Adverse Childhood Experiences and Depression among Homeless Young Adults: A Social Determinants of Health Perspective.

Homelessness is a pervasive issue in the United States that presents significant challenges to public health. Homeless young adults (HYAs) are at particular risk for increased incidence and severity of depression. Using primary survey data (n = 205) collected in the Phoenix Metropolitan Area, Arizona, from June to August 2022, this study aims to examine the relationship between adverse childhood experiences (ACEs) and depression among HYAs. We adopted the ACEs 10-item scale to measure childhood traumatic experiences, whereas depression was measured by using a PHQ-4 depression scale and diagnosed depression. Regression models were conducted to test the relationships between ACEs and depression outcomes while controlling for the covariates at the individual, interpersonal, and socioeconomic/living environment levels. The average PHQ-4 score was 5.01 (SD = 3.59), and 59.69% of HYAs reported being diagnosed previously with depression. The mean ACEs score was 5.22 out of 10. Other things being equal, for every one unit increase in ACEs scores, the odds of being diagnosed with depression increased by 11.5%, yet it was not statistically significant, while the PHQ-4 score increased by 0.445 (p < 0.001). Overall, HYAs were disproportionately affected by depression. This study elucidates the complex relationship between ACEs and depression among HYAs.

Hyperbaric effects on cold stored whole blood following a military dive mission profile.

BACKGROUND: Whole blood (WB) is carried by special operations forces as part of a remote damage control resuscitation strategy. The effects of an underwater mission on the quality and coagulation profile of WB were simulated by exposure to hyperbaric pressures in a chamber. METHODS: WB units collected in CPDA-1 were exposed to three different combinations of hyperbaric pressure and duration of exposure: Group A 153.52 kPa (15.24 msw; 1.52 atm) for 4 h; n = 9, Group B 506.63 kPa (50.29 msw; 5.00 atm) for 1 h; n = 9, Group C 153.52 kPa (15.24 msw; 1.52 atm) for 1 h; n = 7. The following parameters were measured on each unit: prothrombin time/international normalized ratio, activated partial thromboplastin time, thromboelastography and concentration determinations of platelets, lactate, fibrinogen, and lactate dehydrogenase. Each sample underwent baseline, prepressurization, immediate postpressurization, and 6 h postpressurization laboratory testing. RESULTS: Six hours following hyperbaric exposure, the lactate concentration in group C was higher than prepressurization measurement and the platelet concentration in Group A was lower than prepressurization measurement. There were no changes in any of the other analyzed biochemical, coagulation and thromboelastogram parameters following exposure to hyperbaric stress. DISCUSSION: These data suggest that pressurization of WB up to 5 atm did not impact parameters tested. Changes observed in lactate and platelet count need further study, as well as complementary testing of red blood cell integrity. Further investigation of the hyperbaric extremes is necessary to determine if there is a damage inducing pressure to which WB should not be exposed.

Dual-sgRNA CRISPR/Cas9 knockout of PD-L1 in human U87 glioblastoma tumor cells inhibits proliferation, invasion, and tumor-associated macrophage polarization.

Programmed death ligand 1 (PD-L1) plays a key role in glioblastoma multiforme (GBM) immunosuppression, vitality, proliferation, and migration, and is therefore a promising target for treating GBM. CRISPR/Cas9-mediated genomic editing can delete both cell surface and intracellular PD-L1. This systemic deliverable genomic PD-L1 deletion system can be used as an effective anti-GBM therapy by inhibiting tumor growth and migration, and overcoming immunosuppression. To target PD-L1 for CRISPR/Cas9 gene editing, we first identified two single guide RNA (sgRNA) sequences located on PD-L1 exon 3. The first sgRNA recognizes the forward strand of human PD-L1 near the beginning of exon 3 that allows editing by Cas9 at approximately base pair 82 (g82). The second sgRNA recognizes the forward strand of exon 3 that directs cutting at base pair 165 (g165). A homology-directed repair template (HDR) combined with the dual-sgRNAs was used to improve PD-L1 knockout specificity and efficiency. sgRNAs g82 and g165 were cloned into the multiplex CRISPR/Cas9 assembly system and co-transfected with the HDR template in human U87 GBM cells (g82/165 + HDR). T7E1 analysis suggests that the dual-sgRNA CRISPR/Cas9 strategy with a repair template was capable of editing the genomic level of PD-L1. This was further confirmed by examining PD-L1 protein levels by western blot and immunofluorescence assays. Western blot analysis showed that the dual-sgRNAs with the repair template caused a 64% reduction of PD-L1 protein levels in U87 cells, while immunostaining showed a significant reduction of intracellular PD-L1. PD-L1 deletion inhibited proliferation, growth, invasion and migration of U87 cells, indicating intracellular PD-L1 is necessary for tumor progression. Importantly, U87 cells treated with g82/165 + HDR polarized tumor-associated macrophages (TAM) toward an M1 phenotype, as indicated by an increase in TNF-α and a decrease in IL-4 secretions. This was further confirmed with flow cytometry that showed an increase in the M1 markers Ly6C + and CD80 +, and a decrease in the M2 marker CD206 + both in vitro and in vivo. Utilizing dual-sgRNAs and an HDR template with the CRISPR/Cas9 gene-editing system is a promising avenue for the treatment of GBM.

Policies regarding use of medications for opioid use disorder in professional recovery programs: A scoping review.

Background: In the U.S., medications for opioid use disorder (MOUD) include methadone, buprenorphine, and naltrexone. Despite substantial evidence of efficacy, the use of MOUD by health professionals remains controversial. This scoping review sought to identify and describe policies related to the use of MOUD by physicians, pharmacists, and nurses in professional health programs (PHP). Methods: A systematic search of PubMed, Medline, Web of Science, and Google Scholar was performed in August 2020 to identify pertinent articles from the U.S. which were then evaluated for inclusion by a team of trained reviewers. Results: Nine articles were ultimately identified for inclusion, and their years of publication ranged from 1984 to 2012. The treatment of physicians was addressed in seven articles, nurses in four, and pharmacists in two. Data from one veterinarian and several dentists could not be disaggregated from three studies. Naltrexone was the most commonly accepted form of MOUD within PHPs. A 2011 survey of physician and nurse PHP administrators found that 11/22 (50%) physician programs and 15/33 (45%) nursing programs forbade practice reentry while taking buprenorphine with the remainder indicating it could be allowed under some circumstances. The use of methadone within PHPs was extremely rare, and no specific details regarding PHP policies related to its use or practice reentry could be identified. No articles reported specifically on practice reentry policies for pharmacists. Conclusions: This scoping review identified one article detailing explicit policies concerning MOUD use in the target professions. Implicit policies extrapolated from other articles found that naltrexone was the most commonly accepted form of MOUD, with methadone and buprenorphine being avoided due to dubious concerns of impairment. A unified, contemporary, comprehensive survey of current PHP policies and evaluation of actual treatment data to ascertain real-world practices is needed.

Availability of buprenorphine/naloxone films and naloxone nasal spray in community pharmacies in Texas, USA.

BACKGROUND AND AIMS: Patients with opioid use disorder (OUD) must be able to obtain prescribed buprenorphine/naloxone films (BUP/NX) and naloxone nasal spray (NNS) from a pharmacy promptly to reduce risk for a recurrence of use and subsequent morbidity and mortality. Telephone audits have identified concerning gaps in availability of NNS within US pharmacies, but the availability of BUP/NX has not been rigorously evaluated. This study estimated the availability of BUP/NX and NNS in the US state of Texas and compared availability by pharmacy type and metropolitan status. DESIGN: A cross-sectional telephone audit with a secret shopper approach conducted from 18 May 2020 to 7 June 2020. Setting and Participants A random sample of 800 of 5078 (16%) community pharmacies licensed with the Texas State Board of Pharmacy. MEASUREMENTS: Primary outcomes included availability of a 1-week supply of generic BUP/NX 8/2 mg films and a single unit of NNS 4 mg, overall and by pharmacy type. Secondary outcomes included willingness and estimated time-frame to order BUP/NX if unavailable. FINDINGS: Data from 704 pharmacies (471 chain, 233 independent) were included for analyses. Of these, 34.1% of pharmacies (45.0% of chains versus 12.0% of independents, P < 0.0001) were willing and able to dispense a 1-week supply of generic BUP/NX and a single unit of NNS. BUP/NX alone was available in 42.2% of pharmacies (52.4% of chains versus 21.5% of independents, P < 0.0001). NNS alone was available in 60.1% of pharmacies (77.9% of chains versus 24.0% of independents, P < 0.0001). Of the 397 pharmacies with generic BUP/NX unavailable, 62.2% of pharmacies (73.9% of chains versus 48.0% of independents, P < 0.0001) indicated willingness to order. CONCLUSIONS: Most pharmacies in Texas do not appear to be willing and able to dispense prescribed buprenorphine/naloxone films and naloxone nasal spray to patients with opioid use disorder in a timely manner. Deficiencies in availability are markedly more pronounced in independent pharmacies compared with chain pharmacies.

Anterior ankle impingement: diagnosis and treatment.

Anterior ankle impingement is a common clinical condition characterized by chronic anterior ankle pain that is exacerbated on dorsiflexion. Additional symptoms include instability; limited ankle motion; and pain with squatting, sprinting, stair climbing, and hill climbing. Diagnosis is typically confirmed with plain radiographs. Nonsurgical management includes physical therapy, strengthening exercises, activity modification, bracing, and anti-inflammatory medication. Although arthroscopic treatment is sufficient in some patients, most require an open approach to address related pathology. We advocate aggressive range of motion as well as weight bearing postoperatively. Further study is needed to confirm current understanding of anterior ankle impingement and to better define treatment options and prevention strategies.