Postacute Sequelae of COVID (PASC or Long COVID): An Evidenced-Based Approach.

While the acute manifestations of infectious diseases are well known, in some individuals, symptoms can either persist or appear after the acute period. Postviral fatigue syndromes are recognized with other viral infections and are described after coronavirus disease 2019 (COVID-19). We have a growing number of individuals with symptoms that persist for weeks, months, and years. Here, we share the evidence regarding the abnormalities associated with postacute sequelae of COVID-19 (PASC) and therapeutics. We describe physiological and biochemical abnormalities seen in individuals reporting PASC. We describe the several evidence-based interventions to offer patients. It is expected that this growing understanding of the mechanisms driving PASC and the benefits seen with certain therapeutics may not only lead to better outcomes for those with PASC but may also have the potential for understanding and treating other postinfectious sequelae.

Blended learning: Exploring nurse educators' perspectives.

Background: In a rapidly evolving educational landscape, blended learning is becoming an increasingly popular transition from traditional forms of learning and teaching to e-learning. It is therefore important that lecturers adapt their practice and transform their teaching in line with the online platform in use, as this has the potential to benefit students, lecturers and the institution alike. However, little research exists regarding the perspectives of nurse educators on the use of blended learning as a teaching method. Aim: The study aimed to explore and describe the perspectives of nurse educators on the use of blended learning as a teaching method at the Faculty of Health Sciences at a university in Namibia. Setting: The study was conducted at a public nurse education institution in Namibia. Methods: A qualitative exploratory, descriptive design that was contextual was applied to collect data from a convenient sample of 15 lecturers using semi-structured interviews. Results: Four themes emerged in this study, namely, understanding of blended learning, benefits of utilising blended learning, challenges of utilising blended learning, and recommendations to ensure effective use of blended learning. Conclusion: The study findings identified potential areas of both strengths and shortcomings in nurse educators' use of blended learning as a teaching and learning strategy. Contribution: These findings may be used to develop ongoing strategies and targeted interventions that can strengthen nurse educators' abilities to design learning environments that are conducive to blended learning.

Long-Term Health Outcomes of Huntington Disease and the Impact of Future Disease-Modifying Treatments: A Decision-Modeling Analysis.

Background and Objectives: Disease-modifying treatments (DMTs) such as gene therapy are currently under investigation as a potential treatment for Huntington disease (HD). Our objective was to estimate the long-term natural history of HD progression and explore the potential efficacy impacts and value of a hypothetical DMT using a decision-analytic modeling framework. Methods: We developed a health state transition model that separately analyzed 40-year-old individuals with prefunctional decline (PFD, HD Integrated Staging System [HD-ISS] stage <3, total functional score [TFC] 13), active functional decline Shoulson and Fahn category 1 (SF1, HD-ISS stage 3, TFC 13-11), and SF2 (HD-ISS stage 3, TFC 10-7). Three-year outcomes from the TRACK-HD longitudinal study were linearly extrapolated to estimate the long-term health outcomes and costs of each population. For PFD individuals, we used the HD-ISS to predict the onset of functional decline. HD costs and quality-adjusted life years (QALYs) were estimated over a lifetime horizon by applying health state-specific costs and utilities derived from a related HD burden-of-illness study. We then estimated the long-term health impacts of hypothetical DMTs that slowed or delayed onset of functional decline. We conducted sensitivity analyses to assess model uncertainties. Results: The expected life years for 40-year-old PFD, SF1, and SF2 populations were 20.46 (95% credible range [CR]: 19.05-22.30), 13.93 (10.82-19.08), and 10.99 (8.28-22.07), respectively. The expected QALYs for PFD, SF1, and SF2 populations were 15.93 (14.91-17.44), 8.29 (6.36-11.79), and 5.79 (4.14-12.91), respectively. The lifetime costs of HD were $508,200 ($310,300 to $803,700) for the PFD population, $1.15 million ($684,500 to $1.89 million) for SF1 individuals, and $1.07 million ($571,700 to $2.26 million) for SF2 individuals. Although hypothetical DMTs led to cost savings in the PFD population by delaying the cost burdens of functional decline, they increased costs in SF1 and SF2 populations by prolonging time spent in expensive progressive HD states. Discussion: Our novel HD-modeling framework estimates HD progression over a lifetime and the associated costs and QALYs. Our approach can be used for future cost-effectiveness models as positive DMT clinical trial evidence becomes available.

Coping with Huntington's Disease in Patients and At-Risk Individuals.

Background: Huntington's disease (HD) presents patients and individuals at risk for HD with significant levels of stress. However, relatively little research has examined how individuals cope with stress related to the disease or the association of specific coping strategies with psychological symptoms. Objective: This study examined the ways in which HD patients and at-risk individuals cope with HD-related stress using a control-based model of coping and the association of coping strategies with symptoms of depression and anxiety. Methods: HD patients (n = 49) and at-risk individuals (n = 76) completed the Responses to Stress Questionnaire - Huntington's Disease Version to assess coping strategies in response to HD-related stress, as well as standardized measures of depression and anxiety symptoms. Patient health records were accessed to obtain information related to disease characteristics. Results: Patients and at-risk individuals reported using comparable levels of primary control coping, secondary control coping, and disengagement coping strategies. In linear regression analyses, only secondary control coping was significantly associated with lower depression (ß= -0.62, p < 0.001) and anxiety (ß= -0.59, p < 0.001) symptoms in patients and at-risk individuals (ß= -0.55, p < 0.001 and ß= -0.50, p < 0.001, respectively). Conclusions: Secondary control coping may be beneficial for both HD patients and at-risk individuals. Future research using the control-based model of coping in longitudinal studies with the HD population is needed, and future interventions could test the effects of cognitive reframing and acceptance as coping strategies for families affected by HD.

Metabolite comparative variation related lipid metabolisms among fruit, leaf, and stem of Jatropha curcas.

The issue of non-renewable energy scarcity has persisted over an extended period, primarily due to the depletion of fossil fuel reserves and the adverse effects of their utilization. This scarcity stems from the finite nature of fossil energy resources. The development of oil energy or biofuels aims to utilize oil-producing plants such as Jatropha curcas to develop alternative energy resources. However, metabolomic studies in Jatropha curcas are limited and need more investigations. Therefore, this research was essential to find biomarkers of metabolites among the fruit, leaf, and stem of Jatropha curcas using the GC-MS technique. We tested the metabolite profile with the R program, especially the metaboanalystR package, to determine fold change metabolite and pathway analysis. We found that 54 metabolites were detected in both fruit, leaf, and stem tissues of Jatropha curcas L, of which 19 metabolites were upregulated in the fruit, 20 metabolites in the leaf, and 15 up-regulated metabolites in the stem. The metabolites found formed three clusters based on correlation and networking metabolites analysis. The three clusters showed a relationship with the lipid biosynthesis pathway. In this study, provisional information was obtained that there was a different pattern of expression of metabolites between fruit, leaf, and stem tissues in Jatropha curcas, which was thought to be related to the critical metabolites of oleic acid and methylcyclohexane carboxylate in the biosynthetic pathway of fatty acids and unsaturated fatty acids. This information is essential as an initial reference for genetic engineering Jatropha curcas so that it can be used to transform plants, especially lipid-producing plants, as a source of oil.

Hydrodynamic Evaluation of a Filtering Hydrocyclone for Solid Particle/Water Separation.

A conventional hydrocyclones is a versatile equipment with a high processing capacity and low maintenance cost. Currently, several studies aim to alter the typical structure of the conventional hydrocyclone in order to modify its performance and purpose. For this, filtering hydrocyclones have emerged, where a porous membrane replaces the conic or cylindrical wall. During the operation of this equipment, in addition to the traditionally observed streams (feed, underflow, and overflow), there is a liquid stream resulting from the filtration process, commonly referred to as filtrate. This work proposes to numerically investigate the solid particle/liquid water separation process in a filtering hydrocyclone using the commercial software Ansys CFX® 15.0. The proposed mathematical model for the study considers three-dimensional, steady state and turbulent flow, using the Eulerian-Eulerian approach and the Shear Stress Transport (SST) turbulence model. This study presents and analyzes the volume fraction, velocity, and pressure fields, along with flowlines and velocity profiles. The results indicate that the proposed model effectively captures the fluid dynamic behavior within the filtering hydrocyclone, highlighting higher pressures near the porous membrane and a higher concentration of solid particles in the conical region, with water being more concentrated in the cylindrical part of the hydrocyclone. Additionally, the findings show that the volumetric flow rate of the filtrate significantly influences the internal flow dynamics, with conventional hydrocyclones demonstrating higher pressure gradients compared to the proposed filtering hydrocyclone.

Composite Sling: A Strategy for Enhancing Inferolateral Support in Mastopexy with Implant.

Augmentation mastopexy has attracted the attention of numerous authors seeking to improve surgical outcomes and ensure breast implant stability. The utilization of the dual plane technique with a lateral sling, pioneered by Ono and Karner, has demonstrated effectiveness in providing long-term implant support. However, challenges arise in cases of anatomical variations, such as a short pectoralis major (PM) muscle or chest, necessitating alternative approaches like the composite sling. This study presents a technique designed to elongate and broaden the lateral sling to enhance implant support. The composite sling incorporates components from the abdominal part of the PM muscle, the aponeurotic/muscular part of the external oblique muscle, and the cranial part of the rectus abdominis. Procedures were performed on 29 patients using the composite sling technique from July 2022 to October 2023. The follow-up period ranged from 6 to 18 months (average of 11.89 months). The lateral sling approach was successfully extended to cases with a short PM muscle or chest, previously managed using the dual plane technique without inferolateral support. No increase in complications or implant displacements was observed compared with the original lateral sling approach. However, four reoperations addressed issues such as dog ears, scarring, and minor asymmetries. Consistent results were observed throughout the follow-up period, particularly in maintaining upper pole fullness and preventing lower pole ptosis. The composite sling approach provides a viable solution for cases where the original sling technique is impractical. Its implementation could broaden surgical options and optimize results, particularly in cases of unfavorable anatomy.

The layered learning practice model: Ensuring accomplishment of both practice and pharmacy education.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Transition State Stabilizing Effects of Oxygen and Sulfur Chalcogen Bond Interactions.

Non-covalent chalcogen bond (ChB) interactions have found utility in many fields, including catalysis, organic semiconductors, and crystal engineering. In this study, the kinetic effects of ChB interactions of oxygen and sulfur were experimentally measured using a series of molecular rotors. The rotors were designed to form ChB interactions in the bond rotation transition states. This enabled their kinetic influences to be assessed by monitoring changes in rotational barriers. Despite forming weaker ChB interactions, the smaller chalcogens were able to stabilize transition states and had measurable kinetic effects. Sulfur stabilized the bond rotation transition state by as much as -7.2 kcal/mol without electron-withdrawing groups. The key was to design a system where the sulfur ðœŽ-hole was aligned with the lone pairs of the chalcogen bond acceptor. Oxygen rotors also could form transition state stabilizing ChB interactions but required electron-withdrawing groups. For both oxygen and sulfur ChB interactions, a strong correlation was observed between transition state stabilizing abilities and electrostatic potential (ESP) of the chalcogen, providing a useful predictive parameter for the rational design of future ChB systems.

A Scoping Review of Pain Management After Transoral Robotic Surgery.

OBJECTIVE: Pain following transoral robotic surgery (TORS) is a driver of adverse outcomes and can lead to readmission and treatment delays. A scoping review was conducted to characterize TORS-related pain and identify key management strategies utilized in the literature. DATA SOURCES: OVID Medline, CINAHL, Cochrane, Pubmed, and Embase databases were queried. REVIEW METHODS: Two team members independently screened titles and abstracts and completed full-text reviews. Studies examining TORS for OPSCC with quantitative pain data were included. The study followed the PRISMA guidelines. RESULTS: A total of 1467 studies were imported for screening and 25 studies were ultimately included. The average study sample size was 89 participants. 68% were conducted in a single-center academic setting. Pain was assessed on varying timelines up to 3 years using 13 different metrics. Pain peaks days-weeks postoperatively and returns to baseline thereafter. Postoperative pain is a significant cause of morbidity and limited data exist about optimal management. CONCLUSION: Prospective studies are needed to characterize and address TORS-related pain.

Robotic-assisted total hip arthroplasty utilizing a fluoroscopy-guided system produced similar cup accuracy and precision relative to a computerized tomography-based robotic platform.

Robotic assistance for total hip arthroplasty (THA) has been demonstrated to improve accuracy of acetabular cup placement relative to manual, unassisted technique. The purpose of this investigation was to compare the accuracy and precision between a fluoroscopy-based robotic total hip arthroplasty platform (FL-RTHA) and a computerized tomography-based (CT-RTHA) platform. The study included 98 consecutive FL-RTHA and 159 CT-RTHA procedures performed via direct anterior approach (DAA). All cases were performed for a pre-operative diagnosis of osteoarthritis, avascular necrosis, or rheumatoid arthritis. Primary outcome variables included cup implantation accuracy and precision (variance). Implantation accuracy was calculated as the absolute value of the difference between pre-operative target cup angles (inclination and anteversion) and the same post-operative angles. Percentage placement in the Lewinnek safe zone was also measured for both cohorts. The FL-RTHA and CT-RTHA cohorts demonstrated a 1.2° difference in absolute values for cup inclination accuracy (4.6° ± 3.6 vs. 3.4 ± 2.7; p = 0.005), and no difference in absolute values for cup anteversion accuracy (4.7° ± 4.1 vs. 4.6 ± 3.4; p = 0.991). Cohorts demonstrated similar precision for cup inclination and anteversion placement parameters, as well as equivalent Lewinnek safe zone placement. The use of a fluoroscopy-based robotic assistance platform for primary DAA THA resulted in similar accuracy and precision of acetabular cup placement when compared to a CT-based robotic assistance system.

Molecular targets of PXR-dependent ethanol-induced hepatotoxicity in female mice.

The pregnane X receptor (PXR, NR1I2), a xenobiotic-sensing nuclear receptor signaling potentiates ethanol (EtOH)-induced hepatotoxicity in male mice, however, how PXR signaling modulates EtOH-induced hepatotoxicity in female mice is unknown. Wild type (WT) and Pxr-null mice received 5 % EtOH-containing diets or paired-fed control diets for 8 weeks followed by assessment of liver injury, EtOH elimination rates, histology, and changes in gene and protein expression; microarray and bioinformatic analyses were also employed to identify PXR targets in chronic EtOH-induced hepatotoxicity. In WT females, EtOH ingestion significantly increased serum ethanol and alanine aminotransferase (ALT) levels, hepatic Pxr mRNA, constitutive androstane receptor activation, Cyp2b10 mRNA and protein, oxidative stress, endoplasmic stress (phospho-elF2α) and pro-apoptotic (Bax) protein expression. Unexpectedly, EtOH-fed female Pxr-null mice displayed increased EtOH elimination and elevated levels of hepatic acetaldehyde detoxifying aldehyde dehydrogenase 1a1 (Aldh1a1) mRNA and protein, EtOH-metabolizing alcohol dehydrogenase 1 (ADH1), and lipid suppressing microsomal triglyceride transport protein (MTP) protein, aldo-keto reductase 1b7 (Akr1b7) and Cyp2a5 mRNA, but suppressed CYP2B10 protein levels, with evidence of protection against chronic EtOH-induced oxidative stress and hepatotoxicity. While liver injury was not different between the two WT sexes, female sex may suppress EtOH-induced macrovesicular steatosis in the liver. Several genes and pathways important in retinol and steroid hormone biosynthesis, chemical carcinogenesis, and arachidonic acid metabolism were upregulated by EtOH in a PXR-dependent manner in both sexes. Together, these data establish that female Pxr-null mice are resistant to chronic EtOH-induced hepatotoxicity and unravel the PXR-dependent and -independent mechanisms that contribute to EtOH-induced hepatotoxicity.

Transcriptional response of the heart to vagus nerve stimulation.

Heart failure is a major clinical problem, with treatments involving medication, devices, and emerging neuromodulation therapies such as vagus nerve stimulation (VNS). Considering the ongoing interest in using VNS to treat cardiovascular disease it is important to understand the genetic and molecular changes developing in the heart in response to this form of autonomic neuromodulation. This experimental animal (rat) study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity using an optogenetic approach. Vagal preganglionic neurons in the dorsal motor nucleus of the vagus nerve were genetically targeted to express light-sensitive chimeric channelrhodopsin variant ChIEF, and stimulated using light. RNA sequencing of left ventricular myocardium identified 294 differentially expressed genes (DEGs, false discovery rate <0.05). Qiagen Ingenuity Pathway Analysis (IPA) highlighted 118 canonical pathways that were significantly modulated by vagal activity, of which 14 had a z-score of ≥2/≤-2, including EIF-2, IL-2, Integrin, and NFAT-regulated cardiac hypertrophy. IPA revealed the effect of efferent vagus stimulation on protein synthesis, autophagy, fibrosis, autonomic signalling, inflammation, and hypertrophy. IPA further predicted that the identified DEGs were the targets of 50 upstream regulators, including transcription factors (e.g., MYC, NRF1) and microRNAs (e.g., miR-335-3p, miR-338-3p). These data demonstrate that the vagus nerve has a major impact on myocardial expression of genes involved in regulation of key biological pathways. The transcriptional response of the ventricular myocardium induced by stimulation of vagal efferents is consistent with the beneficial effect of maintained/increased vagal activity on the heart.

Pathophysiological processes underlying hidden hearing loss revealed in Kcnt1/2 double knockout mice.

Presbycusis is a prevalent condition in older adults characterized by the progressive loss of hearing due to age-related changes in the cochlea, the auditory portion of the inner ear. Many adults also struggle with understanding speech in noise despite having normal auditory thresholds, a condition termed "hidden" hearing loss because it evades standard audiological assessments. Examination of animal models and postmortem human tissue suggests that hidden hearing loss is also associated with age-related changes in the cochlea and may, therefore, precede overt age-related hearing loss. Nevertheless, the pathological mechanisms underlying hidden hearing loss are not understood, which hinders the development of diagnostic biomarkers and effective treatments for age-related hearing loss. To fill these gaps in knowledge, we leveraged a combination of tools, including transcriptomic profiling and morphological and functional assessments, to identify these processes and examine the transition from hidden to overt hearing loss. As a novel approach, we took advantage of a recently characterized model of hidden hearing loss: Kcnt1/2 double knockout mice. Using this model, we find that even before observable morphological pathology, hidden hearing loss is associated with significant alteration in several processes, notably proteostasis, in the cochlear sensorineural structures, and increased susceptibility to overt hearing loss in response to noise exposure and aging. Our findings provide the first insight into the pathophysiology associated with the earliest and, therefore, most treatable stages of hearing loss and provide critical insight directing future investigation of pharmaceutical strategies to slow and possibly prevent overt age-related hearing loss.

Predictors of urine toxicology and other biologic specimen missingness in randomized trials of substance use disorders.

BACKGROUND: High levels of missing outcome data for biologically confirmed substance use (BCSU) threaten the validity of substance use disorder (SUD) clinical trials. Underlying attributes of clinical trials could explain BCSU missingness and identify targets for improved trial design. METHODS: We reviewed 21 clinical trials funded by the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) and published from 2005 to 2018 that examined pharmacologic and psychosocial interventions for SUD. We used configurational analysis-a Boolean algebra approach that identifies an attribute or combination of attributes predictive of an outcome-to identify trial design features and participant characteristics associated with high levels of BCSU missingness. Associations were identified by configuration complexity, consistency, coverage, and robustness. We limited results using a consistency threshold of 0.75 and summarized model fit using the product of consistency and coverage. RESULTS: For trial design features, the final solution consisted of two pathways: psychosocial treatment as a trial intervention OR larger trial arm size (complexity=2, consistency=0.79, coverage=0.93, robustness score=0.71). For participant characteristics, the final solution consisted of two pathways: interventions targeting individuals with poly- or nonspecific substance use OR younger age (complexity=2, consistency=0.75, coverage=0.86, robustness score=1.00). CONCLUSIONS: Psychosocial treatments, larger trial arm size, interventions targeting individuals with poly- or nonspecific substance use, and younger age among trial participants were predictive of missing BCSU data in SUD clinical trials. Interventions to mitigate missing data that focus on these attributes may reduce threats to validity and improve utility of SUD clinical trials.

Sensitivity analysis for principal ignorability violation in estimating complier and noncomplier average causal effects.

An important strategy for identifying principal causal effects (popular estimands in settings with noncompliance) is to invoke the principal ignorability (PI) assumption. As PI is untestable, it is important to gauge how sensitive effect estimates are to its violation. We focus on this task for the common one-sided noncompliance setting where there are two principal strata, compliers and noncompliers. Under PI, compliers and noncompliers share the same outcome-mean-given-covariates function under the control condition. For sensitivity analysis, we allow this function to differ between compliers and noncompliers in several ways, indexed by an odds ratio, a generalized odds ratio, a mean ratio, or a standardized mean difference sensitivity parameter. We tailor sensitivity analysis techniques (with any sensitivity parameter choice) to several types of PI-based main analysis methods, including outcome regression, influence function (IF) based and weighting methods. We discuss range selection for the sensitivity parameter. We illustrate the sensitivity analyses with several outcome types from the JOBS II study. This application estimates nuisance functions parametrically - for simplicity and accessibility. In addition, we establish rate conditions on nonparametric nuisance estimation for IF-based estimators to be asymptotically normal - with a view to inform nonparametric inference.

Computational identification of potential acetylcholinesterase (AChE) and monoamine oxidase-B inhibitors from Vitis vinifera: a case study of Alzheimer's disease (AD).

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease that affects people aged 60 years and above. Yet, the discovery of potent therapeutic agents against this disease has no utmost progress and a number of drug candidates could not make it out of the clinical trials at varied stages. At the same time, the currently available anti-cholinesterase (AChE) and monoamine oxidase-B (MAO-B) for the treatment of AD can only improve the clinical symptoms while the recently approved immunotherapy agent "remains questionable. Thus, the need for novel therapeutic agents with the potential to treat the aetiology of the disease. Herein, this study sought to examine the potential of a number of bioactive compounds derived from Vitis vinifera as a promising agent against AChE and MAO-B. Using a computational approach via molecular docking 23 bioactive agents were screened against AChE and MAO-B, and the compounds with a binding score below that of the standard ligand were further subjected to drug-likeness and pharmacokinetic screening. Eight and thirteen of the studied agents optimally saturated the active pocket of the AChE and MAO-B respectively, forming principal interactions with a number of amino acids at the active pocket of the targets and among these compounds only rutin failed the drug-likeness test by violating four parameters while all showed moderate pharmacokinetics features. A number of Vitis vinifera-derived bioactive compounds show excellent inhibitory potential against AChE and MAO-B, and moderate pharmacokinetic features when compared to the reference ligand (tacrine). These compounds are therefore proposed as novel AChE and MAO-B inhibitors for the treatment of AD and wet-lab analysis is necessary to affirm their potency.

Perspectives of pregnant women on the utilisation of a maternity waiting home near Onandjokwe Lutheran Hospital in Oshikoto Region, Namibia.

BACKGROUND:  Despite the efforts of Namibia's Ministry of Health and Social Services to build maternity waiting homes (MWHs), few pregnant women make use of them. Long distances among the general population in Namibia limit the utilisation of MWHs. Little research has investigated what factors are limiting the use of these facilities despite the urgent need for them. The aim of this study thus was to explore and describe the perspectives of pregnant women on the utilisation of the MWHs near Onandjokwe Lutheran Hospital in Oshikoto Region. METHODS:  A qualitative, exploratory, descriptive and contextual design was employed. The accessible population in this study comprised 18 participants who were selected for the study using a purposive sampling technique. RESULTS:  Participants reported numerous barriers to visiting MWHs in Namibia, including an inadequate number of rooms, theft, food scarcity and the effects of poverty on the living conditions of the MWH users. Enablers visiting MWHs included the safe delivery of babies by skilled staff, reduced transport costs, access to timely management of labour complications and affordable accommodation. CONCLUSION:  The study revealed that a number of barriers must be overcome before the desired number of women take advantage of MWHs. Multiple factors act as constraints to their use, including inadequate number of rooms, theft, food scarcity and the long distance between patients' homes and MWH services.Contribution: The study's findings can be used to develop targeted interventions and strategies that can be used by MWH providers to address the identified barriers.