Publisher Correction: Genomic insights into the 2016-2017 cholera epidemic in Yemen.

In the HTML version of this Letter, the affiliations for authors Andrew S. Azman, Dhirendra Kumar and Thandavarayan Ramamurthy were inverted (the PDF and print versions of the Letter were correct); the affiliations have been corrected online.

Genomic insights into the 2016-2017 cholera epidemic in Yemen.

Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.

The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice.

STUDY QUESTION: Are sperm phospholipase C zeta (PLCζ) profiles linked to the quality of embryogenesis and pregnancy? SUMMARY ANSWER: Sperm PLCζ levels in both mouse and humans correlate with measures of ideal embryogenesis whereby minimal levels seem to be required to result in successful pregnancy. WHAT IS KNOWN ALREADY: While causative factors underlying male infertility are multivariable, cases are increasingly associated with the efficacy of oocyte activation, which in mammals occurs in response to specific profiles of calcium (Ca2+) oscillations driven by sperm-specific PLCζ. Although sperm PLCζ abrogation is extensively linked with human male infertility where oocyte activation is deficient, less is clear as to whether sperm PLCζ levels or localization underlies cases of defective embryogenesis and failed pregnancy following fertility treatment. STUDY DESIGN, SIZE, DURATION: A cohort of 54 couples undergoing fertility treatment were recruited at the assisted reproductive technology laboratory at the King Faisal Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. The recruitment criteria for males was a minimum sperm concentration of 5×106 sperm/ml, while all female patients had to have at least five oocytes. Sperm PLCζ analysis was performed in research laboratories, while semen assessments were performed, and time-lapse morphokinetic data were obtained, in the fertility clinic as part of routine treatment. The CRISPR/Cas9 system was concurrently used to induce indels and single-nucleotide mutations within the Plcζ gene to generate strains of Plcζ mutant mice. Sperm PLCζ was evaluated using immunofluorescence and immunoblotting with an antibody of confirmed consistent specificity against PLCζ. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated PLCζ profiles in sperm samples from 54 human couples undergoing fertility treatment in the context of time-lapse morphokinetic analysis of resultant embryos, correlating such profiles to pregnancy status. Concurrently, we generated two strains of mutant Plcζ mice using CRISPR/Cas9, and performed IVF with wild type (WT) oocytes and using WT or mutant Plcζ sperm to generate embryos. We also assessed PLCζ status in WT and mutant mice sperm in the context of time-lapse morphokinetic analysis and breeding outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: A significant (P ≤ 0.05) positive relationship was observed between both PLCζ relative fluorescence and relative density with the times taken for both the second cell division (CC2) (r = 0.26 and r = 0.43, respectively) and the third cell division (S2) (r = 0.26). Examination of localization patterns also indicated significant correlations between the presence or absence of sperm PLCζ and CC2 (r = 0.27 and r = -0.27, respectively; P ≤ 0.025). Human sperm PLCζ levels were at their highest in the ideal times of CC2 (8-12 h) compared to time ranges outside the ideal timeframe (<8 and >12 h) where levels of human sperm PLCζ were lower. Following assignment of PLCζ level thresholds, quantification revealed a significantly higher (P ≤ 0.05) rate of successful pregnancy in values larger than the assigned cut-off for both relative fluorescence (19% vs 40%, respectively) and relative density (8% vs 54%, respectively). Immunoblotting indicated a single band for PLCζ at 74 kDa in sperm from WT mice, while a single band was also observed in sperm from heterozygous of Plcζ mutant mouse sperm, but at a diminished intensity. Immunofluorescent analysis indicated the previously reported (Kashir et al., 2021) fluorescence patterns in WT sperm, while sperm from Plcζ mutant mice exhibited a significantly diminished and dispersed pattern at the acrosomal region of the sperm head. Breeding experiments indicated a significantly reduced litter size of mutant Plcζ male mice compared to WT mice, while IVF-generated embryos using sperm from mutant Plcζ mice exhibited high rates of polyspermy, and resulted in significantly reduced numbers of these embryos reaching developmental milestones. LIMITATIONS, REASONS FOR CAUTION: The human population examined was relatively small, and should be expanded to examine a larger multi-centre cohort. Infertility conditions are often multivariable, and it was not possible to evaluate all these in human patients. However, our mutant Plcζ mouse experiments do suggest that PLCζ plays a significant role in early embryo development. WIDER IMPLICATIONS OF THE FINDINGS: We found that minimal levels of PLCζ within a specific range were required for optimal early embryogenesis, correlating with increased pregnancy. Levels of sperm PLCζ below specific thresholds were associated with ineffective embryogenesis and lower pregnancy rates, despite eliciting successful fertilization in both mice and humans. To our knowledge, this represents the first time that PLCζ levels in sperm have been correlated to prognostic measures of embryogenic efficacy and pregnancy rates in humans. Our data suggest for the first time that the clinical utilization of PLCζ may stand to benefit not just a specific population of male infertility where oocyte activation is completely deficient (wherein PLCζ is completely defective/abrogated), but also perhaps the larger population of couples seeking fertility treatment. STUDY FUNDING/COMPETING INTEREST(S): J.K. is supported by a faculty start up grant awarded by Khalifa University (FSU-2023-015). This study was also supported by a Healthcare Research Fellowship Award (HF-14-16) from Health and Care Research Wales (HCRW) to J.K., alongside a National Science, Technology, and Innovation plan (NSTIP) project grant (15-MED4186-20) awarded by the King Abdulaziz City for Science and Technology (KACST) for J.K. and A.M.A. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment and cognitive dysfunctions. It has been shown that hypoglycemia can adversely affect AD neuropathology. It is well-known that chronic hyperglycemia in type 2 diabetes (T2D) is regarded as a potential risk factor for the development and progression of AD. However, the effect of recurrent hypoglycemia on the pathogenesis of AD was not deeply discussed, and how recurrent hypoglycemia affects AD at cellular and molecular levels was not intensely interpreted by the previous studies. The underlying mechanisms for hypoglycaemia-induced AD are diverse such as endothelial dysfunction, thrombosis, and neuronal injury that causing tau protein hyperphosphorylation and the accumulation of amyloid beta (Aß) in the brain neurons. Of note, the glucagon hormone, which controls blood glucose, can also regulate the cognitive functions. Glucagon increases blood glucose by antagonizing the metabolic effect of insulin. Therefore, glucagon, through attenuation of hypoglycemia, may prevent AD neuropathology. Glucagon/GLP-1 has been shown to promote synaptogenesis, hippocampal synaptic plasticity, and learning and memory, while attenuating amyloid and tau pathologies. Therefore, activation of glucagon receptors in the brain may reduce AD neuropathology. A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology.

Cases of Meningococcal Disease Associated with Travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).

The perception of genetic diseases and premarital screening tests in the central region of Saudi Arabia.

The prevalence of consanguineous marriages (CMs) varies worldwide from one country to another. However, the Middle East stands out as a region with a notably high rate of CMs. CM is particularly widespread in Saudi Arabia, where the prevalence of autosomal recessive genetic diseases has increased. This study aims to identify the Saudi population's awareness of genetic diseases and premarital screening tests (PMSTs). It also seeks to understand couples' perceptions of genetic diseases before and after marriage and their attitudes towards PMSTs and genetic counselling (GC) in reducing the risk of CM. Through the administration of online questionnaires, this cross-sectional study surveyed 2,057 participants to assess their awareness of genetic diseases and their understanding of testing and preventive measures for inherited diseases. Descriptive analysis, nonparametric chi-square tests and logistic regressions were performed to assess the association of categorical responses. This study included 2,035 Saudi Arabian respondents. A significant correlation was found between positive family history and partner selection (p = 0.001), as well as between partnering within the same tribe (p = 0.000139), with a different tribe (p = 0.000138) and from another family (p = 0.000489). About 91.3% of participants expressed agreement regarding the need to enhance public awareness and knowledge concerning genetic disorders, while 87% agreed that increased government regulations are required to prevent the spread of genetic diseases in affected families. Despite increased awareness of genetic diseases and PMSTs, there appears to be a lack of understanding regarding the limitations of PMSTs. The persistently high rate of CM underscores the challenge of altering marriage customs. Further governmental efforts are required to promote awareness of alternative reproductive options, establish new regulations and expand screening programmes.

Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).

Connecting Pharmacists and Other Health Care Providers (HCPs) towards Drug Therapy Optimization: A Pharmaceutical Care Approach.

Background: Pharmaceutical care services offered by pharmacists rationalize drug therapy, improve patient quality of life, and save patients' lives. This study was designed to optimize patient drug therapy through pharmaceutical care services offered by a pharmacist in consultation with other health care providers (HCPs) at a tertiary care hospital. Methods: This descriptive study was conducted to assess the role and effectiveness of pharmacists in optimizing drug therapy outcomes. The study was carried out at an internal and pulmonary medicine unit of a tertiary care hospital in Srinagar, Jammu and Kashmir, India, with a total of 50 health care providers (HCPs) (24 doctors, 16 nurses, and 10 pharmacists). A total of 182 patients (males and females) of all age groups were recruited into the study over a period of nine months. Patient-specific pharmaceutical care plans initiated by the pharmacist based on drug therapy-related needs and problems were used to address and optimize drug therapy outcomes in consultation with other HCPs. Results: A total of 388 drug-related problems (DRPs) with an average of 2.29 DRPs per patient were identified, for which 258 pharmaceutical care plans as interventions were proposed, out of which 233 (90.31%) were accepted and implemented. Preassessment and postassessment by HCPs on services rendered by the pharmacist showed a positive change in attitude among HCPs with respect to their endorsement and acceptance of the pharmacist's services in providing direct patient care. Conclusions: Pharmaceutical care services offered by pharmacists helped in optimizing drug therapy and patient care.

CTLA4-Ig mediated immunosuppression favors immunotolerance and restores graft in mouse airway transplants.

CTLA4-Ig is a potent costimulatory blocker that inhibits T cell activation during alloimmune inflammation and increases graft survival and function. CTLA4-Ig-mediated immunosuppression has been demonstrated to support transplant function in various clinical trials and preclinical settings, but its effects on the balance between regulatory T cells (Tregs) and effector T cells (Teffs), as well as complement activation, are less well investigated. In the present study, we proposed to investigate the effects of CTLA4-Ig mediated immunosuppression on the phase of immunotolerance and the subsequent graft microvascular and epithelial repair during the progression of subepithelial fibrosis in a mouse model of orthotopic trachea transplantation. Briefly, CTLA4-Ig treated allografts (2 mg/kg, I.P.), untreated allografts, and syngrafts were serially monitored for peripheral FOXP3+ Tregs, antibody-mediated complement activation (C3d and C4d), tissue oxygenation, donor-recipient microvascular blood flow, and subsequent tissue remodeling following transplantation. Our data demonstrate that CTLA4-Ig mediated immunosuppression significantly results in late increases in both peripheral CD4+/CD8+ FOXP3+ Tregs and serum IL-10, but prevents the microvascular deposition of IgG, complement factor C3d, and epithelial C4d respectively, which proportionally improved blood flow and tissue oxygenation in the graft and, thus, promotes graft repair. Also, it restored the airway lumen, epithelium, and prevented the progression of subepithelial collagen deposition up to 90 days after transplantation. This study demonstrates that CTLA4-Ig-mediated immunosuppression potentially modulates both effector response and a late surge of regulatory activity to preserve graft microvasculature and rescue allograft from sustained hypoxia and ischemia and thereby limits subepithelial fibrosis.

High seroprevalence of SARS-CoV-2 among high-density communities in Saudi Arabia.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection had been investigated utilizing serology. MATERIALS AND METHODS: This community-based sero-survey was carried out in the neighborhoods of three cities in Saudi Arabia. RESULTS: Of 5629 participants, 2766 (49.1%) were women; and 2148 (38.1%) were 18-34 years of age, and 3645 (64.7%) were from South East Asia. Positive serology was seen in 2825 (50.2% (95% CI: 48.8-51.5%) for SARS-CoV-2 anti-S1 IgG antibodies by ECLIA. Being in the age category of 18-34 years and being from Eastern Mediterranean Region (country A) were associated with higher COVID-19 seropositivity with estimated odds ratio of 1.3 [95% CI 1.1-1.8] and 2.5 [95% CI 1.1.5-4.2] respectively. Gender, social status, education, nationality, symptoms, presence of comorbidities and activity style were positively associated with increased seropositivity. Factors associated negatively with the rate of seropositivity were higher education and having outdoor activity with estimated OR of 0.92 [95% CI 0.46-0.95] and 0.59 [95% CI 0.47-0.74], respectively. CONCLUSION: The study showed high seroprevalence of SARS-CoV-2 among high density population. Health education campaigns should target middle-aged, those with low education, those living in lower standards and indoor workers.

Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.

Interleukin-10 (IL-10) is a vital regulatory cytokine, which plays a constructive role in maintaining immune tolerance during an alloimmune inflammation. Our previous study highlighted that IL-10 mediated immunosuppression established the immune tolerance phase and thereby modulated both microvascular and epithelial integrity, which affected inflammation-associated graft malfunctioning and sub-epithelial fibrosis in rejecting allografts. Here, we further investigated the reparative effects of IL-10 on microvasculature and epithelium in a mouse model of airway transplantation. To investigate the IL-10 mediated microvascular and epithelial repair, we depleted and reconstituted IL-10, and monitored graft microvasculature, airway epithelium, and associated repair proteins. Our data demonstrated that both untreated control allografts and IL-10 (-) allografts showed a significant early (d6) increase in microvascular leakiness, drop-in tissue oxygenation, blood perfusion, and denuded airway epithelium, which is associated with loss of adhesion protein Fascin-1 and ß-catenin on vascular endothelial cells at d10 post-transplantation. However, IL-10 (+) promotes early microvascular and airway epithelial repair, and a proportional increase in endothelial Fascin-1, and ß-catenin at d10 post-transplantation. Moreover, airway epithelial cells also express a significantly higher expression of FOXJ1 and ß-catenin in syngrafts and IL-10 (+) allografts as compared to IL-10 (-) and untreated controls at d10 post-transplantation. Collectively, these findings demonstrated that IL-10 mediated microvascular and epithelial changes are associated with the expression of FOXJ1, ß-catenin, and Fascin-1 proteins on the airway epithelial and vascular endothelial cells, respectively. These findings establish a potential reparative modulation of IL-10 associated microvascular and epithelial repair, which could provide a vital therapeutic strategy to facilitate graft repair in clinical settings.

Prevalence of cardiovascular events among patients with type 2 diabetes in the west region of Saudi Arabia.

Background: Diabetes mellitus (DM) remains a concern globally and particularly in Saudi Arabia, where its prevalence is continuously increasing among the Saudi population. DM is known to increase the risk of cardiovascular disease (CVD), which can progress significantly if DM is poorly controlled. Aim: Determine the prevalence of cardiovascular events among patients with type 2 diabetes (T2DM) in the west region of Saudi Arabia, and additionally the use of antidiabetic agents with cardiovascular benefits (ADc) in T2DM patients with cardiovascular events (CVEs). Method: A retrospective cohort study was conducted among all patients with T2DM who presented to the diabetic center of Prince Mansour Military Hospital (PMMH), Taif city, between the 1st of January and 30th of June 2021. Data extracted from patient medical records included demographics, home medications, medications used to treat T2DM, lab results, and ECG data. Descriptive statistics were used to analyze and compare the results. The study was approved by the Research and Ethics Committee of Medical Services General Directorate, Armed Forces Hospitals, Taif region. Result: A total of 349 patients with T2DM were recruited and included in the final analysis. Of this study population, 132 patients had experienced at least one cardiovascular event while 54 were considered to be at risk of future cardiovascular events due to having risk factors for cardiovascular diseases above and beyond the presence of diabetes. A subgroup analysis was conducted to examine HbA1c% among all groups; interestingly, all were similar, with p > 0.05. Of all diabetic patients with CVEs, only 34.8 % were on at least one anti-diabetic agent known to have cardiovascular benefits; the remainder were on other anti-diabetic agents. A similar analysis was conducted on diabetic patients with risk of CVEs, of which only 13 % were on at least one anti-diabetic agent having known cardiovascular benefits; the remainder were on other anti-diabetic agents. Conclusion: The prevalence of CVEs among T2DM patients in Saudi Arabia is very close to the global prevalence, but ADcs are underutilized in this population. Tighter glycemic control is warranted to help rein in and reduce the CVE incidence among patients with T2DM.

Surface‒Aerosol Stability and Pathogenicity of Diverse Middle East Respiratory Syndrome Coronavirus Strains, 2012‒2018.

Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. Although some mutations found in camel-derived MERS-CoV strains have been characterized, most natural variation found across MERS-CoV isolates remains unstudied. We report on the environmental stability, replication kinetics, and pathogenicity of several diverse isolates of MERS-CoV, as well as isolates of severe acute respiratory syndrome coronavirus 2, to serve as a basis of comparison with other stability studies. Although most MERS-CoV isolates had similar stability and pathogenicity in our experiments, the camel-derived isolate C/KSA/13 had reduced surface stability, and another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that although betacoronaviruses might have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the need for continual global viral surveillance.

Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality.

The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.

Meningococcal carriage among Hajj pilgrims, risk factors for carriage and records of vaccination: a study of pilgrims to Mecca.

OBJECTIVE: The Saudi government requires that all pilgrims receive a quadrivalent meningococcal vaccine at least 10 days before the Hajj. We conducted a study to determine the uptake of meningococcal vaccine and antibiotic use. We also investigated risk factors of meningococcal carriage and carriage of Neisseria meningitidis pathogenic serogroups A, C, W and Y. METHODS: A cross-sectional oropharyngeal carriage survey was conducted in 2973 Hajj pilgrims in September 2017. A real-time polymerase chain reaction (rt-PCR) assay was used to identify N. meningitidis from the oropharyngeal swabs. A questionnaire investigated potential risk factors for carriage of N. meningitidis. RESULTS: Two thousand two hundred forty nine oropharyngeal swabs were obtained. The overall prevalence of carriage of N. meningitidis was 4.6% (95% CI: 3.4%-6%). Carriage of pathogenic serogroups was not associated significantly with any of the meningococcal risk factors evaluated. 77% of pilgrims were vaccinated but 22.58 % said they were carrying unofficial vaccination cards. CONCLUSION: Carriage of serogroups A, C, W and Y was not significantly associated with any of the risk factors investigated. Almost a quarter of pilgrims were unlikely to have been vaccinated, highlighting a need to strengthen compliance with the current policy of vaccination to prevent meningococcal disease outbreaks during and after the Hajj.

Concurrent diagnosis of sinus fungus ball and invasive fungal sinusitis: A retrospective case series.

BACKGROUND: Sinus fungal ball (SFB) is the most common type of non-invasive fungal sinusitis and develops mostly in immunocompetent individuals, whereas invasive fungal sinusitis (IFS), with high mortality, develops mostly in immunocompromised patients. SFB may progress to IFS depending on the patient's immune status and underlying diseases. OBJECTIVES: To investigate the possibility of SFB progressing to IFS. PATIENTS/METHODS: A total of 10 patients histopathologically diagnosed with concurrent IFS and SFB from January 2013 to December 2019 were enrolled. Their clinical characteristics, histopathology and clinical course information were obtained and compared with those of 56 patients with IFS alone and 617 patients with SFB alone. RESULTS: Acute, chronic and chronic granulomatous IFS was diagnosed in two (20%), five (50%) and three (30%) patients, respectively. All patients had severe facial pain and/or headache, with the most common comorbidity being diabetes (n = 5, 50%). SFB was identified in the maxillary (60%) and sphenoid (40%) sinuses. The tissue culture was positive for Aspergillus species in five (50%) patients. Eight patients with chronic or chronic granulomatous IFS were successfully treated by debridement with voriconazole, and the two patients with acute IFS and severe neutropenia due to haematologic malignancy died. Compared to patients with IFS alone, patients with combined SFB and IFS were older, female dominant, and commonly had chronic or chronic granulomatous IFS. In addition, they were older and more commonly diabetic and immunocompromised than patients with SFB alone. CONCLUSIONS: SFB may progress to IFS particularly in elderly and immunocompromised patients.

Characteristics and outcome of COVID-19 cases in Saudi Arabia: Review of six-months of data (March-August 2020).

BACKGROUND: This study presents the demographic, epidemiological, and clinical characteristics of Coronavirus Disease 2019 (COVID-19) in Saudi Arabia (KSA). It identifies the important predictors of the disease prognosis. METHODS: The study reviewed and analysed a sample of 307,010 confirmed symptomatic COVID-19 cases, between March and August 2020, available in the health electronic surveillance system (HESN) of the Ministry of Health of KSA. Descriptive and univariate analyses were conducted. RESULTS: The overall estimated prevalence of symptomatic COVID-19 cases in KSA between March and August 2020 was 6.1% . The estimated incidence proportion was 879.7 per 100,000 population. The overall case fatality ratio was 2.0%. Males represented 63.9% , with a mean age of 35.1 ± 16.6 years. Young adults (16-39 years) were the most affected ages (53.3%). Fever (90.5%) with a mean body temperature of 37.4 ± 2.0 Celsius, cough (90%), and sore throat (77.4%) were the most prevalent symptoms. A history of contact with a confirmed COVID-19 case was reported in 98.8% of patients.Males (2.1%) and elderly cases aged 65-99 years (25.6%) had the highest association with mortality (p < .001). Among the clinical characteristics investigated, low oxygen saturation (SpO2 ≤ 93%) had the highest association with hospital admission (50.8%) and mortality (19.1%) (p < .001). Cases with cardiovascular diseases (28.6%) and malignancy (28%) demonstrated the highest associations with mortality compared to other underlying diseases (p < .001). CONCLUSIONS: In KSA, the prevalent symptoms of COVID-19 are fever, cough, and sore throat. Makkah and Almadinah regions are significantly associated with highest burden of mortality. The low level of oxygen saturation, high fever, old age, and underlying cardiovascular disease are the most important predictors for prognosis.

Pharmacists' satisfaction with their involvement in the management of COVID-19 patients in Saudi Arabia.

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) is a public health emergency and during this unprecedented situation, health care providers across the globe are at the frontline in the fight against this disease. Countries that have been severely hit by the pandemic are using pharmacists to help triage patients. In order to ensure the continuity of these services, it is of paramount importance that pharmacists be formally involved and engaged in the management of this pandemic. In response to the underlying knowledge deficit, this study was undertaken as the first of its kind in the entirety of Saudi Arabia. METHODS: This study is a questionnaire based cross-sectional study that was carried out for a period of five months from March 2020 to July 2020 to assess the role of working pharmacists in the management of the COVID-19 pandemic under different health care settings across Saudi Arabia. RESULTS: A total of 398 responses were recorded, in which 51.1% of the respondents were not involved in any learning or awareness activities involving health care providers (HCPs) or patients. The majority of respondents (62.9%) were not involved in creating or evaluating therapeutic plans for COVID19 patients, and 55% were not involved in therapeutic mentoring of COVID19 patients. Only a very low percentage of respondents were participating in COVID19-related research within their institution. Only 37% of respondents reported being satisfied with their role and contribution in the management of COVID-19. CONCLUSION: The present study reveals that pharmacists are underutilized in the management of COVID-19 patients in Saudi Arabia. As such, the findings emphasize the importance of enhancing the role and contribution of pharmacists in patient care management across all hospitals and especially under health care crisis conditions. The establishment of a crisis standard of care guideline for all HCPs, including pharmacists, would help in improving patient overall care under crisis conditions like the present COVID-19 pandemic.

Expression profiling of WD40 family genes including DDB1- and CUL4- associated factor (DCAF) genes in mice and human suggests important regulatory roles in testicular development and spermatogenesis.

BACKGROUND: The WD40-repeat containing proteins, including DDB1-CUL4-associated factors (DCAFs), are abundant and conserved proteins that play important roles in different cellular processes including spermatogenesis. DCAFs are subset of WD40 family proteins that contain WDxR motif and have been proposed to function as substrate receptor for Cullin4-RING-based E3 ubiquitin ligase complexes to recruit diverse proteins for ubiquitination, a vital process in spermatogenesis. Large number of WD40 genes has been identified in different species including mouse and human. However, a systematic expression profiling of WD40 genes in different tissues of mouse and human has not been investigated. We hypothesize that large number of WD40 genes may express highly or specifically in the testis, where their expression is uniquely regulated during testis development and spermatogenesis. Therefore, the objective of this study is to mine and characterize expression patterns of WD40 genes in different tissues of mouse and human with particular emphasis on DCAF genes expressions during mouse testicular development. RESULTS: Publically available RNA sequencing (RNA seq) data mining identified 347 and 349 WD40 genes in mouse and human, respectively. Hierarchical clustering and heat map analyses of RNA seq datasets revealed differential expression patterns of WD40 genes with around 60-73% of the genes were highly or specifically expressed in testis. Similarly, around 74-83% of DCAF genes were predominantly or specifically expressed in testis. Moreover, WD40 genes showed distinct expression patterns during embryonic and postnatal testis development in mice. Finally, different germ cell populations of testis showed specific patterns of WD40 genes expression. Predicted gene ontology analyses revealed more than 80% of these proteins are implicated in cellular, metabolic, biological regulation and cell localization processes. CONCLUSIONS: We have identified large number of WD40 family genes that are highly or specifically expressed in the testes of mouse and human. Moreover, WD40 genes have distinct expression patterns during embryonic and postnatal development of the testis in mice. Further, different germ cell populations within the testis showed specific patterns of WD40 genes expression. These results provide foundation for further research towards understanding the functional genomics and molecular mechanisms of mammalian testis development and spermatogenesis.

Surveillance and Testing for Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, March 2016-March 2019.

During March 2016-March 2019, a total of 200,936 suspected cases of Middle East respiratory syndrome coronavirus infection were identified in Saudi Arabia; infections were confirmed in 698 cases (0.3% [0.7/100,000 population per year]). Continued surveillance is necessary for early case detection and timely infection control response.