ATP and ADP hydrolysis in brain membranes of zebrafish (Danio rerio).
Nucleotides, e.g. ATP and ADP, are important signaling molecules, which elicit several biological responses. The degradation of nucleotides is catalyzed by a family of enzymes called NTPDases (nucleoside triphosphate diphosphohydrolases). The present study reports the enzymatic properties of a NTPDase (CD39, apyrase, ATP diphosphohydrolase) in brain membranes of zebrafish (Danio rerio). This enzyme was cation-dependent, with a maximal rate for ATP and ADP hydrolysis in a pH range of 7.5-8.0 in the presence of Ca(2+) (5 mM). The enzyme displayed a maximal activity for ATP and ADP hydrolysis at 37 degrees C. It was able to hydrolyze purine and pyrimidine nucleosides 5'-di and triphosphates, being insensitive to classical ATPase inhibitors, such as ouabain (1 mM), N-ethylmaleimide (0.1 mM), orthovanadate (0.1 mM) and sodium azide (0.1 mM). A significant inhibition of ATP and ADP hydrolysis (68% and 34%, respectively) was observed in the presence of 20 mM sodium azide, used as a possible inhibitor of ATP diphosphohydrolase. Levamisole (1 mM) and tetramisole (1 mM), specific inhibitors of alkaline phosphatase and P1, P(5)-di (adenosine 5'-) pentaphosphate, an inhibitor of adenylate kinase did not alter the enzyme activity. The presence of a NTPDase in brain membranes of zebrafish may be important for the modulation of nucleotide and nucleoside levels, controlling their actions on specific purinoceptors in central nervous system of this specie.


A review of preclinical absorbable inferior vena cava filters.
Absorbable inferior vena cava filters (IVCFs) could be more effective and safer than standard IVCFs in theory, as they will self-resorb over time, thus rendering the need for filter retrieval and the risks associated with it unnecessary. This scoping review aims to evaluate the design of current absorbable IVCFs, review the development phase of the absorbable IVCFs, assess the efficacy of the absorbable IVCFs and their complications, and discuss the limitations and areas for future research. MEDLINE, PubMed, and Embase databases were electronically searched and citations of relevant studies manually searched. Study selection and data extraction were performed by two independent reviewers using predetermined criteria and stored on premade proforma, respectively. The risk of bias (RoB) for both in vitro and in vivo studies were performed using established RoB tools. Eight studies were suitable for inclusion in this scoping review; five were in vivo and three were in vitro studies. No clinical trials were found. The RoB varied from moderate to high for in vivo studies and from low to moderate for in vitro studies. Overall, there was evidence from both in vivo and in vitro studies that absorbable IVCFs were effective in clot capturing and self-resorption and could decrease complications associated with standard IVCFs. However, there was a broad lack of statistical analyses and control groups to determine the significance of these findings. Absorbable IVCFs have shown promising features and results in preclinical models. However, significant research needs to be further performed to achieve the ideal characteristics of an absorbable IVCF before the first human trial can be conducted safely.


Transition to Adult Health Care Services for Young Adults with Chronic Medical Illness and Psychiatric Comorbidity.
This article provides national data on the lack of transition preparation among youth with special health care needs, including those with emotional, behavioral, and developmental conditions. Consumer and provider transition barriers pertaining to inadequate transition support are summarized. In addition, current US transition goals are presented along with health professional recommendations on transition. The Six Core Elements of Health Care Transition, which are aligned with professional recommendations, are reviewed with practice-based lessons learned from quality improvement efforts. The article concludes with a discussion of transition evaluation needs and opportunities.


Open globe injuries: factors predictive of poor outcome.
Despite advances in ocular and orbital imaging, instrumentation, materials, and surgical procedures, the management of open globe injuries continues to pose difficult management dilemmas. In this retrospective study, we identify clinical characteristics and outcome of a series of open globe injuries presenting to a major UK centre. Operating department records were reviewed to identify all patients who had undergone repair of an open globe injury from 1 January 1998 to 1 January 2003 at the Manchester Royal Eye Hospital. Case notes were examined to determine demographic data, mechanisms of injury, influence of alcohol/drugs, and location of injury. The Snellen visual acuity on presentation and initial clinical signs were recorded. In total, 115 cases of open globe injury were identified of which 107 cases notes were available for review. Injury to the eye with a sharp object accounted for 71/107 (66%) cases and blunt mechanisms for 30/107 (28%) cases. In six (6%) cases the cause of injury was unknown. The rate of secondary enucleation in our series of 107 open globe injuries was 13/107 (12%). Significant risk factors on presentation associated with eventual enucleation included relative afferent pupillary defect (P<0.001), absence of a red reflex (P<0.001), presence of a lid laceration (P<0.02), a blunt mechanism of injury (P<0.02), and an initial VA worse than 6/60 (P=0.03). From this retrospective study, we have identified several factors that may aid the clinician in deciding on the prognostic value of primary repair. Blunt injuries associated with adnexal trauma, with poor initial visual acuity, the presence of an RAPD or retinal detachment, and the absence of a red reflex are associated with a significantly higher rate of subsequent enucleation.


Transient adenylate cyclase activation accompanies differentiation of Trypanosoma brucei from bloodstream to procyclic forms.
Pleomorphic bloodstream forms of Trypanosoma brucei differentiate synchronously into procyclic forms when cultivated at 27 degrees C in the presence of citrate/cis-aconitate. The activity of adenylate cyclase was monitored during this process. Two phases of transient stimulation were observed. The first phase occurred 6-10 h after the triggering of differentiation, a period which immediately follows the release of the bulk of the VSG and immediately precedes both the first cell division and the loss of the bloodstream-specific ESAG 4 transmembrane adenylate cyclase. The second phase occurred between 20 and 40 h, when the cells that emerged from the first division began to proliferate. These observations suggest that cAMP may be involved in differentiation/proliferation of the parasite.


Metabolic characterization of hemolymph in Bombyx mori varieties after Bombyx mori nucleopolyhedrovirus infection by GC-MS-based metabolite profiling.
The "Huakang 2" silkworm variety, bred by the Sericulture Research Institute of the Chinese Academy of Agricultural Sciences, is highly resistant to Bombyx mori nucleopolyhedrovirus (BmNPV) and effectively solves the issue of frequent Bombyx mori nuclear polyhedrosis in sericultural production. The molecular mechanism of its resistance to BmNPV, however, is still unknown. The purpose of the present study was therefore to identify these anti-BmNPV mechanisms by using metabolomics in combination with transcriptomics after subcutaneous injection of budded virus (BV) with high concentrations of BmNPV from specimens of the Baiyu N variety (which is highly resistant to BmNPV) and the Baiyu variety (which is sensitive to BmNPV). A total of 375 differential metabolites were identified, which mainly included sugars, acids, amines, alcohols, glycosides, and other small molecules. KEGG enrichment analysis and functional clustering of differential metabolites identified possible metabolic pathways, including tyrosine metabolism, oxidative phosphorylation, and alanine, aspartate, and glutamate metabolism. The differentially expressed genes (DEGs) identified by transcriptome analysis were annotated in KEGG. Association analysis showed that the metabolic pathways of different silkworm varieties are affected differently by BmNPV infection, triggering a series of complex physiological and biochemical changes in the organism. In particular, oxidative phosphorylation might be an essential pathway involved in regulation of disease resistance.


Assessment and treatment of depression in people with multiple sclerosis: A qualitative analysis of specialist clinicians' experiences.
Depression is common in people with multiple sclerosis (MS), with lifetime prevalence estimates between 25 and 50%. Depression is commonly underdiagnosed and undertreated in people with MS. This qualitative study assessed current practices, as well as facilitators and required resources to improve detection and management of depression in people with MS. MS clinicians living in Australia were recruited through MS healthcare provider clinics and networks for online interviews. Interviews were transcribed and coded in NVivo for framework analysis. Participants included 15 MS specialists: nine nurses and six neurologists. Participants appreciated that depression was a common symptom of MS, and that untreated depression impacted patients' wellbeing, medication adherence, capacity for self-care, employment, and interpersonal relationships. Participants did not routinely screen for depression and noted that they lack the time and skills to manage depression once identified, most often recommending patients see their general practitioner. Clinicians recognised that people with MS commonly experience barriers to identifying and managing depressive symptoms, however few clinics provide information or discussion about depression as a symptom of MS with patients. Participants indicated a need for evidence-based guidance, more education and training to improve practices including screening for depression, and an urgent need for local referral pathways to affordable and accessible mental health services for people with MS. Findings suggest a need for better collaborative management of depression and improvement of systematic practices related to depression information, screening and treatment support.


Neuroimaging in Susac's syndrome: focus on DTI.
Susac's syndrome is an underdiagnosed disease that is thought to occur mainly in young women. It is characterized by the triad of hearing loss, branch retinal artery occlusions, and encephalopathy with predominantly cognitive and psychiatric symptoms. Treatment consists of immunosuppressive therapy. Focal ischemic lesions in the central portion of the corpus callosum detectable by conventional MRI ("snowballs") are a typical feature of Susac's syndrome. The appearance of these lesions is not, however, correlated with the type and severity of the neuropsychological deficits. Nine patients with Susac's syndrome, four men and five women, were investigated using Diffusion Tensor Imaging (DTI), a non-invasive technique for the detection of macro- and microstructural impairment of fiber integrity on the basis of normal values for the fractional anisotropy (FA). Patients were compared to a group of 83 healthy controls on a voxel-by-voxel basis. Several regions of interest were defined. Impairment of fiber integrity was found in every patient. As compared to the controls, every patient showed disruption of fiber integrity in the genu of the corpus callosum. Reduction of FA was found particularly in the prefrontal white matter. The type and severity of the encephalopathic symptoms in Susac's syndrome are much better represented by the prefrontal FA reductions detected by DTI than by the mostly sparse white matter abnormalities seen on conventional MRI. The fiber damage in the genu seems to be specific for patients with Susac's syndrome.


Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol-induced steatosis.
Alcohol-induced hepatic steatosis is a significant risk factor for progressive liver disease. Cyclic adenosine monophosphate (cAMP) signalling has been shown to significantly regulate lipid metabolism; however, the role of altered cAMP homeostasis in alcohol-mediated hepatic steatosis has never been studied. Our previous work demonstrated that increased expression of hepatic phosphodiesterase 4 (Pde4), which specifically hydrolyses and decreases cAMP levels, plays a pathogenic role in the development of liver inflammation/injury. The aim of this study was to examine the role of PDE4 in alcohol-induced hepatic steatosis. C57BL/6 wild-type and Pde4b knockout (Pde4b(-/-) ) mice were pair-fed control or ethanol liquid diets. One group of wild-type mice received rolipram, a PDE4-specific inhibitor, during alcohol feeding. We demonstrate for the first time that an early increase in PDE4 enzyme expression and a resultant decrease in hepatic cAMP levels are associated with the significant reduction in carnitine palmitoyltransferase 1A (Cpt1a) expression. Notably, alcohol-fed (AF) Pde4b(-/-) mice and AF wild-type mice treated with rolipram had significantly lower hepatic free fatty acid content compared with AF wild-type mice. Importantly, PDE4 inhibition in alcohol-fed mice prevented the decrease in hepatic Cpt1a expression via the Pparα/Sirt1/Pgc1α pathway. These results demonstrate that the alcohol- induced increase in hepatic Pde4, specifically Pde4b expression, and compromised cAMP signalling predispose the liver to impaired fatty acid oxidation and the development of steatosis. Moreover, these data also suggest that hepatic PDE4 may be a clinically relevant therapeutic target for the treatment of alcohol-induced hepatic steatosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Dynamics of chlorinated aliphatic hydrocarbons in the Chalk aquifer of northern France.
The Chalk aquifer used for drinking-water production in the southwest of the Lille European Metropolis is threatened by the presence of chlorinated aliphatic hydrocarbons (CHCs), their concentrations in groundwater regularly exceeding the regulatory limits for drinking water in France. This hinders its use for drinking-water production. Understanding the dynamics and spatial distribution of CHC in the aquifer is a key factor for resource sustainability. For that purpose, an intensive monitoring was undertaken in several well fields and at different depths over eight years. To assess a possible migration and/or degradation of the compounds, the water column in several wells was sampled at various depths with passive samplers. Furthermore, CHC degradation mechanisms were investigated with compound-specific carbon-isotope analysis. The CHC concentrations and their distributions in the area depend on past and current industrial activity, causing plumes emphasized by pumping in the wells, such plumes being multi-source with no identified origin in most wells. In the south area of Les Ansereuilles, reductive dechlorination of tetrachloroethylene from a former industrial laundry highly impacted the surrounding area with its main degradation product cis-1,2-dichloroethylene. The same area is also affected by tetrachlroroethylene from several industrial laundries, textile factories and dyeing industries with also an anaerobic degradation. In the northern part of Les Ansereuilles, tetrachloroethylene, trichloroethane, trichloroethylene and 1,1-dichloroethylene were found as primary products, whereas cis-1,2-dichloroethylene appears to be an anaerobic degradation product of TCE. The other well fields (Houplin-Ancoisne, Seclin and Emmerin) are less impacted by CHC pollution, and it was shown that no CHC degradation occurred in the wells. However, the stratification of CHCs in the well-water columns, their constant concentration values over time caused by the large amount of available CHCs, and the minor degradation occurring in wells are of concern for water operators in the future.


MFC-cascade stacks maximise COD reduction and avoid voltage reversal under adverse conditions.
Six continuous-flow Microbial Fuel Cells (MFCs) configured as a vertical cascade and tested under different electrical connections are presented. When in parallel, stable operation and higher power and current densities than individual MFCs were observed, despite substrate imbalances. The cascading dynamic allowed for a cumulative COD reduction of >95% in approximately 5.7h, equivalent to 7.97 kg COD m(-3) d(-1). Under a series configuration, the stack exhibited considerable losses until correct fluidic/electrical insulation of the units was applied, upon which the stack also exhibited superior performance. In both electrical configurations, the 6 MFC system was systematically starved for up to 15 d, with no significant performance degradation. The results from the 14-month trials, demonstrate that cascade-stacking of small units can result in enhanced electricity production (vs single large units) and treatment rates without using expensive catalysts. It is also demonstrated that substrate imbalances and starvation do not necessarily result in cell-voltage reversal.


[Psychological and social anhedonia. Evaluation of a research instrument for measuring a basic psychopathologic disorder].
Scales for the measurement of social and physical anhedonia, the lowered ability to experience pleasure, were investigated. Both scales were devised by Chapman et al. German versions of these two patient populations and two groups of normal subjects. The reliability and scale intercorrelation coefficients were acceptable for the scales overall, but not for the separate subscales. Patients scored higher on both scales than normal subjects, and patients with neurotic depression had higher scores than those with a diagnosis of schizophrenia. A significant correlation with a chronic course was identified in the schizophrenic patients. Item analysis and factor analysis did not reveal any significant common dimensions in the 87 items in the original scales. Only 17 items in the physical anhedonia scale and 26 items in the social anhedonia scale met test-theoretical criteria of acceptability for inclusion in a German version of these scales. Discrepancies and congruencies between American and German studies were discussed, as were further criteria that might make it possible to improve research instruments of this kind.


Prisoners as patients. The experience of delivering mental health nursing care in an Australian prison.
Correctional or prison mental health nursing is a highly specialized area of practice that has undergone substantive role development in recent years. However, little research has explored aspects of prison-based nursing practice or practice arrangements. The experience of delivering mental health nursing care in prison can be disempowering, resulting in feelings of frustration, isolation, and stigma. In developed nations, prison mental health nurses face the rewarding challenge of gaining greater recognition for the specialized nature of their practice and their key role in the correctional and criminal justice continuum.


Endovascular Treatment of Vein of Galen Malformations: A Systematic Review and Meta-Analysis.
Outcomes after endovascular embolization of vein of Galen malformations remain relatively poorly described. We performed a systematic review of the literature to determine outcomes and predictors of good outcomes following endovascular treatment of vein of Galen malformations. We used Ovid MEDLINE, Ovid Embase, and the Web of Science. Our study consisted of all case series with ≥4 patients receiving endovascular treatment of vein of Galen malformations published through January 2017. We studied the following outcomes: complete/near-complete occlusion rates, technical complications, perioperative stroke, perioperative hemorrhage, technical mortality, all-cause mortality, poor neurologic outcomes, and good neurologic outcomes. Outcomes were stratified by age-group (neonate, infant, child). A random-effects meta-analysis was performed. A total of 27 series with 578 patients were included; 41.9% of patients were neonates, 45.0% of patients were infants, and 13.1% of patients were children. All-cause mortality was 14.0% (95% CI, 8.0%-22.0%). Overall good neurologic outcome rates were 62.0% (95% CI, 57.0%-67.0%). Overall poor neurologic outcome rates were 21.0% (95% CI, 17.0%-26.0%). Neonates were significantly less likely to have good neurologic outcomes than infants (48.0%; 95% CI, 35.0%-62.0% versus 77.0%; 95% CI, 70.0%-84.0%; P < .01). Treatment indications following the Bicêtre neonatal evaluation score resulted in significantly higher rates of good neurologic outcome (P = .04). Patients with congestive heart failure had significantly lower rates of good neurologic outcome (OR, 0.50; 95% CI, 0.28-0.88; P = .01). Limitations were selection and publication biases. Patients receiving endovascular embolization of vein of Galen malformations experienced good long-term clinical outcomes in >60% of cases. Appropriate patient selection is key as treatment guided by the Bicêtre neonatal evaluation score was associated with improved neurologic outcomes.


Stabilization of Kv1.5 channel protein by the inotropic agent olprinone.
Olprinone is an inotropic agent that inhibits phosphodiesterase (PDE) III and causes vasodilation. Olprinone has been shown to be less proarrhythmic and possibly affect expression of functional Kv1.5 channels that confer the ultra-rapid delayed-rectifier K+ channel current (IKur) responsible for action potential repolarization. To reveal involvement of Kv1.5 channels in the less arrhythmic effect of olprinone, we examined effects of the agent on the stability of Kv1.5 channel proteins expressed in COS7 cells. Olprinone at 30-1000 nM increased the protein level of Kv1.5 channels in a concentration-dependent manner. Chase experiments showed that olprinone delayed degradation of Kv1.5 channels. Olprinone increased the immunofluorescent signal of Kv1.5 channels in the endoplasmic reticulum (ER) and Golgi apparatus as well as on the cell surface. Kv1.5-mediated membrane currents, measured as 4-aminopyridine-sensitive currents, were increased by olprinone without changes in their activation kinetics. A protein transporter inhibitor, colchicine, abolished the olprinone-induced increase of Kv.1.5-mediated currents. The action of olprinone was inhibited by 4-aminopyridine, and was not mimicked by the application of 8-Bromo-cAMP. Taken together, we conclude that olprinone stabilizes Kv1.5 proteins at the ER through an action as a chemical chaperone, and thereby increases the density of Kv1.5 channels on the cell membrane. The enhancement of Kv1.5 currents could underlie less arrhythmogenicity of olprinone.


Obesity does not adversely impact the outcome of unicompartmental knee arthroplasty for osteoarthritis: a meta-analysis of 80,798 subjects.
Patients with end-stage single compartment osteoarthritis benefit from the less invasive unicompartmental knee arthroplasty (UKA). With increasing financial restraints, some healthcare services have set specific BMI cut-offs when determining patient eligibility for knee arthroplasty due to perceived obesity-related complications. The aim of this systematic review is to determine the effect obesity has on outcomes following UKA, and thus elucidate whether obesity should be a contraindication for UKA. A PRISMA systematic review was conducted using five databases (MEDLINE, EMBASE, Cochrane, PubMed and Web of Science) to identify all clinical studies that examined the effect of obesity on outcomes following UKA. Quantitative meta-analysis was carried out using RevMan 5.3 software. Quality assessment was carried out using the Critical Appraisal Skills Programme (CASP) checklist. Thirty studies, including a total of 80 798 patients were analysed. The mean follow- up duration was 5.42 years. Subgroup meta-analyses showed no statistically significant difference following UKA between patients cohorts with and without obesity in overall complication rates (95% CI, P = 0.52), infection rates (95% CI, P = 0.81), and revision surgeries (95% CI, P = 0.06). When further analysing complications, no differences were identified in minor (95% CI, P = 0.23) and major complications (95% CI, P = 0.68), or venous thromboembolism rates (95% CI, P = 0.06). When further analysing revision surgeries, no differences were identified for revisions specifically for infection (95% CI, P = 0.71) or aseptic loosening (95% CI, P = 0.75). This meta-analysis shows that obesity does not result in poorer post-operative outcomes following UKA and should not be considered a contraindication for UKA. Future studies, including long-term follow-up RCTs and registry-level analyses, should examine factors associated with obesity and consider stratifying obesity to better delineate any potential differences in outcomes.


The modification of human tumour blood flow using pentoxifylline, nicotinamide and carbogen.
To assess the effect of combining oral nicotinamide, oral pentoxifylline and carbogen gas (2% CO2, 98% O2) breathing on human tumour red cell flux. Microregional red blood cell flux was measured in accessible tumour nodules using laser Doppler microprobes in 11 patients with histologically proven malignancy. Patients received single oral doses of nicotinamide 40 mgkg-1 and pentoxifylline 1200 mg 2h before a 10-min period of carbogen gas breathing, corresponding to peak plasma concentrations of these drugs. Red cell flux in up to six microregions in each tumour was measured for 30 min, recording pre-, during and post-carbogen breathing for 10 min each. Data from ten of the 11 patients could be assessed. The red cell flux in 48 microregions was analysed and the mean red cell flux was calculated. A mean relative increase in red cell flux of 1.18 (+/-0.09, 95% confidence interval (CI)) was observed after 6 min of carbogen breathing, 2h after the administration of nicotinamide and pentoxifylline. This compares to relative increases of 1.4 (+/-0.39, 95%CI) after nicotinamide with carbogen and 1.15 (+/-0.10, 95%CI) after pentoxifylline with carbogen. These differences are not statistically significant (P>0.05). The increased red cell flux persisted after the cessation of carbogen gas breathing. A combination of pentoxifylline, nicotinamide and carbogen produces an increase in human tumour red cell flux, similar to that observed when each of the drugs are used alone with carbogen breathing.


Examining the dimensionality, reliability, and invariance of the Chinese version of the Resilience Scale-14: A multicenter cross-sectional survey in Chinese junior nurses.
This study aimed to present the psychometric properties (dimensionality, reliability, and invariance) of the Chinese 14-Item Resilience Scale (RS-14) within Chinese register nurses (RNs) with less than 3 years work experiences. And we aimed to compare the fit of a unidimensional model and a bifactor model. This multicenter cross-sectional survey was conducted from August to September in 2019. A total of 7,231 registered nurses from 90 hospitals were recruited. Data was anonymously obtained through online questionnaires. Both reliability and validity of Chinese RS-14 were assessed. The confirmatory factor analyses (CFA) were used to compare the fit of two different factor structures of the RS-14 (unidimensional model vs. a bifactor model). Moreover, multigroup CFA (MGCFA) were applied to evaluate the measurement invariance (MI) across sociodemographic parameters (gender, educational level, marital status, and et al.). Cross-sectional quantitative analyses. Our study confirmed that the bifactor model presented the best fit within Chinese nurses (CFI = 0.924, TLI = 0.909, RMSEA = 0.095, SRMR = 0.043), and found strong factorial invariance across gender, marital status, and status of receiving standardized training. The reliability of RS-14 was high with a Cronbach's alpha coefficient of 0.939. Moreover, RS-14 was positively correlated with the social support and was negatively correlated with workplace bullying. This is the first study to explore the latent factor structure for the RS-14 among Chinese RNs and evaluated MI across a series of sociodemographic variables. Based on our findings, the Chinese version RS-14 is both valid and reliable.


Possible beneficial effect of olmesartan medoxomil on left atrial function in patients with hypertension : noninvasive assessment by acoustic quantification.
Hypertension alters the diastolic properties of the left ventricle and results in deterioration in the structure and function of the left atrium. We aimed to evaluate whether olmesartan medoxomil has an effect on left atrial function in hypertensive patients. Fifty hypertensive patients and 20 controls were included in the study. Hypertensive patients were treated with olmesartan medoxomil for 8 weeks. Before and after treatment, study participants were examined by acoustic quantification and tissue Doppler imaging. Left atrial reservoir function was assessed by end-diastolic volume (EDV), end-systolic volume (ESV), reservoir volume (RV) and peak filling rate (PFR). Left atrial booster pump function was assessed by atrial emptying volume (AEV), atrial emptying fraction (AEF) and peak atrial emptying rate (PAER). Left atrial conduit function was assessed by rapid emptying volume (REV), rapid emptying fraction (REF), REV/AEV ratio, and the ratio of peak rapid emptying rate and PAER (PRER/PAER). Atrial RV and PFR were significantly increased in hypertensive subjects (48.30 +/- 19.28 mL vs 34.35 +/- 14.26 mL, p < 0.001; 267.26 +/- 126.52 mL/s vs 206.81 +/- 107.17 mL/s, p < 0.05) compared with controls, while the REV/AEV ratio was decreased in hypertensive patients compared with controls (2.86 +/- 0.85 vs 3.69 +/- 2.13, p < 0.001). After therapy with olmesartan medoxomil, atrial RV (48.30 +/- 19.28 mL vs 40.50 +/- 17.59 mL) and PFR decreased (267.26 +/- 126.52 mL/s vs 220.40 +/- 108.56 mL/s, p < 0.05) and the REV/AEV ratio increased (2.86 +/- 0.85 vs 3.14 +/- 0.43, p < 0.05) in hypertensive patients. Our novel findings indicate that left atrial function is impaired in hypertensive patients, and that olmesartan medoxomil can improve left atrial function in this context. Our study also showed that acoustic quantification is useful for non-invasive evaluation of the benefits of treatment on left atrial function.


[Spontaneous perirenal hematoma in infants. Apropos of 2 cases].
The authors report two personal cases and note the special appearance of perirenal hematomas in infants. The pathogenesis is often obscure but this condition should be classified with the spontaneous perirenal hematomas and retroperitoneal tumour masses in infants.


Muscle imaging in neuromuscular disease using computerized real-time sonography.
The results of a study utilizing computerized real-time sonography (CRS) to image muscles in patients with neuromuscular disease are presented for 67 patients, 37 with neuromuscular disease and 4 with upper motor neuron disease, and 26 age-matched healthy controls between the ages of 2 days and 59 years. CRS is a safe, noninvasive, atraumatic method for evaluating a broad range of neuromuscular diseases. It is capable of differentiating myopathies or dystrophies from neurogenic atrophies and floppy infants with "central" hypotonia from those with neuromuscular diseases.


The endemic treponematoses.
Treponemal diseases comprise venereal syphilis (Treponema pallidum subsp. pallidum) and the endemic (non-venereal) treponematoses, i.e. yaws (T. pallidum subsp. pertenue), endemic syphilis (T. pallidum subsp. endemicum) and pinta (T. carateum). Treponemal diseases are distinguished on the basis of epidemiological characteristics and clinical manifestations. They are at present indistinguishable by morphological, immunological or serological methods. Several minor genetic differences have been identified among the subspecies. The endemic treponematoses have not yet been eliminated and are currently thought to affect at least 2.5 million persons. Renewed action towards the elimination of these diseases should be undertaken.


The appropriateness of abdominal X-ray requests in the acute medical initial admissions unit.
Abdominal X-rays are frequently requested by clinicians in the Aberdeen Royal Infirmary acute medical initial assessment unit. The proportion of indicated abdominal X-rays requested within 24 hours of admission was retrospectively examined. This process was repeated after displaying an educational poster with the Royal College of Radiologists guidelines (cycle 2) and a graded assertive communication poster (cycles 3 and 4); a tool to enable junior doctors to challenge inappropriate requests for abdominal X-rays from seniors. Only 47.2% of abdominal X-ray requests were deemed appropriate in cycle 1. A 1.54% reduction in abdominal X-ray requests and an 11.5% increase in indicated abdominal X-rays were noted after cycle 2. Cycle 3 led to a statistically significant improvement with 2.6% fewer patients undergoing an abdominal X-ray and a 24.6% increase in indicated abdominal X-rays. This improvement was sustained in cycle 4. Promoting graded assertive communication is an effective means of helping junior doctors to challenge seniors requesting non-indicated abdominal X-rays.


Numerical analysis of economic and environmental benefits of marine fuel conversion from diesel oil to natural gas for container ships.
Shipping is a significant contributor to global greenhouse gas (GHG) and air pollutant emissions. These emissions mainly come from using diesel fuel for power generation. In this paper, the natural gas is proposed as an alternative marine fuel to be used instead of conventional marine diesel oil. Numerical analysis of environmental and economic benefits of the natural gas-diesel dual-fuel engine is carried out. As a case study, a container ship of class A7 owned by Hapag-Lloyd has been investigated. The results show that the proposed dual-fuel engine achieves environmental benefits for reducing carbon dioxide (CO2), nitrogen oxides (NOx), sulfur oxides (SOx), particulate matter (PM), and carbon monoxide (CO) emissions by 20.1%, 85.5%, 98%, 99%, and 55.7% with cost effectiveness of 109, 840, 9864, 27761, and 4307 US$/ton, respectively. The results show that the conversion process to the dual-fuel engine will comply with the current and future IMO regulations regarding air pollutant emissions. On the other hand, using the proposed dual-fuel engine on the container ship will improve the ship energy efficiency index by 29.6 % with annual fuel cost saving of 4.77 million US dollars.


Blob-like feature extraction and matching for brain MR images.
The cerebral cortex of the human brain is highly folded. It is useful for neuroscientists and clinical researchers to identify and/or quantify cortical folding patterns across individuals. The top (gyri) and bottom (sulci) of these folds resemble the "blob-like" features used in computer vision. In this article, we evaluate different blob detectors and descriptors on brain MR images, and introduce our own, the "brain blob detector and descriptor (BBDD)." For the first time blob detectors are considered as spatial filters under the scale-space framework and their impulse responses are manipulated for detecting the structures in our interest. The BBDD detector is tailored to the scale and structure of blob-like features that coincide with cortical folds, and its descriptors performed well at discriminating these features in our evaluation.


A functional role for vasoactive intestinal polypeptide in anterior cingulate cortex.
Vasoactive intestinal polypeptide (VIP) is present in high concentrations in the cerebral cortex, where it is the putative neurotransmitter of a major intracortical neuronal system. Homogenates of cortical tissue contain high-affinity, specific binding sites for VIP as well as an adenylate cyclase system which is sensitive to this peptide. As with many of the other peptidergic systems which have been identified in the central nervous system (CNS), it has proved extremely difficult to elucidate the nature and extent of the functional role of VIP in specific brain areas. Here, using the quantitative autoradiographic 14C-deoxyglucose technique in rats to provide insight into functional processes, we describe the increases in glucose utilization which occur locally in anterior cingulate cortex following the unilateral injection of VIP (20 pmol) into this key brain area and, additionally, the focal alterations in glucose use in CNS regions having known neuronal connections with the injected region (for example, ipsilateral mediodorsal thalamus, ventral tegmental area, nucleus accumbens, caudate nucleus and contralateral cingulate cortex). These data provide evidence that VIP may modify the processing of afferent and efferent information within the anterior cingulate cortex in the conscious rat.


State-of-the-art and clinically applied pneumatic artificial hearts.
This article is intended to inform the reader of the current state of the art of pneumatically powered artificial hearts, including animal experiments and information available on 11 recipients of orthotopically placed devices.


Diagnostic classification of organic psychiatric disorders after aneurysmal subarachnoid hemorrhage: a comparison between ICD-10, DSM-IV and the Lindqvist & Malmgren classification system.
There is no universally accepted consensus for organic psychiatric disorders (OPDs) between the two major classifications, ICD-10 and DSM-IV. The aim was to compare the coverage of these systems with the Lindqvist & Malmgren (LM) classification system for organic psychiatry. Organic psychiatric disorders were diagnosed according to ICD-10, DSM-IV, and the LM system in 119 patients 12 months after surgery as a result of aneurysmal subarachnoid hemorrhage. Among 35 patients with astheno-emotional (AE) disorder (LM system), 83% (95% CI: 67-92%) had mild cognitive disorder (MCD) according to ICD-10 clinical descriptions and diagnostic guidelines (CDDG), 49% (95% CI: 33-64%) had MCD according to ICD-10 diagnostic criteria for research (DCR), and 34% (95% CI: 21-51%) had mild neurocognitive disorder according to DSM-IV. The coverage for other OPDs did not differ between the systems. The coverage for AE disorder (LM system) was significantly higher than the corresponding diagnoses of the ICD-10 and DSM-IV systems. Modifications of the latter systems are suggested.


Radiation recall dermatitis: case report and review of the literature.
"Radiation recall"-also called "radiation recall dermatitis"-has been defined as the "recalling" by skin of previous radiation exposure in response to the administration of certain response-inducing drugs. Although the phenomenon is relatively well known in the medical world, an exact cause has not been documented. Here, we report a rare occurrence of the radiation recall phenomenon in a breast cancer patient after palliative radiotherapy for bone, brain, and orbital metastases.


Laparoscopic enucleation of an insulinoma of the pancreas tail.
A 29 year-old woman with a tumor of the pancreatic tail was referred to our institute. The tumor was confirmed to be a solitary benign insulinoma that protruded from the pancreas and was distant from the main pancreatic duct. A laparoscopic enucleation was performed with Laparoscopic Coagulating Shears (LCS). The postoperative course was uneventful. The laparoscopic enucleation for benign pancreatic tumor was thought to be a feasible procedure when the appropriate instruments were used.


Fertility preservation with successful pregnancy outcome in a patient with transplanted heart and non-Hodgkin's lymphoma - a case report.
Fertility preservation must be discussed with reproductive age women before cancer treatment. Heart transplantation raises complex issues in pregnancy. Pregnancy in a heart transplant woman after pelvic irradiation involves close multidisciplinary follow-up to avoid complications in the mother and the foetus. We report the first live birth in a heart transplant woman after pelvic irradiation, chemotherapy and fertility preservation. A 36-year-old heart transplant woman with pelvic non-Hodgkin lymphoma spared her fertility, with cryopreservation of oocytes and embryos, before chemotherapy and pelvic irradiation. After multidisciplinary discussion and pre-conception evaluation, pregnancy was achieved. A close follow-up by a multidisciplinary team allowed a normal pregnancy without maternal or foetal complications and the delivery of a healthy infant. Achieving pregnancy in heart transplant women with iatrogenic ovarian failure after oncologic treatment including pelvic irradiation is possible and can be successful. Careful and close surveillance by a multidisciplinary team is mandatory due to increased risk of maternal and foetal complications.


Long-term outcomes of non-ischemic dilated cardiomyopathy patients with left ventricular ejection fraction ≤19% on medical therapy.
Patients with heart failure and reduced ejection fraction in low resource settings may not have access to devices and expensive therapeutic options. We followed up a cohort of patients with non-ischemic dilated cardiomyopathy (DCM) with very low left ventricle ejection fraction (LVEF≤19%) on low cost medical therapy alone. By selecting patients with such low LVEF, this study was restricted to patients with severe disease. We studied long-term transplant free survival of these patients. The study enrolled 130 patients (83 men and 47 women) of DCM cohort with LVEF≤19% from April 2003-December 2018 on medical therapy alone. Mean age was 40.35 ± 13.9 years. Mean follow-up was 45.6 ± 39 months while median follow-up was 39 months (range: 0-176 months). Patients on devices (ICD/CRT) for heart failure management were excluded. Fifty-four patients died and three underwent transplant during the study. Median survival was 86 months (S.E. 22.38). 113 patients had follow-up till end of study. In the worst case scenario, if all 17 patients who were lost to final follow-up were assumed to be dead, the median survival was still 57 (S.E.9.28) months. Higher baseline NYHA class, recurrent heart failure hospitalizations, absence of treatment with beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers and aldosterone antagonists were predictors of death on univariate analysis whereas none of these parameters were significant on multivariate analysis. Median survival of our DCM cohort with LVEF≤19% on medical therapy was over 7 years.


NMR structures of the transmembrane domains of the α4β2 nAChR.
The α4β2 nicotinic acetylcholine receptor (nAChR) is the predominant heteromeric subtype of nAChRs in the brain, which has been implicated in numerous neurological conditions. The structural information specifically for the α4β2 and other neuronal nAChRs is presently limited. In this study, we determined structures of the transmembrane (TM) domains of the α4 and β2 subunits in lauryldimethylamine-oxide (LDAO) micelles using solution NMR spectroscopy. NMR experiments and size exclusion chromatography-multi-angle light scattering (SEC-MALS) analysis demonstrated that the TM domains of α4 and β2 interacted with each other and spontaneously formed pentameric assemblies in the LDAO micelles. The Na(+) flux assay revealed that α4β2 formed Na(+) permeable channels in lipid vesicles. Efflux of Na(+) through the α4β2 channels reduced intra-vesicle Sodium Green™ fluorescence in a time-dependent manner that was not observed in vesicles without incorporating α4β2. The study provides structural insight into the TM domains of the α4β2 nAChR. It offers a valuable structural framework for rationalizing extensive biochemical data collected previously on the α4β2 nAChR and for designing new therapeutic modulators.


Differences in lower extremity stiffness between endurance-trained athletes and untrained subjects.
An understanding of lower extremity stiffness is important for evaluation of sports performance and injury prevention. The aim of this study was to investigate whether stiffness regulation during hopping differed between endurance-trained athletes and untrained subjects. Eight endurance-trained athletes and eight untrained subjects performed two-legged hopping at 2.2 Hz. We determined leg and joint stiffness of hip, knee and ankle from kinetic and kinematics data. The endurance-trained athletes demonstrated significantly higher leg stiffness than untrained subjects. Further, the differences in leg stiffness were attributable to differences in ankle and knee joint stiffness. This study demonstrates a possibility that endurance training, like power training, increases leg and joint stiffness.


Lipoxin A4 counteracts synergistic activation of human fibroblast-like synoviocytes.
Excessive production of interleukin-6 (IL-6) and metalloproteinases (MMPs) have been implicated in the pathogenesis of rheumatoid arthritis. Lipoxin A4 (LXA4) and transforming growth factor beta 2 (TGF-beta 2), mediators with potential anti-inflammatory activities, were tested to determine how they affect IL-1 beta-dependent release of IL-6 and MMPs in human fibroblast like synoviocytes. The results showed dramatic differences between the mediators: TGF-beta 2 acted synergistically with IL-1 beta to stimulate IL-6 protein levels, whereas LXA4 inhibited IL-6 expression in dose- and time-dependent manner. Inhibition, by LXA4 was abrogated when cells were pre-incubated with antibody against the LXA4R whereas TGF-beta 2 by itself had no significant effect on IL-6 or MMP levels. LXA4, at nanomolar concentrations, altered the MMP-1 and MMP-3 expression levels of IL-1 beta and TGF-beta 2 stimulated fibroblast like synoviocytes at 5 days. Furthermore, IL-1 beta and TGF-beta 2 up-regulated LXA4R mRNA. These results demonstrate, for the first time, that LXA4Rs mediate the effects of LXA4 on inflammatory responses after combined stimulation of human fibroblast like synoviocytes with IL-1 beta and TGF-beta 2. These activities might constitute an important mechanism by which LXA4 regulates human synovial fibroblast activation.


11C-coenzyme Q10: a new myocardial imaging tracer for positron emission tomography.
Coenzyme Q10 (CoQ10) is a co-factor of the mitochondrial electron-transfer system. 11C-Labeled CoQ10 was synthesized and its biodistribution in rats was examined comparing two kinds of preparation methods using different emulsifiers as a basic study for application of positron emission tomography. 11C-CoQ10 emulsified in saline with polyoxyethylene hydrogenated castor oil was present in the highest concentration in the blood at 30 min. On the other hand, the 11C-CoQ10 emulsified with phospholipids was rapidly cleared from the blood. The liver and spleen uptakes were high probably due to endocytosis, reflecting the characteristics of liposomes. The myocardial uptake was also high just after administration, and the heart-to-blood concentration ratio was over 10 after 5 min. These results suggest that 11C-CoQ10 prepared with liposomes may be a myocardial imaging tracer.


Alternative routes for production of the drug candidate d-chiro-inositol with Corynebacterium glutamicum using endogenous or promiscuous plant enzymes.
d-chiro-Inositol (DCI) is a promising drug candidate for treating insulin resistance and associated diseases such as type 2 diabetes or polycystic ovary syndrome. In this study, we developed two production processes for DCI using Corynebacterium glutamicum as host. In the first process, myo-inositol (MI) is oxidized to 2-keto-myo-inositol (2KMI) by the inositol dehydrogenase (IDH) IolG and then isomerized to 1-keto-d-chiro-inositol (1KDCI) by the isomerases Cg0212 or Cg2312, both of which were identified in this work. 1KDCI is then reduced to DCI by IolG. Overproduction of IolG and Cg0212 in a chassis strain unable to degrade inositols allowed the production of 1.1 g/L DCI from 10 g/L MI. As both reactions involved are reversible, only a partial conversion of MI to DCI can be achieved. To enable higher conversion ratios, a novel route towards DCI was established by utilizing the promiscuous activity of two plant-derived enzymes, the NAD+-dependent d-ononitol dehydrogenase MtOEPa and the NADPH-dependent d-pinitol dehydrogenase MtOEPb from Medicago truncatula (barrelclover). Heterologous production of these enzymes in the chassis strain led to the production of 1.6 g/L DCI from 10 g/L MI. For replacing the substrate MI by glucose, the two plant genes were co-expressed with the endogenous myo-inositol-1-phosphate synthase gene ino1 either as a synthetic operon or using a novel, bicistronic T7-based expression vector. With the single operon construct, 0.75 g/L DCI was formed from 20 g/L glucose, whereas with the bicistronic construct 1.2 g/L DCI was obtained, disclosing C. glutamicum as an attractive host for of d-chiro-inositol production.


Clinical, laboratory, and mutational profile of children with glucose phosphate isomerase deficiency: a single centre report.
Glucose phosphate isomerase (GPI) deficiency is an autosomal recessive condition with mutations in the GPI gene on chromosome 19q13.1. Patients present with congenital non-spherocytic hemolytic anemia, and occasionally intellectual disability. In this study, we describe the clinical, hematological and biochemical parameters in the largest single-center cohort consisting of 17 GPI-deficient cases. Demographic and clinical data were noted, and red cell enzyme activity levels were estimated. Mutation analysis was done by single-stranded-conformation polymorphism, restriction-fragment length polymorphism and Sanger's sequencing of exon 12 of the GPI gene. The male-to-female ratio was 0.7:1, median age at diagnosis was 5.0 years, 82.3% of patients had severe neonatal jaundice, and 13.3% had subtle neurological manifestations. Median Hb and MCV levels were 6.3 g/dl and 130.2 fl. Splenectomized patients required fewer transfusions. Sixteen of 17 patients had the pathogenic c.1040G > A (p.Arg347His) homozygous mutation in exon12 of the GPI gene, and one had the pathogenic c.1414C > T(p.Arg472Cys) homozygous mutation in exon 16. In summary, we report that neonatal jaundice, macrocytosis and high prevalence of p.Arg347His variant were predominant in GPI deficiency with prominent lack of neurological manifestations, and we emphasize the benefits of splenectomy and the need for genetic counseling.


Meat consumption and the risk of general and central obesity: the Shahedieh study.
This study aimed to investigate the relations of total meat intake and its subtypes, including red and processed meat, white meat, poultry, fish, and organ meat to the risk of general/central obesity. This cross-sectional study included a total of 7312 Iranian adults with the age range of 35-70 years from the Shahedieh cohort study, Yazd, Iran. Dietary intake of subjects was evaluated using a validated 120-item Food Frequency Questionnaire. General obesity was defined as body mass index ≥ 30 kg/m2 and central obesity as waist circumference ≥ 102 cm in men and ≥ 88 cm in women. After controlling for potential covariates including energy intake, age, marital status, gender, physical activity, supplement use, house possession, education, family size, current smoking, night shift working, history of thyroid disease and depression, and intakes of vegetables, legumes, nuts, fruits, whole grains, and dairy, a significant direct association was found between the higher consumption of white meat (OR = 1.31; 95% CI: 1.06-1.61) and poultry (OR = 1.23; 95% CI: 1.04-1.45) with odds of general obesity. Processed meat was a significant predictor for central obesity in the fully adjusted model, so that individuals in the fourth quartile of processed meat intake, compared with those in the first quartile, had a 22% (OR = 1.22; 95% CI: 1.04-1.43) increased risk to be centrally obese. This study reveals that higher intakes of white meat and poultry are associated with increased risk of general obesity, while, processed meat consumption was associated with central obesity.


The effective temperature of ions stored in a linear quadrupole ion trap mass spectrometer.
The extent of internal energy deposition into ions upon storage, radial ejection, and detection using a linear quadrupole ion trap mass spectrometer is investigated as a function of ion size (m/z 59 to 810) using seven ion-molecule thermometer reactions that have well characterized reaction entropies and enthalpies. The average effective temperatures of the reactants and products of the ion-molecule reactions, which were obtained from ion-molecule equilibrium measurements, range from 295 to 350 K and do not depend significantly on the number of trapped ions, m/z value, ion trap q z value, reaction enthalpy/entropy, or the number of vibrational degrees of freedom for the seven reactions investigated. The average of the effective temperature values obtained for all seven thermometer reactions is 318 ± 23 K, which indicates that linear quadrupole ion trap mass spectrometers can be used to study the structure(s) and reactivity of ions at near ambient temperature.


[Effects of recombinant human growth hormone on cortical bone of ovariectomized rats].
To study the effects of recombinant human growth hormone on cortical bone of middle femur and vertebra of variectomized rats. Forty 6 month-old SD rats received low or high dose of growth hormone subcutaneously 3 months after ovariectomy for 8 weeks. Bone density and biomechanical strength of the femur were measured, and the thickness of cortical bone of the middle femur and L(2) vertebra was observed. The results were compared with those in estrogen group. Growth hormone increased the thickness of cortical bone and biomechanical strength and bone density. Estrogen therapy showed no effects on bone density and biomechanical strength of cortical bone. Recombinant human growth hormone can prevent bone loss from cortical bone of ovariectomized rat.


Assessment of the level of social support and associated factors among cancer patients in the comprehensive cancer center at Ethiopia: Ordinal logistic regression analysis level of social support and associated factors among cancer patients.
Cancer is a serious and common disease, which had a substantial problem in the social status of patients. There was no empirical evidence on the effect of cancer on social support. This study aimed to determine the level of social support among cancer patients in a comprehensive cancer center in Ethiopia. An institution-based cross-sectional study was done. About 386 study participants who were selected through systematic random sampling involved in the study. Training and close supervision and monitoring were done. The collected data were analyzed using SPSS-25. Descriptive statistics and Chi-square test were done. Ordinal bivariate and multivariate logistic regression were done to show the net effect of independent variables on the dependent variable. Model fitting information, the goodness of test, and the test of parallel line assumption test of the ordinal logistic regression model were carried out. A total of 386 study subjected were included in the final analysis. The poor, moderate, and strong levels of social support among cancer patients were found to be 45.3%, 34.2%, and 20.5% respectively. The mean score of social support among cancer patients was 10.4 ± 2.6SD. Age, Marital status, residence, educational status, stage III were found to be significant factors for the level of social support. and recommendation: The level of poor, moderate, and strong social support was found to be 45.3%, 34.2 and 20.5 respectively. Emphasis should be given to those cancer patients who had poor social support, and frequent social status assessment should be done.


The effect of cephalosporin antibiotics on alcohol metabolism: a review.
A review is made of the pharmacological, biochemical and chemical aspects of the unpleasant 'Antabuse-like' reaction that may be induced in drinkers of alcohol by pre-treatment with certain beta-lactam antibiotics with a 1-methyltetrazole-5-thiol sidechain (such as moxalactam, cefamandole and cefoperazone). The symptoms are due to abnormally elevated blood acetaldehyde levels consequent upon the inactivation of hepatic aldehyde dehydrogenase. There is very little direct effect of the antibiotics on this enzyme and therefore it is concluded that a reactive metabolite of the antibiotics' essential sidechain is responsible for the reaction. A likely candidate for this active species is either the symmetrical disulphide 5,5'-dithiobis(1-methyltetrazole) formed by oxidation of 1-methyltetrazole-5-thiol, or the related mixed disulphide, methyl 5-(1-methyltetrazolyl) disulphide. The first of these is a potent inactivator of cytoplasmic aldehyde dehydrogenase only, the second affects both cytoplasmic and mitochondrial isoenzymes. 1-Methyltetrazole-5-thiol or derivatives have the potential to be used therapeutically as 'anti-alcohol' compounds in the same way as disulfiram (Antabuse) or calcium cyanamide.


Defects of microtubule cytoskeletal organization in NOA human testes.
The importance of actin and microtubule (MT) cytoskeletons in testis function in rodents is known to some extent, but its role in the etiology of azoospermia in humans remains unexplored. Here, we examined if MT cytoskeleton was defective in NOA (non-obstructive azoospermia) testes versus normal human testes based on histopathological, immunofluorescence (IF), and scRNA-Seq transcriptome profiling. Testis biopsy samples from n = 6 normal men versus n = 3 Sertoli cell only (SCO) and n = 3 MA (meiotic arrest) of NOA patients were used for histopathological analysis. IF analysis was also used to examine MT organization across the seminiferous epithelium, investigating the likely involvement of microtubule-associated proteins (MAPs). scRNA-Seq transcriptome profiling datasets from testes of 3 SCO patients versus 3 normal men in public domain in Gene Expression Omnibus (GEO) Sample (GSM) with identifiers were analyzed to examine relevant genes that regulate MT dynamics. NOA testes of MA and SCO patients displayed notable defects in MT organization across the epithelium with extensive truncation, mis-alignments and appeared as collapsed structures near the base of the tubules. These changes are in contrast to MTs in testes of normal men. scRNA-Seq analyses revealed considerable loss of spermatogenesis capacity in SCO testes of NOA patients versus normal men. An array of genes that support MT dynamics displayed considerable changes in expression and in spatial distribution. In summary, defects in MT cytoskeleton were noted in testes of NOA (SCO) patients, possibly mediated by defective spatial expression and/or distribution of MAPs. These changes, in turn, may impede spermatogenesis in SCO testes of NOA patients.


Neuropeptide modulation of lymphatic smooth muscle tone in the canine forelimb.
Neurokinin A and B are putative inflammatory mediators. We assessed their ability to alter prenodal lymphatic resistance. Intralymphatic neurokinin A (3.0 x 10(-6), 3.0 x 10(-5) and 3.0 x 10(-4) mol l(-1)) significantly constricted lymphatics at the two highest doses. Preliminary experiments suggested that neurokinin B might dilate lymphatics. To test this, lymphatic pressure was increased by norepinephrine (3.1 x 10(-6) mol l(-1)). Neurokinin B (2.7 x 10(-4) mol l(-1)) was then infused intralymphatically during norepinephrine infusion. Norepinephrine increased perfusion pressure from 5.6 +/- 0.6 mmHg to 12.1 +/- 1.4 mmHg. Subsequent infusion of neurokinin B significantly decreased lymphatic perfusion pressure from 11.9 +/- 1.3 mmHg to 9.9 +/- 1.1 mmHg. These data indicate that neurokinin A and B can alter lymphatic resistance and are consistent with the hypothesis that lymph vessel function may be subject to modulation by neurokinins.


Isolated acute cellular rejection of the liver after simultaneous liver and kidney transplantation: a case report.
Simultaneous liver and kidney transplantation (SLKT) is now considered the treatment of choice for patients with concurrent end-stage liver and kidney diseases. Even though the early postoperative mortality rate following SLKT is reported to be high compared to that of liver transplantation alone, the liver graft from the same donor has been argued to induce better kidney graft acceptance as evidenced by a low rate of acute renal rejection episodes. There have been many reports of a low incidence of acute renal rejection following SLKT; however, only a few cases were proven by simultaneous biopsies. The authors experienced a case of biopsy-proven isolated acute cellular rejection of the liver graft following SLKT.


Mutation of the Nrf2 gene in non-small cell lung cancer.
Nrf2 (NFE2L2) is a transcription factor belonging to the Cap'N'Collar subfamily of basic-leucine zipper (bZIP) family of transcription factors, which plays a significant role in adaptive responses to oxidative stress. To investigate the relationship of between the mutation of Nrf2 gene and non-small cell lung cancer (NSCLC), in this study, we sequenced the Nrf2 gene from a total of 103 patients with NSCLC and corresponding blood samples. It is found that there is a discordance of Nrf2 mutations between NSCLC and corresponding blood samples. These differences may indicate that the variants in the Nrf2 gene are associated with an increased risk for lung cancer. In addition, the factor of smoking status is observed to play important roles in triggering the occurrence of the disorder.


An experimental manipulation of food and water: growth and time-space utilization of hatchling lizards (Sceloporus undulatus).
At a site in western Nebraska, we studied the effects of supplemental food and water on growth, survival, and habitat utilization of hatchling iguanid lizards, Sceloporus undulatus. Hatchlings were randomly assigned to one of four experimental groups and received either (1) supplemental food only, (2) supplemental water only, (3) supplemental food and water, or (4) neither supplemental food nor water (control). Neither supplemental food nor supplemental water affected growth rate in length, growth rate in mass, or size-specific body mass (i.e. robustness) at the end of the treatment period. Over the 45 day treatment pierod, there were no significant differences among treatment groups in survival, home-range size, or habitat utilization. There were, however, significant differences in the index of activity. Hatchlings in the treatment groups receiving supplemental water were sighted more often than hatchlings in the control group. We conclude that, during our study, neither food nor water limited growth but that water limited activity.


Application of interleukin-2-secreting syngeneic/allogeneic fibroblasts in the treatment of primary and metastatic brain tumors.
We found previously that mice injected intracerebrally (i.c.) with a mixture of malignant cells and allogeneic fibroblasts genetically engineered to secrete interleukin-2 (IL-2) survived longer than mice in various control groups. The primary goal of this study was to determine if an established i.c. glioma (Gl261) or breast carcinoma (SB-5b) could be treated by injection of IL-2-secreting allogeneic fibroblasts into the tumor region. As an additional objective, these results were compared with the effectiveness of injecting IL-2-secreting allogeneic fibroblasts prior to the introduction of the tumor cells as a means of preventing the development of an i.c. glioma or breast carcinoma. The results demonstrated that treatment of mice bearing an established i.c. glioma or breast carcinoma with IL-2-secreting allogeneic fibroblasts resulted in a prolonged survival. Furthermore, the results demonstrate a significant delay (P<.005) in the development of glioma in the animals treated with either allogeneic nonsecreting or IL-2-secreting fibroblasts prior to introduction of tumor cells. In addition, 50% of the animals pretreated with IL-2-secreting allogeneic fibroblasts injected subsequently with Gl261 glioma cells did not develop a tumor, whereas all of the animals injected with glioma cells alone and 92% of those treated with nonsecreting fibroblasts eventually died. Evidence also exists that long-term immunity was established in the treated animals because there was a significant prolongation of survival in comparison to naïve controls (P<.01) for those animals without evidence of glioma that previously had been immunized with treatment cells when challenged again with tumor cells. In a parallel experiment, 62% of the animals pretreated with nonsecreting allogeneic fibroblasts and 75% of the animals pretreated with allogeneic IL-2-secreting fibroblasts subsequently injected with SB-5b breast carcinoma cells did not develop tumors. The results indicate that IL-2-secreting allogeneic fibroblasts can be effective in the treatment of an established brain tumor. These data also suggest that i.c. injection of allogeneic IL-2-secreting fibroblasts is effective in prevention of the development of a brain tumor when the fibroblasts are introduced into the same site where the tumor is subsequently injected.


A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration.
Receptor tyrosine kinases (RTKs) are often overexpressed or mutated in cancers and drive tumor growth and metastasis. In the current model of RTK signaling, including that of MET, downstream phosphatidylinositol 3-kinase (PI3K) mediates both cell proliferation and cell migration, whereas the small guanosine triphosphatase (GTPase) Rac1 mediates cell migration. However, in cultured NIH3T3 and glioblastoma cells, we found that class I PI3K mediated oncogenic MET-induced cell migration but not anchorage-independent growth. In contrast, Rac1 regulated both processes in distinct ways. Downstream of PI3K, Rac1 mediated cell migration through its GTPase activity, whereas independently of PI3K, Rac1 mediated anchorage-independent growth in a GTPase-independent manner through an adaptor function. Through its RKR motif, Rac1 formed a complex with the kinase mTOR to promote its translocation to the plasma membrane, where its activity promoted anchorage-independent growth of the cell cultures. Inhibiting mTOR with rapamycin suppressed the growth of subcutaneous MET-mutant cell grafts in mice, including that of MET inhibitor-resistant cells. These findings reveal a GTPase-independent role for Rac1 in mediating a PI3K-independent MET-to-mTOR pathway and suggest alternative or combined strategies that might overcome resistance to RTK inhibitors in patients with cancer.


Nutritional and systemic metabolic disorders.
Vitamin deficiency disorders display a wide variety of neurologic signs and symptoms, the pathogenesis of which is not clearly understood. Metabolic encephalopathies (hepatic, hypoglycemic, and uremic) have to be considered in the differential diagnosis of patients with cognitive impairment, motor disturbances, psychiatric symptoms, seizures, and neuropathies. Calcifications (vascular wall and parenchymal) occur in the normal aging brain and in neurodegeneration; some associated genes are already described.


The effect of graded coronary stenosis on myocardial blood flow and left ventricular wall motion.
The effect of graded coronary stenosis on resting regional myocardial flow and left ventricular (LV) wall motion was studied in 18 anesthetized dogs. The left circumflex coronaary artery (LC) was constricted. The degree of LC stenosis and the changes in LV wall motion were determined by cineangiography of the coronary artery and LV. Regional myocardial flow was determined by tracer microspheres (TM), labeled with two different isotopes, Sr85, Sc46 or Ce141. The first TM1 and the second TM2 were infused after LC stenosis, and during a temporary complete LC occlusion respectively. Resting flow in areas with 70% stenosis was reduced, with a greater reduction of subendocardium and posterior papillary muscle, but minimum impairment of LV wall motion. No ST elevation was found. Animals with 80--90% stenosis showed a marked reduction of flow and wall motion, a significant ST-elevation and a delayed antegrade run-off in coronary arteriography.


Regeneration mechanism of a novel high-performance biochar mercury adsorbent directionally modified by multimetal multilayer loading.
Biochar that is directly obtained by pyrolysis exhibits a low adsorption efficiency; furthermore, the process of recycling adsorbents is ineffective. To solve these problems, conventional chemical coprecipitation, sol-gel, multimetal multilayer loading and biomass pyrolysis coking processes have been integrated. After selecting specific components for structural design, a novel high-performance biochar adsorbent was obtained. The effects of the O2 concentration and temperature on the regeneration characteristics were explored. An isothermal regeneration method to repair the deactivated adsorbent in a specific atmosphere was proposed, and the optimal regeneration mode and conditions were determined. The microscopic characteristics of the regenerated samples were revealed along with the mechanism of Hg0 removal and regeneration by using temperature-programmed desorption technology and adsorption kinetics. The results show that doping multiple metals can reduce the pyrolysis reaction barrier of the modified biomass. On the modified surface of the sample, the doped metals formed aggregated oxides, and the resulting synergistic effect enhanced the oxidative activity of the biochar carriers and the threshold effect of Ce oxide. The optimal regeneration conditions (5% O2 and 600 °C) effectively coordinated the competitive relationship between the deep carbonization process and the adsorption/oxidation site repair process; in addition, these conditions provided outstanding structure-effect connections between the physico-chemical properties and Hg0 removal efficiency of the regenerated samples. Hg0 adsorption by the regenerated samples is a multilayer mass transfer process that involves the coupling of physical and chemical effects, and the surface adsorption sites play a leading role.


Noninvasive Brain Stimulation Techniques for Treatment-Resistant Depression: Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation.
Transcranial magnetic stimulation is a safe, effective, and well-tolerated intervention for depression; it is currently approved for treatment-resistant depression. This article summarizes the mechanism of action, evidence of clinical efficacy, and the clinical aspects of this intervention, including patient evaluation, stimulation parameters selection, and safety considerations. Transcranial direct current stimulation is another neuromodulation treatment for depression; although promising, the technique is not currently approved for clinical use in the United States. The final section outlines the open challenges and future directions of the field.


MECP2 deletions and genotype-phenotype correlation in Rett syndrome.
Rett syndrome is a neurodevelopmental disorder that represents one of the most common genetic causes of mental retardation in girls. MECP2 point mutations in exons 2-4 account for about 80% of classic Rett cases and for a lower percentage of variant patients. We investigated the genetic cause in 77 mutation-negative Rett patients (33 classic, 31 variant, and 13 Rett-like cases) by searching missed MECP2 defects. DHPLC analysis of exon 1 and MLPA analysis allowed us to identify the defect in 17 Rett patients: one exon 1 point mutation (c.47_57del) in a classic case and 16 MECP2 large deletions (15/33 classic and 1/31 variant cases). One identical intragenic MECP2 deletion, probably due to gonadal mosaicism, was found in two sisters with discordant phenotype: one classic and one "highly functioning" preserved speech variant. This result indicates that other epigenetic or genetic factors, beside MECP2, may contribute to phenotype modulation. Three out of 16 MECP2 deletions extend to the adjacent centromeric IRAK1 gene. A putative involvement of the hemizygosity of this gene in the ossification process is discussed. Finally, results reported here clearly indicate that MECP2 large deletions are a common cause of classic Rett, and MLPA analysis is mandatory in MECP2-negative patients, especially in those more severely affected (P = 0.044).


Armadillo repeat-containing kinesin represents the versatile plus-end-directed transporter in Physcomitrella.
Kinesin-1, also known as conventional kinesin, is widely used for microtubule plus-end-directed (anterograde) transport of various cargos in animal cells. However, a motor functionally equivalent to the conventional kinesin has not been identified in plants, which lack the kinesin-1 genes. Here we show that plant-specific armadillo repeat-containing kinesin (ARK) is the long sought-after versatile anterograde transporter in plants. In ARK mutants of the moss Physcomitrium patens, the anterograde motility of nuclei, chloroplasts, mitochondria and secretory vesicles was suppressed. Ectopic expression of non-motile or tail-deleted ARK did not restore organelle distribution. Another prominent macroscopic phenotype of ARK mutants was the suppression of cell tip growth. We showed that this defect was attributed to the mislocalization of actin regulators, including RopGEFs; expression and forced apical localization of RopGEF3 partially rescued the growth phenotype of the ARK mutant. The mutant phenotypes were partially rescued by ARK homologues in Arabidopsis thaliana, suggesting the conservation of ARK functions in plants.


Exosomal miR-211 contributes to pulmonary hypertension via attenuating CaMK1/PPAR-γaxis.
Exsomes play a significant role in increasing pathophysiological processes by delivering their content. Recently, a variety of studies have showed exosomal microRNAs (miRNAs) are involved in pulmonary hypertension (PH) notably. In this study, we found that exosomal miR-211 was overexpressed in hypoxia-induced PH rats but its intrinsic regulation was unclear. Therefore, our aim was to reveal the underlying mechanism which overexpressed exosomal miR-211 targeted in the development of PH. 18 male SD rats were randomly divided into normoxia and hypoxia group, housed in normal or hypoxic chamber for 3 weeks respectively. Then, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance(PVR), right ventricular hypertrophy index(RV/(LV + S)), the percentage of medial wall area (WA%) and the percentage of medial wall thickness (WT%) were measured. Expression of miR-211 in exosomes was detected by qRT-PCR. Expression of Ca2+/calmodulin-dependent kinase1(CaMK1)and peroxisome proliferator-activated receptors-γ(PPAR-γ)in lung tissue were detected by Western blot(WB); After miR-211 overexpressed exosomes were injected to rats through caudal vein, mPAP, PVR, RV/(LV + S), WA% and WT% were also measured. Sequentially, hypoxia rats were injected with lentivirus riched in miR-211 inhibitor via tail vein, and PH-related indicators were measured. In vitro, after miR-211 was positively or negatively regulated in pulmonary arterial smooth muscle cell (PASMC) by plasmid transfection, proliferation of PASMC was detected by CCK8, as well as the expression of CaMK1 and PPAR- γ. Further, the relationship between CaMK1 and miR-211 was verified by Dual-Luciferase assay. And the regulatory relationship of CaMK1/PPAR- γ aixs was demonstrated in PASMC. Evident increases of mPAP, PVR, RVHI, WT% and WA% were observed with hypoxia administration. And the concentration of plasma exosomes in hypoxia rats was increased and positively correlated with the above indexes. miR-211 in exosomes of PH was upregulated while the expression of CaMK1 and PPAR-γ decreased in lung tissues. Further, injection of exosomes overexpressed with miR-211 demonstrated that exosomal miR-211 aggravated PH while inhibition of miR-211 attenuated PH in rats. In vitro, overexpression of miR-211 promoted the proliferation of PASMC and inhibited expression of CaMK1 and PPAR-γ in PASMC. And Dual-luciferase assay demonstrated that CaMK1 was a downstream gene of miR-211. Plasmid transfection experiments indicated that CaMK1 can promote PPAR-γ expression. Exosomal miR-211 promoted PH via inhibiting CaMK1/PPAR-γ axis, promoting PASMC proliferation in rats.


Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation.
The LAMC1 gene coding for the laminin gamma1 subunit was targeted by homologous recombination in mouse embryonic stem cells. Mice heterozygous for the mutation had a normal phenotype and were fertile, whereas homozygous mutant embryos did not survive beyond day 5.5 post coitum. These embryos lacked basement membranes and although the blastocysts had expanded, primitive endoderm cells remained in the inner cell mass, and the parietal yolk sac did not develop. Cultured embryonic stem cells appeared normal after targeting both LAMC1 genes, but the embryoid bodies derived from them also lacked basement membranes, having disorganized extracellular deposits of the basement membrane proteins collagen IV and perlecan, and the cells failed to differentiate into stable myotubes. Secretion of the linking protein nidogen and a truncated laminin alpha1 subunit did occur, but these were not deposited in the extracellular matrix. These results show that the laminin gamma1 subunit is necessary for laminin assembly and that laminin is in turn essential for the organization of other basement membrane components in vivo and in vitro. Surprisingly, basement membranes are not necessary for the formation of the first epithelium to develop during embryogenesis, but first become required for extra embryonic endoderm differentiation.


Production and characterisation of activated carbon and carbon nanotubes from potato peel waste and their application in heavy metal removal.
Herein, activated carbon (AC) and carbon nanotubes (CNTs) were synthesised from potato peel waste (PPW). Different ACs were synthesised via two activation steps: firstly, with phosphoric acid (designated PP) and then using potassium hydroxide (designated PK). The AC produced after the two activation steps showed a surface area as high as 833 m2 g-1 with a pore volume of 0.44 cm3 g-1, where the raw material of PPW showed a surface area < 4 m2 g-1. This can help aid and facilitate the concept of the circular economy by effectively up-cycling and valorising waste lignocellulosic biomass such as potato peel waste to high surface area AC and subsequently, multi-walled carbon nanotubes (MWCNTs). Consequently, MWCNTs were prepared from the produced AC by mixing it with the nitrogen-based material melamine and iron precursor, iron (III) oxalate hexahydrate. This produced hydrophilic multi-wall carbon nanotubes (MWCNTs) with a water contact angle of θ = 14.97 °. Both AC and CNT materials were used in heavy metal removal (HMR) where the maximum lead absorption was observed for sample PK with a 84% removal capacity after the first hour of testing. This result signifies that the synthesis of these up-cycled materials can have applications in areas such as wastewater treatment or other conventional AC/CNT end uses with a rapid cycle time in a two-fold approach to improve the eco-friendly synthesis of such value-added products and the circular economy from a significant waste stream, i.e., PPW. Graphical abstract .


The third multidisciplinary conference on drug research, Piła 2002. Effects of 1alpha,25-dihydroxyvitamin D3 and some putative steroid neuroprotective agents on the hydrogen peroxide-induced damage in neuroblastoma-glioma hybrid NG108-15 cells.
Steroids are implicated in the regulation of neurodegenerative processes including oxidative stress. The aim of this study was to compare the effects of 1alpha,25-dihydroxyvitamin D3 (calcitriol) and its low-calcemic analogue (24R)-1,24-dihydroxycholecalciferol (tacalcitol, PRI-2191) and some putative neuroprotective steroids belonging to various pharmacological groups on the hydrogen peroxide-induced cytotoxicity in NG108-15 cell line. Both secosteroids prevented in a concentration-dependent manner (50-500 nM) the hydrogen peroxide-induced lactate dehydrogenase release in the NG108-15 cells. Estrogens (17beta-estradiol and estriol, 100 and 1000 nM) also protected these cells. Of the two neurosteroids tested at micromolar concentrations, dehydroepiandrosterone sulphate markedly reduced cell damage, whereas the allopregnanolone showed a weak neuroprotective effect. These data support some previous observations on the antineurotoxic action of neurosteroids and indicate that calcitriol and its low-calcemic analogue PRI-2191 have neuroprotective properties comparable to those of estrogens. Considering the undesired effects of estrogens, it seems that some calcitriol analogues may be alternative drugs in the treatment of some oxidative stress-related neurodegenerative disorders.


Impaired thymic selection in mice expressing altered levels of the SLP-76 adaptor protein.
Intracellular signaling initiated by ligation of the TCR influences cell fate at multiple points during the lifespan of a T cell. This is especially evident during thymic selection, where the nature of TCR-dependent signaling helps to establish a MHC-restricted, self-tolerant T cell repertoire. The Src homology 2 domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76) adaptor protein is a required intermediate in multiple signaling pathways triggered by TCR engagement, several of which have been implicated in dictating the outcome of thymic selection (e.g., intracellular calcium flux and activation of ERK family MAPKs). To determine if thymocyte maturation and selection at later stages of development are sensitive to perturbations in SLP-76 levels, we analyzed these crucial events using several transgenic (Tg) lines of mice expressing altered levels of SLP-76 in the thymus. In Tg mice expressing low levels of SLP-76 in preselection thymocytes, the CD4:CD8 ratio in the thymus and spleen was skewed in a manner consistent with impaired selection and/or maturation of CD4+ thymocytes. Low SLP-76 expression also correlated with reduced CD5 expression on immature thymocytes, consistent with reduced TCR signaling potential. In contrast, reconstitution of SLP-76 at higher levels resulted in normal thymic CD5 expression and CD4:CD8 ratios in the thymus and periphery. It is curious that thymic deletion of TCR-Tg (HY) thymocytes was markedly impaired in both lines of Tg-reconstituted SLP-76-/- mice. Studies using chimeric mice indicate that the defect in deletion of HY+ thymocytes is intrinsic to the developing thymocyte, suggesting that maintenance of sufficient SLP-76 expression from the endogenous locus is a key element in the selection process.


Gastric cancer with synchronous unresectable hepatic metastasis and a positive response to chemotherapy--report of two cases.
We report herein the clinical events seen in two longterm survivors of gastric cancer with unresectable synchronous hepatic metastases. Partial gastrectomy was performed against the primary lesion and continuous intra-arterial infusion of anti-tumor drugs, followed by prolonged systemic antitumor drug treatment, were prescribed. A 43-year-old man with moderately-differentiated tubular adenocarcinoma had an uneventful course during his first 21 postoperative months. However, multiple liver metastases became manifest at 24 months and enlargement of the intrahepatic foci led to death 27 months after gastrectomy. A 51-year-old woman with moderately-differentiated tubular adenocarcinoma had an uneventful postoperative course and is now well with no signs of recurrence 6 years and 6 months after gastrectomy.


Evaluation of in vitro activity of ciclopirox olamine, butenafine HCl and econazole nitrate against dermatophytes, yeasts and bacteria.
In many instances, a cutaneous fungal infection may exist concomitantly with bacterial involvement. In this study we compared the in vitro activity of three antifungal agents against the dermatophytes, yeasts and bacteria recovered most commonly from cutaneous mycoses and bacterial infections. Using a microdilution method adapted from the National Committee for Clinical Laboratory Standards (NCCLS), we determined the minimum inhibitory concentrations (MICs) of ciclopirox olamine, econazole nitrate and butenafine HCl against a panel of dermatophyte fungi and yeasts (n = 39) and bacterial isolates (n = 45). All three antifungals demonstrated comparable activity against the dermatophytes tested, with a MIC range of 0.03-0.25 micro g/ml for ciclopirox, < 0.001-0.25 micro g/ml for econazole and 0.03-0.25 micro g/ml for butenafine. For yeasts, ciclopirox showed activity against all isolates, with an MIC range of 0.001-0.25 micro g/ml, whereas econazole had a broader range of 0.125-> 0.5 micro g/ml. Butenafine displayed limited activity against the yeast Candida albicans and no activity against Malassezia furfur. For the antibacterial activity studies, ciclopirox demonstrated activity against all isolates tested with a range of 0.06-2 micro g/ml, while econazole showed activity against Gram-positive bacteria only, with a MIC range of 0.004-0.25 micro g/ml. Butenafine HCl had a limited activity against bacterial isolates tested, showing activity against beta-hemolytic Streptococcus Group A and Corynebacterium only. Neither econazole nitrate nor butenafine HCl demonstrated activity against any of the Gram-negative strains evaluated in this study. The data suggest that ciclopirox olamine has the broadest in vitro activity, in comparison to econazole and butenafine HCl, against bacteria, yeasts and bacteria. These findings may have implications in the use of these antimycotics in the treatment of mixed cutaneous infections where bacteria or yeasts are present in addition to dermatophytes.


Basiliximab as maintenance immunosuppression in heart transplant recipients: A single pediatric center experience.
Pediatric heart transplant recipients are at risk for complications from prolonged exposure to immunosuppressive drugs, pharmacokinetic challenges in maintaining consistent immunosuppression, and medication non-adherence. Basiliximab (BAS), an interleukin-2 receptor antagonist, is used for induction therapy across many pediatric heart transplant centers, but use as maintenance immunosuppression has not been well described. This was a retrospective, single pediatric center cohort study of heart transplant recipients who received BAS for maintenance immunosuppression (defined as >2 monthly doses) from January 1, 2011, to December 31, 2021. Ten patients met study criteria with a median age of 17.5 (5-22) years and median 9.6 (1.2-18.9) years since transplant at time of BAS initiation. The primary indications for BAS use were recurrent rejection (n = 4), fluctuating immunosuppression levels (n = 3), and renal dysfunction (n = 3). A median of 5.5 (3-32) monthly BAS doses were received. Three patients had a rejection event while on BAS. Calcineurin inhibitor exposure was reduced in 70% of patients. Three of the 10 patients were alive at last follow-up. There was one documented infection during BAS use, and no hypersensitivity reactions. Monthly BAS infusions were well tolerated and allowed for reduced calcineurin inhibitor exposure in most patients. Mortality commonly occurred despite BAS use, potentially reflecting the acuity of this patient cohort. BAS can be considered for maintenance immunosuppression in pediatric patients with fluctuating immunosuppressive levels and/or renal dysfunction. More studies are needed to determine long-term outcomes and explore expanded use of BAS in the pediatric heart transplant population.


Drug-drug interactions among hospitalized elderly in patients at medical wards of Northwest Ethiopia's Comprehensive Specialized Hospitals: A multicenter observational study.
Drug-drug interactions are of major concern due to links to untoward drug effects, hospitalizations, and serious health impacts. Elderly patients are more predisposed to drug interactions than younger patients. The present study aimed to find out the prevalence of drug-drug interactions at North West Ethiopian compressive specialized hospitals' Internal Medicine wards. From 30 April to 30 July 2021 GC, a multicenter prospective observational study was conducted at north Ethiopian specialized hospitals. Data was collected by using a structured questionnaire adapted from different literature and medical records at the North West Ethiopian Comprehensive Specialized Hospitals' Internal Medicine wards during the study period. Thereafter checked the completeness of the collected data was checked drug-drug interactions by using Medscape. Epi data version 4.6.2 software was used as data clearance and STATA version 14.1 was used for further data analysis. A total of 389 subjects participated in the study of which more than half (55.53%) of them were female with a mean (SD) age of 68.9 ± 7.46 years. A total of 641 drug-drug interactions were detected in this investigation of which, 225(35.1%) were major, 299(46.6%) were significant interactions, and 117(18.3%) were minor interactions. Hospital stay (AOR = 5.95 CI: 3.49-10.12), retire (AOR = 6.71 CI: 1.26-35.78), 5-9 drugs (AOR = 5.30 CI: 2.91-9.67) and more than 10 drugs (AOR = 8.03 CI: 2.47-26.07) were important risk factors for drug-drug interactions. The findings of this study suggest that drug-drug interactions were high among hospitalized elderly patients. The presence of polypharmacy, to be retired, and hospital stayed were all found to be strongly linked with drug-drug interactions.


Quality of life and fatigue before and after radiotherapy in breast cancer patients.
Cancer-related fatigue (CRF) is a common side effect of cancer treatment, particularly in breast cancer patients. Over the past decade, the multimodal management of breast cancer has undergone several changes, such as the establishment of postoperative hypofractionated radiotherapy (RT) as a new standard protocol and the reduced use of chemotherapy. The aim of the current study was to investigate the impact of these changes on quality of life (QoL) and CRF. A total of 66 patients was assessed for QoL and CRF using the FACIT‑F questionnaire. Patients were asked to complete the paper-based questionnaire before (TP1) and at the end of radiotherapy (TP2) as well as at follow-up (TP3). Subgroups were compared based on fractionation and previous application of chemotherapy. For the entire cohort, no significant changes in the severity of fatigue were seen. A mild decrease of physical wellbeing (PWB) from TP1 to TP2 was observed (22.2 vs. 20.7, p = 0.007). Fatigue at TP1 was more severe in patients receiving chemotherapy before RT (37.9 vs. 30.5, p = 0.041). Only patients without preceding chemotherapy showed a significant worsening of fatigue from TP1 to TP2 (37.9 vs 34.8, p = 0.005). The same is true for physical wellbeing (PWB), with a decrease from TP1 to TP2 in chemotherapy-naïve patients only (23.5 vs. 21.4, p = 0.002). Fractionation did not impact any of the investigated endpoints. Patients undergoing postoperative RT for breast cancer constitute a heterogeneous patient population with varying risks of developing CRF influenced by previous treatments. Therefore, patient selection seems to be critical when interventional studies addressing CRF during radiotherapy are designed.


Effects of HIV and antiretroviral therapy on resting energy expenditure in adult HIV-infected women-a matched, prospective, cross-sectional study.
Several studies have reported increased resting energy expenditure (REE) in people with human immunodeficiency virus (HIV). However, limited data exist on REE in HIV-infected women and the effect of antiretroviral therapy (ART) on REE in this population. The purpose of this study was to compare REE in healthy controls to adult HIV-infected women classified in three groups: naïve to ART, on ART with virologic suppression, and on ART with an HIV-1 RNA level >5,000 copies/mL. After a fast, body composition by bioelectrical impedance analysis and REE by indirect calorimetry were determined. Anthropometric measures were also taken. Distributionally appropriate two-sample tests were used for between-group analyses and analysis of covariance was used for confounding adjustment. Eighty-seven women were enrolled and the HIV-infected and control women were matched for age and body mass index. Log-transformed REE was significantly higher in HIV-infected women naïve to ART compared to controls (7.26±0.22 vs 7.14±0.19; P=0.04, respectively) and the difference remained significant after adjustment for body cell mass (P=0.008). Log-transformed REE was not different in HIV-infected women on ART compared to HIV-infected women naïve to ART (7.25±0.25 vs 7.26±0.23; P=0.81, respectively). Adjusting for body cell mass did not change the results (P=0.56). Similarly, REE was not different between women naïve to ART and those on ART with undetectable HIV-1 RNA, regardless of adjustment for body cell mass. REE correlated to current and nadir CD4 count and trended toward a negative correlation with HIV-1 RNA levels. We showed that REE is elevated in ART-naïve, HIV-infected women and continues to be elevated when on ART, regardless of virologic suppression, compared to age and body mass index-matched healthy women. This suggests an effect of HIV infection itself and not ART on REE in these HIV-infected women, and should be considered during nutrition assessment and counseling of HIV-infected adult women.


Parental opinions about clinical research.
To characterize parental perception of clinical research, particularly in emergency settings. To identify specific aspects of clinical research that concern parents and to discuss how these concerns can be addressed. Quantitative and qualitative survey in tertiary care children's hospital and affiliated clinics. Family caregivers (n = 136) participated in this study; 81% of study participants agreed or strongly agreed that physicians should do research involving children, with 5% disagreeing. However, 18% felt that researchers care more about the research than about the patient, and 13% believed that when a child is in a research study, physicians must follow the research protocol even if it is not in the best interest of the child. Participants were significantly less likely to endorse the conduct of research in an emergency setting than in a nonspecified setting (P < .001). Parents' foremost concern about emergency research was that it could delay therapy or distract physicians' attention from the child's needs. Parents largely support pediatric clinical research, but they have specific concerns that should be addressed in research planning and in communicating with parents about clinical research.


Deconvolution-based distortion correction of EPI using analytic single-voxel point-spread functions.
To develop a postprocessing algorithm that corrects geometric distortions due to spatial variations of the static magnetic field amplitude, B0 , and effects from relaxation during signal acquisition in EPI. An analytic, complex point-spread function is deduced for k-space trajectories of EPI variants and applied to corresponding acquisitions in a resolution phantom and in human volunteers at 3 T. With the analytic point-spread function and experimental maps of B0 (and, optionally, the effective transverse relaxation time, T2* ) as input, a point-spread function matrix operator is devised for distortion correction by a Thikonov-regularized deconvolution in image space. The point-spread function operator provides additional information for an appropriate correction of the signal intensity distribution. A previous image combination algorithm for acquisitions with opposite phase blip polarities is adapted to the proposed method to recover destructively interfering signal contributions. Applications of the proposed deconvolution-based distortion correction ("DecoDisCo") algorithm demonstrate excellent distortion corrections and superior performance regarding the recovery of an undistorted intensity distribution in comparison to a multifrequency reconstruction. Examples include full and partial Fourier standard EPI scans as well as double-shot center-out trajectories. Compared with other distortion-correction approaches, DecoDisCo permits additional deblurring to obtain sharper images in cases of significant T2* effects. Robust distortion corrections in EPI acquisitions are feasible with high quality by regularized deconvolution with an analytic point-spread function. The general algorithm, which is publicly released on GitHub, can be straightforwardly adapted for specific EPI variants or other acquisition schemes.


Endovascular Management of Diseases in Relation to Otolaryngology.
Endovascular techniques can be utilized in many common otolaryngologic conditions. Advancements in in these techniques including but not limited to better distal access catheters, new embolization materials and stents allows this to be a relatively safe and successful procedure. Here we highlighted a few related procedures.


The effect of nasal polyp epithelial cells on eosinophil activation.
Eosinophil infiltration into an inflammatory site is a characteristic histological finding in patients with chronic rhinosinusitis and nasal polyps. Most of the eosinophils in chronic rhinosinusitis are activated in the nasal cavity, but the exact activation mechanism of eosinophils is unknown. The study was designed to investigate the effect of human nasal epithelial cells on the activation of eosinophils. Peripheral blood eosinophils were isolated from healthy volunteers and incubated in human nasal polyp epithelial cell conditioned media (HPECM). Superoxide production and eosinophil-derived neurotoxin were measured to determine eosinophils activation. HPECMs were assayed by ELISAs for interleukin-8 (IL-8), granulocyte-macrophage colony stimulating factor (GM-CSF), eotaxin, and regulated on activation normal T expressed and secreted (RANTES). To identify the chemical mediators involved in the activation of eosinophils. HPECM (n = 7) contained 31.48 ng/mL interleukin-8, 533.43 pg/mL GM-CSF, 5.90 pg/mL eotaxin, and 11.06 pg/mL RANTES. Eosinophils were activated by HPECM and inhibited only by anti-GM-CSF antibody, not by the other chemical mediators. The results suggest that eosinophils in nasal secretions are activated by GM-CSF, which is produced by nasal epithelial cells.