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1.
Indian J Otolaryngol Head Neck Surg ; 76(1): 1307-1309, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440446

RESUMO

ROCM is an invasive fungal infection that has seen a substantial rise in the post covid-19 patients. Here we present an intriguing case of ROCM existing as a coinfection with MDR-TB. The purpose of this manuscript is to highlight the dilemma faced by the clinicians whether to take the risks associated with standard treatment protocols of mucormycosis contraindicated due to coexisting MDR-TB or to play safe and face the consequences of inadequate management.

2.
World J Diabetes ; 14(8): 1314-1322, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37664476

RESUMO

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are commonly prescribed to manage patients with diabetes mellitus. These agents may rarely lead to the development of euglycemic diabetic ketoacidosis (EDKA), which may complicate the disease course of these patients. AIM: To analyze the demographic profile, predisposing factors, symptomology, clinical interventions and outcomes of patients presenting with EDKA secondary to SGLT2i use by reviewing the published case reports and series. METHODS: We performed a systematic search of PubMed, Science Direct, Google Scholar and Reference Citation Analysis databases using the terms "canagliflozin" OR "empagliflozin" OR "dapagliflozin" OR "SGLT2 inhibitors" OR "Sodium-glucose cotransporter-2" AND "euglycemia" OR "euglycemic diabetic ketoacidosis" OR "metabolic acidosis". The inclusion criteria were: (1) Case reports or case series with individual patient details; and (2) Reported EDKA secondary to SGLT2i. Furthermore, the data were filtered from the literature published in the English language and on adults (> 18 years). We excluded: (1) Conference abstracts; and (2) Case reports or series which did not have individual biochemical data. All the case reports and case series were evaluated. The data extracted included patient demographics, clinical symptomatology, clinical interventions, intensive care unit course, need for organ support and outcomes. RESULTS: Overall, 108 case reports and 17 cases series with 169 unique patients that met all the inclusion criteria were included. The majority of patients were females (54.4%, n = 92), and the commonly reported symptoms were gastrointestinal (nausea/vomiting 65.1%, abdominal pain 37.3%) and respiratory (breathlessness 30.8%). One hundred and forty-nine (88.2%) patients had underlying type II diabetes, and the most commonly involved SGLT-2 inhibitor reported was empagliflozin (46.8%). A triggering factor was reported in most patients (78.7%), the commonest being acute severe infection (37.9%), which included patients with sepsis, coronavirus disease 2019, other viral illnesses, and acute pancreatitis. 61.5% were reported to require intensive unit care, but only a minority of patients required organ support in the form of invasive mechanical ventilation (13%), vasopressors (6.5%) or renal replacement therapy (5.9%). The overall mortality rate was only 2.4%. CONCLUSION: Patients on SGLT2i may rarely develop EDKA, especially in the presence of certain predisposing factors, including severe acute infections and following major surgery. The signs and symptoms of EDKA may be similar to that of DKA but with normal blood sugar levels, which may make the diagnosis challenging. Outcomes of EDKA are good if recognized early and corrective actions are taken. Hence, physicians managing such patients must be aware of this potential complication and must educate their patients accordingly to ensure early diagnosis and management.

3.
Indian J Urol ; 39(3): 195-201, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575157

RESUMO

Introduction: Oligometastatic prostate cancer (OMPC) has gained profound interest lately due to its different tumor biology and our ability to use multimodality therapy for cure or prolonged survival. Selecting the appropriate patient for treatment has become the aim of treating urologists, medical oncologists, and radiation oncologists. Through this review, we try to highlight the management of OMPC in light of recent literature. Methods: Literature search was performed on Pubmed, Scopus and Embase using keywords "Oligometastatic", " Prostate Cancer" using operators such as "And" & "Or". Relevant articles were screened and all the latest articles on this emerging entity were included in this review. Results: All trials relevant to oligometastatic prostate cancer defining the role of surgery, radiotherapy and systemic therapy were included and appropriate inferences were drawn. Relevant studies were compiled in tabular form for this article. Conclusion: The current standard of care of management for OMPC remains systemic therapy on the lines of hormone-sensitive metastatic prostate cancer. The evolving role of surgery, and radiotherapy along with systemic therapy is highlighted in this article.

4.
Clin Rehabil ; 37(5): 713-724, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36510450

RESUMO

OBJECTIVE: To understand perceptions on rehabilitation after vertebral fracture, non-pharmacological strategies, and virtual care from the perspective of individuals living with vertebral fractures. DESIGN AND SETTING: We conducted semi-structured interviews online and performed a thematic and content analysis from a post-positivism perspective. PARTICIPANTS: Ten individuals living with osteoporotic vertebral fractures (9F, 1 M, aged 71 ± 8 years). RESULTS: Five themes emerged: pain is the defining limitation of vertebral fracture recovery; delayed diagnosis impacts recovery trajectory; living with fear; being dissatisfied with fracture management; and "getting back into the game of life" using non-pharmacological strategies. CONCLUSION: Participants reported back pain and an inability to perform activities of daily living, affecting psychological and social well-being. Physiotherapy, education, and exercise were considered helpful and important to patients; however, issues with fracture identification and referral limited the use of these options. Participants believed that virtual rehabilitation was a feasible and effective alternative to in-person care, but perceived experience with technology, cost, and individualization of programs as barriers.


Assuntos
Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/terapia , Atividades Cotidianas , Fraturas por Osteoporose/terapia , Fraturas por Osteoporose/psicologia , Dor nas Costas , Modalidades de Fisioterapia
5.
J Clin Neurosci ; 105: 122-128, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36182812

RESUMO

OBJECTIVE: Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. METHODS: The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. RESULTS: The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. CONCLUSIONS: This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.


Assuntos
Epilepsia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação do Nervo Vago , Anticoagulantes , Epilepsia/etiologia , Epilepsia/cirurgia , Fibrinolíticos , Humanos , Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral/métodos , Resultado do Tratamento , Nervo Vago , Estimulação do Nervo Vago/métodos
6.
Asian Cardiovasc Thorac Ann ; 30(2): 237-244, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34247490

RESUMO

INTRODUCTION: There are various reports of air leaks with coronavirus disease 2019 (COVID-19). We undertook a systematic review of all published case reports and series to analyse the types of air leaks in COVID-19 and their outcomes. METHODS: The literature search from PubMed, Science Direct, and Google Scholar databases was performed from the start of the pandemic till 31 March 2021. The inclusion criteria were case reports or series on (1) laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, (2) with the individual patient details, and (3) reported diagnosis of one or more air leak syndrome (pneumothorax, subcutaneous emphysema, pneumomediastinum, pneumoperitoneum, pneumopericardium). RESULTS: A total of 105 studies with 188 patients were included in the final analysis. The median age was 56.02 (SD 15.53) years, 80% males, 11% had previous respiratory disease, and 8% were smokers. Severe or critical COVID-19 was present in 50.6% of the patients. Pneumothorax (68%) was the most common type of air leak. Most patients (56.7%) required intervention with lower mortality (29.1% vs. 44.1%, p = 0.07) and intercostal drain (95.9%) was the preferred interventional management. More than half of the patients developed air leak on spontaneous breathing. The mortality was significantly higher in patients who developed air leak with positive pressure ventilation (49%, p < 0.001) and required escalation of respiratory support (39%, p = 0.006). CONCLUSION: Air leak in COVID-19 can occur spontaneously without positive pressure ventilation, higher transpulmonary pressures, and other risk factors like previous respiratory disease or smoking. The mortality is significantly higher if associated with positive pressure ventilation and escalation of respiratory support.


Assuntos
COVID-19 , Enfisema Mediastínico , Pneumotórax , Feminino , Humanos , Masculino , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Mediastínico/etiologia , Enfisema Mediastínico/terapia , Pessoa de Meia-Idade , Pneumotórax/etiologia , Pneumotórax/terapia , SARS-CoV-2 , Resultado do Tratamento
7.
J Bone Joint Surg Am ; 103(13): 1175-1183, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-33764937

RESUMO

BACKGROUND: The Fracture Screening and Prevention Program (FSPP), a fracture liaison service (FLS), was implemented in the province of Ontario, Canada, in 2007 to prevent recurrent fragility fractures and to improve post-fracture care. The objective of this analysis was to determine the cost-effectiveness of the current model of the FSPP compared with usual care (no program) from the perspective of the universal public health-care payer (Ontario Ministry of Health and Long-Term Care [MOHLTC]), over the lifetime of older adults who presented with a fragility fracture of the proximal part of the femur, the proximal part of the humerus, or the distal part of the radius and were not taking medications to prevent or slow bone loss and reduce the risk of fracture (bone active medications). METHODS: We developed a state-transition (Markov) model to conduct a cost-effectiveness analysis of the FSPP in comparison with usual care. The model simulated a cohort of patients with a fragility fracture starting at 71 years of age. Model parameters were obtained from published literature and from the FSPP. Quality-adjusted life-years (QALYs) and costs in 2018 Canadian dollars were predicted over a lifetime horizon using a 1.5% annual discount rate. Health outcomes included subsequent proximal femoral, vertebral, proximal humeral, and distal radial fractures. Scenario and subgroup analyses were reported. RESULTS: The FSPP had lower expected costs ($277 less) and higher expected effectiveness (by 0.018 QALY) than usual care over the lifetime horizon. Ninety-four percent of the 10,000 Monte Carlo simulated incremental cost-effectiveness ratios (ICERs) demonstrated lower costs and higher effectiveness of the FSPP. CONCLUSIONS: The FSPP appears to be cost-effective compared with usual care over a lifetime for patients with fragility fracture. This information may help to quantify the value of the FSPP and to assist policy-makers in deciding whether to expand the FSPP to additional hospitals or to initiate similar programs where none exist. LEVEL OF EVIDENCE: Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Fraturas por Osteoporose/prevenção & controle , Prevenção Secundária/métodos , Idoso , Análise Custo-Benefício , Fraturas do Quadril/prevenção & controle , Humanos , Cadeias de Markov , Método de Monte Carlo , Ontário , Avaliação de Programas e Projetos de Saúde , Anos de Vida Ajustados por Qualidade de Vida , Fraturas do Rádio/prevenção & controle , Recidiva , Prevenção Secundária/economia , Fraturas do Ombro/prevenção & controle , Cobertura Universal do Seguro de Saúde
8.
Biochem J ; 477(12): 2153-2177, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32484216

RESUMO

Scaffold proteins play pivotal role as modulators of cellular processes by operating as multipurpose conformation clamps. 14-3-3 proteins are gold-standard scaffold modules that recognize phosphoSer/Thr (pS/pT) containing conserved motifs, and confer conformational changes leading to modulation of functional parameters of their target proteins. Modulation in functional activity of kinases has been attributed to their interaction with 14-3-3 proteins. Herein, we have annotated and characterized PF3D7_0818200 as 14-3-3 isoform I in Plasmodium falciparum 3D7, and its interaction with one of the key kinases of the parasite, Calcium-Dependent Protein Kinase 1 (CDPK1) by performing various analytical biochemistry and biophysical assays. Molecular dynamics simulation studies indicated that CDPK1 polypeptide sequence (61KLGpS64) behaves as canonical Mode I-type (RXXpS/pT) consensus 14-3-3 binding motif, mediating the interaction. The 14-3-3I/CDPK1 interaction was validated in vitro with ELISA and SPR, which confirmed that the interaction is phosphorylation dependent, with binding affinity constant of 670 ± 3.6 nM. The interaction of 14-3-3I with CDPK1 was validated with well characterized optimal 14-3-3 recognition motifs: Mode I-type ARSHpSYPA and Mode II-type RLYHpSLPA, by simulation studies and ITC. This interaction was found to marginally enhance CDPK1 functional activity. Furthermore, interaction antagonizing peptidomimetics showed growth inhibitory impact on the parasite indicating crucial physiological role of 14-3-3/CDPK1 interaction. Overall, this study characterizes 14-3-3I as a scaffold protein in the malaria parasite and unveils CDPK1 as its previously unidentified target. This sets a precedent for the rational design of 14-3-3 based PPI inhibitors by utilizing 14-3-3 recognition motif peptides, as a potential antimalarial strategy.


Assuntos
Proteínas 14-3-3/metabolismo , Malária Falciparum/parasitologia , Simulação de Dinâmica Molecular , Plasmodium falciparum/crescimento & desenvolvimento , Proteínas Quinases/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas 14-3-3/química , Sequência de Aminoácidos , Animais , Fosforilação , Filogenia , Plasmodium falciparum/isolamento & purificação , Plasmodium falciparum/metabolismo , Conformação Proteica , Proteínas Quinases/química , Proteínas de Protozoários/química , Homologia de Sequência
9.
Urol Ann ; 12(2): 122-127, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565648

RESUMO

INTRODUCTION: The prevalence of infective complications among patients undergoing Retrograde Intrarenal Surgery (RIRS) for renal stone is 1.7%-18%, including fever, Systemic Inflammatory Response Syndrome (SIRS) and sepsis. The infectious complications of RIRS can be minimised by strict aseptic precautions and plasma sterilization. The Sterrad Next Generation (Sterrad NX) System, a low-temperature sterilizer represents the next generation of low-temperature hydrogen peroxide gas plasma sterilizers. This study was conducted to evaluate the efficacy of plasma sterilization among patients undergoing ureterorenoscopy (URS) and RIRS. The primary endpoint of this study was incidence of septicemia or related complications. Till date, there is no study on the incidence of infection rate in RIRS in relation to a specific mode of sterilization. MATERIAL AND METHODS: This is a retrospective study comprising of 198 patients undergoing URS and/or RIRS. The parameters studied were incidence of post-operative fever, Systemic Inflammatory Response Syndrome (SIRS), pyelonephritis or septicemic shock. RESULTS: Out of 198 patients, incidence of post-operative fever was 3.5%, SIRS was 1.7%, pyelonephritis was 0.7% and septicemic shock was 0%. This is statistically significantly low septicemia rate among patients undergoing URS and /or RIRS as compared to the available literature. No health hazards of plasma sterilization were noted. No damage to the endoscopes or instruments was noted. CONCLUSION: Sterrad NX based on hydrogen peroxide gas plasma (HPGP) technology is highly efficacious, safe and the modality for sterilization of instruments, including heat labile instruments such as semi rigid, flexible and chip on the tip endoscopes and other EndoUrology armamentarium.

10.
Radiol Imaging Cancer ; 2(5): e190096, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33778735

RESUMO

Purpose: To calculate the negative predictive value (NPV) and false-negative rate (FNR) of molecular breast imaging (MBI) performed in patients who had low-suspicion index findings on mammograms and US images. Materials and Methods: This retrospective study included patients who had undergone MBI between January 2015 and July 2017, who had index findings on screening mammograms and/or US images, and for whom either histopathologic results or a minimum of 1-year imaging follow-up results were available. A drawn dose of 8 mCi (296 MBq) of technetium 99m sestamibi was administered to all patients for MBI. The NPV and FNR of MBI was calculated for the cohort of 381 findings among 338 women (median age, 56 years; age range, 28-89 years) included in this study. Results: Overall, 292 of the 381 (76.6%) MBI results were interpreted as negative. Of the 292, 27 patients underwent subsequent biopsies, results of which were negative for cancer; one patient underwent biopsy, and the result was positive for cancer; and 264 patients had true-negative findings based on follow-up imaging for a minimum of 1 year. Of the 89 MBI acquisitions interpreted as positive, there were 36 cancers. The NPV was calculated to be 99.7% (291 of 292, 95% confidence interval [CI]: 99.1%, 100%), and the FNR was 2.7% (one of 37, 95% CI: 0%, 7.9%). Interposing MBI reduced the number of biopsies by 67.5%. Conclusion: The concept of the clinical utility of a negative MBI result may be valid but requires further testing.Keywords: Breast, Molecular Imaging-Cancer© RSNA, 2020.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama , Resultados Negativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Retrospectivos , Tecnécio Tc 99m Sestamibi
11.
Sci Rep ; 9(1): 17785, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31780808

RESUMO

Natural products offer an abundant source of diverse novel scaffolds that inspires development of next generation anti-malarials. With this vision, a library of scaffolds inspired by natural biologically active alkaloids was synthesized from chiral bicyclic lactams with steps/scaffold ratio of 1.7:1. On evaluation of library of scaffolds for their growth inhibitory effect against malaria parasite we found one scaffold with IC50 in low micro molar range. It inhibited parasite growth via disruption of Na+ homeostasis. P-type ATPase, PfATP4 is responsible for maintaining parasite Na+ homeostasis and is a good target for anti-malarials. Molecular docking with our scaffold showed that it fits well in the binding pocket of PfATP4. Moreover, inhibition of Na+-dependent ATPase activity by our potent scaffold suggests that it targets parasite by inhibiting PfATP4, leading to ionic imbalance. However how ionic imbalance attributes to parasite's death is unclear. We show that ionic imbalance caused by scaffold 7 induces autophagy that leads to onset of apoptosis in the parasite evident by the loss of mitochondrial membrane potential (ΔΨm) and DNA degradation. Our study provides a novel strategy for drug discovery and an insight into the molecular mechanism of ionic imbalance mediated death in malaria parasite.


Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Indóis/química , Indóis/farmacologia , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/metabolismo , Desenho de Fármacos , Descoberta de Drogas , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Malária Falciparum/tratamento farmacológico , Modelos Moleculares , Plasmodium falciparum/enzimologia , Plasmodium falciparum/crescimento & desenvolvimento
13.
Clin Biomech (Bristol, Avon) ; 68: 212-220, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31325767

RESUMO

Nasal surgery improves symptoms in a majority of patients for whom medical treatment has failed. In rhinosinusitis patients, endoscopic sinus surgery aims to alleviate obstruction and re-establish mucociliary clearance. Surgery alters the structure-function relationship within the nasal passage, which is difficult to assess clinically. Computational modelling has been used to investigate this relationship by simulating air flow and environmental variables inside realistic three-dimensional models of the human nasal airway but many questions remain unanswered and need further investigation. The application of computational models to improve pre-surgical planning and post-surgical treatment may not be currently possible due to the absence of knowledge correlating the model-predicted parameters to physiological variables. Links between these parameters to patient outcomes are yet to be established. This article reviews the recent application of computational modelling to understand the nasal structure-function relationship following surgery in patients with sinusitis and nasal obstruction.


Assuntos
Simulação por Computador , Seios Paranasais/anatomia & histologia , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/cirurgia , Sinusite/diagnóstico por imagem , Doença Crônica , Sistemas de Liberação de Medicamentos , Endoscopia , Humanos , Hidrodinâmica , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Modelos Biológicos , Sprays Nasais , Nebulizadores e Vaporizadores , Período Pós-Operatório , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Chin J Traumatol ; 22(5): 278-280, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31303552

RESUMO

PURPOSE: In medical colleges, resident training programs must provide adequate surgical experiences, making them qualified at the end of residency program. It is generally believed that it would take more time for a surgical resident to perform surgical procedures than a board-certified surgeon. There is no current benchmark with regards to operative time and surgical cases involving orthopedic surgery residents. In this study, we focused on two key aspects of surgical training variables, namely, surgical duration & C-arm shoots when the procedure is done by a faculty surgeon in comparison to done by an orthopedic resident under supervision of faculty surgeon. METHODS: It is an observational prospective study, we observed patients undergoing 1 of 5 common orthopedic trauma operations in a community teaching hospital. We recorded two variables, 'skin to skin' surgical duration & number of image intensifier television/C-arm shoots of faculty surgeons and orthopedic resident (postgraduate-3yr) under supervision of faculty surgeon. We calculated mean difference of two variables with or without resident & determined statistical significance, we also compared functional outcome at final follow-up. RESULTS: The total number of procedure observed was 402. On observing summarized results of all surgical procedures, faculty surgeons took on an average 33 min lesser (p < 0.05) & on an average 37 lesser number of shoots (p < 0.05) than resident surgeons. The difference in surgical duration tended to increase with the greater complexity of the surgical dissection. The difference in number of C-arm shoots tended to increase with the increase in surgical duration in closed procedures. In all the five procedures there was no significant difference (p > 0.05) in functional outcome of cases performed by faulty surgeon and resident. CONCLUSION: Little data has been previously published regarding the impact of teaching orthopedic resident in operating room. We demonstrate that resident participation increases the procedure time for commonly performed orthopedic procedures and also the number of C-arm shoots, hence there is a need for technical training facilities outside the operating room such as in cadaveric labs, saw bone labs & virtual surgery simulation. Also the preoperative plan should be thoroughly discussed by faculty surgeon with residents.


Assuntos
Educação de Pós-Graduação em Medicina , Internato e Residência , Procedimentos Ortopédicos/educação , Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Docentes de Medicina , Humanos , Salas Cirúrgicas , Duração da Cirurgia , Procedimentos Ortopédicos/métodos , Estudos Prospectivos
15.
J Clin Orthop Trauma ; 10(3): 531-534, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061584

RESUMO

BACKGROUND: Identification of the radial nerve is necessary during surgery of the humerus fracture to avoid injury to it. Iatrogenic nerve injury during humerus fracture surgery is a well-known complication. Prevention of this type of injuries would be of great value. Aim of this study is to reduce the chance of iatrogenic nerve injury by defining of a danger zone in the distal upper arm regarding the radial nerve in indian population. METHODS: Thirty six upper limbs of eighteen adult human formalin preserved cadavers (14 males & 4 females) were used in this study. The posterior aspect of the arm was dissected to expose the radial nerve from the triangular space to the point where the radial nerve pierced the lateral intermuscular septum. Systematic identification of radial nerve and multiple measurements were done for each specimen. RESULTS: The mean humeral length was 30.96 + 1.23 cm. Mean Distance of medial epicondyle to entry of radial nerve into spiral groove was 18.5 + 0.79 cm. Mean Distance of lateral epicondyle to exit of radial nerve into spiral groove was 11.34 + 0.41 cm. The mean length of radial nerve groove/spiral groove was 4.3 + 0.75 cm. CONCLUSIONS: Our study has identified the point of intersection of radial nerve to humerus in Indian population. Understanding the safe zones and the zone of danger of the humerus provides more safety during the surgical interference of the humerus. To do this, the radial nerve must be identified and protected. Wide incision and blunt dissection is still recommended to minimize the risk of radial nerve damage.

16.
FEBS Lett ; 593(11): 1223-1235, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31074836

RESUMO

Zeta-toxin is a cognate toxin of epsilon antitoxin of prokaryotic Type II toxin-antitoxin system (TA) and play an important role in cell death. An orthologue of bacterial-zeta-toxin (BzT) was identified in Leishmania donovani with similar structural and functional features. Leishmania zeta-toxin (named Ld_ζ1) harboring similar UNAG and ATP-binding pockets showed UNAG kinase and ATP-binding activity. An active Ld_ζ1 was found to express in infective extracellular promastigotes stage of L. donovani and episomal overexpression of an active Ld_ζ1domain-triggered cell death. This study demonstrates the presence of prokaryotic-like-zeta-toxin in eukaryotic parasite Leishmania and its association with cell death. Conceivably, phosphorylated UNAG or analogues, the biochemical mimics of zeta-toxin function mediating cell death can act as a novel anti-leishmanial chemotherapeutics.


Assuntos
Toxinas Bacterianas/genética , Leishmania donovani/genética , Proteínas Quinases/genética , Proteínas de Protozoários/genética , Homologia de Sequência de Aminoácidos , Trifosfato de Adenosina/metabolismo , Animais , Anticorpos Antiprotozoários/imunologia , Escherichia coli/efeitos dos fármacos , Leishmania donovani/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ligação Proteica , Proteínas Quinases/imunologia , Proteínas Quinases/metabolismo , Proteínas Quinases/toxicidade , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/toxicidade , Uridina Difosfato N-Acetilglicosamina/metabolismo
17.
FEBS Open Bio ; 9(2): 248-264, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30761251

RESUMO

Lipid-based palmitoylation is a post-translation modification (PTM) which acts as a biological rheostat in life cycle progression of a deadly human malaria parasite, Plasmodium falciparum. P. falciparum palmitoylation is catalyzed by 12 putative palmitoyl acyl-transferase enzymes containing the conserved DHHC-CRD (DHHC motif within a cysteine-rich domain) which can serve as a druggable target. However, the paucity of high-throughput assays has impeded the design of drugs targeting palmitoylation. We have developed a novel strategy which involves engineering of Escherichia coli, a PTM-null system, to enforce ectopic expression of palmitoyl acyl-transferase in order to study Plasmodium-specific palmitoylation and screening of inhibitors. In this study, we have developed three synthetic E. coli strains expressing Plasmodium-specific DHHC proteins (PfDHHC7/8/9). These cells were used for validating acyl-transferase activity via acyl-biotin exchange (ABE) and clickable chemistry methods. E. coli proteome was found to be palmitoylated in PfDHHC-expressing clones, suggesting that plasmodium DHHC can catalyze palmitoylation of E. coli proteins. Upon treatment with generic inhibitor 2-bromopalmitate (2-BMP), a predominant reduction in palmitic acid incorporation is detected. Overall, these findings suggest that synthetic E. coli strains expressing PfDHHCs can enforce global palmitoylation in the E. coli proteome. Interestingly, this finding was corroborated by our in silico palmitoylome profiling, which revealed that out of the total E. coli proteome, 108 proteins were predicted to be palmitoylated as represented by the presence of three cysteine consensus motifs (cluster type I, II, III). In summary, our study reports a proof of concept for screening of chemotherapeutics targeting the palmitoylation machinery using a high-throughput screening platform.


Assuntos
Aciltransferases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Engenharia Genética , Ensaios de Triagem em Larga Escala , Ácido Palmítico/antagonistas & inibidores , Plasmodium falciparum/efeitos dos fármacos , Aciltransferases/metabolismo , Biocatálise , Química Click , Inibidores Enzimáticos/química , Escherichia coli/genética , Escherichia coli/metabolismo , Simulação de Acoplamento Molecular , Ácido Palmítico/metabolismo , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/metabolismo
18.
J Wrist Surg ; 8(1): 49-54, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30723602

RESUMO

Background Fractures of the distal end radius are a common upper extremity fracture. Intra-articular distal end radius fractures are recognized as very complex injuries with a variable prognosis. The aim of the study was to assess the long-term functional outcome of patients treated with Joshi's external stabilizing system (JESS) for displaced intra-articular distal end radius fractures. Materials and Methods A total of 170 patients with intra-articular distal end radius fracture were treated with JESS from 2014 to 2017. The patients were followed up at 2, 6 weeks, 6 months, 1, and 2 years (final) after the surgery. The assessment of pain, range of motion, grip strength, and satisfaction were assessed at 6 months, 1, and 2 years (final) follow-up and scored according to modified Mayo wrist scoring system. Results The good and/or excellent results were found in 82.2% of cases. We observed that patients with age less than 50 years had greater prognosis as compared with patients with more than 50 years of age. Final outcome was also found better in males as compared with females at 6 months, 1, and 2 years postoperatively. Conclusion JESS is an effective treatment technique for intra-articular distal end radius fractures in our community. On long-term follow-up of the patients treated with JESS for intra-articular distal end radius fractures, the functional and radiological outcomes were good with low complication rate.

19.
RSC Adv ; 9(68): 39721-39734, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-35541412

RESUMO

Currently, a straightforward fabrication technique for the development of soft actuators to explore their potential in robotic applications using environmentally compatible raw materials represents an important challenge. A conventional conducting polymer, such as polypyrrole (PPy), shows promising conductivity for such applications. This study presents the synthesis of PPy/polyvinyl alcohol (PPy/PVA)-based ion exchange polymer films containing PEDOT:PSS/SWNT/IL electrodes that undergo conformational changes in response to the applied voltage. Four types of ionic polymer actuator films with different sizes of PPy nanoparticles were fabricated to investigate the size-dependent electromechanical actuation performance. The aim of this study is to design and develop a stable, flexible, and reliable film actuator for robotic applications. Scanning electron microscopy and transmittance electron microscopy were performed to observe the surface morphology and detailed structure of the fabricated actuator films. The current density and ionic conductivity are demonstrated by the cyclic voltammogram and linear sweep voltammogram, respectively. The enhanced values of the water uptake, ion exchange capacity and ionic conductivity of the PPy/PVA polymer composite films enhanced the electrical properties and the tip deflection performance as compared to those of the other reported expensive perfluorinated polymer-based membrane actuators. A two finger-based micro gripping device was also developed, in which both the fingers were made up of the O-PPy/PVA/EL-based ion exchange polymer films. This mechanically stable and flexible film actuator fabricated via a synergistic combination of PPy/PVA composition containing PEDOT:PSS/SWNT/IL electrode surfaces possesses a substantial potential as an actuator material for micro robotic applications.

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