Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions

Laparoscopic right hemicolectomy: a SICE (Società Italiana di Chirurgia Endoscopica e Nuove tecnologie) network prospective study on the approach to right colon lymphadenectomy in Italy: is there a standard?—CoDIG 2 (ColonDx Italian Group)

Background: Colon cancer is a disease with a worldwide spread. Surgery is the best option for the treatment of advanced colon cancer, but some aspects are still debated, such as the extent of lymphadenectomy. In Japanese guidelines, the gold standard was D3 dissection to remove the central lymph nodes (203, 213, and 223), but in 2009, Hoenberger et al. introduced the concept of complete mesocolic excision, in which surgical dissection follows the embryological planes to remove the mesentery entirely to prevent leakage of cancer cells and collect more lymph nodes. Our study describes how lymphadenectomy is currently performed in major Italian centers with an unclear indication on the type of lymphadenectomy that should be performed during right hemicolectomy (RH). Methods: CoDIG 2 is an observational multicenter national study that involves 76 Italian general surgery wards highly specialized in colorectal surgery. Each center was asked not to modify their usual surgical and clinical practices. The aim of the study was to assess the preference of Italian surgeons on the type of lymphadenectomy to perform during RH and the rise of any new trends or modifications in habits compared to the findings of the CoDIG 1 study conducted 4 years ago. Results: A total of 788 patients were enrolled. The most commonly used surgical technique was laparoscopic (82.1%) with intracorporeal (73.4%), side-to-side (98.7%), or isoperistaltic (96.0%) anastomosis. The lymph nodes at the origin of the vessels were harvested in an inferior number of cases (203, 213, and 223: 42.4%, 31.1%, and 20.3%, respectively). A comparison between CoDIG 1 and CoDIG 2 showed a stable trend in surgical techniques and complications, with an increase in the robotic approach (7.7% vs. 12.3%). Conclusions: This analysis shows how lymphadenectomy is performed in Italy to achieve oncological outcomes in RH, although the technique to achieve a higher lymph node count has not yet been standardized. Trial registration (ClinicalTrials.gov) ID: NCT05943951

Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March-April 2019 vs March-April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p < 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed > 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 202

The Kenya Chamber of Mines: A Case Study in Public Sector Advocacy

The omasum is the forgotten fore-stomach. Omasal torsion has never been reported as a primary cause of clinical disease though omasal dilatation and displacement secondary to vagal indigestion, dietary factors and abomasal volvulus have been reported. Our case presented as an omasal displacement and torsion following surgical repair of a left displaced abomasum due to increased gastro-intestinal peristalsis linked to a fixed point where the abomasum was stitched to the abdominal wall

Comparison of two oestrus synchronisation protocols administered to dairy cows during routine reproduction services

Progesterone-based oestrus synchronisation protocols are frequently used for treatment of cows presented for examination during routine reproduction management service. This study aimed to evaluate the effect of the addition of gonadotrophin-releasing hormone (GnRH) at the start of a progesterone-based oestrus synchronisation protocol for cows presented for examination during routine veterinary service on a commercial dairy farm over 10 months. Overall 139 animals were retained in the study, of which 78 received a standard progesterone-based treatment (STD) and 61 received the same treatment but with the addition of GnRH on day 0 (STD+). Cows were submitted for artificial insemination following observation of behavioural oestrus. Cow and service specific data were used to create two mixed effects generalised linear models to analyse the effect of treatment group on submission rate (SR) and conception rate (CR). In the final SR model lameness had a significant negative association (p=0.01) and STD+ had a non-significant positive association (p=0.12) with submission. In the final CR model only presence of a new CL at day 7 had a significant positive association (p=0.04) while previous reproductive disease had a non-significant positive association (p=0.83) with conception. These results highlight the difficulties in assessing the real effects of altering reproductive protocols on individual farms when other important explanatory variables are considered

Development of customized fetal growth charts in twins

BACKGROUND: Twin gestations are at significantly higher risk of fetal growth restriction in comparison with singletons. Using fetal biometric charts customized for obstetrical and parental characteristics may facilitate an accurate assessment of fetal growth. OBJECTIVE: The objective of the study was to construct reference charts for the gestation of fetal biometric parameters stratified by chorionicity and customized for obstetrical and parental characteristics. STUDY DESIGN: Fetal biometric measurements obtained from serial ultrasound examinations in uncomplicated twin pregnancies delivering after 36 weeks of gestation were collected by 19 Italian fetal medicine units under the auspices of the Societ\ue0 Italiana di Ecografia Ostetrica e Ginecologica. The measurements acquired in each fetus at each examination included biparietal diameter, head circumference, abdominal circumference, and femur length. Multilevel linear regression models were used to adjust for the serial ultrasonographic measurements obtained and the clustering of each fetus in twin pregnancy. The impact of maternal and paternal characteristics (height, weight, ethnicity), parity, fetal sex, and mode of conception was also considered. Models for each parameter were stratified by fetal chorionicity and compared with our previously constructed growth curves for singletons. RESULTS: The data set included 1781 twin pregnancies (dichorionic, n = 1289; monochorionic diamniotic, n = 492) with 8923 ultrasonographic examinations with a median of 5 (range, 2-8) observations per pregnancy in dichorionic and 6 in (range, 2-11) monochorionic pregnancies. Growth curves of twin pregnancies differed from those of singletons, and differences were more marked in monochorionic twins and during the third trimester. A significant influence of parental characteristics was found. CONCLUSION: Curves of fetal biometric measurements in twins are influenced by parental characteristics. There is a reduction in the growth rate during the third trimester. The reference limits for gestation constructed in this study may provide a useful tool for a more accurate assessment of fetal growth in twin pregnancies

Measurement of nasal bone length at 11-14 weeks of pregnancy and its potential role in Down syndrome risk assessment

To assess the feasibility of measuring nasal bone length in first-trimester pregnancy and to confirm if the absence of a fetal nasal bone is a marker for Down syndrome. Fetal nasal bone assessment was attempted in 1089 consecutive singleton pregnancies between 11 and 14 weeks' gestation. All ultrasound examinations were performed transabdominally in three separate centers. If the nasal bone was present, nasal bone length was measured. Nasal bone assessment was successfully achieved in 1027 of 1089 (94.3%) ultrasound examinations. Within this group nasal bone was absent in 10 of 1000 (1.0%) unaffected cases, 10 of 15 (66.7%) Down syndrome cases and 5 of 12 (41.7%) cases with other pathological conditions. Regression analysis showed a significant increase (P < 0.0001) in nasal bone length from 2.48 mm at a crown-rump length of 45 mm to 3.12 mm at a crown-rump length of 84 mm. The nasal bone length in the five cases of Down syndrome in which the nasal bone was present was less than the median measurement of unaffected cases. Using modeling, the combination of nasal bone with maternal age, nuchal translucency, free beta-human chorionic gonadotropin (hCG) and pregnancy associated plasma protein-A (PAPP-A) achieved a detection rate of 95% with a false-positive rate of 2.9%. At a fixed 1% false-positive rate, the detection rate was 91%. Absence of the nasal bone can be used as a marker for Down syndrome in the first trimester of pregnancy. Inclusion of the nasal bone in the current first-trimester screening protocol along with nuchal translucency, free beta-hCG and PAPP-A can achieve high detection at a very low false-positive rate. Large datasets are needed to confirm whether the measurement of nasal bone length provides additional benefits beyond the assessment of the presence or absence of the nasal bon