Effect of weight loss after gastric bypass surgery on thyroid function in euthyroid people with morbid obesity

Obesity is positively associated with serum thyrotropin (TSH) concentrations at the high end of the normal range. The relationship between weight loss and thyroid function is less clear and studies to date have yielded inconsistent results. Our aim was to describe changes in thyroid function in obese people in relation to durable and significant weight loss after Roux-en-Y gastric bypass (RYGB) surgery. We recorded percentage of excess weight loss (% EWL), serum TSH and free thyroxine (fT4) before and median 4.5, 15 and 24 months after RYGB in 55 euthyroid patients with morbid obesity ranging in age from 18 to 64 years in a retrospective cohort analysis in a university hospital in Greater Manchester. Mean ± standard error preoperative weight was 135.13 ± 4.23 kg and BMI 48.08 ± 1.58 kg m−2. Patients attained nadir %EWL of 68% by median 15 months after RYGB. TSH was 2.00 ± 0.14 mU L−1 at baseline and 2.02 ± 0.22 mU L−1 at 24 months after RYGB (non-significant). Baseline fT4 was 13.46 ± 0.28 pmol L−1, and increased significantly to 15.14 ± 0.55 pmol L−1 at 24 months (P <0.004). In conclusion, we report that weight loss after RYGB was accompanied by significant increase in serum fT4 but no change in TSH concentrations. Further study to elucidate the effect of significant weight loss on the thyroid axis is required

A review of information flow diagrammatic models for product-service systems

A product-service system (PSS) is a combination of products and services to create value for both customers and manufacturers. Modelling a PSS based on function orientation offers a useful way to distinguish system inputs and outputs with regards to how data are consumed and information is used, i.e. information flow. This article presents a review of diagrammatic information flow tools, which are designed to describe a system through its functions. The origin, concept and applications of these tools are investigated, followed by an analysis of information flow modelling with regards to key PSS properties. A case study of selection laser melting technology implemented as PSS will then be used to show the application of information flow modelling for PSS design. A discussion based on the usefulness of the tools in modelling the key elements of PSS and possible future research directions are also presented

Paraperesis: A rare complication after depressed skull fracture

Depressed skull fracture is an inward buckling of the skull bones, often because of direct blow to a small surface area of the skull with a bluntobject. Monoparesis is often among its clinical presentations, but midline depressed skull fracture presenting as motor weakness of both lowerlimbs (Paraperesis) has not yet been reported. We report the case of 55 year old male admitted to emergency department with alleged history ofhit on head by a wooden rod. He had pain, mild swelling and a small cut over scalp without any symptoms & signs of neurological deficit. On daytwo of admission patient developed weakness of both lower limbs. On CT scan patient had bilateral depressed skull fracture of high parietal boneon either side of midline. Patient was managed conservatively, made remarkable recovery and was discharged after 2 weeks.Key words: Fracture, paraperesis, edema, depressed fracture, skul

Effect of Ocimum tenuiflorum Leaf Extract against Infective Endocarditis

The ever increasing resistance of pathogens to antibiotics as well as the undesirable side effects of certain antimicrobial agents has necessitated the discovery of novel natural products. The ethanolic extract of O. tenuiflorum was investigated against S. aureus isolate which is a major pathogen causing infective endocarditis. The total phenolic content in O. tenuiflorum was found to be 1289 μg gallic acid equivalent/g and HPLC profile revealed the presence of catechin, Caffeic acid and p-coumaric acid. The antibacterial profile of O. tenuiflorum against S. aureus isolate from infective endocarditis patients exhibited significant inhibition at the MIC of 50 μg/ml and the standard antibiotic Vancomycin showed inhibition at 40 ng/ml. Percent inhibition of viable growth was found to be >95% and the scanning electron micrographs (SEM) revealed the disruption of the membrane of S. aureus treated with O. tenuiflorum extract. The antimicrobial activity correlates with phenolic content of the extract. These results demonstrate the potency of O. tenuiflorum, could serve as a new source of antimicrobials with potential applications and related health benefits

In Vitro Antioxidant and In Vivo Hepatoprotective Activity of Leave Extract of Raphanus Sativus in Rats Using CCL4 Model

Background: Raphanus sativus is reported to have a variety of biological activities. This work screened the hepato-protective and antioxidant activity of ethanol (ERS), and aqueous (ARS), extracts of leaves of Raphanus sativus in Carbon tetrachloride (CCl4), model in rats.Material and Methods: The extracts were subjected to antioxidant tests (Total reducing power and Total phenolic content), and preliminary phytochemical screening. A pilot study was done on 100 and 300 mg/kg extracts, form which 300 mg was chosen for further experiments. The albino rats (200-250 grams), were divided into 5 groups of 6 animals each (n=6). There were three control groups comprising of normal control (normal saline -1ml/kg), negative control group (CCl4 1ml/kg in olive oil in a ratio of 1:1 v/v), and positive control group (Silymarin 50mg/kg). The Test drugs were given in a dose of 300 mg/kg for both ERS and ARS extract for 7 days. Biochemical parameters (AST, ALT, Alkaline phosphatase, Total Bilirubin), histo-pathological examination of liver and in vivo antioxidant tests [CAT, GSH and MDA] were done.Results: The phytochemical study showed the presence of flavanoids, terpenoids, alkaloids, saponins and sterols. A dose dependent increase in the oxidative potential was observed in both the extracts with total phenolic content 70.1 and 44.4 GAE/g extract for ERS and ARS respectively. ERS 300mg/kg showed a significant (p<0.001) increase in levels of AST, ALT and alkaline phosphatase as compared to negative control (percentage hepatoprotection =45.3%) while ARS 300 mg/kg (p<.01) group showed 30% hepatoprotection. The GSH (p<0.001) and CAT (p<0.05) in ERS and ARS were significantly increased while MDA levels were decreased (P< 0.01), as compared negative control. The findings were confirmed histo-pathological examination.Conclusion: The ethanol and aqueous extract of Raphanus sativus have partial hepatoprotection against CCl4 toxicity.Key words: Raphanus sativus, hepatoprotection, CCl4, antioxidant

Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome

Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0–10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus

Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons

Emerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer’s disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ₄₂ activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ₄₂-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1. Aβ₄₂-induced neurotoxicity was also inhibited by treatment with TPEN used as a Zn²⁺-specific chelator. Cell imaging revealed that Aβ₄₂-induced lysosomal dysfunction, cytosolic Zn²⁺ increase, mitochondrial Zn²⁺ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS. These effects were suppressed by TRPM2-KO, inhibition of TRPM2 or PARP-1, or treatment with TPEN. Bafilomycin-induced lysosomal dysfunction also resulted in TRPM2-dependent cytosolic Zn²⁺ increase, mitochondrial Zn²⁺ accumulation, and mitochondrial generation of ROS, supporting that lysosomal dysfunction and accompanying Zn²⁺ release trigger mitochondrial Zn²⁺ accumulation and generation of ROS. Aβ₄₂-induced effects on lysosomal and mitochondrial functions besides neurotoxicity were also suppressed by inhibition of PKC and NOX. Furthermore, Aβ₄₂-induced neurotoxicity was prevented by inhibition of MEK/ERK. Therefore, our study reveals multiple molecular mechanisms, including PKC/NOX-mediated generation of ROS, activation of MEK/ERK and PARP-1, lysosomal dysfunction and Zn²⁺ release, mitochondrial Zn²⁺ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS, are critically engaged in forming a positive feedback loop that drives Aβ₄₂-induced activation of the TRPM2 channel and neurotoxicity in hippocampal neurons. These findings shed novel and mechanistic insights into AD pathogenesis

Knockdown of a Mosquito Odorant-binding Protein Involved in the Sensitive Detection of Oviposition Attractants

Odorant-binding proteins (OBPs) were discovered almost three decades ago, but there is still considerable debate regarding their role(s) in insect olfaction, particularly due to our inability to knockdown OBPs and demonstrate their direct phenotypic effects. By using RNA interference (RNAi), we reduced transcription of a major OBP gene, CquiOBP1, in the antennae of the Southern house mosquito, Culex quinquefasciatus. Previously, we had demonstrated that the mosquito oviposition pheromone (MOP) binds to CquiOBP1, which is expressed in MOP-sensitive sensilla. Antennae of RNAi-treated mosquitoes showed significantly lower electrophysiological responses to known mosquito oviposition attractants than the antennae of water-injected, control mosquitoes. While electroantennogram (EAG) responses to MOP, skatole, and indole were reduced in the knockdowns, there was no significant difference in the EAG responses from RNAi-treated and water-injected mosquito antennae to nonanal at all doses tested. These data suggest that CquiOBP1 is involved in the reception of some oviposition attractants, and that high levels of OBPs expression are essential for the sensitivity of the insect’s olfactory system

<i>ABCB1</i> (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells

BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients

Comparison of the elastic recovery and strain-in-compression of commercial and novel vinyl polysiloxane impression materials incorporating a novel crosslinking agent and a surfactant

This study aims to formulate experimental vinylpolysiloxane (VPS) impression materials and compare their elastic recovery and strain-in-compressions with three commercial VPS materials (Aquasil, Elite, and Extrude). Five experimental materials (Exp), two hydrophobic (Exp-I and II) and three hydrophilic (Exp-III, IV and V) were developed. Exp 1 contained vinyl-terminated poly-dimethyl siloxane and a conventional cross-linking agent (poly methylhydrosiloxane), while Exp- II contained a novel cross-linking agent that is tetra-functional dimethyl-silyl-ortho-silicate (TFDMSOS). Exp III–V (hydrophilic materials) were formulated by incorporating different concentrations of non-ionic surfactant (Rhodasurf CET-2) into Exp II formulation. Measurement of elastic recovery and strain-in-compression for commercial and experimental materials were performed according to ISO4823 standard using the calibrated mechanical testing machine (Tinius Olsen). One-way analysis of variance (one-way ANOVA) and Tukey’s post-hoc (HSD) test were used for statistical analysis and a p-value of ≤ 0.05 was considered significant. Exp-I has statistically similar values to commercial VPS. The Exp-II showed the highest elastic recovery, while % elastic recovery was reduced with the addition of the non-ionic surfactant (Rhodasurf CET-2). The % reduction was directly related to the concentration of Rhodasurf CET-2. In addition, Exp II had significantly higher strain-in-compression values compared to Exp-I and commercial materials. These values were further increased with the addition of a non-ionic surfactant (Rhodasurf CET-2) was added (Exp-III, IV and V)