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1.
Braz. j. biol ; 83: e246002, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285612

RESUMO

Abstract Economic valuation of ecosystem services is a new concept in forest management. Economic valuation provides basis for payment for ecosystem services (PES). Therefore, objective of this study was to evaluate eco-tourism and carbon stock services of the Maindam valley, District Swat, Pakistan. For the carbon stock calculation, a sample size of 155 plots of 0.1 hectare (Ha) was taken using preliminary survey at 95% confidence interval and 10% allowable error. The data for tourism services was collected from owners of all the hotels, 100 tourists and key informants of the area at 10% sampling intensity on pretested questionnaire for twenty years period (1997-2017). Results showed that Miandam valley has carbon stock worth US$ 16,306,000 while the value of eco-tourism was US$ 1,578,458 on annual basis. The results also showed that trend of tourism has drastically declined after the 9/11 incident for foreigners and locals and the situation was further deteriorated during the era of Talibanization or militancy from 2008-2011. This study recommends implementation of PES strategy at the rate of 5%, thus a total of US$ 78,922 can be earned from eco-tourism and carbon crediting in the study area annually, which could play important role in sustainable forest management.


Resumo A valoração econômica dos serviços ecossistêmicos é um novo conceito no manejo florestal. A avaliação econômica fornece base para o pagamento por serviços ecossistêmicos (PES). Portanto, o objetivo deste estudo foi avaliar o ecoturismo e os serviços de estoque de carbono do vale de Miandam, distrito Swat, Paquistão. Para o cálculo do estoque de carbono, um tamanho de amostra de 155 parcelas de 0,1 hectare (ha) foi tirado, usando pesquisa preliminar com intervalo de confiança de 95% e erro admissível de 10%. Os dados para serviços de turismo foram coletados de proprietários de todos os hotéis, 100 turistas e informantes-chave da área em 10% de intensidade de amostragem em questionário pré-testado para um período de 20 anos (1997-2017). Os resultados mostraram que o vale de Miandam tem estoque de carbono no valor de US$ 16.306.000, enquanto o valor do ecoturismo foi de US$ 1.578.458 anualmente. Os resultados também mostraram que a tendência do turismo diminuiu drasticamente para estrangeiros e locais após o incidente de 11 de Setembro, e a situação se agravou ainda mais durante a era da talibanização ou militância de 2008-2011. Este estudo recomenda a implementação da estratégia de PES na taxa de 5%, portanto um total de US$ 78.922 pode ser ganho com ecoturismo e crédito de carbono na área de estudo anualmente, o que pode desempenhar um papel importante no manejo florestal sustentável.

2.
Braz. j. biol ; 82: e243670, 2022. tab
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1278509

RESUMO

Abstract For the proper growth of fish, it is necessary to feed the fish with a proper and balanced diet. A study was conducted to find out the effect of different protein-based diets on fingerlings of Tor putitora (mahseer). A feed with dietary protein levels of 35%, 40%, 45%, and 50% were prepared. The effect of different protein-based feed on weight gain, standard growth rate (SGR), food conversion ratio (FCR), percent weight gain, food conversion efficiency (FCE), and protein efficiency ratio (PER) was studied. An increase was observed in the growth rate with an increase in protein concentration up to 45%. The fingerlings fed a 45% protein diet shown the highest growth, followed by 50%, 40%, and 35%. The SGR value was greatest for 45% protein diet (8.56) followed by 50% and 40%, while the least values were observed for 35% protein feed (1.57). The same trend was observed for FCE. The highest PER values was observed in fishes fed 45% protein-based feed (0.65) followed by 50% (0.56), 40% (0.38) and35% (0.17). The food conversion ratio was lowest for 45% protein diet (3.41), while the greatest for 35% protein feed (16.85). It was concluded that a 45% protein-based diet was the best feed formulation for higher production of Tor putitora. However, research on the same percentage of protein diet is recommended for yearlings.


Resumo Para o bom crescimento dos peixes, é necessário alimentá-los com uma alimentação adequada e balanceada. Um estudo foi realizado para descobrir o efeito de diferentes dietas à base de proteínas em alevinos de Tor putitora (mahseer). Foi preparado um alimento com níveis de proteína dietética de 35%, 40%, 45% e 50%. O efeito de diferentes alimentos à base de proteína no ganho de peso, taxa de crescimento padrão (SGR), taxa de conversão alimentar (FCR), ganho de peso percentual, eficiência de conversão alimentar (FCE) e taxa de eficiência proteica (PER) foi estudado. Foi observado um aumento na taxa de crescimento com um aumento na concentração de proteína de até 45%. Os alevinos alimentados com dieta de 45% de proteína apresentaram o maior crescimento, seguidos de 50%, 40% e 35%. O valor de SGR foi maior para dieta com 45% de proteína (8,56), seguido de 50% e 40%, enquanto os menores valores foram observados para ração com 35% de proteína (1,57). A mesma tendência foi observada para FCE. Os maiores valores de PER foram observados em peixes alimentados com 45% de ração à base de proteína (0,65), seguido por 50% (0,56), 40% (0,38) e 35% (0,17). A taxa de conversão alimentar foi menor para a dieta com 45% de proteína (3,41), enquanto a maior para a dieta com 35% de proteína (16,85). Concluiu-se que a dieta à base de proteína de 45% foi a melhor formulação alimentar para maior produção de Tor putitora. No entanto, a pesquisa sobre a mesma porcentagem de dieta proteica é recomendada para animais de um ano.

3.
Braz. j. biol ; 82: e243633, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1249273

RESUMO

Abstract Snow trout (Schizothorax plagiostomus) is an economically important freshwater fish, mostly found in northern areas of water reservoirs of Pakistan. The current study was conducted in River Swat to analyze the bioaccumulation of heavy metals (Pb, Cr, Ni, and Zn) in tissues of Schizothorax plagiostomus. Tissues were extracted and dissolved in perchloric acid (HClO4) and nitric acid (HNO3) along with hotplate. The heavy metals, zinc (Zn), lead (Pb), chromium (Cr), and Nickel (Ni) were determined using Perkin Elmer 2380 atomic absorption spectrophotometer. Results shows great variation in the content of the metal related to tissue type and sampling sites. A high concentration of bioaccumulation was reported at Charbagh, whereas lowest at Odigram: Charbagh>Landakai>Odigram. In the same way, Cr was the most accumulated heavy metal followed by lead, nickel, and Zinc:


Resumo A truta das neves (Schizothorax plagiostomus) é um peixe de água doce economicamente importante, encontrado principalmente nas áreas ao norte de reservatórios de água do Paquistão. O presente estudo foi realizado em River Swat para analisar a bioacumulação de metais pesados (Pb, Cr, Ni e Zn) em tecidos de Schizothorax plagiostomus. Os tecidos foram extraídos e dissolvidos em ácido perclórico (HClO4) e ácido nítrico (HNO3) com placa de aquecimento. Os metais pesados zinco (Zn), chumbo (Pb), cromo (Cr) e níquel (Ni) foram determinados usando espectrofotômetro de absorção atômica Perkin Elmer 2380. Os resultados mostram grande variação no conteúdo do metal relacionado ao tipo de tecido e locais de amostragem. Uma alta concentração de bioacumulação foi relatada em Charbagh, enquanto a mais baixa, em Odigram: Charbagh > Landakai > Odigram. Da mesma forma, Cr foi o metal pesado mais acumulado, seguido por Pb, Ni e Zn.

4.
J Community Psychol ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626493

RESUMO

Global warming is occurring at an alarming rate, with climate change creating severe water-related hazards that are at the top of the natural disasters list. The highest human losses have been recorded in the past 50 years based on world meteorological organization calculations. Thus, everyone needs to play their part in environmental sustainability (ES). This will require a change in behavior; therefore, the current study considered pro-environmental behavior (PEB) crucial to ES among university employees. The moderating effect of green organizational culture (GOC) on the relationship between PEB and ES was also investigated. As it is typical of a Thai public university to expend a considerable amount of natural resources in the process of conducting its routine academic and operational activities, it is a setting worthy of investigation. The higher education sector is rarely explored in the areas of resource use and conservation; for this reason, this study was specifically targeted at the human factor in this specialized setting. A survey was performed on the faculty members of Thai public universities to verify the model. It was found that PEB influenced ES, and GOC moderated the relationship between PEB and ES. The results encompassed six dimensions of PEB and the moderating effect of GOC in the context of higher educational institutions. The findings have provided new insights into PEB intervention and modification in the context of higher education institutions whose management may use the results to strengthen employees' PEB by offering information, knowledge, and training.

5.
Br J Neurosurg ; : 1-4, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605339

RESUMO

BACKGROUND: Foramen magnum decompression (FMD) is an established technique for patients with Chiari-1 malformation. However, the extent of decompressive surgery is controversial, in particular whether dural opening is undertaken. OBJECTIVE: In this study, we report outcomes with our technique utilising intraoperative ultrasound (iOU) findings. Decision to proceed for further decompression was based on CSF flow around foramen magnum and visualisation of tip of tonsils. METHODS: Review of adults with CM-1 undergoing FMD 2013-2018. Patients underwent a suboccipital craniectomy ± partial C1 superior laminectomy ± duraplasty in a stepwise manner. Favourable iOU findings of CSF flow around the foramen magnum and pulsation of the tonsillar tips were sought at each step. Post-operative outcomes were assessed using the Chicago Chiari Outcome Score (CCOS). RESULTS: Fifty-seven patients were included. The mean age was 47 years (range 18-77 years). There was a strong female preponderance (48 females to nine males). The mean follow-up was 3.2 years (range 1-5 years). Surgery included: suboccipital craniectomy (52/57, 91%), plus partial C1 superior laminectomy (2/57, 4%), and plus duraplasty (3/57, 6%). Redo surgery was undertaken in 7/57 patients (12%). At final follow-up, 56/57 (98%) patients achieved a good (CCOS 13-16) or satisfactory (CCOS 9-12) outcome based on COSS. CONCLUSIONS: A patient centred approach to surgery utilising findings from iOU can achieve favourable outcomes. Dural opening is not routinely required.

6.
Obes Surg ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34617207

RESUMO

BACKGROUND: Fasting during Ramadan is one of the five pillars of the Muslim faith. Despite the positive effects of fasting on health, there are no guidelines or clear recommendations regarding fasting after metabolic/bariatric surgery (MBS). The current study reports the result of a modified Delphi consensus among expert metabolic/bariatric surgeons with experience in managing patients who fast after MBS. METHODS: A committee of 61 well-known metabolic and bariatric surgeons from 24 countries was created to participate in the Delphi consensus. The committee voted on 45 statements regarding recommendations and controversies around fasting after MBS. An agreement/disagreement ≥ of 70.0% was regarded as consensus. RESULTS: The experts reached a consensus on 40 out of 45 statements after two rounds of voting. One hundred percent of the experts believed that fasting needs special nutritional support in patients who underwent MBS. The decision regarding fasting must be coordinated among the surgeon, the nutritionist and the patient. At any time after MBS, 96.7% advised stopping fasting in the presence of persistent symptoms of intolerance. Seventy percent of the experts recommended delaying fasting after MBS for 6 to 12 months after combined and malabsorptive procedures according to the patient's situation and surgeon's experience, and 90.1% felt that proton pump inhibitors should be continued in patients who start fasting less than 6 months after MBS. There was consensus that fasting may help in weight loss, improvement/remission of non-alcoholic fatty liver disease, dyslipidemia, hypertension and type 2 diabetes mellitus among 88.5%, 90.2%, 88.5%, 85.2% and 85.2% of experts, respectively. CONCLUSION: Experts voted and reached a consensus on 40 statements covering various aspects of fasting after MBS.

7.
J Acoust Soc Am ; 150(3): 1762, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34598625

RESUMO

An objective metric that predicts speech intelligibility under different types of noise and distortion would be desirable in voice communication. To date, the majority of studies concerning speech intelligibility metrics have focused on predicting the effects of individual noise or distortion mechanisms. This study proposes an objective metric, the spectrogram orthogonal polynomial measure (SOPM), that attempts to predict speech intelligibility for people with normal hearing under adverse conditions. The SOPM metric is developed by extracting features from the spectrogram using Krawtchouk moments. The metric's performance is evaluated for several types of noise (steady-state and fluctuating noise), distortions (peak clipping, center clipping, and phase jitters), ideal time-frequency segregation, and reverberation conditions both in quiet and noisy environments. High correlation (0.97-0.996) is achieved with the proposed metric when evaluated with subjective scores by normal-hearing subjects under various conditions.

8.
Biomed Pharmacother ; 144: 112278, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34628166

RESUMO

The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.

9.
Sensors (Basel) ; 21(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34640885

RESUMO

In this paper, a new optimization algorithm called motion-encoded electric charged particles optimization (ECPO-ME) is developed to find moving targets using unmanned aerial vehicles (UAV). The algorithm is based on the combination of the ECPO (i.e., the base algorithm) with the ME mechanism. This study is directly applicable to a real-world scenario, for instance the movement of a misplaced animal can be detected and subsequently its location can be transmitted to its caretaker. Using Bayesian theory, finding the location of a moving target is formulated as an optimization problem wherein the objective function is to maximize the probability of detecting the target. In the proposed ECPO-ME algorithm, the search trajectory is encoded as a series of UAV motion paths. These paths evolve in each iteration of the ECPO-ME algorithm. The performance of the algorithm is tested for six different scenarios with different characteristics. A statistical analysis is carried out to compare the results obtained from ECPO-ME with other well-known metaheuristics, widely used for benchmarking studies. The results found show that the ECPO-ME has great potential in finding moving targets, since it outperforms the base algorithm (i.e., ECPO) by as much as 2.16%, 5.26%, 7.17%, 14.72%, 0.79% and 3.38% for the investigated scenarios, respectively.

10.
PLoS Genet ; 17(10): e1009836, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34634043

RESUMO

A small number of peptide growth factor ligands are used repeatedly in development and homeostasis to drive programs of cell differentiation and function. Cells and tissues must integrate inputs from these diverse signals correctly, while failure to do so leads to pathology, reduced fitness, or death. Previous work using the nematode C. elegans identified an interaction between the bone morphogenetic protein (BMP) and insulin/IGF-1-like signaling (IIS) pathways in the regulation of lipid homeostasis. The molecular components required for this interaction, however, were not fully understood. Here we report that INS-4, one of 40 insulin-like peptides (ILPs), is regulated by BMP signaling to modulate fat accumulation. Furthermore, we find that the IIS transcription factor DAF-16/FoxO, but not SKN-1/Nrf, acts downstream of BMP signaling in lipid homeostasis. Interestingly, BMP activity alters sensitivity of these two transcription factors to IIS-promoted cytoplasmic retention in opposite ways. Finally, we probe the extent of BMP and IIS interactions by testing additional IIS functions including dauer formation, aging, and autophagy induction. Coupled with our previous work and that of other groups, we conclude that BMP and IIS pathways have at least three modes of interaction: independent, epistatic, and antagonistic. The molecular interactions we identify provide new insight into mechanisms of signaling crosstalk and potential therapeutic targets for IIS-related pathologies such as diabetes and metabolic syndrome.

11.
Int J Pept Res Ther ; : 1-17, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34566545

RESUMO

Klebsiella oxytoca is a gram-negative bacterium. It is opportunistic in nature and causes hospital acquired infections. Subtractive proteomics and reverse vaccinology approaches were employed to screen out the best proteins for vaccine designing. Whole proteome of K. oxytoca strain ATCC 8724, consisting of 5483 proteins, was used for designing the vaccine. Total 1670 cytotoxic T lymphocyte (CTL) epitope were predicted through NetCTL while 1270 helper T lymphocyte (HTL) epitopes were predicted through IEDB server. The epitopes were screened for non-toxicity, allergenicity, antigenicity and water solubility. After epitope screening 300 CTL and 250 HTL epitopes were submitted to IFN-γ epitope server to predict their Interferon-γ induction response. The selected IFN-γ positive epitopes were tested for their binding affinity with MHCI-DRB1 by MHCPred. The 15 CTL and 13 HTL epitopes were joined by linkers AAY and GPGPG respectively in vaccine construct. Chain C of Pam3CSK4 (PDB ID; 2Z7X) was linked to the vaccine construct as an adjuvant. A 450aa long vaccine construct was submitted to I-TASSER server for 3D structure prediction. Thirteen Linear B cells were predicted by ABCPred server and 10 sets of discontinues epitopes for 3D vaccine structure were predicted by DiscoTope server. The modeled 3D vaccine construct was docked with human Toll-like receptor 2 (PDB ID: 6NIG) by PatchDock. The docked complexes were refined by FireDock. The selected docked complex showed five hydrogen bonds and one salt bridge. The vaccine sequence was reverse transcribed to get nucleotide sequence for In silico cloning. The reverse transcribed sequence strand was cloned in pET28a(+) expression vector. A clone containing 6586 bp was constructed including the 450 bp of query gene sequence.

12.
J Electrocardiol ; 69: 36-43, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34555557

RESUMO

BACKGROUND: postoperative atrial fibrillation (POAF) is a common cardiac surgery complication that is associated with increased complications and negative outcomes, but the association between presurgical atrial conduction abnormalities and POAF has not been investigated clinically during premature atrial S1S2 stimulation. This clinical study sought to examine whether intraoperative premature atrial stimulation reveals increased areas of slowed and/or blocked conduction in patients that develop POAF. METHODS: High-density intraoperative epicardial left atrial mapping was conducted in 20 cardiac surgery patients with no prior history of atrial fibrillation (AF). In 20 patients, 6 (30%) developed POAF. A flexible-array of 240-electrodes was placed on the posterior left atrial wall in between the pulmonary veins. Activation maps were generated for sinus and premature atrial S1S2 stimulated beats. The area of conduction block (CB), conduction delay (CD) and the combination of both (CDCB) for conduction velocity < 0.1, 0.1 ≤ x < 0.2 and < 0.2 m/s, respectively were quantified. RESULTS: For a premature atrial S2 beat with shortest cycle length captured, conduction velocity maps revealed a significantly higher area for CD (13.19 ± 6.59 versus 6.06 ± 4.22 mm2, p = 0.028) and CDCB (17.36 ± 8.75 versus 7.41 ± 6.39 mm2, p = 0.034), and a trend toward a larger area for CB (4.17 ± 3.66 versus 1.34 ± 2.86 mm2, p = 0.063) in patients who developed POAF in comparison to those that remained in the sinus. Sinus and S1 paced beats did not show substantial differences in abnormal conduction areas between patients with and without POAF. CONCLUSION: In comparison to sinus and S1 beats, premature atrial S2 beats accentuate conduction abnormalities in the posterior left atrial wall of cardiac surgery patients that developed POAF.

13.
BMJ Open ; 11(9): e049673, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489284

RESUMO

OBJECTIVES: In sub-Saharan Africa (SSA) where HIV burden is highest, access to testing, a key entry point for prevention and treatment, remains low for adolescents (aged 10-19). Access may be hampered by policies requiring parental consent for adolescents to receive HIV testing services (HTS). In 2013, the WHO recommended countries to review HTS age of consent policies. Here, we investigate country progress and policies on age of consent for HIV testing. DESIGN: Comprehensive policy review. DATA SOURCES: Policies addressing HTS were obtained through searching WHO repositories and governmental and non-governmental websites and consulting country and regional experts. ELIGIBILITY CRITERIA: HTS policies published by SSA governments before 2019 that included age of consent. DATA EXTRACTION AND SYNTHESIS: Data were extracted on HTS age of consent including exceptions based on risk and maturity. Descriptive analyses of included policies were disaggregated by Eastern and Southern Africa (ESA) and Western and Central Africa (WCA) subregions. RESULTS: Thirty-nine policies were reviewed, 38 were eligible; 19/38 (50%) permitted HTS for adolescents ≤16 years old without parental consent. Of these, six allowed HTS at ≥12 years old, two at ≥13, two at ≥14, five at ≥15 and four at ≥16. In ESA, 71% (n=15/21) allowed those of ≤16 years old to access HTS, while only 24% (n=6/25) of WCA countries allowed the same. Maturity exceptions including marriage, sexual activity, pregnancy or key population were identified in 18 policies. In 2019, 63% (n=19/30) of policies with clear age-based criteria allowed adolescents of 12-16 years old to access HIV testing without parental consent, an increase from 37% (n=14/38) in 2013. CONCLUSIONS: While many countries in SSA have revised their HTS policies, many do not specify age of consent. Revision of SSA consent to HTS policies, particularly in WCA, remains a priority to achieve the 2025 goal of 95% of people with HIV knowing their status.


Assuntos
Infecções por HIV , Adolescente , África ao Sul do Saara , Criança , Feminino , Infecções por HIV/diagnóstico , Humanos , Casamento , Políticas , Gravidez , Comportamento Sexual
14.
Braz J Biol ; 83: e247604, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495156

RESUMO

In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.


Assuntos
COVID-19 , Centaurea , Preparações Farmacêuticas , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases , SARS-CoV-2
15.
Neuroradiol J ; : 19714009211042893, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477042

RESUMO

BACKGROUND: Intractable nasal and oropharyngeal hemorrhage may be treated with endovascular embolization, but limited data are available. We sought to evaluate the efficacy, safety, and factors associated with rebleeding. METHODS: A retrospective analysis of consecutive embolizations for nasal and oropharyngeal hemorrhage over a 10-year period at a single institution was performed. Outcomes included procedural success (defined as cessation of hemorrhage in the immediate postoperative period), rebleeding requiring an additional intervention, and procedural complications. RESULTS: A total of 47 embolizations on 39 patients were included. The mean age was 60 years (standard deviation 16.1), 23.1% of patients were women, and 21 (53.8%) patients had a previously diagnosed head/neck malignancy. Bleeding sites were the nose in 20 patients and oropharynx in 21 (two patients presented with both nasal and oral bleeding). Immediate procedural success was achieved in 45 (95.7%) embolizations. Rebleeding requiring an additional intervention occurred after 11 (23.4%) embolizations at a median of one day after the procedure. In the multivariate analysis, preoperative hypotension (odds ratio 4.78, 95% confidence interval 1.04-24.61) and the use of coils (odds ratio 6.09, 95% confidence interval 1.24-46.69) were associated with rebleeding requiring repeat intervention. Complications included two watershed strokes that were anticipated due to occlusion of the internal carotid artery. CONCLUSIONS: In our experience endovascular embolization was a safe and effective treatment option for stopping oral and nasal hemorrhage. However, rebleeding was present after 23.4% of treatments and was associated with preoperative hypotension and the use of coils. Further study in a large multi-institutional cohort is warranted.

16.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445361

RESUMO

Inflammation promotes endothelial dysfunction, but the underlying mechanisms remain poorly defined in vivo. Using translational vascular function testing in myocardial infarction patients, a situation where inflammation is prevalent, and knock-out (KO) mouse models we demonstrate a role for mitogen-activated-protein-kinases (MAPKs) in endothelial dysfunction. Myocardial infarction significantly lowers mitogen and stress kinase 1/2 (MSK1/2) expression in peripheral blood mononuclear cells and diminished endothelial function. To further understand the role of MSK1/2 in vascular function we developed in vivo animal models to assess vascular responses to vasoactive drugs using laser Doppler imaging. Genetic deficiency of MSK1/2 in mice increased plasma levels of pro-inflammatory cytokines and promoted endothelial dysfunction, through attenuated production of nitric oxide (NO), which were further exacerbated by cholesterol feeding. MSK1/2 are activated by toll-like receptors through MyD88. MyD88 KO mice showed preserved endothelial function and reduced plasma cytokine expression, despite significant hypercholesterolemia. MSK1/2 kinases interact with MAPK-activated proteins 2/3 (MAPKAP2/3), which limit cytokine synthesis. Cholesterol-fed MAPKAP2/3 KO mice showed reduced plasma cytokine expression and preservation of endothelial function. MSK1/2 plays a significant role in the development of endothelial dysfunction and may provide a novel target for intervention to reduce vascular inflammation. Activation of MSK1/2 could reduce pro-inflammatory responses and preserve endothelial vasodilator function before development of significant vascular disease.


Assuntos
Proteínas Quinases S6 Ribossômicas 90-kDa/fisiologia , Doenças Vasculares/genética , Adulto , Idoso , Animais , Estudos de Casos e Controles , Células Cultivadas , Estudos de Coortes , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Transdução de Sinais/fisiologia , Doenças Vasculares/fisiopatologia , Adulto Jovem
17.
Clin Infect Dis ; 73(4): e1018-e1028, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398952

RESUMO

BACKGROUND: We conducted a systematic review and network meta-analysis to identify which human immunodeficiency virus (HIV) self-testing (HIVST) distribution strategies are most effective. METHODS: We abstracted data from randomized controlled trials and observational studies published between 4 June 2006 and 4 June 2019. RESULTS: We included 33 studies, yielding 6 HIVST distribution strategies. All distribution strategies increased testing uptake compared to standard testing: in sub-Saharan Africa, partner HIVST distribution ranked highest (78% probability); in North America, Asia, and the Pacific regions, web-based distribution ranked highest (93% probability), and facility based distribution ranked second in all settings. Across HIVST distribution strategies HIV positivity and linkage was similar to standard testing. CONCLUSIONS: A range of HIVST distribution strategies are effective in increasing HIV testing. HIVST distribution by sexual partners, web-based distribution, as well as health facility distribution strategies should be considered for implementation to expand the reach of HIV testing services.


Assuntos
Infecções por HIV , Autoteste , HIV , Infecções por HIV/diagnóstico , Humanos , Programas de Rastreamento , Metanálise em Rede , Parceiros Sexuais
18.
Sci Transl Med ; 13(607)2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408080

RESUMO

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α4ß7 with an anti-α4ß7 monoclonal antibody (Rh-α4ß7) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α4ß7 integrin blockade, SHIVSF162P3-infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α4ß7 or were left untreated as a control. Treatment with bNAbs alone decreased viremia below 200 copies/ml in all macaques, but seven of eight macaques (87.5%) in the bNAbs-only group rebounded within a median of 3 weeks (95% CI: 2 to 9). In contrast, three of six macaques treated with a combination of Rh-α4ß7 and bNAbs (50%) maintained a viremia below 200 copies/ml until the end of the follow-up period; viremia in the other three macaques rebounded within a median of 6 weeks (95% CI: 5 to 11). Thus, there was a modest delay in viral rebound in the macaques treated with the combination antibody therapy compared to bNAbs alone. Our study suggests that α4ß7 integrin blockade may prolong virologic control by bNAbs in SHIVSF162P3-infected macaques.


Assuntos
Infecções por HIV , HIV-1 , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , Anticorpos Anti-HIV , Infecções por HIV/tratamento farmacológico , Integrinas , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico
19.
Mol Cancer Ther ; 20(10): 1904-1915, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34376577

RESUMO

Itraconazole, an FDA-approved antifungal, has antitumor activity against a variety of cancers. We sought to determine the effects of itraconazole on esophageal cancer and elucidate its mechanism of action. Itraconazole inhibited cell proliferation and induced G1-phase cell-cycle arrest in esophageal squamous cell carcinoma and adenocarcinoma cell lines. Using an unbiased kinase array, we found that itraconazole downregulated protein kinase AKT phosphorylation in OE33 esophageal adenocarcinoma cells. Itraconazole also decreased phosphorylation of downstream ribosomal protein S6, transcriptional expression of the upstream receptor tyrosine kinase HER2, and phosphorylation of upstream PI3K in esophageal cancer cells. Lapatinib, a tyrosine kinase inhibitor that targets HER2, and siRNA-mediated knockdown of HER2 similarly suppressed cancer cell growth in vitro Itraconazole significantly inhibited growth of OE33-derived flank xenografts in mice with detectable levels of itraconazole and its primary metabolite, hydroxyitraconazole, in esophagi and tumors. HER2 total protein and phosphorylation of AKT and S6 proteins were decreased in xenografts from itraconazole-treated mice compared to xenografts from placebo-treated mice. In an early phase I clinical trial (NCT02749513) in patients with esophageal cancer, itraconazole decreased HER2 total protein expression and phosphorylation of AKT and S6 proteins in tumors. These data demonstrate that itraconazole has potent antitumor properties in esophageal cancer, partially through blockade of HER2/AKT signaling.

20.
Cancer Biol Ther ; 22(7-9): 455-464, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34392779

RESUMO

Circulating tumor DNA (ctDNA) is utilized for molecular profiling of cancers, and is under investigation for a growing number of applications based on the assumption that ctDNA levels faithfully reflect disease burden. Our objective was to investigate whether patient and tumor characteristics may impact ctDNA detection or levels and the prognostic significance of ctDNA levels or mutations. We performed a retrospective cohort analysis of a comprehensively annotated cohort of 561 patients at a National Cancer Institute-designated comprehensive cancer center with advanced solid cancers who underwent ctDNA testing using a commercial targeted next-generation sequencing assay. ctDNA detection in advanced cancers was associated with older age, non-obese body mass index, and diabetes, but not with tumor diameter, volume, lesion number, or other pathological features. Regression models indicate that no more than 14.3% of the variance in ctDNA levels between patients was explained by known clinical factors and disease burden. Even after adjusting for established prognostic factors and tumor burden, ctDNA levels were associated with worse survival among patients without prior systemic therapy, while ctDNA mutations were associated with survival among patients who previously received systemic treatment. These findings uncover clinical factors that affect ctDNA detection in patients with advanced cancers and challenge the convention that ctDNA is a surrogate for tumor burden. Our study also indicates that the prognostic value of ctDNA levels and mutations are independent of tumor burden and dependent on treatment context.

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