Mitochondrial Arrest on the Microtubule Highway—A Feature of Heart Failure and Diabetic Cardiomyopathy?

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-03-31, accepted 2021-06-08, epub 2021-07-02Publication status: PublishedA pathophysiological consequence of both type 1 and 2 diabetes is remodelling of the myocardium leading to the loss of left ventricular pump function and ultimately heart failure (HF). Abnormal cardiac bioenergetics associated with mitochondrial dysfunction occurs in the early stages of HF. Key factors influencing mitochondrial function are the shape, size and organisation of mitochondria within cardiomyocytes, with reports identifying small, fragmented mitochondria in the myocardium of diabetic patients. Cardiac mitochondria are now known to be dynamic organelles (with various functions beyond energy production); however, the mechanisms that underpin their dynamism are complex and links to motility are yet to be fully understood, particularly within the context of HF. This review will consider how the outer mitochondrial membrane protein Miro1 (Rhot1) mediates mitochondrial movement along microtubules via crosstalk with kinesin motors and explore the evidence for molecular level changes in the setting of diabetic cardiomyopathy. As HF and diabetes are recognised inflammatory conditions, with reports of enhanced activation of the NLRP3 inflammasome, we will also consider evidence linking microtubule organisation, inflammation and the association to mitochondrial motility. Diabetes is a global pandemic but with limited treatment options for diabetic cardiomyopathy, therefore we also discuss potential therapeutic approaches to target the mitochondrial-microtubule-inflammatory axis

Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera

The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.</p

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Perception of E-Resources on the Learning Process among Students in the College of Health Sciences in King Saud University, Saudi Arabia, during the (COVID-19) Outbreak

Aim: to assess the impact of e-learning through different e-resources among health sciences students. Methodology: A cross-sectional design was conducted among health science students (n = 211; 134 female and 77 male) at King Saud University, Saudi Arabia. The data was collected using a previously used structured questionnaire to assess the impact of e-resources on learning. Results: The four most frequently used e-resources were: Zoom (38%), YouTube (31%), Google applications (29%), and Blackboard (27%). More than one-third of the students (35%) reportedly used e-resources for three or more hours daily. The majority of the students (55.9%) recognized a gender-related and age-related difference among faculty members in terms of e-resources usage. The majority of the students (58.2%) believe that online resources recommended by faculty members were credible. The majority of students believed that their academic performance was primarily influenced by these features of the e-resources: organization/logic of the content (64.5%), the credibility of the video (64.5%), and up to date “look and feel” of the video (60.6%). The study identified the most frequently used e-resources, gender, and age-related differences in faculty members’ use of e-resources, students’ overwhelming reliance on faculty feedback regarding the credibility of e-resources, and three most important characteristics (organization, credibility, and updated status) of e-resources. Conclusion: e-learning resources had a significant impact on participating students’ education as they were used very frequently during their health sciences’ courses

Thrombolytic therapy in cardiac arrest caused by cardiac etiologies or presumed pulmonary embolism: An updated systematic review and meta‐analysis

Abstract Background Many cardiac arrest cases are encountered annually worldwide, with poor survival. The use of systemic thrombolysis during cardiopulmonary resuscitation for the treatment of cardiac arrest remains controversial. Objectives Evaluate the safety and efficacy of systemic thrombolysis in patients with cardiac arrest due to presumed or confirmed pulmonary embolism or cardiac etiology. Methods We searched the PubMed and Cochrane databases from inception through April 2021 to identify relevant randomized controlled trials and observational studies. The primary efficacy and safety outcomes were survival to hospital discharge and reported bleeding, respectively. Sensitivity analysis was performed on the basis of study design and etiology of cardiac arrest. Results Eleven studies were included, with 4696 patients (1178 patients received systemic thrombolysis, and 3518 patients received traditional therapy). There was a higher rate of survival to hospital discharge in patients who received systemic thrombolysis versus no systemic thrombolysis (risk ratio [RR], 1.35; 95% confidence interval [CI], 0.95‐1.91). There were also higher rates of survival at 24 hours (RR, 1.24; 95% CI, 0.97‐1.59) and hospital admission (RR, 1.53; 95% CI, 1.04‐2.24), and return of spontaneous circulation (ROSC) (RR, 1.34; 95% CI, 1.05‐1.71) with the use of systemic thrombolysis. Impacts on survival to discharge and survival at 24 hours were not statistically significant. Patients receiving systemic thrombolysis had a 65% increase in bleeding events compared with no systemic thrombolysis (RR, 1.65; 95% CI, 1.20‐2.27). Conclusion Systemic thrombolysis in cardiac arrest did not improve survival to hospital discharge and led to more bleeding events. However, it increased the rates of hospital admission and ROSC achievement

The The predicting factors of clinical outcomes in patients with COVID-19 in the Kingdom of Saudi Arabia [KSA]: A multi-center cohort study

Background: On March 2020, the first case of coronavirus disease-19 was registered in the Kingdom of Saudi Arabia and subsequently the first mortality case. The predicting factors for patients' outcomes are essential to triage patients with COVID-19. This may provide low-cost facilities that help in the fight against the existing global pandemic.    Objectives: This study aimed to predict hospitalization and death outcomes of COVID-19 patients using the simplest facilities. Method: The electronic medical records of 280 COVID-19 patients between March 2020 and May 2021 were retrieved from a multi-centre of healthcare facilities across Kingdom of Saudi Arabian cites. All demographic and clinical information were examined to determine predictors and outcomes. Results: Of the 280 COVID -19 patients enrolled in our study, 14.3% were aged ≥ 66 years and 62.5% were female. The elderly (≥ 66 years, P= 0.000) and male patients (P= 0.001) were significantly hospitalized by COVID -19 than others. Patients with symptoms were hospitalized significantly more than patients without symptoms (P= 0.001). Patients with chronic conditions were hospitalized more frequently (P= 0.001). Hospitalization status also did not differ by smoking. Fever occurred significantly more frequently in patients with one or more chronic diseases (P = 0.000). Elderly (≥ 66 years, P= 0.000) and male patients of COVID -19 (P= 0.022) had significant evidence of association with death outcome than others. Hospitalization status was associated with death (P = 0.000). Conclusion: This study reported that male gender and advanced age COVID-19 patients are independent predictors for both hospital admission and death outcomes more than others. The COVID-19 patients who complain from symptoms are at risk for hospitalization as well. Additionally, having chronic clinical conditions are predictor factor for hospital admission outcome. Finally, the hospitalized patients of COVID-19 infection are at risk for death outcome

Ginger Oil Nanoemulsion Formulation Augments Its Antiproliferative Effect in Ehrlich Solid Tumor Model

Cancer is a disease that is characterized by uncontrolled cell proliferation. Breast cancer is the most prevalent cancer among women. Ginger oil is a natural cancer fighter and anti-oxidant. However, the minimal absorption of ginger oil from the gastrointestinal tract accounts for its limited medicinal efficacy. The present study was designed to evaluate the efficacy of a nanoemulsion preparation of ginger oil on its oral bioavailability and in vivo anti-cancer efficacy. Ginger oil nanoemulsion was prepared by a high-pressure homogenization technique using different surfactants (Tween 20, 40, and 80). The prepared formulations were evaluated for droplet size, polydispersity index (PDI), zeta potential (ZP), pH, viscosity, and stability by calculating the creaming index percentage. The best formulation was evaluated for shape by TEM. The antitumor activity of the best nano-formulation was determined in comparison with the free oil using the in vivo Ehrlich solid tumor (EST) model. The prepared ginger oil nanoemulsion formulations exhibited acceptable droplet size in the range from 56.67 ± 3.10 nm to 357.17 ± 3.62 nm. A PDI of less than 0.5 indicates the homogeneity of size distribution. The oil globules possessed a negative charge ranging from −12.33 ± 1.01 to −39.33 ± 0.96 mV. The pH and viscosity were in the acceptable range. The TEM image of the best formulation appeared to be spherical with a small size. The ginger oil nanoemulsion reduced in vivo tumor volume and weight, extended animals’ life span, and ameliorated liver and kidney function in EST-bearing mice. These effects were superior to using free ginger oil. Collectively, the present study demonstrated that the ginger oil nanoemulsion improved oral absorption with a subsequent enhancement of its anti-proliferative efficacy in vivo, suggesting a nano-formulation of ginger oil for better therapeutic outcomes in breast cancer patients

The outright regarding abdominal wall hernia among adults in Jazan: A cross-sectional study

Background: Hernias are repeatedly encountered in surgical clinics owing to risks such as constipation, weightlifting, gestation, weight gain, and ongoing ailments similar to bronchial asthma and prostatic enlargement. The study intended to examine various viewpoints of the population's knowledge and beliefs concerning hernia and its management. Methods: Individuals in this cross-sectional study were randomly picked from those at greater risk of acquiring abdominal wall hernias (AWHs). To report their awareness levels toward AWH, the data were calculated as frequency, expressed as a percentage, and displayed as tables and figures. Results: Eighty-six percent of the patients did not have a hernia during the study, but all had experienced hernias before the study date. About 36.9% of participants showed a poor level of knowledge regarding AWHs. Participants' knowledge was notably correlated with gender, age, marital status, previous abdominal surgery, presence of interfamilial hernias, and having asthma or chronic cough (P < 0.05). According to 55% of respondents, pain and discomfort after an operation are the most prevalent complications, while 15.1% reported no postoperative complications. According to 41.4% of respondents, laparoscopic surgery was the best treatment option, followed by open surgery and lifestyle modifications in 28% and 24.8%, respectively. Conclusion: Compared to females, males were more likely to suffer from AWHs. Hernia's risk factors, management methods, and surgical complications were not well understood by participants. This may entail holding seminars to raise awareness of AWHs among the community members

Immunogenicity of High-Dose MVA-Based MERS Vaccine Candidate in Mice and Camels

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime–boost vaccinations in mice and camels. Methods: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. Results: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). Conclusions: MVA-MERS vaccine, administered in a homologous prime–boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans