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As an environmentally friendly material, biochar is increasingly being utilized in the field of heat transfer and thermal conduction. In this study, nano-biochar was prepared from high-pressure homogenization (HPH) using sesame stalks as the raw material. It was incorporated into ethylene glycol (EG) and its dispersion stability, viscosity, and thermal conductivity were investigated. The nano-biochar was stably dispersed in EG for 28 days. When the concentration of the nano-biochar added to EG was less than 1%, the impact on viscosity was negligible. The addition of 5 wt.% nano-biochar to EG improved the thermal conductivity by 6.72%, which could be attributed to the graphitized structure and Brownian motion of the nano-biochar. Overall, nano-biochar has the potential to be applied in automotive thermal management.
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BACKGROUND: Myeloid-derived suppressor cells (MDSCs) have immature morphology, relatively weak phagocytic activity, as well as some immunosuppressive functions. The capacity of MDSCs to inhibit T-cell-mediated immunological responses is their most notable functional characteristic. Down-regulating antitumor immune surveillance is one way that the expansion and activation of MDSCs contribute significantly to the occurrence and progression of tumors. Increased levels of MDSCs in patients with chronic hepatitis C virus (HCV) infection could suppress T-cell responses, promoting viral escape and hepatitis progression. This may make HCV-infected individuals more vulnerable to severe infections, hepatic and extra-hepatic tumors, and a diminished capacity to react to immunization. It is still unknown if effective HCV eradication with directly acting antivirals (DAAs) can restore immune functions and immune surveillance capacity. OBJECTIVE: The purpose of this study was to observe the frequency of M-MDSCs (CD33+, CD11b+, and HLA-DR) in patients with a previous history of HCV, 2-3 years after virus eradication using DAA therapy. METHODS: This study was conducted on 110 subjects: fifty-five subjects without liver cirrhosis who were treated with HCV using DAAs and attained SVR for a period of 2-3 years and 55 age- and gender-matched healthy controls. The study was conducted during the period from January to July 2022. Patients were recruited from the National Viral Hepatitis Treatment Unit, Alexandria University Hepatology outpatient clinic, and the Alexandria University Tropical Medicine outpatient clinic. The frequencies of MDSCs (CD33+CD11b + HLA-DR-) by flow cytometry were assessed. RESULTS: Even after the virus had been eradicated for longer than two years, MDSC levels in HCV-treated individuals were found to be considerably higher. In the HCV-treated group, the median number of MDSCs was 5, with an interquartile range (IQR) of 3.79-7.69. In contrast, the median for the control group was 3.1, with an IQR of 1.4-3.2 (PË0.001). CONCLUSION: Successful DAA therapy leads to slow and partial immunological reconstitution, as demonstrated by the failure to attain normal levels of MDSC's 2 years after successful HCV eradication despite the normalization of laboratory parameters as well as the absence of liver fibrosis. The clinical implications of these findings should be thoroughly studied.
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Antivirais , Hepatite C Crônica , Células Supressoras Mieloides , Humanos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/efeitos dos fármacos , Antivirais/uso terapêutico , Feminino , Masculino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Idoso , Citometria de FluxoRESUMO
Rhabdomyolysis involves significant skeletal muscle injury and destruction, which can be triggered by trauma, intense physical activity, heat, prolonged immobility, certain medications, and endocrine disorders. Rhabdomyolysis in renal transplants can be more complicated, and the prognosis is not well known, especially in the context of coexisting rejection. We present a case of rifampicin-induced rhabdomyolysis with superimposed acute cellular rejection in a kidney transplant patient.
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Nocturnal enuresis (NE) has been associated with neurodevelopmental disorders such as autism spectrum disorder, attention deficit or hyperactivity disorder, and intellectual disability. This study aimed to assess parents' perception of NE in children in the eastern region of Saudi Arabia. We conducted a cross-sectional study from May to August 2023, including parents aged ≥18 years living in the area. We administered an online questionnaire to assess parents' knowledge and attitudes toward NE and its treatment. A total of 616 parents completed the questionnaire, 71.4% of which were women, 35% were aged between 25 and 35 years, 75% were married, 65% had a university degree, and 49% had three or more children. In total, 70% demonstrated a good overall knowledge about NE and its treatment, and nearly 60% had a positive attitude toward the condition. Univariate and multivariate ordinal logistic regression analyses revealed that female sex, a higher level of education, and having more than one child were associated with a higher score regarding attitude toward treatment. The level of education and the number of children were predictors of knowledge and a positive attitude toward NE in children.
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Enurese Noturna , Pais , Humanos , Arábia Saudita , Feminino , Masculino , Enurese Noturna/psicologia , Enurese Noturna/epidemiologia , Estudos Transversais , Adulto , Pais/psicologia , Inquéritos e Questionários , Percepção , Conhecimentos, Atitudes e Prática em Saúde , Criança , Pessoa de Meia-Idade , Adolescente , Adulto JovemRESUMO
Managing patients with liver cirrhosis and gastric hyperplastic polyps (GHPs) is challenging. Despite being the standard technique for resection of GHPs, hot snare polypectomy (HSP) is risky in the setting of coagulation disorders associated with liver cirrhosis. The aim of the study was to assess the efficacy and safety of endoscopic band ligation (EBL), compared to HSP in resecting GHPs in cirrhotic patients. One hundred consecutive adults with liver cirrhosis and sessile or pedunculated GHPs were enrolled from December 2018 to December 2020. Cases were non-blindly randomized (1 : 1) to two groups to have GHPs managed by either EBL (group I) or HSP (group II). Data of demographic, clinical, and pathological factors, hospitalization expenses and outcomes of both treatment maneuvers were collected and statistically analyzed. Upper endoscopy was repeated for all patients at 3, 6 and 12 months after treatment for recurrence detection. Between the two procedures, the mean operational time was significantly shorter in the EBL than the HSP group (15.1 ±3.80 min vs. 36.6 ±6.72 min, p < 0.001). Concerning complications, 94% of EBL cases had reported no complications compared to 78% with HSP. Bleeding occurred only with HSP (20%) with urgent need for adrenaline and/or argon plasma coagulation (p = 0.003). Regarding cost, it was significantly lower in EBL than HSP (280 ±2.02 EGP vs. 390 ±181.8 EGP, p < 0.001). However, the recurrence rate of GHPs and number of needed sessions were not significantly different. EBL proved to be a safer, more rapid, and economic maneuver when compared to HSP on resecting GHPs in patients with liver cirrhosis.
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INTRODUCTION: Microtubules play a vital role in cancer therapeutics. They are implicated in tumorigenesis, thus inhibiting tubulin polymerization in cancer cells, and have now become a significant target for anticancer drug development. A plethora of drug molecules has been crafted to influence microtubule dynamics and presently, numerous tubulin inhibitors are being investigated. This review discusses the recently developed inhibitors including natural products, and also examines the preclinical and clinical data of some potential molecules. AREA COVERED: The current review article summarizes the development of tubulin inhibitors while detailing their specific binding sites. It also discusses the newly designed inhibitors that may be useful in the treatment of solid tumors. EXPERT OPINION: Microtubules play a crucial role in cellular processes, especially in cancer therapy where inhibiting tubulin polymerization holds promise. Ongoing trials signify a commitment to revolutionizing cancer treatment and exploring targeted therapies. Challenges in microtubule modulation, like resistance and off-target effects, demand focused efforts, emphasizing combination therapies and personalized treatments. Beyond microtubules, promising avenues in cancer research include immunotherapy, genomic medicine, CRISPR gene editing, liquid biopsies, AI diagnostics, and stem cell therapy, showcasing a holistic approach for future advancements.
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Antineoplásicos , Desenvolvimento de Medicamentos , Microtúbulos , Terapia de Alvo Molecular , Neoplasias , Moduladores de Tubulina , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Moduladores de Tubulina/farmacologia , Antineoplásicos/farmacologia , Animais , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Desenho de Fármacos , Produtos Biológicos/farmacologia , Tubulina (Proteína)/metabolismoRESUMO
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a frequent clinical condition globally. Single nucleotide polymorphisms (SNPs) associated with NAFLD have been proposed in the literature and based on bioinformatic screening. The association between NAFLD and genetic variants in Egyptians is still unclear. Hence, we sought to investigate the association of some genetic variants with NAFLD in Egyptians. Egyptians have been categorized into either the MASLD group (n = 205) or the healthy control group (n = 187). The severity of hepatic steatosis and liver fibrosis was assessed by a Fibroscan device. TaqMan-based genotyping assays were employed to explore the association of selected SNPs with MASLD. PNPLA3 rs738409 C>G variant is associated with the presence of MASLD with liver fibrosis, the severity of both hepatic steatosis and liver fibrosis, increased systolic and diastolic blood pressure and increased alanine aminotransferase (all p < 0.05), while the TM6SF2 rs58542926 C>T, HSD17B13 rs9992651 G>A, and GCKR rs1260326 T>C variants were not (all p > 0.05). The TM6SF2 rs58542926 T allele is associated with increased fasting blood glucose and a decreased waist circumference. The GCKR rs1260326 C allele is associated with decreased aspartate transaminase and diastolic blood pressure (all p < 0.05). Only after adjusting for the risk factors (age, sex, BMI, WC, HDL, TG, diabetes mellitus, and hypertension) F2 liver fibrosis score is negatively correlated with the HSD17B13 rs9992651 GA genotype. This study offers evidence for the association of the PNPLA3 rs738409 C>G variant with MASLD among Egyptians and for the association of the PNPLA3 rs738409 G allele, the TM6SF2 rs58542926 T allele, and the GCKR rs1260326 C allele with some parameters of cardiometabolic criteria.
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17-Hidroxiesteroide Desidrogenases , Aciltransferases , Proteínas Adaptadoras de Transdução de Sinal , Lipase , Proteínas de Membrana , Hepatopatia Gordurosa não Alcoólica , Fosfolipases A2 Independentes de Cálcio , Polimorfismo de Nucleotídeo Único , Humanos , Proteínas de Membrana/genética , Lipase/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Egito , Masculino , Feminino , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , 17-Hidroxiesteroide Desidrogenases/genética , Predisposição Genética para Doença , Índice de Gravidade de Doença , Cirrose Hepática/genética , Cirrose Hepática/patologia , Estudos de Casos e Controles , GenótipoRESUMO
PURPOSE: Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1 year. METHODS: Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12 months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1 year. RESULTS: Eighty-four HCV patients with a mean age of 56.35 ± 8.12 years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5 cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1 year after ablation were associated with significantly lower recurrence. CONCLUSION: Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated. The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).
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Antivirais , Carcinoma Hepatocelular , Hepacivirus , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Humanos , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/tratamento farmacológico , Masculino , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Feminino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/virologia , Recidiva Local de Neoplasia/prevenção & controle , Hepacivirus/isolamento & purificação , Hepacivirus/efeitos dos fármacos , Sofosbuvir/uso terapêutico , Idoso , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Carbamatos/uso terapêuticoRESUMO
INTRODUCTION: The pathways like Wingless-related integration (Wnt/ß-catenin) and PI3K play an important role in colorectal cancer (CRC) development; however, their roles are distinct in the process of oncogenesis. Despite their differences, these pathways interact through feedback mechanisms and regulate the common effectors both in the upstream and the downstream processes in normal and pathological conditions. Their ability to reciprocally control each other is a primary resistance mechanism for the selective inhibitors in CRC. AREA COVERED: This review highlights the Wnt/ß-catenin and PI3K pathways that are interrelated in CRC, recent advances and some key perspectives in developing inhibitors that could target the tankyrase enzyme and PI3K, apart from a brief description of the potential of dual inhibitors of PI3K and Tankyrases (TNKS). EXPERT OPINION: Recent research has focused on overcoming the challenges particularly relating to the resistance and efficacy of dual inhibitors targeting PI3K and tankyrase proteins. Despite these challenges, PI3K as well as tankyrases remain promising therapeutic targets for the treatment of solid tumors. The design of potent inhibitors is crucial to effectively block these protein signaling pathways. Moreover, it is essential to explore the potential of dual-target inhibition of other signaling pathways in conjunction with PI3K and tankyrase.
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Antineoplásicos , Neoplasias Colorretais , Terapia de Alvo Molecular , Inibidores de Fosfoinositídeo-3 Quinase , Tanquirases , Via de Sinalização Wnt , Humanos , Tanquirases/antagonistas & inibidores , Tanquirases/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Animais , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Antineoplásicos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Desenvolvimento de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
Objective: The legitimacy of published research confronts a real challenge posed by predatory journals. These journals not only distribute inadequately written articles but also undermine the prospects of acknowledgment and citation for high-quality content. It is essential, nevertheless, to differentiate between predatory journals and reputable open-access ones. A worldwide anti-predatory movement seeks to enhance awareness about such journals. Hence, our objective was to assess the awareness, attitudes, and practices of Sudanese orthopedic surgeons concerning both predatory and open-access publishing. Methods: Conducted between January and April 2023, this cross-sectional electronic survey involved Sudanese orthopedic surgeons. The survey, comprising five domains to gauge knowledge, attitudes, and practices related to predatory and open-access publishing, was shared via the Sudanese Orthopedic Surgeons Association email distribution list among the 561 registered surgeons. The targeted sample size was 286. Categorical variables were reported using frequencies, while continuous variables were presented as medians and interquartile ranges. Nonparametric tests and ordinal regression were employed for inferential statistics. Results: Of the 561 surgeons, 104 participants completed the questionnaire, resulting in a response rate of 18.5 %. Approximately 49% exhibited poor knowledge, with 56% unfamiliar with the term "predatory journals," and 74% unaware of Beall's list. Overall attitudes toward publication in open-access and predatory journals were neutral for 60% of participants, and only 26% demonstrated good overall publication practices. Higher knowledge scores positively correlated with attitude and practice scores. Ordinal regression analysis identified variables such as employment in university hospitals, higher academic rank, publication experience, and working in well-resourced countries as factors increasing the likelihood of higher knowledge, attitude, and practice scores. Conclusion: The majority of the study participants reported very low knowledge of predatory journals and their possible detrimental consequences on the integrity and quality of scientific publications. Therefore, educational efforts on the negative impact of predatory publication practices in orthopedics are needed.
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The decreasing status of on IUCN of Koklass pheasant (Pucrasia macrolopha) belongs to the family Phasianidae and the order Galliform needs the attention of researchers. The species with habitats as low as 6,000 feet and as high as 11,000 feet certainly cover a broad variety of habitats, such a wide altitude range embraces a diverse range of habitats. Insufficient research has been conducted on the suitability of moist temperate forests as a potential habitat for the Koklass pheasant. Therefore, this study was carried out to explore habitat suitability in 15 different sites which were located in the 4 districts of Hazara Division using GIS data science and environmental variables. A random sampling technique was used for laying out the transect. Overall, 45 line transects (Length 2-4 km, Width 10-30 m) were laid out in study sites. The size of sample plots for trees was 10x10m, for shrubs (4 x4m), and herbs and grasses 1x1m. The other habitat parameters like elevation, slope, cover, and frequency of plant at each point were also considered. We found the uneven distribution of Koklass pheasant in the Hazara Division. There were 59 occurrence points identified and highlighted the distribution of Koklass pheasant in the study area. Although all environmental variables were preferred by Koklass pheasant in its habitat statistical analysis proved that slope, level of disturbance, tree and shrub frequency of habitat contributed mostly to the presence of Koklass in each study site except the contribution of soil and herbs. The potential suitable habitat of Koklass pheasant was estimated to be 439.6 km2 areas starting from Abbottabad to Mansehra in the Hazara division. Awareness and enforcing legal protection are recommended for the conservation of Koklass Pheasant in Moist temperate forest.
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Ecossistema , Florestas , Animais , Codorniz , Árvores , AltitudeRESUMO
Multiple sclerosis is the predominant autoimmune disorder affecting the central nervous system in adolescents and adults. Specific treatments are categorized as disease-modifying, whereas others are symptomatic treatments to alleviate painful symptoms. Currently, no singular conventional therapy is universally effective for all patients across all stages of the illness. Nevertheless, cannabinoids exhibit significant promise in their capacity for neuroprotection, anti-inflammation, and immunosuppression. This review will examine the traditional treatment for multiple sclerosis, the increasing interest in using cannabis as a treatment method, its role in protecting the nervous system and regulating the immune system, commercially available therapeutic cannabinoids, and the emerging use of cannabis in nanomedicine. In conclusion, cannabinoids exhibit potential as a disease-modifying treatment rather than merely symptomatic relief. However, further research is necessary to unveil their role and establish the safety and advancements in nano-cannabinoid medicine, offering the potential for reduced toxicity and fewer adverse effects, thereby maximizing the benefits of cannabinoids.
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In sodium-ion batteries (SIBs), TiO2or sodium titanates are discussed as cost-effective anode material. The use of ultrafine TiO2particles overcomes the effect of intrinsically low electronic and ionic conductivity that otherwise limits the electrochemical performance and thus its Na-ion storage capacity. Especially, TiO2nanoparticles integrated in a highly conductive, large surface-area, and stable graphene matrix can achieve an exceptional electrochemical rate performance, durability, and increase in capacity. We report the direct and scalable gas-phase synthesis of TiO2and graphene and their subsequent self-assembly to produce TiO2/graphene nanocomposites (TiO2/Gr). Transmission electron microscopy shows that the TiO2nanoparticles are uniformly distributed on the surface of the graphene nanosheets. TiO2/Gr nanocomposites with graphene loadings of 20 and 30 wt% were tested as anode in SIBs. With the outstanding electronic conductivity enhancement and a synergistic Na-ion storage effect at the interface of TiO2nanoparticles and graphene, nanocomposites with 30 wt% graphene exhibited particularly good electrochemical performance with a reversible capacity of 281 mAh g-1at 0.1 C, compared to pristine TiO2nanoparticles (155 mAh g-1). Moreover, the composite showed excellent high-rate performance of 158 mAh g-1at 20 C and a reversible capacity of 154 mAh g-1after 500 cycles at 10 C. Cyclic voltammetry showed that the Na-ion storage is dominated by surface and TiO2/Gr interface processes rather than slow, diffusion-controlled intercalation, explaining its outstanding rate performance. The synthesis route of these high-performing nanocomposites provides a highly promising strategy for the scalable production of advanced nanomaterials for SIBs.
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We have previously shown that the long-acting ß2-adrenergic receptor (ß2-AR) agonist formoterol induced recovery from acute kidney injury in mice. To determine whether formoterol protected against diabetic nephropathy, the most common cause of end-stage kidney disease (ESKD), we used a high-fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment, there was a marked recovery from and reversal of diabetic nephropathy in HFD mice compared with those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. To investigate effects in humans, we performed a competing risk regression analysis with death as a competing risk to examine the association between Veterans with chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), who use ß2-AR agonists, and Veterans with CKD but no COPD, and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011 and 2013. Veterans were followed until 2016 or death. ESKD was defined as the initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared with no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other ß2-AR agonists compared with those with no COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a treatment for diabetic nephropathy and perhaps other forms of CKD.NEW & NOTEWORTHY Diabetic nephropathy is the most common cause of ESKD. Formoterol, a long-acting ß2-adrenergic receptor (ß2-AR) agonist, reversed diabetic nephropathy in murine models of type 1 and 2 diabetes. In humans, there was an association with protection from progression of CKD in patients with COPD, by means of ß2-AR agonist intake, compared with those without COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a new treatment for diabetic nephropathy and other forms of CKD.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Falência Renal Crônica , Doença Pulmonar Obstrutiva Crônica , Humanos , Animais , Camundongos , Nefropatias Diabéticas/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estreptozocina , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fumarato de Formoterol/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/etiologia , Receptores Adrenérgicos/uso terapêuticoRESUMO
ABSTRACT Background: Myeloid-derived suppressor cells (MDSCs) have immature morphology, relatively weak phagocytic activity, as well as some immunosuppressive functions. The capacity of MDSCs to inhibit T-cell-mediated immunological responses is their most notable functional characteristic. Down-regulating antitumor immune surveillance is one way that the expansion and activation of MDSCs contribute significantly to the occurrence and progression of tumors. Increased levels of MDSCs in patients with chronic hepatitis C virus (HCV) infection could suppress T-cell responses, promoting viral escape and hepatitis progression. This may make HCV-infected individuals more vulnerable to severe infections, hepatic and extra-hepatic tumors, and a diminished capacity to react to immunization. It is still unknown if effective HCV eradication with directly acting antivirals (DAAs) can restore immune functions and immune surveillance capacity. Objective: The purpose of this study was to observe the frequency of M-MDSCs (CD33+, CD11b+, and HLA-DR) in patients with a previous history of HCV, 2-3 years after virus eradication using DAA therapy. Methods: This study was conducted on 110 subjects: fifty-five subjects without liver cirrhosis who were treated with HCV using DAAs and attained SVR for a period of 2-3 years and 55 age- and gender-matched healthy controls. The study was conducted during the period from January to July 2022. Patients were recruited from the National Viral Hepatitis Treatment Unit, Alexandria University Hepatology outpatient clinic, and the Alexandria University Tropical Medicine outpatient clinic. The frequencies of MDSCs (CD33+CD11b + HLA-DR-) by flow cytometry were assessed. Results: Even after the virus had been eradicated for longer than two years, MDSC levels in HCV-treated individuals were found to be considerably higher. In the HCV-treated group, the median number of MDSCs was 5, with an interquartile range (IQR) of 3.79-7.69. In contrast, the median for the control group was 3.1, with an IQR of 1.4-3.2 (P˂0.001). Conclusion: Successful DAA therapy leads to slow and partial immunological reconstitution, as demonstrated by the failure to attain normal levels of MDSC's 2 years after successful HCV eradication despite the normalization of laboratory parameters as well as the absence of liver fibrosis. The clinical implications of these findings should be thoroughly studied.
RESUMO Contexto: As células supressoras derivadas de mieloides (CSDMs) possuem morfologia imatura, atividade fagocítica relativamente fraca e algumas funções imunossupressoras. A capacidade das CSDMs de inibir respostas imunológicas mediadas por células T é sua característica funcional mais notável. A expansão e ativação das CSDMs contribuem significativamente para a ocorrência e progressão de tumores, regulando negativamente a vigilância imunológica antitumoral. Níveis aumentados de CSDMs em pacientes com infecção crônica pelo vírus da hepatite C (HCV) poderiam suprimir respostas das células T, promovendo a fuga viral e a progressão da hepatite. Isso pode tornar os indivíduos infectados pelo HCV mais vulneráveis a infecções graves, tumores hepáticos e extra-hepáticos, e a uma capacidade diminuída de reagir à imunização. Ainda não se sabe se a erradicação eficaz do HCV com antivirais de ação direta (AAD) pode restaurar as funções imunológicas e a capacidade de vigilância imunológica. Objetivo: O objetivo deste estudo foi observar a frequência de M-CSDMs (CD33+, CD11b+ e HLA-DR-) em pacientes com histórico anterior de HCV, 2-3 anos após a erradicação do vírus usando terapia com AADs. Métodos: Este estudo foi realizado em 110 indivíduos: 55 indivíduos sem cirrose hepática que foram tratados com AADs para HCV e atingiram resposta virológica sustentada (SVR) por um período de 2-3 anos e 55 controles saudáveis pareados por idade e gênero. O estudo foi conduzido no período de janeiro a julho de 2022. Os pacientes foram recrutados da Unidade Nacional de Tratamento de Hepatites Virais, da clínica ambulatorial de Hepatologia da Universidade de Alexandria e da clínica ambulatorial de Medicina Tropical da Universidade de Alexandria. As frequências de CSDMs (CD33+CD11b+HLA-DR-) foram avaliadas por citometria de fluxo. Resultados: Mesmo após a erradicação do vírus por mais de dois anos, os níveis de CSDMs em indivíduos tratados para HCV foram consideravelmente mais altos. No grupo tratado para HCV, o número mediano de CSDMs foi de 5, com um intervalo interquartil (IQR) de 3,79-7,69. Em contraste, a mediana para o grupo controle foi de 3,1, com um IQR de 1,4-3,2 (P<0,001). Conclusão: A terapia bem-sucedida com AADs leva a uma reconstituição imunológica lenta e parcial, como demonstrado pela falha em atingir níveis normais de CSDMs 2 anos após a erradicação bem-sucedida do HCV, apesar da normalização dos parâmetros laboratoriais e da ausência de fibrose hepática. As implicações clínicas desses achados devem ser estudadas minuciosamente.
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OBJECTIVE: To compare high-para and low-para women with respect to haematological findings, determinants, and consequences secondary to anaemia. STUDY DESIGN: Descriptive cohort study. Place and Duration of the Study: Maternity and Child Hospital, Hail, Saudi Arabia and Specialist Care Hospital (private), Islamabad, Pakistan, from April 2022 to April 2023. METHODOLOGY: The study population comprised of pregnant women in the last trimester, with the exception of those women who had more than one fetus and history of haematological disease. Purposive non-probability sampling technique was adopted. Hospital data were retrieved retrospectively for the past obstetrical, contraception usage, and supplement history. Blood parameters, type of delivery, and maternofetal complications were noted down. For qualitative-variable and quantitative-variable comparisons, Chi-square test and t-test were applied, respectively. Significance level was kept at p ≤0.05. RESULTS: The frequency of severe anaemia in high-para was 52%. High parity and anaemia had a significant dose-response relationship (p <0.05). There was a significant difference (p <0.05) in blood parameters between high-para and low-para groups. Main determinants identified for anaemia were lack of intake of iron-rich food (36%) followed by inadequate intake of oral iron (25%). Preterm birth (68%) and post-partum haemorrhage (96%) were significantly associated (p <0.05) with high parity. There was a significantly high proportion (83%) of high-para women with more than 3 cesarean deliveries and admissions in ICU. CONCLUSION: High parity and anaemia had a significant dose-response relationship. High parity was the main determinant of maternal and fetal admissions in ICU. KEY WORDS: Parity, Comparison, Maternal anaemia, Haematological findings, Diet, Contraception, Cost-effective.
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Anemia , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Anemia/epidemiologia , Anemia/etiologia , Estudos de Coortes , Ferro , Gestantes , Estudos RetrospectivosRESUMO
The impact of microbial muramidase (MMUR) addition to broiler chicken rations was evaluated through growth parameters, liver histoarchitecture, antioxidant status, biochemical analysis, and expression of pro-inflammatory cytokines for 35 days. Four hundred three-day-old chicks (97.68 ± 0.59 g) were distributed to four distinct groups with ten duplicates each (100 chicks/group) consisting of: group 1 (G1): a basal diet without MMUR (control group); G2: a basal diet + 200 mg MMUR kg-1 G3: a basal diet + 400 mg MMUR kg-1; and G4: a basal diet + 600 mg MMUR kg-1. The results showed that the final body weight and total weight gain were increased (p = 0.015) in birds fed with diets supplemented with MMUR at 600 mg kg-1. The feed conversion ratio (FCR) was improved in all treatment groups compared with the control group. Birds fed with a diet supplemented with 600 mg MMUR kg-1 showed the highest body weight gain and improved FCR. The values of thyroxin hormones and growth hormones were increased in all MMUR-supplemented groups. Dietary MMUR increased the activities of antioxidant enzymes (total antioxidant activity, catalase, and superoxide dismutase) and decreased the activity of malondialdehyde (p < 0.05). In addition, it increased the values of interleukin 1 beta and interferon-gamma compared with the control group. Furthermore, dietary MMUR increased the expression of transforming growth factor-beta immunostaining in the liver and spleen tissues. Our results show that supplementing broilers' diets with 600 mg MMUR kg-1 could enhance the chicken growth rate and improve their antioxidant, inflammatory, and anti-inflammatory responses.
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Topoisomerases are very important enzymes that regulate DNA topology and are vital for biological actions like DNA replication, transcription, and repair. The emergence and spread of cancer has been intimately associated with topoisomerase dysregulation. Topoisomerase inhibitors have consequently become potential anti-cancer medications because of their ability to obstruct the normal function of these enzymes, which leads to DNA damage and subsequently causes cell death. This review emphasizes the importance of topoisomerase inhibitors as marketed, clinical and preclinical anti-cancer medications. In the present review, various types of topoisomerase inhibitors and their mechanisms of action have been discussed. Topoisomerase I inhibitors, which include irinotecan and topotecan, are agents that interact with the DNA-topoisomerase I complex and avert resealing of the DNA. The accretion of DNA breaks leads to the inhibition of DNA replication and cell death. On the other hand, topoisomerase II inhibitors like etoposide and teniposide, function by cleaving the DNA-topoisomerase II complex thereby effectively impeding the release of double-strand DNA breaks. Moreover, the recent advances in exploring the therapeutic efficacy, toxicity, and MDR (multidrug resistance) issues of new topoisomerase inhibitors have been reviewed in the present review.
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INTRODUCTION: Intrahepatic vascular shunts "IHVS" are abnormal communications between intra-hepatic vasculature involving the arterial, portal, or hepatic venous system. Arterio-portal fistula "APF" is an intrahepatic communication between the hepatic arterial system and the portal venous system without any communication with the systemic venous circulation. APF is considered a rare cause of portal hypertension and gastrointestinal bleeding in infancy. CASE PRESENTATION: A 3-month-old Mediterranean female with known cardiac congenital anomalies presented to us with abdominal distension and diarrhea. Ultrasonography revealed massive ascites and computerized tomography (CT) abdomen with intravenous (IV) contrast revealed a left hepatic lesion. On further evaluation, an intrahepatic arterio-portal vascular malformation was detected. Attempted trans arterial embolization failed and radiology team successfully carried out direct trans hepatic ultrasound guided coiling of the aneurysmal venous sac followed by successful resection of segment 4 of the liver with the vascular malformation avoiding life threatening intra operative bleeding. CONCLUSION: Any child with recurrent gastrointestinal bleeding, failure to thrive, vomiting, diarrhea, steatorrhea, splenomegaly, or ascites should be investigated for intrahepatic arterio-portal fistula "IAPF". Our novel technique of direct trans hepatic ultrasound guided coiling is an alternative method if trans arterial embolization "TAE" failed.
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Ascite , Fístula , Criança , Feminino , Humanos , Lactente , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Diarreia , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.