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Background and Aims: NASH confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed the safety and efficacy of Meriva in NASH., Approach and Results: In this double-blind trial, 52 patients with biopsy-proven NASH (71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a chronic kidney disease) were randomized 1:1 to receive Meriva 2 g/d or placebo for 72 weeks. The primary endpoint was NASH resolution with no worsening of fibrosis. The secondary endpoints included a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant (ie, stage ≥F2) fibrosis and CKD; and improvement in renal, glucose, lipid, and inflammatory parameters. We also explored the treatment effect on hepatic activation of NF-kB, a key proinflammatory transcription factor and a major target of curcumin. Fifty-one patients (26 on Meriva and 25 on placebo) completed the trial. Sixteen (62%) patients on Meriva versus 3 (12%) patients on placebo had NASH resolution (RR = 5.33 [95% CI = 1.76-12.13]; p = 0.003). Thirteen (50%) patients on Meriva versus 2 (8%) patients on placebo had ≥1 stage fibrosis improvement (RR = 6.50 [1.63-21.20]; p = 0.008). Eleven (42%) patients on Meriva versus 0 (0%) on placebo had regression of significant liver fibrosis (RR = 18.01 [1.43-36.07]; p = 0.02). Hepatic NF-kB inhibition predicted NASH resolution (AUC = 0.90, 95% CI = 0.84-0.95) and fibrosis improvement (AUC = 0.89, 95% CI = 0.82-0.96). Thirteen (50%) patients on Meriva versus 0 (0%) on placebo had chronic kidney disease regression (RR = 10.71 [1.94-17.99)]; p = 0.004). Compared with placebo, Meriva improved eGFR (difference in adjusted eGFR change: +3.59 [2.96-4.11] mL/min/1.73 m 2 /y, p = 0.009), fasting glucose(-17 mg/dL; 95% CI = -22, -12), HbA1c (-0.62%; 95% CI = -0.87%, -0.37%), LDL-C (-39 mg/dL; 95% CI = -45, -33), triglycerides (-36 mg/dL, 95% CI = -46, -26), HDL-C (+10 mg/dL; 95% CI = +8, +11), and inflammatory markers. Adverse events were rare, mild, and evenly distributed., Conclusions: In patients with NASH, Meriva administration for 72 weeks was safe, well-tolerated, and improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a spectrum of liver disease ranging from hepatic fat accumulation to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma in the absence of excessive alcohol consumption. MASLD is characterized by substantial inter-individual variability in terms of severity and rate of progression, with a prevalence that is generally higher in men than in women. Steroids metabolism is characterized by sexual dimorphism and may have an impact on liver disease progression; indeed, several therapeutic strategies targeting hormone receptors are under phase 2/3 development. Despite the fact that the importance of sexual dimorphism in the setting of MASLD is well recognized, the underlying molecular mechanisms that can potentially drive the disease toward progression are not clear. The aim of this review is to delve into the crosstalk between sexual dimorphism and steroid hormone perturbation under nutritional and pharmacological intervention.

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST's long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients. Methods: This was a multicenter, retrospective, observational cohort study that included both naïve and biologic-experienced patients treated with UST who achieved clinical remission or clinical response after at least one year of treatment. Clinical activity was scored according to the Harvey-Bradshaw Index (HBI). The primary endpoints were the maintenance or achievement of clinical remission after a further 12-month period of treatment, defined as an HBI of ≤5, and safety. Other endpoints included steroid-free remission, mucosal healing (MH), steroid discontinuation, and the need for treatment optimization during the follow-up. Results: Out of 562 CD patients, after an overall 24-month follow-up, clinical remission was present in 450 (80.0%) patients, and at 12 months, clinical remission was observed in 417/437 (95.4%) patients; 33/125 (26.4%) showed clinical response at 12 months ( p = 0.000). A total of 38/103 (36.9%) patients achieved MH. Only 2.1% (12/562), 3% (17/562), and 1.1% (6/562) of patients required surgery, optimization, and re-induction, respectively. Adverse events occurred in eight patients (1.42%). According to a multivariate analysis, the only predictor of long-term remission was the presence of remission at the 12-month follow-up ( p = 0.000). Conclusions : Long-term treatment with UST presents good efficacy and safety profiles in CD patients, especially for patients who achieve remission after one year.

This study conducted a systematic review and meta-analysis to explore the relationship between blood oxidative stress biomarkers and exposure to low-dose ionizing radiation in medical radiation workers. The researchers searched PubMed, Scopus, Web of Science, and Google Scholar for relevant studies until February 2023. They assessed the quality of the studies using the Newcastle‒Ottawa Scale (NOS) and used a random-effects model to combine the results. The I-square test was employed to assess study heterogeneity. The effect sizes were represented by standardized mean differences (proxied by Hedges' g) with a 95 % confidence interval. Out of 295 initial articles, 38 studies met the inclusion criteria for the meta-analysis. The systematic review results revealed a significant difference in blood oxidative stress biomarkers with exposure to low-dose ionizing radiation in medical radiation workers. Furthermore, the overall effect size of MDA was notably higher than that of the control group ( p  < 0.05). However, the effect size did not show any significant difference between the two groups for other parameters (SMDs ranged from [-0.92, 2.10] for 8-OHdG, [-3.47, 4.48] for reduced glutathione, [-1.08, 3.61] for CAT, [-5.03, 18.35] for SOD, [-2.52, 2.56] for TAC ( p  > 0.05))., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Our hypothesis centred on the potential to mitigate ascites outbreaks in birds exposed to cold stress by inhibiting pulmonary artery contraction through dietary intervention., Objective: This study aimed to evaluate the effect of natural and synthetic medications on growth performance, ascites-related parameters and the expression of ascites-related genes in the lung tissue of broiler chickens under low ambient temperature., Methods: We randomly assigned 450 one-day-old male Ross 308 chicks to six dietary treatments across five replicate pens, each containing 15 chicks. The treatments included a basal diet (control), and the basal diet was supplemented with hydroalcoholic extracts of sumac (HES, 200 mg/kg), Syrian mesquite (HEM, 200 mg/kg), l-arginine (40% above requirement), captopril (15 mg/kg) and vitamin E (100 mg/kg)., Results: Diets containing HEM, l-arginine and vitamin E resulted in increased average daily gain on days 8-14 and 0-28, whereas HES showed a similar effect only during days 8-14 compared to the control diet (p < 0.05). Additionally, feed additives decreased packed cell volume, left and right ventricle volumes and systolic blood pressure (p < 0.05). Moreover, chickens fed the control and l-arginine diets exhibited higher levels of angiotensin converting enzyme (ACE) mRNA in lung tissue compared to those fed HES, HEM and captopril (p < 0.05). Meanwhile, supplementation with HEM and l-arginine increased the expression of inducible nitric oxide synthase (iNOS) mRNA in lung tissue compared to other treatments (p < 0.05). Regarding Cu/Zn-superoxide dismutase (Cu/Zn-SOD) expression, feed additives increased mRNA level in lung tissue, except for captopril (p < 0.05)., Conclusions: This study demonstrates that the plant extracts may reduce the incidence of ascites syndrome not only through their antioxidant properties but also by modulating the expression of ACE, iNOS and Cu/Zn-SOD genes., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

In this work the effect of combining ultrasound (US) hyperthermia (HT) with radiotherapy (RT) was investigated. The treatment was applied to a GBM xenograft nude mouse model obtained by injecting 2 × 10 6 U87 luc+ cells. The combined treatment group received 6 Gy and HT at 43 ∘ for 8 min. The ultrasound field was generated by a closed-loop computationally controlled system, consisting of a High Intensity Focused Ultrasound (HIFU) transducer with centre frequency 3.57 MHz, a power amplifier, a function generator and a MATLAB controller. A mechanical cone adaptor has been designed to use the HIFU beam at a pre-defined post-focal distance. Two thermocouples were placed between the mechanical cone and the mice skin to measure and control the temperature during the HT treatment. Radiotherapy was carried out by using a dedicated small animal image guided radiotherapy system. Measurements of tumor volume performed with a caliper showed good tumor control for the RT-HT group with respect to the RT or control groups for up to 21 days after treatment. The mean value of the normalized (before therapy) tumor volume was almost equal to 0.5 for two weeks after treatment with an increase to 1.5 at sacrifice. The control and HT groups showed a higher value of about 1.5 during the first two weeks and 3.5 at the end of the follow-up period. We concluded that the use of HT as a radiosensitizer can improve the outcome for glioblastoma treatments., (© 2024. The Author(s).)

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma subtype with a significant relapse rate and poor prognosis in relapsed/refractory (R/R) patients. Polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) has demonstrated promising efficacy and safety as salvage therapy for R/R DLBCL. This systematic review protocol aims to comprehensively evaluate the efficacy of Pola-BR for the treatment of R/R DLBCL by synthesizing data from relevant randomized controlled trials., Methods: This protocol details the eligibility criteria, search strategy, study selection, data extraction, and analysis methods for the systematic review. Randomized controlled trials comparing Pola-BR with other interventions for R/R DLBCL will be included. The primary endpoint is overall survival, with secondary endpoints being progression-free survival and incidence of adverse events. A comprehensive search will be conducted across databases such as Medline/PubMed, Cochrane Library, Web of Science, Scopus, EMBASE, ProQuest, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov from the January 2000 to April 2024. To assess the potential risk of bias, the Cochrane Risk of Bias 1 tool will be used. Data synthesis will utilize fixed-effect or random-effects models, and subgroup and meta-regression analyses will examine heterogeneity. Additionally, publication bias and sensitivity analyses will be performed, and the GRADE approach will be applied to assess the certainty of the evidence., Conclusion: This systematic review and meta-analysis protocol provides a rigorous framework for evaluating the efficacy of Pola-BR in the treatment of R/R DLBCL. The results will inform clinical decision-making and guideline development, addressing the unmet need for effective and tolerable treatments for this challenging patient population. Potential limitations and biases will be acknowledged, and future research directions will be discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Eslami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, and only 50% of patients with T2DM achieve or maintain adequate glycemic control with pharmacological therapies. Metabolic surgery demonstrated superior efficacy compared to medical therapy but is unfeasible for most patients with T2DM. Duodenal mucosal resurfacing (DMR) by hydrothermal mucosal ablation, recellularization via electroporation therapy (ReCET), and photodynamic therapy are novel endoscopic procedures that use thermal, electrical, and photochemical energy, respectively, to ablate and reset dysfunctional duodenal mucosa. We assessed the data on the effects of these techniques on glycemic control and nonalcoholic fatty liver disease (NAFLD)., Methods: We systematically searched independently and in duplicate English and non-English language publications through January 31st, 2024. Outcomes assessed were an improvement in different metabolic health parameters and the safety of duodenal mucosal ablation (DMA) procedures. Outcomes were presented descriptively., Findings: We selected 12 reports reporting results from 3 randomized and 6 uncontrolled trials (seven evaluating DMR, two evaluating ReCET, all with a low risk of bias) for a total of 317 patients enrolled. DMA reduced HbA1c, fasting plasma glucose, and liver fat. When combined with newer antidiabetic drugs, it allowed insulin discontinuation in up to 86% patients. No major safety signal emerged., Conclusions: All DMA techniques improve glucose homeostasis; DMR and ReCET appear to be safe in patients with T2DM. If confirmed by future randomized trials and by trials with histological endpoints in NAFLD, then DMA appears to be a promising alternative or complement option to medications for T2DM and NAFLD treatment., Funding: This study received no funding., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gastrointestinal basidiobolomycosis (GIB) is a rare fungal infection caused by Basidiobolus ranarum, a saprophytic fungus that belongs to the class of Basidiobolomycetes. It mainly infects immunocompetent individuals and is mainly found in arid tropical and subtropical regions, including Southwestern America, Saudi Arabia, Africa, and Asia. Not surprisingly, a great number of human infections have been reported from these warm, humid climate regions that are felicitous for the growth of this fungus, especially from the southern region of Saudi Arabia and Arizona in the United States of America. GIB is easily misdiagnosed as malignancy, inflammatory bowel disease, diverticulitis, lymphoma, and chronic intestinal infections due to its rarity. In this case series, we summarize the clinical features, imaging, histopathological features, and treatment of patients diagnosed with GIB in our institution., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Meeralam et al.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial condition characterized by insulin resistance, oxidative stress, chronic low-grade inflammation, and sometimes fibrosis. To date, no effective pharmacological therapy has been approved for the treatment of metabolic-associated steatohepatitis (MASH), the progressive form of MASLD. Recently, numerous in vitro and in vivo studies have described the efficacy of nutraceutical compounds in the diet has been tested. Among them, curcumin is the most widely used polyphenol in the diet showing potent anti-inflammatory and antifibrotic activities. This review aims to summarize the most important basic studies (in vitro and animal models studies), describing the molecular mechanisms by which curcumin acts in the context of MASLD, providing the rationale for its effective translational use in humans.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social and communication skills, restricted interests, and repetitive behaviors. The prevalence of ASD among children in Qatar was recently estimated to be 1.1%, though the genetic architecture underlying ASD both in Qatar and the greater Middle East has been largely unexplored. Here, we describe the first genomic data release from the BARAKA-Qatar Study-a nationwide program building a broadly consented biorepository of individuals with ASD and their families available for sample and data sharing and multi-omics research., Methods: In this first release, we present a comprehensive analysis of whole-genome sequencing (WGS) data of the first 100 families (372 individuals), investigating the genetic architecture, including single-nucleotide variants (SNVs), copy number variants (CNVs), tandem repeat expansions (TREs), as well as mitochondrial DNA variants (mtDNA) segregating with ASD in local families., Results: Overall, we identify potentially pathogenic variants in known genes or regions in 27 out of 100 families (27%), of which 11 variants (40.7%) were classified as pathogenic or likely-pathogenic based on American College of Medical Genetics (ACMG) guidelines. Dominant variants, including de novo and inherited, contributed to 15 (55.6%) of these families, consisting of SNVs/indels (66.7%), CNVs (13.3%), TREs (13.3%), and mtDNA variants (6.7%). Moreover, homozygous variants were found in 7 families (25.9%), with a sixfold increase in homozygous burden in consanguineous versus non-consanguineous families (13.6% and 1.8%, respectively). Furthermore, 28 novel ASD candidate genes were identified in 20 families, 23 of which had recurrent hits in MSSNG and SSC cohorts., Conclusions: This study illustrates the value of ASD studies in under-represented populations and the importance of WGS as a comprehensive tool for establishing a molecular diagnosis for families with ASD. Moreover, it uncovers a significant role for recessive variation in ASD architecture in consanguineous settings and provides a unique resource of Middle Eastern genomes for future research to the global ASD community., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aims: Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model., Methods: A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM + ) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM + using immunohistochemistry and immunofluorescence., Results: A total of 12 weeks after treatment, 0.5 μg/μl rHAM + brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment., Conclusion: We found that 0.5 μg/μl rHAM + induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment., Competing Interests: The authors declare that they have no competing interests., (© 2023 Author(s) et al.)

Teratomas are germ cell tumors occurring usually in gonadal organs. They are neoplasms composed of one or more of the three germ layers. Extragonadal teratomas are uncommonly reported in the literature. The liver is an extremely rare site for teratoma, constituting < 1% of all teratomas. The majority of the liver teratomas are found in the pediatric population with only a dozen cases reported in adults to the best of our knowledge. We present a case of a 27-year-old male with a history of abdominal pain of 5 months duration. CT scan revealed liver mass suggesting teratoma. The patient underwent cholecystectomy and segmental liver resection. Histopathology revealed mature cystic teratoma. Complete resection remains the best treatment option. Teratomas of the liver are extremely rare, constituting < 1% of all teratomas. An extensive review of the literature yielded < 50 cases of primary hepatic teratomas with only a dozen cases in adults and only two cases in males.

The interaction of metal nanoparticles (MNPs) with blood cells and tissues is essential from the perspectives of biocompatibility and the production of novel drug delivery systems. In the present study, biosynthesized-Fe 3 O 4 nanoparticles (bio-Fe 3 O 4 NPs) were prepared and bio-modified using Daphne mucronata Royle leaf extracts. The physicochemical properties of bio-Fe 3 O 4 NPs were determined using UV-Visible spectroscopy, Energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) analyses. According to the SEM analysis, the bio-Fe 3 O 4 NPs are spherical-shaped with a size range of 10-30 nm. Antibacterial effects of bio-Fe 3 O 4 NPs against Staphylococcus aureus ATCC 43300 and Pseudomonas aeruginosa ATCC 27853 bacteria were measured by minimum inhibition/bactericidal concentrations (MIC and MBC tests). Result showed that the bio-Fe 3 O 4 NPs (300 ppm) revealed highest antibacterial effect on S. aureus ATCC 43300. Also, bio-Fe 3 O 4 NPs have different cell viability in the human breast cancer cell line (MCF-7) and mouse embryonic fibroblast (MEF). The interaction of bio-Fe 3 O 4 NPs with blood cells and the complete blood count (CBC) factor illustrated that the morphology of blood cells and platelet clumping did not influence by nanoparticles. Furthermore, histological analysis of the liver, spleen, and kidney did not show any abnormality upon exposure to 100 mg kg -1 bio-Fe 3 O 4 NPs treated samples. Hence, the biosynthesized Fe 3 O 4 NPs are a good candidate for applications in medical fields., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting up to 30% of the general adult population. NAFLD encompasses a histological spectrum ranging from pure steatosis to non-alcoholic steatohepatitis (NASH). NASH can progress to cirrhosis and is becoming the most common indication for liver transplantation, as a result of increasing disease prevalence and of the absence of approved treatments. Lipidomic readouts of liver blood and urine samples from experimental models and from NASH patients disclosed an abnormal lipid composition and metabolism. Collectively, these changes impair organelle function and promote cell damage, necro-inflammation and fibrosis, a condition termed lipotoxicity. We will discuss the lipid species and metabolic pathways leading to NASH development and progression to cirrhosis, as well as and those species that can contribute to inflammation resolution and fibrosis regression. We will also focus on emerging lipid-based therapeutic opportunities, including specialized proresolving lipid molecules and macrovesicles contributing to cell-to-cell communication and NASH pathophysiology., Competing Interests: Declaration of Competing Interest No author has any present or past competing interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Congenital analbuminaemia (CAA) is a rare autosomal recessive disorder in which affected individuals have absent or extremely low levels of serum albumin. Adults with this condition are mostly asymptomatic. To the best of our knowledge this is the first case of congenital analbuminaemia reported in Pakistan. While being treated for acute respiratory tract infection, a very low albumin level was incidentally detected. This lead to further investigations and eventually the diagnosis was made. The complication of hyperlipidaemia associated with this disease was present in our patient. However, with subsequent treatment by intravenous albumin infusion, the serum albumin level and hyperlipidaemia improved. In this case report, we highlight the importance of diagnosing and treating this condition in adults at an early stage. This prevents complications that have been known to occur in this disease which include hypercholesterolaemia, hyperlipidaemia and recurrent respiratory tract infections. Rarely, it may be complicated by hypercoagulability and osteoporosis.

Background: Psychotic experiences are reported in the general population. The Questionnaire for Psychotic Experiences (QPE) was created to test the phenomenological features of these experiences and compare them with those reported in patients with psychiatric and other medical conditions. The aim of this study was to test the psychometric properties of the Arabic version of the QPE., Methods: We recruited 50 patients with psychotic disorders from the Hamad Medical Hospital in Doha, Qatar. Patients underwent assessment over three sessions with trained interviewees using the Arabic versions of QPE, Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI), and the Global Assessment of Functioning Scale (GAF). Patients were also reassessed using the QPE and GAF after 14-days from the initial assessment in order to test for the stability of the scale. In this respect, this is the first study that assesses the test-retest reliability of the QPE. The psychometric properties including convergent validity, stability, and internal consistency met the benchmarked criteria., Results: Results confirmed that the Arabic version of QPE accurately measured the experiences of patients that were also reported using the PANSS, an internationally accepted, well-established scale for measuring psychotic symptom severity., Conclusion: We propose the use of the QPE to describe the phenomenology of PEs across modalities in Arabic speaking communities., (© 2023. The Author(s).)

Background: Oxidative stress and impaired autophagy are directly and indirectly implicated in exercise-mediated muscle injury. Trehalose, spermidine, nicotinamide, and polyphenols possess pro-autophagic and antioxidant properties, and could therefore reduce exercise-induced damage to skeletal muscle. The aim of this study was to investigate whether a mixture of these compounds was able to improve muscle injury biomarkers in endurance athletes through the modulation of oxidative stress and autophagic machinery., Methods and Results: sNOX2-dp; H 2 O 2 production; H 2 O 2 breakdown activity (HBA); ATG5 and p62 levels, both markers of autophagic process; and muscle injury biomarkers were evaluated in five endurance athletes who were allocated in a crossover design study to daily administration of 10.5 g of an experimental mixture or no treatment, with evaluations conducted at baseline and after 30 days of mixture consumption. Compared to baseline, the mixture intake led to a remarkable reduction of oxidative stress and positively modulated autophagy. Finally, after the 30-day supplementation period, a significant decrease in muscle injury biomarkers was found., Conclusion: Supplementation with this mixture positively affected redox state and autophagy and improved muscle injury biomarkers in athletes, allowing for better muscle recovery. Moreover, it is speculated that this mixture could also benefit patients suffering from muscle injuries, such as cancer or cardiovascular patients, or elderly subjects.

Background: Earlier studies have shown that a modified low-dose bismuth quadruple therapy given for 10 to 14 days is highly effective for the treatment of Helicobacter pylori infection in Sardinia. However, bismuth is not universally available., Aim: We aimed to investigate the efficacy of a simplified low-dose 10-day quadruple therapy containing a galenic formulation of bismuth salicylate for H. pylori infection., Patients and Methods: Adult patients positive for H. pylori infection were assigned to a quadruple therapy containing a galenic formulation of bismuth salicylate (200 mg) plus tetracycline 500 mg, metronidazole 500 mg and rabeprazole 20 mg, given twice a day with the midday and evening meals for 10 days. A negative stool antigen test or 13C-Urea Breath Test defined successful eradication. Compliance and adverse events were recorded 30-40 days after the end of treatment., Results: In this open-label pilot study, 42 patients were enrolled (mean age 54.1 ± 12.0 years; 64% female). Among the study participants, 35 were naïve to H. pylori treatment. The treatment regimen was completed by 41 patients, with an overall success rate of 95.1%. More specifically, the eradication rate was 95.1% PP; 95% confidence interval (CI) = 86.6-100 and 92.9% by ITT; 95%CI = 85.1-100%, respectively. For naïve patients, the cure rate was 97.1%. Compliance was excellent. Side effects were absent or mild overall., Conclusions: The modified low-dose 10-day quadruple therapy provided high eradication rates of H. pylori infection, despite the replacement of colloidal bismuth subcitrate with bismuth salicylate. In regions where bismuth is unavailable in the market, the galenic formulation should be a valid option.

Lipoblastoma is an extremely rare disease and mostly affects the infant to pediatric age group. Primarily, it involves the extremities, head and neck region, and rarely, the retroperitoneal region. Retroperitoneal lipoblastoma mainly presents with either abdominal pain or distension. We report a case of a 24-year-old male who presented with acute cord compression and underwent decompression and fixation with biopsy. Histopathology established the presence of lipoblastoma. Further staging workup showed no metastasis. Immunostaining and cytogenetics were positive for CD34 and negative for desmin, DNA damage-inducible transcript 3 (DDIT3), mouse double minute 2 (MDM2)(12q15), and pleomorphic adenoma gene 1 (PLAG1). The patient underwent resection of the retroperitoneal mass with intraoperative radiation therapy to the tumor bed. The histopathology identified the mass as retroperitoneal lipoblastoma. The postoperative course was uneventful and CT images showed no recurrence or metastasis. This was a unique case of retroperitoneal lipoblastoma in an adult with a unique clinical presentation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alghanmi et al.)

Ocean Water Quality (OWQ) monitoring provides insights into the quality of water in marine and near-shore environments. OWQ measurements can contain the physical, chemical, and biological characteristics of oceanic waters, where low OWQ values indicate an unhealthy ecosystem. Many parameters of water can be estimated from Remote Sensing (RS) data. Thus, RS offers significant opportunities for monitoring water quality in estuaries, coastal waterways, and the ocean. This paper reviews various RS systems and techniques for OWQ monitoring. It first introduces the common OWQ parameters, followed by the definition of the parameters and techniques of OWQ monitoring with RS techniques. In this study, the following OWQ parameters were reviewed: chlorophyll-a, colored dissolved organic matter, turbidity or total suspended matter/solid, dissolved organic carbon, Secchi disk depth, suspended sediment concentration, and sea surface temperature. This study presents a systematic analysis of the capabilities and types of spaceborne systems (e.g., optical and thermal sensors, passive microwave radiometers, active microwave scatterometers, and altimeters) which are commonly applied to OWQ assessment. The paper also provides a summary of the opportunities and limitations of RS data for spatial and temporal estimation of OWQ. Overall, it was observed that chlorophyll-a and colored dissolved organic matter are the dominant parameters applied to OWQ monitoring. It was also concluded that the data from optical and passive microwave sensors could effectively be applied to estimate OWQ parameters. From a methodological perspective, semi-empirical algorithms generally outperform the other empirical, analytical, and semi-analytical methods for OWQ monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to explore the effect of occupational exposure to X-ray on hematological parameters., Research Design and Methods: A systematic search was conducted in the Scopus, PubMed, Web of Science, and Embase databases up to April 2020. The methodological quality was assessed by Joanna Briggs Institute (JBI) Critical Appraisal Checklist . The random-effects model was used to estimate the effect size (standard difference in means (SDMs))., Results: Out of 1750 identified citations, ten studies met the inclusion criteria The overall effect size did not show any significant difference between the two groups (SMDs ranged from -0.382 ± 0.29 for white blood cells (WBC), 0.213 ± 0.40 for platelet, -0.323 ± 0.0.16 for mean corpuscular volume (MCV), 0.553 ± 0.41 for mean corpuscular hemoglobin concentration (MCHC), -1.615 ± 1.41 for monocyte, 0.418 ± 0.49 for lymphocyte (P-value>0.05). Only the effect size of red blood cells was significantly higher than that of the control group (SMD = 1.06 ± 0.28; 95% CI: 0.504, 1.615; P-value = 0.001)., Conclusion: The long-term and low-dose radiation may have no significant effect on blood parameters. Future studies are suggested to use other tests such as dicentric chromosome assay (DCA), cytogenetic tests, and modern tests besides blood count parameters.

We report an unusual case of primary gastric synovial sarcoma in a young woman who presented with chronic abdominal pain. Esophagealgastricendoscopy showed a gastric fundus mass measuring 2 cm × 3 cm. Biopsy confirmed a primary synovial sarcoma. Staging work-up was negative for metastasis. The patient underwent surgery, and the histopathology results did not suggest the need for adjuvant chemotherapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alghanmi et al.)

Objectives: Bone marrow collections are often difficult, and creating quality smears and touch preparations at the bedside can prove challenging. The objective of this study is to compare the quality of bone marrow specimens between unassisted and assisted bone marrow collections by a bone marrow technologist., Methods: Data for this study were collected from 422 hematopathology reports over 14 months. We recorded the bone marrow quality of the different parts (aspirate smears, touch imprints, core biopsy, and clot/particle sections) as adequate, suboptimal, or inadequate. Student t test statistical analysis was performed between the corresponding parts in the two groups., Results: Our results demonstrate that the quality of assisted bone marrow specimens is significantly better compared with unassisted specimens, particularly for the aspirate smears (P < .0001) and touch imprints (P < .0001). Notably, the quality of aspirate smears was improved, which is important for cytologic evaluation., Conclusions: We conclude that assistance by a bone marrow technologist resulted in a significant improvement in the quality of bone marrow collection., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To demonstrate the technical efficacy and safety of CT-guided transforaminal periradicular infiltration in the treatment of the radicular pain without surgical intervention, using CT foot switches and MPR images., Materials and Methods: Four hundred and eighty two patients (286 males and 196 females, age range 27-71 years, mean age 56 years) with a unilateral or bilateral radiculopathy who underwent CT-guided transforaminal periradicular infiltration without surgical intervention, were retrospectively selected in the period from January 2019 to February 2020.  Patients who had received surgery for herniated disc or laminectomy, patients with a previous vertebral fractures, and patients with inflammatory syndrome or risk of bleeding were excluded., Results: There were no major or minor clinically relevant complications. Many patients a marked reduction or resolution of pain after the CT-guided infiltration (P<0.05). No patient required hospitalization. One patient reported an episode of intense headache, which resolved after twenty minutes. In eleven cases, a slight increase in pain related to spinal compression caused by the administration of the drug was reported, even if administrated extremely slowly. Sixteen patients reported pain in the upper limbs during and after the procedure, however this was not related to infiltration but to the forced and prolonged arm position., Conclusion: CT-guided transforaminal periradicular infiltration is a semi-invasive and well tolerated procedure, moreover it has a reduced comorbidity and no observed major or minor complications. The CT foot switches and MPR evaluation may help to make the procedure more efficient.

Hodgkin lymphoma (HL) is today one of the most curable pediatric cancers. Despite survival rates now exceeding 90%, survivors of pediatric HL are still at higher risk to develop late effects of cancer therapy. Premature aging has been proposed as a paradigm to explain the onset of long-term complications in these subjects. High levels of advanced glycation end products (AGEs), together with chronic inflammation and oxidative unbalance, have been shown to be among the main factors contributing to aging. The present study aims to evaluate glycoxydation, inflammatory status, and oxidative stress in plasma and peripheral blood mononuclear cells (PBMC) obtained from 20 adult survivors of pediatric HL and 40 age- and sex-matched healthy controls. After the isolation of PBMC and the collection of plasma, we performed the analyses of gene expression by qRT-PCR and measured inflammatory and oxidative-stress markers. AGEs plasma levels, expressed as Nϵ-carboxymethyl-lysine and methylglyoxal hydroimidazolone, were markedly higher in HL survivors than in healthy subjects. HL survivors also showed a condition of higher oxidative stress, as demonstrated by an increased expression of NADPH oxidase on PBMC. Antioxidant defenses, evaluated in terms of alpha-tocopherol, GSSG/GSH ratio and catalase plasma levels, were strongly impaired in survivors. This pro-oxidative condition led to the over-expression of both NLRP3 and NFkB genes in PBMC and, consequently, to increased plasma levels of interleukin(IL)-1β and IL-6. Finally, the expression of the receptors for AGEs in PBMC confirmed the dysregulated AGE pathways. Data show AGEs accumulation in survivors of pediatric HL. The consequent activation of the receptor for AGEs leads to the persistent activation of intracellular signaling toward inflammation. These results suggest that the co-existence of AGEs accumulation, unbalanced oxidative status, and inflammation could play a role in the onset of late complications in HL survivors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aggregation of huntingtin fragments with expanded polyglutamine repeat regions (HttpolyQ) that cause Huntington's disease depends on the presence of a prion with an amyloid conformation in yeast. As a result of this relationship, HttpolyQ aggregation indirectly depends on Hsp104 due to its essential role in prion propagation. We find that HttQ103 aggregation is directly affected by Hsp104 with and without the presence of [ RNQ + ] and [ PSI + ] prions. When we inactivate Hsp104 in the presence of prion, yeast cells have only one or a few large HttQ103 aggregates rather than numerous smaller aggregates. When we inactivate Hsp104 in the absence of prion, there is no significant aggregation of HttQ103, whereas with active Hsp104, HttQ103 aggregates accumulate slowly due to the severing of spontaneously nucleated aggregates by Hsp104. We do not observe either effect with HttQ103P, which has a polyproline-rich region downstream of the polyglutamine region, because HttQ103P does not spontaneously nucleate and Hsp104 does not efficiently sever the prion-nucleated HttQ103P aggregates. Therefore, the only role of Hsp104 in HttQ103P aggregation is to propagate yeast prion. In conclusion, because Hsp104 efficiently severs the HttQ103 aggregates but not HttQ103P aggregates, it has a marked effect on the aggregation of HttQ103 but not HttQ103P.

Background: Noninvasive stimulation has been widely used in the past 30 years to study and treat a large number of neurological diseases, including movement disorders., Objective: In this critical review, we illustrate the rationale for use of these techniques in movement disorders and summarize the best medical evidence based on the main clinical trials performed to date., Methods: A nationally representative group of experts performed a comprehensive review of the literature in order to analyze the key clinical decision-making factors driving transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in movement disorders. Classes of evidence and recommendations were described for each disease., Results: Despite unavoidable heterogeneities and low effect size, TMS is likely to be effective for treating motor symptoms and depression in Parkinson's disease (PD). The efficacy in other movement disorders is unclear. TMS is possibly effective for focal hand dystonia, essential tremor and cerebellar ataxia. Additionally, it is likely to be ineffective in reducing tics in Tourette syndrome. Lastly, tDCS is likely to be effective in improving gait in PD., Conclusions: There is encouraging evidence for the use of noninvasive stimulation on a subset of symptoms in selected movement disorders, although the means to optimize protocols for improving positive outcomes in routine clinical practice remain undetermined. Similarly, the best stimulation paradigms and responder profile need to be investigated in large clinical trials with established therapeutic and assessment paradigms that could also allow genuine long-term benefits to be determined.

Lateral ligament tears, also known as high-grade ankle sprains, are common, debilitating, and usually heal slowly. Ten to thirty percent of patients continue to suffer from chronic pain and ankle instability even after 3 to 9 months. Previously, we showed that the recombinant human amelogenin (rHAM + ) induced regeneration of fully transected rat medial collateral ligament, a common proof-of-concept model. Our aim was to evaluate whether rHAM + can regenerate torn ankle calcaneofibular ligament (CFL), an important component of the lateral ankle stabilizers. Right CFLs of Sabra rats were transected and treated with 0, 0.5, or 1 µg/µL rHAM + dissolved in propylene glycol alginate (PGA). Results were compared with the normal group, without surgery. Healing was evaluated 12 weeks after treatment by mechanical testing (ratio between the right and left, untransected ligaments of the same rat), and histology including immunohistochemical staining of collagen I and S100. The mechanical properties, structure, and composition of transected ligaments treated with 0.5 μg/μL rHAM + (experimental) were similar to untransected ligaments. PGA (control) treated ligaments were much weaker, lax, and unorganized compared with untransected ligaments. Treatment with 1 μg/μL rHAM + was not as efficient as 0.5 μg/μL rHAM + . Normal arrangement of collagen I fibers and of proprioceptive nerve endings, parallel to the direction of the force, was detected in ligaments treated with 0.5 μg/μL rHAM + , and scattered arrangement, resembling scar tissue, in control ligaments. In conclusion, we showed that rHAM + induced significant mechanical and structural regeneration of torn rat CFLs, which might be translated into treatment for grades 2 and 3 ankle sprain injuries., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder that becomes apparent during early childhood development. The complexity of ASD makes clinically diagnosing the condition difficult. Consequently, by identifying the biomarkers associated with ASD severity and combining them with clinical diagnosis, one may better factionalize within the spectrum and devise more targeted therapeutic strategies. Currently, there are no reliable biomarkers that can be used for precise ASD diagnosis. Consequently, our pilot experimental cohort was subdivided into three groups: healthy controls, individuals those that express severe symptoms of ASD, and individuals that exhibit mild symptoms of ASD. Using next-generation sequencing, we were able to identify several circulating non-coding RNAs (cir-ncRNAs) in plasma. To the best of our knowledge, this study is the first to show that miRNAs, piRNAs, snoRNAs, Y-RNAs, tRNAs, and lncRNAs are stably expressed in plasma. Our data identify cir-ncRNAs that are specific to ASD. Furthermore, several of the identified cir-ncRNAs were explicitly associated with either the severe or mild groups. Hence, our findings suggest that cir-ncRNAs have the potential to be utilized as objective diagnostic biomarkers and clinical targets.

Lymphomas are a diverse group of haematologic malignancies, which occur in infection-fighting cells of the lymphatic system. Long non-coding RNAs (lncRNAs) are non-coding RNAs, which have recently received significant attention as the main mediators of gene expression. In this review, we summarize the current knowledge on lncRNAs involved in lymphomas, their molecular functions, as well as their potential clinical value. Relevant literature was identified by a PubMed search of English language papers using the following terms: Lymphoma, LncRNA, leukemia, proliferation, apoptosis, and prognosis. LncRNAs are imperative for lymphoma carcinogenesis through affecting apoptosis, cell proliferation, invasion, and response to chemotherapy. The expression level of lncRNAs can affect chemotherapy-induced apoptosis. Taken together, lncRNA dysregulation in lymphoma cells is not only an epiphenomenon but also lncRNA transcription is critically related to the initiation and progression of lymphomas. Aberrant expression of lncRNAs can lead to the transformation of normal lymphocytes into lymphoma cells., Competing Interests: The authors report no conflicts of interest regarding the composition of this manuscript., (© 2021 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) showed benefits in type 1 diabetes mellitus (T1DM), but the risk of diabetic ketoacidosis (DKA) limits their use. Ability to predict DKA risk and therapeutic responses would enable appropriate patient selection for SGLT2i. We conducted a meta-analysis and meta-regression of randomized controlled trials (RCTs) evaluating SGLT2i in T1DM to assess moderators of the relative risk (RR) of DKA, of glycemic (HbA1c, fasting plasma glucose, continuous glucose monitoring parameters, insulin dose, and insulin sensitivity indices) and non-glycemic (body mass index (BMI), systolic BP, renal function, albuminuria, and diabetic eye disorders) efficacy, and of other safety outcomes (including hypoglycemia, infections, major adverse cardiovascular events, and death)., Methods and Findings: We searched MEDLINE, Cochrane Library, EMBASE, ClinicalTrials.gov, Cochrane CENTRAL Register of Controlled Trials, and other electronic sources through August 30, 2020, for RCTs comparing SGLT2i with active comparators or placebo in adult patients with T1DM. Reviewers extracted data for relevant outcomes, performed random effects meta-analyses, subgroup analyses, and multivariable meta-regression. The strength of evidence was summarized with the GRADE approach. Among 9,914 records identified, 18 placebo-controlled RCTs (7,396 participants, 50% males, mean age 42 y (range 23 to 55 y), 5 different SGLT2i evaluated), were included. Main outcome measures were effect sizes and moderators of glycemic and non-glycemic efficacy and of safety outcomes. In a multivariable meta-regression model, baseline BMI (β = 0.439 [95% CI: 0.211, 0.666], p < 0.001) and estimated glucose disposal rate (eGDR) (β = -0.766 [-1.276, -0.256], p = 0.001) were associated with the RR of DKA (RR: 2.81; 95% CI:1.97, 4.01; p < 0.001, R2 = 61%). A model including also treatment-related parameters (insulin dose change-to-baseline insulin sensitivity ratio and volume depletion) explained 86% of variance across studies in the risk of DKA (R2 = 86%). The association of DKA with a BMI >27 kg/m2 and with an eGDR <8.3 mg/kg/min was confirmed also in subgroup analyses. Among efficacy outcomes, the novel findings were a reduction in albuminuria (WMD: -9.91, 95% CI: -16.26, -3.55 mg/g, p = 0.002), and in RR of diabetic eye disorders (RR: 0.27[0.11, 0.67], p = 0.005) associated with SGLT2i. A SGLT2i dose-response gradient was consistently observed for main efficacy outcomes, but not for adverse events (AEs). Overall, predictors of DKA and of other AEs differed substantially from those of glycemic and non-glycemic efficacy. A limitation of our analysis was the relatively short (≤52 weeks) duration of included RCTs. The potential relevance for clinical practice needs also to be confirmed by real-world prospective studies., Conclusions: In T1DM, the risk of DKA and main therapeutic responses to SGLT2i are modified by baseline BMI and insulin resistance, by total insulin dose reduction-to-baseline insulin sensitivity ratio, and by volume depletion, which may enable the targeted use of these drugs in patients with the greatest benefit and the lowest risk of DKA., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: no competing interests to declare

Prions are infectious proteins that self-propagate by changing from their normal folded conformation to a misfolded conformation. The misfolded conformation, which is typically rich in β-sheet, serves as a template to convert the prion protein into its misfolded conformation. In yeast, the misfolded prion proteins are assembled into amyloid fibers or seeds, which are constantly severed and transmitted to daughter cells. To cure prions in yeast, it is necessary to eliminate all the prion seeds. Multiple mechanisms of curing have been found including inhibiting severing of the prion seeds, gradual dissolution of the prion seeds, asymmetric segregation of the prion seeds between mother and daughter cells during cell division, and degradation of the prion seeds. These mechanisms, achieved by using different protein quality control machinery, are not mutually exclusive; depending on conditions, multiple mechanisms may work simultaneously to achieve curing. This review discusses the various methods that have been used to differentiate between these mechanisms of curing.

The incidence of enteric viruses in treated wastewater and their potential release into the environment or use for agriculture are very critical matters in public health. In our study, PCR (polymerase chain reaction) analysis of enteric viruses was performed on 59 samples of influents and effluents collected from Tubli wastewater treatment plant (Water Pollution Control Center (WPCC)) and Tubli Bay, where the effluents were discharged, in Kingdom of Bahrain during two sampling periods. Four clinically essential waterborne enteric viruses were examined: enterovirus (EV), hepatitis A virus (HAV), astroviruses (AV), and rotaviruses (RV) and compared to standard bacterial and bacteriophages indicators of fecal pollution. Detection rates of EV, AV, HAV, and RV in the influent samples were 100%, 75%, 12.5%, and 12.5%, respectively, while 50% of the effluent samples from Tubli WPCC contained only EV RNA. None of the tested enteric viruses could be detected in any of the samples collected directly from Tubli Bay. Effluent samples from Tubli plant did not show significant seasonal differences. Since detection of enteric viruses genome does not necessarily indicate infectivity, the infectivity of these viruses was evaluated through isolation and growth of indictor bacteria and bacteriophages. High concentration of fecal bacteriological indicators was detected in all effluents samples (100%): 3.20 × 10 3 cfu/mL for E. coli , 1.32 × 10 3 cfu/mL for Salmonella spp., and 1.92 × 10 3 cfu/mL for Shigella spp. E. coli and Salmonella specific bacteriophages were also detected in the effluent samples in high titers. The combined results of PCR and bacterial enumeration point to a probable public health risk via the use of these wastewaters in agriculture or their discharge into the sea. Continuous surveillance of viral and bacterial prevalence and their resistance to sewage disinfection procedures could contribute to a better control of risks associated with the recycling of effluent wastewater and its release into the environment.

Hepatitis E Virus (HEV) is emerging as the primary cause of acute viral hepatitis in humans. The virus is commonly transmitted by the fecal-oral route via contaminated water in endemic regions or through the consumption of inadequately cooked swine products or game meats in industrialized regions. HEV genotypes 1 and 2 are predominantly associated with waterborne transmission in developing countries, whereas HEV3 and HEV4 are mainly zoonotically transmitted in industrialized countries. Seroprevalence in populations determined by detecting anti-HEV antibodies and serum HEV RNA is commonly used to analyze the presence of HEV. Although HEV RNA-based detection is now standardized, there is a lack of agreement between the assaying methods used for gathering seroprevalence data. Since 2004, HEV has been considered as a transmissible infectious agent through blood transfusion. Recent seroprevalence studies in European countries indicate an underestimated risk for blood transfusion and hence warrant testing the blood supply. HEV infection is usually self-limiting and spontaneously cleared. However, in about 60% of recipients of solid organ transplants, HEV progresses to chronic hepatitis. Immunosuppressive drugs such as tacrolimus are a major cause of chronic hepatitis and reducing its dosage results in viral clearance in about 30% of patients. In hemodialysis patients, the parenteral route is implicated as an important mechanism of transmission. In this review, we explore the clinical and epidemiological characteristics of various HEV genotypes in blood donors, hemodialysis patients, and transplant recipients.

Aims: Factor VIII (FVIII) replacement therapy remains a primary treatment for hemophilia A, however, the development of FVIII antibodies (inhibitors) and short half-life of the FVIII products are the major complications. Erythrocytes may prevent rapid removal of drugs from plasma. Erythrocytes are biocompatible and non-immunogenic drug delivery. In this study, in vitro activity of FVIII encapsulated by human erythrocytes was investigated., Methods: FVIII was loaded into erythrocytes using the hypo-osmotic dialysis technique. FVIII activity assay has been analyzed using Activated Partial Thromboplastin Time (APTT). Presence of FVIII on erythrocytes was detected by western blotting and flowcytometry using specific monoclonal antibody (abcam, U.K) against FVIII. Moreover, the osmotic fragility and hematologic parameters of FVIII-loaded carrier erythrocytes were measured., Results: Our results indicated that FVIII could not cross the membrane, where plenty of FVIII was found on the surface of the carrier erythrocyte. Flow cytometery results showed that 11% of the loaded carrier erythrocytes was positive for FVIII protein on their surface. The greatest activation of FVIII in both groups including lysate and non-lysate FVIII-loaded RBCs was observed on the first day, and the coagulant activity of this factor was gradually reduced on days 3 and 5. In 1:50 dilution of both groups, significant differences in FVIII activity were observed in 1:50 dilution of both groups, especially on the 5th day., Conclusion: This study aims to introduce erythrocytes as appropriate carriers for FVIII to prolong the dosing intervals in the effective and safe levels for a relatively longer time., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To demonstrate the advantages of CT-guided biopsy of subdiaphragmatic small renal nodule with the coaxial technique using MPR images., Methods: The study included retrospectively 12 patients who underwent CT-guided biopsy with 18 G needle of subdiaphragmatic small renal nodule (<15 mm) suspected. Histology reports have been the reference standard., Results: The histology was diagnostic in 12 biopsies (100%): out of 10 neoplastic nodule (83.3%), 8 were malignant (80%) and 2 were benign (20%); 2 out of 12 were non-neoplastic (16.6%). No procedural complications were observed (0%)., Conclusions: By using MPR images there is an effective improvement during coaxial CT-guided biopsy of subdiaphragmatic small renal nodule difficult to reach and to reduce the complication as pneumothorax. (www.actabiomedica.it).

Competing Interests: There are no conflicts of interest.

Aims: To evaluate the diagnostic accuracy of the Dual Energy Computed Tomography (DECT) in the research of the bone marrow edema., Methods and Material: The MRI images of 100 patients with episodes of articular and or bone pains with or without traumatic lesion were prospectively evaluated during a period between March 2018 and February 2019. In the presence of bone marrow edema, a DECT was performed. The measurement of the density of the bone marrow edema in the DECT was compared with healthy bone in the same patient by two operators., Result: The DECT and MRI images of 15 patients with bone marrow edema were compared. The mean of pathologic bone marrow edema was 1008.20 (Standard Deviation (SD) 23.00), for healthy bone marrow 947.53 (SD 16.42), and t = 11.75, with a statistical significance P < 0.05 (Statistical significance 95%). The agreement between the measurements of the two radiologists has a statistical significance ( P < 0.05)., Conclusion: The DECT presents an excellent diagnostic accuracy to detect the bone marrow edema, comparable to MRI. The utility of these recent possibilities is maximum where access to MRI is still very difficult., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Radiology and Imaging.)

Middle East Respiratory Syndrome Corona Virus (MERSCoV) have been reported in Arabian peninsula and sporadic cases in Europe and Asia. This study was conducted to evaluate the genetic analysis of this virus in human and camel at the first time in Iraq. Two hundred samples were collected from camels and human who suffering from respiratory symptoms, these samples treated with RNA extraction kit then amplification the genetic material by PCR which give 5% positive results. The amplicon then sequenced, registration in gene bank of NCBI for getting accession numbers. The local strains give close relationship with neighbor countries as Saudi Arabia and Jordan strains when using MEGA analysis software., (Published under licence by IOP Publishing Ltd.)

The pulsed DC field-induced thermal stability of nanodiamonds (NDs) and their transformation to carbon onions lack detailed understanding. In this study, a comprehensive study was conducted, analyzing the thermal stability of NDs and the optimum conditions required for the formation of carbon onions, using spark plasma sintering (SPS) utilizing ON-OFF DC pulse energizing. X-ray diffraction, Raman spectroscopy and electron microscopy were employed to monitor the phase transformation. Experimental results showed that NDs could almost remain stable until 950 °C under 60 MPa pressure. As the temperature was increased, amorphous carbon appeared on the surface of NDs, and then, graphitization began. At 1300 °C, lamellar graphite structures were formed and kept stable with increasing holding time, but no carbon onion was found. The optimum parameters for the synthesis of carbon onions from NDs via SPS are the temperature of 1400 °C and holding time of 15 minutes under a pressureless condition. The pressureless condition during the SPS processing creates a more favourable environment for the ND graphitization and curling into spherical carbon onions. The existence of pressure during the SPS processing can improve the thermal stability of NDs, delay the initial temperature for the graphitization transition of NDs and inhibit the graphite layer curling to form carbon onions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hepatocellular carcinoma (HCC) is one of the most widespread tumors in the world and its prognosis is poor because of lack of effective treatments. Epidemiological studies show that non-alcoholic steatohepatitis (NASH) and advanced fibrosis represent a relevant risk factors to the HCC development. However little is known of pathophysiological mechanisms linking liver fibrogenesis to HCC in NASH. Recent advances in scientific research allowed to discover some mechanisms that may represent potential therapeutic targets. These include the integrin signaling, hepatic stellate cells (HSCs) activation, Hedgehog signaling and alteration of immune system. In the near future, knowledge of fibrosis-dependent carcinogenic mechanisms, will help optimize antifibrotic therapies as an approach to prevent and treat HCC in patients with NASH and advanced fibrosis.

Objectives: Hypertension has been linked to the presence and severity of nonalcoholic fatty liver disease (NAFLD) through unclear mechanisms. The gain-of-function rs5186 A1166C variant in angtiotensin receptor type 1 (AGTR1) gene has been linked to hypertension, cardiovascular disease and metabolic syndrome. We assessed the impact of AGTR1 A1166C variant on NAFLD incidence and severity and on glucose and lipid metabolism and explored the underlying mechanisms., Methods: We followed up 314 healthy nonobese, nondiabetic, nonhypertensive, insulin-sensitive participants in a population-based study, characterized for AGTR1 rs5186 A1166C variant, adipokine profile, inflammatory and endothelial dysfunction markers. An independent cohort of 78 biopsy-proven nondiabetic NAFLD patients and controls underwent an oral glucose tolerance test with Minimal Model analysis of glucose homeostasis, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, MCP-1, calprotectin, and nuclear factor-κB activation in circulating mononuclear cells., Results: AGTR1 A1166C polymorphism predicted 9.8-year incident NAFLD (odds ratio: 1.67, 95% CI: 1.26-2.21) and hypertension (odds ratio: 1.49, 95% CI: 1.12-2.63) and 9-year increase in cardiovascular disease risk and endothelial dysfunction markers. In the cross-sectional cohort, AGTR1 C allele carriers had higher insulin resistance. Despite comparable fasting lipid profiles, AGTR1 C allele carriers showed postprandial triglyceride-rich and cholesterol-rich VLDL lipoprotein accumulation, higher resistin, MCP-1 and calprotectin responses and nuclear factor-κB activation in mononuclear cells, and a blunted postprandial adiponectin response to fat, which predicted liver histology, hepatocyte apoptosis activation, insulin resistance, and endothelial dysfunction., Discussion: AGTR1 A1166C variant affects liver disease, insulin resistance, and endothelial dysfunction in NAFLD, at least in part by modulating adipokine, chemokine, and pro-inflammatory cell activation in response to fat ingestion.

Objectives: Conjugated linoleic acid (CLA) isomers have been shown to possess anti-inflammatory activity in the central nervous system. In this study, we aimed to evaluate whether modulation of the fatty acid profile by the CLA isomers c9,t11 or t10,c12CLA was associated with changes in the expression of pro-inflammatory molecules in human astrocytes., Methods: Cultured astrocytes were treated for 6 days with 100 µM fatty acids (c9,t11CLA or t10,c12CLA or oleic acid). Following the treatment, the fatty acid profile of the cell and pro-inflammatory molecule expression were assessed., Results: Only the t10,c12CLA isomer induced a significant decrease in arachidonic acid and increased the ratio of docosahexaenoic acid/eicosapentaenoic acid, which constitutes indirect evidence of peroxisome proliferator-activated receptor alpha activation. Inhibition of tumour necrosis factor-α, interleukin-1β, and RANTES expression was observed in astrocytes treated with c9,t11CLA and t10,c12CLA., Discussion: Current data demonstrate that CLA isomers, particularly t10,c12, may affect neuroinflammation by reducing the pro-inflammatory molecules in cultured astrocytes, suggesting a potential nutritional role of CLA isomers in modulating the astrocyte inflammatory response.

Background: The levels of adenosine deaminase (ADA) are increased in tubercular pleural effusion and its determination has acquired popularity as a diagnostic test which is inexpensive and is readily accessible. Pleural fluid ADA showed sensitivity (86.36%), specificity (61.54%), diagnostic accuracy (80.70%), positive predictive value (88.37%), and negative predictive value (82.42%) confirmed by pleural biopsy as a gold standard., Methodology: Our study was a prospective cross-sectional study which was conducted for three years at a tertiary care center in Karachi, Pakistan. The data were collected and analyzed using IBM statistics SPSS vs21., Results: There were 52 patients included in our study. Twenty one were males and thirty one were females. Most patients presented with shortness of breath. There was a significant association found between raised ADA levels and pulmonary tuberculosis (p < 0.05). The ADA levels are 12 times more likely to be raised in tubercular pleural effusion., Conclusion: The ADA level is an important marker for diagnosis of pulmonary tuberculosis in lymphocytic pleural effusion. It is a convenient and an inexpensive method. The ADA levels assessment is economical when compared to other diagnostic methods., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine frequency of electrolyte imbalance including sodium, chloride, potassium and magnesium levels present in patients with uncontrolled diabetes at a tertiary care hospital in Karachi., Methods: This was a descriptive cross sectional study conducted at Medicine Department, Darul Sehat Hospital, Karachi, Pakistan from March 2017 to October 2017. A total of one hundred and eighty one admitted and OPD patients with uncontrolled diabetes (HbA1c more than 7%) were included and their demographics, comorbidities, microvascular complications, drug history, fasting and random blood glucose and serum electrolyte levels were recorded., Results: In uncontrolled diabetes mellitus, decrease in serum sodium and chloride levels were observed to be statistically highly significant (p-value less than or equal to 0.05) while that of potassium and magnesium showed insignificant alterations. Sodium level was also observed to decline with increasing pattern of urine for microalbumin., Conclusion: Electrolyte imbalance is markedly present in patients with uncontrolled blood sugars therefore serum electrolytes should be routinely measured in patients with type 2 diabetes mellitus. Serum fasting blood glucose can be used as a predictor for electrolytes., Competing Interests: Conflict to Interest: There is no conflict of interest.

Bone is one of the most common sites of complication in multiple myeloma (MM) progression and bone remodeling gets definitively perturbed during disease progression. Hypoxia and miR-210 play an important role in hematological malignancies. In an attempt to elucidate the specificity of the pathways of hypoxia and miR-210 in suppression of osteoblastic differentiation in MM patients, we examined the effect of miR-210 and hypoxia on expression of important cytokines and genes of myeloma cells. Differentiation of BM-MSCs towards osteoblastic cells in response to microvesicles (MVs) was also investigated. Finally, we proposed a molecular model on how HIF-1α may promote bone lesions in MM patients. To validate the effect of miR-210 and HIF-1α on targeted genes, the shRNA of HIF-1α and off-hsa-miR-210 were transfected into RPMI-8226 cells. BM-MSCs were cultured in osteoblastic inducer and 50 µg/mL of MVs derived from both hypoxic and normoxic myeloma cells. We designed an in vitro study to establish the effects of HIF-1α and miR-210 on the crosstalk between MM and osteoblasts. We here showed that hypoxia-induced miR-210 increased the mRNA expression of VLA-4, CXCR4, IL-6 and TGF-β in myeloma cells. MiR-210 is mandatory for the hypoxia-increased resistance of MM cells to melphalan. Moreover, MVs derived from hypoxic myeloma cells substantially decreased osteoblast differentiation. Considered comprehensively, our findings explain one of the reasons of bone loss that occurs at the sites of MM and a nascent crosstalk model in MM pathogenesis.

Growth arrest-specific 6 (GAS6) expressed by oral epithelial cells and dendritic cells (DCs) was shown to play a critical role in the maintenance of oral mucosal homeostasis. In this study, we demonstrate that the induction of pathogen-specific oral adaptive immune responses is abrogated in Gas6 -/- mice. Further analysis revealed that GAS6 induces simultaneously both pro- and anti-inflammatory regulatory pathways upon infection. On one hand, GAS6 upregulates expression of adhesion molecules on blood vessels, facilitating extravasation of innate inflammatory cells to the oral mucosa. GAS6 also elevates expression of CCL19 and CCL21 chemokines and enhances migration of oral DCs to the lymph nodes. On the other hand, expression of pro-inflammatory molecules in the oral mucosa are downregulated by GAS6. Moreover, GAS6 inhibits DC maturation and reduces antigen presentation to T cells by DCs. These data suggest that GAS6 facilitates bi-directional trans-endothelial migration of inflammatory cells and DCs, whereas inhibiting mucosal activation and T-cell stimulation. Thus, the orchestrated complex activity of GAS6 enables the development of a rapid and yet restrained mucosal immunity to oral pathogens.