Pre-left ventricular assist device endoscopic evaluation does not reduce the risk of later gastrointestinal bleeding: a multicenter study.

Background: Gastrointestinal bleeding (GIB) is a common complication after placement of a left ventricular assist device (LVAD). Some institutions attempt to mitigate post-LVAD GIB using preoperative endoscopy. Our study evaluated whether preoperative endoscopy was associated with a lower risk of post-LVAD GIB. Methods: This was a multicenter cohort study of patients who underwent LVAD insertion from 2010-2019 at 3 academic sites. A total of 398 study participants were categorized based on whether they underwent preoperative endoscopy or not. The follow-up period was 1 year and the primary outcome was GIB. Secondary outcomes were severe bleeding and intraprocedural complications. Results: A total of 114 patients experienced GIB within 1 year, with a higher rate in the endoscopy cohort (36.4% vs. 24.8%, P=0.015). After adjusting for covariables, the endoscopy cohort remained at increased risk of GIB (adjusted odds ratio 1.77, 95% confidence interval 1.05-2.976; P=0.032). Severe bleeding was common (47.4%). Arteriovenous malformations (48 cases) and peptic ulcer disease (17 cases) were the most identified sources of GIB. Only 1 minor adverse event occurred during preoperative endoscopy. Conclusions: Our study suggests that pre-LVAD endoscopy is associated with a higher risk of GIB post LVAD, despite controlling for confounders. While this was an observational study and may not have captured all confounders, it appears that endoscopic screening may not be warranted.

FBPP: software to design PCR primers and probes for nucleic acid base detection of foodborne pathogens.

Foodborne pathogens can be found in various foods, and it is important to detect foodborne pathogens to provide a safe food supply and to prevent foodborne diseases. The nucleic acid base detection method is one of the most rapid and widely used methods in the detection of foodborne pathogens; it depends on hybridizing the target nucleic acid sequence to a synthetic oligonucleotide (probes or primers) that is complementary to the target sequence. Designing primers and probes for this method is a preliminary and critical step. However, new bioinformatics tools are needed to automate, specific and improve the design sets to be used in the nucleic acid‒base method. Thus, we developed foodborne pathogen primer probe design (FBPP), an open-source, user-friendly graphical interface Python-based application supported by the SQL database for foodborne pathogen virulence factors, for (i) designing primers/probes for detection purposes, (ii) PCR and gel electrophoresis photo simulation, and (iii) checking the specificity of primers/probes.

Improved plant yield of potato through exogenously applied potassium fertilizer sources and biofertilizer.

Excessive usage of chemical fertilizers has detrimental effects on the environment and the safety of food. Conversely, utilizing organic fertilizers such as sage offers several advantages, including cost-effectiveness, soil enhancement, and promotion of root development. A two-year field experiment was conducted to investigate the impact of different potassium fertilizer sources and biofertilizers (specifically Bacillus cereus (MBc)) on potato plants. The experiment employed a split-plot design with three replicates, where the main plot factor was MBc (with and without), and the subplot factor was the sources of potassium fertilizer (control without K fertilizer, 100% Feldspar (FD), 100% Filter cake (FC), 75% FD + 25% FC, 25% FD + 75% FC, and 50% FD + 50% FC). The purpose was to examine the growth response of potato plants to these treatments. The results indicated that all treatments increased plant height, stem count, and tuber dry matter compared to the control. Furthermore, all treatments exhibited a higher uptake of macronutrients (N, P, and K) compared to the control. Notably, the plants treated with 100FC combined with MBc showed a significant 104.74% increase in total tuber weight compared to the control treatment. Additionally, the addition of 100FC with MBc significantly enhanced the availability of N, P, and K by 73.13%, 110.33%, and 51.88% respectively, compared to the control treatment. Apart from the biofertilizers, the individual application of FC and its combination with FD also demonstrated positive effects on soil fertility, potato growth, and yield.

Deep-frying palm olein oil-fried street falafel induces testicular toxicity in rats.

Falafel is the most common Egyptian street food, and deep-frying palm oil is a commonly used for frying it. The main objective of this research was to evaluate the effect of deep-frying palm olein oil-fried street falafel on testes of Wistar rats. Twenty-one adult male Wistar rats were randomly divided into three equal groups and given treatment as follows: control group received only distilled water, fresh palm olein oil (FPO) group received FPO (1 ml/100 g BW/day) and deep-frying palm olein oil (DPO) group received DPO (1 ml/100 g BW/day) orally for 28 days. Serum level of testosterone, testicular tissue oxidative status, and sperm characteristics were determined. Testicular specimens were processed for histopathological examination. The results revealed that DPO group showed a significant (p<0.01) decrease in serum testosterone with significant (p<0.01) reduction of testicular glutathione, superoxide dismutase, and glutathione peroxidase, whereas testicular malondialdehyde was markedly (p<0.001) raised. There were significant decrease in epididymal sperm count (p<0.01), sperm progress motility (p<0.001), and increase abnormal sperm rate (p<0.001) in DPO group. Testicular histology in DPO group showed structural abnormalities which are compatible with lipid peroxidation and antioxidant deficiency. In Conclusion, deep-frying palm olein oil that used for the frying falafel induces testicular abnormalities in rats.

Biosynthesis of Silver and Gold Nanoparticles and Their Efficacy Towards Antibacterial, Antibiofilm, Cytotoxicity, and Antioxidant Activities.

The World Health Organization (WHO) reports that the emergence of multidrug-resistant and the slow advent of novel and more potent antitumor and antimicrobial chemotherapeutics continue to be of the highest concern for human health. Additionally, the stability, low solubility, and negative effects of existing drugs make them ineffective. Studies into alternative tactics to tackle such tenacious diseases was sparked by anticancer and antibacterial. Silver (Ag) and gold (Au) nanoparticles (NPs) were created from Trichoderma saturnisporum, the much more productive fungal strain. Functional fungal extracellular enzymes and proteins carried out the activities of synthesis and capping of the generated nano-metals. Characterization was done on the obtained Ag-NPs and Au-NPs through UV-vis, FTIR, XRD, TEM, and SEM. Additionally, versus methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae, the antibacterial activities of Ag-NPs and Au-NPs were assessed. In particular, the Ag-NPs were more effective against pathogenic bacteria than Au-NPs. Furthermore, antibiofilm study that shown Au-NPs had activity more than Ag-NPs. Interestingly, applying the DPPH procedure, these noble metallic NPs had antioxidant activity, in which the IC50 for Ag-NPs and Au-NPs was 73.5 µg/mL and 190.0 µg/mL, respectively. According to the cytotoxicity evaluation results, the alteration in the cells was shown as loss of their typical shape, partial or complete loss of monolayer, granulation, shrinking, or cell rounding with IC50 for normal Vero cell were 693.68 µg/mL and 661.24 µg/mL, for Ag-NPs and Au-NPs, respectively. While IC50 for cancer cell (Mcf7) was 370.56 µg/mL and 394.79 µg/mL for Ag-NPs and Au-NPs, respectively. Ag-NPs and Au-NPs produced via green synthesis have the potential to be employed in the medical industry as beneficial nanocompounds.

Moving-Target Defense in Depth: Pervasive Self- and Situation-Aware VM Mobilization across Federated Clouds in Presence of Active Attacks.

Federated clouds are interconnected cooperative cloud infrastructures offering vast hosting capabilities, smooth workload migration and enhanced reliability. However, recent devastating attacks on such clouds have shown that such features come with serious security challenges. The oblivious heterogeneous construction, management, and policies employed in federated clouds open the door for attackers to induce conflicts to facilitate pervasive coordinated attacks. In this paper, we present a novel proactive defense that aims to increase attacker uncertainty and complicate target tracking, a critical step for successful coordinated attacks. The presented systemic approach acts as a VM management platform with an intrinsic multidimensional hierarchical attack representation model (HARM) guiding a dynamic, self and situation-aware VM live-migration for moving-target defense (MtD). The proposed system managed to achieve the proposed goals in a resource-, energy-, and cost-efficient manner.

Green Coffee Bean Extract Normalize Obesity-Induced Alterations of Metabolic Parameters in Rats by Upregulating Adiponectin and GLUT4 Levels and Reducing RBP-4 and HOMA-IR.

Obesity is a serious public health issue worldwide. Finding safe and efficacious products to reverse obesity has proven to be a difficult challenge. This study showed the effects of Coffea arabica or green coffee bean extract (GCBE) on obesity disorders and the improvement of obesity-induced insulin resistance, dyslipidemia, and inflammation. The active constituents of GCBE were identified via high-performance liquid chromatography. Twenty-four male albino Wistar rats were divided into two groups. The first group (Group I) was fed a control diet, whereas the second group was fed a high-fat diet (HFD) for eight weeks till obesity induction. The second group was equally subdivided into Group II, which received HFD, and Group III, which received HFD + GCBE for another eight weeks. The body and organ weights of the animals were measured, and blood and adipose tissue samples were collected for analysis. The results indicated that the administration of GCBE significantly decreased the body and organ weights. Furthermore, it had an ameliorative effect on serum biochemical parameters. It dramatically reduced total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, glucose, and insulin levels. In addition, an improvement in homeostasis model assessment-insulin resistance and an enhancement of high-density lipoprotein cholesterol levels were observed compared with the HFD group. In addition, the group treated with GCBE exhibited a marked increase in serum levels of adiponectin (an anti-inflammatory adipokine). In addition, a considerable reduction in adipocyte hypertrophy was found following GCBE treatment. Remarkably, the administration of GCBE resulted in a remarkable decrease in the expression of RBP4 (a pro-inflammatory cytokine), whereas an increase in GLLUT4 expression was observed in the adipose tissue. This improved insulin resistance in GCBE-administered HFD rats compared with other HFD rats. Our study showed that GCBE exhibits anti-obesity activity and may be used as a natural supplement to prevent and treat obesity and its associated disorders.

Antiproliferative Activity of Some Newly Synthesized Substituted Nicotinamides Candidates Using Pyridine-2(1H) thione Derivatives as Synthon.

Some new pyridinethione and thienopyridine derivatives have been synthesized and evaluated for their antiproliferative activity using the MTT assay. Nicotinamide derivatives 3 have been synthesized and used for the preparation of new condensed thieno [2,3-b]pyridines by their reactions with active halo compounds. Finally the synthesized thienopyridine underwent ring closure whenever possible through boiling in a solution of sodium ethoxide. The antiproliferative evaluation against (HCT-116, HepG-2, and MCF-7) human cancer cells and one human healthy cell line (BJ-1) revealed that compounds 3b, 4c-5d, 7b-12a, 10d, and 13b have interesting antitumor activity specifically as antihepatocellular and anticolon cellular carcinoma agents. Besides, the docking results for most active derivatives were in agreement with the in vitro antitumor results.

UAV-Based Privacy-Preserved Trustworthy Seamless Service Agility for NextG Cellular Networks.

Next Generation cellular networks are expected to offer better service quality, secure and reliable service provisioning, and more cooperative operation even in unexpected stressful situations. Service provider cooperation can facilitate reliable service provisioning and extended coverage in disasters situations or partial network failures. However, the current 4G and 5G standards do not offer security and privacy-friendly support for inter-operator agility and service mobility, a key enabler for such cooperation. The situation becomes more critical in presence of attackers, where establishing trust relationships becomes very complicated. This paper presents a novel UAV-assisted user-agility support framework that enables trustworthy seamless service migration in a zero-trust environment. The proposed framework facilitates temporal authentication-authority delegation and proxying to enable preservice, all-party mutual authentication. The framework is implemented and tested on top of the srsRAN open-source 4G/5G software stack. Experiments showed that the presented framework managed to facilitate effective and efficient trustworthy service migration between heterogeneous service provider networks.

The Cost of Guideline Adherence: A Multicenter Analysis of the Financial Implications of Adopting the US Multi-Society Task Force Polypectomy Guidelines.

GOAL: The goal of this study was to determine the financial impact of adopting the US Multi-Society Task Force (USMSTF) polypectomy guidelines on physician reimbursement and disposable equipment costs for gastroenterologists in the academic medical center and community practice settings. BACKGROUND: In 2020, USMSTF guidelines on polypectomy were introduced with a strong recommendation for cold snare rather than cold forceps technique for removing diminutive and small polyps. Polypectomy with snare technique reimburses physicians at a higher rate compared with cold forceps and also requires different disposable equipment. The financial implications of adopting these guidelines is unknown. MATERIALS AND METHODS: Patients that underwent screening colonoscopy where polypectomy was performed at an academic medical center (Loma Linda University Medical Center) and community practice medical center (Ascension Providence Hospital) between July 2018 and July 2019 were identified. The polypectomy technique performed during each procedure was determined (forceps alone, snare alone, forceps plus snare) along with the number and size of polyps as well as disposable equipment. Actual and projected provider reimbursement and disposable equipment costs were determined based on applying the new polypectomy guidelines. RESULTS: A total of 1167 patients underwent colonoscopy with polypectomy. Adhering to new guidelines would increase estimated physician reimbursement by 5.6% and 12.5% at academic and community practice sites, respectively. The mean increase in physician reimbursement per procedure was significantly higher at community practice compared with the academic setting ($29.50 vs. $14.13, P <0.00001). The mean increase in disposable equipment cost per procedure was significantly higher at the community practice setting ($6.11 vs. $1.97, P <0.00001). CONCLUSION: Adopting new polypectomy guidelines will increase physician reimbursement and equipment costs when colonoscopy with polypectomy is performed.

Design, Synthesis and Antitumor Activity of Novel Dispiro[oxindole-cyclohexanone]- pyrrolidines.

BACKGROUND: Spirooxindoles are privileged scaffolds in medicinal chemistry, which were identified through Wang's pioneering work as inhibitors of MDM2-p53 interactions. OBJECTIVE: To design and synthesize 2,6-diarylidenecyclohexanones and dispiro[oxindole-cyclohexanone]- pyrrolidines having potential antitumor effect. METHODS: Dispiro[oxindole-cyclohexanone]-pyrrolidines 6a-h were synthesized in a regioselective manner via 1,3-dipolar cycloaddition reaction of 2,6-diarylidenecyclohexanones 3a-h, isatin, and sarcocine. Compounds 6a-h were alkylated to give (7-10)a,b. All compounds were evaluated in vitro for their antitumor activity and cytotoxic selectivity against breast cancer cell lines (MCF-7 and MDA-MB-231), breast fibrosis cell line (MCF10a), and placental cancer cell line (JEG-3). Molecular modeling inside the MDM2 binding site was performed using AutoDock4.2. RESULTS: Synthesized compounds showed antitumor activity comparable to tamoxifen and compounds 3a,b,f,g and 9a,b showed selective cytotoxicity against tumor cells but reduced toxicity toward MCF-10a cells. Molecular modelling shows that both classes of synthesized compounds are predicted to fit the deep hydrophobic cleft on the surface of MDM2 and mimic the interactions between p53 and MDM2. CONCLUSION: The synthesized compounds have antitumor activity against MCF-7, MDA-MB-231, and JEG-3. Few compounds showed a selective cytotoxic effect and may have the potential to inhibit MDM2 and stimulate p53. In the future, studies regarding the optimization of medicinal chemistry as well as mechanistic studies will be conducted to enhance the inhibition effect of identified compounds and elucidate their mechanism of action.

PeTroShare: Blockchain-Managed, Logistics-Aware, Privacy-Friendly, Comparative, and Efficient Petroleum Transportation.

Crude oil is one of the critically needed resources. It is the main pillar supporting almost everything we rely on in daily life. Unfortunately, due to many factors, crude oil costs too much. Transportation is one of the critical factors that affect such costs. Due to many environmental risks attached to the transportation process, many countries added very high tariffs to cover any hazards during the transportation, loading, and unloading process. Logistics concerns and political conflicts are the other key factors that can massively impact the transportation cost. This paper presents an Industry 4.0-compliant PeTroShare (PTS), a blockchain-powered trustworthy, logistics-friendly, and cost-efficient crude oil trading platform. PTS is a novel ride-sharing platform that enables an anonymous exchange of crude oil between oil producers and customers, focusing mainly on the product quality, not the source of origin. In our scenario, floating crude oil tankers will hold the cargo to an intermediate position in the open ocean. PTS will match the product availability based on the location and the needed quality of the customer requests. Consequently, the time and distance travelled are minimized. Our simulation results show that enabling the anonymous sharing of crude oil products can significantly enhance system efficiency and cost-effectiveness.

Measurement of serum glutathione peroxidase, catalase and superoxide dismutase concentration in patients with external anogenital warts before and after treatment with intralesional tuberculin purified protein derivative.

External anogenital warts are considered the commonest viral sexually transmitted infection that has serious negative psychological effects on both males and females such as anxiety and marked stress. Aim of this work is to measure serum glutathione peroxidase (GSH-Px), catalase and superoxide dismutase enzyme level in patients with external anogenital warts before and after intralesional tuberculin purified protein derivative (PPD) injection. This study carried out 59 patients with anogenital warts recruited from the dermatology clinic and the andrology clinic, Suez Canal University hospital. Each patient was injected with 10 units (0.2 ml) of PPD intralesionally in the mother or largest wart with 2 weeks interval till complete resolution or maximum of six injections. Serum GSH-Px, catalase and superoxide dismutase were measured using ELISA before and after injection. Results of PPD injection showed that 69.5% of patients were responders while 30.5% were nonresponders. The mean level of serum GSH-Px, catalase and superoxide dismutase dropped significantly after injection with levels pre- and post-injection, 91.1 ng/ml versus 52.6 ng/ml, 88.5 ng/ml versus 67.4 ng/ml and 28.6 ng/ml versus 21.8 ng/ml respectively. Antioxidant enzyme levels decrease significantly after PPD injection. Serum GSH-Px and catalase were significantly related to PPD response.

Bacterial nanocellulose from agro-industrial wastes: low-cost and enhanced production by Komagataeibacter saccharivorans MD1.

Bacterial nanocellulose (BNC) has been drawing enormous attention because of its versatile properties. Herein, we shed light on the BNC production by a novel bacterial isolate (MD1) utilizing various agro-industrial wastes. Using 16S rRNA nucleotide sequences, the isolate was identified as Komagataeibacter saccharivorans MD1. For the first time, BNC synthesis by K. saccharivorans MD1 was investigated utilizing wastes of palm date, fig, and sugarcane molasses along with glucose on the Hestrin-Schramm (HS) medium as a control. After incubation for 168 h, the highest BNC yield was perceived on the molasses medium recording 3.9 g/L with an initial concentration of (v/v) 10%. The physicochemical characteristics of the BNC sheets were inspected adopting field-emission scanning electron microscope (FESEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) analysis. The FESEM characterization revealed no impact of the wastes on either fiber diameter or the branching scheme, whereas the AFM depicted a BNC film with minimal roughness was generated using date wastes. Furthermore, a high crystallinity index was estimated by XRD up to 94% for the date wastes-derived BNC, while the FTIR analyses exhibited very similar profiles for all BNC films. Additionally, mechanical characteristics and water holding capacity of the produced BNCs were studied. Our findings substantiated that expensive substrates could be exchanged by agro-industrial wastes for BNC production conserving its remarkable physical and microstructural properties.

Proton pump inhibitor in upper gastrointestinal fecal microbiota transplant: A systematic review and analysis.

BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is used in recurrent Clostridioides difficile infections. However, protocols are facility dependent, and one variable is whether pre-procedural proton pump inhibitors (PPIs) are given. In theory, PPIs reduce acidity and protect the transplanted microbiome for the most potent dose. We conducted a systematic review to study the effect of PPIs on FMT delivered by upper gastrointestinal (GI) routes. METHODS: We searched Pubmed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16, 2018 using variations of keywords "fecal microbiota transplant" and "Clostridium difficile infection." Two authors independently reviewed 4210 results and found 11 qualifying studies with data on upper GI FMT, use of PPIs, and the rate of treatment failure at follow-up. RESULTS: Of 233 included patients, treatment failure occurred in 20.6% of those with use of PPIs versus 22.6% in the group without (relative risk 0.91; confidence interval 0.56-1.50). Limitations include the lack of studies directly comparing outcomes based on use of PPIs and inability to control for possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics. CONCLUSIONS: We did not find evidence supporting a clinically significant benefit from routine use of PPIs in FMT protocol. It is possible that the theoretical benefit from improved survival of transplanted microbiota is offset by negative effects on the microbiome. We suggest that routine use of PPIs in upper GI FMT be reconsidered. Further investigation is needed to optimize protocols for safety and efficacy.

Antitumor effect of exopolysaccharide produced by Bacillus mycoides.

Recently, microbial exopolysaccharides (EPSs) have offered very large field for medical applications owing to their bioactive characteristics. This study aimed to obtain antitumor EPS and to optimize its production using different optimization approaches. Eighty EPSs-producing bacteria were obtained from mud samples. Isolate BS4 was selected as the most potent antitumor EPS-producer and identified as Bacillus mycoides BS4 using 16S rRNA gene sequence analysis. Cell viability and antitumor activity of produced EPS were investigated using microscopic examination and MTT assay. Interestingly, the produced EPS exhibited low cytotoxicity against normal cell baby hamster kidney (BHK) with IC50 at 254 µgml-1 while it exhibited an inhibitory effect against cancer cells of human hepatocellular carcinoma (HepG2) and Colorectal adenocarcinoma cells (Caco-2) with IC50 of 138 µgml-1 and 159 µgml-1, respectively. The purified EPS was characterized using Fourier transform infrared, gel permeation chromatography and gas chromatography-mass spectroscopy. It showed molecular weight of 1.90 × 104 Da and consists of galactose, mannose, glucose and glucuronic acid. The factors affecting EPS production were optimized using one-factor-at-a time and statistical optimization methods. The Placket-Burman (PB) design results indicated that sugarcane molasses, peptone and shaking conditions were the most significant variables, which were further optimized by Response Surface Methodology (RSM). The optimum conditions for EPS production were 8.0% (w/v) sugarcane molasses, 6 gL‒1 peptone and 300 rpm that produce 8.02gL‒1 of EPS. This indicates the potentiality of Bacillus mycoides BS4 for production of EPS with biomedical applications.

Safety of endoscopic retrograde cholangiopancreatography (ERCP) in pregnancy: A systematic review and meta-analysis.

BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically challenging procedure rarely associated with severe postprocedure complications. Hormonal changes during pregnancy promote cholelithiasis, but there are limited clinical data available on the outcomes of ERCP in pregnant women. ERCP techniques without irradiation were recently introduced as potential alternative. We performed a systematic review and meta-analysis to assess the safety of ERCP in pregnancy and to compare outcomes of radiation versus nonradiation ERCP. MATERIALS AND METHODS: A systematic search of PubMed, Medline/Ovid, Web of Science, and Google Scholar through April 18th, 2018 using PRISMA and MOOSE guidelines identified 27 studies reporting the outcomes of ERCP in pregnancy. Random effects pooled event rate and 95% confidence intervals (CIs) were estimated. Heterogeneity was measured by I2, and meta-regression analysis was conducted. Adverse outcomes were divided into fetal, maternal pregnancy-related, and maternal nonpregnancy-related. RESULTS: In all, 27 studies reporting on 1,307 pregnant patients who underwent ERCP were identified. Median age was 27.1 years. All results were statistically significant (P < 0.01). The pooled event rate for overall adverse outcomes was 15.9% (95% CI = 0.132-0.191) in all studies combined, 17.6% (95% CI = 0.109-0.272) in nonradiation ERCP (NR-ERCP) subgroup and 21.6% (95% CI = 0.154-0.294) in radiation ERCP subgroup. There was no significant difference in the pooled event rate for fetal adverse outcomes in NR-ERCP 6.2% (95% CI = 0.027-0.137) versus 5.2% (95% CI = 0.026-0.101) in radiation ERCP group. There was no significant difference in maternal pregnancy-related adverse outcome event rate between NR-ERCP (8.4%) (95% CI = 0.038-0.173) and radiation ERCP (7.1%) (95% CI = 0.039-0.125). Maternal nonpregnancy-related adverse outcome event rate in NR-ERCP was 7.6% (95% CI = 0.038-0.145), which was half the event rate in radiation ERCP group of 14.9% (95% CI = 0.102-0.211). CONCLUSIONS: ERCP done by experienced endoscopists is a safe procedure during pregnancy. Radiation-free techniques appear to reduce the rates of nonpregnancy-related complications, but not of fetal and pregnancy-related complications.

Autoimmune hepatitis in patients with human immunodeficiency virus infection: A systematic review of the published literature.

BACKGROUND: Liver disease in patients with HIV is common and typically has complex and multifactorial presentations that represent a major cause of morbidity and mortality. Autoimmune hepatitis (AIH) is rarely reported in patient with HIV and the disease course and clinical outcomes for treatment have not been well characterized. We are aiming to determine the patient characteristics, disease prevalence, and treatment outcomes from published articles of patients with HIV and AIH. METHOD: A systematic search of PubMed, Web of Science, and Google Scholar through February 20, 2019 identified 15 studies that reported the outcomes of AIH in patients with HIV. Because of the small sample sizes and skewed distributions, resampling tests of mean differences using permutation distributions (MAXn = 10,000 permutations) were utilized; analyses were performed using R (v. 3.5.1). Categorical differences were calculated using Fisher exact test for odds ratio = 1 (equal odds), and Cramer V was calculated for effect size; analyses were completed in SPSS (v. 25). RESULTS: By reviewing 15 studies reporting a total of 35 patients with AIH and HIV, male patients were found to have significantly higher aspartate transaminase and alanine transaminase levels at time of diagnosis. No other significant findings identified. The CD4 count and viral load did not show significant correlation with AIH diagnosis or its prognosis. All patients but one who presented with severe immune deficiency and responded to highly active anti-retroviral therapy received immunosuppressive treatment without side effects and achieved remission except 2 lost to follow-up and 3 expired. CONCLUSION: Although rare, but AIH can develop in patients with HIV and physicians should consider it in the differential diagnosis for HIV patients presented with abnormal liver function tests, especially after excluding hepatitis C virus and drug-induced liver injury.Patients with immune deficiency disorders who present with AIH can be treated safely with steroid either as monotherapy or in combination with another immune suppressant therapy.

High Improvement in Lactic Acid Productivity by New Alkaliphilic Bacterium Using Repeated Batch Fermentation Integrated with Increased Substrate Concentration.

Optically pure lactic acid (LA) is an important chemical platform that has a wide range of industrial and biotechnological applications. Improved parameters for cost effective LA production are of great interest for industrial developments. In the present study, an alkaliphilic lactic acid bacterium, BoM 1-2, was selected among 369 newly obtained bacterial isolates. It was characterized using API 50 CHL kit and identified as Enterococcus hirae BoM 1-2 by 16S rRNA gene sequence analysis. Efficient polymer-grade L-lactic acid production was achieved at pH 9.0 and 40°C. In batch fermentation strategy using 20 g L-1 glucose, 19.6 g L-1 lactic acid was obtained with volumetric productivity of 2.18 g L-1 h-1. While using 100 g L-1 glucose, 96.0 g L-1 lactic acid was obtained with volumetric productivity of 1.07 g L-1 h-1. The highest lactic acid concentration of 180.6 g L-1 was achieved in multipulse fed batch strategy with volumetric productivity of 0.65 g L-1 h-1. To achieve higher productivity, repeated fermentation processes were applied using the two different strategies. In the first strategy, the lactic acid productivity was increased from 1.97 g L-1 h-1 to 4.48 g L-1 h-1 when the total of 10 repeated runs were carried out using 60 g L-1 glucose, but lactic acid productivity decreased to 2.95 g L-1 h-1 using 100 g L-1 glucose. In second strategy, repeated fermentation coupled with gradual increase in glucose concentration from 40 to 100 g L-1 was conducted for 24 runs. A dramatic increase in LA productivity up to 39.9 g L-1 h-1 (18-fold compared to first run) was achieved using 40 g L-1 glucose while volumetric productivity ranging between 24.8 and 29.9 g L-1 h-1 was achieved using 60-100 g L-1 glucose.

Identification of novel small molecule inhibitors against the NS3/4A protease of hepatitis C virus genotype 4a.

BACKGROUND: Hepatitis C virus (HCV) infection poses a considerable threat to the public health. The current standard of care treatment with pegylated interferon-alpha in combination with ribavirin (PEG-IFN- α+RBV) is associated with significant side effects, poorly tolerated, and provides limited efficacy. The development of direct-acting antiviral agents (DAAs) targeting key viral enzymes essential for viral replication represents a significant milestone in the treatment of chronic HCV infection. Given its critical role in the viral polyprotein processing and the evasion of the host innate immunity, the NS3/4A protease has emerged as a promising drug target for the development of anti-HCV therapies. Although several potent NS3/4A protease inhibitors (PIs) have been approved or are in clinical development, the majority of currently available PIs have significant limitations related to untoward adverse events and a lack of pan-genotypic activity, indicating a continuing unmet medical need for the development and optimization of novel PIs with improved efficacy and tolerability, convenient dosing schedules, and shorter treatment durations. METHODS: The inhibitory efficacy of four computer-designed chemically-synthesized compounds was evaluated against in vitro-expressed NS3/4A protease from HCV genotype 4a, the most prevalent genotype in Egypt, using a fluorescence-based enzymatic assay. RESULTS: We successfully identified two non-macrocyclic small molecules, BE113 (7a) and BE114 (7b), which exhibited inhibitory activity against HCV NS3/4A protease from HCV genotype 4a. CONCLUSION: The two compounds presented in this study may be promising inhibitors against NS3/4A protease of HCV genotype 4a and could be novel lead compounds for developing new therapeutics for the treatment of chronic HCV infection.