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1.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38960064

RESUMEN

OBJECTIVE: To assess the association between varicocele and hypogonadism, or erectile dysfunction. METHODS: We searched MEDLINE, EMBASE, LILACS, CENTRAL, and other sources. We included cohort, case-control, and cross-sectional studies. The primary outcome was the association between varicocele and hypogonadism, or erectile dysfunction, and the secondary outcome included semen analysis. We assessed the risk of bias with the Newcastle-Ottawa Scale. We performed statistical analysis in Review Manager 5.3 and reported information about the Odds Ratio (OR) with a 95% confidence interval. We produced a forest plot for the primary outcome. RESULTS: We included ten studies in qualitative analysis and six studies in quantitative analysis. Most of the cross-sectional studies showed a low risk of bias, not so for the two case-control studies, which represented a high risk of bias. Most of the reports described a correlation between having varicocele and presenting low testosterone levels: the meta-analysis showed that there is a significant association between varicocele and hypogonadism (OR 3.27 95% CI 1.23 to 8.68). Regarding varicocele and erectile, only one study showed a significant difference in erectile function in comparison to varicocele patients and men without varicocele. CONCLUSION: There is an association between varicocele presence and hypogonadism, although more studies are needed. Besides, not much is reported about an association between varicocele and erectile dysfunction, but impairment can occur through hormone disturbances.

2.
Kidney Int ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38797326

RESUMEN

Acute kidney injury (AKI) is a common and devastating complication of hospitalization. Here, we identified genetic loci associated with AKI in patients hospitalized between 2002-2019 in the Million Veteran Program and data from Vanderbilt University Medical Center's BioVU. AKI was defined as meeting a modified KDIGO Stage1 or more for two or more consecutive days or kidney replacement therapy. Control individuals were required to have one or more qualifying hospitalizations without AKI and no evidence of AKI during any other observed hospitalizations. Genome-wide association studies (GWAS), stratified by race, adjusting for sex, age, baseline estimated glomerular filtration rate (eGFR), and the top ten principal components of ancestry were conducted. Results were meta-analyzed using fixed effects models. In total, there were 54,488 patients with AKI and 138,051 non-AKI individuals included in the study. Two novel loci reached genome-wide significance in the meta-analysis: rs11642015 near the FTO locus on chromosome 16 (obesity traits) (odds ratio 1.07 (95% confidence interval, 1.05-1.09)) and rs4859682 near the SHROOM3 locus on chromosome 4 (glomerular filtration barrier integrity) (odds ratio 0.95 (95% confidence interval, 0.93-0.96)). These loci colocalized with previous studies of kidney function, and genetic correlation indicated significant shared genetic architecture between AKI and eGFR. Notably, the association at the FTO locus was attenuated after adjustment for BMI and diabetes, suggesting that this association may be partially driven by obesity. Both FTO and the SHROOM3 loci showed nominal evidence of replication from diagnostic-code-based summary statistics from UK Biobank, FinnGen, and Biobank Japan. Thus, our large GWA meta-analysis found two loci significantly associated with AKI suggesting genetics may explain some risk for AKI.

3.
Biomolecules ; 12(12)2022 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-36551269

RESUMEN

Halogenation of bioactive peptides via incorporation of non-natural amino acid derivatives during chemical synthesis is a common strategy to enhance functionality. Bacterial tyrptophan halogenases efficiently catalyze regiospecific halogenation of the free amino acid tryptophan, both in vitro and in vivo. Expansion of their substrate scope to peptides and proteins would facilitate highly-regulated post-synthesis/expression halogenation. Here, we demonstrate novel in vitro halogenation (chlorination and bromination) of peptides by select halogenase enzymes and identify the C-terminal (G/S)GW motif as a preferred substrate. In a first proof-of-principle experiment, we also demonstrate chemo-catalyzed derivatization of an enzymatically chlorinated peptide, albeit with low efficiency. We further rationally derive PyrH halogenase mutants showing improved halogenation of the (G/S)GW motif, both as a free peptide and when genetically fused to model proteins with efficiencies up to 90%.


Asunto(s)
Halogenación , Oxidorreductasas , Oxidorreductasas/metabolismo , Proteínas Bacterianas/metabolismo , Péptidos/metabolismo , Aminoácidos/metabolismo
4.
Osteoporos Int ; 33(3): 725-735, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34643755

RESUMEN

Decreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS. INTRODUCTION: As part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls. METHODS: 396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). RESULTS: Cohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1-3 (724.99 ± 32.09 mg/mm3 (p < 0.001), 0.79 ± 0.11 mm (p < 0.001) and 1910.88 ± 374.75 N/mm2 (p < 0.001), respectively) and (b) those at TOCI-8 (732.28 ± 53.75 mg/mm3 (p < 0.001), 0.84 ± 0.14 mm (p < 0.001), 1889.11 ± 419.37 N/mm2 (p < 0.001), respectively). Cohort-B included 217 girls (12.22 ± 0.89 years old). Subjects at TOCI-4 had higher levels of C-terminal telopeptide of type 1 collagen (1524.70 ± 271.10 pg/L) and procollagen type 1 N-terminal propeptide (941.12 ± 161.39 µg/L) than those at TOCI-8 (845.71 ± 478.55 pg/L (p < 0.001) and 370.08 ± 197.04 µg/L (p < 0.001), respectively). CONCLUSION: AIS girls had decreased cortical bone density and bone mechanical strength with elevated BTMs at PHV. Coupling of PHV with decreased cortical and FEA parameters could provide the link to the previously reported observation that low BMD could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.


Asunto(s)
Escoliosis , Adolescente , Densidad Ósea , Remodelación Ósea , Niño , Hueso Cortical , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Escoliosis/diagnóstico por imagen
5.
Front Bioeng Biotechnol ; 10: 1032707, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36588932

RESUMEN

Biocatalytic C-H halogenation is becoming increasingly attractive due to excellent catalyst-controlled selectivity and environmentally benign reaction conditions. Significant efforts have been made on enzymatic halogenation of industrial arenes in a cost-effective manner. Here we report an unprecedented enzymatic halogenation of a panel of industrially important indole, azaindole and anthranilamide derivatives using a thermostable RebH variant without addition of any external flavin reductase enzyme. The reactions were catalyzed by the RebH variant 3-LSR enzyme with the help of a co-purified E. coli reductase identified as alkyl hydroperoxide reductase F (AhpF).

6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 7148-7151, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34892749

RESUMEN

GABA (Gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the central nervous system of mammals. It is known to be related with various neurological disorders. GABA plays a crucial role in normal neuronal activity, information processing and plasticity, and neuronal network synchronization. To date, microdialysis has been widely used to monitor the level of GABA but the temporal and spatial resolution is limited. Besides, electrochemical sensors for neurotransmitter measurement, having high temporal and spatial resolution, overcome this problem. Here, using a cost-effective method of electrodeposition of platinum black (Pt-black), a highly sensitive, GABA specific, amperometric electrochemical sensor is fabricated. Nanostructured Pt-black increases the active surface area of the electrode contributing to higher sensitivity. Along with that, a self-referencing site and an exclusion layer are integrated to increase the selectivity and the signal-to-noise ratio (SNR) of the biosensor. This provides a prototype for a highly sensitive GABA sensor that could later be used to study various neurological disorders related to GABA concentrations.Clinical Relevance- This electrochemical sensor allows real-time monitoring of major inhibitory neurotransmitter (GABA) with high sensitivity which can be used for studying various neurological disorders.


Asunto(s)
Técnicas Biosensibles , Platino (Metal) , Animales , Técnicas Electroquímicas , Electrodos , Ácido gamma-Aminobutírico
7.
J Clin Med ; 10(21)2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34768447

RESUMEN

Previous studies have reported abnormal muscle morphology and functions in patients with adolescent idiopathic scoliosis (AIS). To answer whether such abnormalities could be reflected in their circulation and their clinical implication for predicting curve progression to the surgical threshold, this preliminary study explored the presence of baseline muscle-related proteins and their association with curve progression. Plasma samples were collected at the first clinical visit for AIS, with patients divided into non-progressive or progressive groups (N = four and four) according to their Cobb angle in six-year follow-ups, with age- and sex-matched healthy subjects (N = 50). Then, the samples were subjected to isobaric tags for relative and absolute quantitation (iTRAQ) for global comparison of untargeted protein expression. Seventy-one differentially expressed proteins (DEPs) were found elevated in progressive AIS. Functional analysis showed that 18 of these are expressed in muscles and play an essential role in muscle activities. Among the muscle-related DEPs, α-actin had the highest fold change in progressive/non-progressive groups. This preliminary study firstly suggested higher circulating levels of muscle structural proteins in progressive AIS, indicating the likelihood of structural damage at the microscopic level and its association with progression to the surgical threshold. Further studies with larger sample sizes are warranted to validate these novel candidates for early diagnosis and predicting progression.

8.
Chembiochem ; 22(18): 2791-2798, 2021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34240527

RESUMEN

Activating industrially important aromatic hydrocarbons by installing halogen atoms is extremely important in organic synthesis and often improves the pharmacological properties of drug molecules. To this end, tryptophan halogenase enzymes are potentially valuable tools for regioselective halogenation of arenes, including various industrially important indole derivatives and similar scaffolds. Although endogenous enzymes show reasonable substrate scope towards indole compounds, their efficacy can often be improved by engineering. Using a structure-guided semi-rational mutagenesis approach, we have developed two RebH variants with expanded biocatalytic repertoires that can efficiently halogenate several novel indole substrates and produce important pharmaceutical intermediates. Interestingly, the engineered enzymes are completely inactive towards their natural substrate tryptophan in spite of their high tolerance to various functional groups in the indole ring. Computational modelling and molecular dynamics simulations provide mechanistic insights into the role of gatekeeper residues in the substrate binding site and the dramatic switch in substrate specificity when these are mutated.


Asunto(s)
Proteínas Bacterianas/metabolismo , Indoles/química , Oxidorreductasas/metabolismo , Triptófano/metabolismo , Actinobacteria/enzimología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Sitios de Unión , Biocatálisis , Halogenación , Indoles/metabolismo , Simulación de Dinámica Molecular , Mutagénesis Sitio-Dirigida , Oxidorreductasas/química , Oxidorreductasas/genética , Especificidad por Sustrato , Triptófano/química
9.
Osteoporos Int ; 32(7): 1287-1300, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33704541

RESUMEN

The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children. INTRODUCTION: This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results. METHODS: Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = - 3.51 nmol/L; 95% confidence interval (CI): - 5.60 to - 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of - 4.35 nmol/L (95% CI: - 6.64 to - 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%). CONCLUSION: This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.


Asunto(s)
Fracturas Óseas , Deficiencia de Vitamina D , Estudios de Casos y Controles , Niño , Estudios Transversales , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Humanos , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Vitaminas
10.
Sci Transl Med ; 13(579)2021 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-33536284

RESUMEN

Longitudinal, remote monitoring of motor symptoms in Parkinson's disease (PD) could enable more precise treatment decisions. We developed the Motor fluctuations Monitor for Parkinson's Disease (MM4PD), an ambulatory monitoring system that used smartwatch inertial sensors to continuously track fluctuations in resting tremor and dyskinesia. We designed and validated MM4PD in 343 participants with PD, including a longitudinal study of up to 6 months in a 225-subject cohort. MM4PD measurements correlated to clinical evaluations of tremor severity (ρ = 0.80) and mapped to expert ratings of dyskinesia presence (P < 0.001) during in-clinic tasks. MM4PD captured symptom changes in response to treatment that matched the clinician's expectations in 94% of evaluated subjects. In the remaining 6% of cases, symptom data from MM4PD identified opportunities to make improvements in pharmacologic strategy. These results demonstrate the promise of MM4PD as a tool to support patient-clinician communication, medication titration, and clinical trial design.


Asunto(s)
Enfermedad de Parkinson , Estudios de Cohortes , Humanos , Estudios Longitudinales , Monitoreo Ambulatorio , Temblor/diagnóstico
11.
Chem Commun (Camb) ; 56(77): 11493-11496, 2020 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-32857086

RESUMEN

A decarboxylative, desulfonylative Smiles rearrangement is presented that employs activated-ester/energy transfer catalysis to decarboxylate ß-amino acid derived starting materials at room-temperature under visible light irradiation. The radical Smiles rearrangement gives a range of biologically active arylethylamine products highly relevant to the pharmaceutical industry, chemical biology and materials science. The reaction is then applied to the synthesis of a chiral unnatural amino acid, 2-thienylalanine, used in the treatment of phenylketonuria. We also show how the reaction can proceed under metal-free and catalyst-free conditions.

12.
J Org Chem ; 84(19): 12686-12691, 2019 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-31496246

RESUMEN

A catalyst system comprising CoCl2/IAd·HBF4 enables the Suzuki-Miyaura cross-coupling reaction of a broad range of aryl triflates and arylboronic esters that are activated by n-butyllithium.

13.
J Child Orthop ; 13(4): 385-392, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31489044

RESUMEN

PURPOSE: The EOS-imaging system is increasingly adopted for clinical follow-up in scoliosis with the advantages of simultaneous biplanar imaging of the spine in an erect position. Skeletal maturity assessment using a hand radiograph is an essential adjunct to spinal radiography in scoliosis follow-up. This study aims at testing the feasibility and validity of a newly proposed EOS workflow with sequential spine-hand radiography for skeletal maturity assessment and bracing recommendation. METHODS: EOS spine-hand radiographs from patients with diagnosis of idiopathic scoliosis, including both sexes and an age range of ten to 14 years, were scored using the Thumb Ossification Composite Index (TOCI), Sanders and Risser methods. Intraclass correlation coefficients (ICCs) were calculated for inter/intraobserver agreement and were tested with Cronbach's alpha values. RESULTS: In all, 60 EOS-spine hand radiographs selected from subjects with diagnosis of adolescent idiopathic scoliosis (AIS), including 32 male patients (mean age 11.53 years; 10 to 14) and 28 female patients (mean age 11.50 years; 10 to 13) who underwent sequential spine-hand low dose EOS imaging were generated for analysis. The overall interobserver (ICC = 0.997) and intraobserver agreement (α > 0.9) demonstrated excellent agreement for TOCI staging; ICC > 0.994 for both TOCI and Sanders staging comparing traditional digital versus EOS hand radiography; ICC ≥ 0.841 for agreement on bracing recommendation among TOCI versus the Risser and Sanders system. CONCLUSION: With the proposed new EOS workflow it was feasible to produce high image quality for skeletal maturity assessment with excellent reliability and validity to inform consistent bracing recommendation in AIS. The workflow is applicable for busy daily clinic settings in tertiary scoliosis centres with reduced time cost, improved efficiency and throughput of the radiology department. LEVEL OF EVIDENCE: III.

14.
Rev Sci Instrum ; 90(5): 053103, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31153278

RESUMEN

We present the design, construction, and characterization of an experimental system capable of supporting a broad class of quantum simulation experiments with hundreds of spin qubits using 9Be+ ions in a Penning trap. This article provides a detailed overview of the core optical and trapping subsystems and their integration. We begin with a description of a dual-trap design separating loading and experimental zones and associated vacuum infrastructure design. The experimental-zone trap electrodes are designed for wide-angle optical access (e.g., for lasers used to engineer spin-motional coupling across large ion crystals) while simultaneously providing a harmonic trapping potential. We describe a near-zero-loss liquid-cryogen-based superconducting magnet, employed in both trapping and establishing a quantization field for ion spin-states and equipped with a dual-stage remote-motor LN2/LHe recondenser. Experimental measurements using a nuclear magnetic resonance (NMR) probe demonstrate part-per-million homogeneity over 7 mm-diameter cylindrical volume, with no discernible effect on the measured NMR linewidth from pulse-tube operation. Next, we describe a custom-engineered inbore optomechanical system which delivers ultraviolet (UV) laser light to the trap and supports multiple aligned optical objectives for topview and sideview imaging in the experimental trap region. We describe design choices including the use of nonmagnetic goniometers and translation stages for precision alignment. Furthermore, the optomechanical system integrates UV-compatible fiber optics which decouple the system's alignment from remote light sources. Using this system, we present site-resolved images of ion crystals and demonstrate the ability to realize both planar and three-dimensional ion arrays via control of rotating wall electrodes and radial laser beams. Looking to future work, we include interferometric vibration measurements demonstrating root-mean-square trap motion of ∼33 nm (∼117 nm) in the axial (transverse) direction; both values can be reduced when operating the magnet in free-running mode. The paper concludes with an outlook toward extensions of the experimental setup, areas for improvement, and future experimental studies.

15.
Osteoarthritis Cartilage ; 27(10): 1462-1469, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31176805

RESUMEN

OBJECTIVES: This study examined ninety-day and one-year postoperative healthcare utilization and costs following total knee arthroplasty (TKA) from the health sector and patient perspectives. DESIGN: This study relied on: 1) patient-reported medical resource utilization data from diaries in the Knee Arthroplasty Pain Coping Skills Training (KASTPain) trial; and 2) Medicare fee schedules. Medicare payments, patient cost-sharing, and patient time costs were estimated. Generalized linear mixed models were used to identify baseline predictors of costs. RESULTS: In the first ninety days following TKA, patients had an average of 29.7 outpatient visits and 6% were hospitalized. Mean total costs during this period summed to $3,720, the majority attributed to outpatient visit costs (84%). Over the year following TKA, patients had an average of 48.9 outpatient visits, including 33.2 for physical therapy. About a quarter (24%) of patients were hospitalized. Medical costs were incurred at a decreasing rate, from $2,428 in the first six weeks to $648 in the last six weeks. Mean total medical costs across all patients over the year were $8,930, including $5,328 in outpatient costs. Total costs were positively associated with baseline Charlson comorbidity score (P < 0.01). Outpatient costs were positively associated with baseline Charlson comorbidity score (P = 0.03) and a bodily pain burden summary score (P < 0.01). Mean patient cost-sharing summed to $1,342 and time costs summed to $1,346. CONCLUSIONS: Costs in the ninety days and year after TKA can be substantial for both healthcare payers and patients. These costs should be considered as payers continue to explore alternative payment models.


Asunto(s)
Cuidados Posteriores/economía , Artroplastia de Reemplazo de Rodilla/economía , Costos de la Atención en Salud , Aceptación de la Atención de Salud/estadística & datos numéricos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo
16.
Diabet Med ; 36(4): 482-490, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30378161

RESUMEN

AIM: To evaluate whether recent low adherence to metformin monotherapy is associated with hypoglycaemia after addition of a sulfonylurea. METHODS: We assembled a retrospective cohort of veterans who filled a new prescription for metformin between 2001 and 2011 and intensified treatment with a sulfonylurea after ≥1 year of metformin use. We calculated metformin adherence from pharmacy data using the proportion of days covered in the 180-day period before intensification. The primary outcome was hypoglycaemia, defined as a hospitalization or emergency department visit for hypoglycaemia or an outpatient blood glucose measurement <3.3 mmol/l in the year following intensification. Cox proportional hazards models were used to compare the risk of hypoglycaemia between participants with low (<80%) and high (≥80%) adherence. Adherence was also modelled as a continuous variable using restricted cubic splines. RESULTS: Of 187 267 participants who initiated metformin monotherapy, 49 424 added a sulfonylurea after ≥1 year. The median (interquartile range) rate of treatment adherence was 87 (50-100)% and 43% had adherence <80%. Hypoglycaemia rates per 1000 person-years were 23.1 (95% CI 21.1-25.4) and 24.5 (95% CI 22.7-26.4) in participants with low and high adherence, respectively (adjusted hazard ratio 0.95, 95% CI 0.84-1.08). The risk of hypoglycaemia was similar across all levels of adherence when adherence was modelled as a continuous variable. CONCLUSIONS: We found no evidence that past low adherence to metformin monotherapy was associated with hypoglycaemia after intensification with a sulfonylurea.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/administración & dosificación , Cumplimiento de la Medicación/estadística & datos numéricos , Metformina/uso terapéutico , Compuestos de Sulfonilurea/administración & dosificación , Anciano , Estudios de Cohortes , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Metformina/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Compuestos de Sulfonilurea/efectos adversos , Factores de Tiempo , Veteranos/estadística & datos numéricos
17.
Chemistry ; 25(8): 1927-1930, 2019 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-30536854

RESUMEN

A light-mediated Truce-Smiles arylative rearrangement is described that proceeds in the absence of any photocatalyst. The protocol creates two C-C bonds from simple starting materials, with the installation of an aryl ring and a difluoroacetate moiety across unactivated alkenes. The reaction proceeds via a radical mechanism, utilizing a light-mediated reduction of ethyl bromodifluoroacetate by N,N,N',N'-tetramethylethylenediamine (TMEDA) to set up intermolecular addition to an unactivated alkene, followed by Truce-Smiles rearrangement.

18.
Diabet Med ; 35(11): 1571-1579, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29978496

RESUMEN

AIM: To determine the association of adherence to oral antidiabetes medication with macrovascular and microvascular complications, time to insulin therapy, revascularization, admissions, and death among veterans with uncomplicated diabetes. METHODS: This was a retrospective cohort study using the Veterans Affairs Corporate Data Warehouse to examine 159 032 veterans diagnosed with uncomplicated diabetes during 2002-2014 and starting oral antidiabetes therapy for the first time. The first uncomplicated diabetes diagnosis was identified and confirmed by subsequent oral antidiabetes therapy initiation. Adherence was calculated from outpatient pharmacy records using the proportion of days covered over the first year of therapy. Health outcomes were observed up to 5 years beyond the first oral antidiabetes agent fill, and compared according to adherence status using Cox proportional hazards models adjusted for baseline demographic and clinical characteristics. RESULTS: During the first 5 years of oral antidiabetes treatment, people initially non-adherent to oral antidiabetes therapy were more likely to experience myocardial infarction (hazard ratio 1.14, 95% CI 1.03-1.27) and ischaemic stroke (hazard ratio 1.22, 95% CI 1.05-0.1.42), or to die (hazard ratio 1.21; 95% CI 1.15-1.28). Veterans with <20% adherence to oral antidiabetes therapy in the first year had particularly high hazards for ischaemic stroke (hazard ratio 1.78, 95% CI 1.27-2.49) and all-cause death (hazard ratio 1.33, 95% CI 1.17-151). Adherent people were more likely to be diagnosed with a microvascular complication or chronic kidney disease. CONCLUSIONS: People who are non-adherent to treatment were more likely to experience detrimental health outcomes within the first 5 years of antidiabetes therapy. Adherence is paramount to disease management and this should be stressed from the time at which treatment is initiated.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemiantes/administración & dosificación , Cumplimiento de la Medicación/estadística & datos numéricos , Veteranos/estadística & datos numéricos , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
19.
Chem Commun (Camb) ; 54(47): 6044-6047, 2018 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-29799033

RESUMEN

The structure-activity relationship of expanded-ring N-heterocyclic carbenes (NHCs) in the iron-catalysed Kumada aryl-aryl coupling reaction was explored. This was achieved by comparing the catalytic performance of Fe-NHC catalysts generated in situ containing NHCs that differ in steric bulk. In particular, the influences of ring sizes (5-8) and N-aryl substituents were explored in terms of spectroscopic and structural features, which affect their %Vbur values. The three best performing ligands were found on a diagonal of a 5 × 4 structural matrix revealing an optimal steric bulk and significant influences of subtle steric variations on the catalytic activities.

20.
Prog Urol ; 28(3): 146-155, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29331568

RESUMEN

BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results. METHOD: A retrospective international multicenter study was conducted in the frame of the French kidney cancer research network (UroCCR). We considered all patients aged≥18 years who underwent surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm) between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS). Comparison between PN and RN was realized after an adjustment by propensity score considering predefined confounding factors: age, sex, tumor size, pT stage of the TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of 267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and 88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2% after PN and 91.0% and 85.0% after RN. No significant difference between groups was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05, P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50-2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a stage kidney tumors. The risk of recurrence is probably more related to prognostic factors than the surgical technique. The decision to perform a PN should depend on technical feasibility rather than tumor size, both to imperative and elective situation. LEVEL OF EVIDENCE: 4.


Asunto(s)
Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Nefrectomía/métodos , Anciano , Investigación Biomédica , Carcinoma de Células Renales/patología , Femenino , Francia , Humanos , Cooperación Internacional , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
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