Intradermal versus subcutaneous immunization: Effects of administration route using a lipid-PLGA hybrid nanoparticle tuberculosis vaccine.

Tuberculosis (TB) remains a significant global health challenge, latently affecting around a quarter of the global population. The sole licensed TB vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), shows variable efficacy, particularly among adolescents and adults, underscoring the pressing need for more effective vaccination strategies. The administration route is crucial for vaccine efficacy, and administration via the skin, being rich in immune cells, may offer advantages over conventional subcutaneous routes, which lack direct access to abundant antigen-presenting cells.

Unraveling the genetic landscape of susceptibility to multiple primary cancers.

With advances in cancer screening and treatment, there is a growing population of cancer survivors who may develop subsequent primary cancers. While hereditary cancer syndromes account for only a portion of multiple cancer cases, we sought to explore the role of common genetic variation in susceptibility to multiple primary tumors. We conducted a cross-ancestry genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) of 10,983 individuals with multiple primary cancers, 84,475 individuals with single cancer, and 420,944 cancer-free controls from two large-scale studies.

Triflyl [F]Fluoride as a Solution for Base-Sensitive Late-Stage Nucleophilic Aromatic F-Fluorination Reactions.

Fluorine-18 is the predominant radionuclide used to label Positron Emission Tomography (PET) tracers. One outstanding challenge in nucleophilic aromatic radiofluorination reactions is the sensitivity of precursors and catalysts for basic reaction conditions, which are necessary for the work-up of [F]fluoride, resulting in limited reproducibility. Triflyl [F]fluoride is a new [F]fluoride source that allows freedom in choice of type and amounts of base and cryptand.

Evaluation of PLGA, lipid-PLGA hybrid nanoparticles, and cationic pH-sensitive liposomes as tuberculosis vaccine delivery systems in a Mycobacterium tuberculosis challenge mouse model - A comparison.

Tuberculosis (TB) continues to pose a global threat for millennia, currently affecting over 2 billion people and causing 10.6 million new cases and 1.3 million deaths annually.

Investigating the Impact of Additional Congenital Malformations on Speech Outcomes at age Five in Children with a Cleft Palate.

Objective: To determine whether children born with a cleft palate ± lip (CP ± L) and additional congenital differences (ACDs - including 'Congenital malformations and deformations' as coded in ICD-10), are less likely to meet the three national speech outcome standards at age five compared to children with CP ± L and no ACDs.

Design: An observational study, utilizing national data from the UK Cleft Registry and Audit NEtwork (CRANE) Database linked to national administrative data of hospital admissions.

Setting: National Health Service, England.

Pancreatitis pain quality changes at year 1 follow-up, but GP130 remains a biomarker for pain.

Background/objectives: Debilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). CP pain is dynamic due to multiple underlying mechanisms. The objective of this study was to 1) evaluate changes in pain phenotype at one year follow-up and 2) validate putative pain biomarkers in a prospective cohort study.

Evaluation of Chronic Pancreatitis Prognosis Score in an American Cohort.

Introduction: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort.

Methods: The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279).

Cationic pH-sensitive liposome-based subunit tuberculosis vaccine induces protection in mice challenged with Mycobacterium tuberculosis.

Tuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current vaccine, BCG, has insufficient impact. In this article, a novel subunit vaccine against TB was developed, using the Ag85B-ESAT6-Rv2034 fusion antigen, two adjuvants - CpG and MPLA, and a cationic pH-sensitive liposome as a delivery system, representing a new TB vaccine delivery strategy not previously reported for TB.

Expression of integrin αβ in medullary thyroid carcinoma.

Tumor markers often remain elevated after intended curative resection of medullary thyroid carcinoma (MTC). The aim of this study was to determine the expression of αβ, a promising theranostics target, in MTC and its metastases. Aβ expression was analyzed in 104 patients using a tissue microarray and correlated with clinicopathological variables and survival.

Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria.

The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages.

Cognitive function and bladder health among midlife adult women in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Objective: The aim of this study was to examine whether different aspects of women's cognitive function are associated with lower urinary tract symptoms (LUTS) and their impact.

Methods: In 2010-2011, women aged 42 to 57 years in the Coronary Artery Risk Development in Young Adults study completed different tests of cognitive function, including the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop test. Two years later, data on LUTS and their impact were collected.

Analysis and Reporting of Randomized Trials in Cleft Palate Surgery: Learning from the Timing of Primary Surgery (TOPS) Trial.

The Timing of Primary Surgery (TOPS) trial was published August 2023 in the New England Journal of Medicine and is a milestone achievement for a study focused on cleft palate. Due to the complexity of outcome reporting in cleft and the rarity of such comparative trials, TOPS presents a useful opportunity to critically review the design, analysis and reporting strategies utilised. This perspective article focused on the inclusion of participants, the choice of the primary outcome measure and the analysis of ordinal data within the trial.

Obstructive sleep apnea severity, circulating biomarkers, and cancer risk.

Study Objectives: To determine whether obstructive sleep apnea (OSA) severity and/or biomarkers of inflammation/angiogenesis are associated with incident cancer in this clinical cohort.

Methods: Consenting adult patients at the University of British Columbia Hospital between 2003 and 2014 completed a questionnaire about their medical history and sleep habits prior to undergoing a polysomnogram. Blood samples were collected the morning after polysomnography and processed for biomarkers of inflammation and angiogenesis.

Identification of kinase modulators as host-directed therapeutics against intracellular methicillin-resistant .

The increasing prevalence of antimicrobial-resistant strains, especially methicillin-resistant (MRSA), poses a threat to successful antibiotic treatment. Unsuccessful attempts to develop a vaccine and rising resistance to last-resort antibiotics urge the need for alternative treatments. Host-directed therapy (HDT) targeting critical intracellular stages of emerges as a promising alternative, potentially acting synergistically with antibiotics and reducing the risk of drug resistance.

Use of pancreatic endotherapy in patients with chronic pancreatitis: results from a multicenter cohort study in the United States.

Background And Aims: Although pancreatic endotherapy (PET) is commonly used for treating adverse events of chronic pancreatitis, data on the frequency and factors associated with the use of PET are limited. Our aim was to define the use of and factors predictive for receiving PET in a well-characterized chronic pancreatitis cohort.

Methods: This is a cross-sectional analysis of data from PROCEED, a multicenter U.

DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer.

Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997-12/31/2006 who did not receive curative treatments.

Are NHS cleft services in England ready for delegation to integrated care systems?

Cleft care services in the UK have been nationally funded since centralisation 25 years ago and during this time have been able to demonstrate improved clinical outcomes. Integrated care systems have been introduced into legislature as part of the Health Care Act of 2022 and will be responsible for the paradigm shift of allocating funds on a regional basis for cleft care services in England from 2024. The proposed population-based funding formulas present an opportunity to improve current inequities in cleft care, including access to speech therapy and adult services.

Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study.

Objective: To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP).

Methods: We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase.

Characterizing the spectrum of bladder health and lower urinary tract symptoms among men: Results from the CARDIA study.

Objectives: To operationalize a new definition for bladder health, we examined the distribution and impact of lower urinary tract symptoms (LUTS), along with risk factors, among men in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Methods: LUTS were defined by American Urologic Association Symptom Index (AUASI) scores and impact on quality of life (QoL). Separate questions assessed urinary incontinence (UI) and postvoid dribbling.

Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite-instable colorectal cancers.

Up to 30% of colorectal cancers (CRCs) develop from sessile serrated lesions (SSLs). Within the serrated neoplasia pathway, at least two principally distinct oncogenetic routes exist generating microsatellite-stable and microsatellite-instable CRCs, respectively. Aberrant DNA methylation (DNAm) is found early in the serrated pathway and might play a role in both oncogenetic routes.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study.

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

The economics of nature's healing touch: A systematic review and conceptual framework of green space, pharmaceutical prescriptions, and healthcare expenditure associations.

Green spaces play a crucial role in promoting sustainable and healthy lives. Recent evidence shows that green space also may reduce the need for healthcare, prescription medications, and associated costs. This systematic review provides the first comprehensive assessment of the available literature examining green space exposure and its associations with healthcare prescriptions and expenditures.

Discrimination and bladder health among women in the CARDIA cohort study: Life course and intersectionality perspectives.

Objective: This study examines whether discriminatory experiences are associated with lower urinary tract symptoms (LUTS) and their impact among 972 women in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study, which recruited participants from 4 cities in the United States.

Method: Exposure to discrimination was assessed 3 times (1992-93, 2000-01, 2010-11) and averaged across assessments. Participants separately reported whether they experienced discrimination on the basis of their gender, race or color, and socioeconomic position or social class.