Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE.

BACKGROUND: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain. OBJECTIVE: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses. RESULTS: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. CONCLUSION: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021238486.

Optimising an intervention to support home-living older adults at risk of malnutrition: a qualitative study.

BACKGROUND: In the UK, about 14% of community-dwelling adults aged 65 and over are estimated to be at risk of malnutrition. Screening older adults in primary care and treating those at risk may help to reduce malnutrition risk, reduce the resulting need for healthcare use and improve quality of life. Interventions are needed to raise older adults' risk awareness, offer relevant and meaningful strategies to address risk and support general practices to deliver treatment and support. METHODS: Using the Person-based Approach and input from Patient and Public Involvement representatives, we developed the 'Eat well, feel well, stay well' intervention. The intervention was optimised using qualitative data from think aloud and semi-structured process evaluation interviews with 23 and 18 older adults respectively. Positive and negative comments were extracted to inform rapid iterative modifications to support engagement with the intervention. Data were then analysed thematically and final adjustments made, to optimise the meaningfulness of the intervention for the target population. RESULTS: Participants' comments were generally positive. This paper focuses predominantly on participants' negative reactions, to illustrate the changes needed to ensure that intervention materials were optimally relevant and meaningful to older adults. Key factors that undermined engagement included: resistance to the recommended nutritional intake among those with reduced appetite or eating difficulties, particularly frequent eating and high energy options; reluctance to gain weight; and a perception that advice did not align with participants' specific personal preferences and eating difficulties. We addressed these issues by adjusting the communication of eating goals to be more closely aligned with older adults' beliefs about good nutrition, and acceptable and feasible eating patterns. We also adjusted the suggested tips and strategies to fit better with older adults' everyday activities, values and beliefs. CONCLUSIONS: Using iterative qualitative methods facilitated the identification of key behavioural and contextual elements that supported engagement, and issues that undermined older adults' engagement with intervention content. This informed crucial revisions to the intervention content that enabled us to maximise the meaningfulness, relevance and feasibility of the key messages and suggested strategies to address malnutrition risk, and therefore optimise engagement with the intervention and the behavioural advice it provided.

Trauma Bay Time Clocks: Influence on Emergency Department Length of Stay.

BACKGROUND: To monitor the time elapsed since patient arrival in the emergency department, Trauma Services at the study institution installed a large digital stopwatch timer placed at the head of each trauma bay on June 5, 2017. This quality improvement endeavor became an essential component of performance evaluation. OBJECTIVE: The purpose of the study is to measure the impact of trauma bay time clocks on emergency department length of stay. METHODS: This is a retrospective before-and-after study of trauma activation patients between June 2015 and May 2019. Two 24-month intervals were compared before and after installation of time clocks. RESULTS: In full activation patients, outcomes of emergency department length of stay ≤50 min (39.2% vs. 61.7%, p < .001) and time to transfer to intensive care unit ≤56 min (45.3% vs. 55.1%, p = .002) were significantly favorable in the postimplementation phase. Time to first computed tomography scan and time to first operating room from arrival to the emergency department were comparable between both phases. For limited activation patients, positive changes were noted in emergency department length of stay ≤87 min (41.4% vs. 60.6%, p < .001), time to first computed tomography scan ≤32 min (47.7% vs. 53.0%, p = .015), and time to transfer to intensive care unit ≤74 min (50.2% vs. 57.2%, p = .008). Time to first operating room remained comparable between two periods. CONCLUSIONS: The study institution improved their provision of immediate care by using time clocks in trauma bays. This is a simple and cost-effective intervention and may benefit similar institutions.

Structural racism and its influence on the severity of atopic dermatitis in African American children.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is the most common skin disease of childhood and is often more severe in African American than white children. The reason for this disparity is unknown, but recent research indicates that it may be due to a combination of environmental and genetic factors. The objective of this article was to explore the relationship between measures of structural racism and residential segregation within pediatric AD. METHODS: An in-office, online survey consisting of 58 questions spanning 5 domains (demographics, in-home crowding, community crowding, air quality, and litter) was administered to a convenience sample of 201 pediatric AD patients (age 0-18 years). Survey data were geocoded and linked to a measure of structural racism (ie, residential segregation). RESULTS: African American children were more likely to live in rented homes, be in lower income families, have caregivers with lower educational attainment, and be exposed to tobacco smoke. The same factors that were associated with worse AD severity in this study were also found in published literature, emphasizing the role of social determinants of health and racial differences in AD severity. Additionally, this study found that living in highly segregated communities was more likely to be associated with severe AD in African American children. CONCLUSIONS: Consistent with reported literature, socioeconomic status, race, and the physical environment appear to affect AD severity. This investigation adds structural racism as an important community characteristic that likely has significant effects on AD severity for African American Children.

The Wequedong Lodge Cancer Screening Program: implementation of an opportunistic cancer screening pilot program for residents of rural and remote Indigenous communities in Northwestern Ontario, Canada.

INTRODUCTION: The rural and remote nature of many First Nations communities in Northwestern Ontario, Canada poses unique obstacles to physically accessing health care, in addition to other barriers. Indigenous peoples face similar challenges globally. First Nations communities experience significant health inequities, including cancer burden, which can be attributed to complex factors associated with colonization and Westernization. One potentially promising intervention to decrease the burden of advanced cancers is the provision of accessible, convenient and culturally sensitive cancer screening services, leading to early detection and treatment. The Wequedong Lodge Cancer Screening Program (WLCSP) was a pilot project aiming to provide cancer screening education and opportunistic cancer screening to residents from rural and remote First Nations communities while accessing health services in the urban center of Thunder Bay, Ontario, Canada. METHODS: Cancer screening education and opportunistic breast, cervical and colorectal cancer screening appointments were offered to individuals and their travel escorts already staying at Wequedong Lodge. Program uptake was determined primarily by education participation, and secondarily by client participation in screening. RESULTS: In total, the WLCSP booked 1033 appointments, with 841 being attended. Over the program's 3 years there was an increase in clients each year. Specifically, 22% (60/275) of age-eligible women completed a mammogram. Pap tests were provided to 8% (45/554) of age-eligible females. Finally, 32% (106/333) of all age-eligible service participants were given a fecal occult blood test kit. An evaluation survey (n=396) demonstrated overall client satisfaction with the program. CONCLUSION: The WLCSP aimed to provide education about, access to and uptake of cancer screening services for First Nations people from rural and remote communities in Northwestern Ontario by targeting inequalities in accessing cancer screening opportunities. Therefore, program uptake may provide helpful numerical comparisons for similar future programs globally. Other entities working to improve cancer screening rates in remote and/or rural populations and/or amongst Indigenous peoples may find consideration of the WLCSP processes, successes and challenges helpful to their efforts.

Development of a Prediction Model for Trauma Registry Chart Abstraction Time.

INTRODUCTION: A Level I trauma center routinely faced challenges with meeting data submission deadlines and frequently struggled with a backlog of cases that limited opportunities for concurrent performance improvement. To provide a validated algorithm through which registry workload could be evaluated, the study institution designed a scientific model that predicted the amount of time required for chart abstraction on a patient-by-patient basis. METHODS: As part of this quality improvement endeavor, registrars documented the amount of time required to complete each chart. A total of 600 patients' data were included by randomly selecting 150 patients from each of the 4 trauma registrars. Given that no previous study has examined the association of patient-related factors with chart abstraction time, study variables utilized to construct this predictive model were determined by the trauma program manager and the lead trauma registrar. RESULTS: Multiple linear regression demonstrated that inhospital mortality; transfer from a referring facility; hospital stay; ventilator days; and number of complications, specialty consults, injuries, blood products, and procedures were significant predictors of chart abstraction time. The equation for the regression line for the multivariate regression was as follows: Y = 38.95 + 31.28 × mortality + 15.33 × referring facility + 4.68 × complications+3.55 × hospital stay + 3.33 × consults + 2.83 × diagnoses + 2.00 × ventilator days + 1.78 × blood products + 1.09 × procedures. CONCLUSIONS: The merit of this prediction model is that it is based on patient-related variables and predicts time on a patient-by-patient basis. This innovative tool can be utilized by other trauma centers to evaluate registry productivity and identify opportunities for improvement retrospectively.

Rate of Nonsurgical Admissions at a Level 1 Trauma Center: Impact of a Trauma Nurse Practitioner Model.

The American College of Surgeons (ACS) mandates all trauma centers conduct individual case reviews of nonsurgical admissions when rates of allocation to this service exceed 10% of all inpatient traumas. Nonsurgical admission rates at the study institution, which is a Level I trauma center, historically exceeded this ACS criterion. In an effort to decrease nonsurgical admissions, the study institution recruited trauma nurse practitioners (TNPs) who began managing low acuity patients with oversight from trauma attending physicians. This study examines the impact of TNPs on the rate of nonsurgical admissions. A retrospective cohort study was conducted with 1,400 patients between January 2017 and October 2018. Two cohorts examined in this study included trauma patients whose care was managed by the TNPs versus those admitted under the care of hospitalists. The rate of admission to nonsurgical services (NSS) was 19.6% in 2017 and 13.9% in 2018, which yielded a significant decrease from previous years' percentages (p < .001). The average hospital length of stay was 1.17 days shorter in the TNP group, which translated into a savings of approximately $876,330 in hospital charges for the study period. Additional significant findings noted in favor of the TNP cohort were for discharge orders placed prior to noon, discharge location, and reduced time to the operating room. This TNP model proved to be successful in significantly reducing admissions to NSS and substantiated the quality of patient care provided by TNPs. Hospitals struggling to meet the ACS criterion for NSS admissions may consider implementing a similar TNP model.

Patients' perspectives about the role of primary healthcare providers in long-term opioid therapy: a qualitative study in Dutch primary care.

BACKGROUND: Over the past decade, long-term use of prescription opioids for chronic non-cancer pain has risen globally despite the associated risks. Most opioid users receive their first prescription in primary care. AIM: To investigate the perspective of patients who are long-term opioid users in primary care regarding the role of healthcare providers (HCPs) in their prolonged opioid use. DESIGN AND SETTING: Semi-structured interviews in Dutch primary care. METHOD: We recruited patients who were long-term users of opioids for chronic non-cancer pain from seven community pharmacies in the Netherlands. In-depth, semi-structured interviews focused on patients' experiences with long-term opioid use, access to opioids, and the guidance of their HCPs (primarily their GPs and pharmacists). A directed content analysis was conducted on the transcribed interviews using NVivo. RESULTS: Participants (n = 25) described ways in which HCPs impacted their long-term use of opioids. These encompassed the initiation of treatment, chronic use of opioids, and discontinuation of treatment. Participants stressed the need for risk counselling during initial prescribing, ongoing medication evaluations including tapering conversations, and more support from their HCP during a tapering attempt. CONCLUSION: Patients' perspectives illustrate the important role of HCPs across the spectrum of opioid use - from initiation to tapering. The results of this study underscore the importance of clear risk counselling starting at initial prescribing, repeated medication assessments throughout treatment, addressing tapering at regular intervals, and strong support during tapering. These insights carry significant implications for clinical practice, emphasising the importance of informed and patient-centred care when it comes to opioid use for chronic non-cancer pain management.

Health promotion: healing through loss.

For many women, miscarriage constitutes an often sudden, unexpected physically as well as psychologically traumatic event. A large percentage of women having miscarriage must present to an outpatient setting, primarily the emergency department, for care during this time. Studies indicate that health care professionals are failing to meet the needs of women and their families during and after miscarriage and that greater emphasis should be placed on psychosocial and interpersonal skills. The problem has been identified as how to assist or prepare emergency nurses to better care for the physical and psychological needs of women having early, unanticipated loss of pregnancy. At 1 rural Midwest medical center, it was the women's health staff who took the initiative to address this problem. They recognized the need for a holistic approach to care for women experiencing pregnancy loss. This would be accomplished through bridging the gap between outpatient services and primary care. This resulted in creating a support group called Ended Beginnings, which was organized to help women convalesce through the physical, emotional, and spiritual hardships associated with pregnancy and infant loss. Positive feedback has been received from both patients and staff with regard to the extent to which collaborative services provide a positive impact for both the patient and staff assisting the patient during a time of sudden, unanticipated loss.

Neuroinfectious diseases in pregnancy.

Pregnancy is associated with impaired T-cell-mediated immunity putting the woman at risk for infectious diseases not typically seen in immunocompetent individuals. When maternal infection is severe, and when a primary herpesvirus infection is acquired during pregnancy, there is a risk of fetal loss, maternal death, neonatal death, or congenital abnormalities from intrauterine infection. In this review, the authors emphasize specific neurologic infectious diseases that occur in pregnancy, the safety of the antimicrobial therapy of these diseases during pregnancy, as well as the congenital and neonatal sequelae of infection.

What Is Genitourinary Syndrome of Menopause and Why Should We Care?

None: Genitourinary syndrome of menopause (GSM; previously known as vulvovaginal atrophy or atrophic vaginitis) involves symptoms of vaginal dryness, burning, and itching as well as dyspareunia, dysuria, urinary urgency, and recurrent urinary tract infections. It is estimated that nearly 60% of women in menopause experience GSM but the majority of these women do not bring up this concern with their health care provider. Studies also show that only 7% of health care providers ask women about this condition. This may be due to embarrassment or thinking this is a normal part of aging, both by patients and health care providers. This condition is progressive and may affect many aspects of a woman's physical, emotional, and sexual health. This article is intended to address the signs, symptoms, and significant impact this condition can have for women and help health care providers be more comfortable knowing how to ask about GSM, diagnosis it, and review the various treatment options that are available.

Comparing the Effectiveness and Safety Associated With Infliximab vs Infliximab-abda Therapy for Patients With Hidradenitis Suppurativa.

IMPORTANCE: Although limited effective and affordable treatment options exist for hidradenitis suppurativa, recent studies describe the effectiveness of a medical therapy, infliximab, for the treatment of hidradenitis suppurativa. Cost-saving biosimilar alternatives have recently become available, but no data currently exist on their safety and effectiveness. OBJECTIVE: To evaluate the effectiveness of infliximab-abda vs infliximab administration associated with the treatment of hidradenitis suppurativa. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study identified patients treated with infliximab or infliximab-abda between 2016 and 2020 at the dermatology clinic at the University of North Carolina at Chapel Hill. The study population included patients who met the clinical criteria for hidradenitis suppurativa and had received a continuous dose of infliximab or infliximab-abda for at least 10 weeks. In total, 62 potential participants were identified using clinical tracking lists on the electronic medical records, and 34 participants were included in the final analysis. EXPOSURES: Patients who started receiving infliximab or infliximab-abda were clinically tracked for a minimum of 10 weeks using the electronic medical record system, beginning at the time of drug initiation. Patients received loading doses of 10 mg/kg at weeks 0, 2, and 6, and then treatment was continued with a maintenance dose administered every 4 to 8 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome measure was Hidradenitis Suppurativa Clinical Response, defined as at least 50% decrease in inflammatory nodule count without any increase in number of abscesses or draining sinuses. RESULTS: Of 34 participants, 20 comprised the infliximab treatment group (mean [SD] age, 42.2 [13.2] years; 17 women [85%]), and 14 comprised the infliximab-abda treatment group (mean [SD] age, 35.5 [10.9] years; 13 women [93%]). The proportions of patients achieving a Hidradenitis Suppurativa Clinical Response were 71% (10 patients) in the infliximab-abda and 60% (12 patients) in the infliximab treatment group, which were not significantly different (P = .47). CONCLUSIONS AND RELEVANCE: This cohort study found that both infliximab administration and infliximab-abda administration were associated with similar and significant improvement in disease as measured by the Hidradenitis Suppurativa Clinical Response. Infliximab-abda is likely a reasonable treatment option for hidradenitis suppurativa, and further research is warranted.

Becoming One with Nature: A Nature Intervention for Individuals Living with Cancer Participating in a Ten-Week Group Exercise and Wellness Program.

Positive outcomes for psychological and physiological health have resulted from a nature experience. However, evidence is limited for nature-based interventions and their effect on a cancer population. The purpose of this mixed-methods study was to determine if incorporating the One Nature Challenge (ONC) into a ten-week group exercise program (WE-Can) for individuals living with cancer could offer additional psychological and/or physiological benefits to those previously observed in WE-Can. For this study, two separate ONCs were implemented throughout two seasons (summer and winter) to formulate a ONC group (n = 18; 60 ± 12yrs). Previous WE-Can graduates were used as a control group (n = 160; 59 ± 11yrs) for this study. Psychological and physiological assessments were administered in a pre- and post-test. In addition, nature relatedness (NR; ones' relationship with nature) was measured at the beginning, middle, and end of WE-Can. Following five weeks, the ONC began and participants tracked the days they experienced nature for at least thirty-minutes (24 ± 6 days), for a thirty-day period. The ONC finished concurrently with WE-Can where post-evaluations and focus groups were administered immediately following. No additional gain in overall health was found between groups. However, aerobic fitness and fatigue significantly improved for the ONC group. This was supported by frequent activities and self-reported restoration of the mind while experiencing nature. In conclusion, the lack of overall improvement could be limited by sample size and the high level of NR prior to ONC, indicating participants were already 'one with nature.'

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial.

OBJECTIVE: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. DESIGN: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. SETTING: 76 general practices in the United Kingdom. PARTICIPANTS: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. INTERVENTIONS: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. MAIN OUTCOME MEASURES: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. RESULTS: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of -3.4 mm Hg (95% confidence interval -6.1 to -0.8 mm Hg) and a mean difference in diastolic blood pressure of -0.5 mm Hg (-1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. CONCLUSIONS: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. TRIAL REGISTRATION: ISRCTN13790648.

Examining bacteria on skin and jewelry since the implementation of hand sanitizer in hospitals.

Nurses currently disinfect their hands with antibacterial soap and hand sanitizer. This comparative, descriptive study evaluated skin bacteria at baseline and 30 days after jewelry removal in intensive care unit nurses. Identified bacteria species were: (1) Bacillus, (2) Micrococcus, (3) coagulase negative Staphylococcus, (4) Diphtheroid, ( 5) Streptococcus, and (6) nonenteric gram-negative rods. The majority of the bacteria was found on skin at baseline. Bacterial counts significantly decreased at 30 days.

The Active Brains Digital Intervention to Reduce Cognitive Decline in Older Adults: Protocol for a Feasibility Randomized Controlled Trial.

BACKGROUND: Increasing physical activity, improving diet, and performing brain training exercises are associated with reduced cognitive decline in older adults. OBJECTIVE: In this paper, we describe a feasibility trial of the Active Brains intervention, a web-based digital intervention developed to support older adults to make these 3 healthy behavior changes associated with improved cognitive health. The Active Brains trial is a randomized feasibility trial that will test how accessible, acceptable, and feasible the Active Brains intervention is and the effectiveness of the study procedures that we intend to use in the larger, main trial. METHODS: In the randomized controlled trial (RCT), we use a parallel design. We will be conducting the intervention with 2 populations recruited through GP practices (family practices) in England from 2018 to 2019: older adults with signs of cognitive decline and older adults without any cognitive decline. Trial participants were randomly allocated to 1 of 3 study groups: usual care, the Active Brains intervention, or the Active Brains website plus brief support from a trained coach (over the phone or by email). The main outcomes are performance on cognitive tasks, quality of life (using EuroQol-5D 5 level), Instrumental Activities of Daily Living, and diagnoses of dementia. Secondary outcomes (including depression, enablement, and health care costs) and process measures (including qualitative interviews with participants and supporters) will also be collected. The trial has been approved by the National Health Service Research Ethics Committee (reference 17/SC/0463). RESULTS: Results will be published in peer-reviewed journals, presented at conferences, and shared at public engagement events. Data collection was completed in May 2020, and the results will be reported in 2021. CONCLUSIONS: The findings of this study will help us to identify and make important changes to the website, the support received, or the study procedures before we progress to our main randomized phase III trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number 23758980; http://www.isrctn.com/ISRCTN23758980. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18929.

The genetic basis of melanism in the gray squirrel (Sciurus carolinensis).

The black squirrel is a melanic variant of the gray squirrel (Sciurus carolinensis). We found 3 coat color variants in the gray squirrel: the wild-type gray, a jet-black, and a brown-black phenotype. These 3 morphs are due to varying distributions of eumelanin and phaeomelanin pigment in hairs. The melanocortin 1 receptor (MC1R) plays a central role in regulating eumelanin and phaeomelanin production. We sequenced the MC1R gene for all 3 coat color phenotypes and found a 24 base-pair deletion. The gray phenotype was homozygous for the wild-type allele E(+), the jet-black phenotype was homozygous for the MC1R-Delta24 allele E(B), and the brown-black phenotype was heterozygous for the E(+) and E(B) alleles. We conclude that melanism in gray squirrels is associated with the MC1R-Delta24 E(B) allele at amino acid positions 87-94 and that this allele is incompletely dominant to the wild-type allele. We predict that the MC1R-Delta24 E(B) allele encodes a constitutively active or hyperactive receptor.

Composition of the Survival Motor Neuron (SMN) Complex in Drosophila melanogaster.

Spinal Muscular Atrophy (SMA) is caused by homozygous mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. SMN is part of an oligomeric complex with core binding partners, collectively called Gemins. Biochemical and cell biological studies demonstrate that certain Gemins are required for proper snRNP assembly and transport. However, the precise functions of most Gemins are unknown. To gain a deeper understanding of the SMN complex in the context of metazoan evolution, we investigated its composition in Drosophila melanogaster Using transgenic flies that exclusively express Flag-tagged SMN from its native promoter, we previously found that Gemin2, Gemin3, Gemin5, and all nine classical Sm proteins, including Lsm10 and Lsm11, co-purify with SMN. Here, we show that CG2941 is also highly enriched in the pulldown. Reciprocal co-immunoprecipitation reveals that epitope-tagged CG2941 interacts with endogenous SMN in Schneider2 cells. Bioinformatic comparisons show that CG2941 shares sequence and structural similarity with metazoan Gemin4. Additional analysis shows that three other genes (CG14164, CG31950 and CG2371) are not orthologous to Gemins 6-7-8, respectively, as previously suggested. In D.melanogaster, CG2941 is located within an evolutionarily recent genomic triplication with two other nearly identical paralogous genes (CG32783 and CG32786). RNAi-mediated knockdown of CG2941 and its two close paralogs reveals that Gemin4 is essential for organismal viability.

Predicting the duration of symptoms in lower respiratory tract infection.

BACKGROUND: Acute lower respiratory tract infection (LRTI) presenting in primary care has a long natural history. Antibiotic treatment makes little or no difference to the duration of cough. Limited information is currently available regarding predictors of illness duration. AIM: To determine predictors of illness duration in acute LRTI in primary care. DESIGN OF STUDY: Secondary analysis of trial data to identify independent predictors of illness severity and duration. SETTING: Primary care. METHOD: Eight-hundred and seven patients aged 3 years and over with acute illness (21 days or less) presenting with cough as the main symptom plus at least one symptom or sign from sputum, chest pain, dyspnoea, or wheeze were recruited to the study. Main outcomes were duration of symptoms (rated at least a slight problem) and more severe symptoms (rated at least moderately bad). RESULTS: The average duration of cough (rated at least a slight problem) was 11.7 days and was shorter among children (duration -1.72 days; 95% confidence interval [CI] = -3.02 to -0.41) or in individuals with a history of fever (-1.22 days; 95% CI = -0.18 to 2.27). The duration of cough was longer among those with restricted activities on the day they saw the doctor (+0.69 days for each point of a 7-point scale). The duration of more severe symptoms was longer in those with a longer duration of symptoms prior to consultation, with a more severe cough on the day of seeing the doctor, and restriction of activities on the day of seeing the doctor. CONCLUSION: Illness duration may be predicted from a limited number of clinical symptoms and from prior history. These findings should be subjected to validation in a separate population. To minimise expectation about rapid resolution of illness, adults who have restricted activities could be advised that they are likely to experience symptoms for longer.

Mutation in KIF5A c.610C>T Causing Hereditary Spastic Paraplegia with Axonal Sensorimotor Neuropathy.

Hereditary spastic paraplegias (HSP) are a rare heterogeneous group of inherited neurodegenerative diseases characterized by progressive lower extremity spasticity and weakness. Mutations of the kinesin family member 5A (KIF5A) gene lead to a spectrum of phenotypes ranging from spastic paraplegia type 10 to Charcot-Marie Tooth Disease type 2. We report the second known case of a mutation in the KIF5A gene at c.610C>T presenting with HSP plus an axonal sensorimotor neuropathy.