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1.
Plant Physiol ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240724

RESUMO

In many eukaryotic algae, CO2 fixation by Rubisco is enhanced by a CO2-concentrating mechanism, which utilizes a Rubisco-rich organelle called the pyrenoid. The pyrenoid is traversed by a network of thylakoid membranes called pyrenoid tubules, which are proposed to deliver CO2. In the model alga Chlamydomonas (Chlamydomonas reinhardtii), the pyrenoid tubules have been proposed to be tethered to the Rubisco matrix by a bestrophin-like transmembrane protein, BST4. Here, we show that BST4 forms a complex that localizes to the pyrenoid tubules. A Chlamydomonas mutant impaired in the accumulation of BST4 (bst4) formed normal pyrenoid tubules, and heterologous expression of BST4 in Arabidopsis (Arabidopsis thaliana) did not lead to the incorporation of thylakoids into a reconstituted Rubisco condensate. Chlamydomonas bst4 mutants did not show impaired growth under continuous light at air level CO2 but were impaired in their growth under fluctuating light. By quantifying the non-photochemical quenching (NPQ) of chlorophyll fluorescence, we propose that bst4 has a transiently lower thylakoid lumenal pH during dark-to-light transition compared to control strains. We conclude that BST4 is not a tethering protein but is most likely a pyrenoid tubule ion channel involved in the ion homeostasis of the lumen with particular importance during light fluctuations.

2.
Cardiovasc Diabetol ; 22(1): 1, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609317

RESUMO

BACKGROUND: Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin. METHODS: A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models. RESULTS: The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74-0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80-0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74-0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68-0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60-0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings. CONCLUSIONS: This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.


Assuntos
Fibrilação Atrial , Diabetes Mellitus , Insuficiência Cardíaca , Acidente Vascular Cerebral , Idoso , Humanos , Anticoagulantes , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Varfarina , Estudos de Coortes , Estudos Retrospectivos , Administração Oral , Rivaroxabana , Diabetes Mellitus/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Acidente Vascular Cerebral/epidemiologia
3.
Osteoporos Int ; 34(9): 1625-1636, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37249610

RESUMO

Previous studies have suggested that bisphosphonates may reduce stroke risk. This meta-analysis, which included 21 studies with 741,274 participants, revealed that bisphosphonates might be associated with lower stroke risk. However, evidence derived from randomized controlled trials identified no statistically significant association. Future high-quality studies are still required to determine causality. PURPOSE: Whether bisphosphonates may reduce the risk of stroke remains inconclusive. We conducted a systematic review and meta-analysis to evaluate the association between bisphosphonate use and the risk of stroke based on up-to-date evidence. METHODS: We searched for studies evaluating the effects of bisphosphonate on the risk of stroke from inception until January 3, 2022, on PubMed, Embase, Scopus, and Cochrane libraries and updated our search until August 22, 2022, using PubMed to identify any new potential published studies. Two or more reviewers independently screened articles, extracted data, and assessed the study quality. We retrieved the data to synthesize the pooled relative risk (RR) of stroke associated with bisphosphonate use compared with controls; random-effects models were used for meta-analysis. RESULTS: A total of 21 studies (7 randomized controlled trials [RCTs] and 14 observational studies) involving 741,274 participants were included in our meta-analysis. Overall, bisphosphonate use was associated with a lower risk of stroke, but the result was only borderline significant (pooled RR = 0.87, 95% confidence interval [CI]: 0.76-0.99, p = 0.048), and high between-study heterogeneity was found (I2 = 83.7%). Subgroup analyses showed that the evidence derived from RCTs suggested no significant association between bisphosphonate use and stroke risk (pooled RR = 0.93, 95% CI: 0.76-1.13, p = 0.462; I2 = 13.4%). CONCLUSION: Our results suggest that bisphosphonate use is associated with a lower risk of stroke. However, the current evidence does not lead to a definite conclusion due to the borderline statistical significance and high between-study heterogeneity. Future studies, especially RCTs, are necessary to assess causality.


Assuntos
Conservadores da Densidade Óssea , Acidente Vascular Cerebral , Humanos , Difosfonatos/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como Assunto
4.
Endocr Pract ; 29(7): 525-528, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37121401

RESUMO

OBJECTIVE: While surgical resection has been the traditional standard treatment for small (≤1 cm), differentiated thyroid cancers, active surveillance (AS) and radiofrequency ablation (RFA) are increasingly considered. The aim of this study was to explore patient preferences in thyroid cancer treatment using a series of clinical vignettes. METHODS: Thyroid cancer survivors and general population volunteers were recruited to rank experience-driven clinical vignettes in order of preference. Rankings were compared using Wilcoxon signed rank. Formative qualitative methods were used to develop and refine clinical vignettes that captured 4 treatments-thyroid lobectomy (TL), total thyroidectomy (TT), AS, and RFA-along with 6 treatment complications. Content was validated via interviews with 5 academic subspecialists. RESULTS: Nineteen volunteers participated (10 survivors, 9 general population). Treatment complications were ranked lower than uncomplicated counterparts in 99.0% of cases, indicating excellent comprehension. Counter to our hypothesis, among uncomplicated vignettes, median rankings were 1 for AS, 2 for RFA, 3.5 for TL, and 5 for TT. Trends were consistent between thyroid cancer survivors and the general population. AS was significantly preferred over RFA (P = .02) and TT (P < .01). Among surgical options, TL was significantly preferred over TT (P < .01). CONCLUSION: When treatments for low-risk thyroid cancer are described clearly and accurately through clinical vignettes, patients may be more likely to choose less invasive treatment options over traditional surgical resection.


Assuntos
Ablação por Radiofrequência , Neoplasias da Glândula Tireoide , Humanos , Projetos Piloto , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Estudos Retrospectivos
5.
Ann Intern Med ; 175(4): 490-498, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35157495

RESUMO

BACKGROUND: Evidence about the association between types of oral anticoagulants and hazards of diabetes complications is limited in patients with atrial fibrillation (AF) and diabetes mellitus (DM). OBJECTIVE: To compare the hazards of diabetes complications and mortality between patients with AF and DM receiving non-vitamin K antagonist oral anticoagulants (NOACs) and those receiving warfarin. DESIGN: A retrospective cohort study. SETTING: Nationwide data obtained from Taiwan's National Health Insurance Research Database. PATIENTS: Patients with AF and DM receiving NOACs or warfarin between 2012 and 2017 in Taiwan were enrolled. Treatment groups were determined by patients' first initiation of oral anticoagulants. MEASUREMENTS: Hazards of diabetes complications (macrovascular complications, microvascular complications, and glycemic emergency) and mortality in the NOAC and warfarin users were investigated with a target trial design. Cause-specific Cox proportional hazards models were used to estimate hazard ratios (HRs). Propensity score methods with stabilized inverse probability of treatment weighting were applied to balance potential confounders between treatment groups. RESULTS: In total, 19 909 NOAC users and 10 300 warfarin users were included. Patients receiving NOACs had significantly lower hazards of developing macrovascular complications (HR, 0.84 [95% CI, 0.78 to 0.91]; P < 0.001), microvascular complications (HR, 0.79 [CI, 0.73 to 0.85]; P < 0.001), glycemic emergency (HR, 0.91 [CI, 0.83 to 0.99]; P = 0.043), and mortality (HR, 0.78 [CI, 0.75 to 0.82]; P < 0.001) than those receiving warfarin. Analyses with propensity score matching showed similar results. Several sensitivity analyses further supported the robustness of our findings. LIMITATION: The claims-based data did not allow for detailed data on patients' lifestyles and laboratory examinations to be obtained. CONCLUSION: Non-vitamin K antagonist oral anticoagulants were associated with lower hazards of diabetes complications and mortality than warfarin in patients with AF and DM. PRIMARY FUNDING SOURCE: Hualien Tzu Chi Hospital.


Assuntos
Anticoagulantes , Fibrilação Atrial , Complicações do Diabetes , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/mortalidade , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Varfarina/administração & dosagem , Varfarina/efeitos adversos
6.
Pain Pract ; 23(8): 914-921, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37395169

RESUMO

AIMS: Transcutaneous magnetic stimulation (TCMS) is successful in decreasing pain in several neurologic conditions. This multicenter parallel double-blind phase II clinical trial is a follow-up to a pilot study that demonstrated pain relief in patients with diabetic peripheral neuropathy (DPN) treated with TCMS. METHODS: Thirty-four participants with confirmed DPN and baseline pain score ≥ 5 were randomized to treatment at two sites. Participants were treated with either TCMS (n = 18) or sham (n = 16) applied to each foot once a week for four weeks. Pain scores using the Numeric Pain Rating Scale after 10 steps on a hard floor surface and answers to Patient-Reported Outcomes Measurement Information System pain questions were recorded by participants daily for 28 days. RESULTS: Thirty-one participants completed the study and were analyzed. Average pain scores decreased from baseline in both the groups. The difference in pain scores between TCMS and sham treatments was -0.55 for morning, -0.13 for evening, and -0.34 overall, below the pre-determined clinically relevant difference of -2. Moderate adverse events that resolved spontaneously were experienced in both treatment arms. CONCLUSION: In this two-arm trial, TCMS failed to demonstrate a significant benefit over sham in patient reported pain suggesting a substantial placebo effect in our previous pilot study. TRIAL REGISTRATION: TCMS for the Treatment of Foot Pain Caused By Diabetic Neuropathy, https://clinicaltrials.gov/ct2/show/NCT03596203, ID-NCT03596203.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Neuropatias Diabéticas/tratamento farmacológico , Projetos Piloto , Dor/tratamento farmacológico , Manejo da Dor , Fenômenos Magnéticos , Método Duplo-Cego , Resultado do Tratamento
7.
Expert Opin Emerg Drugs ; 27(4): 417-430, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36472144

RESUMO

INTRODUCTION: Diabetic nephropathy remains a significant economic and social burden on both the individual patient and health-care systems as the prevalence of diabetes increases in the general population. The complex pathophysiology of diabetic kidney disease poses a challenge in the development of effective medical treatments for the disease. However, the multiple facets of diabetic nephropathy also offer a variety of potential strategies to manage this condition. AREAS COVERED: We retrieved PubMed, Cochrane Library, Scopus, Google Scholar, and ClinicalTrials.gov records to identify studies and articles focused on new pharmacologic advances to treat diabetic nephropathy. EXPERT OPINION: RAAS blockers have remained the mainstay of therapy for DM nephropathy for many years, with only recent advancements with SGLT2 inhibitors and nonsteroidal MRAs. Better understanding of the long-term renal effects of ambient hyperglycemia, ranging from hemodynamic changes to increased production of oxidative and pro-inflammatory substances, has evolved our approach to the treatment of diabetic nephropathy. With continuing research for new therapeutics as well as combination therapy, the medical community may be able to better ease the burden of diabetic kidney disease.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/tratamento farmacológico
8.
J Surg Res ; 275: 273-280, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35306263

RESUMO

INTRODUCTION: The American Thyroid Association (ATA) updated consensus guidelines in 2015 for radioactive iodine (RAI) and resection for low-risk papillary thyroid cancer. The objective of this study was to describe the evolution of institutional practice patterns and estimate the cost implications of these trends. MATERIALS AND METHODS: Patients with cT1-T2N0 papillary thyroid cancer were identified via an institutional tumor registry. Incidences of total thyroidectomy or RAI were tracked longitudinally using cumulative sum. Real-world costs for RAI and each surgical encounter were adjusted for inflation and standardized to national average costs from National Inpatient Sample cost data. RESULTS: Sixty-one patients met inclusion criteria between 2007 and 2018. Among these, 28 patients underwent total thyroidectomies and received RAI treatments based on criteria pre-dating the 2015 ATA guidelines. Cumulative sum revealed significant decreases in the rate of total thyroidectomy following May 2015 (15.8% versus 59.5%, P = 0.002) and RAI following March 2013 (3.0% versus 32.1%, P = 0.002). There were no locoregional recurrences in either period. The average cost savings attributable to these institutional practice changes was $1580 per patient. CONCLUSIONS: De-escalation in surgical and RAI utilization for low-risk papillary thyroid cancer according to 2015 ATA guidelines is associated with a substantial decrease in real-world costs.


Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/cirurgia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
9.
Nano Lett ; 21(1): 51-59, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356325

RESUMO

Plasmonic metasurfaces are promising as enablers of nanoscale nonlinear optics and flat nonlinear optical components. Nonlinear optical responses of such metasurfaces are determined by the nonlinear optical properties of individual plasmonic meta-atoms. Unfortunately, no simple methods exist to determine the nonlinear optical properties (hyperpolarizabilities) of the meta-atoms hindering the design of nonlinear metasurfaces. Here, we develop the equivalent RLC circuit (resistor, inductor, capacitor) model of such meta-atoms to estimate their second-order nonlinear optical properties, that is, the first-order hyperpolarizability in the optical spectral range. In parallel, we extract from second-harmonic generation experiments the first-order hyperpolarizabilities of individual meta-atoms consisting of asymmetrically shaped (elongated) plasmonic nanoprisms, verified with detailed calculations using both nonlinear hydrodynamic-FDTD and nonlinear scattering theory. All three approaches, analytical, experimental, and computational, yield results that agree very well. Our empirical RLC model can thus be used as a simple tool to enable an efficient design of nonlinear plasmonic metasurfaces.

10.
Clin Endocrinol (Oxf) ; 94(2): 322-329, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32735709

RESUMO

OBJECTIVE: For the biochemical follow-up of benign thyroid nodules, some authors recommend periodic lifelong measurement of thyroid-stimulating hormone (TSH) to assess for the development of toxic nodules over time. The purpose of this retrospective study was to assess the incidence of thyroid dysfunction over time in patients with benign thyroid nodule(s), with a normal TSH at diagnosis and to identify any factors that may predict biochemical dysfunction over time. METHODS: Medical records of patients with the diagnosis of thyroid nodule(s) between January 2011 and August 2014 were reviewed. Patients who had TSH measurement within 1 year of initial diagnostic ultrasound (US) were included. RESULTS: One-hundred fifty-seven patients identified with thyroid nodule(s) satisfied inclusion criteria. At a median follow-up of 45 (34-63) months, 13 (8.3%) patients developed thyroid dysfunction. The mean initial TSH in the group which developed subclinical hyperthyroidism (0.65 mIU/mL) was statistically different from the group that did not develop thyroid dysfunction (1.37 mIU/mL, P: 0.007). More patients with TSH <1 mIU/L developed thyroid dysfunction as compared to subjects with TSH ≥1 mIU/L (P: .022). There was no significant difference in the incidence of thyroid dysfunction on the basis of gender, race, smoking status, TPO Ab positivity and number of nodules at diagnosis. CONCLUSIONS: We recommend re-examining the current practice and clinical utility of frequent TSH monitoring in all patients with thyroid nodules, particularly if initial TSH level is ≥1 mIU/L.


Assuntos
Hipotireoidismo , Nódulo da Glândula Tireoide , Seguimentos , Humanos , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Tireotropina
11.
Diabetes Obes Metab ; 23(2): 499-507, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33140538

RESUMO

AIM: To compare the risk of diabetes development in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. MATERIALS AND METHODS: We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Adult patients with new onset of AF, treated with NOACs or warfarin between 2012 and 2016, were included. The NOAC cohort was further divided into dabigatran, rivaroxaban and apixaban groups. The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. Fine and Gray subdistribution hazards models were used to estimate the adjusted hazard ratio (aHR). Propensity score matching was performed for each head-to-head comparison. RESULTS: A total of 10 746 new-onset AF patients were included in our study. During the mean 2.4-year follow-up, NOACs were associated with a lower risk of developing diabetes than warfarin (aHR = 0.80, 95% confidence interval [CI]: 0.68-0.94, P = .007). Subgroup analyses confirmed that dabigatran, rivaroxaban and apixaban each had a reduced diabetes risk. Stratified analyses showed that the lower risk of diabetes associated with NOAC treatment was specific to patients aged 65 years or older (aHR = 0.74, 95% CI: 0.62-0.89, P = .002) and those with good medication adherence (aHR = 0.70, 95% CI: 0.58-0.84, P < .001). CONCLUSIONS: Taking an NOAC was associated with a lower risk of developing diabetes than taking warfarin in patients with AF.


Assuntos
Fibrilação Atrial , Diabetes Mellitus , Acidente Vascular Cerebral , Administração Oral , Adulto , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Humanos , Piridonas/efeitos adversos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Varfarina/efeitos adversos
12.
Nature ; 517(7533): 181-6, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-25567284

RESUMO

Olefin metathesis catalysts provide access to molecules that are indispensable to physicians and researchers in the life sciences. A persisting problem, however, is the dearth of chemical transformations that directly generate acyclic Z allylic alcohols, including products that contain a hindered neighbouring substituent or reactive functional units such as a phenol, an aldehyde, or a carboxylic acid. Here we present an electronically modified ruthenium-disulfide catalyst that is effective in generating such high-value compounds by cross-metathesis. The ruthenium complex is prepared from a commercially available precursor and an easily generated air-stable zinc catechothiolate. Transformations typically proceed with 5.0 mole per cent of the complex and an inexpensive reaction partner in 4-8 hours under ambient conditions; products are obtained in up to 80 per cent yield and 98:2 Z:E diastereoselectivity. The use of this catalyst is demonstrated in the synthesis of the naturally occurring anti-tumour agent neopeltolide and in a single-step stereoselective gram-scale conversion of a renewable feedstock (oleic acid) to an anti-fungal agent. In this conversion, the new catalyst promotes cross-metathesis more efficiently than the commonly used dichloro-ruthenium complexes, indicating that its utility may extend beyond Z-selective processes.

13.
J Environ Manage ; 256: 109924, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31818740

RESUMO

Sustainability in power generation mainly depends on the transition from fossils to sustainable energy resources. Biomass from the crop residue has huge potential for renewable power generation, but it is still not utilized to its full potential. This study presents a comprehensive methodology to evaluate and forecast the current and future availability of selective crop residue to generate renewable energy. A forecast model incorporating historical trends in the crop yield has been developed in MATLAB and implemented for crop residue based biomass resource assessment of five primary crops (wheat straw, rice husk, rice straw, cotton straw, corn stover, and bagasse) in order to estimate the energy generation potential for Pakistan from 2018 till 2035. It was found that about 40 million tonnes of crop residue was available in Pakistan for power generation in the year 2018 considering a residue removal (availability) factor of 50%. This translates to an estimated potential of about 11,000 MW of electricity generation capacity using crop residue derived biomass for 2018. This capacity is predicted to gradually increase up to 16,000 MW by the year 2035 based on the trends in the growth of crop production since 2001. The suitability of a potential region for the installation of 100 MW biomass-fired power plants was also assessed by calculating crop residue density and an equivalent collection radius (Re) of 50 km (km). Punjab province of Pakistan, being an agricultural province, with relatively better road infrastructure can sustain crop residue based power plants of up to 7000 MW cumulative capacity at various locations. The challenges, such as economic, logistics, regulatory and political barriers, in generating renewable energy from biomass along with their potential solutions were also discussed. The study also provides a baseline for future research to evaluate and forecast the growth in bio-power generation potential of any biomass resource in a region based on crop yield and area of the region.


Assuntos
Produtos Agrícolas , Energia Renovável , Agricultura , Biomassa , Paquistão
14.
Opt Lett ; 44(24): 5981-5984, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32628198

RESUMO

We propose a strategy to improve sensing performance of sub-wavelength-grating (SWG) waveguide-based sensors by introducing a substrate-overetch (SOE) geometry. The proposed SOE-SWG waveguide shows enhanced analyte interaction and a reduced group index, which improves the sensitivity of resonator-based sensors. The SiO2 overetch process was realized in Ar/C4F8/O2 plasma for 40 sec with a SiO2/Si selectivity of 10:1, obtaining a 285-nm anisotropic overetch in the SiO2 layer. Sensor performance of the SOE-SWG architecture is characterized by using isopropyl alcohol solutions, indicating an enhanced bulk sensitivity up to 575 nm/RIU (479 nm/RIU before the SOE), and a maximum waveguide mode sensitivity larger than one.

16.
Chemistry ; 24(57): 15215-15218, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30102444

RESUMO

This report discloses the first example of catalytic arylhydroxylation of dehydroalanine with aryldiazonium salts. Aryldiazonium salts, which are generated from aniline precursors under partially aqueous conditions in continuous flow, efficiently reacted with dehydroalanine in the presence of 10-15 mol % ferrocene to furnish α-hydroxyarylalanine derivatives (up to 82 % yield). The reactions proceeded with regioselectivity, broad functional group tolerance, and without polymerization of the dehydroalanine. Furthermore, the products were used to access α-unnatural amino acids, important targets with application in drug development.


Assuntos
Alanina/análogos & derivados , Aminoácidos/química , Compostos Azo/química , Alanina/síntese química , Alanina/química , Aminoácidos/síntese química , Compostos Azo/síntese química , Catálise , Desenho de Fármacos , Hidroxilação , Oxirredução , Estereoisomerismo
17.
Endocr Pract ; 24(6): 517-526, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29624099

RESUMO

OBJECTIVE: Understanding of acromegaly disease management is hampered in the U.S. by the lack of a national registry. We describe medical management in a population with confirmed acromegaly. METHODS: Inpatient and outpatient electronic health records (EHRs) were used to create a database of de-identified patients assigned the Acromegaly and Gigantism International Classification of Diseases, 9th revision (ICD-9) code and/or an appropriate pituitary procedure code at 1 of 4 regional hospital systems over a 6- to 11-year period. Information regarding demographics, medical history, labs, procedures, and medications was collected and supplemented with a chart review to validate the diagnosis of acromegaly. RESULTS: Of 367 patients with validated acromegaly, available records showed that during the years studied, pituitary surgery was performed on 31%, 4% received radiosurgery, and 22% were prescribed a drug indicated for acromegaly. Insulin-like growth factor-1 (IGF-1) levels were measured in 62% of patients, 83% of whom had at least 1 normal value. Coded comorbidities reflect those reported previously in patients with acromegaly, with the exception of esophageal reflux in 20% of patient records. Fewer data regarding acromegaly-specific medications and testing were available for patients aged 65 and older. CONCLUSION: AcroMEDIC is a U.S. multisite retrospective study of acromegaly that captured medical management in the majority of patients included in the cohort. Chart review highlighted the importance of verification of coded diagnoses. Most of the acromegaly-related comorbidities identified here are known to increase with age and obesity. Patients ≥65 appeared to have less active management/monitoring of their disease. Medical attention should be directed to this population to address evolving needs over time. ABBREVIATIONS: AcroMEDIC = Acromegaly Multisite Electronic Data Innovative Consortium; BMI = body mass index; CCI = Charlson Comorbidity Index; EHR = electronic health record; GH = growth hormone; GHRA = growth hormone receptor antagonist; ICD-9 = International Classification of Diseases, 9th revision; IGF-1 = insulin-like growth factor-1; SSA = somatostatin analogue.


Assuntos
Acromegalia/terapia , Registros Eletrônicos de Saúde , Doenças Raras/terapia , Acromegalia/sangue , Acromegalia/diagnóstico , Adulto , Fatores Etários , Idoso , Comorbidade , Feminino , Seguimentos , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Doenças Raras/diagnóstico
18.
Am J Emerg Med ; 36(6): 1124.e1-1124.e2, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29534916

RESUMO

Metoclopramide (MCP) is a commonly used anti-emetic in the emergency department (ED). Its use is generally well tolerated; although infrequent adverse reactions such as extrapyramidal reactions or tardive dyskinesia are reported. However, many ED providers are not familiar with the potentially life-threatening hypertensive emergency that can be precipitated by MCP administration in patients with pheochromocytoma. A previously healthy 36-year-old woman presented to the ED with headache and nausea. She developed acute hypertensive emergency (acute agitation, worsening headache, chest pain and wide complex tachycardia) when her blood pressure (BP) increased to 223/102mmHg (initial BP, 134/86mmHg) after receiving intravenous MCP. Her hospital course was complicated by multi-organ injury, including acute respiratory distress syndrome requiring venous-venous extracorporeal membrane oxygenation, non-ST elevation myocardial infarction, cardiogenic shock, acute liver failure, and oliguric kidney injury requiring continuous renal replacement therapy. CT scan showed previously undiagnosed large right adrenal mass (5.9cm). The diagnosis of pheochromocytoma was confirmed after adrenalectomy. Drug-induced acute pheochromocytoma crisis is a rare event. Early recognition and appropriate blood pressure management with clevidipine, nicardipine, or phentolamine is essential.


Assuntos
Neoplasias das Glândulas Suprarrenais/induzido quimicamente , Antieméticos/efeitos adversos , Serviços Médicos de Emergência , Hipertensão/induzido quimicamente , Metoclopramida/efeitos adversos , Feocromocitoma/induzido quimicamente , Choque Cardiogênico/induzido quimicamente , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Adulto , Antieméticos/administração & dosagem , Feminino , Cefaleia , Humanos , Hipertensão/fisiopatologia , Metoclopramida/administração & dosagem , Náusea/tratamento farmacológico , Feocromocitoma/fisiopatologia , Feocromocitoma/cirurgia , Choque Cardiogênico/fisiopatologia , Resultado do Tratamento
19.
Appl Opt ; 56(19): 5532-5541, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29047512

RESUMO

We propose several designs of nonlinear optical waveguides based on quaternary III-V semiconductors AlGaAsSb and InGaAsP. These semiconductor materials have been widely used for laser sources. Their nonlinear optical properties, however, yet remain unexplored, while the materials definitely hold promise for nonlinear photonics on-a-chip. The latter argument is based on the fact that III-V compounds tend to exhibit high values of the nonlinear optical susceptibilities, while the nonlinear absorption in these materials can be minimized in the wavelength range of interest through a proper selection of the material composition. We present the modal analysis for the designed waveguide structures and show that the effective mode area much less than 1 µm2 can be achieved through a design optimization in each of the two compounds. We also present specific waveguide designs that demonstrate zero dispersion at the wavelengths of interest. The designed AlGaAsSb and InGaAsP waveguides are thus expected to demonstrate high values of the nonlinear coefficient and efficient nonlinear optical interactions.

20.
Opt Lett ; 41(7): 1431-4, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27192254

RESUMO

We experimentally demonstrate that the spectral sensitivity of a Mach-Zehnder (MZ) interferometer can be enhanced through structural slow light. We observe a 20-fold resolution enhancement by placing a dispersion-engineered, slow-light, photonic-crystal waveguide in one arm of a fiber-based MZ interferometer. The spectral sensitivity of the interferometer increases roughly linearly with the group index, and we have quantified the resolution in terms of the spectral density of interference fringes. These results show promise for the use of slow-light methods for developing novel tools for optical metrology and, specifically, for compact high-resolution spectrometers.

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