Background
Quantitative three‐dimensional maps of tau neurofibrillary tangles (NFT) burden derived from dense serial histology have potential application for in‐vivo biomarker studies. We constructed ...a group‐level NFT burden map from 15 medial temporal lobe (MTL) specimens, majority with Primary Age‐Related Tauopathy (PART) or low‐level Alzheimer’s disease neuropathologic change, and showed relatively greater NFT burden in the anterior vs. posterior MTL. We investigated whether in‐vivo MRI and PET measures in ROIs derived from this map show meaningful biological relationships.
Method
Multimodal in‐vivo imaging data from 292 participants in the Aging Brain Cohort were used. The group‐level NFT burden map was mapped to each participant’s MRI to define an ROI mask, further divided into anterior (aMTL) and posterior (pMTL) ROIs. Cortical thickness (N=292) and 18F‐Flortaucipir SUVR maps (N=86) were computed. Participants’ age was correlated with average thickness in the aMTL, pMTL, and anatomically defined MTL ROIs. 18F‐Flortaucipir uptake was compared between aMTL and pMTL. The analyses were repeated in subsets of cognitive normal participants, and those with negative amyloid PET scans.
Result
Cortical thickness in the aMTL ROI showed stronger correlation with age than pMTL and anatomically defined MTL subregional thickness. A polynomial fit provided the best age regression, with older participants showing a parabolic decline in thickness around age 60, when substantial NFT accumulation begins in MTL. Further, tau tracer uptake in aMTL was slightly but significantly higher than in pMTL (SUVR 1.19 vs. 1.18, p=0.02).
Conclusion
We demonstrate the potential use of ex‐vivo NFT burden maps for in‐vivo image analysis. NFT deposition is particularly prominent in the anterior MTL in cases without or with low amyloid burden and at early Braak stage. Prior work suggests that even in the absence of amyloid, this tangle pathology may drive neurodegeneration in the aging population. Here we show that cortical thickness, a biormarker for neurodegeneration, when measured within a histopathologically‐defined region enriched for PART NFTs in the aMTL, is better correlated with age than when measured within anatomically defined subregions, suggesting that the relationship may be driven by PART. Greater tau tracer uptake in the aMTL ROI further supports this notion.
Purpose. To examine the relationships between “westernization” and nutrition and physical activity behaviors among older adolescents in Delhi, India. These relations have not been explored, despite ...increasingly strong and pervasive socio-cultural influences from the West. Methods. Students (n=1818) in 8th and 10th grades in 4 Private (higher SES) and 4 Government (lower SES) schools in Delhi, India participated in a cross-sectional study. Height and weight were measured to determine weight status. Information on “westernization” and nutrition, physical activity, sedentary, and dieting behaviors was collected in a survey. The measure of “westernization” assessed 4 domains of culture on a bi-dimensional scale that focused on these young people’s identification with Indian (α=0.86) and Western (α=0.81) ways of living. Mixed-effects regression models were used to investigate the association between “westernization,” weight status, and health behaviors. Gender, school type (SES), and grade were evaluated as effect modifiers. Results. “Westernization” was not directly associated with weight status or BMI (p>0.500). However, adolescents’ identification with Western ways of living was consistently related to both unhealthy (e.g., fast food consumption, pppConclusions. The influence of “westernization” on nutrition and physical activity behaviors of older adolescents in Delhi, India is complex and not wholly negative, as might be hypothesized.
Colonization with Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stone disease. To improve our limited understanding of host/O.formigenes and microbe/O.formigenes interactions, ...germ-free or altered Schaedler flora (ASF) mice were colonized with O.formigenes Germ-free mice were stably colonized with O.formigenes suggesting O.formigenes does not require other organisms to sustain its survival. Examination of intestinal material indicated no viable O.formigenes in the small intestine, ∼4 × 10
O.formigenes per 100mg contents in the cecum and proximal colon, and ∼0.02% of total cecal O. formigenes cells were tightly associated to the mucosa. O.formigenes did not alter the overall microbial composition of ASF, and ASF did not impact O.formigenes capacity to degrade dietary oxalate in the cecum. 24-hour urine and fecal collections within metabolic cages in semi-rigid isolators demonstrated that introduction of ASF into germ-free mice significantly reduced urinary oxalate excretion. These experiments also showed that mono-colonized O.formigenes mice excrete significantly more urinary calcium compared to germ-free mice, which may be due to degradation of calcium oxalate crystals by O.formigenes and the subsequent intestinal absorption of free calcium. In conclusion, the successful establishment of defined-flora O.formigenes mouse models should improve our understanding of O.formigenes host and microbe interactions. These data support the use of O.formigenes as a probiotic that has limited impact on the composition of the resident microbiota but providing efficient oxalate degrading function.
Despite evidence suggesting a lack of O. formigenes colonization is a risk factor for calcium oxalate stone formation, little is known about O. formigenes biology. This study is the first to utilize germ-free mice to examine the response to mono-colonization with O. formigenes and the impact of a defined bacterial cocktail, altered Schaedler flora, on O. formigenes colonization. This study demonstrates that germ-free mice on their regular diet remain mono-colonized with O. formigenes, and suggests that further studies with O. formigenes gnotobiotic mouse models could improve our understanding of O. formigenes biology and host/O. formigenes and microbe/O. formigenes interactions.
The olfactory epithelium has the unusual ability to replace its neurons.We forced replacement of mouse olfactory sensory neurons by bulbectomy. Microarray, bioinformatics, and in situ hybridization ...techniques detected a rapid shift in favor of pro-apoptotic proteins, a progressive immune response by macrophages and dendritic cells, and identified or predicted 439 mRNAs enriched in olfactory sensory neurons, including gene silencing factors and sperm flagellar proteins. Transcripts encoding cell cycle regulators, axonogenesis proteins, and transcription factors and signaling proteins that promote proliferation and differentiation were increased at 5-7 days after bulbectomy and were expressed by basal progenitor cells or immature neurons. The transcription factors included Nhlhl, Hes6, Lmycl, c-Myc, Mxd4, Idl,Nmycl, Cited2, c-Myb, Mybll, Tead2, Dpl, Gata2, Lmol, and Soxll. The data reveal significant similarities with embryonic neurogenesis and make several mechanistic predictions, including the roles of the transcription factors in the olfactory sensory neuron lineage.
The olfactory epithelium has the unusual ability to replace its neurons. We forced replacement of mouse olfactory sensory neurons by bulbectomy. Microarray, bioinformatics, and in situ hybridization ...techniques detected a rapid shift in favor of pro-apoptotic proteins, a progressive immune response by macrophages and dendritic cells, and identified or predicted 439 mRNAs enriched in olfactory sensory neurons, including gene silencing factors and sperm flagellar proteins. Transcripts encoding cell cycle regulators, axonogenesis proteins, and transcription factors and signaling proteins that promote proliferation and differentiation were increased at 5–7 days after bulbectomy and were expressed by basal progenitor cells or immature neurons. The transcription factors included Nhlh1, Hes6, Lmyc1, c-Myc, Mxd4, Id1, Nmyc1, Cited2, c-Myb, Mybl1, Tead2, Dp1, Gata2, Lmo1, and Sox11. The data reveal significant similarities with embryonic neurogenesis and make several mechanistic predictions, including the roles of the transcription factors in the olfactory sensory neuron lineage.
Tobacco streak virus (TSV) has an extensive plant host range, but until recently has not been a common problem in North American soybean. TSV is associated with bud blight and yield loss due to ...reduced plant height and density, and delayed seed development and plant maturity. TSV has been reported in recent years in Illinois, Iowa, Kansas, and Wisconsin, as well as Ontario, Canada. Presence of the virus was confirmed by ELISA. In an Iowa field with high incidence, regression analysis indicated a significant positive relationship between incidence and seed moisture. TSV is seed and pollen transmitted, as well as being spread by thrips. Increasingly variable weather creating favorable conditions for thrips may be facilitating the rise of TSV. The combination of increased incidence of TSV with associated potential for yield loss and few known management methods brings attention to the need for further research.
Accepted for publication 14 April 2016. Published 26 April 2016.
BackgroundIn 2015, the Minnesota Resuscitation Consortium implemented an advanced perfusion and reperfusion life support strategy designed to improve outcome for patients with out-of-hospital ...refractory VF/VT. We report the outcomes of the initial 5-month period of operations.Methods and ResultsThree emergency medical services systems serving the Minneapolis-St. Paul metro area participated in the protocol. Inclusion criteria included age 18-75 years, body habitus accommodating automated LUCAS CPR, and estimated transfer time from the scene to the cardiac catheterization laboratory of ≤30 minutes. Exclusion criteria included known terminal illness, DNR/DNI status, traumatic arrest, and significant bleeding. Refractory VF/VT arrest was defined as failure to achieve sustained ROSC after treatment with 3 direct current (DC) shocks and administration of 300mg of intravenous/intra-osseous amiodarone. Patients were transported to the University of Minnesota where emergent advanced perfusion strategies, including extra-corporeal membrane oxygenation (ECMO), were provided followed by coronary angiography and PCI when appropriate. Over the first 5 months of the protocol, 27 patients were transported with on-going mechanical CPR and met the inclusion criteria. The average age was 55±6, 73% were men and 85% were white patients. The mean time from 911-call to CCL arrival was 58±7 minute. ECMO was placed in 23/27 patients an average 7±1 minutes from arrival to the CCL. Twenty-two out of 27 patients had significant coronary artery disease and received PCI. Fourteen out of 27 (52%) survived to hospital discharge and 13/14 (93%) survivors were discharged with CPC 1 or 2. Bystander CPR, intermittent ROSC and lactic acid of <12mmol/L and presence of coronary artery disease were associated with favorable outcomes.ConclusionsThe MRC refractory VF/VT protocol is feasible and led to a high functionally favorable survival rate with few complications. It represents the first organized protocol of early mobilization for this patient population in the USA.
The study objectives were to (i) Describe the frequency and priority of family meals, (ii) Compare the family mealtime environment by gender and SES, (iii) Examine the association between family ...meals and weight status among adolescents living in New Delhi, India, (iv) Examine the association between family meals and eating patterns (healthy/unhealthy) among adolescent boys and girls living in New Delhi, India. Survey and anthropometric data were collected from 8th and 10th grade students (n=1818) from four Government (public) schools and four private schools who participated in the HRIDAY study. Chi-square tests were used to evaluate if the distributions of outcomes and exposure varied by gender and SES groups. Logistic regression models were used to obtain the association of weight status (underweight / normal weight Vs overweight / obese) with frequency of family meals as the main exposure. Overall the prevalence of obesity was more among the mid- high SES group and in boys. Over half of the participants had 7 or more family meals in the past week. There was no statistically significant association seen between family meals and weight status. Majority of the participants believed that eating healthy food and maintaining a healthy weight was important and eating at least one family meal was important. Majority of the participants who ate more than 3 or more family meals eat healthy food and also ate fast food. Intervention strategies should focus on the high risk group. Private schools are appropriate settings for interventions. Eating with families should be encouraged and future research should examine family meal patterns.
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