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1.
Animals (Basel) ; 14(4)2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38396535

ABSTRACT

The objective of the study was to determine the influence that initial BW has on growth performance responses, efficiency of dietary net energy (NE) utilization, and carcass traits in feedlot steers. Charolais×Red Angus steers (n = 70) selected from a larger single-source group were used in a 209-d growing-finishing feedlot experiment. Steers were assigned to two groups based on initial BW (light initial weight, LIW = 273 ± 16.0 kg; heavy initial weight, HIW = 356 ± 14.2 kg) and allotted into 10 pens (n = 7 steers per pen; 5 pens per experimental group) the within pen standard deviation for LIW was from 14.1 kg to 20.9 kg and for HIW was from 13.7 kg to 16.0 kg. Steers were fed a common diet once daily. Experimental data were analyzed as a randomized complete block design with pen as the experimental unit. LIW steers had a greater cumulative HH change (p = 0.04). A treatment × day interaction (p = 0.05) was observed for HH with HIW steers having a greater HH at all time points. Final BW and carcass-adjusted (HCW/0.625) BW were greater for HIW steers by 13.1% and 13.4% respectively (p ≤ 0.01). HIW steers had a greater DMI (p = 0.01) compared to LIW. Cumulative ADG was greater for HIW by 3% (p = 0.04). LIW steers had better feed conversion (p = 0.01). HIW steers had greater (p ≤ 0.05) HCW, marbling scores, and yield grade (YG), with decreased REA/HCW (p = 0.01) compared to LIW. The distribution of USDA Yield Grade was altered by initial BW (p = 0.04). No differences were detected (p ≥ 0.22) for the distribution of Quality grade nor liver abscess prevalence and severity. Regression coefficients did not differ between LIW and HIW for urea space calculations of empty body water, fat, or protein (p ≥ 0.70). A quadratic response was noted for empty body fat (EBF), empty body water (EBH20), and carcass protein (CP). In conclusion, HIW steers had greater growth, but poorer feed efficiency compared to LIW steers. Steers with a HIW produced fatter carcasses with a greater degree of marbling.

2.
Drug Alcohol Rev ; 43(2): 551-561, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38291714

ABSTRACT

INTRODUCTION: Prevalence and patterns of alcohol and other drug (AOD) use among specific lesbian, gay, bisexual, transgender (trans) and queer (LGBTQ+) subpopulations are well established. However, patterns of substance-related risk have been less thoroughly explored. This study aimed to determine typologies AOD risk among LGBTQ+ adults in Australia. METHOD: Latent class analyses were performed to determine distinct patterns of AOD risk (n = 6835), as measured by the Alcohol Use Disorder Identification Test and Drug Abuse Screening Tool. Demographic characteristics, experience of harassment, assault and/or threats, mental wellbeing and LGBTQ+ connectedness were compared across emergent classes. RESULTS: AOD risk was characterised as 'no risk' (13.3% of sample), 'low risk' (15.1%), 'moderate risk' (alcohol + other drugs; 30.1%), or 'moderate alcohol only risk' (41.5%). The 'moderate risk' class was the most likely class to report recent sexual assault, verbal abuse, harassment and physical threats compared to other classes, while those in the 'moderate alcohol only risk' group were least likely to report these experiences of all classes. However, both the 'moderate risk' and 'moderate alcohol risk only' classes reported greater mental wellbeing and LGBTQ+ connectedness compared to the 'no risk' and 'low risk' classes. DISCUSSION AND CONCLUSIONS: Our findings indicate that level of AOD risk is not uniform among some LGBTQ+ adults, nor is the distribution of harms experienced by them. Tailored harm-reduction interventions may be fruitful in attenuating harms based on risk profile; most specifically, LGBTQ+ individuals engaging in moderately risky concurrent AOD use.


Subject(s)
Homosexuality, Female , Sexual and Gender Minorities , Transgender Persons , Adult , Female , Humans , Gender Identity , Bisexuality , Sexual Behavior
4.
Dermatitis ; 35(2): 160-166, 2024.
Article in English | MEDLINE | ID: mdl-37669114

ABSTRACT

Background: Polyvinyl chloride (PVC) gloves are recommended as a safe alternative for patients with rubber accelerator allergy. However, allergic contact dermatitis to other chemicals in PVC gloves has been reported. Objective: To analyze single-use PVC medical examination gloves in the United States for the presence of potential contact allergens. Methods: Using liquid chromatography-mass spectrometry, 20 unique PVC gloves were analyzed in triplicate for 6 chemicals: benzisothiazolinone, bisphenol A, mono(2-ethylhexyl) maleate, tricresyl phosphate, triphenyl phosphate, and triphenyl phosphite. Results: All 20 PVC gloves contained detectable quantities of benzisothiazolinone (range, 0.001-1.48 parts per million [ppm]), bisphenol A (0.01-0.11 ppm), triphenyl phosphate (0.01-2.11 ppm), and triphenyl phosphite (0.001-0.22 ppm). Eighteen (90%) gloves contained mono(2-ethylhexyl) maleate (0.001-0.14 ppm) and 3 (15%) contained tricresyl phosphate (0.001-0.002 ppm). Conclusions: Known allergens were present in all 20 PVC gloves. However, the detected levels were mostly low and their relationship with sensitization and elicitation thresholds requires further study.


Subject(s)
Benzhydryl Compounds , Dermatitis, Allergic Contact , Organophosphates , Phenols , Phosphites , Thiazoles , Tritolyl Phosphates , Humans , United States , Allergens/adverse effects , Polyvinyl Chloride/adverse effects , Polyvinyl Chloride/chemistry , Gloves, Protective , Patch Tests , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Maleates , Rubber
5.
Dermatitis ; 35(1): 49-54, 2024.
Article in English | MEDLINE | ID: mdl-37843914

ABSTRACT

Background: Sensitization to (meth)acrylates, the most common nail cosmetic allergens, is rising. In recent years, home acrylic nail kits have become easily available. Objective: To investigate the characteristics of individuals reporting skin reactions associated with acrylic nail cosmetics, particularly home kits. Methods: Cross-sectional survey of Facebook nail allergy support groups. Inclusion criteria were self-reported skin reactions associated with acrylic nails and age ≥18 years. Results: There were 199 respondents, nearly all female (99%), mostly white (83%), and 25-54 years old (83%). Seventy-eight percent reported using home acrylic kits, more than half for the first time during COVID-19. They predominantly learned about kits through social media (68%) and received training through websites/online videos (74%). Most home users (83%) first developed skin reactions after starting to use home kits. Compared with nonhome users, significantly more home users reported skin reaction onset within 1 year of use, as well as nail damage (P < 0.05). Conclusions: Among online nail allergy support group members, home acrylic nail kit use was common and associated with earlier development of skin reactions and more frequent nail damage than professional acrylic manicures. These findings raise important questions about the need to regulate home acrylic nail kits.


Subject(s)
Cosmetics , Dermatitis, Allergic Contact , Nail Diseases , Female , Humans , Adolescent , Nails , Dermatitis, Allergic Contact/etiology , Cross-Sectional Studies , Acrylates/adverse effects , Cosmetics/adverse effects , Self Report
6.
Skin Health Dis ; 3(5): e266, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37799370

ABSTRACT

Despite the high prevalence of psychiatric illness in hospitalised dermatology patients, characterisation of psychiatric comorbidities on an inpatient dermatology consultation service in the United States has yet to be performed. To fill this gap in knowledge, we investigated the prevalence of and factors associated with psychiatric illness on the inpatient dermatology consultation service at the University of Southern California. Of the 429 patients seen by the dermatology consultation service between June 2021 to July 2022, 147 (34%) had psychiatric illness (defined as having at least 1 psychiatric diagnosis). Increasing age was associated with a decreased likelihood of psychiatric illness, while housing instability, chronic dermatologic disease, drug reaction, and pruritus without rash were associated with an increased likelihood of psychiatric illness. The high prevalence of psychiatric illness observed in hospitalised dermatology patients emphasises the importance of collaboration between consultant dermatologists and mental health specialists, particularly when specific sociodemographic or disease factors are present.

7.
Cutis ; 112(2): 78-81, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37820332

ABSTRACT

In 2023, lanolin was named the American Contact Dermatitis Society Allergen of the Year. Despite its widespread use in personal care products and industrial goods, lanolin is thought to be a rare sensitizer in patients with healthy skin; however, those with chronic inflammatory skin conditions are at a higher risk for allergic contact dermatitis (ACD) to lanolin. The proper patch test formulation for lanolin is a source of contention. In this article, we discuss ACD to lanolin with a focus on its paradoxical nature and the subtleties to consider when patch testing to this controversial allergen.


Subject(s)
Allergens , Dermatitis, Allergic Contact , Humans , United States , Allergens/adverse effects , Lanolin/adverse effects , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Patch Tests
8.
bioRxiv ; 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37609173

ABSTRACT

A fundamental question in biology is how a limited number of genes combinatorially govern cellular responses to environmental changes. While the prevailing hypothesis is that relationships between genes, processes, and ontologies could be plastic to achieve this adaptability, quantitatively comparing human gene functional connections between specific environmental conditions at scale is very challenging. Therefore, it remains unclear whether and how human genetic interaction networks are rewired in response to changing environmental conditions. Here, we developed a framework for mapping context-specific genetic interactions, enabling us to measure the plasticity of human genetic architecture upon environmental challenge for ~250,000 interactions, using cell cycle interruption, genotoxic perturbation, and nutrient deprivation as archetypes. We discover large-scale rewiring of human gene relationships across conditions, highlighted by dramatic shifts in the functional connections of epigenetic regulators (TIP60), cell cycle regulators (PP2A), and glycolysis metabolism. Our study demonstrates that upon environmental perturbation, intra-complex genetic rewiring is rare while inter-complex rewiring is common, suggesting a modular and flexible evolutionary genetic strategy that allows a limited number of human genes to enable adaptation to a large number of environmental conditions.

9.
Cutis ; 111(4): 172-175, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37289694

ABSTRACT

Both patients and health care providers commonly suspect laundry detergent as the cause of skin problems; however, research suggests that the prevalence of laundry detergent-associated allergic contact dermatitis (ACD) may be quite low. Herein, we provide a summary of the evidence for the potential allergenicity of laundry detergent, including common allergens present in laundry detergent, the role of machine washing, and the differential diagnosis for laundry detergent-associated ACD.


Subject(s)
Dermatitis, Allergic Contact , Detergents , Humans , Detergents/toxicity , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Allergens/adverse effects , Prevalence , Patch Tests
10.
Nat Immunol ; 24(7): 1200-1210, 2023 07.
Article in English | MEDLINE | ID: mdl-37277655

ABSTRACT

Inflammation of non-barrier immunologically quiescent tissues is associated with a massive influx of blood-borne innate and adaptive immune cells. Cues from the latter are likely to alter and expand activated states of the resident cells. However, local communications between immigrant and resident cell types in human inflammatory disease remain poorly understood. Here, we explored drivers of fibroblast-like synoviocyte (FLS) heterogeneity in inflamed joints of patients with rheumatoid arthritis using paired single-cell RNA and ATAC sequencing, multiplexed imaging and spatial transcriptomics along with in vitro modeling of cell-extrinsic factor signaling. These analyses suggest that local exposures to myeloid and T cell-derived cytokines, TNF, IFN-γ, IL-1ß or lack thereof, drive four distinct FLS states some of which closely resemble fibroblast states in other disease-affected tissues including skin and colon. Our results highlight a role for concurrent, spatially distributed cytokine signaling within the inflamed synovium.


Subject(s)
Arthritis, Rheumatoid , Humans , Cells, Cultured , Arthritis, Rheumatoid/genetics , Synovial Membrane , Cytokines/metabolism , Fibroblasts
11.
Drug Alcohol Rev ; 42(6): 1517-1528, 2023 09.
Article in English | MEDLINE | ID: mdl-37171154

ABSTRACT

INTRODUCTION: This study investigates differences in health and well-being associated with current, past or no injecting drug use (IDU) among people living with HIV (PLHIV) in Australia, identifying key health care considerations between injecting experiences. METHODS: Data were extracted from the HIV Futures 9 study; a survey of PLHIV conducted in 2018-2019. Chi-square and analysis of variance analyses compared clinical and treatment characteristics, major physical and mental comorbidities, sexually transmitted infection diagnoses, and quality of life for those who reported current (last 12 months), past (12+ months ago) or no IDU. RESULTS: Current IDU (n = 106) was associated with higher rates of sexually transmitted infection testing and diagnoses, higher frequency of self-reported antiretroviral therapy non-adherence due to drug use and greater social quality of life than past (n = 126) or no IDU (n = 508; total N = 740). Past and current IDUs were associated with more mental illness diagnoses and self-reported concern about drug use. Past IDU was associated with more physical comorbidities, lower satisfaction with clinical care and greater difficulty in affording health care than current or no IDU. DISCUSSION AND CONCLUSIONS: Past and current IDUs are associated with unique health concerns. However, past IDU appears to be related to greater dissatisfaction in navigating health care than individuals with current IDU experience. Higher social connection and the types of services being accessed by individuals who currently inject may play a role in shaping service satisfaction. Peer-based interventions to help support individuals in accessing services that are affirming of their needs is an ongoing priority.


Subject(s)
HIV Infections , Substance Abuse, Intravenous , Humans , Substance Abuse, Intravenous/epidemiology , Substance Abuse, Intravenous/complications , Nonprescription Drugs/therapeutic use , Quality of Life , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/complications , Comorbidity
12.
Alcohol ; 109: 49-54, 2023 06.
Article in English | MEDLINE | ID: mdl-36584742

ABSTRACT

BACKGROUND: Acute alcohol intoxication impairs cognitive and psychomotor abilities leading to various public health hazards such as road traffic accidents and alcohol-related violence. Intoxicated individuals are usually identified by measuring their blood alcohol concentration (BAC) using breathalyzers that are expensive and labor intensive. In this paper, we developed the Audio-based Deep Learning Algorithm to Identify Alcohol Inebriation (ADLAIA) that can instantly predict an individual's intoxication status based on a 12-s recording of their speech. METHODS: ADLAIA was trained on a publicly available German Alcohol Language Corpus that comprises a total of 12,360 audio clips of inebriated and sober speakers (total of 162, aged 21-64, 47.7% female). ADLAIA's performance was determined by computing the unweighted average recall (UAR) and accuracy of inebriation prediction. RESULTS: ADLAIA was able to identify inebriated speakers - with a BAC of 0.05% or higher - with an UAR of 68.09% and accuracy of 67.67%. ADLAIA had a higher performance (UAR of 75.7%) in identifying intoxicated speakers (BAC > 0.12%). CONCLUSION: Being able to identify intoxicated individuals solely based on their speech, ADLAIA could be integrated into mobile applications and used in environments (such as bars, sports stadiums) to get instantaneous results about inebriation status of individuals.


Subject(s)
Alcoholic Intoxication , Deep Learning , Humans , Female , Male , Blood Alcohol Content , Alcohol Drinking , Violence , Ethanol
13.
AIDS Behav ; 27(2): 591-599, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35838861

ABSTRACT

This paper examines how antiretroviral therapy (ART) use and fears towards the onward transmission of HIV have changed among people living with HIV (PLHIV) in Australia between 1997 and 2018. Participants were recruited as part of the HIV Futures study, a large cross-sectional survey of PLHIV in Australia, in 1997, 2003, 2012 and 2018 (total n = 3889). ART use, viral load detectability, and fear of onward HIV transmission were compared between years. Predictors of onward transmission fear were assessed among the 2018 subsample. While ART use within our sample decreased between 1997 and 2003, it subsequently increased to 97% in 2018. Self-reported viral load undetectability steadily increased over time, up to 88% in 2018. Notably, fewer PLHIV reported being fearful of transmitting HIV in 2018 compared to all other years. Being unfamiliar with the undetectable = untransmissible health movement, and having a detectable or uncertain viral load at last test, were significant predictors of being fearful of onward HIV transmission. Beyond the immediate medical considerations of HIV treatment, these results suggest that the undetectable = untransmissible movement may play a critical role in attenuating burdens experienced by PLHIV in Australia and that such messaging, in tandem with early and consistent ART use, should remain a salient feature of heath messaging among this population.


Subject(s)
Anti-HIV Agents , HIV Infections , Humans , HIV Infections/drug therapy , HIV Infections/epidemiology , Cross-Sectional Studies , Anti-HIV Agents/therapeutic use , Australia/epidemiology , Self Report , Viral Load
14.
Elife ; 112022 12 28.
Article in English | MEDLINE | ID: mdl-36576240

ABSTRACT

CRISPR interference (CRISPRi) enables programmable, reversible, and titratable repression of gene expression (knockdown) in mammalian cells. Initial CRISPRi-mediated genetic screens have showcased the potential to address basic questions in cell biology, genetics, and biotechnology, but wider deployment of CRISPRi screening has been constrained by the large size of single guide RNA (sgRNA) libraries and challenges in generating cell models with consistent CRISPRi-mediated knockdown. Here, we present next-generation CRISPRi sgRNA libraries and effector expression constructs that enable strong and consistent knockdown across mammalian cell models. First, we combine empirical sgRNA selection with a dual-sgRNA library design to generate an ultra-compact (1-3 elements per gene), highly active CRISPRi sgRNA library. Next, we compare CRISPRi effectors to show that the recently published Zim3-dCas9 provides an excellent balance between strong on-target knockdown and minimal non-specific effects on cell growth or the transcriptome. Finally, we engineer a suite of cell lines with stable expression of Zim3-dCas9 and robust on-target knockdown. Our results and publicly available reagents establish best practices for CRISPRi genetic screening.


Subject(s)
Clustered Regularly Interspaced Short Palindromic Repeats , RNA, Guide, CRISPR-Cas Systems , Cell Line , CRISPR-Cas Systems
15.
Health Promot Int ; 37(6)2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36367423

ABSTRACT

It is well documented that lower socio-economic status is associated with poorer health outcomes, while health literacy is considered important for improving health. What is less clear, is the extent to which greater health literacy can improve health outcomes among people for whom poverty or financial insecurity are important barriers to health. The paper presents findings from an Australian survey of people living with HIV (PLHIV) (N = 835) in which we explored the relationship between financial insecurity and health outcomes, looking at the extent to which health literacy mediates this relationship. The study drew on a comprehensive definition of health literacy, measuring participant's confidence to communicate with healthcare providers, navigate the health system and take an active stance in relation to their health. Findings showed that financial insecurity was associated with lower health literacy and poorer self-reported physical and mental health. Health literacy mediated 16.2% of the effect of financial insecurity on physical health scores and 16.6% of the effect of financial insecurity on mental health scores. This suggests that programmes which seek to build health literacy among PLHIV may improve health outcomes among PLHIV who are struggling financially. Health literacy programmes are likely to be effective if they build confidence and resourcefulness among people to engage with health information, decision-making and care.


Subject(s)
HIV Infections , Health Literacy , Humans , Australia , Mental Health , HIV Infections/psychology , Outcome Assessment, Health Care
16.
Alcohol Clin Exp Res ; 46(10): 1837-1845, 2022 10.
Article in English | MEDLINE | ID: mdl-36242596

ABSTRACT

BACKGROUND: Seeing alcohol in media has been demonstrated to increase alcohol craving, impulsive decision-making, and hazardous drinking. Due to the exponential growth of (social) media use it is important to develop algorithms to quantify alcohol exposure efficiently in electronic images. In this article, we describe the development of an improved version of the Alcoholic Beverage Identification Deep Learning Algorithm (ABIDLA), called ABIDLA2. METHODS: ABIDLA2 was trained on 191,286 images downloaded from Google Image Search results (based on search terms) and Bing Image Search results. In Task-1, ABIDLA2 identified images as containing one of eight beverage categories (beer/cider cup, beer/cider bottle, beer/cider can, wine, champagne, cocktails, whiskey/cognac/brandy, other images). In Task-2, ABIDLA2 made a binary classification between images containing an "alcoholic beverage" or "other". An ablation study was performed to determine which techniques improved algorithm performance. RESULTS: ABIDLA2 was most accurate in identifying Whiskey/Cognac/Brandy (88.1%) followed by Beer/Cider Can (80.5%), Beer/Cider Bottle (78.3%), and Wine (77.8%). Its overall accuracy was 77.0% (Task-1) and 87.7% (Task-2). Even the identification of the least accurate beverage category (Champagne, 64.5%) was more than five times higher than random chance (12.5% = 1/8 categories). The implementation of balanced data sampler to address class skewness and the use of self-training to make use of a large, secondary, weakly labeled dataset particularly improved overall algorithm performance. CONCLUSION: With extended capabilities and a higher accuracy, ABIDLA2 outperforms its predecessor and enables the screening of any kind of electronic media rapidly to estimate the quantity of alcohol exposure. Quantifying alcohol exposure automatically through algorithms like ABIDLA2 is important because viewing images of alcoholic beverages in media tends to increase alcohol consumption and related harms.


Subject(s)
Deep Learning , Alcoholic Beverages , Beer , Ethanol , Beverages , Electronics
17.
Front Psychiatry ; 13: 992309, 2022.
Article in English | MEDLINE | ID: mdl-36213894

ABSTRACT

While there is evidence for self-exclusion (SE) as an individual-level harm reduction intervention, its effects on reducing harm from gambling at the population level remain unclear. Based on a review of national legal frameworks and SE programs, including their utilization and enforcement in selected high-income societies, the present analysis aims to explore the reach and strengths of SE in the protection of gamblers in these jurisdictions. It places particular emphasis on SE programs' potential to prevent and minimize gambling harm at the population level. The overview examined SE in Finland, Germany, Italy, Massachusetts (USA), Norway, Sweden, and Victoria (Australia). These jurisdictions differ considerably in how gambling is regulated as well as in how SE is implemented and enforced. The reach and extent of enforcement of SE apparently vary with the polity's general policy balance between reducing gambling problems and increasing gambling revenue. But in any case, though SE may benefit individual gamblers and those around them, it does not appear to be capable of significantly reducing gambling harm at the population level. To render SE programs an effective measure that prevents gamblers and those linked to them from financial, social, and psychological harm, utilization needs to be substantially increased by reforming legal regulations and exclusion conditions.

18.
Dermatol Online J ; 28(3)2022 Jun 15.
Article in English | MEDLINE | ID: mdl-36259803

ABSTRACT

Lucio phenomenon is a rare vasculopathy that can occur in patients with Hansen disease, particularly diffuse lepromatous leprosy. It is characterized by retiform purpura and necrotic ulcerations, most commonly affecting the extremities. Diagnosing Lucio phenomenon can be challenging, especially when secondary bacterial infections occur. We report a patient with Lucio phenomenon who presented with acute necrotizing fasciitis of his left upper extremity and a 10-year history of chronic ulcerations. Shortly following admission, he also developed acute kidney injury. The necrotizing fasciitis was treated with prompt surgical debridement and intravenous antibiotics. Biopsy and PCR of a right upper extremity ulcer confirmed the presence of Mycobacterium lepromatosis. Multidrug therapy and prednisone were used to treat the Lucio phenomenon. After initiating treatment, no new lesions developed, kidney function improved, and the patient underwent successful skin graft of his left upper extremity. Although corticosteroid use is controversial, our patient's marked response to multidrug therapy with prednisone highlights the importance of this regimen in severe presentations of Lucio phenomenon. To the best of our knowledge, only two other cases of Lucio phenomenon confirmed to be caused by M. lepromatosis have been reported in living patients (rather than retrospectively identified post-mortem), underscoring the importance of the presented clinical course and treatment regimen.


Subject(s)
Acute Kidney Injury , Fasciitis, Necrotizing , Panniculitis , Vascular Diseases , Male , Humans , Leprostatic Agents/therapeutic use , Prednisone/therapeutic use , Fasciitis, Necrotizing/complications , Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/therapy , Drug Therapy, Combination , Retrospective Studies , Panniculitis/drug therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/drug therapy , Adrenal Cortex Hormones
19.
Cell ; 185(14): 2559-2575.e28, 2022 07 07.
Article in English | MEDLINE | ID: mdl-35688146

ABSTRACT

A central goal of genetics is to define the relationships between genotypes and phenotypes. High-content phenotypic screens such as Perturb-seq (CRISPR-based screens with single-cell RNA-sequencing readouts) enable massively parallel functional genomic mapping but, to date, have been used at limited scales. Here, we perform genome-scale Perturb-seq targeting all expressed genes with CRISPR interference (CRISPRi) across >2.5 million human cells. We use transcriptional phenotypes to predict the function of poorly characterized genes, uncovering new regulators of ribosome biogenesis (including CCDC86, ZNF236, and SPATA5L1), transcription (C7orf26), and mitochondrial respiration (TMEM242). In addition to assigning gene function, single-cell transcriptional phenotypes allow for in-depth dissection of complex cellular phenomena-from RNA processing to differentiation. We leverage this ability to systematically identify genetic drivers and consequences of aneuploidy and to discover an unanticipated layer of stress-specific regulation of the mitochondrial genome. Our information-rich genotype-phenotype map reveals a multidimensional portrait of gene and cellular function.


Subject(s)
Genomics , Single-Cell Analysis , CRISPR-Cas Systems/genetics , Chromosome Mapping , Genotype , Phenotype , Single-Cell Analysis/methods
20.
Alcohol Clin Exp Res ; 46(4): 628-640, 2022 04.
Article in English | MEDLINE | ID: mdl-35404505

ABSTRACT

BACKGROUND: The possibility of residual impairment of cognitive performance after multiday drinking sessions is particularly important given the potential for the deleterious effects of fatigue and hangover. This pilot study aimed to devise a methodology to compare sober performance on driving-relevant attentional tasks at the end of a 4-day music festival with performance at varying levels of the breath-alcohol curve. METHODS: Fifty-two participants completed selective and sustained attention tasks at a breath alcohol concentration (BrAC) of 0.00%, 0.05%, and 0.08% following acute dosing in a controlled laboratory setting. A subset of participants (n = 13) were then tested at the conclusion of a 4-day music festival at 0.00% BrAC, with task performance compared with laboratory results. RESULTS: During the laboratory phase, sustained attention was poorer at the 0.05% ascending timepoint only (compared to 0.00% BrAC). During the festival phase, participants made a greater number of errors on the selective attention task predeparture than at 0.00% and 0.05% BrAC in the laboratory. Sustained attention performance was poorer while intoxicated in the laboratory. CONCLUSIONS: Our findings suggest that the absence of blood alcohol acutely may not be indicative of unimpaired cognitive performance and that other factors related to multiday drinking may produce driving-related attentional deficits. The findings reinforce the need to measure attentional performance in real-world drinking contexts despite the methodological complexities of doing so. A larger study is warranted to replicate the findings and should include attentional measures that either are more sensitive to the effects of acute alcohol intoxication than those in our study or are based on a driving simulator.


Subject(s)
Alcoholic Intoxication , Automobile Driving , Alcohol Drinking/adverse effects , Alcohol Drinking/psychology , Alcoholic Intoxication/diagnosis , Alcoholic Intoxication/psychology , Breath Tests , Humans , Pilot Projects
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