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BackgroundPsychological resilience is critical to minimize the health effects of traumatic events. Trauma may induce a chronic state of hyperarousal, resulting in problems such as anxiety, insomnia, or posttraumatic stress disorder. Mind-body practices, such as relaxation breathing and mindfulness meditation, help to reduce arousal and may reduce the likelihood of such psychological distress. To better understand resilience-building practices, we are conducting the Biofeedback-Assisted Resilience Training (BART) study to evaluate whether the practice of slow, paced breathing with or without heart rate variability biofeedback can be effectively learned via a smartphone app to enhance psychological resilience. ObjectiveOur objective was to conduct a limited, interim review of user interactions and study data on use of the BART resilience training app and demonstrate analyses of real-time sensor-streaming data. MethodsWe developed the BART app to provide paced breathing resilience training, with or without heart rate variability biofeedback, via a self-managed 6-week protocol. The app receives streaming data from a Bluetooth-linked heart rate sensor and displays heart rate variability biofeedback to indicate movement between calmer and stressful states. To evaluate the app, a population of military personnel, veterans, and civilian first responders used the app for 6 weeks of resilience training. We analyzed app usage and heart rate variability measures during rest, cognitive stress, and paced breathing. Currently released for the BART research study, the BART app is being used to collect self-reported survey and heart rate sensor data for comparative evaluation of paced breathing relaxation training with and without heart rate variability biofeedback. ResultsTo date, we have analyzed the results of 328 participants who began using the BART app for 6 weeks of stress relaxation training via a self-managed protocol. Of these, 207 (63.1%) followed the app-directed procedures and completed the training regimen. Our review of adherence to protocol and app-calculated heart rate variability measures indicated that the BART app acquired high-quality data for evaluating self-managed stress relaxation training programs. ConclusionsThe BART app acquired high-quality data for studying changes in psychophysiological stress according to mind-body activity states, including conditions of rest, cognitive stress, and slow, paced breathing.

BACKGROUND: Omega-3 fatty acid and alpha-tocopherol supplementation reduces gastric ulcer formation in humans and rodents; however, efficacy of prevention in horses is unknown. Equine Omega Complete (EOC) is an oral supplement containing omega-3 fatty acids and alpha-tocopherol. HYPOTHESIS/OBJECTIVE: Determine if EOC supplementation prevents gastric ulcers and increases serum alpha-tocopherol concentrations in healthy horses. ANIMALS: Nine thoroughbred geldings; 5-13 years old. METHODS: Prospective randomized block design, repeated in crossover model. Horses were administered EOC, omeprazole, or water PO for 28 days. Horses underwent an established gastric ulcer induction protocol from days 21-28 via intermittent feed deprivation. Gastroscopies were performed on days 0, 21, and 28. Serum alpha-tocopherol concentrations were measured on days 0 and 28. The effects of treatment and time on ulcer grades were assessed with ordinal logistic regression, with significance at P-value

Bam! Thunk! Bam! I awaken to commotion at my front door. Clash! Boom! It sounds like someone is trying to knock down my door. I hear voices outside my ground-floor apartment. My boyfriend, Kenneth, wakes up immediately. The banging is getting louder and louder. We are convinced that someone's trying to break in. We walk out of my bedroom and down the hallway. I watch as he asks who's at the door, but they don't identify themselves. A battering ram takes the door out. Kenneth, licensed to carry, starts firing to defend against the intruders. The intruders, police officers, return fire. More shots stream in from the window. Several pierce me. I collapse. My clothes become drenched in my blood. As I lay there in my expanding blood bath, my dreams of becoming a nurse and starting a family fade. Soon, I stop breathing. Like an animal, my body remains on the cold, bloody floor. Later, I'm pronounced dead at the scene. My name is Breonna Taylor (Oppel & Taylor, 2023; Riley, 2020).

The military lifestyle imposes unique challenges for military spouses in regards to their education and careers. To help alleviate these challenges, military spouses are encouraged to pursue portable career paths. This causes one to question whether spouses desire these portable careers and what influences spouses place on pursuing specific educational and career paths. This exploratory study seeks to address these questions by investigating the careers, academic majors, and educational degrees that current military spouse students pursue. Further, the factors that influence military spouses to pursue their career and academic majors are investigated. The results of this study demonstrate that military spouses desire advanced, graduate level degrees that are primarily in the healthcare, business, mental health, and educational fields. Further, genuine interest was the greatest influence on military spouse career and educational paths and the military lifestyle provided the least influence.

IntroductionThe majority of new HIV infections occur through mucosal transmission. The availability of readily applicable and accessible platforms for anti-retroviral (ARV) delivery is critical for the prevention of HIV acquisition through sexual transmission in both women and men. There is a compelling need for developing new topical delivery systems that have advantages over the pills, gels and rings, which currently fail to guarantee protection against mucosal viral transmission in vulnerable populations due to lack of user compliance. The silk fibroin (SF) platform offers another option that may be better suited to individual circumstances and preferences to increase efficacy through user compliance. The objective of this study was to test safety and efficacy of SF for anti-HIV drug delivery to mucosal sites and for viral prevention.MethodsWe formulated a potent HIV inhibitor Griffithsin (Grft) in a mucoadhesive silk fibroin (SF) drug delivery platform and tested the application in a non-human primate model in vivo and a pre-clinical human cervical and colorectal tissue explant model. Both vaginal and rectal compartments were assessed in rhesus macaques (Mucaca mulatta) that received SF (n = 4), no SF (n = 7) and SF-Grft (n = 11). In this study, we evaluated the composition of local microbiota, inflammatory cytokine production, histopathological changes in the vaginal and rectal compartments and mucosal protection after ex vivo SHIV challenge.ResultsEffective Grft release and retention in mucosal tissues from the SF-Grft platform resulted in protection against HIV in human cervical and colorectal tissue as well as against SHIV challenge in both rhesus macaque vaginal and rectal tissues. Mucoadhesion of SF-Grft inserts did not cause any inflammatory responses or changes in local microbiota.ConclusionsWe demonstrated that in vivo delivery of SF-Grft in rhesus macaques fully protects against SHIV challenge ex vivo after two hours of application and is safe to use in both the vaginal and rectal compartments. Our study provides support for the development of silk fibroin as a highly promising, user-friendly HIV prevention modality to address the global disparity in HIV infection.

BackgroundCell-free DNA (cfDNA), present in circulating blood plasma, contains information about prenatal health, organ transplant reception, and cancer presence and progression. Originally developed for the genomic analysis of highly degraded ancient DNA, single-stranded DNA (ssDNA) library preparation methods are gaining popularity in the field of cfDNA analysis due to their efficiency and ability to convert short, fragmented DNA into sequencing libraries without altering DNA ends. However, current ssDNA methods are costly and time-consuming.ResultsHere we present an efficient ligation-based single-stranded library preparation method that is engineered to produce complex libraries in under 2.5 h from as little as 1 nanogram of input DNA without alteration to the native ends of template molecules. Our method, called Single Reaction Single-stranded LibrarY or SRSLY, ligates uniquely designed Next-Generation Sequencing (NGS) adapters in a one-step combined phosphorylation/ligation reaction that foregoes end-polishing. Using synthetic DNA oligos and cfDNA, we demonstrate the efficiency and utility of this approach and compare with existing double-stranded and single-stranded approaches for library generation. Finally, we demonstrate that cfDNA NGS data generated from SRSLY can be used to analyze DNA fragmentation patterns to deduce nucleosome positioning and transcription factor binding.ConclusionsSRSLY is a versatile tool for converting short and fragmented DNA molecules, like cfDNA fragments, into sequencing libraries while retaining native lengths and ends.

With almost 2 million new HIV infections worldwide each year, the prevention of HIV infection is critical for stopping the pandemic. The only approved form of pre-exposure prophylaxis is a costly daily pill, and it is recognized that several options will be needed to provide protection to the various affected communities around the world. In particular, many at-risk people would benefit from a prevention method that is simple to use and does not require medical intervention or a strict daily regimen. We show that silk fibroin protein can be formulated into insertable discs that encapsulate either an antibody (IgG) or the potent HIV inhibitor 5P12-RANTES. Several formulations were studied, including silk layering, water vapor annealing and methanol treatment to stabilize the protein cargo and impact the release kinetics over weeks. In the case of IgG, high concentrations were released over a short time using methanol treatment, with more sustained results with the use of water vapor annealing and layering during device fabrication. For 5P12-RANTES, sustained release was obtained for 31 days using water vapor annealing. Further, we show that the released inhibitor 5P12-RANTES was functional both in vitro and in ex vivo colorectal tissue. This work shows that silk fibroin discs can be developed into formidable tools to prevent HIV infection.

Background: Complications are a practical consideration for elective magnetic resonance imaging (MRI) studies performed under general anaesthesia but relatively little is known about their distribution and risk factors. Objectives: To describe the incidence of complications associated with MRI performed under general anaesthesia at a large referral facility and evaluate potential risk factors for these complications. Study design: Retrospective case–control study. Methods: Patient information and details of the MRI procedure were collected retrospectively from medical records of all horses that had undergone an MRI under general anaesthesia at the University of Pennsylvania, New Bolton Center, between September 2005 and April 2012. Complications and categorical variables were examined by chi‐squared or Fisher's exact tests as appropriate. A mixed‐effects logistic regression approach was used to evaluate associations between explanatory variables and the outcome variable (complications or pyrexia). A univariable screen was used to select variables (likelihood ratio test p < 0.2) for inclusion in the multivariable analysis. Statistical significance was inferred when p ≤ 0.05. Results: Complications were noted after MRI in 51 (17.4%) of 293 events eligible for inclusion. Complications included pyrexia (n = 35), pneumonia (n = 14), colic (n = 10), facial/nerve paralysis (n = 6), diarrhoea (n = 4), and other (n = 3). The odds of developing a post‐anaesthetic complication were significantly decreased in horses that received peri‐anaesthetic antimicrobials (OR 0.29, 95% CI 0.14–0.63, p = 0.002). Increased age (OR 0.87, 95% CI, 0.76–0.99, p = 0.03) and peri‐anaesthetic antimicrobial administration (OR 0.23, 95% CI 0.08–0.65, p = 0.005) were associated with a decreased odds of developing pyrexia. Main limitations: Single centre retrospective design. Conclusions: Potential complications including pyrexia, pneumonia and colic should be recognised when pursuing MRI under general anaesthesia. The administration of peri‐anaesthetic antimicrobials decreased the odds of a complication and warrants consideration, particularly in horses that might be classified as high risk. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infection continues to pose a major infectious disease threat worldwide. It is characterized by the depletion of CD4+ T cells, persistent immune activation, and increased susceptibility to secondary infections. Advances in the development of antiretroviral drugs and combination antiretroviral therapy have resulted in a remarkable reduction in HIV-associated morbidity and mortality. Antiretroviral therapy (ART) leads to effective suppression of HIV replication with partial recovery of host immune system and has successfully transformed HIV infection from a fatal disease to a chronic condition. Additionally, antiretroviral drugs have shown promise for prevention in HIV pre-exposure prophylaxis and treatment as prevention. However, ART is unable to cure HIV. Other limitations include drug-drug interactions, drug resistance, cytotoxic side effects, cost, and adherence. Alternative treatment options are being investigated to overcome these challenges including discovery of new molecules with increased anti-viral activity and development of easily administrable drug formulations. In light of the difficulties associated with current HIV treatment measures, and in the continuing absence of a cure, the prevention of new infections has also arisen as a prominent goal among efforts to curtail the worldwide HIV pandemic. In this review, the authors summarize currently available anti-HIV drugs and their combinations for treatment, new molecules under clinical development and prevention methods, and discuss drug delivery formats as well as associated challenges and alternative approaches for the future.

Psychophysical inferences about the neural mechanisms supporting spatial vision can be undermined by uncertainties introduced by optical aberrations and fixational eye movements, particularly in fovea where the neuronal grain of the visual system is fine. We examined the effect of these preneural factors on photopic spatial summation in the human fovea using a custom adaptive optics scanning light ophthalmoscope that provided control over optical aberrations and retinal stimulus motion. Consistent with previous results, Ricco's area of complete summation encompassed multiple photoreceptors when measured with ordinary amounts of ocular aberrations and retinal stimulus motion. When both factors were minimized experimentally, summation areas were essentially unchanged, suggesting that foveal spatial summation is limited by postreceptoral neural pooling. We compared our behavioral data to predictions generated with a physiologically-inspired front-end model of the visual system, and were able to capture the shape of the summation curves obtained with and without pre-retinal factors using a single postreceptoral summing filter of fixed spatial extent. Given our data and modeling, neurons in the magnocellular visual pathway, such as parasol ganglion cells, provide a candidate neural correlate of Ricco's area in the central fovea.

ObjectivesDigital cryotherapy is commonly used for laminitis prophylaxis and treatment. Currently validated methods for distal limb cryotherapy involve wet application or compression technology. There is a need for a practical, affordable, dry cryotherapy method that effectively cools the digit. The objective of this study was to evaluate the hoof wall surface temperatures (HWSTs) achieved with a novel dry cryotherapy technology.DesignRepeated-measures in vivo experimental study.SettingExperimental intervention at a single site.Participants6 systemically healthy horses (3 mares, 3 geldings).InterventionsCryotherapy was applied to six horses for eight hours with a commercially available rubber and rubber and welded fabricice boot, which extended proximally to include the foot and pastern. Reusable malleable cold therapy packs were secured against the foot and pastern with the three built-in hook-and-loop fastener panels.Primary and secondary outcome measuresHWST and pastern surface temperature of the cryotherapy-treated limb, HWST of the control limb and ambient temperature were recorded every five minutes throughout the study period.ResultsResults were analysed with mixed-effects multivariable regression analysis. The HWST (median 11.1°C, interquartile range 8.6°C-14.7°C) in the cryotherapy-treated limb was significantly decreased compared with the control limb (median 29.7°C, interquartile range 28.9°C-30.4°C) (P≤0.001). Cryotherapy limb HWST reached a minimum of 6.75°C (median) with an interquartile range of 4.1°C-9.3°C. Minimum HWST was achieved 68 minutes after cryotherapy pack application.ConclusionsDry application of cryotherapy significantly reduced HWST and reached minimums below the therapeutic target of 10°C. This cryotherapy method might offer an effective alternative for digital cooling.

Antibiotic-resistant bacteria are an emerging threat to global public health. New classes of antibiotics and tools for antimicrobial discovery are urgently needed. Type III secretion systems (T3SS), which are required by dozens of Gram-negative bacteria for virulence but largely absent from nonpathogenic bacteria, are promising virulence blocker targets. The ability of mammalian cells to recognize the presence of a functional T3SS and trigger NF-κB activation provides a rapid and sensitive method for identifying chemical inhibitors of T3SS activity. In this study, we generated a HEK293 stable cell line expressing green fluorescent protein (GFP) driven by a promoter containing NF-κB enhancer elements to serve as a readout of T3SS function. We identified a family of synthetic cyclic peptide-peptoid hybrid molecules (peptomers) that exhibited dose-dependent inhibition of T3SS effector secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa without affecting bacterial growth or motility. Among these inhibitors, EpD-3'N, EpD-1,2N, EpD-1,3'N, EpD-1,2,3'N, and EpD-1,2,4'N exhibited strong inhibitory effects on translocation of the Yersinia YopM effector protein into mammalian cells (>40% translocation inhibition at 7.5 μM) and showed no toxicity to mammalian cells at 240 μM. In addition, EpD-3'N and EpD-1,2,4'N reduced the rounding of HeLa cells caused by the activity of Yersinia effector proteins that target the actin cytoskeleton. In summary, we have discovered a family of novel cyclic peptomers that inhibit the injectisome T3SS but not the flagellar T3SS.

Leydig cells are crucial to the production of testosterone in males. It is unknown if the cancer chemotherapeutic drug, 6-mercaptopurine (6 MP), produces Leydig cell failure among adult survivors of childhood acute lymphoblastic leukemia. Moreover, it is not known whether Leydig cell failure is due to either a loss of cells or an impairment in their function. Herein, we show, in a subset of childhood cancer survivors, that Leydig cell failure is related to the dose of 6 MP. This was extended, in a murine model, to demonstrate that 6 MP exposure induced caspase 3 activation, and the loss of Leydig cells was independent of Bak and Bax activation. The death of these non-proliferating cells was triggered by 6 MP metabolism, requiring formation of both cytosolic reactive oxygen species and thiopurine nucleotide triphosphates. The thiopurine nucleotide triphosphates (with physiological amounts of dATP) uniquely activated the apoptosome. An ABC transporter (Abcc4/Mrp4) reduced the amount of thiopurines, thereby providing protection for Leydig cells. The studies reported here demonstrate that the apoptosome is uniquely activated by thiopurine nucleotides and suggest that 6 MP induced Leydig cell death is likely a cause of Leydig cell failure in some survivors of childhood cancer.

There is a push for universities to equip graduates with desirable employability skills and "hands-on" experience. This article explores the perceptions of students and staff experiences of a research assistantship scheme. Nine students from the University of Worcester were given the opportunity to work as a student vacation researcher for up to 10 weeks. This opportunity gave "hands-on" experience to students to understand real world research, thereby enabling the development of academic and research skills and increasing a student's employability. The scheme received positive feedback from both students and academic staff and was recommended as a means to enhance student's future employment.

The Yersinia type III secretion system (T3SS) translocates Yop effector proteins into host cells to manipulate immune defenses such as phagocytosis and reactive oxygen species (ROS) production. The T3SS translocator proteins YopB and YopD form pores in host membranes, facilitating Yop translocation. While the YopD amino and carboxy termini participate in pore formation, the role of the YopD central region between amino acids 150-227 remains unknown. We assessed the contribution of this region by generating Y. pseudotuberculosis yopD(Δ150-170) and yopD(Δ207-227) mutants and analyzing their T3SS functions. These strains exhibited wild-type levels of Yop secretion in vitro and enabled robust pore formation in macrophages. However, the yopDΔ150-170 and yopD(Δ207-227) mutants were defective in Yop translocation into CHO cells and splenocyte-derived neutrophils and macrophages. These data suggest that YopD-mediated host membrane disruption and effector Yop translocation are genetically separable activities requiring distinct protein domains. Importantly, the yopD(Δ150-170) and yopD(Δ207-227) mutants were defective in Yop-mediated inhibition of macrophage cell death and ROS production in neutrophil-like cells, and were attenuated in disseminated Yersinia infection. Therefore, the ability of the YopD central region to facilitate optimal effector protein delivery into phagocytes, and therefore robust effector Yop function, is important for Yersinia virulence.