Left Main Myocardial Infarction in a Healthy Young Male—A Case Report

Acute left main coronary artery occlusion is a catastrophic and mostly fatal event. Patients may present with sudden death or cardiogenic shock. Intra-aortic balloon pump support and emergency revascularization is indicated to preserve the left ventricular function. We describe a case of left main thrombus in a health 24-year-old young male with no risk factors for coronary atherosclerosis.     

Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population

CONTEXT: Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC. OBJECTIVE: The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC. DESIGN: We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes. RESULTS: PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs. CONCLUSION: A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways.     

Pain After Spinal Cord Injury Is Associated With Abnormal Presynaptic Inhibition in the Posterior Nucleus of the Thalamus

Pain after spinal cord injury (SCI-Pain) is one of the most debilitating sequelae of spinal cord injury, characterized as relentless, excruciating pain that is largely refractory to treatments. Although it is generally agreed that SCI-Pain results from maladaptive plasticity in the pain processing pathway that includes the spinothalamic tract and somatosensory thalamus, the specific mechanisms underlying the development and maintenance of such pain are yet unclear. However, accumulating evidence suggests that SCI-Pain may be causally related to abnormal thalamic disinhibition, leading to hyperactivity in the posterior thalamic nucleus (PO), a higher-order nucleus involved in somatosensory and pain processing. We previously described several presynaptic mechanisms by which activity in PO is regulated, including the regulation of GABAergic as well as glutamatergic release by presynaptic metabotropic gamma-aminobutyric acid (GABA_B) receptors. Using acute slices from a mouse model of SCI-Pain, we tested whether such mechanisms are affected by SCI-Pain. We reveal 2 abnormal changes in presynaptic signaling in the SCI-Pain condition. The substantial tonic activation of presynaptic GABA_B receptors on GABAergic projections to PO—characteristic of normal animals—was absent in mice with SCI-Pain. Also absent in mice with SCI-Pain was the normal presynaptic regulation of glutamatergic projections to the PO by GABA_B receptors. The loss of these regulatory presynaptic mechanisms in SCI-Pain may be an element of maladaptive plasticity leading to PO hyperexcitability and behavioral pain, and may suggest targets for development of novel treatments.

The Collateral Damage of Mass Incarceration: Risk of Psychiatric Morbidity Among Nonincarcerated Residents of High-Incarceration Neighborhoods

Objectives. We examined whether residence in neighborhoods with high levels of incarceration is associated with psychiatric morbidity among nonincarcerated community members.Methods. We linked zip code–linked information on neighborhood prison admissions rates to individual-level data on mental health from the Detroit Neighborhood Health Study (2008–2012), a prospective probability sample of predominantly Black individuals.Results. Controlling for individual- and neighborhood-level risk factors, individuals living in neighborhoods with high prison admission rates were more likely to meet criteria for a current (odds ratio [OR] = 2.9; 95% confidence interval [CI] = 1.7, 5.5) and lifetime (OR = 2.5; 95% CI = 1.4, 4.6) major depressive disorder across the 3 waves of follow-up as well as current (OR = 2.1; 95% CI = 1.0, 4.2) and lifetime (OR = 2.3; 95% CI = 1.2, 4.5) generalized anxiety disorder than were individuals living in neighborhoods with low prison admission rates. These relationships between neighborhood-level incarceration and mental health were comparable for individuals with and without a personal history of incarceration.Conclusions. Incarceration may exert collateral damage on the mental health of individuals living in high-incarceration neighborhoods, suggesting that the public mental health impact of mass incarceration extends beyond those who are incarcerated.The United States leads the world in the percentage of its population that serves time in prison or jail.1,2 As of 2012, nearly 7 million men and women are on probation, parole, or under some other form of community supervision, which means that nearly 3% of the American adult population is currently involved in correctional supervision.3 The burden of incarceration in the United States is not equally distributed in the population. Current estimates from the Bureau of Justice Statistics indicate that 1 of every 3 Black men will serve time in prison in their lifetimes.4 In some communities, these figures are even starker. In Washington, DC, for example, more than 95% of Black men have been in prison in their lifetimes.1 Because of the scope of incarceration within particular subgroups, the current state of the US criminal justice system has been described in such terms as mass imprisonment5 and hyperincarceration.6Research on the health consequences of incarceration falls largely into 2 broad categories. The first, which has received the most empirical attention, has focused on individuals directly involved in the criminal justice system. Individual incarceration exposure is associated with adverse mental7–9 and physical10 health outcomes. A second line of inquiry has evaluated the broader health consequences of incarceration—what has been variously called the “long arm” of corrections,11 the collateral consequences of mass incarceration,5 and “spillover” effects related to incarceration.12 For example, female partners of recently released male prisoners experience depression and anxiety symptoms,13,14 and the children of incarcerated parents are at increased risk for behavioral and mental health problems.15,16 The deleterious health effects of incarceration are not merely confined to the family members of incarcerated individuals, however. Nonincarcerated individuals living in the communities from which inmates are drawn also appear to be at heightened risk for a variety of adverse outcomes, including increased crime rates17 and infectious diseases.18Although this research provides important initial insights into some of the negative consequences of incarceration at the community level, it remains largely unknown whether incarceration influences the mental health of community members who reside in neighborhoods with high-incarceration rates. How might incarceration affect community mental health? High levels of incarceration in neighborhoods can alter the social ecology of communities by eroding social capital and disrupting the kinds of social and family networks and relationships that are necessary for sustaining individuals’ mental health as well as the well-being of communities.1,19–22We examined whether high levels of incarceration in neighborhoods affect the mental health of individuals living in these neighborhoods. We treated incarceration as an ecological or contextual effect, rather than as an individual-level risk factor, which has characterized the majority of research on incarceration and mental health.7,23 That is, rather than examining the mental health consequences of incarceration among those who have themselves been incarcerated or among their family members, we examined the mental health of individuals living in communities that have been exposed to elevated levels of incarceration.     

Incidence of and Risk Factors for Hospital-Acquired Diarrhea in Three Tertiary Care Public Hospitals in Bangladesh

During April 2007–April 2010, surveillance physicians in adult and pediatric medicine wards of three tertiary public hospitals in Bangladesh identified patients who developed hospital-acquired diarrhea. We calculated incidence of hospital-acquired diarrhea. To identify risk factors, we compared these patients to randomly selected patients from the same wards who were admitted > 72 hours without having diarrhea. The incidence of hospital-acquired diarrhea was 4.8 cases per 1,000 patient-days. Children < 1 year of age were more likely to develop hospital-acquired diarrhea than older children. The risk of developing hospital-acquired diarrhea increased for each additional day of hospitalization beyond 72 hours, whereas exposure to antibiotics within 72 hours of admission decreased the risk. There were three deaths among case-patients; all were infants. Patients, particularly young children, are at risk for hospital-acquired diarrhea and associated deaths in Bangladeshi hospitals. Further research to identify the responsible organisms and transmission routes could inform prevention strategies.     

Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma

Background

FoxM1 has been shown to play a critical role in the pathogenesis of various epithelial malignancies. However, its role in lymphoid malignancies has not been fully clarified. We, therefore, investigated the role of FoxM1 expression in a large cohort of diffuse large B-cell lymphoma samples and panel of cell lines.

Design and Methods

FoxM1 expression was investigated in a large series of diffuse large B-cell lymphoma tissues in a tissue microarray format by immunohistochemistry. Apoptosis was measured by flow cytometry and protein expression was detected by immunoblotting using diffuse large B-cell lymphoma cell lines following treatment with either pharmacological inhibitor of FoxM1 or small interference RNA knockdown strategy. Invasion/migration and soft agar colony assays were also performed following treatment with FoxM1 inhibitor.

Results

FoxM1 expression was detected in 84.6% of diffuse large B-cell lymphoma tumors and found to be significantly associated with proliferative tumor marker Ki67 (P<0.0001), matrix metalloproteinases-2 (P=0.0008), matrix metalloproteinases-9 (P=0.0002), S-phase kinase associated protein-2 (P<0.0001) and inversely associated with p27 expression (P=0.0215). Expression of small interference RNA targeted against FoxM1 or treatment of diffuse large B-cell lymphoma cells with thiostrepton caused its downregulation accompanied by decreased expression of matrix metalloproteinases-2 and matrix metalloproteinases-9. Inhibition of FoxM1 in diffuse large B-cell lymphoma cells also decreased invasive and migratory capability, and induced caspase dependent apoptosis via activation of the mitochondrial apoptotic pathway. Finally, combined thiostrepton and bortezomib at sub-toxic doses led to efficient apoptosis in diffuse large B-cell lymphoma cells.

Conclusions

Altogether, these results suggest that FoxM1 is over-expressed in the majority of diffuse large B-cell lymphoma samples. These data also indicate that targeting FoxM1 signaling can serve as a potential therapeutic modality in the management of diffuse large B-cell lymphoma.     

SEX DIFFERENCES IN DNA METHYLATION MAY CONTRIBUTE TO RISK OF PTSD AND DEPRESSION: A REVIEW OF EXISTING EVIDENCE

There are well‐established sex differences in the prevalence of certain mental disorders. Work in animal models has provided us with an emerging understanding of the role that epigenetic factors play in establishing sex differences in the brain during development. Similarly, work in animal models, and a more limited but growing literature based on human studies, has demonstrated that DNA methylation (DNAm) changes occur in response to environmental stress, with some of these occurring in a sex‐specific manner. In this review, we explore whether DNAm plays a role in contributing to the observed sex differences in prevalence of mental disorders in which stress contributes significantly to their etiologies, specifically posttraumatic stress disorder (PTSD) and depression. We propose that investigating sex differences in DNAm among genes known to influence brain development may help to shed light on the sexually dimorphic risk for, or resilience to, developing PTSD and depression.