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OBJECTIVES: This study aimed to investigate whether the format and type of conclusion in Cochrane plain language summaries (PLSs) influence readers' perception of treatment benefit and decision-making. DESIGN: An online parallel group, three-arm randomised controlled trial was conducted. SETTING: The study was conducted online. PARTICIPANTS: The participants were physiotherapy students. INTERVENTIONS: The participants read two Cochrane PLSs, one with a positive conclusion (strong evidence of benefit) and another with a negative conclusion (strong evidence of non-benefit). Each participant read the results of both reviews presented in one of three formats: (1) numerical, (2) textual or (3) numerical and textual. MAIN OUTCOME MEASURES: The primary outcome measure was the participants' perception of treatment benefit. RESULTS: All three groups of participants perceived the treatment to have positive effects when the Cochrane PLS had a positive conclusion, regardless of the format of presentation (mean perception of treatment benefit score: textual 7.7 (SD 2.3), numerical 7.9 (SD 1.8), numerical and textual 7.7 (SD 1.7), p=0.362). However, when the Cochrane PLS had a negative conclusion, all three groups of participants failed to perceive a negative effect (mean perception of treatment benefit score: textual 5.5 (SD 3.3), numerical 5.6 (SD 2.7), numerical and textual 5.9 (SD 2.8), p=0.019). CONCLUSIONS: The format of Cochrane PLSs does not appear to significantly impact physiotherapy students' perception of treatment benefit, understanding of evidence, persuasiveness or confidence in their decision. However, participants' perception of treatment benefit does not align with the conclusion when the Cochrane PLS indicates strong evidence of non-benefit from the intervention. TRIAL REGISTRATION NUMBER: CTRI/2022/10/046476.
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Lenguaje , HumanosRESUMEN
Aims: The objective of this study is to evaluate the outcomes of magnetically guided ablation of atrial fibrillation (AF) rotors in conjunction with magnetically guided pulmonary vein isolation (PVI) in a large consecutive series of patients. Methods and results: A total of 110 consecutive patients with drug-refractory AF underwent rotor ablation followed by conventional PVI and ablation of other spontaneous arrhythmias, all of which were performed with remote magnetic navigation (RMN). The patients were followed to assess the recurrence of atrial arrhythmia. Patients had a mean age of 62.5 ± 9.9 years, 64.5% had persistent AF, and 36.4% had a prior failed PVI. All patients had mapped rotors (3.9 ± 1.5 per patient), with right atrial (RA) rotors in 77.3% (85/110) of patients. After a mean follow-up of 17.6 ± 9.5 months, 90.9% (100/110) were in stable sinus rhythm including patients on previously ineffective antiarrhythmic drugs (AADs). 69.1% (76/110) were in stable sinus rhythm without any AADs. Outcome did not differ between patients with persistent or paroxysmal AF (69.2% vs. 69.0%; P = 0.75), failed prior ablation or those undergoing an initial ablation (77.5% vs. 64.3%; P = 0.193), or patients with and without intra-procedural AF termination (67.3% vs. 70.5%; P = 0.723). Conclusion: Ablation of rotors in combination with PVI using RMN was associated with a high success rate in this large cohort of consecutive patients. Significant proportion of patients exhibited RA rotors, which was associated with persistent AF, obstructive sleep apnoea, and obesity.
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Fibrilación Atrial/cirugía , Cateterismo Cardíaco/métodos , Ablación por Catéter/métodos , Magnetismo/métodos , Venas Pulmonares/cirugía , Tecnología de Sensores Remotos/métodos , Cirugía Asistida por Computador/métodos , Potenciales de Acción , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Ablación por Catéter/instrumentación , Femenino , Frecuencia Cardíaca , Humanos , Magnetismo/instrumentación , Imanes , Masculino , Persona de Mediana Edad , Venas Pulmonares/fisiopatología , Tecnología de Sensores Remotos/instrumentación , Estudios Retrospectivos , Factores de Riesgo , Cirugía Asistida por Computador/instrumentación , Resultado del TratamientoRESUMEN
The MIC(90) of RBx 14255, a novel ketolide, against Clostridium difficile was 4 µg/ml (MIC range, 0.125 to 8 µg/ml), and this drug was found to be more potent than comparator drugs. An in vitro time-kill kinetics study of RBx 14255 showed time-dependent bacterial killing for C. difficile. Furthermore, in the hamster model of C. difficile infection, RBx 14255 demonstrated greater efficacy than metronidazole and vancomycin, making it a promising candidate for C. difficile treatment.
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Antibacterianos/farmacología , Clostridioides difficile/efectos de los fármacos , Enterocolitis Seudomembranosa/tratamiento farmacológico , Cetólidos/farmacología , Animales , Antibacterianos/síntesis química , Clostridioides difficile/crecimiento & desarrollo , Cricetinae , Farmacorresistencia Bacteriana/efectos de los fármacos , Enterocolitis Seudomembranosa/microbiología , Enterocolitis Seudomembranosa/mortalidad , Humanos , Cetólidos/síntesis química , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Tasa de Supervivencia , Vancomicina/farmacologíaRESUMEN
BACKGROUND & OBJECTIVES: In vivo imaging system has contributed significantly to the understanding of bacterial infection and efficacy of drugs in animal model. We report five rapid, reproducible, and non invasive murine pulmonary infection, skin and soft tissue infection, sepsis, and meningitis models using Xenogen bioluminescent strains and specialized in vivo imaging system (IVIS). METHODS: The progression of bacterial infection in different target organs was evaluated by the photon intensity and target organ bacterial counts. Genetically engineered bioluminescent bacterial strains viz. Staphylococcus aureus Xen 8.1, 29 and 31; Streptococcus pneumoniae Xen 9 and 10 and Pseudomonas aeruginosa Xen-5 were used to induce different target organs infection and were validated with commercially available antibiotics. RESULTS: The lower limit of detection of colony forming unit (cfu) was 1.7-log10 whereas the lower limit of detection of relative light unit (RLU) was 4.2-log10 . Recovery of live bacteria from different target organs showed that the bioluminescent signal correlated to the live bacterial count. INTERPRETATION & CONCLUSIONS: This study demonstrated the real time monitoring and non-invasive analysis of progression of infection and pharmacological efficacy of drugs. These models may be useful for pre-clinical discovery of new antibiotics.
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Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/patología , Animales , Infecciones Bacterianas/tratamiento farmacológico , Modelos Animales de Enfermedad , Genes Sintéticos/genética , Humanos , Mediciones Luminiscentes , Pulmón/microbiología , Pulmón/patología , Meningitis/microbiología , Meningitis/patología , Ratones , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidad , Sepsis/microbiología , Sepsis/patología , Piel/microbiología , Piel/patología , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/patología , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidad , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidad , XenodiagnósticoRESUMEN
Brucella abortus, a gram negative, facultative intracellular pathogen causes brucellosis in many animal species and humans. Although live, attenuated vaccines are available against this infection, they suffer from certain limitations. Therefore, the development of an effective subunit vaccine against brucellosis is an area of intense research. The outer membrane proteins (OMPs) of Brucella species have been extensively studied for its immunogenicity and protective ability. We have investigated the potential of CpG ODN to enhance the immunogenicity and protective efficacy of recombinant 28 kDa outer membrane protein (rOMP28) of Brucella melitensis. The study demonstrated vigorous immunoglobulin G (IgG) response of OMP28. The administration of rOMP28 with CpG caused increased cell mediated immune response in terms of induced IgG2a, T-cell proliferation and up-regulation of type I cytokine expression. In contrast, the free antigen suppressed the interferon gamma (type I cytokine) production on in-vitro stimulation of spleenocytes. The result indicates the role of OMP28 in the down regulation of IFN-gamma production. Moreover, the B. abortus S-19 vaccinated mice showed highest production of IL-4 and IFN-gamma. The protective ability of the antigen was evaluated by systemic bacterial clearance after challenging the mouse with B. abortus 544 pathogen. The level of protection was significant in rOMP28+CpG treated mice but was lower than the required level. The results of the present study indicate that rOMP28 could be an immunogen capable of inducing both humoral and cellular immune response. The humoral response was biased towards Th1 type when it was co-administered with CpG.
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Adyuvantes Inmunológicos/farmacología , Vacunas Bacterianas/inmunología , Brucella abortus/inmunología , Brucelosis Bovina/inmunología , Brucelosis Bovina/prevención & control , ADN/farmacología , Proteínas de la Membrana/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Vacunas Bacterianas/farmacología , Western Blotting , Brucelosis Bovina/microbiología , Bovinos , Ensayo de Inmunoadsorción Enzimática , Femenino , Inmunización , Inmunoglobulina G/sangre , Isotipos de Inmunoglobulinas/sangre , Interferón gamma/metabolismo , Interleucina-4/análisis , Modelos Lineales , Proteínas de la Membrana/genética , Ratones , Oligodesoxirribonucleótidos , Conejos , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/farmacologíaRESUMEN
BACKGROUND/AIM: To study the effect of L-arginine on apoptosis and necrosis induced by 1-h ischemia followed by 3-h reperfusion. MATERIALS AND METHODS: Adult Wistar rats underwent 60 min of partial liver ischemia followed by 3-h reperfusion. Eighteen Wistar rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion (I/R) group (0.9 % saline (5 mL/kg, orally) for 7 days) (II) (n = 6), and L-arginine-treated group (10 mg/kg body weight daily orally for 7 days before inducing ischemia-reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, nitric oxide levels in hepatocytes, Bcl-2 mRNA, and Bcl-2 protein were measured. Liver injury was assessed by plasma alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology, and electron microscopy. RESULTS: An ischemic and reperfusion hepatocellular injury occurred as was indicated by increased serum ALT, AST, histopathology, and electron microscopy. Apoptosis and necrosis associated marker gene Bcl-2 mRNA and protein expression were decreased in I/R group. Pretreatment with L-arginine significantly decreased serum ALT and AST level and apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Nitric oxide production in hepatocytes was increased twofold by L-arginine treatment when compared with I/R group. Histopathology and transmission electron microscopy (TEM) studies showed markedly diminished hepatocellular injury in L-arginine-pretreated rats during the hepatic I/R. CONCLUSION: Thus, it may be concluded that L-arginine afforded significant protection from necrosis and apoptosis in I/R injury by upregulated Bcl-2 gene and nitric oxide production.
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Apoptosis/efectos de los fármacos , Arginina/farmacología , Isquemia/prevención & control , Hepatopatías/prevención & control , Hígado/irrigación sanguínea , Daño por Reperfusión/prevención & control , Animales , Apoptosis/genética , Western Blotting , Modelos Animales de Enfermedad , Genes bcl-2/genética , Isquemia/patología , Hígado/ultraestructura , Hepatopatías/etiología , Hepatopatías/patología , Microscopía Electrónica de Transmisión , Necrosis , ARN Mensajero/genética , Ratas , Ratas Wistar , Daño por Reperfusión/complicaciones , Daño por Reperfusión/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
PURPOSE: We prospectively determined whether preimplant myocardial perfusion imaging (MPI) predicts outcome with biventricular pacing (BiVP). METHODS: Single-photon emission computed tomography (SPECT) MPI, left ventricular (LV) volumes, ejection fraction (EF), 6-min hall walk (6MW) were assessed at baseline and at 4 months in 19 patients with ischemic cardiomyopathy undergoing BiVP. Clinical and hemodynamic responses were correlated with MPI. RESULTS: Lower global myocardial scar burden predicted hemodynamic response to BiVP, while higher burden was associated with poor response. Clinical improvement with BiVP occurred in 12 (63%) of the patients. Clinical BiVP responders had lower rest/stress MPI score difference. There was a close negative correlation between MPI reversibility and increased 6MW distance. CONCLUSIONS: Baseline MPI is associated with clinical and hemodynamic response to BiVP: greater myocardial scar burden is predictive of poor hemodynamic response, while higher ischemic burden is predictive of poor clinical response. There is a differential response to BiVP by clinical and hemodynamic criteria.
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Estimulación Cardíaca Artificial , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/terapia , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Isquemia Miocárdica/fisiopatología , Estudios Prospectivos , Calidad de Vida , Radiofármacos , Estadísticas no Paramétricas , Tecnecio Tc 99m SestamibiRESUMEN
Ca(2+) accumulation in mitochondria is responsible for the cell abnormality associated with ischemia and reperfusion injury. The present study was aimed to evaluate the efficacy of Ca(2+) channel blocker- amlodipine on the mitochondrial Ca(2+) accumulation in ischemic and reperfusion (I/R) induced liver injury. Eighteen wistar rats were divided in sham-operated control group-I (n = 6), ischemia and reperfusion group-II (n = 6) and amlodipine treated group-III (1 mg/kg body weight /daily by oral route for 7 days before induced ischemia reperfusion manouver) (n = 6). Rats were subjected to 1h of hepatic ischemia followed by 3 h reperfusion. Mitochondrial Ca(2+) content was measured and damage of mitochondria was confirmed by transmission electron microscopic examination. Bcl-2 gene expression was measured by reverse transcriptase polymerase chain reaction method. Pretreatment with Amlodipine effectively counteracted the alternation in mitochondrial Ca(2+) content. TEM and expression of Bcl-2 protein confirms the restoration of cellular normalcy and accredits the cytoprotective role of Amlodipine against I/R induced hepatic injury. These findings showed that the mechanism of regulation of Bcl-2 gene expression by amlodipine may be the inhibitory action of Ca(2+) entry into mitochondria and prevent apoptosis and necrosis.
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The present study was aimed to evaluate the efficacy of L-arginine on mitochondrial function in ischemic and reperfusion (I/R) induced hepatic injury. Adult Wistar rat were subjected to 1 h of partial liver ischemia followed by 3 hour reperfusion. Eighteen wistar rats were divided into three groups viz. sham-operated control group (I) (n=6), ischemia and reperfusion (I/R) group (II) (n=6), L-arginine treated group (100 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n=6). Mitochondrial injury was assessed in terms of decreased (P<0.05) activities of mitochondrial antioxidant enzymes (GSH, SOD, CAT), respiratory marker enzymes (NADH dehydrogenase, cytochrome c oxidases) and hepatocytes nitric oxide production. Pre-treatment with L-arginine (10 mg/kg/p.o. for 7 days) significantly counteracted the alternations of hepatic enzymes and mitochondrial respiratory and antioxidant enzymes. In addition, electron microscopy and histopathology study showed the restoration of cellular normalcy and accredits the cytoprotective role of L-arginine against I/R induced hepatocellular injury. On the basis of these findings it may be concluded that L-arginine protects mitochondrial function in hepatic ischemic and reperfused liver.
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Arginina/uso terapéutico , Insuficiencia Hepática/tratamiento farmacológico , Mitocondrias Hepáticas/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Complejo Cetoglutarato Deshidrogenasa/metabolismo , Malato Deshidrogenasa/metabolismo , Microscopía Electrónica de Transmisión , Mitocondrias Hepáticas/ultraestructura , NADH Deshidrogenasa/metabolismo , Óxido Nítrico/biosíntesis , Ratas , Ratas Wistar , Succinato Deshidrogenasa/metabolismoRESUMEN
BACKGROUND: Implantation of CS-LV pacing leads is usually accomplished through specialized sheaths with additional use of contrast venography and other steps. Direct implantation at a target pacing site could provide a simplified procedure with appropriate leads. METHODS: A progressive CS-LV lead implant protocol was used, with initial attempts made to place the lead directly using only fluoroscopy and lead stylet or wire manipulation. Coronary sinus (CS) sheaths were only used later if direct lead placement failed. RESULTS: There were 105 attempted implants with 96% (101/105) success. Leads were implanted sheathlessly in 69% (70/101) cases. Pacing parameters and final lead position did not differ significantly between implants that did or did not require sheaths for implants. Three peri-procedural complications occurred in implants where sheaths were used. In 33% (33/101) of implants, the leads were placed without the use of sheaths or contrast venography in 20 minutes or less. CONCLUSIONS: Direct placement of the CS-LV pacing lead without sheaths can be accomplished successfully in a majority of implants and in < or =20 minutes in a third, without inferior pacing parameters. This may provide for shorter or less technically difficult or expensive procedures with low risk.
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Estimulación Cardíaca Artificial/métodos , Electrodos Implantados , Insuficiencia Cardíaca/terapia , Fluoroscopía , Humanos , Marcapaso Artificial , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Hemodynamic improvement from biventricular pacing is well documented; however, its electrophysiologic effects have not been systematically studied. Sporadic case reports suggest a proarrhythmic effect of biventricular pacing resulting primarily in polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF). OBJECTIVES: The purpose of this study was to report a series of patients in whom implantation of a biventricular system resulted in VT/VF storm with predominance of monomorphic VT. METHODS: In a retrospective analysis of all biventricular implants over a 4-year period at a single medical center, we identified 5 of 145 patients (3.4%) who developed VT/VF after they were upgraded to a biventricular system. All patients were male, age 71 +/- 8 years, with ejection fraction of 0.25 +/- 0.1. Four of five patients had ischemic cardiomyopathy. RESULTS: All patients developed incessant VT/VF within 1 week of implantation. Monomorphic VT of single morphology was noted in 3 of 5 patients, monomorphic VT of multiple morphologies in 1, and polymorphic VT/VF in 1. VT was managed by temporary discontinuation of biventricular pacing in all patients, amiodarone in 3 of 5, sotalol in 1, and beta-blocker in 1. During 11 +/- 7 months of follow-up, 4 of 5 patients remain alive and are arrhythmia-free. CONCLUSION: Biventricular pacing may result in precipitation of VT/VF storm in a minority of patients with prior history of VT/VF. This may be the first case series reporting both monomorphic and polymorphic VT after an upgrade to a system with biventricular pacing capabilities. The arrhythmias can be managed by conventional therapy and may require temporary discontinuation of left ventricular pacing. This observation is relevant to patients receiving a biventricular pacemaker without an implantable cardioverter-defibrillator backup.