Unravelling heterogeneous malaria transmission dynamics in the Peruvian Amazon: insights from a cross-sectional survey.

BACKGROUND: Malaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health's "Zero Malaria Plan" targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative. METHODS: A cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors. RESULTS: The survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species. CONCLUSIONS: The study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon.

Transcriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism.

BACKGROUND: Two important questions regarding the genetics of pancreatic adenocarcinoma (PDAC) are 1. Which germline genetic variants influence the incidence of this cancer; and 2. Whether PDAC causally predisposes to associated non-malignant phenotypes, such as type 2 diabetes (T2D) and venous thromboembolism (VTE). METHODS: In this study of 8803 patients with PDAC and 67,523 controls, we first performed a large-scale transcriptome-wide association study to investigate the association between genetically determined gene expression in normal pancreas tissue and PDAC risk. Secondly, we used Mendelian Randomization (MR) to analyse the causal relationships among PDAC, T2D (74,124 cases and 824,006 controls) and VTE (30,234 cases and 172,122 controls). FINDINGS: Sixteen genes showed an association with PDAC risk (FDR <0.10), including six genes not yet reported for PDAC risk (PPIP5K2, TFR2, HNF4G, LRRC10B, PRC1 and FBXL20) and ten previously reported genes (INHBA, SMC2, ABO, PDX1, MTMR6, ACOT2, PGAP3, STARD3, GSDMB, ADAM33). MR provided support for a causal effect of PDAC on T2D using genetic instruments in the HNF4G and PDX1 loci, and unidirectional causality of VTE on PDAC involving the ABO locus (OR 2.12, P < 1e-7). No evidence of a causal effect of PDAC on VTE was found. INTERPRETATION: These analyses identified candidate susceptibility genes and disease relationships for PDAC that warrant further investigation. HNF4G and PDX1 may induce PDAC-associated diabetes, whereas ABO may induce the causative effect of VTE on PDAC. FUNDING: National Institutes of Health (USA).

Genomic characterization and virulence gene profiling of Erysipelothrix rhusiopathiae isolated from widespread muskox mortalities in the Canadian Arctic Archipelago.

BACKGROUND: Muskoxen are important ecosystem components and provide food, economic opportunities, and cultural well-being for Indigenous communities in the Canadian Arctic. Between 2010 and 2021, Erysipelothrix rhusiopathiae was isolated from carcasses of muskoxen, caribou, a seal, and an Arctic fox during multiple large scale mortality events in the Canadian Arctic Archipelago. A single strain ('Arctic clone') of E. rhusiopathiae was associated with the mortalities on Banks, Victoria and Prince Patrick Islands, Northwest Territories and Nunavut, Canada (2010-2017). The objectives of this study were to (i) characterize the genomes of E. rhusiopathiae isolates obtained from more recent muskox mortalities in the Canadian Arctic in 2019 and 2021; (ii) identify and compare common virulence traits associated with the core genome and mobile genetic elements (i.e. pathogenicity islands and prophages) among Arctic clone versus other E. rhusiopathiae genomes; and iii) use pan-genome wide association studies (GWAS) to determine unique genetic contents of the Arctic clone that may encode virulence traits and that could be used for diagnostic purposes. RESULTS: Phylogenetic analyses revealed that the newly sequenced E. rhusiopathiae isolates from Ellesmere Island, Nunavut (2021) also belong to the Arctic clone. Of 17 virulence genes analysed among 28 Arctic clone isolates, four genes - adhesin, rhusiopathiae surface protein-A (rspA), choline binding protein-B (cbpB) and CDP-glycerol glycerophosphotransferase (tagF) - had amino acid sequence variants unique to this clone when compared to 31 other E. rhusiopathiae genomes. These genes encode proteins that facilitate E. rhusiopathiae to attach to the host endothelial cells and form biofilms. GWAS analyses using Scoary found several unique genes to be overrepresented in the Arctic clone. CONCLUSIONS: The Arctic clone of E. rhusiopathiae was associated with multiple muskox mortalities spanning over a decade and multiple Arctic islands with distances over 1000 km, highlighting the extent of its spatiotemporal spread. This clone possesses unique gene content, as well as amino acid variants in multiple virulence genes that are distinct from the other closely related E. rhusiopathiae isolates. This study establishes an essential foundation on which to investigate whether these differences are correlated with the apparent virulence of this specific clone through in vitro and in vivo studies.

Engram Studies: A Call for Historical, Philosophical, and Sociological Approaches.

In this chapter, we identify three distinct avenues of research on the philosophical, historical, and sociopolitical dimensions of engram research. First, we single out the need to refine philosophical understandings of memory within neuroscientific research on the engram. Specifically, we question the place of constructivist and preservationist philosophical claims on memory in the formulation of the engram concept and its operationalization in contemporary neuroscience research. Second, we delve into the received historiography of the engram claiming its disappearance after Richard Semon's (1859-1918) coinage of the concept. Differently from this view, we underline that Semon's legacy is still largely undocumented: Unknown are the ways the engram circulated within studies of organic memory as well as the role Semon's ideas had in specific national contexts of research in neurosciences. Finally, another research gap on the engram concerns a socio-anthropological documentation of the factual and normative resources this research offers to think about memory in healthcare and society. Representations of memory in this research, experimental strategies of intervention into the engram, as well as their translational potential for neurodegenerative (e.g., Alzheimer's disease) and psychiatric (e.g., post-traumatic stress disorder) conditions have not yet received scrutiny notwithstanding their obvious social and political relevance.All these knowledge gaps combined call for a strong commitment towards interdisciplinarity to align the ambitions of a foundational neuroscience of the engram with a socially responsible circulation of this knowledge. What role can the facts, metaphors, and interventional strategies of engram research play in the wider society? With what implications for philosophical questions at the foundation of memory, which have accompanied its study from antiquity? And what can neuro- and social scientists do jointly to shape the social and political framings of engram research?

Flexor Pollicis Longus Weakness Post-proximal Radius Shaft Open Reduction and Internal Fixation: A Case Report.

We report the case of a patient who sustained a right proximal radial shaft fracture. He experienced isolated flexor pollicis longus weakness as a result of a partial anterior interosseous nerve (AIN) injury. The incidence of AIN injury is recognized as an exceptional postoperative complication for this particular type of fracture. It might be helpful to do electrodiagnostic investigations to confirm the diagnosis. A complete clinical recovery of the nerve occurred 16 weeks following the surgical operation.

Causality of genetically determined metabolites on susceptibility to prevalent urological cancers: a two-sample Mendelian randomization study and meta-analysis.

Background: Prevalent urological cancers, including kidney, prostate, bladder, and testicular cancers, contribute significantly to global cancer incidence and mortality. Metabolomics, focusing on small-molecule intermediates, has emerged as a tool to understand cancer etiology. Given the knowledge gap in this field, we employ a two-sample Mendelian randomization (MR) analysis to investigate the causal relationships between genetically determined metabolites (GDMs) and the susceptibility to four common urological cancers. Methods: The study employs genome-wide association studies (GWAS) data from European populations, featuring the most extensive case count available for both blood metabolites and four prevalent urological cancers. Preliminary and secondary MR analyses were separately conducted, employing inverse variance weighted (IVW) as the primary method. Multiple statistical analyses, including the MR-Steiger test, Cochran's Q test, leave-one-out analysis, MR-Egger intercept analysis, and MR-PRESSO analysis, were executed to ensure robustness. Additionally, a meta-analysis was carried out to consolidate findings. The weighted median (WM) method was utilized for a relatively lenient correction (PWM < 0.05). Results: After rigorous genetic variation filtering, 645 out of 1,400 metabolites were included in both preliminary and secondary MR analyses. Preliminary MR analysis identified 96 potential causal associations between 94 distinct metabolites and four urological cancers. Secondary analysis based on Finnish outcome data revealed 93 potential causal associations. Cross-database meta-analysis identified 68 blood metabolites associated with four urological cancers. Notably, 31 metabolites remained significant after using WM for correction, with additional 37 suggestive causal relationships. Reverse MR analysis revealed a significant causal association between genetically predicted prostate cancer and elevated 4-hydroxychlorothalonil levels (IVW, combined OR: 1.039, 95% CI 1.014-1.064, p = 0.002; WM, combined OR: 1.052, 95% CI 1.010-1.095, p = 0.014). Conclusion: This comprehensive MR study provides insights into the causal relationships between blood metabolites and urological cancers, revealing potential biomarkers and therapeutic targets, thereby addressing gaps in understanding and laying the foundation for targeted interventions in urological cancer research and treatment.

Association of food folate with asthma in US children and adolescents: a cross-sectional study.

Background： Asthma is a chronic inflammatory disease. Currently, contradictory findings exist regarding the association between food folate and asthma. Therefore, we hypothesize a positive correlation between food folate and asthma.Purpose： To investigate the possible relationship between food folate intake and the development of asthma in children and adolescents in the United States.Methods： Data from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2009-2018 were analyzed cross-sectionally by covariate adjustment using multivariate logistic regression, restricted triple spline curves, threshold effects, and stratified analyses.Results: There were 8,821 participants, of whom 1,697 (19.2%) self-reported having received a diagnosis of asthma from a physician or other health professional. After accounting for potential confounders, the adjusted odds ratios (ORs) for asthma in the second (T2, 111-178ug/day) and third (T3, >178ug/day) groups were 1.15 (1-1.33) and 1.23 (1.04-1.46), respectively, compared with the group with the lowest food folate intake (T1, <111ug/day). In addition, the association between food folate intake and asthma showed an inverse L-shaped curve (non-linear relationship, p = 0.003), and stratified analysis further validated the robustness of the results. The OR of asthma in subjects with food folate intake less than 263.9ug/day was 1.002 (1.001-1.004).Conclusion: In children and adolescents in the United States, there is a non-linear association (inverted "L" shape) between food folate intake and asthma, with an inflection point at 263.9 micrograms per day.

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

BACKGROUND: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms. METHODS: Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP. RESULTS: A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction (P<0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P=0.018); other outcome measures also indicated benefit with PPoP. CONCLUSIONS: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO. REGISTRATION: URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252.

Where is the research on sport-related concussion in Olympic athletes? A descriptive report and assessment of the impact of access to multidisciplinary care on recovery.

OBJECTIVES: This cohort study reported descriptive statistics in athletes engaged in Summer and Winter Olympic sports who sustained a sport-related concussion (SRC) and assessed the impact of access to multidisciplinary care and injury modifiers on recovery. METHODS: 133 athletes formed two subgroups treated in a Canadian sport institute medical clinic: earlier (≤7 days) and late (≥8 days) access. Descriptive sample characteristics were reported and unrestricted return to sport (RTS) was evaluated based on access groups as well as injury modifiers. Correlations were assessed between time to RTS, history of concussions, the number of specialist consults and initial symptoms. RESULTS: 160 SRC (median age 19.1 years; female=86 (54%); male=74 (46%)) were observed with a median (IQR) RTS duration of 34.0 (21.0-63.0) days. Median days to care access was different in the early (1; nSRC=77) and late (20; nSRC=83) groups, resulting in median (IQR) RTS duration of 26.0 (17.0-38.5) and 45.0 (27.5-84.5) days, respectively (p<0.001). Initial symptoms displayed a meaningful correlation with prognosis in this study (p<0.05), and female athletes (52 days (95% CI 42 to 101)) had longer recovery trajectories than male athletes (39 days (95% CI 31 to 65)) in the late access group (p<0.05). CONCLUSIONS: Olympic athletes in this cohort experienced an RTS time frame of about a month, partly due to limited access to multidisciplinary care and resources. Earlier access to care shortened the RTS delay. Greater initial symptoms and female sex in the late access group were meaningful modifiers of a longer RTS.

Environmental Determinants of Islet Autoimmunity (ENDIA) longitudinal prospective pregnancy to childhood cohort study of Australian children at risk of type 1 diabetes: parental demographics and birth information.

INTRODUCTION: The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort's parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes. RESEARCH DESIGN AND METHODS: Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D. The primary outcome was persistent islet autoimmunity, with children followed until a T1D diagnosis or 10 years of age. Demographic data were collected at enrollment. Lifestyle, clinical and anthropometric data were collected at each visit during pregnancy and clinical pregnancy and birth data were verified against medical case notes. Data were compared between mothers with and without T1D. HLA genotyping was performed on the ENDIA child and all available FDRs. RESULTS: The final cohort comprised 1473 infants born to 1214 gestational mothers across 1453 pregnancies, with 80% enrolled during pregnancy. The distribution of familial T1D probands was 62% maternal, 28% paternal and 11% sibling. The frequency of high-risk HLA genotypes was highest in T1D probands, followed by ENDIA infants, and lowest among unaffected family members. Mothers with T1D had higher rates of pregnancy complications and perinatal intervention, and larger babies of shorter gestation. Parent demographics were comparable to the Australian population for age, parity and obesity. A greater percentage of ENDIA parents were Australian born, lived in a major city and had higher socioeconomic advantage and education. CONCLUSIONS: This comprehensive profile provides the context for understanding ENDIA's scope, methodology, unique strengths and limitations. Now fully recruited, ENDIA will provide unique insights into the roles of early-life factors in the development of islet autoimmunity and T1D in the Australian environment. TRIAL REGISTRATION NUMBER: ACTRN12613000794707.

Is video demonstration for type III sleep studies performance worse than technical face-to-face teaching?

PURPOSE: Obstructive sleep apnea (OSA) is the most common sleep-disordered breathing. The high prevalence makes its diagnosis a priority. To perform type III sleep studies, patients usually receive instructions from a technician. The switch to instructions through a video could save professionals time and make OSA diagnosis more accessible. This study aimed to compare the technical quality of type III sleep studies when instructions are provided by face-to-face technical teaching or via video. METHODS: One hundred consecutive patients aged ≥ 18 years with suspected OSA were randomly assigned to receive device placement instructions in person by a technician or through video (50 in each group). The overall quality of the sleep studies was analyzed by determining the number of technically invalid studies. The recording quality of four sensors (pulse oximeter, nasal flow cannula, chest, and abdominal bands) was evaluated by checking for signal artifacts. RESULTS: The majority (86%) of the studies were valid. 20% of the studies in the face-to-face group and 8% of the studies in the video-instruction group were technically invalid, but no statistically significant difference was found (p = 0.148). The quality of the oximetry signal was better in those who received video instructions (p = 0.05). Regarding the recording quality of the remaining sensors, no significant differences were found. CONCLUSIONS: Type III sleep studies with previous explanation through a video are as effective as those with an explanation performed by a technician, with associated advantages, without increased errors. The quality of the oximetry signal was better in the video group, a critical signal for OSA diagnosis.

Neuroprotective efficiency of celecoxib vesicular bilosomes for the management of lipopolysaccharide-induced Alzheimer in mice employing 23 full factorial design.

The aim of this study was to develop and evaluate bilosomes loaded with Celecoxib (CXB) for the efficient treatment of Alzheimer. The thin-film hydration approach was utilized in the formulation of CXB bilosomes (CXB-BLs). The study used a 23-factorial design to investigate the impact of several formulation variables. Three separate parameters were investigated: bile salt type (X1), medication amount (X2), and lipid-bile salt ratio (X3). The dependent responses included entrapment efficiency (Y1: EE %), particle size (Y2: PS), and zeta potential (Y3: ZP). The formulation factors were statistically optimized using the Design-Expert® program. The vesicles demonstrated remarkable CXB encapsulation efficiency, ranging from 94.16 ± 1.91 to 98.38 ± 0.85%. The vesicle sizes ranged from 241.8 ± 6.74 to 352 ± 2.34 nm. The produced formulations have high negative zeta potential values, indicating strong stability. Transmission electron microscopy (TEM) revealed that the optimized vesicles had a spherical form. CXB release from BLs was biphasic, with the release pattern following Higuchi's model. In vivo studies confirmed the efficiency of CXB-BLs in management of lipopolysaccharide-induced Alzheimer as CXB-BLs ameliorated cognitive dysfunction, decreased acetylcholinesterase (AChE), and inhibited neuro-inflammation and neuro-degeneration through reducing Toll-like receptor (TLR4), and Interleukin-1ß (IL-1ß) levels. The findings suggested that the created CXB-BLs could be a potential drug delivery strategy for Alzheimer's treatment.

Neuropsychiatric Symptom Profile in Alzheimer's Disease and Their Relationship With Functional Decline.

OBJECTIVE: Understanding the course of individual neuropsychiatric symptoms (NPS) and their relationship with function is important for planning targeted interventions for preventing and delaying functional decline. This study aims to disentangle relative contributions of individual NPS on functional decline. METHODS: Longitudinal study of 9,358 well-characterized participants with baseline diagnoses of Mild Cognitive Impairment or AD in the National Alzheimer's Coordinating Center Uniform Data Set. Function was measured using the Functional Assessment Questionnaire (FAQ). Clinician judgment of seven common behavioral symptoms were examined simultaneously: apathy-withdrawal, depressed mood, visual or auditory hallucinations, delusions, disinhibition, irritability, and agitation. RESULTS: Apathy was the most common NPS at baseline (33.7%) and throughout follow-up, endorsed by clinicians in 63.7% of visits. Apathy was the most persistent with 36.7% of participants having clinician-endorsed apathy in ≥50% of their visits. Apathy strongly correlated with faster rate of functional decline. Compared to those who never had apathy, baseline FAQ was worse in those with intermittent or persistent/always apathy (intermittent: estimated coefficient ±SE=1.228±0.210, 95% CI=[0.817, 1.639]; persistent/always: 2.354±0.244 (95% CI=[1.876, 2.832], both p <0.001). Over time, rate of functional decline was faster in those with intermittent and persistent/always apathy (intermittent: 0.454±0.091, 95% CI=[0.276, 0.632]; persistent/always: 0.635±0.102, 95% CI=[0.436, 0.835], both p <0.001). Worse agitation, delusions, and hallucinations also correlated with functional decline, but magnitudes of the estimates were smaller. CONCLUSION: Individual NPS may be sensitive targets for tracking longitudinal change in function. The study raises awareness of the need for more comprehensive assessment of functional decline in AD patients with noncognitive symptoms.

Optimization-Based Stable Balancing Weights Versus Propensity Score Weighting for Samples With High Covariate Imbalance.

PURPOSE: To compare the performance (covariate balance, effective sample size [ESS]) of stable balancing weights (SBW) versus propensity score weighting (PSW). Two applied cases were used to compare performance: (Case 1) extreme imbalance in baseline covariates between groups and (Case 2) substantial discrepancy in sample size between groups. METHODS: Using the Premier Healthcare Database, we selected patients who (Case 1) underwent a surgical procedure with one of two different bipolar forceps between January 2000 and June 2020, or (Case 2) a neurological procedure using one of two different nonabsorbable surgical sutures between January 2000 and March 2020. Average treatment effects on the treated (ATT) weights were generated based on selected covariates. SBW was implemented using two techniques: (1) "grid search" to find weights of minimum variance at the lowest target absolute standardized mean difference (SMD); (2) finding weights of minimum variance at prespecified SMD tolerance. PSW and SBW methods were compared on postweighting SMDs, the number of imbalanced covariates, and ESS of the ATT-weighted control group. RESULTS: In both studies, improved covariate balance was achieved with both SBW techniques. All methods suffered from postweighting ESS that was lower than the unweighted control group's original sample size; however, SBW methods achieved higher ESS for the control groups. Sensitivity analyses using SBW to apply variable-specific SMD thresholds increased ESS, outperforming PSW. CONCLUSIONS: In this applied example, the optimization-based SBW method provided ample flexibility with respect to prespecification of covariate balance goals and resulted in better postweighting covariate balance and larger ESS as compared with PSW.

Review of the recent advances of pyrazole derivatives as selective COX-2 inhibitors for treating inflammation.

Pyrazole heterocycle is regarded as an extremely significant agent for the therapy of inflammation. Celecoxib, lonazolac, deracoxib, and phenylbutazone are examples of commercially approved pyrazole drugs with COX-2 inhibitory potential for curing inflammation. There have been recently many reviews for the biological significance of pyrazole derivatives. This review talks about pyrazole derivatives with anti-inflammatory activity and also sheds the light on the recent updates on pyrazole research with an emphasis on some synthetic pathways utilized to construct this privileged scaffold and structure activity relationship that accounts for the anti-inflammatory activity in an attempt to pave the opportunity for medicinal chemists to develop novel anti-inflammatory agents with better COX-2 selectivity.

The Impact of Metabolic Syndrome on Postoperative Outcomes in Abdominal Body Contouring: A Propensity Score-Matched Nationwide Analysis.

BACKGROUND: Metabolic syndrome (MetS) represents cardiometabolic dysregulation, defined by hypertension, obesity, diabetes, and dyslipidemia. There remains a significant gap in our understanding of whether MetS impacts outcomes of abdominal body contouring procedures. We aimed to assess the influence of MetS on postoperative outcomes of abdominal body contouring by concurrent abdominoplasty and panniculectomy. METHODS: The ACS-NSQIP database was utilized to identify patients who underwent concurrent abdominoplasty and panniculectomy procedures from 2012 to 2022. Through propensity score matching, distinct cohorts were established based on the presence of MetS, characterized by patients receiving medical interventions for diabetes mellitus and hypertension, with a body mass index exceeding 30 kg/m2. Univariate and multivariate analyses were conducted to evaluate differences between groups. RESULTS: A total of 14,642 patients underwent abdominal body contouring from 2012 to 2022. Following propensity score matching, 730 patients were included in the analysis, with 365 in each group (MetS vs. non-MetS). Bivariate analysis revealed a longer hospital length of stay (2.3 vs. 1.6 days; p = 0.007) in the MetS cohort compared to the non-MetS cohort. Patients diagnosed with MetS had an average length of stay of 0.6 days longer than non-MetS patients (95% CI [0.17, 1.01]; p = 0.007). No noteworthy disparities were observed in the rates of 30-day wound complications, mild systemic, and severe systemic complications, and readmission rates between the groups. CONCLUSIONS: Our findings suggest that abdominal body contouring remains a secure option for patients with MetS. Nonetheless, the longer hospital length stays observed in patients with MetS may translate to increased overall costs to the healthcare system. Continued research is warranted to comprehensively assess the economic implications of MetS in the context of abdominal body contouring. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors  www.springer.com/00266 .

Limitations in the clinical utility of vaccine challenge responses in the evaluation of primary antibody deficiency including Common Variable Immunodeficiency Disorders.

Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment. Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis. Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and H. influenzae type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23). This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses.

Long-term follow-up in outpatients with mildly elevated pulmonary artery systolic pressure on echocardiography: a single-centre retrospective cohort study in Shanghai, China.

OBJECTIVE: To investigate the correlation between mildly elevated pulmonary artery systolic pressure (PASP) on echocardiography and mortality, as well as long-term changes in PASP. DESIGN: Retrospective cohort study. SETTING: Shanghai, China, a single centre. PARTICIPANTS: A total of 910 patients were enrolled in this study. From January to June 2016, 1869 patients underwent echocardiography at the Zhongshan Hospital affiliated with Fudan University. Patients with malignant tumours, previous heart or other solid organ transplantation, previous or scheduled ventricular assist device implantation, severe kidney dysfunction (uraemia and patients on dialysis) and a life expectancy of less than 1 year for any medical condition were excluded. INTERVENTIONS: No interventions were done. PRIMARY AND SECONDARY OUTCOME MEASURES: The predictors of death in patients with mild echocardiographic pulmonary hypertension were analysed using univariate and multivariate Cox regression analyses. Paired t-tests were used to calculate changes in the PASP values at baseline and follow-up for different patient groups. RESULTS: The 5-year survival of patients was 93.2%. Patients were grouped according to whether they had combined organic heart disease (OHD). The PASP value was an independent predictor of all-cause mortality in patients with OHD, with each 1 mm Hg increase associated with an HR of 1.02 (95% CI: 1.01-1.03, p=0.038) but not in patients without OHD. Of the total, 46% (419/910) of the patients with 5-6 years of echocardiography were investigated for changes in the PASP value. We found significant PASP reduction in patients without OHD (42.8±2.4 mm Hg vs 39.3±8.2 mm Hg, p<0.001), but no significant change was observed for patients with OHD (42.8±2.5 mm Hg vs 42.4±8.8 mm Hg, p=0.339). CONCLUSIONS: The PASP was associated with all-cause mortality in patients with OHD and mildly elevated PASP compared with patients without OHD. After 5-6 years of follow-up, the PASP on echocardiography was not further elevated in patients without OHD.

Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up.

INTRODUCTION: Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child's neurodevelopment and behaviour development, overall health and mortality. METHODS AND ANALYSIS: This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed using the intention-to-treat approach. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (Dutch WMO-law) did not apply to our study (W21_386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results.

"They Don't Come With a Handbook": Exploring Design Opportunities for Supporting Parent-Child Interaction around Emotions in the Family Context.

Parenting practices have a profound effect on children's well-being and are a core target of several psychological interventions for child mental health. However, there is only limited understanding in HCI so far about how to design socio-technical systems that could support positive shifts in parent-child social practices in situ. This paper focuses on parental socialisation of emotion as an exemplar context in which to explore this question. We present a two-step study, combining theory-driven identification of plausible design directions with co-design workshops with 22 parents of children aged 6-10 years. Our data suggest the potential for technology-enabled systems that aim to facilitate positive changes in parent-child social practices in situ, and highlight a number of plausible design directions to explore in future work.