Caspase-8 is required for HSV-1-induced apoptosis and promotes effective viral particle release via autophagy inhibition

Regulated cell death (RCD) plays an important role in the progression of viral replication and particle release in cells infected by herpes simplex virus-1 (HSV-1). However, the kind of RCD (apoptosis, necroptosis, others) and the resulting cytopathic effect of HSV-1 depends on the cell type and the species. In this study, we further investigated the molecular mechanisms of apoptosis induced by HSV-1. Although a role of caspase-8 has previously been suggested, we now clearly show that caspase-8 is required for HSV-1-induced apoptosis in a FADD-/death receptor-independent manner in both mouse embryo fibroblasts (MEF) and human monocytes (U937). While wild-type (wt) MEFs and U937 cells exhibited increased caspase-8 and caspase-3 activation and apoptosis after HSV-1 infection, respective caspase-8-deficient (caspase-8-/-) cells were largely impeded in any of these effects. Unexpectedly, caspase-8-/- MEF and U937 cells also showed less virus particle release associated with increased autophagy as evidenced by higher Beclin-1 and lower p62/SQSTM1 levels and increased LC3-I to LC3-II conversion. Confocal and electron microscopy revealed that HSV-1 stimulated a strong perinuclear multivesicular body response, resembling increased autophagy in caspase-8-/- cells, entrapping virions in cellular endosomes. Pharmacological inhibition of autophagy by wortmannin restored the ability of caspase-8-/- cells to release viral particles in similar amounts as in wt cells. Altogether our results support a non-canonical role of caspase-8 in both HSV-1-induced apoptosis and viral particle release through autophagic regulation

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Effects of a Dietary Supplement Composed of Baicalin, Bromelain and Escin for Venous Chronic Insufficiency Treatment: Insights from a Retrospective Observational Study

Chronic venous insufficiency (CVI) represents a risk factor for cardiovascular events. The first-line treatment includes the use of compression stockings and lifestyle changes. Natural products, such as flavonoids, could be used to improve the effects of compression therapy due to their anti-inflammatory and anti-oxidant properties. This study aims to evaluate the effects of a dietary supplement containing baicalin, bromeline and escin in CVI patients. A retrospective cohort study was performed by using the medical records of CVI affected outpatients. Patients treated with the dietary supplement were defined as “users”. A modified Venous Clinical Severity Score (VCSS) was calculated, including pain, inflammation, vessels induration and skin pigmentation. All clinical variables were evaluated at baseline (T0), after 30 (T1) and 90(T2) days in “users” and “non-users”. Out of 62 patients, 30 (48.4%) were “users”. No difference was observed between groups at baseline. A lower VCSS value was recorded in “users” than that observed in “non-users” at T2 (7.0 (4.0–9.0) vs. 9.0 (5.0–10.0); p = 0.025). Vessels’ induration and pain significantly reduced in 53.3% and 43.3% of “users” and in 18.8% and 9.4% of “non-users”. Only “users” (33.3%) showed a reduction of the inflammatory signs as well as a decrease in malleolar circumference, from 29.0 (26.5–30.0) to 27.5 (26.0–28.5) (p p = 0.006). These findings suggest that implementation of a dietary supplement could improve the clinical outcomes of CVI patients

Practice of proctology among general surgery residents and young specialists in Italy: a snapshot survey

Anal diseases are very common and, in most of the cases, require surgery of minor or medium complexity, and, therefore, are among the most accessible diseases for surgeons in training. Aim of this study is to investigate the status of the training in proctology in Italy. A 31-items questionnaire was administered to residents and young specialists (<= 2 years) in general surgery, using mailing lists, and the social media accounts of the Italian Society of Colorectal Surgery. Answers from 338 respondents (53.8% males) were included in the final analysis. Overall, 252 respondents (74.5%) were residents and 86 (25.5%) young specialists. Two hundred and fifty-five (75.4%) respondents practiced proctology for the first time early on during their postgraduate training, but only 19.5% did it continuously for >= 24 months. Almost all respondents (334; 98.8%) had the chance to participate in proctological procedures, 205 (60.5%) as first surgeon. This percentage decreases according to the complexity of the surgery. In fact, only 11 (3.3%) and 24 (7.1%) of the respondents were allowed to be the first surgeon in more complex proctological diseases such as surgery for rectal prolapse and fecal incontinence. The present survey suggests that, in Italy, most surgeons in training deal with anal diseases. However, only few of them could achieve sufficient professional skills in the management of proctological diseases to be able to practice autonomously as young specialists