Neuroinflammation and Schizophrenia: New Therapeutic Strategies through Psychobiotics, Nanotechnology, and Artificial Intelligence (AI).

The prevalence of schizophrenia, affecting approximately 1% of the global population, underscores the urgency for innovative therapeutic strategies. Recent insights into the role of neuroinflammation, the gut-brain axis, and the microbiota in schizophrenia pathogenesis have paved the way for the exploration of psychobiotics as a novel treatment avenue. These interventions, targeting the gut microbiome, offer a promising approach to ameliorating psychiatric symptoms. Furthermore, advancements in artificial intelligence and nanotechnology are set to revolutionize psychobiotic development and application, promising to enhance their production, precision, and effectiveness. This interdisciplinary approach heralds a new era in schizophrenia management, potentially transforming patient outcomes and offering a beacon of hope for those afflicted by this complex disorder.

Computational and experimental identification of keystone interactions in Ebola virus matrix protein VP40 dimer formation.

The Ebola virus (EBOV) is a lipid-enveloped virus with a negative sense RNA genome that can cause severe and often fatal viral hemorrhagic fever. The assembly and budding of EBOV is regulated by the matrix protein, VP40, which is a peripheral protein that associates with anionic lipids at the inner leaflet of the plasma membrane. VP40 is sufficient to form virus-like particles (VLPs) from cells, which are nearly indistinguishable from authentic virions. Due to the restrictions of studying EBOV in BSL-4 facilities, VP40 has served as a surrogate in cellular studies to examine the EBOV assembly and budding process from the host cell plasma membrane. VP40 is a dimer where inhibition of dimer formation halts budding and formation of new VLPs as well as VP40 localization to the plasma membrane inner leaflet. To better understand VP40 dimer stability and critical amino acids to VP40 dimer formation, we integrated computational approaches with experimental validation. Site saturation/alanine scanning calculation, combined with molecular mechanics-based generalized Born with Poisson-Boltzmann surface area (MM-GB/PBSA) method and molecular dynamics simulations were used to predict the energetic contribution of amino acids to VP40 dimer stability and the hydrogen bonding network across the dimer interface. These studies revealed several previously unknown interactions and critical residues predicted to impact VP40 dimer formation. In vitro and cellular studies were then pursued for a subset of VP40 mutations demonstrating reduction in dimer formation (in vitro) or plasma membrane localization (in cells). Together, the computational and experimental approaches revealed critical residues for VP40 dimer stability in an alpha-helical interface (between residues 106-117) as well as in a loop region (between residues 52-61) below this alpha-helical region. This study sheds light on the structural origins of VP40 dimer formation and may inform the design of a small molecule that can disrupt VP40 dimer stability.

Genomic scan of a healthcare-associated NDM-1-producing Citrobacter freundii ST18 isolated from a green sea turtle impacted by plastic pollution.

BACKGROUND: Carbapenemase-producing Citrobacter freundii has been reported as a leading cause of healthcare-associated infections. Particularly, C. freundii belonging to the sequence type (ST) 18 is considered to be an emerging nosocomial clone. OBJECTIVES: To report the genomic background and phylogenomic analysis of a multidrug-resistant NDM-1-producing C. freundii ST18 (strain CF135931) isolated from an endangered green sea turtle affected by plastic pollution in Brazil. METHODS: Genomic DNA was extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Workbench, and in silico analysis accomplished by bioinformatics tools. For phylogenomic analysis, publicly available C. freundii (txid:546) genome assemblies were retrieved from the NCBI database. RESULTS: The genome size was calculated at 5 290 351 bp, comprising 5263 total genes, 4 rRNAs, 77 tRNAs, 11ncRNAs, and 176 pseudogenes. The strain belonged to C. freundii ST18, whereas resistome analysis predicted genes encoding resistance to ß-lactams (blaNDM-1, blaOXA-1, blaCMY-117, and blaTEM-1C), aminoglycosides (aph(3'')-Ib, aadA16, aph(3')-VI, aac(6')-Ib-cr, and aph(6)-Id), quinolones (aac(6')-Ib-cr), macrolides (mph(A) and erm(B)), sulphonamides (sul1 and sul2), tetracyclines (tetA and tetD), and trimethoprim (dfrA27). The phylogenomic analysis revealed that CF135931 strain is closely related to international human-associated ST18 clones producing NDM-1. CONCLUSION: Genomic surveillance efforts are necessary for robust monitoring of the emergence of drug-resistant strains and WHO critical priority pathogens within a One Health framework. In this regard, this draft genome and associated data can improve understanding of dissemination dynamics of nosocomial clones of carbapenemase-producing C. freundii beyond hospital walls. In fact, the emergence of NDM-1-producing C. freundii of global ST18 in wildlife deserves considerable attention.

Genomic data of global clones of CTX-M-65-producing Escherichia coli ST10 from South American llamas inhabiting the Andean Highlands of Peru.

BACKGROUND: The global spread of extended-spectrum ß-lactamase (ESßL)-producing Escherichia coli has been considered a One Health issue that demands continuous genomic epidemiology surveillance in humans and non-human hosts. OBJECTIVES: To report the occurrence and genomic data of ESßL-producing E. coli strains isolated from South American llamas inhabiting a protected area with public access in the Andean Highlands of Peru. METHODS: Two ESßL-producing E. coli strains (E. coli L1LB and L2BHI) were identified by MALDI-TOF. Genomic DNAs were extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Genomic Workbench and in silico prediction was accomplished by curated bioinformatics tools. SNP-based phylogenomic analysis was performed using publicly available genomes of global E. coli ST10. RESULTS: Escherichia coli L1LB generated a total of 4 000 11 and L2BHI a total of 4 002 54 paired-end reads of ca.164 × and ca. 157 ×, respectively. Both E. coli strains were assigned to serotype O8:H4, fimH41, and ST10. The blaCTX-M-65 ESßL gene, along with other medically important antimicrobial resistance genes, was predicted. Broad virulomes, including the presence of the astA gene, were confirmed. The phylogenomic analysis revealed that E. coli L1LB and L2BHI strains are closely related to isolates from companion animals and human hosts, as well as environmental strains, previously reported in North America, South America, Africa, and Asia. CONCLUSION: Presence of ESßL-producing E. coli ST10 in South American camelids with historical and cultural importance supports successful expansion of international clones of priority pathogens in natural areas with public access.

Pipeline to Military Orthopaedic Leadership: 20 Years of Race and Gender Diversity Trends Within Military Orthopaedic Surgery Fellowship Training.

Background: The lack of trainees from underrepresented race and gender backgrounds in orthopaedic surgery fellowship training has been well reported in the literature. The purpose of this study was to investigate the demographic trends of federally sponsored military orthopaedic surgery fellows in the Army, Navy, and Air Force. We hypothesize that there has been an increase in women selected for fellowship but that there has been no change in the race demographics of military fellows over the past 2 decades. Methods: A retrospective review of all available demographic data collected by the Army, Air Force, and Navy since the beginning of tracking federally funded fellowship training in orthopaedic surgery was completed (1998-2021). Data were grouped into 4-year periods for analysis to closely mirror the military assignment cycle. Results: Three hundred sixty-two military orthopaedic surgery fellowship board selectees were included in our analysis. The proportion of women fellows increased from 3% (n = 2/69) over 2001 to 2004 to 21% (n = 17/82) during 2017 to 2020 (p < 0.05). Fellows who identified as White comprised 82% (n = 297) of the cohort during the study period. Individuals who identified as Asian were the next highest proportion of fellows at 4% (n = 16), followed by Black (n = 14, 4%) and Hispanic (n = 13, 3%). Individuals who identified as Native Hawaiian/Pacific Islander represented 1% (n = 3), and an additional 6% (n = 20) fellows identified as "other" or "undeclared." Over the 20-year study period, representation of Asian, Black, Native Hawaiian, and Hispanic fellows did not increase (p = 0.79, 0.81, 0.45, 0.34, respectively). Conclusions: Within military orthopaedics, there has been increased representation of women in fellowship training over the past 20 years. However, the proportion of fellows from underrepresented racial and ethnic groups has remained stagnant. One barrier to improving gender and race representation is the currently imprecise and inconsistent collection of demographic information. Importantly, fellowship training has a direct effect on future leadership opportunities within the military orthopaedic surgery community. A more diverse leadership may help to inspire future generations of military orthopaedic surgeons. Level of Evidence: IV.

Sporotrichosis Outbreak Due to Sporothrix brasiliensis in Domestic Cats in Magallanes, Chile: A One-Health-Approach Study.

Sporotrichosis is an implantation mycosis with subcutaneo-lymphatic or, more rarely, a viscerally disseminated affection; it can be acquired through traumatic percutaneous inoculation of the fungus present in soil or plant matter, or by feline scratching. Among the causative agents, Sporothrix brasiliensis is considered the most virulent species with a high prevalence in Brazil and recently in Argentina. OBJECTIVE: To describe a S. brasiliensis outbreak in domestic and feral cats detected in the Magallanes region of southern Chile. MATERIALS AND METHODS: Between the months of July and September 2022, three cats presented with suppurative subcutaneous lesions located mainly on the head and thoracic limbs. The cytology revealed the presence of yeasts with morphological characteristics suggestive of Sporothrix spp. The histopathology confirmed pyogranulomatous subcutaneous lesions associated with the presence of the same yeasts. The fungal culture followed by the partial gene sequence and analysis of the ITS region confirmed the diagnosis of the S. brasiliensis as the causative agent. The cats were treated with itraconazole associated in one case with potassium iodide. The evolution of the patients was favorable in all cases. CONCLUSIONS: An outbreak caused by S. brasiliensis was detected in domestic and feral cats in austral Chile. The correct identification of this fungus and antifungigram is essential for treatment decisions and for designing dissemination control and prevention programs under a one health approach that consider the health of people, animals, and the environment.

Association between Paraoxonase-1 p.Q192R Polymorphism and Coronary Artery Disease susceptibility in the Colombian Population.

BACKGROUND: Paraoxonase-1 (PON1), a glycoprotein associated with serum high-density lipoprotein (HDL), has a central role in metabolizing lipid peroxides, exhibiting antiatherogenic properties. The polymorphism p.Q192R has been previously associated with coronary artery disease (CAD) susceptibility and clopidogrel response. PURPOSE: We aimed at investigating the association of PON1 p.Q192R with CAD and clopidogrel response in Colombian population. PATIENTS AND METHODS: The study was conducted among 163 patients diagnosed with CAD and treated with clopidogrel. The allele frequencies for the PON1 192Q and 192R alleles were determined in cases and Latin-American controls obtained from the public database gnomAD (n = 17,711). Response to clopidogrel was determined by assessing the platelet function using the INNOVANCE PFA-200 System. We determined the association between PON1 p.Q192R polymorphism, increased susceptibility to CAD and high on-treatment platelet reactivity (HPR) by using odds ratio (OR) and 95% confidence interval (CI) on four genetic models. RESULTS: The allele frequencies for the PON1 192Q and 192R alleles were 0.60 and 0.40, respectively. The allele distribution was found to be statistically different from the control group and other ethnic groups. The allele 192R was positively associated with decreased susceptibility to CAD under a dominant model (OR, 0.58; 95% CI, 0.42-0.8; P < 0.01). We found no association between the polymorphism and HPR. CONCLUSION: We propose that PON1 p.Q192R is a potentially useful marker for CAD susceptibility in the Colombian population and lacks association with HPR under clopidogrel treatment.

Medical Student Experiences in Operation Bushmaster 2019: "I Now See Myself as Equal Parts Physician and Leader."

INTRODUCTION: Operation Bushmaster, a 5-day high-fidelity medical practicum bringing together fourth-year medical students, graduate nursing students, international students, and physicians and other medical professionals in emergency and operational medicine from across the world, is the capstone event of the Uniformed Services University of the Health Sciences's Military Unique Curriculum. It is designed to simultaneously test students' medical knowledge, leadership skills, and grace under fire. For many students, this experience represents one of the first times that they concurrently inhabit the dual roles of military officer and (soon-to-be) physician. This is likely the most "tactical" and stressful military simulation that many students have experienced. METHODS: In this qualitative study, we analyzed a data set of 49 de-identified reflective articles written by fourth-year medical students following the completion of Bushmaster, in order to understand what students gained from the experience. Additionally, we evaluated students' responses through the lens of the threshold concept, looking for ontological shifts, integration, discursiveness, and troublesomeness during students' Bushmaster experiences. RESULTS: We identified 10 themes throughout the essays that highlighted the lessons learned during the Bushmaster experience, including its importance in guiding professional identity formation and students' deepened understanding of the unique responsibilities and pressures of the role of military physician. CONCLUSION: One of the resulting themes, "the military physician," met our criteria for a threshold concept, in that it was transformative, integrative, and troublesome. Before Bushmaster, many of the students saw themselves simply as medical students rather than as almost doctors. Following the field practicum, some identified more strongly with the role of military physician, while others continued to overestimate the amount of time remaining to complete the transformation from student to doctor or to integrate the roles of physician and military officer. Moreover, we identified the entirety of Bushmaster as a threshold experience. This work serves to further describe the liminal space in which military medical students reside on their journey to physician, as well as the moment of realization by many that becoming a military physician encompasses more than simply the sum of the roles of physician and military officer.

Presence of Disinfection Byproducts in Public Swimming Pools in Medellín, Colombia.

The quality of water in swimming pools is essential to avoid risks to the health of users. Medellín has more than 1000 public swimming pools, which are supervised by the Medellín Health Authority to monitor and ensure compliance with relevant regulations. The Health Authority has financed several studies related to the quality of drinking and recreational water in Medellín in order to protect consumers and users. One such study involves the evaluation of the presence of disinfection byproducts (DBP). The best known DBPs resulting from disinfection with chlorine are trihalomethanes (THMs) and halogenated acetic acids (HAAs), as well as other minorities such as chloramines or halophenols (HPs). DBPs pose a greater risk in swimming pool water because there is a greater possibility of ingestion, since exposure occurs through several routes at the same time (direct ingestion of water, inhalation of volatile or aerosol solutes, dermal contact and absorption through skin). In the present work, high concentrations of THMs and HAAs were detected in the public swimming pools selected in the study, but the presence of HPs was not detected in the pools.

The role of syringe exchange programs and sexual identity in awareness of pre-exposure prophylaxis (PrEP) for male persons who inject drugs.

BACKGROUND: Male persons who inject drugs (male PWID) are at heightened risk for HIV, particularly if they also have sex with men. Pre-exposure prophylaxis (PrEP) could aid in HIV prevention for this population, but PrEP awareness within different sexual identities among male PWID is not well-understood. We report factors associated with greater awareness among male PWID to identify efficient means of awareness dissemination. METHODS: Data from the 2015 National HIV Behavioral Surveillance (NHBS) system cycle on injection drug use collected in New York City (NYC) were used. Bivariable analyses, using chi-squared statistics, were conducted to examine correlates of awareness of PrEP with socio-demographic, behavioral, and health care variables. Log-linked Poisson regression with robust standard errors was used to estimate adjusted prevalence ratios and determine differences in awareness of PrEP. RESULTS: Among a sample of 332 male PWID (i.e., PWID who identified as male, not transgender) we find awareness of PrEP to be low (23%) among male PWID despite 68% reporting condomless vaginal/anal sex and 32% reporting injection equipment sharing in the last twelve months. Multivariable analysis found greater PrEP awareness associated with gay or bisexual identity (aPR: 2.77, 95% CI: 1.81-4.24) and having a conversation about HIV prevention at a syringe exchange program (SEP) (aPR: 2.71, 95% CI: 1.87-3.94) to be associated with increased PrEP awareness. CONCLUSION: We found low rates of PrEP awareness among male PWID. However, our findings provide insight into information diffusion that can be utilized to increase PrEP awareness among male PWID and among all PWID. We suggest that gay and bisexual social networks and syringe exchange programs are diffusing PrEP awareness among male PWID and can be harnessed to increase PrEP awareness among male PWID.

Manipulating neck temperature alters contagious yawning in humans.

The existence of yawning across a diverse array of species has led many researchers to postulate its neurological significance. One hypothesis, which has garnered recent support, posits that yawns function to cool the brain by flushing hyperthermic blood away from the skull while simultaneously introducing a cooler arterial supply. The current study tested this hypothesis by examining how manipulations aimed at modifying carotid artery temperature, which in turn directly alters cranial temperature, influences contagious yawning in humans. Participants held either a warm (46 °C), cold (4 °C) or room temperature (22 °C) pack firmly to their neck, just over their carotid arteries, for a period of five minutes prior to watching a contagious yawning stimulus. Thermographic imaging verified that these manipulations produced predicted changes in temperature at the superomedial orbital area, a region previously used as a noninvasive measure of brain temperature (i.e., the brain temperature tunnel). As predicted by past research, both the urge to yawn and overall yawn frequency significantly diminished in the cooling condition (p < .05). Less than half (48.5%) of the participants in the cooling condition reported the urge to yawn, while this urge was expressed by the vast majority of participants in the warming condition (84.8%). Moreover, there was a threefold difference in the mean number of yawns per participant between the cooling and warming conditions (0.364 compared to 1.121). These findings are consistent with previous research indicating that yawns function as a compensatory brain cooling mechanism.