Effects of FTO and PPARγ variants on intrauterine growth restriction in a Brazilian birth cohort.

Intrauterine growth restriction (IUGR) is related to a higher risk of neonatal mortality, minor cognitive deficit, metabolic syndrome, and cardiovascular disease in adulthood. In previous studies, genetic variants in the FTO (fat mass and obesity-associated) and PPARγ (peroxisome proliferator-activated receptor-gamma) genes have been associated with metabolic disease, body mass index, and obesity among other outcomes. We studied the association of selected FTO (rs1421085, rs55682395, rs17817449, rs8043757, rs9926289, and rs9939609) and PPARγ (rs10865710, rs17036263, rs35206526, rs1801282, rs28763894, rs41516544, rs62243567, rs3856806, and rs1805151) single-nucleotide polymorphisms (SNPs) with IUGR, through a case-control study in a cohort of live births that occurred from June 1978 to May 1979 in a Brazilian city. We selected 280 IUGR cases and 256 controls for analysis. Logistic regression was used to jointly analyze the SNPs as well as factors such as maternal smoking, age, and schooling. We found that the PPARγ rs41516544 increased the risk of IUGR for male offspring (OR 27.83, 95%CI 3.65-212.32) as well as for female offspring (OR=8.94, 95%CI: 1.96-40.88). The FTO rs9939609 TA genotype resulted in a reduced susceptibility to IUGR for male offspring only (OR=0.47, 95%CI: 0.26-0.86). In conclusion, we demonstrated that PPARγ SNP had a positive effect and FTO SNP had a negative effect on IUGR occurrence, and these effects were gender-specific.

Effects of FTO and PPARγ variants on intrauterine growth restriction in a Brazilian birth cohort

Intrauterine growth restriction (IUGR) is related to a higher risk of neonatal mortality, minor cognitive deficit, metabolic syndrome, and cardiovascular disease in adulthood. In previous studies, genetic variants in the FTO (fat mass and obesity-associated) and PPARγ (peroxisome proliferator-activated receptor-gamma) genes have been associated with metabolic disease, body mass index, and obesity among other outcomes. We studied the association of selected FTO (rs1421085, rs55682395, rs17817449, rs8043757, rs9926289, and rs9939609) and PPARγ (rs10865710, rs17036263, rs35206526, rs1801282, rs28763894, rs41516544, rs62243567, rs3856806, and rs1805151) single-nucleotide polymorphisms (SNPs) with IUGR, through a case-control study in a cohort of live births that occurred from June 1978 to May 1979 in a Brazilian city. We selected 280 IUGR cases and 256 controls for analysis. Logistic regression was used to jointly analyze the SNPs as well as factors such as maternal smoking, age, and schooling. We found that the PPARγ rs41516544 increased the risk of IUGR for male offspring (OR 27.83, 95%CI 3.65-212.32) as well as for female offspring (OR=8.94, 95%CI: 1.96-40.88). The FTO rs9939609 TA genotype resulted in a reduced susceptibility to IUGR for male offspring only (OR=0.47, 95%CI: 0.26-0.86). In conclusion, we demonstrated that PPARγ SNP had a positive effect and FTO SNP had a negative effect on IUGR occurrence, and these effects were gender-specific.

Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls.

PURPOSE: The fusion gene BCR-ABL has an important role to the progression of chronic myeloid leukemia (CML) and several signaling pathways have been characterized as responsible for the terminal blastic phase (BP). However, the initial phase, the chronic phase (CP), is long lasting and there is much yet to be understood about the critical role of BCR-ABL in this phase. This study aims to evaluate transcriptional deregulation in CD34+ hematopoietic cells (CD34+ cells) from patients with untreated newly diagnosed CML compared with CD34+HC from healthy controls. METHODS: Gene expression profiling in CML-CD34 cells and CD34 cells from healthy controls were used for this purpose with emphasis on five main pathways important for enhanced proliferation/survival, enhanced self-renewal and block of myeloid differentiation. RESULTS: We found 835 genes with changed expression levels (fold change ≥ ±2) in CML-CD34 cells compared with CD34 cells. These include genes belonging to PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways. Four of these pathways converge to MYC activation. We also identified five transcripts upregulated in CD34-CML patients named OSBPL9, MEK2, p90RSK, TCF4 and FZD7 that can be potential biomarkers in CD34-CML-CP. CONCLUSION: We show several mRNAs up- or downregulated in CD34-CML during the chronic phase.

Identification and grouping of Dichelobacter nodosus, using PCR and sequence analysis.

Dichelobacter nodosus is the causative agent of ovine foot rot, a disease that is a constant economic burden for many Western sheep ranches. Vaccination is one method of treating foot rot. A higher and more specific immune response is observed when monovalent vaccines are used to treat foot rot, as compared to multivalent vaccines, which incorporate all 10 major New Zealand D. nodosus serogroups. There is no single assay for specifically identifying and grouping D. nodosus for the purpose of incorporating only the desired serogroup(s) in a vaccine. A polymerase chain reaction (PCR)-based assay was used to specifically identify and group D. nodosus from a foot rot lesion. Identification and grouping was determined by predicted fragment size analysis and nucleotide sequence information. The PCR approach vastly improves the accuracy in identifying and grouping D. nodosus from a foot rot lesion.

Factors affecting outcome in the resuscitation of severely injured patients.

This is a retrospective, hospital based study of the resuscitative management of 40 consecutive, multitrauma patients (Injury Severity Score (ISS) > 25) admitted directly from an inner metropolitan environment over a one year period. The aim was to identify physiological, anatomical and time variables that correlated with an adverse outcome. Such information would facilitate the development of management protocols to improve future care. The clinical management of airways, breathing, circulation and head injury was reviewed in both the pre-hospital and Emergency Department (ED) phases of care. Eleven patients died during the resuscitative phase, 10 from blood loss and one from head injury. Nine patients died during the definitive care phase, seven from head injury and two from multiple organ failure. Scene hypotension (systolic blood pressure < or = 80 mmHg), ED Glasgow Coma Scale < 9, ISS > or = 50, and Revised Trauma Score < or = 4 were variables that correlated strongly with fatal outcomes. The median pre-hospital time was 33 min for those hypotensive in the field. The median ED time was 70 min for hypotensive patients who went to operating theatres. Survival following severe trauma may be increased by avoiding secondary insults in head injured patients and improving the management of haemorrhagic shock. The time frame from accident to operating theatre should be kept under 90 min. Warmed blood, fresh frozen plasma and platelets should be used early in the resuscitation. An early move to definitive control of bleeding should accompany vigorous volume resuscitation.

Impact of pedestrian injury on inner city trauma services.

This report describes the epidemiology of pedestrian injury in four inner metropolitan local government areas of Sydney. These data were obtained from the Roads and Traffic Authority of New South Wales. The spectrum of injury and clinical outcome was defined in patients with an Injury Severity Score (ISS) > 15 admitted from the study area, during a 1 year period, to the four inner metropolitan teaching hospitals. The incidence of pedestrian death was 3.3 times the state average of 32/10(6)/year. An average of 235 pedestrians, injured in the study area, were hospitalized each year during the period 1987-89. On average 24 pedestrians died each year, seven at the scene and 17 in hospital. Fifty patients (ISS > 15) were admitted to the four teaching hospitals during a 1 year period 1990-91. Forty-five were adults and five children. Multiplicity of injury was seen in 68% of patients. The pelvis and lower extremities were involved in 70%, the head in 66% and chest in 42%. The hospital mortality rate was 30% with five patients dying on the first day from blood loss and nine dying during subsequent days from head injury. This study has important implications for trauma service development. Successful clinical management of the severely injured pedestrian requires close co-operation between pre-hospital and hospital care providers. An integrated hospital trauma team response is mandatory to ensure appropriate management of what is often a shocked, hypoxic, head-injured patient.