Ca1.1 voltage-sensing domain III exclusively controls skeletal muscle excitation-contraction coupling.

Skeletal muscle contractions are initiated by action potentials, which are sensed by the voltage-gated calcium channel (Ca1.1) and are conformationally coupled to calcium release from intracellular stores. Notably, Ca1.

Ca3.3 Channelopathies.

Ca3.3 is the third member of the low-voltage-activated calcium channel family and the last to be recognized as disease gene. Previously, CACNA1I, the gene encoding Ca3.

Risk factors for diphtheria in Sana'a, Yemen, 2019: a matched case-control study.

Objective: To identify risk factors for diphtheria related to sociodemographic, immunization and household status, and source of infection in Sana'a.

Methods: A retrospective matched case-control study (1:2 ratio) was conducted. Cases were defined as patients who met the World Health Organization's definition of confirmed diphtheria living in Sana'a between January and November 2019.

Circulating PCSK9 Linked to Dyslipidemia in Lebanese Schoolchildren.

In adults, elevated levels of circulating Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) have been associated with increased Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and worse cardiovascular outcomes. However, few studies analyzed the relation between PCSK9 and lipid parameters in pediatric populations. The aim of our study is to evaluate the distribution and the correlation of serum PCSK9 levels with lipid parameters in a sample of Lebanese school children.

Calcium current modulation by the γ1 subunit depends on alternative splicing of CaV1.1.

The skeletal muscle voltage-gated calcium channel (CaV1.1) primarily functions as a voltage sensor for excitation-contraction coupling. Conversely, its ion-conducting function is modulated by multiple mechanisms within the pore-forming α1S subunit and the auxiliary α2δ-1 and γ1 subunits.

Diphtheria resurgence in Sada'a-Yemen, 2017-2020.

Background: Diphtheria is a contagious vaccine-preventable disease that contributes to the high morbidity and mortality among under 5 children, especially in Yemen. As a consequence of war and collapse of the health system, a fatal epidemic occurred at the end of 2017. This study aims to describe the epidemiology of diphtheria by time, place, and person and vaccination status of affected children.

Field Epidemiology Training Program Response to COVID-19 During a Conflict: Experience From Yemen.

COVID-19 pandemic has underscored the need for a well-trained public health workforce to save lives through timely outbreaks detection and response. In Yemen, a country that is entering its seventh year of a protracted war, the ongoing conflict severely limited the country's capacity to implement effective preparedness and response measures to outbreaks including COVID-19. There are growing concerns that the virus may be circulating within communities undetected and unmitigated especially as underreporting continues in some areas of the country due to a lack of testing facilities, delays in seeking treatment, stigma, difficulty accessing treatment centers, the perceived risks of seeking care or for political issues.

Risk Factors of COVID-19 Critical Outcomes in the Eastern Mediterranean Region: Multicountry Retrospective Study.

Background: The establishment of empirical evidence in the Eastern Mediterranean Region necessitates the implementation of wide-scale studies to describe the demographic, clinical features, and severity profile of patients with COVID-19.

Objective: This study aims to assess the patterns of COVID-19 severity and mortality in seven countries, and to determine the risk factors of COVID-19 severity and mortality.

Methods: This multicountry study was based on a retrospective review of medical records of hospitalized patients confirmed to have COVID-19.

Mental health impacts of COVID-19 on healthcare workers in the Eastern Mediterranean Region: a multi-country study.

Background: Healthcare workers (HCWs) fighting against the COVID-19 pandemic are under incredible pressure, which puts them at risk of developing mental health problems. This study aimed to determine the prevalence of depression, anxiety, and stress among HCWs responding to COVID-19 and its associated factors.

Methods: A multi-country cross-sectional study was conducted during July-August 2020 among HCWs responding to COVID-19 in nine Eastern Mediterranean Region (EMR) countries.

Identification of a Variant in Gene as a Major Cause of Hypobetalipoproteinemia in Lebanese Families.

Familial hypobetalipoproteinemia (FHBL) is a codominant genetic disorder characterized by reduced plasma levels of low-density lipoprotein cholesterol and apolipoprotein B. To our knowledge, no study on FHBL in Lebanon and the Middle East region has been reported. Therefore, we conducted genetic studies in unrelated families and probands of Lebanese origin presenting with FHBL, in order to identify the causes of this disease.

Ion-pair interactions between voltage-sensing domain IV and pore domain I regulate Ca1.1 gating.

The voltage-gated calcium channel Ca1.1 belongs to the family of pseudo-heterotetrameric cation channels, which are built of four structurally and functionally distinct voltage-sensing domains (VSDs) arranged around a common channel pore. Upon depolarization, positive gating charges in the S4 helices of each VSD are moved across the membrane electric field, thus generating the conformational change that prompts channel opening.

First COVID-19 cases with high secondary infection among health workers, Sana'a capital, April 2020: Lessons learned and future opportunities.

Objectives: Confirm existence of COVID-19 outbreak, conduct contact tracing, and recommend control measures.

Methods: Two COVID-19 cases in Sana'a Capital met the WHO case definition. Data were collected from cases and contacts who were followed for 14 days.

Structural determinants of voltage-gating properties in calcium channels.

Voltage-gated calcium channels control key functions of excitable cells, like synaptic transmission in neurons and the contraction of heart and skeletal muscles. To accomplish such diverse functions, different calcium channels activate at different voltages and with distinct kinetics. To identify the molecular mechanisms governing specific voltage sensing properties, we combined structure modeling, mutagenesis, and electrophysiology to analyze the structures, free energy, and transition kinetics of the activated and resting states of two functionally distinct voltage sensing domains (VSDs) of the eukaryotic calcium channel Ca1.

CACNA1I gain-of-function mutations differentially affect channel gating and cause neurodevelopmental disorders.

T-type calcium channels (Cav3.1 to Cav3.3) regulate low-threshold calcium spikes, burst firing and rhythmic oscillations of neurons and are involved in sensory processing, sleep, and hormone and neurotransmitter release.

The impact of COVID-19 pandemic on blood supplies and transfusion services in Eastern Mediterranean Region.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spurred a global health crisis. The safety and supply of blood during this pandemic has been a concern of blood banks and transfusion services as it is expected to adversely affect blood system activities. We aim to assess the situation in the Eastern Mediterranean Region (EMR) during the first months of the pandemic.

Pathogenic variants in THSD4, encoding the ADAMTS-like 6 protein, predispose to inherited thoracic aortic aneurysm.

Purpose: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease with often unrecognized inherited forms. We sought to identify novel pathogenic variants associated with autosomal dominant inheritance of TAAD.

Methods: We analyzed exome sequencing data from 35 French TAAD families and performed next-generation sequencing capture panel of genes in 1114 unrelated TAAD patients.

Evaluation of Blood Transfusion Services in Public and Private Blood Bank Centers, Sana'a Capital, Yemen.

The aim of this study was to evaluate blood transfusion services (BTS) at the main blood banks (BBs) of the Sana'a Capital. The 4 main BBs at Sana'a Capital were evaluated according to the safe World Health Organization BTS standards. Qualitative and quantitative data were collected using semi-structured questionnaires covering 6 components: activities, quality assurance system (QAS) and training, donation, grouping and compatibility testing, components, and screening for transfusion-transmitted infections (TTIs).

Correcting the R165K substitution in the first voltage-sensor of Ca1.1 right-shifts the voltage-dependence of skeletal muscle calcium channel activation.

The voltage-gated calcium channel Ca1.1a primarily functions as voltage-sensor in skeletal muscle excitation-contraction (EC) coupling. In embryonic muscle the splice variant Ca1.

Identification of the first Tangier disease patient in Lebanon carrying a new pathogenic variant in ABCA1.

Background: The Middle East region is characterized by low levels of high-density lipoprotein cholesterol (HDL-C). To date, no genetic study has investigated the cause of low HDL-C in the Lebanese population.

Objective: Our objective was to study the genetic causes for hypoalphalipoproteinemia in a Lebanese family with extremely low HDL-C levels.

New Sequencing technologies help revealing unexpected mutations in Autosomal Dominant Hypercholesterolemia.

Autosomal dominant hypercholesterolemia (ADH) is characterized by elevated LDL-C levels leading to coronary heart disease. Four genes are implicated in ADH: LDLR, APOB, PCSK9 and APOE. Our aim was to identify new mutations in known genes, or in new genes implicated in ADH.