Composite pheochromocytoma (CP) is a rare tumor of the adrenal medulla, consisting of neuroendocrine and neural components. Despite similar neural crest origins, pheochromocytomas and neurogenic tumors are distinct entities. Symptoms may arise from hypersecretion of hormones by either component; however, not all patients present with classic symptoms. Moreover, various medical conditions and substances can confound screening tests and complicate the diagnosis. The patient, a 46-year-old male, was seen in the endocrine clinic regarding a 2-year history of paroxysmal headaches, palpitations and diaphoresis. His medical history was significant for hypothyroidism and substance misuse (nicotine, marijuana and cocaine). Family history was negative for pheochromocytoma, hyperparathyroidism or thyroid malignancies. He was found to be hypertensive in clinic, and two cafe-au-lait spots and bilateral axillary freckles were noted on dermatological examination. Pheochromocytoma was suspected and investigations revealed 24-h urinary catecholamines, metanephrines and vanillylmandelic acid levels that were substantially elevated. He was asked to repeat the urine collection while abstaining from cocaine, given the potential confounding with cocaine-induced elevations of catecholamines and their metabolites; however, the patient did not comply with this. His plasma free metanephrines and chromogranin A were later found to be elevated. Abdominal computed tomography revealed a 5.8 × 5 cm mass in the left adrenal gland, with an attenuation of 40 Hounsfield units. He underwent an uncomplicated laparoscopic left adrenalectomy, after which his blood pressure normalized. Histological features of the tumor revealed findings consistent with a typical pheochromocytoma with neuroblastomatous infiltrates comprising < 5% of the tumor. The mitosis karyorrhexis index was low and there was no ganglioneuromatous infiltrate evident. Medical oncology was consulted in view of the histopathological findings, and no adjuvant therapy was recommended. Unfortunately, he did not fully comply with repeat imaging or biochemical evaluation. Six months postoperatively, the patient remains completely asymptomatic and normotensive. Cocaine-induced catecholamine effects can clinically mimic pheochromocytoma, thereby complicating the diagnosis. In addition, the biologic behavior of CP with neuroblastoma is uncertain and warrants oncologic assessment and surveillance.
Anorexia nervosa (AN) is a complex and serious eating disorder, occurring in ~1% of individuals. Despite having the highest mortality rate of any psychiatric disorder, little is known about the aetiology of AN, and few effective treatments exist.Global efforts to collect large sample sizes of individuals with AN have been highly successful, and a recent study consequently identified the first genome-wide significant locus involved in AN. This result, coupled with other recent studies and epidemiological evidence, suggest that previous characterizations of AN as a purely psychiatric disorder are over-simplified. Rather, both neurological and metabolic pathways may also be involved.In order to elucidate more of the system-specific aetiology of AN, we applied transcriptomic imputation methods to 3,495 cases and 10,982 controls, collected by the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED). Transcriptomic Imputation (TI) methods approaches use machine-learning methods to impute tissue-specific gene expression from large genotype data using curated eQTL reference panels. These offer an exciting opportunity to compare gene associations across neurological and metabolic tissues. Here, we applied CommonMind Consortium (CMC) and GTEx-derived gene expression prediction models for 13 brain tissues and 12 tissues with potential metabolic involvement (adipose, adrenal gland, 2 colon, 3 esophagus, liver, pancreas, small intestine, spleen, stomach).We identified 35 significant gene-tissue associations within the large chromosome 12 region described in the recent PGC-ED GWAS. We applied forward stepwise conditional analyses and FINEMAP to associations within this locus to identify putatively causal signals. We identified four independently associated genes; RPS26, C12orf49, SUOX, and RDH16. We also identified two further genome-wide significant gene-tissue associations, both in brain tissues; REEP5, in the dorso-lateral pre-frontal cortex (DLPFC; p=8.52×10−07), and CUL3, in the caudate basal ganglia (p=1.8×10−06). These genes are significantly enriched for associations with anthropometric phenotypes in the UK BioBank, as well as multiple psychiatric, addiction, and appetite/satiety pathways. Our results support a model of AN risk influenced by both metabolic and psychiatric factors.
We-centric services are meant to stimulate and facilitate people to communicate and cooperate with others in dynamic or ad-hoc groups. Typically, a we-centric service provides hints and reasons to contact others, and, because these other people receive similar hints and reasons, stimulates and facilitates people to experience "we". The paper describes the development and evaluation of one we-centric service prototype for police officers. We found that key-issues related to developing we-centric services are (1) finding the proper context elements and information sources to take into account when searching for relevant others, (2) presenting the people found and the context of those people in an appropriate way, i.e. with clear explanations and information on their current availability and (3) supporting reciprocal relationships.
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