Exercise perceptions and practices of people receiving peritoneal dialysis: An international cross-sectional survey.

BACKGROUND: Low physical activity and functional impairment are prevalent and unaddressed in people receiving peritoneal dialysis (PD). Exercise has been shown to improve physical function and mental health for people with kidney disease. METHODS: Cross-sectional descriptive survey aimed at identifying the exercise and physical activity perceptions and practice patterns of people receiving PD. The survey was developed and pretested with persons living with kidney disease, PD clinicians and exercise specialists. RESULTS: There were 108 respondents (people receiving PD) with the majority from Canada (68%) and the United Kingdom (25%). Seventy-one per cent were engaged in physical activity two or more times per week. Most (91.8%) believed that physical activity is beneficial, and 61.7% reported healthcare provider discussion about physical activity. Perceptions regarding weightlifting restrictions varied: 76% were told not to lift weight with a maximum amount ranging from 2 kg to 45 kg. Few (28%) were instructed to drain PD fluid prior to physical activity. Mixed advice regarding swimming ability was common (44% were told they could swim and 44% were told they should not). CONCLUSIONS: Knowledge gaps suggest that education for both healthcare providers and patients is needed regarding the practice of exercise for people living with PD. Common areas of confusion include the maximum weight a person should lift, whether exercise was safe with or without intrabdominal PD fluid in situ and whether swimming is allowed. Further research is needed to provide patients with evidence-based recommendations rather than defaulting to restricting activity.

Structural and genetic diversity in the secreted mucins, MUC5AC and MUC5B.

The secreted mucins MUC5AC and MUC5B play critical defensive roles in airway pathogen entrapment and mucociliary clearance by encoding large glycoproteins with variable number tandem repeats (VNTRs). These polymorphic and degenerate protein coding VNTRs make the loci difficult to investigate with short reads. We characterize the structural diversity of MUC5AC and MUC5B by long-read sequencing and assembly of 206 human and 20 nonhuman primate (NHP) haplotypes. We find that human MUC5B is largely invariant (5761-5762aa); however, seven haplotypes have expanded VNTRs (6291-7019aa). In contrast, 30 allelic variants of MUC5AC encode 16 distinct proteins (5249-6325aa) with cysteine-rich domain and VNTR copy number variation. We grouped MUC5AC alleles into three phylogenetic clades: H1 (46%, ~5654aa), H2 (33%, ~5742aa), and H3 (7%, ~6325aa). The two most common human MUC5AC variants are smaller than NHP gene models, suggesting a reduction in protein length during recent human evolution. Linkage disequilibrium (LD) and Tajima's D analyses reveal that East Asians carry exceptionally large MUC5AC LD blocks with an excess of rare variation (p<0.05). To validate this result, we used Locityper for genotyping MUC5AC haplogroups in 2,600 unrelated samples from the 1000 Genomes Project. We observed signatures of positive selection in H1 and H2 among East Asians and a depletion of the likely ancestral haplogroup (H3). In Africans and Europeans, H3 alleles show an excess of common variation and deviate from Hardy-Weinberg equilibrium, consistent with heterozygote advantage and balancing selection. This study provides a generalizable strategy to characterize complex protein coding VNTRs for improved disease associations.

A qualitative study of supporters of adults following a suicide-related psychiatric emergency.

INTRODUCTION: Family, friends, and romantic partners (i.e., supporters) play a key role in the implementation of safety and support measures for loved ones with elevated risk for suicide; yet despite the link between interpersonal factors and suicide risk, few supporter-focused interventions exist. METHOD: This qualitative study to inform intervention development was conducted from September 2021 to March 2022 and explored (a) the feasibility and acceptability of a single-session phone call to a support person (n = 30, 67% female, 88% White non-Hispanic, Mage = 40.3 [SD = 17.1]) nominated during an emergency department (ED) visit for suicide risk and (b) the needs of supporters during and after a loved one's suicide crisis. RESULTS: Of the 30 supporters nominated, 27 were eligible to participate and were contacted. Eighteen completed an interview (66%). Seven core themes with 26 subthemes were identified characterizing the supporter's experience prior to, during, and following their loved one's suicide crisis. We found moderate acceptability and feasibility of a single-session supportive phone call to a support person following an ED visit for suicide risk. DISCUSSION: Supporters reported a period of stress prior to and during the ED visit as well as adaptive coping with continued barriers and challenges. Brief interventions aimed at improving communication between the supporter, patient, and their care team; defining roles; and enhancing practical and emotional support are likely to be acceptable and feasible. Further study is needed to determine whether brief interventions to improve supporter self-efficacy can benefit both supporter and patient. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Body composition assessment by artificial intelligence can be a predictive tool for short-term postoperative complications in Hartmann's reversals.

BACKGROUND: Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann's reversal procedure in the prediction of short-term postoperative complications. METHODS: A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne. Sarcopenia in our study was defined as a skeletal muscle index (SMI), calculated as Skeletal Muscle Area (SMA) /height2 < 38.5 cm2/m2 in women and < 52.4 cm2/m2 in men. RESULTS: Between 2010 and 2020, 47 patients (mean age 63.1 ± 12.3 years; male, n = 28 (59.6%) underwent body composition analysis. Twenty-one patients (44.7%) were sarcopenic, and 12 (25.5%) had evidence of sarcopenic obesity. The most common postoperative complication was surgical site infection (SSI) (n = 8, 17%). Sarcopenia (n = 7, 87.5%, p = 0.02) and sarcopenic obesity (n = 5, 62.5%, p = 0.02) were significantly associated with SSIs. The risks of developing an SSI were 8.7 times greater when sarcopenia was present. CONCLUSION: Sarcopenia and sarcopenic obesity were related to postoperative complications following Hartmann's reversal. Body composition measured by a validated AI algorithm may be a beneficial tool for predicting short-term surgical outcomes for these patients.

No Common Candidate Genes for Resistance to Fusarium graminearum, F. proliferatum, F. sporotrichioides, and F. subglutanins in Soybean (Glycine max L.) Accessions from Maturity Groups 0 and I: Findings from Genome-Wide Association Mapping.

Seedling diseases and root rot, caused by species of Fusarium, can limit soybean (Glycine max L.) production in the United States. Currently, there are few commercially available cultivars resistant to Fusarium. This study was conducted to assess the resistance of soybean maturity group (MG) accessions from 0 and I to Fusarium proliferatum, F. sporotrichioides, and F. subglutinans, as well as to identify common quantitative trait loci (QTL) for resistance to these pathogens, in addition to F. graminearum, using a genome-wide association study (GWAS). A total of 155, 91, and 48 accessions from the USDA soybean germplasm collection from maturity groups 0 and I were screened with a single isolate each of F. proliferatum, F. sporotrichioides, and F. subglutinans, respectively, using the inoculum layer inoculation method in the greenhouse. The disease severity was assessed 21 days post-inoculation and analyzed using non-parametric statistics to determine the relative treatment effects (RTE). Eleven and seven accessions showed significantly lower RTEs when inoculated with F. proliferatum and F. subglutinans, respectively, compared to the susceptible cultivar 'Williams 82'. One accession was significantly less susceptible to both F. proliferatum and F. subglutinans. The GWAS conducted with 41,985 single-nucleotide markers identified one QTL associated with resistance to both F. proliferatum and F. sporotrichioides, as well as another QTL for resistance to both F. subglutinans and F. graminearum. However, no common QTLs were identified for the four pathogens. The USDA accessions and QTLs identified in this study can be utilized to selectively breed resistance to multiple species of Fusarium.

Food insecurity in children with heart disease.

PURPOSE OF REVIEW: This review discusses the epidemiology of food insecurity (FI) and its consequences in children with congenital heart disease. We aimed to highlight current interventions to screen and address food insecurity in the context of pediatric cardiology and to offer strategies for providers to engage in this meaningful work. RECENT FINDINGS: Food insecurity is consistently associated with poor health outcomes in children. In the United States, 17.3% of households with children experience FI. Nonwhite and single-parent families are disproportionately affected. Interestingly, because of a low-quality diet, FI is associated with childhood obesity, putting affected children at increased risk for cardiovascular morbidity and mortality over time. Children with congenital heart disease are susceptible to poor outcomes due to unique altered metabolic demands, increased risk for growth impairment, frequent need for specialized feeding regimens, and additional morbidity associated with heart surgery in underweight children. SUMMARY: Today, the burden of screening for FI is most commonly placed on general pediatricians. Considering the importance of nutrition to cardiovascular health and general wellbeing, and the ease with which screening can be performed, pediatric cardiologists and other subspecialists should take a more active role in FI screening.

The Association Between Craniofacial Fracture Patterns and Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) is a rare but potentially devastating complication of craniofacial trauma. Approximately half of patients with TON sustain permanent vision loss. In this study, we sought to identify the most common fracture patterns associated with TON. We performed a retrospective review of craniomaxillofacial CT scans of trauma patients who presented to the R Adams Cowley Shock Trauma Center from 2015 to 2017. Included were adult patients who had orbital fractures with or without other facial fractures. Patients diagnosed with TON by a formal ophthalmologic examination were analyzed. Craniofacial fracture patterns were identified. Bivariate analysis and multivariate logistic regression were performed to identify craniofacial fracture patterns most commonly associated with TON. A total of 574 patients with orbital fractures who met inclusion criteria [15 (2.6%)] were diagnosed with TON. The median [interquartile range (IQR)] age was 44 (28-59) years. Patients with optic canal fractures and sphenoid sinus fractures had greater odds of TON compared with patients who did not have these fracture types [adjusted odds ratio (aOR) 95% confidence interval (CI) 31.8 (2.6->100), 8.1 (2.7-24.4), respectively]. Patients who sustain optic canal and sphenoid sinus fractures in the setting of blunt facial trauma are at increased odds of having a TON. Surgeons and other physicians involved in the care of these patients should be aware of this association.

Perceptual decoupling or trigger happiness: the effect of response delays and shorter presentation times on a go-no-go task with a high go prevalence.

In the current investigation, we modified the high Go, low No-Go Sustained Attention to Response Task (SART). Some researchers argue a commission error, an inappropriate response to a No-Go stimulus, in the SART is due to the participant being inattentive, or perceptually decoupled, during stimulus onset. Response delays in the SART reduce commission errors. A response delay may therefore enable a participant who is initially inattentive to recouple their attention in time to appropriately perceive the stimulus and withhold a response to a No-Go stimulus. However, shortening stimulus display duration in the SART should limit the possibility of the participant identifying the stimulus later, if they are initially not attending the stimulus. A response delay should not reduce commission errors if stimulus duration is kept to the minimum duration enabling stimulus recognition. In two experiments, we shortened stimulus onset to offset duration and added response delays of varying lengths. In both experiments, even when stimulus duration was shortened, response delays notably reduced commission errors if the delay was greater than 250 ms. In addition, using the Signal Detection Theory perspective in which errors of commission in the SART are due to a lenient response bias-trigger happiness, we predicted that response delays would result in a shift to a more conservative response bias in both experiments. These predictions were verified. The errors of commission in the SART may not be a measures of conscious awareness per se, but instead indicative of the level of participant trigger happiness-a lenient response bias.

Fragment-Based Discovery of Allosteric Inhibitors of SH2 Domain-Containing Protein Tyrosine Phosphatase-2 (SHP2).

The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signaling and inhibit the proliferation of RTK-driven cancer cell lines. Here, we describe the first reported fragment-to-lead campaign against SHP2, where X-ray crystallography and biophysical techniques were used to identify fragments binding to multiple sites on SHP2. Structure-guided optimization, including several computational methods, led to the discovery of two structurally distinct series of SHP2 inhibitors binding to the previously reported allosteric tunnel binding site (Tunnel Site). One of these series was advanced to a low-nanomolar lead that inhibited tumor growth when dosed orally to mice bearing HCC827 xenografts. Furthermore, a third series of SHP2 inhibitors was discovered binding to a previously unreported site, lying at the interface of the C-terminal SH2 and catalytic domains.

Transcatheter aortic valve replacement achieves similar predicted effective orifice area to surgical aortic valve replacement in bicuspid aortic stenosis.

BACKGROUND: Studies comparing transcatheter and surgical aortic valve replacement (TAVR and SAVR) for patients with trileaflet aortic stenosis (AS) have found similar or larger effective orifice area (EOA) for TAVR prostheses. To our knowledge, no studies have compared EOA in patients undergoing TAVR versus SAVR for bicuspid AS. METHODS: We retrospectively compared prosthetic valvular sizing and predicted EOA for patients with bicuspid AS undergoing TAVR or SAVR at our institution between January 1, 2016, and December 31, 2021. We excluded patients undergoing procedures for indications other than AS and those without a pre-procedural gated Chest CT. Comparisons included demographics, comorbidities, annular size, prosthetic valve size, predicted EOA and prosthesis-patient mismatch (PPM) for TAVR (N = 78) and SAVR (N = 74) cohorts. RESULTS: TAVR patients had smaller pre-procedural annular area (501.7 mm2 vs. 571.8 mm2, p < 0.05) and annular perimeter (80.6 mm vs. 86.5 mm, p < 0.05), but larger mean implanted prosthetic valve size (26.4 mm vs 24.2 mm, p < 0.001) compared to SAVR patients. No differences were observed in predicted EOA, predicted EOA indexed to patient body surface area (EOAi), or predicted PPM grade between TAVR and SAVR groups, including in cohorts sorted by pre-procedural annular size. CONCLUSIONS: For bicuspid AS patients undergoing aortic valve replacement, TAVR achieves similar predicted EOA to SAVR. These data support the use of TAVR in selected patients with bicuspid AS and can inform heart team discussions.

Imaging of Antepartum and Postpartum Hemorrhage.

Severe obstetric hemorrhage is a leading cause of maternal mortality and morbidity worldwide. Major hemorrhage in the antepartum period presents potential risks for both the mother and the fetus. Similarly, postpartum hemorrhage (PPH) accounts for up to a quarter of maternal deaths worldwide. Potential causes of severe antepartum hemorrhage that radiologists should be familiar with include placental abruption, placenta previa, placenta accreta spectrum disorders, and vasa previa. Common causes of PPH that the authors discuss include uterine atony, puerperal genital hematomas, uterine rupture and dehiscence, retained products of conception, and vascular anomalies. Bleeding complications unique to or most frequently encountered after cesarean delivery are also enumerated, including entities such as bladder flap hematomas, rectus sheath and subfascial hemorrhage, and infectious complications of endometritis and uterine dehiscence. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Javitt and Madrazo in this issue.

Validation of the familial chylomicronaemia syndrome (FCS) score in an ethnically diverse cohort from UK FCS registry: Implications for diagnosis and differentiation from multifactorial chylomicronaemia syndrome (MCS).

BACKGROUND AND AIMS: Prognosis and management differ between familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, and multifactorial chylomicronaemia syndrome (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not been validated in other populations. The objective of this study was to validate this score in the UK population and identify any additional factors that might improve it. METHODS: A retrospective validation study was conducted using data from 151 patients comprising 75 FCS and 76 MCS patients. All participants had undergone genetic testing for genes implicated in FCS. Validation was performed by standard methods. Additional variables were identified from clinical data by logistic regression analysis. RESULTS: At the recommended FCS score threshold ≥10 points, the sensitivity and specificity of the score in the UK population were 96% and 75%, respectively. The receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.88 (95% CI 0.83-0.94, p < 0.001). This study identified non-European (predominantly South Asian) ethnicity, parental consanguinity, body mass index (BMI) < 25 kg/m2, and recurrent pancreatitis as additional positive predictors, while BMI >30 kg/m2 was found to be a negative predictor for FCS. However, inclusion of additional FCS predictors had no significant impact on performance of standard FCS score. CONCLUSIONS: Our study validates the FCS score in the UK population to distinguish FCS from MCS. While additional FCS predictors were identified, they did not improve further the score diagnostic performance.

Artificial intelligence measured 3D body composition to predict pathological response in rectal cancer patients.

BACKGROUND: The treatment of locally advanced rectal cancer (LARC) is moving towards total neoadjuvant therapy and potential organ preservation. Of particular interest are predictors of pathological complete response (pCR) that can guide personalized treatment. There are currently no clinical biomarkers which can accurately predict neoadjuvant therapy (NAT) response but body composition (BC) measures present as an emerging contender. The primary aim of the study was to determine if artificial intelligence (AI) derived body composition variables can predict pCR in patients with LARC. METHODS: LARC patients who underwent NAT followed by surgery from 2012 to 2023 were identified from the Australian Comprehensive Cancer Outcomes and Research Database registry (ACCORD). A validated in-house pre-trained 3D AI model was used to measure body composition via computed tomography images of the entire Lumbar-3 vertebral level to produce a volumetric measurement of visceral fat (VF), subcutaneous fat (SCF) and skeletal muscle (SM). Multivariate analysis between patient body composition and histological outcomes was performed. RESULTS: Of 214 LARC patients treated with NAT, 22.4% of patients achieved pCR. SM volume (P = 0.015) and age (P = 0.03) were positively associated with pCR in both male and female patients. SCF volume was associated with decreased likelihood of pCR (P = 0.059). CONCLUSION: This is the first study in the literature utilizing AI-measured 3D Body composition in LARC patients to assess their impact on pathological response. SM volume and age were positive predictors of pCR disease in both male and female patients following NAT for LARC. Future studies investigating the impact of body composition on clinical outcomes and patients on other neoadjuvant regimens such as TNT are potential avenues for further research.

Ecological Momentary Assessment to Explore Fatigue, Mood, and Physical Activity Levels in People Receiving Peritoneal Dialysis.

Introduction: Fatigue is a frequent and debilitating symptom that contributes to poor quality of life for people receiving peritoneal dialysis. Ecological momentary assessment using mobile technology (mEMA) is a novel survey technique that can collect symptom data in real-time and has not been trialed in a peritoneal dialysis cohort. The study aimed to explore real-time fluctuations and associations between fatigue, mood, and physical activity using mEMA. Methods: Adults receiving peritoneal dialysis completed fatigue and mood scales, via a mobile application (app), 5 times daily for 7 days and, concurrently wore an accelerometer. A feasibility questionnaire was completed on the eighth day. Results: Forty-eight adults completed the study. Within-day fatigue fluctuations were observed with severity lowest during mid-morning to early afternoon and peaking at bedtime. Associations between fatigue and mood were observed with a 1-unit change in mood score conferring a 5.2-unit change in fatigue (P < 0.01). Higher volume of physical activity was associated with lower fatigue and enhanced mood. Overall adherence to the app-based surveys was 73% with most participants reporting mobile phones and the mEMA app being easy to use. Conclusion: People receiving peritoneal dialysis experience within day and day-to-day fluctuations in fatigue that appear highly variable. Higher fatigue severity was associated with poorer mood and lower physical activity levels with future studies required to explore if physical activity-based interventions could be a potential strategy for the management of these symptoms. Furthermore, mEMA, and mobile phones, were feasible to capture symptom data with potential to be employed in future research or, as part of improved care.

Progress is impossible without change: understanding the evolving nomenclature of steatotic liver disease and its effect on hepatology practice.

The American, European, and Latin American liver societies have proposed a change in the nomenclature we use to describe alcohol-related liver disease and non-alcoholic fatty liver disease. Additionally, a term encompassing both is now advocated: steatotic liver disease, which includes metabolic dysfunction associated steatotic liver disease (MASLD) and MASLD with greater alcohol consumption (MetALD). These classifications offer increased relevance for clinicians, researchers, and patients alike. In this Viewpoint, we discuss the basis for this nomenclature shift and how it was developed. We also explore the challenges that will be faced in the adoption of such change. The proposed change seeks to banish stigma associated with phrasing such as alcoholic and fatty. However stigma, particularly related to the term fatty, is culturally nuanced, and reflects different entities depending on location. If such a change is internationally accepted, there will be wide-reaching effects on practitioners in primary care and metabolic medicine, and on patients. We discuss those effects and the opportunities the nomenclature change could offer, particularly for patients with alcohol and metabolic risk factors who represent a group previously ignored by clinical trials.

Transcriptomic evaluation of tau and TDP-43 synergism shows tauopathy predominance and reveals potential modulating targets.

Alzheimer's disease (AD), the most common aging-associated neurodegenerative dementia disorder, is defined by the presence of amyloid beta (Aß) and tau aggregates in the brain. However, more than half of patients also exhibit aggregates of the protein TDP-43 as a secondary pathology. The presence of TDP-43 pathology in AD is associated with increased tau neuropathology and worsened clinical outcomes in AD patients. Using C. elegans models of mixed pathology in AD, we have previously shown that TDP-43 specifically synergizes with tau but not Aß, resulting in enhanced neuronal dysfunction, selective neurodegeneration, and increased accumulation of pathological tau. However, cellular responses to co-morbid tau and TDP-43 preceding neurodegeneration have not been characterized. In this study, we evaluate transcriptomic changes at time-points preceding frank neuronal loss using a C. elegans model of tau and TDP-43 co-expression (tau-TDP-43 Tg). We find significant differential expression and exon usage in genes enriched in multiple pathways including lipid metabolism and lysosomal degradation. We note that early changes in tau-TDP-43 Tg resemble changes with tau alone, but a unique expression signature emerges during aging. We test loss-of-function mutations in a subset of tau and TDP-43 responsive genes, identifying new modifiers of neurotoxicity. Characterizing early cellular responses to tau and TDP-43 co-pathology is critical for understanding protective and pathogenic responses to mixed proteinopathies, and an important step in developing therapeutic strategies protecting against pathological tau and TDP-43 in AD.

M-estimation for common epidemiological measures: introduction and applied examples.

M-estimation is a statistical procedure that is particularly advantageous for some comon epidemiological analyses, including approaches to estimate an adjusted marginal risk contrast (i.e. inverse probability weighting and g-computation) and data fusion. In such settings, maximum likelihood variance estimates are not consistent. Thus, epidemiologists often resort to bootstrap to estimate the variance. In contrast, M-estimation allows for consistent variance estimates in these settings without requiring the computational complexity of the bootstrap. In this paper, we introduce M-estimation and provide four illustrative examples of implementation along with software code in multiple languages. M-estimation is a flexible and computationally efficient estimation procedure that is a powerful addition to the epidemiologist's toolbox.