[Transcriptomic characteristics analysis of bone from chronic osteomyelitis].

OBJECTIVE: To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. METHODS: Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. RESULTS: A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKß), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. CONCLUSION: Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKß, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Increasing the Particle Size and Magnetic Property of Iron Oxide Nanoparticles through a Segregated Nucleation and Growth Process.

Iron oxide nanoparticles (IONs) with good water dispersibility were prepared by the thermal decomposition of iron acetylacetonate (Fe(acac)3) in the high-boiling organic solvent polyethylene glycol (PEG) using polyethyleneimine (PEI) as a modifier. The nucleation and growth processes of the crystals were separated during the reaction process by batch additions of the reaction material, which could inhibit the nucleation but maintain the crystal growth, and products with larger particle sizes and high saturation magnetization were obtained. The method of batch addition of the reactant prepared IONs with the largest particle size and the highest saturation magnetization compared with IONs reported using PEG as the reaction solvent. The IONs prepared by this method also retained good water dispersibility. Therefore, these IONs are potentially suitable for the magnetic separation of cells, proteins, or nucleic acids when large magnetic responses are needed.

Microglial gp91phox-mediated neuroinflammation and ferroptosis contributes to learning and memory deficits in rotenone-treated mice.

Apart from dopaminergic neurotoxicity, exposure to rotenone, a commonly used insecticide in agriculture, also adversely affects hippocampal and cortical neurons, resulting in cognitive impairments in mice. We recently established a role of microglia-mediated neuroinflammation in rotenone-elicited deficits of cognition, yet the mechanisms remain elusive. Here, we investigated the involvement of NADPH oxidase 2 (NOX2) catalytic subunit gp91phox in rotenone-induced cognitive deficits and the associated mechanisms. Our study demonstrated that rotenone exposure elevated expression of gp91phox and phosphorylation of the NOX2 cytosolic subunit p47phox, along with NADPH depletion in the hippocampus and cortex of mice, indicating NOX2 activation. Specific knockdown of gp91phox in microglia via adeno-associated virus delivery resulted in reduced microglial activation, proinflammatory gene expression and improved learning and memory capacity in rotenone-intoxicated mice. Genetic deletion of gp91phox also reversed rotenone-elicited cognitive dysfunction in mice. Furthermore, microglial gp91phox knockdown attenuated neuronal damage and synaptic loss in mice. This intervention also suppressed iron accumulation, disruption of iron-metabolism proteins and iron-dependent lipid peroxidation and restored the balance of ferroptosis-related parameters, including GPX4, SLC711, PTGS2, and ACSL4 in rotenone-lesioned mice. Intriguingly, pharmacological inhibition of ferroptosis with liproxstatin-1 conferred protection against rotenone-induced neurodegeneration and cognitive dysfunction in mice. In summary, our findings underscored the contribution of microglial gp91phox-dependent neuroinflammation and ferroptosis to learning and memory dysfunction in rotenone-lesioned mice. These results provided valuable insights into the pathogenesis of cognitive deficits associated with pesticide-induced Parkinsonism, suggesting potential therapeutic avenues for intervention.

Colorimetric aptasensor based on temporally controllable light-stimulated oxidase-mimicking fluorescein for the sensitive detection of exosomes in mild conditions.

Analysis of exosomes provides important information for rapid and non-invasive screening of tumors. However, sensitive and convenient detection of exosomes remains technically challenging to date. Herein, a colorimetric aptasensor based on the light-stimulated oxidase-mimicking activity of FITC was constructed for detecting ovarian cancer (OC) exosomes. The aptasensor contained an EpCAM aptamer to capture OC exosomes. Cholesterol and fluorescein (FITC) were used to modify either end of the DNA (DNA anchor). The DNA anchor could combine with exosomes through a hydrophobic reaction between cholesterol and the lipid membrane. FITC oxidized 3,3',5,5'-tetramethylbenzidine (TMB) under a 365 nm LED light source in a temporally controllable manner under mild conditions, causing the solution to change from colorless to blue, and the corresponding UV-vis absorbance increased. Based on this principle, the exosomes were qualitatively analyzed by observing the color change with the naked eye. In parallel, the exosome concentration was also detected using UV-vis spectrophotometry. The linear range was from 2 × 105 to 100 × 105 particles per mL with a limit of detection of 1.77 × 105 particles per mL. The developed aptasensor also exhibited favorable selectivity and could discriminate the exosomes from OC cells and normal cells. Besides, the receiver operating characteristic (ROC) curve demonstrates that it is possible to distinguish between patients with OC and healthy donors (HDs) using exosomes as the biomarker. Our technology may expand the applications of DNA-based detection method-enabled OC diagnostic tools.

Advances in the study of gastric organoids as disease models.

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

Association between sugar-sweetened beverages and pure fruit juice with risk of six cardiovascular diseases: a Mendelian randomization study.

BACKGROUND: In observational and prospective cohort studies, intake of sugar-sweetened beverages (SSBs) and pure fruit juice (PFJ) has been associated with cardiovascular disease (CVD). Still, the causality of the connection has not yet been determined. Our objective was to uncover the relationship between SSBs/PFJ and CVD. METHODS: Genetically predicted causal associations between SSBs/PFJ (obtained in a published genome-wide association study) and six common CVDs (atrial fibrillation (AF), angina, heart failure (HF), acute myocardial infarction, hypertension, and coronary atherosclerosis) were assessed using MR analytic modeling. The primary analysis method utilized was the inverse variance weighted (IVW) method, complemented by additional methods such as the weighted median method, MR Egger regression, Cochran's Q test, MR pleiotropy residual, funnel plot, Bonferroni correction, and others for MR analysis. To ensure the robustness of the findings, F-values were calculated as a complementary test to set looser thresholds for exposing genetic instrumental variables (P < 1e-5). RESULTS: The results of MR analysis suggested genetically causal associations between SSBs and AF (odds ratio (OR): 1.023; 95% confidence interval (CI) 1.007-1.038; P = 0.0039) as well as between PFJ and angina (OR: 0.968; 95% CI, 0.943-0.993; P = 0.0138) there was genetic causality. However, MR analysis showed no causal association between SSBs/PFJ and other CVD risks. CONCLUSION: This study suggests that there may be a potential causal relationship between SSBs intake and AF and a causal negative association between PFJ intake and angina.

Synthetic Approaches to the New Drugs Approved During 2022.

In 2022, 23 new small molecule chemical entities were approved as drugs by the United States FDA, European Union EMA, Japan PMDA, and China NMPA. This review describes the synthetic approach demonstrated on largest scale for each new drug based on patent or primary literature. The synthetic routes highlight practical methods to construct molecules, sometimes on the manufacturing scale, to access the new drugs. Ten additional drugs approved in 2021 and one approved in 2020 are included that were not covered in the previous year's review.

Spatial and temporal analysis of HIV clinical outcomes in Florida reveals counties with persistent racial and ethnic disparities during 2012-2019.

BACKGROUND: Racial/ethnic disparities in the HIV care continuum have been well documented in the US, with especially striking inequalities in viral suppression rates between White and Black persons with HIV (PWH). The South is considered an epicenter of the HIV epidemic in the US, with the largest population of PWH living in Florida. It is unclear whether any disparities in viral suppression or immune reconstitution-a clinical outcome highly correlated with overall prognosis-have changed over time or are homogenous geographically. In this analysis, we 1) investigate longitudinal trends in viral suppression and immune reconstitution among PWH in Florida, 2) examine the impact of socio-ecological factors on the association between race/ethnicity and clinical outcomes, 3) explore spatial and temporal variations in disparities in clinical outcomes. METHODS: Data were obtained from the Florida Department of Health for 42,369 PWH enrolled in the Ryan White program during 2008-2020. We linked the data to county-level socio-ecological variables available from County Health Rankings. GEE models were fit to assess the effect of race/ethnicity on immune reconstitution and viral suppression longitudinally. Poisson Bayesian hierarchical models were fit to analyze geographic variations in racial/ethnic disparities while adjusting for socio-ecological factors. RESULTS: Proportions of PWH who experienced viral suppression and immune reconstitution rose by 60% and 45%, respectively, from 2008-2020. Odds of immune reconstitution and viral suppression were significantly higher among White [odds ratio =2.34, 95% credible interval=2.14-2.56; 1.95 (1.85-2.05)], and Hispanic [1.70 (1.54-1.87); 2.18(2.07-2.31)] PWH, compared with Black PWH. These findings remained unchanged after accounting for socio-ecological factors. Rural and urban counties in north-central Florida saw the largest racial/ethnic disparities. CONCLUSIONS: There is persistent, spatially heterogeneous, racial/ethnic disparity in HIV clinical outcomes in Florida. This disparity could not be explained by socio-ecological factors, suggesting that further research on modifiable factors that can improve HIV outcomes among Black and Hispanic PWH in Florida is needed.

Sequencing hour-level temporal patterns of polysubstance use among persons who use cocaine, alcohol, and cannabis: A back-translational approach.

BACKGROUND: Polysubstance use is highly prevalent among persons who use cocaine; however, little is known about how alcohol and cannabis are used with cocaine. We identified temporal patterns of cocaine+alcohol and cocaine+cannabis polysubstance use to inform more translationally relevant preclinical models. METHODS: Participants who used cocaine plus alcohol and/or cannabis at least once in the past 30 days (n=148) were interviewed using the computerized Substance Abuse Module and the newer Polysubstance Use-Temporal Patterns Section. For each day in the past 30 days, participants reported whether they had used cocaine, alcohol, and cannabis; if any combinations of use were endorsed, participants described detailed hourly use of each substance on the most "typical day" for the combination. Sequence analysis and hierarchical clustering were applied to identify patterns of timing of drug intake on typical days of cocaine polysubstance use. RESULTS: We identified five temporal patterns among the 180 sequences of reported cocaine polysubstance use: 1) limited cocaine/cocaine+alcohol use (53%); 2) extensive cannabis then cocaine+alcohol+cannabis use (22%); 3) limited alcohol/cannabis then cocaine+alcohol use (13%); 4) extensive cocaine+cannabis then cocaine+alcohol+cannabis use (4%); and 5) extensive cocaine then cocaine+alcohol use (8%). While drug intake patterns differed, prevalence of use disorders did not. CONCLUSIONS: Patterns were characterized by cocaine, alcohol, and cannabis polysubstance use and by the timing, order, duration, and quantity of episode-level substance use. The identification of real-world patterns of cocaine polysubstance use represents an important step toward developing laboratory models that accurately reflect human behavior.

Comorbidity Burden and Health Care Utilization by Substance use Disorder Patterns among People with HIV in Florida.

Substance use disorder (SUD), a common comorbidity among people with HIV (PWH), adversely affects HIV clinical outcomes and HIV-related comorbidities. However, less is known about the incidence of different chronic conditions, changes in overall comorbidity burden, and health care utilization by SUD status and patterns among PWH in Florida, an area disproportionately affected by the HIV epidemic. We used electronic health records (EHR) from a large southeastern US consortium, the OneFlorida + clinical research data network. We identified a cohort of PWH with 3 + years of EHRs after the first visit with HIV diagnosis. International Classification of Diseases (ICD) codes were used to identify SUD and comorbidity conditions listed in the Charlson comorbidity index (CCI). A total of 42,271 PWH were included (mean age 44.5, 52% Black, 45% female). The prevalence SUD among PWH was 45.1%. Having a SUD diagnosis among PWH was associated with a higher incidence for most of the conditions listed on the CCI and faster increase in CCI score overtime (rate ratio = 1.45, 95%CI 1.42, 1.49). SUD in PWH was associated with a higher mean number of any care visits (21.7 vs. 14.8) and more frequent emergency department (ED, 3.5 vs. 2.0) and inpatient (8.5 vs. 24.5) visits compared to those without SUD. SUD among PWH was associated with a higher comorbidity burden and more frequent ED and inpatient visits than PWH without a diagnosis of SUD. The high SUD prevalence and comorbidity burden call for improved SUD screening, treatment, and integrated care among PWH.

The Effect of Veteran Status and Chronic Pain on Past 30-Day Sedative Use Among Community-Dwelling Adult Males.

INTRODUCTION: Given the high sedative prescription rate, the sedative-associated morbidity, and mortality nationally (especially among veterans), we aimed to test the hypothesis that veteran status in the presence of chronic pain would be associated with greater sedative use when compared with nonveteran status. METHODS: The study participants were recruited by Community Health Workers (CHWs) through the ongoing community engagement program (HealthStreet) at the University of Florida. CHWs collected information on sociodemographic factors, health status, and past 30-day drug use patterns. RESULTS: The study sample comprised 4,732 male participants, of which 21% were veterans, 58% were Blacks and 8.4% had used prescription sedatives in the past 30 days. Veterans (vs nonveterans) were twice as likely to have used prescription sedatives in the past 30 days in the presence of chronic pain. CONCLUSIONS: Veterans with chronic pain are a high-risk population for current prescription sedative use.

YTHDF2 Is a Therapeutic Target for HCC by Suppressing Immune Evasion and Angiogenesis Through ETV5/PD-L1/VEGFA Axis.

N6-methyladenosine (m6A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion and angiogenesis are characteristic features of its TME. The role of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), as an m6A reader, in regulating HCC TME are not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 and H3 lysine 27 acetylation modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis. Animal experiments demonstrated that Ythdf2 depletion inhibited spontaneous HCC formation, while its overexpression promoted xenografted HCC progression. Mechanistically, YTHDF2 recognized the m6A modification in the 5'-untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. Elevated ETV5 expression induced the transcription of programmed death ligand-1 and vascular endothelial growth factor A, thereby promoting HCC immune evasion and angiogenesis. Targeting YTHDF2 via small interference RNA-containing aptamer/liposomes successfully both inhibited HCC immune evasion and angiogenesis. Together, this findings reveal the potential application of YTHDF2 in HCC prognosis and targeted treatment.

Learning What Works: A Mixed-Methods Study of American Self-identified Food Conservers.

OBJECTIVE: Identify psychosocial factors influencing food waste mitigation and explore motivations and strategies for successful conservation among self-identified food conservers. METHODS: Mixed-methods study consisting of an online survey estimating food waste production and psychosocial factors and a focus group to explore waste mitigation strategies and motivations. RESULTS: Sampled 27 self-identified conservers (female, aged 18-30 years, White/Asian). Mean household food waste was 6.6 cups/wk (range, 0.0-97.9 cups/wk; median 1.3 cups). Reported waste mitigation strategies include proactive mitigation and adaptive recovery measures in each phase of the food management continuum. Conservers reported various intrinsic and extrinsic motivations to reduce food waste and viewed barriers as manageable. CONCLUSIONS AND IMPLICATIONS: Food conservers act on high intentions to reduce waste by consistently employing both proactive waste mitigation and adaptive food recovery measures. Future research is needed to determine if these findings hold in larger, more diverse samples and link specific behaviors to waste volume.

Intratumoral and peritumoral radiomics predict pathological response after neoadjuvant chemotherapy against advanced gastric cancer.

BACKGROUND: To investigate whether intratumoral and peritumoral radiomics may predict pathological responses after neoadjuvant chemotherapy against advanced gastric cancer. METHODS: Clinical, pathological, and CT data from 231 patients with advanced gastric cancer who underwent neoadjuvant chemotherapy at our hospital between July 2014 and February 2022 were retrospectively collected. Patients were randomly divided into a training group (n = 161) and a validation group (n = 70). The support vector machine classifier was used to establish radiomics models. A clinical model was established based on the selected clinical indicators. Finally, the radiomics and clinical models were combined to generate a radiomics-clinical model. ROC analyses were used to evaluate the prediction efficiency for each model. Calibration curves and decision curves were used to evaluate the optimal model. RESULTS: A total of 91 cases were recorded with good response and 140 with poor response. The radiomics model demonstrated that the AUC was higher in the combined model than in the intratumoral and peritumoral models (training group: 0.949, 0.943, and 0.846, respectively; validation group: 0.815, 0.778, and 0.701, respectively). Age, Borrmann classification, and Lauren classification were used to construct the clinical model. Among the radiomics-clinical models, the combined-clinical model showed the highest AUC (training group: 0.960; validation group: 0.843), which significantly improved prediction efficiency. CONCLUSION: The peritumoral model provided additional value in the evaluation of pathological response after neoadjuvant chemotherapy against advanced gastric cancer, and the combined-clinical model showed the highest predictive efficiency. CRITICAL RELEVANCE STATEMENT: Intratumoral and peritumoral radiomics can noninvasively predict the pathological response against advanced gastric cancer after neoadjuvant chemotherapy to guide early treatment decision and provide individual treatment for patients. KEY POINTS: 1. Radiomics can predict pathological responses after neoadjuvant chemotherapy against advanced gastric cancer. 2. Peritumoral radiomics has additional predictive value. 3. Radiomics-clinical models can guide early treatment decisions and improve patient prognosis.

Demographics, Trends, and Clinical Characteristics of HIV Pre-Exposure Prophylaxis Recipients and People Newly Diagnosed with HIV from Large Electronic Health Records in Florida.

Florida is one of the HIV epicenters with high incidence and marked sociodemographic disparities. We analyzed a decade of statewide electronic health record/claims data-OneFlorida+-to identify and characterize pre-exposure prophylaxis (PrEP) recipients and newly diagnosed HIV cases in Florida. Refined computable phenotype algorithms were applied and a total of 2186 PrEP recipients and 7305 new HIV diagnoses were identified between January 2013 and April 2021. We examined patients' sociodemographic characteristics, stratified by self-reported sex, along with both frequency-driven and expert-selected descriptions of clinical conditions documented within 12 months before the first PrEP use or HIV diagnosis. PrEP utilization rate increased in both sexes; higher rates were observed among males with sex differences widening in recent years. HIV incidence peaked in 2016 and then decreased with minimal sex differences observed. Clinical characteristics were similar between the PrEP and new HIV diagnosis cohorts, characterized by a low prevalence of sexually transmitted infections (STIs) and a high prevalence of mental health and substance use conditions. Study limitations include the overrepresentation of Medicaid recipients, with over 96% of female PrEP users on Medicaid, and the inclusion of those engaged in regular health care. Although PrEP uptake increased in Florida, and HIV incidence decreased, sex disparity among PrEP recipients remained. Screening efforts beyond individuals with documented prior STI and high-risk behavior, especially for females, including integration of mental health care with HIV counseling and testing, are crucial to further equalize PrEP access and improve HIV prevention programs.

Dual-Proton Conductor for Fuel Cells with Flexible Operational Temperature.

The properties of proton conductors determine the operating temperature range of fuel cells. Typically, phosphoric acid (PA) proton conductors exhibit excellent proton conductivity owing to their high proton dissociation and self-diffusion abilities. However, at low temperatures or high current densities, water-induced PA loss causes rapid degradation of cell performance. Maintaining efficient and stable proton conductivity within a flexible temperature range can significantly reduce the start-up temperature of PA-doped proton exchange membrane fuel cells. In this study, a dual-proton conductor composed of an organic phosphonic acid (ethylenediamine tetramethylene phosphonic acid, EDTMPA) and an inorganic PA is developed for proton exchange membranes. The proposed dual-proton conductor can operate within a flexible temperature range of 80-160 °C, benefiting from the strong interaction between EDTMPA and PA, and the enhanced proton dissociation. Fuel cells with the EDTMPA-PA dual-proton conductor showed excellent cell stability at 80 °C. In particular, under the high current density of 1.5 A cm-2 at 160 °C, the voltage decay rate of the fuel cell with the dual-proton conductor is one-thousandth of that of the fuel cell with PA-only proton conductor, indicating excellent stability.

Automated classification of lay health articles using natural language processing: a case study on pregnancy health and postpartum depression.

Objective: Evidence suggests that high-quality health education and effective communication within the framework of social support hold significant potential in preventing postpartum depression. Yet, developing trustworthy and engaging health education and communication materials requires extensive expertise and substantial resources. In light of this, we propose an innovative approach that involves leveraging natural language processing (NLP) to classify publicly accessible lay articles based on their relevance and subject matter to pregnancy and mental health. Materials and methods: We manually reviewed online lay articles from credible and medically validated sources to create a gold standard corpus. This manual review process categorized the articles based on their pertinence to pregnancy and related subtopics. To streamline and expand the classification procedure for relevance and topics, we employed advanced NLP models such as Random Forest, Bidirectional Encoder Representations from Transformers (BERT), and Generative Pre-trained Transformer model (gpt-3.5-turbo). Results: The gold standard corpus included 392 pregnancy-related articles. Our manual review process categorized the reading materials according to lifestyle factors associated with postpartum depression: diet, exercise, mental health, and health literacy. A BERT-based model performed best (F1 = 0.974) in an end-to-end classification of relevance and topics. In a two-step approach, given articles already classified as pregnancy-related, gpt-3.5-turbo performed best (F1 = 0.972) in classifying the above topics. Discussion: Utilizing NLP, we can guide patients to high-quality lay reading materials as cost-effective, readily available health education and communication sources. This approach allows us to scale the information delivery specifically to individuals, enhancing the relevance and impact of the materials provided.

Improved Post-Traumatic Stress Disorder Symptoms and Related Sleep Disturbances after Initiation of Medical Marijuana Use: Evidence from a Prospective Single Arm Pilot Study.

Introduction: Post-traumatic stress disorder (PTSD) is a debilitating disorder experienced by a subgroup of individuals following a life-threatening trauma. Several US states have passed laws permitting the medical use of marijuana (MMJ) by individuals with PTSD, despite very little scientific indication on the appropriateness of marijuana as a therapy for PTSD. This prospective pilot study of adults with confirmed PTSD in Florida (FL) investigated whether PTSD symptoms, sleep quality, affect, and general physical and mental health/well-being improved post-initiation of MMJ treatment. Methods: Participants, N = 15, were recruited from two MMJ clinics in Gainesville and Jacksonville, FL. To be eligible, participants had to be 18 years of age or older, not currently on MMJ, and willing to abstain from recreational marijuana, if using any, until the State Medical Cannabis Card was obtained, screen positive for PTSD. Participants were assessed at baseline (pre-MMJ initiation) and 30 and 70 days post-MMJ initiation using the Pittsburgh Sleep Quality Index (PSQI), PTSD Checklist for DSM-5 (PCL-5), Positive and Negative Affect Schedule (PANAS), PROMIS Global Health V1.2, and semi-structured marijuana and other substance use assessment. Results: PTSD symptom severity as measured by total PCL-5 score improved significantly at 30- and 70-day follow-ups. Similarly, statistically significant reductions in nightmares were reported at 30- and 70-day follow-ups. Corresponding improvements in sleep were noticed with participants reporting increased duration of sleep hours, sleep quality, sleep efficiency, and total PSQI score. Likewise, negative affect and global mental health improved significantly at follow-up. According to the post hoc analyses, the most statistically significant changes occurred between baseline and 30-day follow-up. The exception to this pattern was nightmares, which did not show significant improvement until day 70. Conclusion: The findings of this study highlight the potential of MMJ in improving patient outcomes for those with PTSD, particularly concerning sleep disturbances, which often do not respond to currently available treatments.

Dynamic response and liquefaction potential of porous seabed induced by partial standing ocean waves.

The analysis of ocean wave-induced dynamic response of a porous seabed is particularly important for coastal and geotechnical engineers when designing and constructing maritime structures. In this study, an analytical solution is presented to analyze the dynamic response and liquefaction potential of a poro-elastic seabed induced by partial standing waves with arbitrary reflectivity. The porous seabed is modeled using Biot's theory describing the propagation of elastic waves, and coupled deformation and water flow of porous media, whereas the ocean waves are described using linear ocean wave theory. Based on the mixed boundary-value conditions, explicit expressions of displacements, effective stresses and excess pore water pressure of seabed are derived with consideration of the effects of inertial forces, compressibility of solid and fluid, and arbitrary reflectivity of standing waves. The results of degenerated analytical solutions are compared with the existing ones to verify the correctness of the proposed method. The effects of several pertinent parameters of ocean wave-seabed system, including reflection coefficient, phase lag and period of standing waves, depth of water, permeability, degree of saturation, and shear modulus of seabed deposits, etc., on the dynamic response of seabed and liquefaction potential, are examined and discussed. It is found that the reflection of standing wave has a significant effect on the dynamic response and liquefaction potential of porous elastic seabed. Compared with that of no wave reflection, the liquefaction depth of seabed induced by fully-reflected standing waves increases 82.49% under certain conditions of wave-seabed system. In addition, phase lag, wave period, water depth and mechanical and physical properties of seabed soil such as saturation, permeability and shear modulus have different effects on the dynamic response and liquefaction potential of porous elastic seabed. The investigation of the dynamic response and liquefaction of the porous elastic seabed under partial standing ocean waves will help to better predict the influence of standing waves on breakwaters and seabed soil, and can provide some guidance for the design of offshore structures.