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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 ; 83: e247604, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1339370

RESUMO

Abstract 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.


Resumo No presente relatório, estudamos os possíveis inibidores de Covid-19 de constituintes bioativos de Centaurea jacea usando uma abordagem tripla que consiste em técnicas de química quântica, docking molecular e dinâmica molecular. Centaurea jacea é uma erva perene frequentemente usada em remédios populares de doenças dermatológicas e febre. Além disso, as propriedades anticâncer, antioxidante, antibacteriana e antiviral de seus compostos bioativos também são relatadas. A Mpro (proteases principais) foi acoplada a diferentes compostos de Centaurea jacea por meio de docking molecular. Todos os compostos estudados, incluindo apigenina, axilarina, Centaureidina, Cirsiliol, Eupatorina e Isokaempferide, mostram afinidades de ligação adequadas ao sítio de ligação da protease principal SARS-CoV-2 com suas energias de ligação -6,7 kcal / mol, -7,4 kcal / mol, - 7,0 kcal / mol, -5,8 kcal / mol, -6,2 kcal / mol e -6,8 kcal / mol, respectivamente. Dentre todos os compostos estudados, a axilarina apresentou eficiência máxima de inibidor, seguida pela Centaureidina, Isokaempferida, Apigenina, Eupatorina e Cirsiliol. Nossos resultados sugeriram que a axilarina se liga aos resíduos catalíticos mais cruciais CYS145 e HIS41 do Mpro, além disso a axilarina mostra 5 interações de ligações de hidrogênio e 5 interações hidrofóbicas com vários resíduos de Mpro. Além disso, os cálculos de dinâmica molecular em uma escala de tempo de 60 ns (6 × 106 femtossegundos) também mostraram percepções significativas sobre os efeitos de ligação da axilarina com Mpro de SARS-CoV-2 por imitação de proteínas como o ambiente aquoso. A partir de cálculos de dinâmica molecular, os cálculos RMSD e RMSF indicam a estabilidade e dinâmica do melhor complexo ancorado em ambiente aquoso. As propriedades ADME e a análise de previsão de toxicidade da axilarina também a recomendaram como um candidato a medicamento seguro. Além disso, as investigações in vivo e in vitro são essenciais para garantir a atividade anti-SARS-CoV-2 de todos os compostos bioativos, particularmente a axilarina, para encorajar o uso preventivo de Centaurea jacea contra infecções por Covid-19.

3.
Methods Mol Biol ; 2422: 191-201, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34859407

RESUMO

Proximity ligation assay (PLA), also referred to as Duolink® PLA technology, permits detection of protein-protein interactions in situ (<40 nm distance) at endogenous protein levels. It exploits specific antibodies identifying (either directly or indirectly) the two proteins of interest and takes advantage of specific DNA primers covalently linked to the antibodies. A hybridization step followed by a PCR amplification with fluorescent probes then permits visualization of spots of proximity by fluorescence microscopy.

4.
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.

5.
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.

6.
Elife ; 102021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850681

RESUMO

The dramatic change in morphology of chromosomal DNAs between interphase and mitosis is one of the defining features of the eukaryotic cell cycle. Two types of enzymes, namely cohesin and condensin confer the topology of chromosomal DNA by extruding DNA loops. While condensin normally configures chromosomes exclusively during mitosis, cohesin does so during interphase. The processivity of cohesin's loop extrusion during interphase is limited by a regulatory factor called WAPL, which induces cohesin to dissociate from chromosomes via a mechanism that requires dissociation of its kleisin from the neck of SMC3. We show here that a related mechanism may be responsible for blocking condensin II from acting during interphase. Cells derived from patients affected by microcephaly caused by mutations in the MCPH1 gene undergo premature chromosome condensation but it has never been established for certain whether MCPH1 regulates condensin II directly. We show that deletion of Mcph1 in mouse embryonic stem cells unleashes an activity of condensin II that triggers formation of compact chromosomes in G1 and G2 phases, which is accompanied by enhanced mixing of A and B chromatin compartments, and that this occurs even in the absence of CDK1 activity. Crucially, inhibition of condensin II by MCPH1 depends on the binding of a short linear motif within MCPH1 to condensin II's NCAPG2 subunit. We show that the activities of both Cohesin and Condensin II may be restricted during interphase by similar types of mechanisms as MCPH1's ability to block condensin II's association with chromatin is abrogated by the fusion of SMC2 with NCAPH2. Remarkably, in the absence of both WAPL and MCPH1, cohesin and condensin II transform chromosomal DNAs of G2 cells into chromosomes with a solenoidal axis showing that both cohesin and condensin must be tightly regulated to adjust the structure of chromatids for their successful segregation.

7.
Cureus ; 13(10): e18766, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804647

RESUMO

We report an atypical case of prostate cancer with rectal involvement presenting with gastrointestinal symptoms predominately and a rectal mass. A 51-year-old male patient came to the hospital with abdominal pain and rectal bleeding. Imaging revealed prostate enlargement, perirectal lymphadenopathy, and multiple hepatic and pulmonary nodules. The patient also had an elevated prostate-specific antigen (PSA) of 502 ng/mL (against normal range 0.6-0.7 ng/mL). Biopsies were performed on tissue samples taken from the rectum and prostate gland, which confirmed the diagnosis of prostate adenocarcinoma. The lack of urinary symptoms and close clinical similarity to colorectal cancer presented a diagnostic challenge for us. Familiarity with this specific presentation of prostate cancer is necessary to avoid misdiagnoses and guide correct treatment.

8.
JAC Antimicrob Resist ; 3(4): dlab169, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34806008

RESUMO

Background: Colistin use is increasing with the rise in MDR Gram-negative infections globally. Effective antibiotic stewardship is essential to preserve this antibiotic of last resort. Objectives: This study investigated stewardship and safety errors related to colistin use to identify opportunities for improvement. Patients and methods: A prospective descriptive study involving all patients 13 years and older treated with colistin at a tertiary hospital in Cape Town, South Africa, between August 2018 and June 2019. We collected clinical, laboratory and outcome data and assessed provided treatment for stewardship and safety errors. Results: We included 44 patients. Treatment errors were identified for 34 (77%) patients (median = 1), most commonly inadequate monitoring of renal function (N = 16, 32%). We also identified no rational indication for colistin (N = 9, 20%), loading dose error (N = 12, 27%); maintenance dose error (N = 10, 23%); no prior culture (N = 11, 25%); and failure to de-escalate (2 of 9) or adjust dose to changes in renal function (6 of 15). All cause in-hospital mortality was 47%. Amongst survivors, median ICU stay was 6 days and hospital stay more than 30 days. Eight (18%) patients developed renal injury or failure during treatment. Three (7%) patients in this study were found to have colistin-resistant organisms including two prior to colistin exposure. Conclusions: This study has identified opportunities to enhance colistin stewardship and improve efficacy and safety of prescription. The appearance of colistin-resistant organisms reinforces the urgent need to ensure effective and appropriate use of colistin.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34816378

RESUMO

PURPOSE: The potential of pacing and capturing the His-Purkinje system (HPS) to synchronize VF wavefronts is not known even though the HPS is thought to be electrically linked during VF. In this study the effect of selective His Bundle (HB) pacing was compared with nearby working myocardial (WM) pacing on the left ventricular (LV) endocardial activation rates. METHODS: Rabbit hearts (n = 9) were explanted and Langendorff perfused. Electrodes directly on the HB were identified and paced subsequently using an electrode array. The WM was paced through a silver wire inserted in the right ventricular septal wall. After VF was induced, the HB was paced at rates faster than the intrinsic HB activation rate (n = 18 episodes) and also at rates faster than the LV activation rate (n = 16). A basket array inserted in the LV was used to record electrograms before and during each pacing episode. Activation rates at five LV electrodes each from the earliest and latest activating sinus rhythm regions were analyzed before and during pacing. RESULTS: Both HB and WM pacing reduced LV activation rates during pacing, but WM pacing was more effective (p < 0.005). WM pacing events were more effective (p < 0.05) in reducing LV activation rates than HB pacing in episodes which were faster than LV activation rates. CONCLUSION: This study provides evidence that during early VF in rabbit hearts, the HPS cannot be driven to effectively modulate the LV activation rates.

10.
Polymers (Basel) ; 13(21)2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34771211

RESUMO

Metalla-ynes and poly(metalla-ynes) have emerged as unique molecular scaffolds with fascinating structural features and intriguing photo-luminescence (PL) properties. Their rigid-rod conducting backbone with tunable photo-physical properties has generated immense research interests for the design and development of application-oriented functional materials. Introducing a second d- or f-block metal fragment in the main-chain or side-chain of a metalla-yne and poly(metalla-yne) was found to further modulate the underlying features/properties. This review focuses on the photo-physical properties and opto-electronic (O-E) applications of heterometal grafted metalla-ynes and poly(metalla-ynes).

11.
Transplant Proc ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774307

RESUMO

BACKGROUND: Since 1964 when Indiana University performed its first kidney transplant, immunosuppression protocol was steroid-based until 2004 when steroid-free immunosuppression protocol was adopted. We describe clinical outcomes on our patients administered early steroid withdrawal (ESW) protocol (5 days) compared with our historical cohort (HC), who were on chronic steroid-based immunosuppression. METHODS: We performed a retrospective study evaluating kidney transplant recipients between 1993 and 2003 (HC, n = 1689) and between 2005 and 2016 (ESW cohort, n = 2097) at the Indiana University program, with a median follow-up of 10.5 years and 6.1 years, respectively. Primary outcomes were patient and death-censored graft survival at 1, 3, and 5 years in both study cohorts. Secondary outcomes were 1-year rates of biopsy-proven acute rejection; graft function at 1, 3, and 5 years; and risk of post-transplant infection (BK virus and cytomegalovirus) in the ESW cohort. Cox proportional model and Kaplan-Meier estimates were used to estimate survival probabilities. Fisher exact tests were used to compare episodes of acute rejection in the ESW cohort. RESULTS: No difference was observed in patient survival between the ESW and HC cohorts (P = .13). Compared with the ESW cohort, death-censored graft survival was significantly worse in the HC (5 year: 86.4% vs 90.6%, log-rank P < .001). One-year acute rejection reported in the ESW cohort alone was 15.7% and significantly worse in Black patients and younger patients (P < .05). CONCLUSIONS: In this sizeable single-center cohort study with significant ethnic diversity, ESW is a viable alternative to steroid-based immunosuppression protocol in kidney transplant recipients.

12.
BMC Public Health ; 21(1): 2048, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753433

RESUMO

BACKGROUND: HIV self-testing was proved as an effective tool for increasing testing frequency in gay and bisexual men at high risk of infection. Questions remain about understanding why HIVST encouraged testing and how such success can be translated to programmatic implementation. METHODS: We conducted a qualitative investigation of how FORTH participants experienced and perceived HIVST. Stratified sampling was used to recruit gay and bisexual men participating in the FORTH HIVST intervention to take part in interviews, focusing on infrequent testers and those who had received inaccurate HIVST results. RESULTS: Our analysis identified several prominent themes organized into two overarching domains from the 15 interviews: (i) aspects of HIVST contributing to HIV testing frequency, and (ii) sustaining HIVST into the future. Participants also believed that their use of HIVST in the future would depend on the test kit's reliability, particularly when compared with highly reliable clinic-based testing. CONCLUSION: HIVST increases the frequency of HIV testing among gay and bisexual men due, in part, to the practical, psychological, and social benefits it offers. To capitalize fully on these benefits, however, strategies to ensure the availability of highly reliable HIVST are required to sustain benefits beyond the confines of a structured research study.

13.
Cureus ; 13(10): e18687, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34786263

RESUMO

Background Women remain relatively underrepresented in all subspecialties of academic medicine. While sex disparity is prevalent in a number of specialties, the association between academic productivity and sex in academic cardiology has not been assessed in the Canadian context. Methods Academic faculty of accredited Canadian Resident Matching Service (CaRMS) programs were included from cardiology division websites across 17 universities. Cardiology faculty members' names, academic ranks, leadership positions, and sex were obtained from each institutions' website. The Elsevier database Scopus© was used to extract the Hirsch index (H-index), years of active research, and number of publications of each faculty member. The H-index was used as a metric of academic output and research productivity. Univariate regression was run with the H-Index as the outcome of interest, and multiple linear regression analysis was used to determine factors associated with higher H-index. Results Sex was identified for 1,040 members, of whom 836 (80%) were male. Male members had higher numbers of publications (p <0.001). There was a trend for males in a leadership position to have a higher H-index (p = 0.07). Median H-index was lower for women (p = 0.02). Males across assistant and associate professor ranks had a higher H-index. Women achieving professor rank demonstrated greater productivity with a higher median H-index (p = 0.002). Conclusions There is a prevalent sex gap in academic cardiology with regard to scholarly productivity and academic achievement. Factors that may help narrow the sex gap need to be identified and corrective measures implemented to enhance sex equity.

14.
Obes Surg ; 31(12): 5303-5311, 2021 Dec.
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.

15.
PLoS Genet ; 17(10): e1009836, 2021 10.
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.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Insulina/metabolismo , Lipídeos/fisiologia , Transdução de Sinais/fisiologia , Envelhecimento/metabolismo , Animais , Autofagia/fisiologia , Citoplasma/metabolismo , Diabetes Mellitus/metabolismo , Homeostase/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome Metabólica/metabolismo , Fatores de Transcrição/metabolismo
16.
J Acoust Soc Am ; 150(3): 1762, 2021 09.
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.


Assuntos
Inteligibilidade da Fala , Percepção da Fala , Testes Auditivos , Humanos , Ruído/efeitos adversos
17.
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.

18.
Lancet Reg Health West Pac ; 14: 100214, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34671752

RESUMO

Background: A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. Methods: Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). Findings: Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. Interpretation: In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. Funding: This work was supported by grant 568971 from the National Health and Medical Research Council of Australia.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34687614

RESUMO

The Internet of Things (IoT) has penetrated many aspects of everyday human life. The use of IoT in healthcare has been expanding over the past few years. In this review, we highlighted the current applications of IoT in the medical literature, along with the challenges and opportunities. IoT use mainly involves sensors and wearables, with potential applications in improving the quality of life, personal health monitoring, and diagnosis of diseases. Our literature review highlights that the current main application studied in the literature is physical activity tracking. In addition, we discuss the current technologies that would help IoT-enabled devices achieve safe, quick, and meaningful data transfer. These technologies include machine learning/artificial intelligence, 5G, and blockchain. Data on current IoT-enabled devices are still limited, and future research should address these devices' effect on patients' outcomes and the methods by which their integration in healthcare will avoid increasing costs.

20.
JCO Oncol Pract ; : OP2100662, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709950
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