Clinical effects of a new dispatcher-assisted basic life support training program in a metropolitan city.

This study estimates the effect of a new dispatcher-assisted basic life support training program on the survival outcomes of out-of-hospital cardiac arrest (OHCA). Before-and-after intervention trials were conducted in Seoul. Patients who suffered OHCA in a private place from January 2014 to December 2017 were included. The intervention group was 3 districts; the other 22 districts were regarded as the control group. The primary outcome was survival up to hospital discharge. The difference-in-difference (DID) was calculated to evaluate changes in the survival outcomes of the 2 groups over the period. A total of 10,127 OHCA patients were included in the final analysis. OHCA patients in the intervention group were less likely to receive bystander cardiopulmonary resuscitation (57.8% vs 61.1%; P = .02) and showed lower survival outcomes (5.7% vs 6.4% for survival up to hospital discharge; P = .34 and 2.8% vs 3.7% for good neurological recovery; P = .11), but this was not statistically significant. Compared to 2014, good neurological recovery in 2017 was significantly improved in the intervention group (DID for good neurological recovery = 3.2%; 0.6-5.8). There were no statistically significant differences in return of spontaneous circulation and survival up to hospital discharge between the 2 groups (DID for survival to discharge was 1.8% [-1.7 to 5.3] and DID for return of spontaneous circulation was -2.5% [-9.8 to 4.8]). Improvement in neurological recovery was observed in the 3 districts after implementing the new dispatcher-assisted basic life support training program.

Current systematic reviews and meta-analyses of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has left a significant impact on the world's health, economic and political systems; as of November 20, 2020, more than 57 million people have been infected worldwide, with over 1.3 million deaths. While the global spotlight is currently focused on combating this pandemic through means ranging from finding a treatment among existing therapeutic agents to inventing a vaccine that can aid in halting the further loss of life. AIM: To collect all systematic reviews and meta-analyses published related to COVID-19 to better identify available evidence, highlight gaps in knowledge, and elucidate further meta-analyses and umbrella reviews that are yet to be performed. METHODS: We explored studies based on systematic reviews and meta-analyses with the key-terms, including severe acute respiratory syndrome (SARS), SARS virus, coronavirus disease, COVID-19, and SARS coronavirus-2. The included studies were extracted from Embase, Medline, and Cochrane databases. The publication timeframe of included studies ranged between January 01, 2020, to October 30, 2020. Studies that were published in languages other than English were not considered for this systematic review. The finalized full-text articles are freely accessible in the public domain. RESULTS: Searching Embase, Medline, and Cochrane databases resulted in 1906, 669, and 19 results, respectively, that comprised 2594 studies. 515 duplicates were subsequently removed, leaving 2079 studies. The inclusion criteria were systematic reviews or meta-analyses. 860 results were excluded for being a review article, scope review, rapid review, panel review, or guideline that produced a total of 1219 studies. After screening articles were categorized, the included articles were put into main groups of clinical presentation, epidemiology, screening and diagnosis, severity assessment, special populations, and treatment. Subsequently, there was a second subclassification into the following groups: gastrointestinal, cardiovascular, neurological, stroke, thrombosis, anosmia and dysgeusia, ocular manifestations, nephrology, cutaneous manifestations, D-dimer, lymphocyte, anticoagulation, antivirals, convalescent plasma, immunosuppressants, corticosteroids, hydroxychloroquine, renin-angiotensin-aldosterone system, technology, diabetes mellitus, obesity, pregnancy, children, mental health, smoking, cancer, and transplant. CONCLUSION: Among the included articles, it is clear that further research is needed regarding treatment options and vaccines. With more studies, data will be less heterogeneous, and statistical analysis can be better applied to provide more robust clinical evidence. This study was not designed to give recommendations regarding the management of COVID-19.

An Unusual Case of Prostate Carcinoma With Metastasis to the Iliopsoas Muscle and Nerve Root Impingement.

The majority of prostate cancer cases carry a favorable prognosis due to various screening protocols and the progression of surgical/medical techniques. Prostate cancers that metastasize to the skeletal system bear worse five-year survival rates as they are indicative of widespread dissemination. There are very few cases of prostate cancer invading the iliopsoas muscle described in the medical literature. Here, we present the case of a 61-year-old male who was diagnosed with prostate cancer with metastasis to the bones and iliopsoas muscle. Given the advanced presentation of his disease, the patient underwent a prostate biopsy. He was initiated on bicalutamide and transitioned to leuprolide and docetaxel with eventual radiation therapy.

Bullous drug eruption after second dose of mRNA-1273 (Moderna) COVID-19 vaccine: Case report.

BACKGROUND: In December 2020, Moderna released the mRNA-1273 vaccine. The most common side effects are headache, muscle pain, redness, swelling, and tenderness at the injection site. In addition, there have been dermatological adverse events, such as hypersensitivity reactions. Although rare, various bullous eruptions have been described following vaccination. Bullous pemphigoid has been reported to occur most often after receipt of influenza and the diphtheria-tetanus-pertussis vaccine. To the best of our knowledge, there have been no reports of bullous drug eruptions resulting from mRNA vaccines. CASE SUMMARY: A 66-years-old obese Guyanese male presented with a bullous rash following receipt of a commercial COVID-19 mRNA vaccine. He received the first dose uneventfully. However, within 24 h of receiving the second dose, he developed fever, myalgias, and malaise accompanied by a painful blistering rash of his torso, arms, and legs. His fever and myalgias improved after 24 h, but his painful rash did not, and five days after the initial symptoms, he presented to the hospital. There were many violaceous, poorly demarcated patches on his trunk, arms, and thighs on examination, many of which had large flaccid bullae within, and a few areas on his buttocks, posterior shoulder, and scrotum were eroded. The exam was also significant for lower extremity muscle tenderness, stiffness with preserved strength. A skin biopsy showed epidermal necrosis and sparse perivascular dermatitis concerning Stevens-Johnson syndrome or erythema multiforme. However, in the absence of mucous membrane involvement or targetoid lesions, the diagnosis of an extensive bullous fixed drug eruption was made. CONCLUSION: This case illustrates that the bullae eruption occurred as a result of receiving the Moderna vaccination.

Structural insight into transmissive mutant huntingtin species by correlative light and electron microscopy and cryo-electron tomography.

Aggregates of mutant huntingtin (mHTT) containing an expanded polyglutamine (polyQ) tract are hallmarks of Huntington's Disease (HD). Studies have shown that mHTT can spread between cells, leading to the propagation of misfolded protein pathology. However, the structure of transmissive mHTT species, and the molecular mechanisms underlying their transmission remain unknown. Using correlative light and electron microscopy (CLEM) and cryo-electron tomography (cryo-ET), we identified two types of aggregation-prone granules in conditioned medium from PC12 cells expressing a mHTT N-terminal fragment: densities enclosed by extracellular vesicles (EVs), and uncoated, amorphous meshworks of heterogeneous oligomers that co-localize with clusters of EVs. In vitro assays confirmed that liposomes induce condensation of polyQ oligomers into higher-order assemblies, resembling the uncoated meshworks observed in PC12 conditioned medium. Our findings provide novel insights into formation and architecture of transmissive mHTT proteins, and highlight the potential role of EVs as both carriers and modulators of transmissive mHTT proteins.

FANCM suppresses DNA replication stress at ALT telomeres by disrupting TERRA R-loops.

Cancer cells maintain their telomeres by either re-activating telomerase or adopting the homologous recombination (HR)-based Alternative Lengthening of Telomere (ALT) pathway. Among the many prominent features of ALT cells, C-circles (CC) formation is considered to be the most specific and quantifiable biomarker of ALT. However, the molecular mechanism behind the initiation and maintenance of CC formation in ALT cells is still largely unknown. We reported previously that depletion of the FANCM complex (FANCM-FAAP24-MHF1&2) in ALT cells induced pronounced replication stress, which primarily takes place at their telomeres. Here, we characterized the changes in ALT associated phenotypes in cells deficient of the FANCM complex. We found that depletion of FAAP24 or FANCM, but not MHF1&2, induces a dramatic increase of CC formation. Most importantly, we identified multiple DNA damage response (DDR) and DNA repair pathways that stimulate the dramatic increase of CC formation in FANCM deficient cells, including the dissolvase complex (BLM-TOP3A-RMI1/2, or BTR), DNA damage checkpoint kinases (ATR and Chk1), HR proteins (BRCA2, PALB2, and Rad51), as well as proteins involved in Break-Induced Replication (BIR) (POLD1 and POLD3). In addition, FANCD2, another Fanconi Anemia (FA) protein, is also required for CC formation, likely through promoting the recruitment of BLM to the replication stressed ALT telomeres. Finally, we demonstrated that TERRA R-loops accumulate at telomeres in FANCM deficient ALT cells and downregulation of which attenuates the ALT-associated PML bodies (APBs), replication stress and CC formation. Taken together, our data suggest that FANCM prevents replisomes from stalling/collapsing at ALT telomeres by disrupting TERRA R-loops.

Epicardial adipose tissue volume is associated with non-alcoholic fatty liver disease and cardiovascular risk factors in the general population.

BACKGROUND: Epicardial adipose tissue (EAT) is considered an important source of bioactive molecules that can influence coronary arteries directly and is related to the concurrent presence of both obstructive coronary stenosis and myocardial ischemia independently. Non-alcoholic fatty liver disease (NAFLD) has become an emergent health problem worldwide. AIM: This cross-sectional study aimed to address the relationship between the volume of EAT and NAFLD and other cardiovascular risk factors in the general population. MATERIALS AND METHODS: In this study, we selected a total of 2,238 participants aged at least 40 years from the Jidong community in Tangshan, China. The 64-slice CT was used to survey the volume of EAT and liver ultrasonography was used for the diagnosis of NAFLD. The study cohorts were compared according to EAT volume. RESULTS: Cardiovascular risk factors, such as coronary artery calcium score, carotid intima-media thickness, NAFLD, and ideal cardiovascular health metrics were also found to be related to EAT. In multivariate logistic regression analysis, NAFLD groups showed significant association with higher EAT volume, after correcting for main cardiovascular disease risk factors (OR [95% CI], 1.407 [1.117, 1.773]). CONCLUSION: Our findings in a general community population provide evidence that EAT is strongly associated with NAFLD and other cardiovascular risk factors.

Breaking the end: Target the replication stress response at the ALT telomeres for cancer therapy.

We recently reported that depletion of FANCM in ALT cells induces replication stress mainly at their telomeres. Additionally, we found that co-depletion of FANCM and BLM, or FANCM and BRCA1 induces synthetic lethality in the ALT cells. Our new findings could have important implications for cancer prevention and treatment.

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.

BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors--healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend<0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend<0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend<0.0001) for rectal cancer, respectively (P-difference by cancer sub-site=0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.