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1.
Indian J Med Microbiol ; 49: 100605, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38734140

RESUMO

Cerebral phaeohyphomycosis (CP) stands as an exceedingly uncommon yet severe type of fungal infection affecting the central nervous system, attributable to dematiaceous fungi. Despite the patient's immune status, CP is associated with grave prognosis. In the present study, authors describe the first case of left thalamic fungal abscess due to Rhinocladiella mackenziei in an immunocompetent 39-year-old male patient in Jaipur, Rajasthan. Early diagnosis by direct microscopy of aspirated pus and extensive management with surgical excision and prolonged antifungal coverage showed favourable outcome. The present case is one of the few cases documented globally who has survived.


Assuntos
Antifúngicos , Abscesso Encefálico , Humanos , Masculino , Adulto , Abscesso Encefálico/microbiologia , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/tratamento farmacológico , Antifúngicos/uso terapêutico , Feoifomicose Cerebral/diagnóstico , Feoifomicose Cerebral/microbiologia , Índia , Tálamo/patologia , Tálamo/microbiologia , Tálamo/diagnóstico por imagem , Resultado do Tratamento
2.
Environ Pollut ; 347: 123706, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38467367

RESUMO

Fly ash consists of a considerable amount of hazardous elements with high mobility, posing substantial environmental risks during storage in surface impoundments and landfills. This hinders its efficient reuse in construction or material industries. To enhance the versatility of fly ash applications, a novel surface modification technique, termed SuMo, has been developed to create a hydrophobic polysulfide polymer coating on the surface of fly ash particles. The physicochemical properties of SuMo fly ash samples were examined using atomic force microscopy (AFM), environmental scanning electron microscopy (ESEM), thermal gravimetric analysis (TGA), Fourier Transform Infrared spectroscopy (FTIR), and leaching of hazardous elements was tested under practical environmental conditions (pH 4-12) based on the EPA's leaching environmental assessment framework (LEAF). The successful coating of polysulfide polymer on fly ash surface was verified through an increased percentage of C, S, and O in elemental mapping, coupled with the identification of S-O, CO, and C-H functional groups consistent with the chemical structure of polysulfide polymer. While the SuMo fly ash particles maintained their spherical shape, they exhibited increased surface roughness, robust hydrophobicity, and thermal stability up to 250 °C. Notably, owing to the coating's resilience against water leaching, the SuMo fly ash demonstrated a substantial reduction (up to 60-fold) in leachate concentrations of multiple concerning elements, including B, Be, Ba, Mn, Zn, As, Cr, Hg, etc., under various pH conditions compared to the uncoated fly ash. Furthermore, the polysulphide polymer coating effectively prevented Hg volatilization from fly ash below 163 °C. This study highlights the efficacy of the developed polysulfide polymer coating in mitigating the diffusion of hazardous elements from fly ash, thereby enhancing its potential reutilization in material, construction, and agriculture industries.


Assuntos
Cinza de Carvão , Mercúrio , Sulfetos , Cinza de Carvão/química , Microscopia Eletrônica de Varredura , Agricultura
3.
Environ Res ; 248: 118317, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38301761

RESUMO

The Third Pole (TP) is a high mountain region in the world, and is well-known for its pristine environment, but recent development activities in the region have degraded its air quality. Here, we investigate the spatial and temporal changes of the air pollutants ammonia (NH3), sulphur dioxide (SO2) and carbon monoxide (CO) in TP, and reveal their sources using satellite measurements and emission inventory. We observe a clear seasonal cycle of NH3 in TP, with high values in summer and low values in winter. The intense agriculture activities in the southern TP are the cause of high NH3 (6-8 × 1016 molec./cm2) there. Similarly, CO shows a distinct seasonal cycle with high values in spring in the southeast TP due to biomass burning. In addition, the eastern boundary of TP in the Sichuan and Qinghai provinces also show high values of CO (about 1.5 × 1018 mol/cm2), primarily owing to the industrial activities. There is no seasonal cycle found for SO2 distribution in TP, but relatively high values (8-10 mg/m2) are observed in its eastern boundary. The high-altitude pristine regions of inner TP are also getting polluted because of increased human activities in and around TP, as we estimate positive trends in CO (0.5-1.5 × 1016 mol/cm2/yr) there. In addition, positive trends are also found in NH3 (0.025 × 1016 molec./cm2/yr) during 2008-2020 in most regions of TP and SO2 (about 0.25-0.75 mg/m2/yr) in the Sichuan and Qinghai region during 2000-2020. As revealed by the emission inventory, there are high anthropogenic emissions of NH3, SO2 and CO within TP. There are emissions of pollutants from energy sectors, oil and refinery, agriculture waste burning and manure management within TP. These anthropogenic activities accelerate the ongoing development in TP, but severely erode its environment.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Monitoramento Ambiental , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estações do Ano , Dióxido de Enxofre
5.
Sci Rep ; 13(1): 19311, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37935693

RESUMO

A two-year field study was conducted during Rabi 2018-2019 and 2019-20 to find out the influence of different residue and weed management practices on weed dynamics, growth, yield, energetics, carbon footprint, economics and soil properties in zero-tilled sown wheat at Research Farm, AICRP-Weed management, SKUAST-Jammu. The experiment with four rice residue management practices and four weed management practices was conducted in a Strip-Plot Design and replicated thrice. The results showed that residue retention treatments recorded lower weed density, biomass and higher wheat growth, yield attributes and yields of wheat as compared to no residue treatment. The magnitude of increase in wheat grain yield was 17.55, 16.98 and 7.41% when treated with 125% recommended dose of nitrogen + residue + waste decomposer (RDN + R + WD), 125% RDN + R, and 100% RDN + R, respectively, compared to no residue treatment. Further, all three herbicidal treatments decreased weed density and biomass than weedy treatments. Consequently, a reduction of 29.30, 28.00, and 25.70% in grain yield were observed in control as compared to sulfosulfuron + carfentrazone, clodinafop-propargyl + metasulfuron, and clodinafop-propargyl + metribuzin, respectively. Moreover, 125% RDN + R + WD obtained significantly higher energy output (137860 MJ ha-1) and carbon output (4522 kg CE/ha), but 100% RDN had significantly higher net energy (101802 MJ ha-1), energy use efficiency (7.66), energy productivity (0.23 kg MJ-1), energy profitability (6.66 kg MJ-1), carbon efficiency (7.66), and less carbon footprint (7.66) as compared to other treatments. Despite this, treatments with 125% RDN + R + WD and 125% RDN + R provided 17.58 and 16.96% higher gross returns, and 24.45% and 23.17% net outcomes, respectively, than that of control. However, compared to the control, sulfosulfuron + carfentrazone showed considerably higher energy output (140492 MJ ha-1), net energy (104778 MJ ha-1), energy usage efficiency (4.70), energy productivity (0.14 kg MJ-1), energy profitability (3.70 kg MJ-1), carbon output (4624 kg CE ha-1), carbon efficiency (4.71), and lower carbon footprint (0.27). Furthermore, sulfosulfuron + carfentrazone, clodinafop-propargyl + metasulfuron, and clodinafop-propargyl + metribuzin recorded 29.29% and 38.42%, 27.99%, and 36.91%, 25.69% and 34.32% higher gross returns and net returns over control treatment, respectively. All three herbicides showed higher gross returns, net returns, and benefit cost ratio over control. The soil nutrient status was not significantly affected either by residue or weed management practices. Therefore, based on present study it can be concluded that rice residue retention with 25% additional nitrogen and weed management by clodinafop-propargyl + metasulfuron herbicide found suitable for zero tillage wheat.


Assuntos
Herbicidas , Oryza , Solo/química , Triticum , Agricultura/métodos , Pegada de Carbono , Grão Comestível/química , Herbicidas/farmacologia , Herbicidas/análise , Nitrogênio/análise , Carbono/análise
6.
Heliyon ; 9(10): e20724, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37867881

RESUMO

Chitosan is a naturally occurring linear biopolymer made of partially deacetylated acetyl and N-acetyl glucosamine. Its biocompatible physiochemical and biochemical properties are unmatched. Chitosan is transformed to nanopowder for use in agriculture and associated industries as nanocarriers for existing agrochemicals, ensuring the delayed release of chemicals with better solubility. Chitosan nanopowder applied to leaves or soil can activate a plant's natural defences against insects and pathogens. These studies were carried out because there is a potential for toxicological risk linked with products created utilizing nanotechnology, such as chitosan nanopowder, and therefore researchers felt the need to investigate this. The egg parasitoides Trichogramma Japonicum Ashmead was used as a low-cost biomarker to determine the potential toxicity of chitosan nanopowder. This study looked into the possibility that the adult stage of the egg parasitoids, Trichogramma Japonicum Ashmead might be negatively impacted by chitosan nanopowder (80-100 nm). Unpaired t-test statistical analysis has been carried out. According to the statistical analysis, host eggs exposed to chitosan nanopowder showed noticeably greater parasitization than the control group. As a natural supply of carbohydrate polymers chitosan nanopowder promotes the parasitization of T. Japonicum. The findings showed that T. Japonicum favoured chitosan nanopowder. Through Y dual choice, eight-arm multiple choice, and no-choice olfactometer experiments, as well as images from a stereozoom microscope and a scanning electron microscope (SEM), the data was thoroughly supported. Future agricultural applications of chitosan nanopowder will benefit from a deeper understanding of our findings.

7.
Environ Res ; 238(Pt 1): 117105, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37689338

RESUMO

We analyse the long-term (1980-2020) changes in aerosols over the Third Pole (TP) and assess the changes in radiative forcing (RF) using satellite, ground-based and reanalysis data. The annual mean aerosol optical depth (AOD) varies from 0.06 to 0.24, with the highest values of around 0.2 in the north and southwest TP, which are dominated by dust from Taklimakan and Thar deserts, respectively. However, Organic Carbon (OC), Black Carbon (BC) and sulphate aerosols have significant contributions to the total AOD in the south and east TP. High amounts of dust are observed in spring and summer, but BC in winter. Trajectory analysis reveals that the air mass originated from East and South Asia carries BC and OC, whereas the air from South Asia, Central Asia and Middle East brings dust to TP. Significant positive trends in AOD is found in TP, with high values of about 0.002/yr in the eastern and southern TP. There is a gradual increase in BC and OC concentrations during 1980-2020, but the change from 2000 is phenomenal. The RF at the top of the atmosphere varies from -10 to 2 W/m2 in TP, and high positive RF of about 2 W/m2 is estimated in Pamir, Karakoram and Nyainquentanglha mountains, where the massive glacier mass exists. The RF has increased in much of TP during recent decades (2001-2020) with respect to previous decades (1981-2000), which can be due to the rise in BC and dust during the latter period. Therefore, the positive trend in BC and its associated change in RF can amplify the regional warming, and thus, the melting of glaciers or ice in TP. This is a great concern as it is directly connected to the water security of many South Asian countries.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Mudança Climática , Poeira/análise , Estações do Ano , Aerossóis/análise , Carbono/análise , Monitoramento Ambiental/métodos
8.
3 Biotech ; 13(9): 319, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37641690

RESUMO

Aim: The goal was to evaluate the effect of resveratrol (RS) and combination therapy of RS and donepezil (DPZ), on the numerical expression of microglial cells and astrocytes, in the frontal cortex, regions of the hippocampus in colchicine-induced Alzheimer's disease (AD) model. Methods: The study involved male albino Wistar rats of three months, age and consisted of 6 groups, with six animals each. The immunohistochemical staining with mouse monoclonal anti-human CD 68 and mouse monoclonal anti-GFAP was performed to assess the number of microglial cells and astrocytes, respectively. Results: AD group showed an increase in the number of microglia, and the numbers declined in the treatment groups, RS 10, RS 20, RS10/10 and DPZ + RS (p < 0.001). Astrocyte count was increased in the treatment groups in contrast to the AD group (p < 0.05). The DPZ + RS combination group revealed substantial elevation in the number of astrocytes and decreased microglial number among all the groups (p < 0.001). Conclusion: RS administration has diminished the microglial number and elevated the number of astrocytes. The elevated reactive astrocytes have decreased the microglial population. However, the limitation of our study is utilizing the colchicine for the induction of neurodegeneration. Using the transgenic models of AD may give a better insight into the pathogenesis and effect of RS. Another limitation of this study is the administration of RS and DPZ through different routes. The prospects of this research include studying the probiotic nature of RS and the effect of RS in other neurodegenerative disorders.

10.
Prog Mol Biol Transl Sci ; 196: 125-139, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36813355

RESUMO

GABA (ᵞ-aminobutyric acid), is the principal neurotransmitter known for its inhibitory role in chemical synapses. Being localized primarily in the central nervous system (CNS) it maintains a balance between excitatory (regulated by another neurotransmitter, glutamate) and inhibitory impulses. GABA acts by binding to their specific receptors GABAA and GABAB when released into the post-synaptic nerve terminal. Both of these receptors are responsible for fast and slow inhibition of neurotransmission, respectively. GABAA is a ligand-gated ionopore receptor which opens the Cl- ion channel and decreases the resting potential of the membrane resulting into inhibition of the synapse. On the other hand, GABAB is a metabotropic receptor which increases the K+ ion levels preventing Ca+ ion release inhibiting the release of other neurotransmitters into the presynaptic membrane. The internalization and trafficking of these receptors is also conducted through distinct pathways and mechanism, discussed in detail in the chapter. Without the desired levels of GABA in the body, the psychological and neurological states of brain get hard to maintain. Various neurodegenerative diseases/disorders have been associated to low levels of GABA, such as anxiety, mood disorders, fear, schizophrenia, hungtington's chorea, seizures, epilepsy, etc. The allosteric sites present on GABA receptors have been proved to be potent drug targets to pacify the pathological states of these brain related disorders to an extent. Further in depth studies focussing on the subtypes of GABA receptors and their comprehensive mechanism are required to explore new drug targets and therapeutic avenues for effectual management of GABA related neurological diseases.


Assuntos
Receptores de GABA , Ácido gama-Aminobutírico , Humanos , Ácido gama-Aminobutírico/metabolismo , Sinapses , Endocitose , Neurotransmissores
11.
Chin J Traumatol ; 26(2): 101-105, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35491374

RESUMO

PURPOSE: Various surgical modalities are available to treat Neer types 2 and 5 unstable fractures of lateral end clavicle but none of them are standardized. Arthroscopic fixation of the displaced lateral end clavicle fractures provides good short-term results but mid- to long-term outcomes are not available. The purpose of this study was to show the mid- to long-term radiological and functional outcomes of these fractures treated arthroscopically by a TightRope device, and to show the complications associated with this procedure. METHODS: A retrospective study was conducted over 2 years from January 2014 to December 2015 with a minimum 5-year follow-up. Active patients aged 18-50 years with acute (less than 3 weeks) displaced fracture of lateral end of the clavicle, with a minimum 5-year follow-up were included in the study. Patients with associated fractures of the proximal humerus, glenoid, scapula and acromioclavicular joint injuries were excluded from the study along with open fractures and neurovascular injuries. The outcomes were assessed by objective (complications and radiographic examination) and subjective criteria (quick disabilities of the arm, shoulder and hand score, the Constant-Murley score and the visual pain analogue scale). The data were analyzed by SPSS version 21.0. RESULTS: Totally, 42 patients were operated during the study period and 37 were available with a minimum 5-year follow-up. Thirty were male and 7 were female with a mean age of 29.5 years and a mean follow-up of 6.1 years. The mean quick disabilities of the arm, shoulder and hand score was 68.2 ± 4.6 preoperatively and 1.27 ± 2.32 at final follow-up (p < 0.001); the mean visual pain analogue scale score was 6.85 ± 2.2 preoperatively and 0.86 ± 1.60 at final follow-up (p < 0.001). The average Constant-Murley score was 93.38 ± 3.25 at the end of the follow-up. There were 2 fixation failures, with established non-union and 3 patients developed radiographic acromioclavicular joint arthritis. CONCLUSIONS: Arthroscopic TightRope fixation of displaced lateral end clavicular fractures provides good radiological and functional outcomes at mid- to long-term follow-up. With the low complication rates and high patient satisfaction, this technique can be considered as a primary option in the surgical treatment of these fractures.


Assuntos
Fraturas Ósseas , Fraturas Expostas , Humanos , Masculino , Feminino , Adulto , Seguimentos , Clavícula/cirurgia , Estudos Retrospectivos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas Ósseas/complicações , Fixação Interna de Fraturas/métodos , Dor , Resultado do Tratamento
12.
Ann Oncol ; 34(3): 275-288, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36526124

RESUMO

BACKGROUND: KEAP1 mutations have been associated with reduced survival in lung adenocarcinoma (LUAD) patients treated with immune checkpoint inhibitors (ICIs), particularly in the presence of STK11/KRAS alterations. We hypothesized that, beyond co-occurring genomic events, clonality prediction may help identify deleterious KEAP1 mutations and their counterparts with retained sensitivity to ICIs. PATIENTS AND METHODS: Beta-binomial modelling of sequencing read counts was used to infer KEAP1 clonal inactivation by combined somatic mutation and loss of heterozygosity (KEAP1 C-LOH) versus partial inactivation [KEAP1 clonal diploid-subclonal (KEAP1 CD-SC)] in the Memorial Sloan Kettering Cancer Center (MSK) MetTropism cohort (N = 2550). Clonality/LOH prediction was compared to a streamlined clinical classifier that relies on variant allele frequencies (VAFs) and tumor purity (TP) (VAF/TP ratio). The impact of this classification on survival outcomes was tested in two independent cohorts of LUAD patients treated with immunotherapy (MSK/Rome N = 237; DFCI N = 461). Immune-related features were studied by exploiting RNA-sequencing data (TCGA) and multiplexed immunofluorescence (DFCI mIF cohort). RESULTS: Clonality/LOH inference in the MSK MetTropism cohort overlapped with a clinical classification model defined by the VAF/TP ratio. In the ICI-treated MSK/Rome discovery cohort, predicted KEAP1 C-LOH mutations were associated with shorter progression-free survival (PFS) and overall survival (OS) compared to KEAP1 wild-type cases (PFS log-rank P = 0.001; OS log-rank P < 0.001). Similar results were obtained in the DFCI validation cohort (PFS log-rank P = 0.006; OS log-rank P = 0.014). In both cohorts, we did not observe any significant difference in survival outcomes when comparing KEAP1 CD-SC and wild-type tumors. Immune deconvolution and multiplexed immunofluorescence revealed that KEAP1 C-LOH and KEAP1 CD-SC differed for immune-related features. CONCLUSIONS: KEAP1 C-LOH mutations are associated with an immune-excluded phenotype and worse clinical outcomes among advanced LUAD patients treated with ICIs. By contrast, survival outcomes of patients whose tumors harbored KEAP1 CD-SC mutations were similar to those with KEAP1 wild-type LUADs.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Fator 2 Relacionado a NF-E2/genética , Mutação , Perda de Heterozigosidade , Imunoterapia
13.
J Laryngol Otol ; 137(7): 725-731, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36380503

RESUMO

OBJECTIVE: Children with single-sided deafness often receive inconsistent clinical recommendations because there is currently no clear best practice in paediatric single-sided deafness. This systematic review of the literature aimed to compare commonly used treatments and attempted to support the use of a particular treatment modality. METHOD: This was a comprehensive literature review from 1 January 2000 to 22 February 2022; the study compared the outcomes of bone conduction devices and cochlear implantation in paediatric patients with single-sided deafness. RESULTS: Fifteen studies consisting of 202 patients were examined. Variables including speech reception in quiet and noise, as well as quality of life measures were compared. Both cochlear implantation and bone-anchored hearing aids demonstrated benefits in sound perception. Quality of life measures improved with both modalities. CONCLUSION: Although both bone-anchored hearing aids and cochlear implantation appear to provide significant improvements, additional research with more direct comparisons is needed to provide more decisive results.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Auxiliares de Audição , Perda Auditiva Unilateral , Percepção da Fala , Criança , Humanos , Implante Coclear/métodos , Surdez/cirurgia , Perda Auditiva Unilateral/cirurgia , Qualidade de Vida , Resultado do Tratamento
14.
Sci Rep ; 12(1): 17688, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36271112

RESUMO

The present investigation aims to analyze higher-order endothermic/exothermic chemical reactions with activation energy by considering thermophoresis and Brownian motion effects on MHD mixed convective flow across a vertical stretching surface. The influence of velocity slip, thermal slip, and concentration slip along with an inclined external magnetic field is also considered. The governing coupled non-linear partial differential equations are transformed into ordinary differential equations using similarity transformation. The resulting system of non-linear ODEs is solved by the Newton Raphson shooting technique using the RK-4 algorithm. The impact of various physical parameters discovered in the problem viz. endothermic/exothermic reaction variable, thermophoresis parameter, activation energy parameter, Brownian motion parameter, chemical reaction parameter have been analyzed on velocity profile, temperature profile, and concentration profile. The effects of these parameters on skin-friction coefficient, Nusselt number, and Sherwood number are displayed in tabular form as well as surface plots. The impact of various physical parameters that appeared in the entropy generation is shown using surface and contour plots. The numerical findings are in good agreement with the previously published results. It is observed that an increment in thermophoresis and Brownian motion parameters results in a declination of entropy profiles, whereas an increment in Bejan number profiles is observed. A small region near the surface exhibits an inclination in concentration profiles with an increase in the order of the chemical reaction. In contrast, the opposite effect is analyzed near the boundary layer. Also, the contour and surface plots are displayed to portray real-world applications in industrial and technical processes and the physical depiction of flow characteristics that arise in the current study.

16.
Ann Oncol ; 33(10): 1029-1040, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35872166

RESUMO

BACKGROUND: Allele-specific KRAS inhibitors are an emerging class of cancer therapies. KRAS-mutant (KRASMUT) non-small-cell lung cancers (NSCLCs) exhibit heterogeneous outcomes, driven by differences in underlying biology shaped by co-mutations. In contrast to KRASG12C NSCLC, KRASG12D NSCLC is associated with low/never-smoking status and is largely uncharacterized. PATIENTS AND METHODS: Clinicopathologic and genomic information were collected from patients with NSCLCs harboring a KRAS mutation at the Dana-Farber Cancer Institute (DFCI), Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, and Imperial College of London. Multiplexed immunofluorescence for CK7, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), Foxp3, and CD8 was carried out on a subset of samples with available tissue at the DFCI. Clinical outcomes to PD-(L)1 inhibition ± chemotherapy were analyzed according to KRAS mutation subtype. RESULTS: Of 2327 patients with KRAS-mutated (KRASMUT) NSCLC, 15% (n = 354) harbored KRASG12D. Compared to KRASnon-G12D NSCLC, KRASG12D NSCLC had a lower pack-year (py) smoking history (median 22.5 py versus 30.0 py, P < 0.0001) and was enriched in never smokers (22% versus 5%, P < 0.0001). KRASG12D had lower PD-L1 tumor proportion score (TPS) (median 1% versus 5%, P < 0.01) and lower tumor mutation burden (TMB) compared to KRASnon-G12D (median 8.4 versus 9.9 mt/Mb, P < 0.0001). Of the samples which underwent multiplexed immunofluorescence, KRASG12D had lower intratumoral and total CD8+PD1+ T cells (P < 0.05). Among 850 patients with advanced KRASMUT NSCLC who received PD-(L)1-based therapies, KRASG12D was associated with a worse objective response rate (ORR) (15.8% versus 28.4%, P = 0.03), progression-free survival (PFS) [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.45-2.00, P = 0.003], and overall survival (OS; HR 1.45, 1.05-1.99, P = 0.02) to PD-(L)1 inhibition alone but not to chemo-immunotherapy combinations [ORR 30.6% versus 35.7%, P = 0.51; PFS HR 1.28 (95%CI 0.92-1.77), P = 0.13; OS HR 1.36 (95%CI 0.95-1.96), P = 0.09] compared to KRASnon-G12D. CONCLUSIONS: KRASG12D lung cancers harbor distinct clinical, genomic, and immunologic features compared to other KRAS-mutated lung cancers and worse outcomes to PD-(L)1 blockade. Drug development for KRASG12D lung cancers will have to take these differences into account.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Fatores de Transcrição Forkhead , Genômica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Receptor de Morte Celular Programada 1 , Proteínas Proto-Oncogênicas p21(ras)/genética
17.
Pharmacol Rep ; 74(3): 481-492, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35396697

RESUMO

BACKGROUND: Vascular dementia is the second most prevalent form of dementia. Hypertension is the leading risk factor for endothelial dysfunction and the progression of dementia that is of vascular origin. This study investigates the role of ulinastatin (UTI) and quercetin alone as well as in combination in hypertension-induced endothelial dysfunction and vascular dementia (VaD). METHOD: Two-kidney one-clip (2K1C) renovascular model was set up to induce hypertension in the Albino Wistar rats (males). Rats were assessed for mean arterial blood pressure, behavioral function (Morris water maze, attention set-shifting tests), vascular endothelial function, and biochemical levels (aortic superoxide anion and serum nitrite/nitrate), as well as brains' thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, interleukin-6, 10, tumor necrosis factor-TNF-α and acetylcholinesterase-AChE). UTI (10,000 U/kg, ip) and quercetin (60 mg/kg) were used alone and in combination for treatment. Donepezil (0.5 mg/kg) was used as a positive control. RESULTS: 2K1C rats showed impairment in learning, memory, executive functioning, and reversal learning. These rats further showed endothelial dysfunction as well as an increase in mean arterial blood pressure, brains' oxidative stress, inflammation, and AChE-activity. Treatment with UTI and quercetin alone as well in combination significantly attenuated the 2K1C model induced impairments in the behavioural, biochemical, and endothelial parameters. CONCLUSION: 2K1C renovascular hypertension-induced impairment in behavioural, biochemical, and endothelial parameters were attenuated by the treatment with UTI and quercetin alone as well as in combination. Therefore, the utility of these agents might be studied further to understand their full potential in hypertension-induced VaD.


Assuntos
Demência Vascular , Hipertensão , Acetilcolinesterase/metabolismo , Animais , Demência Vascular/tratamento farmacológico , Demência Vascular/etiologia , Glicoproteínas , Hipertensão/induzido quimicamente , Masculino , Aprendizagem em Labirinto , Estresse Oxidativo , Quercetina/farmacologia , Ratos
18.
Physiol Behav ; 249: 113767, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35245527

RESUMO

Metabolic conditions like diabetes, is a major risk factor for the development of dementia of vascular origin. This study investigates the efficacy of atomoxetine (ATX) and N-acetylcysteine (NAC) in streptozotocin (STZ) diabetes induced vascular endothelium dysfunction and related dementia. Single dose STZ (50 mg/kg i.p) was administered to Albino Wistar rats (male, 200-250 g) by dissolving in citrate buffer. Morris water maze (MWM) and attentional set shifting tests (ASST) were used to assess the spatial learning, memory, reversal learning, and executive functioning in animals. Body weight, serum glucose, serum nitrite/nitrate, vascular endothelial function, aortic superoxide anion, brains' oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), inflammatory markers (IL-6, IL-10, TNF-α, and myeloperoxidase-MPO), acetylcholinesterase activity-AChE and histopathological changes were also assessed. Atomoxetine - ATX (2 mg kg-1/ 4 mg kg-1) and N-acetylcysteine- NAC (250 mg kg-1/ 500 mg kg-1) were used alone as well as in combination, as the treatment drugs. Donepezil (0.5 mg kg-1) was used as a positive control. STZ administered rats showed increase in serum glucose levels and decrease in body weight. Rats administered with STZ also showed reduction in learning, memory, reversal learning, executive functioning, impairment in endothelial function, increase in brains' oxidative stress, inflammation, AChE activity and histopathological changes. Administration of ATX and NAC in two different doses as well as in combination, significantly attenuated the STZ induced diabetes induced impairments in the behavioral, endothelial, biochemical parameters and histopathological changes. Co-treatment of ATX and NAC was better in comparison to the doses when given alone. Hence, STZ administration caused diabetes induced dementia of vascular origin which was attenuated by the administration of ATX and NAC. Therefore, these agents may be studied further for the assessment of their full potential in diabetes induced dementia of vascular origin conditions.


Assuntos
Demência Vascular , Diabetes Mellitus Experimental , Acetilcolinesterase/metabolismo , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico , Animais , Cloridrato de Atomoxetina/farmacologia , Cloridrato de Atomoxetina/uso terapêutico , Peso Corporal , Encéfalo/metabolismo , Demência Vascular/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Masculino , Aprendizagem em Labirinto , Estresse Oxidativo , Ratos , Estreptozocina/toxicidade
19.
Clin Radiol ; 77(6): 399-408, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35177229

RESUMO

Castleman Disease (CD) is a rare entity that typically presents as an enhancing nodal mass in the mediastinum or head and neck region on computed tomography (CT). It may manifest as unicentric or multicentric regions of lymph node enlargement. A key clinical issue in the context of CD is delayed diagnosis, which contributes adversely to patient outcome, given that accurate diagnosis facilitates earlier treatment of this curable disease. This article will address relevant imaging aspects, with reference to typical and atypical imaging features of CD, illustrated using examples from our specialist centre; the imaging journey for patients with CD; and will provide practical pointers to radiologists in differentiating CD from other benign and malignant causes of enhancing lymphadenopathy, including lymphoma and neoplastic adenopathy. We will also review current classification tools and staging challenges with reference to World Health Organization guidelines, International Working Group guidelines as well as the Lugano classification. Finally, we will discuss the potential role of additional imaging techniques in CD, highlighting novel imaging methods and expanded utilities from our specialist centre.


Assuntos
Hiperplasia do Linfonodo Gigante , Linfadenopatia , Radiologia , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/patologia , Diagnóstico Diferencial , Humanos , Linfadenopatia/diagnóstico por imagem , Radiografia , Tomografia Computadorizada por Raios X
20.
Biomech Model Mechanobiol ; 21(3): 797-825, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35157174

RESUMO

A numerical investigation of MHD blood flow through a stenosed permeable curved artery has been done in this study. Blood flow is considered in two-phases; core and plasma region, respectively. Viscosity of the core region is considered as temperature-dependent, while constant viscosity is considered in plasma region. The governing equations of the proposed two-phase blood flow model are considered in the toroidal coordinate system. The second-order finite difference method is adopted to solve governing equations with [Formula: see text] tolerance in the iteration process. A comparative study of Darcy number (Da) is performed to understand the influence of permeable and impermeable wall conditions. The effect of various physical parameters such as magnetic field (M), viscosity variation parameter ([Formula: see text]), Darcy number (Da), heat source (H) and chemical reaction parameter ([Formula: see text]) is displayed graphically on the flow velocity, temperature, concentration, wall shear stress and frictional resistance profiles. A comparison with published work has also been displayed through the graph to validate the present model, and it is in fair agreement with the existing work. The present study suggested that the curvature and permeability of the arterial wall raise the risk of atherosclerosis formation, while the implication of heat source on the blood flow lower this risk.


Assuntos
Hemodinâmica , Temperatura Alta , Artérias , Estresse Mecânico , Viscosidade
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