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1.
Sci Total Environ ; 926: 171838, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38518820

ABSTRACT

Safe and hygienic management of human waste is essential in humanitarian settings. Urine-diverting dry toilets (UDDTs) can enable this management in some humanitarian emergency settings. A seeded, longitudinal environmental study was conducted in Hiloweyn refugee camp, Dollo Ado, Ethiopia, to measure Escherichia coli and Ascaris suum ova inactivation within closed UDDT vaults and to document environmental conditions (temperature, moisture content, and pH) that could influence inactivation. Hiloweyn camp represented an optimal location for a desiccation-based sanitation technology such as the UDDT. E. coli and Ascaris ova inactivation was observed in UDDTs under warm, dry, alkaline conditions at 6, 9, and 12 months of storage; UDDTs with samples containing <1000 E. coli/g total solids increased from 30 % to 95 % over 12 months, and a >2.8-log10 reduction in Ascaris ova viability was observed after 6 months. Additional laboratory-based studies were conducted to provide insights into the field study findings and study the impact of hydrated lime on E. coli and Ascaris ova inactivation. Results suggest that adding hydrated lime to elevate pH > 12 may increase inactivation and decrease storage time. Overall, UDDTs could contribute to the safe and hygienic management of human waste in comparable warm and dry humanitarian settings.


Subject(s)
Bathroom Equipment , Escherichia coli , Oxides , Animals , Humans , Ethiopia , Calcium Compounds/chemistry , Ascaris/physiology
3.
Psychol Sex ; 14(2): 399-415, 2023.
Article in English | MEDLINE | ID: mdl-37378301

ABSTRACT

Transgender and gender expansive emerging adults experience multiple forms of gender minority stress, which affect their mental health and wellbeing. Belongingness has been identified as a factor that fosters resilience among this population, with potential protective effects. Few studies have explored the role of thwarted belongingness and its potential moderating effect on the relation between gender minority stress and mental health. This study recruited a sample of 93 transgender and gender expansive emerging adults between the ages of 18 and 21 to examine whether thwarted belongingness significantly moderates the relations between gender minority stressors and mental health symptoms. We found evidence that thwarted belongingness moderates the relation between social rejection and depressive symptoms and the interaction effect between thwarted belongingness and victimization was significantly associated with psychological stress. For both of these associations, high levels of thwarted belongingness amplified the positive relation between gender minority stress and mental health symptoms. In contrast, at low levels of thwarted belongingness, the relation between rejection and depression was negative and the association between victimization and psychological stress was no longer statistically significant. Findings suggest that factors that minimize or interrupt thwarted belongingness among transgender and gender expansive emerging adults may be points of intervention to improve mental health outcomes in this population.

4.
Am J Hum Genet ; 110(4): 663-680, 2023 04 06.
Article in English | MEDLINE | ID: mdl-36965478

ABSTRACT

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development and developmental regression after the first year of life, followed by progressive spasticity that led to gait alterations, paraparesis, and oromotor dysfunction. Most individuals had cerebral, cerebellar, or basal ganglia volume loss by brain MRI. In the available cells from affected individuals, SNAPC4 abundance was decreased compared to unaffected controls, suggesting that the bi-allelic variants affect SNAPC4 accumulation. The depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing. Analysis of available fibroblasts from affected individuals showed decreased snRNA expression and global dysregulation of alternative splicing compared to unaffected cells. Altogether, these data suggest that these bi-allelic SNAPC4 variants result in loss of function and underlie the neuroregression and progressive spasticity in these affected individuals.


Subject(s)
Alternative Splicing , DNA-Binding Proteins , Paraparesis, Spastic , Transcription Factors , Paraparesis, Spastic/genetics , Humans , DNA-Binding Proteins/genetics , Transcription Factors/genetics , HeLa Cells , Protein Isoforms/genetics , RNA-Seq , Male , Female , Pedigree , Alleles , Infant , Child, Preschool , Child , Adolescent , Protein Structure, Secondary , RNA, Small Nuclear/genetics
5.
Ann. intern. med ; 176(3): 388-397, 20230301.
Article in English | BIGG - GRADE guidelines | ID: biblio-1436082

ABSTRACT

In May 2022, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the use of opioids when managing chronic pain. This synopsis summarizes the recommendations that the authors believe are the most important to highlight. In December 2020, the VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2017 VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain. The guideline development team included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy clinical practice guidelines. The guideline team developed key questions to guide a systematic evidence review that was done by an independent third party and distilled 20 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The guideline team also created 3 one-page algorithms to help guide clinical decision making. This synopsis presents the recommendations and highlights selected recommendations on the basis of clinical relevance. This guideline is intended for clinicians who may be considering opioid therapy to manage patients with chronic pain. This synopsis reviews updated recommendations for the initiation and continuation of opioid therapy; dose, duration, and taper of opioids; screening, assessment, and evaluation; and risk mitigation. New additions are highlighted, including recommendations about the use of buprenorphine instead of full agonist opioids; assessing for behavioral health conditions and factors associated with higher risk for harm, such as pain catastrophizing; and the use of pain and opioid education to reduce the risk for prolonged opioid use for postsurgical pain.


Subject(s)
Humans , Adult , Pain Clinics , Chronic Pain/drug therapy , Pain, Postoperative/drug therapy , Buprenorphine/therapeutic use , Opiate Substitution Treatment , Analgesics, Opioid/therapeutic use
6.
NPJ Genom Med ; 8(1): 4, 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36765070

ABSTRACT

Autophagy regulates the degradation of damaged organelles and protein aggregates, and is critical for neuronal development, homeostasis, and maintenance, yet few neurodevelopmental disorders have been associated with pathogenic variants in genes encoding autophagy-related proteins. We report three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment, and similar facial characteristics. Rare, conserved, bi-allelic variants were identified in ATG4D, encoding one of four ATG4 cysteine proteases important for autophagosome biogenesis, a hallmark of autophagy. Autophagosome biogenesis and induction of autophagy were intact in cells from affected individuals. However, studies evaluating the predominant substrate of ATG4D, GABARAPL1, demonstrated that three of the four ATG4D patient variants functionally impair ATG4D activity. GABARAPL1 is cleaved or "primed" by ATG4D and an in vitro GABARAPL1 priming assay revealed decreased priming activity for three of the four ATG4D variants. Furthermore, a rescue experiment performed in an ATG4 tetra knockout cell line, in which all four ATG4 isoforms were knocked out by gene editing, showed decreased GABARAPL1 priming activity for the two ATG4D missense variants located in the cysteine protease domain required for priming, suggesting that these variants impair the function of ATG4D. The clinical, bioinformatic, and functional data suggest that bi-allelic loss-of-function variants in ATG4D contribute to the pathogenesis of this syndromic neurodevelopmental disorder.

7.
Ann Intern Med ; 176(3): 388-397, 2023 03.
Article in English | MEDLINE | ID: mdl-36780654

ABSTRACT

DESCRIPTION: In May 2022, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the use of opioids when managing chronic pain. This synopsis summarizes the recommendations that the authors believe are the most important to highlight. METHODS: In December 2020, the VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2017 VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain. The guideline development team included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy clinical practice guidelines. The guideline team developed key questions to guide a systematic evidence review that was done by an independent third party and distilled 20 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The guideline team also created 3 one-page algorithms to help guide clinical decision making. This synopsis presents the recommendations and highlights selected recommendations on the basis of clinical relevance. RECOMMENDATIONS: This guideline is intended for clinicians who may be considering opioid therapy to manage patients with chronic pain. This synopsis reviews updated recommendations for the initiation and continuation of opioid therapy; dose, duration, and taper of opioids; screening, assessment, and evaluation; and risk mitigation. New additions are highlighted, including recommendations about the use of buprenorphine instead of full agonist opioids; assessing for behavioral health conditions and factors associated with higher risk for harm, such as pain catastrophizing; and the use of pain and opioid education to reduce the risk for prolonged opioid use for postsurgical pain.


Subject(s)
Chronic Pain , Veterans , Humans , United States , Chronic Pain/drug therapy , Analgesics, Opioid/adverse effects , United States Department of Veterans Affairs
8.
J Sch Health ; 93(7): 537-546, 2023 07.
Article in English | MEDLINE | ID: mdl-36825483

ABSTRACT

BACKGROUND: Schools have become a primary access point for mental health services to cover the gap between need and service utilization that has long existed, particularly among vulnerable populations. This study aims to identify the profiles of comprehensive school mental and behavioral health system (CSMBHS) needs and examine related characteristics. METHODS: We used the 2019 National Survey of Drug Use and Health (NSDUH) collected from a nationally representative sample in the United States. The sample included 6th through 12th-grade adolescents who had received CSMBHS services in the last 12 months (N = 1346). The study conducted latent class analysis and multinomial logistic regression using Vermunt's 3-step approach. RESULTS: The analysis identified 3 profiles of student CSMBHS service need: depression needs (42%), multiple endorsements in most needs (depressed, friend, and school problems; 6.5%), and low endorsement (51.4%). Findings suggest that the profiles differed by age, a lifetime major depressive episode, family income, and use of other mental health services. IMPLICATIONS FOR SCHOOL HEALTH, POLICY, PRACTICE, AND EQUITY: Emphasis should be placed on proactively identifying student needs and advocating for appropriate interventions based on student needs. CONCLUSIONS: The study reveals important information regarding how schools best support students in need and in seeking services.


Subject(s)
Depressive Disorder, Major , Mental Health Services , Substance-Related Disorders , Humans , Adolescent , United States , Health Surveys , Substance-Related Disorders/epidemiology , Substance-Related Disorders/therapy , School Health Services
9.
Mol Genet Metab ; 138(3): 107525, 2023 03.
Article in English | MEDLINE | ID: mdl-36796138

ABSTRACT

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood. The clinical continuum encompasses hepatic, cardiac, muscular, and neurologic manifestations that range in severity. The adult-onset form of GSD IV, referred to as adult polyglucosan body disease (APBD), is a neurodegenerative disease characterized by neurogenic bladder, spastic paraparesis, and peripheral neuropathy. There are currently no consensus guidelines for the diagnosis and management of these patients, resulting in high rates of misdiagnosis, delayed diagnosis, and lack of standardized clinical care. To address this, a group of experts from the United States developed a set of recommendations for the diagnosis and management of all clinical phenotypes of GSD IV, including APBD, to support clinicians and caregivers who provide long-term care for individuals with GSD IV. The educational resource includes practical steps to confirm a GSD IV diagnosis and best practices for medical management, including (a) imaging of the liver, heart, skeletal muscle, brain, and spine, (b) functional and neuromusculoskeletal assessments, (c) laboratory investigations, (d) liver and heart transplantation, and (e) long-term follow-up care. Remaining knowledge gaps are detailed to emphasize areas for improvement and future research.


Subject(s)
Glycogen Storage Disease Type IV , Glycogen Storage Disease , Neurodegenerative Diseases , Child, Preschool , Humans , Glycogen Storage Disease Type IV/diagnosis , Glycogen Storage Disease Type IV/genetics , Glycogen Storage Disease Type IV/therapy , Glycogen Storage Disease/diagnosis , Glycogen Storage Disease/genetics , Glycogen Storage Disease/therapy , Glycogen
10.
Pain Pract ; 23(4): 338-348, 2023 04.
Article in English | MEDLINE | ID: mdl-36527287

ABSTRACT

OBJECTIVE: Cognitive behavioral therapy for chronic pain (CBT-CP) is an evidence-based treatment for improving functioning and pain intensity for people with chronic pain with extensive evidence of effectiveness. However, there has been relatively little investigation of the factors associated with successful implementation and uptake of CBT-CP, particularly clinician and system level factors. This formative evaluation examined barriers and facilitators to the successful implementation and uptake of CBT-CP from the perspective of CBT-CP clinicians and referring primary care clinicians. METHODS: Qualitative interviews guided by the Consolidated Framework for Implementation Research were conducted at nine geographically diverse Veterans Affairs sites as part of a pragmatic clinical trial comparing synchronous, clinician-delivered CBT-CP and remotely delivered, technology-assisted CBT-CP. Analysis was informed by a grounded theory approach. RESULTS: Twenty-six clinicians (CBT-CP clinicians = 17, primary care clinicians = 9) from nine VA medical centers participated in individual qualitative interviews conducted by telephone from April 2019 to August 2020. Four themes emerged in the qualitative interviews: (1) the complexity and variability of referral pathways across sites, (2) referring clinician's lack of knowledge about CBT-CP, (3) referring clinician's difficulty identifying suitable candidates for CBT-CP, and (4) preference for interventions that can be completed from home. CONCLUSIONS: This formative evaluation identified clinician and system barriers to widespread implementation of CBT-CP and allowed for refinement of the subsequent implementation of two forms of CBT-CP in an ongoing pragmatic trial. Identification of relative difference in barriers and facilitators in the two forms of CBT-CP may emerge more clearly in a pragmatic trial that evaluates how treatments perform in real-world settings and may provide important information to guide future system-wide implementation efforts.


Subject(s)
Chronic Pain , Cognitive Behavioral Therapy , Self-Management , Telemedicine , Humans , Chronic Pain/therapy , Chronic Pain/psychology
11.
Contemp Clin Trials ; 125: 107041, 2023 02.
Article in English | MEDLINE | ID: mdl-36496154

ABSTRACT

BACKGROUND: Chronic low back pain (cLBP) is a common and highly disabling problem world-wide. Although many treatment options exist, it is unclear how to best sequence the multitude of care options to provide the greatest benefit to patients. METHODS: The Sequential and Comparative Evaluation of Pain Treatment Effectiveness Response (SCEPTER) trial uses a pragmatic, randomized, stepped design. Enrollment targets 2529 participants from 20 Veterans Affairs (VA) medical centers. Participants with chronic low back pain will first be randomized to one of three options: 1) an internet-based self-management program (Pain EASE); 2) a tailored physical therapy program (Enhanced PT); or 3) continued care with active monitoring (CCAM), a form of usual care. Participants not achieving a 30% or 2-point reduction on the study's primary outcome (Brief Pain Inventory Pain Interference (BPI-PI) subscale), 3 months after beginning treatment may undergo re-randomization in a second step to cognitive behavioral therapy for chronic pain, spinal manipulation therapy, or yoga. Secondary outcomes include pain intensity, back pain-related disability, depression, and others. Participants will be assessed every three months until 12 months after initiating their final trial therapy. Companion economic and implementation analyses are also planned. RESULTS: The SCEPTER trial is currently recruiting and enrolling participants. CONCLUSIONS: Trial results will inform treatment decisions for the stepped management of chronic low back pain - a common and disabling condition. Additional analyses will help tailor treatment selection to individual patient characteristics, promote efficient resource use, and identify implementation barriers of interventions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT04142177.


Subject(s)
Chronic Pain , Cognitive Behavioral Therapy , Low Back Pain , Humans , Back Pain , Chronic Pain/therapy , Chronic Pain/psychology , Cognitive Behavioral Therapy/methods , Low Back Pain/therapy , Low Back Pain/psychology , Treatment Outcome
12.
Anthrozoos ; 35(1): 143-163, 2022.
Article in English | MEDLINE | ID: mdl-35241874

ABSTRACT

Human-animal interaction research is growing in popularity and methodological rigor; however, there remains a need for psychometrically validated measures and inclusion of broader populations. This study addressed these gaps by reporting on the psychometric properties of the Comfort from Companion Animals Scale (CCAS) in a sample of sexual and gender minority emerging adults. Participants included 138 emerging adults between the ages of 18-21 years (M = 19.33 years, SD = 1.11; 38.4% racial/ethnic minority) who identified as a gender (48.6%) and/or sexual minority (98.6%) and who reported living with a companion animal in the past year. We utilized the following analytic methods: (a) confirmatory factor analyses to compare the unidimensional structure of the CCAS with the two alternative models, (b) multiple group analyses to test measurement invariance across demographic groups, and (c) structural equation models to evaluate construct validity. Preliminary analysis found that the majority of participants did not endorse the two lowest response options. To conduct invariance testing, we eliminated items 3, 5, and 8 from the CCAS and collapsed the lowest response options. The results of the confirmatory factor analysis supported the use of this revised unidimensional model. We found evidence of measurement invariance across gender identity, sexual orientation, and race/ethnicity groups. Construct validity was supported by comparing the CCAS with factors on the Pet Attachment and Life Impact Scale; the positive association between the CCAS and anxiety are discussed in the context of prior research. Overall, our findings highlight the importance of validating human-animal interaction measures across samples from diverse backgrounds. We recommend that future studies continue to test the CCAS and other measures of human-animal attachment among diverse samples to delineate which aspects of human-animal interaction may be most beneficial in promoting mental health in vulnerable populations.

13.
Psychol Serv ; 19(1): 95-102, 2022 Feb.
Article in English | MEDLINE | ID: mdl-32986454

ABSTRACT

The U.S. Department of Veterans Affairs (VA) has been training clinicians in its cognitive behavioral therapy for chronic pain (CBT-CP) structured protocol since 2012. The aim of this project was to review patient outcomes to determine the effectiveness of the VA's CBT-CP treatment. From 2012-2018, 1,331 Veterans initiated individual CBT-CP treatment as part of the training program. Patient outcomes were assessed with measures of patient-reported pain intensity, pain catastrophizing, depression, pain interference, and quality of life (physical, psychological, social, and environmental). Mixed models of the effects of time indicated significant changes across pretreatment, midtreatment, and treatment conclusion on all outcomes. There was a large effect size (Cohen's d = 0.78) for pain catastrophizing, and there were medium to large effect sizes (d > 0.60) for worst pain intensity, pain interference, depression, and physical quality of life. Systematic training of therapists and implementation of the VA's CBT-CP protocol yielded significant patient improvements across multiple domains. This offers strong support for the VA's CBT-CP as an effective, safe treatment for Veterans with chronic pain and highlights it as a model to increase the availability of training in standardized, pain-focused, evidence-based, behavioral interventions. The findings suggest that the broad dissemination of such training, including in routine, nonpain specialty settings, would improve patient access to effective, nonpharmacological treatment options in both the public and private sectors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Chronic Pain , Cognitive Behavioral Therapy , Veterans , Chronic Pain/psychology , Chronic Pain/therapy , Cognitive Behavioral Therapy/methods , Humans , Quality of Life , Treatment Outcome , Veterans/psychology
14.
J Interpers Violence ; 37(19-20): NP17205-NP17226, 2022 10.
Article in English | MEDLINE | ID: mdl-34275347

ABSTRACT

Childhood exposure to intimate partner violence (IPV) is associated with serious psychological outcomes including increased odds of developing callous-unemotional (CU) traits and behaviors. Recent studies suggest that concomitant exposure to animal cruelty (AC) may increase this risk. However, even under these circumstances, bonds with companion animals may still be a protective factor that buffers the deleterious impact of IPV on child adjustment. This cross-sectional study evaluates whether, and to what extent, the association between exposure to IPV and children's CU and empathic-prosocial (EP) traits vary as a function of children's positive engagement with pets and exposure to AC. Participants included 204 children (aged 7-12 years; 57% Latinx) and their maternal caregiver who were recruited from domestic violence agencies in a western US state. We conducted multiple moderation analyses to evaluate each outcome individually (i.e., CU traits, EP traits), adjusting for the effects of child age, gender, and Hispanic ethnicity. Positive engagement with pets significantly moderated the relationship between IPV and CU traits, ∇R = 0.03, F (1, 195) = 7.43, ß = -0.17, t(195) = -2.73, p = .007. Specifically, when high levels of positive engagement with pets is present, IPV is negatively associated with CU traits, whereas the reverse was true at low levels of positive engagement with pets. Evidence of moderation by AC was not supported. Our findings suggest that children who form close relationships with their pets in the context of IPV appear to derive important support from these animals; safeguarding the well-being of these animals may be critical to their long-term emotional health.


Subject(s)
Conduct Disorder , Exposure to Violence , Intimate Partner Violence , Animals , Cross-Sectional Studies , Exposure to Violence/psychology , Humans , Intimate Partner Violence/psychology
15.
Fam Syst Health ; 39(2): 351-357, 2021 06.
Article in English | MEDLINE | ID: mdl-34410777

ABSTRACT

Introduction: Brief Cognitive Behavioral Therapy for Chronic Pain (Brief CBT-CP) is a biopsychosocial treatment designed to improve access to nonpharmacological pain care in primary care. Results from a clinical demonstration project in Veterans Health Administration (VHA) clinics showed rapid improvement in pain outcomes following Brief CBT-CP treatment in Primary Care Behavioral Health (PCBH). As part of this larger project, the current work aimed to understand patients' perspectives of Brief CBT-CP via a self-report survey completed posttreatment. Method: Thirty-four primary care patients received Brief CBT-CP as part of their usual VHA care and subsequently completed an anonymous survey that included questions regarding treatment modality, intervention content, utility, and satisfaction, as well as global assessment of change in pain-related functioning. Results: Participants reported that Brief CBT-CP content was useful (91%) and that they were satisfied with the intervention overall (89%), including appointment length, frequency of encounters, and comprehensibility of content. On average (M = 4.50, SD = 1.71), participants reported "somewhat better" to "moderately better" pain-related functioning following treatment. Exploratory descriptive analysis indicated that self-reported change in function following treatment may vary by patient characteristics, including gender and opioid use history. Discussion: Patients were receptive to Brief CBT-CP, were satisfied with their experience during treatment, and reported benefit in pain-related functioning after treatment. Further development and evaluation of Brief CBT-CP as a feasible biopsychosocial treatment option for pain in primary care clinics using the PCBH model of integration is warranted. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Chronic Pain , Cognitive Behavioral Therapy , Chronic Pain/therapy , Humans , Pain Management , Patient Satisfaction , Personal Satisfaction , Treatment Outcome
16.
Mol Genet Metab ; 134(1-2): 195-202, 2021.
Article in English | MEDLINE | ID: mdl-34412939

ABSTRACT

Neurobeachin (NBEA) was initially identified as a candidate gene for autism. Recently, variants in NBEA have been associated with neurodevelopmental delay and childhood epilepsy. Here, we report on a novel NBEA missense variant (c.5899G > A, p.Gly1967Arg) in the Domain of Unknown Function 1088 (DUF1088) identified in a child enrolled in the Undiagnosed Diseases Network (UDN), who presented with neurodevelopmental delay and seizures. Modeling of this variant in the Caenorhabditis elegans NBEA ortholog, sel-2, indicated that the variant was damaging to in vivo function as evidenced by altered cell fate determination and trafficking of potassium channels in neurons. The variant effect was indistinguishable from that of the reference null mutation suggesting that the variant is a strong hypomorph or a complete loss-of-function. Our experimental data provide strong support for the molecular diagnosis and pathogenicity of the NBEA p.Gly1967Arg variant and the importance of the DUF1088 for NBEA function.


Subject(s)
Carrier Proteins/genetics , Epilepsy/genetics , Genetic Variation , Nerve Tissue Proteins/genetics , Neurodevelopmental Disorders/genetics , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Child , Female , Gene Editing , Humans , Pathology, Molecular , Potassium Channels/metabolism
17.
J Microbiol Methods ; 189: 106279, 2021 10.
Article in English | MEDLINE | ID: mdl-34271057

ABSTRACT

We report a specific region of Giardia spp. 18S ribosomal RNA (18S rDNA) that serves as an ideal target for quantitative PCR (qPCR) detection and sequencing to identify Giardia species, including the clinically-relevant G. duodenalis, in clinical and environmental samples. The presence of multiple copies of the 18S rDNA gene and variations in the selected 18S genomic region enabled the development of a rapid, sensitive qPCR screening method for the detection of Giardia spp. The analytical sensitivity of the Giardia qPCR assay was determined to be a cyst equivalent of 0.4 G. duodenalis cysts per PCR reaction. Amplicon sequencing of the PCR product confirmed Giardia spp. detection and among the 35 sequences obtained, 31, 3 and 1 isolates were classified as belonging to G. duodenalis, G. microti and G. muris, respectively. The TaqMan assay reported here may be useful for the detection of low levels of Giardia in clinical and environmental samples, and further enables the effective use of direct sequencing of the PCR product for Giardia confirmation and to identify major species of Giardia, including G. duodenalis.


Subject(s)
Giardia/genetics , Real-Time Polymerase Chain Reaction/methods , Sequence Analysis, DNA/methods , DNA, Ribosomal/genetics , Feces/parasitology , Genotype , Giardia/classification , Giardiasis/diagnosis , Giardiasis/parasitology , RNA, Ribosomal, 18S/genetics , Real-Time Polymerase Chain Reaction/standards
18.
Animals (Basel) ; 11(3)2021 Mar 21.
Article in English | MEDLINE | ID: mdl-33801041

ABSTRACT

This cross-sectional study examined whether, and to what extent, attachment to pets was associated with changes in latent patterns of adults' perceived mental health symptoms during the COVID-19 pandemic (n = 1942). We used latent transition analysis to determine the stability of subgroup membership pre- and post-COVID and the effect of attachment to pets on transition probabilities. Mental health before COVID-19 was measured retrospectively. Five subgroups were identified: low symptoms, mild symptoms, moderate symptoms, high symptoms, and severe symptoms. Among individuals in the moderate and high symptoms subgroups, those who reported high attachment to pets generally had greater odds of transitioning to a less severe symptom profile (OR = 2.12) over time than those with low attachment to pets (OR = 1.39). However, those who had a severe symptom profile and high attachment to pets had lower odds of transitioning to a less severe symptom profile (OR = 0.30) and higher odds of maintaining a severe symptom profile (OR = 3.33) than those with low attachment to pets. These findings suggest that the protective and risk effects of attachment to pets differ based on individuals' psychological symptom patterns across multiple indicators. We discuss the implications of these findings for research, policy, and practice.

19.
Environ Sci Technol ; 55(4): 2674-2683, 2021 02 16.
Article in English | MEDLINE | ID: mdl-33533250

ABSTRACT

It is imperative to understand the behavior of enveloped viruses during water treatment to better protect public health, especially in the light of evidence of detection of coronaviruses in wastewater. We report bench-scale experiments evaluating the extent and mechanisms of removal and/or inactivation of a coronavirus surrogate (ϕ6 bacteriophage) in water by conventional FeCl3 coagulation and Fe(0) electrocoagulation. Both coagulation methods achieved ∼5-log removal/inactivation of ϕ6 in 20 min. Enhanced removal was attributed to the high hydrophobicity of ϕ6 imparted by its characteristic phospholipid envelope. ϕ6 adhesion to freshly precipitated iron (hydr)oxide also led to envelope damage causing inactivation in both coagulation techniques. Fourier transform infrared spectroscopy revealed oxidative damages to ϕ6 lipids only for electrocoagulation consistent with electro-Fenton reactions. Monitoring ϕ6 dsRNA by a novel reverse transcription quantitative polymerase chain reaction (RT-qPCR) method quantified significantly lower viral removal/inactivation in water compared with the plaque assay demonstrating that relying solely on RT-qPCR assays may overstate human health risks arising from viruses. Transmission electron microscopy and computationally generated electron density maps of ϕ6 showed severe morphological damages to virus' envelope and loss of capsid volume accompanying coagulation. Both conventional and electro- coagulation appear to be highly effective in controlling enveloped viruses during surface water treatment.


Subject(s)
Iron , Water Purification , Electrocoagulation , Humans , Virus Inactivation , Wastewater
20.
Pain Med ; 22(2): 430-443, 2021 02 23.
Article in English | MEDLINE | ID: mdl-33496787

ABSTRACT

OBJECTIVE: Despite empirical support for interdisciplinary pain rehabilitation programs improving functioning and quality of life, access to this treatment approach has decreased dramatically over the last 20 years within the United States but has grown significantly in the Department of Veterans Affairs (VA). Between 2009 and 2019, VA pain rehabilitation programs accredited by the Commission on Accreditation of Rehabilitation Facilities increased 10-fold in the VA, expanding from two to 20. The aim of this collaborative observational evaluation was to examine patient outcomes across a subset of six programs at five sites. METHODS: Outcomes were assessed using agreed-upon measures of patient-reported pain intensity, pain interference across various domains, pain catastrophizing, and sleep. RESULTS: A total of 931 patients enrolled in the selected VA interdisciplinary pain programs, with 84.1% of participants completing the full course of treatment. Overall, all programs showed significant improvements from pretreatment to posttreatment in nearly all patient-reported outcomes. The effect sizes ranged from medium to large. Notably, the results demonstrate that positive outcomes were typical despite differences in structure and resources across programs. CONCLUSIONS: The adverse impacts of opioid use have highlighted the importance of chronic pain treatment approaches that emphasize team-based care focused on functional improvements. This study represents the first and largest analysis of outcomes across chronic pain rehabilitation programs and demonstrates the need for increased access to similar comprehensive approaches to pain management across the health care system. Further, it suggests that a variety of structures may be effective, encouraging flexibility in adopting this interdisciplinary approach.


Subject(s)
Chronic Pain , Veterans , Humans , Pain Management , Quality of Life , United States , United States Department of Veterans Affairs
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