A human DCC variant causing mirror movement disorder reveals that the WAVE regulatory complex mediates axon guidance by netrin-1-DCC.

The axon guidance cue netrin-1 signals through its receptor DCC (deleted in colorectal cancer) to attract commissural axons to the midline. Variants in DCC are frequently associated with congenital mirror movements (CMMs). A CMM-associated variant in the cytoplasmic tail of DCC is located in a conserved motif predicted to bind to a regulator of actin dynamics called the WAVE (Wiskott-Aldrich syndrome protein-family verprolin homologous protein) regulatory complex (WRC).

Numb positively regulates Hedgehog signaling at the ciliary pocket.

Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation.

Defining the Genetic Landscape of Congenital Mirror Movements in 80 Affected Individuals.

Background: Congenital mirror movements (CMM) is a rare neurodevelopmental disorder characterized by involuntary movements from one side of the body that mirror voluntary movements on the opposite side. To date, five genes have been associated with CMM, namely DCC, RAD51, NTN1, ARHGEF7, and DNAL4.

Objective: The aim of this study is to characterize the genetic landscape of CMM in a large group of 80 affected individuals.

When proprioceptive feedback enhances visual perception of self-body movement: rehabilitation perspectives.

Introduction: Rehabilitation approaches take advantage of vision's important role in kinesthesia, using the mirror paradigm as a means to reduce phantom limb pain or to promote recovery from hemiparesis. Notably, it is currently applied to provide a visual reafferentation of the missing limb to relieve amputees' pain. However, the efficiency of this method is still debated, possibly due to the absence of concomitant coherent proprioceptive feedback.

Genetics of mirror movements identifies a multifunctional complex required for Netrin-1 guidance and lateralization of motor control.

Mirror movements (MM) disorder is characterized by involuntary movements on one side of the body that mirror intentional movements on the opposite side. We performed genetic characterization of a family with autosomal dominant MM and identified , a RhoGEF, as a candidate MM gene. We found that Arhgef7 and its partner Git1 bind directly to Dcc.

Toward A Serious Game to Help Future Military Doctors Face Mass Casualty Incidents.

Introduction: To prepare military doctors to face mass casualty incidents (MCIs), the French Army Health Service contributed to the development of TRAUMASIMS, a serious game (SG) for training medical responders to MCIs.

Methods: French military doctors participated in a three-phase training study. The initial war trauma training was a combination of didactic lectures (Phase 1), laboratory exercises (Phase 2), and situational training exercises (STX) (Phase 3).

Attending lectures in person, hybrid or online-how do students choose, and what about the outcome?

As a consequence of the COVID-19 pandemic, most courses at a large technical university were adapted so that students had a free choice of whether to attend lectures on-site or online; in addition, in many courses, lecture recordings were available. At the subsequent exam session, over 17,000 student-survey responses were collected regarding attendance choices, learning behavior, interest in the course, perception of the exam, and recommendations to future students. A total of 27 learner attributes and their relationships were investigated.

Severe trauma patients requiring undelayable combined cranial and extracranial surgery: A scoping review of an emerging concept.

Objectives: Although patients suffering from severe traumatic brain injury (sTBI) and severe trauma patients (STP) have been extensively studied separately, there is scarce evidence concerning STP with concomitant sTBI. In particular, there are no guidelines regarding the emergency surgical management of patients presenting a concomitant life-threatening intracranial hematoma (ICH) and a life-threatening non-compressible extra-cranial hemorrhage (NCEH).

Materials And Methods: A scoping review was conducted on Medline database from inception to September 2021.

Imprint of Initial Education and Loss of Ly49C/I in Activated Natural Killer Cells of TAP1-KO and C57BL/6 Wildtype Mice.

Natural killer (NK) cells are important effectors of the innate immune system and participate in the first line of defense against infections and tumors. Prior to being functional, these lymphocytes must be educated or licensed through interactions of their major histocompatibility complex class I molecules with self-specific inhibitory receptors that recognize them. In the absence of such contacts, caused by either the lack of expression of the inhibitory receptors or a very low level of major histocompatibility complex class I (MHC class I) proteins, NK cells are hypo-reactive at baseline ().

Hospitalization Rates in Patients with Heart Failure and Reduced Ejection Fraction Initiating Sacubitril/Valsartan or Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers: A Retrospective Cohort Study.

Introduction: The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (SAC/VAL) has shown benefit in patients with symptomatic heart failure (HF), including those naïve to renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and is considered the preferred RAASi for chronic HF. Real-world data on ARNI, specifically in RAASi-naïve patients, are limited. This study compared real-world outcomes of ARNI (SAC/VAL) vs.

Development and Characterization of a Novel Non-Lytic Cancer Immunotherapy Using a Recombinant Arenavirus Vector Platform.

Engineered viral vectors represent a promising strategy to trigger antigen-specific antitumor T cell responses. Arenaviruses have been widely studied because of their ability to elicit potent and protective T cell responses. Here, we provide an overview of a novel intravenously administered, replication-competent, non-lytic arenavirus-based vector technology that delivers tumor antigens to induce antigen-specific anti-cancer T cell responses.

Rabaptin5 targets autophagy to damaged endosomes and Salmonella vacuoles via FIP200 and ATG16L1.

Selective autophagy of damaged organelles is important to maintain cellular homeostasis. The mechanisms how autophagy selects specific targets is often poorly understood. Rabaptin5 was previously known as a major regulator of early endosome identity and maturation.

Mononucleoside phosphorodithiolates as mononucleotide prodrugs.

The synthesis and in vitro anti-HIV activity of a novel series of pronucleotides are reported. These prodrugs were characterized by a phosphorodithiolate structure, incorporating two O-pivaloyl-2-oxyethyl substituents as biolabile phosphate protections. The compounds were obtained following an original one-pot three-step procedure, involving the formation of a phosphorodithioite intermediate which is in situ oxidized.

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

Purpose: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication.

Methods: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included.

Intra-pancreatic distal cholangiocarcinoma and pancreatic ductal adenocarcinoma: a common short and long-term prognosis?

The aim of the study was to compare histological features, postoperative outcomes, and long-term prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. From 2005 to 2017, 188 pancreaticoduodenectomies (pancreatic ductal adenocarcinoma n = 151, distal cholangiocarcinoma n = 37) were included. Postoperative outcomes were compared after matching on pancreatic gland texture and main pancreatic duct size.

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Objective: To describe the unaccompanied minors' reasons for consulting and their health problems managed in a permanence of access to health care (PASS) at the Hospices civils de Lyon.

Methods: Consultation data of the unaccompanied minors cared for in 2016 and 2017 at the Edouard Herriot Hospital PASS, Lyon, were collected and coded according to the International Classification of Primary Care (CISP-2).

Results: The majority of unaccompanied minors were male adolescents from French-speaking sub-Saharan African countries.

Eligibility criteria for ambulatory colectomy.

Purpose Of The Study: To determine the statistical indicators aimed at identifying patients for whom ambulatory colectomy could be proposed without additional risk.

Patients And Methods: The medical charts of patients who benefited from scheduled colonic or rectal resection during conventional hospitalization stays between 2018 and 2019 were reviewed. Eligibility for ambulatory colectomy was defined by hospital stay≤4 days and absence of any postoperative complication.

Heart failure signs and symptoms, hospital referrals, and prescription patterns in patients receiving sacubitril/valsartan in primary care and cardiologist settings in Germany.

Aims: The aim of this paper was to analyse heart failure (HF) signs and symptoms, hospital referrals, and prescription patterns in patients receiving sacubitril/valsartan (sac/val) in primary care and cardiology settings in Germany.

Methods And Results: A retrospective cohort study of electronic medical records identified 1263 adults (aged ≥18 years) in the German IMS® Disease Analyzer database who were prescribed sac/val during 2016 and had at least 6 months of data following sac/val initiation. Clinical characteristics were collected during the 12 months before the first recorded sac/val prescription (index date) and 6 months post-index.

The obesity treatment dilemma: Why dieting is both the answer and the problem? A mechanistic overview.

Restricted-calorie diets are the most worldwide used treatments for obesity. Although such strategies are based on the first law of thermodynamics, the real life clinical practice demonstrates that the observed weight losses are divergent from those theoretically predicted. Loosely adherence to recommendations is one of the main causes for the limited efficacy of dieting, but many additional factors can be involved in the hurdles to weight loss.

Risk reduction of diarrhea and respiratory infections following a community health education program - a facility-based case-control study in rural parts of Kenya.

Background: Diarrheal and acute respiratory infections remain a major cause of death in developing countries especially among children below 5 years of age. About 80% of all hospital attendances in Kenya can be attributed to preventable diseases and at least 50% of these preventable diseases are linked to poor sanitation. The purpose of this study was to assess the impact of a community-based health education program, called Familia Nawiri, in reducing the risk of diarrhea and respiratory infections among people living in three rural Kenyan communities.

Outcomes of vaginal squamous cell carcinoma of patients treated with radiation therapy: a series of 37 patients from a single expert center.

Introduction: The aim is to assess the outcome of patients treated for vaginal carcinoma with radiation therapy in terms of long-term tolerance and survival.

Materials And Methods: This single-center retrospective study included patients with squamous cell carcinoma of the vagina treated with pelvic external beam radiation therapy (EBRT) with or without vaginal brachytherapy (VB) between 1990 and 2013.

Results: Thirty-seven patients were included with stage I (24%), II (60%), III (8%), or IV (8%) vaginal tumors.

Tactical tourniquet: Surgical management must be within 3 hours.

Despite longstanding controversy, tourniquets are widely used in tactical combat casualty care, with undisputed benefits for recent conflicts in Iraq and Afghanistan. Increased time delays are a particular issue in large areas, such as the Sahel-Saharan band. Complications associated with tourniquet use are predominantly related to acute ischemia with risk of amputation and ischaemia-reperfusion injury, as shown in the first clinical case.

Association between vildagliptin and risk of angioedema, foot ulcers, skin lesions, hepatic toxicity, and serious infections in patients with type 2 diabetes mellitus: A European multidatabase, noninterventional, postauthorization safety study.

Objectives: This noninterventional, multidatabase, analytical cohort study explored whether vildagliptin is associated with an increased risk of specific safety events of interest, namely angioedema, foot ulcers, or skin lesions, adverse hepatic events, or serious infections compared with other noninsulin antidiabetic drugs (NIADs) using real-world data from five European electronic healthcare databases.

Design: Patients with type 2 diabetes mellitus aged ≥18 years on NIAD treatment were included between January 2005 and June 2014. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the outcomes of interest were estimated using negative binomial regression.