Stemmed Tibial Fixation for Primary Total Knee Arthroplasty in Obese Patients-A National Registry Study.

Background: We investigated if the use of augmented tibial fixation with stems in primary total knee arthroplasty (TKA) in obese patients was associated with a difference in reason for revision, type of revision, or overall revision rate.

Methods: Data from the Australian Orthopaedic Association National Joint Replacement Registry compared reason for revision, rate, and type of revision between primary TKA using stemmed tibial prostheses to nonstemmed prostheses, stratified by body mass index (BMI) and obesity. The cumulative percent revision was obtained using the Kaplan-Meier method, and Cox proportional hazards models estimated hazard ratios (HRs) adjusted for age and sex with 95% confidence intervals (CIs).

BIANCA-MS: An optimized tool for automated multiple sclerosis lesion segmentation.

In this work we present BIANCA-MS, a novel tool for brain white matter lesion segmentation in multiple sclerosis (MS), able to generalize across both the wide spectrum of MRI acquisition protocols and the heterogeneity of manually labeled data. BIANCA-MS is based on the original version of BIANCA and implements two innovative elements: a harmonized setting, tested under different MRI protocols, which avoids the need to further tune algorithm parameters to each dataset; and a cleaning step developed to improve consistency in automated and manual segmentations, thus reducing unwanted variability in output segmentations and validation data. BIANCA-MS was tested on three datasets, acquired with different MRI protocols.

Next-Generation JAK2 Inhibitors for the Treatment of Myeloproliferative Neoplasms: Lessons from Structure-Based Drug Discovery Approaches.

Unlabelled: Selective inhibitors of Janus kinase (JAK) 2 have been in demand since the discovery of the JAK2 V617F mutation present in patients with myeloproliferative neoplasms (MPN); however, the structural basis of V617F oncogenicity has only recently been elucidated. New structural studies reveal a role for other JAK2 domains, beyond the kinase domain, that contribute to pathogenic signaling. Here we evaluate the structure-based approaches that led to recently-approved type I JAK2 inhibitors (fedratinib and pacritinib), as well as type II (BBT594 and CHZ868) and pseudokinase inhibitors under development (JNJ7706621).

Efficacy and safety of oral immunotherapy for peanut, cow's milk, and hen's egg allergy: A systematic review of randomized controlled trials.

Background: Oral immunotherapy (OIT) is a promising treatment for food allergies; however, safety is a concern. We synthesized evidence from the best randomized controlled trials (RCTs) on efficacy/safety of OIT for desensitization (DS) and remission (sustained unresponsiveness (SU)) in IgE mediated allergy to peanut, hen's eggs, and cow's milk. BODY: We searched Pubmed, EMBASE, and Cochrane databases (Until Oct 22) identifying 16 eligible RCTs published in English measuring food allergy by food challenge at the beginning and at the end of the study.

Immune modulation in chronic myeloid leukaemia patients treated with nilotinib and interferon-alpha.

The addition of interferon to tyrosine kinase inhibitors (TKIs), to improve deep molecular response (DMR) and potentially treatment-free remission (TFR) rates in chronic-phase chronic myeloid leukaemia (CP-CML) patients is under active investigation. However, the immunobiology of this combination is poorly understood. We performed a comprehensive longitudinal assessment of immunological changes in CML patients treated with nilotinib and interferon-alpha (IFN-α) within the ALLG CML11 trial (n = 12) or nilotinib alone (n = 17).

Craniofacial anomalies in a murine model of heterozygous fibroblast growth factor 10 gene mutation.

Objective: Dysregulation of Fibroblast Growth Factor 10 (FGF10), a member of the family of Fibroblast Growth Factor (FGF) proteins, has been implicated in craniofacial and dental anomalies, including craniosynostosis, cleft palate, and Lacrimo-Auriculo-Dento-Digital Syndrome. The aim of this murine study was to assess the craniofacial and dental phenotypes associated with a heterozygous FGF10 gene (FGF10 ) mutation at skeletal maturity.

Methods: Skulls of 40 skeletally mature mice, comprising two genotypes (heterozygous FGF10 mutation, n = 22; wildtype, n = 18) and two sexes (male, n = 23; female, n = 17), were subjected to micro-computed tomography.

Corrigendum: Twenty-four-hour time-use composition and cognitive function in older adults: cross-sectional findings of the ACTIVate study.

[This corrects the article DOI: 10.3389/fnhum.2022.

An effective hyper-parameter can increase the prediction accuracy in a single-step genetic evaluation.

The H-matrix best linear unbiased prediction (HBLUP) method has been widely used in livestock breeding programs. It can integrate all information, including pedigree, genotypes, and phenotypes on both genotyped and non-genotyped individuals into one single evaluation that can provide reliable predictions of breeding values. The existing HBLUP method requires hyper-parameters that should be adequately optimised as otherwise the genomic prediction accuracy may decrease.

Receptor Recycling by Retromer.

The highly conserved retromer complex controls the fate of hundreds of receptors that pass through the endolysosomal system and is a central regulatory node for diverse metabolic programs. More than 20 years ago, retromer was discovered as an essential regulator of endosome-to-Golgi transport in yeast; since then, significant progress has been made to characterize how metazoan retromer components assemble to enable its engagement with endosomal membranes, where it sorts cargo receptors from endosomes to the -Golgi network or plasma membrane through recognition of sorting motifs in their cytoplasmic tails. In this review, we examine retromer regulation by exploring its assembled structure with an emphasis on how a range of adaptor proteins shape the process of receptor trafficking.

The association between diet quality, plant-based diets, systemic inflammation, and mortality risk: findings from NHANES.

Purpose: To our knowledge, no studies have examined the association of diet quality and plant-based diets (PBD) with inflammatory-related mortality in obesity. Therefore, this study aimed to determine the joint associations of Healthy Eating Index-2015 (HEI-2015), plant-based dietary index (PDI), healthy PDI (hPDI), unhealthy PDI (uPDI), pro-vegetarian dietary index (PVD), and systemic inflammation with all-cause, cardiovascular disease (CVD), and cancer mortality risks by obesity status.

Methods: Participants from NHANES were included in cross-sectional (N = 27,915, cycle 1999-2010, 2015-2018) and longitudinal analysis (N = 11,939, cycle 1999-2008).

Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

Background: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content.

Phenotypic variance partitioning by transcriptomic gene expression levels and environmental variables for anthropometric traits using GTEx data.

Phenotypic variation in human is the results of genetic variation and environmental influences. Understanding the contribution of genetic and environmental components to phenotypic variation is of great interest. The variance explained by genome-wide single nucleotide polymorphisms (SNPs) typically represents a small proportion of the phenotypic variance for complex traits, which may be because the genome is only a part of the whole biological process to shape the phenotypes.

Host genetic determinants of COVID-19 susceptibility and severity: A systematic review and meta-analysis.

Genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) associated with susceptibility and severity of coronavirus disease 2019 (COVID-19). However, identified SNPs are inconsistent across studies, and there is no compelling consensus that COVID-19 status is determined by genetic factors. Here, we conducted a systematic review and meta-analysis to determine the effect of genetic factors on COVID-19.

A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects against cardiovascular disease by metabolising the risk factor asymmetric dimethylarginine (ADMA). However, the question whether the second DDAH isoform, DDAH2, directly metabolises ADMA has remained unanswered. Consequently, it is still unclear if DDAH2 may be a potential target for ADMA-lowering therapies or if drug development efforts should focus on DDAH2's known physiological functions in mitochondrial fission, angiogenesis, vascular remodelling, insulin secretion, and immune responses.

Obesity is associated with an increased risk of undergoing hip replacement in Australia.

Background: Obesity is a known risk factor for the development of hip osteoarthritis. The aim of this study was to investigate whether obesity is associated with the risk of undergoing total hip replacement (THR) in Australia.

Methods: A cohort study was conducted comparing data from the Australian Bureau of Statistics and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from 2017 to 2018.

Differential Structural Brain Changes Between Responders and Nonresponders After Physical Exercise Therapy for Chronic Nonspecific Neck Pain.

Objectives: Physical exercise therapy is effective for some people with chronic nonspecific neck pain but not for others. Differences in exercise-induced pain-modulatory responses are likely driven by brain changes. We investigated structural brain differences at baseline and changes after an exercise intervention.

Peripheral and central neuroplasticity in a mouse model of endometriosis.

Chronic pelvic pain (CPP) is the most debilitating symptom of gynaecological disorders such as endometriosis. However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and transmit nociceptive events and how these signals are processed within the central nervous system (CNS). Using a previously characterized mouse model of endometriosis, we investigated whether the increased pain sensitivity occurring in endometriosis could be attributed to (i) changes in mechanosensory properties of sensory afferents innervating the reproductive tract, (ii) alterations in sensory input from reproductive organs to the spinal cord or (iii) neuroinflammation and sensitization of spinal neural circuits.

The kidney failure risk equation predicts kidney failure: Validation in an Australian cohort.

Aims: Predicting progression to kidney failure for patients with chronic kidney disease is essential for patient and clinicians' management decisions, patient prognosis, and service planning. The Tangri et al Kidney Failure Risk Equation (KFRE) was developed to predict the outcome of kidney failure. The KFRE has not been independently validated in an Australian Cohort.

Primary, allied health, geriatric, pain and palliative healthcare service utilisation by aged care residents, 2012-2017.

Objectives: To examine the incidence and trends in primary care, allied health, geriatric, pain and palliative care service use by permanent residential aged care (PRAC) residents and the older Australian population.

Methods: Repeated cross-sectional analyses on PRAC residents (N = 318,484) and the older (≥65 years) Australian population (N ~ 3.5 million).

You are What You Drink? How Associations Between Profiles of Beverage Consumption and Type 2 Diabetes Risk are Mediated by Biomarker Networks.

Background: Multiple studies have independently investigated the associations of the consumption of individual beverage types and specific plasma biomarkers with the risk of type 2 diabetes (T2D). However, as individuals do not consume single beverage types exclusively and plasma biomarkers do not act in isolation, it remains unclear how patterns of beverage consumption and plasma biomarker networks associate both with each other and T2D risk.

Objectives: We aimed to elucidate potential dietary determinants of T2D risk by defining a model that describes habitual beverage consumption profiles in relation to identified networks of circulating plasma biomarkers.

Obesity is associated with an increased risk of undergoing shoulder arthroplasty in Australia.

Background: The aim of this study was to examine the incidence of overweight and obesity in patients undergoing primary total shoulder arthroplasty (TSA) for osteoarthritis (OA) in Australia compared to the incidence of obesity in the general population.

Materials And Methods: A 2017/18 cohort consisting of 2997 patients from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) who underwent TSA were compared with matched controls from the Australian Bureau of Statistics (ABS) National Health Survey from the same time period. The 2 groups were analyzed according to body mass index (BMI) category, sex, and age.

TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms.

Revised diagnostic criteria for myeloid neoplasms (MN) issued by the International Consensus Classification (ICC) and the World Health Organization (WHO) recommended major change pertaining to TP53-mutated (TP53) MN. However, these assertions have not been specifically examined in therapy-related myeloid neoplasm (t-MN), a subset enriched with TP53. We analyzed 488 t-MN patients for TP53.

The effects of age and biological sex on the association between I-wave recruitment and the response to cTBS: An exploratory study.

The neuroplastic response to continuous theta burst stimulation (cTBS) is inherently variable. The measurement of I-wave latencies has been shown to strongly predict the magnitude and direction of the response to cTBS, whereby longer latencies are associated with stronger long-term depression-like responses. However, potential differences in this association relating to age and sex have not been explored.

Factors predicting survival following alloSCT in patients with therapy-related AML and MDS: a multicenter study.

Therapy-related myeloid neoplasms (t-MN) are aggressive myeloid neoplasms. Factors predicting post-allogeneic stem cell transplant (alloSCT) survival are not well-known. We studied the prognostic utility of factors at: t-MN diagnosis, pre-alloSCT, and post-alloSCT.