Ultrasound promoted green synthesis,anticancer evaluation,and molecular docking studies of hydrazines: a pilot trial

We reported herein an efficient, environmentally friendly synthesis of hydrazine carboxamides (6a–l) in a water-glycerol (6:4) solvent system using ultrasonic irradiation. Ultrasonicated reactions were found to be much faster and more productive than conventional synthesis. The prepared compounds (6a–l) were tested against nine panels of 60 cancer cell lines according to the National Cancer Institute (NCI US) protocol. N-(4-Chlorophenyl)-2-(2-oxoindolin-3-ylidene)hydrazine-1-carboxamide (6b) was discovered to be promising anticancer agents with higher sensitivity against CCRF-CEM, HOP-92, UO-31, RMPI-8226, HL-60(TB), and MDA-MB-468 with percent growth inhibitions (%GIs) of 143.44, 33.46, 33.21, 33.09, 29.81, and 29.55 respectively. Compounds (6a–l) tested showed greater anticancer activity than Imatinib, except for compound 6k. Compounds 6b and 6c were found to be lethal on the CCRF-CEM leukaemia cell line, with %GIs of 143.44 and 108.91, respectively. Furthermore, molecular docking analysis was performed to investigate ligand binding affinity at the active site of epidermal growth factor (EGFR).     

Safety and Effectiveness of Mycophenolate in Systemic Sclerosis. A Systematic Review

BackgroundMycophenolate is increasingly being used in the rheumatic diseases. Its main adverse effects are gastrointestinal, myelosuppression, and infection. These may limit use in systemic sclerosis (SSc) since gastrointestinal involvement is common. The objective of this study is to evaluate gastrointestinal adverse events of mycophenolate in SSc. Secondarily we evaluated other adverse events, and the effectiveness of mycophenolate in skin and lung disease.MethodsA literature search of Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL (inception-2013) was performed. Studies reporting use of mycophenolate in SSc patients, adverse events, modified Rodnan skin score (MRSS), forced vital capacity (FVC), or diffusing capacity of carbon monoxide (DLCO) were included. The primary outcome was gastrointestinal events occurring after the initiation of mycophenolate. Secondary safety outcomes included myelosuppression, infection, malignancy, and death after the initiation of mycophenolate.Results617 citations were identified and 21 studies were included. 487 patients were exposed to mycophenolate. The mean disease duration ranged between 0.8-14.1 years. There were 18 deaths and 90 non-lethal adverse events. The non-lethal adverse events included 43 (47.7%) gastrointestinal events, 34 (26%) infections, 6 (5%) cytopenias and 2 (2%) malignancies. The most common gastrointestinal events included diarrhea (n=18 (14%)), nausea (n=12 (9%)), and abdominal pain (n=3 (2%)). The rate of discontinuation ranged between 8%-40%. Seven observational studies reported improvement or stabilization in FVC, and 5 studies report stabilization or improvement in MRSS.ConclusionMycophenolate-associated gastrointestinal adverse events are common in SSc, but not severe enough to preclude its use. Observational data suggests mycophenolate may be effective in improving or stabilizing interstitial lung disease, and skin involvement.     

Cessation of Mass Drug Administration for Lymphatic Filariasis in Zanzibar in 2006: Was Transmission Interrupted?

BackgroundLymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4–6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped.ConclusionsOur findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.     

Diagnostic accuracy of the TIMI risk score in patients with chest pain in the emergency department: a meta-analysis

Background

The Thrombolysis in Myocardial Infarction (TIMI) risk score uses clinical data to predict the short-term risk of acute myocardial infarction, coronary revascularization or death from any cause. It was originally developed for use in patients with unstable angina or non–ST-elevation myocardial infarction. We sought to expand the clinical application of the TIMI risk score by assessing its prognostic accuracy in patients in the emergency department with potential acute coronary syndromes.

Methods

We searched five electronic databases, hand-searched reference lists of included studies and contacted content experts to identify articles for review. We included prospective cohort studies that validated the TIMI risk score in emergency department patients. We performed a meta-regression to determine whether a linear relation exists between TIMI risk score and the cumulative incidence of cardiac events.

Results

We included 10 prospective cohort studies (with a total of 17 265 patients) in our systematic review. Data were available for meta-analysis in 8 of the 10 studies. Of patients with a score of zero, 1.8% had a cardiac event within 30 days (sensitivity 97.2%, 95% CI 96.4–97.8; specificity 25.0%, 95% CI 24.3–25.7; positive likelihood ratio 1.30, 95% CI 1.28–1.31; negative likelihood ratio 0.11, 95% CI 0.09–0.15). Meta-regression analysis revealed a strong linear relation between TIMI risk score (p < 0.001) and the cumulative incidence of cardiac events.

Interpretation

Although the TIMI risk score is an effective risk stratification tool for patients in the emergency department with potential acute coronary syndromes, it should not be used as the sole means of determining patient disposition.Chest pain is a common presenting complaint in the emergency department that requires efficient risk stratification, timely initiation of treatment in high-risk patients and safe determination of patient disposition. Several studies have been published that stratify the risk of patients in the emergency department with chest pain.^1–5 However, only the Thrombolysis in Myocardial Infarction (TIMI) risk score, which was initially developed for use in patients with unstable angina or non–ST-segment elevation myocardial infarction or both,⁶ has been broadly validated in several independent emergency department populations with chest pain and thus constitutes the highest level of evidence available.The TIMI risk score assigns each of seven predictors a value of one point, allowing stratification of patients into one of eight prognostic categories (Box 1).⁶ The clinical end points are acute myocardial infarction, coronary revascularization and death from any cause.

Box 1.?Predictor variables included in the TIMI risk score^*

• Age of more than 65 years
• Three or more risk factors for atherosclerosis
• Known coronary artery disease
• Two or more episodes of anginal chest pain in the preceding 24 hours
• Acetylsalicylic acid use in the seven days before hospitalization
• ST-segment deviation of 0.05 mV or more
• Elevated cardiac markers

A robust estimate of the performance of the TIMI risk score obtained from a systematic review may prove useful to both clinicians and researchers. Clinicians would have a reliable quantitative estimate of a patient’s short-term risk of a cardiac event. This could be used as an adjunct to clinical acumen and as a tool to communicate risk to patients in a shared decision-making model of care.⁷ Researchers would also have an estimate of the prognostic accuracy of the TIMI risk score derived from different practice settings and patient populations that represent a wide variety of ethnic backgrounds. This estimate may serve as a useful baseline for comparison as emerging clinical prediction rules and imaging modalities continue to refine our approach to diagnosis and risk stratification in patients in the emergency department with potential acute coronary syndromes.We conducted a comprehensive systematic review and meta-analysis to assess the methodological quality and prognostic performance of studies that had prospectively validated the TIMI risk score in patients in the emergency department.     

Homozygosity for a Missense Mutation in SERPINH1, which Encodes the Collagen Chaperone Protein HSP47, Results in Severe Recessive Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is characterized by bone fragility and fractures that may be accompanied by bone deformity, dentinogenesis imperfecta, short stature, and shortened life span. About 90% of individuals with OI have dominant mutations in the type I collagen genes COL1A1 and COL1A2. Recessive forms of OI resulting from mutations in collagen-modifying enzymes and chaperones CRTAP, LEPRE1, PPIB, and FKBP10 have recently been identified. We have identified an autosomal-recessive missense mutation (c.233T>C, p.Leu78Pro) in SERPINH1, which encodes the collagen chaperone-like protein HSP47, that leads to a severe OI phenotype. The mutation results in degradation of the endoplasmic reticulum resident HSP47 via the proteasome. Type I procollagen accumulates in the Golgi of fibroblasts from the affected individual and a population of the secreted type I procollagen is protease sensitive. These findings suggest that HSP47 monitors the integrity of the triple helix of type I procollagen at the ER/cis-Golgi boundary and, when absent, the rate of transit from the ER to the Golgi is increased and helical structure is compromised. The normal 3-hydroxylation of the prolyl residue at position 986 of the triple helical domain of proα1(I) chains places the role of HSP47 downstream from the CRTAP/P3H1/CyPB complex that is involved in prolyl 3-hydroxylation. Identification of this mutation in SERPINH1 gives further insight into critical steps of the collagen biosynthetic pathway and the molecular pathogenesis of OI.     

Characterization of a variant <Emphasis Type="Italic">vlhA</Emphasis> gene of <Emphasis Type="Italic">Mycoplasma synoviae</Emphasis>, strain WVU 1853, with a highly divergent haemagglutinin region

Background  

In Mycoplasma synoviae, type strain WVU 1853, a single member of the haemaglutinin vlhA gene family has been previously shown to be expressed. Variants of vlhA are expressed from the same unique vlhA promoter by recruiting pseudogene sequences via site-specific recombination events, thus generating antigenic variability. Using a bacterial stock of M. synoviae WVU 1853 that had been colony purified thrice and maintained in our laboratory at low passage level, we previously identified a vlhA gene-related partial coding sequence, referred to as MS2/28.1. The E. coli-expressed product of this partial coding sequence was found to be immunodominant, suggesting that it might be expressed.     

Schizogony in Haemoproteus columbae Kruse.

To fill in some of the gaps in our knowledge of Schizogony of Haemoproteus columbae Kruse, transmission experiments involving inoculation into pigeons (Columba livia Gmelin) of sporozonites from salivary glands of the hippoboscid fly Pseudolynchia canariensis (Macquart) were carried out. We were unable to detect prepatent schizonts or to observe schizogonic development when infection became chronic. Schizonts were mainly confined to lung tissue. Observations of parapatent schizonts were made in smears and tissue sections. A variety of forms was found. Cytomeres were rarely encountered. Two types of morphologically distinct merozoites were seen. One type was twice as large as large as the other and was thought to repeat the process of schizogony several times before invading erythrocytes. Schizonts with cytoplasmic clefts were not common in our material due to the fixatives used (Bouin's and Carnoy's). Merozoites were occasionally observed inside monocytes, probably being phagocytosed.     

Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat

We report the optimization of a series of non-steroidal GR antagonists that led to the identification of compound 7. This compound is efficacious when dosed orally in an olanzapine-induced weight gain model in rats.     

Overview of the management of heavy metals toxicity by microalgae

Journal of Applied Phycology - Microalgae are among the oldest life forms on Earth and over centuries of evolution they have developed adaptive mechanisms that allow them to survive harsh...     

Attitude and awareness of public towards genetic testing in Riyadh,Saudi Arabia

The current study was designed to evaluate the attitude of the Saudi general population towards knowledge, perception and awareness about genetic testing. Using a convenience sampling technique, an online survey was used to collect the data. The survey consisted of 16 questions that covered basic demographics and several scenarios that assess subjects’ perceptions regarding genetic testing. Answering all questions was required for completing the survey. Among 333 subjects, 53.5% were male, 18.9% were married, and 99.4% were muslims. Around 75% has/will have a bachelor degree. About 59% were students. About 87% would consider genetic testing before marriage and similar percentage would not consider conceiving a child if the genetic screening indicated that there is 100% chance the child will be born with genetic disorder. Neither marital status (Single = 87.04%, married = 87.30% (P = 0.955)) nor gender (male = 85.96, female = 88.39 (P = 0.509)) affected the aforementioned decision. When subjects were asked if they would choose abortion knowing that the embryo has a severe genetic disorder, 62.7% answered yes. In general, 80.4% were willing to be recruited into a genetics study, married subjects were more reluctant to be recruited compared to singles (30% and 17% (P = 0.018) respectively). There was no difference between males and females in the decision of joining a genetic study. Also 78.4% supported creation of genetic disease database and family maps. 69.7% of the participants supported government enforcement of the genetic testing, 56.2% supported government-run facilities for Saudi citizens to have genetic tests. We conclude that married people were in favor of genetic testing than the single counterparts, secondly, single status people supported the idea of having genetic tests before their marriage they were supportive of the idea of the government taking a leading role in enforcing the genetic testing and creation of the genetic banks.