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While individuals have demonstrated gender diversity throughout history, the use of medication and/or surgery to bring a person’s physical sex characteristics into alignment with their gender identity is relatively recent, with origins in the first half of the 20th century. Adolescent gender-affirming care, however, did not emerge until the late 20th century and has been built upon pioneering work from the Netherlands, first published in 1998. Since that time, evolving protocols for gender-diverse adolescents have been incorporated into clinical practice guidelines and standards of care published by the Endocrine Society and World Professional Association for Transgender Health, respectively, and have been endorsed by major medical and mental health professional societies around the world. In addition, in recent decades, evidence has continued to emerge supporting the concept that gender identity is not simply a psychosocial construct but likely reflects a complex interplay of biological, environmental, and cultural factors. Notably, however, while there has been increased acceptance of gender diversity in some parts of the world, transgender adolescents and those who provide them with gender-affirming medical care, particularly in the USA, have been caught in the crosshairs of a culture war, with the risk of preventing access to care that published studies have indicated may be lifesaving. Despite such challenges and barriers to care, currently available evidence supports the benefits of an interdisciplinary model of gender-affirming medical care for transgender/gender-diverse adolescents. Further long-term safety and efficacy studies are needed to optimize such care.

Purpose This study aimed to characterize two developmental cohorts of transgender and nonbinary youth enrolled in the Trans Youth Care Network Study and describe their gender identity–related milestones and baseline mental health and psychosocial functioning. Methods Trans Youth Care participants were recruited from four pediatric academic medical centers in the U.S. before initiating medical treatment for gender dysphoria either with gonadotropin-releasing hormone agonists (GnRHa) or gender-affirming hormones (GAH). GnRHa cohort data were collected from youth and a parent; GAH cohort data were collected from youth only. Results A total of 95 youth were enrolled in the GnRHa cohort. Mean age was 11.22 years (standard deviation = 1.46), and the majority were white (52.6%) and designated male at birth (51.6%). Elevated depression symptoms were endorsed by 28.6% of GnRHa cohort youth, and 22.1% endorsed clinically significant anxiety. Approximately one fourth (23.6%) endorsed lifetime suicidal ideation, with 7.9% reporting a past suicide attempt. A total of 316 youth were enrolled in the GAH cohort. The mean age was 16.0 years (standard deviation = 1.88), and the majority were white (62%) and designated female at birth (64.9%). Elevated depression symptoms were endorsed by 51.3% of the GAH cohort, and 57.3% endorsed clinically significant anxiety. Two-thirds (66.6%) endorsed lifetime suicidal ideation, with 24.6% reporting a past suicide attempt. Life satisfaction was lower among both cohorts compared with population-based norms. Conclusions GnRHa cohort youth appear to be functioning better from a psychosocial standpoint than GAH cohort youth, pointing to possible benefits of accessing gender-affirming treatment earlier in life.

Background In the United States, injection is an increasingly common route of administration for opioids and other substances. Estimates of the number of persons who inject drugs (PWID) are needed for monitoring risk-specific infectious disease rates and health services coverage. Methods We reviewed design and instruments for 4 national household surveys, 2012–2016, for their ability to produce unbiased injection drug use (IDU) prevalence estimates. We explored potential analytic adjustments for reducing biases through use of external data on (1) arrest, (2) narcotic overdose mortality, and (3) biomarker-based sensitivity of self-reported illicit drug use. Results Estimated national past 12 months IDU prevalence ranged from 0.24% to 0.59% across surveys. All surveys excluded unstably housed and incarcerated persons, and estimates were based on Conclusions PWID population size estimates in the United States are based on small numbers and are likely biased by undercoverage of key populations and self-report. Novel methods as discussed in this article may improve our understanding of PWID population size and their health needs.

Background Imported cases of infectious disease provide invaluable information about epidemiological conditions abroad, and should guide treatment decisions at home and abroad. Here, we examined cases of malaria imported from Africa to China for mutations eroding the efficacy of sulfadoxine-pyrimethamine (SP), sometimes used as an intermittent preventive treatment during for pregnant women and infants. Methods A total of 208 blood samples were collected from P. falciparum-infected workers who had returned from Western and Central Africa to Guangxi Province Frequency distribution. Samples were analyzed for the mutations in dhfr and dhps genes by PCR -sequencing. The prevalence of dhfr and dhps polymorphisms was analyzed. Among the isolates, polymorphisms were detected in mutants N51I, C59R, S108N and I164L of Pfdhfr and I431V, S436 A/F, A437G, K540 E/N, A581G and A613T of pfdhps. Results Mutations promoting drug resistance were widespread in this cohort. For pfdhfr and pfdhps, wild types were equally rare among patients returned from Western Africa and Central Africa. A triple-mutant dhfr haplotype was most prevalent (>70%). We report for the first time mutation I164L-dhfr and I431V-dhps in Ghana, and for the first time we found A581G to exceed a clinically-relevant threshold that may counter-indicate current clinical practices. For Pfdhps, the double-mutant IAGKAA was high prevalent haplotype in Ghana, Western Africa. The single-mutant ISGKAA was a majority haplotype in Cameroon. Alarmingly, a “super resistance” quintuple mutant was detected, for the first time, in parasites of West African origin (defined by IAGKAA/IRNI in combination with pfdhps 581G and dhfr I164L). This may limit the efficacy of this drug combination for even intermittent clinical applications. Conclusions These data are cause for great concern and call for continued surveillance of the efficacy of SP in source and recipient populations, and should be considered when developing treatment policy for imported malaria cases in China and elsewhere., Graphical abstract Image 1

Sudden cardiac death is a substantial cause of mortality in patients with cardiomyopathy, but evidence supporting implantable cardioverter-defibrillator (ICD) implantation is less robust in nonischemic cardiomyopathy (NICM) than in ischemic cardiomyopathy. Improved risk stratification is needed. We assessed whether absolute quantification of stress myocardial blood flow (sMBF) measured by positron emission tomography (PET) predicts ventricular arrhythmias (VA) and/or death in patients with NICM.In this pilot study, we prospectively followed patients with NICM (left ventricular ejection fraction ≤ 35%) and an ICD who underwent cardiac PET stress imaging with sMBF quantification. NICM was defined as the absence of angiographic obstructive coronary stenosis, significant relative perfusion defects on imaging, coronary revascularization, or acute coronary syndrome. Endpoints were appropriate device therapy for VA and all-cause mortality. Subgroup analysis was performed in patients who had no prior history of VA (ie, the primary prevention population).We followed 37 patients (60 ± 14 years, 46% male) for 41 ± 23 months. The median sMBF was 1.56 mL/g/min (interquartile range: 1.00-1.82). Lower sMBF predicted VA, both in the whole population (hazard ratio [HR] for each 0.1 mL/g/min increase: 0.84, P = .015) and in the primary prevention subset (n = 27; HR for each 0.1 mL/g/min increase: 0.81, P = .049). Patients with sMBF below the median had significantly more VA than those above the median, both in the whole population (P = .004) and in the primary prevention subset (P = .046). Estimated 3-year VA rates in the whole population were 67% among low-flow patients vs 13% among high-flow patients, and 39% vs 8%, respectively, among primary-prevention patients. sMBF did not predict all-cause mortality.In patients with NICM, lower sMBF predicts VA. This relationship may be useful for risk stratification for ventricular arrhythmia and decision making regarding ICD implantation.

Hepatitis E virus (HEV) RNA was detected in 6.3% and HEV IgG in 40% of 5,033 serum samples from market-weight pigs at 25 slaughterhouses in 10 US states. The prevalent HEV genotype was zoonotic genotype 3, group 2. Blood of HEV-viremic pigs from slaughterhouses may contaminate pork supply chains.

Purpose To assess whether publication of Comparison of Age-related macular degeneration Treatment Trial (CATT) results and introduction of aflibercept to the marketplace affected intravitreal bevacizumab and ranibizumab utilization. Design Retrospective analysis of treatment patterns. Methods We calculated weekly bevacizumab and ranibizumab utilization during 3 timeframes: (1) before CATT publication, (2) between CATT publication (April 28, 2011) and assignment of a unique aflibercept billing code (January 1, 2013), and (3) afterward for 164,188 Medicare beneficiaries with neovascular macular degeneration receiving ≥1 anti–vascular endothelial growth factor injection(s) from January 1, 2008 to December 31, 2014. We identified ophthalmologists who predominantly (≥80%) administered bevacizumab or ranibizumab and evaluated changes in preferences over the 3 periods. We replicated analyses on 881,381 commercially insured beneficiaries. Results Among 317 ophthalmologists administering predominantly ranibizumab to Medicare beneficiaries pre-CATT, 221 (69.7%) reduced ranibizumab use post-CATT, whereas 96 (30.3%) continued using ranibizumab ≥80% of the time. Findings were reversed among 1041 ophthalmologists who predominantly administered bevacizumab pre-CATT—777 (74.6%) continued bevacizumab-predominant use while 264 (25.4%) reduced bevacizumab use post-CATT. Among the 145 ophthalmologists who predominantly administered ranibizumab before aflibercept's availability, 77 (53.1%) reduced ranibizumab utilization and 68 (46.9%) continued using ranibizumab ≥80% of the time after aflibercept became available. Corresponding numbers among the 909 ophthalmologists who predominantly administered bevacizumab pre-aflibercept were 381 (41.9%) reducing and 528 (58.1%) continuing bevacizumab-predominant use. Similar results were observed for commercially insured patients. Conclusions Many ophthalmologists who favored ranibizumab switched to bevacizumab after CATT publication, while most who favored bevacizumab before CATT publication continued favoring it afterward. Aflibercept's introduction had little impact on preferences for ranibizumab or bevacizumab.

INTRODUCTION: Transgender/gender-diverse (TGD) youth are treated with gonadotropin-releasing hormone agonists (GnRHa) to halt endogenous puberty and prevent the development of secondary sex characteristics discordant with their gender identity. This treatment may have significant impact on growth and height velocity (HV). METHODS: Participants were recruited prior to GnRHa initiation from four gender specialty clinics in the United States. Anthropometric, laboratory, and Tanner-stage data were abstracted from medical records. RESULTS: Fifty-five TGD youth (47% designated male at birth) with a mean ± standard deviation age of 11.5 ± 1.2 years were included in the analysis. HV in the first year of GnRHa use was median (interquartile range) 5.1 (3.7 – 5.6) cm/year. Later Tanner stage at GnRHa initiation was associated with lower HV: 5.3 (4.4 – 5.6) cm/year for Tanner stage II, 4.4 (3.3 – 6.0) cm/year for Tanner stage III, and 1.6 (1.5 – 2.9) cm/year for Tanner stage IV (p = 0.001). When controlled for age, there was not a significant difference in mean HV between TGD youth and pre-pubertal youth; however, when stratified by Tanner stage individuals starting GnRHa at Tanner stage IV had a HV below that of prepubertal youth (1.6 (1.5 – 2.9) vs. 6.1 (4.3 – 6.5) cm/year, p =0.006). CONCLUSIONS: Overall, TGD youth treated with GnRHa have HV similar to that of prepubertal children, but TGD youth who start GnRHa later in puberty have a HV below the pre-pubertal range. Ongoing follow-up of this cohort will determine the impact of GnRHa treatment on adult height. IMPLICATIONS AND CONTRIBUTIONS: This study describes the HV in the first year of GnRHa treatment in pubertal participants in a large multi-site cohort of TGD youth in the United States. Overall, TGD youth treated with GnRHa have HV similar to that of prepubertal children, but TGD youth who start GnRHa later in puberty have a HV below the pre-pubertal range.

Background Species of Trichinella are globally important foodborne parasites infecting a number of domestic and wild vertebrates, including humans. Free-ranging carnivores can act as sentinel species for detection of Trichinella spp. Knowledge of the epidemiology of these parasites may help prevent Trichinella spp. infections in northern Canadian animals and people. Previous research on Trichinella spp. in wildlife from Yukon did not identify risk factors associated with infection, or the diversity and identity of species of Trichinella in regional circulation, based on geographically extensive sampling with large sample sizes. Methods In a cross-sectional study, we determined the prevalence, infection intensity, risk factors, and species or genotypes of Trichinella in wolverine (Gulo gulo) in two regions of Yukon, Canada, from 2013–2017. A double separatory funnel digestion method followed by mutiplex PCR and PCR-RFLP were used to recover and identify species of Trichinella, respectively. Results We found larvae of Trichinella in the tongues of 78% (95% CI 73–82) of 338 wolverine sampled. The odds of adult (≥ 2 years) and yearling (1 year) wolverine being Trichinella spp.-positive were four and two times higher, respectively, compared to juveniles (Trichinella spp. presence were three times higher in wolverine from southeast than northwest Yukon. The mean intensity of infection was 22.6 ± 39 (SD, range 0.1–295) larvae per gram. Trichinella T6 was the predominant genotype (76%), followed by T. nativa (8%); mixed infections with Trichinella T6 and T. nativa (12%) were observed. In addition, T. spiralis was detected in one wolverine. Out of 22 isolates initially identified as T. nativa in multiplex PCR, 14 were analyzed by PCR-RFLP to distinguish them from T. chanchalensis, a recently discovered cryptic species, which cannot be distinguished from the T. nativa on multiplex PCR. Ten isolates were identified either as T. chanchalensis alone (n = 7), or mixed infection with T. chanchalensis and T. nativa (n = 2) or T. chanchalensis and Trichinella T6 (n = 1)]. Conclusions Wolverine hosted high prevalence, high larval intensity, and multiple species of Trichinella, likely due to their scavenging habits, apex position in the food chain, and wide home range. Wolverine (especially adult males) should be considered as a sentinel species for surveys for Trichinella spp. across their distributional range. Graphical Abstract

ImportanceNew York State (NYS) is an epicenter of the United States’ COVID-19 epidemic. Reliable estimates of cumulative incidence of SARS-CoV-2 infection in the population are critical to tracking the extent of transmission and informing policies, but US data are lacking, in part because societal closure complicates study conduct.ObjectiveTo estimate the cumulative incidence of SARS-CoV-2 infection and percent of infections diagnosed in New York State, overall and by region, age, sex, and race and ethnicity.DesignStatewide cross-sectional seroprevalence study, conducted April 19-28, 2020.SettingGrocery stores (n=99) located in 26 counties throughout NYS, which were essential businesses that remained open during a period of societal closure and attract a heterogenous clientele.ParticipantsConvenience sample of patrons ≥18 years and residing in New York State, recruited consecutively upon entering stores and via an in-store flyer.ExposuresRegion (New York City, Westchester/Rockland, Long Island, Rest of New York State), age, sex, race and ethnicity.Main OutcomesPrimary outcome: cumulative incidence of SARS-CoV-2 infection, based on dry-blood spot (DBS) SARS-CoV-2 antibody reactivity; secondary outcome: percent of infections diagnosed.ResultsAmong 15,101 adults with suitable DBS specimens, 1,887 (12.5%) were reactive using a validated SARS-CoV-2 IgG microsphere immunoassay (sensitivity 87.9%, specificity 99.75%). Following post-stratification weighting on region, sex, age, and race and ethnicity and adjustment for assay characteristics, estimated cumulative incidence through March 29 was 14.0% (95% CI: 13.3-14.7%), corresponding to 2,139,300 (95% CI: 2,035,800-2,242,800) infection-experienced adults. Cumulative incidence was higher among Hispanic/Latino (29.2%, 95% CI: 27.2-31.2%), non-Hispanic black/African American (20.2% 95% CI, 18.1-22.3%), and non-Hispanic Asian (12.4%, 95% CI: 9.4-15.4%) adults than non-Hispanic white adults (8.1%, 95% CI: 7.4-8.7%, pConclusions and RelevanceOver 2 million adults were infected through late March 2020, with substantial variations by subpopulations. As this remains below herd immunity thresholds, monitoring, testing, and contact tracing remain essential public health strategies.

To assess the role of white-tailed deer (Odocoileus virginianus, WTD) in the epidemiology of toxoplasmosis, we conducted a national survey of WTD across the USA for Toxoplasma gondii infection. To do this, we combined serology with parasite isolation to evaluate the prevalence and genetic diversity of T. gondii in this game species. From October 2012 to March 2019, serum and tissues were collected from 914 WTD across the USA. Serum samples were screened for antibodies to T. gondii, and then the tissues of seropositive WTD were bioassayed in mice. Antibodies were detected in 329 (36%) of 914 WTD tested by the modified agglutination test (positive reaction at 1:25 or higher). Viable T. gondii was isolated from the heart of 36 WTD from 11 states. Three of the 36 isolates were pathogenic but not highly virulent to outbred Swiss Webster mice and all 36 isolates could be propagated further in cell culture and were genotyped. For genotyping, DNA extracted from cell culture-derived tachyzoites was characterized by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using the genetic markers SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico. Genotyping revealed seven ToxoDB PCR-RFLP genotypes, including 24 isolates for genotype #5 (haplogroup 12), four isolates for #2 (type III, haplogroup 3), three isolates for genotypes #1 (type II, haplogroup 2), two isolates for genotypes #3 (type II, haplogroup 2) and one isolate each for #39, #221 and #224. Genotype #5 was the most frequently isolated, accounting for 66.6% (24 of 36) of the isolates. Combining the 36 isolates from this study with previously reported 69 isolates from WTD, 15 genotypes have been identified. Among these, 50.4% (53/105) isolates belong to genotype #5. Our results indicate moderate genetic diversity of T. gondii in WTD. The results also indicate that undercooked venison should not be consumed by humans or fed to cats.

Purpose To enhance pediatric trainees' and students' knowledge of the psychosocial and medical issues facing transgender youth through a comprehensive curriculum. Methods During the 2015–2016 academic year, we administered a transgender youth curriculum to fourth-year medical students, pediatric interns, psychiatry interns, and nurse practitioner students on their 1-month adolescent and young adult medicine rotation. The curriculum included six interactive, online modules and an observational experience in a multidisciplinary pediatric gender clinic. The online modules had a primary care focus with topics of general transgender terminology, taking a gender history, taking a psychosocial history, performing a sensitive physical examination, and formulating an assessment, psychosocial plan, and medical plan. At the completion of the curriculum, learners completed an evaluation that assessed change in perceived awareness and knowledge of transgender-related issues and learner satisfaction with the curriculum. Results Twenty learners participated in the curriculum with 100% completing the curriculum evaluations, 100% reporting completing all six online modules, and 90% attending the gender clinic. Learners demonstrated a statistically significant improvement in all pre-post knowledge/awareness measures. On a Likert scale where 5 indicated very satisfied, learners' mean rating of the quality of the curriculum was 4.5 ± .7; quality of the modules was 4.4 ± .7; and satisfaction with the observational experience was 4.5 ± .8. Conclusions A comprehensive curriculum comprised interactive online modules and an observational experience in a pediatric gender clinic was effective at improving pediatric learners' perceived knowledge of the medical and psychosocial issues facing transgender youth. Learners also highly valued the curriculum.

Several published investigations demonstrated that a longer T-peak to T-end interval (Tpe) implies increased risk for ventricular tachyarrhythmia (VT/VF) and mortality. Tpe has been measured using diverse methods. We aimed to determine the optimal Tpe measurement method for screening purposes.We evaluated 305 patients with LVEF ≤ 35% and an implantable cardioverter-defibrillator implanted for primary prevention. Tpe was measured using seven different methods described in the literature, including six manual methods and the automated algorithm '12SL', and was corrected for heart rate. Endpoints were VT/VF and death. To account for differences in the magnitude of Tpe measurements, results are expressed in standard deviation (SD) increments. We evaluated the clinical utility of each measurement method based on predictive ability, fraction of immeasurable tracings, and intra- and interobserver correlation.Over 31 ± 23 months, 82 (27%) patients had VT/VF, and over 49 ± 21 months, 91 (30%) died. Several rate-corrected Tpe measurement methods predicted VT/VF (HR per SD 1.20-1.34; all P0.05), and nearly all methods (both corrected and uncorrected) predicted death (HR per SD 1.19-1.35; all P0.05). Optimal predictive ability, readability, and correlation were found in the automated 12SL method and the manual tangent method in lead V2.For the prediction of VT/VF, the utility of Tpe depends upon the measurement method, but for the prediction of mortality, most published Tpe measurement methods are similarly predictive. Heart rate correction improves predictive ability. The automated 12SL method performs as well as any manual measurement, and among manual methods, lead V2 is most useful.

Background Rituximab (RTX) is increasingly used in the treatment of neuromyelitis optica spectrum disorder (NMO-SD). Administration regimen is not consensual as there is no reliable biomarker of RTX efficacy. In most cases, after induction, RTX is administered systematically every 6 months. Objective To assess efficacy and safety of a maintenance regimen based on CD19 + CD27 + memory B-cell (mBc) detection. Methods We conducted a study in two French centers, including patients with NMO-SD who received an induction therapy with RTX. We compared the number of administered infusions, relapses and EDSS depending on two maintenance schemes (S1: administration of 1 g RTX infusion every 6 months or S2: a scheme based on regular mBc detection. 1 g RTX was administered if mBc was > 0.05%) Results 40 patients were included (mean age: 40.2 years, F/M sex ratio: 5/1). Aquaporin-4 antibodies were positive in 75% patients. Under S1 regimen, all patients received 2 infusions per year, whereas under S2, they received 1.62 infusion per year. The mean interval between infusions under S2 was 7.4 months, without decrease of clinical efficacy. Conclusion In our study, mBc-based administration of RTX allowed personalizing treatment administration and in several cases to lower the cumulative dose without loss of efficacy.

Purpose Adolescents aged 13–18 years bear a large burden of sexually transmitted infections (STIs) and changing adolescent sexual risk behavior is a key component of reducing this burden. We demonstrate a novel publicly available modeling tool (teen-SPARC) to help state and local health departments predict the impact of behavioral change on gonorrhea, chlamydia, and HIV burden among adolescents. Methods Teen-SPARC is built in Excel for familiarity and ease and parameterized using data from CDC's Youth Risk Behavior Surveillance System. We present teen-SPARC's methods, including derivation of national parameters and instructions to obtain local parameters. We model multiple scenarios of increasing condom use and estimate the impact on gonorrhea, chlamydia, and HIV incidence, comparing national and New York State (NYS) results. Results A 1% annual increase in condom use (consistent with Healthy People 2020 goals) could prevent nearly 10,000 cases of STIs nationwide. Increases in condom use of 17.1%, 2.2%, and 25.5% in NYS would be necessary to avert 1000 cases of gonorrhea, 1000 cases of chlamydia, and 10 cases of HIV infection, respectively. Additional results disaggregate outcomes by age, sex, partner sex, jurisdiction, and pathogen. Conclusion Teen-SPARC may be able to assist health departments aiming to tailor behavioral interventions for STI prevention among adolescents.

This cohort study analyzes the association of sex steroids with cholesterol in different sex-chromosome contexts.

The journal of neuroscience 39(33), 6555-6570 (2019). doi:10.1523/JNEUROSCI.2956-18.2019, Published by Society for Neuroscience, Washington, DC

Sarcocystis sarcocysts are common in many species of domestic and wild animals. Here, we report sarcocystosis in muscles from 91 free range elk (Cervus elaphus) from Pennsylvania, USA, tested by histopathology, transmission electron microscopy (TEM), and DNA sequencing. Sarcocysts were detected in hematoxylin and eosin (HE)-stained sections from 83 of 91 (91.2%) elk, including 83/91 (91.2%) tongues and 15/17 (88.2%) hearts. With respect to age, sarcocysts were found in 0/5 calves, 8/9 (88.8%) yearlings, and 75/77 (97.4%) adults. Sarcocysts were identified in 62/69 (89.4%) females and 21/22 (91.2%) males. Associated lesions were mild and consisted of inflammatory foci around degenerate sarcocysts. There were two morphologically distinct sarcocysts based on wall thickness, thin ( 0.5 μm) and thick-walled ( 4.0 μm). Thin-walled sarcocysts had a TEM "type 2" and villar protrusions (vps), identical to Sarcocystis wapiti previously described from elk in western USA. This species was present both in tongue and heart samples and was detected in all infected elk. Thick-walled sarcocysts consisted of three morphologic variants, referred to herein as subkinds A, B, C. Subkind A sarcocysts were rare; only four sarcocysts were found in three elk. Histologically, they had a 5-8-μm thick wall with tufted vp. By TEM, the sarcocyst wall was "type 12" and appeared similar to Sarcocystis sybillensis, previously described from elk in USA. Subkind B, Sarcocystis sp.1 sarcocysts were also rare, found in only 1 elk. These sarcocysts had 6.7-7.3-μm-thick wall with TEM "type 15b" vp. Subkind C Sarcocystis sp.2 sarcocysts were more common (22/91). Morphologically, the sarcocyst wall was 6.1-6.8 μm thick and contained "type 10b" vp. Comparisons of ribosomal DNA loci with published sequences indicated all sarcocysts were similar to what has previously been isolated from cervid hosts across the northern hemisphere. Phylogenetic analysis placed the thin-walled S. wapiti within a strongly supported clade with S. linearis and S. taeniata, while the thick-walled cysts were very closely related to S. truncata, S. elongata, S. silva, and S. tarandi. Further sequencing is needed to produce molecular diagnostics to distinguish among these species. North American elk are hosts to multiple Sarcocystis species with diverse morphology, deriving from two separate evolutionary lineages.

We have identified a discrete, focal telomere DNA expansion phenotype in the photoreceptor cell layer of normal, non-neoplastic human retinas. This phenotype is similar to that observed in a subset of human cancers, including a large fraction of tumors of the central nervous system, which maintain their telomeres via the non-telomerase-mediated alternative lengthening of telomeres (ALT) mechanism. We observed that these large, ultra-bright telomere DNA foci are restricted to the rod photoreceptors and are not observed in other cell types. Additionally, focus-positive rod cells are dispersed homogeneously throughout the posterior retinal photoreceptor cell layer and appear to be human-specific. We examined 108 normal human retinas obtained at autopsy from a wide range of ages. These large, ultra-bright telomere DNA foci were not observed in infants before 6 months of age; however, the prevalence of focus-positive rod cells dramatically increased throughout life. To investigate associations between this phenotype and retinal pathology, we assessed adult glaucoma (N = 29) and diabetic retinopathy (N = 38) cases. Focus-positive rod cells were prominent in these diseases. When compared to the normal group, after adjusting for age, logistic regression modeling revealed significantly increased odds of falling in the high category of focus-positive rod cells for glaucoma and diabetic retinopathy. In summary, we have identified a dramatic telomere alteration associated with aging and diseases affecting the retina.

Objective Despite the high prevalence of chronic multisite pain, there is little consensus on methods to characterize it. Commonly used assessments report only one dimension of pain, that is, intensity, thus ignoring the spatial aspect of pain. We developed a novel pain quantification index, the Integrated Pain Quantification Index (IPQI), on a scale of 0 to 1 that integrates multiple distinct pain measures into a single value, thus representing multidimensional pain information with a single value. Design Single-visit, noninterventional, epidemiological study. Setting Fourteen outpatient multidisciplinary pain management programs. Patients Patients with chronic pain of the trunk and/or limbs for at least six months with average overall pain intensity of at least 5 on the numeric rating scale. Methods Development of IPQI was performed in a large population (N = 810) of chronic pain patients from the Multiple Areas of Pain (MAP) study. Results Prevalence of two or more noncontiguous painful areas was at 88.3% (95% confidence interval [CI] = 0.86-0.90), with a mean of 6.3 areas (SD = 5.57 areas). Prevalence of more than 10% body area in pain was at 52.8% (95% CI = 0.49-0.56), with a mean at 16.1% (17.16%). On average, IPQI values were near the middle of the scale, with mean and median IPQI at 0.52 (SD = 0.13) and 0.55, respectively. The IPQI was generalizable and clinically relevant across all domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. Conclusions IPQI provided a single pain score for representing complex, multidimensional pain information on one scale and has implications for comparing pain populations across longitudinal clinical trials.

BackgroundGynandromorphophilia (GAMP) is sexual interest in gynandromorphs (GAMs; colloquially, shemales). GAMs possess a combination of male and female physical characteristics. Thus, GAMP presents a challenge to conventional understandings of sexual orientation as sexual attraction to the male v. female form. Speculation about GAMP men has included the ideas that they are homosexual, heterosexual, or especially, bisexual.MethodWe compared genital and subjective sexual arousal patterns of GAMP men with those of heterosexual and homosexual men. We also compared these groups on their self-ratings of sexual orientation and sexual interests.ResultsGAMP men had arousal patterns similar to those of heterosexual men and different from those of homosexual men. However, compared to heterosexual men, GAMP men were relatively more aroused by GAM erotic stimuli than by female erotic stimuli. GAMP men also scored higher than both heterosexual and homosexual men on a measure of autogynephilia.ConclusionsResults provide clear evidence that GAMP men are not homosexual. They also indicate that GAMP men are especially likely to eroticize the idea of being a woman.

Gender variant and transgender youth are seeking medical care at younger ages. Pediatricians and other primary care physicians are often the first professionals who encounter such youth and their families. The goals of this article are to provide information on the epidemiology and natural history of gender variant and transgender youth, current clinical practice guidelines regarding the use of puberty blockers and cross-sex hormones for transgender youth, and limitations and challenges to optimal care.

Patterns of genital arousal in response to gendered sexual stimuli (i.e., sexual stimuli presenting members of only one sex at a time) are more predictive of men's than of women's sexual orientations. Additional lines of evidence may shed light on the nature of these differences. We measured neural activation in homosexual and heterosexual men and women using fMRI while they viewed three kinds of gendered sexual stimuli: pictures of nude individuals, pictures of same-sex couples interacting, and videos of individuals self-stimulating. The primary neural region of interest was the ventral striatum (VS), an area of central importance for reward processing. For all three kinds of stimuli and for both VS activation and self-report, men's responses were more closely related to their sexual orientations compared with women's. Furthermore, men showed a much greater tendency to respond more positively to stimuli featuring one sex than to stimuli featuring the other sex, leading to higher correlations among men's responses as well as higher correlations between men's responses and their sexual orientations. Whole-brain analyses identified several other regions showing a similar pattern to the VS, and none showed an opposite pattern. Because fMRI is measured identically in men and women, our results provide the most direct evidence to date that men's sexual arousal patterns are more gender specific than women's.

Studies of subjective and genital sexual arousal in monosexual (i.e. heterosexual and homosexual) men have repeatedly found that erotic stimuli depicting men’s preferred sex produce strong responses, whereas erotic stimuli depicting the other sex produce much weaker responses. Inconsistent results have previously been obtained in bisexual men, who have sometimes demonstrated distinctly bisexual responses, but other times demonstrated patterns more similar to those observed in monosexual men. We used fMRI to investigate neural correlates of responses to erotic pictures and videos in heterosexual, bisexual, and homosexual men, ages 25–50. Sixty participants were included in video analyses, and 62 were included in picture analyses. We focused on the ventral striatum (VS), due to its association with incentive motivation. Patterns were consistent with sexual orientation, with heterosexual and homosexual men showing female-favoring and male-favoring responses, respectively. Bisexual men tended to show less differentiation between male and female stimuli. Consistent patterns were observed in the whole brain, including the VS, and also in additional regions such as occipitotemporal, anterior cingulate, and orbitofrontal cortices. This study extends previous findings of gender-specific neural responses in monosexual men, and provides initial evidence for distinct brain activity patterns in bisexual men.

OBJECTIVE: To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009.PARTICIPANTS: The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer.EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.CONSENSUS PROCESS: Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines.CONCLUSION: Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.

Here, we report a new species of Sarcocystis with red-tailed hawk (RTH, Buteo jamaicensis) as the natural definitive host and IFN-gamma gene knockout (KO) mice as an experimental intermediate host in which sarcocysts form in muscle. Two RTHs submitted to the Carolina Raptor Center, Huntersville, North Carolina, were euthanized because they could not be rehabilitated and released. Fully sporulated 12.5 x 9.9-mu m sized sporocysts were found in intestinal scrapings of both hawks. Sporocysts were orally fed to laboratory-reared outbred Swiss Webster mice (SW, Mus musculus) and also to KO mice. The sporocysts were infective for KO mice but not for SW mice. All SW mice remained asymptomatic, and neither schizonts nor sarcocysts were found in any SW mice euthanized on days 54, 77, 103 (n = 2) or 137 post-inoculation (PI). The KO mice developed neurological signs and were necropsied between 52 to 68 days PI. Schizonts/merozoites were found in all KO mice euthanized on days 52, 55 (n = 3), 59, 61 (n = 2), 66, and 68 PI and they were confined to the brain. The predominant lesion was meningoencephalitis characterized by perivascular cuffs, granulomas, and necrosis of the neural tissue. The schizonts/merozoites were located in neural tissue and were apparently extravascular. Brain homogenates from infected KO mice were infective to KO mice by subcutaneous inoculation and when seeded on to CV-1 cells. Microscopic sarcocysts were found in skeletal muscles of 5 of 8 KO mice euthanized between 55-61 days PI. Only a few sarcocysts were detected. Sarcocysts were microscopic, up to 3.5 mm long. When viewed with light microscopy, the sarcocyst wall appeared thin (< 1 mu m thick) and smooth. By transmission electron microscopy, the sarcocyst wall classified as "type 1j'' (new designation). Molecular characterization using 18S rRNA, 28S rRNA, ITS-1, and cox1 genes revealed a close relationship with Sarcocystis microti and Sarcocystis glareoli; both species infect birds as definitive hosts. The parasite in the present study was biologically and molecularly different from species so far described in RTHs and we therefore propose a new species name, Sarcocystis jamaicensis n. sp. National Science Foundation Historically Black Colleges and Universities Undergraduate Program [1505407]; Internal Research Competition (IRC) grant from the Virginia-Maryland College of Veterinary Medicine This work was supported in part by grant no. 1505407 from the National Science Foundation Historically Black Colleges and Universities Undergraduate Program to A.R.V.D. and an Internal Research Competition (IRC) grant from the Virginia-Maryland College of Veterinary Medicine to D.S.L. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture (USDA); USDA is an equal opportunity provider and employer. Public domain – authored by a U.S. government employee

Bovine besnoitiosis, caused by Besnoitia besnoiti, is an economically important disease of cattle in many countries but its transmission remains a mystery. Wild felids are suspected to be its definitive hosts. The domestic cat (Felis catus) is known experimental definitive host for Besnoitia species of rodents. Here, we report for Besnoitia darlingi the first identification of a natural definitive host, the bobcat (Lynx rufus). Oocysts resembling Toxoplasma gondii (unsporulated; 10.9 ± 0.8 × 12.1 ± 0.2 μm; n = 5) were detected microscopically in the feces of two of 25 free ranging wild bobcats from Mississippi, USA. After detailed investigation, we identified these oocysts as B. darlingi and not T. gondii. The IFN-γ gene knockout (KO) mice fed oocysts from bobcats died of acute besnoitiosis and tachyzoites were found in their tissues. Oocysts were also mildly pathogenic to outbred Swiss Webster mice (SW) (Mus musculus). The SW mice fed oocysts became ill but generally survived and developed characteristic thick-walled Besnoitia tissue cysts in their tongue and heart muscles and brains. Two laboratory-raised domestic cats (Felis catus) excreted B. darlingi oocysts after ingesting murine tissues infected with bobcat-derived oocysts. The parasite was successfully cultivated in African green monkey kidney fibroblast cells (CV-1 cell line) seeded with infected murine tissue homogenate. The multilocus PCR-DNA sequencing (18S rDNA, 28S rDNA, and ITS-1) from culture-derived tachyzoites confirmed the parasite as B. darlingi. Our results suggest that bobcats may be an important link in the sylvatic cycle of Besnoitia species and bioassay or molecular tests are needed to differentiate Toxoplasma gondii-like oocysts in feces of felids, both domestic and wild cats.

A 57-year-old woman presented with a 3-year history of a progressive firm plaque on the right cheek. Skin biopsies revealed a bland, storiform, spindle-cell proliferation involving the deep dermis and subcutaneous fat. By immunohistochemistry, the tumor cells were diffusely positive for CD34 and caldesmon with multifocal reactivity for epithelial membrane antigen and focal, weak staining for smooth muscle actin. Retinoblastoma protein expression was not detectable in tumor cells by immunohistochemistry. An interphase fluorescence in situ hybridization analysis for platelet-derived growth factor B (PDGFB) gene rearrangement was negative. A single-nucleotide polymorphism array study detected 1) a gain of chromosome segment 17q21.33-q25.3 which overlapped the entire COL1A1 gene with a breakpoint at 17q21.33, approximately 250 Kb centromeric to the 3' end of COL1A1 gene, 2) several segmental gains on chromosome 11, and 3) an RB1 gene locus with normal copy number and allele frequency. Although the current case resembles dermatofibrosarcoma protuberans, it is unique in that it demonstrates a copy number gain of chromosome 17q in the absence of fusion of COL1A1 and PDGFB genes and an unusual immunohistochemical staining profile. The morphologic and molecular findings suggest a novel molecular variant of dermatofibrosarcoma protuberans not detectable with standard fluorescence in situ hybridization for PDGFB rearrangement. This variant appears to respond to imatinib after 9 months of follow-up.

Studies of subjective and genital sexual arousal in monosexual (i.e. heterosexual and homosexual) men have repeatedly found that erotic stimuli depicting men’s preferred sex produce strong responses, whereas erotic stimuli depicting the other sex produce much weaker responses. Inconsistent results have previously been obtained in bisexual men, who have sometimes demonstrated distinctly bisexual responses, but other times demonstrated patterns more similar to those observed in monosexual men. We used fMRI to investigate neural correlates of responses to erotic pictures and videos in heterosexual, bisexual, and homosexual men, ages 25–50. Sixty participants were included in video analyses, and 62 were included in picture analyses. We focused on the ventral striatum (VS), due to its association with incentive motivation. Patterns were consistent with sexual orientation, with heterosexual and homosexual men showing female-favoring and male-favoring responses, respectively. Bisexual men tended to show less differentiation between male and female stimuli. Consistent patterns were observed in the whole brain, including the VS, and also in additional regions such as occipitotemporal, anterior cingulate, and orbitofrontal cortices. This study extends previous findings of gender-specific neural responses in monosexual men, and provides initial evidence for distinct brain activity patterns in bisexual men.

Compelling studies have demonstrated that "gender identity"--a person's inner sense of self as male, female, or occasionally a category other than male or female--is not simply a psychosocial construct, but likely reflects a complex interplay of biological, environmental, and cultural factors. An increasing number of preadolescents and adolescents, identifying as "transgender" (a transient or persistent identification with a gender different from their "natal gender"--ie, the gender that is assumed based on the physical sex characteristics present at birth), are seeking medical services to enable the development of physical characteristics consistent with their affirmed gender. Such services, including the use of agents to block endogenous puberty at Tanner stage 2 and subsequent use of cross-sex hormones, are based on longitudinal studies demonstrating that those individuals who were first identified as gender-dysphoric in early or middle childhood and who still meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. Furthermore, onset of puberty in transgender youth is often accompanied by increased "gender dysphoria"--clinically significant distress related to the incongruence between one's affirmed gender and one's "assigned (or natal) gender." Studies have shown that such distress may be ameliorated by a "gender-affirming" model of care. Although endocrinologists are familiar with concerns surrounding gender identity in patients with disorders of sex development, many providers are unfamiliar with the approach to the evaluation and management of transgender youth without a disorder of sex development. The goals of this article are to review studies that shed light on the biological underpinnings of gender identity, the epidemiology and natural history of transgenderism, current clinical practice guidelines for transgender youth, and limitations and challenges to optimal care. Prospective cohort studies focused on long-term safety and efficacy are needed to optimize medical and mental health care for transgender youth.

Gender nonconforming (GN) children and adolescents, collectively referred to as GN youth, may seek care to understand their internal gender identities, socially transition to their affirmed genders, and/or physically transition to their affirmed genders. Because general pediatricians are often the first point of contact with the health care system for GN youth, familiarity with the psychological and medical approaches to providing care for this population is crucial. The objective of this review is to provide an overview of existing clinical practice guidelines for GN youth. Such guidelines emphasize a multidisciplinary approach with collaboration of medical, mental health, and social services/advocacy providers. Appropriate training needs to be provided to promote comprehensive, culturally competent care to GN youth, a population that has traditionally been underserved and at risk for negative psychosocial outcomes.

Autogynephilia, or paraphilic sexual arousal in a man to the thought or image of himself as a woman, manifests in a variety of different behaviors and fantasies. We examined the psychometric structure of 22 items assessing five known types of autogynephilia by subjecting them to exploratory factor analysis in a sample of 149 autogynephilic men. Results of oblique factor analyses supported the ability to distinguish five group factors with suitable items. Results of hierarchical factor analyses suggest that the five group factors were strongly underlain by a general factor of autogynephilia. Because the general factor accounted for a much greater amount of the total variance of the 22 items than did the group factors, the types of autogynephilia that a man has seem less important than the degree to which he has autogynephilia. However, the five types of autogynephilia remain conceptually useful because meaningful distinctions were found among them, including differential rates of endorsement and differential ability to predict other relevant variables like gender dysphoria. Factor-derived scales and subscales demonstrated good internal consistency reliabilities, and validity, with large differences found between autogynephilic men and heterosexual male controls. Future research should attempt to replicate our findings, which were mostly exploratory.

Purpose To explore providers' clinical experiences, comfort, and confidence with and barriers to providing care to transgender youth. Methods An online survey was administered to members of the Society for Adolescent Health and Medicine and the Pediatric Endocrine Society with items querying about clinical exposure to transgender youth, familiarity with and adherence to existing clinical practice guidelines, perceived barriers to providing transgender-related care, and comfort and confidence with providing transgender-related care. The response rate was 21.9% (n = 475). Results Of the respondents, 66.5% had provided care to transgender youth, 62.4% felt comfortable with providing transgender medical therapy, and 47.1% felt confident in doing so. Principal barriers to provision of transgender-related care were lack of the following: training, exposure to transgender patients, available qualified mental health providers, and insurance reimbursement. Conclusions This study suggests that more training in transgender-related care, available qualified mental health providers, and insurance reimbursement for transgender-related care are needed.

The goal of this work was to identify novel, early antigens present in Trichinella spiralis. To this end, a cDNA library generated from 3-day old adult worms (Ad3) was immunologically screened using serum from a pig infected with 20,000 muscle larvae. The serum was obtained from multiple, time course bleeds coinciding with early worm development. Seventeen positive clones were isolated using serum obtained at 20 days post infection (dpi). All clones corresponded to one gene that exhibited high sequence identity with the T. spiralis ATP-dependent RNA helicase DDX19B which is involved in parasite growth and development. In addition, nine additional positive clones representing 5 unique genes were identified when the library was screened with 30 dpi serum; four of these five genes displayed high similarity with members of a putative T. spiralis serine protease family known to be involved in host invasion and host-parasite interactions. The remaining gene aligned with the T. spiralis hypothetical ORF 11.30. The identification of these antigens provides potential candidates for the early diagnosis of trichinellosis and for the development of a vaccine against this parasite.

The role of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of targeted therapies is currently undefined. In recent years, neutrophil-to-lymphocyte ratio (NLR) has emerged as a prognostic marker in several cancers, including mRCC. In this multicentre retrospective study, we aim to assess the impact of CN in mRCC and the value of NLR in risk stratification and patient selection.Retrospective data from patients with de novo mRCC from four large Australian hospitals were collected. Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards method.Our study identified 91 de novo mRCC patients. Patients who underwent CN (n = 46, 51%) were more likely to be younger (59.0 years vs 64.6 years, P = 0.019) and to have received systemic therapy (91% vs 76%, P = 0.043). Median overall survival (mOS) was significantly improved in patients who underwent CN (23.0 months vs 10.9 months, hazard ratios (HR) 0.33, 95% confidence interval (CI) 0.20-0.55, P 0.0001). Patients with NLR ≥ 5 also had inferior mOS (6.2 months vs 16.7 months, HR 1.94, 95% CI 1.14-3.29, P = 0.014). CN was associated with substantially improved survival in patients with both NLR 5 (mOS 31.1 months vs 7.0 months, HR 0.41, 95% CI, 0.18-0.64, P = 0.0009) and NLR ≥ 5 (mOS 10.9 months vs 2.3 months, HR 0.33, 95% CI, 0.11-0.69, P = 0.009). Significant survival benefits associated with CN were maintained in multivariate analyses (HR 0.39, 95% CI 0.22-0.70, P = 0.0014).CN is associated with significantly improved overall survival in de novo mRCC. The incremental survival benefit associated with CN was seen irrespective of NLR.

The review summarizes relevant research focused on prevalence and natural history of gender nonconforming/transgender youth, and outcomes of currently recommended clinical practice guidelines. This review identifies gaps in knowledge, and provides recommendations foci for future research.Increasing numbers of gender nonconforming youth are presenting for care. Clinically useful information for predicting individual psychosexual development pathways is lacking. Transgender youth are at high risk for poor medical and psychosocial outcomes. Longitudinal data examining the impact of early social transition and medical interventions are sparse. Existing tools to understand gender identity and quantify gender dysphoria need to be reconfigured to study a more diverse cohort of transgender individuals. Increasingly, biomedical data are beginning to change the trajectory of scientific investigation.Extensive research is needed to improve understanding of gender dysphoria, and transgender experience, particularly among youth. Recommendations include identification of predictors of persistence of gender dysphoria from childhood into adolescence, and a thorough investigation into the impact of interventions for transgender youth. Finally, examining the social environments of transgender youth is critical for the development of appropriate interventions necessary to improve the lives of transgender people.

Gynandromorphophilia (GAMP) is attraction to gynandromorphs (GAMs), who are natal males with both breasts and a penis, colloquially known as “she-males.” Men with GAMP (n = 314) and heterosexual men not attracted to GAMs (n = 211) completed an Internet survey regarding their sexual attraction patterns, relationship history, and potential correlates of GAMP. Men with GAMP reported much higher attraction to natal women than to men, although they also reported slightly higher levels of bisexual feelings compared with controls. Men with GAMP were equally attracted to natal women and GAMs, on average. Thus, GAMP is best considered an unusual form of heterosexuality rather than a separate sexual orientation. Indeed, men with GAMP scored much higher than controls on a measure of autogynephilia, or sexual arousal by the idea or fantasy of being a woman, which is also considered a variant of heterosexual attraction.

Three distinct promoters control the master regulator of major histocompatibility complex (MHC) class II expression, class II transactivator (CIITA), in a cell type-specific manner. Promoter I (pI) CIITA, expressed primarily by dendritic cells (DCs) and macrophages, expresses a unique isoform that contains a caspase-recruitment domain (CARD). The activity and function of this isoform are not understood, but are believed to enhance the function of CIITA in antigen-presenting cells. To determine whether isoform I of CIITA has specific functions, CIITA mutant mice were created in which isoform I was replaced with isoform III sequences. Mice in which pI and the CARD-encoding exon were deleted were also created. No defect in the formation of CD4 T cells, the ability to respond to a model antigen or bacterial or viral challenge was observed in mice lacking CIITA isoform I. Although CIITA and MHC-II expression was decreased in splenic DCs, pI knockout animals expressed CIITA from downstream promoters, suggesting that control of pI activity is mediated by unknown distal elements that could act at pIII, the B-cell promoter. Thus, no critical function is linked to the CARD domain of CIITA isoform I with respect to basic immune system development, function and challenge.

Self-identified bisexual men report high sexual arousal to both male and female stimuli, but no study to date has compellingly demonstrated that such men have a bisexual pattern of genital arousal. We examined sexual arousal patterns among bisexual men recruited using stringent criteria designed to exclude those who were less likely to have sexual interest in both sexes. Furthermore, we included a bisexual stimulus depicting a man engaged in sex simultaneously with another man and a woman. On average, the bisexual men showed a bisexual arousal pattern, with respect to both self-reported and genital arousal. Additionally, the bisexual men were more aroused by the bisexual stimulus compared with the homosexual and heterosexual men. Some bisexual-identified men have bisexual genital arousal patterns, although it remains unclear how common they are.

Key Points Question During 2013 to 2016, what proportion of adults were living with hepatitis C virus (HCV) infection in each US state? Findings In this survey study, US national HCV prevalence during 2013 to 2016 was 0.93% and varied by jurisdiction between 0.45% and 2.34%. Three of the 10 states with the highest prevalence and 5 of the 9 states with the highest number of HCV infections were in the Appalachian region. Meaning Regions with long-standing HCV epidemics, and those with newly emergent ones partly driven by the opioid crisis, face substantial HCV prevalence., This survey study estimates the prevalence of current hepatitis C virus infection among adults in each US state and the District of Columbia from 2013 to 2016 using data from the National Health and Nutrition Examination Survey., Importance Infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in the United States, and incidence has increased rapidly in recent years, likely owing to increased injection drug use. Current estimates of prevalence at the state level are needed to guide prevention and care efforts but are not available through existing disease surveillance systems. Objective To estimate the prevalence of current HCV infection among adults in each US state and the District of Columbia during the years 2013 to 2016. Design, Setting, and Participants This survey study used a statistical model to allocate nationally representative HCV prevalence from the National Health and Nutrition Examination Survey (NHANES) according to the spatial demographics and distributions of HCV mortality and narcotic overdose mortality in all National Vital Statistics System death records from 1999 to 2016. Additional literature review and analyses estimated state-level HCV infections among populations not included in the National Health and Nutrition Examination Survey sampling frame. Exposures State, accounting for birth cohort, biological sex, race/ethnicity, federal poverty level, and year. Main Outcomes and Measures State-level prevalence estimates of current HCV RNA. Results In this study, the estimated national prevalence of HCV from 2013 to 2016 was 0.84% (95% CI, 0.75%-0.96%) among adults in the noninstitutionalized US population represented in the NHANES sampling frame, corresponding to 2 035 100 (95% CI, 1 803 600-2 318 000) persons with current infection; accounting for populations not included in NHANES, there were 231 600 additional persons with HCV, adjusting prevalence to 0.93%. Nine states contained 51.9% of all persons living with HCV infection (California [318 900], Texas [202 500], Florida [151 000], New York [116 000], Pennsylvania [93 900], Ohio [89 600], Michigan [69 100], Tennessee [69 100], and North Carolina [66 400]); 5 of these states were in Appalachia. Jurisdiction-level median (range) HCV RNA prevalence was 0.88% (0.45%-2.34%). Of 13 states in the western United States, 10 were above this median. Three of 10 states with the highest HCV prevalence were in Appalachia. Conclusions and Relevance Using extensive national survey and vital statistics data from an 18-year period, this study found higher prevalence of HCV in the West and Appalachian states for 2013 to 2016 compared with other areas. These estimates can guide state prevention and treatment efforts.

The range of vertebrates that serve as intermediate hosts for parasites in the genus Sarcocystis remains incompletely defined. Here, we provide the first report of infections in treeshrews, describe the morphology of encysted parasites using light and transmission electron microscopy, and place this agent within a phylogenetic context by sequencing and comparing its 18S ribosomal DNA to that of related parasites. Muscle infections were diagnosed in four of 45 wild treeshrews captured in the vicinity of Kunming, Yunnan Province, Mainland China. Thread-like cysts (10.773+/-2.411mm in length, 0.106+/-0.009mm in width) had walls (0.538-0.746microm thick) that lacked perpendicular protrusions. The interior of the cyst was packed full with cyst merozoites, the shape of which was typical of Sarcocystis. The primary cyst wall consisted of a thin membrane supported by osmiophilic material, 31-60nm in thickness. The ground substance was about 105-526nm thickness. Cysts conformed to typical of 'type 1' sarcocysts. Freshly examined and frozen specimens did not differ in their cyst wall structure, however, the appearance of bradyzoites did differ: the conoid, rhoptries and micronemes were all visible in fresh bradyzoites; in stored bradyzoites, by contrast, the rhoptries appeared smaller, and although the conoid was visible, the micronemes were not. 18S rRNA gene was distinct from any previously reported sequence in GenBank. Their genetic and morphological uniformity suggest that these parasites, derived from treeshrews, represent a single biological species, Sarcocystis tupaia, sp. nov.

XIncreasing evidence supports a role for CD8+ T cells in multiple sclerosis. In an attempt to isolate the contribution of CD8+ T cells in a murine model of MS, we immunized mice with a dominant CD8 epitope MOG37-46, a truncated version of MOG35-55. The data presented here show mild disease induced with MOG37-46, characterized by lower clinical scores, a decrease in CNS infiltration and a decrease in microglial activation. CD8+ T cells reactive to MOG37-46 are pro-inflammatory and traffic to the CNS; however, the presence of CD4+ T cells elicits more severe disease and sustained inflammation of the CNS.

This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction (F(eNO)) and no bronchodilator responsiveness (BDR12%)) is uncommon in paediatric DA. We report on 102 children, mean+/-sd age 11.6+/-2.8 yrs, with DA in a cross-sectional study. 89 children underwent spirometry, BDR and F(eNO) before and after 2 weeks of systemic corticosteroids (corticosteroid response study). Bronchoscopy was performed after the corticosteroid trial. Of the 102 patients in the cross-sectional study, 88 (86%) were atopic, 60 (59%) were male and 52 (51%) had additional or alternative diagnoses. Out of the 81 patients in the corticosteroid response study, nine (11%) were complete responders. Of the 75 patients with symptom data available, 37 (49%) responded symptomatically, which was less likely if there were smokers in the home (OR 0.31, 95% CI 0.02-0.82). Of the 75 patients with available spirometry data, 35 (46%) had normal spirometry, with associations being BAL eosinophilia (OR 5.43, 95% CI 1.13-26.07) and high baseline forced expiratory volume in 1 s (FEV(1)) (OR 1.08, 95% CI 1.02-1.12). Of these 75 patients, BDR data were available in 64, of whom 36 (56%) had12% BDR. F(eNO) data was available in 70 patients, of whom 53 (75%) had normal F(eNO). Airflow limitation data was available in 75 patients, of whom 17 (26%) had persistent airflow limitation, which was associated with low baseline FEV(1) (OR 0.93, 95% CI 0.90-0.97). Only 11% of DA children exhibited complete corticosteroid responsiveness. The rarity of complete corticosteroid responsiveness suggests alternative therapies are needed for children with DA.

Rationale: The Third National Health and Nutrition Examination Survey (NHANES III) reference is currently recommended for interpreting spirometry results, but it is limited by the lack of subjects younger than 8 years and does not continuously model spirometry across all ages. Objectives: By collating pediatric data from other large-population surveys, we have investigated ways of developing reference ranges that more accurately describe the relationship between spirometric lung function and height and age within the pediatric age range, and allow a seamless transition to adulthood. Methods: Data were obtained from four surveys and included 3,598 subjects aged 4–80 years. The original analyses were sex specific and limited to non-Hispanic white subjects. An extension of the LMS (lambda, mu, sigma) method, widely used to construct growth reference charts, was applied. Measurements and Main Results: The extended models have four important advantages over the original NHANES III analysis as follows: (1) they extend the reference data down to 4 years of age, (2) they incorporate the relationship between height and age in a way that is biologically plausible, (3) they provide smoothly changing curves to describe the transition between childhood and adulthood, and (4) they highlight the fact that the range of normal values is highly dependent on age. Conclusions: The modeling technique provides an elegant solution to a complex and longstanding problem. Furthermore, it provides a biologically plausible and statistically robust means of developing continuous reference ranges from early childhood to old age. These dynamic models provide a platform from which future studies can be developed to continue to improve the accuracy of reference data for pulmonary function tests.

Trichinella spiralis can cause immunosuppression during the intestinal phase of early infection. However, changes in the peripheral blood during T. spiralis early infection remain unclear. Here, select immune cells in mice infected with 500 muscle larvae (ML) of T. spiralis during the intestinal phase of infection were studied. First, the recovery rates of the intestinal worms and female fecundity were determined, and the results showed that the intestinal worms were completely eliminated at 17 days post-infection (dpi) and that large numbers of new-born larvae (NBL) were generated from 5 to 9dpi. Using flow cytometry, it was shown that the number of CD4+ T cells and CD8+ T cells increased over the entire intestinal phase, except on 7dpi when CD4+ T cells decreased significantly compared to the control groups. Although both CD4+ and CD8+ T cells increased, CD8+ T cells increased more than CD4+ T cells, leading to a lower CD4+/CD8+ ratio compared to the control group. Subsequently, a depression of the proliferative response of T cells to concanavalin A (Con A) was noticed at 7 and 11dpi. Although the proliferative response of B cells to LPS was enhanced, the number of B cells from mouse peripheral blood stimulated by T. spiralis antigens showed no differences with the control group prior to 11dpi. The expression of CD14 on monocyte-macrophages decreased during the same period, which meant that the antigen-presenting response was reduced in the immune system of the infected mice. Moreover, the alternatively activated macrophages were induced in T. spiralis early infection. These data provide a better understanding of the development of the intestinal immune response in mice infected with T. spiralis.

Thyroid nodules are rare in children compared to adults. Although most thyroid nodules are benign, the risk of malignancy is greater in pediatric patients. Papillary and follicular cell tumors account for the majority of thyroid neoplasms; Hürthle cell tumors account for less than 5%. Despite being uncommon, malignant Hürthle cell tumors are potentially more aggressive than papillary and follicular cell tumors. Therefore, distinguishing between types of thyroid neoplasms in a timely fashion has implications for prognosis and therapy. We describe a 12-year-old peripubertal girl who presented with a large right-sided thyroid nodule that was subsequently diagnosed as a Hürthle cell adenoma. To our knowledge, she represents the youngest patient with a Hürthle cell neoplasm.

The utility of pulmonary function testing (PFT) to detect bleomycin-induced pneumonitis is controversial. We describe its impact on bleomycin dosing in a phase 2 trial of accelerated BEP (bleomycin, etoposide, cisplatin) for advanced germ cell tumours.There were 12 planned weekly bleomycin doses for intermediate-risk and poor-risk disease and nine for good-risk disease. Clinical assessments, chest X-ray, diffusing capacity of lung for carbon monoxide (DLCO) and forced vital capacity (FVC) were performed bi-weekly. Bleomycin was ceased for predefined clinical/radiological evidence of pulmonary toxicity and a25% reduction in DLCO or FVC. We determined doses planned, received and omitted and patients receiving all, ≥two-thirds, two-thirds of planned bleomycin doses.Of 43 eligible patients, 30% had lung metastases. Of 471, 375 (80%) of planned bleomycin doses were received, and 30% receivedtwo-thirds of their planned doses, all for reductions in DLCO. No patient developed other evidence of pulmonary toxicity. Patients with lung metastases were 1.5 times as likely to have a25% reduction in DLCO (35 vs 24%, P = 0.4) and 1.5 times as likely to receivetwo-thirds of their planned doses (35 vs 24%, P = 0.4). Patients who received less than full doses of bleomycin had worse outcomes if they were of good or poor prognosis.Asymptomatic reductions in DLCO caused 20% of bleomycin doses to be omitted and 30% of patients to receivetwo-thirds of their planned doses. A 25% reduction in DLCO appears too cautious a threshold. Given the potential negative impact of this practice on anti-cancer effect, routine use of PFT to monitor for bleomycin toxicity should be questioned.