Prevalence of Connective Tissue Diseases in Egyptian Patients Presenting with Fever of Unknown Origin

Objective To estimate the prevalence of connective tissue diseases in patients presenting with fever of unknown origin (FUO). Patients and Methods In this study thirty patients diagnosed as FUO (Group 1), in 2008, were included in an observational study and diagnostic workup. Additionally, retrospective analysis of seventy patients’ files (Group 2), for patients who presented with prolonged unexplained pyrexia to the same hospital in the previous two years, was performed. Patients were subjected to: full clinical assessment including full history taking, thorough clinical examination, laboratory investigations including the basic investigations for patients with prolonged fever, complete blood count, erythrocytes sedimentation rate, urine analysis and culture, blood culture, sputum culture and plain chest X ray. Further diagnostic work up and/or procedures were requested according to the potential diagnostic clues (PDC) present in every patient. Results Out of 100 FUO patients, 50% were found to have infectious diseases, 24% were found to have connective tissue diseases, 8% miscellaneous causes and 7% neoplastic diseases ( P < 0.05). In 11 patients no definite cause for FUO could be identified. Connective tissue patients were: eight systemic lupus patients (33.3%), five patients with familial mediterranean fever (20.8%), four patients with rheumatoid arthritis (16.6%), three patients (12.5%) with Still's disease and Rheumatic fever and one patient with Behçet syndrome/Crohn's disease (4.3%), ( P < 0.05). Conclusions Despite the advanced technology, FUO remains a challenging medical problem. Infections were the most common cause of FUO in Egypt, confirming the trends found in other parts of the world. There was an increased prevalence of connective tissue patients presented with prolonged unexplained fever. A keen clinical eye, meticulous history taking and repeated physical examination remained the most important diagnostic tools in FUO patients

In vitro studies on CNGRC-CPG2 fusion proteins for ligand-directed enzyme prodrug therapy for targeted cancer therapy

The sequence asparagine-glycine arginine (NGR), flanked by Cysteine (Cys) residues so as to form a disulfide-bridge (CNGRC), has previously been found to target and bind specifically to aminopeptidase N (APN), which is highly expressed on the surface of tumor cells. The goal of this study was to develop and evaluate the potential of fusion proteins carrying the CNGRC sequence linked to the enzyme carboxypeptidase G2 (CPG2) for targeted cancer therapy. We refer to this strategy as ligand-directed enzyme prodrug therapy (LDEPT). We constructed two forms of the CNGRC-CPG2 fusions, containing one or two copies of the cyclic NGR motif and designated CNGRC-CPG2 (X-CPG2) and CNGRC-CPG2-CNGRC (X-CPG2-X), respectively. binding assays of the purified constructs showed that both X-CPG2 and X-CPG2-X bound with high affinity to cancer cells expressing high levels of APN, compared to their binding to cells expressing low levels of APN. Further studies of the constructs to assess the therapeutic potential of LDEPT were carried out using cells expressing high and low levels of APN. Using methotrexate, it was demonstrated that cancer cell survival was significantly higher in the presence of the fusion proteins, due to the hydrolysis of this cytotoxic drug by CPG2. Conversely, when the prodrug ZD2767P was used, cancer cell killing was higher in the presence of the fused CPG2 constructs than in their absence, which is consistent with CPG2-mediated release of the cytotoxic drug from the prodrug. Furthermore, the doubly-fused CPG2 construct (X-CPG2-X) was significantly more effective than the singly-fused construct (X-CPG2)

Production of "biobetter" variants of glucarpidase with enhanced enzyme activity

Glucarpidase, also known as carboxypeptidase G(2), is a Food and Drug Administration-approved enzyme used in targeted cancer strategies such as antibody-directed enzyme prodrug therapy (ADEPT). It is also used in drug detoxification when cancer patients have excessive levels of the anti-cancer agent methotrexate. The application of glucarpidase is limited by its potential immunogenicity and limited catalytic efficiency. To overcome these pitfalls, mutagenesis was applied to the glucarpidase gene of Pseudomonas sp. strain RS-16 to isolate three novels "biobetter" variants with higher specific enzyme activity. DNA sequence analysis of the genes for the variants showed that each had a single point mutation, resulting in the amino acid substitutions: I100 T, G123S and T239 A. K-m, V-max and K-cat measurements confirmed that each variant had increased catalytic efficiency relative to wild type glucarpidase. Additionally, circular dichroism studies indicated that they had a higher alpha-helical content relative to the wild type enzyme. However, three different software packages predicted that they had reduced protein stability, which is consistent with having higher activities as a tradeoff. The novel glucarpidase variants presented in this work could pave the way for more efficient drug detoxification and might allow dose escalation during chemotherapy. They also have the potential to increase the efficiency of ADEPT and to reduce the number of treatment cycles, thereby reducing the risk that patients will develop antibodies to glucarpidase

Musculoskeletal radiology teaching at a UK medical school-do we need to improve?

The United Kingdom is currently facing crisis due to a shortage of radiology consultants despite ever‐increasing demand for medical imaging. The specifics of how best to teach radiology has generated increasing interest. This study aims to determine whether musculoskeletal (MSK) radiology teaching at the University of Nottingham (UoN) Medical School is perceived to be satisfactory by medical students, Foundation‐Year doctors, and senior medical professionals in preparing students for the demands working as Foundation‐Year doctors. Questionnaires were distributed to all medical students and Foundation‐Year doctors that graduated from UoN (n = 307). Semi‐structured interviews were conducted with consultants and teaching staff (n = 13). Forty‐nine percent of preclinical medical students, 43% of clinical students and 27% of Foundation‐Year doctors thought MSK radiology teaching was not sufficient in preparing them for the radiology challenges Foundation‐Year doctors’ face. This difference was statistically significant (P < 0.001). The consensus from senior medical professionals was that MSK Radiology teaching is currently adequate and producing competent students. Interestingly, only 5% of students were considering a career in radiology compared to 34% of Foundation‐Year doctors. Overall, there seems to be concern among students regarding MSK radiology teaching and students have a lack of confidence with MSK radiology. Foundation‐Year doctors and senior medical professionals do not share this view. This may be due to medical students’ lack of clarity on what is required of them. Formal documentation of set learning objectives for MSK radiology throughout the curriculum may address this

Optical character recognition on heterogeneous SoC for HD automatic number plate recognition system

Automatic number plate recognition (ANPR) systems are becoming vital for safety and security purposes. Typical ANPR systems are based on three stages: number plate localization (NPL), character segmentation (CS), and optical character recognition (OCR). Recently, high definition (HD) cameras have been used to improve their recognition rates. In this paper, four algorithms are proposed for the OCR stage of a real-time HD ANPR system. The proposed algorithms are based on feature extraction (vector crossing, zoning, combined zoning, and vector crossing) and template matching techniques. All proposed algorithms have been implemented using MATLAB as a proof of concept and the best one has been selected for hardware implementation using a heterogeneous system on chip (SoC) platform. The selected platform is the Xilinx Zynq-7000 All Programmable SoC, which consists of an ARM processor and programmable logic. Obtained hardware implementation results have shown that the proposed system can recognize one character in 0.63 ms, with an accuracy of 99.5% while utilizing around 6% of the programmable logic resources. In addition, the use of the heterogenous SoC consumes 36 W which is equivalent to saving around 80% of the energy consumed by the PC used in this work, whereas it is smaller in size by 95%

Effects of Goat Manure Fertilization on Grain Nutritional Value in Two Contrasting Quinoa (Chenopodium quinoa Willd.) Varieties Cultivated at High Altitudes

In this study, the effects of goat manure fertilization (2, 4, 8, and 12 Tn/ha) on the grain yield, organic compounds, and mineral composition of two quinoa varieties (CICA-17 and Regalona Baer) were evaluated under field conditions in Northwest Argentina. The results indicate that fertilization improved the quinoa grain yield and total protein content. Low manure doses positively affected the fatty acid (FA) profile, and significant changes were determined for the monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acid contents of CICA-17 and on the saturated fatty acid (SFA) contents of R. Baer seeds. The amino acid contents were positively affected in CICA-17 and negatively in R. Baer. Soluble sugars (glucose, fructose, and sucrose), major elements (K, Si, P, Mg, Ca, and Na), minor elements (Fe, Mn, Al, Zn, and Cu), and ultratrace elements (Cr and Li) were detected and discussed in terms of their impact on human nutrition and health. Conclusively, manure addition affected some essential amino acids, the desaturase activity, the n6:n3 and SFA/UFA ratios, the atherogenic index, soluble sugars, and mineral content, and the fatty acid metabolism of each variety was differently affected, especially the C16 and C18 desaturase activity, which responded differently to various manure doses. Manure addition is a promising alternative to improve the nutritional quality and functionality of quinoa grains, but the response is not linear

Effects of Goat Manure Fertilization on Grain Nutritional Value in Two Contrasting Quinoa (Chenopodium quinoa Willd.) Varieties Cultivated at High Altitudes

In this study, the effects of goat manure fertilization (2, 4, 8, and 12 Tn/ha) on the grain yield, organic compounds, and mineral composition of two quinoa varieties (CICA-17 and Regalona Baer) were evaluated under field conditions in Northwest Argentina. The results indicate that fertilization improved the quinoa grain yield and total protein content. Low manure doses positively affected the fatty acid (FA) profile, and significant changes were determined for the monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acid contents of CICA-17 and on the saturated fatty acid (SFA) contents of R. Baer seeds. The amino acid contents were positively affected in CICA-17 and negatively in R. Baer. Soluble sugars (glucose, fructose, and sucrose), major elements (K, Si, P, Mg, Ca, and Na), minor elements (Fe, Mn, Al, Zn, and Cu), and ultratrace elements (Cr and Li) were detected and discussed in terms of their impact on human nutrition and health. Conclusively, manure addition affected some essential amino acids, the desaturase activity, the n6:n3 and SFA/UFA ratios, the atherogenic index, soluble sugars, and mineral content, and the fatty acid metabolism of each variety was differently affected, especially the C16 and C18 desaturase activity, which responded differently to various manure doses. Manure addition is a promising alternative to improve the nutritional quality and functionality of quinoa grains, but the response is not linear.EEA FamailláFil: González, Juan A. Fundación Miguel Lillo. Instituto de Ecología, Comportamiento y Conservación; ArgentinaFil: Yousif, Sawsan K.M. Al-Baha University. College of Arts and Science in Baljurashi. Department of Chemistry; Arabia SauditaFil: Erazzu, Luis Ernesto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Erazzu, Luis Ernesto. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Martinez Calsina, Luciana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Lizarraga, Emilio. Fundación Miguel Lillo. Instituto de Fisiología Animal; ArgentinaFil: Lizarraga, Emilio. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Omer, Rihab M. Al-Baha University. College of Arts and Science in Baljurashi. Department of Chemistry; Arabia SauditaFil: Bazile, D. CIRAD, UMR SENS; FranciaFil: Bazile, D. University Paul Valery Montpellier 3. CIRAD, IRD; FranciaFil: Fernandez-Turiel, J.L. CSIC. Geosciences Barcelona; EspañaFil: Buedo, Sebastián E. Fundación Miguel Lillo. Instituto de Ecología, Comportamiento y Conservación; ArgentinaFil: Rejas, M. CSIC. Geosciences Barcelona; EspañaFil: Fontana, Paola Daniela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: González, D.A. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Bioprospección y Fisiología Vegetal (INBIOFIV); ArgentinaFil: González, D.A. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Bioprospección y Fisiología Vegetal (INBIOFIV); ArgentinaFil:Oviedo, A. Fundación Miguel Lillo. Instituto de Fisiología Animal; ArgentinaFil: Alzuaibr, Fahad Mohammed. University of Tabuk. Faculty of Science. Department of Biology; Arabia SauditaFil: Al-Qahtani, Salem Mesfer. University of Tabuk. University College of Tayma. Biology Department; Arabia SauditaFil: Al-Harbi, Nadi Awad. University of Tabuk. University College of Tayma. Biology Department; Arabia SauditaFil: Ibrahim, Mohamed F.M. Ain Shams University. Faculty of Agriculture. Department of Agricultural Botany; EgiptoFil: Van Nieuwenhove, Carina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Van Nieuwenhove, Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos. Laboratorio de Ecofisiología Tecnológica; Argentin

Recent advances in vaccine and immunotherapy for COVID-19

The COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of cases and hundreds of thousands of deaths. Beyond there being no available antiviral therapy, stimulating protective immunity by vaccines is the best option for managing future infections. Development of a vaccine for a novel virus is a challenging effort that may take several years to accomplish. This mini-review summarizes the immunopathological responses to SARS-CoV-2 infection and discusses advances in the development of vaccines and immunotherapeutics for COVID-19