Is consanguinity prevalence decreasing in Saudis?: A study in two generations

Background: Saudi population is unique in that there is a strong  preference for cousin marriages in the general population. We studied the prevalence of consanguinity in educated Saudi females and compared the results with the results obtained in their parents, to access if a generation difference in which extensive educational activities have prevailed to inform the people of the influence of cousin marriages on health, has made any difference in prevalence of consanguineous marriages.Method: A total of 600 Saudi women (421 university students and 179 women attending outpatients’ clinics) were interviewed about their own and their parents’ consanguinity.Results: The total consanguinity (first and second cousins) was 29.7% in the parents. Consanguinity was significantly higher among the daughters than the parents, where 37.9% of the 293 married women had  consanguineous marriages. The prevalence of consanguinity was studied in different age groups, though no significant pattern was observed. A strong correlation was found between consanguinity of parents and their  daughters; consanguinity was highest (52.3%) in the daughters of parents who were themselves consanguineous.Conclusion: The results did not reveal any decrease in the prevalence of consanguinity over a generation. This shows that the tradition of marrying within the family is a preferred practice, despite the awareness that certain genetic disorders occur at a higher frequency in cousin marriages. There is a need at the primary health care level to inform the public of the consequences of this common practice.Key words: Consanguinity; Saudis; First cousin marriage; second cousin marriage; Middle East

Perception and clinical practice regarding mucus clearance devices with chronic obstructive pulmonary disease: a cross-sectional study of healthcare providers in Saudi Arabia

OBJECTIVES: Clearing secretions from the airway can be difficult for people with chronic obstructive pulmonary disease (COPD). Mucus clearance devices (MCDs) are an option in disease management to help with this, but healthcare provider awareness and knowledge about them as well as current clinical practice in Saudi Arabia are not known. DESIGN: A cross-sectional online survey consisting of four themes; demographics, awareness, recommendations and clinical practice, for MCDs with COPD patients. SETTING: Saudi Arabia. PARTICIPANTS: 1188 healthcare providers including general practitioners, family physicians, pulmonologists, nursing staff, respiratory therapists and physiotherapists. PRIMARY OUTCOME MEASURES: Healthcare providers' level of awareness about MCDs, and the identification of current clinical practices of COPD care in Saudi Arabia. RESULTS: 1188 healthcare providers (44.4% female) completed the survey. Regarding devices, 54.2% were aware of the Flutter, 23.8% the Acapella and 5.4% the positive expiratory pressure mask. 40.7% of the respondents identified the Acapella, and 22.3% the Flutter as first choice for COPD management. 75% would usually or always consider their use in COPD patients reporting daily difficulty clearing mucus, whereas 55.9% would sometimes or usually consider the use of MCDs with COPD patients who produced and were able to clear mucus with cough. In clinical practice, 380 (32%) of the respondents would prescribe MCDs, 378 (31.8%) would give MCDs without prescriptions, 314 (26.4%) would not provide them at all and 116 (9.8%) would only advise patients about them. CONCLUSION: Healthcare providers are aware of the existence of MCDs and their benefits for sputum clearance and believe that MCDs are beneficial for sputum clearance in some COPD patients. TRIAL REGISTRATION NUMBER: ISRCTN44651852

In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis

Metformin (MET) is a clinically used anti-hyperglycemic agent that shows activities against chemically-induced animal models of cancer. A study from our laboratory showed that MET protectes against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in vitro human non-cancerous epithelial breast cells (MCF10A) via activation of the aryl hydrocarbon receptor (AhR). However, it is unclear whether MET can prevent the initiation of breast carcinogenesis in an in vivo rat model of AhR-induced breast carcinogenesis. Therefore, the main aims of this study are to examine the effect of MET on protecting against rat breast carcinogenesis induced by DMBA and to explore whether this effect is medicated through the AhR pathway. In this study, treatment of female rats with DMBA initiated breast carcinogenesis though inhibiting apoptosis and tumor suppressor genes while inducing oxidative DNA damage and cell cycle proliferative markers. This effect was associated with activation of AhR and its downstream target genes; cytochrome P4501A1 (CYP1A1) and CYP1B1. Importantly, MET treatment protected against DMBA-induced breast carcinogenesis by restoring DMBA effects on apoptosis, tumor suppressor genes, DNA damage, and cell proliferation. Mechanistically using in vitro human breast cancer MCF-7 cells, MET inhibited breast cancer stem cells spheroids formation and development by DMBA, which was accompanied by a proportional inhibition in CYP1A1 gene expression. In conclusion, the study reports evidence that MET is an effective chemopreventive therapy for breast cancer by inhibiting the activation of CYP1A1/CYP1B1 pathway in vivo rat model

Comparative genomics of European Avian Pathogenic E. coli (APEC)

Background Avian pathogenic Escherichia coli (APEC) causes colibacillosis, which results in significant economic losses to the poultry industry worldwide. However, the diversity between isolates remains poorly understood. Here, a total of 272 APEC isolates collected from the United Kingdom (UK), Italy and Germany were characterised using multiplex polymerase chain reactions (PCRs) targeting 22 equally weighted factors covering virulence genes, R-type and phylogroup. Following these analysis, 95 of the selected strains were further analysed using Whole Genome Sequencing (WGS). Results The most prevalent phylogroups were B2 (47%) and A1 (22%), although there were national differences with Germany presenting group B2 (35.3%), Italy presenting group A1 (53.3%) and UK presenting group B2 (56.1%) as the most prevalent. R-type R1 was the most frequent type (55%) among APEC, but multiple R-types were also frequent (26.8%). Following compilation of all the PCR data which covered a total of 15 virulence genes, it was possible to build a similarity tree using each PCR result unweighted to produce 9 distinct groups. The average number of virulence genes was 6-8 per isolate, but no positive association was found between phylogroup and number or type of virulence genes. A total of 95 isolates representing each of these 9 groupings were genome sequenced and analysed for in silico serotype, Multilocus Sequence Typing (MLST), and antimicrobial resistance (AMR). The UK isolates showed the greatest variability in terms of serotype and MLST compared with German and Italian isolates, whereas the lowest prevalence of AMR was found for German isolates. Similarity trees were compiled using sequencing data and notably single nucleotide polymorphism data generated ten distinct geno-groups. The frequency of geno-groups across Europe comprised 26.3% belonging to Group 8 representing serogroups O2, O4, O18 and MLST types ST95, ST140, ST141, ST428, ST1618 and others, 18.9% belonging to Group 1 (serogroups O78 and MLST types ST23, ST2230), 15.8% belonging to Group 10 (serogroups O8, O45, O91, O125ab and variable MLST types), 14.7% belonging to Group 7 (serogroups O4, O24, O35, O53, O161 and MLST type ST117) and 13.7% belonging to Group 9 (serogroups O1, O16, O181 and others and MLST types ST10, ST48 and others). The other groups (2, 3, 4, 5 and 6) each contained relatively few strains. However, for some of the genogroups (e.g. groups 6 and 7) partial overlap with SNPs grouping and PCR grouping (matching PCR groups 8 (13 isolates on 22) and 1 (14 isolates on 16) were observable). However, it was not possible to obtain a clear correlation between genogroups and unweighted PCR groupings. This may be due to the genome plasticity of E. coli that enables strains to carry the same virulence factors even if the overall genotype is substantially different. Conclusions The conclusion to be drawn from the lack of correlations is that firstly, APEC are very diverse and secondly, it is not possible to rely on any one or more basic molecular or phenotypic tests to define APEC with clarity, reaffirming the need for whole genome analysis approaches which we describe here. This study highlights the presence of previously unreported serotypes and MLSTs for APEC in Europe. Moreover, it is a first step on a cautious reconsideration of the merits of classical identification criteria such as R typing, phylogrouping and serotyping

The effect of disgust-related side-effects on symptoms of depression and anxiety in people treated for cancer: a moderated mediation model

As maladaptive disgust responses are linked to mental health problems, and cancer patients may experience heightened disgust as a result of treatments they receive, we explored the associations between disgust-related side-effects and symptoms of depression and anxiety in people treated for cancer. One hundred and thirty two (83 women, Mage = 57.48 years) participants answered questions about their treatments, side-effects, disgust responding, and mental health. Experiencing bowel and/or bladder problems, sickness and/or nausea (referred to here as “core” disgust-related side-effects) was significantly related to greater symptoms of depression and borderline increased anxiety. Further, these links were explained by a moderated mediation model, whereby the effects of core disgust side-effects on depression and anxiety were mediated by (physical and behavioural) self-directed disgust, and disgust propensity moderated the effect of core disgust side-effects on self-disgust. These findings stress the importance of emotional responses, like disgust, in psychological adaptation to the side-effects of cancer treatments

Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)

Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs

Parameters for the mathematical modelling of Clostridium difficile acquisition and transmission: a systematic review

INTRODUCTION: Mathematical modelling of Clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. The objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of Clostridium difficile transmission. METHODS: Six electronic healthcare databases were searched and all screening, data extraction and study quality assessments were undertaken in duplicate. Results were synthesised using a narrative approach. RESULTS: Fifty-four studies met the inclusion criteria. Reproduction numbers for hospital based epidemics were described in two studies with a range from 0.55 to 7. Two studies provided consistent data on incubation periods. For 62% of cases, symptoms occurred in less than 4 weeks (3-28 days) after infection. Evidence on contact patterns was identified in four studies but with limited data reported for populating a mathematical model. Two studies, including one without clinically apparent donor-recipient pairs, provided information on serial intervals for household or ward contacts, showing transmission intervals of <1 week in ward based contacts compared to up to 2 months for household contacts. Eight studies reported recovery rates of between 75%-100% for patients who had been treated with either metronidazole or vancomycin. Forty-nine studies gave recurrence rates of between 3% and 49% but were limited by varying definitions of recurrence. No study was found which specifically reported force of infection or net reproduction numbers. CONCLUSIONS: There is currently scant literature overtly citing estimates of the parameters required to inform the quantitative modelling of Clostridium difficile transmission. Further high quality studies to investigate transmission parameters are required, including through review of published epidemiological studies where these quantitative estimates may not have been explicitly estimated, but that nonetheless contain the relevant data to allow their calculation

2nd International Workshop on Machine Learning Methods for Recommender Systems

Most existing reciprocal recommender systems use either profile similarity or interaction similarity to recommend new matches, assuming that user preferences are static and ignoring temporal aspects of user behaviour. This paper takes a different approach, and addresses the issue of representing user preferences as dynamic. We introduce a new representation for changes in user preferences and use that representation in creating a reciprocal recommender system applied to online dating.In this paper, we develop a general framework for combining a Hidden Markov model (HMM) content-based reciprocal recommender system with collaborative filtering techniques to create a unified hybrid recommender. Additionally, a new similarity measure is introduced to rank the recommendations generated by this hybrid recommender. Moreover, we propose, design and implement a reciprocal recommender system using the suggested framework and the new similarity measure. Evaluation of this system shows that it generates better recommendations than existing systems in a time-efficient manner