Cerebral palsy and placental infection: a case-cohort study

BACKGROUND: The association between cerebral palsy in very preterm infants and clinical, histopathologic and microbiological indicators of chorioamnionitis, including the identification of specific micro-organisms in the placenta, was evaluated in a case-cohort study. METHODS: Children with a diagnosis of cerebral palsy at five years of age were identified from amongst participants in a long-term follow-up program of preterm infants. The comparison group was a subcohort of infants randomly selected from all infants enrolled in the program. The placentas were examined histopathologically for chorioamnionitis and funisitis, and the chorioamnionic interface was aseptically swabbed and comprehensively cultured for aerobic and anaerobic bacteria, yeast and genital mycoplasmas. Associations between obstetric and demographic variables, indicators of chorioamnionitis and cerebral palsy status were examined by univariate analysis. RESULTS: Eighty-two infants with cerebral palsy were compared with the subcohort of 207 infants. Threatened preterm labor was nearly twice as common among the cases as in the subcohort (p < 0.01). Recorded clinical choroamnionitis was similar in the two groups and there was no difference in histopathologic evidence of infection between the two groups. E. coli was cultured from the placenta in 6/30 (20%) of cases as compared with 4/85 (5%) of subcohort (p = 0.01). Group B Streptococcus was more frequent among the cases, but the difference was not statistically significant. CONCLUSIONS: The association between E. coli in the chorioamnion and cerebral palsy in preterm infants identified in this study requires confirmation in larger multicenter studies which include microbiological study of placentas

Comparative analysis of slot dimension in lingual bracket systems

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Muscle invasive bladder cancer in Upper Egypt: the shift in risk factors and tumor characteristics

<p>Abstract</p> <p>Background</p> <p>In Egypt, where bilharziasis is endemic, bladder cancer is the commonest cancer in males and the 2^ndin females; squamous cell carcinoma (SCC) is the commonest type found, with a peculiar mode of presentation. The aim of this study is to identify and rank the risk factors of muscle invasive bladder cancer (MIBC) in Upper Egypt and describe its specific criteria of presentation and histopathology.</p> <p>Methods</p> <p>This is an analytical, hospital based, case controlled study conducted in south Egypt cancer institute through comparing MIBC cases (n = 130) with age, sex and residence matched controls (n = 260) for the presence of risk factors of MIBC. Data was collected by personal interview using a well designed questionnaire. Patients' records were reviewed for histopathology and Radiologic findings.</p> <p>Results</p> <p>The risk factors of MIBC were positive family history [Adjusted odds ratio (AOR) = 7.7], exposure to pesticides [AOR = 6.2], bladder stones [AOR = 5], consanguinity [AOR = 3.9], recurrent cystitis [AOR = 3.1], bilharziasis [odds ratio (OR) = 5.8] and smoking [OR = 5.3]. SCC represented 67.6% of cases with burning micturition being the presenting symptom in 73.8%.</p> <p>Conclusion</p> <p>MIBC in Upper Egypt is usually of the SCC type (although its percentage is decreasing), occurs at a younger age and presents with burning micturition rather than hematuria. Unlike the common belief, positive family history, parents' consanguinity, exposure to pesticides and chronic cystitis seem to play now more important roles than bilharziasis and smoking in the development of this disease in this area.</p

Smoking and COX-2 Functional Polymorphisms Interact to Increase the Risk of Gastric Cardia Adenocarcinoma in Chinese Population

BACKGROUND: Over-expression and increased activity of cyclooxygenase (COX)-2 induced by smoking has been implicated in the development of cancer. This study aimed to explore the interaction between smoking and functional polymorphisms of COX-2 in modulation of gastric cardia adenocarcinoma (GCA) risk. METHODS AND FINDINGS: Three COX-2 polymorphisms, including -1195G>A (rs689466), -765G>C (rs20417), and 587Gly>Arg (rs3218625), were genotyped in 357 GCA patients and 985 controls. In the multivariate logistic regression analysis, we found that the -1195AA, -765GC, and 587Arg/Arg genotypes were associated with increased risk of GCA (OR = 1.50, 95% CI = 1.05-2.13; OR = 2.06, 95% CI = 1.29-3.29 and OR = 1.67, 95% CI = 1.04-2.66, respectively). Haplotype association analysis showed that compared with G(-1195)-G(-765)- G(Gly587Arg), the A(-1195)-C(-765)-A(Gly587Arg) conferred an increased risk of GCA (OR = 2.49, 95% CI = 1.54-4.01). Moreover, significant multiplicative interactions were observed between smoking and these three polymorphisms of -1195G>A, -765G>C, and 587Gly>Arg, even after correction by false discovery rate (FDR) method for multiple comparisons (FDR-P(interaction) = 0.006, 5.239×10(-4) and 0.017, respectively). Similarly, haplotypes incorporating these three polymorphisms also showed significant interaction with smoking in the development of GCA (P for multiplicative interaction = 2.65×10(-6)). CONCLUSION: These findings indicated that the functional polymorphisms of COX-2, in interaction with smoking, may play a substantial role in the development of GCA

Soluble egg antigen of Schistosoma Haematobium induces HCV replication in PBMC from patients with chronic HCV infection

BACKGROUND: This study was conducted to examine, in vitro , the effect of soluble egg antigen (SEA) of S. haematobium on intracellular HCV RNA load in peripheral mononuclear cells (PBMC) as well as on cell proliferation in patients with chronic HCV infection. METHODS: PBMC from 26 patients with chronic HCV infection were cultured for 72 hours in presence and absence of 50 μg SEA/ml medium. Intracellular HCV RNA quantification of plus and minus strands was assessed before and after stimulation. PBMC from five healthy subjects were cultured for 7 days, flow cytometric analysis of DNA content was used to assess the mitogenic effect of SEA on PBMC proliferation compared to phytoheamaglutinine (PHA). RESULTS: Quantification of the intracellular viral load showed increased copy number/cell of both or either viral strands after induction with SEA in 18 of 26 patients (69.2%) thus indicating stimulation of viral replication. Flow cytometric analysis showed that mean ± S.D. of percent values of cell proliferation was induced from 3.2 ± 1.5% in un-stimulated cells to 16.7 ± 2.5 % and 16.84 ± 1.7 % in cells stimulated with PHA and SEA respectively. CONCLUSION: the present study supports earlier reports on SEA proliferative activity on PBMC and provides a strong evidence that the higher morbidity observed in patients co-infected with schistosomiasis and HCV is related, at least in part, to direct stimulation of viral replication by SEA

Rare copy number variation in cerebral palsy

As per publisher: published online 22 May 2013Recent studies have established the role of rare copy number variants (CNVs) in several neurological disorders but the contribution of rare CNVs to cerebral palsy (CP) is not known. Fifty Caucasian families having children with CP were studied using two microarray designs. Potentially pathogenic, rare (<1% population frequency) CNVs were identified, and their frequency determined, by comparing the CNVs found in cases with 8329 adult controls with no known neurological disorders. Ten of the 50 cases (20%) had rare CNVs of potential relevance to CP; there were a total of 14 CNVs, which were observed in <0.1% (<8/8329) of the control population. Eight inherited from an unaffected mother: a 751-kb deletion including FSCB, a 1.5-Mb duplication of 7q21.13, a 534-kb duplication of 15q11.2, a 446-kb duplication including CTNND2, a 219-kb duplication including MCPH1, a 169-kb duplication of 22q13.33, a 64-kb duplication of MC2R, and a 135-bp exonic deletion of SLC06A1. Three inherited from an unaffected father: a 386-kb deletion of 12p12.2-p12.1, a 234-kb duplication of 10q26.13, and a 4-kb exonic deletion of COPS3. The inheritance was unknown for three CNVs: a 157-bp exonic deletion of ACOX1, a 693-kb duplication of 17q25.3, and a 265-kb duplication of DAAM1. This is the first systematic study of CNVs in CP, and although it did not identify de novo mutations, has shown inherited, rare CNVs involving potentially pathogenic genes and pathways requiring further investigation.Gai McMichael, Santhosh Girirajan, Andres Moreno-De-Luca, Jozef Gecz, Chloe Shard, Lam Son Nguyen, Jillian Nicholl, Catherine Gibson, Eric Haan, Evan Eichler, Christa Lese Martin and Alastair MacLenna

Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation

Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation

Burden of musculoskeletal disorders in the Eastern Mediterranean Region, 1990-2013: findings from the Global Burden of Disease Study 2013.

OBJECTIVES: We used findings from the Global Burden of Disease Study 2013 to report the burden of musculoskeletal disorders in the Eastern Mediterranean Region (EMR). METHODS: The burden of musculoskeletal disorders was calculated for the EMR's 22 countries between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, death, years of live lost, years lived with disability and disability-adjusted life years (DALYs). RESULTS: For musculoskeletal disorders, the crude DALYs rate per 100 000 increased from 1297.1 (95% uncertainty interval (UI) 924.3-1703.4) in 1990 to 1606.0 (95% UI 1141.2-2130.4) in 2013. During 1990-2013, the total DALYs of musculoskeletal disorders increased by 105.2% in the EMR compared with a 58.0% increase in the rest of the world. The burden of musculoskeletal disorders as a proportion of total DALYs increased from 2.4% (95% UI 1.7-3.0) in 1990 to 4.7% (95% UI 3.6-5.8) in 2013. The range of point prevalence (per 1000) among the EMR countries was 28.2-136.0 for low back pain, 27.3-49.7 for neck pain, 9.7-37.3 for osteoarthritis (OA), 0.6-2.2 for rheumatoid arthritis and 0.1-0.8 for gout. Low back pain and neck pain had the highest burden in EMR countries. CONCLUSIONS: This study shows a high burden of musculoskeletal disorders, with a faster increase in EMR compared with the rest of the world. The reasons for this faster increase need to be explored. Our findings call for incorporating prevention and control programmes that should include improving health data, addressing risk factors, providing evidence-based care and community programmes to increase awareness

Global, regional, and national incidence, prevalence, and years lived with disability for 354 Diseases and Injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017

Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury