Expanding the clinical phenotype of IARS2-related mitochondrial disease.

BACKGROUND: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. METHODS: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. RESULTS: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. CONCLUSIONS: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia

A new design of cryptographic hash function: gear

A hash function is any function that can be used to map data of arbitrary size to data of fixed size. A hash function usually has two main components: a permutation function or compression function and mode of operation. We will propose a new concrete novel design of a permutation based hash functions called Gear in this paper. It is a hash function based on block cipher in Davies-Meyer mode. It uses the patched version of Merkle-Damgård, i.e. the wide pipe construction as its mode of operation. Thus, the intermediate chaining value has at least twice larger length than the output hash. And the permutations functions used in Gear are inspired from the SHA-3 finalist Grøestl hash function which is originally inspired from Rijndael design (AES). There is a very strong confusion and diffusion in Gear as a result

Achieving security by combining Huffman and SLSB algorithms

Stenography is the art of hiding secret message into a cover media. Some of the usage for this algorithm is to protect the digital Holly Quran. This paper presents a novel stenographic algorithm based on the spatial domain. THE NEW ALGORITHM refers to a combined stenographic techniques; mainly Huffman algorithm and SLSB algorithm. The new method will both provide a less distortion images and increase the security. THE NEW ALGORITHM will use the hash digest from the Gear hash function as a secret message

A new design of cryptographic hash function: gear

A hash function is any function that can be used to map data of arbitrary size to data of fixed size. A hash function usually has two main components: a permutation function or compression function and mode of operation. We will propose a new concrete novel design of a permutation based hash functions called Gear in this paper. It is a hash function based on block cipher in Davies-Meyer mode. It uses the patched version of Merkle-Damgård, i.e. the wide pipe construction as its mode of operation. Thus, the intermediate chaining value has at least twice larger length than the output hash. And the permutations functions used in Gear are inspired from the SHA-3 finalist Grøestl hash function which is originally inspired from Rijndael design (AES). There is a very strong confusion and diffusion in Gear as a result

Anti-S and Anti-N Antibody Responses of COVID-19 Vaccine Recipients

The long-term immunoglobulin responses of COVID-19 vaccinations is important to determine the efficacy of these vaccinations. This study aimed to investigate and compare the long-term immunoglobulin response of COVID-19 vaccination recipients, using anti-S IgG, anti-N IgG, and IgM titer levels. This study included 267 participants, comprising individuals who tested positive for COVID-19 through PCR testing (n = 125), and those who received the Pfizer (n = 133), Sinopharm (n = 112), AstraZeneca (n = 20), or Sputnik (n = 2) vaccines. Female participants comprised the largest share of this study (n = 147, 55.1%). This study found that most participants had positive IgG antibodies, with 96.3% having anti-S IgG and 75.7% having anti-N IgG. Most participants (90.3%) tested negative for anti-N IgM antibodies. Sinopharm-vaccinated individuals exhibited a notably lower rate of positive anti-S IgG (93.8%) and a significantly higher rate of positive anti-N IgG antibodies (91%). Anti-N IgG levels were significantly correlated with the number of prior COVID-19 infections (p = 0.015). Specifically, individuals with a history of four COVID-19 infections had higher anti-N IgG titers (14.1 ± 1.4) than those with only one experience of COVID-19 infection (9.4 ± 7.2). Individuals who were infected with COVID-19 after receiving the vaccine demonstrated higher levels of anti-N IgG, exhibiting a 25% increase in mean titer levels compared to those who were infected prior to vaccination. There was a statistically significant association between anti-N IgG positivity with age (p = 0.034), and smoking status (p = 0.006) of participants. Participants younger than 20 and older than 60 showed the highest positivity rate of anti-N (>90%). Smokers had a low positivity rate of anti-N (68.8%) compared to nonsmokers (83.6%). In conclusion, this study demonstrated that most COVID-19 vaccination recipients had positive IgG antibodies, with differences in the long-term immunoglobulin response depending on the type of vaccine administered and occurrence of COVID-19 infection

Willingness of Healthcare Workers to Recommend or Receive a Third COVID-19 Vaccine Dose: A Cross-Sectional Study from Jordan

Background: The availability of COVID-19 vaccines worldwide necessitates measuring healthcare workers’ (HCWs’) willingness to recommend or receive these vaccines. Therefore, we conducted a local study in Jordan to assess HCWs’ willingness to recommend or receive a third dose of a COVID-19 vaccine and the predictors of such a decision. A cross-sectional study investigated Jordanian HCWs’ willingness regarding a third dose of a COVID-19 vaccine using a self-administered online questionnaire through WhatsApp, a mobile phone application. A total of 300 HCWs participated in the current study. Of these HCWs, 65.3% were physicians, 25.3% were nurses, and 9.3% were pharmacists. HCWs’ overall willingness regarding a third vaccine dose was 68.4% (49.4% certainly and 19.0% probably), whereas the overall willingness of HCWs to recommend a third dose to their patients was 73.3% (49.0% certainly and 24.3% probably). Males had significantly higher willingness than females (82.1% vs. 60.1%, p < 0.05). Physicians reported more willingness than nurses and pharmacists. HCWs’ willingness was not significantly affected by direct contact with a patient infected with COVID-19 or by a personal history of COVID-19 infection. Only 31% of HCWs were certainly willing to recommend the vaccine to their patients with chronic diseases, and only 28% of the participants were certainly willing to recommend it to people aged 65 or older. HCWs’ willingness to receive a third dose of a COVID-19 vaccine is limited in Jordan. This has affected their certainty in recommending this vaccine to their patients or people older than 60. Decision-makers and health-promotion programs in Jordan should focus on addressing this public health problem

The Effect of Telemedicine on Patients' Compliance in Family Medicine Follow-ups in Qatar

Introduction: Telemedicine is the delivery of health care services to patients distantly. During the Coronavirus Disease 2019 (COVID-19) pandemic, telemedicine has become an essential implement in delivering healthcare services worldwide. Accordingly, in March 2020, the Primary Health Care Centers (PHCCs) in Qatar has started telephone consultation follow-up appointments in Family Medicine (FM) clinics instead of conventional consultation. Given the limited data about telephone consultations in Qatar, our aim of this study is to investigate the possible impact of telemedicine on chronic disease patients' follow-up compliance. Methods: This study compares the compliance of adult patients with chronic diseases following-up within FM clinics in Qatar's PHCC through telephone consultations with a minimum of three telephone consultations ordered between April to November 2020, in comparison to the compliance of the same group of patients to their prior face-to-face follow-up consultations in FM clinics with a minimum of three face-to-face ordered follow up appointments between April to November 2019. A cross-sectional study will be carried out to investigate the effect of telephone consultation in PHCC on patients' compliance with reference to conventional face-to-face consultation. Patients' data will be received from Health Information Management in twenty-seven PHCCs in Qatar. Conclusion: Due to the limited studies on the effectiveness of telemedicine on patient compliance in FM follow-ups within Qatar's PHCC, comparing patients' follow-up compliance with telephone consultations to their prior face-to-face consultations would be helpful in assessing patients' quality of care delivering within FM clinics. With telecommunication being easily accessible and time-efficient, it is believed, when used correctly, it might improve compliance and adherence to the management prescribed by the physician and follow-up appointments in Qatar's PHCC. In addition, this study will help in providing recommendations that could guide the organization on forming policies to be applied in PHCCs after the resolution of the COVID-19 pandemic.Qscienc

COVID-19 Booster Doses: A Multi-Center Study Reflecting Healthcare Providers’ Perceptions

(1) Background: During 2019, the COVID-19 pandemic was threatening healthcare services and workers, and acquiring immunity was an option to stop or limit the burden of this pandemic. Herd immunity was a top priority worldwide as the virus was spreading rapidly. It was estimated that 67% of the total global population should be immunized against COVID-19 to achieve herd immunity. The aim of the current study is to investigate different perceptions of healthcare workers in the Kingdom of Bahrain and Egypt using an online survey in an attempt to evaluate their awareness and concerns regarding new variants and booster doses. (2) Methods: This study conducted a survey on healthcare workers in the Kingdom of Bahrain and Egypt about their perception and concerns on the COVID-19 vaccines. (3) Results: The study found that out of 389 healthcare workers 46.1% of the physicians were not willing to take the booster doses (p = 0.004). Physicians also did not support taking the COVID-19 vaccine as an annual vaccine (p = 0.04). Furthermore, to assess the association between the type of vaccine taken with the willingness of taking a booster vaccine, healthcare workers beliefs on vaccine effectiveness (p = 0.001), suspension or contact with patients (p = 0.000), and infection after COVID-19 vaccination (p = 0.016) were significant. (4) Conclusion: Knowledge about vaccine accreditation and regulation should be dispersed more widely to ensure that the population has a positive perception on vaccine safety and effectiveness

Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience

Kuwait is a small Arabian Gulf country with a high rate of consanguinity and where a national newborn screening program was expanded in October 2014 to include a wide range of endocrine and metabolic disorders. A retrospective study conducted between January 2015 and December 2020 revealed a total of 304,086 newborns have been screened in Kuwait. Six newborns were diagnosed with classic homocystinuria with an incidence of 1:50,000, which is not as high as in Qatar but higher than the global incidence. Molecular testing for five of them has revealed three previously reported pathogenic variants in the CBS gene, c.969G&gt;A, p.(Trp323Ter); c.982G&gt;A, p.(Asp328Asn); and the Qatari founder variant c.1006C&gt;T, p.(Arg336Cys). This is the first study to review the screening of newborns in Kuwait for classic homocystinuria, starting with the detection of elevated blood methionine and providing a follow-up strategy for positive results, including plasma total homocysteine and amino acid analyses. Further, we have demonstrated an increase in the specificity of the current newborn screening test for classic homocystinuria by including the methionine to phenylalanine ratio along with the elevated methionine blood levels in first-tier testing. Here, we provide evidence that the newborn screening in Kuwait has led to the early detection of classic homocystinuria cases and enabled the affected individuals to lead active and productive lives

Review of national research ethics regulations and guidelines in Middle Eastern Arab countries

<p>Abstract</p> <p>Background</p> <p>Research ethics guidelines are essential for conducting medical research. Recently, numerous attempts have been made to establish national clinical research documents in the countries of the Middle East. This article analyzes these documents.</p> <p>Methods</p> <p>Thirteen Arab countries in the Middle East were explored for available national codes, regulations, and guidelines concerning research ethics, and 10 documents from eight countries were found. We studied these documents, considering the ethical principles stated in the Declaration of Helsinki, the Council for International Organizations of Medical Sciences (CIOMS) guidelines, and the International Conference of Harmonization - Guidelines for Good Clinical Practice (ICH-GCP). Our paper comprises a complete list of protections, such as confidentiality, informed consent, ethics committees, and others.</p> <p>Results</p> <p>This study found different levels and kinds of research ethics regulations and guidelines in the countries examined. Two groups can be distinguished: the countries in the first group have one or more research ethics regulations or guidelines, while the countries in the second group have not yet established any. Most of the documents showed various degrees of deficiencies in regard to ethical protection. The majority of the documents that were examined refer to one or more international documents on biomedical research ethics.</p> <p>Conclusions</p> <p>Recently, a lot of efforts have been made in many countries in the Middle East. However, compared with international documents, most of the research ethics documents in use in this region demonstrate numerous deficiencies. As it relates to these documents, extensive differences could be observed in regard to development, structure, content, and reference to international guidelines.</p