Geographic disparities impacting oral vaccine performance: Observations and future directions.

Oral vaccines have several advantages compared with parenteral administration: they can be relatively cheap to produce in high quantities, easier to administer, and induce intestinal mucosal immunity that can protect against infection. These characteristics have led to successful use of oral vaccines against rotavirus, polio, and cholera. Unfortunately, oral vaccines for all three diseases have demonstrated lower performance in the highest-burden settings where they are most needed.

Monitoring the Risk of Type-2 Circulating Vaccine-Derived Poliovirus Emergence During Roll-Out of Type-2 Novel Oral Polio Vaccine.

Although wild poliovirus type 2 has been eradicated, the prolonged transmission of the live- attenuated virus contained in the type-2 oral polio vaccine (OPV2) in under-immunized populations has led to the emergence of circulating vaccine-derived poliovirus type 2 (cVDPV2). The novel OPV2 (nOPV2) was designed to be more genetically stable and reduce the chance of cVDPV2 emergence while retaining comparable immunogenicity to the Sabin monovalent OPV2 (mOPV2). This study aimed to estimate the relative reduction in the emergence risk due to the use of nOPV2 instead of mOPV2.

Bioinspired designer DNA NanoGripper for virus sensing and potential inhibition.

DNA has shown great biocompatibility, programmable mechanical properties, and precise structural addressability at the nanometer scale, rendering it a material for constructing versatile nanorobots for biomedical applications. Here, we present the design principle, synthesis, and characterization of a DNA nanorobotic hand, called DNA NanoGripper, that contains a palm and four bendable fingers as inspired by naturally evolved human hands, bird claws, and bacteriophages. Each NanoGripper finger consists of three phalanges connected by three rotatable joints that are bendable in response to the binding of other entities.

Timeliness of 24 childhood immunisations and evolution of vaccination delay: Analysis of data from 54 low- and middle-income countries.

Vaccination timeliness is often not considered among standard performance indicators of routine vaccination programmes, such as vaccination coverage, yet quantifying vaccination delay could inform policies to promote in-time vaccination and help design vaccination schedules. Here, we analysed vaccination timeliness for 24 routine childhood immunisations for 54 countries. We extracted individual vaccination status and timing from Demographic and Health Surveys data from 54 countries with surveys from 2010 onwards.

Non-Designated Preliminary to Categorical Resident: Is It All About the ABSITE?

Introduction: Obtaining a categorical general surgery residency position is recognized as a highly challenging process, and many aspiring surgeons find themselves matching into a preliminary position. The American Board of Surgery In-Training Examination (ABSITE) is relevant as a discriminator, as it is the only national evaluation metric that compares residents between programs. This study examines the correlation between ABSITE performance and the likelihood of obtaining a categorical position for non-designated preliminary surgery residents.

Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification.

Severe coronavirus disease 2019 and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with neurological complications that may be linked to direct infection of the central nervous system (CNS), but the selective pressures ruling neuroinvasion are poorly defined. Here we assessed SARS-CoV-2 evolution in the lung versus CNS of infected mice. Higher levels of viral divergence were observed in the CNS than the lung after intranasal challenge with a high frequency of mutations in the spike furin cleavage site (FCS).

N-Substituted Pyrrole-Based Heterocycles as Broad-Spectrum Filoviral Entry Inhibitors.

Since the largest and most fatal Ebola virus epidemic during 2014-2016, there have been several consecutive filoviral outbreaks in recent years, including those in 2021, 2022, and 2023. Ongoing outbreak prevalence and limited FDA-approved filoviral therapeutics emphasize the need for novel small molecule treatments. Here, we showcase the structure-activity relationship development of N-substituted pyrrole-based heterocycles and their potent, submicromolar entry inhibition against diverse filoviruses in a target-based pseudovirus assay.

Non-Covalent Inhibitors of SARS-CoV-2 Papain-Like Protease (PLpro): In Vitro and In Vivo Antiviral Activity.

The SARS-CoV-2 papain-like protease (PLpro), essential for viral processing and immune response disruption, is a promising target for treating acute infection of SARS-CoV-2. To date, there have been no reports of PLpro inhibitors with both submicromolar potency and animal model efficacy. To address the challenge of PLpro's featureless active site, a noncovalent inhibitor library with over 50 new analogs was developed, targeting the PLpro active site by modulating the BL2-loop and engaging the BL2-groove.

Suppression of interferon α and γ response by Huwe1-mediated Miz1 degradation promotes SARS-CoV-2 replication.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been demonstrated to limit the host interferon response; however, the underlying mechanism remains unclear. Here, we found that SARS-CoV-2 infection upregulated the E3 ubiquitin ligase Huwe1, which in turn facilitated the degradation of the transcription factor Miz1. The degradation of Miz1 hampered interferon alpha and gamma responses, consequently fostering viral replication and impeding viral clearance.

First report of ivermectin resistance in cyathostomins (small strongyles) of horses in Argentina.

In Argentina, as in the rest of the world, cyathostomins are the most common nematodes parasitizing horses. Control is based almost exclusively on the administration of benzimidazoles, pyrimidines, and macrocyclic lactones. However, intensive use of these drugs is resulting in the development of anthelmintic resistance (AR).

Modelling control strategies for pneumococcal meningitis outbreaks in the African meningitis belt.

Introduction: Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal but not pneumococcal meningitis. Mathematical modelling is a useful tool for assessing the potential impact of different pneumococcal control strategies.

Novel Oral Polio Vaccine Type 2 Use for Polio Outbreak Response: A Global Effort for a Global Health Emergency.

A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led to the accelerated development of the novel oral polio vaccine type 2 (nOPV2), a vaccine with enhanced genetic stability and lower likelihood of reversion to neuroparalytic variants compared to its Sabin counterpart. In November 2020, nOPV2 became the first vaccine to be granted an Emergency Use Listing (EUL) by the World Health Organization (WHO) Prequalification Team (PQT), allowing close to a billion doses to be used by countries within three years after its first rollout and leading to full licensure and WHO prequalification (PQ) in December 2023. The nOPV2 development process exemplifies how scientific advances and innovative tools can be applied to combat global health emergencies in an urgent and adaptive way, building on a collaborative effort among scientific, regulatory and implementation partners and policymakers across the globe.

Using risk-adjusted cumulative sum to evaluate surgeon, divisional, and institutional outcomes-a feasibility study.

Background: Few objective, real-time measurements of surgeon performance exist. The risk-adjusted cumulative sum is a novel method that can track surgeon-level outcomes on a continuous basis. The objective of this study was to demonstrate the feasibility of using risk-adjusted cumulative sum to monitor outcomes after colorectal operations and identify clinically relevant performance variations.

Polyvalent Nanobody Structure Designed for Boosting SARS-CoV-2 Inhibition.

Coronavirus transmission and mutations have brought intensive challenges on pandemic control and disease treatment. Developing robust and versatile antiviral drugs for viral neutralization is highly desired. Here, we created a new polyvalent nanobody (Nb) structure that shows the effective inhibition of SARS-CoV-2 infections.

An orally active entry inhibitor of influenza A viruses protects mice and synergizes with oseltamivir and baloxavir marboxil.

Seasonal or pandemic illness caused by influenza A viruses (IAVs) is a major public health concern due to the high morbidity and notable mortality. Although there are several approved drugs targeting different mechanisms, the emergence of drug resistance calls for new drug candidates that can be used alone or in combinations. Small-molecule IAV entry inhibitor, ING-1466, binds to hemagglutinin (HA) and blocks HA-mediated viral infection.

Early Implementation of Robotic Training in Surgical and Surgical Subspecialty Residency.

Background: Robotic surgery has emerged as an operative tool for many elective and urgent surgical procedures. The purpose of this study was to evaluate early surgical trainees' experiences and opinions of robotic surgery.

Methods: An introductory robotic training course consisting of online da Vinci Xi/X training and in-person, hands on training was implemented for residents and medical students across surgical subspecialties at a single institution.

Effectiveness of poliovirus vaccines against circulating vaccine-derived type 2 poliomyelitis in Nigeria between 2017 and 2022: a case-control study.

Background: Between 2018 and 2022, Nigeria experienced continuous transmission of circulating vaccine-derived type 2 poliovirus (cVDPV2), with 526 cases of cVDPV2 poliomyelitis detected in total and approximately 180 million doses of monovalent type 2 oral poliovirus vaccine (mOPV2) and 450 million doses of novel type 2 oral poliovirus vaccine (nOPV2) delivered in outbreak response campaigns. Inactivated poliovirus vaccine (IPV) was introduced into routine immunisation in 2015, with a second dose added in 2021. We aimed to estimate the effectiveness of nOPV2 against cVDPV2 paralysis and compare nOPV2 effectiveness with that of mOPV2 and IPV.

Physiotherapy-led, community-based airway clearance services for people with chronic lung conditions: a retrospective descriptive evaluation of an existing model of care.

Objectives: Airway clearance interventions are recommended for people with chronic lung conditions and mucus hypersecretion, but there are few published models of care or descriptions of airway clearance service provision. This evaluation describes a dedicated, physiotherapy-led, community-based airway clearance service in a metropolitan local health network.

Design: Retrospective evaluation using existing airway clearance service administrative database.

Analysis of 10 years of open, laparoscopic, and robotic rectal surgeries in the community setting.

Background: Colorectal cancer is the fourth most common cancer in the US. Many of these patients will require operations. Although there is significant data in the literature that supports minimally invasive colorectal operations in the academic setting, few studies have examined their performance in community hospitals.

Use of inactivated poliovirus vaccine for poliovirus outbreak response.

With continued wild poliovirus transmission in Afghanistan and Pakistan and circulating vaccine-derived poliovirus in certain countries, there exists an ongoing risk of importation of polioviruses into other countries, including those that have been polio-free for decades. Diversifying the poliovirus outbreak response toolkit is essential to account for different public health and epidemiological contexts. In this Personal View, we discuss data on intestinal and pharyngeal mucosal immunity induced by inactivated poliovirus vaccine (IPV), previous programmatic experience of poliovirus outbreak response with IPV, and outbreak response guidelines in countries that exclusively use IPV.

The Role of Artificial Intelligence in Surgery: What do General Surgery Residents Think?

Background: Artificial intelligence (AI) holds significant potential in medical education and patient care, but its rapid emergence presents ethical and practical challenges. This study explored the perspectives of surgical residents on AI's role in medicine.

Methods: We performed a cross-sectional study surveying general surgery residents at a university-affiliated teaching hospital about their views on AI in medicine and surgical training.

SARS-CoV-2 Bottlenecks and Tissue-Specific Adaptation in the Central Nervous System.

Severe COVID-19 and post-acute sequelae of SARS-CoV-2 infection are associated with neurological complications that may be linked to direct infection of the central nervous system (CNS), but the selective pressures ruling neuroinvasion are poorly defined. Here, we assessed SARS-CoV-2 evolution in the lung versus CNS of infected mice. Higher levels of viral diversity were observed in the CNS than the lung after intranasal challenge with a high frequency of mutations in the Spike furin cleavage site (FCS).