Why and how have drug discovery strategies in pharma changed? What are the new mindsets?
In the pharmaceutical industry the long-term challenge of drug innovation is the key phrase throughout R&D that refers to increasing the output of original drug candidate molecules. To increase R&D productivity, implementation of new and strategic R&D orientations to develop new approaches or systems to identify hits and leads efficiently has taken place and enabled all scientists working in the drug discovery domain to develop innovative medicines for the 21st century.


Long Non-coding RNA SNHG7 Suppresses Inflammation and Apoptosis of Chondrocytes Through Inactivating of p38 MAPK Signaling Pathway in Osteoarthritis.
This study aims to explore the molecular mechanism of LncRNA SNHG7 in Osteoarthritis (OA). Cartilage tissues of OA patients or patients with trauma or amputation were collected. Compared to normal cartilage tissues, SNHG7 was downregulated while miR-324-3p was upregulated in cartilage tissues of OA patients. IL-1β was used to induce damage to chondrocytes and treatment with IL-1β reduced SNHG7 expression in OA chondrocytes. In IL-1β-treated OA chondrocytes, SNHG7 overexpression reduced the levels of TNF-α and IL-6, inhibited cell apoptosis, and increased cell viability. Additionally, the luciferase reporter assay proved that SNHG7 upregulated dual-specificity phosphatase 1 (DUSP1) by sponging miR-324-3p, thereby inactivating the p38 MAPK signaling pathway by regulating the miR-324-3p/DUSP1 axis. Anisomycin (a p38 MAPK activator) enhanced OA chondrocytes inflammation, promoted cell apoptosis, and reduced cell viability; however, this was reversed by SNHG7 overexpression. This study demonstrates that the SNHG7/miR-324-3p/DUSP1 axis suppresses OA chondrocytes inflammation and apoptosis by inhibiting the p38 MAPK signaling pathway. Thus, this study indicates that SNHG7 is a novel target for OA treatment.


Emergency surgical treatment for bleeding duodenal ulcer: oversewing plus vagotomy versus gastric resection, a controlled randomized trial. French Associations for Surgical Research.
The best surgical procedure to treat bleeding bulbar peptic ulcer is unknown. The rates of postoperative bleeding recurrence, duodenal leakage, and mortality were compared in patients undergoing oversewing plus vagotomy (O+V) or gastric resection (GR) with ulcer excision. Of 202 patients undergoing emergency surgery for massive, persistent, or recurrent bleeding from bulbar peptic ulcer, 120 patients were enrolled in a prospective randomized trial. Fifty-nine were assigned to O+V and 61 to GR. One patient in each group was excluded after randomization. The two groups were well matched with respect to clinical and prognostic factors. The rate of postoperative bleeding recurrence was 17% after O+V and 3% after GR (p < 0.05). The duodenal leak rate was higher after GR than after O+V (13% vs. 3%) (p < 0.10) but was not different when the morbidity of reoperations for bleeding recurrence after O+V was considered on an "intention to treat" basis (12% vs. 13%). Overall postoperative mortality was similar: 22% (O+V) versus 23% (GR). Sixteen deaths were unrelated to the surgical procedure itself. Of 82 nonrandomized patients, 10 were not analyzed. In the 72 other nonrandomized patients, bleeding recurrence, duodenal leakage, and postoperative mortality rates were consistent with the results of the controlled trial, as they were 29% (O+V 32%; GR 0.7%), 16% (O+V 0.7%; GR 26%) and 27% (O+V 18%; GR 33.3%), respectively. We conclude that GR with ulcer excision is the procedure of choice for the emergency surgical treatment of bleeding duodenal ulcer because postoperative bleeding recurrence is lower, and the overall rates of mortality and duodenal leakage are the same as with O+V.


Inactivation of a functional HLA-A gene: a 4-kb deletion turns HLA-A*24 into a pseudogene.
An unusual haplotype without a detectable human leukocyte antigen (HLA)-A allele by serologic or molecular typing methods segregates in a Caucasian family. Microsatellite analysis and fluorescence in situ hybridization implicated that the deletion encompasses a narrow region. To identify the deleted region, five different fragments in close proximity to HLA-A, known to be highly polymorphic, were amplified and sequenced. The presence of heterozygous sequences in all five fragments of the individuals carrying the haplotype with the HLA-A deletion, indicates that the fragments are not involved in the deletion. Therefore, the 5' primer from the fragment closest to the centromeric side of HLA-A was combined with the 3' primer closest to the telomeric side encompassing an 11-kb region. Sequencing revealed that a deletion of 4089 bp was present, located upstream of HLA-A, including exons and introns 1-3 of the HLA gene. Sequence information of the 3' part of HLA-A, downstream the deletion, identified that the deleted allele originates from an A*24 allele. Although different repeat sequences are present in the region both inside and outside the deletion, no evidence points to a retrotransposon mechanism. The detected partial deletion of HLA-A turns this functional gene into a pseudogene.


Brother and sister with trisomy 10p. 46,XY,(22p+)mat; 46,XX,(22p+)mat.
Since the usefulness of chromosome differential banding techniques has become fully established, several descriptions of chromosome 10 short arm trisomy have been published (Schleiermacher et al., 1974; Roux et al., 1974; Cantu et al., 1975; Grosse et al., 1975; Moric-Petrovic et al., 1976; Turleau et al., 1976; Johnson et al., 1977; Yunis and Lewandowski, 1977). The present report deals with a mother who is a carrier of a reciprocal translocation between chromosome 22 and 10, which has resulted in two children with a 10p trisomy.


Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT.
Autologous SCT (ASCT) remains an effective therapy for eligible patients with myeloma. Previous studies have suggested a lack of impact of the initial therapy on the outcome after ASCT. It is not clear if incorporation of new agents in the initial treatment regimens will have any impact on the outcome after ASCT. We studied 472 patients undergoing ASCT within 12 months of diagnosis to assess the effect of initial therapy on the outcome after ASCT. Patients received initial therapy with vincristine, adriamycin and dexamethasone (VAD), dexamethasone, thalidomide and dexamethasone or lenalidomide and dexamethasone. While patients treated with dexamethasone alone had higher disease burden at ASCT, no differences were observed in the response rates to ASCT, post transplant complications or treatment-related mortality among the groups. The median time to progression after ASCT was 27.1, 24.7, 21.1 months and did not reach the VAD, Dex, Thal-Dex and Len-Dex group, respectively, P=0.11. The median overall survival from ASCT was 62 months for VAD, 69.6 months for Dex and were not reached for Thal-Dex and Len-Dex groups, P=0.2. For patients undergoing early ASCT for myeloma, the nature of initial treatment utilized has no long-term impact on the outcome of ASCT.


Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in Sweden.
Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers. Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780. In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (β = 0.74; p < 0.001) and myocardium (β = 0.65; p < 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality. Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10.


Contrasting patterns and frequency of antibodies to the surface, core, and e antigens of hepatitis B virus in blood donors and in homosexual patients.
An attempt was made to assess the significance of the relatively frequent low-titre positive reactions in radioimmunoassays for antibody to hepatitis B surface antigen. Serum specimens negative for surface antigen were assayed for antibodies to the surface, core, and e antigens of the Hepatitis B virus. Two populations were studied - one of low hepatitis B incidence (2000 blood donors) and one of high incidence (200 male patients attending a clinic for sexually transmitted diseases). The validity of some singly occurring low-titre anti-HBs and anti-HBc reactions is questioned, and the occurrence of positive reactions unrelated to previous hepatitis B infection inferred.


Management of complications of flexor tendon injuries.
Innovations in operative techniques, biomaterials, and rehabilitation protocols have improved outcomes after treatment of flexor tendon injuries. However, despite these advances, treatment of flexor tendon injuries remains challenging. The purpose of this review is to highlight the complications of flexor tendon injuries and review the management of these complications.


Is the electron wavelength an observable?
This paper is concerned with a problem often overlooked; it stems from the fact that the electron wave is also influenced by the magnetic vector potential. If one considers this influence, problems arise from the ambiguities in the gauge of the vector potential. They bear on the question of whether the electron wavelength can be considered observable or not. The answer lies, probably, in the definition of measurability.


'Telling our story... Creating our own history': caregivers' reasons for participating in an Australian longitudinal study of Indigenous children.
Improving the wellbeing of Indigenous populations is an international priority. Robust research conducted with Aboriginal and Torres Strait Islander peoples is key to developing programs and policies to improve health and wellbeing. This paper aims to quantify the extent of participation in a national longitudinal study of Aboriginal and Torres Strait Islander (Indigenous Australian) children, and to understand the reasons why caregivers participate in the study. This mixed methods study uses data from Wave 6 of Footprints in Time, the Longitudinal Study of Indigenous Children. We conducted descriptive analysis of quantitative variables to characterise the sample and retention rates. We applied conventional content analysis to 160 caregivers' open-ended responses to the question, 'Why do you stay in the study?', identifying themes and overarching meta-themes. The study has maintained a high retention rate, with 70.4% (n = 1239/1671) of the baseline sample participating in the study's 6th wave. We identified seven themes related to why participants stay in the study: telling our story, community benefit, satisfaction, tracking Study Child's progress, study processes, receiving study gifts, and valuing what the study stands for. These related to two meta-themes: reciprocity, and trust and connection. Caregivers reported that participation was associated with benefits for their family and community as well as for the study. They identified specific features of the Footprints in Time study design that built and maintained trust and connection between participants and the study. Our findings support the assertion that Aboriginal and Torres Strait Islander people want to be involved in research when it is done 'the right way'. Footprints in Time has successfully recruited and retained the current-largest cohort of Aboriginal and Torres Strait Islander children in Australia through the use of participatory research methodologies, suggesting effective study implementation and processes. Participants indicated ongoing commitment to the study resulting from perceptions of reciprocity and development of trust in the study. Footprints in Time can serve as a successful model of Aboriginal and Torres Strait Islander health research, to promote good research practice and provides lessons for research with other Indigenous populations.


The pattern of population growth as a function of redundancy and repair.
A basic model of hierarchical structure, expressed by simple, linear differential equations, shows that the pattern of population growth is essentially determined by conditions of redundancy in the sub-structure of individuals. There does not exist any possible combination between growth rate and accident rate that could balance population numbers and/or the level of redundancy within the population; all possible combinations either lead to extinction or to positive population growth with a decline of the fraction of individuals with redundant substructure. Declining populations, however, can be held fluctuating between certain limits by periodic phases of sub-unit repair. These results are particularly pertinent to the population dynamics of diploid (polyploid) organisms.


[Analysis of maternal mortality in China from 1996 to 2000].
To study the trend and characteristics of maternal mortality in China from 1996 to 2000. Population-based epidemiological survey in 116 monitoring units in China were used. Maternal mortality in China dropped by 17.1% from 63.9 per 100,000 live births in 1996 to 53.0 in 2000, in rural area dropped by 22.2% from 86.4 per 100,000 live births to 67.2, and in urban area only 1.0% from 29.2 per 100 000 live births to 28.9, the leading causes of maternal mortality in China are hemorrhage, preeolampsia/eclampsia and amniotic fluid embolism the maternal mortality due to hemorrhage in national level and rural level has declined by 33.8%, 34.9% respectively. The maternal mortality appears a declined trend on both the national and rural levels in China from 1996 to 2000, the maternal mortality due to hemorrhage dose also, bur the maternal mortality in urban area keeps unstable.


A PET study of adenosine A1 receptor in anesthetized monkey brain.
We demonstrated the distribution of adenosine A1 receptors in the anesthetized monkey brain with positron emission tomography (PET) using [(11)C]KF15372 ([1-propyl-(11)C]8-dicyclopropylmethyl-1, 3-dipropylxanthine). [(11)C]KF15372 was injected intravenously. The regional standardized uptake values and the distribution volume were calculated. We also investigated the effect of carrier on the uptake and regional brain distribution of [(11)C]KF15372. The use of [(11)C]KF15372 with dynamic PET scanning could be an appropriate method to analyze the regional binding potential of adenosine A1 receptors in living brain.


Closed reduction of prosthetic hip dislocation by emergency physicians.
The purpose of this study was to determine the frequency of successful closed reduction (CR) of dislocated prosthetic hips performed by emergency physicians (EPs) as well as the incidence of acute complications. The study design was an explicit chart review set at an academic ED with an annual census of 55,000. The study was performed on March 1, 1999 to February 28, 2004. Patients were identified using coded ED diagnoses, and data were obtained by a trained abstractor. One hundred twelve dislocations in 66 patients had attempted CR in the ED. Eighty-one had CR attempted solely by an EP with 91% success. Twenty-eight of the remaining 31 (90%) had successful CR performed by either an orthopedic surgeon or both an EP and an orthopedic surgeon. Overall, 10 patients (9%) failed ED CR. No postreduction complications were identified in any patient. EPs can safely and successfully perform CR on patients with dislocated total hip arthroplasties.


Economic crisis and suicides in Spain. Socio-demographic and regional variability.
Evidence from previous recessions suggests that at times of economic deterioration, suicides increase. Spain has been one of the European countries hardest hit by the financial crisis that started in 2008. The aim of this paper is to examine the impact of the double-dip recession in Spain on the most recent trends in suicide. Suicide data from the years 2002-2012 were obtained from the 'Death Statistic according to Cause of Death' of the National Statistics Institute (NSI). Population figures were obtained from the population estimates of the NSI. While the suicide rate decreased between 2002 and 2012, the downward trend has reversed twice, in 2008-2009, and in 2012. This rise was particularly pronounced in males, with the rate ratio of 1.12 (95 % CI 1.05-1.20) in 2008 and 1.10 (95 % CI 1.03-1.18) in 2009. Following a decrease in 2010 and 2011, suicides among males have increased again in 2012-with RR of 1.10 (95 % CI 1.03-1.18) compared to 2007, however the difference between 2011 amounted to 14 % rise-the biggest interannual change in a decade. There was a similar but less pronounced pattern in females. Regional data showed variable results. These results suggest that the Spanish economic crisis has been associated with suicide rates in 2008, 2009, and 2012. These findings are consistent with the double-dip recession that Spain experienced.


A light and scanning electron microscopic study of osteocyte activity in calcium-deficient rats.
The material herein is an extension of an earlier study of osteocyte lacunae in calcium-deficient rats, utilizing morphometric measurements in undecalcified bone sections and scanning electron microscopy. The results confirm our earlier finding that bone resorption resulting from a low-calcium diet is not accompanied by osteocytic resorption.


Salivary antibody titers in adults challenged with a human rotavirus.
To determine whether salivary antibody is a reliable indicator of rotavirus infection and mucosal rotavirus antibody concentrations, salivary rotavirus antibody titers were determined as a function of time following inoculation of 24 adult volunteers with a virulent strain of human rotavirus (CJN). Twenty of the subjects became infected and all produced detectable amounts of salivary rotavirus IgA. These antibody concentrations remained undetectable in the four uninfected subjects. Rises of greater than or equal to fourfold in either salivary rotavirus IgA or neutralizing antibody to the challenge virus were detected in all but two subjects. The titers of both antibodies were maximal at 13 days after inoculation and decreased significantly (p less than .02) by 27 days, a result very similar to that previously found with stool rotavirus IgA in CJN-infected subjects. These results suggest that salivary rotavirus antibody titers are an accurate reflection of mucosal rotavirus antibody and a possible surrogate for intestinal rotavirus antibody.


Molecular detection of Mikrocytos mackini in Pacific oysters using quantitative PCR.
Mikrocytos mackini is an internationally regulated pathogen and causative agent of Denman Island disease in Pacific oysters Crassostrea gigas. Recent phylogenetic breakthroughs have placed this parasite within a highly divergent and globally distributed eukaryotic lineage that has been designated a new taxonomic order, Mikrocytida. The discovery of this new radiation of parasites is accompanied by a heightened awareness of the many knowledge gaps that exist with respect to the general biology, epizootiology, and potential impact of mikrocytid parasites on hosts, ecosystems, and commercial fisheries. It has also highlighted current shortcomings regarding our ability to detect these organisms. In this study, we developed a species-specific, sensitive, and quantitative method for detecting M. mackini DNA from host tissues using probe-based real-time qPCR technology. A limit of sensitivity between 2 and 5 genome copy equivalents was achieved in a reaction matrix containing ≥ 40 ng/μL host gDNA without inhibition. This detection proved superior to existing methods based on conventional PCR, histology or gross pathology and is the first species-specific diagnostic test for M. mackini. Quantitative assessment of parasite DNA using this assay remained accurate to between 10 and 50 copies identifying that during infection, M. mackini DNA was significantly more prevalent in hemolymph, labial palp, and mid-body cross-sections compared to mantle or adductor muscle. DNA extracted from a mid-body cross-section also provided the highest likelihood for detection during diagnostic screening of infected oysters. Taken together, these findings provide strong analytical evidence for the adoption of qPCR as the new reference standard for detecting M. mackini and give preliminary insight into the distribution of the parasite within host tissues. Standardised operating methodologies for sample collection and qPCR testing are provided to aid in the international regulatory diagnosis of M. mackini and serve as a useful platform for the future development of multiplexed or alternate mikrocytid species detection.


Chondroitin sulfate proteoglycan phosphacan associates with parallel fibers and modulates axonal extension and fasciculation of cerebellar granule cells.
Phosphacan is a nervous system-specific chondroitin sulfate proteoglycan and one of the major components of extracellular matrix in the brain. In the present study, we examined its spatiotemporal expression, ultrastructural localization, binding manner, and in vitro analysis on cell adhesion, axonal extension, and fasciculation in rat cerebellum. The present light microscopic immunohistochemistry showed that phosphacan immunoreactivity was localized mainly at the molecular layer in the cerebellum, but not at the external granular layer. Further double labeling immunohistochemical and immunoelectron microscopic studies revealed that phosphacan was localized around parallel fibers, but not at synapses. The binding of phosphacan to membrane and/or extracellular matrix partly required Ca2+ and was mediated through its core glycoprotein. Phosphacan inhibited adhesion and axonal extension of cerebellar granule cells in dissociated culture, while it promoted axonal fasciculation of their aggregated culture. These results indicate that phosphacan around parallel fibers may be the repulsive substratum for adhesion and extension of granule cells and promote the fasciculation of parallel fibers.


Risk Factors for Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study.
Many patients with ocular myasthenia gravis (OMG) progress to generalized disease within the first 2 years of the onset of ocular symptoms. Several retrospective studies have identified risk factors associated with generalization, however these studies included patients on immunosuppression therapy or those undergoing thymectomy, which may reduce the generalization risk. In this study we explored the risk factors for generalization in non-immunosuppressed and non-thymectomized patients with OMG. Data from patients with OMG treated at seven tertiary hospitals in China were retrospectively reviewed. Clinical characteristics, including sex, age at onset, symptoms at onset, comorbid autoimmune diseases, neostigmine test response, repetitive nerve stimulation (RNS) findings, presence of serum anti-acetylcholine receptor antibody (AChR-Ab), and thymic status based on radiological and pathological studies, were collected. The main outcome measure was disease generalization. The follow-up period was defined as the date of ocular symptom onset to the date of confirmation of generalization or immunotherapy initiation, or last follow-up (defined as 60 months). The Cox proportional hazards model was used to assess the risk factors for generalization. Overall, 572 patients (269 women) were eligible for inclusion in the analysis, of whom 144 developed generalization. The mean (standard deviation) onset age was 45.5 (19.8) years, and the median (interquartile range) follow-up period was 14.5 (7.0-47.3) months. Multivariable Cox regression analysis demonstrated that both early-onset (adjusted hazard ratio [aHR] 5.34; 95% confidence interval [CI] 1.64-17.36; p = 0.005) and late-onset (aHR 7.18; 95% CI 2.22-23.27; p = 0.001) in adulthood, abnormal RNS findings (aHR 3.01; 95% CI 1.97-4.61; p < 0.001), seropositivity for AChR-Ab (aHR 2.58; 95% CI 1.26-5.26; p = 0.01), and thymoma (aHR 1.62; 95% CI 1.05-2.49; p = 0.03) were independently associated with increased risk of generalization. The risk of generalization increased significantly in patients with adult-onset OMG, abnormal RNS findings, seropositivity for AChR-Ab, and thymoma, suggesting that these risk factors may predict OMG generalization.


Generation of a Retargeted Oncolytic Herpes Virus Encoding Adenosine Deaminase for Tumor Adenosine Clearance.
Oncolytic viruses are immunotherapeutic agents that can be engineered to encode payloads of interest within the tumor microenvironment to enhance therapeutic efficacy. Their therapeutic potential could be limited by many avenues for immune evasion exerted by the tumor. One such is mediated by adenosine, which induces pleiotropic immunosuppression by inhibiting antitumor immune populations as well as activating tolerogenic stimuli. Adenosine is produced starting from the highly immunostimulatory ATP, which is progressively hydrolyzed to ADP and adenosine by CD39 and CD73. Cancer cells express high levels of CD39 and CD73 ectoenzymes, thus converting immunostimulatory purinergic signal of ATP into an immunosuppressive signal. For this reason, CD39, CD73 and adenosine receptors are currently investigated in clinical trials as targets for metabolic cancer immunotherapy. This is of particular relevance in the context of oncovirotherapy, as immunogenic cell death induced by oncolytic viruses causes the secretion of a high amount of ATP which is available to be quickly converted into adenosine. Here, we took advantage of adenosine deaminase enzyme that naturally converts adenosine into the corresponding inosine derivative, devoid of immunoregulatory function. We encoded ADA into an oncolytic targeted herpes virus redirected to human HER2. An engineered ADA with an ectopic signal peptide was also generated to improve enzyme secretion (ADA-SP). Insertion of the expression cassette was not detrimental for viral yield and cancer cell cytotoxicity. The THV_ADA and THV_ADA-SP successfully mediated the secretion of functional ADA enzyme. In in vitro model of human monocytes THP1, this ability of THV_ADA and THV_ADA-SP resulted in the retrieval of eADO-exposed monocytes replication rate, suggesting the proficiency of the viruses in rescuing the immune function. Encoding ADA into oncolytic viruses revealed promising properties for preclinical exploitation.


Meta-analysis suggests that the electromagnetic technique is better than the free-hand method for the distal locking during intramedullary nailing procedures.
To evaluate the comparative effectiveness and accuracy of electromagnetic technique (EM) verses free-hand method (FH) for distal locking in intramedullary nailing procedure. Relevant original studies were searched in Medline, Pubmed, Embase, China National Knowledge Infrastructure, and Cochrane Central Database (all through October 2015). Comparative studies providing sufficient data of interest were included in this meta-analysis. The Stata 11.0 was used to analyze all data. Eight studies involving 611 participants were included, with 305 in EM group and 306 in FH group. EM outperformed FH with reduced distal locking time of 4.1 minutes [standardized mean difference (SMD), 1.61; 95 % confidence interval (95 %CI), 0.81 to 2.41] and the reduced fluoroscopy time of 25.3 seconds (SMD, 2.64; 95 %CI, 2.12 to 3.16). Regarding the accuracy of distal screw placement, no significant difference was observed between two techniques (OR, 2.39; 95 %CI, 0.38 to 15.0). There was a trend of longer operative time in FH versus EM by 10 minutes (79.0 and 69.0 minutes), although the difference was not statistically significant (SMD, 0.341; 95 % CI, -0.02 to 0.703). The existing evidence suggests EM technique is a better alternative for distal locking in intramedullary nailing procedure, and this might aid in the management of diaphyseal fractures in lower extremities.


Pathological, biochemical and molecular variability of Colletotrichum truncatum incitant of anthracnose disease in chilli (Capsicum annuum L.).
The present study aims to establish pathogenic variability among Colletotrichum truncatum, an incitant of anthracnose disease across different chilli growing regions of Karnataka. Thirty suspected C. truncatum isolates were identified based on their morphological and conidial characteristics and further confirmed by Internal Transcribed Spacer DNA sequence analysis. Pathogenicity test was carried out by in vitro detached leaf and fruit assay, and also under greenhouse conditions using 20 different chilli cultivars grown across Karnataka. Colletotrichum truncatum isolates recorded the varied degree of pathogenicity index (PI) on different chilli cultivars. Isolate UOM-02 was found highly virulent (PI > 80 against 12 tested cultivars) and cultivar cv. 4 was found highly resistant to C. truncatum infection (Average PI, 48.21). Further, the involvement of enzymes such as cellulase, pectin methylesterase and ascorbate peroxidase in determining the virulence of the pathogen was established. The highest activity of catalase (UOM-24; 7.38 units), ascorbate peroxidase (UOM-02; 2.9 units), cellulase (UOM-02; 0.58 units), and pectin methylesterase (UOM-02; 6.7 units), was recorded by different C. truncatum isolates. Cellulase and pectin methylesterase activities were positively correlated with their pathogenicity, while catalase activity was found least correlated. Results of RAPD and ISSR analysis recorded higher polymorphism among the isolates. Interestingly these isolates were not clustered based on their geographical origin, Pathogenicity index and biochemical characters. From this study, the existence of highly virulent C. truncatum isolate (UOM-02), which can cause severe loss under favourable conditions, was revealed. Further, possible use of specific enzymes as an indicator of virulence of the pathogen is discussed.


Relationship between [123 I]-FP-CIT SPECT and clinical progression in Parkinson's disease.
The demonstration of presynaptic dopaminergic deficiency on [123 I]-FP-CIT SPECT imaging is a useful ancillary tool in the diagnosis of Parkinson's disease (PD). Whilst there is evidence of a cross-sectional relationship between the degree of dopaminergic deficiency and severity of bradykinesia and rigidity, longitudinal studies are rare. Moreover, the relationship between motor subtypes and their dopaminergic deficient state is not well characterized. Our primary aim was to assess the correlations between dopaminergic deficiency on baseline [123 I]-FP-CIT SPECT imaging with the progression of motor severity in patients classified by motor subtype, and the development of motor complications. Our secondary aim was to assess the correlation between UPDRS-III subscores and the time to onset of motor complications. 42 PD patients with abnormal baseline [123 I]-FP-CIT SPECT scans and at least 3 years of clinical follow-up were classified by motor subtype: akinetic-rigid, tremor-dominant or mixed. UPDRS-III scores at baseline and at 3-year follow-up, and time to onset of motor complications were recorded. [123 I]-FP-CIT uptake ratios were inversely correlated with UPDRS-III scores at 3 years only in akinetic-rigid patients (r=-.51, P=.04). Time to onset of motor complications was inversely correlated with UPDRS-III subscores for bradykinesia and rigidity at baseline (r=-.52, P=.02) and at 3 years (r=-.54, P=.01). The degree of dopaminergic deficiency on baseline [123 I]-FP-CIT SPECT inversely correlates with motor severity at 3-year follow-up in akinetic-rigid patients only. Furthermore, UPDRS-III subscores for bradykinesia and rigidity at baseline show an inverse correlation with time to onset of motor complications across all PD subtypes.


Chicken thymocyte-specific antigen identified by monoclonal antibodies: ontogeny, tissue distribution and biochemical characterization.
Two monoclonal antibodies, CT-1 (IgG1, kappa) and CT-1a (IgG3, kappa) were prepared against chicken thymocytes. The antigen identified by these antibodies was found to be a glycoprotein with a major polypeptide component having an apparent molecular weight of 63 000 and a minor polypeptide component of approximately 103 000. Immunoprecipitation and blocking experiments revealed that the two antibodies react with different antigenic determinants of the molecule. Ontogenic studies employing immunofluorescence failed to reveal the antigenic determinants on cells from the embryo or embryonic yolk sac on days 3 and 6 of incubation. The number of embryonic thymocytes bearing the molecules detected by these antibodies increased from 6% on day 12 to 54% on day 13; the frequency of thymocytes expressing this glycoprotein reached adult levels (greater than 90%) by the 15th day of embryonic age. In contrast, the CT-1 and CT-1a antibodies reacted with only 2-5% of blood and splenic cells and less than 0.05% of cells from bursa or bone marrow of young adult chickens. In the quail CT-1 reacted with cortical, but not medullary, thymocytes, while the CT-1a antibody was unreactive with quail thymocytes. The surface glycoproteins detected by these discriminating monoclonal antibodies may provide an important discriminating marker for thymic lymphocytes in the chicken and the quail.


Role of serotonin (5-HT) in the antidepressant-like properties of neuropeptide Y (NPY) in the mouse forced swim test.
Neuropeptide Y (NPY) is thought to be implicated in depressive disorders. The mouse forced swim test (FST) is an animal model widely used as a predictor of the efficacy of antidepressant drugs. The present study was undertaken to explore the possible contribution of endogenous serotonin (5-HT) systems in the behavioral effects elicited by NPY in this model. The selective serotonin re-uptake inhibitor (SSRI), fluoxetine, was also tested for comparison. 5-HT was depleted prior to testing by the administration of the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA; 300 mg/kg, i.p., each day for 3 days; control mice received saline-vehicle over the same period). On the fourth day, mice received NPY (3 nmol, I.C.V.), fluoxetine (16 mg/kg, i.p.) or saline injections before testing in the FST. Both NPY and fluoxetine significantly reduced immobility time in saline-treated control animals. Pre-treatment with PCPA significantly blocked the effects of fluoxetine in the FST, confirming the role of endogenous 5-HT. Similarly, pre-treatment with PCPA also significantly attenuated the anti-immobility effects of NPY, thus suggesting a role for 5-HT in the effects of NPY in the FST. Quantitative receptor autoradiography revealed increases in specific [125I][Leu31, Pro34]PYY sites that were sensitive to BIBP3226 (Y1-like sites) in various brain regions. Specific [125I]GR231118 and [125I]PYY(3-36) binding levels were not changed following PCPA treatment, suggesting that depletion of endogenous 5-HT resulted in an apparent increase in the level of Y1 sites in their high-affinity state. Taken together, these results suggest a role for 5-HT-related systems in the antidepressant-like properties of NPY.


The sequential use of estradiol and prostaglandin E2 topical gels for cervical ripening in high-risk term pregnancies requiring induction of labor.
We compared the safety and efficiency of 200 mg of estradiol valerate prepared as a topical cervical gel as a preripening agent when used 6 hours before the application of 2 mg of prostaglandin E2 gel for the purpose of cervical ripening in 40 high-risk obstetric patients before indicated oxytocin induction of labor. When compared with a placebo prostaglandin E2 dosage, the estradiol had no effect on the change of Bishop score, length of labor, amount of oxytocin required, or the cesarean delivery rate. While no uterine contractions were noted after the application of the estradiol, 85% of patients had recordable uterine activity after the application of prostaglandin E2, suggesting that even at the 2 mg dosage this sequential regimen is not appropriate for local cervical ripening.


Studies on the stability of pancreatic enzymes in duodenal fluid to storage temperature and pH.
The effects of storage pH and temperature on pancreatic amylase, lipase and trypsin in duodenal fluid were studied. All the enzymes were most stable when stored at --20 degrees C, while the optimum storage pH was found to depend on the particular enzyme under investigation.


Myocardial ischemia in Kawasaki disease: follow-up study by cardiac catheterization and coronary angiography.
The clinical course of ischemic heart disease due to Kawasaki disease was analyzed. The subjects (children aged two months to eight years) were divided into two groups. Group 1 (n = 23) consisted of children who had sustained myocardial infarction (MI) and group 2 (n = 13) of those without clinical symptoms or signs of MI, but in whom signs of an obstructive lesion had appeared on coronary arteriography during the follow-up period. Changes in the left ventricular ejection fraction (LVEF) and the appearance of coronary arterial lesions on first and second angiography were analyzed in the two groups. It was found that (a) LVEF (51.4 +/- 13.4%, mean +/- SD) at the first study, obtained after MI in group 1, was significantly lower than that (64.3 +/- 3.7%) at the second one in group 2, which revealed recently developed obstructive lesions; (b) there was no significant difference between the two groups as to the severity of stenotic lesions on coronary arteriography; and (c) comparison of LVEF at the first angiography with that at the second study showed significant improvement in group 1 (1st, 54.2 +/- 12.0%; and 2nd, 60.8 +/- 9.7%) and significant depression in group 2 (1st, 68.1 +/- 4.4%; and 2nd, 64.3 +/- 3.7%).


A spiking neural network-based long-term prediction system for biogas production.
Efficient energy production from biomass is a central issue in the context of clean alternative energy resource. In this work we propose a novel model based on spiking neural networks cubes in order to model the chemical processes that goes on in a digestor for the production of usable biogas. For the implementation of the predictive structure, we have used the NeuCube computational framework. The goals of the proposed model were: develop a tool for real applications (low-cost and efficient), generalize the data when the system presents high sensitivity to small differences on the initial conditions, take in account the "multi-scale" temporal dynamics of the chemical processes occurring in the digestor, since the variations present in the early stages of the processes are very quick, whereas in the later stages are slower. By using the first ten days of observation the implemented system has been proven able to predict the evolution of the chemical process up to the 100th day obtaining a high degree of accuracy with respect to the experimental data measured in laboratory. This is due to the fact that the spiking neural networks have shown to be able to modeling complex information processes and then it has been shown that spiking neurons are able to handle patterns of activity that spans different time scales. Thanks to such properties, our system is able to capture the multi-scale trend of the time series associated to the early-stage evolutions, as well as their interaction, which are crucial in the point of view of the information content to obtain a good long-term prediction.


DOG1 expression in neuroendocrine neoplasms: Potential applications and diagnostic pitfalls.
Neuroendocrine neoplasms represent a heterogeneous group of rare tumors, more frequently arising from gastroenteropancreatic tract and lungs. At the time of diagnosis, 20% of cases are metastatic, and 10% of cases are considered as cancer of unknown primary origin. Several immunohistochemical markers are routinely used to confirm the neuroendocrine differentiation, first among all Synaptophysin and Chromogranin-A; on the other hand, different immunohistochemical markers are used to establish primary anatomical site, as TTF1, CDX2, Islet-1 and Calcitonin, but no marker is available in order to distinguish among different sites of the digestive tract. DOG1 (discovered on GIST-1) is a gene normally expressed in interstitial cells of Cajal and, in routine practice, DOG1 immunostaining is used in diagnosis of GIST (gastrointestinal stromal tumor). DOG1 expression has been described in several neoplasms other than GIST, both in mesenchymal and epithelial neoplasms. In the present study, DOG1 immunostaining has been performed in a large cohort of neuroendocrine neoplasms, including neuroendocrine tumors and neuroendocrine carcinomas, in order to evaluate frequency, intensity and pattern of expression in different anatomical site and in different tumor grade. DOG1 expression was detected in a large percentage of neuroendocrine tumors, with statistically significant association between DOG1 expression and gastrointestinal tract neuroendocrine tumors. As a consequence, DOG1 could be included in marker panel for the identification of primary site in neuroendocrine metastases of unknown primary origin; moreover, these results recommend careful evaluation of DOG1 expression in gastrointestinal neoplasms, in particular in differential diagnosis between epithelioid GIST and neuroendocrine tumors.


Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer.
Identification of lymph node (LN) metastasis is essential for staging of solid tumors, and as a result, surgeons focus on harvesting significant numbers of LNs during ablative procedures for pathological evaluation. Isolating those LNs most likely to harbor metastatic disease can allow for a more rigorous evaluation of fewer LNs. Here we evaluate the impact of a systemically injected, near-infrared fluorescently-labeled, tumor-targeting contrast agent, panitumumab-IRDye800CW, to facilitate the identification of metastatic LNs in the ex vivo setting for head and neck cancer patients. Molecular imaging demonstrates a significantly higher mean fluorescence signal in metastatic LNs compared to benign LNs in head and neck cancer patients undergoing an elective neck dissection. Molecular imaging to preselect at-risk LNs may thus allow a more rigorous examination of LNs and subsequently lead to improved prognostication than regular neck dissection.


A Structural Guide to the Bloom Syndrome Complex.
The Bloom syndrome complex is a DNA damage repair machine. It consists of several protein components which are functional in isolation, but interdependent in cells for the maintenance of accurate homologous recombination. Mutations to any of the genes encoding these proteins cause numerous physical and developmental markers as well as phenotypes of genome instability, infertility, and cancer predisposition. Here we review the published structural and biochemical data on each of the components of the complex: the helicase BLM, the type IA topoisomerase TOP3A, and the OB-fold-containing RMI and RPA subunits. We describe how each component contributes to function, interacts with each other, and the DNA that it manipulates/repairs.


Conscious sedation during subcutaneous implantable cardioverter-defibrillator implantation using the intermuscular technique.
The subcutaneous implantable cardioverter-defibrillator (S-ICD) system is an established therapy for the prevention of sudden cardiac death (SCD) and an alternative to a transvenous implantable cardioverter-defibrillator (ICD) system in selected patients. S-ICDs are usually implanted under general anesthesia. The purpose of the present study was to describe the technical feasibility and safety of local anesthesia with conscious sedation as an alternative to general anesthesia during S-ICD implantation using the intermuscular technique. We conducted a retrospective, single-center study on patients undergoing S-ICD implantation using the intermuscular technique at our center between February 2016 and May 2018. All procedures were performed under controlled sedation with propofol and midazolam. Local anesthesia was used for all procedures. Twenty-two patients (17 men and 5 women) with a mean age of 51.1 ± 16.2 years were included. The indication for S-ICD implantation was primary prevention in 18 (81.8%) patients. The mean dose of midazolam and propofol administered was 7.8 ± 2.3 mg and 72.7 ± 37.4 mg, respectively. The procedural success rate was 100%, with no apneic or hypoxic episodes or other complications requiring therapeutic intervention. None of the patients required conversion to general anesthesia. All patients were comfortable with the position and appearance of the device. Our findings suggest that local anesthesia with conscious sedation using propofol and midazolam is a safe and feasible option for S-ICD implantation procedures using an intermuscular technique.


Caffeine enhances doxorubicin cardiac toxicity in an animal model.
Based on in vitro data suggesting an interaction between methylxanthines and doxorubicin in regulating Ca2+ across muscle sarcoplasmic reticulum, this study was designed to test the hypothesis that a commonly used methylxanthine, caffeine, might influence the cardiac toxicity of doxorubicin. Three days following doxorubicin treatment, in vivo intracardiac pressures, cardiac outputs, in vitro cardiac weights, and cardiac electron microscopy were performed. Guinea pigs were treated with doxorubicin alone, doxorubicin plus caffeine, caffeine alone, and sterile saline as a control measure. Animals treated with doxorubicin had no significant differences in in vivo hemodynamics compared to the control animals. The average histology score was slightly but not statistically greater than the control animals, score (1.19 +/- 0.36 vs 1.60 +/- 0.34, respectively, P = NS). Animals receiving both doxorubicin and caffeine compared to the control animals had important differences in left ventricular systolic pressure (67 +/- 10 vs 92 +/- 7 mmHg; P = .003), cardiac output (154 +/- 35 vs 217 +/- 41 mL/min; P = .0174), stroke volume (.59 +/- 12 vs .79 +/- .07 mL; P = .0045), and histology score (2.36 +/- 0.21 vs 1.19 +/- 0.36; P = .028). There were no differences in left or right heart filling pressures between treatment groups. As an independent confirmation, there was a weak but statistically significant negative correlation between the biopsy score and cardiac output or stroke volume for all four groups of animals (r = .44, P = .031 and r = -.42, P = .040, respectively). These data are consistent with caffeine and doxorubicin having additive or potentiating effects on cardiac toxicity in this animal model.


Kainate neurotoxicity and glutamate inactivation.
Dihydrokainate, an inhibitor of high affinity L-glutamate as an excitant of cat spinal neurones in vivo. This action of dihydrokainate was selective in that the effects of excitants taken up actively in vitro by CNS tissue (L-aspartate, D- and L-glutamate and L-homocysteate) were enhanced whereas those of other substances not taken up (acetylcholine, D-homocysteate, kainate and N-methyl-D-aspartate) were not. Since kainate and dihydrokainate have similar potencies as inhibitors of L-glutamate uptake, interference with the inactivation of synaptically released L-glutamate may contribute to the neurotoxic effects of kainate.


Clinical interpretation of the Uremic Pruritus in Dialysis Patients (UP-Dial) scale: a novel instrument for the assessment of uremic pruritus.
The Uremic Pruritus in Dialysis Patients (UP-Dial) scale is valid and reliable for uremic pruritus (UP) assessment. However, it remains unknown how the scores should be interpreted in clinical practices. To establish a clinical interpretation of the UP-Dial by identifying severity cut-off scores according to the disease severity and burden of pruritus. This cross-sectional study developed a classification system for the UP-Dial scores using the patient-based anchors method. From May 2012 through January 2017, 697 dialysis patients were screened. Of these, a total of 258 met the criteria for UP and completed the UP-Dial scale and three sets of patient-assessed anchor questions: (i) global UP intensity by visual analogue scale (VAS)-UP, (ii) Dermatology Life Quality Index and (iii) global kidney disease-related quality of life. The cut-off scores were generated based on the kappa (κ) coefficient of agreement and the area under receiver operating characteristic curve (AuROC) statistics. Subgroup analyses were performed to explore associations between patient characteristics and the UP-Dial severity bands. The proposed scores were ≤12 (mild), 13-21 (moderate) and ≥22 (severe) with κ coefficient ranging between 0.39 and 0.46. Assigned scores were associated with all patient-based anchors. The highest association was with the VAS-UP, and AuROC was 0.80 (mild; 95% CI, 0.75-0.86), 0.66 (moderate; 0.60-0.71) and 0.83 (severe; 0.77-0.89). In subgroup analysis according to patient characteristics, we did not find any significant difference. The estimated UP-Dial severity band can facilitate the interpretation of UP in practice-based research settings and can be used to support treatment decisions.


Evaluation of the methylation profile of exfoliated cell samples from patients with head and neck squamous cell carcinoma.
Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. The purposes of this study were to determine the methylation profile of exfoliated tumors cells collected from patients with head and neck squamous cell carcinoma (HNSCC) and to evaluate its prognostic significance. The methylation profile and level of a 20-gene panel were evaluated by quantitative methylation-specific polymerase chain reaction (qMSP) in exfoliated tumor cell samples from 96 patients with HNSCC. CCNA1 (60.4%), DCC (54.2%), and TIMP3 (35.4%) were frequently methylated in these samples. Patients with exfoliated tumors cells positive for DCC methylation showed a trend toward a lower local recurrence-free survival. These findings indicate that a low invasive method could be used to access the methylation profile of exfoliated cells from patients with HNSCC. Moreover, our data provide evidence that hypermethylation of DCC could be useful as prognostic indicator for this malignancy.


Development of glycopeptide-intermediate resistance by Staphylococcus aureus leads to attenuated infectivity in a rat model of endocarditis.
Glycopeptide-intermediate resistant Staphylococcus aureus (GISA) are characterized by multiple changes in the cell wall and an altered expression of global virulence regulators. We investigated whether GISA are affected in their infectivity in a rat model of experimental endocarditis. The glycopeptide-susceptible, methicillin-resistant S. aureus M1V2 and its laboratory-derived GISA M1V16 were examined for their ability to (i) adhere to fibrinogen and fibronectin in vitro, (ii) persist in the bloodstream after intravenous inoculation, (iii) colonize aortic vegetations in rats, and (iv) compete for valve colonization by co-inoculation. Both GISA M1V16 and M1V2 adhered similarly to fibrinogen and fibronectin in vitro. In rats, GISA M1V16 was cleared faster from the blood (P < 0.05) and required 100-times more bacteria than parent M1V2 (10(6) versus 10(4)CFU) to infect 90% of vegetations. GISA M1V16 also had 100 to 1000-times lower bacterial densities in vegetations. Moreover, after co-inoculation with GISA M1V16 and M1V2Rif, a rifampin-resistant variant of M1V2 to discriminate them in organ cultures, GISA M1V16 was out-competed by the glycopeptide-susceptible counterpart. Thus, in rats with experimental endocarditis, GISA showed an attenuated virulence, likely due to a faster clearance from the blood and a reduced fitness in cardiac vegetations. The GISA phenotype appeared globally detrimental to infectivity.


Effects of inorganic lead on delta-aminolevulinic acid dehydratase activity and hematological variables in the rainbow trout, Salmo gairdnerii.
The activity of the enzyme delta-aminolevulinic acid dehydratase (ALA-D) was strongly depressed in erythrocytes, spleen and renal tissue of rainbow trouts (Salmo gairdnerii) exposed to sublethal levels of inorganic lead (10, 75 and 300 microgram Pb2+/L) for 30 days. The fish exposed to the highest lead concentration also showed an anemic response and basophilic stippling of erythrocytes. The lead exposure did not cause any alteration of the white blood cell picture. The ALA-D inhibition, the anemia and basophilic stippling seemed to persist in the lead-exposed fish even after a recovery period of seven weeks in lead-free water.


Frustration- and doping-induced magnetism in a Fermi-Hubbard simulator.
Geometrical frustration in strongly correlated systems can give rise to a plethora of novel ordered states and intriguing magnetic phases, such as quantum spin liquids1-3. Promising candidate materials for such phases4-6 can be described by the Hubbard model on an anisotropic triangular lattice, a paradigmatic model capturing the interplay between strong correlations and magnetic frustration7-11. However, the fate of frustrated magnetism in the presence of itinerant dopants remains unclear, as well as its connection to the doped phases of the square Hubbard model12. Here we investigate the local spin order of a Hubbard model with controllable frustration and doping, using ultracold fermions in anisotropic optical lattices continuously tunable from a square to a triangular geometry. At half-filling and strong interactions U/t ≈ 9, we observe at the single-site level how frustration reduces the range of magnetic correlations and drives a transition from a collinear Néel antiferromagnet to a short-range correlated 120° spiral phase. Away from half-filling, the triangular limit shows enhanced antiferromagnetic correlations on the hole-doped side and a reversal to ferromagnetic correlations at particle dopings above 20%, hinting at the role of kinetic magnetism in frustrated systems. This work paves the way towards exploring possible chiral ordered or superconducting phases in triangular lattices8,13 and realizing t-t' square lattice Hubbard models that may be essential to describe superconductivity in cuprate materials14.


Synergistic catalysis induced by a multi-component system constructed by DBD plasma combined with α-Fe2O3/FeVO4/HCP and peroxymonosulfate for gatifloxacin removal.
The dielectric barrier discharge (DBD) multi-component system containing plasma, α-Fe2O3/FeVO4, and peroxymonosulfate (PMS) with high catalytic activity was successfully constructed. Thereinto, α-Fe2O3/FeVO4 was loaded on the honeycomb ceramic plate (HCP) surface (α-Fe2O3/FeVO4/HCP) and placed under the water surface below the discharge area. The catalytic activity was evaluated by the removal rate of gatifloxacin (GAT), and the DBD+α-Fe2O3/FeVO4+PMS system exhibited the optimal catalytic activity. The enhanced catalytic activity can be attributed to the fact that the occurrence of synergistic catalysis that simultaneously includes plasma oxidation, photocatalysis, PMS oxidation, O3 catalysis, and Fenton reaction. The effect of various initial degradation parameters including input power, PMS dosage, pH, etc. On GAT removal was investigated. DBD+α-Fe2O3/FeVO4+PMS system has a significant increase in the concentration of H2O2 and O3, and the role played in the multi-component system was analyzed. The identification and analysis of organic matters during GAT degradation were visualized with the help of 3D EEMs. HPLC-MS and theoretical calculations identified the major intermediates and further deduced the possible GAT degradation pathways. Additionally, the acute toxicity of the major intermediates was predicted by the QSAR model. Finally, the possible mechanisms of synergistic catalysis to enhance catalytic activity were discussed based on the characteristics of several advanced oxidation processes (AOPs) and the results of experimental and characterization. This work provides a feasible technical route and theoretical basis for wastewater treatment by plasma combined with other AOPs.


Peripheral neurological complications during COVID-19: A single center experience.
We highlight the peripheral neurologic complications of coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an ongoing global health emergency. We evaluated twenty-five patients admitted to the COVID-19 Recovery Unit (CRU) at New York-Presbyterian Weill Cornell University Medical Center after intensive care hospitalization with confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whom neurology was consulted for weakness and/or paresthesias. All patients were clinically evaluated by a neuromuscular neurologist who performed electrodiagnostic (EDX) studies when indicated. Magnetic resonance imaging (MRI) of the affected regions, along with nerve and muscle biopsies were obtained in select patients to better elucidate the underlying diagnosis. We found fourteen out of twenty-five patients with prolonged hospitalization for COVID-19 infection to have peripheral neurological complications, identified as plexopathies, peripheral neuropathies and entrapment neuropathies. The other eleven patients were not found to have peripheral neurologic causes for their symptoms. Patients with peripheral neurological complications often exhibited more than one type of concurrently. Specifically, there were four cases of plexopathies, nine cases of entrapment neuropathies, and six cases of peripheral neuropathies, which included cranial neuropathy, sciatic neuropathy, and multiple mononeuropathies. We explore the possibility that the idiopathic peripheral neurologic complications could be manifestations of the COVID-19 disease spectrum, possibly resulting from micro-thrombotic induced nerve ischemia.


Determinants of helmet use among health-care providers in urban India: Leveraging the theory of planned behavior.
Wearing helmet during road traffic accidents among motorcycle riders decreases the likelihood of death by 39%. The theory of planned behavior (TPB), a psychological model helps to explain the failure in helmet usage, by assuming a causal chain. The current study was taken up as no studies have elicited the determinants of helmet usage in terms of TPB among health-care providers, the role models for healthful behavior by virtue of their profession in the current urban Indian context. The aims of the study were (1) to determine the proportion of proper use of helmets and (2) to identify TPB-related factors and other factors influencing the use of helmets. A cross-sectional study was conducted among 147 students and staff of a tertiary health-care center, Bengaluru, using a pretested, validated, semi-structured, self-administered questionnaire. Convenience sampling was used. Hierarchical regression model was used to explain variation in the scores of helmet-use behavior on the basis of TPB variables. P < 0.05 was considered as statistically significant. About 65% of respondents practiced "proper use" of helmets. Intention, perceived behavioral control (direct), and attitude (indirect) were significant predictors of helmet use (P < 0.05). Mean scores of knowledge on helmet use and behavior showed positive correlation (P > 0.05). Application of TPB in urban Indian context was successful in identifying precursors of helmet use. This study throws a light on the strong influencers of helmet use which can assist policy developers in developing effective programs to successfully promote the "proper use" of helmets.


Participation in community walking following stroke: the influence of self-perceived environmental barriers.
Community walking is limited among survivors of stroke; however, the contributing factors are not clearly understood. This study examined the association of features in the environment with frequency of community walking following stroke. An observational study design was used, with frequency of community walking data collected prospectively. Thirty survivors of stroke (mean age=67 years; mean months since stroke=40), and 30 older adults without stroke (mean age=68 years) participated. Frequency of community walking (number of trips, walking-related activities [WRA], and the ratio of WRA to trips) and satisfaction were measured using self-report. The Environmental Analysis of Mobility Questionnaire (EAMQ) was used to determine frequency of encounter with versus avoidance of environmental features during community walking. Negative binomial and linear regression models were used to analyze the association of environmental features with measures of community walking. Survivors of stroke reported reduced community walking and fewer encounters with and greater avoidance of features within 8 dimensions of the environment compared with a control group of adults without stroke. Following stroke, avoidance of features in some environmental dimensions was associated with frequency of community walking as measured by number of trips, number of WRA, and the ratio of WRA to trips. Environmental features explained little of the variability in community walking. Limitations included a small sample size and limited diversity among participants. This study examined only physical features in the environment and did not include other environmental factors, such as social support, which may influence participation. Avoidance of features within some, but not all, environmental dimensions was associated with self-reported frequency of community walking following stroke, suggesting that some environmental features may limit community walking more than others.


Association between serum total bilirubin level and leukoaraiosis in Korean adults.
Leukoaraiosis is associated with cerebrovascular microangiopathy. Increasing evidence suggests that bilirubin is a potent cytoprotectant in the development of cardiovascular diseases. This study aimed to determine whether total bilirubin is related to leukoaraiosis. We examined the relationship of total bilirubin with leukoaraiosis in 1005 Korean adults. The odds ratios for leukoaraiosis were calculated using multivariate logistic regression across serum total bilirubin tertiles. In comparison with the subjects in the reference group (total bilirubin: 15-26 μmol/L), the odds ratio (95% CI) for leukoaraiosis in the 3rd tertile (total bilirubin ≤10 μmol/L) was 5.50 (1.24-24.40) in women after adjusting for confounding variables. However, this inverse association between serum total bilirubin and the prevalence of leukoaraiosis was not found in men after adjusting for the same co-variables. Total bilirubin level was inversely associated with leukoaraiosis regardless of classical cardiovascular risk factors in Korean women.


The distribution of degenerative changes in INH neuropathy. Further evidence for focal axonal lesions.
Rats were given isoniazid either in a single large dose or continuously in drinking water and killed 5--105 days later. The distribution of degenerating fibres in various nerves (sensory and mixed) and in various sites along nerves and spinal roots was studied by light and electron microscopy. It was found that sensory nerves tended to be less affected than motor, and degeneration was more proximal in the latter. It was concluded that the pattern of degeneration and regeneration supported the view that the initial metabolic lesion is in the axon, rather than in the cell body.


Implant cement spacer-a cost-effective solution for reconstruction of proximal humerus defects after tumor resection.
The proximal humerus is a common location for both primary benign and malignant bone tumors and may require sacrificing deltoid muscles, axillary nerve and/or rotator cuff along with proximal humerus resection. Thus, post operatively shoulder movements are restricted. The main goals of reconstruction are to maintain a stable shoulder so that the function of elbow and hand can be optimized. Various reconstruction options are available after proximal humerus resection. We present our experience in using implant-cement spacers as a primary reconstruction option for limb salvage in the primary tumors of proximal humerus. All cases were retrieved from our prospectively maintained surgical database. 142 patients (96 males and 46 females) with a median age of 17.5 years (3-70 years) were operated with implant cement spacer between January 2006 and April 2019. Median follow up was 34 months (1-174 months). Functional outcome of the surgery was assessed in survivors by Musculoskeletal Tumor Society score (MSTS). Implant survival was assessed by Kaplan Meier analysis and competing risk analysis. On last follow up, out of 142 cases, 81 patients had died, 54 are alive and seven were lost to follow up. 18(13%) patients underwent revision surgery for symptomatic proximal migration, implant failure or infection. Four (2.8%) patients underwent forequarter amputation for local recurrence. The five years implant survival (IS) by Kaplan Meier analysis was 79.6% and as per competing risk analysis, the chances of implant revision are 12% and 18% at five and ten years respectively. Mean MSTS score in survivors was 71% (60-80%). Implant cement spacer is a cost-effective alternative for reconstruction of proximal humerus with revision rates and function comparable to other reconstructions in cases where deltoid, axillary nerve and/or rotator cuff are excised.


Tissue specific hormonal regulation of the rat angiotensinogen gene expression.
Angiotensinogen is the precursor of the most potent pressor substance, angiotensin. Angiotensinogen levels are increased in some forms of human hypertension. Its levels are modulated by various factors including glucocorticoids, estrogens, and prostaglandins. We have recently reported the isolation of a human angiotensinogen cDNA clone and provided evidence for the presence of its mRNA in rat liver, brain, and heart. In this communication we report the effect of dexamethasone and estradiol on angiotensinogen mRNA levels in rat liver, brain, and heart. Our results indicate that angiotensinogen levels are increased to different extents in these three tissues as a result of glucocorticoid or estrogen administration.


Attitudes Toward Restricting the Sexual and Reproductive Rights of Women Living With HIV Infection in Yemen.
A considerable amount of research has demonstrated the pervasive and destructive power of discrimination against people living with HIV, which limits their full and equal participation in society. This study surveyed 613 young adults from Yemen about their attitudes toward the sexual and reproductive rights of women living with HIV (WLWH). Among survey respondents, 80% believed that WLWH should be sterilized and not allowed to get married. Furthermore, 62% thought that WLWH should be forced to have abortions if they became pregnant. Men were more likely than women to impose restrictions on the sexual and reproductive rights of WLWH. HIV stigma predicted respondent attitudes toward WLWH, but religiosity and knowledge about HIV did not. The results of the study have implications for developing programs to protect and promote the rights of WLWH in Yemen.


Synthesis and DNA interaction of a mixed proflavine-phenanthroline Tröger base.
We report the synthesis of an asymmetric Tröger base containing the two well characterised DNA binding chromophores, proflavine and phenanthroline. The mode of interaction of the hybrid molecule was investigated by circular and linear dichroism experiments and a biochemical assay using DNA topoisomerase I. The data are compatible with a model in which the proflavine moiety intercalates between DNA base pairs and the phenanthroline ring occupies the DNA groove. DNase I cleavage experiments were carried out to investigate the sequence preference of the hybrid ligand and a well resolved footprint was detected at a site encompassing two adjacent 5'-GTC.5-GAC triplets. The sequence preference of the asymmetric molecule is compared to that of the symmetric analogues.


Antimicrobial activity of metal derivatives of sulfonamides.
Antimicorbial activities of a series of metal derivatives of some sulfa drugs were examined. Such metal derivatives showed higher antimicorbial activity than the parent sulfa drugs, and among the metals, gold derivatives are seen to be the most effective.


Rebamipide Suppresses Monosodium Urate Crystal-Induced Interleukin-1β Production Through Regulation of Oxidative Stress and Caspase-1 in THP-1 Cells.
This study investigated the effect of rebamipide on activation of the NLRP3 inflammasome and generation of reactive oxygen species (ROS) in monosodium urate (MSU) crystal-induced interleukin-1β (IL-1β) production. Human monocyte cell line THP-1 and human umbilical venous endothelial cells (HUVECs) were used to assess the inflammatory response to MSU crystals. NADP/NADPH activity assays were used as a marker of ROS generation. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to evaluate levels of IL-1β, caspase-1, NLRP3, associated speck-like protein (ASC), nuclear factor-κB (NF-κB), p65, IκBα, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Experimental pharmaceuticals included rebamipide, colchicine, dexamethasone, and ascorbic acid. In THP-1 cells, treatment with MSU crystals increased NADP/NADPH ratios and IL-1β expression, and both of these responses were potently inhibited by addition of rebamipide. Rebamipide also attenuated enhanced expression of caspase-1 gene by MSU crystals (p < 0.05). Western blotting demonstrated that MSU crystals stimulated caspase-1 but not NLRP3 and ASC activation. Similarly, MSU crystals activated the NF-κB pathway, which in turn was blocked by rebamipide. Stimulation of HUVECs with MSU crystals increased expression of VCAM-1 and ICAM-1, which were markedly inhibited by both rebamipide and dexamethasone. This study demonstrated that rebamipide inhibits IL-1β activation through suppression of ROS-mediated NF-κB signaling pathways and caspase-1 activation in MSU crystal-induced inflammation.


Hyperprolactinaemia and the empty sella.
Hyperprolactinaemia is an endocrine abnormality seen not infrequently in the population with empty sella; a radiological and anatomical diagnosis of a deformed and enlarged sella turcica. Often there is no associated pathology within the pituitary gland itself, lending to the hypothesis that the empty sella syndrome per se has a yet-to-be defined role in hyperprolactinemia. We report a patient who presented initially with non-specific symptoms of meningeal irritation and viral illness on a long background of galactorrhoea. The patient demonstrated elevated serum prolactin, and a diagnosis of empty sella was made on the basis of MRI findings.


Octreotide ameliorates alendronate-induced gastric injury.
Alendronate causes serious gastrointestinal adverse effects. The aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue, improves the alendronate-induced gastric injury. Rats were administered 20mg/kg alendronate by gavage for 4 days, either alone or following treatment with octreotide (0.1 ng/kg, i.p.). On the last day, following drug administration, pilor ligation was performed and 2h later, rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation (as assessed by malondialdehyde, MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity as well as the histologic appearance of the stomach tissues were determined. Chronic oral administration of alendronate induced significant gastric damage, increasing lipid peroxidation (37.1+/-3.2 nmol/g) and myeloperoxidase activity (57.6+/-3.7 U/g), while tissue glutathione levels (09.+/-0.1 micromol/g) decreased. Treatment with octreotide prevented this damage as well as the changes in biochemical parameters (MDA: 23.4+/-1.3 nmol/g; MPO: 31.68 U/g; GSH: 15.+/-0.1 micromol/g). Findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect, and that octreotide ameliorates this damage by inhibiting neutrophil infiltration and reducing lipid peroxidation. Therefore, its therapeutic role as a "ulcer healing" agent must be further elucidated in alendronate-induced gastric mucosal injury.


222 Rn emanation measurements for the XENON1T experiment.
The selection of low-radioactive construction materials is of utmost importance for the success of low-energy rare event search experiments. Besides radioactive contaminants in the bulk, the emanation of radioactive radon atoms from material surfaces attains increasing relevance in the effort to further reduce the background of such experiments. In this work, we present the 222 Rn emanation measurements performed for the XENON1T dark matter experiment. Together with the bulk impurity screening campaign, the results enabled us to select the radio-purest construction materials, targeting a 222 Rn activity concentration of 10 μ Bq / kg in 3.2 t of xenon. The knowledge of the distribution of the 222 Rn sources allowed us to selectively eliminate problematic components in the course of the experiment. The predictions from the emanation measurements were compared to data of the 222 Rn activity concentration in XENON1T. The final 222 Rn activity concentration of ( 4.5 ± 0.1 ) μ Bq / kg in the target of XENON1T is the lowest ever achieved in a xenon dark matter experiment.


Gerontological nursing content in baccalaureate nursing programs: comparison of findings from 1997 and 2003.
In 2003, the John A. Hartford Foundation Institute for Geriatric Nursing (Hartford Institute), in collaboration with the American Association of Colleges of Nursing, conducted a survey of baccalaureate schools of nursing in the United States to compare gerontological content to baseline data collected by the Hartford Institute in 1997. Since last surveyed in 1997, baccalaureate nursing programs have been the recipients of substantial new resources and initiatives focused on gerontological curriculum enhancement. While these initiatives are ongoing, and some are in an early stage of development, resurveying baccalaureate programs was seen as a means of taking a midcourse "pulse" as to the effectiveness of these efforts. Data suggest that there has been a fundamental shift in baccalaureate curriculum toward incorporation of a greater amount of gerontological content, integration of gerontological content in a greater number of nursing courses, and more diversity of clinical sites used for gerontological clinical experiences. As baccalaureate programs increasingly address the need to enhance gerontological nursing curricula, there continues to be an obligation to address the growing shortage of faculty with qualifications in gerontological nursing.


C4 photosynthesis in the vegetation of Aldabra Atoll.
The occurrence of the C4 photosynthetic system, based upon an examination of leaf anatomy, of nearly all species of the vegetation of Aldabra Atoll, western Indian Ocean, is reported. About 19% of the flora has the C4 system. It only occurs in herbaceous plants, which grow either in grasslands or as an understorey to tall shrubs. Both C3 and C4 species compete side by side in the mixed-species communities.


Young woman with Guillain-Barré syndrome and cervical transverse myelitis-A new GBS variant, not coincidence.
A case of antibody proven Guillain Barré Syndrome in a previously healthy young female with extra clinical features, scans, and physical exam findings consistent with cervical spine and cervical medullary junction myelitis, together a new variant to consider.


Overview of the current use of levosimendan in France: a prospective observational cohort study.
Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.


Primary structure of the site on bovine hormone-sensitive lipase phosphorylated by cyclic AMP-dependent protein kinase.
The primary structure of a region on hormone-sensitive lipase was determined to be: Lys-Thr-Glu-Pro-Met-Arg-Arg-Ser- Val-Ser-Glu-Ala-Ala-Leu-Thr-Gln-Pro-Glu-Gly-Pro-Leu-Gly-Thr-Asp-Ser-Leu-Lys. Ser-8 was the only residue in the intact protein phosphorylated by cyclic AMP-dependent protein kinase. However, Ser-10 also appeared to be present in a phosphorylated form, suggesting that it is a target for a distinct protein kinase in vivo.


Breast Magnetic Resonance Imaging Audit: Pitfalls, Challenges, and Future Considerations.
Breast magnetic resonance (MR) imaging is the most sensitive imaging modality for breast cancer detection and guidelines recommend its use, in addition to screening mammography, for high-risk women. The most recent American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) manual coordinated cross-modality BI-RADS terminology and established an outcome monitoring section that helps guide a medical imaging outcomes audit. This article provides a framework for performing a breast MR imaging audit in clinical practice, incorporating ACR BI-RADS guidance and more recently published data, clarifies common pitfalls, and discusses audit challenges related to evolving clinical practice.


Are fixed-dose oestrogen/progestogen combinations ideal for all HRT users?
Although progestogens protect the endometrium against excessive oestrogen-induced stimulation, they can cause adverse symptomatic and psychological effects and may have undesirable metabolic consequences. Thus, the minimum progestogen dose which results in consistent endometrial transformation should be prescribed. To define this dose for norethisterone and dl-norgestrel, 197 endometrial samples obtained from postmenopausal women receiving conjugated equine oestrogens (0.625 mg or 1.25 mg daily) with one of six doses of norethisterone (or the acetate), or one of three doses of dl-norgestrel added for the first 12 days of each calendar month were examined with the light microscope; 109 samples were also assessed by transmission electron microscopy. There was an inverse relation between the percentage of samples showing proliferative features and the progestogen dose. However, proliferative endometrium was observed in 6% of samples with the highest dose of dl-norgestrel (500 micrograms) and in 3% of samples with 2.5 mg norethisterone. Conversely, complete secretory transformation was observed in 25% of samples with the lowest dose of norethisterone (0.1 mg) and in 40% of samples with 75 micrograms dl-norgestrel. Mild atypical hyperplasia was diagnosed in four samples. There was a wide inter-patient variation in response and none of the nine progestogen dose regimens induced secretory change in every patient.


Development and validation of a solid-phase extraction-liquid chromatographic method for determination of amoxicillin in plasma.
A bioanalytic method for the determination of amoxicillin in plasma by hydrophilic interaction solid-phase extraction and liquid chromatography has been developed and validated. Plasma was precipitated with acetonitrile before samples were loaded onto a zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) solid-phase extraction column. Amoxicillin was analyzed by liquid chromatography on an Aquasil (150 x 4.6 mm) LC column with mobile-phase acetonitrile: phosphate buffer (pH 2.5; 0.1 mol/L) (7:93, v/v) and UV detection at 230 nm. A regression model using 1/concentration weighting was found the most appropriate for quantification. The intraassay precision for plasma was 3.3% at 15.0 microg/mL and 10.9% at 0.200 microg/mL. The interassay precision for plasma was 1.8% at 15.0 microg/mL and 7.5% at 0.200 microg/mL. The total-assay precision for plasma over 4 days using a total of 20 replicates was 13.2%, 5.5%, and 3.8% at 0.200 microg/mL, 3.00 microg/mL, and 15.0 microg/mL, respectively. The lower limit of quantification and the limit of detection were 0.050 microg/mL and 0.025 microg/mL, respectively, for 100 microL plasma. Long-term storage stability studies of amoxicillin in plasma indicate that a temperature of -80 degrees C is necessary to prevent degradation of amoxicillin.


[Cytomegalovirus (CMV) congenital infection].
Human Cytomegalovirus (CMV) is the main cause of mental retardation and sensorineural hearing loss related to congenital infections. Justification of systematic screening for fetal CMV infection is still controversial and is not recommended in most developed countries. This is mainly justified by the paucity of antenatal prognostic factors and the lack of established intrauterine treatment when fetal infection has been diagnosed. Our aim was to review the current state of the knowledge about the CMV congenital infection and to highlight recent advances in the diagnosis as well as in the identification of prognostic factors.


The generation of 'cytotoxic' macrophages in mice during infection with influenza A or Sendai virus.
Injection of infectious but not of non-infectious influenza A virus or of infectious or non-infectious Sendai virus intraperitoneally into mice induces the generation of plastic-adherent cells that are able to effect release of 51Cr from labelled virus-infected target cells but not from labelled, uninfected cells. Their activity is greatly diminished by exposure to silica or carrageenan but not by anti-Thy 1 antibody and complement treatment. Similarly, the activity of the cell preparation cannot be explained by contamination with natural killer or 'K' cells. Thus, the effector cells were identified as macrophages and for convenience are called 'cytotoxic macrophages'. The maximum cytotoxic activity was recovered from the peritoneal cavity 5 days after virus injection and declined thereafter. Although the effector cells are cross-reactive in that cells activated by an influenza A strain virus lyse target cells infected with the same or other A strain viruses or with Sendai virus, there is preferential lysis of cells infected with the homologous virus. The action of the effector cells is not h-2-restricted. Preliminary experiments showed that similar effector cells can be recovered from the lungs of mice 5 days after intranasal inoculation of infectious influenza virus, so they may contribute to the host control of the disease.


The effect of luteinizing hormone releasing hormone (LHRH) on steroidogenesis by the human luteal tissue.
The effect of luteinizing hormone releasing hormone (LHRH) on progesterone and estradiol production was studied in human luteal tissue. Tissue slices were incubated in Ham's F-10 medium under an atmosphere of 95% O2: 5% CO2 at 37 degrees C for 4 h. Slices were treated with or without human chorionic gonadotropin (HCG) in the presence or absence of LHRH. HCG stimulated progesterone and estradiol production by human luteal tissue in a time- and dose-related manner. LHRH stimulated the basal progesterone production in five (one early luteal and four mid-luteal) of 17 corpora lutea, and stimulated the basal estradiol production in three (all mid-luteal) of 16 corpora lutea. On the other hand, LHRH inhibited HCG-stimulated progesterone production in four (two early luteal and two mid-luteal) of 22 corpora lutea, and inhibited HCG-stimulated estradiol production in four (one early luteal and three mid-luteal) of 18 corpora lutea. In the acute short-term incubations of human luteal tissue, therefore, LHRH had little effect on basal and HCG-stimulated steroidogenesis. However, in a few corpora lutea taken in the early or mid-luteal phase, LHRH stimulated basal steroidogenesis and inhibited HCG-stimulated steroidogenesis.


Hansenula polymorpha Pex37 is a peroxisomal membrane protein required for organelle fission and segregation.
Here, we describe a novel peroxin, Pex37, in the yeast Hansenula polymorpha. H. polymorpha Pex37 is a peroxisomal membrane protein, which belongs to a protein family that includes, among others, the Neurospora crassa Woronin body protein Wsc, the human peroxisomal membrane protein PXMP2, the Saccharomyces cerevisiae mitochondrial inner membrane protein Sym1, and its mammalian homologue MPV17. We show that deletion of H. polymorpha PEX37 does not appear to have a significant effect on peroxisome biogenesis or proliferation in cells grown at peroxisome-inducing growth conditions (methanol). However, the absence of Pex37 results in a reduction in peroxisome numbers and a defect in peroxisome segregation in cells grown at peroxisome-repressing conditions (glucose). Conversely, overproduction of Pex37 in glucose-grown cells results in an increase in peroxisome numbers in conjunction with a decrease in their size. The increase in numbers in PEX37-overexpressing cells depends on the dynamin-related protein Dnm1. Together our data suggest that Pex37 is involved in peroxisome fission in glucose-grown cells. Introduction of human PXMP2 in H. polymorpha pex37 cells partially restored the peroxisomal phenotype, indicating that PXMP2 represents a functional homologue of Pex37. H.polymorpha pex37 cells did not show aberrant growth on any of the tested carbon and nitrogen sources that are metabolized by peroxisomal enzymes, suggesting that Pex37 may not fulfill an essential function in transport of these substrates or compounds required for their metabolism across the peroxisomal membrane.


Measurements of the photodegradation of PABA and some PABA derivatives.
The photodegradation of 4-aminobenzoic acid, 2-ethylhexyl N,N-dimethyl 4-aminobenzoate (Escalol 507) and 1-glyceryl 4-aminobenzoate (Escalol 106), resulting from irradiation by sun lamps, was examined by UV spectroscopy. 2-ethylhexyl N,N-dimethyl 4-aminobenzoate showed the longest half-life, indicating the highest photostability.


A comparison of the in-vitro antibacterial and complement activating effect of 'OpSite' and 'Tegaderm' dressings.
Two readily available semipermeable polyurethane dressings, 'OpSite' and 'Tegaderm', were tested for their in vitro ability to kill potential bacterial pathogens and activate complement C3. In bacterial killing tests, 'OpSite' was superior to 'Tegaderm' and in addition only 'OpSite' activated C3. It is concluded that in the practical situation, 'OpSite' could well confer a greater margin of safety.


The treatment of hypospadias by a modified one-stage van der Meulen dorsal axial flap repair.
A modified van der Meulen operation has been designed to reduce even further the low complication rate associated with this method of hypospadias repair. Our experiences with the first 20 cases are reported.


Calcium and available phosphorus requirements of Japanese quails in early egg-laying stage.
An experiment was conducted to estimate the nutritional requirements of calcium (Ca) and available phosphorus (aP) for Japanese quails (Coturnix coturnix japonica) in the egg-laying stage (64-168 D). The experiment was an entirely randomized design, in a factorial scheme (Ca = 1.70, 2.40, 3.10, and 3.80% and aP = 0.15, 0.30, 0.45, and 0.60%), with 3 replicates and 10 quails per experimental unit. No interactions were found for quail body weight and daily feed intake (DFI) (P > 0.05). However, body weight decreased linearly (P < 0.05) as the levels of Ca increased, whereas DFI exhibited a quadratic effect (P < 0.05) for both Ca and aP. The lowest values of DFI were estimated in 2.79 and 0.36% for Ca and aP, respectively. Egg production, egg mass, and feed conversion ratio per egg dozen presented significant interaction in which all of them had a quadratic effect (P < 0.05), with estimations for maximum yield in feed containing 2.74, 2.71, 2.75, and 2.74% Ca and 0.40, 0.39, 0.39, and 0.40% aP. The concentration of Ca in the eggshell increased linearly as per the levels of Ca studied, having a quadratic effect for aP levels, with a maximum point of 0.44%. In relation to the bone parameters, there was a linear interaction for Ca and aP in bone density and bone resistance (BR) of the femur, with a quadratic effect in BD estimating 2.84 and 0.50% for Ca and aP, respectively. In BR, the estimation was 3.27% Ca, with linear increase for aP. The BR of the tibiotarso increased linearly as per the Ca levels, obtaining the same Ca concentration response in this bone. As conclusion, when considering the estimations obtained through overlapped contour plots, the best responses to the effects of Ca and aP on productive characteristics were estimated at 2.68% Ca and 0.38% aP to produce feed for egg-laying Japanese quails.


Electrochemical degradation of trichloroethylene in aqueous solution by bipolar graphite electrodes.
In this study, we tested the use of the bipolar electrodes to enhance electrochemical degradation of trichloroethylene (TCE) in an undivided, flow-through electrochemical reactor. The bipolar electrode forms when an electrically conductive material polarizes between feeder electrodes that are connected to a direct current source and, therefore, creates an additional anode/cathode pair in the system. We hypothesize that bipolar electrodes will generate additional oxidation/reduction zones to enhance TCE degradation. The graphite cathode followed by graphite anode sequence were operated without a bipolar electrode as well as with one and two bipolar graphite electrodes. The system without bipolar electrodes degraded 29% of TCE while the system with one and two bipolar electrodes degraded 38% and 66% of TCE, respectively. It was found that the removal mechanism for TCE in bipolar mode includes hydrodechlorination at the feeder cathode, and oxidation through reaction with peroxide. The results show that the bipolar electrodes presence enhance TCE removal efficiency and rate and imply that they can be used to improve electrochemical treatment of contaminated groundwater.


Immunogenetics of gastrointestinal cancers: A systematic review and retrospective survey of inborn errors of immunity in humans.
Humans with inborn errors of immunity (IEI), or primary immunodeficiencies, may be associated with a potential risk factor for early-onset gastrointestinal (GI) cancer. We systematically reviewed all cases with clinical diagnoses of both an IEI and a GI cancer in three databases (MEDLINE, SCOPUS, and EMBASE). In total, 76 publications satisfying our inclusion criteria were identified, and data for 149 cases were analyzed. We also searched our institutional cancer registry for such cases. We identified 149 patients with both an IEI and a GI cancer, 95 presented gastric cancer, 13 small bowel cancer, 35 colorectal cancer, and 6 had an unspecified cancer or cancer at another site. Gastric and colon adenocarcinomas were the most common. For both gastric and colorectal cancers, age at onset was significantly earlier in patients with IEIs than in the general population, based on the SEER database. Common variable immunodeficiency (CVID) was the most common IEI associated with gastrointestinal cancer. About 12% of patients had molecular genetic diagnoses, the three most frequently implicated genes being ATM, CARMIL2, and CTLA4. Impaired humoral immunity and Epstein-Barr virus (EBV) infection were frequently reported as factors potentially underlying early-onset GI cancers in patients with IEIs. We identified one patient with CVID and early-onset gastric adenocarcinoma, recurrent diarrhea, and gastrointestinal CMV infection from a retrospective survey. Patients with IEIs should be considered at risk of early-onset GI cancers and should therefore undergo cancer screening at an earlier age.


Structural and EPR characterisation of single electron and alkyl transfer products from reaction of dimethyl magnesium with bulky alpha-diimine ligands.
Treatment of dimethylmagnesium with bulky alpha-diimine ligands provides either the biradical methyl-bridged complexes [(alpha-diimine-.)Mg+(mu-CH3)]2 via single electron transfer (SET), or the product of methyl transfer to an imine carbon atom depending upon conditions.


Inhibition of FAAH and activation of PPAR: new approaches to the treatment of cognitive dysfunction and drug addiction.
Enhancing the effects of endogenously-released cannabinoid ligands in the brain might provide therapeutic effects more safely and effectively than administering drugs that act directly at the cannabinoid receptor. Inhibitors of fatty acid amide hydrolase (FAAH) prevent the breakdown of endogenous ligands for cannabinoid receptors and peroxisome proliferator-activated receptors (PPAR), prolonging and enhancing the effects of these ligands when they are naturally released. This review considers recent research on the effects of FAAH inhibitors and PPAR activators in animal models of addiction and cognition (specifically learning and memory). These studies show that FAAH inhibitors can produce potentially therapeutic effects, some through cannabinoid receptors and some through PPAR. These effects include enhancing certain forms of learning, counteracting the rewarding effects of nicotine and alcohol, relieving symptoms of withdrawal from cannabis and other drugs, and protecting against relapse-like reinstatement of drug self-administration. Since FAAH inhibition might have a wide range of therapeutic actions but might also share some of the adverse effects of cannabis, it is noteworthy that at least one FAAH-inhibiting drug (URB597) has been found to have potentially beneficial effects but no indication of liability for abuse or dependence. Although these areas of research are new, the preliminary evidence indicates that they might lead to improved therapeutic interventions and a better understanding of the brain mechanisms underlying addiction and memory.


Predictive variables for poor long-term physical recovery after intensive care unit stay: An exploratory study.
Elucidating factors that influence physical recovery of survivors after an intensive care unit (ICU) stay is paramount in maximizing long-term functional outcomes. We examined potential predictors for poor long-term physical recovery in ICU survivors. Based on secondary analysis of a trial of 50 ICU patients who underwent mobilization in the ICU and were followed for one year, linear regression analysis examined the associations of exposure variables (baseline characteristics, severity of illness variables, ICU-related variables, and lengths of ICU and hospital stay), with physical recovery variables (muscle strength, exercise capacity, and self-reported physical function), measured one year after ICU discharge. When the data were adjusted for age, female gender was associated with reduced muscle strength (P = .003), exercise capacity (P < .0001), and self-reported physical function (P = .01). Older age, when adjusted for gender, was associated with reduced exercise capacity (P < .001). After adjusting for gender and age, an association was observed between a lower score on one or two physical recovery variables and exposure variables, specifically, high body mass index, low functional independence, comorbidity and low self-reported physical function at baseline, muscle weakness at ICU discharge, and longer hospital stay. No adjustment was made for cumulative type I error rate due to small number of participants. Elucidating risk factors for poor long-term physical recovery after ICU stay, including gender, may be critical if mobilization and exercise are to be prescribed expediently during and after ICU stay, to ensure maximal long-term recovery.