Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.

This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06-2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85-1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17-1.45), and naproxen 400-440 mg (MDp, 1.44; 95% CI, 1.07-1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.

TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.

Statistical enhancement of lipase extracellular production by Bacillus stratosphericus PSP8 in a batch submerged fermentation process.

AIM: The aim of this study was to isolate and identify lipolytic bacteria. Perform a statistical stepwise physicochemical optimization for maximum production of extracellular lipase and its validation in a bioreactor. METHODS AND RESULTS: Several lipolytic bacteria were isolated from petroleum hydrocarbon-polluted soil. The strain expressing the highest lipase activity (47 U ml-1 ) was genetically identified as Gram-positive Bacillus stratosphericus PSP8 (NCBI GenBank accession no. MH120423). The response surface methodology (RSM)-central composite face centre (CCF) design of experiments was performed based on the preselected levels of the studied parameters obtained from the performed one-factor-at-a-time sequential experiments. A second-order polynomial model was predicted and improved the lipase production by approximately 1·6-fold. Preliminary scaling up of the validated optimized process was carried out in a batch 10-l stirred tank bioreactor, applying the optimum predicted operating conditions; pH 6·98, 34·8°C, 2·2 × 106 cells per ml, 200 rev min-1 , 4·82 g l-1 tributyrine concentration, 1% sucrose and 0·1% yeast extract. This yielded 89 U ml-1 at the late log phase of bacterial growth (48 h). Logistic kinetic model effectively characterized the submerged fermentation process, and the maximum specific growth and lipase production rates were estimated to be 0·338 and 0·164 h-1 respectively. CONCLUSIONS: The mesophilic and neutrophilic B. stratosphericus PSP8 isolated from petroleum hydrocarbon-contaminated soil is a proper source of lipase. The closeness of the predicted response with that of the experimental value and the enhancement of lipase productivity in fermenter scale by approximately 1·9-fold, showed that statistically optimized design can be used in order to improve the lipase production to meet the increasing demand. SIGNIFICANCE AND IMPACT OF THE STUDY: The RSM-CCF statistical optimization is useful for optimizing a large number of variables and studying their interactive effects on extracellular lipase production.

Dietary patterns and the risk of coronary heart disease among Jordanians: A case-control study.

BACKGROUND AND AIMS: Dietary pattern and lifestyle have been reported to be significant risk factors in the development of coronary heart diseases (CHD). The contribution degree of these dietary risk factors in CHD development in non-westernized countries is unclear. This study aimed to evaluate several dietary choices and their potential association with CHD. METHODS AND RESULTS: A case-control study was conducted at Prince Hamza Hospital, a referral center for coronary angiography in Amman, Jordan. Four-hundred patients referring for elective coronary angiography with clinical suspicion of coronary artery disease were enrolled. Data was collected using interview-based questionnaires. Dietary patterns were derived using Principal Component Analysis. Multivariate logistic regression was used to estimate the relationship between dietary choices and CHD. Three dietary patterns were identified. The "Healthy Dietary Pattern", which presented a diet rich in olive oil, fruits, vegetables, legumes, whole grains, fish, and low meat intake, was associated with a significant decrease in the odds of CHD (OR = 0.53, 95% CI = 0.28-0.98). The "High-Fiber Pattern", which is mainly composed of legumes and bulgur, significantly reduced the odd of CHD (OR = 0.55, 95% CI = 0.27-0.92) for the fourth quartile compared to the first one. No significant association was found between CHD and the "Western Dietary Pattern", which is loaded with refined grains, sweets and deserts, sugary drinks, and deep fried foods. CONCLUSIONS: The "Healthy Dietary Pattern" and the "High-Fiber Pattern" were associated with a decrease in odds of CHD among Jordanians.

Assessment of seminal mast cells in infertile men with varicocele after surgical repair.

This study aimed to assess seminal mast cells in infertile men associated with varicocele (Vx) pre- and post-surgical repair. Forty-five infertile men associated with Vx were subjected to history taking and clinical examination. In addition, semen parameters and seminal mast cells stained with 1% toluidine blue were estimated pre-varicocelectomy and three months post-varicocelectomy. Vx surgical repair revealed a significant improvement in the mean sperm concentration, progressive sperm motility, total sperm motility and sperm abnormal morphology and a significant decrement in seminal mast cells (mean ± SD, 3.56 ± 2.23 cells per high-power field (HPF) vs. 2.22 ± 1.06 cells per HPF, p = .01). The pre-operative mean mast cell count demonstrated significant increases in cases with Vx grade III compared with other Vx grades and in cases with bilateral Vx compared with unilateral Vx cases. Seminal mast cells demonstrated a significant correlation with sperm concentration, progressive sperm motility and total sperm motility and a nonsignificant correlation with age and sperm abnormal morphology. It is concluded that seminal mast cells decrease significantly in infertile men with Vx after surgical repair showing a significant negative correlation with sperm concentration, progressive sperm motility and total sperm motility.

Genetic diversity of multidrug resistant Staphylococcus aureus isolated from clinical and non clinical samples in Egypt.

In recent years, the increasing incidence of diseases caused by Staphylococcus aureus (S. aureus) has been noted in the university hospitals of El-Sharkia and Assuit governorates - Egypt. Therefore, we studied the genetic relatedness of multidrug resistant S. aureus isolates from different sources in the above mentioned governorates. One hundred and fifty six S. aureus isolates were divided into 5 different groups, 1 non clinical isolates from different food products and 4 different clinical isolates of human and animal sources in the 2 different governorates. Epidemiological characteristics of 156 S. aureus isolates were determined by phenotypic methods including quantitative antibiogram typing and biofilm production. Genetic typing of 35 multidrug resistant (MDR) isolates (7 from each group) based on 16S rRNA gene sequence, virulence and antimicrobial resistance gene profiles was done. The genetic relatedness of the highest virulent strain from each group was detected based on different single locus sequence typing and multi-locus sequence typing (MLST). S. aureus strains isolated from different sources and geographical areas showed high diversity. The genetic typing revealed different sequence types and different sequences of coa and spa genes. S. aureus isolates were found highly diverse in Egypt.

Characterization of Methicillin Resistant Staphylococcus aureus isolated from human and animal samples in Egypt.

Staphylococcus aureus (S. aureus) has been one of the most problematic pathogens. Methicillin Resistant S. aureus (MRSA) has emerged as a major concern for both human and animal. Antibiotic resistance genes dissemination might be possible between human and animal bacteria. The aim of this study is to show phenotypic and genotypic diversity of human and animal MRSA isolates. Antibiogram typing and biofilm production were used as a primary phenotypic typing tool for the characterization of (40) animal and (38) human MRSA isolates. Genetic typing based on sequencing of 16S rRNA gene and virulence gene profiles were done. Antimicrobial resistance profiles of the animal isolates showed little evidence of widespread of resistance, although this was seen in many human isolates. The biofilm production was detected in higher percentage among animal isolates. Based on the genetic typing and multiple antibiotic resistance (MAR) index, the majority of animal isolates clustered into lineages that were not found in human isolates. Animal and human MRSA isolates showed diversity in antibiotic resistance and virulence gene profiles may be due to host adaptation or chances for contamination between the two hosts were not present in our study.

Assessment of genotoxicity of waterpipe smoking using 8-OHdG biomarker.

Waterpipe tobacco smoking is increasing in popularity, particularly among young adults. This popularity is related to the lack knowledge regarding the health effects of waterpipe smoking. In this study, we examined the genotoxicity of waterpipe smoking using an 8-hydroxy deoxyguanosine (8-OHdG) assay. Genotoxicity was evaluated in the saliva, urine, and serum of 66 waterpipe adult smokers and 46 healthy nonsmokers. The level of addiction to waterpipe smoking was evaluated using the Lebanon Waterpipe Dependence Scale-11. Levels of 8-OHdG in the samples were measured using commercially available enzyme-linked immunosorbent assays. Levels of 8-OHdG in the saliva (52,430 ± 2923 vs 48,430 ± 4189 pg/mL), urine (2815 ± 312 vs 2608 ± 180 pg/mL), and serum (19,720 ± 202 vs 19,670 ± 254 pg/mL) were similar between waterpipe smokers and nonsmokers (P > 0.05). In addition, no correlations were found between dependence score and levels of 8-OHdG in all sample types. In conclusion, 8-OHdG is not a good biomarker for genotoxic effect of waterpipe smoking.

Mesial Temporal Sclerosis: Accuracy of NeuroQuant versus Neuroradiologist.

BACKGROUND AND PURPOSE: We sought to compare the accuracy of a volumetric fully automated computer assessment of hippocampal volume asymmetry versus neuroradiologists' interpretations of the temporal lobes for mesial temporal sclerosis. Detecting mesial temporal sclerosis (MTS) is important for the evaluation of patients with temporal lobe epilepsy as it often guides surgical intervention. One feature of MTS is hippocampal volume loss. MATERIALS AND METHODS: Electronic medical record and researcher reports of scans of patients with proved mesial temporal sclerosis were compared with volumetric assessment with an FDA-approved software package, NeuroQuant, for detection of mesial temporal sclerosis in 63 patients. The degree of volumetric asymmetry was analyzed to determine the neuroradiologists' threshold for detecting right-left asymmetry in temporal lobe volumes. RESULTS: Thirty-six patients had left-lateralized MTS, 25 had right-lateralized MTS, and 2 had bilateral MTS. The estimated accuracy of the neuroradiologist was 72.6% with a κ statistic of 0.512 (95% CI, 0.315-0.710) [moderate agreement, P < 3 × 10(-6)]), whereas the estimated accuracy of NeuroQuant was 79.4% with a κ statistic of 0.588 (95% CI, 0.388-0.787) [moderate agreement, P < 2 × 10(-6)]). This discrepancy in accuracy was not statistically significant. When at least a 5%-10% volume discrepancy between temporal lobes was present, the neuroradiologists detected it 75%-80% of the time. CONCLUSIONS: As a stand-alone fully automated software program that can process temporal lobe volume in 5-10 minutes, NeuroQuant compares favorably with trained neuroradiologists in predicting the side of mesial temporal sclerosis. Neuroradiologists can often detect even small temporal lobe volumetric changes visually.

Evening primrose oil and celecoxib inhibited pathological angiogenesis, inflammation, and oxidative stress in adjuvant-induced arthritis: novel role of angiopoietin-1.

Rheumatoid arthritis is a chronic inflammatory disease characterized by overproduction of inflammatory mediators along with undermined oxidative defensive mechanisms. Pathological angiogenesis was found to play a critical role in the progression of this disease. The current study was carried out to evaluate the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the right hind paw of male albino rats. All treatments were administered orally from day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till day 27 after CFA injection. In the arthritic group, the results revealed significant decrease in the body weight and increase in ankle circumference, plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-α) levels. Anti-oxidant status was suppressed as manifested by significant decline in reduced glutathione content along with decreased enzymatic activity of superoxide dismutase and increased lipid peroxidation. Oral administration of EPO exerted normalization of body weight, ANG-1, and TNF-α levels with restoration of activity as shown by reduced malondialdehyde levels. Moreover, histopathological examination demonstrated that EPO significantly reduced the synovial hyperplasia and inflammatory cells invasion in joint tissues, an effect that was enhanced by combination with aspirin or celecoxib. The joint use of GLA-rich natural oils, which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities, with traditional analgesics represents a promising strategy to restrain the progression of rheumatoid arthritis.

Deletion of thioredoxin-interacting protein preserves retinal neuronal function by preventing inflammation and vascular injury.

BACKGROUND AND PURPOSE: Retinal neurodegeneration is an early and critical event in several diseases associated with blindness. Clinically, therapies that target neurodegeneration fail. We aimed to elucidate the multiple roles by which thioredoxin-interacting protein (TXNIP) contributes to initial and sustained retinal neurodegeneration. EXPERIMENTAL APPROACH: Neurotoxicity was induced by intravitreal injection of NMDA into wild-type (WT) and TXNIP-knockout (TKO) mice. The expression of apoptotic and inflammatory markers was assessed by immunohistochemistry, elisa and Western blot. Microvascular degeneration was assessed by periodic acid-Schiff and haematoxylin staining and retinal function by electroretinogram. KEY RESULTS: NMDA induced early (1 day) and significant retinal PARP activation, a threefold increase in TUNEL-positive nuclei and 40% neuronal loss in ganglion cell layer (GCL); and vascular permeability in WT but not TKO mice. NMDA induced glial activation, expression of TNF-α and IL-1ß that co-localized with Müller cells in WT but not TKO mice. In parallel, NMDA triggered the expression of NOD-like receptor protein (NLRP3), activation of caspase-1, and release of IL-1ß and TNF-α in primary WT but not TKO Müller cultures. After 14 days, NMDA induced 1.9-fold microvascular degeneration, 60% neuronal loss in GCL and increased TUNEL-labelled cells in the GCL and inner nuclear layer in WT but not TKO mice. Electroretinogram analysis showed more significant reductions in b-wave amplitudes in WT than in TKO mice. CONCLUSION AND IMPLICATIONS: Targeting TXNIP expression prevented early retinal ganglion cell death, glial activation, retinal inflammation and secondary neuro/microvascular degeneration and preserved retinal function. TXNIP is a promising new therapeutic target for retinal neurodegenerative diseases.

15-PGDH inhibitors: the antiulcer effects of carbenoxolone, pioglitazone and verapamil in indomethacin induced peptic ulcer rats.

BACKGROUND AND AIM: 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the enzyme responsible for prostaglandins (PGs) metabolism. PGs have an important role in the protection of stomach mucosa against destructive stimuli. The aim of the present study is to investigate the inhibitory effect of carbenoxolone, pioglitazone and verapamil on 15-PGDH enzyme. MATERIALS AND METHODS: The experiments were carried out in the Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt from May 2011 to August 2011. Adult male albino rats were fasted for 18 hours before administration of high dose of indomethacin (30 mg/kg, p.o.), except for the negative control group which received saline only, followed by pyloric ligation to induce acute gastric ulcers. The rats were pretreated orally with saline, pioglitazone (20 mg/kg), verapamil (25 mg/kg), carbenoxolone (30 mg/kg) or their combinations 30 minutes before indomethacin. The rats were sacrificed after four hours of pyloric ligation. The effects of the previous treatments on the ulcer index (Ui), the microscopic appearance of gastric mucosa, the gastric acid output, the gastric barrier mucus content, and 15-PGDH enzyme activity were determined. RESULTS: Indomethacin resulted in severe ulceration and increased gastric acid output (p < 0.05) compared to negative control. The rats pretreated with carbenoxolone, pioglitazone, verapamil had reduced ulcer index, gastric acid output and 15-PGDH activity (p < 0.05) compared to either indomethacin group or the negative control group. Individual treatments with carbenoxolone, pioglitazone or verapamil increased gastric barrier mucus (p < 0.05) compared to either indomethacin group or the negative control group. The combinations of verapamil with either carbenoxolone or pioglitazone caused further reduction in ulcer index, gastric acid output and 15-PGDH activity (p < 0.05), while causing further increase in gastric barrier mucus (p < 0.05) compared to their respective individual treatment group. CONCLUSIONS: The antiulcer properties of pioglitazone and verapamil are, in part, consequences of their inhibitory effect on the enzyme 15-PGDH, responsible for PGs degradation, and the resultant prolongation of PGE2 biological activity in rat stomach mucosa.

Residue levels of organochlorine pesticides in some ecosystem components of Manzala Lake.

To evaluate the organochlorine pesticide (OCP) contamination of Manzala Lake, its ecosystem was investigated during the winter season (December to March). The studied ecosystem components were water, sediment, aquatic weeds, and fishes in four locations. The samples were analyzed by gas chromatography with electron capture detector. Pollutant levels of total OCPs showed significantly high levels in the water areas of Round road (46.253 ng/ml), Port-Said Damietta road (19.301 ng/ml), followed by Bughas El-Rasoah (5.539 ng/ml), then Ashtoum El Gamel (natural reserve area now) (0.289 ng/ml). Organochlorines were detected in sediment only in Round road (3.359 µg/kg) and Port-Said Damietta road (0.171 µg/kg) by significant order while they were undetectable in Ashtoum El Gamel and Bughas El-Rasoah. Total OCPs in aquatic weeds ranged between 0.194 µg/kg in Port-Said Damietta and 0.026 µg/kg in Ashtoum El Gamel. While OCPs were 0.160 and 0.153 µg/kg in Round road and Bughas El-Rasoah, respectively. Concerning fish muscles OCPs were significantly higher in the Round road area (0.397 µg/kg) followed by the Port-Said Damietta road (0.258 µg/kg), and finally, Ashtoum El Gamel samples (0.126 µg/kg). The results revealed the direct relation for the accumulation of OCPs between studied ecosystem parameters at the Manzala Lake during the winter season. Results also demonstrated that fish samples collected from the Manzala Lake in the studied areas were contaminated with levels of organochlorines, not higher than the maximum permissible level recorded by FAO/WHO, and that the public is not at risk with fish consumption.

SGI-110: DNA Methyltransferase Inhibitor Oncolytic.

SGI-110 is a second-generation hypomethylating prodrug whose active metabolite is the well-characterized drug decitabine. This novel compound is an oligonucleotide consisting of decitabine linked through a phosphodiester bond to the endogenous nucleoside deoxyguanosine. The dinucleotide configuration provides protection from drug clearance by deamination, while maintaining at least equivalent effects on gene-specific and global hypomethylation both in vitro and in animal model systems. This agent is currently being tested in phase I and II clinical trials in humans and has been demonstrated to be safe and well tolerated as a single agent, with evidence of promising activity in heavily pretreated (including currently FDA approved hypomethylating drugs) myelodysplastic syndrome and acute myeloid leukemia patients. Ongoing trials are also open in platinum-resistant ovarian cancer and hepatocellular carcinoma.

Waterpipe tobacco and cigarette smoking among university students in Jordan.

SETTING: While waterpipe and cigarette smoking have been well studied in Syria and Lebanon, data from Jordan are limited. OBJECTIVES: To characterize the relative prevalence of waterpipe tobacco and cigarette smoking among university students in Jordan, and to compare the demographic and environmental factors associated with each form of tobacco use. DESIGN: We surveyed 1845 students randomly recruited from four universities in Jordan. We used multivariable logistic regression controlling for clustering of individuals within universities to determine associations between demographic and environmental covariates and waterpipe tobacco and cigarette use. RESULTS: Waterpipe tobacco smoking rates were 30% in the past 30 days and 56% ever, while cigarette smoking rates were 29% in the past 30 days and 57% ever. Past 30-day waterpipe tobacco smoking rates were 59% for males and 13% for females. Females had substantially lower odds than males of being current waterpipe (OR 0.12, 95%CI 0.10-0.15) or cigarette (OR 0.08, 95%CI 0.05-0.14) smokers. Current cigarette smoking was more significantly associated with markers of high socio-economic status (SES) than waterpipe tobacco smoking. CONCLUSION: Waterpipe tobacco smoking is as common as cigarette smoking among Jordanian university students. While cigarette smoking is consistently associated with high SES, waterpipe tobacco smoking is more evenly distributed across various populations.

Eicosapentaenoic acid ablates valproate-induced liver oxidative stress and cellular derangement without altering its clearance rate: dynamic synergy and therapeutic utility.

The omega-3 fatty acid eicosapentaenoic acid (EPA) is a superb nature's medicine, with still unfolding health benefits. Because hepatotoxicity is a prominent adverse drug reaction, we currently attempted a new approach in which EPA was challenged to both alleviate hepatotoxicity and provide synergy with anticonvulsant effects of valproate (VPA). Besides, we verified whether EPA may kinetically modulate the clearance rate of VPA. VPA (500mg/kg p.o., for 2weeks) caused rat hepatotoxicity that was manifested as notable (2- to 4-fold) rise in serum liver enzymes (GGT, ALT, and ALP), increased hepatic levels of lipid peroxides and TNF-α (3- and 7-fold) and activity of myeloperoxidase (MPO, 4-fold), lowering of serum albumin (42%), and depletion of liver reduced glutathione (GSH, 36%). Furthermore, histopathologic examination revealed hepatocellular degeneration, focal pericentral necrosis, infiltration of inflammatory cells, and steatosis. Joint treatment with EPA (300mg/kg) blunted the oxidative stress, TNF-α levels and MPO activity, while enhanced levels of serum albumin and hepatic GSH. EPA also ameliorated most of the hepatocellular anomalies evoked by VPA. Additionally, in a mouse PTZ convulsion model, EPA markedly augmented the anticonvulsant effects of VPA far beyond their single responses. On the other hand, pharmacokinetic analyses revealed that joint EPA administration had no effect on serum VPA concentrations. Collectively, results demonstrate for the first time that the ω-3 FA (EPA) markedly alleviated VPA-induced hepatotoxicity, oxidative stress, and inflammation, while enhanced its anticonvulsant effects without altering its clearance. Therapeutically, these protective and synergy profiles for EPA foster a more safe and efficacious drug combination regimen than VPA.

Evaluation of renal protective effects of the green-tea (EGCG) and red grape resveratrol: role of oxidative stress and inflammatory cytokines.

Epigallocatechin-gallate (EGCG) and resveratrol (RSVL) are two of the most promising natural medicines. We verified their capacity to ameliorate cisplatin (CP)-induced disruption of renal glomerular filtration rate (GFR) in rats, and sought the mediatory involvement of lipid peroxidation (malondialdehyde [MDA]-level) and inflammatory cytokine (TNF-α) therein. CP (10 mg kg⁻¹), a single i.p. dose, disrupted GFR (11-fold-rise in proteinuria, 2-5-fold rise in serum creatinine/urea levels) after 7 days, and killed all animals after 10 days. Kidney-homogenates from CP-treated rats displayed higher MDA and TNF-α, but lower reduced-glutathione (GSH) levels. Rats treated with EGCG (50 mg kg⁻¹, but not 25 mg kg⁻¹) had no fatalities and showed significantly-recovered GFR; while their kidney-homogenates had markedly reduced MDA, TNF-α and enhanced GSH levels at 7 days. Conversely, RSVL or quercetin (25, 50 mg kg⁻¹) neither improved GFR nor reduced (MDA)/TNF-α levels after 7 days. Resuming treatment with 50 mg kg⁻¹ for 10 days rescued only 25% of animals (p > 0.05). Correlation studies showed a significant association between creatinine level, and each of MDA (r = 0.91), GSH (r = -0.87), and TNF-α (0.91). The study showed for the first time that EGCG, unlike RSVL, can protect against CP-induced nephrotoxicity. At the molecular level, CP triggers a high level of oxidative stress and systemic inflammation, events that were all abrogated with EGCG; better than RSVL or quercetin.

Sentinel surveillance for patients with acute hepatitis in Egypt, 2001-04.

Viral hepatitis is a major problem in Egypt. To define the epidemiology of the disease, sentinel surveillance was established in 5 hospitals in diverse areas of the country in 2001. Data were completed for patients meeting the case definition for viral hepatitis. Of a total of 5909 patients evaluated, 4189 (70.9%) showed positive antibody markers for hepatitis. Out of those, 40.2% had evidence of hepatitis A virus (HAV) infection, 30.0% hepatitis B virus (HBV) and 29.8% hepatitis C virus (HCV) infection. This surveillance system was useful in identifying the variable endemicity of acute HAV infection in different regions and for better understanding the epidemiology of HBV and HCV infection.

Sentinel surveillance for patients with acute hepatitis in Egypt, 2001-04

Viral hepatitis is a major problem in Egypt. To define the epidemiology of the disease, sentinel surveillance was established in 5 hospitals in diverse areas of the country in 2001. Data were completed for patients meeting the case definition for viral hepatitis. Of a total of 5909 patients evaluated, 4189 [70.9%] showed positive antibody markers for hepatitis. Out of those, 40.2% had evidence of hepatitis A virus [HAV] infection, 30.0% hepatitis B virus [HBV] and 29.8% hepatitis C virus [HCV] infection. This surveillance system was useful in identifying the variable endemicity of acute HAV infection in different regions and for better understanding the epidemiology of HBV and HCV infection