Assessing men with opioid use disorder for testosterone deficiency after the development of symptoms.

OBJECTIVE: Individuals with opioid use disorder (OUD) have reduced life expectancy and inferior outcomes when treated for depression, diabetes, and fractures. Their elevated risk of testosterone deficiency may contribute to all of these relationships, however few individuals prescribed opioids are evaluated with testosterone assays. The purpose of this study is to determine whether patients with opioid use disorder are evaluated for testosterone deficiency after development of a symptom that may merit investigation, such as erectile dysfunction (ED). METHOD: We conducted a retrospective longitudinal cohort study that utilized data from a national database called TriNetX. Patients were eligible for inclusion if they were 20 to 90 years of age, male, and diagnosed with erectile dysfunction. We utilized descriptive statistics and logistic regression to address study aims. RESULTS: Testosterone testing was uncommon for all patients with ED. Among 20,658 patients, it was assessed in 11.2% with OUD and 15.1% without OUD. Among those screened, 40% individuals with OUD and ED had testosterone deficiency. Odds of screening those with OUD were lower than matched controls (RR 0.74). CONCLUSIONS: Individuals with OUD are at increased risk of testosterone deficiency than the general population, but nearly 90% are not evaluated for this condition even after development symptoms. That 40% of individuals assessed were classified as testosterone deficient suggests endocrine disorders may be contributing to increased fracture risk, chronic pain, and severe depression commonly encountered in patients with OUD. Addressing this care gap may reduce morbidity and mortality associated with opioid use disorder.

Active avoidance under social conditions recruits the anterior cingulate cortex in male and female rats.

Actively avoiding potential threats is necessary for survival. Most research has focused on the behavioral and neurobiological processes when individuals avoid potential threats alone, under solitary conditions. Therefore, little is known about how social context affects active avoidance. Using a modified version of the platform-mediated avoidance task, we investigated whether the presence of a social partner attenuates freezing responses and promotes greater avoidance learning compared to avoidance learned under solitary conditions. Rats spent a similar percentage of time avoiding during the conditioned tone under both conditions; however, rats trained under social conditions exhibited greater freezing during the tone and lower pressing for food reward compared to solitary rats. Under solitary conditions, we observed greater avoidance in female compared to male rats, which was not present in rats under social conditions. To gain greater mechanistic insight, we optogenetically inactivated glutamatergic projection neurons in the anterior cingulate cortex (ACC) following avoidance training. Photoinactivation of ACC neurons impaired avoidance expression under social conditions both in the presence and absence of the partner. Under solitary conditions, photoinactivation of ACC delayed avoidance in males but blocked avoidance in females. Our findings suggest that avoidance is mediated by the ACC, regardless of social context, and may be dysfunctional in those suffering from trauma-related disorders. Furthermore, sex differences in prefrontal circuits mediating active avoidance warrant further investigation, given that females experience a higher risk of developing anxiety disorders.

SPR-1/CoREST facilitates the maternal epigenetic reprogramming of the histone demethylase SPR-5/LSD1.

Maternal reprogramming of histone methylation is critical for reestablishing totipotency in the zygote, but how histone-modifying enzymes are regulated during maternal reprogramming is not well characterized. To address this gap, we asked whether maternal reprogramming by the H3K4me1/2 demethylase SPR-5/LSD1/KDM1A, is regulated by the chromatin co-repressor protein, SPR-1/CoREST, in Caenorhabditis elegans and mice. In C. elegans, SPR-5 functions as part of a reprogramming switch together with the H3K9 methyltransferase MET-2. By examining germline development, fertility, and gene expression in double mutants between spr-1 and met-2, as well as fertility in double mutants between spr-1 and spr-5, we find that loss of SPR-1 results in a partial loss of SPR-5 maternal reprogramming function. In mice, we generated a separation of function Lsd1 M448V point mutation that compromises CoREST binding, but only slightly affects LSD1 demethylase activity. When maternal LSD1 in the oocyte is derived exclusively from this allele, the progeny phenocopy the increased perinatal lethality that we previously observed when LSD1 was reduced maternally. Together, these data are consistent with CoREST having a conserved function in facilitating maternal LSD1 epigenetic reprogramming.

Trends in characteristics of the recipients of new prescription stimulants between years 2010 and 2020 in the United States: An observational cohort study.

Background: Stimulant prescriptions increased by 250% in the United States from 2006-2016 while diagnoses for ADHD minimally increased. There is insufficient data regarding who may be the recipients of these new stimulant prescriptions and safety of stimulants have come under scrutiny in some populations. We aim to describe trends in stimulant prescriptions across biopsychosocial patient level factors between 2010 and 2020. Methods: We applied a retrospective observational cohort design utilizing electronic health records from 52 healthcare organizations sourced from the TriNetX research network database in the United States. We assessed new stimulant prescriptions across biopsychosocial variables for recipients of prescriptions. We utilized linear regression to assess longitudinal trends of all participants and also conducted an age stratified logistic regression analysis. Findings: There was an increase in stimulants to people categorized as white (OR 1.24 CI 1.20-1.28), female (OR 1.28 CI 1.23-1.31), and to those with diagnosed anxiety disorders (OR 1.39 CI 1.35-1.44) as well as obesity (OR 1.34 CI 1.28-1.41). The average age of recipients increased throughout the study, and among people sixty-five and older, there was an increase in prescriptions to people with multiple cardiovascular risk factors. Interpretation: Prescription stimulant dispensing may have liberalized during the study period in some demographics as a greater number of new prescriptions were dispensed to individuals with risk of adverse outcomes (i.e. older individuals, obese individuals, and geriatric patients with CV risk factors) between 2010 and 2020. Similar trends in prescription medications were witnessed through the opioid epidemic and warrant attention given concerning trends with illicit stimulants. Additional research that investigates patient and provider motivation for stimulant prescriptions, as well as risk perception of stimulants, may be warranted. Funding: This study was made possible by institutional resources at Penn State Hershey Medical Center.

Descriptive Analysis of Orthopaedic Surgery Residency Program Directors.

The purpose of this study was to analyze the demographics and backgrounds of U.S. orthopaedic surgery residency program directors (PDs). We collected publicly available information on 189 orthopaedic surgery residency PDs. Of those PDs, 90% were male MDs with an average age of 52. The average age at PD appointment was 45. The average duration of appointment was 7 years. About 81% of programs were university-affiliated, and 61% were in an urban environment. PDs attended 100 medical schools, 129 residencies, and 96 fellowships. of PDs, 87% completed fellowships, commonly in trauma and sports medicine. There was no significant difference between male and female PDs when comparing age, academic appointment, or urban/rural environment. Most female PDs (89%) were at university-based hospitals. Of PDs at osteopathic-focused programs, 28% had an MD/PD. No program with an allopathic focus had a DO/PD. Lastly, 38% of PDs worked at the center where they completed residency. (Journal of Surgical Orthopaedic Advances 31(4):252-255, 2022).

Trends in Propeller Strike-Induced Mortality in Harbor Seals (Phoca vitulina) of the Salish Sea.

Documenting human impacts on marine mammals is critical for understanding and mitigating harm. Although propeller strike injuries in small marine mammals are often debilitating and fatal, little is known about the occurrence or demographics of these types of injuries in pinniped populations. Using data of stranded harbor seals (Phoca vitulina) in the Salish Sea from 2002-19, we identified 27 cases of fatal propeller strikes. Weaned pups were the most frequently affected (64% of cases) with a much higher rate of propeller strikes than expected for the age class. Although they do represent animal welfare concerns, harbor seals in the Salish Sea probably are not threatened by these types of injuries at the population level; nevertheless, propeller strike cases increased significantly over the time of this study period, indicating increased interactions between boats and seals in the region. Continued monitoring and increased efforts to consistently quantify vessel traffic in the area are recommended to create and monitor long-term effectiveness of mitigation measures.

A comparison of orthopaedic surgery and internal medicine perceptions of USMLE Step 1 pass/fail scoring.

BACKGROUND: United States Medical Licensing Examination Step 1 will transition from numeric grading to pass/fail, sometime after January 2022. The aim of this study was to compare how program directors in orthopaedics and internal medicine perceive a pass/fail Step 1 will impact the residency application process. METHODS: A 27-item survey was distributed through REDCap to 161 U.S. orthopaedic residency program directors and 548 U.S. internal medicine residency program directors. Program director emails were obtained from the American Medical Association's Fellowship and Residency Electronic Interactive Database. RESULTS: We received 58 (36.0%) orthopaedic and 125 (22.8%) internal medicine program director responses. The majority of both groups disagree with the change to pass/fail, and felt that the decision was not transparent. Both groups believe that the Step 2 Clinical Knowledge exam and clerkship grades will take on more importance. Compared to internal medicine PDs, orthopaedic PDs were significantly more likely to emphasize research, letters of recommendation from known faculty, Alpha Omega Alpha membership, leadership/extracurricular activities, audition elective rotations, and personal knowledge of the applicant. Both groups believe that allopathic students from less prestigious medical schools, osteopathic students, and international medical graduates will be disadvantaged. Orthopaedic and internal medicine program directors agree that medical schools should adopt a graded pre-clinical curriculum, and that there should be a cap on the number of residency applications a student can submit. CONCLUSION: Orthopaedic and internal medicine program directors disagree with the change of Step 1 to pass/fail. They also believe that this transition will make the match process more difficult, and disadvantage students from less highly-regarded medical schools. Both groups will rely more heavily on the Step 2 clinical knowledge exam score, but orthopaedics will place more importance on research, letters of recommendation, Alpha Omega Alpha membership, leadership/extracurricular activities, personal knowledge of the applicant, and audition electives.

Congenital Diseases in Harbor Seals (Phoca vitulina richardsii) from the Salish Sea.

Postmortem data for harbor seals (Phoca vitulina richardsii) in the Salish Sea were analyzed for epidemiologic trends in congenital diseases. Cleft palate, cleft lips, or both (n=8) and cardiac defects (n=5) were the most common congenital abnormalities, followed by cases with multiple defects (n=4). No temporal trends or spatial clusters of cases were seen from 2003 to 2019, during which time monitoring effort was consistent. Cases could not be linked to specific causes such as environmental contamination or maternal malnutrition. Our study suggests that a yearly prevalence of 2.9%±2.2 is the endemic level of congenital disease in this stable harbor seal population. Continued monitoring of birth defects and overall harbor seal population status could help to identify emerging teratogens.

Do Targets with Persistent Responses Affect the Efficiency of Instruction?

The efficacy and efficiency of instruction may be reduced as a result of persistent response patterns to targets. The current project exposed participants to tact training with one set of targets. Thereafter, the efficacy and efficiency of teaching different responses to the previously trained set of targets was compared to tact training with a novel set of targets. Results showed that targets with pre-established responses took longer to acquire than targets without pre-existing responses for both participants.

Trends in Cancer Incidence in US Adolescents and Young Adults, 1973-2015.

Importance: Previous studies have demonstrated that adolescents and young adults (AYAs) with cancer are a distinct cancer population; however, research on long-term epidemiological trends and characteristics of cancers in AYAs is lacking. Objective: To characterize the epidemiology of cancer in AYAs aged 15 to 39 years with respect to (1) patient demographic characteristics, (2) frequencies of cancer types, and (3) cancer incidence trends over time. Design, Setting, and Participants: This retrospective, serial cross-sectional, population-based study used registry data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 1973, to December 31, 2015 (SEER 9 and SEER 18). The study population was from geographically distinct US regions, chosen to represent the racial and ethnic heterogeneity of the country. Initial analyses were performed from January 1 to August 31, 2019. Main Outcomes and Measures: Incidence rates and descriptive epidemiological statistics for patients aged 15 to 39 years with invasive cancer. Results: A total of 497 452 AYAs diagnosed from 1973 to 2015 were included in this study, with 293 848 (59.1%) female and 397 295 (79.9%) White participants. As AYAs aged, an increase in the relative incidence of carcinomas and decrease in the relative incidence of leukemias, lymphomas, germ cell and trophoblastic neoplasms, and neoplasms of the central nervous system occurred. Among the female AYAs, 72 564 (24.7%) were diagnosed with breast carcinoma; 48 865 (16.6%), thyroid carcinoma; and 33 828 (11.5%), cervix and uterus carcinoma. Among the male AYAs, 37 597 (18.5%) were diagnosed with testicular cancer; 20 850 (10.2%), melanoma; and 19 532 (9.6%), non-Hodgkin lymphoma. The rate of cancer in AYAs increased by 29.6% from 1973 to 2015, with a mean annual percentage change (APC) per 100 000 persons of 0.537 (95% CI, 0.426-0.648; P < .001). Kidney carcinoma increased at the greatest rate for both male (APC, 3.572; 95% CI, 3.049-4.097; P < .001) and female (APC, 3.632; 95% CI, 3.105-4.162; P < .001) AYAs. Conclusions and Relevance: In this cross-sectional, US population-based study, cancer in AYAs was shown to have a unique epidemiological pattern and is a growing health concern, with many cancer subtypes having increased in incidence from 1973 to 2015. Continued research on AYA cancers is important to understanding and addressing the distinct health concerns of this population.

Exploring movement patterns and changing distributions of baleen whales in the western North Atlantic using a decade of passive acoustic data.

Six baleen whale species are found in the temperate western North Atlantic Ocean, with limited information existing on the distribution and movement patterns for most. There is mounting evidence of distributional shifts in many species, including marine mammals, likely because of climate-driven changes in ocean temperature and circulation. Previous acoustic studies examined the occurrence of minke (Balaenoptera acutorostrata) and North Atlantic right whales (NARW; Eubalaena glacialis). This study assesses the acoustic presence of humpback (Megaptera novaeangliae), sei (B. borealis), fin (B. physalus), and blue whales (B. musculus) over a decade, based on daily detections of their vocalizations. Data collected from 2004 to 2014 on 281 bottom-mounted recorders, totaling 35,033 days, were processed using automated detection software and screened for each species' presence. A published study on NARW acoustics revealed significant changes in occurrence patterns between the periods of 2004-2010 and 2011-2014; therefore, these same time periods were examined here. All four species were present from the Southeast United States to Greenland; humpback whales were also present in the Caribbean. All species occurred throughout all regions in the winter, suggesting that baleen whales are widely distributed during these months. Each of the species showed significant changes in acoustic occurrence after 2010. Similar to NARWs, sei whales had higher acoustic occurrence in mid-Atlantic regions after 2010. Fin, blue, and sei whales were more frequently detected in the northern latitudes of the study area after 2010. Despite this general northward shift, all four species were detected less on the Scotian Shelf area after 2010, matching documented shifts in prey availability in this region. A decade of acoustic observations have shown important distributional changes over the range of baleen whales, mirroring known climatic shifts and identifying new habitats that will require further protection from anthropogenic threats like fixed fishing gear, shipping, and noise pollution.

KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in mice.

The proper regulation of spermatogenesis is crucial to ensure the continued production of sperm and fertility. Here, we investigated the function of the H3K4me2 demethylase KDM1A/LSD1 during spermatogenesis in developing and adult mice. Conditional deletion of Kdm1a in the testis just prior to birth leads to fewer spermatogonia and germ cell loss before 3 weeks of age. These results demonstrate that KDM1A is required for spermatogonial differentiation, as well as germ cell survival, in the developing testis. In addition, inducible deletion of Kdm1a in the adult testis results in the abnormal accumulation of meiotic spermatocytes, as well as apoptosis and progressive germ cell loss. These results demonstrate that KDM1A is also required during adult spermatogenesis. Furthermore, without KDM1A, the stem cell factor OCT4 is ectopically maintained in differentiating germ cells. This requirement for KDM1A is similar to what has been observed in other stem cell populations, suggesting a common function. Taken together, we propose that KDM1A is a key regulator of spermatogenesis and germ cell maintenance in the mouse.