Is a Consensus Case Definition for Viral Associated Lower Respiratory Tract Disease (LRTD) in Clinical Trials Possible?

Lower respiratory tract illness or disease (LRTI/LRTD) represents a significant source of morbidity and mortality following viral respiratory illnesses, yet a consensus definition for this outcome is lacking. Recent studies of novel vaccines against respiratory syncytial virus (RSV) for older adults used LRTI/LRTD as the primary outcome to assess vaccine efficacy. However, the different vaccine trials have used highly variable criteria to define this outcome, leading to difficulty in comparison of vaccine efficacy results between trials.

Maternal Perinatal Depression, Alexithymia, and Couple Functioning: Which Relationship Exists with Prenatal Attachment.

Background: Prenatal attachment refers to the affective investment that parents develop towards their unborn baby during pregnancy. Studies have identified depressive symptoms, affect dysregulation, and poor marital adjustment as potential risk factors for poor prenatal attachment. However, no research has concurrently examined these factors.

Dynamic and structural insights into allosteric regulation on MKP5 a dual-specificity phosphatase.

Dual-specificity mitogen-activated protein kinase (MAPK) phosphatases (MKPs) directly dephosphorylate and inactivate the MAPKs. Although the catalytic mechanism of dephosphorylation of the MAPKs by the MKPs is established, a complete molecular picture of the regulatory interplay between the MAPKs and MKPs still remains to be fully explored. Here, we sought to define the molecular mechanism of MKP5 regulation through an allosteric site within its catalytic domain.

A Very Early Diagnosis of Complete Androgen Insensitivity Syndrome Due to a Novel Variant in the AR Gene: A Neonatal Case Study.

Androgen insensitivity syndrome (AIS) is one of the most common Disorders of Sexual Differentiation (DSDs). AIS is characterized by an X-linked recessive inheritance pattern associated with variants in the androgen receptor (AR) gene that affects the masculinization process in individuals with XY karyotype. Here, we report a neonatal case of a very early diagnosis of complete AIS due to a novel variant in the AR gene.

Medullary carcinomas of the nonampullary small intestine: association with coeliac disease, mismatch repair deficiency, PD-L1 expression, and favourable prognosis.

Aim: Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs).

Methods And Results: Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs.

Interplay of Dyadic Consensus, Reflective Functioning, and Perinatal Affective Difficulties in Modulating Fear of COVID-19 among First-Time Mothers: A Mediation Analysis.

Background: The COVID-19 pandemic has exacerbated fears and anxieties, potentially influencing maternal perinatal mental health. This study addresses a gap in the literature on fear of COVID-19 in pregnant women, aiming to identify contributing factors.

Method: Participants were 401 primiparous women with an average age of 34 years (SD = 4.

Redox-dependent plasticity of oxMIF facilitates its interaction with CD74 and therapeutic antibodies.

MIF is a ubiquitous protein involved in proinflammatory processes, which undergoes an oxidation-driven conformational change to oxidized (ox)MIF. We demonstrate that hypochlorous acid, produced by neutrophil-released myeloperoxidase (MPO) under inflammatory conditions, effectively oxidizes MIF into the oxMIF isoform, which is specifically recognized by the anti-oxMIF therapeutic antibody, ON104. NMR investigation of MIF oxidized by the MPO system revealed increased flexibility throughout the MIF structure, including at several catalytic and allosteric sites.

Successful Treatment with Patisiran in Amyloid Polyneuropathy Harboring His90Asn Mutation in the Gene.

Hereditary transthyretin amyloidosis (hATTR) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensory-motor nerves, heart, autonomic function, and other organs. There are over 130 mutations known in the gene. The His90Asn mutation has been previously reported in several reports, but its pathogenetic role is still debated.

Global 30-day morbidity and mortality of surgery for perforated peptic ulcer: GRACE study.

Background: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these.

Method: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022.

Global 30-Day Morbidity and Mortality of Primary Bariatric Surgery Combined with Another Procedure: The BLEND Study.

Background: No robust data are available on the safety of primary bariatric and metabolic surgery (BMS) alone compared to primary BMS combined with other procedures.

Objectives: The objective of this study is to collect a 30-day mortality and morbidity of primary BMS combined with cholecystectomy, ventral hernia repair, or hiatal hernia repair.

Setting: This is as an international, multicenter, prospective, and observational audit of patients undergoing primary BMS combined with one or more additional procedures.

Atomistic Tuning of the GeoCas9 Recognition Lobe Modulates Allosteric Motions and Guide RNA Interactions.

The intuitive manipulation of specific amino acids to alter the activity or specificity of CRISPR-Cas9 has been a topic of great interest. As a large multi-domain RNA-guided endonuclease, the intricate molecular crosstalk within the Cas9 protein hinges on its conformational dynamics, but a comprehensive understanding of the extent and timescale of the motions that drive its allosteric function and association with nucleic acids remains elusive. Here, we investigated the structure and multi-timescale molecular motions of the recognition (Rec) lobe of GeoCas9, a thermophilic Cas9 from Geobacillus stearothermophilus.

Diagnosis and Management of Congenital H-Type Tracheoesophageal Fistula: Results of a National Survey.

Background: Congenital h-type tracheoesophageal fistula (H-TEF) without esophageal atresia (EA) represents about 4% of congenital esophageal anomalies. The diagnosis is challenging, and surgery is considered curative. The aim was to report a national survey on the diagnosis, management, and outcome of patients with congenital H-TEF.

Short and Long-Term Outcomes of PSARP versus LAARP and Single versus Staged Repair for Infants with High-Type Anorectal Malformations: A Systematic Review and Meta-Analysis.

Background: We aimed to compare among patients with high-type anorectal malformations (ARM): (i) short- and long-term outcomes of laparoscopic-assisted anorectoplasty (LAARP) compared to classic posterior sagittal anorectoplasty (PSARP) and (ii) the results of single-stage versus staged PSARP.

Methods: Using a defined search strategy, two independent investigators systematically reviewed the English literature. PRISMA guidelines were followed, and meta-analysis was performed using RevMan5.

High-throughput prediction of protein conformational distributions with subsampled AlphaFold2.

This paper presents an innovative approach for predicting the relative populations of protein conformations using AlphaFold 2, an AI-powered method that has revolutionized biology by enabling the accurate prediction of protein structures. While AlphaFold 2 has shown exceptional accuracy and speed, it is designed to predict proteins' ground state conformations and is limited in its ability to predict conformational landscapes. Here, we demonstrate how AlphaFold 2 can directly predict the relative populations of different protein conformations by subsampling multiple sequence alignments.

High-fidelity, hyper-accurate, and evolved mutants rewire atomic-level communication in CRISPR-Cas9.

The high-fidelity (HF1), hyper-accurate (Hypa), and evolved (Evo) variants of the CRISPR-associated protein 9 (Cas9) endonuclease are critical tools to mitigate off-target effects in the application of CRISPR-Cas9 technology. The mechanisms by which mutations in recognition subdomain 3 (Rec3) mediate specificity in these variants are poorly understood. Here, solution nuclear magnetic resonance and molecular dynamics simulations establish the structural and dynamic effects of high-specificity mutations in Rec3, and how they propagate the allosteric signal of Cas9.

Congenital lung malformations: a nationwide survey on management aspects by the Italian Society of Pediatric Surgery.

Introduction: Over the years, congenital lung malformations (CLM) management remains a controversial topic in pediatric thoracic surgery. The Italian Society of Pediatric Surgery performed a national survey to study the current management variability among centers, trying to define national guidelines and a standardized approach of children with congenital lung malformations.

Methods: Following a National Society approval, an electronic survey including 35 items on post-natal management was designed, focusing on surgical, anesthesiology, radiology and pneumology aspects.

A Structured Training for Trans Anal Irrigation in Pediatric Patients Improves Outcomes and Reduce Failures: Results of an Interventional Multicenter Prospective Study.

Background: Continence issues due to organic causes including previous colorectal surgery or neurological issues might benefit from Transanal irrigation (TAI) that proved to be highly effective but with a number of limitations including a relatively high discontinuation rates. Our study was aimed at evaluating the efficacy of an advanced protocol tailored to each patient to prevent dropout and increase satisfaction, independence, and quality of life.

Materials And Methods: This was a prospective, interventional, multicenter, nonrandomized study involving children aged 4-18 years with bowel dysfunction unresponsive to conventional treatments who required TAI.

Colorectal Cancer: Current Updates and Future Perspectives.

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age.

European Society of Coloproctology: Guidelines for diagnosis and treatment of cryptoglandular anal fistula.

Aim: The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the management of cryptoglandular anal fistula with input from a multidisciplinary group and using transparent, reproducible methodology.

Methods: Previously published methodology in guideline development by the ESCP has been replicated in this project. The guideline development process followed the requirements of the AGREE-S tool kit.

Management and outcomes of acute appendicitis in children during the COVID-19 pandemic: a systematic review and meta-analysis.

The COVID-19 pandemic has changed the way to manage the emergencies, as people faced fear of the hospitals, with possible delay in the diagnosis. Moreover, clinicians had to rearrange protocols for diagnosis and treatment. We aimed to assess whether COVID-19 pandemic influenced severity of inflammation, management, and outcomes of acute appendicitis (AA), when compared to the pre-COVID era.

Pathophysiological Hypothesis of COVID-19 Psychosis.

In December 2019, a new coronavirus called SARS-CoV-2 was discovered in patients with pneumonia of unknown cause. Although respiratory symptoms mainly characterize infection by this virus, neuropsychiatric manifestations of the disease are becoming more and more frequent. Among them, the appearance of psychotic outbreaks in patients experiencing the infection or after a short time after it has resolved is remarkable.