Gene Silencing Is a CpG Island Methylator Phenotype-Associated Factor That Predisposes Colon Cancer Cells to Irinotecan and Olaparib.

Chemotherapy is a mainstay of colorectal cancer treatment, and often involves a combination drug regime. CpG island methylator phenotype (CIMP)-positive tumors are potentially more responsive to the topoisomerase-inhibitor irinotecan. The mechanistic basis of the increased sensitivity of CIMP cancers to irinotecan is poorly understood.

Tetranucleotide and Low Microsatellite Instability Are Inversely Associated with the CpG Island Methylator Phenotype in Colorectal Cancer.

gene or protein deficiency or loss-of-function in colorectal cancer can cause a DNA mismatch repair defect known as "elevated microsatellite alterations at selected tetranucleotide repeats" (EMAST). A high percentage of MSI-H tumors exhibit EMAST, while MSI-L is also linked with EMAST. However, the distribution of CpG island methylator phenotype (CIMP) within the EMAST spectrum is not known.

Comparison of patient reported outcomes following clavicle operative fixation using supraclavicular nerve sparing and supraclavicular nerve sacrificing techniques- A cohort study.

Introduction: Supraclavicular nerve injury is one of the common complications after clavicle open reduction internal fixation (ORIF) affecting up to 55% of patients. There is debate about whether sparing supraclavicular nerves improves functional outcomes and patient satisfaction. The purpose of this study was to compare numbness, patient-reported outcomes and surgical time in patients undergoing clavicle ORIF using supraclavicular nerve sparing and supraclavicular nerve sacrificing techniques.

Molecular patterns in salivary duct carcinoma identify prognostic subgroups.

Salivary duct carcinoma (SDCa) is a rare cancer with high rate of metastases and poor survival despite aggressive multimodality treatment. This study analyzes the genetic changes in SDCa, their impact on cancer pathways, and evaluates whether molecular patterns can identify subgroups with distinct clinical characteristics and outcome. Clinicopathologic details and tissue samples from 66 patients (48 males, 18 females) treated between 1995 and 2018 were obtained from multiple institutions.

When the liver gets stiff, the tough get moving.

Liver stiffness measurement (LSM) by FibroScan-determined transient elastography is a noninvasive approach to estimate liver fibrosis severity. In non-alcoholic fatty liver disease (NAFLD), advanced liver fibrosis is excluded by normal liver stiffness, but a wide range of cutoffs have been used to predict advanced liver fibrosis or cirrhosis. This may be partly because steatosis (measured by controlled attenuation parameter [CAP]) contributes to liver stiffness and also because LSM fluctuates in NAFLD.

Microsatellite Instability in Mouse Models of Colorectal Cancer.

Microsatellite instability (MSI) is caused by DNA mismatch repair deficiency and is an important prognostic and predictive biomarker in colorectal cancer but relatively few studies have exploited mouse models in the study of its clinical utility. Furthermore, most previous studies have looked at MSI in the small intestine rather than the colon of mismatch repair deficient -knockout (KO) mice. Here we compared -KO, -KO, and wild type (WT) mice that were treated with the carcinogen azoxymethane (AOM) and the nonsteroidal anti-inflammatory drug sulindac or received no treatment.

Septic Cavernous Sinus Thrombosis: Case Report and Review of the Literature.

Septic cavernous sinus thrombosis is a rare but serious complication of infection of the cavernous sinuses. There are no randomised, controlled trials of management of this condition and existing reviews of the literature are somewhat dated. The authors report a case with a favourable outcome and then present the findings of a literature review of the management of this condition.

HIF1α deficiency reduces inflammation in a mouse model of proximal colon cancer.

Hypoxia-inducible factor 1α (HIF1α) is a transcription factor that regulates the adaptation of cells to hypoxic microenvironments, for example inside solid tumours. Stabilisation of HIF1α can also occur in normoxic conditions in inflamed tissue or as a result of inactivating mutations in negative regulators of HIF1α. Aberrant overexpression of HIF1α in many different cancers has led to intensive efforts to develop HIF1α-targeted therapies.

Type 2 diabetes across generations: from pathophysiology to prevention and management.

Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena.

Midbrain cleft as a cause of chronic internuclear ophthalmoplegia, progressive ataxia, and facial weakness.

A 44-year-old man with progressive ataxia, facial weakness, bilateral adduction deficits, and abducting nystagmus was initially misdiagnosed and treated for multiple sclerosis because a midbrain anatomic cleft had been overlooked on brain MRI. Six cases of "midbrain (or mesencephalic) cleft" or "keyhole aqueduct syndrome" have been previously reported. This developmental anatomic abnormality always manifests bilateral internuclear ophthalmoplegia (INO), often together with ataxia, which may be progressive and debilitating.

Serum leptin levels in older patients with hip fracture--impact on peri-operative myocardial injury.

To evaluate whether there is a relationship between admission serum leptin concentrations and peri-operative myocardial injury, 238 consecutive older patients (mean age 81.9+/-7.9 years; 172 women) with low-trauma hip fracture were assessed.

Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression.

Background And Aims: We examined extrinsic and intrinsic (endogenous) mitochondrial apoptosis pathways in experimental non-alcoholic steatohepatitis (NASH).

Methods: To assess extrinsic pathways, we measured hepatic expression of death-inducing cytokine receptors (tumor necrosis factor-alpha-receptor (TNF-R)1, TNF-R2, Fas, and TNFalpha-related apoptosis-inducing ligand-receptor (TRAIL-R) mRNA, TUNEL, caspase 3 activation, liver injury and liver pathology in mice fed a methionine and choline deficient (MCD) diet. For endogenous stress pathways, we determined serum insulin-like growth factor-1 (IGF-1), hepatic p53, Bcl-XL, tBid and p21 expression.

Job variation in Australian advanced training in neurology.

Background: Like training posts in other medical specialties, many of the 38 Australian core training posts in neurology have been criticized over a variety of issues relating to the quality of training provided. These issues include excessive hours of work (often related to understaffing), high inpatient workload and inadequate exposure to outpatients and/or specialist procedures. To examine these issues, we conducted an audit of Australian advanced training posts in neurology to obtain baseline data.