Impact of resilience and environmental stress on burnout of students in public and private dental schools in Western Saudi Arabia.

Background: Dental students' burnout has been repeatedly reported in the literature; however, there is little information about the contributing factors in different contexts and settings. Aims: This study aimed to investigate the correlation between burnout among undergraduate dental students and sociodemographic (specifically gender), psychological (resilience), and structural factors (dental environment stress). Subjects and Methods: An online cross-sectional survey questionnaire was distributed among a convenience sample of 500 undergraduate Saudi dental students. The survey included questions about sociodemographic factors (gender, level of education, academic achievement, type of school [public or private], and living arrangements). The study also included items that allowed assessment of students' burnout using the Maslach Burnout Inventory (MBI) and assessment of student environmental stress and resilience using the Dental Environment Stress Scale (DESS) and the Brief Resilience Scale (BRS). Descriptive statistics, univariate, and linear regression analyses were performed. Results: The response rate was 67% (male = 119, female = 216). Univariable analysis showed that gender, level of education, and DESS and BRS scores correlated significantly (P <.05) with MBI scores. Adjusted multiple linear regression lends further support to that the MBI scores negatively correlated with the BRS score but positively correlated with the DESS score (ß = -0.29, P <.001; ß = 0.44, P <.001, respectively). Conclusions: Within the limitations of this study, the findings demonstrated that increases in resilience correlated significantly with decreases in burnout and increases in environmental stress correlated significantly with increases in burnout among dental students. However, gender had no influence on burnout.

Novel Platforms for Biomedical HIV Prevention Delivery to Key Populations - Community Mobile Clinics, Peer-Supported, Pharmacy-Led PrEP Delivery, and the Use of Telemedicine.

PURPOSE OF REVIEW: A gap exists between PrEP interest and PrEP uptake in key populations (KP) for HIV prevention that may be ascribed to PrEP delivery services not being acceptable. This review summarizes novel platforms for HIV prevention outside of the traditional health facilities environment. RECENT FINDINGS: Mobile health clinics provide highly acceptable integrated, KP-focused services at convenient locations with the potential of high PrEP uptake. Telemedicine and health apps decongest health systems and allow for personal agency and informed decision-making on personal health. Pharmacy-led PrEP delivery provides de-medicalized, confidential PrEP services at extended hours in community locations, from trusted medical professionals. Peer-supported delivery encourages continued PrEP use. Community-based, differentiated and de-medicalized PrEP delivery can address uptake and continued use barriers in key populations. Future research should assess scalability, cost-effectiveness and sustainability of these PrEP delivery platforms, as well as focus on ways to simplify PrEP provision.

Process-Structure-Property Relationships of Copper Parts Manufactured by Laser Powder Bed Fusion.

The process-structure-property relationships of copper laser powder bed fusion (L-PBF)-produced parts made of high purity copper powder (99.9 wt %) are examined in this work. A nominal laser beam diameter of 100 µm with a continuous wavelength of 1080 nm was employed. A wide range of process parameters was considered in this study, including five levels of laser power in the range of 200 to 370 W, nine levels of scanning speed from 200 to 700 mm/s, six levels of hatch spacing from 50 to 150 µm, and two layer thickness values of 30 µm and 40 µm. The influence of preheating was also investigated. A maximum relative density of 96% was obtained at a laser power of 370 W, scanning speed of 500 mm/s, and hatch spacing of 100 µm. The results illustrated the significant influence of some parameters such as laser power and hatch spacing on the part quality. In addition, surface integrity was evaluated by surface roughness measurements, where the optimum Ra was measured at 8 µm ± 0.5 µm. X-ray photoelectron spectroscopy (XPS) and energy-dispersive X-ray spectroscopy (EDX) were performed on the as-built samples to assess the impact of impurities on the L-PBF part characteristics. The highest electrical conductivity recorded for the optimum density-low contaminated coils was 81% IACS.

Radiographic evaluation and determination of hypercementosis patterns in Al-Madinah Al-Munawwarah, Saudi Arabia: A retrospective cross-sectional study.

OBJECTIVES: Hypercementosis (HC) is an asymptomatic excessive cementum deposition at the dental root apex. There is a lack of research that determines the pattern and associated factors of HC in Saudi Arabia. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted on a random sample of 815 Orthopantomograms (OPGs) that was obtained from a total of 14003 female patients archived OPGs. The OPGs were retrieved from the Kodak Carestream-R4 database for the period between 2015 and 2017 at Taibah University Dental College and Hospital (TUDCH), Al-Madinah Al-Munawwarah, Saudi Arabia. Width and radiodensity of HC were measured and the distribution was calculated. Association between HC and factors including age and nationality were explored. Descriptive and inferential analyses were performed. RESULTS: The mean/SD age of HC affected patients (9.8%) was 30.16 ± 13.1 years, of whom 55% were Saudis. The mean/SD width and radiodensity of the hypercementosed roots were 4.14 ± 1.2 mm and 119.86 ± 29.83, respectively. The mandibular teeth were more frequently associated with hypercementosis (65%) specifically first molars (47.5%), while the majority (64%) had a single unilateral distribution pattern. There was a non-significant association between nationality, age, and HC (P = 0.921, P = 0.633, respectively). CONCLUSION: Hypercementosis observed in 9.8% of female patients attending TUDCH which was primarily unilateral and prominently confined to the mandibular teeth roots. The complication of teeth extraction among female patients in Almadinah region should be anticipated.

Process-Structure-Property Relationships of AISI H13 Tool Steel Processed with Selective Laser Melting.

Due to a good combination of high hardness, wear resistance, toughness, resistance to high operating temperatures, and fairly low material cost, AISI H13 tool steel is commonly used in the manufacture of injection molds. Additive manufacturing (AM) such as selective laser melting (SLM), due to the layer-wise nature of the process, offers substantial geometric design freedom in comparison with conventional subtractive manufacturing methods, thereby enabling a construction of complex near-net shape parts with internal cavities like conformal cooling channels. The quality of SLM-manufactured parts mainly depends on the part geometry, build orientation and scanning strategy, and processing parameters. In this study, samples of H13 tool steel with a size of 10 × 10 × 15 mm3 were SLM-manufactured using a laser power of 100, 200, and 300 W; scanning speed of 200, 400, 600, 800, 1000, and 1200 mm/s; and hatch spacing of 80 and 120 µm. A constant layer thickness of 40 µm, 67° scanning rotation between subsequent layers, and a stripe scanning strategy were maintained during the process. The samples were built considering a preheating of 200 °C. The relative density, surface roughness, crack formation, microstructure, and hardness were evaluated. The relative density is shown to increase with increasing the volumetric energy density up to a value of about 60 J/mm3 and then no significant increase can be pointed out; the maximum relative density of 99.7% was obtained. A preheating of 200 °C generally aids to increase the relative density and eliminate the crack formation. The microstructure of built samples shows fine equiaxed cellular-dendritic structure with martensite and some retained austenite. The microhardness of the as-built samples was found to vary from 650 to 689 HV 0.2, which is comparable to a conventionally produced H13 tool steel.

Socioeconomic inequality in the provision of specific preventive dental interventions among children in the UK: Children's Dental Health Survey 2003.

Aim To assess socioeconomic inequality regarding specific preventive interventions (fissure sealants or any treatment to prevent caries) and dental visits among UK children.Method Data were from the Children's Dental Health Survey 2003, which included participants from England, Wales, Scotland, and Northern Ireland. The number of children in the analysis was 2,286. Variables were sex, age, area of residency (for example, England), mother's education, family social class, and deprivation level. Descriptive and regression analyses were performed.Results There were no significant socioeconomic differences in the use of preventive services. Deprivation and family social class (for example, intermediate and manual) were significantly associated with less regular dental visits (odd ratio 0.41, 95% CI [0.28, 0.63]; odd ratio 0.53, 95% CI [0.31, 0.89]; odd ratio 0.37, 95% CI [0.24, 0.58], respectively). Regular dental visits were associated with reporting preventive care for caries (odds ratio 2.25, 95% CI [1.45, 3.49]) and with the number of sealed tooth surfaces (rate ratio 1.73, 95% CI [1.16, 2.60]).Conclusion Despite apparent socioeconomic inequalities in regular dental visits, there was no significant inequality in using specific preventive interventions by children in the UK. This finding should be interpreted with caution considering the relatively small subsample included in this analysis.

The accuracy and cost-effectiveness of hepatitis C core antigen assay in the monitoring of anti-viral therapy in patients with chronic hepatitis C genotype 4.

BACKGROUND: Quantitative hepatitis C (HCV) polymerase chain reaction (qtHCV-PCR), the gold standard for monitoring HCV therapy, is an expensive, time-consuming procedure that requires equipped laboratories and trained personnel. AIMS: To assess the accuracy and cost-effectiveness of the automated Abbott ARCHITECT HCV Ag assay (Wiesbaden, Germany) in monitoring response to pagylated interferon (PEG-IFN) and ribavirin therapy for chronic HCV genotype 4 (G4). METHODS: This longitudinal, non-inferiority study compared the efficacy and cost benefit of an All-HCV core antigen assay protocol and a hybrid qtHCV RNA PCR and HCV core Ag assay protocol to the standard All-qtHCV-PCR protocol in chronic HCV G4 patients treated with pegylated interferon (PEG IFN) and ribavirin. RESULTS: Four hundred and ten patients with chronic hepatitis C genotype 4 met inclusion criteria and were enrolled in the study. The sustained virological response rate (SVR) was 66.34%. The All-HCV core antigen and hybrid monitoring assays resulted in the significant cost savings without compromising performance. A good correlation existed between HCV viral load and HCV core antigen levels (r = 0.944; P < 0.0001). Baseline HCV RNA values <600 IU/mL, baseline HCV core Ag levels <2000 fmol/L, rapid virological response, rapid decline in HCV core antigen were strong predictors of SVR. CONCLUSION: Hepatitis C core Ag assay is a point-of-care, reproducible, reliable, cost-effective monitoring tool with rapid turnaround time that, which can effectively replace or adjunct to qRT-PCR in monitoring interferon based or interferon-free anti-viral therapy in chronic hepatitis genotype 4 patients in resource-limited countries with a high burden of hepatitis C.

Availability and use of Naswar: an exploratory study.

BACKGROUND: Naswar is a niche smokeless tobacco product from Pakistan. There is little information about its availability and user characteristics. METHODS: This cross-sectional survey identified outlets selling Naswar in two wards of one London borough and interviewed a purposively recruited sample of 73 Naswar purchasers. Data were analysed using descriptive and chi-square tests (significance, P ≤ 0.05). RESULTS: Of 65 outlets identified 15 sold Naswar. The purchasers' mean (SD) age was 32 (± 10) years and 63% had completed only secondary education. Naswar consumption was significantly associated with tobacco dependency, whilst starting Naswar use at a younger age, having lower education levels, using Naswar more frequently and being of Pakhtunkhwa origin was associated with high monthly consumption (P ≤ 0.05). CONCLUSIONS: Naswar was widely available. Naswar purchasers of Pakistani origin were employed and young, but with limited education and little knowledge of Naswar's health impacts. Naswar dependency and consumption was linked to behavioural and socio-demographic factors. Further evidence is needed to support policy development.

Exercise capacity, muscle strength and fatigue in sarcoidosis.

The aim of this case-control study was to investigate the prevalence of exercise intolerance, muscle weakness and fatigue in sarcoidosis patients. Additionally, we evaluated whether fatigue can be explained by exercise capacity, muscle strength or other clinical characteristics (lung function tests, radiographic stages, prednisone usage and inflammatory markers). 124 sarcoidosis patients (80 males) referred to the Maastricht University Medical Centre (Maastricht, the Netherlands) were included (mean age 46.6±10.2 yrs). Patients performed a 6-min walk test (6MWT) and handgrip force (HGF), elbow flexor muscle strength (EFMS), quadriceps peak torque (QPT) and hamstring peak torque (HPT) tests. Maximal inspiratory pressure (P(I,max)) was recorded. All patients completed the Fatigue Assessment Scale (FAS) questionnaire. The 6MWT was reduced in 45% of the population, while HGF, EFMS, QPT and HPT muscle strength were reduced in 15, 12, 27 and 18%, respectively. P(I,max) was reduced in 43% of the population. The majority of the patients (81%) reported fatigue (FAS ≥22). Patients with reduced peripheral muscle strength of the upper and/or lower extremities were more fatigued and demonstrated impaired lung functions, fat-free mass, P(I,max), 6MWT and quality of life. Fatigue was neither predicted by exercise capacity, nor by muscle strength. Besides fatigue, exercise intolerance and muscle weakness are frequent problems in sarcoidosis. We therefore recommend physical tests in the multidisciplinary management of sarcoidosis patients, even in nonfatigued patients.

Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, urban Kenya, Zimbabwe, and urban Haiti.

OBJECTIVE: To determine whether observed changes in HIV prevalence in countries with generalised HIV epidemics are associated with changes in sexual risk behaviour. METHODS: A mathematical model was developed to explore the relation between prevalence recorded at antenatal clinics (ANCs) and the pattern of incidence of infection throughout the population. To create a null model a range of assumptions about sexual behaviour, natural history of infection, and sampling biases in ANC populations were explored to determine which factors maximised declines in prevalence in the absence of behaviour change. Modelled prevalence, where possible based on locally collected behavioural data, was compared with the observed prevalence data in urban Haiti, urban Kenya, urban Cote d'Ivoire, Malawi, Zimbabwe, Rwanda, Uganda, and urban Ethiopia. RESULTS: Recent downturns in prevalence observed in urban Kenya, Zimbabwe, and urban Haiti, like Uganda before them, could only be replicated in the model through reductions in risk associated with changes in behaviour. In contrast, prevalence trends in urban Cote d'Ivoire, Malawi, urban Ethiopia, and Rwanda show no signs of changed sexual behaviour. CONCLUSIONS: Changes in patterns of HIV prevalence in urban Kenya, Zimbabwe, and urban Haiti are quite recent and caution is required because of doubts over the accuracy and representativeness of these estimates. Nonetheless, the observed changes are consistent with behaviour change and not the natural course of the HIV epidemic.

Telomerase activity, and tissue polypeptide specific antigen (TPS) in Egyptian breast cancer patients.

OBJECTIVES: Breast cancer is the most common malignancy among Egyptian women. The aim of this study is to evaluate the role of both telomerase and TPS estimation in assessment of breast cancer. METHODS: The study included 40 patients with breast cancer, and 20 patients with benign breast diseases. Telomerase activity in breast tissues was assessed using TRAP assay. TPS was measured in sera of the patients by ELISA. RESULTS: Telomerase positivity was 15% in benign group vs. 60% in malignant group (p = 0.0009). It was significantly correlated to stage, and lymph node status (p < 0.02). Telomerase positivity showed significant correlation to tumor recurrence (p = 0.0076) in a follow-up period of 36 months. Mean rank of TPS was significantly higher in malignant than benign groups (p < 0.001), and in telomerase positive than telomerase negative patients (p < 0.001). In malignant group, mean rank of TPS was significantly higher in late stages (p < 0.002), in higher grade (p < 0.05), in larger tumor size (p < 0.01), and in lymph node positive patients (p < 0.001). ROC curve was utilized to choose the best cutoff for serum TPS (88 U/L). At this cutoff, the sensitivity was 95%, and the specificity was 75%. At a higher cutoff (109 U/L), TPS positivity was significantly correlated to stage, grade, lymph node status, and telomerase positivity (p < 0.05). CONCLUSION: Telomerase positivity and serum TPS might be used as additional markers for assessment of breast cancer.

Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase.

Myeloperoxidase uses hydrogen peroxide (H2O2) to generate hypochlorous acid (HOCl), a potent cytotoxic oxidant. We demonstrate that HOCl regulates the activity of matrix metalloproteinase-7 (MMP-7, matrilysin) in vitro, suggesting that this oxidant activates MMPs in the artery wall. Indeed, both MMP-7 and myeloperoxidase were colocalized to lipid-laden macrophages in human atherosclerotic lesions. A highly conserved domain called the cysteine switch has been proposed to regulate MMP activity. When we exposed a synthetic peptide that mimicked the cysteine switch to HOCl, HPLC analysis showed that the thiol residue reacted rapidly, generating a near-quantitative yield of products. Tandem mass spectrometric analysis identified the products as sulfinic acid, sulfonic acid, and a dimer containing a disulfide bridge. In contrast, the peptide reacted slowly with H2O2, and the only product was the disulfide. Moreover, HOCl markedly activated pro-MMP-7, an MMP expressed at high levels in lipid-laden macrophages in vivo. Tandem mass spectrometric analysis of trypsin digests revealed that the thiol residue of the enzyme's cysteine switch domain had been converted to sulfinic acid. Thiol oxidation was associated with autolytic cleavage of pro-MMP-7, strongly suggesting that oxygenation activates the latent enzyme. In contrast, H2O2 failed to oxidize the thiol residue of the protein or activate the enzyme. Thus, HOCl activates pro-MMP-7 by converting the thiol residue of the cysteine switch to sulfinic acid. This activation mechanism is distinct from the well-studied proteolytic cleavage of MMP pro-enzymes. Our observations raise the possibility that HOCl generated by myeloperoxidase contributes to MMP activation, and therefore to plaque rupture, in the artery wall. HOCl and other oxidants might regulate MMP activity by the same mechanism in a variety of inflammatory conditions.

Tuberculin skin testing to assess the occupational risk of Mycobacterium tuberculosis infection among health care workers in Abidjan, Côte d'Ivoire.

SETTING: Tuberculin skin test (TST) survey of health care workers (HCWs) in selected clinical services in Abidjan, Côte d'Ivoire. OBJECTIVE: To assess whether HCWs in Abidjan are at increased risk for occupationally acquired Mycobacterium tuberculosis infection. DESIGN: From October 1996 to January 1997, consenting HCWs from four services where tuberculosis (TB) prevalence among patients was high and two services where it was low were evaluated with a questionnaire, TST (including evaluation of anergy) and chest radiograph. RESULTS: Of the 512 participants, 405 (79%) had a TST reaction of > or =10 mm, eight (2%) were anergic, five (1%) had a radiograph compatible with TB, and two had confirmed TB. Using a cut-off of 10 mm, we found a higher prevalence of TST positivity in services with high TB prevalence than in those with low TB prevalence (92% vs 72%; odds ratio [OR] 4.3; 95% confidence interval [CI] 2.3-8.0]) and among HCWs with direct (87%; OR 2.9; 95%CI 1.6-5.1) and indirect patient contact (80%, OR 1.7; 95%CI 1.0-2.3) than among those with minimal patient contact (69%). CONCLUSION: These findings indicate that TST positivity among HCWs is related to level of exposure to TB patients, and suggest that HCWs in Abidjan are at risk for the nosocomial transmission of TB.

Increased bcl-2 expression is associated with primary resistance to chemotherapy in human epithelial ovarian cancer.

OBJECTIVE: bcl-2, an anti-apoptotic factor, has a role in the pathogenesis of ovarian cancer as well as in resistance to chemotherapy. DESIGN AND METHODS: 20 benign, and 26 malignant epithelial ovarian tissues were analyzed for bcl-2 protein and mutant p53 by enzyme-immunoassay (EIA). Flowcytometric analysis was also performed. Patients of malignant group were followed up to monitor overall survival and primary resistance to chemotherapy. RESULTS: bcl-2 was significantly higher in malignant group than benign group (p < 0.001). A cutoff value was determined for bcl-2 (63.8 kU/g protein). At this cutoff, sensitivity is 80.7%, and specificity is 85%. Using chi square analysis, a significant correlation was found between bcl-2 and FIGO stage (p = 0.01), overall survival (p = 0.01), as well as primary resistance to chemotherapy (p = 0.03). By correlation coefficient analysis the relation between bcl-2 and synthetic phase fraction was highly significant (p = 0.002). Bcl-2, p53, and FIGO stage were significantly correlated to poor survival (p = 0.01) in univariate analysis. However, in multivariate analysis, only FIGO stage, and p53 were independent risk factors. CONCLUSION: EIA could be a useful tool for investigating the prognostic value of bcl-2, and its possible prediction of platinum resistance in epithelial ovarian cancer. This might help in selecting patients for future anti-bcl-2 therapy.

Correlation between EBV DNA and rearrangement and expression of Bcl-2 gene in aggressive non-Hodgkin's lymphoma.

Previous in vitro studies have shown that bcl-2 expression can be induced by transfection of Epstein-Barr virus (EBV)-negative non-Hodgkin's lymphoma (NHL) cell lines with EBV. This induced expression of bcl-2 is important for the long survival of EBV-positive cells and might be a first step in tumorigenesis. The purpose of the present study was to investigate the possibility of similar correlation between bcl-2 expression and EBV infection in vivo in a cohort of patients with aggressive NHL, who were uniformly evaluated and treated with effective chemotherapy. The 42 patients included were 25-65 years old. None had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Fresh biopsied samples were obtained and stored frozen for analysis of bcl-2 gene rearrangement major break point and of EBV DNA by PCR. Bcl-2 protein expression was estimated by Western blot, and enzyme immunoassay. With a median follow-up of 30 months, overall survival (OS) and disease-free survival (DFS) were measured to determine the prognostic significance of these variables. Analyzable DNA was present in all samples, 24% demonstrating bcl-2 rearrangement and 33% showing EBV DNA. Patients with bcl-2 gene rearrangement tended to have shorter DFS, and OS than patients without translocation. Bcl-2 protein expression was not correlated to gene rearrangement and had no significant influence on survival. The presence of EBV DNA in NHL had no prognostic significance but was correlated to bcl-2 expression. EBV-positive tumors showed higher bcl-2 expression than EBV-negative tumors did. Our results suggest a role of EBV infection in inducing bcl-2 expression as a survival factor for EBV-positive cells.

Transforming growth factor-beta and nitrates in epithelial ovarian cancer.

The role of transforming growth factor-beta (TGF-beta) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-beta by enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-beta, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 = 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2 = 17.6, P = 0.000). A significant correlation was shown between TGF-beta, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-beta (290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-beta had 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-beta above the cut-off had worse prognosis (X2 = 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-beta and NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-beta could be of prognostic significance.

Ovarian cancer-induced immunosuppression: relationship to tumor necrosis factor-alpha (TNF-alpha) release from ovarian tissue.

Cytokines have been reported to be potential biological markers of, disease status in cancer patients. Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine released from monocytes and macrophages. TNF-alpha is involved in essential biological functions such as immunoregulation, modulation of cell growth and differentiation. In this work, the role of TNF-alpha release in ovarian cancer patients was investigated. Fifty-five patients with ovarian cancer and 20 controls of matched age and parity were included in this study. TNF-alpha concentrations were measured in sera and cytosolic fractions of both groups. The results demonstrated a significant increase in TNF-alpha concentrations among patients compared to the control subjects (P < 0.001). Furthermore, a non-significant increase (P = 0.05, was observed between the different types (serous, Mucinous, and endometrioid) of epithelial ovarian cancers. Also TNF-alpha concentrations did not correlate with the disease stage. Moreover, immunohistochemical analysis of tissue specimens stained for TNF-alpha was positive in malignant lesions and negative for the normal ovarian tissue. These findings confirmed the TNF-alpha kinetics obtained by ELISA assays. Interestingly, TNF-alpha levels were also elevated in culture supernatants of PBMC stimulated by cytosolic fractions from malignant ovarian tissues. Blastogenic assays using cytosolic fractions from malignant ovarian specimens to stimulate healthy donor peripheral blood mononuclear cells (PBMC) showed a marked decrease in 3H-thymidine uptake compared to the cells stimulated by normal cytosols. To establish a cause-effect relationship between TNF-alpha release and inhibition of cell proliferation, the experiments showed that 3H-thymidine uptake by PBMC was markedly inhibited by recombinant human TNF-alpha (rh TNF-alpha) and that inhibition was significantly reversed when TNF-alpha monoclonal antibody was added to the cells. The data presented in this work indicate that TNF-alpha may play an important role in the biology of ovarian cancer and hence, tumor pathogenesis.

Cis-platinum-induced immunosuppression: relationship to melatonin in human peripheral blood mononuclear cells.

OBJECTIVES: The purpose of this study was to investigate the immunomodulatory effect of melatonin (MLT) on human peripheral blood mononuclear cells (PBMC) and to address its effects on Cis-platinum (CDDP)-induced cytotoxicity. METHODS AND RESULTS: The obtained data from this study revealed that treatment of cells with MLT (100 microg/ml) for 24 h enhanced cell viability. When cells were exposed to CDDP (5 microg/ml), cell proliferation in response to phytohaemagglutinin (PHA) stimulation was reduced by 49.63% compared to control cells as detected by 3[H]-thymidine uptake. Furthermore, Cis-platinum significantly depleted intracellular glutathione (GSH) levels by approximately 47% below that of untreated cells and led to apoptotic changes in the target cells as evidenced by DNA fragmentation (45% compared to 5% in control cells as measured by diphenylamine assay). DNA fragmentation was also confirmed by agarose gel electrophoresis. However, MLT enhanced cell proliferation by approximately 8.63% above the control values, and counteracted the antiproliferative effect of CDDP. The GSH levels were significantly increased in response to MLT (71% above control values) and it protected the cells against GSH depletion induced by CDDP. Moreover, DNA fragmentation and laddering produced by CDDP were significantly reduced or even disappeared when the cells were pretreated with MLT or the latter was simultaneously added with CDDP. CONCLUSIONS: The findings from this study indicated that melatonin is a potent immunomodulatory hormone that protects PBMC against cis-platinum-induced immunosuppressive effects. These effects might improve the patients' response to cis-platinum therapy and, therefore, their survival rates.

Epstein-Barr virus, human papillomavirus, and flow cytometric cell cycle kinetics in nasopharyngeal carcinoma and inverted papilloma among Egyptian patients.

It is widely accepted that the Epstein-Barr virus is etiologically associated with the development of nasopharyngeal carcinoma. The human papillomavirus is also associated with inverted papilloma. We used the polymerase chain reaction technique to detect both viruses in both types of tumors. Flow cytometry was also used to study the DNA pattern and proliferative behavior of the tumors in relation to the viruses. EBV was detected in 13/20 (65%) of NPC specimens, and in none of IP (n = 10) or control specimens (n = 10). This indicates the contribution of EBV as an etiologic factor in NPC. Five cases of NPC (25%) were positive for HPV 16, two of them were EBV positive. Four HPV 16 positive cases were found among cases with inverted papilloma, but none among the control cases. Flow cytometry revealed that all NPC, IP, and control samples were diploid except one aneuploid NPC sample. Proliferative capacity (PC) of primary tumors was predictive of tumor recurrence in NPC. Using 13.6% as a cut-off point for PC, we were able to discriminate between high risk and low risk groups with 100% sensitivity and 86% specificity. PC can be used as a baseline prognostic parameter in NPC, making it possible to modify courses of treatment in an attempt to inhibit tumor recurrence.

Synthesis and purification of hydrophobic peptides for use in biomimetic ion channels.

The synthesis and subsequent purification of several hydrophobic peptides is described. These peptides include the 24-residue M3 transmembrane domain of the rat connexin 32 protein, a peptide sequence that contains only seven amino acids with hydrophilic side-chains (71% hydrophobic). Moreover, for comparison, a much smaller hydrophobic octapeptide, designed to exist with alpha-helical secondary structure, was also studied. Optimum conditions for the RP-HPLC purification of these peptides was dependent on peptide length and solubility properties.