Longitudinal progression of blood biomarkers reveals a key role of astrocyte reactivity in preclinical Alzheimer's disease.

Defining the progression of blood biomarkers of Alzheimer's disease (AD) is essential for targeting treatments in patients most likely to benefit from early intervention. We delineated the temporal ordering of blood biomarkers a decade prior to the onset of AD symptoms in participants in the Baltimore Longitudinal Study of Aging. We show that increased astrocyte reactivity, assessed by elevated glial fibrillary acidic protein (GFAP) levels is an early event in the progression of blood biomarker changes in preclinical AD. In AD-converters who are initially cognitively unimpaired (N=158, 377 serial plasma samples), higher plasma GFAP levels are observed as early as 10-years prior to the onset of cognitive impairment due to incident AD compared to individuals who remain cognitively unimpaired (CU, N=160, 379 serial plasma samples). Plasma GFAP levels in AD-converters remain elevated 5-years prior to and coincident with the onset of cognitive impairment due to AD. In participants with neuropathologically confirmed AD, plasma GFAP levels are elevated relative to cognitively normal individuals and intermediate in those who remain cognitively unimpaired despite significant AD pathology (asymptomatic AD). Higher plasma GFAP levels at death are associated with greater severity of both neuritic plaques and neurofibrillary tangles. In the 5XFAD transgenic model of AD, we observed greater GFAP levels in the cortex and hippocampus of transgenic mice relative to wild-type prior to the development of cognitive impairment. Reactive astrocytosis, an established biological response to neuronal injury, may be an early initiator of AD pathogenesis and a promising therapeutic target.

A review on decentralized wastewater treatment systems in India.

Pollution of water resources and a lack of potable water are two important issues that city dwellers in India encounter. The passage of untreated sewage down municipal drains is one of the most significant sources of water resource pollution. In densely populated areas, effective sanitation and wastewater management is becoming increasingly difficult. In many developing nations, centralized sewage and wastewater treatment facilities serve only a section of big cities, and on-site sanitation is frequently insufficient in heavily populated areas. There is a demand for complementary and intermediate solutions. DEWATS (community-managed anaerobic decentralized wastewater treatment systems) is a good option for the possibility of relatively fast sanitation improvements in high-priority neighbourhoods where the local authority is not providing a full sanitation service. The following technical treatment modules are typically seen in DEWATS. The primary treatment consists of sedimentation ponds, settlers, septic tanks or bio digester, secondary treatment consists of anaerobic baffled reactors, anaerobic filters or anaerobic and facultative pond systems, secondary aerobic/facultative treatment consists of horizontal gravel filters and post-treatment consists of aerobic polishing ponds. The experience of India in establishing community-managed DEWATS on a large scale is examined in this review.

Optimal ferrofluids for magnetic cooling devices.

Superior passive cooling technologies are urgently required to tackle device overheating, consequent performance degradation, and service life reduction. Magnetic cooling, governed by the thermomagnetic convection of a ferrofluid, is a promising emerging passive heat transfer technology to meet these challenges. Hence, we studied the performance metrics, non-dimensional parameters, and thermomagnetic cooling performance of various ferrite and metal-based ferrofluids. The magnetic pressure, friction factor, power transfer, and exergy loss were determined to predict the performance of such cooling devices. We also investigated the significance of the magnetic properties of the nanoparticles used in the ferrofluid on cooling performance. γ-Fe2O3, Fe3O4, and CoFe2O4 nanoparticles exhibited superior cooling performance among ferrite-based ferrofluids. FeCo nanoparticles had the best cooling performance for the case of metallic ferrofluids. The saturation magnetization of the magnetic nanoparticles is found to be a significant parameter to enhance heat transfer and heat load cooling. These results can be used to select the optimum magnetic nanoparticle-based ferrofluid for a specific magnetic cooling device application.

Physical and chemical indicators of transformations of poultry carcass parts and broiler litter during short term thermophilic composting.

Short-term on-site composting of poultry carcasses and broiler litter (BL) is considered as a feasible technology for pathogen elimination during events of mass mortality in poultry houses. However, factors related to mass losses and physical transformation of the poultry carcass, and associated emissions of volatile organic compounds (VOCs) and odors, have not been thoroughly evaluated. This study aims to characterize the degradation of separated carcass parts co-composted with BL and the associated air emissions during 30 days of enclosed composting at 50 °C with constant aeration. The study was carried out in lab-scale simulators using five mixtures containing feathers, rib bones, skins, breast muscles, and hearts and livers, prepared at a 1:2 volumetric ratio (carcass:BL). Dry mass losses reached 59.5, 41.1, 60.8 and 103.5% (based on weight) or 48.4, 29.6, 49.7, and 94.8% (based on CO2-C and NH3-N emissions), for rib bones, skins, breast muscles, and hearts and livers, respectively. Visually, most of the carcass parts were degraded, and the typical carcass odor had disappeared by the end of the 30 days. Out of 24 VOCs, dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS) contributed 80.7-88.3% of the total VOC flux, considering the partial contribution of each part to the emissions involved with the whole carcass. DMDS, DMTS, benzaldehyde, methanethiol, pentanoic acid, and NH3, contributed 90.5-97.9% of the odor activity values during composting. DMDS/DMTS ratio is suggested as a potential biomarker of stabilization and readiness of the compost for transportation toward further treatment or safe burial.

Minimizing Hepatic Artery Thrombosis and Establishing Safety of Grafts With Dual Arteries in Living Donor Liver Transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) is a dreaded complication following living donor liver transplantation (LDLT) and can lead to graft failure and biliary complications. We evaluated the results of our arterial anastomotic technique and outcomes in grafts with dual arterial supply. PATIENTS AND METHODS: Between July 2010 and June 2015, 225 patients underwent LDLT. The hepatic artery anastomosis was done using our "W technique". In grafts with a dual arterial supply, two anastomoses were performed unless there was significant pulsatile back-bleeding in the smaller artery after the larger anastomosis. RESULTS: The mean age of the recipients was 43±15.2 years (6 months to 66 years). There were 184 right liver, 30 left liver, 10 left lateral segment, and 1 dual lobe (right liver and left lateral segment) grafts. Twenty-three (10.2%) patients had 2 graft arteries, 10 of which required 2 separate anastomoses, and an interposition saphenous vein conduit was used in one. HAT occurred in 3 (1.3%) patients. The median intensive care unit and postoperative hospital stays were 5 and 14 days, respectively. Post-transplant operative mortality was 12.4%. There was no difference in mortality (8.7% vs 12.4%, P = >.99) and biliary complications (11.9% vs 21.7%, P = .19) between recipients of grafts with single or dual graft arteries, respectively. CONCLUSIONS: A careful surgical "W technique" and intraoperative confirmation of a good arterial flow helps in reducing the incidence of early HAT. The presence of two arteries in the graft was not associated with increased incidence of HAT, mortality, or biliary complications.

A flexible control system designed for lab-scale simulations and optimization of composting processes.

Understanding and optimization of composting processes can benefit from the use of controlled simulators of various scales. The Agricultural Research Organization Composting Simulator (ARO-CS) was recently built and it is flexibly automated by means of a programmable logic controller (PLC). Temperature, carbon dioxide, oxygen and airflow are monitored and controlled in seven 9-l reactors that are mounted into separate 80-l water baths. The PLC program includes three basic heating modes (pre-determined temperature profile, temperature-feedback ("self-heating"), and carbon dioxide-dependent temperature), three basic aeration modes (airflow dependence on temperature, carbon dioxide, or oxygen) and enables all possible combinations among them. This unique high flexibility provides a robust and valuable research tool to explore a wide range of research questions related to the science and engineering of composting. In this article the logic and flexibility of the control system is presented and demonstrated and its potential applications are discussed.

Magnetic Janus particles synthesized using droplet micro-magnetofluidic techniques for protein detection.

Magnetic droplets on a microfluidic platform can act as micro-robots, providing wireless, remote, and programmable control. This field of droplet micro-magnetofluidics (DMMF) is useful for droplet merging, mixing and synthesis of Janus structures. Specifically, magnetic Janus particles (MJP) are useful for protein and DNA detection as well as magnetically controlled bioprinting. However, synthesis of MJP with control of the functional phases is a challenge. Hence, we developed a high flow rate, surfactant-free, wash-less method to synthesize MJP by integration of DMMF with hybrid magnetic fields. The effects of the flow rate, flow rate ratio, and hybrid magnetic field on the magnetic component of the Janus droplets and the MJP were investigated. It was found that the magnetization, particle size, and phase distribution inside MJP could be readily tuned by the flow rates and the magnetic field. The magnetic component in the MJP could be concentrated after mixing at flow rate ratio values less than 7.5 and flow rates less than 3 ml h-1. The experimental results and our simulations are in good agreement. The synthesized magnetic-fluorescent Janus particles were used for protein detection, with BSA as a model protein.

Pregnancy-related acute kidney injury: An analysis of 165 cases.

Pregnancy-related acute kidney injury (PRAKI) contributes to 3-7% of overall acute kidney injury (AKI) cases in Indian subcontinent. The aim of this study was to determine the outcomes of PRAKI and risk factors associated with renal injury and maternal mortality. One hundred and sixty-five patients with PRAKI, seen at M. S. Ramaiah Medical College between 2005 and 2014, were included in this, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per Risk, Injury, Failure, Loss of function, and End-stage renal disease (RIFLE) criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal, and fetal mortality. Incidence of PRAKI was 1.56%, and the mean age of the study population was 25 years. Fifty percent of the patients were diagnosed with PRAKI during their first pregnancy. PRAKI was observed most commonly in the postpartum period (60%), followed by third trimester (32%); as per RIFLE criteria, failure was seen in 36% and injury in 34%. Thirty percent of cases required RRT. Sepsis (59%), pre-eclampsia, and eclampsia (56%) were the leading causes of PRAKI, while sepsis was the leading cause of maternal mortality. Maternal and fetal mortality were 20% and 22%, respectively. In univariate analysis, shock, hemorrhage requiring transfusion of >5 units packed red blood cells, oliguria, and "Loss" category of RIFLE were significantly associated with mortality. Majority of the patients (57%) required Intensive Care Unit care with a mean duration of admission at 7.3 days, and 75% was diagnosed with AKI at the time of admission. We report the lowest incidence of PRAKI in contemporary Indian literature. PRAKI was associated with high maternal and fetal mortality, with sepsis being the leading cause. No association was noted between mortality and initial stages of RIFLE criteria.

Recent Advances in Nanosystems and Strategies for Managing Leishmaniasis.

BACKGROUND: Parasitic infection such as leishmaniasis, a neglected tropical disease, presents a significant global burden which is responsible for high mortality rate especially in less developed countries. Its intracellular nature and disseminated locations of parasite, limited number of chemotherapeutic agents, increasing incidences of resistance to first line drugs and toxicities, pose a great challenge to formulation scientists that have necessitated effective management of leishmanial infection by modulating the delivery of existing drugs. Over the past decade, research on development of alternative treatments such as nanotechnology-based drug delivery systems (nanoparticles, nanosuspensions, liposomes etc.), use of natural products as well as development of antileishmanial vaccine has been extensively investigated. OBJECTIVE: The present review focuses on different facets of therapeutic strategies, existing miscellaneous drug delivery systems and approaches intended for management, as well as treatment of the infection, with an objective to summarize the current trends and strategies adopted for antileishmanial therapy in a systematic manner. Moreover, the article encloses an eclectic collection of patents allied to new-fangled chemotherapeutics for antileishmanial therapy. CONCLUSION: The reported miscellaneous novel drug delivery systems along with the diverse approaches are seem to be precise, secure and relatively effective; and in an outcome, could lead to the new track for management of leishmaniasis.

Optimization of waste combinations during in-vessel composting of agricultural waste.

In-vessel composting of agricultural waste is a well-described approach for stabilization of compost within a short time period. Although composting studies have shown the different combinations of waste materials for producing good quality compost, studies of the particular ratio of the waste materials in the mix are still limited. In the present study, composting was conducted with a combination of vegetable waste, cow dung, sawdust and dry leaves using a 550 L rotary drum composter. Application of a radial basis functional neural network was used to simulate the composting process. The model utilizes physico-chemical parameters with different waste materials as input variables and three output variables: volatile solids, soluble biochemical oxygen demand and carbon dioxide evolution. For the selected model, the coefficient of determination reached the high value of 0.997. The complicated interaction of agricultural waste components during composting makes it a nonlinear problem so it is difficult to find the optimal waste combinations for producing quality compost. Optimization of a trained radial basis functional model has yielded the optimal proportion as 62 kg, 17 kg and 9 kg for vegetable waste, cow dung and sawdust, respectively. The results showed that the predictive radial basis functional model described for drum composting of agricultural waste was well suited for organic matter degradation and can be successfully applied.

Alpha-2 macroglobulin in Alzheimer's disease: a marker of neuronal injury through the RCAN1 pathway.

Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that inflammation is closely associated with AD pathogenesis and may be a promising target pathway for such interventions. However, little is known about the association between systemic inflammation and preclinical AD pathophysiology. We first examined whether the acute-phase protein, alpha-2 macroglobulin (A2M), a major component of the innate immune system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury in preclinical AD and risk of incident AD in the predictors of cognitive decline among normal individuals (BIOCARD) cohort. We find that A2M concentration in blood is significantly associated with CSF concentrations of the neuronal injury markers, tau and phosphorylated tau, and that higher baseline serum A2M concentration is associated with an almost threefold greater risk of progression to clinical symptoms of AD in men. These findings were replicated in the Alzheimer's Disease Neuroimaging (ADNI) study. Then, utilizing a systems level approach combining large multi-tissue gene expression datasets with mass spectrometry-based proteomic analyses of brain tissue, we identified an A2M gene network that includes regulator of calcineurin (RCAN1), an inhibitor of calcineurin, a well-characterized tau phosphatase. A2M gene and protein expression in the brain were significantly associated with gene and protein expression levels of calcineurin. Collectively these novel findings suggest that A2M is associated with preclinical AD, reflects early neuronal injury in the disease course and may be responsive to tau phosphorylation in the brain through the RCAN1-calcineurin pathway.

Droplet Merging on a Lab-on-a-Chip Platform by Uniform Magnetic Fields.

Droplet microfluidics offers a range of Lab-on-a-chip (LoC) applications. However, wireless and programmable manipulation of such droplets is a challenge. We address this challenge by experimental and modelling studies of uniform magnetic field induced merging of ferrofluid based droplets. Control of droplet velocity and merging was achieved through uniform magnetic field and flow rate ratio. Conditions for droplet merging with respect to droplet velocity were studied. Merging and mixing of colour dye + magnetite composite droplets was demonstrated. Our experimental and numerical results are in good agreement. These studies are useful for wireless and programmable droplet merging as well as mixing relevant to biosensing, bioassay, microfluidic-based synthesis, reaction kinetics, and magnetochemistry.

A Single Centre Analysis of Clinical Characteristics and Treatment of Endocrine Pancreatic Tumours.

Background. Endocrine Pancreatic Tumours (PENs) are rare and can be nonfunctioning or functioning. They carry a good prognosis overall though high grade lesions show a relatively shorter survival. The aim of the current study is to describe a single centre analysis of the clinical characteristics and surgical treatment of PENs. Patients and Methods. This is a cohort analysis of 40 patients of PENs who underwent surgery at Sir Ganga Ram Hospital, New Delhi, India, from 1995 to 2013. Patient particulars, clinical features, surgical interventions, postoperative outcome, and followup were done and reviewed. The study group was divided based on grade (G1, G2, and G3) and functionality (nonfunctioning versus functioning) for comparison. Results. PENs comprised 6.3% of all pancreatic neoplasms (40 of 634). Twenty-eight patients (70%) had nonfunctioning tumours. Eighteen PENs (45%) were carcinomas (G3), all of which were nonfunctioning. 14 (78%) of these were located in the pancreatic head and uncinate process (P = 0.09). The high grade (G3) lesions were significantly larger in size than the lower grade (G1 + G2) tumours (7.0 ± 3.5 cms versus 3.1 ± 1.6 cms, P = 0.007). Pancreatoduodenectomy was performed in 18 (45%), distal pancreatectomy in 10 (25%), and local resection in 8 (20%) and nonresective procedures were performed in 4 patients (10%). Fourteen patients (35%) had postoperative complications. All G3 grade tumours which were resected had positive lymph nodes (100%) and 10 had angioinvasion (71%). Eight neoplasms (20%) were cystic, all being grade G3 carcinomas, while the rest were solid. The overall disease related mortality attributable to PEN was 14.3% (4 of 28) and for malignant PENs was 33.3% (4 of 12) after a mean follow-up period of 49.6 months (range: 2-137 months). Conclusion. Majority of PENs are nonfunctioning. They are more likely malignant if they are nonfunctioning and large in size, show cystic appearance, and are situated in the pancreatic head. Early surgery leads to good long term survival with acceptable postoperative morbidity.

Carbon decomposition by inoculating Phanerochaete chrysosporium during drum composting of agricultural waste.

The effect of Phanerochaete chrysosporium inoculation during drum composting of agricultural waste was performed at different composting stages. Three trials were carried out with (5:4:1) combination of vegetable waste, cattle manure, and sawdust along with 10 kg of dried leaves with a total mass of 100 kg in a 550 L rotary drum composter. Trial 1 was a control without inoculation of fungus, while trial 2 was inoculated during the initial day (0th day of composting), and trial 3 was inoculated after the thermophilic phase, i.e., on the 8th day of composting period. The inoculation of fungus increased the volatile solids reduction by 1.45-fold in trial 2 and 1.7-fold in trial 3 as compared to trial 1 without any fungal inoculation. Total Kjeldahl Nitrogen (TKN) was observed with 2.31, 2.62, and 2.59% in trials 1, 2, and 3, respectively, at the end of 20 days of composting period. Hence, it can be concluded that inoculation of white-rot fungus increased the decomposition rate of agricultural waste within shorter time in drum composting. However, inoculation after the thermophilic phase was found more effective than inoculation during initial days of composting for producing more stabilized and nutrient-rich compost.

Effect of thermal annealing on the thermoluminescent properties of nano-calcium fluoride and its dose-response characteristics.

Nano-CaF2, prepared by the co-precipitation method, was annealed under different annealing conditions to improve its thermoluminescence (TL) characteristics. Different annealing parameters, such as temperature (400-700°C), duration (1-4 h) and environment (vacuum and air), were explored. The effect on TL sensitivity, peak position (Tm) and full-width at half-maximum (FWHM) with respect to the different annealing conditions are discussed as they are the measure of crystallinity of the material. Annealing temperature of 500°C with annealing duration of two and a half hours in vacuum provided the highest luminescence response (i.e. maximum sensitivity, minimum peak temperature and FWHM). Wide detectable dose range (5 mGy to 2 kGy), absence of thermal quenching and sufficient activation energy (1.04 eV) of this phosphor make it suitable for dosimetric applications.

Probiotic and prebiotic-probiotic PEC microparticles for sustaining and enhancing intestinal probiotic growth.

The aim of the study was to develop and evaluate Polyelectrolyte complex (PEC) microparticles composing Lactobacillus Acidophilus (probiotic) and Fructo oligosaccharide-Lactobacillus Acidophilus (prebiotic-probiotic), for sustaining and enhancing intestinal growth of probiotic bacteria. Gum Karaya-Chitosan(GK-CH) was used to fabricate PEC microparticles by extrusion method. The prepared microparticles were characterized for FT-IR, DSC and particle size and evaluated for percentage yield, swelling, surface morphology, entrapment rate and further studied for influence of prebiotic over probiotic growth. The fabricated PEC microparticles composed of Probiotic and Prebiotic- Probiotic have exhibited sustainability of probiotic bacteria for 12 hrs in GIT conditions and presence of prebiotic in the preparation enhanced the probiotic cell growth. Hence, it can be concluded that PEC between GK-CH was found to be successful in sustaining cell release and presence of prebiotic was found to enhance the probiotic cell growth.

TAR DNA-binding protein 43 pathology in Alzheimer's disease with psychosis.

BACKGROUND: TAR DNA-binding protein 43 (TDP-43) has been identified as a major disease protein in frontotemporal lobar degeneration. More recently, TDP-43 proteinopathy has also been observed in Alzheimer's disease (AD) with a characteristic distribution of TDP-43 predominantly in the mesial temporal lobe, and to a lesser degree in the neocortical areas. AD subjects with psychotic symptoms (AD+P) represent a subgroup characterized by greater impairment of frontal cortex-dependent cognitive functions and more severe frontal cortical neuropathology. The aim of this study is to determine whether there is an association between TDP-43 pathology and AD+P. We hypothesized that TDP-43 pathology would be more frequent in AD+P than in AD without psychosis. METHODS: We studied the presence and distribution of TDP-43 pathology by immunohistochemistry in the dentate gyrus (DG) and prefrontal cortex (FC) of postmortem brain specimens from 68 subjects with a primary neuropathologic diagnosis of AD as determined by the Neuropathology Core of the University of Pittsburgh Alzheimer's Disease Research Center. RESULTS: Forty-five (66%) subjects were classified as AD+P. Fourteen (20.6%) subjects had TDP-43 pathology in DG, eight (11.8%) had TDP-43 pathology in FC, and six (8.8%) had TDP-43 pathology in both regions. TDP-43 in DG was not significantly associated with AD+P. However, TDP-43 in FC demonstrated a trend toward reduced likelihood of psychosis (p = 0.068). TDP-43 pathology in DG, but not FC, was significantly associated with greater age at death and longer duration of illness. CONCLUSIONS: Our findings indicate that there was no association between concomitant TDP-43 pathology in DG or FC and AD+P.

Calcipotriol delivery into the skin as emulgel for effective permeation.

The objective of this work is to formulate and evaluate an emulgel containing calcipotriol for treatment of psoriasis. Emulgels have emerged as a promising drug delivery system for the delivery of hydrophobic drugs. Isopropyl alcohol and polyethylene glycol have been employed as permeation enhancers. Formulation chart is made with seven formulations, evaluated for physical parameters, drug content, viscosity, thixotropy, spreadability, extrudability, mucoadhesion, diffusion studies, skin irritation test along with short term stability studies. Carbopolis is reported to have a direct influence on appearance and viscosity of final formulation. The photomicroscopic evaluations showed the presence of spherical globules in size range of 10-15 µm. Rheograms revealed that all the formulations exhibited pseudoplastic flow. Optimized formulation (F6) had shown 86.42 ± 2.0% drug release at the end of 8 h study. The release rate through dialysis membrane and rat skin is higher when compared to commercial calcipotriol ointment. Hence it is concluded that calcipotriol can be delivered topically with enhanced penetration properties when formulated as emulgel.

Use of acupuncture in the management of chronic haemophilia pain.

Persons with haemophilia experience persistent pain resulting in chronic arthritic symptoms. The older person with haemophilia who did not benefit from primary prophylaxis are particularly at risk for persistent pain in multiple target joints as a result of repeated joint bleeding with delayed treatment received. The National Pain Study, Ref. [11] identified over 700 persons with haemophilia who rated daily persistent pain as 4.22/10 (SD ± 2.05) using a visual analogue scale. The study suggests that persons are continually seeking additional resources to relieve pain. This study seeks to identify: (i) effects of acupuncture use for persons with haemophilia who experience persistent joint pain as a result of repeated haemarthrosis and (ii) document no reported increased bleeding risk as a result of acupuncture use. End points include the subjects reported perception of reduction in pain via the 10-point visual analogue pain scale and bleeding. Nine subjects participated in the study, some who received a factor replacement to 15% correction and others who did not receive factor prior to any acupuncture sessions totaling 14 acupuncture treatments. No one of the subjects experienced bleeding or bruising. Six of the nine subjects reported an improvement in pain scores by at least 50%. Seven of the nine quality of life (QOL) domains within the QOL SF-36 questionnaire improved, suggesting a perception by subjects of improvement. This study suggests that acupuncture therapy can be a safe additional modality for pain management therapies in persons with haemophilia, although larger randomized studies are needed for further validation.