Mental health and associated risk factors of Puerto Rico Post-Hurricane María.

BACKGROUND: Mental health disorders have an increased prevalence in communities that experienced devastating natural disasters. Maria, a category 5 hurricane, struck Puerto Rico on September 20, 2017, weakening the island's power grid, destroying buildings and homes, and limiting access to water, food, and health care services. This study characterized sociodemographic and behavioral variables and their association with mental health outcomes in the aftermath of Hurricane Maria. METHODS: A sample of 998 Puerto Ricans affected by Hurricane Maria was surveyed between December 2017 and September 2018. Participants completed a 5-tool questionnaire: Post-Hurricane Distress Scale, Kessler K6, Patient Health Questionnaire 9, Generalized Anxiety Disorder (GAD) 7, and Post-Traumatic Stress Disorder checklist for DSM-V. The associations of sociodemographic variables and risk factors with mental health disorder risk outcomes were analyzed using logistic regression analysis. RESULTS: Most respondents reported experiencing hurricane-related stressors. Urban respondents reported a higher incidence of exposure to stressors when compared to rural respondents. Low income (OR = 3.66; 95% CI = 1.34-11.400; p < 0.05) and level of education (OR = 4.38; 95% CI = 1.20-15.800; p < 0.05) were associated with increased risk for severe mental illness (SMI), while being employed was correlated with lower risk for GAD (OR = 0.48; 95% CI = 0.275-0.811; p < 0.01) and lower risk for SIM (OR = 0.68; 95% CI = 0.483-0.952; p < 0.05). Abuse of prescribed narcotics was associated with an increased risk for depression (OR = 2.94; 95% CI = 1.101-7.721; p < 0.05), while illicit drug use was associated with increased risk for GAD (OR = 6.56; 95% CI = 1.414-39.54; p < 0.05). CONCLUSION: Findings underline the necessity for implementing a post-natural disaster response plan to address mental health with community-based social interventions.

Prevalence of Cardiovascular Disease and Comorbid Risk Factors in Patients in Puerto Rico with Schizophrenia.

OBJECTIVE: The mortality rate of schizophrenia patients is higher than that of the general population; cardiovascular disease (CVD) is their leading cause of death. This issue must be studied since people with schizophrenia are disproportionately burdened with CVD. Therefore, our goal was to identify the prevalence of CVD and other comorbidities, stratified by age and gender, in patients with schizophrenia living in Puerto Rico. METHODS: A retrospective, case-control, descriptive study was conducted. Subjects in this study were admitted to Dr. Federico Trilla's hospital from 2004 through 2014 for both psychiatric- and non psychiatric conditions. The sample populations were stratified by the confounding variables of tobacco use and alcohol abuse, and the resulting stratification was analyzed with the Cochran-Mantel-Haenszel method. RESULTS: A higher frequency of CVDs was noted in the patients with schizophrenia compared to those in the control group. Although hypertension was the most frequent pathology encountered in both groups, ischemic heart disease was approximately four times more frequent in the patients with schizophrenia. CVD represented 58.4% and 52.7% in the schizophrenia and non-schizophrenia groups, respectively, although a statistically significant difference was not observed. The prevalence of malignancies in patients without schizophrenia was higher than in patients with schizophrenia. Moreover, the prevalence of asthma was 10.9% in the control group compared to 5.3% in the schizophrenia group. CONCLUSION: These findings should motivate a systematic approach to prioritizing the aggressive management, early diagnosis, and prevention of comorbid risk factors in patients with schizophrenia.

Blockade of endothelin-1 receptor B regulates molecules of the major histocompatibility complex in sickle cell disease.

Major Histocompatibility Complex (MHC) molecules have been proposed to play a role in Sickle Cell Disease (SCD) pathophysiology. Endothelial cells express MHC molecules following exposure to cytokines. SCD is characterized, in part, by vascular endothelial cell activation, increased oxidative stress, sickle cell adhesion, and excess levels of endothelin-1 (ET-1) contributing to vaso-occlusive crises. ET-1 activates endothelial cells, induces oxidative stress and inflammation, and alters erythrocyte volume homeostasis. However, the role of ET-1 on MHC regulation in SCD is unclear. We first studied two sickle transgenic knockout mouse models of moderate to severe disease phenotype, ßS-Antilles and Berkeley (BERK) mice. We observed significant increases in H2-Aa mRNA levels in spleens, lungs, and kidneys from transgenic sickle mice when compared to transgenic knockout mice expressing human hemoglobin A (HbA). Mice treated for 14 days with ET-1 receptor antagonists significantly reduced H2-Aa mRNA levels. We characterized the effect of ET-1 on MHC class II expression in the human endothelial cell line EA.hy926. We observed dose-dependent increases in the expression of MHC class II (HLA-DRA) and MHC transcription factor (CIITA) that were significantly blocked by treatment with BQ788, a selective blocker of ET-1 type B receptors. Chromatin immunoprecipitation studies in EA.hy926 cells showed that ET-1 increased Histone H3 acetylation of the HLA-DRA promoter, an event blocked by BQ788 treatment. These results implicate ET-1 as a novel regulator of MHC class II molecules and suggest that ET-1 receptor blockade represents a promising therapeutic approach to regulate both immune and vascular responses in SCD.

Magnesium homeostasis in deoxygenated sickle erythrocytes is modulated by endothelin-1 via Na+ /Mg2+ exchange.

Painful crises in sickle cell disease (SCD) are associated with increased plasma cytokines levels, including endothelin-1 (ET-1). Reduced red cell magnesium content, mediated in part by increased Na+ /Mg2+ exchanger (NME) activity, contributes to erythrocyte K+ loss, dehydration and sickling in SCD. However, the relationship between ET-1 and the NME in SCD has remained unexamined. We observed increased NME activity in sickle red cells incubated in the presence of 500 nM ET-1. Deoxygenation of sickle red cells, in contrast, led to decreased red cell NME activity and cellular dehydration that was reversed by the NME inhibitor, imipramine. Increased NME activity in sickle red cells was significantly blocked by pre-incubation with 100 nM BQ788, a selective blocker of ET-1 type B receptors. These results suggest an important role for ET-1 and for cellular magnesium homeostasis in SCD. Consistent with these results, we observed increased NME activity in sickle red cells of three mouse models of sickle cell disease greater than that in red cells of C57BL/J6 mice. In vivo treatment of BERK sickle transgenic mice with ET-1 receptor antagonists reduced red cell NME activity. Our results suggest that ET-1 receptor blockade may be a promising therapeutic approach to control erythrocyte volume and magnesium homeostasis in SCD and may thus attenuate or retard the associated chronic inflammatory and vascular complications of SCD.

Renin-angiotensin-system increases phosphorylated tau and Reactive Oxygen Species in human cortical neuron cell line.

Alzheimer's Disease (AD) is the most common cause of dementia. AD patients had increased extracellular amyloid ß plaques and intracellular hyperphosphorylated tau (p-tau) in neurons. Recent studies have shown an association between the Renin-Angiotensin System (RAS) and AD. The involvement of RAS has been mediated through Angiotensin II (AngII), which is overexpressed in aging brains. However, the exact mechanism of how AngII contributes to AD is unknown. Thus, we hypothesize that AngII increases p-tau by activating its kinases, CDK5 and MAPK. In the human cortical neuron cell line, HCN2, treatment with AngII upregulated the gene expression of CDK5 (2.9 folds, p < 0.0001) and MAPTK (1.9 folds, p < 0.001). The AT1R antagonist, Losartan, blocked the changes in tau kinases. Also, AngII-induced the MAPK activation, increasing its phosphorylation by 400% (p < 0.0001), an increase that was also blocked by Losartan. An increase in p-tau by AngII was observed using fluorescent microscopy. We then quantified Reactive Oxygen Species (ROS) production, and it was significantly increased by AngII (p < 0.01), and treatment with Losartan blunted their production (p < 0.05). The data obtained demonstrated that AngII might contribute to the pathogenesis of AD.

Inhibitory effects of Syzygium jambos extract on biomarkers of endothelial cell activation.

BACKGROUND: Disordered endothelial cell activation plays an important role in the pathophysiology of atherosclerosis, cancer, sepsis, viral infections, and inflammatory responses. There is interest in developing novel therapeutics to regulate endothelial cell function in atherothrombotic, metabolic, vascular, and hematological diseases. Extracts from leaves of the Syzygium jambos (L.) Alston (S. jambos) trees have been proposed to treat cardiovascular diseases and diabetes through unclear mechanisms. We investigated the effects of the S. jambos extract on biomarkers of endothelial dysfunction and immune responses in the human endothelial cell line, EA.hy926. METHODS: Leaves of S. jambos were collected, concocted and lyophilized. To study the effects of S. jambos on endothelial cell activation, we used the human endothelial cell line. IL-6 levels were measured using qPCR and ELISA. PDI activity was measured using Insulin Turbidity and Di-E-GSSG assays. CM-H2DCFDA was used to study ROS levels. Migration assay was used to study S. jambos effect on ex vivo human polymorphonuclear and human mononuclear cells. RESULTS: Our results show that incubation of EA.hy926 cells with ET-1 led to a 6.5 ± 1.6 fold increase in IL-6 expression by qPCR, an event that was blocked by S. jambos. Also, we observed that ET-1 increased extracellular protein disulfide isomerase (PDI) activity that was likewise dose-dependently blocked by S. jambos (IC50 = 14 µg/mL). Consistent with these observations, ET-1 stimulated ex vivo human polymorphonuclear and mononuclear cell migration that also was dose-dependently blocked by S. jambos. In addition, ET-1 stimulation led to significant increases in ROS production that were sensitive to S. jambos. CONCLUSION: Our results suggest that the S. jambos extract represents a novel cardiovascular protective pharmacological approach to regulate endothelial cell activation, IL-6 expression, and immune-cell responses.

A Retrospective Cohort Study on the Increasing Trend of Suicide Ideations and Risks in an Opioid-Dependent Population of Puerto Rico 2015-2018.

The rate of suicide attempts among people with substance abuse disorders in the U.S. is six times higher than in the general population. The prevalence of suicidal ideations and attempts continues to increase in Puerto Rico, with a significant incidence in substance-abusing populations. This retrospective cohort study evaluate the suicide profile of 4,347 opioid dependent participants in ASSMCA's methadone center in San Juan, PR, from 2015 to 2018 using questions related to suicidal ideation and attempts included in the admission questionnaire. Participants reporting suicide ideation increase from 8.5% in 2015 to 17.0% in 2018. In 2015 only 7.0% claimed to have had a history of a suicide attempt, increasing to 12.4% in 2018. Our data support the need for screening for suicide risk among substance abusing populations to identify targeted interventions. The identification of high-risk populations for suicide can help during rehabilitation and finding the adequate resources needed.

Integrating Distance Strategies to Meet the 2020 Summer Research Internship Competencies and Objectives.

Knowledge of research skills such as information literacy, critical thinking, ability to ask questions, and evidence-based decisions are necessary for all medical students. They will use these skills for clinical decisions, translate research findings to clinical practice, and educate their patients. Research also plays an essential role in the selection process for many residency programs, and it has only become more critical over time. Therefore, research activities are a central component of medical schools' curriculum throughout the 4 years. One of the research opportunities offered to medical students is their participation in a research summer internship. Nevertheless, due to the COVID-19 pandemic, summer 2020 was impacted by the rapid shut down of academic and research activities to minimize infection. In this article, the authors describe the methodology changes to maintain the summer research internship offering amongst the coronavirus pandemic compared to the previous 6 years (2014-2019). Students answered a survey to assess their insight regarding general aspects of the summer research internship, structure, mentorship, faculty, and research skills development. Overall, students had a positive perception of all the survey areas, especially in mentor performance and research skills development. In conclusion, the authors found 2 critical attitudes toward facing unexpected challenges, such as the impact of COVID-19. These are essential to open new opportunities for the future of medical education research: (1) assuming a fast, encouraging, and constant response from the academic leaders, and (2) facilitating the stakeholders' interest, resilience, and commitment to help and support.

Role of Sug1, a 19S proteasome ATPase, in the transcription of MHC I and the atypical MHC II molecules, HLA-DM and HLA-DO.

The 19S proteasome regulatory particle plays a critical role in cellular proteolysis. However, emerging evidence suggests roles for 19S proteasome subunits in regulating yeast and mammalian transcription. It has been previously shown that Sug1 is important for the transcription of MHC II molecules. We report here that Sug1 also has a role in regulating transcription of class I MHC and the MHC II-like molecules, HLA-DM and HLA-DO. Reduction of Sug1 expression causes a decrease in the transcription of MHC I and MHC II-like molecules. In addition, we show that association of Sug1 with MHC promoters is followed by the recruitment of the CREB-binding protein (CBP) and the class II transactivator (CIITA). Reduction of Sug1 expression is accompanied by decreased recruitment of CBP and CIITA to the MHC promoters and decreased histone H3 acetylation in these promoters. These studies suggest that Sug1 plays a critical role in transcription of MHC class I, and the MHC class II-like molecules, HLA-DM and HLA-DO.