Assessing the value of CAN-gene mutations using MALDI-TOF MS

Purpose

To identify cancer-linked genes, Sjöblom et al. and Wood et al. performed a genome-wide mutation screening in human breast and colorectal cancers. 140 CAN-genes were found in breast cancer, which in turn contained overall 334 mutations. These mutations could prove useful for diagnostic and therapeutic purposes.

Methods

We used a MALDI-TOF MS 40-plex assay for testing 40 loci within 21 high-ranking breast cancer CAN-genes. To confirm mutations, we performed single-plex assays and sequencing.

Results

In general, the mutation rate of the analyzed loci in our sample cohort was very low. No mutation from the 40 loci analyzed could be found in the 6 cell lines. In tissue samples, a single breast cancer tissue sample showed heterozygosity at locus c.5834G>A within the ZFYVE26 gene (Zinc finger FYVE domain-containing gene 26).

Conclusions

Sjöblom et al./Wood et al. already showed that the vast majority of CAN-genes are mutated at very low frequency. Due to the fact that we only found one mutation in our cohort, we therefore assume that at the selected loci, mutations might be low-frequency events and therefore, more rarely detectable. However, further evaluation of the CAN-gene mutations in larger cohorts should be the aim of further studies.     

Efficacy of pharmacological and non-pharmacological interventions on low sexual interest/arousal of peri- and post-menopausal women: a meta-analysis

ABSTRACT

The aim of our study was to investigate the therapeutic efficacy of pharmacological and non-pharmacological interventions on low sexual interest/arousal of peri- and post-menopausal women. In this systematic review and meta-analysis, randomized clinical trials (RCTs) that published up to 22 June 2016 were retrieved from several online electronic databases, including Cochrane Library, PubMed, Ovid, Scopus, Medline, CINHAL, and EBSCO. Fifty-seven studies were included in the meta-analysis. The results showed that both pharmacological interventions (mean difference (MD) = –0.86, 95% confidence interval (CI) = –1.49 to –0.90, p = 0.0001) and non-pharmacological interventions (MD = –0.92, 95% CI = –1.35 to –0.49, p = 0.0001) had statistically significant effects on improving sexual interest/arousal. Among pharmacological interventions, hormone therapy with dehydroepiandrosterone, testosterone, tibolone and estrogen in combination with progesterone, estrogen in combination with testosterone as well as estrogen in combination with progesterone and testosterone were found to be effective. Non-hormonal medications including flibanserin and sildenafil as well as herbal medicines were also shown to be effective. However, due to high heterogeneity of the findings and scarcity of the studies in certain domains, there is uncertainty of their true effect. So, further well-designed RCTs with larger samples are required to ascertain the long-term effects of studies.     

Prevalence of CagA and antimicrobial sensitivity of <Emphasis Type="Italic">H. pylori</Emphasis> isolates of patients with gastric cancer in Egypt

Background

Helicobacter pylori (H. pylori) infection has been recognized as a significant threat for gastric cancer. However, studies that investigated the oncogenic factors and antimicrobial resistance of H. pylori in Egyptian isolates with gastric cancer are rare. The current study aimed to examine: (1) The pattern of antimicrobial resistance of H. pylori isolates of Egyptian gastric cancer patients, and (2) the prevalence of Cytotoxin-associated gene A (CagA).

Methods

Samples were collected from patients with gastric cancer. Isolation of H. pylori was performed using Columbia blood agar supplemented with 10% horse blood, and selective supplement of H. pylori for 3 to 5 days at 37 °C under microaerophilic condition. Isolates were identified by biochemical traits of H. pylori: oxidase, urease and catalase tests. Antimicrobial susceptibility of H. pylori isolates was examined against five antimicrobial agents using disc diffusion method. After that, extraction of DNA and Polymerase Chain Reaction (PCR) were performed to amplify the target genes.

Results

Twelve samples were collected from six males and six females Egyptian patients with cancer with an age range from 22 to 65 years. These cases are scarce and samples were collected over a period of almost eleven months. All isolates were confirmed as positive H. pylori through colony morphology and biochemical tests. The most effective antibiotic found was ciprofloxacin whereas all isolates showed resistance to metronidazole and erythromycin. The target CagA oncogene gene with expected product size was reported and seven (out of twelve) isolates (58%) were identified as CagA positive.

Conclusion

The current study is unique in two main aspects. First, it reported the pattern of antimicrobial susceptibility and prevalence of CagA gene in H. pylori from Egyptian patients. Second, it exclusively recruited isolates from gastric cancer patients which were confirmed by clinical and laparoscopic examination. The moderately high prevalence of CagA gene in Egyptian cancer patients calls for more vigilance against that oncogene.

     

Opiate agonist treatment to improve health of individuals with opioid use disorder in Lebanon

Background

Opioid agonist therapy has been widely used to reduce harms among individuals with opioid use disorder but its effectiveness has not been evaluated in the Middle East North African (MENA) region. This study aims to evaluate the effectiveness of a program using opioid agonist therapy in combination with psychosocial support on improving psychological and social well-being, reducing arrest, and reducing risky behavior in individuals with opioid use disorder in Lebanon.

Methods

A one-group pre-test post-test design study was performed at SKOUN Lebanese Addiction Centre between January 2013 and December 2014. Eighty-six out of 181 patients agreed to participate and completed the 3-month assessment and 38 concluded the 12-month assessment. Psychological (depression and anxiety, quality of life), substance dependence/abuse, behavioral (injecting behavior, sharing needles and paraphernalia), and social outcomes were evaluated at baseline, 3, and 12 months post-treatment.

Results

Remarkable statistical significance improvements were observed 3 months after treatment in most outcome variables including quality of life, anxiety, substance dependence, overdose, employment, and injecting behavior. Improvements were sustained 12 months after treatment.

Conclusion

Results support expanding the access to opioid agonist therapy in other MENA countries to treat substance dependence and reduce harms among individuals with opioid use disorder.

     

Corticosteroids and mortality in children with bacterial meningitis

Jillian Mongelluzzo, BA; Zeinab Mohamad, MS; Thomas R. Ten Have, PhD; Samir S. Shah, MD, MSCE

JAMA. 2008;299(17):2048-2055.

Context  In adults, adjuvant corticosteroids significantly reduce mortality associated with bacterial meningitis; however, in children, studies reveal conflicting results.

Objective  To determine the association between adjuvant corticosteroids and clinical outcomes in children with bacterial meningitis.

Design, Setting, and Patients  A retrospective cohort study conducted between January 1, 2001, and December 31, 2006, of 2780 children discharged with bacterial meningitis as their primary diagnosis from 27 tertiary care children's hospitals located in 18 US states and the District of Columbia that provide data to the Pediatric Health Information System’s administrative database.

Main Outcome Measures  Propensity scores, constructed using patient demographics and markers of illness severity at presentation, were used to determine each child's likelihood of receiving adjuvant corticosteroids. Primary outcomes of interest, time to death and time to hospital discharge, were analyzed by using propensity-adjusted Cox proportional hazards regression models stratified by age categories.

Results  The median age was 9 months (interquartile range, 0-6 years); 57% of the patients were males. Streptococcus pneumoniae was the most commonly identified cause of meningitis. Adjuvant corticosteroids were administered to 248 children (8.9%). The overall mortality rate was 4.2% (95% confidence interval [CI], 3.5%-5.0%), and cumulative incidences were 2.2% and 3.1% at 7 days and 28 days, respectively, after admission. Adjuvant corticosteroids did not reduce mortality, regardless of age (children <1 year: hazard ratio [HR], 1.09; 95% CI, 0.53-2.24; 1-5 years: HR, 1.28; 95% CI, 0.59-2.78; and >5 years: HR, 0.92; 95% CI, 0.38-2.25). Adjuvant corticosteroids were also not associated with time to hospital discharge. In subgroup analyses, the results did not change in either children identified with pneumococcal or meningococcal meningitis or children with a cerebrospinal fluid culture performed at the admitting hospital.

Conclusion  In this multicenter observational study of children with bacterial meningitis, adjuvant corticosteroid therapy was not associated with time to death or time to hospital discharge.

     

Toxicity bioassay and sub-lethal effects of profenofos-based insecticide on behavior,biochemical, hematological,and histopathological responses in Grass carp (Ctenopharyngodon idella)

Profenofos (organophosphate) is among the major toxicant polluting freshwater bodies, exerting a significant effect on fish health. The LC₅₀ value of Profenofos (PRO) was resolved in Grass carp (Ctenopharyngodon idella) with average body weight (55.82?±?5.42?g) and determined the 96?h LC₅₀ value as 7.2?µg/L for the assay. Twenty-one-day exposures to 1.8?µg/ L and 3.6?µg/ L doses were conducted to evaluate the sub-lethal effects, and various toxicological endpoints were assessed on the 1^st, 7^th, 15^th and 21^st days of exposure. Acute toxic stress was observed with fish displaying behavioral toxicity. The most hematological change was extreme microcytic hypochromic anemia. Leucocyte count increased in experimented fish. Moderate neutrophilia, monocytosis and lymphocytosis were observed. Serum total protein, albumin, and globulin concentrations were significantly diminished. Overall, increments over control were recognized in serum urea, creatinine and acid phosphatase. However, serum glucose, total lipid, cholesterol, serum ALT and AST activity showed a significant decrease in fish exposed to both concentrations of PRO. Serum IgM concentrations insignificantly changed in treated fish except for on the 21^st day of exposure to 3.6?µg/ L of PRO, while serum lysozyme significantly decreased. Furthermore, total protein, lipid and glycogen concentrations in muscles and the liver exhibited a decreasing trend at all concentrations. Moreover, histopathological alterations in the liver, kidney, and muscles occurred exclusively after treatment. From the obtained results, it is assumed that profenofos induced general toxic impacts under field conditions and might disturb ecologically relevant processes.