Obstetric violence in a group of Italian women: socio-demographic predictors and effects on mental health

This study had two aims: (1) to explore the types and incidence of obstetric violence (OV) in a group of Italian women, as well as associated socio-demographic factors; and (2) to assess whether OV affects women’s mental health (e.g. psychological distress and post-traumatic stress). A web-based cross-sectional study was conducted with 282 Italian women. Women answered questions on socio-demographic factors, childbirth characteristics, OV and mental health. Multiple linear regression analyses assessing the predictive role of socio-demographic and childbirth characteristics on OV were conducted. Additionally, hierarchical multiple linear regression analyses assessing whether OV affected women’s mental health were also carried out. More than three quarters of the sample (78.4%) had experienced at least one type of OV (55.5% of non-consented care and 66.4% of abuse and violence). The factors most associated with OV were younger age, low educational level, not having attended a prenatal childbirth preparedness course, and having given birth naturally. The form of OV that most affected women’s mental health was that linked to abuse and violence rather than non-consented care. Study findings shed light into addressing OV from a multidimensional perspective

CRISPR/Cas9-Mediated In Situ Correction of LAMB3 Gene in Keratinocytes Derived from a Junctional Epidermolysis Bullosa Patient

Deficiency of basement membrane heterotrimeric laminin 332 component, coded by LAMA3, LAMB3, and LAMC2 genes, causes junctional epidermolysis bullosa (JEB), a severe skin adhesion defect. Herein, we report the first application of CRISPR/Cas9-mediated homology direct repair (HDR) to in situ restore LAMB3 expression in JEB keratinocytes in vitro and in immunodeficient mice transplanted with genetically corrected skin equivalents. We packaged an adenovector carrying Cas9/guide RNA (gRNA) tailored to the intron 2 of LAMB3 gene and an integration defective lentiviral vector bearing a promoterless quasi-complete LAMB3 cDNA downstream a splice acceptor site and flanked by homology arms. Upon genuine HDR, we exploited the in vitro adhesion advantage of laminin 332 production to positively select LAMB3-expressing keratinocytes. HDR and restored laminin 332 expression were evaluated at single-cell level. Notably, monoallelic-targeted integration of LAMB3 cDNA was sufficient to in vitro recapitulate the adhesive property, the colony formation typical of normal keratinocytes, as well as their cell growth. Grafting of genetically corrected skin equivalents onto immunodeficient mice showed a completely restored dermal-epidermal junction. This study provides evidence for efficient CRISPR/Cas9-mediated in situ restoration of LAMB3 expression, paving the way for ex vivo clinical application of this strategy to laminin 332 deficiency

A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C

Rabies, caused by RNA viruses in the Genus Lyssavirus, is the most fatal of all infectious diseases. This neglected zoonosis remains a major public health problem in developing countries, causing the death of an estimated 25,000-159,000 people each year, with more than half of them in children. The high incidence of human rabies in spite of effective vaccines is mainly linked to the lack of compliance with the complicated administration schedule, inadequacies of the community public health system for local administration by the parenteral route and the overall costs of the vaccine. The goal of our work was the development of a simple, affordable and effective vaccine strategy to prevent human rabies virus infection. This next generation vaccine is based on a replication-defective chimpanzee adenovirus vector belonging to group C, ChAd155-RG, which encodes the rabies glycoprotein (G). We demonstrate here that a single dose of this vaccine induces protective efficacy in a murine model of rabies challenge and elicits strong and durable neutralizing antibody responses in vaccinated non-human primates. Importantly, we demonstrate that one dose of a commercial rabies vaccine effectively boosts the neutralizing antibody responses induced by ChAd155-RG in vaccinated monkeys, showing the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Finally, we demonstrate that antibodies induced by ChAd155-RG can also neutralize European bat lyssaviruses 1 and 2 (EBLV-1 and EBLV-2) found in bat reservoirs

Correction: A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C.

[This corrects the article DOI: 10.1371/journal.pntd.0008459.]

Search for heavy neutral lepton production in K+ decays

A search for heavy neutral lepton production in K + decays using a data sample collected with a minimum bias trigger by the NA62 experiment at CERN in 2015 is reported. Upper limits at the 10−7 to 10−6 level are established on the elements of the extended neutrino mixing matrix |Ue4| 2 and |Uμ4| 2 for heavy neutral lepton mass in the ranges 170–448 MeV/c2 and 250–373 MeV/c2, respectively. This improves on the previous limits from HNL production searches over the whole mass range considered for |Ue4|2 and above 300 MeV/c2 for |Uμ4|2

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Measurement of the very rare K+→π+ννˉK^+ \to \pi^+ \nu \bar\nu decay

The decay K+→π+νν¯ , with a very precisely predicted branching ratio of less than 10−10 , is among the best processes to reveal indirect effects of new physics. The NA62 experiment at CERN SPS is designed to study the K+→π+νν¯ decay and to measure its branching ratio using a decay-in-flight technique. NA62 took data in 2016, 2017 and 2018, reaching the sensitivity of the Standard Model for the K+→π+νν¯ decay by the analysis of the 2016 and 2017 data, and providing the most precise measurement of the branching ratio to date by the analysis of the 2018 data. This measurement is also used to set limits on BR(K+→π+X ), where X is a scalar or pseudo-scalar particle. The final result of the BR(K+→π+νν¯ ) measurement and its interpretation in terms of the K+→π+X decay from the analysis of the full 2016-2018 data set is presented, and future plans and prospects are reviewed

Antioxidant properties of hydroxytyrosyl acetate compared with hydroxytyrosol and their protective capacity against oxidative stress in human neuroblastoma cells

929-937This study analyses antioxidant activity of synthetic hydroxytyrosol (HTy) and hydroxytyrosyl acetate (HTy-ac) against different reactive species. Both phenols were found to be able to scavenge superoxide anion as well as hydroxyl radical with comparable efficacy (40% and 80% scavenging activity, respectively). HTy-ac was found to be more effective than HTy or a-tocopherol as hydrogen peroxide scavenger (53%, 29% and 25% scavenging activity, respectively) (p£0.05). Human neuroblastoma cell line SH-SY5Y was chosen as an ex vivo model and cellular oxidative stress was assessed through the measurement of total free sulfhydryl groups and protein carbonyls. HTy displayed a high antioxidant ability against thiols oxidation at 10 M, whereas HTy-ac showed a great capacity in preventing carbonyl groups generation. Different antioxidant ability showed by tested compounds against oxidative stress in biological system can be attributed to molecular concentration, reducing power and lipophilicity

Antioxidant properties of hydroxytyrosyl acetate compared with hydroxytyrosol and their protective capacity against oxidative stress in human neuroblastoma cells

This study analyses antioxidant activity of synthetic hydroxytyrosol (HTy) and hydroxytyrosyl acetate (HTy-ac) against. different reactive species. Both phenols were found to be able to scavenge superoxide anion as well as hydroxyl radical with comparable efficacy (40% and 80% scavenging activity, respectively). HTy-ac was found to be more effective than HTy or a-tocopherol as hydrogen peroxide scavenger (53%, 29% and 25% scavenging activity, respectively) (p <= 0.05). Human neuroblastoma cell line SH-SY5Y was chosen as an ex vivo model and cellular oxidative stress was assessed through the measurement of total free sulfhydryl groups and protein carbonyls. HTy displayed a high antioxidant ability against thiols oxidation at 10 mu M, whereas HTy-ac showed a great capacity in preventing carbonyl groups generation. Different antioxidant ability showed by tested compounds against oxidative stress in biological system can be attributed to molecular concentration, reducing power and lipophilicity