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1.
Indian J Plast Surg ; 56(3): 218-227, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37435335

RESUMO

Objectives Arteriovenous malformations (AVMs) are high-flow, aggressive lesions that cause systemic effects and may pose a risk to life. These lesions are difficult to treat as they have a tendency to recur aggressively after excision or embolization. So, it requires a regulating free flap with robust vascular flow averting the postexcisional ischemia-induced collateralization, parasitization, and recruitment of neovessels from the surrounding mesenchyme-a phenomenon precipitating and perpetuating the recurrence of AVM. Materials and Methods Sixteen patients (12 males and 4 females) with AVMs Schobinger type 4 involving face were treated from March 2015 to March 2021 with various free flaps: three free rectus abdominis flaps, one free radial forearm flap, and twelve free anterolateral thigh flaps were used for reconstruction following the wide local excision of Schobinger type 4 facial AVM. The records of these patients were analyzed retrospectively. The average follow-up period was 18.5 months. The functional and aesthetic outcomes were analyzed with institutional assessment scores. Results The average size of the flap harvested was 113.43 cm 2 . Fourteen patients (87.5%) had good-to-excellent score ( p = 0.035) with institutional aesthetic and functional assessment system. The remaining two patients (12.5%) had only fair results. There was no recurrence (0%) in the free flap group versus 64% recurrence in the pedicled flap and skin grafting groups ( p = 0.035). Conclusion Free flaps with their robust and homogenized blood supply provide a good avenue for void filling and an excellent regulating effect in inhibiting any locoregional recurrences of AVMs.

2.
J Clin Orthop Trauma ; 31: 101927, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35799882

RESUMO

Objective: This study aimed to evaluate if the acetabulum's conservative reaming with preservation of the medial acetabular bone and anatomic placement of the acetabular implant in cementless total hip arthroplasty (THA) has any adverse effect on the radiological outcome, long term implant survival and patient satisfaction. Methods: 106 consecutive patients were identified from a single surgeon practice who underwent cementless THA from 2005 to 2010. Twenty-one were lost to follow up, and five patients died unrelated to THA. Eighty patients were available for the study. The mean follow-up was 8.6 years (range 5.7-11.6). The mean age was 61.9 years. Immediate pre- and postoperative radiographs were reviewed to calculate combined offset (Acetabular offset - AO, plus Femoral offset - FO). Implant failure, aseptic loosening, revision surgery, patient satisfaction and complications were assessed on long-term follow-up. Results: Acetabular component survival was 100% with no aseptic failure. None of the patients had revision surgery for any cause. The mean difference in the acetabular offset and combined offset postoperatively was within 3 mm. One patient had a dislocation, and one had a prosthetic joint infection (PJI). 95% of the patients in this series would recommend the hip replacement procedure to others, with a mean satisfaction score of 8.7 (range; 1-10). Conclusion: Conservative acetabular reaming with preservation of medial acetabulum bone with the anatomic placement of the acetabular implant in cementless THA is safe with no adverse effects on implant survival and patient satisfaction. It offers the advantage of preserving the patient's bone stock, which would potentially be of significant advantage to the patient and the surgeon in case of revision arthroplasty.

3.
Syst Rev ; 11(1): 78, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473819

RESUMO

BACKGROUND: Vaccination, albeit a necessity in the prevention of infectious diseases, requires appropriate strategies for addressing vaccine hesitancy at an individual and community level. However, there remains a glaring scarcity of available literature in that regard. Therefore, this review aims to scrutinize globally tested interventions to increase the vaccination uptake by addressing vaccine hesitancy at various stages of these interventions across the globe and help policy makers in implementing appropriate strategies to address the issue. METHODS: A systematic review of descriptive and analytic studies was conducted using specific key word searches to identify literature containing information about interventions directed at vaccine hesitancy. The search was done using PubMed, Global Health, and Science Direct databases. Data extraction was based on study characteristics such as author details; study design; and type, duration, and outcome of an intervention. RESULTS: A total of 105 studies were identified of which 33 studies were included in the final review. Community-based interventions, monetary incentives, and technology-based health literacy demonstrated significant improvement in the utilization of immunization services. On the other hand, media-based intervention studies did not bring about a desired change in overcoming vaccine hesitancy. CONCLUSION: This study indicates that the strategies should be based on the need and reasons for vaccine hesitancy for the targeted population. A multidimensional approach involving community members, families, and individuals is required to address this challenging issue.


Assuntos
Vacinas , Saúde Global , Humanos , Projetos de Pesquisa , Vacinação , Hesitação Vacinal
4.
Int J Adv Manuf Technol ; 120(3-4): 1473-1530, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35228769

RESUMO

There is a tremendous increase in the demand for converting biomaterials into high-quality industrially manufactured human body parts, also known as medical implants. Drug delivery systems, bone plates, screws, cranial, and dental devices are the popular examples of these implants - the potential alternatives for human life survival. However, the processing techniques of an engineered implant largely determine its preciseness, surface characteristics, and interactive ability with the adjacent tissue(s) in a particular biological environment. Moreover, the high cost-effective manufacturing of an implant under tight tolerances remains a challenge. In this regard, several subtractive or additive manufacturing techniques are employed to manufacture patient-specific implants, depending primarily on the required biocompatibility, bioactivity, surface integrity, and fatigue strength. The present paper reviews numerous non-degradable and degradable metallic implant biomaterials such as stainless steel (SS), titanium (Ti)-based, cobalt (Co)-based, nickel-titanium (NiTi), and magnesium (Mg)-based alloys, followed by their processing via traditional turning, drilling, and milling including the high-speed multi-axis CNC machining, and non-traditional  abrasive water jet machining (AWJM), laser beam machining (LBM), ultrasonic machining (USM), and electric discharge machining (EDM) types of subtractive manufacturing techniques. However, the review further funnels down its primary focus on Mg, NiTi, and Ti-based alloys on the basis of the increasing trend of their implant applications in the last decade due to some of their outstanding properties. In the recent years, the incorporation of cryogenic coolant-assisted traditional subtraction of biomaterials has gained researchers' attention due to its sustainability, environment-friendly nature, performance, and superior biocompatible and functional outcomes fitting for medical applications. However, some of the latest studies reported that the medical implant manufacturing requirements could be more remarkably met using the non-traditional subtractive manufacturing approaches. Altogether, cryogenic  machining among the traditional routes and EDM among the non-traditional means along with their variants, were identified as some of the most effective subtractive manufacturing techniques for achieving the dimensionally accurate and biocompatible metallic medical implants with significantly modified surfaces.

5.
Small ; 18(1): e2105424, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34786844

RESUMO

Reconfiguration of amorphous complex oxides provides a readily controllable source of stress that can be leveraged in nanoscale assembly to access a broad range of 3D geometries and hybrid materials. An amorphous SrTiO3 layer on a Si:B/Si1- x Gex :B heterostructure is reconfigured at the atomic scale upon heating, exhibiting a change in volume of ≈2% and accompanying biaxial stress. The Si:B/Si1- x Gex :B bilayer is fabricated by molecular beam epitaxy, followed by sputter deposition of SrTiO3 at room temperature. The processes yield a hybrid oxide/semiconductor nanomembrane. Upon release from the substrate, the nanomembrane rolls up and has a curvature determined by the stress in the epitaxially grown Si:B/Si1- x Gex :B heterostructure. Heating to 600 °C leads to a decrease of the radius of curvature consistent with the development of a large compressive biaxial stress during the reconfiguration of SrTiO3 . The control of stresses via post-deposition processing provides a new route to the assembly of complex-oxide-based heterostructures in 3D geometry. The reconfiguration of metastable mechanical stressors enables i) synthesis of various types of strained superlattice structures that cannot be fabricated by direct growth and ii) technologies based on strain engineering of complex oxides via highly scalable lithographic processes and on large-area semiconductor substrates.

6.
Cureus ; 13(8): e16984, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34540389

RESUMO

Aim During the COVID-19 pandemic, there has been worldwide cancellation of elective surgeries to protect patients from nosocomial viral transmission and peri-operative complications. With the unfolding situation, there is a definite need for an exit strategy to reinstate elective services. Therefore, more literature evidence supporting exit plans for elective surgical services is imperative to adopt a safe working principle. This study aims to provide evidence for safe elective surgical practice during the pandemic. Methodology This single centre, prospective, observational study included adult patients who were admitted and underwent elective surgical procedures in the trust's COVID-free environment at the Birmingham Treatment Centre between May 19 and July 14, 2020. Data were collected on demographic parameters, peri-operative variables, surgical specialities, COVID-19 reverse transcription polymerase chain reaction (RT-PCR) testing results, post-operative complications and mortality. The study also highlighted the protocols it followed for the elective services during the pandemic. Results A total of 303 patients were included with mean age of 49.9 years (SD 16.5) comprising of 59% (178) female and 41% (125) male. They were classified according to the American Society of Anaesthesiologist Grade, different surgical specialities and types of anaesthesia used. Ninety-six percent (96%) of patients were discharged on the same day. Hundred percent (100%) compliance with pre-operative COVID-19 RT-PCR testing was maintained. There was no 30-day mortality or major respiratory complications. Conclusion Careful patient selection, simultaneous involvement of the pre-assessment and anaesthetic team, strict adherence to peri-operative protocols and delivering vigilant post-operative care for COVID-19 infection can help provide safe elective surgical services if the community transmission is under reasonable control. However, it is particularly important to maintain COVID-free safe environment for such procedures.

7.
Indian J Plast Surg ; 54(2): 144-151, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34239235

RESUMO

Introduction and Methods The glabrous, thin, and pliable texture of lateral arm flap with no loss of any axial vessel of the limb renders it a good choice for hemiglossectomy defect reconstruction. The main caveat of this flap harvest is the loss of sensation in the distribution of posterior antebrachial cutaneous nerve (PABCN). In this article, we present two strategic sites and techniques to preserve the integrity of PABCN and at the same time harvesting lateral arm flap with a lengthy lower lateral cutaneous nerve of arm for the neurotization. The outcome of this function-preserving neurotized lateral arm free flap in the reconstruction of hemiglossectomy defects is analyzed and presented in this article. Results Ninety percent of the patients attained grade 3 score in objective assessment, leading to a significant p -value of 0.02 with this technique. All had preservation of sensation in the distribution of PABCN. Conclusion Our technique of harvest and neurotization has brought good functional recovery of the oral cavity with preservation of PABCN.

8.
ACS Nano ; 15(1): 1229-1239, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33337861

RESUMO

We present a transformative route to obtain mass-producible helical slow-wave structures for operation in beam-wave interaction devices at THz frequencies. The approach relies on guided self-assembly of conductive nanomembranes. Our work coordinates simulations of cold helices (i.e., helices with no electron beam) and hot helices (i.e., helices that interact with an electron beam). The theoretical study determines electromagnetic fields, current distributions, and beam-wave interaction in a parameter space that has not been explored before. These parameters include microscale diameter, pitch, tape width, and nanoscale surface finish. Parametric simulations show that beam-wave interaction devices based on self-assembled and electroplated helices will potentially provide gain-bandwidth products higher than 2 dBTHz at 1 THz. Informed by the simulation results, we fabricate prototype helices for operation as slow-wave structures at THz frequencies, using metal nanomembranes. Single and intertwined double helices, as well as helices with one or two chiralities, are obtained by self-assembly of stressed metal bilayers. The nanomembrane stiffness and built-in stress control the diameter of the helices. The in-plane geometry of the nanomembrane determines the pitch, the chirality, and the formation of single vs intertwined double helices.

9.
BMC Microbiol ; 20(1): 323, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33096982

RESUMO

BACKGROUND: The production of methane by methanogens is dependent on numerous iron-sulfur (Fe-S) cluster proteins; yet, the machinery involved in Fe-S cluster biogenesis in methanogens remains largely unknown. Methanogen genomes encode uncharacterized homologs of the core components of the ISC (IscS and IscU) and SUF (SufBC) Fe-S cluster biogenesis systems found in bacteria and eukaryotes. Methanosarcina acetivorans contains three iscSU and two sufCB gene clusters. Here, we report genetic and biochemical characterization of M. acetivorans iscSU2. RESULTS: Purified IscS2 exhibited pyridoxal 5'- phosphate-dependent release of sulfur from L-cysteine. Incubation of purified IscU2 with IscS2, cysteine, and iron (Fe2+) resulted in the formation of [4Fe-4S] clusters in IscU2. IscU2 transferred a [4Fe-4S] cluster to purified M. acetivorans apo-aconitase. IscU2 also restored the aconitase activity in air-exposed M. acetivorans cell lysate. These biochemical results demonstrate that IscS2 is a cysteine desulfurase and that IscU2 is a Fe-S cluster scaffold. M. acetivorans strain DJL60 deleted of iscSU2 was generated to ascertain the in vivo importance of IscSU2. Strain DJL60 had Fe-S cluster content and growth similar to the parent strain but lower cysteine desulfurase activity. Strain DJL60 also had lower intracellular persulfide content compared to the parent strain when cysteine was an exogenous sulfur source, linking IscSU2 to sulfur metabolism. CONCLUSIONS: This study establishes that M. acetivorans contains functional IscS and IscU, the core components of the ISC Fe-S cluster biogenesis system and provides the first evidence that ISC operates in methanogens.


Assuntos
Liases de Carbono-Enxofre/metabolismo , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Proteínas Ferro-Enxofre/metabolismo , Methanosarcina/genética , Liases de Carbono-Enxofre/genética , Cisteína/metabolismo , Ativação Enzimática , Proteínas de Escherichia coli/genética , Ferro/metabolismo , Proteínas Ferro-Enxofre/genética , Methanosarcina/enzimologia , Enxofre/metabolismo
10.
Proc Natl Acad Sci U S A ; 116(51): 25917-25922, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31801875

RESUMO

Flavodoxins, electron transfer proteins essential for diverse metabolisms in microbes from the domain Bacteria, are extensively characterized. Remarkably, although genomic annotations of flavodoxins are widespread in microbes from the domain Archaea, none have been isolated and characterized. Herein is described the structural, biochemical, and physiological characterization of an unusual flavodoxin (FldA) from Methanosarcina acetivorans, an acetate-utilizing methane-producing microbe of the domain Archaea In contrast to all flavodoxins, FldA is homodimeric, markedly less acidic, and stabilizes an anionic semiquinone. The crystal structure reveals an flavin mononucleotide (FMN) binding site unique from all other flavodoxins that provides a rationale for stabilization of the anionic semiquinone and a remarkably low reduction potentials for both the oxidized/semiquinone (-301 mV) and semiquinone/hydroquinone couples (-464 mV). FldA is up-regulated in acetate-grown versus methanol-grown cells and shown here to substitute for ferredoxin in mediating the transfer of low potential electrons from the carbonyl of acetate to the membrane-bound electron transport chain that generates ion gradients driving ATP synthesis. FldA offers potential advantages over ferredoxin by (i) sparing iron for abundant iron-sulfur proteins essential for acetotrophic growth and (ii) resilience to oxidative damage.


Assuntos
Flavodoxina/química , Flavodoxina/metabolismo , Methanosarcina/metabolismo , Acetatos/metabolismo , Proteínas de Bactérias/química , Sítios de Ligação , Clonagem Molecular , Cristalografia por Raios X , Ferredoxinas/química , Ferredoxinas/metabolismo , Mononucleotídeo de Flavina/química , Flavodoxina/genética , Flavodoxina/isolamento & purificação , Flavoproteínas/química , Aquecimento Global , Hidroquinonas , Metano/metabolismo , Modelos Moleculares , Oxirredução , Conformação Proteica
11.
Sci Adv ; 5(8): eaaw9059, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31457094

RESUMO

Although two-thirds of the nearly 1 billion metric tons of methane produced annually in Earth's biosphere derives from acetate, the in situ process has escaped rigorous understanding. The unresolved question concerns the mechanism by which the exceptionally marginal amount of available energy supports acetotrophic growth of methanogenic archaea in the environment. Here, we show that Methanosarcina acetivorans conserves energy by Fe(III)-dependent respiratory metabolism of acetate, augmenting production of the greenhouse gas methane. An extensively revised, ecologically relevant, biochemical pathway for acetotrophic growth is presented, in which the conservation of respiratory energy is maximized by electron bifurcation, a previously unknown mechanism of biological energy coupling. The results transform the ecological and biochemical understanding of methanogenesis and the role of iron in the mineralization of organic matter in anaerobic environments.


Assuntos
Methanosarcina/fisiologia , Modelos Teóricos , Termodinâmica , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Algoritmos , Redes e Vias Metabólicas , Metano/biossíntese
12.
IDCases ; 18: e00579, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367519

RESUMO

Vision impairment is one of the devastating complications of central nervous system tuberculosis (CNS TB). Optic atrophy is a sequelae of various forms of CNS TB which, ultimately, is responsible for vision impairment. It is usually the secondary optic atrophy which occurs in CNS TB. In this case report, we present the story of an immunocompetent woman presenting as bilateral visual loss. She was found to have primary optic atrophy. Neuroimaging revealed features of chronic meningitis. Polymerase chain reaction test for Mycobacterium tuberculosis was positive in cerebrospinal fluid. Although secondary optic atrophy is common in the CNS TB, as a complication of meningitis, primary optic atrophy per se is infrequently reported.

13.
Pediatr Surg Int ; 35(11): 1197-1210, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31300851

RESUMO

PURPOSE: This exclusively surgical series on pediatric non-variceal gastrointestinal bleed (NVGIB) defines three levels of bleed site and describes etiology, bleed severity, diagnostic algorithm, and surgical management for each bleed site. Management challenges are detailed. METHODS: Patients aged ≤ 18 years treated surgically for NVGIB were analysed. RESULTS: Bleed site (n = 87) was classified as: upper gastrointestinal bleed (UGIB; n = 11); small bowel bleed (SBB: n = 52); and lower GIB (n = 24). Four etiology-based groups were identified: lesions with ectopic gastric mucosa (EGM; n = 33), tumours (n = 23), ulcers (n = 21), and vascular pathology (n = 8). Bleed severity spectrum was: acute severe bleed (n = 12); subacute overt bleed (n = 59); and occult GIB (n = 16). Preoperative diagnosis was obtained in all UGIB and LGIB lesions. Eighty-two percent of surgical SB lesions were diagnosed preoperatively on Tc99m pertechnetate scan, computed tomography enterography-angiography, and capsule endoscopy; remaining 18% were diagnosed at laparotomy with intra-operative enteroscopy (IOE). Surgical management was tailored to bleed site, severity, and etiology. Indications of IOE and approach to management challenges are detailed. CONCLUSIONS: The commonest site-specific bleed etiologies were duodenal ulcers for UGIB, EGM lesions for SBB, and tumours for LGIB. SBB presented diagnostic challenge. Diagnostic algorithm was tailored to bleed site, age-specific etiology, bleed severity, and associated abdominal/systemic symptoms. Management challenges were acute severe bleed, occult GIB, SBB, obscure GIB, and rare etiologies. IOE has a useful role in SBB management.


Assuntos
Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Adolescente , Algoritmos , Falso Aneurisma/complicações , Endoscopia por Cápsula , Criança , Pré-Escolar , Coristoma/complicações , Doença de Crohn/complicações , Úlcera Duodenal/complicações , Feminino , Mucosa Gástrica , Hemorragia Gastrointestinal/diagnóstico por imagem , Neoplasias Gastrointestinais/complicações , Artéria Hepática , Humanos , Lactente , Masculino , Divertículo Ileal/complicações , Compostos Radiofarmacêuticos , Pertecnetato Tc 99m de Sódio , Tomografia Computadorizada por Raios X , Malformações Vasculares/complicações
14.
J Family Med Prim Care ; 8(6): 2042-2046, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31334177

RESUMO

BACKGROUND: Hypertension (HTN) is difficult to diagnose since it is asymptomatic. Most of the patients with HTN are unaware of their disease, and hence a large number of these subjects have target organ damage (TOD) on their first arrival at hospital or clinic. Hence, early detection and treatment of TOD determines the cardiovascular prognosis in hypertensive patient and can retard or prevent further damage. METHODS: An observational and cross-sectional study was carried out in a tertiary care hospital and clinical profile was collected. Newly detected hypertensive men and women were recruited from outpatient and inpatient departments of medicine based on a set of inclusion and exclusion criteria. The study was carried out over a duration of 18 months from March 2014 to August 2015. RESULTS: A total of 150 participants were included in the study with a mean age of 51.64 ± 11.64 years. A total of 91 participants had presence of at least one TOD. In our study, retinopathy (20.67%), macroalbuminuria (MA) (44.67%), electrocardiographic left ventricular hypertrophy (LVH) (20.67%), echocardiographic LVH (29.33%), diastolic dysfunction (21.33%), and systolic dysfunction (3.33%) were particularly notable. Grade 3 retinopathy, microalbuminria, and diastolic dysfunction were associated with severity of HTN. CONCLUSION: We conclude that a strong relationship exists between HTN and TOD. The evidence for TOD was found to be greater than that expected in newly detected hypertensive patients. Hence, a tight control of blood pressure represents the first step in treating essential HTN, which not only keep the blood pressure under control and further steps to be taken to prevent or retard the onset/progression of TOD.

15.
J Biol Chem ; 293(24): 9198-9209, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29720404

RESUMO

Disulfide reductases reduce other proteins and are critically important for cellular redox signaling and homeostasis. Methanosarcina acetivorans is a methane-producing microbe from the domain Archaea that produces a ferredoxin:disulfide reductase (FDR) for which the crystal structure has been reported, yet its biochemical mechanism and physiological substrates are unknown. FDR and the extensively characterized plant-type ferredoxin:thioredoxin reductase (FTR) belong to a distinct class of disulfide reductases that contain a unique active-site [4Fe-4S] cluster. The results reported here support a mechanism for FDR similar to that reported for FTR with notable exceptions. Unlike FTR, FDR contains a rubredoxin [1Fe-0S] center postulated to mediate electron transfer from ferredoxin to the active-site [4Fe-4S] cluster. UV-visible, EPR, and Mössbauer spectroscopic data indicated that two-electron reduction of the active-site disulfide in FDR involves a one-electron-reduced [4Fe-4S]1+ intermediate previously hypothesized for FTR. Our results support a role for an active-site tyrosine in FDR that occupies the equivalent position of an essential histidine in the active site of FTR. Of note, one of seven Trxs encoded in the genome (Trx5) and methanoredoxin, a glutaredoxin-like enzyme from M. acetivorans, were reduced by FDR, advancing the physiological understanding of FDR's role in the redox metabolism of methanoarchaea. Finally, bioinformatics analyses show that FDR homologs are widespread in diverse microbes from the domain Bacteria.


Assuntos
Archaea/enzimologia , Bactérias/enzimologia , Dissulfetos/metabolismo , Ferredoxinas/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Methanosarcina/enzimologia , NADH NADPH Oxirredutases/metabolismo , Oxirredutases/metabolismo , Archaea/química , Archaea/metabolismo , Bactérias/química , Bactérias/metabolismo , Domínio Catalítico , Dissulfetos/química , Transporte de Elétrons , Ferredoxinas/química , Proteínas Ferro-Enxofre/química , Methanosarcina/química , Methanosarcina/metabolismo , Modelos Moleculares , NADH NADPH Oxirredutases/química , Oxirredução , Oxirredutases/química , Spinacia oleracea/química , Spinacia oleracea/enzimologia , Spinacia oleracea/metabolismo
16.
Proc Natl Acad Sci U S A ; 113(22): 6172-7, 2016 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-27140643

RESUMO

Ruminants, such as cows, sheep, and goats, predominantly ferment in their rumen plant material to acetate, propionate, butyrate, CO2, and methane. Whereas the short fatty acids are absorbed and metabolized by the animals, the greenhouse gas methane escapes via eructation and breathing of the animals into the atmosphere. Along with the methane, up to 12% of the gross energy content of the feedstock is lost. Therefore, our recent report has raised interest in 3-nitrooxypropanol (3-NOP), which when added to the feed of ruminants in milligram amounts persistently reduces enteric methane emissions from livestock without apparent negative side effects [Hristov AN, et al. (2015) Proc Natl Acad Sci USA 112(34):10663-10668]. We now show with the aid of in silico, in vitro, and in vivo experiments that 3-NOP specifically targets methyl-coenzyme M reductase (MCR). The nickel enzyme, which is only active when its Ni ion is in the +1 oxidation state, catalyzes the methane-forming step in the rumen fermentation. Molecular docking suggested that 3-NOP preferably binds into the active site of MCR in a pose that places its reducible nitrate group in electron transfer distance to Ni(I). With purified MCR, we found that 3-NOP indeed inactivates MCR at micromolar concentrations by oxidation of its active site Ni(I). Concomitantly, the nitrate ester is reduced to nitrite, which also inactivates MCR at micromolar concentrations by oxidation of Ni(I). Using pure cultures, 3-NOP is demonstrated to inhibit growth of methanogenic archaea at concentrations that do not affect the growth of nonmethanogenic bacteria in the rumen.


Assuntos
Metano/química , Simulação de Acoplamento Molecular , Animais , Euryarchaeota/metabolismo , Oxirredutases/química , Rúmen/metabolismo , Ruminantes/metabolismo
17.
Biochemistry ; 55(2): 313-21, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26684934

RESUMO

Glutaredoxins (GRXs) are thiol-disulfide oxidoreductases abundant in prokaryotes, although little is understood of these enzymes from the domain Archaea. The numerous characterized GRXs from the domain Bacteria utilize a diversity of low-molecular-weight thiols in addition to glutathione as reductants. We report here the biochemical and structural properties of a GRX-like protein named methanoredoxin (MRX) from Methanosarcina acetivorans of the domain Archaea. MRX utilizes coenzyme M (CoMSH) as reductant for insulin disulfide reductase activity, which adds to the diversity of thiol protectants in prokaryotes. Cell-free extracts of M. acetivorans displayed CoMS-SCoM reductase activity that complements the CoMSH-dependent activity of MRX. The crystal structure exhibits a classic thioredoxin-glutaredoxin fold comprising three α-helices surrounding four antiparallel ß-sheets. A pocket on the surface contains a CVWC motif, identifying the active site with architecture similar to GRXs. Although it is a monomer in solution, the crystal lattice has four monomers in a dimer of dimers arrangement. A cadmium ion is found within the active site of each monomer. Two such ions stabilize the N-terminal tails and dimer interfaces. Our modeling studies indicate that CoMSH and glutathione (GSH) bind to the active site of MRX similar to the binding of GSH in GRXs, although there are differences in the amino acid composition of the binding motifs. The results, combined with our bioinformatic analyses, show that MRX represents a class of GRX-like enzymes present in a diversity of methane-producing Archaea.


Assuntos
Proteínas Arqueais/metabolismo , Glutarredoxinas/metabolismo , Mesna/metabolismo , Methanosarcina/metabolismo , Proteínas Arqueais/química , Glutarredoxinas/química , Proteína Dissulfeto Redutase (Glutationa)/química , Proteína Dissulfeto Redutase (Glutationa)/metabolismo , Estrutura Secundária de Proteína
18.
Biochemistry ; 54(47): 7019-28, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26536144

RESUMO

Two subtypes of class III anaerobic ribonucleotide reductases (RNRs) studied so far couple the reduction of ribonucleotides to the oxidation of formate, or the oxidation of NADPH via thioredoxin and thioredoxin reductase. Certain methanogenic archaea contain a phylogenetically distinct third subtype of class III RNR, with distinct active-site residues. Here we report the cloning and recombinant expression of the Methanosarcina barkeri class III RNR and show that the electrons required for ribonucleotide reduction can be delivered by a [4Fe-4S] protein ferredoxin disulfide reductase, and a conserved thioredoxin-like protein NrdH present in the RNR operon. The diversity of class III RNRs reflects the diversity of electron carriers used in anaerobic metabolism.


Assuntos
Methanosarcina barkeri/enzimologia , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Ribonucleotídeo Redutases/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Ácido Cítrico/metabolismo , Clonagem Molecular , Elétrons , Ferredoxinas/metabolismo , Methanosarcina barkeri/química , Methanosarcina barkeri/genética , Methanosarcina barkeri/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Oxirredução , Filogenia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ribonucleotídeo Redutases/química , Ribonucleotídeo Redutases/genética , Ribonucleotídeos/metabolismo
19.
Clin J Am Soc Nephrol ; 10(8): 1364-70, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26220816

RESUMO

BACKGROUND AND OBJECTIVES: Inappropriate medication use is common in the care of patients with CKD. The feasibility of a simple mobile health tool designed to advise patients on safe medication usage in CKD was examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants with predialysis CKD (defined as eGFR<60 ml/min per 1.73 m(2)) in the Safe Kidney Care Cohort Study were recruited for home usability testing of a novel medication inquiry system between January and September of 2013. Testing was through two mobile platforms: (1) short messaging service text or (2) personal digital assistant (e.g., iPod Touch). Twenty participants (one half assigned to one device and one half assigned to the other device) were enrolled and received an in-center tutorial on device usage before the end of the study visit. Participants were subsequently mailed three sample pill bottles with the name of randomly selected medications and asked to input these medications into the medication inquiry system. The medication inquiry system response options were as follows: (1) safe in CKD, (2) not safe in CKD, (3) use with caution/speak with your health care provider, or (4) error message (for an incorrectly inputted medication). Participants were asked to record the response issued by the medication inquiry system for each medication sent for usability testing. A user satisfaction survey was administered after completion of the protocol. RESULTS: All participants owned a mobile telephone, but few owned a smartphone. Of 60 total medication queries, there were only three recorded errors, two of which occurred in the short messaging service texting group. Overall satisfaction with the application was high, with slightly higher satisfaction noted in the personal digital assistant group compared with the short messaging service group. CONCLUSIONS: The mobile health medication inquiry system application had general ease of use and high acceptance across two platforms among individuals representative of the CKD population. Tailored mobile health technology may improve medication safety in CKD.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Serviços de Assistência Domiciliar , Erros de Medicação/prevenção & controle , Satisfação do Paciente , Insuficiência Renal Crônica/terapia , Telemedicina/métodos , Idoso , Atitude Frente aos Computadores , Telefone Celular , Computadores de Mão , Estudos de Viabilidade , Feminino , Letramento em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Inquéritos e Questionários , Telemedicina/instrumentação , Envio de Mensagens de Texto
20.
Environ Sci Technol ; 49(15): 9237-46, 2015 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-26158600

RESUMO

The first detailed seasonal validation has been carried out for the Moderate Resolution Imaging Spectroradiometer (MODIS) Terra and Aqua satellites Level 2.0 Collection Version 5.1 AOT (τMODIS) with Aerosol Robotic Network (AERONET) Level 2.0 AOT (τAERONET) for the years 2009-2012 over semi-arid region Jaipur, northwestern India. The correlation between τMODIS versus τAERONET at 550 nm is determined with different spatial and temporal size windows. The τMODIS overestimates τAERONET within a range of +0.06 ± 0.24 during the pre-monsoon (April-June) season, while it underestimates the τAERONET with -0.04 ± 0.12 and -0.05 ± 0.18 during dry (December-March) and post-monsoon (October-November) seasons, respectively. Correlation without (with) error envelope has been found for pre-monsoon at 0.71 (0.89), post-monsoon at 0.76 (0.94), and dry season at 0.78 (0.95). τMODIS is compared to τAERONET at three more ground AERONET stations in India, i.e., Kanpur, Gual Pahari, and Pune. Furthermore, the performance of MODIS Deep Blue and Aqua AOT550 nm (τDB550 nm and τAqua550 nm) with τAERONET is also evaluated for all considered sites over India along with a U.S. desert site at White Sand, Tularosa Basin, NM. The statistical results reveal that τAqua550 nm performs better over Kanpur and Pune, whereas τDB550 nm performs better over Jaipur, Gual Pahari, and White Sand High Energy Laser Systems Test Facility (HELSTF) (U.S. site).


Assuntos
Aerossóis/análise , Bases de Dados como Assunto , Clima Desértico , Fenômenos Ópticos , Imagens de Satélites/métodos , Geografia , Índia , Estações do Ano , Estados Unidos
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