A Perplexing Case of a Germ Cell Tumor: A Case Report.

Germ cell tumors (GCTs) are associated with pure gonadal dysgenesis or Swyer syndrome. Swyer syndrome usually presents with primary amenorrhea, streak ovaries, and mixed GCT. However, our patient presented with secondary amenorrhea, normal female external genitalia, and a mixed GCT. Constitutional karyotype was suggestive of 46,XY. Management comprised chemotherapy, followed by surgery. Histopathology was suggestive of dysgerminoma complicating a gonadoblastoma. The purpose of reporting this case is its rarity and the importance of diagnosing an XY karyotype, as the incidence of GCTs is higher in these patients.

Frailty screening in older adults: is annual screening necessary in primary care?

BACKGROUND: The Case-finding for Complex Chronic Conditions in Adults 75+ (C5-75) involves annual frailty screening in primary care using dual-trait screening measures of handgrip strength and gait speed, with additional screening for co-existing conditions in those deemed frail. OBJECTIVE: To identify low-risk individuals who could be screened for frailty every 2 years, rather than annually. METHODS: This study examined a prospective cohort of patients who completed at least two annual C5-75 screenings between April 2014 and December 2018. Handgrip strength and gait speed on initial assessment were categorized based on proximity to frailty thresholds and were used to predict frailty risk on the second assessment. We used Fisher's exact test to assess differences in risk. Logistic regression models tested associations between independent variables of age, patient activity level, falls history, grip strength and gait speed on first assessment and dependent variable of frailty on subsequent assessment. RESULTS: Analyses included 571 patients with two annual assessments. Frailty risk on the second assessment was significantly higher for patients who had gait speed or grip strength within 20% of the frailty threshold (5.7%), compared with the other categories (0.7%, 0.9%, 0%; P = 0.002); 60% of patients fell within these lower risk categories. Controlling for grip strength and gait speed, no other measures had significant associations with frailty risk. CONCLUSIONS: Our results demonstrate that 60% patients are at low risk (<1%) of transitioning to frailty by the next annual assessment. Reducing screening frequency from annually to every 2 years may be appropriate for these patients.

Frail older adults are at greater risk for illness, functional decline, increased health service use and institutionalization. Adults 75 years of age and older should be screened regularly for frailty to provide early treatment for co-occurring conditions that may impact frailty but that may also be affected by frailty. Walking (gait) speed and handgrip strength are feasible measures of frailty to use on an annual basis in primary care. This study assesses the transition to frailty over a 1-year time period for the purpose of streamlining frailty screening in primary care for those patients who do not require annual screening. We found that when patients' grip strength and gait speed scores were 20% higher than the point at which people are identified as frail, they are at low risk for becoming frail by their next annual assessment. Frailty screening every 2 years may be appropriate for these patients. This streamlined screening process may make it more feasible for busy family practices to implement this type of frailty screening.

The C5-75 Program: Meeting the Need for Efficient, Pragmatic Frailty Screening and Management in Primary Care.

Case-Finding for Complex Chronic Conditions in Seniors 75+ (C5-75) is a systematic approach to identify frailty using gait speed and hand-grip strength and to screen for co-morbid conditions. We identified the C5-75 features offering the highest yield for identifying frailty and to streamline the screening program. Analyses included 1,948 C5-75 assessments completed from 2013 to 2018. Age 85 or older, less than regular physical activity, and more than two falls in the previous six months had the strongest associations with frailty. Exempting patients under 85 who reported regular physical activity and less than two falls excluded 39.1 per cent of the cohort while maintaining a sensitivity of 95.2 per cent and a negative predictive value of 99.4 per cent for frailty. These findings provide insight into optimizing screening for frailty, making it more feasible to implement and to identify co-existing conditions that may contribute to or be affected by frailty.

Congenital hyperinsulinism due to mutations in HNF1A.

Congenital hyperinsulinism is a rare but significant cause of severe and persistent hypoglycaemia in infancy. Although a biphasic phenotype of congenital hyperinsulinism in infancy followed by Maturity-Onset Diabetes of the Young (MODY) in later life has been established for HNF4A, the existence of a similar phenotype for a related MODY gene, HNF1A, is less clear. We describe two cases of congenital hyperinsulinism in association with dominantly inherited variants in HNF1A. They presented in the early neonatal period with unequivocal biochemical evidence of congenital hyperinsulinism and persistence into childhood with ongoing need for medical therapy. Both cases inherited HNF1A variants from a parent with a diabetes phenotype consistent with MODY, without obesity, insulin resistance or other metabolic syndrome features. In the first case, a paternally inherited novel c.-230_-101del variant was found that deletes the minimal promoter region presumably required for HNF1A expression. In the second case, a maternally inherited missense variant (c.713G>T, p.(Arg238Met)) was identified. This variant is predicted to cause haploinsufficiency via aberrant splicing and has previously been associated with MODY but not congenital hyperinsulinism. Our cases further strengthen the evidence for HNF1A as a CHI-causing gene requiring long-term follow-up.

Fanconi Bickel Syndrome with Hypercalciuria due to GLUT 2 Mutation.

BACKGROUND: Fanconi Bickel Syndrome is a rare, autosomal recessive, disorder of carbohydrate metabolism. Presence of hypercalciuria is rare. CASE CHARACTERISTICS: 4.5-years-old boy presented with growth failure, hepatomegaly, rickets, fasting hypoglycemia with postprandial hyperglycemia, fanconi syndrome and hypercalciuria. OUTCOME: A rare mutation in GLUT-2 gene suggestive of Fanconi Bickel Syndrome. MESSAGE: Fanconi Bickel Syndrome may present with hypercalciuria with proximal renal tubulopathy along with fasting hypoglycemia and postprandial hyperglycemia.

PSD-95 regulates CRFR1 localization, trafficking and ß-arrestin2 recruitment.

Corticotropin-releasing factor (CRF) is a neuropeptide commonly associated with the hypothalamic-pituitary adrenal axis stress response. Upon release, CRF activates two G protein-coupled receptors (GPCRs): CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2). Although both receptors contribute to mood regulation, CRFR1 antagonists have demonstrated anxiolytic and antidepressant-like properties that may be exploited in the generation of new pharmacological interventions for mental illnesses. Previous studies have demonstrated CRFR1 capable of heterologously sensitizing serotonin 2A receptor (5-HT2AR) signaling: another GPCR implicated in psychiatric disease. Interestingly, this phenomenon was dependent on Postsynaptic density 95 (PSD-95)/Disc Large/Zona Occludens (PDZ) interactions on the distal carboxyl termini of both receptors. In the current study, we demonstrate that endogenous PSD-95 can be co-immunoprecipitated with CRFR1 from cortical brain homogenate, and this interaction appears to be primarily via the PDZ-binding motif. Additionally, PSD-95 colocalizes with CRFR1 within the dendritic projections of cultured mouse neurons in a PDZ-binding motif-dependent manner. In HEK 293 cells, PSD-95 overexpression inhibited CRFR1 endocytosis, whereas PSD-95 shRNA knockdown enhanced CRFR1 endocytosis. Although PSD-95 does not appear to play a significant role in CRF-mediated cAMP or ERK1/2 signaling, PSD-95 was demonstrated to suppress ß-arrestin2 recruitment: providing a potential mechanism for PSD-95's inhibition of endocytosis. In revisiting previously documented heterologous sensitization, PSD-95 shRNA knockdown did not prevent CRFR1-mediated enhancement of 5-HT2AR signaling. In conclusion, we have identified and characterized a novel functional relationship between CRFR1 and PSD-95 that may have implications in the design of new treatment strategies for mental illness.

Neonatal diabetes with intractable epilepsy: DEND syndrome.

Permanent Neonatal Diabetes Mellitus (PNDM), is a rare monogenic disorder, caused by activating mutations of the KATP channel. The most severe clinical form of PNDM presents as Developmental delay, Epilepsy and Neonatal Diabetes (DEND) syndrome. Diagnosis is confirmed by genetic mutation testing. Oral sulfonylurea therapy improves neurological outcome.

An in-vitro microtensile test of Scotchbond Multi-Purpose adhesive applied at different priming times.

Adhesive bonding to dentin can fail if the dentin is too wet during application of the bonding resin. This study compared the in vitro 24-hour microtensile bond strength of teeth restored at four different priming times at the gingival cavity wall of Class II resin composite restorations. After IRB approval, six pairs of extracted third molars (yielding 12 teeth) received a proximal Class II prep/restoration in each tooth. Each pair was from the same patient. Four treatment groups were randomly assigned for each pair. The treatment groups were: TM-primer applied and dried according to manufacturer's directions; T30-primer allowed to dry for an additional 30 seconds; T60-primer dried for an additional 60 seconds; T120-primer dried for an additional 120 seconds. The teeth were restored with 3M ESPE Scotchbond Multi-Purpose Dental Adhesive and 3M ESPE Z100 Restorative. Manufacturers' directions were followed except for the additional primer dwelling times. The teeth were sectioned to obtain rectangular specimens with a surface area of approximately 0.5 mm2. Samples were tested on the Instron at 1.0 mm/minute until failure. The results in megapaschals were TM (n=15) 25.5+/-12.2; T30 (n=14) 22.7+/-13.6; T60 (n=15) 28.1+/-14.7; T120 (n=20) 27.7+/-15.2. Samples that debonded during the preparation phase and could not be tested from each group were TM=5, T30=6, T60=5, T120=1. A one-way ANOVA found no statistically significant difference between groups. Ninety percent of the samples broke through the adhesive layer as observed under the scanning electron microscope at 2000x. A chi square analysis found no difference in the number of debonds between groups. Increasing the primer drying time did not increase the microtensile bond strength of adhesive bonded to the dentin gingival wall.