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The present study was aimed to evaluate the suitability of agro-wastes and crude vegetable oils for the cost-effective production of poly-β-hydroxybutyrate (PHB), to evaluate growth kinetics and PHB production in Alcaligenes faecalis RZS4 and Pseudomonas sp. RZS1 with these carbon substrates and to study the biodegradation of PHB accumulated by these cultures. Alcaligenes faecalis RZS4 and Pseudomonas sp. RZS1 accumulates higher amounts of PHB corn (79.90% of dry cell mass) and rice straw (66.22% of dry cell mass) medium respectively. The kinetic model suggests that the Pseudomonas sp. RZS1 follows the Monod model more closely than A. faecalis RZS4. Both the cultures degrade their PHB extract under the influence of PHB depolymerase. Corn waste and rice straw appear as the best and cost-effective substrates for the sustainable production of PHB from Alcaligenes faecalis RZS4 and Pseudomonas sp. RZS1. The biopolymer accumulated by these organisms is biodegradable in nature. The agro-wastes and crude vegetable oils are good and low-cost sources of nutrients for the growth and production of PHB and other metabolites. Their use would lower the production cost of PHB and the low-cost production will reduce the sailing price of PHB-based products. This would promote the large-scale commercialization and popularization of PHB as an ecofriendly bioplastic/biopolymer.

The objective of the present study was to develop a tablet formulation of S-(-)-amlodipine besylate chiral separation drug and nebivolol hydrochloride for better management of hypertension, while reducing or avoiding undesirable adverse effects, which are often associated with administration of a racemic mixture of amlodipine. The composition containing the optically pure S-(-)- isomer of amlodipine 2.5 mg has calcium channel blocking activity and, nebivolol hydrochloride 5 mg has beta-receptor blocking activity. The study was also carried out to design a suitable dissolution medium for S-(-) - amlodipine besylate and nebivolol hydrochloride. Amlodipine besylate and nebivolol hydrochloride had maximum solubility in pH 1.2 and thus pH 1.2 was selected as the most suitable media for S-(-) - amlodipine besylate and nebivolol hydrochloride dissolution studies. The RSD below 2% indicated insignificant batch-to-batch variation. The accelerated stability study of the optimized formulation was performed as the ICH guidelines. The results indicated no change in optical rotation of S-(-) - amlodipine besylate. Hence, combination of two drugs can be formulated into the tablet by wet granulation technique having satisfactory release profile.

Objective: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021., Design: Descriptive multi-country secondary data analysis., Setting: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021., Population: Liveborn infants., Methods: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study., Results: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%)., Conclusions: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Listeria Monocytogenes is transmitted via ingestion of contaminated food products and can cause invasive disease in susceptible hosts. Risk factors include immunocompromise; pregnancy; being elderly; and new-born. Listeriosis is uncommon but can occur in immunocompetent individuals and has a high mortality rate. We report a case of a 62-year-old female with no obvious risk factors who presented with atypical meningism. The patient was subsequently diagnosed with listeria meningitis and made a good recovery. The patient was a gardener regularly handling soil and ingested vegetables from her allotment patch; this case is reported to highlight less common risk factors and atypical ways in which listeria may present to the acute medical take.

Purple non-sulphur bacteria (PNSB) are of interest for biorefinery applications to create biomolecules, but their production cost is expensive due to substrate and biomass separation costs. This research has utilized fuel synthesis wastewater (FSW) as a low-cost carbon-rich substrate to produce single-cell protein (SCP) and examines PNSB biofilm formation using this substrate to achieve a more efficient biomass-liquid separation. In this study, PNSB were grown in Ca, Mg, S, P, and N-deficient media using green shade as biofilm support material. Among these nutrient conditions, only N-deficient and control (nutrient-sufficient) conditions showed biofilm formation. Although total biomass growth of the control was 1.5 times that of the N-deficient condition and highest overall, the total biofilm-biomass in the N-deficient condition was 2.5 times greater than the control, comprising 49% of total biomass produced. Total protein content was similar between these four biomass samples, ranging from 35.0 ± 0.2% to 37.2 ± 0.0%. The highest protein content of 44.7 ± 1.3% occurred in the Mg-deficient condition (suspended biomass only) but suffered from a low growth rate. Overall, nutrient sufficient conditions are optimal for overall protein productivity and dominated by suspended growth, but where fixed growth systems are desired for cost-effective harvesting, N-deficient conditions provide an effective means to maximize biofilm production without sacrificing protein content., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: This study reviews the demographic, clinical and radiographic features of adenomatoid odontogenic tumor(AOT) diagnosed in an Indian population over 50 years and also evaluate and compare follicular AOT(F-AOT) and extra-follicular AOT(EF-AOT)., Material and Methods: 55 diagnosed cases of AOT from 1971-2020 were studied retrospectively. The data regarding the age, sex, location, variant of AOT, duration, clinical features, radiographic appearance, treatment and recurrence were collected and analysed., Results: Of the 722 odontogenic tumors diagnosed, 7.6% were AOTs with higher prevalence of extra-follicular (67.3%) than follicular (32.7%) variant. All the tumors were intraosseous with a marked predilection for maxilla over mandible, ratio 2:1. The patients mean age was 19.8 years with slightly higher female predilection (male:female ratio - 1:1.5). The anterior region (76.4%) was more frequently affected and entire quadrant was involved in 21.8% cases. Clinically, asymptomatic, slow-growing swelling was seen in 81.8% cases with duration of 15 days to 10 years. Radiographically, AOT appeared as well-corticated radiolucent lesion. Canine was the most commonly impacted tooth. Recurrence was seen in 3 cases., Conclusions: Interestingly, in this series extra-follicular was twice more common than follicular AOT. Few cases involved the entire quadrant or crossed the midline of either jaws.

Background: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse., Methods: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further., Results: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively., Conclusion: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Anastomotic leak is a common complication after colorectal surgery, associated with increased morbidity and mortality, and poorer long-term survival after oncological resections. Early diagnosis improves short-term outcomes, and may translate into reduced cancer recurrence. Multiple studies have attempted to identify biomarkers to enable earlier diagnosis of anastomotic leak. One study demonstrated that the trajectory of C-reactive protein (CRP) levels was highly predictive of anastomotic leak requiring intervention, with an area under the curve of 0·961. The aim of the present study was to validate this finding externally., Methods: This was a prospective international multicentre observational study of adults undergoing elective colorectal resection with an anastomosis. CRP levels were measured before operation and for 5 days afterwards, or until day of discharge if earlier than this. The primary outcome was anastomotic leak requiring operative or radiological intervention., Results: Between March 2017 and July 2018, 933 patients were recruited from 20 hospitals across Australia, New Zealand, England and Scotland. Some 833 patients had complete CRP data and were included in the primary analysis, of whom 41 (4·9 per cent) developed an anastomotic leak. A change in CRP level exceeding 50 mg/l between any two postoperative days had a sensitivity of 0·85 for detecting a leak, and a high negative predictive value of 0·99 for ruling it out. A change in CRP concentration of more than 50 mg/l between either days 3 and 4 or days 4 and 5 after surgery had a high specificity of 0·96-0·97, with positive likelihood ratios of 4·99-6·44 for a leak requiring intervention., Conclusion: This study confirmed the value of CRP trajectory in accurately ruling out an anastomotic leak after colorectal resection., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Aim: The peritoneal cancer index (PCI) is one of the strongest prognostic factors in patients undergoing cytoreductive surgery (CRS) for colorectal peritoneal metastases. Using pathological evaluation, however, the disease extent differs in a large proportion of patients. Our aim was to study the correlation between the radiological (rPCI), surgical (sPCI) and pathological (pPCI) PCI in order to determine factors affecting the discordance between these indices and their potential therapeutic implications., Method: From July 2018 to December 2019, 128 patients were included in this study. The radiological, pathological and surgical findings were compared. A protocol for pathological evaluation was followed at all centres., Results: All patients underwent a CT scan and 102 (79.6%) had a peritoneal MRI. The rPCI was the same as the sPCI in 81 (63.2%) patients and the pPCI in 93 (72.6%). Concordance was significantly lower for moderate-volume (sPCI 13-20) and high-volume (sPCI > 20) disease than for low-volume disease (sPCI 0-12) (P < 0.001 for sPCI; P = 0.001 for pPCI). The accuracy of imaging in predicting presence/absence of disease upon pathological evaluation ranged from 63% to 97% in the different regions of the PCI. The pPCI concurred with the sPCI in 86 (68.8%) patients. Of the nine patients with sPCI > 20, the pPCI was less than 20 in six., Conclusion: The rPCI and sPCI both concurred with pPCI in approximately two thirds of patients. Preoperative evaluation should focus on the range in which the sPCI lies and not its absolute value. Radiological evaluation did not overestimate sPCI in any patient with high/moderate-volume disease. The benefit of CRS in patients with a high r/sPCI (> 20) who respond to systemic therapies should be prospectively evaluated., (© 2020 The Association of Coloproctology of Great Britain and Ireland.)

Cell fusion is involved in the development of some adult organs, is implicated in the pathogenesis of specific types of cancer, and is known to participate in repair/regeneration processes mediated by bone-marrow-derived cells (BMDCs). Endometriosis is a disease characterized by growth of functional endometrial tissue outside of the uterine cavity. Endometriosis shares some molecular properties with cancer and BMDCs home to endometriosis lesions in a mouse model. Our objective was to determine if cell fusion can occur in endometriosis and establish whether bone-marrow-derived cells participate in cell fusion events in lesions. We employed a Cre-Lox system to identify cell fusion events in a mouse model of endometriosis. Fused cells were detected in endometriotic lesions, albeit at a low frequency (∼1 in 400 cells), localized to the stromal compartment, and displayed restricted proliferation. Using 5-fluorouracil-based nongonadotoxic bone marrow transplantation model, we demonstrate that bone marrow cells represent a principal cell source for fusion events in lesions. Cell fusion progeny uniformly lacked expression of selected markers of hematopoietic, endothelial, and epithelial markers, though they expressed the mesenchymal/stromal markers Sca-1 and CD29. This study is the first to describe the phenomenon of cell fusion in endometriosis and points to a mesenchymal population derived from cell fusion events with limited proliferative activity, properties previously attributed to endometrial stem cells. Their putative role in the pathogenesis of the disease remains to be elucidated., (© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Caries lesion progression is difficult to determine with visual and tactile examinations. The hypothesis of this study was that reflection and roughness measurements could determine caries progression. Ground/polished sound human enamel specimens were analyzed at baseline (sound) and after two four-day demineralization periods for reflection using optical reflectometry (ORef) and for roughness using optical surface profilometry (SPro). Specimens were demineralized using a microbial- Streptococcus mutans aries model. Comparisons among the periods for ORef and SPro were performed using repeated measures analysis of variance. Two-sample t-tests were used for differences in transverse microradiography. The integrated mineral loss and depth of the four-day demineralization period were significantly smaller than those for the eight-day demineralization period ( p<0.01). With increased demineralization time, reflection was significantly decreased and roughness was significantly increased ( p<0.01). Correlation between ORef and SPro was moderate ( r=-0.63). Both reflection and roughness can be characterized for nondestructive longitudinal assessment of caries lesion progression.

Stromal-interaction molecule 1 (STIM1)-mediated store-operated Ca 2+ entry (SOCE) plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in vivo. Moreover, there is growing support for the contribution of SOCE to the Ca 2+ overload associated with ischemia/reperfusion injury. Therefore, STIM1 inhibition is proposed as a novel target for controlling both hypertrophy and ischemia/reperfusion-induced Ca 2+ overload. Our aim was to evaluate the effect of ML9, a STIM1 inhibitor, on cardiomyocyte viability. ML9 was found to induce cell death in cultured neonatal rat cardiomyocytes. Caspase-3 activation, apoptotic index and release of the necrosis marker lactate dehydrogenase to the extracellular medium were evaluated. ML9-induced cardiomyocyte death was not associated with increased intracellular ROS or decreased ATP levels. Moreover, treatment with ML9 significantly increased levels of the autophagy marker LC3-II, without altering Beclin1 or p62 protein levels. However, treatment with ML9 followed by bafilomycin-A1 did not produce further increases in LC3-II content. Furthermore, treatment with ML9 resulted in decreased LysoTracker® Green staining. Collectively, these data suggest that ML9-induced cardiomyocyte death is triggered by a ML9-dependent disruption of autophagic flux due to lysosomal dysfunction., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Increasingly patients and clients of health services are using social media to locate information about medical procedures and outcomes. There is increasing pressure for health professionals to engage in on-line spaces to provide clear and accurate information to their patient community. Research suggests there are some anxieties on the part of practitioners to do this. This study aimed to explore the attitudes of the NHS breast screening programme workforce towards engaging in online discussions with clients about breast screening., Method: 78 practitioners, representing a range of professional roles within the NHS Breast Screening Programme, attended one of 4 workshops. We used a Nominal Group Technique to identify and rank responses to the question: "What are the challenges that practitioners face in using SoME as part of their role?" Responses were categorised into themes. Participants were also asked to identify solutions to these challenges., Results: Challenges: We identified two overarching themes: (1) Working within boundaries: which was further categorised into (a) Professional/legal accountability; (b) Information accuracy and (c)Time as a boundary, and (2) Support: further categorised into (a) Employer and (b) Manager. Solutions: These included: training in technical and interactional aspects of on-line communication and a responsibility to better understand employer and professional body SoMe policies., Conclusion: The study participants appeared willing and motivated to engage in SoMe. However, in keeping with the literature from other disciplines, a number of challenges need to be overcome for its use to be adopted more widely by breast screening professionals., (Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

Introduction: Despite National Health Service (NHS) information strategy promoting the use of Social Media (SoMe) to encourage greater engagement between service users and providers, a team investigating online SoMe interaction between breast screening practitioners and clients found that practitioners alleged discouragement from employers' policies. This study aimed to investigate whether this barrier was genuine, and illuminate whether local policy differed from national strategy., Method: The study used a qualitative grounded theory approach to generate a theory. Nine policies from the North West of England were analysed. A framework was derived from the data, and an analysis of policy tone followed by a detailed coding of policy content was undertaken. Comparative analysis continued by reviewing the literature, and a condensed framework revealed five broad categories that policies addressed., Results: The analysis revealed the policies varied in content, but not in tone, which was mostly discouraging. Coding the content revealed that the most frequently addressed point was that of protecting the employers' reputation, and after further analysis, the resultant condensed framework showed that policies were imbalanced and heavily skewed towards Security, Conduct & Behaviour and Reputation., Conclusion: Practitioners within breast screening services are discouraged by overly prohibitive and prescriptive SoMe policies; with these varying tremendously in comprehensiveness, but with a narrow focus on security and employers reputation; in contrast with national strategy. Recommendations are that policy revision is undertaken with consultation by more than one stakeholder, and SoMe training is offered for all members of NHS staff., (Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Bacterial pathogens producing CTX-M beta-lactamases are emerging around the world as a source of resistance to oxyimino cephalosporins such as cefotaxime. In this study, we have investigated the prevalence of blaCTX-M genes among clinical isolates of Escherichia coli and Klebsiella pneumoniae. Of the double-disk synergy test-positive E. coli (n = 94) and Kl. pneumoniae (n = 73) strains isolated during the study period, 41 (44·08%) E. coli and 32 (43·24%) Kl. pneumoniae isolates were found to be positive for blaCTX-M genes. Twenty-two integrons (13 for E. coli and 9 for Kl. pneumoniae) were detected whose sizes ranged from 600 bp to 1·5 kb. All these integrons were found to be of Class1 type and were invariably PCR positive for int1 and sul1 genes. Marker transfer experiments demonstrated plasmid-mediated transfer of cefotaxime and ceftazidime resistance markers. In addition, analysis of the enterobacterial repetitive intergenic consensus (ERIC)-PCR typing of the blaCTX-M -carrying isolates showed that they were genetically diverse and heterogeneous suggesting that multiple subtypes of the species were involved in infection., Significance and Impact of the Study: A high frequency of blaCTX-M -resistant marker has been found in Escherichia coli and Klebsiella pneumoniae isolates of clinical origin. Analysis of the ERIC-PCR typing of the blaCTX-M -carrying isolates showed that they were genetically diverse and heterogeneous suggesting that multiple subtypes of the species were involved in infection., (© 2016 The Society for Applied Microbiology.)

Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. However, there is no evidence of the existence of Borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of Borrelia biofilm in infected human skin tissues. Archived skin biopsy tissues from borrelial lymphocytomas (BL) were reexamined for the presence of B. burgdorferi sensu lato using Borrelia-specific immunohistochemical staining (IHC), fluorescent in situ hybridization, combined fluorescent in situ hybridization (FISH)-IHC, polymerase chain reaction (PCR), and fluorescent and atomic force microscopy methods. Our morphological and histological analyses showed that significant amounts of Borrelia-positive spirochetes and aggregates exist in the BL tissues. Analyzing structures positive for Borrelia showed that aggregates, but not spirochetes, expressed biofilm markers such as protective layers of different mucopolysaccharides, especially alginate. Atomic force microscopy revealed additional hallmark biofilm features of the Borrelia/alginate-positive aggregates such as inside channels and surface protrusions. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in human infected skin tissues.

Background: Fluorine-18-labelled fluoroxdeoxyglucose (FDG) positron emission tomography (PET) has been used to evaluate atherosclerotic plaque metabolic activity, and through its uptake by macrophages is believed to have the potential to identify vulnerable plaques. The aims were to compare FDG uptake in carotid plaques from patients who had sustained a recent thromboembolic cerebrovascular event with that in femoral artery plaques from patients with leg ischaemia, and to correlate FDG uptake with the proportion of M1 and M2 macrophages present., Methods: Consecutive patients who had carotid endarterectomy for symptomatic, significant carotid stenosis and patients with severe leg ischaemia and significant stenosis of the common femoral artery underwent FDG-PET and histological plaque analysis. The voxel with the greatest activity in the region of interest was calculated using the Patlak method over 60 min. Plaques were dual-stained for CD68, and M1 and M2 macrophage subsets., Results: There were 29 carotid and 25 femoral artery plaques for study. The maximum dynamic uptake was similar in carotid compared with femoral plaques: median (range) 9·7 (7·1-12·2) versus 10·0 (7·4-16·6) respectively (P = 0·281). CD68 macrophage counts were significantly increased in carotid compared with femoral plaques (39·5 (33·9-50·1) versus 11·5 (7·7-21·3) respectively; P < 0·001), as was the proportion of M1 proinflammatory macrophages. The degree of carotid stenosis correlated with the maximum dynamic FDG uptake (rs  = 0·48, P = 0·008)., Conclusion: FDG uptake was no greater in symptomatic carotid plaques than in the less inflammatory femoral plaques. In patients on statin therapy. FDG uptake occurred in areas of significant arterial stenosis, irrespective of the degree of inflammation., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Objective: To compare differences in macrophage heterogeneity and morphological composition between atherosclerotic plaques obtained from recently symptomatic patients with carotid artery disease and femoral plaques from patients with severe limb ischemia., Design: Experimental study., Methods: Plaques were obtained from 32 patients undergoing carotid endarterectomy and 25 patients undergoing common femoral endarterectomy or lower limb bypass. Macrophages and T cell numbers were detected in plaque sections by immunohistochemistry and anti CD68 and CD3 antibodies. Dual staining for CD68 and M1- and M2-macrophage markers and morphometric analysis of hematoxylin and eosin stained plaque sections was performed., Results: Carotid plaques had significantly increased percentage areas of confluent lipid and leukocytic infiltrates. In contrast, areas of fibroconnective tissue were significantly greater in femoral plaques and percentage areas of confluent calcification and collagen were elevated. Carotid artery plaques had greater numbers per plaque area of macrophages and T cells consistent with a more inflammatory phenotype. Proportions displaying M1-activation markers were significantly increased in the carotid compared to femoral plaques whereas femoral plaques displayed a greater proportion of M2-macrophages., Conclusion: Plaques from patients with recently symptomatic carotid disease have a predominance of M1-macrophages and higher lipid content than femoral plaques, consistent with a more unstable plaque., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

A sensitive, accurate, precise and validated ion-pairing reverse-phase liquid chromatographic method for the quantitative determination of atenolol and indapamide in bulk and tablet dosage form was developed. The proposed ion-pairing reverse-phase high performance liquid chromatography method utilises C(18) column with 5 μm, 150×4.6 mm i.d. column and mobile phase consisting of 0.1% w/v solution of octane sulphonic acid, sodium salt and methanol (55:45 v/v), (pH 2.8) and ultraviolet detection at 235 nm. A linearity range of 1-250 μg/ml and 1-25 μg/ml for atenolol and indapamide, respectively, was obtained. The mean recoveries are 100.48 and 99.82% for atenolol and indapamide, respectively. The method was validated as per International Conference on Harmonization guidelines.

Antipsychotic-induced weight gain has emerged as a serious complication in the treatment of patients with most antipsychotics. We have conducted the first in-depth examination of dopamine receptor genes in antipsychotic-induced weight gain. A total of 206 patients (139 of European descent and 56 African Americans) who underwent treatment for chronic schizophrenia or schizoaffective disorder were evaluated after on average over 6 weeks of treatment. Thirty-six tag single nucleotide polymorphisms (SNPs) and one variable-number tandem repeat, spanning the five dopamine receptor genes (DRD1-DRD5) were analyzed. In the total sample, we found a nominally significant association between the DRD2 rs1079598 marker and weight change using a cutoff of 7% gain (P=0.03). When stratifying the sample according to ethnicity and antipsychotics with highest risk for weight gain, we found significant associations in three DRD2 SNPs: rs6277 (C957T), rs1079598 and rs1800497 (TaqIA). The other genes were primarily negative. We provide evidence that dopamine receptor DRD2 gene variants might be associated with antipsychotic-induced weight gain in chronic schizophrenia patients.

The study was undertaken to investigate the effects of pacing on aspects of performance at an assembly task and on the operators' responses related to work behaviour, perceived workload and perceived stress. A particular objective of the study was to investigate whether physical and cognitive demands may interact in their influences on these effects. An assembly task was simulated in the laboratory and the level of pacing imposed, work height and memory load within the task were all varied. The results showed that the type of pacing commonly imposed (as is common with a lean manufacturing Takt time system in industry) can significantly affect both performance and perceived workload and stress. Physical demands (through work height affecting posture) and mental demand (through memory load) were also found to have significant effects, as would be expected from the many studies of these in the literature. More importantly, some interactions were found between pacing and work height in their effects on quality of assembly and the operator's own rating of performance, and between work height and memory load in their effects on errors. These findings will need to be taken into account by companies when implementing Takt time systems.

Aim: To evaluate two nanoparticle-enhanced polymer root-end filling materials (NERP1 and NERP2) on the initial apical seal as compared to a polymer-based commercial compomer., Methodology: One hundred and forty extracted roots with completely formed apices were resected 3 mm from the apex. Cavities were then prepared in the apical openings of the resected root ends using an ultrasonic handpiece to a depth of 3 mm. The roots were then randomly divided into five groups to receive one of five root-end filling materials. Roots in groups 1 and 2 received NERP1 and NERP2, whilst those in groups 3 and 4 received identical polymers as groups 1 and 2 but without nanoparticle addition (RP1 and RP2, respectively). The root-end cavities for the fifth group were filled with commercially available root-end filling compomer. Roots were mounted in a dual-chamber leakage apparatus and inoculated coronally with Enterococcus faecalis. Turbidity of the apical broth was assessed daily for 4 weeks as a sign of initial leakage. The results were statistically analysed using odds ratio and Fisher's chi-square analysis., Results: Nanoparticle-enhanced root-end filling polymer 1 displayed significantly fewer leaked samples compared to all other tested groups as early as 5 days, whilst NERP2 was not significantly different compared to other groups. Odds ratio analysis revealed leakage of the commercial compomer was 12 times more likely than NERP1., Conclusion: Nanoparticle-enhanced root-end filling polymer 1 can reduce apical microleakage significantly under laboratory conditions., (© 2011 International Endodontic Journal.)

Aim: To evaluate the cytotoxicity of two forms of the novel root-end filling materials, polymer nanocomposite (PNC) resins [C-18 Amine montmorillonate (MMT) and VODAC MMT] both containing Chlorhexidine Diacetate Salt Hydrate 2%, and to compare it to that of two widely accepted commercially available materials, ProRoot® MTA and Geristore®., Methodology: Elutes of experimental materials extracted after 24 h, 1, 2 and 3 weeks were interacted with the mouse fibroblasts L-929 using a colorimetric cell viability assay (MTS) based on mitochondrial dehydrogenases activity. Using 100% and 50% concentrations of the extracted elutes of the experimental materials the effect of different concentrations of elutes on the cells was analysed. In the positive control group Hygrogold® was added to the cell culture to arrest cells bioactivity. In the negative control group, fresh Dulbecco's Eagle's minimum essential medium supplemented with 10% foetal bovine serum was used to enhance cell bioactivity. Differences in mean bioactivity values were assessed using a t-test and one-way anova (P<0.05)., Results: No significant difference was found in cytotoxicity between ProRoot® MTA, Geristore® and PNC resin C-18 Amine MMT on 24 h, 1, 2 and 3 weeks samples. Sample elutes of PNC resin VODAC MMT, however, revealed cytotoxic activity during most of these experiments., Conclusion: Cytotoxicity of the elutes of PNC resin C-18 Amine MMT was not significantly different from that of ProRoot® and Geristore®. PNC resin VODAC MMT, revealed significantly more cytotoxicity compared to the other tested materials., (© 2010 International Endodontic Journal.)

Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction., (© 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.)

Background: The diagnostic tools to predict the prognosis in patients suffering from breast cancer (BC) need further improvements. New technological achievements like the gene profiling of circulating tumour cells (CTC) could help identify new prognostic markers in the clinical setting. Furthermore, gene expression patterns of CTC might provide important informations on the mechanisms of tumour cell metastasation., Materials and Methods: We performed realtime-PCR and multiplex-PCR analyses following immunomagnetic separation of CTC. Peripheral blood (PB) samples of 63 patients with breast cancer of various stages were analyzed and compared to a control group of 14 healthy individuals. After reverse-transcription, we performed multiplex PCR using primers for the genes ga733.3, muc-1 and c-erbB2. Mammaglobin1, spdef and c-erbB2 were analyzed applying realtime-PCR., Results: ga733.2 overexpression was found in 12.7% of breast cancer cases, muc-1 in 15.9%, mgb1 in 9.1% and spdef in 12.1%. In this study, c-erbB2 did not show any significant correlation to BC, possibly due to a highly ambient expression. Besides single gene analyses, gene profiles were additionally evaluated. Highly significant correlations to BC were found in single gene analyses of ga733.2 and muc-1 and in gene profile analyses of ga733.3*muc-1 and GA7 ga733.3*muc-1*mgb1*spdef., Conclusion: Our study reveals that the single genes ga733.3, muc-1 and the gene profiles ga733.3*muc-1 and ga733.3*3muc-1*mgb1*spdef can serve as markers for the detection of CTC in BC. The multigene analyses found highly positive levels in BC patients. Our study indicates that not single gene analyses but subtle patterns of multiple genes lead to rising accuracy and low loss of specificity in detection of breast cancer cases.

Background: Breast cancer (BC) represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting., Materials and Methods: Circulating tumour cells (CTC) of 63 BC patients were isolated from peripheral blood (PB) through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes ga733.2, muc-1, c-erbB2, mgb-1, spdef and c-erbB2 were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls., Results: Significant correlations with tumour stages were found in single gene analyses of ga733.2, muc-1 and in multi-gene analyses of ga733.2/muc-1/mgb1/ spdef. Furthermore, a significant correlation of Ca 15-3 and all studied genes was also observed., Conclusion: Herein, we demonstrated a positive correlation of a gene signature consisting of ga733.2, muc-1, mgb1 and spdef and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with Ca 15-3 positive cases.

A live oral cholera vaccine developed from a non-toxigenic Vibrio cholerae O1 El Tor strain VA1.3 was tested in a double-blind randomized placebo controlled study for safety and immunogenicity in 304 men aged between 16 and 50 years from Kolkata, India. A dose of 5 x 10(9)CFU (n=186) or a placebo (n=116) containing the diluent buffer was administered. The vaccine did not elicit adverse events except in two vaccine recipients with mild diarrhoea and vomiting. None excreted the vaccine strain. Vibriocidal antibody response developed in 105/186 (57%) and 5/116 (4%) in vaccine and placebo recipients, respectively. In a subgroup, anti-CT antibody rose (> or =2-folds) in 23/30 (77%) and 6/19 (32%) in vaccine and placebo recipients, respectively. These studies demonstrate that VA1.3 at a dose of 5 x 10(9) is safe and immunogenic in adults from a cholera endemic region.