Boosting-based ensemble machine learning models for predicting unconfined compressive strength of geopolymer stabilized clayey soil.

The present research employs new boosting-based ensemble machine learning models i.e., gradient boosting (GB) and adaptive boosting (AdaBoost) to predict the unconfined compressive strength (UCS) of geopolymer stabilized clayey soil. The GB and AdaBoost models were developed and validated using 270 clayey soil samples stabilized with geopolymer, with ground-granulated blast-furnace slag and fly ash as source materials and sodium hydroxide solution as alkali activator. The database was randomly divided into training (80%) and testing (20%) sets for model development and validation. Several performance metrics, including coefficient of determination (R2), mean absolute error (MAE), root mean square error (RMSE), and mean squared error (MSE), were utilized to assess the accuracy and reliability of the developed models. The statistical results of this research showed that the GB and AdaBoost are reliable models based on the obtained values of R2 (= 0.980, 0.975), MAE (= 0.585, 0.655), RMSE (= 0.969, 1.088), and MSE (= 0.940, 1.185) for the testing dataset, respectively compared to the widely used artificial neural network, random forest, extreme gradient boosting, multivariable regression, and multi-gen genetic programming based models. Furthermore, the sensitivity analysis result shows that ground-granulated blast-furnace slag content was the key parameter affecting the UCS.

Numerical simulation and diagnosis geotechnical parameters of historical buildings in Najran City, Kingdom of Saudi Arabia.

This research aims to assess geoenvironmental risks and identify the primary deterioration drivers in ancient buildings in Najran City, utilizing various analytical tools to help make informed judgments. The samples extruded from historical buildings were examined using field inspection, experimental data, SEM, EDX, and XRD analyses, in addition to lab and field observations and meteorological data. The dissolution of clay minerals and salt crystallization are the key contributors to the degradation and cracking of historical buildings in Najran City, according to lab and field observations. When the daytime high temperature surpasses 44 °C, wind erosion and humidity might cause continuous wetting-drying cycles on the investigated building surfaces. Test results indicated that the average unconfined compressive strength of the extruded earthen wall samples was 2 MPa and the water absorption was within the upper allowed limit (i.e., 15%). A finite element model of a typical earthen historical building was developed using PLAXIS 3D software to assess the behavior and nonlinear response of the silty sand soil layer underlying the building and the earthen historical buildings themselves using a plastic material model. The field observations confirm the results of the simulation, which clearly explained the failure mechanism. The integrated geotechnical and numerical simulations could provide insights for assessing geoenvironmental risks, identify the primary deterioration drivers in ancient buildings, and provide an understanding of material qualities and failure causes not only in the studied area but in other similar regions elsewhere.

miRNAs as potential game-changers in melanoma: A comprehensive review.

Melanoma is the sixth most frequent malignancy. It represents 1.7% of all cancer cases worldwide. Many risk factors are associated with melanoma including ultraviolet radiation skin phenotype, Pigmented Nevi, Pesticides, and genetic and epigenetic factors. Of the main epigenetic factors affecting melanoma are microribonucleic acids (miRNAs). They are short nucleic acid chains that have the potential to prevent the expression of a number of target genes. They could target a number of genes related to melanoma initiation, stemness, angiogenesis, apoptosis, proliferation, and potential resistance to treatment. Additionally, they can control several melanoma signaling pathways, including P53, WNT/-catenin, JAK/STAT, PI3K/AKT/mTOR axis, TGF- ß, and EGFR. MiRNAs also play a role in the resistance of melanoma to essential treatment regimens. The stability and abundance of miRNAs might be important factors enhancing the use of miRNAs as markers of prognosis, diagnosis, stemness, survival, and metastasis in melanoma patients.

Impact of combined component separation technique and shoelace repair on big medline abdominal wall defect.

BACKGROUND: Closure of large anterior abdominal wall defects, regardless of their etiology, is challenging. There is no standardized information describing definitive management. Therefore, we conducted this study to illustrate our experience on large midline abdominal wall defect repair using an effective modified reconstructive technique. METHODS: This retrospective study was conducted at Al Naqib Hospital in Aden/Yemen between 2012 and 2019. Twenty-six patients with large midline abdominal wall defects of various etiologies underwent surgical repair using a combination of shoelace repair and the component separation technique. The procedure involved bilateral longitudinal division of the anterior rectus sheet and creation of a posterior layer by approximation of the medial edges of the divided rectus sheet (shoelace abdominoplasty) and anterior external oblique muscle aponeurosis separation (component separation technique) to approximate the lateral edges of the divided rectus sheet and move the rectus muscles toward the midline for constructing the anterior abdominal wall layer. The posterior and anterior layers and bilateral separated sheets were covered with a polypropylene mesh in all patients, except in those who underwent emergency damage control surgery. RESULTS: Four, one, and two patients developed seroma, skin necrosis and chronic pain, and post-surgical wound infection, respectively. No recurrent herniation was recorded during the median follow-up of 5 years. CONCLUSION: This technique is effective in restoring the integrity of the abdominal wall in large midline abdominal wall defects and has an acceptable aesthetic appearance. In our study, minimal complications were reported, and no cases of recurrent hernias were diagnosed during follow-up.

Advances on concrete strength properties after adding polypropylene fibers from health personal protective equipment (PPE) of COVID-19: Implication on waste management and sustainable environment.

Using Health personal protective equipment (PPE) such as face masks, safety foot shoes and protective suits has expanded dramatically due to COVID-19 pandemic leading to a widespread distribution of the PPE, particularly the face masks, in the environments including streets, dump sites, seashores and other risky locations. The environmental degradation of polypropylene, the essential plastic component in single-use face masks (SUM), takes between 20 and 30 years and thus it is essential to develop experimental approaches to recycle the polypropylene or to reuse it in different ways. This paper explores the integration of SUM into concrete structures to improve its mechanical properties. We first to cut the inner nose wire and ear loops, then distribute the PPE material among five different mixed styles. The PPE were applied by volume at 0%, 1%, 1.5%, 2.0%, and 2.5%, with tests focusing on UCS, STS, FS, and PV to determine the concrete's overall consistency and assess the improvement in its mechanical properties. The results showed that adding PPE improves the strength properties and general performance of the concrete specimens. The pattern of rising intensity started to fade after 2%. The findings demonstrated that adding PPE fibers enhanced the UCS by 9.4% at the optimum 2% PPE. The PPE fibers, on the other side, are crucial in calculating the STS and FS of the reinforcement concrete.

Galangin attenuates cadmium-evoked nephrotoxicity: Targeting nucleotide-binding domain-like receptor pyrin domain containing 3 inflammasome, nuclear factor erythroid 2-related factor 2, and nuclear factor kappa B signaling.

The kidney is highly vulnerable to cadmium-evoked oxidative injury. Galangin is a natural flavone with reported antioxidant properties. This study investigated the potential modulating activity of galangin against cadmium-induced nephrotoxicity and explored the underlining mechanisms. Western blot analysis, spectrophotometric, ELISA, and histopathological techniques were employed. The results revealed that galangin suppressed tubular injury and improved glomerular function in the cadmium-intoxicated rats as evidenced by downregulation of kidney injury molecule-1, serum creatinine, and blood urea nitrogen. Galangin reduced cadmium-evoked inflammatory response and oxidative stress as indicated by reduced levels of interleukin-1 beta and TNF-α, decreased DNA damage, and improved antioxidant potential of the renal tissues. Mechanistically, galangin suppressed the nucleotide-binding domain-like receptor pyrin domain containing 3 inflammasome and efficiently decreased caspase-1 activity in the cadmium-intoxicated rats. Equally important, it inhibited the cadmium-induced nuclear translocation of nuclear factor kappa B and upregulated nuclear factor erythroid 2-related factor 2 signaling. The results highlight the ability of galangin to attenuate cadmium-evoked nephrotoxicity and support its therapeutic implementation although clinical investigations are warranted.

A long-term study of liver-related events in Caucasian hepatitis B patients with normal ALT values and high viremia.

Background and study aims: There is ongoing debate whether antiviral therapy should be initiated in hepatitis B e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) levels but high HBV DNA levels >2,000 IU/mL. Since the need for antiviral therapy might be different between Asian and Caucasian patients, we studied the long-term disease outcome in Caucasian patients living in Western Europe. Patients and methods: One hundred sixteen patients with high HBV DNA levels (>2,000 IU/mL) at diagnosis were included in the high viremia group, while those with HBV DNA <2,000 IU/mL were used as controls (n = 327). All patients were Caucasian, HBeAg negative, had normal ALT levels and had no significant liver disease at diagnosis. Results: Median follow-up was 7 + 9.8 years in the high viremia group and this was 10 + 12.5 years in controls. The cumulative probability of a liver-related event over 10 years was 4.8% vs 0.0% in the control group (p=.008). In multivariable analysis, high viremia group was associated with the occurrence of a liver-related event (hazards ratio (HR) 95% confidence interval (CI): 1.20-11.98, p=.023). In this subgroup, older age at diagnosis (HR 95% CI: 1.01-1.16, p=.023) predicted a higher risk of liver-related event. In the high viremia group, liver-related mortality was 0.9% and none of the patients developed hepatocellular carcinoma. Conclusions: HBV DNA >2,000 IU/mL influences the long-term disease outcome in Caucasian HBeAg-negative patients living in Western Europe. Nevertheless, the risk of liver-related events is low.

Assessment of the reuse of Covid-19 healthy personal protective materials in enhancing geotechnical properties of Najran's soil for road construction: Numerical and experimental study.

The COVID-19 pandemic has not only caused a global health crisis, but it has also had significant environmental and human consequences. During the COVID-19 pandemic, this study focused on emerging challenges in managing healthy personal protective materials (HPPM) in Kingdom of Saudi Arabia, using silty sand (SM) soil as an example since it covers large areas in KSA and in the whole world. The main objective of this paper is to find a novel way to minimize pandemic-related waste by using HPPM as waste materials in road construction. For the first time, a series of experiments was conducted on a mixture of different percentages of shredded HPPM (0, 0.5, 1 and 2%) added to the silty sand (SM) soil for road applications, including soil classification according to the USCS, modified compaction, UCS, UPV, and CBR. In addition, a numerical simulation was performed using geotechnical-based software Plaxis 3D to study the performance of the soil-HPPM mix as a subbase layer in the paving structure under heavy traffic loading. The modified compaction test results show that there is an increase in the optimum moisture content with increasing the HPPM contents from 0.5% to 1% and 2%. However, a reduction in the maximum dry density is observed. The values of dry density and water content at 0%, 0.5%, 1% and 2% pf HPPM are 2.045, 1.98, 1.86 and 1.8 g/cm3 and 7.65% 8%, 8.5% and 9.5%, respectively. The soaked CBR values at 0, 0.5, 1 and 2% HPPM are 23, 30, 8, 2% with the maximum value attained with the addition of 0.5% HPPM. The results of UCS were with the same percentages of HPPM 430, 450, 430 and 415 kPa, respectively, with the maximum value attained with 0.5% HPPM addition as well. In contrast, the values of UVP at 0%, 0.5%, 1% and 2% are 978.5, 680.3, 489.4 and 323.6 m/s, respectively, confirming the trends obtained by modified compaction test results. The simulation results confirm this conclusion that the soil-HPPM mix show a superior performance when used as a subbase layer and reduced vertical displacement by a percentage of 11% compared to the normal subbase material. By eliminating HPPM especially facemasks from the landfill lifecycle, incorporating them into high quality construction material production has the potential to deliver significant environmental benefits.

Ergothioneine mitigates cisplatin-evoked nephrotoxicity via targeting Nrf2, NF-κB, and apoptotic signaling and inhibiting γ-glutamyl transpeptidase.

AIM: Cisplatin is a potent chemotherapeutic agent whose therapeutic application is hindered by the associated nephrotoxicity. Cisplatin-evoked nephrotoxicity has been largely attributed to the induction of oxidative stress and inflammatory responses. The current study aimed at investigating the ability of ergothioneine to mitigate cisplatin-evoked nephrotoxicity and to elucidate the underlining molecular mechanisms. MAIN METHODS: Wistar rats were treated with a daily dose of ergothioneine (70 mg/kg, po) for fourteen days and a single dose of cisplatin (5 mg/kg, ip) on day ten. On day fifteen, kidneys and blood specimens were collected and subjected to Western blotting, ELISA, histopathological, and spectrophotometric analysis. KEY FINDINGS: Ergothioneine significantly enhanced renal function in cisplatin-treated rats as manifested by increased GFR and decreased serum creatinine and blood urea nitrogen. Ergothioneine effectively reduced the cisplatin-induced oxidative stress and mitigated apoptosis and the histopathological changes. Mechanistically, ergothioneine induced the expression of the antioxidant transcription factor Nrf2 and up-regulated its downstream targets NQO1 and HO-1. Equally important, ergothioneine inhibited γ-glutamyl transpeptidase that plays crucial roles in biotransformation of cisplatin into a toxic metabolite. Additionally, it reduced the pro-apoptotic protein p53 and the inflammatory transcription factor NF-κB along with its downstream pro-inflammatory cytokines TNF-α and IL-1ß. SIGNIFICANCE: The results of the current work shed the light on the ameliorating effect of ergothioneine on cisplatin-evoked nephrotoxicity that is potentially mediated through modulation of Nrf2, p53, and NF-κB signaling and inhibition of γ-glutamyl transpeptidase. This findings support the potential application of ergothioneine in controlling cisplatin-associated nephrotoxicity although clinical investigations are warranted.

Polymorphism of interleukin-1ß and interleukin-1 receptor antagonist genes in children with autism spectrum disorders.

In this study, we first investigated interleukin-1 beta (IL-1ß) and IL-1 receptor antagonist (IL-1RA) levels in a cohort of Egyptian children with autism spectrum disorder (ASD) and in healthy controls. Second, we examined the single-nucleotide polymorphisms (SNPs) at positions -31 and - 511 of the IL-1ß gene promoter and IL1RA and assessed the association between IL1B and IL1RA polymorphisms with ASD. We examined IL1ß promoter polymorphism at -511 (IL-1ß-511) and - 31 (IL-1ß-31) and IL1RA gene polymorphism in 80 children with ASD and 60 healthy children. The children with ASD had significantly higher levels of IL-1ß and IL-1RA than the controls. The children with ASD also had significantly higher frequencies of homozygous (CC) and heterozygous (TC) genotype variants of IL-1ß-511, and IL-1RA than the controls. Moreover, the frequency of the IL-1ß-511 allele (C) was higher in the ASD group than in the controls (p = .001). The homozygous and heterozygous variants of IL-1RA allele II were also significantly higher in the ASD group than in the control group. There was no significant association between the IL-1ß-31 genotype and autism classes. However, there were significant differences in the distribution of the IL-1RA heterogeneous genotype and allele II among children with severe autism. The inflammatory role of cytokines has been implicated in a variety of neuropsychiatric pathologies, including autism. Our data show alterations in the IL-1ß system, with abnormally increased serum levels of IL-1ß and IL-1RA in the children with ASD. Further, polymorphisms in the IL-1ß-511 and IL-1RA genotype variants correlated positively with autism severity and behavioral abnormalities. IL-1ß-511 and IL-1RA gene polymorphisms could impact ASD risk and may be used as potential biomarkers of ASD. Variations in the IL-1ß and IL-1RA systems may have a role in the pathophysiology of ASD.

Effect of Hydroxyurea Treatment on the Inflammatory Markers Among Children With Sickle Cell Disease.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential inflammatory marker in sickle cell disease (SCD). This study aimed to evaluate the impact of hydroxyurea (HU) treatment on the value of NLR and some inflammatory mediators in SCD. METHODS: The hematological parameters and clinical events were analyzed in 35 children with SCD under HU treatment and followed up for 1 year and in 20 healthy controls. Enzyme-linked immunosorbent assay was performed for the evaluation of proinflammatory cytokines, including interleukin (IL) 6, IL-8, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor α (TNF-α). RESULTS: Hydroxyurea significantly improves most of the hematological parameters in children with SCD. The percentages of hemoglobin fraction S, serum levels of TNF-α and IL-6 were significantly decreased when compared to baseline value but did not reach the value of the healthy control. The HU treatment led to a significant decrease in NLR compared to the baseline values and reached healthy control values. Neutrophil-to-lymphocyte ratio was positively correlated with hs-CRP, TNF-α, and IL-8 serum levels and negatively correlated with percentage of fetal hemoglobin and hematocrit values. The cutoff value of NLR to expect a response to HU among SCD was 3.0, with 76% specificity and 85% sensitivity (area under the curve: 0.85, P < .0001). In conclusion, hydroxyurea induced a decrease in NLR and inflammatory cytokines, which represent a biomarker of inflammation in SCD. The calculation of NLR is a straightforward and cheap method for SCD outcome prediction in young children.

High dose dexamethasone as an alternative rescue therapy for active bleeding in children with chronic ITP: clinical and immunological effects.

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83. Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources.

Antibodies to extractable nuclear antigens (ENAS) in systemic lupus erythematosus patients: correlations with clinical manifestations and disease activity.

The aim was to explore possible correlations of antibodies to extractable nuclear antigens (ENA) with clinical manifestations and disease activity indices in systemic lupus erythematosus (SLE) patients. A total of 70 consecutive SLE patients (64 females) were included. Disease activity was assessed by SLE activity index (SLEDAI), and British Isles Lupus Assessment Group (BILAG). Anti-Ro/SSA correlated positively with, headache (r=0.24, p=0.04), blurring of vision (r=0.25, p=0.03) and SLEDAI (r=0.25, p=0.04) and negatively with C3 (r=-0.35, p=0.003). Anti-Ro/SSA correlated with anti La/SSB antibodies (r=0.69, p<0.001), but not with anti-DNA, anti-RNP and anti-Sm antibodies. Anti-La/SSB antibodies correlated with headache (r=0.26, p=0.03), SLEDAI (r=0.25, p=0.03) and negatively with C3 (r=-0.34, p=0.004). Anti-La/SSB did not correlate with anti-RNP or anti-Sm antibodies. Anti-Sm antibodies correlated with disease duration (r=0.34, p=0.003), 24 hours urinary proteins (r=0.31, p=0.008), SLEDAI (r=0.31, p=0.009), BILAG renal score (r=0.29, p=0.02) and negatively with age at onset (r=-0.27, p=0.02), WBCs (r=-0.29, p=0.014) and C4 (r=-0.25, p=0.049). In multivariate analyses, anti-Ro/SSA antibodies remained associated with headache, blurring of vision and C3 and anti-La/SSB antibodies remained associated with C3 and with headache. Anti-Sm antibodies were independently associated with disease duration and total SLEDAI scores, while anti-RNP antibodies remained significantly associated with BILAG mucocutaneous scores only. Antibodies to ENAs are associated with clinical aspects of SLE and may play a role in the assessment of disease activity. Insight into these ENAs may lead to new approaches to diagnostic testing, accurate evaluation of disease activity and lead to target approach for SLE.

L-carnitine mitigates UVA-induced skin tissue injury in rats through downregulation of oxidative stress, p38/c-Fos signaling, and the proinflammatory cytokines.

UVA comprises more than 90% of the solar UV radiation reaching the Earth. Artificial lightening lamps have also been reported to emit significant amounts of UVA. Exposure to UVA has been associated with dermatological disorders including skin cancer. At the molecular level, UVA damages different cellular biomolecules and triggers inflammatory responses. The current study was devoted to investigate the potential protective effect of L-carnitine against UVA-induced skin tissue injury using rats as a mammalian model. Rats were distributed into normal control group (NC), L-carnitine control group (LC), UVA-Exposed group (UVA), and UVA-Exposed and L-carnitine-treated group (UVA-LC). L-carnitine significantly attenuated UVA-induced elevation of the DNA damage markers 8-oxo-2'-deoxyguanosine (8-oxo-dG) and cyclobutane pyrimidine dimers (CPDs) as well as decreased DNA fragmentation and the activity of the apoptotic marker caspase-3. In addition, L-carnitine substantially reduced the levels of lipid peroxidation marker (TBARS) and protein oxidation marker (PCC) and significantly elevated the levels of the total antioxidant capacity (TAC) and the antioxidant reduced glutathione (GSH) in the skin tissues. Interestingly, L-carnitine upregulated the level of the DNA repair protein proliferating cell nuclear antigen (PCNA). Besides it mitigated the UVA-induced activation of the oxidative stress-sensitive signaling protein p38 and its downstream target c-Fos. Moreover, L-carnitine significantly downregulated the levels of the early response proinflammatory cytokines TNF-α, IL-6, and IL-1ß. Collectively, our results highlight, for the first time, the potential attenuating effects of L-carnitine on UVA-induced skin tissue injury in rats that is potentially mediated through suppression of UVA-induced oxidative stress and inflammatory responses.

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children. METHODS: This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4 months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial number: UMIN000020281. RESULTS: Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. CONCLUSIONS: This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to critically validate the efficacy of vitamin D in ASD.

Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection.

The phase 2, open-label ACCORDION (ClinicalTrials.gov: NCT02349048) study investigated the efficacy, safety and pharmacokinetics of a 6- or 8-week regimen of simeprevir, daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype (GT) 1 infection and either early-stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early-stage fibrosis: simeprevir 150 mg, daclatasvir 60 mg, sofosbuvir 400 mg once daily for 6 weeks; compensated cirrhosis: same regimen for 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty-eight patients were treated (6-week group: n = 59; 8-week group: n = 9). SVR12 was achieved by 86.4% (51/59) of patients with early-stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR12 in the 6-week group was viral relapse (11.9%; 7/59). One patient had on-treatment failure due to an early withdrawal (lost to follow-up due to incarceration). One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24. No clinically significant drug-drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct-acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve, HCV GT1-infected patients with early-stage fibrosis or compensated cirrhosis.

Neurologic Complications in Children With Scorpionism: A Retrospective Study in Upper Egypt.

Scorpion envenomation is a life-threatening health problem in tropical and subtropical regions, particularly among children. The aim of this study was to describe the epidemiologic characteristics, clinical profile, and prognosis of neurologic complications among children with scorpionism in Upper Egypt. In this retrospective study, the neurologic complications of scorpionism in 2 university hospitals were analyzed from the points of epidemiologic and clinical picture and outcomes. The neurologic manifestations were found at a high percentage (85%). Irritability was the main manifestation (83.4%), followed by sweating (81.5%), hyperthermia (33.6%), and priapism (48.2% of males). Moreover, convulsion and coma were found in 14.7% and 11% of children, respectively. Neurologic manifestations were common in children with scorpionism and they correlated with poor outcome. Identification of epidemiologic and clinical features of central nervous system complications of scorpionism in children provide important data, helping in development of management policies aiming at preventive control of scorpionism and decrease its mortality.

Simeprevir plus sofosbuvir for eight or 12 weeks in treatment-naïve and treatment-experienced hepatitis C virus genotype 4 patients with or without cirrhosis.

The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4-infected patients with METAVIR F0-F4 fibrosis. Sixty-three patients (33 treatment-naïve and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced) enrolled in a partly randomized, open-label, multicentre, phase IIa study. Patients with F0-F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82-97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders. The most commonly reported treatment-emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens.

Effects of bovine colostrum on recurrent respiratory tract infections and diarrhea in children.

BACKGROUND: Bovine colostrum (BC) has direct antimicrobial and endotoxin-neutralizing effects throughout the alimentary tract, as well as other bioactivities that suppress gut inflammation and promote mucosal integrity and tissue repair under various conditions related to tissue injury. The precise role of BC in respiratory and gastrointestinal (GI) infections in children is not well defined. The aim of this study was to evaluate the efficacy and tolerability of BC administration in preventing recurrent upper respiratory tract infections (URTI) and diarrhea in children. METHODS: One hundred sixty children (aged 1-6 years) having recurrent episodes of URTI or diarrhea received BC for 4 weeks. The number of episodes of URTI, diarrhea, and frequency of hospitalization required for URTI and diarrhea occurring during the study period were assessed at weeks 8 and 24. RESULTS: From a total number of 160 children, 81 patients (50.63%) were males. The mean age (± SD) was 3.65 (± 2.01) years. The mean (± SD) total number of infections was significantly decreased after BC therapy from 8.6 ±â€Š5.1 at baseline to 5.5 ±â€Š1.2 after 2 months (P < 0.001) and to 5.7 ±â€Š1.6 after 6 months (P < 0.001). The mean (± SD) total number of URTI (P < 0.0001), number of episodes of diarrhea (P < 0.001), and number of hospital admissions (P < 0.001) were significantly decreased after BC therapy. CONCLUSION: BC is effective in the prophylaxis of recurrent URTI and diarrhea as it reduces the number of episodes and the hospitalization due to these infections. Results of this study suggest that BC could be provided as a therapeutic option for children with recurrent URTI and diarrhea.

Photothermal therapeutic effect of PEGylated gold nano-semicubes in chemically-induced skin cancer in mice.

BACKGROUND: The photothermal properties of gold nanoparticles (GNPs) are promising therapeutic modality for cancer. The study objective is to evaluate the therapeutic effect of the prepared PEGylated gold nano-semicubes (PEG-GNSCs) in skin cancer. The synthesized PEG-GNSCs were intermediate between cubic and rod shapes (low aspect ratio- rods). METHODS: In vitro toxicity was investigated in human skin melanoma Sk-Mel-28 cells, and skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). RESULTS: The calculated IC50 in Sk-Mel-28 cells was 3.41µg/ml of PEG-GNSCs, in presence of laser exposure. Photothermal therapy using laser-stimulated PEG-GNSCs resulted in inhibited volume of skin tumors. Our findings indicated that the inflammatory mediators, nitric oxide and cycloxygenase-2, were inhibited in mice after being treated with low and high doses of PEG-GNSCs, accompanied with laser exposure. However, the tumor necrosis factor -α was markedly elevated, while there was no change in 5-lipoxygenase. The pro-angiogenic factor vascular endothelial growth factor was inhibited, while histone acetylation and apoptosis were induced in tumor-bearing groups, after being treated with laser-stimulated PEG-GNSCs. CONCLUSION: The present study indicated the promising photothermal therapeutic effect of laser-stimulated PEG-GNSCs as an effective modality to inhibit the tumor growth, the angiogenesis and partially the inflammation.