10 Simple Rules for a Supportive Lab Environment.

The transition to principal investigator (PI), or lab leader, can be challenging, partially due to the need to fulfil new managerial and leadership responsibilities. One key aspect of this role, which is often not explicitly discussed, is creating a supportive lab environment. Here, we present ten simple rules to guide the new PI in the development of their own positive and thriving lab atmosphere. These rules were written and voted on collaboratively, by the students and mentees of Professor Mark Stokes, who inspired this piece.

Typical 22q11.2 deletion syndrome appears to confer a reduced risk of schwannoma.

PURPOSE: The LZTR1 gene has been associated with schwannomatosis tumor predisposition and is located in a region that is deleted in the great majority (89%) of patients with 22q11.2 deletion syndrome (22q11.2DS). Since it is known that approximately 1 in 500 people in the general population will develop a sporadic schwannoma and there are no reports of the occurrence of schwannoma in 22q11.2DS, we investigated whether whole-gene deletion of LZTR1 occurs in schwannomatosis and assessed the risk of schwannoma in 22q11.2DS. METHODS: We assessed the genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. RESULTS: There were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with an apparently sporadic vestibular schwannoma had a constitutional whole-gene deletion of LZTR1. CONCLUSION: People with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population.

Interprofessional education for complex neurological cases.

There is a growing necessity for healthcare professionals to collaborate across disciplines in order to adequately treat patients. Interprofessional education (IPE) is one strategy that can be used to strengthen student attitudes, skill mastery, and preparedness toward working in interprofessional teams prior to joining the healthcare workforce. The current study evaluated the effects of a four-session IPE training program for students from four New England universities across nine different health professions. Participants (N = 46) were placed into teams to create an assessment plan, evaluated their patient volunteer, developed a treatment plan, and presented treatment plan decisions to the group. Students reported attitudes, skills and readiness to work on interprofessional teams before and after the training; additionally, students completed a free-response posttest questionnaire. Paired samples t-tests, repeated measures ANCOVA, and thematic analysis were conducted to analyze the data. Results showed that following program completion, participants expressed more positive attitudes toward team collaboration and demonstrated higher skill mastery to function within healthcare teams. The presence of prior IPE experience did not positively or negatively influence changes in attitudes, skills, or readiness from pretest to posttest. Results suggest that this IPE program demonstrated preliminary feasibility and effectiveness by actively improving the attitudes and skills of healthcare students to engage in interprofessional teamwork.

The Use of Point-of-Care Ultrasound to Accurately Measure Cardiac Output in Flight.

Cardiac point-of-care ultrasound (POCUS) is a quick and accurate tool to assess a patient's cardiovascular and hemodynamic status by measuring the E-point septal separation (EPSS) and left ventricular ejection fraction. The case presented here highlights the potential for increased use of POCUS to guide resuscitation in the prehospital setting and during critical care transport. A 56-year-old male presented to a rural emergency department with chest pain and was found to have an inferior STelevation myocardial infarction (STEMI). Local helicopter air ambulance was called to transport the patient to a facility capable of cardiac catheterization. In route, the flight physician performed a cardiac POCUS exam which revealed decreased cardiac perfusion, a hypokinetic inferior wall, and overall decreased contractility. EPSS was measured at 0.77cm, indicating moderate left ventricular ejection fraction (LVEF) reduction. A cardiac left ventriculogram later confirmed a 40% ejection fraction as well as wall motion abnormalities of the inferior wall. The patient was found to have 100% occlusion of the right coronary artery that was revascularized with balloon angioplasty and a drug-eluting stent. He ultimately did well and was discharged home.

The phenotype of Sotos syndrome in adulthood: A review of 44 individuals.

Sotos syndrome is an overgrowth-intellectual disability (OGID) syndrome caused by NSD1 pathogenic variants and characterized by a distinctive facial appearance, an intellectual disability, tall stature and/or macrocephaly. Other associated clinical features include scoliosis, seizures, renal anomalies, and cardiac anomalies. However, many of the published Sotos syndrome clinical descriptions are based on studies of children; the phenotype in adults with Sotos syndrome is not yet well described. Given that it is now 17 years since disruption of NSD1 was shown to cause Sotos syndrome, many of the children first reported are now adults. It is therefore timely to investigate the phenotype of 44 adults with Sotos syndrome and NSD1 pathogenic variants. We have shown that adults with Sotos syndrome display a wide spectrum of intellectual ability with functioning ranging from fully independent to fully dependent. Reproductive rates are low. In our cohort, median height in adult women is +1.9 SD and men +0.5 SD. There is a distinctive facial appearance in adults with a tall, square, prominent chin. Reassuringly, adults with Sotos syndrome are generally healthy with few new medical issues; however, lymphedema, poor dentition, hearing loss, contractures and tremor have developed in a small number of individuals.

Ensuring Sustainability for UK Burns Services: Workforce Planning for Burns Consultants.

INTRODUCTION: Workforce planning is an essential component of organizing any health service. Centralization of burns services pools expertise, although trainees can struggle to achieve adequate exposure to burns training. We aim to review current staffing levels and predict the future consultant numbers required for UK services to remain staffed with appropriately trained surgeons. METHODS: We have compiled a database of all UK burns consultants. Basic demographic data, such as age and sex, were collated. Projected UK population data have been used to estimate whether the number of patients under the care of the UK burns network will change in the coming years. Access to burns fellowship training has also been factored in. RESULTS: There are 34 burns facilities in the United Kingdom and 86 burns consultants. On average, these consultants are 13 years from retirement age. 22 will reach this age within the next decade. During this time, the UK population is expected to increase by 10%, translating to approximately another 6 consultant posts. Since there are only 2 UK recognized burns fellowships, many of the required consultants will have to seek training abroad. CONCLUSIONS: Workforce planning is essential to avoid a short fall in the number of upcoming burns consultants. Plans must be in place to anticipate additional workload with a 10% population rise. With the current struggles of NHS funding, a comprehensive review of burns workforce planning should be undertaken to ensure that sufficient numbers of trainees are completing appropriate burns-specific training and are ready to fill these posts.

The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence.

Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus, ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4(+) T cells. In this review, we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate.

Measuring recall of medical information in non-English-speaking people with cancer: A methodology.

BACKGROUND: Many patients who require an interpreter have difficulty remembering information from their medical consultations. Memory aids such as consultation audio-recordings may be of benefit to these patients. However, there is no established means of measuring patients' memory of medical information. OBJECTIVES: This study aimed to develop a method for eliciting and coding recall of medical information in non-English-speaking patients. DESIGN: This method, called Patient-Interpreter-Clinician coding (PICcode), was developed in the context of a phase II trial conducted in two outpatient oncology clinics in Melbourne, Australia, and was refined iteratively through consultation with an expert panel and piloting. Between-coder differences in early versions of the coding system were resolved through discussion and consensus resulting in refinements to PICcode. RESULTS: The final version of PICcode involved transcribing, translating and coding of audio-recorded consultations and semi-structured interviews (SSI). The SSIs were designed to elicit patients' free-recall of medical information. Every unit of medical information in the consultation was identified and categorized in a coding tree. SSIs were coded to identify the extent to which information was recalled from the consultation. DISCUSSION: The iterative changes involved in developing PICcode assisted in clarifying precise details of the process and produced a widely applicable coding system. PICcode is the most comprehensively described method of determining the amount of information that patients who use an interpreter recall from their medical consultations. PICcode can be adapted for English-speaking patients and other healthcare populations.

Uptake of risk-reducing surgery in BRCA gene carriers in Wales, UK.

Women who inherit a mutated copy of the BRCA gene have a higher lifetime risk of developing breast cancer. No large epidemiological studies exist looking at BRCA mutation carriers in UK populations. All patients with BRCA1/BRCA2 mutation identified between 1995 and 2015 were included. Individuals were identified from a prospectively gathered data base. Genetics case-notes were obtained and retrospective analysis performed. 581 female BRCA mutation carriers were identified with a median age of 34 (18-81) at the time of testing. Of the 301 women who underwent diagnostic testing (symptomatic) 246 had been diagnosed with breast cancer, 89 with ovarian cancer and 37 had both at time of testing. Median age at diagnostic test was 51 (25-81). 33% of women underwent risk-reducing mastectomies (RRM); median age at surgery 45. This compares with 37% of women in this diagnostic group who underwent Risk-reducing bilateral salpingo-oopherectomies (RRBSO) at a median age of 46. Two hundred and eighty women underwent predictive testing (family history, asymptomatic), median age 36 (18-81). 34% of women in this predictive group underwent RRM, median age 37. There was a 29% uptake of RRBSO (median age 44 years). Fifteen women (5%) developed breast cancer after being tested; none of these had undergone RRS. This unique study of all BRCA mutation carriers in Wales shows considerable variation in uptake of RRS. The decision to undergo RRS is complex and involves a number of factors, including a woman's age and life stage. As BRCA testing becomes more frequent and more gene mutation carriers are identified there will be significant implications for service allocation, screening demands, and provision of risk-reducing surgery for this high-risk patient group.

Suicidal ideation in patients with coronary heart disease and hypertension: Baseline results from the DEPSCREEN-INFO clinical trial.

BACKGROUND: A high proportion of cardiac patients suffers from depression, which is an antecedent for suicidal ideation. This study identifies clinical vulnerabilities for suicidal ideation in cardiac patients. METHODS: The primary outcome of the study was severity of suicidal ideation as measured with the Patient Health Questionnaire (PHQ-9) item No. 9. Covariates were demographics, cardiac characteristics (i.e., Canadian Cardiovascular Society angina rating of chest pain and New York Heart Association rating of shortness of breath), depression (PHQ-8,i.e., PHQ-9 minus item No. 9), anxiety (Generalized Anxiety Disorder-7, GAD-7), somatic symptoms (PHQ-15), illness perception (Brief-Illness Perception Questionnaire), and health-related quality of life (EuroQol-5D, EQ 5D). RESULTS: Data from 1,976 patients were analysed. At least 14% (95% CI [12%, 16%]) of patients indicated suicidal ideations within the last 2 weeks. Bivariate analyses yielded associations between suicidal ideation and higher levels of depression severity, anxiety severity, somatic symptom burden, chest pain, shortness of breath, negative illness perceptions, reduced health-related quality of life, and a higher probability of living alone (all p < 0.001). A multivariable ordinal regression revealed depression severity and anxiety severity to show the highest associations with suicidal ideation (ORPHQ-8  = 1.22, p < 0.001; ORGAD-7  = 1.09, p < 0.001). Having a defibrillator implant was associated with a lower probability of suicidal ideation (OR = 0.27, p = 0.017). CONCLUSIONS: This study identified several clinical vulnerabilities of suicidal ideation. The results stress the importance of screening for suicidal ideation in clinical practice.

Depression screening with patient-targeted feedback in cardiology: DEPSCREEN-INFO randomised clinical trial.

BACKGROUND: International guidelines advocate depression screening in patients with coronary heart disease (CHD) and other chronic illnesses, but evidence is lacking. AIMS: To test the differential efficacy of written patient-targeted feedback v. no written patient feedback after depression screening. METHOD: Patients with CHD or hypertension from three cardiology settings were randomised and screened for depression (ClinicalTrials.gov Identifier: NCT01879111). Compared with the control group, where only cardiologists received written feedback, in the intervention group both cardiologists and patients received written feedback regarding depression status. Depression severity was measured 1 month (primary outcome) and 6 months after screening. RESULTS: The control group (n = 220) and the patient-feedback group (n = 155) did not differ in depression severity 1 month after screening. Six months after screening, the patient-feedback group showed significantly greater improvements in depression severity and was twice as likely to seek information about depression compared with the control group. CONCLUSIONS: Patient-targeted feedback in addition to screening has a significant but small effect on depression severity after 6 months and may encourage patients to take an active role in the self-management of depression.

Development and Validation of the Somatic Symptom Disorder-B Criteria Scale (SSD-12).

OBJECTIVE: To develop and validate a new self-report questionnaire for the assessment of the psychological features of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder. METHODS: The Somatic Symptom Disorder-B Criteria Scale (SSD-12) was developed in several steps from an initial pool of 98 items. The SSD-12 is composed of 12 items; each of the three psychological subcriteria is measured by four items. In a cross-sectional study, the SSD-12 was administered to 698 patients (65.8% female, mean [standard deviation] age = 38.79 [14.15] years) from a psychosomatic outpatient clinic. Item and scale characteristics as well as measures of reliability and validity were determined. RESULTS: The SSD-12 has good item characteristics and excellent reliability (Cronbach α = .95). Confirmatory factor analyses suggested that a three-factorial structure that reflects the three psychological criteria interpreted as cognitive, affective, and behavioral aspects (n = 663, Comparative Fit Index > 0.99, Tucker-Lewis Index > 0.99, Root Mean Square Error of Approximation = 0.06, 90% confidence interval = 0.01-0.08). SSD-12 total sum score was significantly associated with somatic symptom burden (r = 0.47, p < .001) and health anxiety (r = 0.71, p < .001), and moderately associated with general anxiety (r = 0.35, p < .001) and depressive symptoms (r = 0.22, p < .001). Patients with a higher SSD-12 psychological symptom burden reported higher general physical and mental health impairment and significantly higher health care use. CONCLUSIONS: The SSD-12 is the first self-report questionnaire that operationalizes the new psychological characteristics of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder. Initial assessment indicates that the SSD-12 has sufficient reliability and validity to warrant further testing in both research and clinical settings.

Experiences of Women Who Underwent Predictive BRCA 1/2 Mutation Testing Before the Age of 30.

This qualitative interview study focuses on the experiences of a sample of British female BRCA 1/2 carriers who had predictive testing before the age of 30, which is the minimum age for breast screening in the UK. Following appropriate informed consent procedures participants were recruited through the Cancer Genetics Service for Wales. Semi-structured interviews were conducted face-to-face with seven participants, transcribed in full and analyzed using thematic analysis. The motives for testing and perceived advantages described by participants were similar to those identified in previous studies with older participants, such as increased awareness and knowledge and feeling more in control. However some of the perceived disadvantages were specific to younger women, including feeling pressured to make important life decisions earlier than they would have liked, such as about family planning and risk reducing surgery. Participants also reported feeling abandoned or forgotten because of lack of ongoing clinical contact, or feeling "stuck waiting" for screening to begin. However, none felt that these disadvantages were a reason to regret having testing. Findings in this small study suggest that having BRCA 1/2 predictive testing can have positive outcomes for young women even though they may be unable to access interventions such as breast screening. However it may be helpful to encourage young women during pre-test counseling to explore the decisions and choices they may face. These young women could benefit from ongoing support and follow up and increased interaction with healthcare professionals.

Rhes, a striatal-selective protein implicated in Huntington disease, binds beclin-1 and activates autophagy.

The protein mutated in Huntington disease (HD), mutant huntingtin (mHtt), is expressed throughout the brain and body. However, the pathology of HD is characterized by early and dramatic destruction selectively of the striatum. We previously reported that the striatal-specific protein Rhes binds mHtt and enhances its cytotoxicity. Moreover, Rhes-deleted mice are dramatically protected from neurodegeneration and motor dysfunction in mouse models of HD. We now report a function of Rhes in autophagy, a lysosomal degradation pathway implicated in aging and HD neurodegeneration. In PC12 cells, deletion of endogenous Rhes decreases autophagy, whereas Rhes overexpression activates autophagy. These effects are independent of mTOR and opposite in the direction predicted by the known activation of mTOR by Rhes. Rhes robustly binds the autophagy regulator Beclin-1, decreasing its inhibitory interaction with Bcl-2 independent of JNK-1 signaling. Finally, co-expression of mHtt blocks Rhes-induced autophagy activation. Thus, the isolated pathology and delayed onset of HD may reflect the striatal-selective expression and changes in autophagic activity of Rhes.

Stacked abdominal flap for unilateral breast reconstruction.

BACKGROUND: The abdominal flap can be used in a stacked, double-pedicle configuration for unilateral breast reconstruction. Aided by preoperative mapping, this is a good option when a single-pedicle flap is deemed unsuitable. We present reliable outcomes using the stacked flap and a logical classification system for its use. METHODS: From 2008 to 2013, 18 patients underwent a stacked abdominal flap for unilateral breast reconstruction. Flaps utilized deep inferior epigastric (D) and superficial inferior epigastric (S) pedicle combinations. Preoperative computed tomography angiogram was performed on all patients. Medical records were reviewed for complications and clinical data, and a thorough clinical evaluation was performed on all patients at follow-up. Flaps were all double-pedicled, with the secondary pedicle anastomosed onto the primary pedicle (type 1 to 3) or onto a second recipient vessel (type 4). Flaps were then classified into groups, based on pedicle dominance and intraflap anastomosis. RESULTS: Twelve reconstructions were immediate and six delayed. Mean operative time was 7 hours, the most frequently used configuration being a type 1 DD, that is, secondary pedicle (D) anastomosed end-to-end onto the superior continuation of the primary pedicle (D). Average hospital stay was 6 days. There were no flap losses and minimal complications, and mean follow-up was 20 months. CONCLUSION: Use of this flap poses a greater challenge to the microsurgical breast reconstruction. We demonstrate its reliable use in women deemed unsuitable for a single-pedicle flap. Our structured system clarifies vascular options, and preoperative perforator mapping tools are essential to the success of this technique.

Attention biases visual activity in visual short-term memory.

In the current study, we tested whether representations in visual STM (VSTM) can be biased via top-down attentional modulation of visual activity in retinotopically specific locations. We manipulated attention using retrospective cues presented during the retention interval of a VSTM task. Retrospective cues triggered activity in a large-scale network implicated in attentional control and led to retinotopically specific modulation of activity in early visual areas V1-V4. Importantly, shifts of attention during VSTM maintenance were associated with changes in functional connectivity between pFC and retinotopic regions within V4. Our findings provide new insights into top-down control mechanisms that modulate VSTM representations for flexible and goal-directed maintenance of the most relevant memoranda.

Immunonutrition as an adjuvant therapy for burns.

BACKGROUND: With burn injuries involving a large total body surface area (TBSA), the body can enter a state of breakdown, resulting in a condition similar to that seen with severe lack of proper nutrition. In addition, destruction of the effective skin barrier leads to loss of normal body temperature regulation and increased risk of infection and fluid loss. Nutritional support is common in the management of severe burn injury, and the approach of altering immune system activity with specific nutrients is termed immunonutrition. Three potential targets have been identified for immunonutrition: mucosal barrier function, cellular defence and local or systemic inflammation. The nutrients most often used for immunonutrition are glutamine, arginine, branched-chain amino acids (BCAAs), omega-3 (n-3) fatty acids and nucleotides. OBJECTIVES: To assess the effects of a diet with added immunonutrients (glutamine, arginine, BCAAs, n-3 fatty acids (fish oil), combined immunonutrients or precursors to known immunonutrients) versus an isonitrogenous diet (a diet wherein the overall protein content is held constant, but individual constituents may be changed) on clinical outcomes in patients with severe burn injury. SEARCH METHODS: The search was run on 12 August 2012. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), ISI WOS SCI-EXPANDED & CPCI-S and four other databases. We handsearched relevant journals and conference proceedings, screened reference lists and contacted pharmaceutical companies. We updated this search in October 2014, but the results of this updated search have not yet been incorporated. SELECTION CRITERIA: Randomised controlled trials comparing the addition of immunonutrients to a standard nutritional regimen versus an isonitrogenated diet or another immunonutrient agent. DATA COLLECTION AND ANALYSIS: Two review authors were responsible for handsearching, reviewing electronic search results and identifying potentially eligible studies. Three review authors retrieved and reviewed independently full reports of these studies for inclusion. They resolved differences by discussion. Two review authors independently extracted and entered data from the included studies. A third review author checked these data. Two review authors independently assessed the risk of bias of each included study and resolved disagreements through discussion or consultation with the third and fourth review authors. Outcome measures of interest were mortality, hospital length of stay, rate of burn wound infection and rate of non-wound infection (bacteraemia, pneumonia and urinary tract infection). MAIN RESULTS: We identified 16 trials involving 678 people that met the inclusion criteria. A total of 16 trials contributed data to the analysis. Of note, most studies failed to report on randomisation methods and intention-to-treat principles; therefore study results should be interpreted with caution. Glutamine was the most common immunonutrient and was given in seven of the 16 included studies. Use of glutamine compared with an isonitrogenous control led to a reduction in length of hospital stay (mean stay -5.65 days, 95% confidence interval (CI) -8.09 to -3.22) and reduced mortality (pooled risk ratio (RR) 0.25, 95% CI 0.08 to 0.78). However, because of the small sample size, it is likely that these results reflect a false-positive effect. No study findings suggest that glutamine has an effect on burn wound infection or on non-wound infection. All other agents investigated showed no evidence of an effect on mortality, length of stay or burn wound infection or non-wound infection rates. AUTHORS' CONCLUSIONS: Although we found evidence of an effect of glutamine on mortality reduction, this finding should be taken with care. The number of study participants analysed in this systematic review was not sufficient to permit conclusions that recommend or refute the use of glutamine. Glutamine may be effective in reducing mortality, but larger studies are needed to determine the overall effects of glutamine and other immunonutrition agents.

Do young people who self-harm experience cognitions and emotions related to post-traumatic growth?

Background: Adolescent self-harm is a vast public health concern with self-harm rates increasing each year. Looked-after adolescents are a group at increased risk of self-harm owing to adverse life-events and attachment issues, giving rise to difficulties with problem solving and relationship difficulties (Ogundele, 2020). Whilst research into risk factors of self-harm is plentiful, fewer studies have explored what factors might facilitate self-harm recovery. This paper investigates whether looked-after adolescents with experience of self-harm can experience cognitions and emotions related to post-traumatic growth (PTG). Methods: Secondary Data Analysis was conducted on a primary qualitative data set from a study including twenty-four looked-after young people aged between 14 and 21 with experience of self-harm; 20 females and 4 males. An Interpretive Phenomenological Analysis was conducted. Results: Five themes were identified, four of which shared similarities to prior research into the recovery of self-harm and manifestations of PTG: 1) Self-Reflection, 2) Communication, 3) Embracing and Appreciating Support, 4) Better Management of feelings. The fifth theme suggested a potential barrier to experiencing PTG; 5) Reliance on Self-Harm. Findings revealed four relevant themes suggesting that individuals who self-harm can indeed experience cognitions and emotions relevant to PTG. Limitations: This study utilised a homogeneous sample, limiting the generalisability of the findings to other populations. Perhaps future research should consider other populations of individuals who self-harm. Conclusions: We suggest there is a need for interventions for self-harm to focus on protective factors to increase PTG within an individual, potentially moderating the risk of suicide.