Characterization of the most frequent ATP7B mutation causing Wilson disease in hepatocytes from patient induced pluripotent stem cells

H1069Q substitution represents the most frequent mutation of the copper transporter ATP7B causing Wilson disease in Caucasian population. ATP7B localizes to the Golgi complex in hepatocytes but moves in response to copper overload to the endo-lysosomal compartment to support copper excretion via bile canaliculi. In heterologous or hepatoma-derived cell lines, overexpressed ATP7B-H1069Q is strongly retained in the ER and fails to move to the post-Golgi sites, resulting in toxic copper accumulation. However, this pathogenic mechanism has never been tested in patients' hepatocytes, while animal models recapitulating this form of WD are still lacking. To reach this goal, we have reprogrammed skin fibroblasts of homozygous ATP7B-H1069Q patients into induced pluripotent stem cells and differentiated them into hepatocyte-like cells. Surprisingly, in HLCs we found one third of ATP7B-H1069Q localized in the Golgi complex and able to move to the endo-lysosomal compartment upon copper stimulation. However, despite normal mRNA levels, the expression of the mutant protein was only 20% compared to the control because of endoplasmic reticulum-associated degradation. These results pinpoint rapid degradation as the major cause for loss of ATP7B function in H1069Q patients, and thus as the primary target for designing therapeutic strategies to rescue ATP7B-H1069Q function

Dietary effects of oregano (Origanum vulgaris L.) plant or sweet chestnut (Castanea sativa Mill.) wood extracts on microbiological, chemical-physical characteristics and lipid oxidation of cooked ham during storage

The aim of this study was to evaluate the dietary effect of feeding pigs with diets enriched with sweet chestnut wood (Castanea sativa Mill.) or oregano (Origanum vulgaris L.) extract on the microbiological and chemical characteristics of cooked pork ham. Three groups of 10 pigs were fed with a control diet (CTRL), with the CTRL diet enriched with 0.2% of oregano extract (OR) and with the CTRL diet enriched with 0.2% of sweet chestnut wood extract (SCW), respectively. Six cooked hams per group were produced, sliced and packaged under a modified atmosphere (N2:CO2=80:20) and stored at refrigeration temperature (4±1°C). Three packages per cooked ham were sampled for analyses at three different storage times (0, 10 and 20 days). At day 0 time, antioxidant capacity of the products (ORACFL assay) and chemical composition were performed. At each sampling time, from all the samples the following analyses were performed: Total Microbial Count (TMC), Lactic Acid Bacteria count (LAB), Enterobacteriaceae count, Listeria monocytogenes, pH value, colour coordinates (L*, a*, b*), total basic volatile nitrogen (TBVN) and thio-barbituric reactive substances (TBARs) determinations. No differences in TMC, LAB and Enterobacteriaceae count, pH, TBVN, chemical composition and L* values were registered between the three groups at all the sampling times considered. No Listeria monocytogenes was detected in the samples tested. Significant differences were registered for ORACFL at 0 days, a* and b* values and TBARs value at 10 and 20 days of storage, with higher values for ORACFL, a* and b* values and lower values for TBARs in SCW and OR than CTRL. No antimicrobial effect could be recorded for OR and SCW but a higher oxidative stability, also highlighted by the colour maintenance, was observed in both OR and SCW

Olive mill wastewater phenolic concentrate as natural antioxidant against lipid-protein oxidative deterioration in chicken meat during storage

Considering that many plant-derived substances show antioxidant and antimicrobial properties, natural antioxidant administered through feed in livestock animals could increase the shelf life of meat and meat products. The aim of this work was to study the effect of olive oil by-products on chicken meat lipid and protein oxidation and oxidative stability during storage. Two hundred and ninety-seven 22-day-old fast growing (Ross 308) female chicks were randomly assigned to three experimental grower-finisher diets: i) a basal control diet (CTR), ii) CTR diet supplemented with a low dosage (4.8%) of olive mill wastewater extract (L-OW) and iii) CTR diet supplemented with a high dosage (9.9%) of olive mill wastewater extract (H-OW). Breast meat of animals belonging to each experimental group was sliced, overwrapped with oxygen-permeable packaging and analysed at three different storage times (zero, three and seven days). At the three sampling times considered, for all samples, colour coordinates (a*), saturation index, Hue angle, peroxide value, thiobarbituric reactive substance, carbonyl assay and the oxygen radical absorbance capacity determinations were performed. No differences in colour were detected among the groups in all the sampling times considered. In conclusion, the supplementation of chicken diet with olive mill wastewater extract (OW) affected oxidation of meat, retarding lipid and protein oxidation and improving antioxidant activity during storage

Does hunted wild boar meat meet modern consumer nutritional expectations?

The present study aimed to evaluate the nutritional characteristics of hunted wild boar (WB) meat and compare them with those of meat from analogous domestic animals (pigs) reared in two different rearing systems: indoor-intensive (PI) and outdoor-extensive (PO). WB meat showed a lower amount of lipid content compared to pork and a higher antioxidant activity compared to PI and PO. The comparison of the fatty acid composition of WB and domestic pig reveals significant differences in saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), with WB having the highest PUFA level and the lowest SFA. The omega 6/omega 3 (n-6/n-3) PUFA ratio, PUFA/SFA, atherogenic and thrombogenic indices (AI and TI), as well as the hypocholesterolemic/hypercholesterolemic index (h/H), were calculated. The n-6/n-3 PUFA ratio was higher in pork independently of the rearing system. The PUFA/SFA ratio of WB meat was above the minimum ratio of 0.40 recommended to contribute to a reduction in the risk of coronary diseases in pork from both rearing systems. AI and TI were lower in meat from hunted wild boars compared to commercially reared pigs, while h/H was higher in WB in comparison with pork meat. WB meat shows good nutritional quality; therefore, the use of game meat as a food source could be appropriate and could benefit contemporary consumers looking for “green” and high-nutritional products

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Evaluation of the Effectiveness of Functional Chewing Training Compared with Standard Treatment in a Population of Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials

Background: Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food and environmental adjustments. The aim of this systematic review was to evaluate the effectiveness of FuCT in improving chewing function and the severity of tongue thrust and drooling in children with cerebral palsy as compared with standard treatment. Methods: We conducted a systematic review of randomized controlled trials. The search was performed between October 2021 and January 2022 using the following databases: PubMed, Scopus, Web of Science, and CINAHL. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: The initial search yielded 56 articles. After reading the studies in full, 3 articles were chosen based on the inclusion criteria. Included participants were people with PCI; the studies reported a sample size ranging from 40–80 individuals, one study was on a pediatric population, while the others on adults. The selected studies were then evaluated using Jadad and PEDro scales. Conclusion: Our study confirmed the value of FuCT in improving chewing function and the severity of tongue thrust and drooling. Our results may be useful in optimizing appropriate therapeutic management

Microbiological, chemical-physical and sensory characteristics of Fabriano salami from pigs fed Oregano vulgaris extract

This study aimed at evaluating the effect of Oregano vulgaris extract supplementation of heavy pig diet on the microbiological, chemical-physical and sensory characteristics of Fabriano salami. Fabriano salamis were produced processing meat derived from pigs belonging to two dietary groups of 16 pigs each: CTRL group fed a commercial pelleted feed, and OR group fed the CTRL diet integrated with 0.2% of oregano extract. Ten salamis per group were collected at 0, 7, 20 and 45 days of ripening and analysed for total viable count, enumeration of Enterobacteriaceae, Enterococcus spp, coagulase negative and positive staphylococci, Lactobacillus spp., Lactococcus spp., presence of Salmonella spp. and Listeria monocytogens, pH, water activity (aw) and colour (CIE L*a*b* colour system). At the end of the ripening (day 45) chemical composition (AOAC, 1990), total antioxidant capacity (ORACFL), thiobarbituric reactive substances (TBARS), total phenolic content (TPC) (Folin-Ciocalteu method) and consumer tests were performed. The integration of oregano extract in pig diets did not interfere with the microbial evolution, chemical composition, pH and aw. After 20 days of ripening the OR salami were redder then CTRL samples, which were also yellower at the end of ripening. Furthermore, the diet has significantly improved the oxidative status, the polyphenolic content and antioxidant power in OR salami. The consumers gave a higher score to OR salami in informed condition