing oxidative stress, such as smoking, UV light exposure, and infections, which have been associated with lupus onset or disease activity. Other studies demonstrate that demethylated T cells cause only anti-DNA antibodies in mice lacking a genetic predisposition to lupus, but are sufficient to cause lupus-like autoimmunity in genetically predisposed mice and likely people, and that estrogens augment the disease. Collectively, these studies suggest that environmental agents that inhibit DNA methylation, together with lupus genes and estrogens or endocrine disruptors, combine in a dose-dependent fashion to cause lupus flares.

Associations between child temperament, maternal feeding practices and child body mass index during the preschool years: a systematic review of the literature.

It is a research priority to identify modifiable risk factors to improve the effectiveness of childhood obesity prevention strategies. Research, however, has largely overlooked the role of child temperament and personality implicated in obesogenic risk factors such as maternal feeding and body mass index (BMI) of preschoolers. A systematic review of relevant literature was conducted to investigate the associations between child temperament, child personality, maternal feeding and BMI and/or weight gain in infants and preschoolers; 18 papers were included in the review. The findings revealed an association between the temperament traits of poor self-regulation, distress to limitations, low and high soothability, low negative affectivity and higher BMI in infants and preschool-aged children. Temperament traits difficult, distress to limitations, surgency/extraversion and emotionality were significantly associated with weight gain rates in infants. The results also suggested that child temperament was associated with maternal feeding behaviours that have been shown to influence childhood overweight and obesity, such as using restrictive feeding practices with children perceived as having poor self-regulation and feeding potentially obesogenic food and drinks to infants who are more externalizing. Interestingly, no studies to date have evaluated the association between child personality and BMI/weight gain in infants and preschoolers. There is a clear need for further research into the association of child temperament and obesogenic risk factors in preschool-aged children.

Increased collagen deposition in the heart of chronically hypoxic ovine fetuses.

This study determined the effect of chronic intrauterine hypoxia on collagen deposition in the fetal sheep heart. Moderate or severe hypoxia was induced by placental embolization in chronically catheterized fetal sheep for 15 days starting at gestational day 116 ± 2 (term ∼147 days). The fetal right and left ventricle were evaluated for collagen content using a Sirius red dye and for changes in signaling components of pathways involved in collagen synthesis and remodeling using quantitative polymerase chain reaction and Western blot. In severely hypoxic fetuses (n = 6), there was a two-fold increase (P < 0.05) in the percentage staining for collagen in the right ventricle, compared with control (n = 6), whereas collagen content was not altered in the moderate group (n = 4). Procollagen I and III mRNA levels were increased in the right ventricle, two-fold (P < 0.05) and three-fold (P < 0.05), respectively, in the severe group relative to control. These changes were paralleled by a two-fold increase (P < 0.05) in mRNA levels of the pro-fibrotic cytokine, transforming growth factor ß (TGF-ß1), in the right ventricle. In the right ventricle, the mRNA levels of matrix metalloproteinase 2 (MMP-2) and its activator, membrane-type MMP (MTI-MMP) were increased five-fold (P = 0.06) and three-fold (P < 0.05), respectively, relative to control. Protein levels of TGF-ß were increased in the left ventricle (P < 0.05). Thus, up-regulated collagen synthesis leading to increased collagen content occurs in the chronically hypoxic fetal heart and may contribute to the right ventricular diastolic and systolic dysfunction reported in human intrauterine growth restriction fetuses.

Childhood cruelty to animals in China: the relationship with psychological adjustment and family functioning.

BACKGROUND: The current study broadened the general scope of research conducted on childhood cruelty to animals by examining the association between psychological adjustment, family functioning and animal cruelty in an Eastern context, China. METHOD: The mothers and fathers of 729 children attending primary school in Chengdu, China participated in this study. Each parent completed the Strengths and Difficulties Questionnaire, the Chinese Family Assessment Instrument, and the Children's Attitudes and Behaviours towards Animals questionnaire. RESULTS: Findings from an actor partner interdependence model demonstrated that parents' ratings of family functioning and of their child's externalizing coping style predicted only modest amounts of variance in animal cruelty. In particular, parents' ratings of their child's externalizing coping style most consistently predicted animal cruelty. Family functioning, fathers' ratings in particular, played a minor role, more so for boys compared with girls. CONCLUSION: This study provided the first insight into childhood animal cruelty in China, and suggests that further research may enhance our understanding of these phenomena.

Neonatal outcomes are associated with latency after preterm premature rupture of membranes.

OBJECTIVE: To determine factors associated with latency time to birth after preterm premature rupture of membranes (PPROM) and the impact on neonatal outcomes. STUDY DESIGN: Data on singleton pregnancies with PPROM (n=1535 infants) were prospectively collected in a computerized perinatal/neonatal database at a tertiary care perinatal center. Latency was characterized as ≤72h versus >72 h after PPROM. RESULT: The percentage of women with latency to birth >72 h decreased from 67% in very preterm (gestational age (GA) 25 to 28 weeks) to 10% in late preterm women (GA 33 to 36 weeks). PPROM women with latency ≤72 h were more likely to have pregnancy-induced hypertension and birth weight <3%; PPROM women with latency >72 h were more likely to have received steroids and develop clinical chorioamnionitis. PPROM <32 weeks GA with latency ≤72 h was associated with a two-fold higher incidence of severe neonatal morbidity, while PPROM between 29 to 34 weeks GA and latency ≤72 h was associated with a higher incidence of moderate neonatal morbidity. CONCLUSION: A latency period >72 h was associated with a decreased incidence of adverse neonatal outcomes up to 32 weeks GA for severe and 34 weeks GA for moderate morbidity indices.

Distribution, fate and risk assessment of antibiotics in sewage treatment plants in Hong Kong, South China.

Occurrence, removal, consumption and environmental risks of sixteen antibiotics were investigated in several sewage treatment plants (STPs) featuring different treatment levels in Hong Kong, China. Cefalexin, ofloxacin and erythromycin-H(2)O were predominant with concentrations of 1020-5640, 142-7900 and 243-4740 ng/L in influent, respectively; their mass loads were comparable to levels reported in urban regions in China and were at the high end of the range reported for western countries. The target antibiotics behaved differently depending on the treatment level employed at the STPs and relatively higher removal efficiencies (>70%) were observed for cefalexin, cefotaxime, amoxicillin, sulfamethoxazole and chloramphenicol during secondary treatment. ß-lactams were especially susceptible to removal via the activated sludge process while macrolides were recalcitrant (<20%) in the dissolved phase. Two fluoroquinolones, ofloxacin (4%) and norfloxacin (52%), differed greatly in their removal efficiencies, probably because of disparities in their pK(a) values which resulted in different sorption behaviour in sludge. Overall antibiotic consumption in Hong Kong was back-calculated based on influent mass flows and compared with available prescription and usage data. This model was verified by a good approximation of 82% and 141% to the predicted consumption of total ofloxacin, but a less accurate estimate was obtained for erythromycin usage. Risk assessment indicated that algae are susceptible to the environmental concentrations of amoxicillin as well as the mixture of the nine detected antibiotics in receiving surface waters.

HBV lamivudine resistance among hepatitis B and HIV coinfected patients starting lamivudine, stavudine and nevirapine in Kenya.

Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg positive and anti-HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤ 10,000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV coinfected patients with low baseline HBV DNA levels.