A comprehensive introduction to the genetic basis of non-syndromic hearing loss in the Saudi Arabian population

<p>Abstract</p> <p>Background</p> <p>Hearing loss is a clinically and genetically heterogeneous disorder. Mutations in the <it>DFNB1 </it>locus have been reported to be the most common cause of autosomal recessive non-syndromic hearing loss worldwide. Apart from <it>DFNB1</it>, many other loci and their underlying genes have also been identified and the basis of our study was to provide a comprehensive introduction to the delineation of the molecular basis of non-syndromic hearing loss in the Saudi Arabian population. This was performed by screening <it>DFNB1 </it>and to initiate prioritized linkage analysis or homozygosity mapping for a pilot number of families in which <it>DFNB1 </it>has been excluded.</p> <p>Methods</p> <p>Individuals from 130 families of Saudi Arabian tribal origin diagnosed with an autosomal recessive non-syndromic sensorineural hearing loss were screened for mutations at the <it>DFNB1 </it>locus by direct sequencing. If negative, genome wide linkage analysis or homozygosity mapping were performed using Affymetrix GeneChip^®Human Mapping 250K/6.0 Arrays to identify regions containing any known-deafness causing genes that were subsequently sequenced.</p> <p>Results</p> <p>Our results strongly indicate that <it>DFNB1 </it>only accounts for 3% of non-syndromic hearing loss in the Saudi Arabian population of ethnic ancestry. Prioritized linkage analysis or homozygosity mapping in five separate families established that their hearing loss was caused by five different known-deafness causing genes thus confirming the genetic heterogeneity of this disorder in the kingdom.</p> <p>Conclusion</p> <p>The overall results of this study are highly suggestive that underlying molecular basis of autosomal recessive non-syndromic deafness in Saudi Arabia is very genetically heterogeneous. In addition, we report that the preliminary results indicate that there does not seem to be any common or more prevalent loci, genes or mutations in patients with autosomal recessive non-syndromic hearing loss in patients of Saudi Arabian tribal origin.</p

Epidemiology and antimicrobial resistance trends of Acinetobacter species in the United Arab Emirates: a retrospective analysis of 12 years of national AMR surveillance data

Introduction: Acinetobacter spp., in particular A. baumannii, are opportunistic pathogens linked to nosocomial pneumonia (particularly ventilator-associated pneumonia), central-line catheter-associated blood stream infections, meningitis, urinary tract infections, surgical-site infections, and other types of wound infections. A. baumannii is able to acquire or upregulate various resistance determinants, making it frequently multidrug-resistant, and contributing to increased mortality and morbidity. Data on the epidemiology, levels, and trends of antimicrobial resistance of Acinetobacter spp. in clinical settings is scarce in the Gulf Cooperation Council (GCC) and Middle East and North Africa (MENA) regions. Methods: A retrospective 12-year analysis of 17,564 non-duplicate diagnostic Acinetobacter spp. isolates from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010-2021, collected by trained personnel and reported by participating surveillance sites to the UAE National AMR Surveillance program. Data analysis was conducted with WHONET. Results: Species belonging to the A. calcoaceticus-baumannii complex were mostly reported (86.7%). They were most commonly isolated from urine (32.9%), sputum (29.0%), and soft tissue (25.1%). Resistance trends to antibiotics from different classes during the surveillance period showed a decreasing trend. Specifically, there was a significant decrease in resistance to imipenem, meropenem, and amikacin. Resistance was lowest among Acinetobacter species to both colistin and tigecycline. The percentages of multidrug-resistant (MDR) and possibly extensively drug-resistant (XDR) isolates was reduced by almost half between the beginning of the study in 2010 and its culmination in 2021. Carbapenem-resistant Acinetobacter spp. (CRAB) was associated with a higher mortality (RR: 5.7), a higher admission to ICU (RR 3.3), and an increased length of stay (LOS; 13 excess inpatient days per CRAB case), as compared to Carbapenem-susceptible Acinetobacter spp. Conclusion: Carbapenem-resistant Acinetobacter spp. are associated with poorer clinical outcomes, and higher associated costs, as compared to carbapenem-susceptible Acinetobacter spp. A decreasing trend of MDR Acinetobacter spp., as well as resistance to all antibiotic classes under surveillance was observed during 2010 to 2021. Further studies are needed to explore the reasons and underlying factors leading to this remarkable decrease of resistance over time

High–temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high–temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses

Retrofitting solid wall buildings: energy and carbon costs and savings

Regulations and technological advances over the last decade have led to improved energy efficiency for new buildings. However much of the existing European building stock has poorly insulated fabric leading to low energy efficiency and high carbon emissions. In the UK we have a particular problem with homes built prior to 1930 with un-insulated solid walls. This paper briefly reviews the multiple barriers to retrofitting solid wall insulation in the UK. It then quantifies the whole life (operational and embodied) carbon of a solid-walled dwelling, first in its original state and then retrofitted with one of four solid wall insulation products. The results show that all of the products modelled repay their cradle to grave embodied energy and carbon costs within 13 months of installation through the operational savings achieved. The authors conclude that retrofitting with solid wall insulation can result in considerable whole life carbon reductions. While the barriers remain considerable, greater understanding of the issues will help contractors, home owners and developers to make informed design choices

Recent Major Transcriptomics and Epitranscriptomics Contributions toward Personalized and Precision Medicine

With the advent of genome-wide screening methods—beginning with microarray technologies and moving onto next generation sequencing methods—the era of precision and personalized medicine was born. Genomics led the way, and its contributions are well recognized. However, “other-omics” fields have rapidly emerged and are becoming as important toward defining disease causes and exploring therapeutic benefits. In this review, we focus on the impacts of transcriptomics, and its extension—epitranscriptomics—on personalized and precision medicine efforts. There has been an explosion of transcriptomic studies particularly in the last decade, along with a growing number of recent epitranscriptomic studies in several disease areas. Here, we summarize and overview major efforts for cancer, cardiovascular disease, and neurodevelopmental disorders (including autism spectrum disorder and intellectual disability) for transcriptomics/epitranscriptomics in precision and personalized medicine. We show that leading advances are being made in both diagnostics, and in investigative and landscaping disease pathophysiological studies. As transcriptomics/epitranscriptomics screens become more widespread, it is certain that they will yield vital and transformative precision and personalized medicine contributions in ways that will significantly further genomics gains.Medicine, Faculty ofNon UBCMedical Genetics, Department ofReviewedFacultyResearche

الكشف عن حالات سرطان الدم الحاد بواسطة تقنية التدفق الخلوي في منطقة عسير بالمملكة العربية السعودية

Objective: To determine and to estimate the occurrence of acute leukemia's in Aseer Area, Saudi Arabia And to identify the common immunophenotypes of acute leukemia using flow cytometric analysis. Methods: Thirty five patients were included in this descriptive study which was conducted at the Armed Forces Hospital in collaboration with Aseerالهدف: معرفة مدى انتشار مرض سرطان الدم الحاد في منطقة عسير بالمملكة العربية السعودية وللتعرف على المكونات المناعية للخلايا السرطانية باستخدام تقنية التدفق الخلوي. الطريقة: تعتبر هذه الدراسة دراسة وصفيه وقد أجريت في مستشفيات القوات المسلحة بمنطقة عسير بالتعاون مع مستشفى عسير المركزي خلال الفترة من يناير 2009 إلى يناير 2010 وقد تم الحصول على عينات الدم ونخاع العظام من المرضى المصابين. وقد شملت التحاليل ألمخبريه عد الدم الكامل, أفلام للدم ونخاع العظام بالإضافة إلى استخدام تقنيه التدفق الخلوي. وتم تحليل النتائج إحصائيا باستخدام برنامج SPSS 15 . النتائج: تم تشخيص 35 حاله من المصابين بسرطان الدم الحاد وكان من بين هذا العدد 13 حاله مصابه باللوكيميا النخاعية الحادة (AML)بنسبة 37?1% كما كانت 22 حاله مصابه باللوكيميا الليمفاويه الحادة (ALL) وبنسبة 62?9% . وقد تم تأكيد التشخيص اعتمادا على المعيار الفرنسي الأمريكي البريطاني لتقسيم مرض سرطان الدم الحاد بالاضافة إلى الكشف عن المكونات المناعية لخلايا الدم المصابة. وقد كانت معظم الحالات عند البالغين بنسبة 68?6% بينما كانت النسبة عند الأطفال 31?4%. وقد تراوحت أعمار المرضى من سنه واحده إلى 74 سنه بمتوسط 26?5 سنه. وكانت نسبة الذكور 60% والإناث 40%. وقد كان المكون المناعي الشائع عند المرضى المصابين باللوكيميا الليمفاويه الحادة هو Pre-B ثم يليه Pre-T ثم B-mature وكانت المكونات المناعية الأكثر شيوعا عند المرضى المصابين باللوكيميا النخاعية الحادة هي M1-M2 ثم M4-M5 ويليها M3 ثم M0. الاستنتاج: أظهرت هذه الدراسة أن تعزيز الطرق التقليدية (عد الدم الكامل, أفلام الدم ونخاع العظام) بالكشف عن المكونات المناعية للخلايا السرطانية بواسطة تقنية التدفق الخلوي له أهميه كبيرة في تشخيص الأنواع المختلفة من سرطان الدم الحاد مثل M0وكذلك M3 وتمييزها عن باقي الأنواع الأخرى من اللوكيميا الليمفاوية الحادة ويوصي الباحثون بإجراء المزيد من الأبحاث لتحديد النمط الجيني والمظهري لخلايا الدم المستهدفة مما سيساعد في تحديد نظام العلاج المناسب

High temporal resolution transcriptomic profiling delineates distinct patterns of interferon response following Covid-19 mRNA vaccination and SARS-CoV2 infection

ABSTRACT Knowledge of the factors contributing to the development of protective immunity after vaccination with COVID-19 mRNA vaccines is fragmentary. Thus we employed high- temporal-resolution transcriptome profiling and in-depth characterization of antibody production approaches to investigate responses to COVID-19 mRNA vaccination. There were marked differences in the timing and amplitude of the responses to the priming and booster doses. Notably, two distinct interferon signatures were identified, that differed based on their temporal patterns of induction. The first signature (S1), which was preferentially induced by type I interferon, peaked at day 2 post-prime and at day 1 post-boost, and in both instances was associated with subsequent development of the antibody response. In contrast, the second interferon signature (S2) peaked at day 1 both post-prime and post- boost but was found to be potently induced only post-boost, where it coincided with a robust inflammation peak. Notably, we also observed “post-prime-like” (S1 ++ ,S2 0/+ ) and “post-boost-like” (S1 ++ ,S2 ++ ) patterns of interferon response among COVID-19 patients. A post-boost-like signature was observed in most severely ill patients at admission to the intensive care unit and was associated with a shorter hospital stay. Interestingly, severely ill patients who stayed hospitalized the longest showed a peculiar pattern of interferon induction (S1 -/0 ,S2 + ), that we did not observe following the administration of mRNA vaccines. In summary, high temporal resolution profiling revealed an elaborate array of immune responses elicited by priming and booster doses of COVID-19 mRNA vaccines. Furthermore, it contributed to the identification of distinct interferon-response phenotypes underpinning vaccine immunogenicity and the course of COVID-19 disease