A suite of automated sequence analyses reduces the number of candidate deleterious variants and reveals a difference between probands and unaffected siblings.

Purpose: Develop an automated exome analysis workflow that can produce a very small number of candidate variants yet still detect different numbers of deleterious variants between probands and unaffected siblings.

Methods: Ninety-seven outbred nuclear families from the Undiagnosed Diseases Program/Network included single probands and the corresponding unaffected sibling(s). Single-nucleotide polymorphism (SNP) chip and exome analyses were performed on all, with proband and unaffected sibling considered independently as the target.

The Use of Botulinum Toxin Type A in the Healing of Thyroidectomy Wounds: A Randomized, Prospective, Placebo-Controlled Study.

Background: Recent research has indicated that botulinum toxin type A may have an inhibitory effect on the formation of fibroblasts and thus possibly decreases the severity of scar formation. Therefore, a trial was designed to assess the effects of botulinum toxin type A on scar formation after thyroid surgery.

Methods: A double-blind, randomized, controlled trial was designed.

Concordance of Fingerstick and Venipuncture Sampling for Fertility Hormones.

Background: Minimally invasive fingerstick sampling allows testing of reproductive hormone levels at home, providing women with increased access to tests that can screen for conditions such as polycystic ovarian syndrome, primary ovarian insufficiency, and pituitary and thyroid dysfunction.

Method: We present a measurement procedure comparison study of matched venipuncture and fingerstick samples from 130 women aged 18-40 years, tested on menstrual cycle day 3. Samples were measured for anti-müllerian hormone, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone, thyroid-stimulating hormone (TSH), and free thyroxine (T4) levels.

Thermal Burn Injury from a Wedding Ring: An Unusual Case.

Thermal ring injuries are rarely reported in the literature. For this reason, treatment is varied without a standard approach. We describe a case of a thermal wedding ring injury sustained during a welding accident.

Comparison of Distraction Osteogenesis and Single-Stage Remodeling for Correction of Unilateral Coronal Craniosynostosis.

Background: Unilateral coronal craniosynostosis is a challenging condition in craniofacial surgery. Frontoorbital advancement by single-stage resorbable remodeling and distraction osteogenesis (DO) techniques have known intraoperative differences, but their comparative outcomes are less well characterized.

Methods: A systematic literature search of the MEDLINE, EMBASE, LILACS, and Web of Science databases was conducted.

Large intra-abdominal desmoid tumour posing diagnostic and therapeutic challenges, a case report.

We present the case of a 46-year-old gentleman originally from China who presented to the acute surgical assessment unit complaining of upper abdominal discomfort, dyspepsia and early satiety ongoing for the previous 6 months. On exam he had a palpable mass in the left upper quadrant. He underwent an esophagogastroduodenoscopy which was normal and later received a CT abdomen which identified a well-circumscribed soft tissue mass in the mesenteric fat and lying adjacent to the transverse colon with no obvious cleavage plane between them.

Effect of a region-wide incorporation of an algorithm based on the 2012 international consensus guideline on the practice pattern for the management of pancreatic cystic neoplasms in an integrated health system.

Aim: To examine the practice pattern in Kaiser Permanente Southern California (KPSC), ., gastroenterology (GI)/surgery referrals and endoscopic ultrasound (EUS), for pancreatic cystic neoplasms (PCNs) after the region-wide dissemination of the PCN management algorithm.

Methods: Retrospective review was performed; patients with PCN diagnosis given between April 2012 and April 2015 (18 mo before and after the publication of the algorithm) in KPSC (integrated health system with 15 hospitals and 202 medical offices in Southern California) were identified.

Providing mental health peer support 2: Relationships with empowerment, hope, recovery, quality of life and internalised stigma.

Objective: Qualitative research has identified personal costs and benefits for peer supporters associated with their role; however, quantitative evidence is sparse. This study used quantitative methods to explore relationships in experiences of providing peer support with constructs of empowerment, hope, recovery, quality of life and internalised stigma. Differences were examined for those in statutory versus non-statutory services; who had themselves received peer support versus those who had not and who identified having had negative experiences in clinical teams versus those without such experiences.

Effect of Fetal Growth on 1-Year Mortality in Neonates With Critical Congenital Heart Disease.

Background Infants with critical congenital heart disease ( CCHD ) are more likely to be small for gestational age (GA). It is unclear how this affects mortality. The authors investigated the effect of birth weight Z score on 1-year mortality separately in preterm (GA <37 weeks), early-term (GA 37-38 weeks), and full-term (GA 39-42 weeks) infants with CCHD .

Introduction of an academic internship in Ireland: views of undergraduate medical students.

Introduction: A combined academic and clinical training programme for junior doctors in Ireland, the academic track for internship, has recently been launched. The academic track offers newly graduated doctors protected time within the working week to undertake a research project in addition to funding, an academic supervisor, and additional training in research skills. This study seeks to investigate the views of undergraduate medical students.

Helping Postpartum Women in Mali Achieve Their Fertility Intentions: Perspectives From Introduction of the Dedicated Postpartum IUD Inserter.

Background: Mali has one of the highest maternal mortality ratios in the world coupled with one of the lowest modern contraceptive use rates. Nearly a quarter of the country's 750,000 annual births occur within 24 months of a previous birth, increasing the risks for mothers and babies. Nearly 70% of postpartum women have an unmet need for family planning.

HO oxidation of cysteine residues in c-Jun N-terminal kinase 2 (JNK2) contributes to redox regulation in human articular chondrocytes.

Reactive oxygen species (ROS), in particular HO, regulate intracellular signaling through reversible oxidation of reactive protein thiols present in a number of kinases and phosphatases. HO has been shown to regulate mitogen-activated protein kinase (MAPK) signaling depending on the cellular context. We report here that in human articular chondrocytes, the MAPK family member c-Jun N-terminal kinase 2 (JNK2) is activated by fibronectin fragments and low physiological levels of HO and inhibited by oxidation due to elevated levels of HO The kinase activity of affinity-purified, phosphorylated JNK2 from cultured chondrocytes was reversibly inhibited by 5-20 μm HO Using dimedone-based chemical probes that react specifically with sulfenylated cysteines (RSOH), we identified Cys-222 in JNK2, a residue not conserved in JNK1 or JNK3, as a redox-reactive site.

Land-use emissions play a critical role in land-based mitigation for Paris climate targets.

Scenarios that limit global warming to below 2 °C by 2100 assume significant land-use change to support large-scale carbon dioxide (CO) removal from the atmosphere by afforestation/reforestation, avoided deforestation, and Biomass Energy with Carbon Capture and Storage (BECCS). The more ambitious mitigation scenarios require even greater land area for mitigation and/or earlier adoption of CO removal strategies. Here we show that additional land-use change to meet a 1.

Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

Background: Guidelines regarding specific resection margins for primary Merkel cell carcinoma (MCC) are not well established. The current National Comprehensive Cancer Network (NCCN) guidelines recommend 1- to 2-cm resection margins. This study aimed to determine the impact of margin width on local recurrence (LR), disease-specific survival (DSS), overall survival (OS), and type of wound closure.

Surgical management of melanoma.

Surgery remains one of the key treatment modalities for melanoma. Wide excision of the primary site with sentinel lymph node biopsy for selected patients has been recognized as the standard surgical approach for patients with early-stage disease. Controversies persist regarding margin width, indications for sentinel lymph node biopsy, and surgical management of regional nodal basins.

How best to support individuals with IDD as they become frail: Development of a consensus statement.

Background: While higher rates and earlier onset of frailty have been reported among adults with intellectual and developmental disabilities (IDD), research on how best to support these individuals is lacking.

Method: An international consultation relied on three consensus building methods: the Nominal Group Technique, an NIH consensus conference approach, and a Delphi survey.

Results: There is agreement that person-centered planning and aging in place should be guiding principles.

A case of ectopic liver tissue adherent to the gallbladder.

We report a case of a 30-year-old lady who presented to the emergency department with a 1 day history of severe epigastric pain which radiated to the back. Focused history, physical exam findings, haematological and radiological investigations, including ultrasound scanning of the abdomen, supported the diagnosis of acute gallstone pancreatitis. She was managed conservatively and underwent elective laparoscopic cholecystectomy at a later date.

A comparison of testosterone and cortisol levels between gay fathers and non-fathers: A preliminary investigation.

Humans are unique among great apes and most other mammals, in that our wide range of offspring investment behaviors includes significant paternal care and provisioning of children. Moreover, hormones play an important role in modulating male paternal investment. Despite a growing body of research on the hormonal associations with paternal care in humans, fathers who self-identify as gay have not received the same level of research attention.

Prevalence and associated factors of problem behaviours among older adults with intellectual disabilities in Ireland.

A growing number of adults with intellectual disabilities (ID) are reaching old age, however, little is known about epidemiology of problem behaviours (PBs) in this population. The aim was to identify the prevalence and associated factors of PBs among older adults with ID in Ireland. Data was generated from Wave 2 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a nationally representative sample of adults with ID aged ≥40.

Brown bowel syndrome, an unusual cause of sigmoid volvulus.

We report a case of a 79-year-old gentleman who presented to the emergency department with a 5-day history of abdominal pain, constipation, a progressively distending abdomen and new onset feculent vomiting on a background of a recent endoscopic decompression of a sigmoid volvulus. Investigations confirmed the presence of a recurrent sigmoid volvulus. Attempts to reduce this endoscopically failed and laparotomy with sub-total colectomy and ileostomy formation was performed.

Pharmacokinetic drug evaluation of talimogene laherparepvec for the treatment of advanced melanoma.

Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma.

Lymphatic dysfunction in critical illness.

Purpose Of Review: The essential role of the lymphatic system in fluid homeostasis, nutrient transport, and immune trafficking is well recognized; however, there is limited understanding of the mechanisms that regulate lymphatic function, particularly in the setting of critical illness. The lymphatics likely affect disease severity and progression in every condition, from severe systemic inflammatory states to respiratory failure. Here, we review structural and functional disorders of the lymphatic system, both congenital and acquired, as they relate to care of the pediatric patient in the intensive care setting, including novel areas of research into medical and procedural therapeutic interventions.