Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy.

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency

Systematic review of multi-symptom conditions in Gulf War veterans

Background. GulfWar veterans have a number of health complaints. We therefore decided to carry out a systematic review to identify and summarize the findings from studies that have assessed multi-symptom conditions in Gulf War veterans and in an unexposed comparison group. Method. Studies published between January 1990 and May 2004 were identified by searching a large number of electronic databases. Reference lists and websites were also searched and key researchers were contacted. Studies were included if they compared the prevalence of chronic fatigue syndrome, multiple chemical sensitivity, CDC-defined chronic multi-symptom illness, fibromyalgia,or symptoms of either fatigue or numbness and tingling in Gulf War veterans and non-Gulf veterans. A total of 2401 abstracts were independently reviewed by two authors. Results. Twenty-three publications fulfilled the inclusion criteria. Gulf deployment was most strongly associated with chronic fatigue syndrome (OR 3.8, 95% CI 2.2–6.7). Gulf War veterans were also approximately three and a half times more likely than non-Gulf veterans to report multiple chemical sensitivity or chronic multi-symptom illness as defined by CDC. The methodological quality of the studies varied but the later and larger studies were of a high methodological standard with robust sampling strategies, adequate response rates and good adjustment for confounders. Conclusions. The results support the hypothesis that deployment to the Gulf War is associated with greater reporting of multi-symptom conditions

Randomized, Controlled Trial Evaluating a Baby Wash Product on Skin Barrier Function in Healthy, Term Neonates

Objectives To examine the hypothesis that the use of a wash product formulated for newborn (<1 month of age) bathing is not inferior (no worse) to bathing with water only. Design Assessor‐blinded, randomized, controlled, noninferiority trial. Setting A teaching hospital in the Northwest of England and in participants’ homes. Participants Three‐hundred‐and‐seven healthy, term infants recruited within 48 hours of birth. Method We compared bathing with a wash product (n = 159) to bathing with water alone (n = 148). The primary outcome was transepidermal water loss (TEWL) at 14 days postbirth; the predefined difference deemed to be unimportant was 1.2. Secondary outcomes comprised changes in stratum corneum hydration, skin surface pH, clinical observations of the skin, and maternal views. Results Complete TEWL data were obtained for 242 (78.8%) infants. Wash was noninferior to water alone in terms of TEWL (intention‐to‐treat analysis: 95% confidence interval [CI] for difference [wash–water, adjusted for family history of eczema, neonate state, and baseline] −1.24, 1.07; per protocol analysis: 95% CI −1.42, 1.09). No significant differences were found in secondary outcomes. Conclusion We were unable to detect any differences between the newborn wash product and water. These findings provide reassurance to parents who choose to use the test newborn wash product or other technically equivalent cleansers and provide the evidence for health care professionals to support parental choice

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the eff ect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computergenerated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0–14 of 15% (95% CI –3 to 30; p=0·10) with MMS and 11% (–7 to 27; p=0·21) with USS. The Royston-Parmar fl exible parametric model showed that in the MMS group, this mortality eff ect was made up of 8% (–20 to 31) in years 0–7 and 23% (1–46) in years 7–14, and in the USS group, of 2% (–27 to 26) in years 0–7 and 21% (–2 to 42) in years 7–14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly diff erent death rates (p=0·021), with an overall average mortality reduction of 20% (–2 to 40) and a reduction of 8% (–27 to 43) in years 0–7 and 28% (–3 to 49) in years 7–14 in favour of MMS. Interpretation Although the mortality reduction was not signifi cant in the primary analysis, we noted a signifi cant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7–14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-eff ectiveness of ovarian cancer screening

Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection

Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino acid transporter 2 (CAT2) is essential for transport of l-arginine (L-Arg) into monocytic immune cells during H. pylori infection. Once within the cell, this amino acid is utilized by opposing pathways that lead to elaboration of either bactericidal nitric oxide (NO) produced from inducible NO synthase (iNOS), or hydrogen peroxide, which causes macrophage apoptosis, via arginase and the polyamine pathway. Because of its central role in controlling L-Arg availability in macrophages, we investigated the importance of CAT2 in vivo during H. pylori infection. CAT2−/− mice infected for 4 months exhibited decreased gastritis and increased levels of colonization compared to wild type mice. We observed suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor in CAT2−/− mice suggesting that CAT2 is involved in enhancing the innate immune response. In addition, cytokine expression in CAT2−/− mice was altered from an antimicrobial Th1 response to a Th2 response, indicating that the transporter has downstream effects on adaptive immunity as well. These findings demonstrate that CAT2 is an important regulator of the immune response during H. pylori infection

Log odds of carrying an Ancestral Mutation in BRCA1 or BRCA2 for a Defined personal and family history in an Ashkenazi Jewish woman (LAMBDA)

INTRODUCTION: Ancestral mutations in BRCA1 and BRCA2 are common in people of Ashkenazi Jewish descent and are associated with a substantially increased risk of breast and ovarian cancer. Women considering mutation testing usually have several personal and family cancer characteristics, so predicting mutation status from one factor alone could be misleading. The aim of this study was to develop a simple algorithm to estimate the probability that an Ashkenazi Jewish woman carries an ancestral mutation, based on multiple predictive factors. METHODS: We studied Ashkenazi Jewish women with a personal or family history of breast or ovarian cancer and living in Melbourne or Sydney, Australia, or with a previous diagnosis of breast or ovarian cancer and living in the UK. DNA samples were tested for the germline mutations 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2. Logistic regression was used to identify, and to estimate the predictive strength of, major determinants. RESULTS: A mutation was detected in 64 of 424 women. An algorithm was developed by combining our findings with those from similar analyses of a large study of unaffected Jewish women in Washington. Starting with a baseline score, a multiple of 0.5 (based on the logistic regression estimates) is added for each predictive feature. The sum is the estimated log odds ratio that a woman is a carrier, and is converted to a probability by using a table. There was good internal consistency. CONCLUSIONS: This simple algorithm might be useful in the clinical and genetic counselling setting. Comparison and validation in other settings should be sought

Women's experience of intrapartum transfer from a Western Australian birth centre co-located to a tertiary maternity hospital

© 2016 Kuliukas et al. Background: The aim of this Western Australian study was to describe the overall labour and birth experience of women who were transferred during the first and second stages of labour from a low risk woman-centred, midwifery-led birth centre to a co-located tertiary maternity referral hospital. Methods: Using a descriptive phenomenological design, fifteen women were interviewed up to 8weeks post birth (July to October, 2013) to explore their experience of the intrapartum transfer. Giorgi's method of analysis was used. Results: The following themes and subthemes emerged: 1) The midwife's voice with subthemes, a) The calming effect and b) Speaking up on my behalf; 2) In the zone with subthemes, a) Hanging in there and b) Post birth rationalizing; 3) Best of both worlds with subthemes a) The feeling of relief on transfer to tertiary birth suite and b) Returning back to the comfort and familiarity of the birth centre; 4) Lost sense of self; and 5) Lost birth dream with subthemes a) Narrowing of options and b) Feeling of panic. Women found the midwife's voice guided them through the transfer experience and were appreciative of continuity of care. There was a sense of disruption to expectations and disappointment in not achieving the labour and birth they had anticipated. There was however appreciation that the referral facility was nearby and experts were close at hand. The focus of care altered from woman to fetus, making women feel diminished. Women were glad to return to the familiar birth centre after the birth with the opportunity to talk through and fully understand their labour journey which helped them contextualise the transfer as one part of the whole experience. Conclusions: Findings can inform midwives of the value of a continuity of care model within a birth centre, allowing women both familiarity and peace of mind. Maternity care providers should ensure that the woman remains the focus of care after transfer and understand the significance of effective communication to ensure women are included in all care discussions

Accelerometer-Measured Daily Steps, Physical Function, and Subsequent Fall Risk in Older Women

Steps per day were measured by accelerometer for 7 days among 5,545 women aged 63–97 years between 2012 and 2014. Incident falls were ascertained from daily fall calendars for 13 months. Median steps per day were 3,216. There were 5,473 falls recorded over 61,564 fall calendar-months. The adjusted incidence rate ratio comparing women in the highest versus lowest step quartiles was 0.71 (95% confidence interval [0.54, 0.95]; ptrend across quartiles = .01). After further adjustment for physical function using the Short Physical Performance Battery, the incidence rate ratio was 0.86 ([0.64, 1.16]; ptrend = .27). Mediation analysis estimated that 63.7% of the association may be mediated by physical function (p = .03). In conclusion, higher steps per day were related to lower incident falls primarily through their beneficial association with physical functioning. Interventions that improve physical function, including those that involve stepping, could reduce falls in older adults

Template for Rapid Iterative Consensus of Experts (TRICE)

From MDPI via Jisc Publications RouterHistory: accepted 2021-09-03, pub-electronic 2021-09-29Publication status: PublishedBackground: Public health emergencies require rapid responses from experts. Differing viewpoints are common in science, however, “mixed messaging” of varied perspectives can undermine credibility of experts; reduce trust in guidance; and act as a barrier to changing public health behaviours. Collation of a unified voice for effective knowledge creation and translation can be challenging. This work aimed to create a method for rapid psychologically-informed expert guidance during the COVID-19 response. Method: TRICE (Template for Rapid Iterative Consensus of Experts) brings structure, peer-review and consensus to the rapid generation of expert advice. It was developed and trialled with 15 core members of the British Psychological Society COVID-19 Behavioural Science and Disease Prevention Taskforce. Results: Using TRICE; we have produced 18 peer-reviewed COVID-19 guidance documents; based on rapid systematic reviews; co-created by experts in behavioural science and public health; taking 4–156 days to produce; with approximately 18 experts and a median of 7 drafts per output. We provide worked-examples and key considerations; including a shared ethos and theoretical/methodological framework; in this case; the Behaviour Change Wheel and COM-B. Conclusion: TRICE extends existing consensus methodologies and has supported public health collaboration; co-creation of guidance and translation of behavioural science to practice through explicit processes in generating expert advice for public health emergencies