Pulmonary Nontuberculous Mycobacterial Infection. A Multisystem, Multigenic Disease

Rationale: The clinical features of patients infected with pulmonary nontuberculous mycobacteria (PNTM) are well described, but the genetic components of infection susceptibility are not

The FiCTION dental trial protocol - fillings children's teeth: indicated or not?

Background: There is a lack of evidence for effective management of dental caries (decay) in children’s primary (baby) teeth and an apparent failure of conventional dental restorations (fillings) to prevent dental pain and infection for UK children in Primary Care. UK dental schools’ teaching has been based on British Society of Paediatric Dentistry guidance which recommends that caries in primary teeth should be removed and a restoration placed. However, the evidence base for this is limited in volume and quality, and comes from studies conducted in either secondary care or specialist practices. Restorations provided in specialist environments can be effective but the generalisability of this evidence to Primary Care has been questioned. The FiCTION trial addresses the Health Technology Assessment (HTA) Programme’s commissioning brief and research question “What is the clinical and cost effectiveness of restoration caries in primary teeth, compared to no treatment?” It compares conventional restorations with an intermediate treatment strategy based on the biological (sealing-in) management of caries and with no restorations. Methods/Design: This is a Primary Care-based multi-centre, three-arm, parallel group, patient-randomised controlled trial. Practitioners are recruiting 1461 children, (3–7 years) with at least one primary molar tooth where caries extends into dentine. Children are randomized and treated according to one of three treatment approaches; conventional caries management with best practice prevention, biological management of caries with best practice prevention or best practice prevention alone. Baseline measures and outcome data (at review/treatment during three year follow-up) are assessed through direct reporting, clinical examination including blinded radiograph assessment, and child/parent questionnaires. The primary outcome measure is the incidence of either pain or infection related to dental caries. Secondary outcomes are; incidence of caries in primary and permanent teeth, patient quality of life, cost-effectiveness, acceptability of treatment strategies to patients and parents and their experiences, and dentists’ preferences. Discussion: FiCTION will provide evidence for the most clinically-effective and cost-effective approach to managing caries in children’s primary teeth in Primary Care. This will support general dental practitioners in treatment decision making for child patients to minimize pain and infection in primary teeth. The trial is currently recruiting patients

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Warming the postpartum body as a form of postnatal care: An ethnographic study of medical injections and traditional health practices in Cambodia.

Postpartum care is a critical element for ensuring survival and health of mothers and newborns but is often inadequate in low- and middle-income countries due to barriers to access and resource constraints. Newly delivered mothers and their families often rely on traditional forms of postnatal care rooted in social and cultural customs or may blend modern and traditional forms of care. This ethnographic study sought to explore use of biomedical and traditional forms of postnatal care. Data were collected through unstructured observation and in-depth interviews with 15 mothers. Participants reported embracing traditional understandings of health and illness in the post-partum period centered on heating the body through diet, steaming, and other applications of heat, yet also seeking injections from private health care providers. Thematic analysis explored concepts related to transitioning forms of postnatal care, valuing of care through different lenses, and diverse sources of advice on postnatal care. Mothers also described concurrent use of both traditional medicine and biomedical postnatal care, and the importance of adhering to cultural traditions of postnatal care for future health. Maternal and newborn health are closely associated with postnatal care, so ensuring culturally appropriate and high-quality care must be an important priority for stakeholders including understand health practices that are evolving to include injections

Assessing the Implementation of a Behavior Change Intervention: Process Evaluation of a Stepped-Wedge Cluster Randomized Controlled Trial for Newborn Health

Maternal and under five-year-old mortality rates have reduced in the last two decades globally due to concerted effort, yet newborn deaths remain unacceptably prevalent. Behavior change is an important component of interventions to address newborn health problems in low-income countries. In Cambodia, maternal and newborn mortality has markedly decreased, and continued improvements will allow the country to achieve further reduction in newborn morbidity. The results of an implementation study of the Newborn Care and Infection Control Initiative using process evaluation are presented to provide insight into the trial implementation and context of the program that may have contributed to intervention results. The study utilized a mixed method process to explore the context, mechanisms, and implementation of intervention components: training of village health support group volunteers to provide home visits, training of midwives on infection prevention and control around the perinatal period, counseling on newborn care, and provision of training materials for counseling and intervention. Implementation was evaluated through quantitative and qualitative data collection including surveys, observation, semi-structured interviews, focus groups, and visual media. Descriptive statistics summarized the quantitative data and thematic analysis was used to explore the qualitative data. The evaluation identified several factors that might have influenced the outcomes of the trial: continuity of health center staff communication, timing and ability to complete home visits, and training quality. Additional support for parents in the perinatal period, preferably provided at the community level, will contribute to further improvement in health outcomes for newborns in this area. Researchers in this context should consider mechanisms to improve the coordination of health facility staff counseling while providing support and resources to ensure home visits to families with newborns are made on time. Attention to staffing, training, and quality of newborn health interventions is critical in planning for the scaling-up of newborn health programming

Effects of leptin administration and feed restriction on thecal leucocytes in the preovulatory rat ovary and the effects of leptin on meiotic maturation, granulosa cell proliferation, steroid hormone and PGE2 release in cultured rat ovarian follicles

Leptin is expressed by adipocytes and is thought to play a role in regulating food intake and in reproduction. It has been demonstrated that acute leptin administration to immature gonadotrophin-primed rats in vivo inhibits ovulation and causes a decline in food intake. However, feed restriction alone does not inhibit ovulation. Two experiments were designed to investigate the mechanism of leptin-induced inhibition of ovulation. In the first experiment, which was prompted by the importance of ovarian leucocytes in ovulation, the role of leucocytes in leptin-induced inhibition of ovulation was investigated. The second experiment investigated whether high leptin concentrations could inhibit other factors important to ovulation, such as meiotic competence of oocytes, granulosa cell proliferation, steroid or PGE(2) release, and interleukin 1beta production, in vitro. In the first experiment, the populations of neutrophils and monocytes-macrophages in the preovulatory follicles of gonadotrophin-primed, leptin-treated and -untreated rats were examined. A decrease in food intake, as a result of either leptin treatment or feed restriction, specifically reduced the numbers of neutrophils and monocytes-macrophages infiltrating the theca interna of preovulatory follicles without affecting the numbers found in the stroma. The findings show that reduced infiltration of thecal neutrophils and macrophages into preovulatory follicles is a response to reduced food intake. Furthermore, this reduction is not the direct cause of the leptin-induced inhibition of ovulation. In the second experiment, ovarian follicles were cultured for 4 or 12 h in the presence or absence of the following hormones: FSH (500 miu), insulin-like growth factor I (IGF-I) (50 ng ml(-1)), LH (100 ng ml(-1)) and leptin (300 ng ml(-1)). The results demonstrated that high concentrations of leptin in follicle culture do not affect meiotic maturation or steroid release, but tend to inhibit release of PGE 2 (although this result was not significant). DNA synthesis in granulosa cells was not inhibited by leptin in FSH- and IGF-I-supplemented culture media. These results are in agreement with previous studies that have shown that leptin inhibits the stimulatory effects of IGF-I on FSH-stimulated oestradiol production in rat granulosa cells without affecting progesterone production. In summary, leptin does not appear to have an adverse effect on the components of ovulation tested in this study, and therefore must impact on the ovulatory cascade in a way that remains to be defined.P. S. Duggal, N. K. Ryan, K. H. Van der Hoek, L. J. Ritter, D. T. Armstrong, D. A. Magoffin and R. J. Norma

Pulmonary nontuberculous mycobacterial infection a multisystem, multigenic disease

Rationale: The clinical features of patients infected with pulmonary nontuberculous mycobacteria (PNTM) are well described, but the genetic components of infection susceptibility are not

Morphological changes, reduction in cell diameter, permeability increase and disruption of intercellular junctions induced by CE.

<p>(A) Gills of zebrafish were exposed to either CE (150 ppm) or held as controls for 24 hours or 56 hours and stained with H&E. Digital micrographs were obtained at 20 x magnifications. Arrows point to edema and blebbing of gill epithelium. The ratios of gill area/gill length were calculated using Image Software (NIH, Bethesda, MD, USA) and presented as 1-dimensional area measurements. Data is quantified and shown as mean ± SD of three independent experiments. ** <i>p</i> < 0.01 vs control by a one-way ANOVA with HSD test. (B) Cell diameter measurements. BEAS-2B cells were grown to confluence in 65 mm dishes and exposed to 0 to 150 ppm of CE for 2 hours (n = 3). Data are shown as a mean ± SD. * <i>p</i> < 0.05 and ** <i>p</i> < 0.01 vs control by a one-way ANOVA with HSD test. (C) Permeability measurement of the bronchial epithelium of the airway. The sub-acute response to CE exposure was modeled by ECIS. BEAS-2B cells were seeded into the ECIS array. Cells were allowed to cover the gold electrodes in each well of the array prior to exposure to CE (0 ppm to 70 ppm). Real-time measurements of the electric resistance of the bronchial epithelial monolayers were obtained at 64 kHz. Resistance measurements were normalized with respect to the values in each well 1 hour prior to the initiation of the exposure. This time period corresponded to 16 hours after the seeding of the cells and was designated as t = 0 hour in the graph. The data are representative of three independent experiments. (D) BREA-2B cells were culture with or without 100 ppm CE for 1 hour. Protein expression of ZO-1 and actin filaments was detected using immunofluorescence microscopy (original magnification, ×40) with rabbit anti-ZO-1 (green) and phalloidin (red). Representative images captured from BEAS-2B cells are shown.</p

HO-1 protects CE-induced injury, permeability increase and apoptosis.

<p>HO-1 WT and HO-1 KO mice were exposed to either 20 μl of CE or held as controls for 24 hours. (A) The lung tissues were stained with H&E and images under a laser scanning microscopy. Data shown are representative of three donors. (B) Lung inflammation was detected by BAL cell counts. (C) Lung permeability was evaluated by BAL protein content. (D) The quantitative results from TUNEL assay were presented as percentage of TUNEL positive cells per field. Data are shown as a mean ± SD from three different experiments. * <i>p</i> < 0.05, ** <i>p</i> < 0.01 vs HO-1 WT (-) CE; ## <i>p</i> < 0.01 vs HO-1 KO (-) CE; && <i>p</i> < 0.01 vs HO-1 WT (+) CE by a one-way ANOVA with HSD test.</p