Incidence of Severe Hepatotoxicity Related to Antiretroviral Therapy in HIV/HCV Coinfected Patients

Introduction. Hepatotoxicity is a concern in HIV/hepatitis C virus (HCV) coinfected patients due to their underlying liver disease. This study assessed the incidence of hepatotoxicity in HIV/HCV co-infected patients in two outpatient infectious diseases clinics. Methods. HIV/HCV co-infected adults were included in this retrospective study if they were PI or NNRTI naïve at their first clinic visit and were initiated on an NNRTI- and/or PI-based antiretroviral regimen. Patients were excluded if they had active or chronic hepatitis B virus (HBV). The primary objective was to determine the overall incidence of severe hepatotoxicity. Results. Fifty-six of the 544 patients identified met inclusion criteria. The incidence of severe hepatotoxicity was 10.7% (6/56 patients). Severe hepatotoxicity occurred with efavirenz (N = 2), nevirapine (N = 1), indinavir (N = 1), nelfinavir (N = 1), and saquinavir/ritonavir (N = 1). Conclusion. The incidence of severe hepatotoxicity appears to be low in this retrospective analysis of HIV/HCV co-infected patients receiving a PI-and/or NNRTI-based regimen

Effectiveness of an Intensive Drowning Prevention Program and Skills Retention by Children with and without Disabilities

This study examined the effectiveness of a drowning prevention program and the retention of swimming and water safety skills for 3-14 year-old children with and without disabilities. The intensive program, SWIM Central, used a top-down approach to teach 6 swimming and water safety skills during 10, 30-minute sessions. A post-participation parent survey results suggested that children ages 3-14 with and without disabilities who had previously participated in SWIM Central retained swimming and water safety skills to a similar degree. The current swim skill assessments showed that there was not an overall difference in swim skill performance in the presence of a disability; therefore, the SWIM Central program was effective in increasing overall swimming performance for children with and without disabilities

Efficacy of conjoint behavioral consultation in developmental-behavioral pediatric services.

• Purpose: To evaluate the effects of the CBC model in addressing presenting concerns for children across home, school, and health care systems. • What are the general effects of CBC in addressing identified concerns in a medically-referred sample? • How do parents and teachers perceive CBC in terms of its perceived effectiveness and acceptability? • How satisfied are parents and teachers with CBC consultants and services when provided across homeschool- medical settings

Development of a Multiplex Real-Time PCR Assay for Predicting Macrolide and Tetracycline Resistance Associated with Bacterial Pathogens of Bovine Respiratory Disease

Antimicrobial resistance (AMR) in bovine respiratory disease (BRD) is an emerging concern that may threaten both animal and public health. Rapid and accurate detection of AMR is essential for prudent drug therapy selection during BRD outbreaks. This study aimed to develop a multiplex quantitative real-time polymerase chain reaction assay (qPCR) to provide culture-independent information regarding the phenotypic AMR status of BRD cases and an alternative to the gold-standard, culture-dependent test. Bovine clinical samples (297 lung and 111 nasal) collected in Nebraska were subjected to qPCR quantification of macrolide (MAC) and tetracycline (TET) resistance genes and gold-standard determinations of AMR of BRD pathogens. Receiver operating characteristic curve analysis was used to classify AMR based on the qPCR results. For lung tissues, the qPCR method showed good agreement with the gold-standard test for both MACs and TETs, with a sensitivity of 67–81% and a specificity higher than 80%. For nasal swabs, qPCR results passed validation criteria only for TET resistance detection, with a sensitivity of 88%, a specificity of 80% and moderate agreement. The culture-independent assay developed here provides the potential for more rapid AMR characterization of BRD cases directly from clinical samples at equivalent accuracy and higher time efficiency compared with the gold-standard, culture-based test

Community screening for visual impairment in older people.

BACKGROUND: Visual problems in older people are common and frequently under-reported. The effects of poor vision in older people are wide reaching and include falls, confusion and reduced quality of life. Much of the visual impairment in older ages can be treated (e.g. cataract surgery, correction of refractive error). Vision screening may therefore reduce the number of older people living with sight loss. OBJECTIVES: The objective of this review was to assess the effects on vision of community vision screening of older people for visual impairment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 23 November 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared vision screening alone or as part of a multi-component screening package as compared to no vision screening or standard care, on the vision of people aged 65 years or over in a community setting. We included trials that used self-reported visual problems or visual acuity testing as the screening tool. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We graded the certainty of the evidence using GRADE. MAIN RESULTS: Visual outcome data were available for 10,608 people in 10 trials. Four trials took place in the UK, two in Australia, two in the United States and two in the Netherlands. Length of follow-up ranged from one to five years. Three of these studies were cluster-randomised trials whereby general practitioners or family physicians were randomly allocated to undertake vision screening or no vision screening. All studies were funded by government agencies. Overall we judged the studies to be at low risk of bias and only downgraded the certainty of the evidence (GRADE) for imprecision.Seven trials compared vision screening as part of a multi-component screening versus no screening. Six of these studies used self-reported vision as both screening tool and outcome measure, but did not directly measure vision. One study used a combination of self-reported vision and visual acuity measurement: participants reporting vision problems at screening were treated by the attending doctor, referred to an eye care specialist or given information about resources that were available to assist with poor vision. There was a similar risk of "not seeing well" at follow-up in people screened compared with people not screened in meta-analysis of six studies (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.97 to 1.14, 4522 participants high-certainty evidence). One trial reported "improvement in vision" and this occurred slightly less frequently in the screened group (RR 0.85, 95% CI 0.52 to 1.40, 230 participants, moderate-certainty evidence).Two trials compared vision screening (visual acuity testing) alone with no vision screening. In one study, distance visual acuity was similar in the two groups at follow-up (mean difference (MD) 0.02 logMAR, 95% CI -0.02 to 0.05, 532 participants, high-certainty evidence). There was also little difference in near acuity (MD 0.02 logMAR, 95% CI -0.03 to 0.07, 532 participants, high-certainty evidence). There was no evidence of any important difference in quality of life (MD -0.06 National Eye Institute 25-item visual function questionnaire (VFQ-25) score adjusted for baseline VFQ-25 score, 95% CI -2.3 to 1.1, 532 participants, high-certainty evidence). The other study could not be included in the data analysis as the number of participants in each of the arms at follow-up could not be determined. However the authors stated that there was no significant difference in mean visual acuity in participants who had visual acuity assessed at baseline (39 letters) as compared to those who did not have their visual acuity assessed (35 letters, P = 0.25, 121 participants).One trial compared a detailed health assessment including measurement of visual acuity (intervention) with a brief health assessment including one question about vision (standard care). People given the detailed health assessment had a similar risk of visual impairment (visual acuity worse than 6/18 in either eye) at follow-up compared with people given the brief assessment (RR 1.07, 95% CI 0.84 to 1.36, 1807 participants, moderate-certainty evidence). The mean composite score of the VFQ-25 was 86.0 in the group that underwent visual acuity screening compared with 85.6 in the standard care group, a difference of 0.40 (95% CI -1.70 to 2.50, 1807 participants, high-certainty evidence). AUTHORS' CONCLUSIONS: The evidence from RCTs undertaken to date does not support vision screening for older people living independently in a community setting, whether in isolation or as part of a multi-component screening package. This is true for screening programmes involving questions about visual problems, or direct measurements of visual acuity.The most likely reason for this negative review is that the populations within the trials often did not take up the offered intervention as a result of the vision screening and large proportions of those who did not have vision screening appeared to seek their own intervention. Also, trials that use questions about vision have a lower sensitivity and specificity than formal visual acuity testing. Given the importance of visual impairment among older people, further research into strategies to improve vision of older people is needed. The effectiveness of an optimised primary care-based screening intervention that overcomes possible factors contributing to the observed lack of benefit in trials to date warrants assessment; trials should consider including more dependent participants, rather than those living independently in the community

Artificial intelligence in digital pathology: a diagnostic test accuracy systematic review and meta-analysis

Ensuring diagnostic performance of AI models before clinical use is key to the safe and successful adoption of these technologies. Studies reporting AI applied to digital pathology images for diagnostic purposes have rapidly increased in number in recent years. The aim of this work is to provide an overview of the diagnostic accuracy of AI in digital pathology images from all areas of pathology. This systematic review and meta-analysis included diagnostic accuracy studies using any type of artificial intelligence applied to whole slide images (WSIs) in any disease type. The reference standard was diagnosis through histopathological assessment and / or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. We identified 2976 studies, of which 100 were included in the review and 48 in the full meta-analysis. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model. 100 studies were identified for inclusion, equating to over 152,000 whole slide images (WSIs) and representing many disease types. Of these, 48 studies were included in the meta-analysis. These studies reported a mean sensitivity of 96.3% (CI 94.1-97.7) and mean specificity of 93.3% (CI 90.5-95.4) for AI. There was substantial heterogeneity in study design and all 100 studies identified for inclusion had at least one area at high or unclear risk of bias. This review provides a broad overview of AI performance across applications in whole slide imaging. However, there is huge variability in study design and available performance data, with details around the conduct of the study and make up of the datasets frequently missing. Overall, AI offers good accuracy when applied to WSIs but requires more rigorous evaluation of its performance.Comment: 26 pages, 5 figures, 8 tables + Supplementary material

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

Background and objective Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. Methods Data from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. Results In M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = −3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. Conclusions Our data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects

Role for zinc transporter gene SLC39A12 in the nervous system and beyond

The SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including cellular zinc influx across the plasma membrane. Genome-wide association and exome sequencing studies have shown that brain susceptibility-weighted magnetic resonance imaging (MRI) intensity is associated with ZIP12 polymorphisms and rare mutations. ZIP12 is required for neural tube closure and embryonic development in Xenopus tropicalis. Frog embryos depleted of ZIP12 by antisense morpholinos develop an anterior neural tube defect and lack viability. ZIP12 is also necessary for neurite outgrowth and mitochondrial function in mouse neural cells. ZIP12 mRNA is increased in brain regions of schizophrenic patients. Outside of the nervous system, hypoxia induces ZIP12 expression in multiple mammalian species, including humans, which leads to endothelial and smooth muscle thickening in the lung and contributes towards pulmonary hypertension. Other studies have associated ZIP12 with other diseases such as cancer. Given that ZIP12 is highly expressed in the brain and that susceptibility-weighted MRI is associated with brain metal content, ZIP12 may affect neurological diseases and psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and schizophrenia. Furthermore, the induction of ZIP12 and resultant zinc uptake under pathophysiological conditions may be a critical component of disease pathology, such as in pulmonary hypertension. Drug compounds that bind metals like zinc may be able to treat diseases associated with impaired zinc homeostasis and altered ZIP12 function.Human Sciences Research and Graduate StudiesGraduate CollegeNutritional Science

The allergen profile of two edible insect species—Acheta domesticus and hermetia illucens

Scope: Edible insect proteins are increasingly introduced as an alternative sustainable food source to address the world\u27s need to feed the growing population. Tropomyosin is the main insect allergen; however, additional potential allergens are not well characterized and the impact of extraction procedures on immunological reactivity is unknown. Methods and results: Proteins from different commercial food products derived from cricket (Acheta domesticus) and black soldier fly (BSF) (Hermetia illucens) are extracted using five different extraction buffers. The proteins are analyzed by SDS-PAGE and immunoblotting using allergen-specific antibodies and crustacean allergic patient sera. IgE binding bands are analyzed by mass spectrometry as well as the complete allergen profile of all 30 extracts. Urea-based buffers are most efficient in extracting insect allergens. Shrimp-specific antibody cross-reactivity to tropomyosin from cricket and BSF indicates high sequence and structural similarity between shrimp and insects. Additional unique allergens are identified in both species, including hemocyanin, vitellogenin, HSP20, apolipophorin-III, and chitin-binding protein. Conclusions: Identifying potential allergenic proteins and their isoforms in cricket and BSF requires specific extraction approaches using urea-based methods. While tropomyosin is the most abundant and immunoreactive allergen, seven unique allergens are identified, highlighting the need for insect species-specific allergen detection in food products