Risky Sexual Behaviors and Associated Factors Among College Students in Lusaka, Zambia.

Risky sexual behaviors are important factors driving the HIV/AIDS epidemic. Although Zambia experiences a high HIV prevalence, especially among youth, there is a dearth of information regarding risky sexual behaviors among young adults. Therefore, we investigated the prevalence and associated factors of risky sexual behaviors among college students in Lusaka, Zambia. A cross-sectional study was conducted in February 2017 among 427 college students at the University of Zambia. Participants reported their sexual behaviors, sexual attitudes, and lifestyle using self-administered questionnaires. Multinomial logistic regression models were employed to assess potential determinants of risky sexual behaviors. Among the 205 students who reported ever having sex, 148 (72.2%) engaged in risky sexual behaviors in the last 12 months. Participants who were older (OR 1.30, 95% CI 1.12-1.51), engaged in low physical activity (OR 2.25, 95% CI 1.05-4.84), and reported liberal sexual attitudes (OR 1.88, 95% CI 1.02-3.47) were more likely to engage in any risky sexual behavior, while frequent alcohol use (OR 8.38, 95% CI 4.60-15.27) and suicide attempts (OR 6.42, 95% CI 2.03-20.29) predicted multiple risky sexual behaviors. In conclusion, this study indicates that Zambian college students' risky sexual behaviors are associated with multiple behavioral health risks. Future research should consider using a multiple-behavior change intervention.

Long noncoding RNA TUG1 promotes renal cell carcinoma cell proliferation, migration and invasion by downregulating microRNA­196a.

Long noncoding RNA taurine upregulated gene 1 (lncRNA TUG1) and microRNA­196a (miR­196a) have been reported to serve important roles in the development of renal cell carcinoma (RCC). However, their potential mechanisms have not been completely elucidated. The aim of the present study was to clarify the biological functions of lncRNA­TUG1 and miR­196a, in addition to investigating the interaction between lncRNA­TUG1 and microRNA­196a, providing a novel insight into RCC tumorigenesis. The present study comprised two parts. In the first part, lncRNA­TUG1 was confirmed as an oncogene, via reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis, MTT assay, flow cytometry analysis, and migration and invasion assays. In the second part, the association between lncRNA­TUG1 and miR­196a, and the molecular mechanism, was illustrated via RT­qPCR analysis, MTT assay, dual luciferase reporter assay and western blotting. The results of the present study demonstrated that lncRNA­TUG1 was able to promote RCC cell proliferation, migration and invasion in vitro by suppressing miR­196a. Additionally, lncRNA­TUG1 achieved its biological functions by regulating the expression levels of RAC­α serine/threonine­protein kinase, mitogen­activated protein kinase and extracellular signal­regulated kinase via inhibition of miR­196a. In conclusion, the present findings proposed a novel potential therapeutic target, the lncRNA­TUG1­miR­196a axis, which may be applicable to the treatment of RCC.

Viral mimic polyinosine-polycytidylic acid potentiates liver injury in trichloroethylene-sensitized mice - Viral-chemical interaction as a novel mechanism.

Occupational trichloroethylene (TCE) exposure can induce hypersensitivity dermatitis and severe liver injury. Recently, several clinical investigations indicate that viral infection, such as human herpesvirus-6, is associated with hepatic dysfunction in patients with TCE-related generalized skin disorders. However, whether viral infection potentiates TCE-induced liver injury remains unknown. This study aimed to explore the contribution of viral infection to the development of TCE-sensitization-induced liver injury in BALB/c mice. Female BALB/c mice were randomly assigned into four groups: solvent control group (n = 20), TCE group (n = 80), poly(I:C) group (n = 20) and combination of TCE and poly(I:C) (poly(I:C)+TCE) group (n = 80). Poly(I:C) (50 µg) was i.p. administrated. TCE and poly(I:C)+TCE groups were further divided into sensitization and non-sensitization subgroup. Complement 3 and C3a protein levels, and complement factors were measured. Combination treatment significantly enhanced TCE-induced liver injury, decreased complement 3, but increased C3a in serum and liver tissues in sensitization group. These changes were not correlated with the hepatic complement 3 transcription. Moreover, combination treatment specifically promoted complement factor B, but not factor D and factor H expressions. These data provide first evidence that poly(I:C) potentiates liver injury in BALB/c mouse model of TCE-sensitization. Upregulated C3a and factor B contributes to the poly(I:C) action in TCE-induced liver injury. This new mode of action may explain increased risk of chemical-sensitization induced tissue damage by viral infection.

Potential immunotoxic effects of trichloroethylene-induced IV allergic reaction in renal impairment.

Trichloroethylene (TCE) is known to induce allergic contact dermatitis and subsequent occupational medicamentosa-like dermatitis (OMLD) with multi-system injuries, including liver, kidney, and skin injuries. However, the mechanisms underlying immune system dysfunction that result in organ injury have not yet been clearly elucidated. In the present study, we measured the levels of secreted cytokines by effect or T cells in TCE-treated guinea pigs to better understand the contribution of allergic disorders in renal injuries. We immunized guinea pigs with trichloroethylene using the Guinea Pig Maximization Test (GPMT) and scored the inflammation on the guinea pigs' skin. The kidney function and ultra-structural changes in the kidneys were detected using biochemical methods and electron microscopy. The deposition of cytokines was determined using immunohistochemistry. The sensitization rate was 63.16% in the TCE-sensitized groups. The electron microscopy results showed tubular epithelial cell mitochondrial swelling, vacuolar degeneration, and atrophy of the microvillus in the sensitized groups. A high degree of cytokine deposition was observed in the renal tubular proximal epithelial cells in the TCE-sensitized groups. As observed in this study, the variation in the level of immune system activation not only indicates that TCE can largely magnify the immune reaction but also suggests a potential role of immune dysfunction in renal impairment.

Diosmetin protects against ischemia/reperfusion-induced acute kidney injury in mice.

BACKGROUND: Renal ischemia/reperfusion (I/R)-induced acute kidney injury remains to be a troublesome condition in clinical practice. Although the exact molecular mechanisms underlying renal I/R injury are incompletely understood, the deleterious progress of renal I/R injury involves inflammation, apoptosis, and oxidative stress. Diosmetin is a member of the flavonoid glycosides family, which suppresses the inflammatory response and cellular apoptosis and enhances antioxidant activity. The purpose of this study was to investigate the protective effect of diosmetin on I/R-induced renal injury in mice. METHODS: Thirty BALB/c mice were randomly divided into five groups. Four groups of mice received diosmetin (0.25, 0.5, and 1 mg/kg) or vehicle (I/R group) before ischemia. Another group received vehicle without ischemia to serve as a negative control (sham-operated group). Twenty-four hours after reperfusion, serum and renal tissues were harvested to evaluate renal function and histopathologic features. In addition, the expression of inflammation-related proteins, apoptotic molecules, and antioxidant enzymes was analyzed. RESULTS: Compared with sham mice, the I/R group significantly exacerbated renal function and renal tube architecture and increased the inflammatory response and renal tubule apoptosis. Nevertheless, pretreatment with diosmetin reversed these changes. In addition, diosmetin treatment resulted in a marked increase in antioxidant protein expression compared with I/R mice. CONCLUSIONS: The renoprotective effects of diosmetin involved suppression of the nuclear factor-κB and mitochondrial apoptosis pathways, as well as activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Diosmetin has significant potential as a therapeutic intervention to ameliorate renal injury after renal I/R.

Proteomics-based identification of haptoglobin as a favourable serum biomarker for predicting long-term response to splenectomy in patients with primary immune thrombocytopenia.

BACKGROUND: Splenectomy is the most effective treatment for patients with primary immune thrombocytopenia (ITP) who fail to respond to steroid therapy. Thus far, there is no effective means to predict the long-term haematological response of the procedure. The purpose of this study was to identify serum biomarkers as predictors of long-term response based on a proteomics approach. METHODS: The serum samples of ITP patients were collected before splenectomy and seven days after surgery. After depletion of the abundant serum proteins, pooled preoperative serum samples from four responders to splenectomy, four nonresponders and four healthy controls were subjected to two-dimensional gel electrophoresis (2-DE). Nine protein spots with at least a five-fold alteration in expression between responders and nonresponders were all identified as haptoglobin (Hp) by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometer (MS) analysis. The validation of serum Hp expression was performed using enzyme-linked immunosorbent assays (ELISA) in thirty-seven responders, thirteen nonresponders and twenty-one healthy controls. RESULTS: The preoperative serum levels of Hp in the nonresponders (925.9 ± 293.5 µg/ml) were significantly lower than those in the responders (1417.4 ± 315.0 µg/ml, p <0.001) and the healthy controls (1409.1 ± 354.2 µg/ml, p <0.001), while there was no significant difference between the latter two groups. The postoperative serum levels of Hp in responders and nonresponders were (1414.1 ± 225.0 µg/ml) and (952.9 ± 202.4 µg/ml), respectively. There were no significant differences between the serum Hp levels before and after surgery in both responders and nonresponders (p>0.05). The preoperative serum levels of Hp did not significantly correlate with preoperative platelet count of the same blood samples (r = 0.244, p = 0.087), while it positively correlated with postoperative peak platelet count (r = 0.622, p < 0.001). The optimal cutoff value of preoperative serum Hp levels (1173.80 µg/ml) derived from the receiver operating characteristic (ROC) curve led to 78.4% sensitivity and 84.6% specificity. CONCLUSIONS: These results suggest that serum Hp levels may serve as a favourable predictor for the long-term response to splenectomy in ITP and may help to understand the pathophysiological differences between responders and nonresponders.

Possible role of complement activation in renal impairment in trichloroethylene-sensitized guinea pigs.

Recent studies have revealed that trichloroethylene (TCE) can induce occupational medicamentosa-like dermatitis (OMLD) with multi-system injuries, including liver, kidney and skin injuries, which can subsequently cause multiple organ failure later. But the mechanism of immune dysfunction leading to organ injury was rarely clarified. The present study was initiated to analyze the influence of trichloroethylene on renal injury and study the relevant mechanism in guinea pigs. Guinea pig maximization test (GPMT) was carried out. Inflammation on the guinea pigs' skin was scored. Kidney function, urine protein and ultra-structural change of kidney were determined by biochemical detection and electron microscope. Deposition of complement 3 and membrane attack complex (MAC, C5b-9) were determined by immunohistochemistry. Erythema and edema of skin impairment were observed in TCE sensitized groups, and sensitization rate was 63.16%. Through electron microscope, tubular epithelial cell mitochondrial swelling, vacuolar degeneration and atrophy of microvillus were observed in TCE sensitized groups. The parameters of urease and urinary protein elevated markedly, and a high degree of C3 and MAC deposition was found in the renal tubular epithelial cells in TCE sensitized groups. By demonstrating that TCE and its metabolites can cause the deposition of C3 and MAC in renal epithelial cells, we found that activated complement system may be the mechanism of the acceleration and the development of TCE-induced kidney disease.

Laparoscopic splenectomy for immune thrombocytopenic purpura at a teaching institution.

BACKGROUND: High anatomic location, fragility, and generous blood supply of the spleen makes laparoscopic splenectomy (LS) difficult to master, and few patients need splenectomy for benign disorders. The aim of this research was to assess operative outcomes and hematological results of a large series of patients treated with LS for chronic immune thrombocytopenic purpura (ITP) and to determine which clinical variables predict favorable hematological outcome. METHODS: LS was successfully performed for 154 patients with chronic ITP from September 1999 to April 2009 at the First Affiliated Hospital of Sun Yat-sen University. Operative outcomes were assessed retrospectively. Long-term follow-up data were obtained from outpatient medical records and phone interviews. Clinical and laboratory variables (including gender, age, disease duration before surgery, previous response to steroids, preoperative platelet count, and postoperative peak platelet count) were evaluated by univariate analysis to identify potential predictors of hematological outcome. Multivariate Logistic regression model was used to determine independent predictors of hematological outcome. RESULTS: One patient died from subphrenic abscess and postoperative sepsis. The overall major morbidity rate was 8.4%. None of the patients required a second surgery for complications. Of the 127 patients available for a mean follow-up of 43.6 months (range 9 - 114 months), the overall initial response (i.e., at two months after LS) and long-term response to LS were achieved in 89.0% and 80.3%, respectively. Five patients (3.9%) developed pneumonia 3 - 35 months after LS. Univariate analysis showed a significant difference in mean age between responders (29.1 years) and nonresponders (38.8 years; P < 0.05). Patients who responded to steroid therapy had better hematological outcome than those who did not respond (P < 0.05). Compared to nonresponders, responders to LS had a significantly higher postoperative peak platelet count (404 × 10(9)/L versus 213 × 10(9)/L, P < 0.001). Multivariate Logistic regression analysis identified postoperative peak platelet count as the only independent predictor of favorable response to LS (P < 0.001). CONCLUSIONS: LS is a safe and effective treatment for chronic ITP. Postoperative peak platelet count may serve as a major predictor of long-term response.

[Changes of nitric oxide after trichloroethylene irritation in hairless mice skin and protection of ginkgo biloba extract and vitamin E].

OBJECTIVE: To study the changes of nitric oxide (NO) in the BALB/c hairless mice skin after trichloroethylene (TCE) irritation and the protection of ginkgo biloba extract (GbE) and vitamin E (VE). METHODS: 132 BALB/c hairless mice were randomly divided into blank control group, solvent group (olive oil), TCE groups (20%TCE, 40%TCE, 80%TCE and 100%TCE), GbE groups (0.1%GbE, 1%GbE and 10%GbE) and VE groups (5%VE, 10% VE and 20% VE), with 11 animals in each group, 5 for acute irritation test and 6 for the cumulative irritation test. The skin irritation was observed, and the levels of NO in the dorsal skin of BALB/C hairless mice were detected. The kit of NO was used to detect the levels of NO in the dorsal skin of BALB/c hairless mice. RESULTS: (1) The skin presented erythema and edema after TCE irritation both in acute irritation and cumulative irritation test and the skin inflammation showed time-dose effect relationship; the mice skin was protected in GbE or VE groups. (2) In the acute stimulation test, the levels of NO in 80%TCE group (69.895 +/- 9.605 micromol/mg pro) and 100%TCE group (77.273 +/- 9.290 micromol/mg pro) were significantly different compared with blank control group and solvent control group (P < 0.05 or P < 0.01). In the protection group, the NO level were reduced, with the statistically significant differences. (3) In acute irritation test, the levels of NO in 80%TCE group (60.362 +/- 9.817 micromol/mg pro) and 100%TCE group (68.027 +/- 9.354 micromol/mg pro) were significantly different compared with blank control group and solvent control group, (P < 0.05 or P < 0.01); In the protection group, 1% GbE, 10% GbE, 10% VE and 20%VE could reduce the levels of NO, with statistically significant differences. CONCLUSION: TCE can produce the irritation on the dorsal skin of BALB/c hairless mice and induce the significant increase of the NO levels. GbE and VE can protect the skin from TCE irritation damage.

[Role of apoptosis in trichloroethylene induced irritant injury in the skin].

OBJECTIVE: To investigate the expression of apoptosis and caspase-8, cyt c in the skin of the BALB/c mice exposed to trichloroethylene (TCE). METHODS: 30 BALB/c mice were divided in random into the solvent control group, 10% TCE group, 20% TCE group, 40% TCE group, 80% TCE group and 100% TCE group. Apoptotic cells were detected by TUNEL and EM. The expressions of caspase-8 and cyt c were detected with immunohistochemical method. RESULTS: EM showed that the apoptosis of cells was found in the high dosage groups. The immunohistochemical results showed that there were significant differences in the apoptosis rate and the activity of cyt c between the different dosage groups. There was the significant difference in the apoptosis rate between the 40%, 80%, 100% TCE groups the control group (P < 0.01). There was the significant difference in the expression of cyt c between the 20%, 40%, 80%, 100% TCE groups [(2.60 +/- 0.54), (3.42 +/- 0.56), (5.81 +/- 1.30) and (6.00 +/- 0.70), respectively] and the control group (P < 0.01). The expressions of caspase-8 had no significant differences (P > 0.05). CONCLUSION: Apoptosis plays an important role in trichloroethylene induced irritant injury in skin and the apoptosis may be related with the mitochondrial injury.

[Cytotoxicity of trichloroethylene in keratinocytes involving alterations of mitochondrial function and ultrastructure].

OBJECTIVE: To explore mechanism of dermal toxicity of trichloroethylene(TCE). METHODS: Normal human keratinocytes (KC) were isolated from foreskins of healthy donors undergoing circumcision by two-step trypsin digestion and cultured in serum-free medium. Cells were treated with medium, 1% acetone (volume fraction) 0.125, 0.500 or 2.000 mmol/L TCE for different time (4, 8, 12 or 24) hours. After treatment, MTT assay and ATPase activity detected, inhibition ratio of mitochondrial enzyme was calculated according to optical density (A) value of MTT assay. Mitochondrial membrane potential (MMP) was detected by flow cytometry FCM after being stained with Rhodamine123 (Rh123). Morphological changes were also observed through transmission electron microscope (TEM). RESULTS: Cellular viability and ATPase activity declined with dose of TCE, while inhibition ratio of mitochondrial enzyme increased with dose of TCE. FCM results showed that after treatment with 2.000 mmol/L TCE, fluorescence density of Rh123 decreased quickly from 18.73 +/- 0.45(0 h) to 8.20 +/- 0.66(8 h) (P < 0.01). After 8 h, fluorescence density maintained at the level equal to that of 8 h (fluorescence density of Rh123 were 8.20 +/- 0.36 and 8.20 +/- 0.40 for 12 and 24 h respectively, compared with that for 8 h group, P > 0.05). The results also showed that MMP diminished with dose of TCE. Under TEM, mitochondria in TCE-treated group appeared extensive swelling and vacuolar degeneration with less matrix and obscure or vanished mitochondria cristae but in control group, mitochondrial structure was integrated, with uniform matrix and visible mitochondria cristae. CONCLUSIONS: TCE could inhibit mitochondrial metabolic enzyme, reduce ATP production, diminish MMP, and destroy ultrastructure of mitochondria in KC, all these contributing to the cytotoxicity of TCE.