Guptaarthur1563

Furthermore, mTOR inhibition was associated with enhanced PD-L1 expression via TFE3 activation in translocation RCC. These data support the feasibility of combination therapy based on mTOR inhibition and PD-L1 blockade as a novel strategy for the treatment of patients with translocation RCC.Lung adenocarcinoma (LUAD) is a major health problem with minimal prognosis. Heterogeneity is a central determinant of the treatment outcome, requiring the identification of new subclasses of LUAD. Senescence has emerged as a crucial regulator of metastasis and drug response. Ionizing radiation- and doxorubicin-induced senescence associated genes in lung fibroblasts and K-means clustering were used to identify high- and low-senescence (HS and LS) classes among LUAD patients identified in The Cancer Genome Atlas (TCGA-LUAD). The LS group showed significantly poorer survival (P = 0.01) and greater activation of proliferative signaling pathways, proliferation, wound healing, and genetic aberrations. The TP53 mutation rate was significantly greater in the HS group (P less then 0.0001), explaining the phenotype. Also, genome-wide hypomethylation was significantly greater in the LS group than in the HS group. Interestingly, pathway analysis identified silencing of Wnt signaling in the HS group. The machine learning-based recursive feature elimination technique was used to identify a 20-gene senescence signature in TCGA-LUAD samples. The presence of a senescence phenotype with poor survival was validated in an independent patient cohort and a cell-line cohort using unsupervised clustering of samples based on a 20-gene signature. On further analysis, HS cells were more resistant to drugs, particularly histone deacetylase inhibitors. Taken together, a novel subtype of LUAD with reduced Wnt signaling and high drug resistance was identified.Metallothioneins (MTs) are crucial for metal ion homeostasis in mammalian cells. Specialized mass spectrometry methods have been developed to detect MTs in tissue extracts, though facile methods with scalable throughput are lacking. To improve analytical throughput and repeatability, we developed a standardised liquid chromatography tandem mass spectrometry (LC-MS/MS) method for robust determination of metallothionein-3 (MT3) that is amenable to microplate processing. This method uses standard protein digestion conditions with commercially available reagents and commonly practiced reversed-phase chromatography, detecting MT3 at low ng/mL levels in human brain tissue extracts. We found that trypsin digestion largely underestimated MT3 levels, whereas endopeptidase Lys-C yielded vastly higher signals with low replicate variance. The choice of target peptide was critical for accurate MT3 detection - a peptide in the α-domain yielded the most robust signals. We demonstrate the utility of this method by comparing the expression of MT3 in post-mortem brain tissues of a cohort of Alzheimer's disease (AD) individuals and age-matched controls.Considering the fact that new, safe and incorporable treatment alternatives to therapeutic prophylaxis for tungiasis are lacking and sometimes proving difficult, this present study evaluated the potentials of integrating control approach involving focal premise treatment using 5% emulsifiable concentrate of cypermethrin, and topical application of Piper guineense oil with personal protection. Of the 90 houses selected, their floors were classified into paved rooms & unpaved verandas, paved verandas & unpaved rooms, paved rooms & verandas, and unpaved rooms & verandas, and tested for the presence of sand fleas using the sweeping and beating as well as soil collection and extraction by tullgren funnel method before fumigation. A total of 100 individuals partitioned into four groups of 25 individuals each were assigned 3%, 5%, 10% and 15% of P. guineense oil irrespective of stages of embedded fleas. The mean of sand fleas decreased from 1.14, 0.07, 0.21, and 1.66 to 0.37, 0.02, 0.09 and 1.08 after two weeks of single spray compared to the untreated location (p less then 0.001). Furthermore, the mean lesions of stage I reduced to 0 after 2 to 6 days of 3%, 5%, 10% and 15% ointment application, and stage II and III after 10 to 12 days of 10% and 15% application respectively. The difference between tungiasis stages and exposure time for P. guineense ointment was highly significant p = 0.007 and p = 0.0002. Notable reduction in severity score of acute and chronic tungiasis was observed thus indicating effectiveness of the topical ointment. Hexanolic oil extracts of P. guineense in 10% and 15% concentration would kill embedded sand flea and ameliorate the sufferings in endemic settings.

On May 2, 2017, an outbreak of unexplained fever with rashes was reported in Lu'an, China. In this study, we aimed to identify the possible pathogens, epidemiological characteristics, and risk factors of this outbreak.

We conducted descriptive field epidemiological studies. Blood samples were tested using an indirect immunofluorescence assay for Rickettsia rickettsii antibody, and nested polymerase chain reaction and gene sequencing assays were performed.

We recruited 39 cases who had symptomatic onset from April 20 to June 8, 2017. Among these, 9 were suspected cases, 18 were probable cases, and 12 were confirmed cases. No one died. The main clinical manifestations were fever (100%), rash (100%), fatigue (97.3%), myalgia (83.8%), and anorexia (83.8%). None of the patients died. Thirty-seven patients who were treated with antibiotics during hospitalization showed significant improvement. The cases were distributed across 14 townships in 2 counties. The median age was 59 (43.0-81.0) years, of which 93.3% had a history of tea picking (28/30), and 77.3% (17/22) had a history of tick bites. The mean incubation period was 5.0 days (2.0-13.0 days). Serum IgG titers were higher in convalescent patients than in the general population (p=0.016). Phylogenetic analysis revealed that the ompA sequences of Rickettsia sp. Lu'an-2018 had an 86.8%-99.0% sequence identity with the 23 strains of Rickettsia found worldwide.

This was the first reported outbreak of an undetermined species of a human infection with the spotted fever group of Rickettsia in China, which might be caused by ticks biting local residents when picking tea.

This was the first reported outbreak of an undetermined species of a human infection with the spotted fever group of Rickettsia in China, which might be caused by ticks biting local residents when picking tea.Schistosomiasis is a Neglected Tropical Disease caused by trematode species of the genus Schistosoma. Sulfosuccinimidyl oleate sodium mouse Both, autochthonous and imported cases of urogenital schistosomiasis have been described in Europe. The present study focuses on eggs, considered pure S. haematobium by genetic characterisation (intergenic ITS region of the rDNA and cox1 mtDNA). A phenotypic characterisation of S. haematobium eggs was made by morphometric comparison with experimental populations of S. bovis and S. mansoni, to help in the diagnosis of S. haematobium populations infecting sub-Saharan migrants in Spain. Analyses were made by Computer Image Analysis System (CIAS) applied on the basis of new standardised measurements and geometric morphometric tools. The principal component analysis (PCA), including seventeen non-redundant measurements, showed three phenotypic patterns in eggs of S. haematobium, S. bovis and S. mansoni. PCA showed that the S. bovis population presented a large egg size range with a pronouncedly larger maximum size. Similarly, S. bovis shows bigger spine values than S. haematobium. Mahalanobis distances between each pair of groups were calculated for each discriminant analysis performed. In general, S. mansoni and S. bovis present larger distances between them than with S. haematobium, i.e. they present the greatest differences. Regarding the spine, S. haematobium and S. mansoni are the most distant species. Results show the usefulness of this methodology for the phenotypic differentiation between eggs from these Schistosoma species, capable of discerning morphologically close eggs, as is the case of the haematobium group. Schistosoma egg phenotyping approaches may be applied to assess not only hybrid forms but also potential influences of a variety of other factors.Compared internationally, the history of the Swiss Tropical and Public Health Institute (Swiss TPH) is unusual. Founded in 1944, at a time of utmost isolation, it was a response to specific needs of the government of Switzerland during the Second World War. In 1943, the Swiss Federal Council approached universities in Switzerland and asked them to submit project proposal that had the potential to mitigate possible post-war unemployment and threatening economic isolation. Members of the University of Basel proposed to establish a Swiss Tropical Institute (today Swiss TPH). With its harbour at the River Rhine, Basel was an important international transport hub. The city was and still is the headquarters of important pharmaceutical companies, such as Novartis Pharma AG and F. Hoffmann-La Roche AG, which were looking for new markets overseas. Last but not least, scientific expeditions to Africa were rather common in the 19th and the beginning of the 20th century for members of Basel's bourgeoisie. Initially, Swiss TPH focused primarily on basic research into diseases of poverty, but over the years it has developed into an important player in public, international and global health. This article sees the development of the institute as a reflection of the visions of its directors from the founder Professor Rudolf Geigy to Professor Jürg Utzinger, who is the current Swiss TPH director. It includes interviews with the four latest of them, discussing their experiences and attempts to adapt the institute to an ever changing global environment. From these lessons learnt we hope to gain insights that could be relevant for today's leaders of scientific institutes; foster public-private partnerships and contribute to solve some of the most pressing global health challenges.Free living amoebae (FLA) can be found in different environments, where they feed on diverse microorganisms. Some bacteria preyed by FLA are called amoeba-resistant bacteria (ARB), as they can resist to lysosomal fusion and are capable of multiplying and evading FLA after internalization, propagating in the environment. Despite the health risks due to the existence of pathogenic and opportunistic species that are ARB and the pathogenicity of some FLA species, there are no water quality protocols to analyze the presence of ARB or FLA. In this sense, our study aimed to isolate FLA through amoebal enrichment and to identify ARB using amoebal coculture in water samples from a public park and two hospitals in southern Brazil. As a result, 9 different microorganisms genera have been identified through amoebal coculture, including fastidious Legionella spp. and Bosea vestrisii. From the positive samples for FLA, by amoebal enrichment, Acanthamoeba spp., Vermamoeba vermiformis and Naegleria spp. were identified in 14 amoebic isolates. The methodologies used in this work proved to be effective as simple and low-cost methods to be used in the implementation in water quality control of anthropogenic environments.