Analyzing Factors Enabling Prostate Cancer Screening Behaviors Among African American Males in the South Region Using the Andersen's Behavioral Model of Healthcare Services Utilization.

Prostate cancer is the second leading cause of cancer death among men in the United States, and African American men especially represent a high risk population for prostate cancer. Although the overall prostate cancer incidence rates have been declining since 1992, the average annual prostate cancer incidence rates among African American men were still higher than any other racial groups, and the mortality rates were 2.1 times higher than that of Caucasian men. This study examined what factors including cultural mistrust were related with the prostate cancer screening behaviors among African American males in the South East region. Out of 496 prostate educational seminar attendees, 304 volunteers completed the survey about the behaviors of prostate cancer, cultural mistrust for health providers and general health beliefs and health behaviors. Using Anderson's Behavioral Model of Health Services Use, hierarchical multivariate logistic regression analysis was conducted to identify which predisposing, enabling, and need factors could predict prostate cancer screening behaviors and whether there was any interaction effects among these predictors. Findings revealed that annual household income and annual health check-up were significantly related with the prostate cancer screening behaviors while the effect of health insurance was diminished among older African American males. Overall, results highlight the importance of financial resources as a determinant of prostate cancer screening behaviors among African American males implying the need of substantial support to overcome the obstacles from financial adversity.

An Alarming Mimicry of Intra-Abdominal Infections: Acute Appendiceal Diverticulitis.

A 65-year-old woman presented with three days of colicky abdominal pain. Abdominal imaging illustrated small bowel enteritis, ascites in both paracolic gutters, and incidental hepatic steatosis. Although ascites fluid demonstrated high neutrophil count consistent with peritonitis and the patient received adequate antibiotics, she clinically deteriorated. Subsequent exploratory laparotomy revealed necrotic appendix and multiple intra-abdominal abscesses. Histopathology showed acute suppurative appendicitis with multiple other intact small diverticula, indicating likely perforation of inflamed appendiceal diverticula with subsequent abscess formation and abdominal peritonitis. This case highlights the importance of ascites fluid analysis and continued clinical correlation, especially in cases of rare entities with atypical presentations.

Gender-Specific Risk Factors Contributing to Mortality in Patients Hospitalized With Alcoholic Cirrhosis.

Introduction Identification of gender-specific prognostic factors in patients with alcoholic liver cirrhosis (ALC) is integral to understanding disease severity and mortality rates. We gathered data on various widely-used laboratory values and comorbid conditions among male and female patients with ALC after initial hospitalization. These individual risk factors were assessed for their relationship with mortality based on gender. Methods We performed a retrospective observational study of hospitalized patients with either a new or prior diagnosis of ALC from 2008 to 2016 with follow-up through June 2018. The electronic medical record (EMR) was queried for demographics, comorbidities, lab values, and mortality. The cumulative risks of mortality after the first hospitalization were estimated using Kaplan-Meier curves and compared among both genders. Demographic data, lab values, and comorbidities associated with cirrhosis were assessed using multivariate Cox proportional hazard analysis to determine risk factors associated with mortality. Results We identified 247 male patients (mean age 54.19 ± 13.14 years) and 78 female patients (mean age 51.10 ± 11.60 years) hospitalized at Carilion Clinic with a diagnosis of ALC. About 70% (male) and 46% (female) endorsed alcohol use at the time of admission, 10% (male) and 13% (female) endorsed illicit drug use, and 56% (male and female) endorsed tobacco use. The one-, three- and five-year cumulative mortality after the first hospitalization was 43.4%, 53.2%, and 61.6%, respectively for males and 24.1%, 59.0%, and 67.2%, respectively for females. Median survival for younger male patients with ALC (age < 40 years old) after the first hospitalization was significantly different compared to the older male patients (age > 40 years) (p=0.0009), but age was not a significant factor for survival of female patients. Multivariate analysis further shows that illicit drug use, creatinine level at the time of admission, and age > 40 years had the highest hazard ratios for risk of mortality in male patients. For female patients, history of hepatic encephalopathy (HE) and blood urea nitrogen (BUN) level at the time of discharge were both associated with increased risk of mortality, with a history of HE being associated with a higher hazard ratio for risk of mortality. Conclusion Age, illicit drug use, and creatinine level were risk factors associated with mortality for male patients with ALC but not female patients. Hepatic encephalopathy and BUN were risk factors associated with mortality for female patients. The mortality for male patients was about twice the mortality of female patients at one year, but three-year and five-year mortality was higher in female patients.

PABA/NO lead optimization: Improved targeting of cytotoxicity to glutathione S-transferase P1-overexpressing cancer cells.

PABA/NO [O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino) diazen-1-ium-1,2-diolate] is a nitric oxide (NO)-releasing arylating agent designed to be selectively activated by reaction with glutathione (GSH) on catalysis by glutathione S-transferase P1 (GSTP1), an enzyme frequently overexpressed in cancer cells. PABA/NO has proven active in several cancer models in vitro and in vivo, but its tendency to be metabolized via a variety of pathways, some that generate inactive metabolites and hydrolysis products, limits its potential as a drug. Here we show that a simple replacement of cyano for nitro at the 4 position to give compound 4b ('p-cyano-PABA/NO') has the dual effect of slowing the undesired side reactions while enhancing the proportion of NO release and arylating activity on catalysis by GSTP1. Compound 4b showed increased resistance to hydrolysis and uncatalyzed reaction with GSH, along with a more favorable product distribution in the presence of GSTP1. It also showed significant proapoptotic activity. The data suggest p-cyano-PABA/NO to be a more promising prodrug than PABA/NO, with better selectivity toward cancer cells.

Synthesis and biological evaluation of isoxazoline derivatives as potent M1 muscarinic acetylcholine receptor agonists.

A series of azacyclic compounds substituted with isoxazole and 5-substituted isoxazolines were synthesized as acyclic modifications of the oxime class M1 mACh receptor agonist. Among them, 3-(tetrahydropyrin-3-yl)-5-(2-pyrrolodin-1-yl)isoxazoline compound 4f displayed potent and selective M1 mACh receptor agonist activity in the functional calcium mobilization assay (EC50=31 nM). Introduction of 2-pyrrolidinone and 3-tetrahydropyridine groups are pivotal to the high potency. Moreover, 4f was found to facilitate non-amyloidogenic amyloid precursor protein (APP) processing by significantly increasing ERK1/2 phosphorylation and sAPPα secretion, known disease-modifying effects related to M1 mAChR agonists in Alzheimer's disease (AD).

Nitric oxide (NO) releasing poly ADP-ribose polymerase 1 (PARP-1) inhibitors targeted to glutathione S-transferase P1-overexpressing cancer cells.

We report the antitumor effects of nitric oxide (NO) releasing derivatives of the PARP-1 inhibitor olaparib (1). Compound 5b was prepared by coupling the carboxyl group of 3b and the free amino group of arylated diazeniumdiolated piperazine 4. Analogue 5a has the same structure except that the F is replaced by H. Compound 13 is the same as 5b except that a Me2N-N(O)═NO- group was added para and ortho to the nitro groups of the dinitrophenyl ring. The resulting prodrugs are activated by glutathione in a reaction accelerated by glutathione S-transferase P1 (GSTP1), an enzyme frequently overexpressed in cancers. This metabolism generates NO plus a PARP-1 inhibitor simultaneously, consuming reducing equivalents, leading to DNA damage concomitant with inhibition of DNA repair, and in the case of 13 inducing cross-linking glutathionylation of proteins. Compounds 5b and 13 reduced the growth rates of A549 human lung adenocarcinoma xenografts with no evidence of systemic toxicity.

The course of postdisaster psychiatric disorders in directly exposed civilians after the US Embassy bombing in Nairobi, Kenya: a follow-up study.

PURPOSE: While disasters are common in Africa, disaster studies in Africa are underrepresented in the published literature. This study prospectively examined the longitudinal course of psychopathology, coping, and functioning among 128 directly exposed Kenyan civilian survivors of the 1998 US Embassy bombing in Nairobi. METHODS: The Diagnostic Interview Schedule/Disaster Supplement assessed predisaster and postdisaster psychiatric disorders and variables related to coping, functioning, safety, and religion near the end of the first and third postdisaster years. RESULTS: Total postdisaster prevalence of posttraumatic stress disorder (PTSD) at the 3-year follow-up was 49; 28% of the sample still had active PTSD. Delayed-onset PTSD was not observed. Posttraumatic symptoms decayed more slowly in individuals with than those without PTSD. PTSD was more prevalent and chronic than major depression. Those with current PTSD or major depression reported more functioning problems than those without. The length of hospitalization for injuries after the bombing predicted major depression remission, but no predictors of PTSD remission were found. CONCLUSIONS: Despite differences in coping and social variables, longitudinal psychopathology in the Nairobi terrorism survivors appeared broadly similar to results in Western disaster populations. These findings contribute to the understanding of disaster mental health in Africa and may have implications for generalizability of psychiatric effects of terrorist attacks around the globe.

Workplace response of companies exposed to the 9/11 World Trade Center attack: a focus-group study.

The terrorist attacks of 11 September 2001 (9/11) left workplaces in pressing need of a mental health response capability. Unaddressed emotional sequelae may be devastating to the productivity and economic stability of a company's workforce. In the second year after the attacks, 85 employees of five highly affected agencies participated in 12 focus groups to discuss workplace mental health issues. Managers felt ill prepared to manage the magnitude and the intensity of employees' emotional responses. Rapid return to work, provision of workplace mental health services, and peer support were viewed as contributory to emotional recovery. Formal mental health services provided were perceived as insufficient. Drawing on their post-9/11 workplace experience, members of these groups identified practical measures that they found helpful in promoting healing outside of professional mental health services. These measures, consistent with many principles of psychological first aid, may be applied by workplace leaders who are not mental health professionals.

Synthesis of 3,4-dimethylidene oxacycles through Prins-type cyclization of allenylmethylsilanes.

An efficient synthesis of 3,4-dimethylidene oxacycles including oxolanes and oxepanes through Prins-type cyclization of hydroxy(allenylmethyl)silanes is described. We have shown that 2-substituted tetrahydrofuran derivatives could be produced by using this strategy although the 5-endo-trig cyclization mode is stereoelectronically disfavored. We also applied our method to the stereoselective synthesis of 2,7-cis-3,4-dimethylidene oxepanes, which were used for constructing more complex ring systems, such as polyether bicycles or tricycles.

The business of healing: focus group discussions of readjustment to the post-9/11 work environment among employees of affected agencies.

OBJECTIVE: Understanding postdisaster workplace adjustment may help guide interventions for postdisaster emotional functioning and recovery. METHODS: One to two years after the September 11, 2001, terrorist attacks, 12 focus groups were conducted with 85 employees of companies directly affected by the 9/11 attacks on New York City, to discuss mental health issues surrounding return to the workplace after the disaster. RESULTS: Risk communication, tension between workplace productivity and employees' emotional needs, and postdisaster work space were topics discussed in the focus groups. Employees identified many effective responses by their companies after 9/11 relating to these areas of concern as well as gaps in response. CONCLUSIONS: Recommended risk communication procedures were applied but not systematically. Little direction was available for balancing workplace productivity and employees' emotional needs or for strategic management of postdisaster workspace, suggesting areas for future disaster workplace research.

Stereocontrolled synthesis of oxaspirobicycles via Prins-pinacol annulation.

We have developed the stereoselective synthesis of 2-oxaspiro[m,n]alkane derivatives using the Prins-pinacol annulation of alkene diols with a wide range of aliphatic or aromatic aldehydes and ketones. This approach was further applied for the synthesis of oxatricyclic ring system.

Intermolecular double Prins-type cyclization: a facile and efficient synthesis of 1,6-dioxecanes.

Double or nothing: The title reaction converts a range of aromatic aldehydes and allenylmethyl/allyl silanes into 1,6-dioxecane derivatives in good to excellent yields (see scheme; Ar = aryl, Tf = triflate, THF = tetrahydrofuran, TMS = trimethylsilyl). In addition, the bisdiene product has been transformed into the corresponding tricyclic compound through a Diels-Alder reaction.

5- And 6-exocyclic products, cis-2,3,5-trisubstituted tetrahydrofurans, and cis-2,3,6-trisubstituted tetrahydropyrans via Prins-type cyclization.

Exocyclic products having cis-2,5 and cis-2,6 substitution were synthesized from terminally substituted alkynyl alcohols with various aldehydes via Prins-type cyclization in good yields. It is of interest that synthesized 5- and 6-exocyclic vinyl cations generated as a result of Prins-type cyclization could be trapped as a vinyl triflate in CH2Cl2 to give 3-furanylidenes and 3-pyranylidenes. Those 3-furanylidenes and 3-pyranylidenes underwent hydrolysis to give the corresponding 3-acyl-substituted products having all-cis-configured isomers, such as 2,3,5-trisubstituted tetrahydrofurans and 2,3,6-trisubstituted tetrahydropyrans.

Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers.

Morpholin-2-one-5-carboxamide derivatives were prepared by using the one-pot Ugi multicomponent reaction and evaluated for blocking effects on T- and N-type Ca(2+) channels. Among them, compound 5i produced the highest potency (IC(50)=0.45+/-0.02 microM), while compounds 5d, 5f, 5k, 5n, 5o, and 6m produced relatively high potency as well as selectivity on T-type Ca(2+) channels. These novel scaffolds showed potent and selective T-type Ca(2+) channel blocking activities.

Indium-mediated one-pot three-component reaction of aromatic amines, enol ethers, and allylic bromides.

[reaction: see text] A new and efficient indium-mediated one-pot three-component reaction for the synthesis of N-aryl-substituted homoallylamines from aromatic amines, enol ethers, and allylic bromides in THF at room temperature is described.

Stereoselective syntheses of rolliniastatin 1, rollimembrin, and membranacin.

A radical cyclization of beta-alkoxyvinyl sulfoxides-Pummerer rearrangement-allylation protocol was successfully applied to the synthesis of the threo/cis/threo/cis/erythro bis-oxolane moiety in rolliniastatin 1 (1), rollimembrin (2), and membranacin (3).

Comparison of post-disaster psychiatric disorders after terrorist bombings in Nairobi and Oklahoma City.

BACKGROUND: African disaster-affected populations are poorly represented in disaster mental health literature. AIMS: To compare systematically assessed mental health in populations directly exposed to terrorist bombing attacks on two continents, North America and Africa. METHOD: Structured diagnostic interviews compared citizens exposed to bombings of the US Embassy in Nairobi, Kenya (n=227) and the Oklahoma City Federal Building (n=182). RESULTS: Prevalence rates of post-traumatic stress disorder (PTSD) and major depression were similar after the bombings. No incident (new since the bombing) alcohol use disorders were observed in either site. Symptom group C was strongly associated with PTSD in both sites. The Nairobi group relied more on religious support and the Oklahoma City group used more medical treatment, drugs and alcohol. CONCLUSIONS: Post-disaster psychopathology had many similarities in the two cultures; however, coping responses and treatment were quite different. The findings suggest potential for international generalisability of post-disaster psychopathology, but confirmatory studies are needed.

Drosophila serpin 4 functions as a neuroserpin-like inhibitor of subtilisin-like proprotein convertases.

The proteolytic processing of neuropeptide precursors is believed to be regulated by serine proteinase inhibitors, or serpins. Here we describe the molecular cloning and functional expression of a novel member of the serpin family, Serine protease inhibitor 4 (Spn4), that we propose is involved in the regulation of peptide maturation in Drosophila. The Spn4 gene encodes at least two different serpin proteins, generated by alternate splicing of the last coding exon. The closest vertebrate homolog to Spn4 is neuroserpin. Like neuroserpin, one of the Spn4 proteins (Spn4.1) features a unique C-terminal extension, reminiscent of an endoplasmic reticulum (ER) retention signal; however, Spn4.1 and neuroserpin have divergent reactive site loops, with Spn4.1 showing a generic recognition site for furin/SPC1, the founding member of the intracellularly active family of subtilisin-like proprotein convertases (SPCs). In vitro, Spn4.1 forms SDS-stable complexes with the SPC furin and directly inhibits it. When Spn4.1 is overexpressed in specific peptidergic cells of Drosophila larvae, the animals exhibit a phenotype consistent with disrupted neuropeptide processing. This observation, together with the unique combination of an ER-retention signal, a target sequence for SPCs in the reactive site loop, and the in vitro inhibitory activity against furin, strongly suggests that Spn4.1 is an intracellular regulator of SPCs.

Stereoselection in radical cyclization of beta-alkoxyvinyl sulfoxides: synthesis of tetrahydrofuranyl allyl carbinols.

[reaction: see text] Tetrahydrofuranyl allyl carbinols may be prepared stereoselectively via radical cyclization of beta-alkoxyvinyl sulfoxides, Pummerer rearrangement, and reaction with allylstannane.