Long-term epidemiological dynamics of dengue in Barbados - one of the English-speaking Caribbean countries.

Using the dengue surveillance program, we prospectively collected data on all the suspected and confirmed cases of dengue in Barbados from 2006 to 2015. Data were analysed for demographic, seasonal and temporal dynamics of this disease in this country. The overall mean annual incidence rate of suspected and confirmed dengue over the study period was 0.49% (range 0.15%-0.99%) and 0.16% (range 0.05%-0.48%), respectively. There was a significant correlation between the mean monthly number of confirmed cases, the mean monthly rainfall and the mean monthly relative humidity percentage. Dengue in this population is predominantly an infection affecting children and young adults. The median age of the patients with both, suspected and confirmed dengue was 25 years and the highest proportion of cases was seen in the age group 0-15 years. The annual incidence rates of both the suspected and the confirmed cases showed an upward trend during the study period and this upward trend was more pronounced among children.

Chronic maternal inflammation or high-fat-feeding programs offspring obesity in a sex-dependent manner.

BACKGROUND/OBJECTIVES: The current world-wide obesity epidemic partially results from a vicious circle whereby maternal obesity during pregnancy predisposes the offspring for accelerated weight gain and development of metabolic syndrome. Here we investigate whether low-grade inflammation, characteristic of the obese state, provides a causal role for this disastrous fetal programming in mice. METHODS: We exposed pregnant and lactating C57BL/6JBom female mice to either high-fat diet (HFD), or continuous infusion of lipopolysaccharide (LPS), a potent trigger of innate immunity, and studied offspring phenotypes. RESULTS: Both maternal LPS or HFD treatments rendered the offspring hyperphagic and inept of coping with a HFD challenge during adulthood, increasing their adiposity and weight gain. The metabolic effects were more pronounced in female offspring, while exposed male offspring mounted a larger inflammatory response to HFD at adulthood. CONCLUSIONS: This supports our hypothesis and highlights the programming potential of inflammation in obese pregnancies.

Epidemiological Trend and Clinical Observations among Children and Adults with Dengue in Barbados.

OBJECTIVE: To describe the epidemiological characteristics and the clinical manifestations of the confirmed dengue cases over a ten-year period in Barbados, one of the English-speaking Caribbean countries. METHODS: All the cases of confirmed dengue from 2000 to 2009 were retrospectively studied. Long-term trends in incidence rate, demographic characteristics such as age, gender and seasonal distribution; clinical manifestations, immunological characteristics, need for hospitalization and mortality were studied. RESULTS: There were 3413 confirmed cases of dengue including 778 (22.8%) children and 2635 (77.2%) adults. The mean annual incidence rate of dengue was 1.36/1000 population. The median age of the persons with confirmed dengue was 27 years. The largest number of cases was seen in the 11 to 16-year age group. Hospitalization was required in 13.1% of dengue cases; 72.5% and 84% of all dengue were secondary infections among the children and adults, respectively. Dengue haemorrhagic fever accounted for 2.2% and 6% of all confirmed dengue among children and adults, respectively. The overall case fatality rate in this study was 0.35%. CONCLUSIONS: Dengue is a significant health problem primarily in adolescents and young adults. It is characterized by less severe cases and lower mortality rate.

A 24-h a la carte food service as support for patients at nutritional risk: a pilot study.

BACKGROUND: Undernutrition and insufficient energy and protein intake is a common problem in hospitalised patients. The aim of this pilot study was to investigate whether a novel hospital menu would be an effective strategy for increasing nutritional intake in patients at nutritional risk. METHODS: A historically controlled intervention pilot study was conducted. Forty patients at nutritional risk were offered a novel hospital menu as a supplement to the ordinary hospital menu. The menu consisted of 36 naturally energy-enriched small dishes served on demand 24 h a day. Energy and protein intake were calculated as the mean over a period of 3 days. RESULTS: No significant difference in energy and protein intake was observed between the groups; however, a significant (P = 0.001) time gradient in total energy intake was observed in the intervention group. Moreover, a significant (P = 0.03) time gradient in energy intake received from the novel menu was observed. The dishes from the novel menu were mainly ordered from 11.00 h to 14.00 h and from 17.00 h to 18.00 h. CONCLUSIONS: No overall significant differences in energy and protein intake between the groups were found. However, the present pilot study revealed a significant time gradient in total energy intake (P = 0.001) and in energy intake from the novel menu (P = 0.03). This indicates the need to include a run-in period when investigating novel hospital menus as a support for patients at nutritional risk. Additionally, food service, available 24 h a day, appears to be unnecessary.

Using IPM-CPR as a Management Program for Apple Orchards.

We have demonstrated how management of key orchard pests including the insect invasive species Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) can be accomplished using a systems-level approach termed IPM-CPR (Integrated Pest Management-Crop Perimeter Restructuring) in apple. We conducted on-farm comparisons of IPM-CPR to standard management program for managing H. halys, Cydia pomonella (L.) (Lepidoptera: Tortricidae), Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae) in commercial apple orchards in 2014, 2016, and 2017 in New Jersey, Maryland, and Virginia. The presence and abundance of key pests and fruit injury at harvest were used as a measure of success of the program. We compared the amount of insecticide applied for each management program. In majority of instances, there were no differences in the IPM-CPR and the standard management program in terms of H. halys numbers in baited pyramid traps and stink bug injury at harvest. Damage from C. pomonella and G. molesta in the IPM-CPR treatment was significantly lower than the standard management program in 2014 and 2017. Amount of active ingredient used was on average 62.1% lower in the IPM-CPR treatment compared with standard management program. Despite a reduction in insecticide use, there were minimal impacts on beneficial insects. Overall, IPM-CPR in apples successfully managed key orchard pests, including H. halys, and used significantly less insecticide than a standard insecticide-based management program and could be adopted as a systems-level approach for pest population reduction.

Murine helix-loop-helix transcriptional activator proteins binding to the E-box motif of the Akv murine leukemia virus enhancer identified by cDNA cloning.

The enhancer region of Akv murine leukemia virus contains the sequence motif ACAGATGG. This sequence is homologous to the E-box motif originally defined as a regulatory element in the enhancers of immunoglobulin mu and kappa genes. We have used double-stranded oligonucleotide probes, corresponding to the E box of the murine leukemia virus Akv, to screen a randomly primed lambda gt11 cDNA expression library made from mouse NIH 3T3 fibroblast RNA. We have identified seven lambda clones expressing DNA-binding proteins representing two different genes termed ALF1 and ALF2. The results of sequencing ALF2 cDNA suggests that we have recovered the gene for the basic-helix-loop-helix transcription factor A1, the murine analog of the human transcription factor E47. The cDNA sequence of ALF1 codes for a new member of the basic-helix-loop-helix protein family. Two splice variants of ALF1 cDNA have been found, differing by a 72-bp insertion, coding for putative proteins of 682 and 706 amino acids. The two ALF1 mRNAs are expressed at various levels in mouse tissues. In vitro DNA binding assays, using prokaryotically expressed ALF1 proteins, demonstrated specific binding of the ALF1 proteins to the Akv murine leukemia virus E-box motif ACAGATGG. Expression in NIH 3T3 fibroblasts of GAL4-ALF1 chimeric protein stimulated expression from a minimal promoter linked to a GAL4 binding site, indicating the existence of a transcriptional activator domain in ALF1.

MET amplification and epithelial-to-mesenchymal transition exist as parallel resistance mechanisms in erlotinib-resistant, EGFR-mutated, NSCLC HCC827 cells.

Although many epidermal growth factor receptor (EGFR)-mutated lung cancer patients initially benefit from the EGFR-inhibitor erlotinib, all acquire resistance. So far, several mechanisms implicated in resistance have been identified, but the existence of multiple resistance mechanisms in parallel have only been sparsely investigated. In this study, we investigated parallel resistance mechanisms acquired by HCC827, an EGFR-mutated adenocarcinoma cell line dependent on EGFR activity and sensitive to erlotinib. The cell line was treated with erlotinib by stepwise escalation of the drug-concentration and erlotinib-resistant (HCC827ER) cells created. HCC827ER cells depicted a mixed epithelial and mesenchymal phenotype. To clarify potential parallel resistance mechanisms, 14 resistant subclones were established by limited dilution. Interestingly, all HCC827ER subclones harbored either a MET-amplification (6/14) or underwent EMT (8/14), mechanisms both found in previous studies, but not in co-occurrence. Both subclone-types were resistant to erlotinib, but only MET-subclones responded to the MET-inhibitors crizotinib and capmatinib. EMT-subclones on the other hand had markedly increased FGFR1 expression and responded to the FGFR-inhibitor AZD4547, whereas MET-subclones did not. Monitoring gene expression through the development of HCC827ER revealed upregulation of FGFR1 expression as an early response to erlotinib. In addition, FGFR1 expression increased upon short-term erlotinib treatment (48 h) identifying a physiological role immediately after erlotinib exposure. The high FGFR1 expression seen in EMT-subclones was stable even after five passages without erlotinib. Here we show, that parallel resistance mechanisms appear during erlotinib-resistance development in EGFR-mutated NSCLC cells and highlight a role for FGFR1 expression changes as an early response to erlotinib as well as a bypass-signaling mechanism.

CACNA1C hypermethylation is associated with bipolar disorder.

The CACNA1C gene, encoding a subunit of the L-type voltage-gated calcium channel is one of the best-supported susceptibility genes for bipolar disorder (BD). Genome-wide association studies have identified a cluster of non-coding single-nucleotide polymorphisms (SNPs) in intron 3 to be highly associated with BD and schizophrenia. The mechanism by which these SNPs confer risk of BD appears to be through an altered regulation of CACNA1C expression. The role of CACNA1C DNA methylation in BD has not yet been addressed. The aim of this study was to investigate if CACNA1C DNA methylation is altered in BD. First, the methylation status of five CpG islands (CGIs) across CACNA1C in blood from BD subjects (n=40) and healthy controls (n=38) was determined. Four islands were almost completely methylated or completely unmethylated, while one island (CGI 3) in intron 3 displayed intermediate methylation levels. In the main analysis, the methylation status of CGI 3 was analyzed in a larger sample of BD subjects (n=582) and control individuals (n=319). Out of six CpG sites that were investigated, five sites showed significant hypermethylation in cases (lowest P=1.16 × 10(-7) for CpG35). Nearby SNPs were found to influence the methylation level, and we identified rs2238056 in intron 3 as the strongest methylation quantitative trait locus (P=2.6 × 10(-7)) for CpG35. In addition, we found an increased methylation in females, and no difference between bipolar I and II. In conclusion, we find that CACNA1C methylation is associated with BD and suggest that the regulatory effect of the non-coding risk variants involves a shift in DNA methylation.

E-box variants direct formation of distinct complexes with the basic helix-loop-helix protein ALF1.

The murine transcription factor ALF1 belongs to the class of basic helix-loop-helix proteins specific for the NCAGNTGN-version of the E-box. Binding of homodimeric ALF1 to variants of this motif was studied by a combination of binding site selection technology and DNA modification interference analysis. The results showed that substitutions at the non-conserved positions in the E-box sequence could cause profound alterations in the patterns of specific contacts at the protein-DNA interface. Thus, both the overall extent of the binding region and the backbone phosphate contact pattern differed markedly between closely related E-boxes with similar affinities for ALF1. The identity of the base at the inner N was an important determinant of contact pattern specification. The E-box variants differed in their ability to mediate ALF1 dependent transcriptional activation in vivo. We discuss the possibility that adaptability in basic helix-loop-helix protein-DNA interactions can result in complexes with different functional properties.

Malignant bronchial oncocytoma: case report and review of the literature.

An oncocytoma of the bronchus with an infiltrative growth pattern and a lymph node metastasis were examined by light and electron microscopy. Lobectomy, with removal of all tumor-bearing tissue, was the only treatment. Two years after surgery the patient had no local recurrences or metastases.

Malignant giant cell tumor of synovium and locally destructive pigmented villonodular synovitis: ultrastructural and immunohistochemical study and review of the literature.

The first reported case of an intraarticular malignant giant cell tumor of synovium studied with electron microscopic and immunohistochemical examination is presented, together with a case of diffuse intraarticular pigmented villonodular synovitis with extensive bone destruction. The malignant case was dominated by uniform cells positive for histiocytic markers, the fine structure showing a gradual change from cells dominated by organelles serving a secretory function to cells with phagocytic activity. The reported cases of giant cell tumor of the tendon sheath indicate that the pertinent histologic changes regarding malignancy are an increase in cell polymorphism and in the number of mitoses, and a decrease in the number of multinucleated giant cells.

Proliferating cell nuclear antigen in endometrial adenocarcinomas of endometrioid type correlated with histologic grade, stage, previous hormonal treatment, and survival.

Only a small number of endometrial carcinomas have been examined for proliferating cell nuclear antigen. The results indicate that a high proliferating cell nuclear antigen content correlates with a poor prognosis. One hundred eight endometrial carcinomas of endometrioid type were examined with the monoclonal antibody PC10 (48 tumors from postmenopausal estrogen users and 60 tumors from nonusers). The PC10 content was weakly but significantly correlated with mitotic count and architectural grade, but not with nuclear grade, stage, or survival. PC10 values in estrogen users were much lower (median, 14%) than in nonusers (median, 26%); the difference was independent of histologic grade and stage. After a median follow-up of 30 months (range, 12 to 66 months) 17 patients had died. The cause of death was established as cancer in only nine cases. No overall difference in PC10 values existed between survivors and nonsurvivors. However, if only the estrogen nonusers were examined the survivors showed a mean PC10 value of 27%, while the nonsurvivors showed a mean PC10 value of 45%. The present study indicates that carcinomas from patients with and without previous hormonal treatment are different with regard to their PC10 content. The quantitative and qualitative estimates of PC10 correlated well.

p53 protein and c-erbB-2 protein (p185) expression in endometrial adenocarcinoma of endometrioid type. An immunohistochemical examination on paraffin sections.

The expression of both the nuclear protein p53 tumor suppressor gene product and the transmembrane C-erbB-2 protein oncogene product (p185) correlates to risk factors and outcomes in different tumor types. Their value as prognosticators in endometrial adenocarcinoma of endometrioid type (EC) has not been determined. Paraffin sections were examined immunohistochemically to study the expression of p53 protein and p185 in 112 patients with EC. p53 protein was overaccumulated in 34% and p185 in 13% of the tumors. p53 protein correlated with mitotic count and nuclear grade. Both p53 protein and p185 correlated significantly with outcome. However, they did not correlate with each other or with architectural grade or stage (which defines a high risk group), indicating a role as adjuvant prognosticators in EC. Stage and outcome did correlate, however. Both p53 protein and p185 antibodies work well on routine, formalin-fixed, paraffin-embedded tissue and are easily used in routine diagnostic procedures.

TIF1alpha: a possible link between KRAB zinc finger proteins and nuclear receptors.

Ligand-induced gene activation by nuclear receptors (NRs) is thought to be mediated by transcriptional intermediary factors (TIFs), that interact with their ligand-dependent AF-2 activating domain. Included in the group of the putative AF-2 TIFs identified so far is TIF1alpha, a member of a new family of proteins which contains an N-terminal RBCC (RING finger-B boxes-coiled coil) motif and a C-terminal bromodomain preceded by a PHD finger. In addition to these conserved domains present in a number of transcriptional regulatory proteins, TIF1alpha was found to contain several protein-protein interaction sites. Of these, one specifically interacts with NRs bound to their agonistic ligand and not with NR mutants that are defective in the AF-2 activity. Immediately adjacent to this 'NR box', TIF1alpha contains an interaction site for members of the chromatin organization modifier (chromo) family, HP1alpha and MOD1, which both are heterochromatinic proteins. Finally, TIF1alpha also has a binding site for KRAB silencing domains of C2H2 zinc finger proteins. TIF1beta, another member of the TIF1 gene family, has some interacting partners in common with TIF1alpha. TIF1beta can interact with HP1alpha, MOD1 and KRAB domains, but apparently not with NRs. Both TIF1alpha and TIF1beta repress transcription when fused to a DNA binding domain in transiently transfected mammalian cells. A model discussing the potential function(s) of TIF1s in the control of transcription at the level of the chromatin template will be presented.

Serum tetranectin and CA125 in endometrial adenocarcinoma.

BACKGROUND: CA125 and tetranectin (TN) are prognostic markers in ovarian cancer. This study examines the values of these markers in endometrial cancer. MATERIALS AND METHODS: TN and CA125 were determined preoperatively in 99 patients with primary endometrioid adenocarcinoma and evaluated in relation to tumor grade, stage and cancer survival. RESULTS: The CA125 levels correlated significantly with tumor stage. Dichotomized according to a cut-off level of 35 U/ml, CA125 significantly correlated with cancer death. Multivariate regression analysis of cancer survival time showed that CA125 > 35 U/ml was not an independent factor when stage was introduced. TN levels were within the normal range in all patients and did not show any association with tumor grade, stage or survival. CONCLUSIONS: The study confirmed the role of CA125 as a prognostic factor in endometrial cancer and may be of aid in pointing out patients at high risk, whereas tetranectin did not show any prognostic effect.

Estrogen receptor determination in endometrial carcinoma: ligand binding assay versus enzyme immunoassay.

We compared concentrations of cytosolic estrogen receptors (ERc) measured in 35 postmenopausal endometrial carcinomas by ligand binding method (LBA) (dextran-coated charcoal assay) and enzyme immunoassay (EIA). Correlations between ERc, nuclear estrogen receptors (ERn) determined by EIA, and cytosolic progesterone receptors (PR) measured by LBA were also studied. While ERc concentrations determined by LBA and EIA were highly correlated (r: 0.94), ERc values detected by LBA were approximately twice those found by EIA (median values of ERc: 155 vs. 64 fmol/mg cytosol protein, DCC vs. EIA). The percentages of ERc positive tumors were 89% by LBA and 77% by EIA. The median fraction of total ER present as ERn was 63%. PR levels correlated positively with ERn concentrations (r: 0.73). We explore possible reasons why greater concentrations of ERc are determined by estradiol binding than by the ER-EIA kit in endometrial cancer.

Integrating the therapeutic community and work release for drug-involved offenders. The CREST Program.

As the nation's first therapeutic community (TC) and work release center for drug involved offenders, CREST combines the basic elements of both modalities into an effective agent for behavioral change. This article explores the ways in which these elements are integrated and applied, and the outcome of such treatment as determined by subsequent substance abuse and criminal activity. Clients entering the program from prison progress through several phases of counseling, group interaction, confrontation, and education before they enter the work release phase, where they gain realistic experience and can implement what they learned in the TC concerning living drug free. Follow-up data collected at 6 and 18 months after entry into the program indicate that CREST clients have significantly lower relapse and recidivism rates than a comparable comparison group. CREST has similar effects on relapse and recidivism across sexes, racial/ethnic groups, and different age categories, although length of time in treatment and whether clients graduated do impact outcome variables.

Examining drinking patterns and problems among hispanic groups: results from a national survey.

OBJECTIVE: This study examines and compares the drinking patterns and problems of members of four Hispanic groups (Cubans, Mexican Americans, Puerto Ricans and other Hispanics) in the United States, with information presented by gender and age. METHOD: The 1993 National Household Survey on Drug Abuse, a recent national probability sample of the household population aged 18 and over in the United States, is used. Data are obtained through in-person interviews. The sample includes 4,462 Hispanics of Cuban (n = 620), Mexican (n = 2,467), Puerto Rican (n = 619) and Central and South American (n = 756) origin. Analyses are conducted using SUDAAN. RESULTS: There are significant differences across the Hispanic groups in their drinking patterns and problems. Among men, Mexican Americans report the most frequent and heavy drinking, and the greatest prevalence of drunkenness and alcohol-related problems. Cubans report the lowest percentages of such respondents, and Puerto Ricans and other Hispanics are in between the other two groups. For women, fewer ethnic differences are evidenced than for men. In general, Puerto Ricans and Mexican Americans drink more often and heavily and experience more problems than the other groups. Even after controlling for predictors of adult alcohol use, some ethnic differences in drinking persist. CONCLUSIONS: The four Hispanic groups have different drinking patterns. More research is necessary to determine the factors associated with differences in drinking across Hispanic groups.

Drinking in adulthood: similarities and differences in effects of adult roles for Hispanic ethnic groups and Anglos.

OBJECTIVE: This study examines whether the adult social roles perspective. an approach that explains drinking behaviors for Anglos, similarly affects alcohol use by Cubans, Mexican Americans, Puerto Ricans and Other Hispanics (Central and South Americans). METHOD: The 1993 National Household Survey on Drug Abuse, a national probability sample of the household population in the United States, is used. The sample utilized here (N= 13,822; 56.2% female) consisted of 9,388 Anglos, 611 Cubans, 2,459 Mexican Americans, 611 Puerto Ricans and 753 Central/South Americans age 18 and older. The outcome measures include past-year drinking, and for drinkers, heavy drinking and alcohol-related problems. Logistic regression analyses are conducted using Stata. RESULTS: The results show that there are some ethnic differences in the effects of the adult social roles. Of particular importance is the finding that being married has anomalous effects for Cubans (heavy drinking), Mexican Americans (problems) and Other Hispanics (problems) compared with Anglos and the other Hispanic ethnic groups. CONCLUSIONS: The adult social roles perspective has some utility for explaining Hispanic drinking patterns. Future research should consider not only traditional predictors of drinking but also such socio-cultural factors as acculturation and familism, to better understand adult alcohol use by members of Hispanic ethnic groups.

Drinking patterns among Hispanic adolescents: results from a national household survey.

OBJECTIVE: This is one of the first studies to examine and compare alcohol use for adolescent Cubans, Mexican Americans, Puerto Ricans and other Hispanics. METHOD: The data come from the 1993 National Household Survey on Drug Abuse (NHSDA), a national probability sample of the U.S. household population. The sample examined here (N = 1,865, 52% male) comprises 200 Cubans, 1,133 Mexican Americans, 255 Puerto Ricans and 277 Central/South Americans who were 12 to 17 years old. Drinking patterns are measured using a quantity-frequency index, and analyses are conducted using Stata. RESULTS: In the cross-tabulations, no ethnic differences in drinking patterns are found for males or females, nor is there evidence of gender differences within ethnic groups, although there are some age differences in alcohol use. In the logistic regression analyses, two ethnic differences emerge, although the factors most consistently associated with drinking behaviors in these analyses are age, Spanish language use and urban residence. Additional analyses using the 1998 NHSDA suggest that ethnic differences in alcohol use may emerge in late adolescence/early adulthood. CONCLUSIONS: Given the established findings of ethnic and gender differences in drinking among adult Hispanics, it is surprising that few differences are evidenced in adolescence. Future research should explore whether such differences emerge during the transition into adulthood and, if so, identify factors that produce them. In addition, to increase understanding of these ethnic groups' drinking patterns, future research should further investigate the factors associated with Hispanic adolescents' alcohol use, including both consideration of whether the predictors are the same across groups and of the role of sociocultural factors.