Endotoxin and bone turnover markers in postmenopausal women with and without osteoporosis

Bacterial lipopolysaccharide (LPS) also known as endotoxin, which represents the outer cell wall membrane of gram-negative bacteria has been implicated as the major bacterial bone-resorbing factor. Recently, the most prevalent form of clinically significant osteopenia and osteoporosis involves periodontitis and otitis media by gram-negative bacteria. The aim of the study is to evaluate circulating endotoxin levels and to study the association amongst endotoxin and bone turnover markers in a cohort of Saudi postmenopausal women with or without osteoporosis. We determined the levels of endotoxin, bone turnover markers, 25-OH vitamin D total and corrected calcium in 100 Saudi postmenopausal women with osteoporosis and 100 women without osteoporosis were taken under the supervision of qualified physicians in the primary care centers in Riyadh. Serum endotoxin, NTx, osteocalcin, PTH, 25-OH vitamin D total and calcium were analyzed. Serum NTX and PTH levels in patients with osteoporosis were significant higher than controls. Serum endotoxin was significantly and positively associated with calcium in all subject and controls. Endotoxin was positively associated with NTX in both groups but not with osteocalcin, PTH or 25-OH vitamin D. Findings of the present study implicate a role for endotoxin-mediated inflammation in patients with osteoporosis

Identification of the genomic mutation in Epha4rb-2J/rb-2J mice

The EphA4 receptor tyrosine kinase is involved in numerous cell-signalling activities during embryonic development. EphA4 has the ability to bind to both types of ephrin ligands, the ephrinAs and ephrinBs. The C57BL/6J-Epha4rb-2J/GrsrJ strain, denoted Epha4rb-2J/rb-2J, is a spontaneous mouse mutant that arose at The Jackson Laboratory. These mutants exhibited a synchronous hind limb locomotion defect or “hopping gait” phenotype, which is also characteristic of EphA4 null mice. Genetic complementation experiments suggested that Epha4rb-2J corresponds to an allele of EphA4, but details of the genomic defect in this mouse mutant are currently unavailable. We found a single base-pair deletion in exon 9 resulting in a frame shift mutation that subsequently resulted in a premature stop codon. Analysis of the predicted structure of the truncated protein suggests that both the kinase and sterile α motif (SAM) domains are absent. Definitive determination of genotype is needed for experimental studies of mice carrying the Epha4rb-2J allele, and we have also developed a method to ease detection of the mutation through RFLP. Eph-ephrin family members are reportedly expressed as numerous isoforms. Hence, delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein–protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype

Molecular epidemiology of antibiotic-associated diarrhoea due to Clostridium difficile and clostridium perfringens in Ain Shams University Hospitals

Background: As we are living in the era of antibiotic overuse, antibiotic associated diarrhea (AAD) is considered now a distinct health problem with a need for more attention. Aim of the Study: was to perform a highly specific detection and definition of pathogenic Clostridium perfringens and Clostridium difficile related AAD in children compared to adults and geriatircs. Patients and Methods: One hundred and fifty patients diagnosed for AAD were included in this study (50 children, 50 adults and 50 geriatric patients). All of them were subjected to full medical history including complete therapeutic history of antibiotics and collection of stool sample during the attack for detection of Clostridium perfringenes enterotoxin (CPEnt) and Clostridium difficile cytotoxin by (EIA) kit. PCR detection of Clostridium perfringenes cpe gene (Coding gene for CPEnt) was performed as well. Results: Results showed that prevalence of Clostridium difficile cytotoxin was 24% while Clostridium perfringenes enterotoxin was 12% as detected by EIA in faecal specimens as a whole. Detection of cpe gene by PCR was positive in 16% of all cases. Children (OR: 4.2, 95% CI: 1.3-14.8, P_0.01) and geriatric patients (OR: 3.4, 95% CI: 1.2-13.5, P_0.02) were significantly more prone to Clostridium difficile AAD compared to adults. Also, childhood was a significant risk for Clostridium perfringens AAD (OR: 2.1, 95% CI: 0.54-7.4, P_0.04). In Conclusion: children and geriatric patients are more vulnerable to develop AAD with antibiotic abuse compared to adults. Abbreviations: AAD=Antibiotic associated diarrhea, CI=Confidence interval, ELISA=Enzyme-linked immunosorbent assay, OR=Odd ratio, PCR=Polymerase chain reaction. Keywords: Antibiotic-associated diarrhea, children, Clostridium perfringens, Clostridium difficile. Egypt. J. Hum. Genet Vol. 8 (2) 2007: pp. 121-13

Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities

Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country.To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt.Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software.The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health.Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians

Impact of asthma on educational attainment in a socioeconomically deprived population: a study linking health, education and social care datasets

BACKGROUND: Asthma has the potential to adversely affect children's school examination performance, and hence longer term life chances. Asthma morbidity is especially high amongst UK ethnic minority children and those experiencing social adversity, populations which also have poor educational outcomes. We tested the hypothesis that asthma adversely affects performance in national school examinations in a large cohort from an area of ethnic diversity and social deprivation. METHODS AND FINDINGS: With a novel method (using patient and address-matching algorithms) we linked administrative and clinical data for 2002-2005 for children in east London aged 5-14 years to contemporaneous education and social care datasets. We modelled children's performance in school examinations in relation to socio-demographic and clinical variables. The dataset captured examination performance for 12,136 children who sat at least one national examination at Key Stages 1-3. For illustration, estimates are presented as percentage changes in Key Stage 2 results. Having asthma was associated with a 1.1% increase in examination scores (95%CI 0.4 to 1.7)%,p = 0.02. Worse scores were associated with Bangladeshi ethnicity -1.3%(-2.5 to -0.1)%,p = 0.03; special educational need -14.6%(-15.7 to -13.5)%,p = 0.02; mental health problems -2.5%(-4.1 to -0.9)%,p = 0.003, and social adversity: living in a smoking household -1.2(-1.7 to -0.6)%,p<0.001; living in social housing -0.8%(-1.3 to -0.2)% p = 0.01, and entitlement to free school meals -0.8%(-1.5 to -0.1)%,p<0.001. CONCLUSIONS: Social adversity and ethnicity, but not asthma, are associated with poorer performance in national school examinations. Policies to improve educational attainment in socially deprived areas should focus on these factors

Inflammation in embryology: A review of neuroinflammation in spina bifida

The occurrence of neuroinflammation after the failure of neural tube closure, resulting in spina bifida aperta, is well established but whether or not neuroinflammation contributes to damage to the neuroepithelium prior to and during closure is not known. Neuroinflammation may occur at different time periods after perturbation to the developing spinal cord. Evidence suggests that early neuroinflammation is detrimental, whereas the later chronic phase of neuroinflammation may have useful roles. The role of neuroinflammation in neural tube defects is complex. It is important to make the distinction of whether neuroinflammation is important for neuroprotection or detrimental to the neural tissue. This may directly be influenced by the location, magnitude and duration of the insult, as well as the expression of neurotrophic or neurotoxic molecules. The current understanding remains that the chronic damage to the developing spinal cord is likely due to the chemical and mechanical damage of the exposed neural tissue owing to the aggressive intrauterine environment, described as the “two-hit mechanism”. Astrogliosis in the exposed spinal cord has been described in animal models of spina bifida after the failure of closure during embryonic life. Still, its association with neuroinflammatory processes is poorly understood. In this review, we will discuss the current understanding of neuroinflammation in neural tube defects, specifically spina bifida, and highlight inflammation-targeted strategies that may potentially be used to treat this pathophysiological condition

Antimicrobial potential of alkaloids and flavonoids extracted from Tamarix aphylla leaves against common human pathogenic bacteria

Background: Alkaloids and flavonoids are secondary metabolites extracted from different medicinal plants. Tamarix aphylla a traditionally valuable medicinal plant; was used for the extraction of alkaloids and flavonoids in order to evaluate their antibacterial activity.Methodology: The leaves of the plant were collected from district Kohat, Pakistan, and their alkaloids and flavonoids were extracted with ethanol and methanol, respectively. Four bacteria i.e. Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) were selected for the biological screening of these phyto-constituents.Results: The concentration of alkaloids was found to be more in the leaves of Tamarix aphylla than flavonoids. The extracted phytochemicals showed varied inhibition zones against tested bacterial isolates. Alkaloids showed highest inhibitory activity against Staphylococcus aureus (14±0.6 mm) followed by Pseudomonas aeruginosa (13±0.7 mm). Conversely, flavonoids showed the highest inhibitory affect against Salmonella typhi (17±0.7 mm) followed by Staphylococcus aureus (14±0.7 mm). However, both extracts showed the lowest inhibitory effects against Escherichia coli.Conclusions: It was concluded that the alkaloids and flavonoids from Tamarix aphylla leaves have antimicrobial potential against common human bacterial pathogens. However, flavonoids were found to be more active phytochemical against tested bacterial strains as compared to alkaloids.Keywords: Kohat; Medicinal plants; Phytochemical screening; In-vitro activity; Bacterial strains

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

A closer look at neuron interaction with track-etched microporous membranes

Microporous membranes support the growth of neurites into and through micro-channels, providing a different type of neural growth platform to conventional dish cultures. Microporous membranes are used to support various types of culture, however, the role of pore diameter in relation to neurite growth through the membrane has not been well characterised. In this study, the human cell line (SH-SY5Y) was differentiated into neuron-like cells and cultured on track-etched microporous membranes with pore and channel diameters selected to accommodate neurite width (0.8 µm to 5 µm). Whilst neurites extended through all pore diameters, the extent of neurite coverage on the non-seeded side of the membranes after 5 days in culture was found to be directly proportional to channel diameter. Neurite growth through membrane pores reduced significantly when neural cultures were non-confluent. Scanning electron microscopy revealed that neurites bridged pores and circumnavigated pore edges – such that the overall likelihood of a neurite entering a pore channel was decreased. These findings highlight the role of pore diameter, cell sheet confluence and contact guidance in directing neurite growth through pores and may be useful in applications that seek to use physical substrates to maintain separate neural populations whilst permitting neurite contact between cultures

The Galabat-Metema cross-border onchocerciasis focus: The first coordinated interruption of onchocerciasis transmission in Africa.

BACKGROUND: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. METHODS/PRINCIPLE FINDINGS: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission. CONCLUSION: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed