Wildfire Smoke Is Associated With an Increased Risk of Cardiorespiratory Emergency Department Visits in Alaska.

Alaskan wildfires have major ecological, social, and economic consequences, but associated health impacts remain unexplored. We estimated cardiorespiratory morbidity associated with wildfire smoke (WFS) fine particulate matter with a diameter less than 2.5 µm (PM2.5) in three major population centers (Anchorage, Fairbanks, and the Matanuska-Susitna Valley) during the 2015-2019 wildfire seasons. To estimate WFS PM2.5, we utilized data from ground-based monitors and satellite-based smoke plume estimates. We implemented time-stratified case-crossover analyses with single and distributed lag models to estimate the effect of WFS PM2.5 on cardiorespiratory emergency department (ED) visits. On the day of exposure to WFS PM2.5, there was an increased odds of asthma-related ED visits among 15-65 year olds (OR = 1.12, 95% CI = 1.08, 1.16), people >65 years (OR = 1.15, 95% CI = 1.01, 1.31), among Alaska Native people (OR = 1.16, 95% CI = 1.09, 1.23), and in Anchorage (OR = 1.10, 95% CI = 1.05, 1.15) and Fairbanks (OR = 1.12, 95% CI = 1.07, 1.17). There was an increased risk of heart failure related ED visits for Alaska Native people (Lag Day 5 OR = 1.13, 95% CI = 1.02, 1.25). We found evidence that rural populations may delay seeking care. As the frequency and magnitude of Alaskan wildfires continue to increase due to climate change, understanding the health impacts will be imperative. A nuanced understanding of the effects of WFS on specific demographic and geographic groups facilitates data-driven public health interventions and fire management protocols that address these adverse health effects.

Transoral robotic resection of oropharyngeal synovial sarcoma in a pediatric patient.

Localized synovial cell sarcomas are treated with surgical resection followed by chemo-radiation. Surgical resection of synovial sarcoma of the oropharynx and hypopharynx involves lip-splitting mandibulotomy resulting in treatment related morbidity. We report the successful use of Trans Oral Robotic Surgery for resection of localized synovial sarcoma of the lateral pharyngeal wall in a 15 year old patient. We were able to achieve negative surgical margins and avoid open surgery with its associated morbidity. At 2 years follow-up, patient is disease free, with no deficits in speech or swallowing functions and no cosmetic deformity.

Ammonia inhibits long-term potentiation via neurosteroid synthesis in hippocampal pyramidal neurons.

Neurosteroids are a class of endogenous steroids synthesized in the brain that are believed to be involved in the pathogenesis of neuropsychiatric disorders and memory impairment. Ammonia impairs long-term potentiation (LTP), a synaptic model of learning, in the hippocampus, a brain region involved in memory acquisition. Although mechanisms underlying ammonia-mediated LTP inhibition are not fully understood, we previously found that the activation of N-methyl-d-aspartate receptors (NMDARs) is important. Based on this, we hypothesize that metabolic stressors, including hyperammonemia, promote untimely NMDAR activation and result in neural adaptations that include the synthesis of allopregnanolone (alloP) and other GABA-potentiating neurosteroids that dampen neuronal activity and impair LTP and memory formation. Using an antibody against 5α-reduced neurosteroids, we found that 100 µM ammonia acutely enhanced neurosteroid immunostaining in pyramidal neurons in the CA1 region of rat hippocampal slices. The enhanced staining was blocked by finasteride, a selective inhibitor of 5α-reductase, a key enzyme required for alloP synthesis. Finasteride also overcame LTP inhibition by 100 µM ammonia, as did picrotoxin, an inhibitor of GABA-A receptors. These results indicate that GABA-enhancing neurosteroids, synthesized locally within pyramidal neurons, contribute significantly to ammonia-mediated synaptic dysfunction. These results suggest that the manipulation of neurosteroid synthesis could provide a strategy to improve cognitive function in individuals with hyperammonemia.

Female receptivity phenotype of icebox mutants caused by a mutation in the L1-type cell adhesion molecule neuroglian.

Relatively little is known about the genes and brain structures that enable virgin female Drosophila to make the decision to mate or not. Classical genetic approaches have identified several mutant females that have a reluctance-to-mate phenotype, but most of these have additional behavioral defects. However, the icebox (ibx) mutation was previously reported to lower the sexual receptivity of females, without apparently affecting any other aspect of female behavior. We have shown that the ibx mutation maps to the 7F region of the Drosophila X chromosome to form a complex complementation group with both lethal and viable alleles of neuroglian (nrg). The L1-type cell adhesion molecule encoded by nrg consists of six immunoglobulin-like domains, five fibronectin-like domains, one transmembrane domain and one alternatively spliced intracellular domain. The ibx strain has a missense mutation causing a glycine-to-arginine change at amino acid 92 in the first immunoglobulin domain of nrg. Defects in the central brain of ibx mutants are similar to those observed in another nrg mutant, central brain deranged(1) (ceb(1)). However, both ceb(1) homozygous and ceb(1)/ibx heterozygous females are receptive. The expression of a transgene containing the non-neural isoform of nrg rescues both the receptivity and the brain structure phenotypes of ibx females.

Sexual health innovations in undergraduate medical education.

Recent national and global initiatives have drawn attention to the importance of sexual health to individuals' well-being. These initiatives advocate enhancement of efforts to address this under-represented topic in health professions curricula. University of Massachusetts Medical School (UMMS) has undertaken a comprehensive effort to develop an integrated curriculum in sexual health. The UMMS project draws upon the expertise of a multidisciplinary faculty of clinicians, basic scientists, a medical ethicist, and educators. This article describes the project's genesis and development at UMMS, and reports on three innovations in sexual health education implemented as part of this endeavor.

Technical knockout, a Drosophila model of mitochondrial deafness.

Mutations in mtDNA-encoded components of the mitochondrial translational apparatus are associated with diverse pathological states in humans, notably sensorineural deafness. To develop animal models of such disorders, we have manipulated the nuclear gene for mitochondrial ribosomal protein S12 in Drosophila (technical knockout, tko). The prototypic mutant tko(25t) exhibits developmental delay, bang sensitivity, impaired male courtship, and defective response to sound. On the basis of a transgenic reversion test, these phenotypes are attributable to a single substitution (L85H) at a conserved residue of the tko protein. The mutant is hypersensitive to doxycyclin, an antibiotic that selectively inhibits mitochondrial protein synthesis, and mutant larvae have greatly diminished activities of mitochondrial redox enzymes and decreased levels of mitochondrial small-subunit rRNA. A second mutation in the tko gene, Q116K, which is predicted to impair the accuracy of mitochondrial translation, results in the completely different phenotype of recessive female sterility, based on three independent transgenic insertions. We infer that the tko(25t) mutant provides a model of mitochondrial hearing impairment resulting from a quantitative deficiency of mitochondrial translational capacity.

The utility of laboratory screening in medically III patients with psychiatric symptoms.

The presence of psychiatric illness in general hospital medical inpatients can complicate a patient's clinical course. Currently, there is no standard laboratory work-up recommended for this patient population. To begin to assess the utility of a routine panel of tests, the results of serum vitamin B12 (cobalamin) levels, folate levels, thyroid stimulating hormone levels, and syphilis serology of 349 patients were reviewed. These patients had been admitted to the hospital for nonpsychiatric conditions but either had preexisting psychiatric disturbances or developed a mood spectrum disorder or cognitive spectrum disorder during their hospitalization. The incidence of vitamin B12 and folate deficiencies in these patients was found to be higher than has been reported for the general population. Thus, routine screening for these vitamin deficiencies may be indicated because of their prevalence in this patient population.

Depressive symptoms, stress, and coping among women recovering from addiction.

This article focuses on the variability in well-being of 102 women in continuous recovery from addiction for 1 to 5 years. Univariate and bivariate analyses of cross-sectional data on recent depressive symptomatology, and psychosocial stress and coping strategies before and during recovery yielded the following findings: (a) Nearly a third of the sample reported scores above the 16-point cut-off on the Center for Epidemiologic Studies Depression Scale, indicating risk for depression; (b) over half had a history of diagnosed depression; (c) perceived stress in 16 life domains significantly decreased from prerecovery to recovery; (d) by recovery, participants significantly increase their use of positive strategies, but they continued use some negative ones; and (e) risk for high depressive symptomatology was greatest among those who were married or cohabiting, had a history of clinical of depression, high perceived stress in areas of money and emotional and physical health. Findings are discussed in terms of their implications for treatment and aftercare.

The effects of ectopic white and transformer expression on Drosophila courtship behavior.

The sex determining genes of Drosophila males and females function to establish the potential for sex-specific behaviors. Previous studies suggest that ectopic GAL4-directed misexpression of the female-specific isoform of the sex-determining gene transformer (tra) in specific sub-domains of an otherwise male brain can lead to bisexual courtship behavior, thus identifying brain domains that may mediate sex-specific behavior. However, expression of mini-white, the marker gene used in both P[GAL4] and P[UAS(G)] constructs, also induces males to court other males, questioning whether GAL4-mediated tra expression alone can induce bisexual behavior. Here we demonstrate the consequences of inducing mutations in the mini-white genes within P[GAL4] and P[UAS(G)] constructs to generate flies in which a white mutant phenotype is revealed. In these mini-white mutant strains, P[GAL4]-mediated transformer expression alone is both sufficient and necessary to generate bisexual behavior. In addition, using RT-PCR, we reveal the presence of female transcripts of doublesex and fruitless in the brains of otherwise male (XY) flies exhibiting P[GAL4]-directed tra-expression, demonstrating that P[GAL4]-directed tra is functional at the molecular level. We conclude that P[GAL4]-directed misexpression of tra is responsible for the bisexual behavior previously described and that this is mediated via sex-specific splicing of dsx and fru. Our results support the validity of such strategies for identifying regions of the fly brain that underlie sex-specific behaviors.

Screening for prostate cancer with the prostate-specific antigen test: are patients making informed decisions?

BACKGROUND: The benefits of early detection of prostate cancer are uncertain, and the American College of Physicians and the American Academy of Family Physicians recommend individual decision making in prostate cancer screening. This study reports the knowledge of male primary care patients about prostate cancer and prostate-specific antigen (PSA) testing and examines how that knowledge is related to PSA testing, preferences for testing in the future, and desire for involvement in physician-patient decision making. METHODS: The sample included 160 men aged 45 to 70 years with no history of prostate cancer who presented for care at a university-based family medicine clinic. Before scheduled office visits, patients completed a questionnaire developed for this study that included a 10-question measure of prostate cancer knowledge, the Deber-Kraestchmer Problem-Solving Decision-Making Scale, sociodemographic indicators, and questions on PSA testing. RESULTS: In general, patients who were college graduates were more knowledgeable about prostate cancer and early detection than those with a high school education or less. Aside from college graduates, most patients could not identify the principle advantages and disadvantages of PSA testing. Patients indicating previous or future plans for PSA testing demonstrated greater knowledge than other patients. Desire for involvement in decision making varied by patient education but was not related to past PSA testing. CONCLUSIONS: Patients lack knowledge about prostate cancer and early detection. This knowledge deficit may impede the early detection of prostate cancer and is a barrier to making an informed decision about undergoing PSA testing.

Abnormal courtship conditioning in males mutant for the RI regulatory subunit of Drosophila protein kinase A.

The previously described site-selected P-element mutagenesis of a Drosophila gene encoding the regulatory subunit of cAMP-dependent protein kinase generates mutants that have defective behavior in the olfactory learning test. Here we describe the effect of the same mutations in a courtship conditioning assay. Wild-type males can distinguish between virgin females (which they court vigorously), and fertilized females (which they court less vigorously). After exposure to fertilized females, wild-type males modify their behavior by decreasing courtship to subsequent target virgins, an effect that may last for many hours. Like wild-type males, PKA-RI mutant males are also able to distinguish between virgin and fertilized females. PKA-RI males also modify their behavior towards virgin females after prior exposure to a fertilized female, but such an effect is short-lived, suggesting a defect in memory rather than learning. We also show that under these conditions the behavior of PKA-RI males is similar to that of amnesiac, dunce and rutabaga males.

Women in recovery from drug misuse: an exploratory study of their social networks and social support.

This cross-sectional research examined the effects of ethnicity, age, and primary drug (alcohol or other drug) on recovering women's social network size and social support. Study participants included 21 African-American, 39 Anglo-American, and 3 Mexican-American women in continuous recovery for a minimum of 6 months. Study findings demonstrated statistically significant increases in social network size and in the amount of social support received from pretreatment to posttreatment recovery periods. Ethnicity, age, and primary drug had little effect on social network size and amount of social support received.

Community's role in the promotion of recovery from addiction and prevention of relapse among women: an exploratory study.

OBJECTIVE: This exploratory study examined the community's role in the promotion of recovery from addiction and the prevention of relapse among women, and the differences in women's addiction and recovery by ethnicity. Community was defined as six institutions: home, church, workplace, school, law enforcement and medical care system. METHODS: The study sample consisted of 39 Anglo and 24 ethnic minority women (21 African American; 3 Hispanic) between the ages of 21 and 70, living along the Gulf Coast of Texas, who had been in continuous recovery from addiction to alcohol or other drugs for at least six months. The study was cross-sectional, and data were collected through the use of structured interviews utilizing the Women in Recovery Questionnaire, an instrument developed by the investigative team. RESULTS: This study found that community institutions (church, school, home, workplace and law enforcement and medical systems) were seldom involved in promoting recovery or preventing relapse in women, with the exception of the home, which supported recovery. Anglo and ethnic minority women differed by primary drug usage, number of times in treatment, religion, perception of sexism, and likelihood of citations for traffic violations. CONCLUSION: Large, randomized studies are needed to investigate the community's role in women's recovery from alcohol and other drugs.

Sexual behaviour: secrets and flies.

Recent studies of Drosophila courtship mutants provide a molecular foundation for sexual orientation and behaviour.

Metazoan nuclear genes for mitoribosomal protein S12.

We have characterized nuclear genes for mitoribosomal protein S12 (mt-rps12) a major component of the ribosomal accuracy centre, in human, mouse and Drosophila melanogaster. In human and Drosophila, and probably also in mouse, there is a single intron within the coding region, located in the mitochondrial targeting pre-sequence. In humans, the mRNA structure is highly suggestive of translational regulation. In all three species, there is an amino-acid substitution with respect to eubacterial homologues in a residue implicated in aminoglycoside resistance. The only viable mutant allele of the Drosophila gene, associated with a bang-sensitive phenotype (paralysis upon mechanical vibration, arising from a mechanoreceptor cell defect) also has a novel substitution in a conserved region implicated in translational fidelity. Given the involvement of the mitoribosomal accuracy centre in human sensorineural deafness by virtue of rRNA mutations, our results indicate that this fly mutant may be a useful animal model of this disorder, and earmark the gene for mt-rps12 as a candidate in human hearing impairment.

Functional dissection of the Drosophila mushroom bodies by selective feminization of genetically defined subcompartments.

Relatively little is known about the neural circuitry underlying sex-specific behaviors. We have expressed the feminizing gene transformer in genetically defined subregions of the brain of male Drosophila, and in particular within different domains of the mushroom bodies. Mushroom bodies are phylogenetically conserved insect brain centers implicated in associative learning and various other aspects of behavior. Expression of transformer in lines that mark certain subsets of mushroom body intrinsic neurons, and in a line that marks a component of the antennal lobe, causes males to exhibit nondiscriminatory sexual behavior: they court mature males in addition to females. Expression of transformer in other mushroom body domains, and in control lines, has no such effect. Our data support the view that genetically defined subsets of mushroom body intrinsic neurons perform different functional roles.

The inactive mutation leads to abnormal experience-dependent courtship modification in male Drosophila melanogaster.

Flies carrying the inactive mutation of Drosophila melanogaster have only 15% wild-type titers of the putative neurotransmitter octopamine. With a view to discovering whether the inactive mutation impairs learning, I describe the effect of the inactive mutation on experience-dependent courtship modification (EDCM). Wild-type males rapidly condition to immature males and modify their behaviour toward subsequent target flies. The weaker EDCM phenotype of inactive males is similar to that of dunce males. Using time-sampling, habituation is most rapid for wild-type males and slowest for dunce males, with inactive males showing an intermediate phenotype. These results support the notion that octopamine plays a significant role in the manifestation of Drosophila learning behavior.