Genomic analysis of spermatocytic tumors demonstrates recurrent molecular alterations in cases with malignant clinical behavior.

Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, their genomic and epigenomic features remain incompletely described. Twenty-seven samples from 25 individual patients were analyzed with a combination of DNA sequencing panels, genomic methylation profiling, SNP array, isochromosome (12p) [i(12p)] FISH, and immunohistochemistry. The series included five metastasizing tumors (three with sarcomatoid transformation, one anaplastic, and one conventional) and 20 non-metastasizing tumors (14 anaplastic and six conventional). Anaplastic tumors comprised a monomorphic population of intermediate-sized neoplastic cells, as previously described. Multiomic analyses demonstrated that there were two genomic subgroups of STs: one with diploid genomes and hotspot RAS/RAF variants and the other with global ploidy shift and absence of recurrent mutations. Relative gain of chromosome 9 was a consistent finding in both subgroups. A comparison of metastasizing and non-metastasizing cases demonstrated that aggressive behavior was associated with the acquisition of pathogenic TP53 mutations and/or relative gains of 12p/i(12p). In cases with sarcomatoid transformation, TP53 mutations seem to underlie the transition to sarcomatoid histology. Genomic methylation analysis demonstrated that aggressive cases with gains of 12p cluster closer to pure seminomas than to STs without gains of 12p. In conclusion, STs include two genomic subgroups, characterized by global ploidy shifts without recurrent mutations and diploid genomes with RAS/RAF hotspot mutations, respectively. Biologic progression was associated with relative gains of 12p and TP53 mutations. The findings in STs with relative gains of 12p suggest that they may exhibit biologic characteristics akin to those seen in germ cell neoplasia in situ-related germ cell tumors rather than non-germ cell neoplasia in situ-derived STs. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Tissue-specific regulation of lipid polyester synthesis genes controlling oxygen permeation into Lotus japonicus nodules.

Legumes establish endosymbiotic associations with nitrogen-fixing rhizobia, which they host inside root nodules. Here, specific physiological and morphological adaptations, such as the production of oxygen-binding leghemoglobin proteins and the formation of an oxygen diffusion barrier in the nodule periphery, are essential to protect the oxygen-labile bacterial nitrogenase enzyme. The molecular basis of the latter process remains elusive as the identification of required genes is limited by the epistatic effect of nodule organogenesis over nodule infection and rhizobia accommodation. We overcame this by exploring the phenotypic diversity of Lotus japonicus accessions that uncouple nodule organogenesis from nodule infection when inoculated with a subcompatible Rhizobium strain. Using comparative transcriptomics, we identified genes with functions associated with oxygen homeostasis and deposition of lipid polyesters on cell walls to be specifically up-regulated in infected compared to noninfected nodules. As hydrophobic modification of cell walls is pivotal for creating diffusion barriers like the root endodermis, we focused on two Fatty acyl-CoA Reductase genes that were specifically activated in the root and/or in the nodule endodermis. Mutant lines in a Fatty acyl-CoA Reductase gene expressed exclusively in the nodule endodermis had decreased deposition of polyesters on this cell layer and increased nodule permeability compared to wild-type plants. Oxygen concentrations were significantly increased in the inner cortex of mutant nodules, which correlated with reduced nitrogenase activity, and impaired shoot growth. These results provide the first genetic evidence for the formation of the nodule oxygen diffusion barrier, a key adaptation enabling nitrogen fixation in legume nodules.

Antiretrovirals and Weight Change: Weighing the Evidence.

Body weight is influenced by an interplay of individual and environmental factors. In people with HIV (PWH), weight is also influenced by disease status with loss accompanying disease progression that is reversed with effective antiretroviral therapy (ART). Weight changes in comparative ART trials differ by regimen, with greater gains observed with the integrase strand transfer inhibitors (INSTIs) dolutegravir and bictegravir, particularly when co-administered with tenofovir alafenamide fumarate (TAF), compared to regimens that include agents such as tenofovir disoproxil fumarate (TDF) that attenuate weight gain. We review weight changes in major randomized trials of pre-exposure prophylaxis (PrEP) and initial and switch HIV therapy, highlighting the challenges to assessing the role of ART in weight change. This examination forms the basis for a model that questions assumptions regarding an association between INSTI and TAF and excessive weight gain and calls for more careful consideration of these data when making HIV treatment decisions.

Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.

Gene duplication as a major force driving the genome expansion in some giant viruses.

IMPORTANCE: Giant viruses are noteworthy not only due to their enormous particles but also because of their gigantic genomes. In this context, a fundamental question has persisted: how did these genomes evolve? Here we present the discovery of cedratvirus pambiensis, featuring the largest genome ever described for a cedratvirus. Our data suggest that the larger size of the genome can be attributed to an unprecedented number of duplicated genes. Further investigation of this phenomenon in other viruses has illuminated gene duplication as a key evolutionary mechanism driving genome expansion in diverse giant viruses. Although gene duplication has been described as a recurrent event in cellular organisms, our data highlights its potential as a pivotal event in the evolution of gigantic viral genomes.

Lack of association of impaired upper airway sensation with the presence or absence of obstructive sleep apnoea or chronic rhinosinusitis in World Trade Center responders.

OBJECTIVE: Examine sensory function of the upper airway in four groups of subjects recruited from the World Trade Centre General Responder Cohort (WTCGRC), with/without obstructive sleep apnoea (OSA), and with/without chronic rhinosinusitis (CRS). METHODS: Upper airway sensory function was determined using 2-point discrimination (2-PD) and vibration threshold (VT) in 163 WTCGRC subjects with both OSA and CRS (cases), OSA or CRS alone and without OSA or CRS (controls). Presence of OSA was determined from clinical sleep studies or home sleep testing. Presence of CRS was determined by nasal symptom questionnaire. The relationship between the presence of OSA and CRS and upper airway sensory impairment was assessed using linear regression analysis with each of 2PD and VT sensory threshold values as the dependent variable; OSA, CRS and their interaction were the independent variables. Age, gender and body mass index were covariates in the statistical model. The primary analysis was comparison of OSA+CRS versus controls (no OSA and no CRS) evaluated by linear contrasts. RESULTS: There were no differences in 2-PD or VT in those with OSA+CRS, OSA and CRS alone or controls. However, both 2-PD and VT were significantly higher in the WTCGRC controls compared with values seen in historical controls using the same methodology (median 2-PD 13.0; CI (11.0 to 13.5) vs 10.5; CI (8 to 11); VT: mean±SEM (9.3±0.6 vs 2.2±0.1)). CONCLUSION: While no differences were found in upper airway sensation between cases of OSA and CRS versus controls in the WTGRC population, there was evidence of impaired upper airway sensation in the WTGRC overall.

Quick Estimation of Minimum Hearing Levels Using a Binaural Multifrequency Stimulus Paradigm: Proof of Concept.

OBJECTIVES: Objective estimation of minimum hearing levels using auditory brainstem responses (ABRs) elicited by single frequency tone-bursts presented monaurally is currently considered the gold standard. However, the data acquisition time to estimate thresholds (for both ears across four audiometric frequencies) using this method usually exceeds the sleep time (ranging between 35 and 49 minutes) in infants below 4 months, thus providing incomplete information of hearing status which in turn delays timely clinical intervention. Alternate approaches using faster rate, or tone-burst trains have not been readily accepted due to additional hardware and software requirements. We propose here a novel binaural multifrequency stimulation paradigm wherein several stimuli of different frequencies are presented binaurally in an interleaved manner. The rationale here is that the proposed paradigm will increase acquisition efficiency, significantly reduce test time, and improve accuracy by incorporating an automatic wave V detection algorithm. It is important to note that this paradigm can be easily implemented in most commercial ABR systems currently used by most clinicians. DESIGN: Using this binaural multifrequency paradigm, ear specific ABRs were recorded in 30 normal-hearing young adults to both tone-bursts, and narrow-band (NB) iChirps at 500, 1000, 2000, and 4000 Hz. Comparison of ABRs elicited by tone-bursts and narrow-band chirps allowed us to determine if NB iChirps elicited a more robust wave V component compared with the tone-bursts. ABR data were characterized by measures of minimum hearing levels; wave V amplitude; and response detectability for two electrode configurations (high forehead-C7; and high forehead-linked mastoids). RESULTS: Consistent with the research literature, wave V response amplitudes were relatively more robust for NB iChirp stimuli compared with tone-burst stimuli. The easier identification and better detectability of wave V for the NB iChirps at lower stimulus levels contributed to their better thresholds compared with tone-burst elicited responses. It is important to note that binaural multifrequency hearing levels close to minimum hearing levels were determined in approximately 22 minutes using this paradigm-appreciably quicker than the 45 to 60 minutes or longer time required for threshold determination using the conventional single frequency method. CONCLUSIONS: Our novel and simple paradigm using either NB iChirps or tone-bursts provides a reliable method to rapidly estimate the minimum hearing levels across audiometric frequencies for both ears. Incorporation of an automatic wave V detection algorithm increases objectivity and further reduce test time and facilitate early hearing identification and intervention.

New 2-nitroimidazole-N-acylhydrazones, analogs of benznidazole, as anti-Trypanosoma cruzi agents.

Chagas disease is a neglected tropical parasitic disease caused by the protozoan Trypanosoma cruzi. Worldwide, an estimated 8 million people are infected with T. cruzi, causing more than 10,000 deaths per year. Currently, only two drugs, nifurtimox and benznidazole (BNZ), are approved for its treatment. However, both are ineffective during the chronic phase, show toxicity, and produce serious side effects. This work aimed to obtain and evaluate novel 2-nitroimidazole-N-acylhydrazone derivatives analogous to BNZ. The design of these compounds used the two important pharmacophoric subunits of the BNZ prototype, the 2-nitroimidazole nucleus and the benzene ring, and the bioisosterism among the amide group of BNZ and N-acylhydrazone. The 27 compounds were obtained by a three-step route in 57%-98% yields. The biological results demonstrated the potential of this new class of compounds, since eight compounds were potent and selective in the in vitro assay against T. cruzi amastigotes and trypomastigotes using a drug-susceptible strain of T. cruzi (Tulahuen) (IC50 = 4.3-6.25 µM) and proved to be highly selective with low cytotoxicity on L929 cells. The type I nitroreductase (TcNTR) assay suggests that the new compounds may act as substrates for this enzyme.

Scale-Fractal Detrended Fluctuation Analysis for Fault Diagnosis of a Centrifugal Pump and a Reciprocating Compressor.

Reciprocating compressors and centrifugal pumps are rotating machines used in industry, where fault detection is crucial for avoiding unnecessary and costly downtime. A novel method for fault classification in reciprocating compressors and multi-stage centrifugal pumps is proposed. In the feature extraction stage, raw vibration signals are processed using multi-fractal detrended fluctuation analysis (MFDFA) to extract features indicative of different types of faults. Such MFDFA features enable the training of machine learning models for classifying faults. Several classical machine learning models and a deep learning model corresponding to the convolutional neural network (CNN) are compared with respect to their classification accuracy. The cross-validation results show that all models are highly accurate for classifying the 13 types of faults in the centrifugal pump, the 17 valve faults, and the 13 multi-faults in the reciprocating compressor. The random forest subspace discriminant (RFSD) and the CNN model achieved the best results using MFDFA features calculated with quadratic approximations. The proposed method is a promising approach for fault classification in reciprocating compressors and multi-stage centrifugal pumps.

Cobalt-Mediated Photochemical C-H Arylation of Pyrroles.

Precious metal complexes remain ubiquitous in photoredox catalysis (PRC) despite concerted efforts to find more earth-abundant catalysts and replacements based on 3d metals in particular. Most otherwise plausible 3d metal complexes are assumed to be unsuitable due to short-lived excited states, which has led researchers to prioritize the pursuit of longer excited-state lifetimes through careful molecular design. However, we report herein that the C-H arylation of pyrroles and related substrates (which are benchmark reactions for assessing the efficacy of photoredox catalysts) can be achieved using a simple and readily accessible octahedral bis(diiminopyridine) cobalt complex, [1-Co](PF6)2. Notably, [1-Co]2+ efficiently functionalizes both chloro- and bromoarene substrates despite the short excited-state lifetime of the key photoexcited intermediate *[1-Co]2+ (8 ps). We present herein the scope of this C-H arylation protocol and provide mechanistic insights derived from detailed spectroscopic and computational studies. These indicate that, despite its transient existence, reduction of *[1-Co]2+ is facilitated via pre-assembly with the NEt3 reductant, highlighting an alternative strategy for the future development of 3d metal-catalyzed PRC.

The polymicrobial infection affects the infection recurrence rate (not failure) in treating femoral and tibial bone defects with the Masquelet technique-a comparative retrospective analysis of 54 patients with mono- and polymicrobial infections.

INTRODUCTION: This study evaluated whether polymicrobial infection affects reoperation rates due to infection recurrence and treatment failure with the Masquelet technique in infected posttraumatic segmental bone defects of the femur and tibia. METHODS:  We retrospectively analyzed patients treated between 2012 and 2021 in two trauma referral centers. We evaluated demographic data, injury, treatment, infection recurrence, failures, and bone healing rates according to whether the infection was mono- or polymicrobial. After uni-bivariate analysis between patients with polymicrobial and monomicrobial infection, we identified the variables associated with infection recurrence and failure through multivariate analysis. RESULTS:  We analyzed 54 patients, 30 (55.55%) with tibial and 24 (44.44%) femoral segmental bone defects, with a mean follow-up of 41.7 ± 15.0 months. Forty-four (81.48%) presented monomicrobial, and 10 (18.51%) polymicrobial infections. Comparatively, the need for soft tissue reconstruction and the infection recurrence rate was significantly higher in patients with polymicrobial infections. There was no significant difference in the failure rate (20 vs. 6.81% p = 0.23). Multivariable logistic regression analysis identified the polymicrobial infection as the only independent variable associated with infection recurrence (Odds Ratio = 11.07; p = 0.0017). CONCLUSION:  Our analysis suggests that polymicrobial infection is associated with a higher risk of infection recurrence in treating the femur and tibia segmental bone defects with the Masquelet technique. This information can help surgeons to inform patients about this and give them a realistic expectation of the outcome and the possibility of reoperation.

Mechanistic Insights into the Formation of Hydroxyacetone, Acetone, and 1,2-Propanediol from Electrochemical CO2 Reduction on Copper.

Studies focused on the mechanism of CO2 electroreduction (CO2RR) aim to open up opportunities to optimize reaction parameters toward selective synthesis of desired products. However, the reaction pathways for C3 compound syntheses, especially for minor compounds, remain incompletely understood. In this study, we investigated the formation pathway for hydroxyacetone, acetone, and 1,2-propanediol through CO(2)RR, which are minor products that required long electrolysis times to be detected. Our proposed reaction mechanism is based on a systematic investigation of the reduction of several functional groups on a Cu electrode, including aldehydes, ketones, ketonealdehydes, hydroxyls, hydroxycarbonyls, and hydroxydicarbonyls, as well as the coupling between CO and C2-dicarbonyl (glyoxal) or C2-hydroxycarbonyl (glycolaldehyde). This study allowed us to derive the fundamental principles of the reduction of functional groups on Cu electrodes. Our findings suggest that the formation of ethanol does not follow the glyoxal pathway, as previously suggested but instead likely occurs via the coupling of CH3* and CO. For the C3 compounds, our results suggest that 1,2-propanediol and acetone follow the hydroxyacetone pathway during CO2RR. Hydroxyacetone is likely formed through the coupling of CO and a C2-hydroxycarbonyl intermediate, such as a glycolaldehyde-like compound, as confirmed by adding glycolaldehyde to the CO(2)-saturated solution. This finding is consistent with CO2RR product distribution, as glycolaldehyde formation during CO2RR is limited, which, in turn, limits hydroxyacetone production. Our study contributes to a better understanding of the reaction mechanism for hydroxyacetone, acetone, and 1,2-propanediol synthesis from CO2RR and gives insights into these interesting compounds that may be formed electrochemically.

Deepfake Histologic Images for Enhancing Digital Pathology.

A pathologist's optical microscopic examination of thinly cut, stained tissue on glass slides prepared from a formalin-fixed paraffin-embedded tissue blocks is the gold standard for tissue diagnostics. In addition, the diagnostic abilities and expertise of pathologists is dependent on their direct experience with common and rarer variant morphologies. Recently, deep learning approaches have been used to successfully show a high level of accuracy for such tasks. However, obtaining expert-level annotated images is an expensive and time-consuming task, and artificially synthesized histologic images can prove greatly beneficial. In this study, we present an approach to not only generate histologic images that reproduce the diagnostic morphologic features of common disease but also provide a user ability to generate new and rare morphologies. Our approach involves developing a generative adversarial network model that synthesizes pathology images constrained by class labels. We investigated the ability of this framework in synthesizing realistic prostate and colon tissue images and assessed the utility of these images in augmenting the diagnostic ability of machine learning methods and their usability by a panel of experienced anatomic pathologists. Synthetic data generated by our framework performed similar to real data when training a deep learning model for diagnosis. Pathologists were not able to distinguish between real and synthetic images, and their analyses showed a similar level of interobserver agreement for prostate cancer grading. We extended the approach to significantly more complex images from colon biopsies and showed that the morphology of the complex microenvironment in such tissues can be reproduced. Finally, we present the ability for a user to generate deepfake histologic images using a simple markup of sematic labels.

Reduction of Nitrous Oxide by Light Alcohols Catalysed by a Low-Valent Ruthenium Diazadiene Complex.

Decomposition of the environmentally harmful gas nitrous oxide (N2 O) is usually performed thermally or catalytically. Selective catalytic reduction (SCR) is currently the most promising technology for N2 O mitigation, a multicomponent heterogeneous catalytic system that employs reducing agents such as ammonia, hydrogen, hydrocarbons, or a combination thereof. This study reports the first homogenous catalyst that performs the reduction of nitrous oxide employing readily available and cheap light alcohols such as methanol, ethanol or ethylene glycol derivatives. During the reaction, these alcohols are transformed in a dehydrogenative coupling reaction to carboxylate derivatives, while N2 O is converted to N2 and H2 O, later entering the reaction as substrate. The reaction is catalysed by the low-valent dinuclear ruthenium complex [Ru2 H(µ-H)(Me2 dad)(dbcot)2 ] that carries a diazabutadiene, Me2 dad, and two rigid dienes, dbcot, as ligands. The reduction of nitrous oxide proceeds with low catalyst loadings under relatively mild conditions (65-80 °C, 1.4 bar N2 O) achieving turnover numbers of up to 480 and turnover frequencies of up to 56 h-1 .

Transmission and Risk Factors of COVID-19 among Health Care Workers.

Coronavirus disease 2019 (COVID-19) poses a significant occupational risk factor to health care workers (HCWs). As in previous events, this occupational risk amplifies and compounds the adverse impact of the pandemic. We conducted a narrative review summarizing risk factors associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) transmission in HCWs. We searched for original observational studies (including case-control, cross-sectional, prospective and retrospective cohorts) using PubMed, Scopus, and Google Scholar. A total of 22 articles were reviewed, including eligible English articles published between April 2020 and May 2022. Job category, work environment, personal protective equipment (PPE) noncompliance, lack of PPE awareness and training, unvaccinated status, and competing community and household exposures were identified as risk factors for SARS-CoV-2 transmission among HCWs. Effective measures to protect HCWs from SARS-CoV-2 need to account for the identified occupational risk factors. Identifying and understanding COVID-19 risk factors among HCWs must be considered a public health priority for policy makers to mitigate occupational and community transmission in current and future epidemics.

Penile Implant Instrument Innovations.

PURPOSE OF REVIEW: Numerous innovations have been made since the first inflatable penile prosthesis was introduced in 1973-not just of the implant apparatus itself, but crucially also in the surgical instruments used for prosthetic surgery. Starting with Dr. Furlow's revolutionary inserter tool, advancements were quickly made in dilators, retractors, and cavernotomes. RECENT FINDINGS: More recent innovations have been made in inserter tools, forceps, needle holders, clamps, and disposable instruments. Leading companies Boston Scientific and Coloplast have contributed significantly to the evolution of IPP surgical placement, and companies such as Uramix and Rigicon are developing a wide array of new specialized tools. We aim to summarize the instruments needed for IPP placement, with a focus on describing the variety of instrument innovations since Dr. Brantley Scott designed and placed the first IPP.

Association of World Trade Center (WTC) Occupational Exposure Intensity with Chronic Obstructive Pulmonary Disease (COPD) and Asthma COPD Overlap (ACO).

INTRODUCTION: Reported associations between World Trade Center (WTC) occupational exposure and chronic obstructive pulmonary disease (COPD) or asthma COPD overlap (ACO) have been inconsistent. Using spirometric case definitions, we examined that association in the largest WTC occupational surveillance cohort. METHODS: We examined the relation between early arrival at the 2001 WTC disaster site (when dust and fumes exposures were most intense) and COPD and ACO in workers with at least one good quality spirometry with bronchodilator response testing between 2002 and 2019, and no physician-diagnosed COPD before 9/11/2001. COPD was defined spirometrically as fixed airflow obstruction and ACO as airflow obstruction plus an increase of ≥ 400 ml in FEV1 after bronchodilator administration. We used a nested 1:4 case-control design matching on age, sex and height using incidence density sampling. RESULTS: Of the 17,928 study participants, most were male (85.3%) and overweight or obese (84.9%). Further, 504 (2.8%) and 244 (1.4%) study participants met the COPD and ACO spirometric case definitions, respectively. In multivariable analyses adjusted for smoking, occupation, cohort entry period, high peripheral blood eosinophil count and other covariates, early arrival at the WTC site was associated with both COPD (adjusted odds ratio [ORadj] = 1.34, 95% confidence interval [CI] 1.01-1.78) and ACO (ORadj = 1.55, 95%CI 1.04-2.32). CONCLUSION: In this cohort of WTC workers, WTC exposure intensity was associated with spirometrically defined COPD and ACO. Our findings suggest that early arrival to the WTC site is a risk factor for the development of COPD or of fixed airway obstruction in workers with pre-existing asthma.

Activation of the unfolded protein response by Connexin47 mutations associated with Pelizaeus-Merzbacher-like disease.

Pelizaeus-Merzbacher-like disease type 1 (PMLD1) is a hypomyelinating disorder arising in patients with mutations in GJC2, encoding Connexin47 (Cx47). PMLD1 causes nystagmus, cerebellar ataxia, spasticity and changes in CNS white matter detected by MRI. At least one mutation (p.I33M) yields a much milder phenotype, spastic paraplegia type 44 (SPG44). Cx47 contributes to gap junction communication channels between oligodendrocytes (OLs), the myelinating cells in the central nervous system (CNS), and between OLs and astrocytes. Prior studies in cell lines have shown that PMLD1 mutants such as p.P87S display defective protein trafficking, intracellular retention in the ER and loss-of-function. Here we show that when expressed in primary OLs, three PMLD1 associated mutants (p.P87S, p.Y269D and p.M283T) show ER retention of Cx47 and evidence of activation of the cellular stress (unfolded protein response, UPR) and apoptotic pathways. On the other hand, the milder SPG44 associated mutation p.I33M shows a wild-type-like subcellular distribution and no activation of the UPR or apoptotic pathways. These studies provide new insight into a potential element of toxic gain of function underlying the mechanism of PMLD1 that should help guide future therapeutic approaches.

Perceived Stress, Religiosity, and Substance Use Among African American and Latinx College Students with Asthma in the USA.

This study examined associations among perceived stress, religiosity, and substance use in African American and Latinx college students with asthma. Participants included 194 college students with asthma (18-20 years, 63.4% African American, 21.1% Latinx). Eligible students completed an online questionnaire that included measures of asthma control, perceived stress, religiosity, alcohol misuse, and last 30-day tobacco use and marijuana use. Over one-quarter (25.3%) of participants reported using tobacco and 31.9% reported using marijuana in the past 30 days. Perceived stress and religiosity were each independently associated with multiple indicators of substance use. Asthma control moderated associations between religiosity and tobacco use in the past 30 days (b = - .014, p = .002), such that the association between religiosity and tobacco use was stronger among those with better asthma control. Participant gender significantly moderated the association between perceived stress and alcohol misuse (b = - .099, p = .029); a stronger, positive association between stress and alcohol misuse was found among men. Students' perceived stress levels were associated with marijuana use in the past 30 days and high alcohol misuse. Religiosity was inversely linked to substance use. There is a need for healthcare providers to recognize and focus on substance use prevention specifically among African American and Latinx college students with asthma.