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Gastrointestinal (GI) endoscopies are essential for detecting and treating various digestive tract problems. While typically safe, these treatments can entail the risk of severe adverse events (SAEs), especially in individuals with a low body mass index (BMI). The current study aimed to evaluate whether post-endoscopy SAEs are more common in patients with low BMI and find risk factors for serious adverse outcomes in Saudi Arabian patients from Khamis Mushait, Aseer region, Saudi Arabia. The data of 398 adult patients with abdominal endoscopies between April and November 2023 were analyzed. Patients were divided into two groups: low BMI (BMI ≤ 18.5) and control (18.5 ≤ BMI ≤ 30). They were matched for age, gender, comorbidities, endoscopy type, and other pertinent characteristics. Low-BMI patients (Group I, n = 108) were substantially younger and had lower levels of albumin and total protein than the control group (Group II, n = 209). Comorbidities varied between groups, with diabetes mellitus more prevalent in Group II and inflammatory bowel disease (IBD) more commonplace in Group I. Treatment options also differed, with Group I receiving more biological treatments, steroids, and feeding tubes. Endoscopic procedures and indications were comparable among groups, with no significant variations in post-endoscopy complications. The endoscopy results varied from gastritis to colon malignancy, with no SAEs recorded in either group. Unlike earlier findings, this study found no higher incidence of SAEs in low-BMI individuals having abdominal endoscopy. This might be because of the restricted guidelines of different medical authorities, including clear informed consent that illustrates any risks, benefits, alternatives, sedation plan, and potential diagnostic or therapeutic interventions. Also, professional endoscopists and consultants who ensure adequate visualization of the GI mucosa, using mucosal cleansing and insufflation as necessary, should avoid any risk of abdominal hemorrhage. These findings highlight the significance of personalized risk assessment and pre-procedural optimization, including nutritional assistance, in this patient population. More prospective research with larger sample sizes is needed to validate these findings and create targeted techniques for improving outcomes in individuals with a low BMI having endoscopic operations.
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The small intestinal diaphragms are a rare condition characterized by focal or diffuse luminal narrowing in the small intestine. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with the development of small intestinal diaphragms, particularly in long-term and high-dose users. In the current report, a Saudi adult female complained of abnormal bowel motions, which caused severe abdominal pain. She had long-term treatment with NSAID. Systemic and physical examination was unremarkable, apart from poorly localized, nonspecific tenderness to abdominal palpation. Two endoscopic investigations (upper and lower endoscopy) were performed to identify any abnormalities in the digestive system; also, a biopsy was taken for histopathological analysis. In addition, another capsule endoscopy was done to investigate any abnormal bowel motion. The findings of two endoscopic investigations and histopathological analysis of duodenum biopsies revealed different features of small intestinal diaphragms and stricture. The biopsies showed mild chronic inflammation. The esophagogastroduodenoscopy (EGD) and colonoscopy showed multiple strictures and ulcerations in the small bowel. Also, a diffused mucosal erythema of the stomach and a remarkable scar on the third part of the duodenum were detected. That might be due to the excessive use of NSAIDs. The investigations revealed multiple small bowel diaphragmatic stenosis and strictures in the proximal and distal small bowel. These are distinct signs of NSAID-induced small bowel diaphragms and strictures.
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Objective: To prepare interleukin-1ß-targeted nanoantibodies and observe their effects on apoptosis in hypoxic cardiomyocyte of mice. Methods: Using DNA recombination technology, the pET-16b and pHEN1 expression vectors were used to construct the prokaryotic expression plasmids of interleukin-1ß-targeted nanobodies (pET-16b-4G6M-VHH, pET-16b-5BVP-VHH, pET-16b-5MVZ-VHH, pHEN1-4G6M-VHH, pHEN1-5BVP-VHH and pHEN1-5MVZ-VHH, where VHH is a variable domain of heavy chain antibody, 4G6M-VHH, 5BVP-VHH, 5MVZ-VHH were three interleukin-1ß-targeted nanoantibodies respectively). The constructed plasmids were transferred into Escherichia coli Rosetta2 (DE3) for induction of expression and nickel column purification, respectively. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting were employed to identify the expression product and purified product, and the enzyme-linked immune sorbent assay (ELISA) was performed to determine their affinity. The cardiomyocyte hypoxia model was used with the highest affinity IL-1ß-targeted nanobody (pHEN1-5MVZ-VHH), and cell survival and apoptosis rates were detected (the experiment was divided into normal control group, hypoxia model group, blank plasmid group and 12.5, 25.0, 50.0 µg/ml pHEN1-5MVZ-VHH treatment groups). Results: SDS-PAGE and Western blotting results showed that the anti-interleukin-1ß (IL-1ß) nanobodies with a relative molecular mass of about 15 000 were successfully obtained. Likewise, ELISA results found that the nanobodies expressed in pHEN1 vector group had higher affinity for IL-1ß antigen compared with pET-16b vector group (4G6M-VHH group: 3.20±0.03 vs 1.20±0.03, P<0.001; 5BVP-VHH group: 3.18±0.06 vs 1.21±0.02, P<0.001; 5MVZ-VHH group: 3.38±0.05 vs 1.62±0.04, P<0.001). Additionally, the results of cell survival assay and apoptosis assay detected that compared with the hypoxia model group, HL-1 cell activity was significantly increased in the 25.0 µg/ml and 50.0 µg/ml pHEN1-5MVZ-VHH treatment groups [(75.55±2.23)% vs (46.90±2.51)%, P<0.001; (74.36±1.96)% vs (46.90±2.51)%, P<0.001], and apoptosis rate was significantly reduced [(6.83±0.27)% vs (10.24±0.76)%, P<0.001; (6.68±0.38)% vs (10.24±0.76)%, P<0.001]. Conclusions: 4G6M-VHH, 5BVP-VHH, and 5MVZ-VHH are expressed by both pET-16b and pHEN1 expression vectors and the nanobodies produced by the pHEN1 vector display enhanced antigen affinity. Furthermore, in hypoxic cardiomyocytes, pHEN1-5MVZ-VHH treatment reduces cell apoptosis.
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Apoptosis , Interleucina-1beta , Miocitos Cardíacos , Animales , Interleucina-1beta/metabolismo , Ratones , Miocitos Cardíacos/metabolismo , Anticuerpos de Dominio Único , Plásmidos , Escherichia coli , HipoxiaRESUMEN
In the digital age, social media has emerged as a significant platform, generating a vast amount of raw data daily. This data reflects the opinions of individuals from diverse backgrounds, races, cultures, and age groups, spanning a wide range of topics. Businesses can leverage this data to extract valuable insights, improve their services, and effectively reach a broader audience based on users' expressed opinions on social media platforms. To harness the potential of this extensive and unstructured data, a deep understanding of Natural Language Processing (NLP) is crucial. Existing approaches for sentiment analysis (SA) often rely on word co-occurrence frequencies, which prove inefficient in practical scenarios. Identifying this research gap, this paper presents a framework for concept-level sentiment analysis, aiming to enhance the accuracy of sentiment analysis (SA). A comprehensive Urdu language dataset was constructed by collecting data from YouTube, consisting of various talks and reviews on topics such as movies, politics, and commercial products. The dataset was further enriched by incorporating language rules and Deep Neural Networks (DNN) to optimize polarity detection. For sentiment analysis, the proposed framework employs predefined rules to trigger sentiment flow from words to concepts, leveraging the dependency relations among different words in a sentence based on Urdu language grammatical rules. In cases where predefined patterns are not triggered, the framework seamlessly switches to its sub-symbolic counterpart, passing the data to the DNN for sentence classification. Experimental results demonstrate that the proposed framework surpasses state-of-the-art approaches, including LSTM, CNN, SVM, LR, and MLP, achieving an improvement of 6-7% on Urdu dataset. In conclusion, this research paper introduces a novel framework for concept-level sentiment analysis of Urdu language data sourced from social media platforms. By combining language rules and DNN, the proposed framework demonstrates superior performance compared to existing methodologies, showcasing its effectiveness in accurately analyzing sentiment in Urdu text data.
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BACKGROUND: Hypericum species are widely acknowledged for their biological attributes, with notable attention being paid to Hypericum perforatum, commonly known as St. John's wort (SJW) within the Hypericum section of the Hypericaceae family. This species is among the most thoroughly investigated herbal medicines, particularly in terms of its application in the management of mild to moderate depression. SJW is used to treat depression, menopausal symptoms, attention-deficit hyperactivity disorder (ADHD), somatic symptom disorder, obsessive-compulsive disorder, and skin conditions, such as wounds and muscle pain. However, the usefulness and effectiveness of SJW for male sexual and reproductive health (SRH) are not well known. OBJECTIVE: To assess the current evidence in the literature on the effect of SJW on male SRH. METHODS: This narrative review followed a predetermined protocol and used MEDLINE and PubMed to identify articles published in English on the effects of SJW on male SRH. The search used various keywords, such as "Hypericum Perforatum", "St. John's Wort", and terms related to sexual and reproductive health issues. Articles published between the inception of the database and August 2023 were included. RESULTS: We identified 12 articles published from 1999 to 2019, the majority of which were experimental and conducted on animals. These studies demonstrate variability in terms of design, sample size, type of SJW extract used, the dosage administered, and duration of treatment. Studies have indicated potential sexual dysfunction (SD) due to SJW, which includes reduced libido, delayed ejaculation, delayed orgasm, and erectile dysfunction. Additionally, reproductive toxicity has been suggested, as evidenced by spermicidal effects through the inhibition of sperm motility, abnormal spermatozoa, chromosomal aberrations, and DNA denaturation. Furthermore, some studies have reported potential adverse events during maternal exposure, inhibition of fertilization, and disruption of reproductive parameters. CONCLUSIONS: Our review suggests that the safety and efficacy of SJW in the treatment of human SRH remain unclear. Further comprehensive, well-designed studies with larger samples, longer exposure periods, and specific dosages are needed to clarify SJW's effects of SJW. Therefore, consultation with healthcare professionals before using herbal remedies or supplements is crucial.
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BACKGROUND: Professional values provide a road map for guiding the behaviors of nursing students during practice and are considered standards for acceptable actions during the provision of nursing care. Nursing educators play a vital role in helping their students embrace professional values in their future career. PURPOSE: This study was designed to assess and compare professional values among Jordanian and Palestinian undergraduate nursing students. METHODS: In this descriptive, cross-sectional study, 182 Jordanian and 353 Palestinian nursing students completed the Nurses Professional Values Scale-Revised (NPVS-R), which covers five domains (caring, trust, justice, activism, and professionalism). RESULTS: The mean age of the participants was 22.5 years, and most (56.6%) were female. The mean total score for the NPVS-R was 3.85, with the "justice" dimension receiving the highest mean score (4.07) and the "activism" dimension receiving the lowest mean score (3.63). The differences in mean NPVS-R total and dimension scores between the Jordanian and Palestinian students were not statistically significant. CONCLUSIONS: The results of this study support that Jordanian and Palestinian undergraduate nursing students have an acceptable level of professional values, with the NPVS-R justice domain scoring relatively high and the NPVS-R activism domain scoring relatively low. The authors hope that the results of this study encourage nursing educators to continue improving professional values among their students, especially with regard to the relatively low-rated dimensions.
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Bachillerato en Enfermería , Estudiantes de Enfermería , Humanos , Femenino , Adulto Joven , Adulto , Masculino , Estudios Transversales , Árabes , Jordania , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The association of malnutrition with congenital heart disease (CHD) is well documented. Studies comparing the effects of parenteral nutrition (PN) and enteral feeding (EF) on the post-surgical correction of CHD are not available. We compared the effects of PN with EF on the nutritional status of children post-cardiac surgery. METHODS: A retrospective cohort study was conducted with 72 children aged ≤6 years who had at least one heart surgery between 2010 and 2016. Malnutrition was defined as a weight for height Z-score (WHZ) below -2. The primary endpoint was the change in the mean WHZ Z-score from the baseline. All statistical analyses were performed using SPSS 21.0 [Release 21.0.0.0, IBM, USA]. RESULTS: The sample size realized as 72 (n = 72). The overall prevalence of malnutrition was 48%. The change in height of the PN group was significantly higher than the EF group (14.2 ± 7.6 cm vs. 7.4 ± 6.3, P = 0.010), but the weight change was not significantly different (P = 0.28). The post-surgery Z-scores were significantly lower in the PN group and the Z-score change was marginally smaller (P = 0.086), indicating lower growth levels post-surgery. The PN group had a significantly higher incidence of post-surgical malnutrition (P = 0.046). Patients who received PN had significantly less improvement (more negative change) in the Z-score levels compared to the EF group (PE = -1.42, 95% confidence interval [CI] = [-2.48, -0.35]; P = 0.011). CONCLUSION: Malnutrition occurs frequently with CHD. PN does not add any nutritional benefits compared with EF. EF should always be the preferred method of nutrition unless contraindicated.
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Tracheocutaneous fistula presents a challenge to the surgeon as different factors affect its formation and healing. A multidisciplinary approach and proper patient counseling, duration of cannulation, and comorbidities help in prognosis and outcome.
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PURPOSE: Metacarpal bone fractures represent one-fifth of upper extremity fractures. The most commonly affected bone was the fifth metacarpal also known as boxer's fracture with a range 9.7-50%. Different techniques have been described for fracture fixation with K-wires being the most described technique. In this paper, we present a new technique utilizing k-wires to reduce and fix metacarpal fractures in an easy less traumatic way aiming to optimize the clinical outcomes in regards of range of motion and stiffness. METHODOLOGY: Retrospective chart review including all the patients that were managed with the new technique. RESULTS: 24 fractures were fixed with the new technique without violating the MCP joint with different fingers involvement and different presenting deformity. At the end of the splinting time, 80% of the cases had full ROM at the time of splint removal. The remaining 20% had some stiffness that improved with further physiotherapy. CONCLUSION: This approach is easy to teach, fast with good clinical outcomes. However, a larger sample size study comparing this technique to the existing treatment options is needed. TYPE OF STUDY: Case Series and literature review, Level IV.
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The present study estimated the ability of four aquatic macrophytes (Eichhornia crassipes (Mart.) Solms, Ludwigia stolonifera (Guill. & Perr.) P.H. Raven, Echinochloa stagnina (Retz.) P. Beauv. and Phragmites australis (Cav.) Trin. ex Steud.) to accumulate Cd, Ni and Pb and their use for indicating and phytoremediating these metals in contaminated wetlands. Three sites at five locations in the Kitchener Drain in Gharbia and Kafr El-Sheikh Governorates (Egypt) were selected for plant, water and sediment sampling. The water in the Kitchener Drain was polluted with Cd, while Pb and Ni were far below the maximum level of Pb and Ni in the irrigation water. In comparison to the other species, P. australis accumulated the highest concentrations of Cd and Ni, while E. crassipes accumulated the highest concentration of Pb in its tissues. The four species had bioaccumulation factors (BAFs) greater than one, while their translocation factors (TFs) were less than 1 for most heavy metals, except Cd in the leaf and stem of E. stagnina and L. stolonifera, respectively, and Ni in the stem and leaf of E. stagnina. The BAF and TF results indicated that the studied species are suitable for phytostabilizing the studied heavy metals, except Ni in E. stagnina and Cd in L. stolonifera, which are suitable for phytoextracting these metals. Significant positive correlations were found between the investigated heavy metals in the water or sediment and the plant tissues. Their high BAFs, with significant proportional correlations, supported the potential of these species to serve as bioindicators and biomonitors of heavy metals in general and in the investigated metals specifically.
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Eichhornia , Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , Biodegradación Ambiental , EgiptoRESUMEN
Several stressors like different types of heavy metals are found in the soil and can affect the growth and genomic integrity of wheat grains (Triticum aestivum L.). The aim of this study was to compare the effect of exogenous Cd (30, 60, 120 mg kg-1), Ni (50, 100 and 150 mg kg-1) or Pb (100, 200 and 300 mg kg-1) on wheat agronomic characteristics through the assessment of oxidative stress indices at protein and gene expression levels, photosynthetic pigments and genetic aberrations using RAPD analysis that were studied during two winter seasons (2015/2016 and 2016/2017). The results showed that all stressors significantly decreased the vegetative growth parameters, altered the activities of antioxidants enzymes in seedlings (after 30 days) and grains (after 5 months) and differently affected their expression levels in seedlings leaves and roots. Pb treated plants showed the poorest agronomic characteristics as it exhibited the worst affected wheat height, number of tillers, fresh and dry weight, flag leaf area as well as yield. Pb treatment caused poorest plant performance, it showed the highest proline content, least protein and chlorophyll contents, thus affects the overall plants growth followed by Cd and Ni, respectively. Furthermore, high Pb and Cd doses revealed highest degree of polymorphism and lowest degree of genome stability. Altogether, heavy metals accumulated mainly in wheat straw and induced genotoxic effect which consequently altered normal plant metabolism and pigment content which resulted in a significant reduction in wheat yield and quality. Moreover, Pb induced more genotoxic and phytotoxic effects than Cd and Ni.
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Triticum , Cadmio , Plomo , Níquel , Técnica del ADN Polimorfo Amplificado Aleatorio , Contaminantes del SueloRESUMEN
OBJECTIVE OF THE STUDY: To evaluate the value of serum creatine phosphokinase-brain specific (CK-BB) and urinary lactate/creatinine (L/C) ratio as early indicators of brain damage in full-term newborns with hypoxic ischemic encephalopathy (HIE). PATIENTS AND METHODS: A case-control study including 25 full-term new-born infants with perinatal asphyxia who were admitted to neonatal intensive care unit (NICU) with a proven diagnosis of HIE, compared to 20 healthy age- and sex-matched full-term newborns. All newborn infants were subjected to full history taking, clinical examination, routine investigations (cord blood gases and complete blood picture), and assessment of serum CK-BB (cord blood, 6 and 24 hours after birth) and urinary L/C ratio (collected within the first 6 hours, on the 2nd and 3rd day after birth). RESULTS: The serum CK-BB and urinary L/C ratio in infants with HIE were significantly higher in samples collected throughout the monitoring period when compared with the control group (all P<0.001). The cord CK-BB and urinary L/C ratio within the first 6 hours were significantly higher in infants with severe HIE than in infants with mild and moderate HIE (P<0.001). Cord CK-BB level at 12.5 U/L had 100% sensitivity and 84% specificity in the detection of severe HIE infants. Urinary L/C ratio of more than 10.5 collected within the first 6 hours after birth had 100% sensitivity and 78% specificity for the detection of severe HIE infants. CONCLUSION: The serum CK-BB and urinary L/C ratio in HIE infants were significantly increased early in the course of the disease, which can be used as useful indicators for predicting the development of HIE.
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BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children worldwide. Among anti-inflammatory cytokines, interleukin-10 (IL-10) is a key immunosuppressive cytokine involved in the pathogenesis of JIA. To date, only a few studies concerned the association of interleukin-10 gene polymorphisms with JIA. In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions -1082(G/A), -819(C/T), and -592(C/A) in the promoter region of the IL-10 gene to determine whether this polymorphism could be a marker of susceptibility to JIA in Egyptian children and adolescents. We also measured the serum level of IL-10 to assess its relation to such polymorphism. METHODS: This was a case-control study included 100 patients diagnosed with JIA, and matched with age, gender, ethnicity 100 healthy control subjects. Interleukin-10 -1082(G/A), -819(C/T), and -592(C/A) polymorphisms were genotyped by amplification refractory mutation system- polymerase chain reaction (ARMS)-PCR methodology, while the serum IL10 levels were measured by ELISA method. RESULTS: Compared to the controls subjects, the frequency of IL-10- AA genotype and A allele at the -1082 position were overrepresented in patients with JIA (OR = 2.7; 95% CI: 1.1-6.4 for the AA genotype; P <0.05 and OR: 1.5; 95% CI: 1.03-2.3 for the A allele; P <0.05 respectively). On the other hand, no significant differences were found between the 2 groups in the genotype or allele frequencies for the -819 and -592 positions. Of note, we found a significant positive association between the IL-10 (-1082) AA genotype and susceptibility to polyarticular JIA (OR: 4.3; 95% CI: 1.5-12.7; P <0.01). We observed that patients with the IL-10 (-1082) AA genotype had significantly lower serum IL-10 levels (2.3 ± 0.9 pg/ml) compared to those with AG genotype (7.6 ± 1.5 pg/ml) and GG genotype (9.5 ± 1.2 pg/ml); P < 0.01, respectively. CONCLUSION: We demonstrate for the first time, to the best of our knowledge, that the presence of an A allele or AA gene variant at the -1082 position of the promoter region of the interleukin-10 gene may constitute risk factors for developing JIA in Egyptian children and adolescents. Moreover, we observed a significant positive association between the IL10 -1082 AA gene variant and susceptibility to polyarticular JIA.
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Artritis Juvenil/diagnóstico , Artritis Juvenil/genética , Interleucina-10/genética , Mutación , Polimorfismo de Nucleótido Simple/genética , Adolescente , Alelos , Artritis Juvenil/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Egipto , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interleucina-10/sangre , Masculino , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. To date, only a few studies concerned the association of the VDR gene polymorphisms with childhood-onset SLE.In this study, we aimed to investigate the BsmI polymorphisms in the VDR gene, for the first time in Egyptian children and adolescents with SLE, to determine whether this polymorphism could be a marker of susceptibility to or severity of SLE and we also measured the serum level of 25-hydroxyvitamin D (25[OH] D) to assess its relation to such polymorphism.This was a case-control study including 100 patients with SLE and matched with age, sex, and ethnicity and 100 healthy controls. All subjects were genotyped for the VDR gene BsmI polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), whereas the serum 25(OH) D levels were measured by enzyme-linked immunosorbent assay method.Compared to the contros subjects, the VDR BsmI BB genotype and B allele were overrepresented among SLE patients (odda ratio [OR]: 5.5; 95% confidence interval [CI]: 1.9-15.9; Pâ=â0.002 and OR: 1.84; 95% CI: 1.21-2.80; Pâ=â0.003; respectively). We found a significant association between VDR BsmI BB genotype with lupus nephritis (OR: 6.8; 95% CI: 1.18-50.5; Pâ=â0.001). However, we did not observe any significant association of studied polymorphisms with other clinical manifestations, laboratory profiles of SLE, or disease activity score. Our data revealed no association between VDR BsmI genotypes or alleles and serum 25-hydroxyvitamin D levels among studied patients with SLE (all Pâ>â0.05).We demonstrate for the first time, to the best of our knowledge, that the VDR BsmI gene polymorphisms may contribute to susceptibility to SLE in Egyptian children and adolescents. Moreover, we found that the BB genotype constituted a risk factor for the development of nephropathy among studied patients with SLE. However, we did not find any significant association of the VDR BsmI gene variants with other clinical manifestations, laboratory profiles of SLE, disease activity index score, or serum 25-hydroxyvitamin D levels.
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Lupus Eritematoso Sistémico/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Adolescente , Estudios de Casos y Controles , Niño , Egipto , Femenino , Humanos , Lupus Eritematoso Sistémico/sangre , Masculino , Estudios Prospectivos , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP.In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism.This was a case-control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method.Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5-5.3 for the AA genotype; Pâ<â0.01) and (70%; OR: 1.95; 95% CI: 1.27-3.00 for the A allele; Pâ<â0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7â±â9.5âpg/mL) compared to those with AG genotype (21.8â±â4.5âpg/mL) and AA genotype (11.5â±â3.3âpg/mL); Pâ<â0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3-11.2; Pâ<â0.01).We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis, acute respiratory failure, and hospital mortality among patients with CAP.
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Interleucina-10/genética , Neumonía Bacteriana/genética , Polimorfismo de Nucleótido Simple , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Infecciones Comunitarias Adquiridas/genética , Egipto , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Interleucina-10/sangre , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Mixed fibrolamellar hepatocellular carcinoma (mFL-HCC) is a rare liver tumor defined by the presence of both pure FL-HCC and conventional HCC components, represents up to 25% of cases of FL-HCC, and has been associated with worse prognosis. Recent genomic characterization of pure FL-HCC identified a highly recurrent transcript fusion (DNAJB1:PRKACA) not found in conventional HCC. PATIENTS AND METHODS: We performed exome and transcriptome sequencing of a case of mFL-HCC. A novel BAC-capture approach was developed to identify a 400 kb deletion as the underlying genomic mechanism for a DNAJB1:PRKACA fusion in this case. A sensitive Nanostring Elements assay was used to screen for this transcript fusion in a second case of mFL-HCC, 112 additional HCC samples and 44 adjacent non-tumor liver samples. RESULTS: We report the first comprehensive genomic analysis of a case of mFL-HCC. No common HCC-associated mutations were identified. The very low mutation rate of this case, large number of mostly single-copy, long-range copy number variants, and high expression of ERBB2 were more consistent with previous reports of pure FL-HCC than conventional HCC. In particular, the DNAJB1:PRKACA fusion transcript specifically associated with pure FL-HCC was detected at very high expression levels. Subsequent analysis revealed the presence of this fusion in all primary and metastatic samples, including those with mixed or conventional HCC pathology. A second case of mFL-HCC confirmed our finding that the fusion was detectable in conventional components. An expanded screen identified a third case of fusion-positive HCC, which upon review, also had both conventional and fibrolamellar features. This screen confirmed the absence of the fusion in all conventional HCC and adjacent non-tumor liver samples. CONCLUSION: These results indicate that mFL-HCC is similar to pure FL-HCC at the genomic level and the DNAJB1:PRKACA fusion can be used as a diagnostic tool for both pure and mFL-HCC.
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Carcinoma Hepatocelular/genética , Subunidades Catalíticas de Proteína Quinasa Dependientes de AMP Cíclico/genética , Proteínas del Choque Térmico HSP40/genética , Neoplasias Hepáticas/genética , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Exoma/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Genómica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Mutación , Proteínas de Fusión Oncogénica/genética , Transcriptoma/genéticaRESUMEN
There is increasing interest in developing noninvasive means to evaluate liver fibrosis in patients with chronic liver disease to determine disease severity, prognosis and optimal treatment. Transient elastography (TE) has previously been demonstrated to predict the presence or absence of advanced fibrosis. The current study was conducted to determine whether TE can identify patients with chronic liver disease at risk of clinical decompensation. A total of 667 patients underwent TE and were followed for a median of 861 days and 57 patients achieved the primary outcome, a composite of clinical endpoints including death, ascites, encephalopathy, increased Child Score ≥ 2, variceal bleed, hepatocellular carcinoma or listing for transplant. Overall, TE had an area under the receiver operating characteristic curve of 0.87 for predicting clinical outcome. Using a cut-off of 10.5 kPa, TE has a sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 94.7%, 63.0%, 19.3% and 99.2%, respectively. A predictive model for clinical events was developed using generalized cross-validation for clinical endpoints considering TE, liver biopsy results and multiple other predictors. Individually, TE performed better than biopsy, or any other variable, for predicting clinical outcome [Harrell's C Statistic 0.86 for TE, 0.78 for stage]. Patients with a TE score of >12.5 kPa were found to have a relative hazard for clinical event of 18.99 compared with patients with TE score <10.5. A combined variable model including TE, aspartate aminotransferase/alanine aminotransferase ratio and model for end-stage liver disease (MELD) yielded the highest predictive accuracy with Harrell's C value of 0.93. In the subset of patients with cirrhosis, TE was not found to be independently associated with clinical outcomes in univariate or multivariate analysis although it retained a high sensitivity and NPV of 97.5% and 92.3%, respectively, at a kPa cut-off of 10.5. TE can successfully identify patients with chronic liver disease who are at low risk of clinical decompensation over a time period of 2 years.
Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Hepatitis Crónica/complicaciones , Hepatitis Crónica/diagnóstico , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y EspecificidadRESUMEN
In the present work we studied: (a) biochemical changes; (b) serum immunoglobulins (IGs); and (c) mitogenecity of peripheral blood lymphocytes (PBL) in workers directly exposed to high concentrations of pollutants in several sectors of a major copper company in Alexandria. These sectors included the aluminum utensils refining of copper semicontinuous aluminum casting, brass foundries, and steel furnaces. Toxicants in these sectors included aluminum, hexachloroethan, silica, cadmium, copper, mercury, lead, abestos, nickels, zinc, silver, carbon iron, and sulfate present in high concentrations in the sectors where workers are directly exposed. Administrative personnel (indirectly exposed) were included as positive controls; negative controls were people living in areas of Alexandria where the concentrations of these toxicants are extremely low. All personnel of the aluminum utensils area showed reduction in serum levels of IgG, IgA, and IgM assayed by enzyme-linked immunosorbent assay (ELISA) while workers directly exposed in the other sectors showed elevated Igs. Mitogenic activity in cultured PBL assayed by 3H-thymidine uptake was impaired in all plant personnel. However, experimentals showed increases in the interleukins IL-2, IL-4, IL-6, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha and-beta (TNF-alpha and beta) assayed by ELISA. Changes were directly related to duration of exposure. Some workers showed autoimmune symptoms such as arthritis and spondylitis. Allergic manifestations were also recorded. Thus, abnormalities were greatest in directly exposed workers, while other plant personnel showed some form of toxicity in the parameters studied. Clinical significance of the immunologic abnormalities seen is under further study.