Lifetime HIV testing among three samples of adults with histories of incarceration in Southern California.

ABSTRACTJustice-impacted persons may inconsistently access HIV testing. This cross-sectional secondary analysis investigates lifetime HIV testing prevalence among adults with prior histories of incarceration in Southern California, United States, participating in health-focused programming (n = 3 studies). Self-reported demographic and lifetime HIV testing data were collected between 2017-2023; descriptive analyses were conducted. Across the three samples, at least 74% of participants were male; Latino and African American individuals accounted for nearly two-thirds of participants. Lifetime HIV testing ranged from 72.8% to 84.2%. Males were significantly more likely than females to report never being tested in two samples and accounted for >95% of those never tested. No statistically significant differences in testing were observed by race/ethnicity. Single young adults (ages 18-26) were less likely than their partnered peers to report testing. HIV testing is critical for ensuring that individuals access prevention and treatment. HIV testing among justice-impacted adults in this study was higher than in the general population, potentially due to opt-out testing in correctional settings. Nevertheless, these findings underscore the importance of implementing targeted interventions to reduce structural (e.g., health insurance, access to self-testing kits) and social barriers (e.g., HIV stigma) to increase HIV testing among justice-impacted males and single young adults.

Daily olive oil intake is feasible to reduce trigeminal neuralgia facial pain: A pilot study.

Extra virgin olive oil (EVOO) is thought to contribute to neuroprotection and, thus, may influence pain symptoms experienced by adults with demyelination-related trigeminal neuralgia (TN). This study aimed to determine the feasibility of daily intake of EVOO and its potential to alleviate facial pain of TN. Adults, self-reporting as female and affected by TN, were enrolled in a 16-week nonblinded, parallel study. After a 4-week baseline, participants were randomized to 60 mL/day EVOO or control (usual diet and no supplemental EVOO) for 12 weeks. Participants completed a daily questionnaire on pain intensity and compliance, the Penn Facial Pain Scale weekly, the 36-Item Short Form Survey monthly, and dietary assessment during baseline and intervention. Participants (n = 52; 53.3 ± 12.9 years) were recruited nationally; 42 completed the study. The EVOO group, with 90% intake compliance, showed significant decreases in the Penn Facial Pain Scale items of interference with general function, interference with orofacial function, and severity of pain from baseline, whereas the control group showed no improvements. EVOO benefit, compared with control, trended for the interference with orofacial function (P = .05). The 36-Item Short Form Survey items of role limitations resulting from emotional problems and role limitations from physical health favored EVOO. The EVOO group significantly improved their Healthy Eating Index 2015 component scores of fatty acids (primarily from increased oleic acid), sodium, and refined grains. EVOO intake of 60 mL/day was feasible for participants experiencing TN and may mitigate pain and improve quality of life. This trial was registered at clinicaltrials.gov (NCT05032573).

Multiplex gRNAs Synergically Enhance Detection of SARS-CoV-2 by CRISPR-Cas12a.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) diagnostic methods have a large potential to effectively detect SARS-CoV-2 with sensitivity and specificity nearing 100%, comparable to quantitative polymerase chain reaction. Yet, there is room for improvement. Commonly, one guide CRISPR RNA (gRNA) is used to detect the virus DNA and activate Cas collateral activity, which cleaves a reporter probe. In this study, we demonstrated that using 2-3 gRNAs in parallel can create a synergistic effect, resulting in a 4.5 × faster cleaving rate of the probe and increased sensitivity compared to using individual gRNAs. The synergy is due to the simultaneous activation of CRISPR-Cas12a and the improved performance of each gRNA. This approach was able to detect as few as 10 viral copies of the N-gene of SARS-CoV-2 RNA after a preamplification step using reverse transcription loop-mediated isothermal amplification. The method was able to accurately detect 100% of positive and negative clinical samples in ∼25 min using a fluorescence plate reader and ∼45 min with lateral flow strips.

Diastereomeric Separation of Chiral fac-Tricarbonyl(iminopyridine) Rhenium(I) Complexes and Their Cytotoxicity Studies: Approach toward an Action Mechanism against Glioblastoma.

A series of new (tricarbonyl)rhenium(I) complexes were synthesized using chiral bidentate ligands (+)/(-)-iminopyridines (LR/LS). The reaction yielded a mixture of mononuclear Re(I) diastereoisomers, formulated as fac-[Br(CO)3Re(S/R)L(S/R)]. Each single diastereoisomer was isolated and fully characterized. X-ray crystallography and circular dichroism spectra verified their enantiomeric nature. The cytotoxicity of each complex was evaluated against six cancer cell lines. The effect of the two complexes on viability, proliferation, and migration was analyzed on glioblastoma cell lines (U251 and LN229). Changes in the expression of histones, apoptotic, and key signaling proteins, as well as alterations in DNA structure, were also observed. These experiments showed that the chirality associated with both metal and ligand has a strong influence on cytotoxicity.

Diagnostics of COVID-19 Based on CRISPR-Cas Coupled to Isothermal Amplification: A Comparative Analysis and Update.

The emergence of the COVID-19 pandemic prompted fast development of novel diagnostic methods of the etiologic virus SARS-CoV-2. Methods based on CRISPR-Cas systems have been particularly promising because they can achieve a similar sensitivity and specificity to the benchmark RT-qPCR, especially when coupled to an isothermal pre-amplification step. Furthermore, they have also solved inherent limitations of RT-qPCR that impede its decentralized use and deployment in the field, such as the need for expensive equipment, high cost per reaction, and delivery of results in hours, among others. In this review, we evaluate publicly available methods to detect SARS-CoV-2 that are based on CRISPR-Cas and isothermal amplification. We critically analyze the steps required to obtain a successful result from clinical samples and pinpoint key experimental conditions and parameters that could be optimized or modified to improve clinical and analytical outputs. The COVID outbreak has propelled intensive research in a short time, which is paving the way to develop effective and very promising CRISPR-Cas systems for the precise detection of SARS-CoV-2. This review could also serve as an introductory guide to new labs delving into this technology.

Transmission of Respiratory Syncytial Virus genotypes in Cali, Colombia.

BACKGROUND: Colombia's climatological variety, added to pathogen diversity, creates local niches for infectious diseases. In Bogotá, respiratory syncytial virus causes 30%-52% of the cases of respiratory infections. In coastal or inter-Andean cities with higher temperature and longer dry seasons, frequency of this virus is 7%-13%. By 2017, increased hospitalizations due to airway infections occurred in regions whose weather is differently influenced by "El Niño Southern Oscillation" than in Bogotá, although microbial diversity might have also been involved. METHODS: For Cali, an inter-Andean city with warm tropical weather, records of respiratory syncytial virus from 2014 to 2018, in children two years old or younger, were analyzed, and genotypes transmitted during 2016-2017 were identified based on partial sequences of glycoprotein G. RESULTS: Most cases of respiratory syncytial virus in Cali occur in the first semesters, with peaks expressed around March-April, without a clear association with pluviosity. Unlike the biannual rotating pattern of Bogotá, co-circulation of types A and B was detected. As years pass, transmission seasons are becoming longer and frequencies of the virus augment. The viral genotypes identified follow international trends with dominance of Ontario and Buenos Aires clades. Similar to other isolates in these clades, viruses from Cali exhibit glycosylation variability that may account for their fitness. CONCLUSIONS: The pattern of respiratory syncytial virus transmission in Cali differs from that in Bogotá. Its epidemiology is shifting and will remain so with the advent of novel respiratory diseases. This may impact the introduction of vaccination schemes for these or other respiratory viruses.

Identifying Clinical and Genomic Features Associated With Chronic Kidney Disease.

We apply a pattern-based classification method to identify clinical and genomic features associated with the progression of Chronic Kidney disease (CKD). We analyze the African-American Study of Chronic Kidney disease with Hypertension dataset and construct a decision-tree classification model, consisting 15 combinatorial patterns of clinical features and single nucleotide polymorphisms (SNPs), seven of which are associated with slow progression and eight with rapid progression of renal disease among African-American Study of Chronic Kidney patients. We identify four clinical features and two SNPs that can accurately predict CKD progression. Clinical and genomic features identified in our experiments may be used in a future study to develop new therapeutic interventions for CKD patients.

Short-term availability of adult-born neurons for memory encoding.

Adult olfactory neurogenesis provides waves of new neurons involved in memory encoding. However, how the olfactory bulb deals with neuronal renewal to ensure the persistence of pertinent memories and the flexibility to integrate new events remains unanswered. To address this issue, mice performed two successive olfactory discrimination learning tasks with varying times between tasks. We show that with a short time between tasks, adult-born neurons supporting the first learning task appear to be highly sensitive to interference. Furthermore, targeting these neurons using selective light-induced inhibition altered memory of this first task without affecting that of the second, suggesting that neurons in their critical period of integration may only support one memory trace. A longer period between the two tasks allowed for an increased resilience to interference. Hence, newly formed adult-born neurons regulate the transience or persistence of a memory as a function of information relevance and retrograde interference.

Protein and nucleotide biosynthesis are coupled by a single rate-limiting enzyme, PRPS2, to drive cancer.

Cancer cells must integrate multiple biosynthetic demands to drive indefinite proliferation. How these key cellular processes, such as metabolism and protein synthesis, crosstalk to fuel cancer cell growth is unknown. Here, we uncover the mechanism by which the Myc oncogene coordinates the production of the two most abundant classes of cellular macromolecules, proteins, and nucleic acids in cancer cells. We find that a single rate-limiting enzyme, phosphoribosyl-pyrophosphate synthetase 2 (PRPS2), promotes increased nucleotide biosynthesis in Myc-transformed cells. Remarkably, Prps2 couples protein and nucleotide biosynthesis through a specialized cis-regulatory element within the Prps2 5' UTR, which is controlled by the oncogene and translation initiation factor eIF4E downstream Myc activation. We demonstrate with a Prps2 knockout mouse that the nexus between protein and nucleotide biosynthesis controlled by PRPS2 is crucial for Myc-driven tumorigenesis. Together, these studies identify a translationally anchored anabolic circuit critical for cancer cell survival and an unexpected vulnerability for "undruggable" oncogenes, such as Myc. PAPERFLICK:

Alteration of olfactory perceptual learning and its cellular basis in aged mice.

Olfactory perceptual learning reflects an ongoing process by which animals learn to discriminate odorants thanks to repeated stimulations by these odorants. Adult neurogenesis is required for this learning to occur in young adults. The experiments reported here showed that olfactory perceptual learning is impaired with aging and that this impairment is associated with a reduction of neurogenesis and a decrease in granule cell responsiveness to the learned odorant in the olfactory bulb. Interestingly, we showed that the pharmacological stimulation of the noradrenergic system using dexefaroxan mimics olfactory perceptual learning in old mice, which is accompanied by an increase of granule cell responsiveness in response to the learned odorant without any improvement in neurogenesis. We provide the first published evidence that, in contrast to young adult mice, the improvement of olfactory performances in old mice is independent of the overall level of neurogenesis. In addition, restoring behavioral performances in old mice by stimulation of the noradrenergic system underlies the importance of this neuromodulatory system in regulating bulbar network plasticity.

The translational landscape of the mammalian cell cycle.

Gene regulation during cell-cycle progression is an intricately choreographed process, ensuring accurate DNA replication and division. However, the translational landscape of gene expression underlying cell-cycle progression remains largely unknown. Employing genome-wide ribosome profiling, we uncover widespread translational regulation of hundreds of mRNAs serving as an unexpected mechanism for gene regulation underlying cell-cycle progression. A striking example is the S phase translational regulation of RICTOR, which is associated with cell cycle-dependent activation of mammalian target of rapamycin complex 2 (mTORC2) signaling and accurate cell-cycle progression. We further identified unappreciated coordination in translational control of mRNAs within molecular complexes dedicated to cell-cycle progression, lipid metabolism, and genome integrity. This includes the majority of mRNAs comprising the cohesin and condensin complexes responsible for maintaining genome organization, which are coordinately translated during specific cell cycle phases via their 5' UTRs. Our findings illuminate the prevalence and dynamic nature of translational regulation underlying the mammalian cell cycle.

Action of the noradrenergic system on adult-born cells is required for olfactory learning in mice.

We have previously shown that an experience-driven improvement in olfactory discrimination (perceptual learning) requires the addition of newborn neurons in the olfactory bulb (OB). Despite this advance, the mechanisms which govern the selective survival of newborn OB neurons following learning remain largely unknown. We propose that activity of the noradrenergic system is a critical mediator providing a top-down signal to control the selective survival of newly born cells and support perceptual learning. In adult mice, we used pharmacological means to manipulate the noradrenergic system and neurogenesis and to assess their individual and additive effects on behavioral performance on a perceptual learning task. We then looked at the effects of these manipulations on regional survival of adult-born cells in the OB. Finally, using confocal imaging and electrophysiology, we investigated potential mechanisms by which noradrenaline could directly influence the survival of adult-born cells. Consistent with our hypotheses, direct manipulation of noradrenergic transmission significantly effect on adult-born cell survival and perceptual learning. Specifically, learning required both the presence of adult-born cell and noradrenaline. Finally, we provide a mechanistic link between these effects by showing that adult-born neurons receive noradrenergic projections and are responsive to noradrenaline. Based upon these data we argue that noradrenergic transmission is a key mechanism selecting adult-born neurons during learning and demonstrate that top-down neuromodulation acts on adult-born neuron survival to modulate learning performance.

SLIT/ROBO1 signaling suppresses mammary branching morphogenesis by limiting basal cell number.

In the field of breast biology, there is a growing appreciation for the "gatekeeping function" of basal cells during development and disease processes yet mechanisms regulating the generation of these cells are poorly understood. Here, we report that the proliferation of basal cells is controlled by SLIT/ROBO1 signaling and that production of these cells regulates outgrowth of mammary branches. We identify the negative regulator TGF-ß1 upstream of Robo1 and show that it induces Robo1 expression specifically in the basal layer, functioning together with SLIT2 to restrict branch formation. Loss of SLIT/ROBO1 signaling in this layer alone results in precocious branching due to a surplus of basal cells. SLIT2 limits basal cell proliferation by inhibiting canonical WNT signaling, increasing the cytoplasmic and membrane pools of ß-catenin at the expense of its nuclear pool. Together, our studies provide mechanistic insight into how specification of basal cell number influences branching morphogenesis.

Effect of escalating versus fixed voltage treatment on stone comminution and renal injury during extracorporeal shock wave lithotripsy: a prospective randomized trial.

PURPOSE: ESWL is a minimally invasive, efficacious therapy for most renal stones. However, an optimal voltage treatment protocol ensuring effective stone comminution while minimizing tissue injury is not well established. We performed a prospective, randomized trial of the stone-free rate and renoprotective effect of an escalating vs a fixed voltage treatment strategy during ESWL. MATERIALS AND METHODS: Between February 2006 and June 2008 we enrolled 45 patients undergoing ESWL for a renal stone in this institutional review board approved trial. A Dornier DoLi 50 lithotriptor was used. Patients were randomized to receive the escalating strategy of 500 shocks at 14k V, 1,000 at 16 kV and 1,000 at 18 kV or the fixed strategy of 2,500 shocks at 18 kV. Abdominal x-ray was done to determine the stone-free rate at 1 month. Voided urine was analyzed for beta2-microglobulin and microalbumin before, immediately after and 1 week after ESWL to evaluate renal damage. RESULTS: Median patient age was 48 years. Median stone size was 8 mm. Of patients in the escalating group 81% were stone-free vs 48% in the fixed group (p <0.03). There was a significant difference between microalbumin and beta2-microglobulin 1 week after the procedure (p = 0.046 vs 0.045). There was trend toward a difference in microalbumin and beta2-microglobulin immediately after the procedure (p = 0.17 and 0.25, respectively). CONCLUSIONS: This prospective, randomized study shows that an escalating voltage treatment strategy produces better stone comminution than a fixed strategy. The study suggests that there may be a protective effect against damage caused by ESWL with an escalating treatment strategy.

Olfactory perceptual learning requires adult neurogenesis.

Perceptual learning is required for olfactory function to adapt appropriately to changing odor environments. We here show that newborn neurons in the olfactory bulb are not only involved in, but necessary for, olfactory perceptual learning. First, the discrimination of perceptually similar odorants improves in mice after repeated exposure to the odorants. Second, this improved discrimination is accompanied by an elevated survival rate of newborn inhibitory neurons, preferentially involved in processing of the learned odor, within the olfactory bulb. Finally, blocking neurogenesis before and during the odorant exposure period prevents this learned improvement in discrimination. Olfactory perceptual learning is thus mediated by the reinforcement of functional inhibition in the olfactory bulb by adult neurogenesis.

A computer-assisted odorized hole-board for testing olfactory perception in mice.

The present paper describes a behavioral setup, designed and built in our laboratory, allowing the systematic and automatic recording of performances in a large number of olfactory behavioral tests. This computerized monitoring system has the capability of measuring different aspects of olfactory function in mice using different paradigms including threshold evaluation, generalization tasks, habituation/dishabituation, olfactory associative learning, short-term olfactory memory with or without a spatial component, and olfactory preferences. In this paper, we first describe the hole-board apparatus and its software and then give the experimental results obtained using this system. We demonstrate that one single, easy-to-run experimental setup is a powerful tool for the study of olfactory behavior in mice that has many advantages and broad applications.