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1.
Org Biomol Chem ; 22(8): 1721-1726, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38318984

RESUMO

Catalyst-free hydroamination and hydrothiolation of alkenes have been achieved in an aqueous medium. The anti-Markovnikov addition works efficiently in suspended water at room temperature and allows straightforward access to centhaquine, a drug used for the management of hypovolemic shocks in critically ill patients, and its derivatives. Various primary and secondary amines, thiols, and hydrazides were successfully reacted with a number of heteroaryl/aryl-alkenes. The scalability of the process has been demonstrated by synthesizing centhaquine at a 19.65 g scale. A comparative analysis of the present process with previous approaches has been provided on the basis of green chemistry metrics.

2.
J Am Acad Orthop Surg ; 31(24): 1211-1220, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37883429

RESUMO

The Surgical Management of Osteoarthritis of the Knee Evidence-Based Clinical Practice Guideline is based on a systematic review of published studies for surgical management of osteoarthritis of the knee in skeletally mature patients. This guideline contains 16 recommendations and seven options to assist orthopaedic surgeons and all qualified physicians with the surgical management of patients with osteoarthritis of the knee based on the best current available evidence. It is also intended to serve as an information resource for professional healthcare practitioners and developers of practice guidelines and recommendations. In addition to providing pragmatic practice recommendations, this guideline also highlights gaps in the literature and informs areas for future research and quality measure development.


Assuntos
Cirurgiões Ortopédicos , Osteoartrite do Joelho , Guias de Prática Clínica como Assunto , Humanos , Prática Clínica Baseada em Evidências , Articulação do Joelho , Osteoartrite do Joelho/cirurgia , Estados Unidos
3.
Org Lett ; 25(36): 6638-6642, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37672675

RESUMO

A palladium(II)-catalyzed regio- and stereoselective difunctionalization of alkynoic acids has been achieved using sodium sulfinates and isocyanides to synthesize (E)-ß-sulfonylacrylamides. The reaction proceeds via decarboxylative isocyanide addition, followed by sulfonylation. This three-component process works well with aromatic, heteroaromatic, and aliphatic alkynoic acids with good functional group tolerance and excellent regio- and stereoselectivity. DFT calculations were carried out to explain the reaction mechanism and the stereoselective formation of (E)-ß-sulfonylacrylamides.

4.
J Org Chem ; 88(19): 13568-13583, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37738300

RESUMO

A robust synthesis of phenanthridines has been described via Pd(II)-catalyzed domino C(sp2)-H activation/N-arylation using oxime esters with aryl acyl peroxides in a highly regioselective manner. This protocol is compatible with acetophenone as well as benzophenone-derived oxime esters and allows modular construction of functionalized phenanthridines with wide tolerance of electronic functionality. Further transformations were conducted to synthesize key building blocks, and control experiments were performed to understand the plausible reaction mechanism.

5.
Nanoscale ; 15(37): 15179-15195, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37548288

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) infection is becoming a severe health hazard and needs early diagnosis with high specificity. However, the non-specific binding of a biosensor is a challenge to the current bacterial detection system. For the first time, we chemically synthesized a galactose tripod (GT) as a P. aeruginosa-specific ligand. We conjugated GT to a photothermally active fluorescent nanocomposite (Au@SiO2-TCPP). P. aeruginosa can be detected using Au@SiO2-TCPP-GT, and additionally ablated as well using synergistic photothermal and photodynamic therapy. Molecular dynamics and simulation studies suggested better binding of GT (binding energy = -6.6 kcal mol-1) with P. aeruginosa lectin than that of galactose monopod (GM) (binding energy = -5.9 kcal mol-1). Furthermore, a binding study was extended to target P. aeruginosa, which has a galactose-binding carbohydrate recognition domain receptor. The colorimetric assay confirmed a limit of detection (LOD) of 104 CFU mL-1. We also looked into the photosensitizing property of Au@SiO2-TCPP-GT, which is stimulated by laser light (630 nm) and causes photoablation of bacteria by the formation of singlet oxygen in the surrounding media. The cytocompatibility of Au@SiO2-TCPP-GT was confirmed using cytotoxicity assays on mammalian cell lines. Moreover, Au@SiO2-TCPP-GT also showed non-hemolytic activity. Considering the toxicity analysis and efficacy of the synthesized glycan nanocomposites, these can be utilized for the treatment of P. aeruginosa-infected wounds. Furthermore, the current glycan nanocomposites can be used for bacterial detection and ablation of P. aeruginosa in contaminated food and water samples as well.

6.
Iowa Orthop J ; 43(1): 123-129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37383845

RESUMO

Background: Knee injuries induce swelling and resolution of swelling may be a useful factor in identifying states of healing and time to return to sports activities. Recent work has suggested that bioimpedance can provide an objective measure of swelling following total knee arthroplasty (TKA) and therefore may also provide guidance for clinical decision-making following knee injury. This study measures knee bioimpedance in young, active people to help define baseline variability and factors that influence limb to limb differences. Methods: Bioimpedance was measured via sensors placed at the foot/ankle and thigh, in positions similar to those suggested for monitoring post-TKA swelling. Initial tests were performed to verify method repeatability, then bioimpedance was measured in a convenience sample of 78 subjects (median age 21yrs). The influence of age, BMI, thigh circumference, and knee function (KOOS-JR) on the impedance measures and difference in impedance between the subject's knees were examined using a generalized multivariable linear regression. Results: The repeatability study measurements were highly consistent with a COV of 1.5% for resistance and an ICC of 97.9%. Women exhibited significantly larger dominant limb impedance and larger limb to limb difference in impedance than men. Regression analysis indicated that subject sex and BMI significantly influenced bioimpedance but joint score and age did not. The limb to limb differences in impedance were small on average (<5%), with larger magnitudes of difference associated with female sex, lower knee function scores, and larger limb to limb differences in thigh circumference. Conclusion: Bioimpedance measurements across right and left knees of healthy young people were similar, supporting use of bioimpedance measures from a patient's uninjured knee as a benchmark to monitor healing of a contralateral injured knee. Future work should focus on understanding how knee function scores and bioimpedance are related, and further explore how sex and side to side anatomic differences impact the measurement. Level of Evidence: IV.


Assuntos
Artroplastia do Joelho , Traumatismos do Joelho , Masculino , Feminino , Adulto Jovem , Humanos , Adolescente , Adulto , Extremidade Inferior , Articulação do Joelho/cirurgia , Coxa da Perna , Traumatismos do Joelho/diagnóstico , Traumatismos do Joelho/cirurgia
7.
J Biomed Opt ; 28(6): 065003, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37325190

RESUMO

Significance: We present a fiberless, portable, and modular continuous wave-functional near-infrared spectroscopy system, Spotlight, consisting of multiple palm-sized modules-each containing high-density light-emitting diode and silicon photomultiplier detector arrays embedded in a flexible membrane that facilitates optode coupling to scalp curvature. Aim: Spotlight's goal is to be a more portable, accessible, and powerful functional near-infrared spectroscopy (fNIRS) device for neuroscience and brain-computer interface (BCI) applications. We hope that the Spotlight designs we share here can spur more advances in fNIRS technology and better enable future non-invasive neuroscience and BCI research. Approach: We report sensor characteristics in system validation on phantoms and motor cortical hemodynamic responses in a human finger-tapping experiment, where subjects wore custom 3D-printed caps with two sensor modules. Results: The task conditions can be decoded offline with a median accuracy of 69.6%, reaching 94.7% for the best subject, and at a comparable accuracy in real time for a subset of subjects. We quantified how well the custom caps fitted to each subject and observed that better fit leads to more observed task-dependent hemodynamic response and better decoding accuracy. Conclusions: The advances presented here should serve to make fNIRS more accessible for BCI applications.


Assuntos
Hemodinâmica , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Hemodinâmica/fisiologia , Mãos
8.
J Arthroplasty ; 38(12): 2556-2560.e2, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37286060

RESUMO

BACKGROUND: Current research indicates that total joint arthroplasty patients who are discharged to skilled nursing facilities (SNFs) have higher complication rates as compared to home. Many factors like age, sex, race, Medicare status, and past medical history have been shown to influence discharge destination. The present study sought to gather patient-indicated reasons for SNF discharge and identify potentially modifiable factors influencing the decision. METHODS: Primary total joint arthroplasty patients were asked to complete surveys at their presurgical and 2-week postsurgical follow-up appointments. The surveys included home access and social support questions as well as patient-reported outcome measures: Patient-Reported Outcomes Measurement and Information System, Risk Assessment and Prediction Tool, Knee injury and Osteoarthritis Outcome Score for Joint Replacement, or Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement. RESULTS: Of 765 patients who met inclusion criteria, 3.9% were discharged to an SNF and these were more frequently post-THA, women, older, Black, and persons living alone. Regression analyses indicated that lower Risk Assessment and Prediction Tool score, higher age, no caregiver presence, and Black race were significantly associated with SNF discharge. Patients discharged to an SNF most commonly reported social concerns rather than medical or home access concerns as the main factor for SNF discharge. CONCLUSIONS: While age and sex are nonmodifiable factors, the availability of a caregiver and social support represents an important modifiable factor in regard to discharge destination. Dedicated attention during the preoperative planning period may help augment social support and avoid unnecessary discharges to SNFs.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Osteoartrite , Humanos , Feminino , Idoso , Estados Unidos , Artroplastia do Joelho/efeitos adversos , Instituições de Cuidados Especializados de Enfermagem , Artroplastia de Quadril/efeitos adversos , Medicare , Alta do Paciente
9.
J Arthroplasty ; 38(7S): S247-S251, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37084923

RESUMO

BACKGROUND: Recently, a state-wide registry identified fracture as a major cause of total hip arthroplasty revision. There were 52.8% of revisions occurring within 6 months (fracture leading cause). Registry sites have a 'surgeon champion' who acts as liaison and advocate. This study evaluated the effect of surgeon volume and role of 'surgeon champion' on fracture rates. METHODS: There were 95,948 cases from 2012 to 2019 queried with peri-implant femoral fractures identified (within 6 months). Funnel plots were generated to compare individual surgeon-specific fracture rates. Surgeons who had a fracture rate below the confidence interval were labeled 'green' (lower than mean), within were 'yellow' (no difference), and above were 'red' (significantly higher). RESULTS: For all surgeons, 19.6% were red, 72.1% yellow, and 8.3% green. There were 17.2% 'surgeon champions' and 6.2% 'nonchampions' that were green (P = .01), while 20.7 and 19.3% were red (P = .82). There was a significant association between volume and performance (P < .01). No surgeons in the lower two quartiles (<84; 84 to 180 cases), while 4 and 29% of higher-volume surgeons (181 to 404; >404 cases) were green. There was no statistical difference in red status by volume (P = .53). CONCLUSION: 'Surgeon champions' and high-volume surgeons were more likely to be high performers but not less likely to be low performers. Active involvement in quality improvement and/or high volume was associated with better outcomes but did not impart complication immunity. 'Green' surgeons should mentor colleagues to help reduce fractures by re-evaluating modifiable factors. Analyzing outcomes to promote quality and decrease complications is paramount.


Assuntos
Artroplastia de Quadril , Fraturas do Fêmur , Fraturas Periprotéticas , Humanos , Melhoria de Qualidade , Fraturas Periprotéticas/epidemiologia , Fraturas Periprotéticas/etiologia , Fraturas Periprotéticas/cirurgia , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/cirurgia , Fêmur/cirurgia , Artroplastia de Quadril/efeitos adversos , Sistema de Registros , Reoperação
10.
Molecules ; 28(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36838654

RESUMO

Complexes of curcumin with metals have shown much-improved stability, solubility, antioxidant capability, and efficacy when compared to curcumin. The present research investigates the relative bioavailability, antioxidant, and ability to inhibit inflammatory cytokine production of a curcuminoid metal chelation complex of tetrahydrocurcumin-zinc-curcuminoid termed TurmiZn. In vitro uptake assay using pig intestinal epithelial cells showed that TurmiZn has an ~3-fold increase (p ≤ 0.01) in uptake compared to curcumin and a ~2-fold increase (p ≤ 0.01) over tetrahydrocurcumin (THC). In a chicken model, an oral 1-g dose of TurmiZn showed a ~2.5-fold increase of a specific metabolite peak compared to curcumin (p = 0.004) and a ~3-fold increase compared to THC (p = 0.001). Oral doses (5 g/Kg) of TurmiZn in rats also showed the presence of curcumin and THC metabolites in plasma, indicating bioavailability across cell membranes in animals. Determination of the antioxidant activity by a 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging assay indicated that TurmiZn was about 13x better (p ≤ 0.0001) than curcumin and about 4X better (p ≤ 0.0001) than THC, in reducing free radicals. In vitro experiments further showed significant (p ≤ 0.01) reductions of lipopolysaccharide (LPS)-induced proinflammatory cytokines such as interleukin (IL) IL-6, IL-8, IL-15, IL-18, and tumor necrosis factor (TNF)-alpha, while showing a significant (p ≤ 0.01) increase of granulocyte-macrophage colony-stimulating factor (GM-CSF) in dog kidney cells. In vivo cytokine modulations were also observed when TurmiZn was fed for 6 weeks to newborn chickens. TurmiZn reduced IL-1 and IL-6, but significantly reduced (p ≤ 0.01) IL-10 levels while there was a concurrent significant (p = 0.02) increase in interferon gamma compared to controls. Overall, these results indicate that TurmiZn has better bioavailability and antioxidant capability than curcumin or THC and has the ability to significantly modulate cytokine levels. Thus, TurmiZn could be an excellent candidate for a novel ingredient that can be incorporated into food and supplements to help overall health during the aging process.


Assuntos
Curcumina , Citocinas , Animais , Ratos , Suínos , Cães , Antioxidantes/farmacologia , Curcumina/farmacologia , Interleucina-6 , Diarileptanoides , Disponibilidade Biológica , Zinco , Galinhas , Fator de Necrose Tumoral alfa
11.
Int J Cardiovasc Imaging ; 39(1): 201-208, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36598681

RESUMO

Transthyretin (ATTR) amyloidosis is a debilitating systemic disease often associated with symptomatic cardiac involvement. Diagnosis has dramatically changed with the advent of Technetium-99 m pyrophosphate (Tc-PYP) single-photon emission computed tomography (SPECT). With the ability to diagnose ATTR amyloidosis noninvasively and offer newer therapies, it is increasingly important to identify which patients should be referred for this testing. Relative apical sparing of longitudinal strain on echocardiogram can be potentially used to screen such patients. We sought to describe electrocardiogram (ECG) and echocardiogram (TTE) findings, including relative apical sparing of longitudinal strain, in ATTR amyloidosis patients diagnosed non-invasively with 99mTc-PYP imaging. This was a single-center, retrospective study with 64 patients who underwent 99mTc-PYP imaging between June 2016 and February 2019. Relative apical longitudinal strain was calculated from left ventricular longitudinal strain (LV LS) values. No ECG parameters were meaningfully associated with of 99 m Tc-PYP positive patients. LV mass index (p = 0.001), IVSd (p < 0.001), and LVPWd (< 0.001) demonstrated a highly significant difference between positive and negative 99mTc-PYP groups. 99mTc-PYP positive patients had a higher relative apical sparing of LV LS (p < 0.001), and notably, no 99mTc-PYP negative patient had a ratio > 1.0. The finding of relative apical sparing of longitudinal strain can reliably guide clinicians in triaging which patients to consider ordering 99mTc-PYP imaging for the noninvasive diagnosis of wild type cardiac amyloidosis. A patient with clinically suggestive features and an LV LS relative apical sparing ratio > 0.8 can be considered for 99mTc-PYP imaging to evaluate for ATTR cardiac amyloidosis.


Assuntos
Amiloidose , Cardiomiopatias , Humanos , Difosfatos , Tecnécio , Pirofosfato de Tecnécio Tc 99m , Estudos Retrospectivos , Cardiomiopatias/diagnóstico por imagem , Valor Preditivo dos Testes , Amiloidose/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Compostos Radiofarmacêuticos
12.
N Engl J Med ; 388(5): 395-405, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36342143

RESUMO

BACKGROUND: Aldosterone synthase controls the synthesis of aldosterone and has been a pharmacologic target for the treatment of hypertension for several decades. Selective inhibition of aldosterone synthase is essential but difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. In preclinical and phase 1 studies, baxdrostat had 100:1 selectivity for enzyme inhibition, and baxdrostat at several dose levels reduced plasma aldosterone levels but not cortisol levels. METHODS: In this multicenter, placebo-controlled trial, we randomly assigned patients who had treatment-resistant hypertension, with blood pressure of 130/80 mm Hg or higher, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo. The primary end point was the change in systolic blood pressure from baseline to week 12 in each baxdrostat group as compared with the placebo group. RESULTS: A total of 248 patients completed the trial. Dose-dependent changes in systolic blood pressure of -20.3 mm Hg, -17.5 mm Hg, -12.1 mm Hg, and -9.4 mm Hg were observed in the 2-mg, 1-mg, 0.5-mg, and placebo groups, respectively. The difference in the change in systolic blood pressure between the 2-mg group and the placebo group was -11.0 mm Hg (95% confidence interval [CI], -16.4 to -5.5; P<0.001), and the difference in this change between the 1-mg group and the placebo group was -8.1 mm Hg (95% CI, -13.5 to -2.8; P = 0.003). No deaths occurred during the trial, no serious adverse events were attributed by the investigators to baxdrostat, and there were no instances of adrenocortical insufficiency. Baxdrostat-related increases in the potassium level to 6.0 mmol per liter or greater occurred in 2 patients, but these increases did not recur after withdrawal and reinitiation of the drug. CONCLUSIONS: Patients with treatment-resistant hypertension who received baxdrostat had dose-related reductions in blood pressure. (Funded by CinCor Pharma; BrigHTN ClinicalTrials.gov number, NCT04519658.).


Assuntos
Anti-Hipertensivos , Citocromo P-450 CYP11B2 , Hipertensão , Humanos , Aldosterona/sangue , Aldosterona/metabolismo , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Citocromo P-450 CYP11B2/antagonistas & inibidores , Método Duplo-Cego , Hipertensão/tratamento farmacológico , Hipertensão/etiologia
13.
PLoS One ; 17(12): e0279831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584203

RESUMO

Tillage and crop residue management play an imperative role in soil physico-chemical properties that eventually affects crop productivity. The objective of the study to find out a compatible combination of tillage and crop residue management for achieving sustainable food production by improving soil properties, providing favorable environment to crop plants. Secondly, managing crop residues effectively to reduce environmental pollution arising due to crop residue burning. With this aim, a field experiment was conducted on six years continued running experiment under conservation agricultural practices during rabi season of 2019-20 on chickpea. The experiment was comprised of five tillage operations with or without crop residue in main plot and three levels of nutrients in sub plots laid out in split plot design with three replications. Reduced Tillage with 60cm residue height (RT60) was recorded higher growth and yield attributes over conventional tillage practice that attributed to economic yield enhancement. The percent yield increment under NT and RT with 30 and 60cm height residue retention varied from 6.91% to 9.67% over conventional tillage. Maximum grain (2380 kg ha-1) and biological output (5762 kg ha-1) was recorded under RT60 (T4), which ascribed to higher net return (Rs 60551 ha-1) and benefit-cost ratio (2.97). The augmentation in net monetary benefit among tillage systems was lies between 24.32% to 37.78% over conventional tillage. The seed protein content ranged between 20.38 to 21.69% among the treatments. Moreover, total N uptake was maximum under RT60, while total P and K uptake was higher in No Tillage with 30cm residue height (T1). No-Tillage with 60cm residue height (NT60) recorded relatively higher soil moisture content (SMC) (22.71 and 15.40%). Treatment NT30 accrued relatively higher value of soil bulk density (1.42 Mg m-3) followed by NT60 and RT60 in comparison to conventional tillage (1.34 Mg m-3). In conclusion, NT and RT with 60cm residue height along with STCR (N3) nutrient dose was found effective for sustainable food production.


Assuntos
Cicer , Agricultura , Solo/química , Índia , Nutrientes
14.
Am J Cardiol ; 185: 46-52, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36280472

RESUMO

Advanced heart failure (HF) therapies improve survival in patients with stage D HF. We sought to evaluate differences by race/ethnicity and sex in advanced HF therapy referrals and decision-making across a multicenter survey. We performed a retrospective analysis of patients referred for evaluation for advanced HF therapies at 9 centers (n = 515) across the United States. The median age was 58 years, and 73% were male. White patients comprised 55.7% of referrals, whereas non-White patients comprised 44.3%. Non-ischemic etiology was more common in non-White patients (66.6% vs 47.4% p = 0.0005), and ischemic etiology was more common in men (37.8% vs 20.4% p = 0.0005). The primary reason for referral differed by race/ethnicity but not sex, with ventricular arrhythmias (7.6% vs 3%, p = 0.024) and pulmonary hypertension (3.4% vs 0.4% p = 0.018) being more common in White patients, whereas worsening HF was less common (25.4% vs 35.9%; p = 0.009). White patients were offered left ventricular assist devices (LVADs) (60.3% vs 54.7 p = 0.039) and heart transplants (51.8% vs 33.1% p = 0.0007) more often than non-White patients. The preference not to pursue LVAD therapy was more common in non-White patients (17.6% vs 9.6%; p = 0.049). Men were more often declined for a heart transplant because of psychosocial contraindications (34% vs 15%, p = 0.005). In conclusion, in this multicenter analysis of referrals for advanced HF therapies, we observed significant differences by race, ethnicity, and sex in both referral characteristics and evaluation outcomes. Further investigation is warranted to better understand why rates of LVAD and transplantation may be lower in non-White patients who are referred for advanced therapies.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Humanos , Masculino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Etnicidade , Coração Auxiliar/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Encaminhamento e Consulta
15.
Org Lett ; 24(41): 7632-7636, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36222482

RESUMO

Stereoselective difunctionalizations of the terminal and internal alkynes with various sulfinates and isocyanides have been achieved to prepare (Z)-/(E)-ß-sulfonylacrylamides. The (Z)-ß-sulfonylacrylamides were generated via a one-pot process that involves the reaction of terminal alkynes with sulfinates and isocyanides in the presence of iodine in sequential manner. The (E)-ß-sulfonylacrylamides were prepared in a two-step synthesis via palladium(II)-catalyzed addition of isocyanide to (E)-ß-iodovinylsulfones synthesized from alkynes.


Assuntos
Alcinos , Iodo , Paládio , Cianetos , Catálise
16.
Am J Cardiol ; 184: 90-95, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36163050

RESUMO

The objective of this study was to assess ambulatory hemodynamics after transcatheter edge-to-edge repair (TEER) of the mitral valve. Pulmonary artery pressure (PAP) measurements from implanted sensors were collected through a remote monitoring database and linked to Medicare fee-for-service claims data. Among patients with linked data, those undergoing TEER were included if the ambulatory PAP monitor was implanted ≥3 months before TEER and ≥3 months of PAP data after TEER were available. The primary end point was diastolic PAP (dPAP) at 3 months after TEER compared with baseline. A total of 50 patients undergoing TEER between July 2014 and March 2020 were included, with an average age of 75 ± 8 years and 70% were men. dPAP was significantly lower at 3 months after TEER than baseline, -1.8 ± 4.8 mm Hg, p = 0.010. The cumulative reduction in dPAP (area under the curve) was significantly lower at 3 months after TEER, 113 ± 267 mm Hg-days, p = 0.004. A reduction in dPAP at 3 months after TEER was independently associated with a significantly lower risk of heart failure hospitalization (p = 0.023). TEER of the mitral valve is associated with a clinically relevant and sustained reduction in dPAP.


Assuntos
Insuficiência Cardíaca , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Idoso , Masculino , Humanos , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Feminino , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/complicações , Valva Mitral/cirurgia , Artéria Pulmonar , Medicare , Insuficiência Cardíaca/complicações , Resultado do Tratamento , Cateterismo Cardíaco
17.
J Org Chem ; 87(19): 12799-12815, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36149815

RESUMO

A convenient synthesis of less explored pyrrolo[1,2-a]pyrazine-3,6(2H,4H)-diones is described in two steps from Ugi adducts. The method involves acid-mediated cyclization of Ugi adducts to form dihydropyrazinones followed by gold(I)-catalyzed regioselective annulation. The generality of the transformation was established by reacting a variety of substituted dihydropyrazinones under the optimized reaction conditions to form densely functionalized pyrrolo[1,2-a]pyrazine-3,6(2H,4H)-diones in good-to-excellent yields. It was also observed some of the acetone-derived Ugi adducts furnish 7-acyl-pyrroloimidazolones as a byproduct during TFA-mediated cyclization via alkyne-carbonyl metathesis and condensation.


Assuntos
Ouro , Pirazinas , Acetona , Alcinos , Catálise , Ciclização
18.
J Dev Biol ; 10(3)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36135369

RESUMO

Reliable animal model systems are an integral part of biological research. Ever since Thomas Hunt Morgan won a Nobel Prize for genetic work done using the fruit fly (Drosophila melanogaster) as a model organism, it has played a larger and more important role in genetic research. Drosophila models have long been used to study neurodegenerative diseases and have aided in identifying key disease progression biological pathways. Due to the availability of a vast array of genetic manipulation tools, its relatively short lifespan, and its ability to produce many progenies, D. melanogaster has provided the ability to conduct large-scale genetic screens to elucidate possible genetic and molecular interactions in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's Disease, and Amyotrophic Lateral Sclerosis (ALS). With regards to ALS, many of the gene mutations that have been discovered to be linked to the disease have been modeled in Drosophila to provide a look into a detailed model of pathogenesis. The aim of this review is to summarize key and newer developments in ALS research that have utilized Drosophila and to provide insight into the profound use of Drosophila as a tool for modeling this disease.

19.
RSC Med Chem ; 13(6): 746-760, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35814931

RESUMO

A series of uniquely functionalized 2,3,-dihydro-1H-pyyrolo[3,4-b]quinolin-1-one derivatives were synthesized in one to two steps by utilizing a post-Ugi modification strategy and were evaluated for antileishmanial efficacy against visceral leishmaniasis (VL). Among the library compounds, compound 5m exhibited potential in vitro antileishmanial activity (CC50 = 65.11 µM, SI = 7.79, anti-amastigote IC50 = 8.36 µM). In vivo antileishmanial evaluation of 5m demonstrated 56.2% inhibition in liver and 61.1% inhibition in spleen parasite burden in infected Balb/c mice (12.5 mg kg-1, i.p.). In vitro pharmacokinetic study ascertained the stability of 5m in both simulated gastric fluid and simulated intestinal fluid. All the active compounds passed the PAINS filter and showed no toxicity in in silico predictions.

20.
J Org Chem ; 87(11): 7350-7364, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35587158

RESUMO

Pyrazolo[1,5-a]quinoxalin-4(5H)-one derivatives as novel opioid receptor modulators have been synthesized via copper-catalyzed oxidative [3 + 2]-annulation of quinoxalin-2(1H)-one and oxime-O-acetates. This hydrazine-free C-C and N-N bond formation strategy starts with the generation of C2N1 synthon using oxime acetate, which reacts in a [3 + 2] manner with quinoxalin-2(1H)-one, followed by oxidative aromatization. The synthesized compounds were tested against opioid receptors, of which eight compounds exhibited an antagonistic effect with EC50 < 5 µM at various opioid receptors. Molecular docking studies were performed to identify the binding of active pyrazolo[1,5-a]quinoxalin-4(5H)-one ligands with hKOR protein. Docking results indicated that compounds 3d and 3g participate in hydrogen bonding with the hydroxyl group of T111 of the active site pocket residue.


Assuntos
Oximas , Quinoxalinas , Catálise , Cobre , Ésteres , Simulação de Acoplamento Molecular , Estresse Oxidativo , Oximas/farmacologia , Quinoxalinas/química , Quinoxalinas/farmacologia , Receptores Opioides
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