Oncologic Safety of Sentinel Lymph Node Biopsy Alone After Neoadjuvant Chemotherapy for Breast Cancer.

Background: The oncologic safety of sentinel lymph node biopsy (SLNB) alone for clinically node-positive (cN1-2) patients who convert to pathologic node-negativity (ypN0) after neoadjuvant chemotherapy (NAC) is not well established.

Methods: This study retrospectively identified 244 consecutive patients with a diagnosis of cT1-3cN0-2 breast cancer who underwent NAC followed by SLNB at the authors' institution between 2013 and 2018. The patients were categorized as clinically node-negative (cN0) or cN1-2 before the onset of NAC, and the Kaplan-Meier method was used to compare locoregional and distant recurrence rates after SLNB alone for ypN0 patients.

Spontaneous Uterine Rupture in a Multigravid Pregnant Woman with Unscarred Uterus on Chronic Steroid Use: A Case Report.

Background: Uterine rupture in pregnancy is associated with severe maternal and fetal complications. Although it is a rare event, uterine rupture has been associated with certain risk factors. Glucocorticoids are known to weaken skeletal muscles; however, there have been no studies on the effects of chronic steroid use on the uterine myometrium.

Prenatal S-Adenosine Methionine (SAMe) Induces Changes in Gene Expression in the Brain of Newborn Mice That Are Prevented by Co-Administration of Valproic Acid (VPA).

In previous studies, we produced changes in gene expression in the brain of mice by early postnatal administration of valproic acid (VPA), with distinct differences between genders. The addition of S-adenosine methionine (SAMe) normalized the expression of most genes in both genders, while SAMe alone induced no changes. We treated pregnant dams with a single injection of VPA on day 12.

Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior?

In previous studies we produced autism like behavioral changes in mice by Valproic acid (VPA) with significant differences between genders. S-adenosine methionine (SAM) prevented the autism like behavior in both genders. The expression of 770 genes of pathways involved in neurophysiology and neuropathology was studied in the prefrontal cortex of 60 days old male and female mice using the NanoString nCounter.

Relationship(s) between obesity and inflammatory bowel diseases: possible intertwined pathogenic mechanisms.

The inflammatory bowel diseases, Crohn's and ulcerative colitis have increased in incidence and prevalence from the mid-eighteen to the late nineteen centuries. From then to the current twenty-first century there has been a more rapid expansion of these disease to areas previously experiencing low rates. This latter expansion coincides with the current obesity pandemic which also began toward the end of the last century.

Entospletinib monotherapy in patients with relapsed or refractory chronic lymphocytic leukemia previously treated with B-cell receptor inhibitors: results of a phase 2 study.

Entospletinib (GS-9973), an oral, selective inhibitor of spleen tyrosine kinase (SYK), was evaluated as monotherapy in this multicenter, phase 2 study (NCT01799889) of 49 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), including those with Richter's transformation (RT), who had received prior therapy with a B-cell receptor (BCR) inhibitor. Patients were treated with entospletinib 400 mg BID as the starting dose. Sixteen patients achieved partial response and 21 had stable disease.

Identifying cirrhosis, decompensated cirrhosis and hepatocellular carcinoma in health administrative data: A validation study.

Background: To evaluate screening and treatment strategies, large-scale real-world data on liver disease-related outcomes are needed. We sought to validate health administrative data for identification of cirrhosis, decompensated cirrhosis and hepatocellular carcinoma among patients with known liver disease.

Methods: Primary patient data were abstracted from patients of the Toronto Center for Liver Disease with viral hepatitis (2006-2014), and all patients with liver disease from the Kingston Health Sciences Centre Hepatology Clinic (2013).

The Role of DNA Methylation in Drug Addiction: Implications for Diagnostic and Therapeutics.

Drug addiction is a devastating health problem that is a very heavy burden on the individual affected and the society in general. Recent research defines addiction as a neurobehavioral disorder. Underpinning biological mechanisms of drug addiction are abnormal neuronal and brain activity following acute and repeated drug exposure.

Personalized Cardio-Metabolic Responses to an Anti-Inflammatory Nutrition Intervention in Obese Adolescents: A Randomized Controlled Crossover Trial.

Scope: Chronic inflammation and hypoadiponectinemia are characteristics of obesity-induced insulin resistance (IR). The effect of an anti-inflammatory nutrition supplement (AINS) on IR and adiponectin biology in overweight adolescents was investigated. The secondary objective was to examine the extent to which individuals' biomarker profiles, derived from baseline phenotypes, predicted response or not to the AINS.

S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice.

Introduction: A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model.

Methods: ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight.

DNA methylation controls unmethylated transcription start sites in the genome in trans.

Aim: DNA methylation downregulates transcription. However, a large number of genes, which are unmethylated in the promoter region, are inactive. We tested the hypothesis that these genes are regulated by DNA methylation of upstream regulators.

A comparison of mesopic visual acuity and objective visual quality following cataract surgery with hydrophobic acrylic intraocular lenses.

Purpose: To evaluate mesopic visual acuity and visual quality as measured by objective scatter index (OSI) in pseudophakic eyes with long-term follow-up after implantation of hydrophobic acrylic lenses made from two different lens materials.

Setting: This study was carried out in a private clinic.

Design: This study was an observational cohort study.

A systematic review of complications associated with direct implants vs. tissue expanders following Wise pattern skin-sparing mastectomy.

Introduction: With proven oncological safety and improved aesthetic outcomes, the Type IV or "Wise pattern" skin-sparing mastectomy (SSM) is a procedure that is being performed with increasing frequency. Unfortunately, it is also associated with an increased risk of complications. The purpose of this investigation was to determine the complications associated with direct-to-implant and two-step tissue-expander breast reconstruction following Wise pattern SSM.

Consensus-based recommendations for the management of rapid cognitive decline due to Alzheimer's disease.

Introduction: Rapid cognitive decline (RCD) occurs in dementia due to Alzheimer's disease (AD).

Methods: Literature review, consensus meetings, and a retrospective chart review of patients with probable AD were conducted.

Results: Literature review showed that RCD definitions varied.

Point-of-Care Ultrasound Use to Differentiate Hematoma and Sarcoma of the Thigh in the Pediatric Emergency Department.

Hematomas and soft tissue sarcomas can be difficult to differentiate clinically, even with the addition of traditional imaging modalities. There are several case reports of sarcomas being misdiagnosed as hematomas, most commonly with a history of mild trauma. In this case report, we described a sarcoma initially misinterpreted as a hematoma on ultrasound.

The elusive role of 5'-hydroxymethylcytosine.

5'-hydroxymethylcytosine (5hmC) is a variant of the common covalent epigenetic modification of DNA 5'-methylcytosine (5mC). Although the presence of this modified base in mammalian DNA has been recognized for several decades, it has recently gained center stage as a suspected intermediate in enzymatic active demethylation of 5mC. The role of 5hmC remains elusive in spite of a large body of studies.

Tocotrienol Treatment in Familial Dysautonomia: Open-Label Pilot Study.

Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy, primarily presented in Ashkenazi Jews. The most common mutation in FD patients results from a single base pair substitution of an intronic splice site in the IKBKAP gene which disrupts normal mRNA splicing and leads to tissue-specific reduction of IKBKAP protein (IKAP). To date, treatment of FD patients remains preventative, symptomatic and supportive.

The dynamic epigenome and its implications for behavioral interventions: a role for epigenetics to inform disorder prevention and health promotion.

The emerging field of behavioral epigenetics is producing a growing body of evidence that early life experience and social exposure can alter the way by which genes are marked with DNA methylation. We hypothesize that changes in DNA methylation as well as other epigenetic markers could generate stable phenotypes. Early life adversity appears to result in altered DNA methylation of genes in the brain and peripheral tissues, and these changes are associated with adverse phenotypic changes.

A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness.

Unlabelled: Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from non-invasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses.

Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform.

Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities.

Nongenetic inheritance and transgenerational epigenetics.

The idea that inherited genotypes define phenotypes has been paramount in modern biology. The question remains, however, whether stable phenotypes could be also inherited from parents independently of the genetic sequence per se. Recent data suggest that parental experiences can be transmitted behaviorally, through in utero exposure of the developing fetus to the maternal environment, or through either the male or female germline.

DNA demethylation and invasive cancer: implications for therapeutics.

One of the hallmarks of cancer is aberrant DNA methylation, which is associated with abnormal gene expression. Both hypermethylation and silencing of tumour suppressor genes as well as hypomethylation and activation of prometastatic genes are characteristic of cancer cells. As DNA methylation is reversible, DNA methylation inhibitors were tested as anticancer drugs with the idea that such agents would demethylate and reactivate tumour suppressor genes.

Effects of specific DNMT gene depletion on cancer cell transformation and breast cancer cell invasion; toward selective DNMT inhibitors.

A hallmark of cancer is aberrant DNA methylation, consisting of global hypomethylation and regional hypermethylation of tumor suppressor genes. DNA methyltransferase inhibitors have been recognized as promising candidate anticancer drugs. Drug development has focused on DNA methylation inhibitors with the goal of activating tumor suppressor genes silenced by DNA methylation.