Molecular mechanism of androgen receptor mutation in multigenerational mild androgen insensitivity syndrome.

Objective: Androgen insensitivity syndrome (AIS) due to androgen receptor (AR) mutations creates a spectrum of clinical presentations based on residual AR function with the mildest impairment creating mild AIS (MAIS) whose undefined molecular mechanism and subtle clinical features leave it less understood and underdiagnosed.

Design: In silico modeling and in vitro androgen bioassay of the mutated AR are used to identify its structural and physiological mechanism. Clinical features and responses to high-dose testosterone treatment of three cases of MAIS across a six-generation family pedigree are described.

Use of glucose sensors for post-discharge care triaging of insulin-treated patients with type 2 diabetes: a feasibility study.

The use of glucose sensors to triage post-discharge follow-up was investigated among hospital inpatients with type 2 diabetes. Feasibility, utility and patient satisfaction with this model of care were studied. Feasibility was 36.

Application and Diagnostic Performance of Two-Dimensional Shear Wave Elastography and Liver Fibrosis Scores in Adults with Class 3 Obesity.

There are no ideal non-invasive tests for assessing the severity of liver fibrosis in people with metabolic dysfunction-associated steatotic liver disease (MASLD) and class 3 obesity, where body habitus often makes imaging technically challenging. This study aimed to assess the applicability and diagnostic performance of two-dimensional shear wave elastography (2D-SWE), alongside several serum-based liver fibrosis scoring methods, in individuals with class 3 obesity. A cross-sectional study was conducted in patients aged ≥18 years and with a body mass index (BMI) ≥ 40 kg/m who were participants in a publicly funded multidisciplinary weight management program in South Western Sydney.

Atypical femoral fracture in a bisphosphonate-naïve patient on denosumab for osteoporosis.

Unlabelled: A post-menopausal Caucasian woman sustained an atypical femoral fracture (AFF) after 5-years continuous denosumab for osteoporosis without prior bisphosphonate exposure. This is only the fifth case reported of AFF in a bisphosphonate-naïve patient receiving denosumab for osteoporosis. Although rare, physicians should consider AFF in patients taking denosumab even without prior bisphosphonate exposure.

Navigating through perplex morphologic changes after exogenous hormone usage.

Clinical application of exogenous hormone as a method of contraception and/or treatment of various gynecologic disorders is exceedingly common. Unfortunately, the concurrent use of these agents also complicates the interpretation of pathology specimens. Various studies have shown that morphologic changes induced by hormonal therapies are present in both non-neoplastic and neoplastic tissues within the women's reproductive tract.

Tumoral Morphologic Features From Cervical Biopsies That Are Predictive of a Negligible Risk for Nodal Metastasis and Tumor Recurrence in Usual-type Cervical Adenocarcinomas: A Multi-institutional Study.

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients.

Musculoskeletal magnetic resonance imaging in the DE50-MD dog model of Duchenne muscular dystrophy.

The DE50-MD canine model of Duchenne muscular dystrophy (DMD) has a dystrophin gene splice site mutation causing deletion of exon 50, an out-of-frame transcript and absence of dystrophin expression in striated muscles. We hypothesized that the musculoskeletal phenotype of DE50-MD dogs could be detected using Magnetic Resonance Imaging (MRI), that it would progress with age and that it would reflect those in other canine models and DMD patients. 15 DE50-MD and 10 age-matched littermate wild type (WT) male dogs underwent MRI every 3 months from 3 to 18 months of age.

Sex Cord Tumor With Annular Tubules-Like Histologic Pattern in Adult Granulosa Cell Tumor: Case Report of a Hitherto Unreported Morphologic Variant.

Adult granulosa cell tumor (AGCT) and sex cord tumor with annular tubules (SCTAT) are distinct sex cord stromal tumors with different molecular signatures. We present a unique case of an incidental ovarian tumor with mixed AGCT and SCTAT morphologic patterns. Due to the unusual co-occurrence, molecular testing was separately performed on both components.

For diagnosis of liver masses, fine-needle aspiration versus needle core biopsy: which is better?

Introduction: Both fine needle aspiration (FNA) and needle core biopsy (NCB) are widely accepted methods for obtaining diagnostic material. There is variability in how different institutions use these techniques in assessing liver masses. The aim of this study is to compare the diagnostic accuracy and tissue quality between FNA and NCB, and create a cost-effective algorithm for evaluating liver masses.

Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy.

Activation of the inflammatory pathway is increasingly recognized as an important mechanism of injury following neonatal asphyxia and encephalopathy. This process may contribute to the poor prognosis seen in some cases, despite therapeutic hypothermia. Our group has previously identified raised interleukin (IL)-6 and IL-16, measured in umbilical cord blood at birth, to be predictive of grade of hypoxic-ischaemic encephalopathy (HIE).

Systemic administration of guanosine promotes functional and histological improvement following an ischemic stroke in rats.

Previously we have found that extracellular guanosine (Guo) has neuroprotective properties in in vitro and in vivo. Moreover, extracellular Guo significantly increased in the ipsilateral hemisphere within 2h following focal stroke in rats, and remained elevated for one week. Therefore, we hypothesized that Guo could be a potential candidate for a non-toxic neuroprotective agent.

Immunotherapy can reject intracranial tumor cells without damaging the brain despite sharing the target antigen.

Although vaccines targeting tissue differentiation Ags represent a promising strategy for cancer immunotherapy, the risk of triggering autoimmune damage to normal tissues remains to be determined. Immunizing against a melanoma-associated Ag, dopachrome tautomerase (DCT), which normal melanocytes and glial cells also express, allowed concurrent analysis of autoimmune consequences in multiple tissues. We show that vaccination with recombinant adenovirus expressing DCT elicited a strong CTL response in C57BL/6 mice, leading to protection against intracranial challenge with B16-F10 melanoma cells.

Neuroprotective effects of guanosine on stroke models in vitro and in vivo.

Deprivation of oxygen and glucose for 5h induces apoptosis in SH-SY5Y neuroblastoma cell cultures. After combined glucose and oxygen deprivation (CGOD) addition of guanosine (100 microM), a non-adenine-based purine nucleoside, significantly reduced the proportion of cells undergoing apoptosis. To determine whether guanosine was also neuroprotective in vivo, we undertook middle cerebral artery occlusion (MCAo) on male Wistar rats and administered guanosine (8mg/kg), intraperitoneally, or saline (vehicle control) daily for 7 days.