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1.
J Mol Cell Cardiol ; 176: 58-67, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36739943

RESUMO

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and a major indicator for heart transplant. Human genetic studies have identified over a thousand causal mutations for DCM in genes involved in a variety of cellular processes, including sarcomeric contraction. A substantial clinical challenge is determining the pathogenicity of novel variants in disease-associated genes. This challenge of connecting genotype and phenotype has frustrated attempts to develop effective, mechanism-based treatments for patients. Here, we identified a de novo mutation (T237S) in TPM1, the gene that encodes the thin filament protein tropomyosin, in a patient with DCM and conducted in vitro experiments to characterize the pathogenicity of this novel variant. We expressed recombinant mutant protein, reconstituted it into thin filaments, and examined the effects of the mutation on thin filament function. We show that the mutation reduces the calcium sensitivity of thin filament activation, as previously seen for known pathogenic mutations. Mechanistically, this shift is due to mutation-induced changes in tropomyosin positioning along the thin filament. We demonstrate that the thin filament activator omecamtiv mecarbil restores the calcium sensitivity of thin filaments regulated by the mutant tropomyosin, which lays the foundation for additional experiments to explore the therapeutic potential of this drug for patients harboring the T237S mutation. Taken together, our results suggest that the TPM1 T237S mutation is likely pathogenic and demonstrate how functional in vitro characterization of pathogenic protein variants in the lab might guide precision medicine in the clinic.


Assuntos
Cardiomiopatia Dilatada , Humanos , Cardiomiopatia Dilatada/patologia , Tropomiosina/genética , Tropomiosina/metabolismo , Cálcio/metabolismo , Citoesqueleto de Actina/metabolismo , Mutação/genética
2.
J Environ Manage ; 326(Pt B): 116740, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36413952

RESUMO

Rainwater retention and water content in green roofs are primarily influenced by structural configurations (i.e., soil layer, vegetation layer, and water storage layer) and climatic factors (i.e., rainfall and evapotranspiration (ET)). Based on the principle of water balance, this study proposes a conceptual model for simulating water flow in green roofs with water storage layers. Three green roof model experiments were conducted from August 1st, 2020 to July 31st, 2021 for calibrating and verifying the conceptual model. The proposed model was solved iteratively using a newly developed program in Visual Basic. The results showed that the conceptual model can capture the dynamic variations in the rainwater retention and water content of green roofs well. The average Nash-Sutcliffe efficiency coefficient is 0.65 and the average error is 6%. The annual rainwater retention capacity (RRC) of green roofs in the perennial rainy climate model was on average 28% higher than that in the seasonal rainy climate model. At the expense of water stress, high ET plants significantly increased the annual RRC of green roofs at a low level. As the water storage layer depth increased from zero to 150 mm, the annual RRC of green roofs increased by 41%, and the water stress decreased by 49%. Compared with an increase in water holding capacity and soil depth, the response of the annual RRC and water stress of green roofs for increasing water storage layer depth is much greater. As per climate of Southern China region, the water storage layer depth of 100 mm is found to obtain optimal rainwater retention and irrigation management in green roof with similar soil thickness (100 mm).


Assuntos
Conservação dos Recursos Naturais , Movimentos da Água , Humanos , Desidratação , Chuva , Solo/química
3.
Environ Monit Assess ; 195(1): 231, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36572829

RESUMO

The marine aquaculture industry has caused a suite of adverse environmental consequences, including offshore eutrophication. However, little is known about the extent to which aquaculture effluents affect nearby wetland ecosystems. We carried out a field experiment in a mangrove stand located between two effluent-receiving creeks to estimate the extent to which marine aquaculture affects the soil nutrient distribution and plant nutrient status of adjacent mangroves. Carbon (C), nitrogen (N), and phosphorus (P) contents and C isotopic signatures were determined seasonally in creeks, pore water, surface soils, and in the leaves of the dominant mangrove species Kandelia obovata. The creeks exhibited nutrient enrichment (2.44 mg N L-1 and 0.09 mg P L-1 on average). The soils had N (from 1.40 to 2.70 g kg-1) and P (from 0.58 to 2.76 g kg-1) much greater than those of pristine mangrove forests. Combined analyses of the N:P ratio, nutrient resorption efficiency, and proficiency indicated that soil P met plant demands, but plants in most plots showed N limitation, suggesting that soil nutrient accumulation did not fundamentally impact the plant nutrient status. Collectively, this case study shows that marine aquaculture farms can affect adjacent mangrove stands even though their effluents are not directly discharged into the mangrove stands, but mangrove forests may have substantial buffering capabilities for long-term nutrient loading.


Assuntos
Ecossistema , Solo , Monitoramento Ambiental , Áreas Alagadas , Aquicultura
4.
Cardiol Young ; 31(11): 1850-1852, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33879276

RESUMO

DiGeorge syndrome is a rare spectrum of disorder affecting structures derived from third and fourth pharyngeal pouches characterised by aplasia or hypoplasia of thymus and parathyroid glands, and conotruncal anomalies. Presentation includes infants with hypocalcemic seizures, CHD, or recurrent infection. This case report illustrates a unique combination of proximal interruption of right pulmonary artery and aberrant right subclavian artery in a 3-month-old infant who was subsequently diagnosed as DiGeorge syndrome. This constellation of vascular anomalies in an infant with DiGeorge syndrome has not been previously reported in the literature.


Assuntos
Anormalidades Múltiplas , Síndrome de DiGeorge , Cardiopatias Congênitas , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Humanos , Lactente , Artéria Pulmonar/diagnóstico por imagem , Artéria Subclávia/diagnóstico por imagem
5.
Water Sci Technol ; 84(8): 1839-1857, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34695014

RESUMO

Rainfall infiltration, rainwater retention, runoff and evapotranspiration (ET) are important components of the water balance in green roofs. These components are expected to be influenced by variations in the structural configurations (i.e., substrate layers) of green roofs. This study explores the influence of layered soil and green roof configurations on the rainwater retention capacity (RRC) of the roofs as compared to conventional improvements (i.e., soil conditioning and enhanced substrate depth). Ten different extensive green roof modules were designed by varying the substrate materials, substrate depths, storage/drainage layers and vegetation layers. For all modules, the RRCs ranged from 34 to 59%. The RRCs of layered soil were 1-4% higher than that for single-layer soil. The RRC increased by 13% in the presence of a water storage module. It can be concluded that highest RRC corresponds to a combination of high-permeability soil in the upper layer along with a relatively large water holding capacity in the deep layer. Water storage layer and layered soil could significantly delay the water stress in vegetation. The importance of wick irrigation, vegetation types, back-to-back rain events and the ET rate on the RRC were also discussed.


Assuntos
Conservação dos Recursos Naturais , Movimentos da Água , Chuva , Solo , Água
6.
Can J Physiol Pharmacol ; 96(11): 1184-1187, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30265814

RESUMO

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to prevent heart failure and reduce cardiovascular death in patients with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Whether or not SGLT2 inhibitors improve indices of cardiorespiratory fitness (CRF), an independent predictor of mortality in patients with CVD, remains unknown. We evaluated the effects of empagliflozin on indices of CRF in patients with T2DM. Twenty patients with T2DM received either empagliflozin 10 mg or usual care. Baseline and 3- to 6-month post-treatment measurements of CRF were evaluated using cardiopulmonary exercise testing on a cycle ergometer. Treatment with empagliflozin led to an increased peak oxygen consumption (VO2), reduction in VE/VCO2 slope, and improvement in heart rate recovery. Our results suggest that SGLT2 inhibitors may improve markers of CRF in patients with T2DM. This may help provide important clues into the mechanism of benefit of SGLT2 inhibitors in clinical trials and provide a translational framework for the ongoing large studies of SGLT2 inhibitors in the treatment of heart failure.


Assuntos
Compostos Benzidrílicos/farmacologia , Aptidão Cardiorrespiratória , Diabetes Mellitus Tipo 2/fisiopatologia , Glucosídeos/farmacologia , Insuficiência Cardíaca/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Idoso , Compostos Benzidrílicos/uso terapêutico , Biomarcadores , Teste de Esforço , Feminino , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
7.
Gastrointest Endosc ; 86(5): 881-889, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28366440

RESUMO

BACKGROUND AND AIMS: A structured comprehensive curriculum (SCC) that uses simulation-based training (SBT) can improve clinical colonoscopy performance. This curriculum may be enhanced through the application of progressive learning, a training strategy centered on incrementally challenging learners. We aimed to determine whether a progressive learning-based curriculum (PLC) would lead to superior clinical performance compared with an SCC. METHODS: This was a single-blinded randomized controlled trial conducted at a single academic center. Thirty-seven novice endoscopists were recruited and randomized to either a PLC (n = 18) or to an SCC (n = 19). The PLC comprised 6 hours of SBT, which progressed in complexity and difficulty. The SCC included 6 hours of SBT, with cases of random order of difficulty. Both groups received expert feedback and 4 hours of didactic teaching. Participants were assessed at baseline, immediately after training, and 4 to 6 weeks after training. The primary outcome was participants' performance during their first 2 clinical colonoscopies, as assessed by using the Joint Advisory Group Direct Observation of Procedural Skills assessment tool (JAG DOPS). Secondary outcomes were differences in endoscopic knowledge, technical and communication skills, and global performance in the simulated setting. RESULTS: The PLC group outperformed the SCC group during first and second clinical colonoscopies, measured by JAG DOPS (P < .001). Additionally, the PLC group had superior technical and communication skills and global performance in the simulated setting (P < .05). There were no differences between groups in endoscopic knowledge (P > .05). CONCLUSIONS: Our findings demonstrate the superiority of a PLC for endoscopic simulation, compared with an SCC. Challenging trainees progressively is a simple, theory-based approach to simulation whereby the performance of clinical colonoscopies can be improved. (Clinical trial registration number: NCT02000180.).


Assuntos
Competência Clínica , Colonoscopia/educação , Aprendizagem Baseada em Problemas/métodos , Treinamento por Simulação/métodos , Adulto , Educação de Pós-Graduação em Medicina , Feminino , Gastroenterologia/educação , Cirurgia Geral/educação , Humanos , Medicina Interna/educação , Masculino , Método Simples-Cego
8.
Mol Cell Biochem ; 433(1-2): 97-102, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28391552

RESUMO

The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin was recently reported to reduce heart failure-associated hospitalizations and cardiovascular mortality amongst individuals with type 2 diabetes at high cardiovascular risk. We sought to elucidate the underlying mechanism(s) for these protective effects using a validated zebrafish heart failure model to evaluate the impact of empagliflozin on the expression of biomarkers of heart failure and mortality. We used aristolochic acid (AA) to induce heart failure in developing cmlc2::GFP transgenic zebrafish embryos and monitored BNP signaling in nppb::Luc transgenic zebrafish with a luciferase reporter assay. Empagliflozin markedly reduced the morphological and functional cardiac changes induced by AA; dampened AA-enhanced expression of brain natriuretic peptide and atrial natriuretic peptide; and reduced embryonic mortality. Furthermore, morpholino-mediated knockdown of the slc5A2 gene mimicked the changes evoked by empagliflozin in developing zebrafish embryos previously exposed to AA. We report herein the first mechanistic data demonstrating a salutary benefit of SGLT2 inhibition on critical pathways of heart failure signaling. These findings provide important translational clues to the cardiovascular benefits documented in the EMPA-REG OUTCOME study.


Assuntos
Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Insuficiência Cardíaca , Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Ácidos Aristolóquicos/farmacologia , Ácidos Aristolóquicos/toxicidade , Biomarcadores/metabolismo , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Peixe-Zebra/genética
9.
Gastrointest Endosc ; 82(6): 1072-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26007221

RESUMO

BACKGROUND: GI endoscopy simulation-based training augments early clinical performance; however, the optimal manner by which to deliver training is unknown. OBJECTIVE: We aimed to validate a simulation-based structured comprehensive curriculum (SCC) designed to teach technical, cognitive, and integrative competencies in colonoscopy. DESIGN: Single-blinded, randomized, controlled trial. SETTING: Endoscopic simulation course at an academic hospital. PARTICIPANTS AND INTERVENTIONS: Thirty-three novice endoscopists were allocated to an SCC group or self-regulated learning (SRL) group. The SCC group received a curriculum consisting of 6 hours of didactic lectures and 8 hours of virtual reality simulation-based training with expert feedback. The SRL group was provided a list of desired objectives and was instructed to practice on the simulator for an equivalent time (8 hours). MAIN OUTCOME MEASUREMENTS: Clinical transfer was assessed during 2 patient colonoscopies using the Joint Advisory Group Direct Observation of Procedural Skills (JAG DOPS) scale. Secondary outcome measures included differences in procedural knowledge, immediate post-training simulation performance, and delayed post-training (4-6 weeks) performance during an integrated scenario test on the JAG DOPS communication and integrated scenario global rating scales. RESULTS: There was no significant difference in baseline or post-training performance on the simulator task. The SCC group performed superiorly during their first and second clinical colonoscopies. Additionally, the SCC group demonstrated significantly better knowledge and colonoscopy-specific performance, communication, and global performance during the integrated scenario. LIMITATIONS: We were unable to measure SRL participants' effort outside of mandatory training. In addition, feedback metrics and number of available simulation cases are limited. CONCLUSIONS: These results support integration of endoscopy simulation into a structured curriculum incorporating instructional feedback and complementary didactic knowledge as a means to augment technical, cognitive, and integrative skills acquisition, as compared with SRL on virtual reality simulators. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01991522.)


Assuntos
Competência Clínica , Colonoscopia/educação , Currículo , Treinamento por Simulação/métodos , Adulto , Feminino , Humanos , Masculino , Ontário , Estudos Prospectivos , Método Simples-Cego
10.
Catheter Cardiovasc Interv ; 84(6): 955-62, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24174334

RESUMO

OBJECTIVES: The objective of this study is to compare the long-term safety of new generation drug-eluting stents (DES) with early generation DES and bare metal stents (BMS) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Early generation DES for STEMI have reduced target vessel revascularization, but have more very late ST compared with BMS raising concerns about their safety. New compared with early generation DES have lower rates of ST, but there are limited data in STEMI patients. METHODS: From 2003 to 2011, 3,464 STEMI patients were treated with BMS (n = 1,187), early generation DES (n = 1,525), or new generation DES (n = 752) and were followed for 1-9 years. RESULTS: Patients with new generation DES were younger, had less cardiogenic shock, and less prior infarction versus BMS, and more hypertension versus early generation DES. At 2 years, new generation DES had lower mortality (4.0% vs. 12.4%, P < 0.001), similar reinfarction (4.4% vs. 5.1%, P = 0.35), and less ST (1.4% vs. 3.8%, P = 0.031) versus BMS; and similar mortality (4.0% vs. 5.8%, P = 0.23), similar reinfarction (4.4% vs. 5.2%, P = 0.64), and trends for less ST (1.4% vs. 3.3%, P = 0.17) versus early generation DES. By Cox multivariable analyses, BMS had more ST than new generation DES (HR [95% CI] = 1.93 [1.01-3.66], P = 0.045). CONCLUSIONS: New generation DES in STEMI patients have less ST compared to BMS and trends for less ST compared to early generation DES. These data suggest a new safety paradigm and should encourage the use of new generation DES in most STEMI patients treated with primary percutaneous coronary intervention (PCI).


Assuntos
Stents Farmacológicos , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/instrumentação , Idoso , Distribuição de Qui-Quadrado , Feminino , Hospitais com Alto Volume de Atendimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Minnesota , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , North Carolina , Segurança do Paciente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Modelos de Riscos Proporcionais , Desenho de Prótese , Recidiva , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
J Interv Cardiol ; 27(1): 21-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24372979

RESUMO

OBJECTIVES: This study compares very late outcomes following primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) with stenting versus balloon angioplasty (BA). BACKGROUND: Stenting compared with BA for STEMI improves outcomes at 6-12 months, but comparisons beyond 6-12 months have not been studied. Recent studies have shown that stent thrombosis (ST) continues to increase beyond 3-5 years and may be higher with drug-eluting stents (DES) than bare metal stents (BMS). We hypothesized that there may be a very late hazard with stenting versus BA due to very late ST. METHODS: From 1994 to 2010 consecutive patients with STEMI treated with BA (n = 601) or stenting (n = 1,594) were prospectively enrolled in our registry and followed for 1-16 years. RESULTS: Patients treated with BA were older, were more often female, had more three-vessel disease, and had smaller vessels. Stented patients had trends for less stent/lesion thrombosis (ST/LT) and target vessel (TV) reinfarction at 1 year. In landmark analyses >1 year, stented patients had more very late ST/LT (6.1% vs. 2.9%, P = 0.002) and more TV reinfarction (7.9% vs. 3.1%, P < 0.001) which remained significant after adjusting for baseline risk. The greatest differences in very late outcomes were between DES and BA, but there were also significant differences between BMS and BA. CONCLUSIONS: There appears to be a very late hazard with stenting versus BA for STEMI. These data should encourage new strategies for prevention of very late ST with both BMS and DES including the development of bio-absorbable polymers and stent platforms.


Assuntos
Angioplastia com Balão/efeitos adversos , Infarto do Miocárdio/terapia , Stents/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
13.
Indian Heart J ; 76 Suppl 1: S104-S107, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38599724

RESUMO

The leading cause of mortality worldwide is atherosclerotic cardiovascular disease. Atherosclerotic plaques are well known to originate early in the childhood. Identifying hyperlipidemia in early childhood creates an opportunity to prevent major cardiovascular events in adults. Children with identified risk factors are at an increased risk of developing cardiovascular incidents in later life. This article emphasizes the diagnosis and management of pediatric hyperlipidemia with reference to the recent guidelines. In terms of etiology pediatric hyperlipidemia are divided into primary and secondary causes. The mainstay of management includes high-risk target screening, early risk factor identification and lifestyle modifications in vulnerable population. Drug therapy is recommended in primary hyperlipidemia and in children with no response to lifestyle changes.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Hiperlipidemias , Placa Aterosclerótica , Adulto , Humanos , Criança , Pré-Escolar , Hiperlipidemias/complicações , Hiperlipidemias/diagnóstico , Hiperlipidemias/epidemiologia , Fatores de Risco , Medição de Risco , Aterosclerose/etiologia , Placa Aterosclerótica/complicações , Doenças Cardiovasculares/prevenção & controle
14.
JACC Basic Transl Sci ; 9(3): 414-439, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38559627

RESUMO

Fundamentally, the heart needs to generate sufficient force and power output to dynamically meet the needs of the body. Cardiomyocytes contain specialized structures referred to as sarcomeres that power and regulate contraction. Disruption of sarcomeric function or regulation impairs contractility and leads to cardiomyopathies and heart failure. Basic, translational, and clinical studies have adapted numerous methods to assess cardiac contraction in a variety of pathophysiological contexts. These tools measure aspects of cardiac contraction at different scales ranging from single molecules to whole organisms. Moreover, these studies have revealed new pathogenic mechanisms of heart disease leading to the development of novel therapies targeting contractility. In this review, the authors explore the breadth of tools available for studying cardiac contractile function across scales, discuss their strengths and limitations, highlight new insights into cardiac physiology and pathophysiology, and describe how these insights can be harnessed for therapeutic candidate development and translational.

15.
bioRxiv ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38559046

RESUMO

Skeletal muscle actin (ACTA1) mutations are a prevalent cause of skeletal myopathies consistent with ACTA1's high expression in skeletal muscle. Rare de novo mutations in ACTA1 associated with combined cardiac and skeletal myopathies have been reported, but ACTA1 represents only ~20% of the total actin pool in cardiomyocytes, making its role in cardiomyopathy controversial. Here we demonstrate how a mutation in an actin isoform expressed at low levels in cardiomyocytes can cause cardiomyopathy by focusing on a unique ACTA1 mutation, R256H. We previously identified this mutation in multiple family members with dilated cardiomyopathy (DCM), who had reduced systolic function without clinical skeletal myopathy. Using a battery of multiscale biophysical tools, we show that R256H has potent functional effects on ACTA1 function at the molecular scale and in human cardiomyocytes. Importantly, we demonstrate that R256H acts in a dominant manner, where the incorporation of small amounts of mutant protein into thin filaments is sufficient to disrupt molecular contractility, and that this effect is dependent on the presence of troponin and tropomyosin. To understand the structural basis of this change in regulation, we resolved a structure of R256H filaments using Cryo-EM, and we see alterations in actin's structure that have the potential to disrupt interactions with tropomyosin. Finally, we show that ACTA1R256H/+ human induced pluripotent stem cell cardiomyocytes demonstrate reduced contractility and sarcomeric disorganization. Taken together, we demonstrate that R256H has multiple effects on ACTA1 function that are sufficient to cause reduced contractility and establish a likely causative relationship between ACTA1 R256H and clinical cardiomyopathy.

16.
Cureus ; 16(5): e60639, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38903304

RESUMO

Background Managing intertrochanteric fractures presents challenges for orthopedic surgeons, not only in fixing the fracture but also in preventing and managing associated complications, especially in the vulnerable geriatric population. Cephalomedullary nails are commonly used for surgical fixation due to their favorable functional profile, which preserves the hip's abductor lever arm and proximal femur anatomy. However, there's a lack of data comparing two major options: proximal femoral nail (PFN) and proximal femoral nail anti-rotation (PFNA). This study aimed to compare the radiological fracture reduction and fixation as well as functional outcomes of these two implants in treating intertrochanteric fractures. Methods The study, spanning 24 months, involved a prospective comparative design. Participants included patients diagnosed with intertrochanteric femur fractures classified as AO Type 31 A1, AO Type 31 A2, and AO Type 31 A3. Fifty patients were evenly distributed into PFN and PFNA groups. Preoperatively, clinical and radiological assessments were conducted, along with serum vitamin D level measurements. Surgeries, performed under anesthesia with image intensifier guidance, followed defined reduction and implant insertion protocols for each group. Postoperatively, evaluations were conducted up to six months, examining parameters such as tip-apex distance (TAD), Cleveland index, and modified Harris hip score, while documenting intraoperative duration and blood loss. Data analysis utilized the statistical software Statistical Package for Social Sciences (SPSS), version 22.0 (IBM Corp., Armonk, NY), employing descriptive statistics, chi-square tests, independent t-tests, and paired t-tests, with significance set at p < 0.05. Results In our study, 50 patients were enrolled, with equal gender distribution (64.0% male, 36.0% female, p=1.000). The mean ages in the PFN and PFNA groups were 66.2 ± 9.8 years and 66.4 ± 11.3 years, respectively (p=0.936). All fractures united by six months, with no implant-related complications reported. PFNA showed significantly lower blood loss and shorter surgery durations (p<0.001). TAD and neck shaft angle were similar between groups (p=0.826, p=0.555). Cleveland index placement and modified Harris hip score improvement were comparable (p=0.836, p<0.001). Predominant vitamin D deficiency was observed in both groups. Conclusion PFNA offers measurable intraoperative benefits over conventional PFN in terms of operative time, blood loss, and need for fluoroscopic imaging. However, no statistically observable benefits were noted in postoperative functional outcomes or complications between the two implants.

17.
J ISAKOS ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909905

RESUMO

The Subscapularis (SSC) muscle is a crucial anterior glenohumeral stabilizer and internal rotator of the shoulder joint. The partial tears of the SSC might result from traumatic injury or intrinsic degeneration. Partial SSC tears can range in severity and be classified into different categories based on the location of the tear, size of the lesion, and associated pathology. The tear usually begins from the superolateral margin in the first facet and propagates downwards. It is frequently associated with biceps pathology or anterosuperior lesions. These tears are now increasingly recognized as distinct pathology that requires specific diagnostic and management approaches. The current management approaches are shifting towards operative, as partial SSC tears are increasing recognized as distinct pathology. At present, there is no consensus regarding the timing of repair, but the relative tendency of the SSC to retract much faster than other rotator cuff muscles, and difficulty in mobilization, advocates an early repair for SSC irrespective of the lesion size. An associated biceps pathology can be treated with either tenotomy (biceps delamination/erosion) or tenodesis. The techniques of partial SSC repair are constantly improving. There is no reported difference in use of 2-anchor-based conventional single-row (SR), a 3-anchor-based interconnected double-row technique, or a 2-anchor-based interconnected hybrid double-row construct in the repair construct. However, the 2-anchor-based interconnected double-row provides an advantage of better superolateral coverage with the leading-edge protection, as it helps in placing the superolateral anchor superior and lateral to the original footprint. A timely intervention and restoration of the footprint will help restore and rehabilitate the shoulder. Future directions should prioritise injury prevention, early diagnosis with clinic-radiological cues and targeted interventions to mitigate risk.

18.
J Biol Chem ; 287(9): 6604-14, 2012 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-22157755

RESUMO

The tumor suppressor breast cancer susceptibility gene 2 (BRCA2) plays an important role in the repair of DNA damage, and loss of BRCA2 predisposes carriers to breast and ovarian cancers. Doxorubicin (DOX) remains the cornerstone of chemotherapy in such individuals. However, it is often associated with cardiac failure, which once manifests carries a poor prognosis. Because BRCA2 regulates genome-wide stability and facilitates DNA damage repair, we hypothesized that loss of BRCA2 may increase susceptibility to DOX-induced cardiac failure. To this aim, we generated cardiomyocyte-specific BRCA2 knock-out (CM-BRCA2(-/-)) mice using the Cre-loxP technology and evaluated their basal and post-DOX treatment phenotypes. Although CM-BRCA2(-/-) mice exhibited no basal cardiac phenotype, DOX treatment resulted in markedly greater cardiac dysfunction and mortality in CM-BRCA2(-/-) mice compared with control mice. Apoptosis in left ventricular (LV) sections from CM-BRCA2(-/-) mice compared with that in corresponding sections from wild-type (WT) littermate controls was also significantly enhanced after DOX treatment. Microscopic examination of LV sections from DOX-treated CM-BRCA2(-/-) mice revealed a greater number of DNA double-stranded breaks and the absence of RAD51 focus formation, an essential marker of double-stranded break repair. The levels of p53 and the p53-related proapoptotic proteins p53-up-regulated modulator of apoptosis (PUMA) and Bax were significantly increased in samples from CM-BRCA2(-/-) mice. This corresponded with increased Bax to Bcl-2 ratios and elevated cytochrome c release in the LV sections of DOX-treated CM-BRCA2(-/-) mice. Taken together, these data suggest a critical and previously unrecognized role of BRCA2 as a gatekeeper of DOX-induced cardiomyocyte apoptosis and susceptibility to overt cardiac failure. Pharmacogenomic studies evaluating cardiac function in BRCA2 mutation carriers treated with doxorubicin are encouraged.


Assuntos
Apoptose/efeitos dos fármacos , Proteína BRCA2/genética , Doxorrubicina/toxicidade , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/patologia , Miócitos Cardíacos/patologia , Animais , Antibióticos Antineoplásicos/toxicidade , Proteína BRCA2/deficiência , Insuficiência Cardíaca/epidemiologia , Camundongos , Camundongos Knockout , Miocárdio/patologia , Fenótipo , Fatores de Risco , Proteína Supressora de Tumor p53/genética
19.
Indian J Orthop ; 57(Suppl 1): 45-48, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38107804

RESUMO

Background: India has a population capacity of 1.2 billion people. With a worldwide aging population, the prevention and management of osteoporosis has become a significant healthcare challenge. It is crucial to recognize the factors impacting poor bone health and appreciate the many hurdles to treat the disease to provide a better quality of life and decrease the financial burden on healthcare. Purpose: In this review article, we discuss the epidemiology of osteoporosis and address the definition, incidence, and prevalence, geographical variation in the occurrence of osteoporosis, and the risk factors for osteoporosis. Methods: Search terms using various combinations of the keywords 'osteoporosis,' 'epidemiology,' 'incidence,' 'prevalence,' 'fracture,' 'India,' 'world,' 'screening,' and 'FRAX' was done to review all relevant literature till June 2023. Results & Conclusion: India has a recent estimate of population capacity of 1.2 billion people. Various studies have revealed an osteoporosis prevalence in Indian women ranging from 8% to 62%. Poor dietary calcium intake, low vitamin D, and lifestyle changes contribute to osteoporosis.

20.
Heliyon ; 9(5): e16042, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37234627

RESUMO

Vegetation has been commonly used in sponge city to remediate problems related to rainstorm events. Unlike uniform rainfall which has been widely studied, effects of early-peak rainfall on hydrological responses in vegetated soils are unclear. Besides, there is a lack of quantitative method of accurately measuring wetting front (WF). This study aims to propose a new WF tracing method, and explore the hydrological responses to early-peak rainfall in unsaturated soils vegetated with dwarf mondo grass. During soil column tests, WF position, matric suction, volumetric water content, surface ponding and overflow drainage were measured. The new WF tracing method works reasonably well for all cases. As compared to uniform rainfalls, early-peak rainfalls caused (1) earlier onsets of ponding (by 20 minutes for vegetation case and by 5 minutes for bare soil) and overflow (by 52 minutes for vegetation case and by 37 minutes for bare soil), (2) greater overflow velocity (by 28% for vegetation case and by 41% for bare soil), and (3) slightly more total overflow amount. Vegetation delayed the ponding/overflow generations, and decreased total overflow drainage, due to enhanced infiltration of surface soil. At 5 cm depth, high-density mixture of fine and coarse roots caused an increase in the saturated water content (θs) and a reduction in the residual water content (θr), because of root-induced changes in soil structure. At 10 cm depth, low-density fine roots caused reductions in both θs and θr, and increased air-entry value, as roots occupy the pores.

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