Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic disorder of motile cilia dysfunction generally inherited as an autosomal recessive disease. Genetic testing is increasingly considered an early step in the PCD diagnostic workflow. We used targeted panel next generation sequencing (NGS) for genetic screening of 33 Egyptian families with highly clinically suspected PCD. All variants prioritized were Sanger confirmed in the affected individuals and correctly segregated within the family. Targeted NGS yielded a high diagnostic output (70%) with bi‐allelic mutations identified in known PCD genes. Mutations were identified in 13 genes overall, with CCDC40 and CCDC39 the most frequently mutated genes among Egyptian patients. Most identified mutations were predicted null effect variants (79%) and not reported before (85%). This study reveals that the genetic landscape of PCD among Egyptians is highly heterogeneous, indicating that a targeted NGS approach covering multiple genes will provide a superior diagnostic yield than Sanger sequencing for genetic diagnosis. The high diagnostic output achieved here highlights the potential of placing genetic testing early within the diagnostic workflow for PCD, in particular in developing countries where other diagnostic tests can be less available

Genetic Diversity, Morphological Uniformity and Polyketide Production in Dinoflagellates (Amphidinium, Dinoflagellata)

Dinoflagellates are an intriguing group of eukaryotes, showing many unusual morphological and genetic features. Some groups of dinoflagellates are morphologically highly uniform, despite indications of genetic diversity. The species Amphidinium carterae is abundant and cosmopolitan in marine environments, grows easily in culture, and has therefore been used as a ‘model’ dinoflagellate in research into dinoflagellate genetics, polyketide production and photosynthesis. We have investigated the diversity of ‘cryptic’ species of Amphidinium that are morphologically similar to A. carterae, including the very similar species Amphidinium massartii, based on light and electron microscopy, two nuclear gene regions (LSU rDNA and ITS rDNA) and one mitochondrial gene region (cytochrome b). We found that six genetically distinct cryptic species (clades) exist within the species A. massartii and four within A. carterae, and that these clades differ from one another in molecular sequences at levels comparable to other dinoflagellate species, genera or even families. Using primers based on an alignment of alveolate ketosynthase sequences, we isolated partial ketosynthase genes from several Amphidinium species. We compared these genes to known dinoflagellate ketosynthase genes and investigated the evolution and diversity of the strains of Amphidinium that produce them

Isolation and Characterization of Maize PMP3 Genes Involved in Salt Stress Tolerance

Plasma membrane protein 3 (PMP3), a class of small hydrophobic polypeptides with high sequence similarity, is responsible for salt, drought, cold, and abscisic acid. These small hydrophobic ploypeptides play important roles in maintenance of ion homeostasis. In this study, eight ZmPMP3 genes were cloned from maize and responsive to salt, drought, cold and abscisic acid. The eight ZmPMP3s were membrane proteins and their sequences in trans-membrane regions were highly conserved. Phylogenetic analysis showed that they were categorized into three groups. All members of group II were responsive to ABA. Functional complementation showed that with the exception of ZmPMP3-6, all were capable of maintaining membrane potential, which in turn allows for regulation of intracellular ion homeostasis. This process was independent of the presence of Ca2+. Lastly, over-expression of ZmPMP3-1 enhanced growth of transgenic Arabidopsis under salt condition. Through expression analysis of deduced downstream genes in transgenic plants, expression levels of three ion transporter genes and four important antioxidant genes in ROS scavenging system were increased significantly in transgenic plants during salt stress. This tolerance was likely achieved through diminishing oxidative stress due to the possibility of ZmPMP3-1's involvement in regulation of ion homeostasis, and suggests that the modulation of these conserved small hydrophobic polypeptides could be an effective way to improve salt tolerance in plants

Neuromuscular disease genetics in under-represented populations: increasing data diversity

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses \u27solved\u27 or \u27possibly solved\u27 ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% \u27solved\u27 and ∼13% \u27possibly solved\u27 outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

ICAR: endoscopic skull‐base surgery

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A pilot study of the Leicester ED medical infrared imaging protocol in fever and sepsis.

BACKGROUND: Medical Infrared Imaging (MII) is an investigative method that can be potentially used in emergency care to non-invasively detect thermal signatures associated with change in blood flow. We have developed a protocol for the use of MII in the Emergency Department (ED) and shown that it is feasible. To derive initial data for sample size calculations, we performed an exploratory study in patients with fever and sepsis. METHODS: The Leicester MII protocol was used to image the temperature patterns along the arm among three patient groups (control, fever and sepsis) of a total 56 patients. Anatomical markers were used to divide this gradient into upper arm, forearm, hand and finger regions. Variations in measurements within and between these regions were described. RESULTS: The thermal gradient down the arm was successfully extracted in all patients. The distribution of values in each region of the arm was described in control, fever and sepsis patients. There was a significant gradient between upper arm and finger in controls (2.75, p < 0.0001), but no gradient in fever (p = 0.944) or sepsis (p = 0.710). This was reflected in the finger/arm difference, which was of -2.74°C (±3.50) in controls, -0.39C (±2.48) in fever, and -1.80°C (±3.09) in sepsis. CONCLUSIONS: This study found different thermal gradients along the arm in control and febrile groups, and defined the degree of individual variation. It is likely that the difference between upper arm temperature and finger temperature (representing the temperature gradient down the arm) may be more useful than absolute measurements in future studies

Body Mass Index as a Major Prognostic Contributing Factor in COVID-19: A Multicentral Egyptian Study

Hossam Abd El-Moez Mohammed,1 Mohammed H Hassan,2 Hytham Abdalla,3 Marwa Ahmed Mahmoud,4 Amira Maher,5 Mohamed Malak,6 Mohammed Tag-Adeen,7 Mohamed Ramadan Izzaldin,8 Sara Adel,8 Wael Esmat Ali,8 Alyaa Abo-Rahma,9 Mona Gouda Maghrabi Abd Elnabi,10 Ibrahim Ahmed Mosa Abdalla,11 Mohamed Fakhry Mohamed Morsy,12 Mohamed Abdel Fattah Mohamed Sayed,13 Usama Mohamed Abdelaal6 1Department of Chest Diseases, Faculty of Medicine, Luxor University, Luxor, Egypt; 2Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, Egypt; 3Department of Chest Diseases, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt; 4Department of Medical Physiology, Faculty of Medicine, Sohag University, Sohag, Egypt; 5Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Sohag University, Sohag, Egypt; 6Department of Internal Medicine, Faculty of Medicine, Sohag University, Sohag, Egypt; 7Department of Internal Medicine, Division of Gastroenterology and Hepatology, Faculty of Medicine, South Valley University, Qena, 83523, Egypt; 8Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt; 9Department of Public Health and Community Medicine, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt; 10Department of Diagnostic Radiology, Faculty of Medicine, Luxor University, Luxor, Egypt; 11Anasthesia and Critical Care Department, Faculty of Medicine, Luxor University, Luxor, Egypt; 12Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt; 13Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Aswan University, Aswan, EgyptCorrespondence: Mohammed H Hassan, Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, Egypt, Tel +20 1009097968, Email [email protected]; [email protected]: Extreme body mass index (BMI) is an influential pathophysiological risk factor for serious illnesses following lower respiratory tract infection. The purpose of the current study was to examine how the BMI of Coronavirus disease-19 (COVID-19) patients affects their prognosis.Methods: Two hundred patients with COVID-19 admitted to Al-Azhar, Qena, Aswan, and Sohag University hospitals in Egypt were included and categorized into four groups according to their BMI. The diagnosis was made according to a real-time reverse transcription-polymerase chain reaction (rRT-PCR) positive result for the SARS-CoV-2 nucleic acid in swabs from upper respiratory tract. A detailed history, clinical examination, and outcomes (disease severity and complications, hospital stay, ICU admission, mortality) were recorded for all patients. SPSS version 24 software was used for data analysis.Results: Average age of participants (19– 90 years old), 92 (46%) males and 108 females (54%). ICU admission was significantly higher among underweight patients (75%) and obese patients (78.6%). The majority of underweight (62.5%) and obese (57.1%) patients had critical disease. Invasive mechanical ventilation (MV) is frequently used in underweight (50%) and obese patients (42.9%) patients. Adult respiratory distress syndrome (ARDS), cardiac, neurological, and hematological complications, and incidence of myalgia and bed sores were most frequent among obese and overweight patients. Acute kidney injury was significantly higher among underweight patients (37.5%) and obese patients (28.6%) than among other classes (p=0.004). Frequency of endocrine complications was significantly higher in underweight patients than that in other classes (p=0.01). The majority of underweight (75%) and obese patients (50%) deteriorated and died, whereas the majority of normal-weight patients (90.3%) and overweight patients (75.8%) improved and were discharged (p< 0.001).Conclusion: Body mass index is a major contributing factor to the outcome of patients with COVID-19, and patients with extreme of body mass index were associated with the worst prognosis.Keywords: body mass index, COVID-19, obese, underweight, intensive care uni