Metabolic profiling, antimicrobial, anticancer, and in vitro and in silico immunomodulatory investigation of Aspergillus niger OR730979 isolated from the Western Desert, Egypt.

Ten fungal species were isolated from soil in the Western Desert and Wadi El-Natron in Egypt. All fungal isolates were morphologically recognized down to the species level. Methanol extracts of fungal mycelia and ethyl acetate extracts of culture filtrate from the isolated fungi were evaluated for antimicrobial activity against six pathogenic bacteria and one pathogenic yeast (Candida albicans ATCC20231). Only ethyl acetate extracts of Fusarium circinatum, Aspergillus niger, and Aspergillus terreus culture filtrates showed significant antimicrobial activity against the majority of the investigated pathogens. The culture filtrate extract of Aspergillus niger exhibited notable cytotoxicity towards the breast cancer (MCF-7) cell line, with the lowest detected IC50 recorded at 8 µg/µl. Whereas Fusarium circinatum and Aspergillus terreus had IC50s of 15.91 µg/µl and 18 µg/µl, respectively. A gas chromatography-mass spectroscopy (GC-MS) investigation of A. niger's potent extract revealed 23 compounds with different biological activities. Glycidyleoleate was found to be the main extract component. Aspergillus niger extract was chosen to study its possible cytotoxic mechanism. The extract was found to induce apoptosis and cell cycle arrest at the < 2n stage. Despite a significant increase in caspases 8 and 9, the production levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) have shown a significant decrease. The high interaction of glycidyleoleate against the studied cytokines' binding receptors was demonstrated via docking studies. In conclusion, the available data revealed that the culture filtrate extract of A. niger possesses promising antimicrobial, cytotoxic, and immunomodulatory properties.

Clinical factors associated with illness perception, worry and mental health in sclerosing cholangitis: A single centre prospective study.

BACKGROUND: A reduced quality of life and symptoms of depression and anxiety are reported in patients with primary sclerosing cholangitis (PSC), however specific risk factors and the effect of sclerosing cholangitis (SC) with autoimmune features are not known. OBJECTIVE: To integrate mental wellbeing assessment into routine clinical care for patients with SC, and evaluate factors associated with measures relating to quality of life, illness perception and mental health. METHODS: A prospective study of adult non-transplant patients with SC attending the outpatient clinic over a 1 year period. Self-reported questionnaires were sent to patients electronically prior to clinic to assess worry, illness perception, depression and anxiety. Demographic and clinical information was collected. RESULTS: Questionnaires were completed in 52/130 (40 %) patients with SC who attended clinic. Worry related to quality of life, mental and physical health, and future health were common. There was no difference in overall worry or illness perception in patients treated with ursodeoxycholic acid; whilst patients with PSC had a higher illness perception (P = 0.04) than those with SC and autoimmune features. Both worry (P = 0.047) and illness perception (P = 0.01) were higher in patients with elevated alkaline phosphatase, whilst there was no difference in patients with and without cirrhosis. There were high screening test scores for both depression (21.1 %) and anxiety (9.6 %), with no association with patient factors. CONCLUSIONS: We integrated an electronic questionnaire for completion prior to clinic for patients with SC with good uptake. We identified a high prevalence of patient worries and symptoms of depression and anxiety, which may be more common in PSC with elevated alkaline phosphatase and without autoimmune features. We recommend the adoption of similar tools into routine clinical practice for patients with SC.

Utility of interventional endoscopic ultrasound in pancreatic cancer.

Endoscopic ultrasound (EUS) has an important role in the management algorithm of patients with pancreatic ductal adenocarcinoma (PDAC), typically for its diagnostic utilities. The past two decades have seen a rapid expansion of the therapeutic capabilities of EUS. Interventional EUS is now one of the more exciting developments within the field of endoscopy. The local effects of PDAC tend to be in anatomical areas which are difficult to target and endoscopy has cemented itself as a key role in managing the clinical sequelae of PDAC. Interventional EUS is increasingly utilized in situations whereby conventional endoscopy is either impossible to perform or unsuccessful. It also adds a different dimension to the host of oncological and surgical treatments for patients with PDAC. In this review, we aim to summarize the various ways in which interventional EUS could benefit patients with PDAC and aim to provide a balanced commentary on the current evidence of interventional EUS in the literature.

EUS-guided through the needle microbiopsy: a useful adjunct in the investigation of pancreatic cystic lesions.

OBJECTIVE: Endoscopic ultrasound-guided through-the-needle microbiopsy (EUS-TTNB) forceps is a recent development that facilitates sampling of the walls of pancreatic cystic lesions (PCL) for histological analysis. We aimed to assess the impact of EUS-TTNB and its influence on patient management in a tertiary pancreas centre. DESIGN: A prospective database of consecutive patients who underwent EUS-TTNB from March 2020 to August 2022 at a tertiary referral centre was retrospectively analysed. RESULTS: Thirty-four patients (22 women) were identified. Technical success was achieved in all cases. Adequate specimens for histological diagnosis were obtained in 25 (74%) cases. Overall, EUS-TTNB led to a change in management in 24 (71%) cases. Sixteen (47%) patients were downstaged, with 5 (15%) discharged from surveillance. Eight (24%) were upstaged, with 5 (15%) referred for surgical resection. In the 10 (29%) cases without change in management, 7 (21%) had confirmation of diagnosis with no change in surveillance, and 3 (9%) had insufficient biopsies on EUS-TTNB. Two (6%) patients developed post-procedural pancreatitis, and 1 (3%) developed peri-procedural intracystic bleeding with no subsequent clinical sequelae. CONCLUSION: EUS-TTNB permits histological confirmation of the nature of PCL, which can alter management outcomes. Care should be taken in patient selection and appropriately consented due to the adverse event rate.

Horizontal Ridge Augmentation of the Atrophic Maxilla Using Pericardium Membrane Versus Titanium Mesh: A Clinical and Histologic Randomized Comparative Study.

PURPOSE: To compare the outcomes of maxillary horizontal alveolar ridge augmentation in the esthetic area, using either pericardium membrane or titanium mesh, clinically, radiographically, and histologically. MATERIALS AND METHODS: A randomized clinical study was performed on 20 patients with insufficient edentulous ridge width. Subjects were equally allocated into two groups. For both groups, autogenous tenting bone blocks were harvested from the symphysis area. Bone block was covered by an equal mixture (1:1) of particulate graft of inorganic bovine bone and autogenous bone matrix. The barrier membrane used in group 1 (PM) was bovine pericardium membrane, and in group 2 (TM), it was titanium mesh. RESULTS: Both groups had a clinically statistically significant difference in buccopalatal alveolar ridge dimension between baseline and after 4 months. Radiographically, at both intervals, there was no significant difference in 3D volume between both groups. Within both groups, there was a significant volume increase postoperatively. Histologically, the PM group had a lower area fraction of the mean value of newly formed bone than the TM group, yet the difference was not significant. The PM group had a higher mean osteocyte count than the TM group, but again, the difference was not significant. CONCLUSION: Guided bone regeneration using either pericardium membrane or titanium mesh is a reliable treatment for horizontal augmentation of insufficient maxillary alveolar ridge width. No significant differences between both treatment modalities were noticed clinically and histologically. However, percentage change in radiographic volumetric measurements using TM was significantly higher than that of PM. Int J Oral Maxillofac Implants 2023;38:451-461. doi: 10.11607/jomi.9715.

Early cancer detection using the fluorescent Ashwagandha chitosan nanoparticles combined with near-infrared light diffusion characterization: in vitro study.

Early cancer diagnosis through characterizing light propagation and nanotechnology increases the survival rate. The present research is aimed at evaluating the consequence of using natural nanoparticles in cancer therapy and diagnosis. Colon cancer cells were differentiated from the normal cells via investigating light diffusion combined with the fluorescence effect of the Ashwagandha chitosan nanoparticles (Ash C NPs). Ionic gelation technique synthesized the Ash C NPs. High-resolution transmission electron microscope, dynamic light scattering, and zeta potential characterized Ash C NPs. Fourier transform infrared spectroscopy analyzed Ash C NPs, chitosan, and Ashwagandha root water extract. Moreover, the MTT assay evaluated the cytotoxicity of Ash C NPs under the action of near-infrared light (NIR) irradiation. The MTT assay outcomes were statistically analyzed by Bonferroni post hoc multiple two-group comparisons using one-way variance analysis (ANOVA). Based on the Monte-Carlo simulation technique, the spatially resolved steady-state diffusely reflected light from the cancerous and healthy cells is acquired. The diffuse equation reconstructed the optical fluence rate using the finite element technique. The fluorescent effect of the nanoparticles was observed when the cells were irradiated with NIR. The MTT assay revealed a decrease in the cell viability under the action of Ash C NPs with and without laser irradiation. Colon cancer and normal cells were differentiated based on the optical characterization after laser irradiation. The light diffusion equation was successfully resolved for the fluence rate on cells' surfaces showing different normal and cancer cells values. Ash C NPs appeared its fluorescent effect in the presence of NIR laser.

Intraductal fully covered self-expanding metal stents in the management of post-liver transplant anastomotic strictures: a UK wide experience.

Background: Fully covered intraductal self-expanding metal stents (IDSEMS) have been well described in the management of post-liver transplant (LT) anastomotic strictures (ASs). Their antimigration waists and intraductal nature make them suited for deployment across the biliary anastomosis. Objectives: We conducted a multicentre study to analyse their use and efficacy in the management of AS. Design: This was a retrospective, multicentre observational study across nine tertiary centres in the United Kingdom. Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with IDSEMS insertion were analysed retrospectively. Recorded variables included patient demographics, procedural characteristics, response to therapy and follow-up data. Results: In all, 162 patients (100 males, 62%) underwent 176 episodes of IDSEMS insertion for AS. Aetiology of liver disease in this cohort included hepatocellular carcinoma (n = 35, 22%), followed by alcohol-related liver disease (n = 29, 18%), non-alcoholic steatohepatitis (n = 20, 12%), primary biliary cholangitis (n = 15, 9%), acute liver failure (n = 13, 8%), viral hepatitis (n = 13, 8%) and autoimmune hepatitis (n = 12, 7%). Early AS occurred in 25 (15%) cases, delayed in 32 (20%) cases and late in 95 (59%) cases. Age at transplant was 54 years (range, 12-74), and stent duration was 15 weeks (range, 3 days-78 weeks). In total, 131 (81%) had complete resolution of stricture at endoscopic re-evaluation. Stricture recurrence was observed in 13 (10%) cases, with a median of 19 weeks (range, 4-88 weeks) after stent removal. At removal, there were 21 (12%) adverse events, 5 (3%) episodes of cholangitis and 2 (1%) of pancreatitis. In 11 (6%) cases, the removal wires unravelled, and 3 (2%) stents migrated. All were removed endoscopically. Conclusion: IDSEMS appears to be safe and highly efficacious in the management of post-LT AS, with low rates of AS recurrence.

Nasobiliary drainage: an effective treatment for pruritus in cholestatic liver disease.

Introduction: Nasobiliary drains (NBDs) have been successfully used to manage intrahepatic cholestasis, bile leaks and obstructive cholangitis. It allows external drainage of bile, bypassing the ileum where bile salts are reabsorbed. We assessed the utility of placement with effect on markers of cholestasis and patient symptoms. Methods: Consecutive patients undergoing NBD over 12 years for the management of pruritus were retrospectively analysed. Recorded variables included patient demographics, procedural characteristics and response to therapy. Results: Twenty-three patients (14, 61% male) underwent 30 episodes of NBD. The median age was 26 years old (range 2-67 years old). A single procedure was carried out in 20. One patient each had two, three and five episodes of NBD. The most common aetiologies were hereditary cholestatic disease (n=17, 74%) and drug-induced cholestasis (n=5, 22%),NBD remained in situ for a median of 8 days (range 1-45 days). Significant improvement in bilirubin was seen at 7 days post-NBD (p=0.0324), maintained at day 30 (335 µmol/L vs 302 µmol/L vs 167 µmol/L). There was symptomatic improvement in pruritus in 20 (67%, p=0.0494) episodes. One patient underwent NBD during the first trimester of pregnancy after medical therapy failure with a good symptomatic response. The catheters were well tolerated in 27 (90%) of cases. Mild pancreatitis occurred in 4 (13%) cases. Conclusion: NBD can be used to provide symptomatic improvement to patients with pruritus associated with cholestasis. It is well tolerated by patients. They can be used in pregnancy where medical management has failed.

GC-MS Analysis of Potentially Volatile Compounds of Pleurotus ostreatus Polar Extract: In vitro Antimicrobial, Cytotoxic, Immunomodulatory, and Antioxidant Activities.

One strategy to manage resistant pathogens and develop potential anticancer drugs is the search for new, promising, and cost-effective medicinal benefits in the field of bioactive metabolites derived from mushrooms. In the current study, Egyptian cultivated Pleurotus ostreatus fruiting bodies polar extract was prepared to evaluate its antimicrobial activities as well as its cytotoxic effect on various cancer cell lines. The Pleurotus ostreatus polar extract (PoPE) was characterized by its phenolic and flavonoid content. The phenolics and flavonoids of PoPE were 6.94 and 0.15 mg/g, respectively. P. ostreatus polar extract showed potent antimicrobial activity against four pathogens, including Candida albicans, Staphylococcus aureus, Micrococcus luteus, and Escherichia coli. PoPE was found to inhibit Fusarium oxysporum (47%), Fusarium solani (28%) as well as Rhizoctonia solani (21%). PoPE was found to be 13 times more selective and toxic to MCF-7 cells than Vero normal cells, with the lowest IC50 value (4.5 µg/mL), so they were selected to examine the potential cytotoxic effects of PoPE. In MCF-7 cells, PoPE appeared to promote cell cycle arrest in the sub-G1 stage, as well as apoptosis. It significantly increased TNF-α production while decreasing IL-6 levels. PoPE's total antioxidant capacity, lipid peroxide, and glutathione reductase activity were recorded 0.14 ± 0.02 mM/L, 15.60 ± 0.015 nmol/mL, and 9.50 ± 1.30 U/L, respectively. The existence of different bioactive metabolites was investigated via GC-MS, which confirmed the presence of 15 compounds with well-known biological activity.

The Fluorescent Effect of Withania Somnifera Chitosan Nanocomposite as an Effective Contrast Agent for Cancer Theragnostic: Experimental Study in Vitro.

Nanomedicine and fluorescent optical imaging are effective in early cancer detection. The current study synthesized biocompatible nanocomposites from natural biomaterials towards inexpensive and safe cancer theragnostic. Two forms of nanocomposites were synthesized using the ionic gelation method: 1. Chitosan/ Withania Somnifera /tripolyphosphate nanocomposites, 2. Withania Somnifera/Chitosan nanocomposites. The nanocomposites were characterized by dynamic light scattering, zeta potential, and the transmission electron microscope. Fourier transform infrared spectroscopy analyzed the Withania Somnifera root water extract, Chitosan, and the synthesized nanocomposites. The cytotoxicity of the nanocomposites was investigated against the colon cancer cells (Caco2 cells) in the absence and the presence of laser (665 nm, 5 mW) irradiation. MTT assay evaluated the cytotoxicity, and Trypan blue assay assessed the cell viability. Cancerous cells were photographed under the inverted microscope in the presence and the absence of laser irradiation. Results were analyzed statistically using one-way variance (ANOVA) analysis with Bonferroni post-Hoc multiple two-group comparisons. The characterization results ensured the successful synthesis of Withania Somnifera/Chitosan nanocomposites. The results showed an increase in the cytotoxicity against colon carcinoma and a decrease in cell viability in the presence and absence of Near-infrared laser irradiation under the action of nanocomposites. The cytotoxicity of the synthesized nanocomposites increased by exposing the cells to the laser. The shining light of the nanocomposites appeared on the cells photographed under the inverted microscope. The synthesized natural nanocomposites promise systemic cytotoxicity will be efficient in molecular imaging in vivo applications.

EUS-guided choledochoduodenostomy with electrocautery-enhanced lumen-apposing metal stents in patients with malignant distal biliary obstruction: multicenter collaboration from the United Kingdom and Ireland.

BACKGROUND AND AIMS: EUS-guided choledochoduodenostomy (EUS-CDD) with an electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has emerged as a viable method of establishing biliary drainage in patients with malignant distal biliary obstruction (MDBO). Our aim was to assess the efficacy, safety, and outcomes in patients with MDBO who underwent EUS-CDD with an EC-LAMS. METHODS: A retrospective review of consecutive patients with MDBO who underwent EUS-CDD with EC-LAMSs at 8 tertiary institutions across the United Kingdom and Ireland between September 2016 and November 2020 was undertaken. RESULTS: One hundred twenty patients (55% men) with a median age of 73 years (interquartile range, 17; range, 43-94) were included. The median follow-up period in 117 patients was 70 days (interquartile range, 169; range, 3-869), and 23 patients (19.2%) were alive at the end of the follow-up. Three patients were lost to follow-up. Technical success was achieved in 109 patients (90.8%). Clinical success (reduction of serum bilirubin to ≤50% of original value within 14 days) was achieved in 94.8% of patients (92/97). The adverse event rate was 17.5% (n = 21). Biliary reintervention after initial technical success was required in 9 patients (8.3%). CONCLUSIONS: EUS-CDD with EC-LAMSs at tertiary institutions within a regional hepatopancreatobiliary network for treatment of MDBO was effective in those where ERCP was not possible or was unsuccessful. When technical failures or adverse events occur, most patients can be managed with conservative or endoscopic therapy.

Diagnostic, Prognostic, Predictive, and Monitoring Role of Neutrophil CD11b and Monocyte CD14 in Neonatal Sepsis.

BACKGROUND: Sepsis is a critical medical condition that requires additional diagnostic considerations. Recently, focus has shifted to the diagnosis of sepsis using new markers to overcome the limitations of traditional laboratory diagnostic modalities. Neutrophil CD11b (nCD11b) and monocyteCD14 (mCD14) cell surface antigens have been shown to be useful in such diagnostic consideration. AIM: To investigate the diagnostic, monitoring, prognostic, and predictive roles of nCD11b and mCD14 as sepsis biomarkers in comparison to each other and to traditional laboratory sepsis parameters in order to select the best fit for routine daily use in neonatal intensive care units (NICUs). SUBJECT: The study included 188 neonates from Ain Shams University Hospitals' NICUs, who were divided into two groups: the control group (n = 100) and the sepsis group (n = 88). Highly sensitive CRP (hs-CRP), complete blood count (CBC), blood culture, and nCD11b and mCD14 evaluations were all part of the laboratory sepsis evaluation (done by flow cytometry technology). Positive blood culture results (BACT/ALERT system) confirmed the sepsis diagnosis. Twenty-four enrolled sepsis neonates were subjected to follow-up assessments, and they were divided into two groups based on clinical improvement: improved sepsis and sepsis without improvement. In order to predict performance evaluation, the subjected neonates were reclassified according to their outcome into survivors' and nonsurvivors' group. RESULTS: Sepsis patients had a significant increase in mCD14 MFI values when compared to controls. With sensitivity 75.4 percent, specificity 71.9 percent, efficacy 73.3 percent, and AUC 0.703, mCD14 MFI at cutoff 9.36 could distinguish the presence of septicemia. Significant increases in both mCD14 MFI and nCD11b MFI (P = 0.001) were observed in the severe sepsis/septic shock group compared to the nonsevere sepsis group. The combined measurement of CD14 MFI at cutoff 9.97 and CD14 percent at cutoff 44.7 percent yielded the best predictive performance. CONCLUSION: Sepsis patients had a significant increase in mCD14 MFI comparable to the controls. mCD14 MFI demonstrated better diagnostic, prognostic, and predictive results than nCD11b. hs-CRP outperformed mCD14 and nCD11b in terms of diagnostic efficacy and AUC. In the monitoring of sepsis patients, both mCD14 and nCD11b produced unsatisfactory results. Currently, the routine use of mCD14 or nCD11b as sepsis biomarkers in neonatal ICUs is not justified.

Hydroxyapatite nanocomposite as a potential agent in osteosarcoma PDT.

Using Nanoplatforms as a hauler for photosensitizers is a bespoke paradigm to improve its bioavailability and to boost the PDT efficacy. Herein, the photodynamic cytotoxicity of methylene blue (MB) loaded on hydroxyapatite nanoparticles (HA-NPs) was tested against human osteosarcoma-derived cells (Saos-2 cell line). HA-NPs and HA-NPs loaded with MB (HA-NPs-MB) were prepared by a chemical precipitation method and characterized by TEM, Zeta potential, FTIR, and XRD. TEM images revealed that HA-NPs have a rod shape with a diameter of 14-17 nm and length around 46-64 nm. FTIR and Zeta potential confirmed the adsorption of cationic MB on HA-NPs. XRD pattern was identical to the standard XRD pattern of HA-NPs. Incubation of Saos-2 cells (24 h) with HA-NPs-MB then irradiation of cells (5 min) with a diode laser (808 nm), causes a higher decrement of cell viability (determined by MTT assay) than that caused by free MB. The LC50 was 57.53 µg/mL and 86.99 µg/mL for HA-NPs-MB and free MB, respectively. Thus, the nanoformulation of MB greatly reduced the dose of MB required for effective PDT. This study also investigated the mode of cell death after incubation of cells with free MB or HA-NPs-MB composite then exposure to laser radiation. The results revealed that the majority of cells died by apoptosis while a minor fraction of cells died by necrosis, especially in the case of HA-NPs-MB. Levels of caspase-3 and death receptor-4 (DR-4) were more elevated in the case of HA-NPs-MB than free MB. The effect of the prepared nanocomposite and free MB on Raw murine macrophage (RAW 264.7) viability was also examined using the MTT assay. The results indicated that HA-NPs-MB in the presence of laser has a great cytotoxic effect on macrophage cells compared to other treatments. This may present an advantage through decreasing macrophage that promotes tumor growth. In conclusion, HA-NPs-MB nanocomposite surmounts free MB and HA-NPs in destroying macrophage cells and Saos-2 cells through apoptosis in the presence of laser irradiation. This study introduces a thorough and new insight on osteosarcoma (cancer cell line Saos-2) PDT using HA-NPs-MB exploiting the biosafety of HA-NPs.

New benzenesulfonamide scaffold-based cytotoxic agents: Design, synthesis, cell viability, apoptotic activity and radioactive tracing studies.

A new series of thiazolidinone (5a-g), thiazinone (9a-g) and dithiazepinone (9a-g) heterocycles bearing a benzenesulfonamide scaffold was synthesized. Cytotoxicity of these derivatives was assessed against MCF-7, HepG2, HCT-116 and A549 cancer cell lines and activity was compared to the known cytotoxic agents doxorubicin and 5-FU where the most active compounds displayed better to nearly similar IC50 values to the reference compounds. For assessing selectivity, the most active derivatives against MCF-7, 5b, 5c and 5e, were also assessed against the normal breast cell line MCF-10 A where they demonstrated high selective cytotoxicity to cancerous cells over that to normal cells. Further, the effect of the most active compounds 5b-e on MCF-7 and HepG2 cell cycle phase distribution was assessed and the tested sulfonamide derivatives were found to induce accumulation of cells in the <2n phase. To further confirm apoptosis induction, caspase 8 and 9 levels in MCF-7 and HepG2 were evaluated before and after treatment with compounds 5b-e and were found to be significantly higher after exposure to the test agents. Since 5c was the most active, its effect on the cell cycle regulation was confirmed where it showed inhibition of the CDK2/cyclin E1. Finally, in vivo biodistribution study using radioiodinated-5c revealed a significant uptake and targeting ability into solid tumor in a xenograft mouse model.

Toward Highly Efficient Cancer Imaging and Therapy Using the Environment-Friendly Chitosan Nanoparticles and NIR Laser.

Chitosan-tripolyphosphate nanoparticles (C-TPP NPs) were synthesized to investigate their cytotoxicity against colon cancer cells (Caco2 cells) in the absence and the presence of a near-infrared (NIR) laser to evaluate their influence in cancer detection using the NIR laser and to evaluate the NIR laser on cancer treatment. The synthesized NPs were characterized by Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), zeta potential (ZP), and transmission electronic microscope (TEM). The cytotoxicity was analyzed by the MTT test and the cell viability was assessed using the Trypan blue method. C-TPP NPs showed increased cytotoxicity and decreased cell viability against Caco2 cells. Upon laser exposure only, the cell viability decreased. The C-TPP NPs appeared to have a shining light on the cancerous cells which were photographed under the inverted microscope.

Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line.

Objective To evaluate the antioxidant and apoptotic inductive effects of Withania somnifera (Ashwagandha) leaf extract against a hepatocellular carcinoma cell line. Methods After treating HepG2cells with Ashwagandha water extract (ASH-WX; 6.25 mg/ml-100 mg/ml), cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activities (total antioxidant, glutathione S-transferase and glutathione reductase), Fas-ligand level, tumour necrosis factor-α (TNF-α) level and caspase-3, -8, and -9 activities were measured. Molecular modelling assessed the binding-free energies of Ashwagandha in the cyclin D1 receptor. Results The MTT assay demonstrated increased cytotoxicity following treatment of HepG2 cells with ASH-WX compared with control untreated cells and theIC50was 5% (approximately 5.0 mg/ml). Antioxidant activities, Fas-ligand levels and caspase-3, -8 and -9 activities significantly increased, while TNF-α level significantly decreased following ASH-WX treatment compared with control untreated cells. Molecular docking analysis revealed a good prediction of binding between cyclin D1 and Ashwagandha. There was significant accumulation of ASH-WX-treated HepG2cells in the G0/G1 and G2/M phases compared with the control untreated cells. Conclusion Ashwagandha could be a powerful antioxidant and a promising anticancer agent against HCC.

Hospital admission for hyperemesis gravidarum in women at increased risk of spontaneous preterm birth.

BACKGROUND: Progesterone administration prevents spontaneous preterm birth (sPTB) in women at increased risk. Progesterone concentration is lower in women with subsequent sPTB. Conversely, high concentrations of progesterone are implicated in the pathogenesis of hyperemesis gravidarum (HG). We hypothesized that women at increased risk of sPTB or spontaneous late miscarriage would be less likely to have a diagnosis of HG. To explore this hypothesis, we compared the incidence of HG in women at increased risk of sPTB and women with no identifiable risk factors. METHODS: Women at increased risk of sPTB were identified from a specialist Preterm Birth Clinic (PTBC) database where criteria for PTBC attendance are previous cervical surgery, previous sPTB <34 weeks, previous spontaneous late miscarriage, incidental sonographic cervical shortening, and uterine anomaly. Hospital antenatal booking and coding records for the same time period were examined to identify HG admissions. Women with multiple gestations, trophoblastic disease, or pre-existing abnormal thyroid function were excluded. The incidence of HG among PTBC (n=394) and non-PTBC attendees (n=4762) was calculated. RESULTS: The incidence of HG was lower in women at increased risk of sPTB (1.52%, n=6) compared with women with no identifiable risk factor for sPTB (3.33%, n=159; P=.049). CONCLUSION: Hospital admission for HG is reduced in women with risk factors for sPTB compared with those without risk factors. Exploration of the pathogenesis of HG may improve understanding of the mechanisms underlying sPTB.

Duodenal biopsies for the diagnosis of coeliac disease: are we adhering to current guidance?

BACKGROUND: The British Society of Gastroenterology guidelines recommend taking at least four duodenal biopsy specimens at the time of upper gastrointestinal (UGI) endoscopy if coeliac disease (CD) is suspected and it has been shown to increase the diagnostic yield of CD. We assessed the compliance to these guidelines within our institution. We then applied measures to improve our compliance rate and assessed the resulting impact on our diagnostic rate of CD. METHODS: We performed a retrospective audit of electronic records for all patients, with no prior diagnosis of CD, who underwent UGI endoscopy with duodenal biopsies between August 2014 and May 2015. We implemented measures to raise awareness among endoscopy users at our institution and carried out a reaudit between February and May 2016. RESULTS: 924 patients were found to be eligible in the first part of the study and 278 in the second part. The proportion of patients who had ≥4 biopsy specimens submitted increased from 21.9% to 60.8% (p<0.001). The diagnostic rate of CD increased from 3.5% in the audit group to 7.6% in the reaudit group (p=0.004). A positive serology result and suspected CD as an indication for biopsy were found to be independent predictors of the likelihood of complying with guidelines. CONCLUSIONS: Our study suggests that taking <4 duodenal biopsy specimens to assess for the presence of CD may lead to the diagnosis of CD being missed. Simple measures can improve the local compliance rate to current guidelines.