Surgical outcomes and revision rates for velopharyngeal insufficiency (VPI) in syndromic and non-syndromic children: A systematic review and meta-analysis.

PURPOSE: To evaluate pre- and post-operative resonance, surgical technique, revision rate, and revision indication among syndromic and non-syndromic children with velopharyngeal insufficiency (VPI). MATERIALS AND METHODS: A systematic review was conducted through July 2022. Children surgically treated for VPI were included. A meta-analysis of single means, proportions, comparison of proportions, and mean differences with 95 % confidence interval [CI] was conducted. RESULTS: Twenty-three articles (n = 1437) were included in the analysis. The most common surgery was Sphincter Pharyngoplasty (SP), 62.6 % [31.3-88.9] for syndromic and 76.3 % [37.5-98.9] for non-syndromic children. Among all surgical techniques, for syndromic and non-syndromic children, 54.8 % [30.9-77.5] and 73.9 % [61.3-84.6] obtained normal resonance post-operatively, respectively. Syndromic patients obtained normal resonance post-operatively in 83.3 % [57.7-96.6] of Combined Furlow Palatoplasty and Sphincter Pharyngoplasty (CPSP), 72.6 % [54.5-87.5] of Pharyngeal Flap (PF), and 45.1 % [13.2-79.8] of Sphincter Pharyngoplasty (SP) surgeries. Non-syndromic patients obtained normal resonance post-operatively in 79.2 % [66.4-88.8] of PF and 75.2 % [61.8-86.5] of SP surgeries. The revision rate for syndromic and non-syndromic patients was 19.9 % [15.0-25.6] and 11.3 % [5.8-18.3], respectively. The difference was statistically significant, 8.6 % [2.9-15.0, p = 0.003]. Syndromic patients who underwent PF were least likely to undergo revision surgery as compared to SP and CPSP, 7.7 % [2.3-17.9] vs. 23.7 % [15.5-33.1] and 15.3 % [2.8-40.7], respectively. CONCLUSIONS: Syndromic children had higher revision rates and were significantly less likely to obtain normal resonance following primary surgery than non-syndromic patients. Among syndromic children, PF and CPSP have been shown to improve resonance and reduce revision rates more so than SP alone.

Leveraging computational tools to combat malaria: assessment and development of new therapeutics.

As the world grapples with the relentless challenges posed by diseases like malaria, the advent of sophisticated computational tools has emerged as a beacon of hope in the quest for effective treatments. In this study we delve into the strategies behind computational tools encompassing virtual screening, molecular docking, artificial intelligence (AI), and machine learning (ML). We assess their effectiveness and contribution to the progress of malaria treatment. The convergence of these computational strategies, coupled with the ever-increasing power of computing systems, has ushered in a new era of drug discovery, holding immense promise for the eradication of malaria. SCIENTIFIC CONTRIBUTION: Computational tools remain pivotal in drug design and development. They provide a platform for researchers to explore various treatment options and save both time and money in the drug development pipeline. It is imperative to assess computational techniques and monitor their effectiveness in disease control. In this study we examine renown computational tools that have been employed in the battle against malaria, the benefits and challenges these tools have presented, and the potential they hold in the future eradication of the disease.

Unveiling the Biocontrol Potential of Rhizoplane Bacillus Species against Sugarcane Fusarium Wilt through Biochemical and Molecular Analysis.

BACKGROUND: Biocontrol is regarded as a viable alternate technique for managing sugarcane wilt disease caused by Fusarium sacchari. Many fungal antagonists against F. sacchari, have been reported, but the potential of bacterial antagonists was explored to a limited extent, so the present study evaluated the antagonistic potential of rhizoplane Bacillus species and their mode of action. RESULTS: A total of twenty Bacillus isolates from the rhizoplane of commercially grown sugarcane varieties were isolated. The potential isolate SRB2 had shown inhibition of 52.30, 33.33, & 44.44% and SRB20 of 35.00, 33.15, & 36.85% in direct, indirect, and remote confrontation respectively against F. sacchari. The effective strains were identified as Bacillus inaquosorum strain SRB2 and B. vallismortis strain SRB20, by PCR amplification of 16S-23S intergenic region. The biochemical studies on various direct and indirect biocontrol mechanisms revealed the production of IAA, Protease, Cellulase, Siderophores, and P solubilization. The molecular analysis revealed the presence of antimicrobial peptides biosynthetic genes like fenD (Fengycin), bmyB (Bacyllomicin) ituC (Iturin) and spaS (Subtilin) which provided a competitive edge to these isolates compared to other Bacillus strains. Under greenhouse experiments, the sett bacterization with SRB2, significantly (P < 0.001) reduced the seedling mortality by > 70% followed by SRB20 in F. sacchari inoculated pots. CONCLUSION: The study revealed that the isolates B. inaquosorum SRB2 and B. vallismortis SRB20 can be used as potential bioagents against sugarcane Fusarium wilt.

Structural Support for Large to Total Nasal Reconstruction.

When large defects of the nose are present, it is imperative to address all 3 layers: the external skin envelope, the osteocartilaginous support, and the inner mucosal lining. The middle structural framework is the primary factor in determining the overall shape of the nose, in addition to facilitating a functional and patent airway. As such, its reconstruction must be robust enough to provide lasting osteocartilaginous support while minimizing disfiguring bulk. The goal is replacement of missing tissue with grafts of similar strength, size, and shape. This article will review approaches to the reconstruction of structural support in large nasal defects.

High-Grade Pleomorphic Sarcoma in Postauricular Keloid Scar After Surgical Excision and Radiation.

Keloid scars can cause significant morbidity to the patient including substantial cosmetic disfigurement, particularly in the head and neck region. Surgical excision followed by immediate postoperative radiation therapy has been shown to be more effective than single modality treatment. Radiation therapy increases risk for radiation-induced malignancy, though very few cases have been reported in the treatment of keloids. We report the case of a patient with a large postauricular keloid treated with excision and immediate post-operative radiation who developed a high-grade pleomorphic sarcoma in the scar bed. Laryngoscope, 134:3143-3145, 2024.

Speech Intelligibility in Patients with Facial Paralysis.

Background: Patients with facial paralysis often report frustration with communication; however, there are limited data regarding intelligibility deficiencies. Objective: To compare speech intelligibility in patients with severe and non-severe facial paralysis, and in patients with or without synkinesis. Methods: Video and audio data were reviewed retrospectively. Groups were stratified as follows: Group A - severe paralysis (Sunnybrook 0-20) without synkinesis; Group B - non-severe (Sunnybrook >20) paralysis without synkinesis; and Group C - non-severe paralysis with synkinesis. Intelligibility was assessed by lay-people and a speech and language pathologist (SLP) using the Frenchay Dysarthria Assessment Version 2 (FDA-2). A receiver operating characteristic (ROC) curve was used to determine a Sunnybrook cutoff for intelligibility. Results: Eighty cases were reviewed with mean age 55.6, 53.8% female. 25.0% were in Group A, 30.0% Group B, and 45.0% in Group C. Lay-people rated 15.0% and the SLP rated 28.7% as having intelligibility deficiency. An ROC curve demonstrated that patients with Sunnybrook ≤18.5 were more likely to have intelligibility abnormality. Conclusion: Patients with Sunnybrook ≤18.5 are more likely to demonstrate intelligibility deficiency. Clinicians with a more trained ear are more likely to identify intelligibility abnormality compared with lay-people. Those with synkinesis are more intelligible compared with those without it.

Association Between Marijuana Use and Clinical Outcomes After Coronary Artery Bypass Grafting.

INTRODUCTION: Though marijuana use has been linked to an increase in heart failure admissions, no prior study has explored the association between its use and outcomes after coronary artery bypass grafting (CABG). This study examines the relationship between marijuana use and postoperative outcomes in CABG patients. METHODS: We utilized data from the National Inpatient Sample database from 2008 to 2018 for CABG patients ≥18 y old. Patients were divided into two groups based on marijuana use (abuse/dependency versus nonuse). Primary outcomes include in-hospital mortality, favorable discharge, and length of stay (LOS). Secondary outcomes include acute kidney injury (AKI), acute myocardial infarction (AMI), and transient ischemic attack (TIA)/stroke. A multivariable model, adjusted for confounding variables, was utilized for each outcome. RESULTS: A total of 343,796 patients met inclusion criteria for the study, 590 of which were marijuana users. In both marijuana user and nonuser groups, most patients were male and White with an average age of 56.0 and 66.3 y, respectively. There was a nonsignificant decreased odds of in-hospital mortality among marijuana users (odds ratio [OR] = 0.41, [0.141-1.124]). Marijuana users exhibited significantly decreased odds of home discharge (OR = 1.50, [1.24-1.81]), and increased odds of longer LOS (mean 10.4 d versus 9.8 d; OR = 1.14, [1.09-1.20]), AKI (OR = 1.40, [1.11-1.78]), AMI (OR = 1.56, [1.32-1.84]), and TIA/stroke (OR = 1.64, [1.21-2.22]). CONCLUSIONS: Marijuana use and dependency are associated with increased nonhome discharge, AKI, AMI, TIA/stroke, and longer LOS. Further studies are needed to delineate the pathophysiologic derangements that contribute to these unfavorable post-CABG outcomes.

Reactions to serum eye drops-New Zealand experience and review of the literature.

BACKGROUND: Serum eye drops (SED) are used to treat ocular surface disease. Reactions to SED are poorly documented. METHODS: We present our experience of self-reported reactions in New Zealand to SED (25%; autologous, allogeneic, or both) between 2003 and 2023, and a focused review of the literature. RESULTS: In total, 1067 patients received SED treatment (562 autologous, 318 allogeneic, and 187 both). Three (0.5% of those treated with allogeneic SED) reported reactions. All appeared to be allergic. All were associated with allogeneic SED. We have information on two patients: one had an eye reaction; in the other, the gastrointestinal tract was involved. The literature contains few reports of reactions to SED. They have involved both autologous and allogeneic SED, and various SED concentrations. None appears to have been severe. Notably, no eye or systemic infections have been reported. CONCLUSIONS: Information on the types and frequencies of reactions to SED is poor. This may be due to: serum being less likely to cause reactions; eyes being resistant to reactions; reactions being rare, and insufficient use of SED having occurred; under-reporting related to SED use at home and reactions being mild. More robust monitoring for reactions to SED is needed.

Cleft Lip and/or Palate Repair in Children With Hypopituitarism: Analysis of the Kids' Inpatient Database.

OBJECTIVE: Children with hypopituitarism (CwHP) can present with orofacial clefting, frequently in the setting of multiple midline anomalies. Hypopituitarism (HP) can complicate medical and surgical care; the perioperative risk in CwHP during the traditionally lower risk cleft lip and/or palate (CL/P) repair is not well described. The objective of this study is to examine the differences in complications and mortality of CL/P repair in CwHP compared to children without hypopituitarism (CwoHP). DESIGN: A retrospective cross-sectional analysis. SETTING: The 1997 to 2019 Kids' Inpatient Databases (KID). PATIENTS: Children 3 years old and younger who underwent CL/P repair. MAIN OUTCOME MEASURE(S): Complications and mortality. RESULTS: A total of 34 106 weighted cases were analyzed, with 86 having HP. CwHP had a longer length of stay (3.0 days [IQR 2.0-10.0] vs 1.0 day [IQR 1.0-2.0], P < .001) and higher rates of complications and mortality (12.8% vs 2.9%, P < .001) compared to CwoHP. Controlling for demographic factors, CwHP had 6.61 higher odds of complications and mortality than CwoHP (95% CI 3.38-12.94, P < .001). CONCLUSIONS: CwHP can present with a CL/P and other midline defects that can increase the complexity of their care. These data show a significant increase in length of stay, complications, and mortality in CwHP undergoing CL/P repair. Increased multidisciplinary attention and monitoring may be needed for these children peri- and postoperatively, especially if additional comorbidities are present. Further studies on perioperative management in this population are warranted to reduce morbidity and mortality.

Identification of resistance to Sugarcane mosaic virus, Sugarcane streak mosaic virus, and Sugarcane bacilliform virus in new elite sugarcane accessions in India.

Sugarcane mosaic and leaf fleck diseases are significant viral diseases affecting sugarcane crops in India. The use of resistant sugarcane varieties is considered the most economical and effective approach to manage viral diseases, especially in vegetatively propagated crops such as sugarcane. Sugarcane mosaic virus (SCMV) and Sugarcane streak mosaic virus (SCSMV) are the primary pathogens responsible for mosaic disease in sugarcane-growing regions of India. Sugarcane bacilliform virus (SCBV), causing leaf fleck disease, is also often found in mixed infections with mosaic symptoms. The study aimed to identify new sources of resistance by screening sugarcane germplasm for resistance to SCMV, SCSMV, and SCBV. The screening was carried out under high inoculum using the infector row method in both plant and ratoon crops. Out of 129 genotypes tested, only 8 were found to be free of mosaic viruses, indicating a rare occurrence of resistant sources. The study revealed that mosaic disease is widespread, with nearly 95% of tested varieties/genotypes being infected with mosaic viruses. SCMV, SCSMV, and SCBV were detected in 121 out of 129 genotypes using the RT-PCR and PCR assays. Based on their response to the viruses, the tested genotypes were categorized into different resistance grades: highly resistant (grade 1), resistant (grade 2), moderately resistant (grade 3), susceptible (grade 4), and highly susceptible (grade 5). The results of the study provide valuable information about elite resistance resources that can be used for the prevention and control of mosaic disease. These resistant genotypes could also serve as potential donors for mosaic and leaf fleck disease resistance in breeding programs.

Detection of Sugarcane bacilliform virus in diseased sugarcane plants in Andhra Pradesh, India by serological and molecular methods.

Sugarcane leaf fleck incited by Sugarcane bacilliform virus is emerging as a major disease and affecting exchange of sugarcane germplasm and cultivation worldwide. Roving surveys conducted in 162 fields belonging to 81 villages spread over 14 sugarcane growing districts of Andhra Pradesh during 2021-2022 revealed 8 to 44% incidence of the disease. Mean maximum fleck disease incidence was reported in Anakapalli district (33.00%) followed by Srikakulam district (22.66%), whereas least incidence was observed in Alluri Sitharamaraju district (9.33%). The early and sensitive detection of pathogens is vital and necessary to reduce the danger of introducing new diseases or pathogen strains into sugarcane growing regions. Both serological and molecular methods were used in proposed investigation to identify the virus at the protein and nucleic acid levels. DAS-ELISA results were positive for 50 suspected SCBV infected sugarcane leaf samples out of 81, with mean absorbance (A405) values ranging from 0.50 to 2.20. Further PCR assays were performed using SCBV-specific primers targeting RT/RNase H coding region which is frequently employed as a taxonomic marker for species delineation in Badnaviruses. Out of 81 symptomatic samples collected, 61 samples gave positive results, and no amplification was observed in healthy control and negative control. Results made it evident that PCR was more sensitive than DAS-ELISA. Low virus concentration or variation in virus strains may be the reason for the low detection rate in DAS-ELISA in the current study. Extensive roving surveys conducted for the incidence of leaf fleck disease for the first time in the state of Andhra Pradesh revealed severe occurrence of leaf fleck disease under field conditions.

Severe deterioration in food-energy-ecosystem nexus due to ongoing Russia-Ukraine war: A critical review.

The Russia-Ukraine war is having far-reaching negative impacts on the food-energy-ecosystem nexus and has resulted in an increase in environmental pollution not only in the war-affected regions. The purpose of this review is to critically evaluate the degradation caused by the war and its implications for the food-energy-ecosystem nexus. By examining the specific environmental impacts, this review provides an in-depth understanding of the extent of the damage and its consequences for the interconnected systems of food production, energy supply, and the overall ecosystem. Furthermore, this review addresses the impacts of the ongoing war on the food-energy-ecosystem nexus and underlines the challenges associated with resource recovery in the aftermath of the war. It also highlights the war impacts on the essential commodities' supply chain. Moreover, a plausible strategy for post-war ecosystem restoration has been presented in order to prioritize on the recovery and rejuvenation of the environment. This review also attempts to act as a wake-up call to the urgency of achieving a cease-fire, as the long-term effects of the war would include permanent environmental harm in addition to human and economic losses.

Common- and rare-variant genetic architecture of heart failure across the allele frequency spectrum.

Heart failure (HF) is a complex trait, influenced by environmental and genetic factors, that affects over 30 million individuals worldwide. Historically, the genetics of HF have been studied in Mendelian forms of disease, where rare genetic variants have been linked to familial cardiomyopathies. More recently, genome-wide association studies (GWAS) have successfully identified common genetic variants associated with risk of HF. However, the relative importance of genetic variants across the allele-frequency spectrum remains incompletely characterized. Here, we report the results of common- and rare-variant association studies of all-cause heart failure, applying recently developed methods to quantify the heritability of HF attributable to different classes of genetic variation. We combine GWAS data across multiple populations including 207,346 individuals with HF and 2,151,210 without, identifying 176 risk loci at genome-wide significance (p < 5×10-8). Signals at newly identified common-variant loci include coding variants in Mendelian cardiomyopathy genes (MYBPC3, BAG3), as well as regulators of lipoprotein (LPL) and glucose metabolism (GIPR, GLP1R), and are enriched in cardiac, muscle, nerve, and vascular tissues, as well as myocyte and adipocyte cell types. Gene burden studies across three biobanks (PMBB, UKB, AOU) including 27,208 individuals with HF and 349,126 without uncover exome-wide significant (p < 3.15×10-6) associations for HF and rare predicted loss-of-function (pLoF) variants in TTN, MYBPC3, FLNC, and BAG3. Total burden heritability of rare coding variants (2.2%, 95% CI 0.99-3.5%) is highly concentrated in a small set of Mendelian cardiomyopathy genes, and is lower than heritability attributable to common variants (4.3%, 95% CI 3.9-4.7%) which is more diffusely spread throughout the genome. Finally, we demonstrate that common-variant background, in the form of a polygenic risk score (PRS), significantly modifies the risk of HF among carriers of pathogenic truncating variants in the Mendelian cardiomyopathy gene TTN. These findings suggest a significant polygenic component to HF exists that is not captured by current clinical genetic testing.

A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.

Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPSMult, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPSMult strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPSMult was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPSMult demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPSMult for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.

Genome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program.

The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and cell types and provide human genetic evidence that TAAD is a non-atherosclerotic aortic disorder distinct from other forms of vascular disease. Our results demonstrate that the genetic architecture of TAAD mirrors that of other complex traits and that it is not solely inherited through protein-altering variants of large effect size.

Quantitative Brain MRI Metrics Distinguish Four Different ALS Phenotypes: A Machine Learning Based Study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease whose diagnosis depends on the presence of combined lower motor neuron (LMN) and upper motor neuron (UMN) degeneration. LMN degeneration assessment is aided by electromyography, whereas no equivalent exists to assess UMN dysfunction. Magnetic resonance imaging (MRI) is primarily used to exclude conditions that mimic ALS. We have identified four different clinical/radiological phenotypes of ALS patients. We hypothesize that these ALS phenotypes arise from distinct pathologic processes that result in unique MRI signatures. To our knowledge, no machine learning (ML)-based data analyses have been performed to stratify different ALS phenotypes using MRI measures. During routine clinical evaluation, we obtained T1-, T2-, PD-weighted, diffusion tensor (DT) brain MRI of 15 neurological controls and 91 ALS patients (UMN-predominant ALS with corticospinal tract CST) hyperintensity, n = 21; UMN-predominant ALS without CST hyperintensity, n = 26; classic ALS, n = 23; and ALS patients with frontotemporal dementia, n = 21). From these images, we obtained 101 white matter (WM) attributes (including DT measures, graph theory measures from DT and fractal dimension (FD) measures using T1-weighted), 10 grey matter (GM) attributes (including FD based measures from T1-weighted), and 10 non-imaging attributes (2 demographic and 8 clinical measures of ALS). We employed classification and regression tree, Random Forest (RF) and also artificial neural network for the classifications. RF algorithm provided the best accuracy (70-94%) in classifying four different phenotypes of ALS patients. WM metrics played a dominant role in classifying different phenotypes when compared to GM or clinical measures. Although WM measures from both right and left hemispheres need to be considered to identify ALS phenotypes, they appear to be differentially affected by the degenerative process. Longitudinal studies can confirm and extend our findings.

Living Donor Liver transplantation in an alloimmunised patient: Immunological challenges and Management in Indian Settings.

Liver transplantation (LT) is often associated with hematological abnormalities with immune or non-immune etiologies and require timely diagnosis and interventions. We report a case of a patient suffering from non-alcoholic steato-hepatitis (NASH) related end stage liver disease (ESLD) with multiple red cell antibodies who underwent LT surgery. In postoperative phase, she developed immune hemolysis as well as acute antibody mediated rejection (AMR) which was managed with therapeutic plasma exchange and IVIG. The case highlights the need to develop an algorithm for red cell and HLA antibody screening in high-risk patients for timely detection and management.

Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation.

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.