A hermaphrodite dog with bilateral ovotestes and pyometra

Hermaphroditism was identified in a 3-year-old American Cocker spaniel with an enlarged os clitoridis that was shown as reddish finger-like structure protruding from the vulva. The urethral orifice was located cranially to the base of the os clitoridis. The gonads were situated caudal to the kidneys at the cranial tips of the uterine horns, and were composed mainly of seminiferous tubules and interstitial cells and had ovarian follicles in the cortices. The uterus was enlarged and revealed pyometra. Gross and histopathological findings of the dog suggested hermaphroditism with bilateral ovotestes and pyometra

Correspondence between geometrical and differential definitions of the sine and cosine functions and connection with kinematics

In classical physics, the familiar sine and cosine functions appear in two forms: (1) geometrical, in the treatment of vectors such as forces and velocities, and (2) differential, as solutions of oscillation and wave equations. These two forms correspond to two different definitions of trigonometric functions, one geometrical using right triangles and unit circles, and the other employing differential equations. Although the two definitions must be equivalent, this equivalence is not demonstrated in textbooks. In this manuscript, the equivalence between the geometrical and the differential definition is presented assuming no a priori knowledge of the properties of sine and cosine functions. We start with the usual length projections on the unit circle and use elementary geometry and elementary calculus to arrive to harmonic differential equations. This more general and abstract treatment not only reveals the equivalence of the two definitions but also provides an instructive perspective on circular and harmonic motion as studied in kinematics. This exercise can help develop an appreciation of abstract thinking in physics.Comment: 6 pages including 1 figur

Learning executable models of physical social agent behavior

Issued as final reportNational Science Foundation (U.S.

Hypoactive Sexual Desire Disorder:International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel Review

The objective of the International Society for the Study of Women\u27s Sexual Health expert consensus panel was to develop a concise, clinically relevant, evidence-based review of the epidemiology, physiology, pathogenesis, diagnosis, and treatment of hypoactive sexual desire disorder (HSDD), a sexual dysfunction affecting approximately 10% of adult women. Etiologic factors include conditions or drugs that decrease brain dopamine, melanocortin, oxytocin, and norepinephrine levels and augment brain serotonin, endocannabinoid, prolactin, and opioid levels. Symptoms include lack or loss of motivation to participate in sexual activity due to absent or decreased spontaneous desire, sexual desire in response to erotic cues or stimulation, or ability to maintain desire or interest through sexual activity for at least 6 months, with accompanying distress. Treatment follows a biopsychosocial model and is guided by history and assessment of symptoms. Sex therapy has been the standard treatment, although there is a paucity of studies assessing efficacy, except for mindfulness-based cognitive behavior therapy. Bupropion and buspirone may be considered off-label treatments for HSDD, despite limited safety and efficacy data. Menopausal women with HSDD may benefit from off-label testosterone treatment, as evidenced by multiple clinical trials reporting some efficacy and short-term safety. Currently, flibanserin is the only Food and Drug Administration-approved medication to treat premenopausal women with generalized acquired HSDD. Based on existing data, we hypothesize that all these therapies alter central inhibitory and excitatory pathways. In conclusion, HSDD significantly affects quality of life in women and can effectively be managed by health care providers with appropriate assessments and individualized treatments

Seasonal patterns and controls on net ecosystem CO2 exchange in a boreal peatland complex

We measured seasonal patterns of net ecosystem exchange (NEE) of CO2 in a diverse peatland complex underlain by discontinuous permafrost in northern Manitoba, Canada, as part of the Boreal Ecosystems Atmosphere Study (BOREAS). Study sites spanned the full range of peatland trophic and moisture gradients found in boreal environments from bog (pH 3.9) to rich fen (pH 7.2). During midseason (July‐August, 1996), highest rates of NEE and respiration followed the trophic sequence of bog (5.4 to −3.9 μmol CO2 m−2 s−1) \u3c poor fen (6.3 to −6.5 μmol CO2 m−2 s−1) \u3c intermediate fen (10.5 to −7.8 μmol CO2 m−2 s−1) \u3c rich fen (14.9 to −8.7 μmol CO2m−2 s−1). The sequence changed during spring (May‐June) and fall (September‐October) when ericaceous shrub (e.g., Chamaedaphne calyculata) bogs and sedge (Carex spp.) communities in poor to intermediate fens had higher maximum CO2 fixation rates than deciduous shrub‐dominated (Salix spp. and Betula spp.) rich fens. Timing of snowmelt and differential rates of peat surface thaw in microtopographic hummocks and hollows controlled the onset of carbon uptake in spring. Maximum photosynthesis and respiration were closely correlated throughout the growing season with a ratio of approximately 1/3 ecosystem respiration to maximum carbon uptake at all sites across the trophic gradient. Soil temperatures above the water table and timing of surface thaw and freeze‐up in the spring and fall were more important to net CO2 exchange than deep soil warming. This close coupling of maximum CO2 uptake and respiration to easily measurable variables, such as trophic status, peat temperature, and water table, will improve models of wetland carbon exchange. Although trophic status, aboveground net primary productivity, and surface temperatures were more important than water level in predicting respiration on a daily basis, the mean position of the water table was a good predictor (r2 = 0.63) of mean respiration rates across the range of plant community and moisture gradients. Q10 values ranged from 3.0 to 4.1 from bog to rich fen, but when normalized by above ground vascular plant biomass, the Q10 for all sites was 3.3

Pseudopeptides with a centrally positioned alkene-based disulphide bridge mimetic stimulate kallikrein-related peptidase 3 activity

Peer reviewe

Disorders of Sex Development

The birth of a new baby is one of the most dramatic events in a family, and the first question is usually "is it a boy or a girl?" The newborn infant with ambiguous external genitalia often comes as a surprise for the doctors as well as the parents and is sometimes described as an endocrine emergency situation presenting a problem of sex assignment. The nomenclature such as 'intersex', 'hermaphrodite', and 'pseudohermaphrodite' is out of date as well as confusing, and many urologists are concerned that these confusing terms could be perceived to be pejorative by some affected families. In response to concerns regarding outdated and controversial terms, the Chicago Consensus held in 2005 recommended new terminology based on the umbrella term disorders of sex differentiation (DSDs). The term DSD has a comprehensive definition including any problem noted at birth in which the genitalia are atypical in relation to the chromosomes or gonads. The karyotype is used as a prefix defining the classification of DSD. DSDs are rare and complex. The optimal management of patients with DSD must be individualized and multidisciplinary, considering all aspects, including psychological care and full disclosure of alternatives relating to surgery type and timing. Although further studies are necessary to confirm guidelines and recommendations fitting for the individual patients with DSD, this article is an attempt to provide a balanced perspective for new taxonomy, clinical evaluation, and medical, surgical, and psychological management of DSD

Comprehensive molecular characterization of urachal adenocarcinoma reveals commonalities with colorectal cancer, including a hypermutable phenotype

Purpose Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported.Wehypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. Patients and Methods We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti-programmed death-ligand 1 antibody, atezolizumab. Results Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability (MSH2 and MSH6) and hypermutation (POLE).Apatient with anMSH6mutation was treated withimmunecheckpoint blockade, which resulted in stable disease. Conclusion Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level ofRNA expression, are the first report, to our knowledge, of MSH2andMSH6mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor

Neoadjuvant pazopanib and molecular analysis of tissue response in renal cell carcinoma

BACKGROUND. Surgery remains the frontline therapy for patients with localized clear cell renal cell carcinoma (ccRCC); however, 20%–40% recur. Angiogenesis inhibitors have improved survival in metastatic patients and may result in responses in the neoadjuvant setting. The impact of these agents on the tumor genetic heterogeneity or the immune milieu is largely unknown. This phase II study was designed to evaluate safety, response, and effect on tumor tissue of neoadjuvant pazopanib. METHODS. ccRCC patients with localized disease received pazopanib (800 mg daily; median 8 weeks), followed by nephrectomy. Five tumors were examined for mutations by whole exome sequencing from samples collected before therapy and at nephrectomy. These samples underwent RNA sequencing; 17 samples were available for posttreatment assessment. RESULTS. Twenty-one patients were enrolled. The overall response rate was 8 of 21 (38%). No patients with progressive disease. At 1-year, response-free survival and overall survival was 83% and 89%, respectively. The most frequent grade 3 toxicity was hypertension (33%, 7 of 21). Sequencing revealed strong concordance between pre- and posttreatment samples within individual tumors, suggesting tumors harbor stable core profiles. However, a reduction in private mutations followed treatment, suggesting a selective process favoring enrichment of driver mutations. CONCLUSION. Neoadjuvant pazopanib is safe and active in ccRCC. Future genomic analyses may enable the segregation of driver and passenger mutations. Furthermore, tumor infiltrating immune cells persist during therapy, suggesting that pazopanib can be combined with immune checkpoint inhibitors without dampening the immune response. FUNDING. Support was provided by Novartis and GlaxoSmithKline as part of an investigator-initiated study