Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension.

Genome-wide association studies of blood pressure (BP) have identified >1,000 loci, but the effector genes and biological pathways at these loci are mostly unknown. Using published association summary statistics, we conducted annotation-informed fine-mapping incorporating tissue-specific chromatin segmentation and colocalization to identify causal variants and candidate effector genes for systolic BP, diastolic BP, and pulse pressure. We observed 532 distinct signals associated with ≥2 BP traits and 84 with all three. For >20% of signals, a single variant accounted for >75% posterior probability, 65 were missense variants in known (SLC39A8, ADRB2, and DBH) and previously unreported BP candidate genes (NRIP1 and MMP14). In disease-relevant tissues, we colocalized >80 and >400 distinct signals for each BP trait with cis-eQTLs and regulatory regions from promoter capture Hi-C, respectively. Integrating mouse, human disorder, gene expression and tissue abundance data, and literature review, we provide consolidated evidence for 436 BP candidate genes for future functional validation and discover several potential drug targets.

Analyzing the roles of some species of arthropods in the transmission of the Middle East respiratory syndrome coronavirus.

BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is still listed on the WHO Research and Development Blueprint of emerging pathogens. Dromedary camels remain the only known animal reservoir of the virus. The animal-to-animal as well as the animal-to-human transmission in the MERS-CoV cycles were reported. However, many aspects of these transmission chains are not well studied. One of these directions is the potential roles of various species of arthropods in the transmission of the virus. OBJECTIVES: The main goal of the current work was to study the roles of several species of arthropods in the transmission of MERS-CoV. METHODOLOGY: To achieve this goal, we identified some MERS-CoV naturally infected dromedary camel populations. We conducted a longitudinal study among these animals for more than 2 months. This was done by repeated testing of nasal swabs biweekly from some selected animals in this population for the presence of MERS-CoV-RNAs by real-time PCR. During the duration of this study, we collected several species of arthropods (Culicoides, Stomoxys, Musca domestica and some Culex species) that shared the habitat and were circulating in this farm during this longitudinal study. RESULTS: Our results showing, despite the detection of the viral RNAs in some animals throughout this study, none of the examined species of arthropods tested positive for the viral RNA. CONCLUSIONS: These results are suggesting that at least the tested species of arthropods may not play roles in the transmission of MERS-CoV. However, more large-scale studies are required to explore any potential roles of arthropods in the transmission cycle of MERS-CoV.

The association of metabolic risk factors with ischemic heart disease and heart failure in Saudi Arabia - A cross sectional study.

Background: Cardiovascular diseases (CVDs) are the leading non-communicable cause of morbidity and mortality worldwide. This study aimed at determining the association of metabolic risk factors with ischemic heart disease (IHD) and heart failure (HF). Methods: A cross-sectional study including 104 participants was conducted in three major hospitals between October 2020 and October 2021. All adult patients of either gender, over the age of 35, attending the CVD screening program at the family medicine clinics of the hospitals were included in the study. The physician collected demographic details, history of CVD, diabetes or hypertension, and current medication. Each patient's body mass index (BMI) was calculated, electrocardiogram (ECG) and blood tests were done. Univariate and multivariate logistic regressions were checked. Results: The mean age of the participants was 47.6 (SD = 13.5) years. Diabetes and hypertension had increased odds of IHD by 129 (CI = 6.20 - 2698.42, P = 0.002) and 195 (CI = 13.87 - 2743.11, P < 0.001) times, respectively. Diabetes mellitus (Chi2 = 11.93, P < 0.001) and hypertension (Chi2 = 14.74, P < 0.001) had significant association with HF. Dyslipidemia was significantly associated with IHD (OR = 12.41, CI = 1.15 - 134.12, P = 0.038) and high-grade HF (OR = 14.91 CI = 3.61 - 61.40, P < 0.001). Conclusion: Age, dyslipidemia, diabetes, hypertension, and left ventricular hypertrophy have significant association with IHD or HF among the study population.

Etiology of Hydronephrosis in adults and children: Ultrasonographic Assessment in 233 patients.

OBJECTIVES: Hydronephrosis (HN) is dilatation of the collecting system of the kidney due to obstruction of urine outflow. This study intended firstly, to investigate the efficacy of ultrasound (US) imaging to determine the cause of HN, and secondly, to list the causes of HN. METHODS: In this retrospective study, 233 patients with HN were scanned to determine the cause of the HN in the period from 1st January 2016 to 31st October 2017. Categorical results were written as frequencies and percentages. RESULTS: Out of 233, 91.41% were adults and 8.58% were children (P<0.001), 66.10% were male and 33.90% were female (P<0.001). In 55.36%, HN was in the right kidney and 44.64% was in the left (P=0.116). Exactly 58% of patients were suffering from grade-2, 21.5% grade-3, 11.6% grade-1, and 8.2% grade-4 HN. US imaging can determine the cause of HN in 70.4% of patients. Kidney or ureteric calculi were the cause of HN in 54.1% of cases, reflux was in 7.3%, and pelviureteric junction (PUJ) stenosis was in 3.9%.In cases of calculi induced HN, 25.3% of the calculi were in the vesicoureteric (VUJ) junction, 21.5% were in the renal pelvis, 6.4% were in the PUJ or upper ureter, and only 0.9% were in the middle ureter. CONCLUSION: Ultrasound imaging can determine the cause of HN in more than two thirds of patients. Calculi are the most common cause of HN even in children and are most common in the VUJ junction.

Exploring the potential roles of some rodents in the transmission of the Middle East respiratory syndrome coronavirus.

Middle East respiratory syndrome coronavirus (MERS-CoV) is one of the recently identified zoonotic coronaviruses. The one-hump camels are believed to play important roles in the evolution and transmission of the virus. The animal-to-animal, as well as the animal-to-human transmission in the context of MERS-CoV infection, were reported. The camels shed the virus in some of their secretions, especially the nasal tract. However, there are many aspects of the transmission cycle of the virus from animals to humans that are still not fully understood. Rodents played important roles in the transmission of many pathogens, including viruses and bacteria. They have been implicated in the evolution of many human coronaviruses, especially HCoV-OC43 and HCoV-HKU1. However, the role of rodents in the transmission of MERS-CoV still requires more exploration. To achieve this goal, we identified MERS-CoV that naturally infected dromedary camel by molecular surveillance. We captured 15 of the common rodents (rats, mice, and jerboa) sharing the habitat with these animals. We collected both oral and rectal swabs from these animals and then tested them by the commercial MERS-CoV real-time-PCR kits using two targets. Despite the detection of the viral shedding in the nasal swabs of some of the dromedary camels, none of the rodents tested positive for the virus during the tenure of this study. We concluded that these species of rodents did not harbor the virus and are most unlikely to contribute to the transmission of the MERS-CoV. However, further large-scale studies are required to confirm the potential roles of rodents in the context of the MERS-CoV transmission cycle, if any.

Lack of detection of the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleic acids in some Hyalomma dromedarii infesting some Camelus dromedary naturally infected with MERS-CoV.

OBJECTIVE: The Middle East respiratory syndrome coronavirus (MERS-CoV) is one of the zoonotic coronaviruses [Hemida Peer J 7:e7556, 2019; Hemida et al. One Health 8:100102, 2019]. The dromedary camels remained the only known animal reservoir for this virus. Several aspects of the transmission cycle of the virus between animals, including arthropod-borne infection, is still largely unknown. The main objective of the current work was to study the possibility of MERS-CoV transmission through some arthropod vectors, particularly the hard ticks. To achieve this objective, we identified a positive MERS-CoV dromedary camel herd using the commercial available real-time PCR kits. We collected some arthropods, particularly the ticks from these positive animals as well as from the animal habitats. We tested these arthropods for the presence of MERS-CoV viral RNAs. RESULTS: Our results showing the absence of any detectable MERS-CoV-RNAs in these arthropods despite these animals were actively shedding the virus in their nasal secretions. Our results are confirming for the first the failure of detection of the MERS-CoV in ticks infesting dromedary camels. Failure of the detection of MERS-CoV in ticks infesting positive naturally infected MERS-CoV camels is strongly suggesting that ticks do not play roles in the transmission of the virus among the animals and close contact humans.

The Middle East respiratory syndrome coronavirus in the breath of some infected dromedary camels (Camelus dromedarius).

Dromedary camels remain the currently identified reservoir for the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus is released in the secretions of the infected camels, especially the nasal tract. The virus shedding curve through the nasal secretions was studied. Although human transmission of the virus through the respiratory tract of close contact people with dromedary reported previously, the exact mechanism of transmission is still largely unknown. The main goal of this study was to check the possibility of MERS-CoV shedding in the exhaled air of the infected camels. To achieve this goal, we conducted a follow-up study in one of the dromedary camel herds, December 2018-April 2019. We tested nasal swabs, breath samples from animals within this herd by the real-time PCR. Our results showed that some of the tested nasal swabs and breath were positive from 24 March 2019 until 7 April 2019. The phylogenetic analysis of the obtained S and N gene sequences revealed the detected viruses are clustering together with some human and camel samples from the eastern region, especially from Al-Hufuf city, as well as some samples from Qatar and Jordon. These results are clearly showing the possibility of shedding of the virus in the breath of the infected camels. This could explain, at least in part, the mechanism of transmission of MERS-CoV from animals to humans. This study is confirming the shedding of MERS-CoV in the exhaled air of the infected camels. Further studies are needed for a better understanding of the MERS-CoV.

Prevalence and molecular characterization of some circulating strains of the peste-des-petits-ruminants virus in Saudi Arabia between 2014-2016.

BACKGROUND: The peste-des-petits-ruminants virus (PPRV) is a highly devastating virus of small ruminants in many parts of the world, including the Kingdome of Saudi Arabia. Therefore, our objectives were (1) to conduct a molecular prevalence study of PPRV in sheep and goat across the KSA and (2) to isolate and identify currently circulating PPRV lineages. Swabs and tissue specimens were collected from 97 herds suspected to be infected with PPRV across the Kingdome of Saudi Arabia (KSA). Testing for the presence of the virus was done by the real-time PCR. Confirmation of the identity of the reactions was done by the gel-based-PCR then by sequencing of the partial PPRV genome. RESULTS: Our results revealed that 24.1% of the tested specimens were PPRV-positive. Isolation of PPRV was successful from samples using the Vero cell line. Sequence analysis of some partial PPRV genes (N, F, M, L, P, and H) revealed that these strains were belonging to lineage IV of the PPRV. CONCLUSIONS: This is the first study to conduct both the nationwide prevalence, isolation, and molecular characterizations of the PPRV in the KSA. Continuous surveillance and monitoring of the circulating strains of PPRV among sheep and goats will contribute substantially to the global eradication campaign of such a virus.