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1.
Neth J Med ; 78(5): 261-268, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33093251

RESUMO

BACKGROUND: The study aimed to look at alterations in expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and their potential use as biomarkers in the pathogensis of SLE. METHODS: SLE patients (n = 41) and healthy controls (n = 50) were recruited. Quantitative RT-PCR/ELISA assays were performed for expression of MMP and TIMP mRNA in whole blood and PBMC; and corresponding serum protein levels. Intracellular levels of MMP-2 and MMP-9 proteins were analysed by flow cytometry. RESULTS: Based on SLEDAI scores patients were grouped into active (SLEDAI ≥ 10) and inactive cases (SLEDAI < 10). In active cases, MMP-2 expression significantly increased and TIMP-2 expression was decreased (p < 0.0001) both at serum secretion (p = 0.0003) and mRNA (p < 0.0001) levels as compared to inactive cases. MMP-9 and TIMP-1 showed significantly reduced serum secretion and mRNA expression (p < 0.0001) in active cases as compared to inactive cases. Intracellular concentration of MMP-9 was reported to be higher in neutrophils, while MMP-2 was mainly found in lymphocytes of SLE patients as compared to controls. MMP/TIMP ratio profile was altered as SLE disease progresses. INTERPRETATION & CONCLUSIONS: Findings suggest disturbed MMP and TIMP levels have a role in the pathogenesis of SLE.

2.
Int Orthop ; 44(12): 2819, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32970201

RESUMO

The published online version contains mistake, as the Fig. 1 legend should read "Kaplan-Meier survival curve for 30-day survival for 2020 cohort COVID-19 positive vs COVID-19 negative" whilst the Fig. 2 legend should read "Kaplan-Meier survival curve for 30-day survival 2020 COVID-19 negative group vs 2019 cohort".

3.
Int Orthop ; 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32862265

RESUMO

PURPOSE: Thirty-day mortality of patients with hip fracture is well researched and predictive; validated scoring tools have been developed (Nottingham Hip Fracture Score, NHFS). COVID-19 has significantly greater mortality in the elderly and comorbid patients which includes hip fracture patients. Non-operative treatment is not appropriate due to significantly higher mortality, and therefore, these patients are often exposed to COVID-19 in the peri-operative period. What is unclear is the effect of concomitant COVID-19 infection in these patients. METHODS: A multicentre prospective study across ten sites in the United Kingdom (responsible for 7% of hip fracture patients per annum in the UK). Demographic and background information were collected by independent chart review. Data on surgical factors included American Society of Anesthesiologists (ASA) score, time to theatre, Nottingham Hip fracture score (NHFS) and classification of fracture were also collected between 1st March 2020 and 30th April 2020 with a matched cohort from the same period in 2019. RESULTS: Actual and expected 30-day mortality was found to be significantly higher than expected for 2020 COVID-19 positive patients (RR 3.00 95% CI 1.57-5.75, p < 0.001), with 30 observed deaths compared against the 10 expected from NHFS risk stratification. CONCLUSION: COVID-19 infection appears to be an independent risk factor for increased mortality in hip fracture patients. Whilst non-operative management of these fractures is not suggested due to the documented increased risks and mortality, this study provides evidence to the emerging literature of the severity of COVID-19 infection in surgical patients and the potential impact of COVID-19 on elective surgical patients in the peri-operative period.

4.
SAR QSAR Environ Res ; 31(6): 439-455, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32539470

RESUMO

The human breast cancer resistance protein (BCRP), one of the members of the large ATP binding cassette (ABC) transporter superfamily, is crucial for resistance against chemotherapeutic agents. Currently, it has been emerged as one of the best biological targets for the designing of small molecule drugs capable of eliminating multidrug resistance in breast cancer. In order to gain insights into the relationship between the molecular structure of compounds and the ABCG2 inhibition, a multi-QSAR approach using different methods was performed on a dataset of 294 ABCG2 inhibitors with diverse scaffolds. The best models obtained by different chemometric methods have the following statistical characteristics: Monte Carlo Optimization-based QSAR (sensitivity = 0.905, specificity = 0.6255, accuracy = 0.756, and MCC = 0.545), Bayesian classification model (sensitivity = 0.735, specificity = 0.775, and concordance = 0.757); structural and physicochemical interpretation analysis-random forest method (balance accuracy = 0.750, sensitivity = 0.810, and specificity = 0.700). Additionally, structural fingerprints modulating the ABCG2 inhibitory properties were identified from the best models of each method and also validated with each other. The current modelling study is an attempt to get a deep insight into the different important structural fingerprints modulating ABCG2 inhibition.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Mapeamento de Nucleotídeos , Relação Quantitativa Estrutura-Atividade , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/química , Teorema de Bayes , Estrutura Molecular , Método de Monte Carlo , Proteínas de Neoplasias/química
6.
Cancer Lett ; 483: 1-11, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32247870

RESUMO

The recurrence rate of soft tissue and bone sarcomas strongly correlates to the status of the surgical margin after excision, yet excessive removal of tissue may lead to distinct, otherwise avoidable morbidity. Therefore, adequate margination of sarcomas both pre- and intra-operatively is a clinical necessity that has not yet fully been met. Current guidance for soft-tissue sarcomas recommends an ultrasound scan followed by magnetic resonance imaging (MRI). For bone sarcomas, two plane radiographs are required, followed similarly by an MRI scan. The introduction of more precise imaging modalities may reduce the morbidity associated with sarcoma surgery; the PET-CT and PET-MRI approaches in particular demonstrating high clinical efficacy. Despite advancements in the accuracy in pre-operative imaging, translation of an image to surgical margins is difficult, regularly resulting in wider resection margins than required. For soft tissue sarcomas there is currently no standard technique for image guided resections, while for bone sarcomas fluoroscopy may be used, however margins are not easily discernible during the surgical procedure. Near infra-red (NIR) fluorescence guided surgery offers an intra-operative modality through which complete tumour resection with adequate tumour-free margins may be achieved, while simultaneously minimising surgical morbidity. NIR imaging presents a potentially valuable adjunct to sarcoma surgery. Early reports indicate that it may be able to provide the surgeon with helpful information on anatomy, perfusion, lymphatic drainage, tumour margins and metastases. The use of NIR fluorochromes have also been demonstrated to be well tolerated by patients. However, prior to widespread implementation, studies related to cost-effectiveness and the development of protocols are essential. Nevertheless, NIR imaging may become ubiquitous in the future, carrying the potential to transform the surgical management of sarcoma.

7.
Lupus ; 28(4): 545-554, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30857465

RESUMO

Several studies have demonstrated associations between interleukin-18 polymorphisms and risk of systemic lupus erythematosus in different populations except one of Indian origin. We therefore investigated for the influence of interleukin-18 (-1297T/C, -607A/C, -137G/C; + 105A/C) polymorphisms on genetic susceptibility and clinical expression of the disease in Indian systemic lupus erythematosus patients. A total of 200 systemic lupus erythematosus patients and 201 controls were recruited. Genotyping of interleukin-18 polymorphisms were performed by polymerase chain reaction-restriction fragment length polymorphism. Serum interleukin-18 levels were measured by enzyme-linked immunosorbent assay. Interleukin-18 (-1297T/C; -137G/C) polymorphisms showed significant association with genetic susceptibility to the disease in our systemic lupus erythematosus cohort. Stratification analysis revealed -1297CC and -1297C associated with renal involvement (odds ratio = 3.4, correcting p value = 0.0207), (odds ratio = 2.0, correcting p value = 0.0054) respectively. Additionally, -1297C allele frequency was significantly increased in patients with anti-nucleosome antibody (odds ratio = 2.1, correcting p value = 0.0301). Haplotype analysis showed CC haplotype strongly associated with serositis (odds ratio = 9.1, correcting p values = 0.0009) and neurologic involvement (odds ratio = 9.3, correcting p value = 0.0018). We reported a 2.7-fold increase in serum interleukin-18 levels in patients (511.5 ± 242.3 pg/ml) compared to controls (189.4 ± 80.8 pg/ml) ( p < 0.0001). Furthermore, interleukin-18 levels were positively correlated with disease activity ( r = 0.548, p = 0.0001) and renal involvement in the patients with lupus nephritis ( r = 0.569, p < 0.0001). In summary, interleukin-18 polymorphisms elucidated in this study appear to confer genetic susceptibility to the disease and are associated with renal, serositis and neurologic involvement in Indian systemic lupus erythematosus patients.


Assuntos
Predisposição Genética para Doença , Interleucina-18/genética , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Índia/epidemiologia , Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Estatísticas não Paramétricas , Adulto Jovem
11.
Proc Inst Mech Eng H ; 232(4): 412-417, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29473455

RESUMO

Single-radius femoral total knee design aims to deliver improved kinematic behaviour when compared to the standard two-radii geometry. This study has evaluated the behaviour, through a functional range of motion in the sagittal plane, of a single-radius femoral component compared to a dual-radius standard knee construct. Particular focus was placed on how the flexion axes of the native and replaced knee approximated to the transepicondylar axis through a loaded navigated knee design. Significant differences in flexion arcs were noted between the native and total knee arthroplasty state. These arcs were not uniform in all knees and did not display single-radius behaviour. There were no significant differences in the location of flexion axes in the native and total knee arthroplasty knee. Both exhibited similar posterior and inferior transverse axes of motion with respect to the anatomical epicondylar axis. This work has cast doubt on the reliability under loaded conditions of the single-radius concept, but the close proximity of the flexion axes of each replaced knee in relation to the functional flexion axis of the native knee may be the true basis of this purported improved kinematic performance.


Assuntos
Artroplastia do Joelho , Fêmur , Fenômenos Mecânicos , Desenho de Prótese , Fenômenos Biomecânicos
12.
Mymensingh Med J ; 27(1): 149-158, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29459607

RESUMO

Ureteral stent placement is a common procedure in urologic practice. Forgotten, encrusted D/J stents represent a difficult problem for urologists. The major complications are infection, impaired renal function, migration, encrustation, stone formation and multiple fragmentation of stent. A consensus on the best therapeutic approach is still lacking. Here we present our experience with endoscopic management of this challenging problem and discuss the multimodal endourologic approaches for treating forgotten, encrusted ureteral stents. In this prospective observational study 29 patients (17 males and 12 females), age ranges from 19 to 57 years with 35 (23 unilateral and 6 bilateral) encrusted ureteral stents, indwelling for 5 to 78 months were treated in the Department of Urology, Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh from January 2011 to December 2015. All patients were evaluated by urine culture and sensitivity, renal function. Stent encrustation and the associated stone burden were estimated by plain radiograph. Treatment decisions were made based on the clinical presentation, degree of encrustation, stone burden and image findings. Patients were followed up to 06 months. The main indications for stenting were pyelolithotomy, ureterolithotomy, ureteroneocystostomy, URS and pyeloplasty. In kidney, mild encrustation was common (48.3%) moderate encrustation (27.6%) was less common; where as in ureter and urinary bladder, moderate encrustation was common (72.4% and 44.8%). Over three-quarters 22(75.9%) of the patients underwent extracorporeal shockwave lithotripsy (ESWL) and 10(34.5%) percuteneousnephrostomy preoperatively. Retrograde ureteroscopy with intracorporeal lithotripsy (URS & ICPL) was done in 29 cases and cystolitholapaxy (CLL) in 16(55%) cases. Cystolithotomy & PCNL was rarely done. The mean number of procedures was 2.8 (range: 1-7). Using these multimodal approaches, all stents and associated stones were eventually removed with minor complications. Nine patients developed haematuria, 5 urosepsis and 4 both haematuria & urosepsis. Multimodal endourologic approaches can safely remove forgotten, encrusted D/J stents, if treatment is tailored to the volume of encrustation and associated stone. Imaging evaluation and documentation of negative urine culture are imperative prior to any attempt to remove the stent.


Assuntos
Nefrostomia Percutânea , Stents , Ureter , Adulto , Bangladesh , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Stents/efeitos adversos , Adulto Jovem
13.
Br J Cancer ; 118(5): 634-638, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29381684

RESUMO

BACKGROUND: Indeterminate pulmonary nodules in patients diagnosed with osteosarcoma present a challenge for accurate staging and prognosis. The aim of this study was to explore the significance of this finding. METHODS: A retrospective cohort study of 120 patients with osteosarcoma was performed in the North East of England. Chest computed tomographies (CTs) at presentation were reviewed and the incidence of 'indeterminate' nodules recorded. Follow-up scans were reviewed and survival as well as prognostic features were analysed. RESULTS: 25% of our cohort presented with indeterminate nodules. Of these, 33% were subsequently confirmed as metastases, the majority within a year. Kaplan-Meier survival analysis showed that patients with indeterminate nodules fared better than those with frank metastatic disease, and similar to those who presented with a normal chest CT. We found no radiographic features that predicted survival. CONCLUSIONS: Indeterminate nodules remain a clinical and diagnostic dilemma. Close monitoring of patients is advised during the first year from presentation, and there is potential for indeterminate nodules to develop into frank metastases later than five years from presentation.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Adolescente , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Criança , Inglaterra , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteossarcoma/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Adulto Jovem
14.
J Helminthol ; 92(1): 125-127, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28181472

RESUMO

Filariasis is very common in tropical countries. It is endemic in the coastal areas of India. We report four cases of haematological malignancy where peripheral blood and bone marrow smears did not show any microfilariae but conventional cytogenetic preparations from all the four cases showed the presence of parasites. Their morphology confirmed the diagnosis of all cases as bancroftian filariasis. Therefore all types of cytogenetic preparations should be screened carefully in the endemic areas along the coastal zones of India for the presence of this parasite.


Assuntos
Filariose/sangue , Filariose/complicações , Leucemia de Células B/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Microfilárias , Mieloma Múltiplo/complicações , Adulto , Idoso , Animais , Análise Citogenética/métodos , Filariose/diagnóstico , Filariose/epidemiologia , Humanos , Leucemia de Células B/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Masculino , Mieloma Múltiplo/epidemiologia , Parasitemia , Fatores de Risco , Adulto Jovem
15.
Int J Lab Hematol ; 40(2): 196-200, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29160616

RESUMO

INTRODUCTION: Haemoglobin estimation is one of the most important clinical investigations. Many techniques are available to measure haemoglobin; still there is a need for a haemoglobin assay technique which is cheap, robust and simple and can be used in field conditions very quickly using figure prick sample. We evaluated a cyanmethaemoglobin-based haemoglobin estimation using a microtitre plates for the purpose. METHODS: Microtitre plate-based haemoglobin estimation was developed using cyanmethaemoglobin-based assay and was compared with standard haematology analyser-based haemoglobin estimation in a large number of samples from a population of voluntary blood donors. Various tests were performed to evaluate the stability of colour, variation of the results during duplicate assay on the same days and on different days as well as linearity of the test was performed against broad range of haemoglobin values for the new microtitre plate-based technique. Standard statistical test of significance was applied to validate the assay. RESULTS: Total 200 samples from in-house and field conditions were evaluated. 10 µL blood sample in 300 µL Drabkin's solution provided optimum and comparable results after 10 minutes of incubation. The colour was stable up to 6 hours, the coefficient of variation was less than 3%, and the cost per test including everything was less than 3 cent/2P. Turnaround time for 90 samples was only 30 minutes. CONCLUSION: Cyanmethaemoglobin-based assay in microtitre plate is feasible, robust, rapid, cheap and cost-effective method for haemoglobin estimation in field conditions.


Assuntos
Hemoglobinas/análise , Análise em Microsséries/normas , Análise Custo-Benefício , Hemoglobinas/economia , Humanos , Metemoglobina/análogos & derivados
17.
Sci Rep ; 7(1): 11256, 2017 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-28900169

RESUMO

The high field phenomena of inter-valley transfer and avalanching breakdown have long been exploited in devices based on conventional semiconductors. In this Article, we demonstrate the manifestation of these effects in atomically-thin WS2 field-effect transistors. The negative differential conductance exhibits all of the features familiar from discussions of this phenomenon in bulk semiconductors, including hysteresis in the transistor characteristics and increased noise that is indicative of travelling high-field domains. It is also found to be sensitive to thermal annealing, a result that we attribute to the influence of strain on the energy separation of the different valleys involved in hot-electron transfer. This idea is supported by the results of ensemble Monte Carlo simulations, which highlight the sensitivity of the negative differential conductance to the equilibrium populations of the different valleys. At high drain currents (>10 µA/µm) avalanching breakdown is also observed, and is attributed to trap-assisted inverse Auger scattering. This mechanism is not normally relevant in conventional semiconductors, but is possible in WS2 due to the narrow width of its energy bands. The various results presented here suggest that WS2 exhibits strong potential for use in hot-electron devices, including compact high-frequency sources and photonic detectors.

18.
Mol Biol Rep ; 44(5): 413-417, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28879539

RESUMO

Co-inheritance of gamma and beta globin gene mutations in a compound heterozygous state is rare but of clinical interest as it provides an important data on understanding the HbF expression. Hematological analysis was carried out (Sysmex KX-21). F-cells were enumerated using flow cytometry. Beta globin gene was analysed by CRDB technique and by DNA sequencing. Gamma globin promoter region was sequenced and expression studies were carried out using real time Taqman assay. We report a family, where two inherited defects of the ß globin gene cluster segregate. The proband and her sibling were compound heterozygotes for a novel Gγ promoter mutation and the 619 bp deletion a common Indian ß thalassemia mutation. Molecular characterization revealed that the father (HbA2 5.1%, HbF 5.4%), proband (HbA2 3.6%, HbF 31.7%) and her brother (HbA2 3.9%, HbF 23.6%) were heterozygous for the 619 bp deletion. The mother (HbA2 2.1%, HbF 3.4%) had a normal ß globin gene. As both the children showed high HbF levels, the γ globin gene work up was carried out. The Gγ-globin gene promoter analysis revealed that the mother and the two children were heterozygous for a 5 bp deletion -ATAAG (-533 to -529) that resides in the GATA binding site. These findings suggest that the 5 bp deletion in the Gγ globin promoter has a functional role in silencing the γ-globin gene expression in adults by disrupting GATA-1 binding and the associated repressor complex and results in the up-regulation of gamma globin gene expression. When co-inherited with ß -thalassemia trait it leads to a phenotype of HPFH.


Assuntos
Hemoglobina Fetal/genética , Globinas beta/genética , Adulto , Sequência de Bases , Criança , Feminino , Hemoglobina Fetal/metabolismo , Globinas/genética , Globinas/metabolismo , Humanos , Masculino , Família Multigênica , Mutação , Linhagem , Fenótipo , Regiões Promotoras Genéticas , Deleção de Sequência , Globinas beta/metabolismo , Talassemia beta/genética , gama-Globinas/genética
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