Medical and pharmacy student concerns about participating on international service-learning trips.

BACKGROUND: International Service Learning Trips (ISLT) provide health professional students the opportunity to provide healthcare, under the direction of trained faculty, to underserved populations in developing countries. Despite recent increases in international service learning trips, there is scant literature addressing concerns students have prior to attending such trips. This study focuses on identifying concerns before and after attending an ISLT and their impact on students. METHODS: A survey comprised of closed and open-ended questions was developed to elucidate student concerns prior to attending an ISLT and experiences which might influence concerns. A five-point Likert-scale (extremely concerned = 1, minimally concerned = 5) was used to rate apprehension and satisfaction. Paired t-test was used to compare pre- and post-trip concerns; Chi-Square test was used to compare groups. RESULTS: Thirty-five students (27 medical, 8 pharmacy) attended ISLTs in December 2013. All completed pre and post-trip surveys. Significant decreases were seen in concerns related to cultural barriers (4.14 vs 4.46, P = .047), disease/epidemics (3.34 vs 4.60, P < .001), natural disasters (3.94 vs 4.94, P < .001), terrorism (4.34 vs 4.94, P < .001), travel (3.86 vs 4.51, P < .001) monetary issues (3.80 vs 4.60, P < .001), hospitality (3.94 vs 4.74, P = .001) and food (3.83 vs 4.60, P < .001). Language and group dynamics remained concerns post-trip. On open-ended questions, students described benefits of attending an ISLT. CONCLUSIONS: Students had multiple concerns prior to attending an ISLT. Most decreased upon return. Addressing concerns has the potential to decrease student apprehension. The results of this study highlight the benefits of providing ISLTs and supporting development of a curriculum incorporating trip-related concerns.

In-patient diabetes care: the impact of diabetes outreach team on long-term glycaemic control.

AIM: Our aim is to assess the impact of inpatient diabetes services on glycaemic control in patient with diabetes admitted to a secondary care hospital in UK. METHODS: We performed a retrospective analysis of all diabetes mellitus (DM) in-patients who were seen by our Diabetes Outreach Team from June 2007 to December 2010. Those with an admission diagnosis of hypoglycaemia were excluded. Blood samples including HbA1c at the initial visit and subsequent outpatient follow-up at 3-6 months were collected. Patients admitted with newly diagnosed diabetes were analysed separately. RESULTS: In total 2002 patient data were captured. 778 patients were eliminated initially because of failure to attend follow-up clinic, lack of follow-up HbA1c data, and because of planned discharge to the community. Complete blood samples were available for 1224 patients. Of this, 235 patients (19.2% of those with complete data) were analysed separately as their primary diagnosis was hypoglycaemia. In the remaining 989 patients, 31 (3.1%) new onset Type 1 DM patients and 91 (9.2%) new onset Type 2 patients were analysed separately. In patients with known DM (n = 867) HbA1c improved from 75 mmol/mol (9.0% ± 2.39) to 69 mmol/mol (8.46% ± 2.0) (p < 0.001). In the newly diagnosed Type 1 DM (n = 31) patients HbA1c improved from 114 mmol/mol (12.55% ± 2.27) to 58 mmol/mol (7.43% ± 2.05) (p < 0.001). In the newly diagnosed Type 2 DM (n = 91) patients HbA1c improved from 93 mmol/mol (10.70% ± 3.04) to 56 mol/mol (7.29% ± 1.74) (p < 0.001). In those who presented with hypoglycaemia (n = 235) HbA1c changed from 58 mmol/mol (7.48% ± 1.59) to 59 mmol/mol (7.59% ± 1.57) (p = 0.2). CONCLUSION: By providing a comprehensive care, structured education and appropriate intervention through our Diabetes Outreach Team, we have shown a significant reduction in HbA1c for recently hospitalised patients.

Twenty-four hour hormone profiles of TSH, Free T3 and free T4 in hypothyroid patients on combined T3/T4 therapy.

The benefits of using thyroxine (T4) plus triiodothyronine (T3) in combination in thyroid hormone replacement are unproven but many individuals continue to be treated with this regime. When T3 is used alone for hypothyroidism, it results in wide fluctuations of thyroid hormone levels. However, only limited data exists on combined T3/T4 therapy. In this study, we have compared 24-hour profiles of thyroid stimulating hormone (TSH), free T4 (fT4) and free T3 (fT3) and cardiovascular parameters in 10 hypothyroid patients who had been on once daily combined T3/T4 therapy for more than 3 months with 10 patients on T4 alone. Twenty patients, who were part of a larger study, investigating the long-term benefits of combined T3/T4 therapy, were recruited into this sub-study. Over 24-hours, 12 samples were taken for thyroid hormones. Their 24-hour pulse and BP is also monitored on a separate occasion. On T4 alone, a modest 16% rise in fT4 with no change in fT3 was seen in the first 4-hours post-dose. In contrast, on combined treatment, fT3 levels showed a marked rise of 42% within the first 4-hours post-dose (T3/T4:T4=6.24: 4.63 mU/L, p<0.001). Mean exposure to fT3 calculated by area under the curve (AUC) was higher (T3/T4:T4=1148:1062, p<0.0001) on T3. Circadian rhythm of TSH was maintained on both treatments. No difference in pulse or blood pressure over the 24-hours was seen between the groups. Our data suggests that despite chronic combined T3/T4 therapy, wide peak-to-trough variation in fT3 levels persists. Although no immediate cardiovascular effects were seen, the long-term consequences for patients on combined therapy are unknown.

The BRCA2 is a histone acetyltransferase.

Patients carrying mutations in BRCA1 or BRCA2 tumor suppressor genes have shown to have high risk in developing breast and ovarian cancers. Two potential functions of BRCA2 were proposed which includes role in the regulation of transcription and also in DNA repair. Forty-five-amino acid region encoded by exon 3 of BRCA2 was shown to have transcriptional activation function. Recent studies of the several enzymes involved in acetylation and deacetylation of histone residues have revealed a possible relationship between gene transcriptional activation and histone acetylation. Since BRCA2 appear to function as a transcriptional factor, we have tested for Histone acetyl transferase (HAT) activity of BRCA2. Here, we present evidence that BRCA2 has intrinsic HAT activity, which maps to the amino-terminal region of BRCA2. Our results demonstrate that BRCA2 proteins acetylate primarily H3 and H4 of free histones. These observations suggest that HAT activity of BRCA2 may play an important role in the regulation of transcription and tumor suppressor function.

EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function.

The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a chimeric protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo. Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans-activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.

Characterization of the DNA binding and transcriptional activation domains of the erg protein.

erg, an ets related gene encodes a sequence specific DNA binding transcriptional activator protein. We have identified four functional domains of erg protein that are responsible for DNA binding, transcriptional activation and negative regulation of transcriptional activation. Deletion analysis revealed that the 3'-ets domain of the erg protein is sufficient for DNA binding activity. Analysis of these deletion mutants also revealed the presence of two autonomous transcriptional activation domains, one at the amino and the other at the carboxyterminal region. This aminoterminal transcriptional activator domain (5'-ets domain) is conserved in six of the ets genes suggesting that it (ETA, ets Transcriptional Activation domain) may contribute to a common function among these genes. The transcriptional activation function of the carboxy terminal transcriptional activation domain (CTA) was inhibited by the presence of a Negative Regulatory Transcriptional activation domain (NRT), which is located at the amino terminal region of erg DNA binding domain. These results may help in understanding the structure/function relationship of other erg/ets related proteins.

The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator.

Molecular characterization of malignant melanoma of soft parts or soft tissue clear cell sarcoma which shares t(12;22) chromosome translocation revealed fusion of EWS with a transcriptional factor gene ATF-1. The EWS gene, which encodes an RNA binding protein, was also shown to be involved in Ewing sarcoma, related primitive neuroectodermal tumors and desmoplastic small round cell tumors. In order to understand the functional role of EWS-ATF-1 chimeric protein in human solid tumors, we have cloned the aberrant human ATF-1 (EWS-ATF-1) cDNA and studied its DNA binding, transcriptional activation properties and compared with normal ATF-1 protein. Our results demonstrate that EWS-ATF-1 binds weakly to DNA in vitro but functions as an efficient constitutive transcriptional activator unlike the normal ATF-1 which needs to be induced with cAMP. Deletion analysis revealed that EWS-fusion domain functions as a regulatory domain for the transcriptional activation properties of EWS-ATF-1 chimeric protein. Deletion of leucine zipper domain results in a loss of transcriptional activation of EWS-ATF-1 chimeric protein suggesting that protein-protein interaction play a role in the transcriptional activation properties of EWS-ATF-1. We demonstrate that EWS-fusion domain negatively regulates the DNA binding activity of EWS-ATF-1 chimeric protein. Therefore replacement of part of the amino-terminal kinase regulatory domain of ATF-1 protein with EWS regulatory domain results in an altered DNA binding, protein-protein interactions and transcriptional activation properties of EWS-ATF-1 causing deregulated gene expression which may be responsible for the genesis of t(12;22) chromosome translocation-bearing human solid tumors. Targeting the transcriptional cofactors (CBP, etc) by EWS-fusion proteins could be one of the mechanisms of activation of EWS-fusion proteins in human neoplasia.

Structure and expression of variant BRCA2a lacking the transactivation domain.

BRCA1 and BRCA2 are tumor suppressor genes shown to be involved in 90% of familial breast cancers and also known to be involved in ovarian and prostate cancers. Both BRCA1 and BRCA2 gene products are regulated in a cell cycle-dependent manner and have potential transactivation function. Here, we show that BRCA2 undergoes differential splicing giving rise to a novel variant protein BRCA2a, lacking putative transcriptional activation domain. Both BRCA2a and BRCA2 are expressed at high levels in thymus and testis but moderate levels in mammary gland and prostate suggesting that BRCA2a and BRCA2 may have a role in the development and differentiation of these tissues.

Lipoatrophy is a thing of the past, or is it?

We describe the development of severe lipoatrophy in a patient treated with biphasic aspart. This complication of insulin therapy was common in the past with the use of animal insulins and became less common with the increasing purification of these and the introduction of recombinant human insulin. This patient developed severe lipoatrophy with the use of a premixed insulin containing the analogue insulin aspart. Lipoatrophy although rare can still occur even with the use of technologically advanced insulin preparations.

Comparative toxic potential of market formulation of two organophosphate pesticides in transgenic Drosophila melanogaster (hsp70-lacZ).

This study investigated the working hypothesis that two widely used organophosphate pesticides; Nuvan and Dimecron, exert toxic effects in Drosophila. Transgenic D. melanogaster (hsp70-lacZ) was used as a model for assaying stress gene expression and AchE activity as an endpoint for toxicity and also to evaluate whether stress gene expression is sufficient to protect against toxic insult of the chemicals and to prevent tissue damage. The study was extended to investigate the effect of the pesticides on the life cycle and reproduction of the organism. The study showed that Nuvan affected emergence of the exposed flies more drastically than Dimecron and the effect was lethal at the highest tested concentration (0.075 ppm). While Nuvan at 0.0075 and 0.015 ppm concentrations affected reproduction of the flies significantly, the effect of Dimecron was significant only at 0.015 and 0.075 ppm. Nuvan-exposed third-instar larvae exhibited a 1.2-fold to 1.5-fold greater hsp70 expression compared to Dimecron at concentrations ranging from 0.0075 to 0.075 ppm following 12 and 18 h exposure. While maximum expression of hsp70 was observed in Nuvan-exposed third-instar larval tissues following 18 h exposure at 0.075 ppm, Dimecron at the same dietary concentration induced a maximum expression of hsp70 following 24 h exposure. Further, concomitant with a significant induction of hsp70, significant inhibition of AchE was observed following chemical exposure and temperature shock. Concurrent with a significant decline in hsp70 expression in Nuvan-exposed larvae after 48 h at 0.075 ppm, tissue damage was evident. Dimecron-exposed larvae exhibited a plateau in hsp70 induction even after 48 h exposure and moderate tissue damage was observed in these larvae. The present study suggests that Nuvan is more cytotoxic than Dimecron in transgenic Drosophila melanogaster.

The interaction of a c-Jun/Fos related protein factor with the U3 sequences of the mouse mammary tumor virus LTR.

Using polyacrylamide gel mobility shift assay we have detected a nuclear factor (NF-S) in a mouse mammary tumor cell line (GR) that binds to an upstream sequence domain (-766 to -737) near the 5'-end of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). Antibodies to the products of the Jun and Fos oncogenes interfered with the binding potential of this factor, indicating that the factor shares antigenic determinants with c-Jun/AP-1. In vitro translated c-Jun and c-Fos were also found to bind to the NF-S binding domain consisting of the sequence TGA(A/G)TCA that are known to be recognized by c-Jun/AP-1. Our results raise the possibility that the MMTV-LTR sequence element-766 to -737 by interacting with a Jun/Fos related protein play a role in MMTV transcription and/or the activation of int protooncogenes that are associated with murine mammary tumorigenesis.

Hematological and enzymatic results of aluminum intoxication in rats.

1. The study has been carried out on Wistar rats. The aim of the present study was to trace the effect of aluminum on enzyme activities and hematological parameters on erythrocytes. 2. Aluminum decreased activities of acetylcholinesterase, glutathione reductase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase in the erythrocytes of the animals tested. 3. In the peripheral blood, a significant decrease in the erythrocyte count, hemoglobin level and hematocrit index and increased percentage of reticulocytes and polychromatophilic erythrocytes were observed. 4. The increase in the neutrophilic granulocyte and lymphocyte count was significant. 5. An inhibitory effect of aluminum on the phagocytic activity of granulocytes was also observed.

The effect of aluminum on the stromal cells (in vitro) on bone marrow in rats.

The aim of this study was to describe the effects of aluminum on the stromal cells of rat bone marrow using a combination of in vivo exposure and in vitro culture of bone marrow. The toxic effects of aluminum are manifested by a decrease in the erythrocyte count and hemoglobin level in the peripheral blood. Aluminum stimulated an increase in the number of fibroblasts while the macrophage count dropped. The number of adipocytes remained unaffected. An increase in mean corpuscular hemoglobin (MCH) was also found in the peripheral blood of experimental animals.