The Milan Score Predicts Objective Gastroesophageal Reflux Disease in Patients With Type 2 Esophagogastric Junction.

Introduction: High-resolution manometry (HRM) allows assessment of esophagogastric junction (EGJ) disruption. While type 3 EGJ predicts definitive gastroesophageal reflux disease (GERD), type 2 EGJ is less clearly implicated in GERD pathogenesis. This study aimed to characterize physiologic findings in type 2 EGJ to determine if the HRM-based Milan Score can define GERD within type 2 EGJ.

Skin Care of Infants Born at 21-23 Weeks' Gestation.

As more neonatal centers are caring for premature infants at 21-23 weeks' gestational age (GA), a growing need for improved practices related to routine skin care exists. Approach to skin care in this GA is challenging because the skin barrier is not completely formed at this developmental stage, leading to an increased risk of insensible water loss; increased sodium and nutritional requirement; and greater susceptibility to injury, infection, and temperature instability. Effective skin care in this population requires a proactive, standardized, multidisciplinary approach.

Effect of the National Enhanced Service for weight management on the content of annual review consultations for patients living with obesity and hypertension and/or diabetes.

Guidelines specify that clinicians should support patients living with obesity by referring to weight management programmes (WMPs), but clinicians do so infrequently. To provide additional support to patients living with obesity and weight-related conditions, the UK government instated the National Enhanced Service (NES) for weight management in England, including a reimbursement to general practices for referring eligible patients to WMPs. To assess the impact of the NES on conversations regarding weight and relevant behavioural risk factors in primary care consultations we recruited 11 medical practices in England where the NES was operating and six comparator practices from Scotland and Wales where the NES was not implemented.

The role of the district nurse providing care to service users with obsessive compulsive disorder.

Service users living with Obsessive compulsive disorder (OCD) often delay or avoid seeking diagnosis or treatment because of a fear of judgement or feelings of shame associated with their obsessions and compulsions. They may feel that their behaviour defies societal norms, which can lead to social isolation, and in turn, further contribute to health inequality. When such individuals present with physical illness and are seen by district nurses, it is imperative that behaviours are understood and approached appropriately.

Structure Determination of FTCNQ on Ag(111): A Systematic Trend in Metal Adatom Incorporation.

A structure determination of the commensurate phase formed by 7,7,8,8-tetracyano-2,3,5,6-tetrafluoroquinodimethane (FTCNQ) absorbed on Ag(111) is reported. Initial characterization was performed using low-energy electron diffraction and synchrotron radiation photoelectron spectroscopy, with quantitative structural data being provided by normal incident X-ray standing waves (NIXSW) and surface X-ray diffraction (SXRD). NIXSW data show the FTCNQ molecule to adopt a "twisted" conformation on the surface, previously found to be associated with metal adatom incorporation into a 2d-metal-organic framework for FTCNQ on Au(111), Ag(100), and Cu(111).

ABBV-319: a CD19-targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies.

Glucocorticoids are key components of the standard-of-care treatment regimens for B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate engineered to reduce glucocorticoid-associated toxicities while possessing 3 distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of a glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced fragment crystallizable (Fc)-mediated effector function via afucosylation of the antibody backbone.

The Role of Telemedicine in Rural Specialty Care: Priorities and Recommendations From Rural Primary Care Physicians.

Introduction: The study goal was to understand telemedicine's role in improving access to rural specialty care. Other outcomes included assessing specialty availability and frequency of referrals at rural sites.

Methods: This mixed methods study included surveys and semi-structured interviews of rural primary care physicians (PCPs).

The prevalence of rumination syndrome and rumination disorder: A systematic review and meta-analysis.

Background: Rumination is characterized by the repeated regurgitation of food. Rumination syndrome is a disorder of gut-brain interaction diagnosed by Rome criteria, whereas rumination disorder is a feeding and eating disorder diagnosed by DSM-5 criteria. We aimed to determine the global prevalence of rumination according to these criteria across all age groups.

The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease.

Objective: A definitive diagnosis of gastroesophageal reflux disease (GERD) depends on endoscopic and/or pH-study criteria. However, high resolution manometry (HRM) can identify factors predicting GERD, such as ineffective esophageal motility (IEM), esophago-gastric junction contractile integral (EGJ-CI), evaluating esophagogastric junction (EGJ) type and straight leg raise (SLR) maneuver response. We aimed to build and externally validate a manometric score (Milan Score) to stratify the risk and severity of the disease in patients undergoing HRM for suspected GERD.

Correction: Minimising the payload solvent exposed hydrophobic surface area optimises the antibody-drug conjugate properties.

[This corrects the article DOI: 10.1039/D3MD00540B.].

The medicinal chemistry evolution of antibody-drug conjugates.

Antibody-drug conjugates (ADCs) comprise 3 components of wildly differing sizes: antibody (150 000 Da), linker (typically <500 Da) and payload (typically <500 Da). While the drug-linker makes up only a small percent of the ADC it has a disproportionately massive impact on all aspects of the ADC. Replacing maleimide with bromoacetamide (BrAc) affords stable attachment of the linker to the antibody cysteine, supports total flexibility for linker design and affords a more homogenous ADC.

An anti-TNF-glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases.

Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti-tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; therefore, an anti-TNF antibody-drug conjugate (ADC) would be mechanistically similar, where lysosomal catabolism could release a GC receptor modulator (GRM) payload to dampen immune cell activity.

Linker substitution influences succinimide ring hydrolysis equilibrium impacting the stability of attachment to antibody-drug conjugates.

Maleimide chemistry is widely used in antibody-drug conjugate (ADC) generation to connect drugs to antibodies through a succinimide linker. The resulting ADC is prone to payload loss a reverse Michael reaction, leading to premature drug release . Complete succinimide hydrolysis is an effective strategy to overcome the instability of ADC.

Impact of dipeptide on ADC physicochemical properties and efficacy identifies Ala-Ala as the optimal dipeptide.

Side chains of natural occurring amino acids vary greatly in terms of charge state, polarity, size and hydrophobicity. Using a linear synthetic route, two amino acids were sequentially coupled to a potent glucocorticoid receptor modulator (GRM) to afford a library of dipeptide-GRM linker payloads with a range of properties. The linker payloads were conjugated to a mouse anti-TNF antibody through interchain disulfide Cys.

Effect of planned pauses versus continuous energy restriction on weight loss and attrition: a systematic review.

Objective: The objective of this study was to investigate whether pausing a weight loss program for a defined period of time could enhance weight loss and reduce attrition.

Methods: Five databases and two trial registries were searched from inception to July 2023. Randomized-controlled trials of adults with overweight and/or obesity were included if they compared planned-pause interventions with continuous energy restriction (CER), usual care, or a minimal intervention.

A Behaviorally Informed Mobile App to Improve the Nutritional Quality of Grocery Shopping (SwapSHOP): Feasibility Randomized Controlled Trial.

Background: Interventions targeting the nutritional quality of grocery shopping have the potential to help improve diet and health outcomes.

Objective: This study aims to assess the feasibility and acceptability of receiving advice on healthier food purchases through SwapSHOP, a behaviorally informed smartphone app that allows users to scan barcodes of grocery products from the United Kingdom, providing nutritional information and personalized swap suggestions to encourage healthier purchases.

Methods: We randomized adult volunteers in a 6-arm parallel-group controlled feasibility trial.

Consensus statement on the interhospital transfer of patients with acute aortic syndrome: TRAVERSING Delphi study.

Background: Standardisation of referral pathways and the transfer of patients with acute aortic syndromes (AAS) to regional centres are recommended by NHS England in the Acute Aortic Dissection Toolkit. The aim of the Transfer of Thoracic Aortic Vascular Emergencies to Regional Specialist INstitutes Group study was to establish an interdisciplinary consensus on the interhospital transfer of patients with AAS to specialist high-volume aortic centres.

Methods: Consensus on the key aspects of interhospital transfer of patients with AAS was established using the Delphi method, in line with Conducting and Reporting of Delphi Studies guidelines.

Antibody drug conjugates beyond cytotoxic payloads.

For many years, antibody drug conjugates (ADC) have teased with the promise of targeted payload delivery to diseased cells, embracing the targeting of the antibody to which a cytotoxic payload is conjugated. During the past decade this promise has started to be realised with the approval of more than a dozen ADCs for the treatment of various cancers. Of these ADCs, brentuximab vedotin really laid the foundations of a template for a successful ADC with lysosomal payload release from a cleavable dipeptide linker, measured DAR by conjugation to the Cys-Cys interchain bonds of the antibody and a cytotoxic payload.

Does FTCNQ Adsorption on Cu(111) Form a 2D-MOF?

The results of a quantitative experimental structural investigation of the adsorption phases formed by 2,3,5,6-tetrafluoro-7,7',8,8'-tetracyanoquinodimethane (FTCNQ) on Cu(111) are reported. A particular objective was to establish whether Cu adatoms are incorporated into the molecular overlayer. A combination of normal incidence X-ray standing waves, low-energy electron diffraction, scanning tunneling microscopy, and X-ray photoelectron spectroscopy measurements, complemented by dispersion-inclusive density functional theory calculations, demonstrates that FTCNQ on Cu(111) does cause Cu adatoms to be incorporated into the overlayer to form a two-dimensional metal-organic framework (2D-MOF).

An insight into the functional alterations in the gut microbiome of healthy adults in response to a multi-strain probiotic intake: a single arm open label trial.

Background: Probiotic supplements, by definition, provide a benefit to the host, but few studies have investigated the effect of probiotic supplements in healthy adult populations.

Purpose: The present, single arm, open label clinical trial, evaluated compositional and functional changes in the fecal microbiome of healthy adults after supplementation with a 14-strain probiotic.

Methods: We analysed the effect of a 14-strain probiotic blend ( NCIMB 30223, NCIMB 30179, NCIMB 30180, NCIMB 30181, NCIMB 30182, NCIMB 30184, subsp.