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1.
Mol Metab ; 86: 101971, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925249

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality, and its incidence is increasing due to endemic obesity. HCC is sexually dimorphic in both humans and rodents with higher incidence in males, although the mechanisms contributing to these correlations remain unclear. Here, we examined the role of sphingosine kinase 2 (SphK2), the enzyme that regulates the balance of bioactive sphingolipid metabolites, sphingosine-1-phosphate (S1P) and ceramide, in gender specific MASH-driven HCC. METHODS: Male and female mice were fed a high fat diet with sugar water, a clinically relevant model that recapitulates MASH-driven HCC in humans followed by physiological, biochemical cellular and molecular analyses. In addition, correlations with increased risk of HCC recurrence were determined in patients. RESULTS: Here, we report that deletion of SphK2 protects both male and female mice from Western diet-induced weight gain and metabolic dysfunction without affecting hepatic lipid accumulation or fibrosis. However, SphK2 deficiency decreases chronic diet-induced hepatocyte proliferation in males but increases it in females. Remarkably, SphK2 deficiency reverses the sexual dimorphism of HCC, as SphK2-/- male mice are protected whereas the females develop liver cancer. Only in male mice, chronic western diet induced accumulation of the autophagy receptor p62 and its downstream mediators, the antioxidant response target NQO1, and the oncogene c-Myc. SphK2 deletion repressed these known drivers of HCC development. Moreover, high p62 expression correlates with poor survival in male HCC patients but not in females. In hepatocytes, lipotoxicity-induced p62 accumulation is regulated by sex hormones and prevented by SphK2 deletion. Importantly, high SphK2 expression in male but not female HCC patients is associated with a more aggressive HCC differentiation status and increased risk of cancer recurrence. CONCLUSIONS: This work identifies SphK2 as a potential regulator of HCC sexual dimorphism and suggests SphK2 inhibitors now in clinical trials could have opposing, gender-specific effects in patients.

2.
Heliyon ; 10(10): e30897, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38778954

RESUMO

Background: Vaccination against Human papillomavirus (HPV) is recommended to avoid HPV infections and its associated diseases, including cervical cancer. However, there is no awareness study among Bangladeshi population. Hence, this nationwide study was conducted to explore HPV vaccine awareness and its determinants among parents of eligible adolescent girls. Methods: This study was conducted among the parents of daughters aged 9-15 years from 42 out of 64 randomly selected districts of Bangladesh between June 28 to August 2, 2023. A multistage sampling method was used to enroll 2151 study participants from all eight divisions of Bangladesh. A semi-structured questionnaire was used for face-to-face interviews in this study. The statistical software Stata (Version 17) was used for statistical analyses. Results: The average age of the participants was 38.18 (±5.86) years. Only 22.32 % of the participants were aware of the HPV vaccine. Every additional year of age increased the likelihood of being aware of the HPV vaccine by 3 % (AOR: 1.03; 95%CI: 1.00-1.06). Participants residing in the urban area had 3.56 times higher odds of awareness than rural and semi-urban people. Businessmen and housewives had 60 % (AOR: 0.40; 95 % CI: 0.22-0.69) and 77 % (AOR: 0.23; 95 % CI: 0.16-0.33) lower odds in comparison to job holders. The lower-income group exhibited significantly higher odds of awareness (AOR: 0.25, 95%CI: 0.16-0.39) compared to the middle and the higher-income group. Participants who never went through routine health check-ups had 77 % lower odds of being aware than those who availed of regular routine check-ups (AOR: 0.23; 95%CI: 0.16-0.34). Conclusion: Awareness of the HPV vaccine among the general population of Bangladesh is very low. Age, residence, occupation, monthly income, and routine medical check-ups were associated with HPV vaccine awareness. A nationwide awareness campaign would increase this awareness level among the Bangladeshi population, especially among the parents of daughters.

3.
Chemosphere ; 346: 140576, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303401

RESUMO

Photocatalytic dye degradation employing polyoxometalates (POMs) has been a research focus for several years. We report the facile synthesis of tungsten-based Lindqvist and Keggin-type POMs that degrade toxic chemical dyes, methyl orange (MO) and methylene blue (MB), respectively. The Lindqvist POM, sodium hexatungstate, Na2W6O19, degrades MO under 100 W UV light irradiation within 15 min, whereas the Keggin POM, Ag4PW11VO40, degrades MB under 20 W visible light source within 180 min. The effect of various operating parameters, such as photocatalyst concentration, pH, time, and initial dye concentration, were assessed in the degradation of both dyes. The photoelectrochemical performance of the as-synthesized polyoxometalates shows that the Ag4PW11VO40 shows 2.4 times higher photocurrent density than Na2W6O19 at a potential of 0.9 V vs. Ag/AgCl. Electrochemical impedance analysis reveals that Ag4PW11VO40 exhibits much lower charge transfer resistance as compared to Na2W6O19, which indicates facile charge transfer at the electrode-electrolyte interface. Further Mott-Schottky measurements reveal that both the catalysts possess n-type semiconductivity and the charge carrier concentration of Ag4PW11VO40 (5.89 × 1019 cm-3) is 1.4 times higher as compared to Na2W6O19 (4.25 × 1019 cm-3). This work offers a new paradigm for designing polyoxometalates suitable for efficient photocatalytic degradation of organic dyes.


Assuntos
Ânions , Compostos Azo , Corantes , Polieletrólitos , Tungstênio , Luz
4.
Eur J Gastroenterol Hepatol ; 36(3): 281-291, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38179874

RESUMO

OBJECTIVES: This study compared the real-world effectiveness and safety of α 4 ß 7 -integrin inhibitor vedolizumab and anti-tumor necrosis factor alpha (anti-TNFα) inhibitor infliximab in biologic-naive patients with Crohn's disease (CD). METHODS: EVOLVE was a retrospective, multicenter, medical chart review of biologic-naive adults with inflammatory bowel disease receiving vedolizumab or anti-TNFα treatment as first-line biologics in Canada, Greece, and the USA. Twelve-month outcomes were analyzed in vedolizumab- or infliximab-treated patients with moderate-to-severe CD (and subgroups with complicated and noncomplicated CD) including cumulative rates of clinical response, clinical remission, and mucosal healing, and incidence rates of serious adverse events (SAEs) and serious infections (SIs). Inverse probability weighting (IPW) was used to account for baseline differences between treatment groups. RESULTS: Data were analyzed from 167 patients. In the IPW dataset (99 vedolizumab-treated and 63 infliximab-treated), adjusted 12-month clinical remission rates were 73.1% and 55.2%, respectively ( P  = 0.31). Overall, effectiveness rates were similar across treatment and complicated/noncomplicated disease subgroups. Adjusted 12-month incidence rates (first occurrence/1000 person-years) of SAEs for vedolizumab vs. infliximab: 43.6 vs. 200.9 [hazard ratio (HR) 0.36 (0.09-1.54)]; SIs: 10.8 vs. 96.0 [HR 0.08 (<0.01-2.64)]. AE incidence was significantly lower in vedolizumab- vs. infliximab-treated patients for complicated [131.6 vs. 732.2; HR 0.19 (0.05-0.65)] and noncomplicated [276.3 vs. 494.8; HR 0.59 (0.35-0.99)] disease subgroups. CONCLUSION: These real-world data on first-line biologics show no differences in 12-month effectiveness outcomes for vedolizumab- vs. infliximab-treated biologic-naive patients with CD. Vedolizumab may have a more favorable safety profile vs. infliximab in patients with complicated and noncomplicated disease.


Assuntos
Anticorpos Monoclonais Humanizados , Produtos Biológicos , Doença de Crohn , Adulto , Humanos , Infliximab/efeitos adversos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Estudos Retrospectivos , Fator de Necrose Tumoral alfa , Produtos Biológicos/uso terapêutico , Resultado do Tratamento
5.
Int J Mol Sci ; 24(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37894760

RESUMO

Diabetic cardiomyopathy is a critical diabetes-mediated co-morbidity characterized by cardiac dysfunction and heart failure, without predisposing hypertensive or atherosclerotic conditions. Metabolic insulin resistance, promoting hyperglycemia and hyperlipidemia, is the primary cause of diabetes-related disorders, but ambiguous tissue-specific insulin sensitivity has shed light on the importance of identifying a unified target paradigm for both the glycemic and non-glycemic context of type 2 diabetes (T2D). Several studies have indicated hyperactivation of the mammalian target of rapamycin (mTOR), specifically complex 1 (mTORC1), as a critical mediator of T2D pathophysiology by promoting insulin resistance, hyperlipidemia, inflammation, vasoconstriction, and stress. Moreover, mTORC1 inhibitors like rapamycin and their analogs have shown significant benefits in diabetes and related cardiac dysfunction. Recently, FDA-approved anti-hyperglycemic sodium-glucose co-transporter 2 inhibitors (SGLT2is) have gained therapeutic popularity for T2D and diabetic cardiomyopathy, even acknowledging the absence of SGLT2 channels in the heart. Recent studies have proposed SGLT2-independent drug mechanisms to ascertain their cardioprotective benefits by regulating sodium homeostasis and mimicking energy deprivation. In this review, we systematically discuss the role of mTORC1 as a unified, eminent target to treat T2D-mediated cardiac dysfunction and scrutinize whether SGLT2is can target mTORC1 signaling to benefit patients with diabetic cardiomyopathy. Further studies are warranted to establish the underlying cardioprotective mechanisms of SGLT2is under diabetic conditions, with selective inhibition of cardiac mTORC1 but the concomitant activation of mTORC2 (mTOR complex 2) signaling.


Assuntos
Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Hiperlipidemias , Resistência à Insulina , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Cardiomiopatias Diabéticas/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Transportador 2 de Glucose-Sódio , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Sódio/metabolismo , Hiperlipidemias/tratamento farmacológico
6.
Pharm Dev Technol ; 28(7): 678-696, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37427544

RESUMO

Evolving therapeutic landscape through combinatorial chemistry and high throughput screening have resulted in an increased number of poorly soluble drugs. Drug delivery strategies quickly adapted to convert these drugs into successful therapies. Amorphous solid dispersion (ASD) technology is widely employed as a drug delivery strategy by pharmaceutical industries to overcome the challenges associated with these poorly soluble drugs. The development of ASD formulation requires an understanding of polymers and manufacturing techniques. A review of US FDA-approved ASD-based products revealed that only a limited number of polymers and manufacturing technologies are employed by pharmaceutical industries. This review provides a comprehensive guide for the selection and overview of polymers and manufacturing technologies adopted by pharmaceutical industries for ASD formulation. The various employed polymers with their underlying mechanisms for solution-state and solid-state stability are discussed. ASD manufacturing techniques, primarily implemented by pharmaceutical industries for commercialization, are presented in Quality by Design (QbD) format. An overview of novel excipients and progress in manufacturing technologies are also discussed. This review provides insights to the researchers on the industrially accepted polymers and manufacturing technology for ASD formulation that has translated these challenging drugs into successful therapies.


Assuntos
Química Farmacêutica , Polímeros , Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Solubilidade , Preparações Farmacêuticas , Excipientes
7.
Int J Mol Sci ; 24(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36835206

RESUMO

Kinesin family motors are microtubule (MT)-stimulated ATPases known best as transporters of cellular cargoes through the cytoplasm, regulators of MT dynamics, organizers of the mitotic spindle, and for insuring equal division of DNA during mitosis. Several kinesins have also been shown to regulate transcription by interacting with transcriptional cofactors and regulators, nuclear receptors, or with specific promotor elements on DNA. We previously showed that an LxxLL nuclear receptor box motif in the kinesin-2 family motor KIF17 mediates binding to the orphan nuclear receptor estrogen related receptor alpha (ERR1) and is responsible for the suppression of ERR1-dependent transcription by KIF17. Analysis of all kinesin family proteins revealed that multiple kinesins contain this LxxLL motif, raising the question as to whether additional kinesin motors contribute to the regulation of ERR1. In this study, we interrogate the effects of multiple kinesins with LxxLL motifs on ERR1-mediated transcription. We demonstrate that the kinesin-3 family motor KIF1B contains two LxxLL motifs, one of which binds to ERR1. In addition, we show that expression of a KIF1B fragment containing this LxxLL motif inhibits ERR1-dependent transcription by regulating nuclear entry of ERR1. We also provide evidence that the effects of expressing the KIF1B-LxxLL fragment on ERR1 activity are mediated by a mechanism distinct from that of KIF17. Since LxxLL domains are found in many kinesins, our data suggest an expanded role for kinesins in nuclear receptor mediated transcriptional regulation.


Assuntos
Regulação da Expressão Gênica , Cinesinas , Mitose , Receptores de Estrogênio , Núcleo Celular/metabolismo , Cinesinas/metabolismo , Microtúbulos/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Motivos de Aminoácidos/genética
8.
Technol Cancer Res Treat ; 22: 15330338231152083, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36718541

RESUMO

Cancer is recognized as one of the world's deadliest diseases, with more than 10 million new cases each year. Over the past 2 decades, several studies have been performed on cancer to pursue solutions for effective treatment. One of the vital benefits of utilizing nanoparticles (NPs) in cancer treatment is their high adaptability for modification and amalgamation of different physicochemical properties to boost their anti-cancer activity. Various nanomaterials have been designed as nanocarriers attributing nontoxic and biocompatible drug delivery systems with improved bioactivity. The present review article briefly explained various types of nanocarriers, such as organic-inorganic-hybrid NPs, and their targeting mechanisms. Here a special focus is given to the synthesis, benefits, and applications of polymeric NPs (PNPs) involved in various anti-cancer therapeutics. It has also been discussed about the drug delivery approach by the functionalized/encapsulated PNPs (without/with targeting ability) that are being applied in the therapy and diagnostic (theranostics). Overall, this review can give a glimpse into every aspect of PNPs, from their synthesis to drug delivery application for cancer cells.


Assuntos
Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Fármacos por Nanopartículas , Sistemas de Liberação de Medicamentos/métodos , Polímeros/química , Neoplasias/tratamento farmacológico , Nanopartículas/química
9.
Int J Biol Macromol ; 226: 1547-1559, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36455824

RESUMO

In the present study, the inhibitory effect of propylthiouracil (PTU) on bovine liver catalase (BLC) activity was studied in the presence of curcumin (CUR). The results suggest that the PTU-induced decrease in BLC activity was caused by a change in conformation of BLC with reduced α-helical content and decrease in zeta potential. Nevertheless, temperature-dependent activation of CUR protects the activity of BLC by restoring the secondary conformation and zeta potential of BLC. CUR inhibited the time-induced reduction in BLC activity and the protection was increased with increasing concentrations of CUR and found to be significant even from 1:0.1 molar ratios. The enzyme kinetics confirmed the high catalytic efficiency of BLC in presence of CUR than PTU. The protective role of CUR was due to the formation of a more stabilized complex as demonstrated by molecular docking, and fourier-transform infrared study. Isothermal titration calorimetric study supports for a favourable reaction between BLC and PTU or CUR due to the negative ΔH, and positive TΔS. Although the number of binding sites for PTU and CUR was found to be 10 and 7, respectively, the binding affinity between CUR and BLC is approximately 3.72 fold stronger than BLC-PTU complex. The increased melting temperature of BLC was noticed in presence of CUR suggesting the protective potential of CUR towards biomolecules. Indeed, this is the first biophysical study to describe the molecular mechanism of PTU-induced reduction in BLC activity and alleviation by CUR with detail kinetics. Thus, CUR can be further extended to other antioxidant enzymes or compromised biomolecules for therapeutic interventions.


Assuntos
Curcumina , Animais , Bovinos , Catalase/metabolismo , Curcumina/farmacologia , Curcumina/metabolismo , Simulação de Acoplamento Molecular , Propiltiouracila/farmacologia , Propiltiouracila/metabolismo , Fígado/metabolismo , Ligação Proteica , Antioxidantes/metabolismo
10.
Nanoscale ; 14(48): 18051-18059, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36448343

RESUMO

Metal-thiolate complexes have been the focus of research for several years because of their unique photophysical properties and their use as a precursor for synthesizing various well-defined metal nanoclusters. A rational understanding of their structure-property relationship is necessary to realize their full potential in practical applications. Herein, we demonstrate the synthesis of a unique copper-thiolate complex with reversibly switchable catalytic and photoluminescence (PL) properties. The as-synthesized complex at basic pH (Complex B) showed cyan PL with a strong peak at ∼488 nm (cyan) and a small shoulder peak at ∼528 nm (green). When the pH of the complex was changed to acidic (Complex A), the PL was switched to light green. Such pH-responsive PL properties were demonstrated to be useful for pH and CO2 sensing. The switchable properties originate from their two distinct structural states at two different pHs. We found that Complex A was resistant to high concentrations of a strong reducing agent, and had an intermediate oxidation state of copper (Cu+) with good thermodynamic stability. Furthermore, the switchable catalytic property was investigated with a 4-nitrophenol reduction and 3,3',5,5'-tetramethylbenzidine (TMB) oxidation reaction. The reduction kinetics followed pseudo-first-order, where the catalytic activity was enhanced by more than 103 times when Complex B was switched to Complex A. A similar trend was also observed for TMB oxidation. Our design strategy demonstrates that redox switchable metal-thiolate complexes could be a powerful candidate for a plethora of applications.

11.
Nanoscale ; 14(38): 13950-13989, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36124943

RESUMO

The current agricultural sector is not only in its most vulnerable state but is also becoming a threat to our environment due to expanding population and growing food demands along with worsening climatic conditions. In addition, numerous agrochemicals presently being used as fertilizers and pesticides have low efficiency and high toxicity. However, the rapid growth of nanotechnology has shown great promise to tackle these issues replacing conventional agriculture industries. Since the last decade, nanomaterials especially metal oxide nanoparticles (MONPs) have been attractive for improving agricultural outcomes due to their large surface area, higher chemical/thermal stability and tunable unique physicochemical characteristics. Further, to achieve sustainability, researchers have been extensively working on ecological and cost-effective biological approaches to synthesize MONPs. Hereby, we have elaborated on recent successful biosynthesis methods using various plants/microbes. Furthermore, we have elucidated different mechanisms for the interaction of MONPs with plants, including their uptake/translocation/internalization, photosynthesis, antioxidant activity, and gene alteration, which could revolutionize crop productivity/yield through increased nutrient amount, photosynthesis rate, antioxidative enzyme level, and gene upregulations. Besides, we have briefly discussed about functionalization of MONPs and their application in agricultural-waste-management. We have further illuminated recent developments of various MONPs (Fe2O3/ZnO/CuO/Al2O3/TiO2/MnO2) as nanofertilizers, nanopesticides and antimicrobial agents and their implications for enhanced plant growth and pest/disease management. Moreover, the potential use of MONPs as nanobiosensors for detecting nutrients/pathogens/toxins and safeguarding plant/soil health is also illuminated. Overall, this review attempts to provide a clear insight into the latest advances in biosynthesized MONPs for sustainable crop production, protection and management and their scope in the upcoming future of eco-friendly agricultural nanotechnology.


Assuntos
Nanopartículas Metálicas , Praguicidas , Óxido de Zinco , Agricultura/métodos , Agroquímicos , Antioxidantes , Produção Agrícola/métodos , Fertilizantes/análise , Compostos de Manganês , Nanopartículas Metálicas/toxicidade , Nanotecnologia/métodos , Óxidos , Solo
12.
J Biotechnol ; 355: 21-41, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35752390

RESUMO

Plant nutrition is crucial in crop productivity and providing food security to the ever-expanding population. Application of chemical/biological fertilizers and pesticides are the mainstays for any agricultural economy. However, there are unintended consequences of using chemical fertilizers and pesticides. The environment and ecological balance are adversely affected by their usage. Biofertilizers and biopesticides counter some undesired environmental effects of chemical fertilizers/pesticides; despite some drawbacks associated with their use. The recent developments in nanotechnology offer promise toward sustainable agriculture. Sustainable agriculture involves addressing the concerns about agriculture as well as the environment. This review briefs about important nanomaterials used in agriculture as nanofertilizers, nanopesticides, and a combination called nanobiofertilizers. Both nanofertilizers and nanopesticides enable slow and sustained release besides their eco-friendly nature. They can be tailored to the specific needs of to crop. Nanofertilizers also offer greater stress tolerance and, therefore, are of considerable value in the era of climate change. Furthermore, nanofertilizers/nanopesticides are applied in minute amounts, reducing transportation costs associated and thus positively affecting the economy. Their uses extend beyond such as if nanoparticles (NPs) are used at high concentrations; they affect plant pathogens adversely. Polymer-based biodegradable nanofertilizers and nanopesticides offer various benefits. There is also a dark side to the use of nanomaterials in agriculture. Nanotechnology often involves the use of metal/metal oxide nanoparticles, which might get access to human bodies leading to their accumulation through bio-magnification. Although their effects on human health are not known, NPs may reach toxic concentrations in soil and runoff into rivers, and other water bodies with their removal to become a huge economic burden. Nevertheless, a risk-benefit analysis of nanoformulations must be ensured before their application in sustainable agriculture.


Assuntos
Fertilizantes , Praguicidas , Agricultura , Produção Agrícola , Fertilizantes/análise , Humanos , Nanotecnologia , Plantas
13.
ChemSusChem ; 15(11): e202200281, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35377969

RESUMO

It is estimated that all fossil fuels will be depleted by 2060 if we continue to use them at the present rate. Therefore, there is an unmet need for an alternative source of energy with high calorific value. In this regard, hydrogen is considered the best alternative renewable fuel that could be used in practical conditions. Accordingly, researchers are looking for an ideal hydrogen storage system under ambient conditions for feasible applications. In many respects, carbon-based sorbents have emerged as the best possible hydrogen storage media. These carbon-based sorbents are cost-effective, eco-friendly, and readily available. In this Review, the present status of carbon-based materials in promoting solid-state hydrogen storage technologies at the operating temperature and pressure was reported. Experimental studies have shown that some carbon-based materials such as mesoporous graphene and doped carbon nanotubes may have hydrogen storage uptake of 3-7 wt %, while some theoretical studies have predicted up to 13.79 wt % of hydrogen uptake at ambient conditions. Also, it was found that different methods used for carbon materials synthesis played a vital role in hydrogen storage performance. Eventually, this Review will be helpful to the scientific community for finding the competent material and methodology to investigate the existing hydrogen uptake issues at operating conditions.


Assuntos
Grafite , Nanotubos de Carbono , Combustíveis Fósseis , Hidrogênio , Energia Renovável
14.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(2): 201-211, Apr.-June 2021. tab, ilus
Artigo em Inglês | LILACS | ID: biblio-1286682

RESUMO

ABSTRACT The COVID-19 pandemic has pushed the world towards social, economic, and medical challenges. Scientific research in medicine is the only means to overcome novel and complex diseases like COVID-19. To sum up the therapeutic wild-goose chase, many available antivirals and repurposed drugs have failed to show successful clinical evidence in patient recovery, several vaccine candidates are still waiting in the trial pipelines and a few have become available to the common public for administration in record time.However, with upcoming evidence of coronavirus mutations, available vaccines may thrive on the spirit of doubt about efficacy and effectiveness towards these new strains of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV2). In all these collective uncertainties, plasma therapy has shown a ray of hope for critically ill patients. To date, with very few published case studies of convalescent plasma in COVID-19, there are two school of thought process in the scientific community regarding plasma therapy efficiency and this leads to confusion due to the lack of optimal randomized and controlled studies.Without undertaking any robust scientific studies, evidence or caution, accepting any therapy unanimously may cause more harm than good, but with a clearer understanding of SARS-CoV2 immunopathology and drug response, plasma therapy might be the silver lining against COVID-19 for the global community.


Assuntos
Plasma , COVID-19/terapia
15.
Hematol Transfus Cell Ther ; 43(2): 201-211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33903854

RESUMO

The COVID-19 pandemic has pushed the world towards social, economic, and medical challenges. Scientific research in medicine is the only means to overcome novel and complex diseases like COVID-19. To sum up the therapeutic wild-goose chase, many available antivirals and repurposed drugs have failed to show successful clinical evidence in patient recovery, several vaccine candidates are still waiting in the trial pipelines and a few have become available to the common public for administration in record time. However, with upcoming evidence of coronavirus mutations, available vaccines may thrive on the spirit of doubt about efficacy and effectiveness towards these new strains of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV2). In all these collective uncertainties, plasma therapy has shown a ray of hope for critically ill patients. To date, with very few published case studies of convalescent plasma in COVID-19, there are two school of thought process in the scientific community regarding plasma therapy efficiency and this leads to confusion due to the lack of optimal randomized and controlled studies. Without undertaking any robust scientific studies, evidence or caution, accepting any therapy unanimously may cause more harm than good, but with a clearer understanding of SARS-CoV2 immunopathology and drug response, plasma therapy might be the silver lining against COVID-19 for the global community.

16.
Vasc Endovascular Surg ; 54(8): 752-755, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32783501
17.
J Phys Chem Lett ; 11(18): 7575-7582, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32818381

RESUMO

Organometallic complexes including metal carbonyls have been widely utilized in academic and industrial settings for purposes ranging from teaching basic catalytic reactions to developing state-of-the-art electronic circuits. Characterization of these materials can be obtained via steady-state measurements; however, the intermediate photochemical events remain unclear, hindering effective and rational molecular engineering methods for new materials. We employed femtosecond transient absorption (fs-TA) and ground-state femtosecond stimulated Raman spectroscopy (FSRS) on triphenylbismuth-tungsten pentacarbonyl complex, a solution precursor for bimetallic oxide thin films. Upon 280 nm excitation into a charge-transfer band, an ultrafast bimetallic bond dissociation occurs within ∼140 fs. The subpicosecond nondiffusive solvation events are followed by ∼10 ps (15 ps) methanol (ethanol) complexation of the nascent tungsten pentacarbonyl intermediate, which mainly undergoes vibrational relaxation after crossing into a hot ground state. The trans ligand to axial CO is revealed to play a key role in the electronic and vibrational structure and dynamics of the complex. These findings could power rational design of bimetallic and functional solution precursors for the light-driven nanopatterning of thin films.

18.
Ann Vasc Surg ; 69: 448.e15-448.e18, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32474149

RESUMO

BACKGROUND: Gender-reassignment surgeries are technically challenging and associated with detrimental vascular complications. METHODS: A 49 year-old female status-post phalloplasty presented with peripheral vascular complication resulting in disabling claudication. Initial anastomotic attempt was rendered nonviable to sustain the constructed phallus resulting in superficial femoral artery stenosis. Covered stent placement corrected the stenosis and alleviated the claudication. RESULTS: As gender-reassignment surgeries increase, greater understanding of potential vascular complications is needed. Involvement of multidisciplinary teams is necessary to optimize patient safety and outcomes. CONCLUSIONS: Vascular surgery should play a larger role in these complex revascularizations and vessel anastomoses to ensure quality blood flow to the reconstructed genitalia.


Assuntos
Procedimentos Endovasculares , Artéria Femoral , Claudicação Intermitente/terapia , Doença Arterial Periférica/terapia , Cirurgia de Readequação Sexual/efeitos adversos , Constrição Patológica , Procedimentos Endovasculares/instrumentação , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Claudicação Intermitente/diagnóstico por imagem , Claudicação Intermitente/etiologia , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/fisiopatologia , Stents , Resultado do Tratamento , Grau de Desobstrução Vascular
19.
Environ Toxicol Chem ; 38(12): 2651-2658, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31441966

RESUMO

Recently, monoalkyl oxo-hydroxo tin clusters have emerged as a new class of metal-oxide resist to support the semiconductor industry's transition to extreme ultraviolet (EUV) lithography. Under EUV exposure, these tin-based clusters exhibit higher performance and wider process windows than conventional polymer materials. A promising new monoalkyl precursor, [(BuSn)12 O14 (OH)6 ][OH]2 (BuSn), is still in its infancy in terms of film formation. However, understanding potential environmental effects could significantly affect future development as a commercial product. We synthesized and explored the toxicity of nano-BuSn in the alga Chlamydomonas reinhardtii and the crustacean Daphnia magna at exposure concentrations ranging from 0 to 250 mg/L. Nano-BuSn had no effect on C. reinhardtii growth rate irrespective of concentration, whereas high nanoparticle concentrations (≥100 mg/L) increased D. magna immobilization and mortality significantly. To simulate an end-of-life disposal and leachate contamination, BuSn-coated film wafers were incubated in water at various pH values and temperatures for 14 and 90 d to investigate leaching rates and subsequent toxicity of the leachates. Although small quantities of tin (1.1-3.4% of deposited mass) leached from the wafers, it was insufficient to elicit a toxic response regardless of pH, incubation time, or temperature. The low toxicity of the tin-based thin films suggests that they can be an environmentally friendly addition to the material sets useful for semiconductor manufacturing. Environ Toxicol Chem 2019;38:2651-2658. © 2019 SETAC.


Assuntos
Chlamydomonas/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Estanho/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Chlamydomonas/crescimento & desenvolvimento , Daphnia/crescimento & desenvolvimento , Óxidos/análise , Óxidos/toxicidade , Estanho/análise , Poluentes Químicos da Água/análise
20.
Gerontol Geriatr Med ; 5: 2333721419858735, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31259206

RESUMO

Objective: Geriatric admissions to trauma centers have increased, and in 2013, our center integrated geriatrician consultation with the management of admitted patients. Our goal is to describe our experience with increasing geriatric fall volume to help inform organized geriatric trauma programs. Method: We retrospectively analyzed admitted trauma patients ≥65 years old, suffering falls from January 1, 2006, to December 31, 2017. We examined descriptive statistics and changes in outcomes after integration. Results: A total of 1,335 geriatric trauma patients were admitted, of which 1,054 (79%) had suffered falls. Falls increased disproportionately (+280%) compared with other mechanisms of injury (+97%). After 2013, patient discharge disposition to skilled nursing facility decreased significantly (-67%, p < .001), with a concomitant increase in safe discharges home with outpatient services. Regression analysis revealed association between integration of geriatrician consultation and outcomes. Discussion: Geriatrician consultation is associated with optimized discharge disposition of trauma patients. We recommend geriatrician consultation for all geriatric trauma activations.

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