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Aims: The Oxford Shoulder Score (OSS) is a 12-item measure commonly used for the assessment of shoulder surgeries. This study explores whether computerized adaptive testing (CAT) provides a shortened, individually tailored questionnaire while maintaining test accuracy. Methods: A total of 16,238 preoperative OSS were available in the National Joint Registry (NJR) for England, Wales, Northern Ireland, the Isle of Man, and the States of Guernsey dataset (April 2012 to April 2022). Prior to CAT, the foundational item response theory (IRT) assumptions of unidimensionality, monotonicity, and local independence were established. CAT compared sequential item selection with stopping criteria set at standard error (SE) < 0.32 and SE < 0.45 (equivalent to reliability coefficients of 0.90 and 0.80) to full-length patient-reported outcome measure (PROM) precision. Results: Confirmatory factor analysis (CFA) for unidimensionality exhibited satisfactory fit with root mean square standardized residual (RSMSR) of 0.06 (cut-off ≤ 0.08) but not with comparative fit index (CFI) of 0.85 or Tucker-Lewis index (TLI) of 0.82 (cut-off > 0.90). Monotonicity, measured by H value, yielded 0.482, signifying good monotonic trends. Local independence was generally met, with Yen's Q3 statistic > 0.2 for most items. The median item count for completing the CAT simulation with a SE of 0.32 was 3 (IQR 3 to 12), while for a SE of 0.45 it was 2 (IQR 2 to 6). This constituted only 25% and 16%, respectively, when compared to the 12-item full-length questionnaire. Conclusion: Calibrating IRT for the OSS has resulted in the development of an efficient and shortened CAT while maintaining accuracy and reliability. Through the reduction of redundant items and implementation of a standardized measurement scale, our study highlights a promising approach to alleviate time burden and potentially enhance compliance with these widely used outcome measures.
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Background: Cubital tunnel syndrome (CUTS) is a common upper limb compression neuropathy with significant consequences when left untreated. Surgical decompression remains gold-standard treatment for moderate to severe disease, however the optimal operative technique remains unclear. This network meta-analysis (NMA) of Level I and II randomised prospective studies aims to discern superiority between open in-situ, endoscopic and anterior transposition (subcutaneous or submuscular techniques) with respect to the primary outcome of response-to-treatment and secondary outcomes which include complications, post-operative chronic pain VAS scale, return to work and re-operation. Methods: This NMA adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Web of Science, Cochrane Central, Science direct and Embase were searched. The MESH database was further searched with the terms 'cubital tunnel' to improve sensitivity of the search. Data pertaining to the primary and secondary outcomes were pooled for NMA. Results: Following abstract and full-text screening, 10 randomised prospective trials were included. There was no statistical difference in the response-to-treatment between the four studied techniques. Endoscopic decompression conferred a significantly higher complication rate compared to open decompression (Odds Ratio [OR], 4.21; 95% CI, 1.22-14.59). Endoscopic decompression had a statistically significant lower risk of post-operative chronic pain compared to open in-situ decompression (OR, 0.03, 95% CI, 0.00-0.32). There were no differences between techniques with respect to return to work or re-operation rates. Conclusion: Response-to-treatment was similar between the four operative techniques for CUTS. Endoscopic decompression was found to be more hazardous when compared to open-in situ decompression but conferred significantly less post-operative chronic pain. There was significant heterogeneity in reported outcomes between the included articles. The authors suggest conducting more high-quality research with standardised outcome reporting to facilitate comparison. Level of evidence ii: Systematic Review and Meta-analysis of Randomised Prospective Trials- Therapeutic study.
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BACKGROUND: Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss, improve visualization in the surgical field, and to potentially reduce surgical time. There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure, placement site, and duration of use. There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery. AIM: To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery. METHODS: Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken. Intraoperative tourniquet duration, tourniquet pressure and site, and postoperative pain scores using Visual Analogue Score were collected in immediate recovery, at six hours and at 24 h post-op. Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure, duration, site, and pain scores using Pearson correlation coefficient. RESULTS: All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh. There was no correlation between the site of the tourniquet and pain scores in recovery, at six hours and after 24 h. There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op (r = 0.14, P = 0.04) but not at six or 24 h post-operatively. CONCLUSION: This study shows that there was no statistically significant correlation between tourniquet pressure, site and post-op pain in patients undergoing foot and ankle surgery. The choice of using a tourniquet is based on the surgeon's preference, with the goal of minimizing the duration of its application at the operative site.
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BACKGROUND: Self-reported adherence to sling wear is unreliable due to recall bias. We aim to assess the feasibility and accuracy of quantifying sling wear and non-wear utilising slings pre-fitted with a GENEActiv accelerometer that houses triaxial acceleration and temperature sensors. METHODS: Ten participants were asked to wear slings for 480 min (8 h) incorporating 180 min of non-wear time in durations varying from 5-120 min. GENEActiv devices were fitted in sutured inner sling pockets and participants logged sling donning and doffing times. An algorithm based on variability in acceleration in three axes and temperature change was developed to identify sling wear and non-wear and compared to participants' logs. RESULTS: There was no significant difference between algorithm detected non-wear duration (mean ± standard deviation = 172.0 ± 6.8 min/participant) and actual non-wear (179.7 ± 1.0 min/participant). Minute-by-minute agreement of sensor-detected wear and non-wear with participant reported wear was 97.3 ± 1.5% (range = 93.9-99.0), with mean sensitivity 94.3 ± 3.5% (range = 86.1-98.3) and specificity 99.1 ± 0.8% (range = 93.7-100). CONCLUSION: An algorithm based on accelerometer-assessed acceleration and temperature can accurately identify shoulder sling wear/non-wear times. This method may have potential for assessing whether sling wear adherence after shoulder surgeries have any bearing on patient functional outcomes.
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Acelerometria , Ombro , Humanos , Temperatura , Estudos de Viabilidade , Acelerometria/métodos , AceleraçãoRESUMO
Despite the worldwide prevalence and huge burden of pain, pain is an undertreated phenomenon. Currently used analgesics have several limitations regarding their efficacy and safety. The discovery of analgesics possessing a novel mechanism of action has faced multiple challenges, including a limited understanding of biological processes underpinning pain and analgesia and poor animal-to-human translation. Computational pharmacology is currently employed to face these challenges. In this review, we discuss the theory, methods, and applications of computational pharmacology in pain research. Computational pharmacology encompasses a wide variety of theoretical concepts and practical methodological approaches, with the overall aim of gaining biological insight through data acquisition and analysis. Data are acquired from patients or animal models with pain or analgesic treatment, at different levels of biological organization (molecular, cellular, physiological, and behavioral). Distinct methodological algorithms can then be used to analyze and integrate data. This helps to facilitate the identification of biological molecules and processes associated with pain phenotype, build quantitative models of pain signaling, and extract translatable features between humans and animals. However, computational pharmacology has several limitations, and its predictions can provide false positive and negative findings. Therefore, computational predictions are required to be validated experimentally before drawing solid conclusions. In this review, we discuss several case study examples of combining and integrating computational tools with experimental pain research tools to meet drug discovery challenges.
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Analgésicos , Farmacologia , Animais , Humanos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Descoberta de Drogas/métodos , Dor/tratamento farmacológico , Transdução de Sinais , Biologia Computacional/métodosRESUMO
BACKGROUND: Type C3 distal tibial plafond fractures consistently show poor outcomes with high complication rates and significant risk of posttraumatic arthritis. We describe a minimally invasive technique of performing a primary ankle fusion using an anterograde tibial nail and compare our early results to traditional methods of fixation. METHODS: During the acute admission, the patient undergoes an arthroscopic preparation of the ankle joint and insertion of an anterograde nail into the talus. This technique is described in detail and presented alongside a retrospective 5-year review of all adult C3 distal tibial plafond fractures from our center. RESULTS: Twenty-six patients (8 open fractures) had been fixed traditionally using open reduction internal fixation (24 patients) and circular frames (2 patients) with an average follow-up of 20 months. Those internally fixed had protected weightbearing for 3 months. Complications included deep infection (12%), nonunion (8%), malunion (4%), severe posttraumatic osteoarthritis (27%), and the secondary conversion to ankle replacement/fusion (12%) requiring an average of 3 reoperations.Six patients underwent primary fusion (3 open fractures) with an average follow-up of 18 months. Patients were allowed to immediately weightbear. There were no reported complications and the primary fusion group demonstrated shorter hospital stays, faster return to work, and higher mean self-reported foot and ankle score (SEFAS) compared to those treated with ORIF. CONCLUSION: C3 distal tibial plafond fractures are difficult to manage and there has not been a satisfactory method of treating them that allows early return to work, has a low risk of complications, and reduces the risk of posttraumatic tibiotalar arthritis.We present our initial results with a method that uses traditional arthroscopic techniques to prepare the tibiotalar joint together with minimally invasive anterograde tibiotalar nailing. In this initial report of a small group of patients, we found that surgery can be performed once the swelling has subsided after injury and that allowing weightbearing as tolerated did not appear to have a negative effect on initial outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Fraturas do Tornozelo , Artrite , Fraturas Expostas , Tálus , Fraturas da Tíbia , Adulto , Humanos , Tálus/cirurgia , Fixação Interna de Fraturas/métodos , Tornozelo , Estudos Retrospectivos , Consolidação da Fratura , Fraturas da Tíbia/cirurgia , Fraturas do Tornozelo/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Newcastle Disease Virus (NDV) causes severe economic losses in the poultry industry worldwide. Hence, this study aimed to discover a novel bioactive antiviral agent for controlling NDV. Streptomyces misakiensis was isolated from Egyptian soil and its secondary metabolites were identified using infrared spectroscopy (IR), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. The inhibitory activity of bioactive metabolite against NDV were examined. Three experimental groups of 10-day-old specific pathogen-free embryonated chicken eggs (SPF-ECEs), including the bioactive metabolite control group, NDV control positive group, and α-sitosterol and NDV mixture-treated group were inoculated. RESULTS: α-sitosterol (Ethyl-6-methylheptan-2-yl]-10,13-dimethyl-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol), a secondary metabolite of S. misakiensis, completely inhibited hemagglutination (HA) activity of the NDV strain. The HA activity of the NDV strain was 8 log2 and 9 log2 for 0.5 and 0.75% RBCs, respectively. The NDV HA activity for the two concentrations of RBCs was significantly (P < 0.0001) inhibited after α-sitosterol treatment. There was a significant (P < 0.0001) decrease in the log 2 of HA activity, with values of - 0.500 (75%, chicken RBCs) before inoculation in SPF-ECEs and - 1.161 (50%, RBCs) and - 1.403 (75%, RBCs) following SPF-ECE inoculation. Compared to ECEs inoculated with NDV alone, the α-sitosterol-treated group showed improvement in histological lesion ratings for chorioallantoic membranes (CAM) and hepatic tissues. The CAM of the α-sitosterol- inoculated SPF-ECEs was preserved. The epithelial and stromal layers were noticeably thicker with extensive hemorrhages, clogged vasculatures, and certain inflammatory cells in the stroma layer in the NDV group. However, mild edema and inflammatory cell infiltration were observed in the CAM of the treated group. ECEs inoculated with α-sitosterol alone showed normal histology of the hepatic acini, central veins, and portal triads. Severe degenerative alterations, including steatosis, clogged sinusoids, and central veins, were observed in ECEs inoculated with NDV. Mild hepatic degenerative alterations, with perivascular round cell infiltration, were observed in the treated group. CONCLUSION: To the best of our knowledge, this is the first study to highlight that the potentially bioactive secondary metabolite, α-sitosterol, belonging to the terpene family, has the potential to be a biological weapon against virulent NDV. It could be used for the development of innovative antiviral drugs to control NDV after further clinical investigation.
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Doença de Newcastle , Doenças das Aves Domésticas , Streptomycetaceae , Animais , Vírus da Doença de Newcastle , Antivirais/farmacologia , Antivirais/uso terapêutico , Sitosteroides/farmacologia , Sitosteroides/uso terapêutico , Galinhas , Doença de Newcastle/tratamento farmacológico , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/prevenção & controleRESUMO
Soil serves as a reservoir for organic carbon stock, which indicates soil quality and fertility within the terrestrial ecosystem. Therefore, it is crucial to comprehend the spatial distribution of soil organic carbon stock (SOCS) and the factors influencing it to achieve sustainable practices and ensure soil health. Thus, the present study aimed to apply four machine learning (ML) models, namely, random forest (RF), k-nearest neighbors (kNN), support vector machine (SVM), and Cubist model tree (Cubist), to improve the prediction of SOCS in the Srou catchment located in the Upper Oum Er-Rbia watershed, Morocco. From an inventory of 120 sample points, 80% were used for training the model, with the remaining 20% set aside for model testing. Boruta's algorithm and the multicollinearity test identified only nine (9) factors as the controlling factors selected as input data for predicting SOCS. As a result, spatial distribution maps for SOCS were generated for all models, then compared, and further validated using statistical metrics. Among the models tested, the RF model exhibited the best performance (R2 = 0.76, RMSE = 0.52 Mg C/ha, NRMSE = 0.13, and MAE = 0.34 Mg C/ha), followed closely by the SVM model (R2 = 0.68, RMSE = 0.59 Mg C/ha, NRMSE = 0.15, and MAE = 0.34 Mg C/ha) and Cubist model (R2 = 0.64, RMSE = 0.63 Mg C/ha, NRMSE = 0.16, and MAE = 0.43 Mg C/ha), while the kNN model had the lowest performance (R2 = 0.31, RMSE = 0.94 Mg C/ha, NRMSE = 0.24, and MAE = 0.63 Mg C/ha). However, bulk density, pH, electrical conductivity, and calcium carbonate were the most important factors for spatially predicting SOCS in this semi-arid region. Hence, the methodology used in this study, which relies on ML algorithms, holds the potential for modeling and mapping SOCS and soil properties in comparable contexts elsewhere.
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Erosão do Solo , Solo , Carbono , Ecossistema , Monitoramento Ambiental , Aprendizado de MáquinaRESUMO
INTRODUCTION: Lag screw cut-out is a serious complication of dynamic hip screw fixation of trochanteric hip fractures. The lag screw position has been acknowledged as one of the important factors affecting the lag screw cut-out. We propose a modification of the Tip Apex Distance (TAD) and hypothesise that it could improve the reliability of predicting lag screws cut-out in these injuries. MATERIALS AND METHODS: A retrospective study was conducted for hip fracture entries in the period from Jan 2018 to July 2022. A hundred and nine patients were suitable for the final analysis. The modified TAD was measured in millimetres based on the sum of the traditional TAD in the lateral view and the net value of two distances in the AP view, the first distance is from the tip of the lag screw to the opposite point on the femoral head along the axis of the lag screw while the second distance is from that point to the femoral head apex. The first distance is a positive value, whereas the second distance is positive if the lag screw is superior and negative if inferior. A receiver operating characteristic curve was used to evaluate the reliability of the different parameters assessing the lag screw position within the femoral head. RESULTS: Reduction quality, fracture pattern as per the AO/OTA classification, TAD, Calcar Referenced TAD, Axis Blade Angle, Parker's ration in the AP view, Cleveland Zone 1, and modified TAD were statistically associated with lag screw cut-out. Among the tested parameters, the modified TAD had 90.1% sensitivity and 90.9% specificity for lag screw cut-out at a cut-off value of 25 mm with a P-value < 0.001. CONCLUSION: The modified TAD had the highest reliability in the prediction of lag screw cut-out. A value ≤ 25 mm could potentially protect against lag screw cut-out in trochanteric hip fractures.
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STUDY DESIGN: randomized, prospective, and level I clinical study. PURPOSE: To compare the clinical outcomes and radiological findings of revision discectomy alone versus revision discectomy with fusion as surgical treatment for recurrent lumbar disc herniation (RDH). OVERVIEW OF LITERATURE: RDH is a common complication following a primary discectomy. The optimal surgical procedure for RDH is still debated. METHODS: Sixty patients with RDH were randomly divided into two equal groups: the first group underwent revision discectomy alone and the second underwent revision discectomy with fusion. The primary outcomes evaluated were Visual Analog Scale (VAS) for low back and limb pains, Oswestry Disability Index (ODI), disc height indexes, foraminal height index, and disc height subsidence. Secondary outcomes included operative time, blood loss, postoperative hospital stay, and complications. RESULTS: Revision discectomy with fusion showed superior pain relief and improved functional outcomes, including better VAS scores for both back and leg pain and ODI at 24-month follow-up. Additionally, it restored the stability of the spine better with lower disc height subsidence without significant complications. However, these advantages came at the cost of increased blood loss and longer operative time and hospital stays. CONCLUSIONS: Revision discectomy with fusion is recommended for RDH; however, the choice of the procedure should be made caseby- case basis, considering many factors related to the patient and surgical facilities.
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Background: Antimicrobial resistance is a serious threat to public health globally. It is a slower-moving pandemic than COVID-19, so we are fast running out of treatment options. Purpose: Thus, this study was designed to search for an alternative biomaterial with broad-spectrum activity for the treatment of multidrug-resistant (MDR) bacterial and fungal pathogen-related infections. Methods: We isolated Streptomyces species from soil samples and identified the most active strains with antimicrobial activity. The culture filtrates of active species were purified, and the bioactive metabolite extracts were identified by thin-layer chromatography (TLC), preparative high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentrations (MICs) of the bioactive metabolites against MDR bacteria and fungi were determined using the broth microdilution method. Results: Preliminary screening revealed that Streptomyces misakiensis and S. coeruleorubidus exhibited antimicrobial potential. The MIC50 and MIC90 of S. misakiensis antibacterial bioactive metabolite (ursolic acid methyl ester) and antifungal metabolite (tetradecamethylcycloheptasiloxane) against all tested bacteria and fungi were 0.5 µg/ml and 1 µg/mL, respectively, versus S. coeruleorubidus metabolites: thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC50: 2 µg/ml and MIC90: 4 µg/mL) and fungi (MIC50: 4 µg/ml and MIC90: 8 µg/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of Streptococcus pyogenes, S. agalactiae, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovars, colistin-resistant Aeromonas hydrophila and K. pneumoniae, and vancomycin-resistant Staphylococcus aureus. Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant Candida albicans, Cryptococcus neoformans, C. gattii, Aspergillus flavus, A. niger, and A. fumigatus. Ursolic acid methyl ester was applied in vivo for treating S. aureus septicemia and K. pneumoniae pneumonia models in mice. In the septicemia model, the ursolic acid methyl ester-treated group had a significant 4.00 and 3.98 log CFU/g decrease (P < 0.05) in liver and spleen tissue compared to the infected, untreated control group. Lung tissue in the pneumonia model showed a 2.20 log CFU/g significant decrease in the ursolic acid methyl ester-treated group in comparison to the control group. The haematological and biochemical markers in the ursolic acid methyl ester-treated group did not change in a statistically significant way. Moreover, no abnormalities were found in the histopathology of the liver, kidneys, lungs, and spleen of ursolic acid methyl ester-treated mice in comparison with the control group. Conclusion: S. misakiensis metabolite extracts are broad-spectrum antimicrobial biomaterials that can be further investigated for the potential against MDR pathogen infections. Hence, it opens up new horizons for exploring alternative drugs for current and reemerging diseases.
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Anti-Infecciosos , COVID-19 , Staphylococcus aureus Resistente à Meticilina , Pneumonia , Sepse , Camundongos , Animais , Staphylococcus aureus , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Bactérias , Fungos , Testes de Sensibilidade Microbiana , Pneumonia/tratamento farmacológico , Klebsiella pneumoniae , Sepse/tratamento farmacológico , Ácido UrsólicoRESUMO
BACKGROUND: The distinction between foot and ankle wound healing complications as opposed to infection is crucial for the appropriate and efficacious allocation of antibiotic therapy. Multiple reports have focused on the diagnostic accuracy of different inflammatory markers, however, mainly in the diabetic population. AIM: To evaluate the diagnostic accuracy of white cell count (WCC) and C-reactive protein (CRP) as diagnostic tools for this distinction in the non-diabetic cohort. METHODS: Data was reviewed from a prospectively maintained Infectious Diseases Unit database of 216 patients admitted at Leicester University Hospitals-United Kingdom with musculoskeletal infections over the period between July 2014 and February 2020 (68 mo). All patients with confirmed diagnosis of diabetes were excluded while only those with confirmed microbiological or clinical diagnosis of foot or ankle infection were included in our study. For the included patients, we retrospectively retrieved the inflammatory markers (WCCs and CRP) at the time of presentation. Values of CRP 0-10 mg/L and WCC 4.0-11.0 × 109/L were considered normal. RESULTS: After exclusion of patients with confirmed diabetes, 25 patients with confirmed foot or ankle infections were included. All infections were confirmed microbiologically with positive intra-operative culture results. 7 (28%) patients with osteomyelitis (OM) of the foot, 11 (44%) with OM of the ankle, 5 (20%) with ankle septic arthritis and 2 (8%) patients with post-surgical wound infection were identified. Previous bony surgery was identified in 13 (52%) patients, either a corrective osteotomy or an open reduction and internal fixation for a foot or ankle fracture with the infection developing on top of the existing metalwork. 21 (84%) patients did have raised inflammatory markers while 4 (16%) patients failed to mount an inflammatory response even with subsequent debridement and removal of metal work. CRP sensitivity was 84%, while WCC sensitivity was only 28%. CONCLUSION: CRP has a relatively good sensitivity in the diagnosis of foot and ankle infections in non-diabetic patients, whereas WCC is a poor inflammatory marker in the detection of such cases. In presence of clinically high level of suspicion of foot or ankle infection, a normal CRP should not rule out the diagnosis of OM.
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Purpose: The development and study of hepatitis C virus (HCV) vaccine candidates' individualized responses are of great importance. Here we report on an HCV DNA vaccine candidate based on selected envelope (E1/E2) epitopes. Besides, we assessed its expression and processing in human peripheral blood mononuclear cells (PBMCs) and in vivo cellular response in mice. Materials and Methods: HCV E1/E2 DNA construct (EC) was designed. The antigen expression of EC was assayed in PBMCs of five HCV-uninfected donors via a real-time quantitative polymerase chain reaction. Serum samples from 20 HCV antibody-positive patients were used to detect each individual PBMCs expressed antigens via enzyme-linked immunosorbent assay. Two groups, five Swiss albino mice each, were immunized with the EC or a control construct. The absolute count of lymph nodes' CD4+ and CD8+ T-lymphocytes was assessed. Results: Donors' PBMCs showed different levels of EC expression, ranging between 0.83-2.61-fold in four donors, while donor-3 showed 34.53-fold expression. The antigens expressed in PBMCs were significantly reactive to the 20 HCV antibody repertoire (all p=0.0001). All showed comparable reactivity except for donor-3 showing the lowest reactivity level. The absolute count % of the CD4+ T-cell significantly increased in four of the five EC-immunized mice compared to the control group (p=0.03). No significant difference in CD8+ T-cells % was observed (p=0.89). Conclusion: The inter-individual variation in antigen expression and processing dominance was evident, showing independence in individuals' antigen expression and reactivity levels to antibodies. The described vaccine candidate might result in a promising natural immune response with a possibility of CD4+ T-cell early priming.
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This study aimed at exploring the proteomic profile of PBMCs to predict treatment response in pulmonary tuberculosis (PTB). This was a pilot study conducted among 8 adult patients from Zanzibar, Tanzania with confirmed PTB. Blood samples were collected at baseline, at 2 months of treatment, and at the end of treatment at 6 months. Proteins were extracted from PBMCs and analyzed using LC-MS/MS based label free quantitative proteomics. Overall, 3,530 proteins were quantified across the samples, and 12 differentially expressed proteins were identified at both 2 months of treatment and at treatment completion, which were involved in cellular and metabolic processes, as well as binding and catalytic activity. Seven were downregulated proteins (HSPA1B/HSPA1A, HSPH1, HSP90AA1, lipopolysaccharide-binding protein, complement component 9, calcyclin-binding protein, and protein transport protein Sec31A), and 5 proteins were upregulated (SEC14 domain and spectrin repeat-containing protein 1, leucine-rich repeat-containing 8 VRAC subunit D, homogentisate 1,2-dioxygenase, NEDD8-activating enzyme E1 regulatory subunit, and N-acetylserotonin O-methyltransferase-like protein). The results showed that proteome analysis of PBMCs can be used as a novel technique to identify protein abundance change with anti-tuberculosis treatment. The novel proteins elucidated in this work may provide new insights for understanding PTB pathogenesis, treatment, and prognosis.
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Leucócitos Mononucleares , Tuberculose Pulmonar , Adulto , Humanos , Leucócitos Mononucleares/metabolismo , Projetos Piloto , Tanzânia , Proteômica/métodos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Proteoma/metabolismo , Tuberculose Pulmonar/metabolismoRESUMO
From 2010 to 2013, genotype I avian influenza A(H9N2) viruses of the G1-lineage were isolated from several poultry species in Egypt. In 2014, novel reassortant H9N2 viruses were detected in pigeons designated as genotype II. To monitor the subsequent genetic evolution of Egyptian A(H9N2) viruses, we characterized the full genomes of 173 viruses isolated through active surveillance from 2017 to 2022. In addition, we compared the virological characteristics and pathogenicity of representative viruses. Phylogenetic analysis of the HA indicated that all studied sequences from 2017-2021 were grouped into G1-like H9N2 viruses previously detected in Egypt. Phylogenetic analysis indicated that the Egyptian A(H9N2) viruses had undergone further reassortment, inheriting four genes (PB2, PB1, PA, NS) from genotype II, with their remaining segments deriving from genotype I viruses (these viruses designated as genotype III). Studying the virological features of the two most dominant genotypes (I and III) of Egyptian H9N2 viruses in vitro and in vivo indicated that both replicated well in mammalian cells, but did not show any clinical signs in chickens, ducks, and mice. Monitoring avian influenza viruses through surveillance programs and understanding the genetic and antigenic characteristics of circulating H9N2 viruses are essential for risk assessment and influenza pandemic preparedness.
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Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Influenza Humana , Animais , Galinhas , Egito/epidemiologia , Humanos , Influenza Aviária/epidemiologia , Mamíferos , Camundongos , Filogenia , Vírus ReordenadosRESUMO
BACKGROUND: Tibial shaft fractures are usually treated by interlocking nails or plates. The ideal implant choice depends on many variables. AIM: To assess the mechanical behavior of interlocking nails and plates in the treatment of closed comminuted midshaft fractures of the tibia using finite element analysis. MATERIAL AND METHODS: This is a prospective study of 50 patients with a mean age of 28.4 years with closed comminuted fractures of the midshaft of the tibia. Data evaluation was done by Finite element analysis (FEA). Fixation was revised in two cases. RESULTS: After load application, there were significant differences in both bending (P = 0.041) and strain percent (P = 0.017), reflecting that interlocking nails were superior to plates. There were also significant differences between titanium and stainless-steel materials in bending (p = 0.041) and strain percent (p = 0.017) after applying load, indicating that titanium was superior to stainless steel. CONCLUSION: Interlocking nails are superior to plates in treating midshaft tibial fractures. The use of blocking screws may be needed in interlocking nails depending on the pattern and extension of the fracture.
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BACKGROUND: Newcastle disease virus (NDV) is a severe disease that affects domestic and wild birds. Controlled antibiotics derived from probiotics have been examined as prospective solutions for preserving seroconversion in NDV-vaccinated fowl. In this study, the secondary metabolite "telomycin" was extracted from Streptomyces coeruleorubidus (S. coeruleorubidus) isolated from Egypt's cultivated soil. The structure of telomycin was determined by the elucidation of spectroscopic analysis, including nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectra, and comparison with the literature. The antiviral activity of the secondary metabolite was tested by checking its effect on NDV hemagglutination activity (HA). Moreover, HA of NDV was tested after inoculation of NDV (control) and a combination of telomycin and NDV in 10- days- specific pathogen-free embryonated chicken eggs (SPF-ECE) daily candling. Histopathological examination was performed for chorioallantoic membranes and liver of SPF-ECE. RESULTS: S. coeruleorubidus secondary metabolite "telomycin" showed complete hemagglutination inhibition (HI) activity of NDV strain (MN635617) with log106 infectivity titers (EID50/mL). The HA of NDV strain was 8 log2 and 9 log2 with 0.5% and 0.75% of chicken RBCs, respectively. Preserved structures of chorioallantoic-membranes (CAM) with dilated capillary networks were observed in the treated group inoculated with telomycin and NDV. Histological changes in SPF-ECE liver were examined after inoculation in ova to further characterize the telomycin effect. Telomycin and NDV mixture inoculated group showed preserved cytoarchitecture of hepatocytes with the presence of perivascular foci of lymphocytes. The group that was inoculated with telomycin alone showed normal histology of hepatic acini, central veins, and portal triads. CONCLUSION: S. coeruleorubidus telomycin is a promising bioactive agent that might be a biological weapon against a deadly chicken NDV that costs farmers a lot of money.
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Doença de Newcastle , Streptomyces , Vacinas Virais , Animais , Galinhas , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle , Estudos Prospectivos , Vacinas Virais/farmacologiaRESUMO
Introduction: Meckel's diverticulum is a congenital anomaly that is often detected incidentally. When it presents symptomatically, it causes painless gastrointestinal bleeding. Nevertheless, in rare instances, it can cause acute intestinal obstruction, often obscuring the true clinical picture. Case presentation: A 31-year-old male presented to the emergency department with a 24-h history of unremitting nausea, biliary emesis, abdominal distension, and absolute constipation. After ruling out the most common etiologies of acute bowel obstruction, radiological imaging was obtained and was suggestive of meckel's diverticulum. Laparoscopic meckel's diverticulectomy was performed, with the subsequent histopathological analysis confirming ectopic gastric tissue. Discussion: Meckel's diverticulum occurs consequent to incomplete obliteration of the vitelline or omphalomesenteric duct, which connects the developing intestines to the yolk sac. It is found in roughly 2% of the population, of which only about 4% may become symptomatic due to any number of complications. Specifically, small bowel obstruction (SBO) and diverticulitis secondary to ectopic gastric or pancreatic tissue are the most common presentations of symptomatic MD. Conclusion: Although relatively rare in adults, MD should be considered in the list of differentials in patients with intussusception leading to SBO, especially on a background history unremarkable for the most common etiologies causing SBO including post-operative adhesions and hernias.
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ABSTRACT: Burrowing behaviour is used to assess pain-associated behaviour in laboratory rodents. To gain insight into how models of disease-associated persistent pain and analgesics affect burrowing behaviour, we performed a systematic review and meta-analysis of studies that assessed burrowing behaviour. A systematic search in March 2020 and update in September 2020 was conducted in 4 databases. Study design characteristics and experimental data were extracted, followed by a random-effects meta-analysis. We explored the association between burrowing and monofilament-induced limb withdrawal. Dose response relationship was investigated for some analgesics. Forty-five studies were included in the meta-analysis, in which 16 model types and 14 drug classes were used. Most experiments used rat (79%) and male (72%) animals. Somatic inflammation and trauma-induced neuropathy models were associated with reduced burrowing behaviour. Analgesics (nonsteroidal anti-inflammatory drug and gabapentinoids) attenuated burrowing deficits in these models. Reporting of measures to reduce risk of bias was unclear except for randomisation which was high. There was not a correlation ( R2 = 0.1421) between burrowing and monofilament-induced limb withdrawal. Opioids, gabapentin, and naproxen showed reduced burrowing behaviour at high doses, whereas ibuprofen and celecoxib showed opposite trend. The findings indicate that burrowing could be used to assess pain-associated behaviour. We support the use of a portfolio of composite measures including spontaneous and stimulus-evoked tests. The information collected here could help in designing experiments involving burrowing assessment in models of disease-associated pain.
Assuntos
Ibuprofeno , Naproxeno , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Comportamento Animal/fisiologia , Celecoxib/uso terapêutico , Modelos Animais de Doenças , Gabapentina/farmacologia , Gabapentina/uso terapêutico , Ibuprofeno/farmacologia , Ibuprofeno/uso terapêutico , Masculino , Naproxeno/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Ratos , RoedoresRESUMO
BACKGROUND: H1N1 and H3N2 influenza A viruses circulate in people as seasonal influenza viruses. Data on influenza infection rates and circulation in demographic subpopulations in Egypt are limited. In this study, we aimed to determine the incidence and seroprevalence of seasonal influenza A virus infections in a cohort of rural Egyptians between 2017 and 2020. METHODS: A total of 2383 subjects were enrolled from 390 households in five study sites in Northern Egypt. Informed consents were obtained. Sera were collected from participants on an annual basis (Baseline: 2016-2017, Follow up 1: 2017-2018, Follow up 2: 2018-2019, and Follow up 3: 2019-2020) to determine seroprevalence of antibodies against H1N1 and H3N2 viruses by hemagglutination inhibition assay and to estimate incidence based on seroconversion. RESULTS: Seropositivity against H1N1 was over 40% and over 60% against H3N2. The high seroprevalence was due to natural infection because participants were mostly unvaccinated. Seropositive participants were younger than seronegative participants indicating that the infection rate is higher in children. Incidence of both viruses ranged from 4% to 28% depending on study year. The incidence and seroprevalence of H3N2 and H1N1 infections at Follow up 1, 2, and 3 showed an increase at Follow up 2 observed for all age categories corresponding to season 2018-2019, at which the vaccine efficacy was the lowest worldwide compared with preceding and following seasons. CONCLUSIONS: This cohort study provided estimates of influenza A infection rates among rural Egyptians. We recommend updating influenza vaccination programs to focus on such populations.