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In vivo positron emission tomography (PET) using [C11]-labeled Pittsburgh Compound B ([C11]PiB) has previously been shown to detect amyloid-β (Aβ) in late-onset Alzheimer disease (LOAD) brain; however, the sensitivity of this technique for detecting β-amyloidosis in autosomal dominant Alzheimer disease (ADAD) has not been systematically investigated. To validate [C11]PiB PET as a useful biomarker of β-amyloidosis, we measured the cortical and regional standardized uptake value ratios (SUVRs) in 16 ADAD and 15 LOAD cases and compared them with histopathologic measures of β-amyloidosis in postmortem brain. The PiB-PET data were obtained between 40–70 min after bolus injection of ∼15 mCi of [11C]PiB. MRI and PiB-PET images were co-registered and SUVRs were generated for several brain regions. Using Aβ immunohistochemistry (10D5, Eli Lilly), the burden of Aβ plaques was quantified in 16 regions of interest using an area fraction fractionator probe (Stereo Investigator, MicroBrightfield, VT). There were regional variations in Aβ plaque burden with highest densities observed in the neocortical areas and the striatum. On spearman correlations, in vivo PiB-PET correlated with postmortem Aβ plaque burden in both LOAD and ADAD, with strongest correlations seen in neocortical areas. In summary, [C11]PiB-PET has utility as a biomarker in both ADAD and LOAD.
This presentation will enable the learner to:
1.Discuss how PET-PiB beta-amyloid imaging is used as a potential biomarker of Alzheimer disease (AD)
2.Correlate postmortem neuropathologic evidence of beta-amyloidosis with PET-PiB data, and learn that PET-PiB is a potentially useful tool to detect beta-amyloidosis in presymptomatic and symptomatic individuals
A cross-sectional study was conducted from 2014 to 2017 in 13 organised pig farms located in eight states of India (Northern, North-Eastern and Southern regions) to identify the risk factors, pathotype and antimicrobial resistance of Escherichia coli associated with pre- and post-weaning piglet diarrhoea. The data collected through questionnaire survey were used to identify the risk factors by univariable analysis, in which weaning status, season, altitude, ventilation in the shed, use of heater/cooler for temperature control in the sheds, feed type, water source, and use of disinfectant, were the potential risk factors. In logistic regression model, weaning and source of water were the significant risk factors. The piglet diarrhoea prevalence was almost similar across the regions. Of the 909 faecal samples collected (North – 310, North-East – 194 and South – 405) for isolation of E. coli, pathotyping and antibiotic screening, 531 E. coli were isolated in MacConkey agar added with cefotaxime, where 345 isolates were extended spectrum β-lactamase (ESBL) producers and were positive for blaCTX-M-1 (n = 147), bla TEM (n = 151), qnrA (n = 98), qnrB (n = 116), qnrS (n = 53), tetA (n = 46), tetB (n = 48) and sul1 (n = 54) genes. Multiple antibiotic resistance (MAR) index revealed that 14 (2.64%) isolates had MAR index of 1. On the virulence screening of E. coli, 174 isolates harboured alone or combination of Stx1, Stx2, eaeA, hlyA genes. The isolates from diarrhoeic and post-weaning samples harboured higher number of virulence genes than non-diarrhoeic and pre-weaning. Alleviating the risk factors might reduce the piglet diarrhoea cases. The presence of multidrug-resistant and ESBL-producing pathogenic E. coli in piglets appears a public health concern.
A novel microfilarial sheath protein (MfP) of the human filarial parasite Wuchereria bancrofti and its proinflammatory activity on host macrophages were identified recently. MfP is a homolog of the nematode bestrophin-9 superfamily that acts as a ligand of macrophage Toll-like receptor 4 (TLR4) to induce inflammation through NF-κB activation. Therefore, the presence and functional implication of this novel protein in adult-stage parasites were open questions to answer. In this study, the bovine filarial parasite Setaria cervi was used to simulate adult W. bancrofti. We detected the presence of MfP in adult-stage S. cervi through clear immunological cross-reactivity and immunolocalization employing an anti-MfP antibody developed in mice. Therefore, our findings put forward S. cervi as a cost-effective source of immunodominant filarial antigen MfP to simulate its future utilization in the immunotherapeutic intervention of lymphatic filariasis.
Efficacious therapeutic strategies against lymphatic filariasis are always sought after. However, natural products are a promising resource for developing effective antifilarial agents. Azadirachtin, a significant tetranortriterpenoid phytocompound found in Azadirachta indica, was evaluated in vitro for antifilarial potential against the filarial parasite Setaria cervi. Dye exclusion and MTT assay confirmed the antifilarial potential of azadirachtin against S. cervi with a median lethal dose (LC50) of 6.28 μg/ml for microfilariae (mf), and 9.55 μg/ml for adult parasites. Morphological aberrations were prominent in the histological sections of the azadirachtin-exposed parasites. Moreover, alterations in the reactive oxygen species (ROS) parameters in treated parasites were evident. Induction of apoptosis in treated parasites was confirmed by DNA laddering, acridine orange (AO)/ethidium bromide (EtBr) double staining and in situ DNA fragmentation. The downregulation of anti-apoptotic CED-9 and upregulation of proapoptotic EGL-1, CED-4 and CED-3 at both the transcription and translation levels confirmed apoptosis execution at the molecular level. Changes in the gene expressions of nuc-1, cps-6 and crn-1 further clarified the molecular cause of DNA degradation. Furthermore, azadirachtin was found to be non-toxic in both in vitro and in vivo toxicity analyses. Therefore, the experimental evidence detailed the pharmacological effectiveness of azadirachtin as a possible therapeutic agent against filariasis.
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β. This immune polarization was also evidenced by upregulation of nuclear factor-κ light-chain enhancer of activated B cells p50 and regulated expression of suppressor of mother against decapentaplegic protein-4. rLd-iPGAM stimulation also promoted lymphocyte proliferation and boosted the leishmaniacidal activity of macrophages by upregulating reactive oxygen species. It also induced 1·8-fold higher release of nitric oxide (NO) by promoting the transcription of inducible nitric oxide synthase gene. Besides, in silico analysis suggested the presence of major histocompatibility complex class I and II restricted epitopes, which can proficiently trigger CD8+ and CD4+ cells, respectively. This study reports rLd-iPGAM as an effective immunoprophylactic agent, which can be used in future vaccine design.
Deformation characteristics of polycrystalline ice and their dependence on time, temperature, and stress have been analysed on the basis of a phenomenological relation which describes creep in terms of initial elastic, delayed elastic, and permanent strain. It is shown that the effective modulus of ice observed in the laboratory or in the field can be examined on the basis of this model. The model also provides a basis on which the observed flow law of ice can be examined conveniently. Some apparent inconsistencies in the results of earlier investigations of the mechanical property of ice appear of be reconciled by the model.
A method is described for preparing the surface of ice and for forming etch pits on the prismatic surfaces with whisker replicas that correspond to basal dislocations. The technique removes the ambiguity sometimes associated with etch pits and dislocations, and allows direct observation of dislocation glide, pile-up against barriers, and other features in deformed ice.
A test program undertaken in April 1981 on the uniaxial compressive strength of freshly recovered first-year columnar-grained sea ice at a portable field laboratory floating on top of the ice cover in Eclipse Sound, Baffin Island, Canadian Arctic, is reported. Using a small battery-operated test machine, both vertical and horizontal samples were tested so that the load could be applied either parallel or perpendicular to the axis of the columns. Rate sensitivity of the observed strength is discussed in terms of measured average strain-rate and average stress-rate to upper yield or failure. Strain and time aspects of the test results are considered as well. Although vertical samples showed considerably greater strength than horizontal samples, no significant differences were detected in the failure strains. Examination of the interdependence of failure stress and failure time revealed certain anomalies in the results for vertical samples that could be linked to the performance characteristics of the test machine. As such problems could be common to any test system, methods of analysis are proposed for rational examination of the results.
This paper describes the growth of sea ice and the salinity profiles observed in Eclipse Sound near Pond Inlet, Baffin Island, Canada, during the winter of 1977–78. A numerical method of calculation has been developed to incorporate the variations in snow conditions and physical properties of ice and snow during the growth season. It is shown that the growth rate can be predicted reasonably well. It is also shown that the vertical salinity profile in the ice towards the end of the season, provides a record of previous climatological conditions. A dependence has been shown between the predicted growth rate and the measured salinity.
Cassava germplasm collection is important for the preservation of genetic variability, allowing the development of improved cultivars with desirable traits such as drought and disease tolerance, better starch quality and yield. Therefore, the assessment of diversity in cassava germplasm maintained by farmers is important for maintaining biodiversity and crop improvement. Herein, we report genetic diversity relationships of 52 farmer-preferred cassava landraces from the eastern zone of Tanzania based on morphological descriptors and single nucleotide polymorphisms (SNPs). Cluster analysis was performed for both morphological traits (genetic distance 1.18–0.15) and SNPs (genetic distance 0.078–0.002). The analysis revealed that there were a total of 17,393 variant positions, and that several of the SNPs were distributed across all the chromosomes. The abundance of SNP varied remarkably among the 18 cassava chromosomes, with chromosome 2 having the highest number of SNPs (1335) and chromosome 18 having the lowest number of SNPs (734). The power of SNPs in distinguishing morphologically similar landraces was shown. Both analyses did not group landraces according to geographical locations, suggesting that farmers were moving cassava germplasm to different areas. Their diversity was mainly due to adaptation and preferential selection by farmers. This further implied that within a geographical location, the cultivars were more diverse and there was no misnaming of cassava cultivars by farmers. The collection revealed a wide range of genetic diversity, and represented a valuable resource for trait improvement, allowing the capture of farmer-preferred traits in future cassava breeding programmes.
Purpose: Hemangiopericytoma and Meningioma appear similar on routine diagnostic imaging. Diffusion weighted images (DWI) has been used to characterize different types of tumors. The purpose of this study was to assess whether DWI can be used to differentiate hemangiopericytoma from meningioma on diagnostic imaging. Materials and Methods: In a retrospective study, our tumor database was analyzed for diagnosis of hemangiopericytoma with DWI available at the time of diagnostic imaging. These patients were then matched based on location and size of the tumor in a ratio of 1 hemangiopericytoma vs. 2 matched meningioma. The minimum and mean Apparent Diffusion Coefficient (ADC) was measured in the tumor and the contralateral Normal Appearing White Matter (NAWM) to calculate a normalized ADC (nADC) as the ratio of the two. The two tumors were also subjectively assessed for their heterogeneity. Results: Seven patients with histopathological diagnosis of hemangiopericytoma were matched based on size and location with 14 patients of meningioma. Primary meningioma were significantly homogeneous (p<0.001) in appearance compared to hemangiopericytomas. Hemangiopericytomas had a higher mean ADC compared to that of meningioma (p<0.001). Conclusion: Hemangiopericytoma showed heterogeneity on DWI and significantly higher ADC compared to that of meningiomas in our small study. This needs to be confirmed in a study with a larger sample size.
The vestibulocochlear nerve is a sensory nerve that serves the organs of hearing and equilibrium. Neuropathies of the nerve, particularly auditory neuropathy, may be caused by primary demyelination or axonal disease. Cochlear amplification function is normal in cases of auditory neuropathy, but afferent neural conduction in the auditory pathway is disordered. It is highly probable that the vestibular nerve has some involvement in disorders affecting the cochlear nerve.
To provide an overview of vestibular test findings in individuals with auditory neuropathy.
A structured literature search was carried out, with no restrictions to the dates searched.
Auditory neuropathy implicated the vestibular branch of the VIIIth cranial nerve as well as the cochlear nerve. However, there was variability in terms of vestibular test findings.
We report on disruption of the log layer in the resolved bottom boundary layer in large-eddy simulations (LES) of full-depth Langmuir circulation (LC) in a wind-driven shear current in neutrally-stratified shallow water. LC consists of parallel counter-rotating vortices that are aligned roughly in the direction of the wind and are generated by the interaction of the wind-driven shear with the Stokes drift velocity induced by surface gravity waves. The disruption is analysed in terms of mean velocity, budgets of turbulent kinetic energy (TKE) and budgets of TKE components. For example, in terms of mean velocity, the mixing due to LC induces a large wake region eroding the classical log-law profile within the range . The dependence of this disruption on wind and wave forcing conditions is investigated. Results indicate that the amount of disruption is primarily determined by the wavelength of the surface waves generating LC. These results have important implications for turbulence parameterizations for Reynolds-averaged Navier–Stokes simulations of the coastal ocean.
Manipur is a state in northeastern India and in civil war for > 45 years. Healthcare delivery and access is affected due to poor security, restricted accessibility, and the incapacity of this fragile state.
The burden of morbidity and mortality in the conflict area of Manipur was estimated using data sources (hospital attendance, hospital inpatient, and death registries, national family and health registries, and in-depth interviews of healthcare providers) and compared to national averages. These findings were co-related with violent events reported in the local newspaper.
Excess mortality was observed in the 21–50 year age group, but not in females or the elderly. The major causes of deaths were non-communicable diseases, cerebrovascular accidents, and chronic pulmonary disease. Chronic conflict increased the burden of alcohol liver disease and of mental health diseases. Suicidal deaths were common in the mid-twenty age group and usually due to agricultural pesticide consumption. These deaths were higher in men, and suicide attempts were higher in women. The prevalence of intravenous drug users and of HIV was reported to be five times as higher than the national average. High rates of disappearances, mutilation, torture, kidnapping, and hostage-taking, spousal physical violence and attacks on healthcare facilities and medical personnel were events of concern. There were no reported events of suicide bombers.
Protracted conflict dramatically changes the demographics and disease burden. Humanitarian space constantly is under threat of attack and the insecurity interferes with the provision of sustained preventive and curative services. Recommendations to be implemented would measures to continue treatment in the insecure environment through telephonic or online medical helplines, vaccination, and drug supplies during negotiated ceasefires or curfew times and protecting humanitarian spaces. However, militarization of healthcare may not be favorable solution.
The 26–29 November 2008, terrorist attacks in Mumbai, have been referred to as “India's 9/11”. Violent events in Mumbai over the past six decades were researched to understand the changing pattern of violent injuries.
A complex, retrospective, descriptive study on terrorist events was performed, using event reports, legal reports, newspaper reports, and police and hospital lists. The distribution of victims to various city hospitals, the critical radius, surge capacity, and nature of interventions required were assessed. The profile of those killed in the attacks was noted by sex, nationality, and occupation. Besides the overall mortality and case-fatality ratio, the critical mortality was calculated based on the death rates among the critically injured.
In 51 violent events in Mumbai over a 60-year period (1950–2009), 1,582 people were killed and 4,145 were injured. In the Mumbai terrorist attacks of 2008, the financial loss due to direct physical damage was INR 847,612,971 (US$18.5 million). Among those killed, the average age was 33.4 years, 80% were male, and 12% were foreign nationals. The case-fatality ratio for this event was 36.2% and the mortality among the critically injured (critical mortality rate) was 11%. Among the injured, 79% were male and the average age was 33.21 years (three months–85 years); 38.5% of patients arriving at the hospitals required major surgical intervention.
The injuries of violent events in Mumbai have been changing due to the use of heavy firepower and explosives. Strengthening the public hospitals for trauma care is a medical counter-terrorism response for future terrorist attacks. These attacks have affected the lives of the common person in Mumbai, in terms of increased security checks, alerts, and fear of further attacks. These are areas of further research.
The properties of thin films prepared by coevaporation of Y, Cu and Ba.F2, followed by post anneals in O2/H2O, are described. In particular, we emphasize what is known about. the relationship between the processing variables and the physical and chemical structure of the resulting films.
Preliminary work suggests that Acoustic Resonance Spectroscopy (ARS) can non-invasively determine gas pressurization of waste drums. This is done by exciting the various mechanical vibrational modes of the test drum and analyzing the characteristics of the resulting resonance frequencies and their higher harmonics. If the contained waste is a liquid, the liquid level and also some properties of the liquid including density can be determined. Additional work is needed to exploit this novel acoustic technique for noninvasive characterization of waste storage drums.