Age- and AD-related redox state of NADH in subcellular compartments by fluorescence lifetime imaging microscopy

Abstract

Nicotinamide adenine dinucleotide (reduced form: NADH) serves as a vital redox-energy currency for reduction-oxidation homeostasis and fulfilling energetic demands. While NADH exists as free and bound forms, only free NADH is utilized for complex I to power oxidative phosphorylation, especially important in neurons. Here, we studied how much free NADH remains available for energy production in mitochondria of old living neurons. We hypothesize that free NADH in neurons from old mice is lower than the levels in young mice and even lower in neurons from the 3xTg-AD Alzheimer's disease (AD) mouse model. To assess free NADH, we used lifetime imaging of NADH autofluorescence with 2-photon excitation to be able to resolve the pool of NADH in mitochondria, cytoplasm, and nuclei. Primary neurons from old mice were characterized by a lower free/bound NADH ratio than young neurons from both non-transgenic (NTg) and more so in 3xTg-AD mice. Mitochondrial compartments maintained 26 to 41% more reducing NADH redox state than cytoplasm for each age, genotype, and sex. Aging diminished the mitochondrial free NADH concentration in NTg neurons by 43% and in 3xTg-AD by 50%. The lower free NADH with age suggests a decline in capacity to regenerate free NADH for energetic supply to power oxidative phosphorylation which further worsens in AD. Applying this non-invasive approach, we showed the most explicit measures yet of bioenergetic deficits in free NADH with aging at the subcellular level in live neurons from in-bred mice and an AD model.

http://bit.ly/2GfaZTE

‘May you live in interesting times’: blessing or curse for an intensivist?

No abstract available

http://bit.ly/2GtB94y

A Novel Approach of Mathematical Theory of Shape and Neuro-Fuzzy Based Diagnostic Analysis of Cervical Cancer

Abstract

This study aims to detect the abnormal growth of tissue in cervix region for diagnosis of cervical cancer using Pap test of patients. The proposed methodology classifies cervical cancer for pattern recognition either benign or malignant stages using shape and neuro-fuzzy based diagnostic model. In this experiment, firstly the authors segment Pap smear images of cervical cells using fuzzy c-means clustering algorithm and shape theory to classify them according to the presence of abnormality of the cells. Secondly the features extraction process is performed in the part of nucleus and cytoplasm on the squamous and glandular cells and the authors used input variables such as cytoplasm area (CA), cytoplasm circularity (CC), nucleus area (NA), nucleus circularity (NC), nucleus-cytoplasm ratio (NCR), and maximum nucleus brightness (MNB) in fuzzy tools and used fuzzy rules to evaluate the cervical cancer risk status as an output variable. The proposed neuro-fuzzy network system was developed for early detection of cervical cancer. A neural network was trained with 15-Pap image datasets where Levenberg–Marquardt(LM) a feed-forward back-propagation algorithm was used to get the status of the cervical cancer. Out of 15 samples database, 11 data set for training, 2 data set for validation and 2 data set for test were used in the ANN classification system. The presented fuzzy expert system(FES) successfully identified the presence of cervical cancer in the Pap smear images using the extracted features and the use of neuro-fuzzy system(NFS) for the identification of cervical cancer at the early stages and achieve a satisfactory performance with 100% accuracy.

http://bit.ly/2SbttLg

Differential risk of disease progression between isolated anastomotic ulcers and mild ileal recurrence after ileocolonic resection in patients with Crohn’s disease

It is standard of care to perform ileocolonoscopy within a year of ileocolonic resection for Crohn's disease (CD) and to guide management decisions based on the Rutgeert score (RS). The modified RS subdivides i2 into lesions confined to the anastomosis (i2a) or >5 aphthous lesions in the neoterminal ileum (i2b). There is uncertainty, however, if i2a lesions incur an increased risk of disease recurrence. The primary aim of this study was to compare the rates of endoscopic progression between i2a and i2b when compared with i0-i1.

http://bit.ly/2GoUIuV

Survival differences in multiple myeloma in Latin America and Asia: a comparison involving 3664 patients from regional registries

Abstract

In previous observational studies, we have separately characterized patients with multiple myeloma (MM) both from Latin America (LA) and from Asia. Here, we analyze these two datasets jointly, in order to assess the overall survival (OS) in these two world regions. Data were available from 3664 patients (1968 from LA and 1696 from Asia); all of whom diagnosed between 1998 and 2007. Approximately, 26% of patients in both world regions underwent transplantation. OS (from diagnosis of MM) was explored with Kaplan–Meier analyses and Cox proportional hazards models. Patients from LA were significantly younger and had hypercalcemia more often than Asian patients, who in turn had higher proportions of anemia and International Staging System (ISS) stage III disease. The median OS was 56 months in LA, and 47 months in Asia (hazard ratio [HR] = 0.83; 95% confidence interval [CI], 0.76 to 0.91; P < 0.001). In multivariable analysis, age, ISS stage III, anemia, hypercalcemia, and world region remained significantly associated with OS (P < 0.001 for all covariates). These results were largely driven by patients not undergoing transplantation, as no difference in OS emerged between the two world regions in univariable or multivariable analysis for transplanted patients. Despite adverse prognostic features differentially favoring each region, and adjusting for such differences, we found an OS advantage for patients from LA, in comparison with contemporaneous patients from Asia. Whether this is due to different biological features, differences in access to novel agents (especially thalidomide in earlier periods of the study), unmeasured confounders, or the play of chance, remain unknown.

http://bit.ly/2GeNx9l

Bisphosphonates

The bisphosphonates are stable analogues of pyrophosphate, a naturally occurring regulator of bone metabolism. They have a high affinity for calcium ions, and bind rapidly to hydroxyapatite crystals in mineralized bone. Bisphosphonates are subsequently released and taken up by osteoclasts, interfering with their function and/or inducing their apoptosis (programmed cell death). Nitrogen-containing bisphosphonates (e.g. alendronate, ibandronic acid, pamidronate disodium, zoledronic acid) inhibit the mevalonate pathway vital for normal cellular function (e.g.

http://bit.ly/2SeFlMO

Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth

To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment.

http://bit.ly/2Sw52HJ