Engineered myocardial tissues constructed in vivo using cardiomyocyte-like cells derived from bone marrow mesenchymal stem cells in rats.
To explore the feasibility of constructing engineered myocardial tissues (EMTs) in vivo, using polylactic acid -co-glycolic acid (PLGA) for scaffold and cardiomyocyte-like cells derived from bone marrow mesenchymal stem cells (BMMSCs) for seeded cells. BMMSCs were isolated from femur and tibia of Sprague-Dawley (SD) rats by density-gradient centrifugation. The third passage cells were treated with 10 μmol/L 5-azacytidine (5-aza) and 0.1 μmol/L angiotensin II (Ang II) for 24 h, followed by culturing in complete medium for 3 weeks to differentiated into cardiomyocyte-like cells. The cardiomyocyte-like cells were seeded into PLGA scaffolds to form the grafts. The grafts were cultured in the incubator for three days and then implanted into the peritoneal cavity of SD rats. Four weeks later, routine hematoxylin-eosin (HE) staining, immunohistochemical staining for myocardium-specific cardiac troponin I (cTnI), scanning electron microscopy and transmission electron microscopy were used to analyze the morphology and microconstruction of the EMTs in host rats. HE staining showed that the cardiomyocyte-like cells distributed equally in the PLGA scaffold, and the nuclei arranged in the spindle shape. Immunohistochemical staining revealed that majority of engrafted cells in the PLGA -Cardiomyocyte-like cells group were positive for cTnI. Scanning electron microscopy showed that the inoculated cells well attached to PLGA and grew in 3 dimensions in construct. Transmission electron microscopy showed that the EMTs contained well arranged myofilaments paralleled to the longitudinal cell axis, the cells were rich in endoplasmic reticulum and mitochondria, while desmosomes, gap junction and Z line-like substances were also can be observed as well within the engrafted cells. We have developed an in vivo method to construct engineered myocardial tissue. The in vivo microenvironment helped engrafted cells/tissue survive and share similarities with the native heart tissue.


Predictive value of pretreatment positron emission tomography/computed tomography in patients with newly diagnosed extranodal natural killer/T-cell lymphoma.
The role of (18)Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in extranodal natural killer/T-cell lymphoma (ENKL) is not well established. This study aimed to investigate the prognostic role of the pretreatment maximum standardized uptake value (SUV(max)) on PET/CT in patients with newly diagnosed ENKL. Among 364 consecutive patients with newly diagnosed ENKL, 81 patients were included and reviewed. The impact of SUV(max) on survival and the relationship between SUV(max) and other clinicopathological parameters were analyzed. The median SUV(max) was 14.6 (range 2.0-45.4). The optimal cutoff value of SUV(max) to predict overall survival (OS) was 15. Patients with high SUV(max) (SUVmax >15) were associated with bulky disease (P < 0.001), local invasion (P = 0.030), high score of Korean Prognostic Index (KPI, P = 0.046), resistance to primary treatment (P = 0.014), poor OS (P < 0.001), and unfavorable progression-free survival (P < 0.001). With a median follow-up of 25.0 months, the median OS was 63.0 months (range 2.0-99.0 months). Multivariate analyses revealed the following independent prognostic factors for OS: age >60 years (P = 0.001), stage III-IV (P = 0.023), SUV(max) >15 (P = 0.020), and bulky disease (>5 cm) (P = 0.002). By using the SUV(max), patients in most subgroups stratified by the KPI or the International Prognostic Index (IPI) were further discriminated in OS with significant statistical difference. Our results suggest the pretreatment SUV(max) is predictive of prognosis in patients with newly diagnosed ENKL. The SUV(max) may provide additional prognostic information for IPI and KPI.


Bépridil a new effector of oxidative phosphorylations.
Bépridil action on oxidative phosphorylations depends on the nature of the oxidized substrate. Thus it seemed to act as an uncoupler on the FAD-linked substrates as we have shown with succinate. But this property could not be applied to the NAD-linked substrates. Thus, in the presence of Bépridil, ADP would have opposite effects on the electron flow across the first site of oxidative phosphorylations; from one side the direct electron flow was decreased while from the other side, the reverse one was increased. Confirming this difference in its action, Bépridil did not affect the oxidative phosphorylation property of the cytochrome oxidase as could be deduced from the invariability of TMPD + ascorbate oxidation whether Bépridil was added or not. Moreover the effect of Bépridil on the P/O ratio was a dramatic demonstration of its selectivity. As a matter of fact this ratio was increased to a value near 5 for the NAD-linked substrate while it was decreased to near 0.4 with the FAD-linked substrate.


Atrial fibrillation ablation in a patient complicated by persistent left superior vena cava and absent right superior vena cava.
A comparison between the three-dimensional contact mapping created by the Ensite system and that created by contrast-enhanced computed tomography angiography (CTA). Right atrial appendage was not well delineated on CTA.


Melody recognition at fast and slow tempos: effects of age, experience, and familiarity.
Eighty-one listeners defined by three age ranges (18-30, 31-59, and over 60 years) and three levels of musical experience performed an immediate recognition task requiring the detection of alterations in melodies. On each trial, a brief melody was presented, followed 5 sec later by a test stimulus that either was identical to the target or had two pitches changed, for a same-different judgment. Each melody pair was presented at 0.6 note/sec, 3.0 notes/sec, or 6.0 notes/sec. Performance was better with familiar melodies than with unfamiliar melodies. Overall performance declined slightly with age and improved substantially with increasing experience, in agreement with earlier results in an identification task. Tempo affected performance on familiar tunes (moderate was best), but not on unfamiliar tunes. We discuss these results in terms of theories of dynamic attending, cognitive slowing, and working memory in aging.


Limbic correlates of fearlessness and disinhibition in incarcerated youth: Exploring the brain-behavior relationship with the Hare Psychopathy Checklist: Youth Version.
The purpose of this study was to determine whether scores on two temperament dimensions (fearlessness and disinhibition) correlated differentially with gray matter volumes in two limbic regions (amygdala and hippocampus). It was predicted that the fearlessness dimension would correlate with low gray matter volumes in the amygdala and the disinhibition dimension would correlate with low gray matter volumes in the hippocampus after controlling for age, IQ, regular substance use, and total brain volume. Participants were 191 male adolescents (age range=13-19 years) incarcerated in a maximum-security juvenile facility. Structural magnetic resonance imaging (MRI) analysis of the limbic and paralimbic regions of the brain was conducted. The temperament dimensions were estimated with items from the Psychopathy Checklist: Youth Version (PCL: YV: Forth et al., 2003). Analyses showed that the fearlessness dimension correlated negatively with gray matter volumes in the amygdala and the disinhibition dimension correlated negatively with gray matter volumes in the hippocampus but not vice versa. These findings provide preliminary support for the construct validity of the fearlessness and disinhibition temperament dimensions and offer confirmatory evidence for involvement of the amygdala and hippocampus in fear conditioning and behavioral inhibition, respectively.


[A 4-year-old girl with a recurrent infection in the neck: a familiar picture with a rare cause].
Infections of the neck are frequently seen in young children and are usually harmless and transient. In the case of atypical symptoms, however, it is important to be alert to the possibility of less common causes requiring specific treatment. A 4-year-old girl was seen in the outpatient clinic with a recurrent, inflamed swelling in the neck. The swelling persisted despite repeated incision and drainage. Further investigation with MRI revealed a primary branchial cleft fistula, Work type 2. The epithelialized cartilaginous fistula tract ran from the external auditory canal to the neck, very close to the facial nerve, but could be surgically removed without damage to the nerve. In a child with a recurrent swelling or abscess in the neck, with or without a fistula, an extensive differential diagnosis is required including branchial cleft fistula.


Quantitation of Na+/K(+)-ATPase and glucose transporter isoforms in rat adipocyte plasma membrane by immunogold labeling.
We have quantitated and studied the topology of isoforms of the Na+/K(+)-ATPase and of the glucose transporter in rat adipocyte plasma membranes. Adipocytes were incubated with or without insulin for 15 min. Sheets of native plasma membrane, with the cytoplasmic face exposed, were prepared by adsorption to EM grids. Grids were incubated in parallel with monoclonal antibodies against the Na+/K(+)-ATPase isoforms alpha 1 and alpha 2, and the glucose transporter isoforms GLUT1 and GLUT4, followed by immunogold labeling, negative staining and quantitation by counting of the gold particles in electron micrographs. In addition, the distribution of glucose transporters and Na+/K(+)-ATPase isoforms in subcellular membrane fractions prepared by an established fractionation procedure was monitored by Western blotting. We found that the Na+/K(+)-ATPases and the glucose transporters were confined to the planar part of the plasma membrane, without association to caveolar invaginations. The vast majority of the Na+/K(+)-ATPase molecules in the adipocyte plasma membrane were of the alpha 2 isoform; GLUT4 was the dominating glucose transporter isoform. The total number of Na+/K(+)-ATPase molecules labeled in the plasma membrane was 3.5 x 10(5) per cell, independent of insulin stimulation. Concomitantly, insulin increased GLUT4 labeling sevenfold to a value of 3.5 x 10(5) per cell.


A Graph Based Framework to Model Virus Integration Sites.
With next generation sequencing thousands of virus and viral vector integration genome targets are now under investigation to uncover specific integration preferences and to define clusters of integration, termed common integration sites (CIS), that may allow to assess gene therapy safety or to detect disease related genomic features such as oncogenes. Here, we addressed the challenge to: 1) define the notion of CIS on graph models, 2) demonstrate that the structure of CIS enters in the category of scale-free networks and 3) show that our network approach analyzes CIS dynamically in an integrated systems biology framework using the Retroviral Transposon Tagged Cancer Gene Database (RTCGD) as a testing dataset.


RadWise: A Rank-Based Hybrid Feature Weighting and Selection Method for Proteomic Categorization of Chemoirradiation in Patients with Glioblastoma.
Glioblastomas (GBM) are rapidly growing, aggressive, nearly uniformly fatal, and the most common primary type of brain cancer. They exhibit significant heterogeneity and resistance to treatment, limiting the ability to analyze dynamic biological behavior that drives response and resistance, which are central to advancing outcomes in glioblastoma. Analysis of the proteome aimed at signal change over time provides a potential opportunity for non-invasive classification and examination of the response to treatment by identifying protein biomarkers associated with interventions. However, data acquired using large proteomic panels must be more intuitively interpretable, requiring computational analysis to identify trends. Machine learning is increasingly employed, however, it requires feature selection which has a critical and considerable effect on machine learning problems when applied to large-scale data to reduce the number of parameters, improve generalization, and find essential predictors. In this study, using 7k proteomic data generated from the analysis of serum obtained from 82 patients with GBM pre- and post-completion of concurrent chemoirradiation (CRT), we aimed to select the most discriminative proteomic features that define proteomic alteration that is the result of administering CRT. Thus, we present a novel rank-based feature weighting method (RadWise) to identify relevant proteomic parameters using two popular feature selection methods, least absolute shrinkage and selection operator (LASSO) and the minimum redundancy maximum relevance (mRMR). The computational results show that the proposed method yields outstanding results with very few selected proteomic features, with higher accuracy rate performance than methods that do not employ a feature selection process. While the computational method identified several proteomic signals identical to the clinical intuitive (heuristic approach), several heuristically identified proteomic signals were not selected while other novel proteomic biomarkers not selected with the heuristic approach that carry biological prognostic relevance in GBM only emerged with the novel method. The computational results show that the proposed method yields promising results, reducing 7k proteomic data to 7 selected proteomic features with a performance value of 93.921%, comparing favorably with techniques that do not employ feature selection.


Comprehensive assessment of quality of life and psychosocial adjustment in patients with renal tumors undergoing open, laparoscopic and nephron sparing surgery.
We prospectively evaluated the general and cancer specific quality of life, and psychosocial adjustment of patients with a renal mass treated with radical vs partial nephrectomy via a laparoscopic or an open approach. A total of 172 patients with renal tumors completed questionnaires before surgery, and 3 weeks, and 2, 3, 6 and 12 months postoperatively. We assessed general quality of life using SF-36™ and cancer specific quality of life using the Cancer Rehabilitation Evaluation System-Short Form, in addition to intrusive thoughts, avoidance behaviors and fear of recurrence. We used mixed model regression analysis to compare these measures across surgery types during the study course, adjusted for tumor size, histology, stage and renal function. The SF-36 physical component score differed significantly by surgery type with time (p = 0.04). Patients treated with laparoscopy improved by month 2 while those treated with open surgery had poorer quality of life until month 3. Better cancer specific quality of life was reported in patients who underwent radical vs partial nephrectomy. Age also had a significant effect on outcomes. We report one of the most comprehensive patient reported prospective quality of life studies in patients with renal cell carcinoma. There were significant differences in quality of life and psychosocial adjustment outcomes during 1 year among patients treated with 1 of 4 commonly accepted surgical renal procedures. These outcomes must be evaluated in the context of tumor characteristics, cancer specific outcomes and renal function. These quality of life issues may be important to consider when choosing surgical procedures for patients with renal tumors.


Effects of chlordecone exposure on brain neurotransmitters: possible involvement of the serotonin system in chlordecone-elicited tremor.
The purpose of this study was to correlate the chlordecone-elicited tremor activity with alterations of brain neurotransmitters. A single injection of chlordecone (80 mg/kg, ip) significantly increased the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) but did not affect the concentrations of dopamine, dihydroxphenylacetic acid, aspartate, taurine, glutamate, glycine, and gamma-aminobutyric acid (GABA). There was a dose- and time-related correlation between the increases in striatal 5-HIAA levels and tremor after chlordecone treatment. A subsequent study with pargyline indicated that the increase in striatal 5-HIAA level represented an increase in the turnover of serotonin. This study plus the previous finding that pizotifen (BC-105), a serotonin receptor blocker, attenuated chlordecone-elicited tremor strongly suggests a possible involvement of the serotonin system in mediating the tremor elicited by this insecticide.


[X-ray microanalysis of the fundamental composition of the hemolymph of the mollusk Mytilus edulis].
X-ray microanalysis of the content of Na, K, Cl, Ca, P, S and Mg has been made in ultrasmall samples of haemolymph of the mussel Mytilus edulis living in habitats with lowered salinity. It was shown that the content of potassium in the haemolymph is higher than in the environment, both natural and artificial. Coefficient of potassium accumulation in relation to the environment increases with the decrease of external salinity.


Interventions for oropharyngeal dysphagia in acute and critical care: a protocol for a systematic review and meta-analysis.
Oropharyngeal dysphagia or swallowing difficulties are common in acute care and critical care, affecting 47% of hospitalised frail elderly, 50% of acute stroke patients and approximately 62% of critically ill patients who have been intubated and mechanically ventilated for prolonged periods. Complications of dysphagia include aspiration leading to chest infection and pneumonia, malnutrition, increased length of hospital stay and re-admission to hospital. To date, most dysphagia interventions in acute care have been tested with acute stroke populations. While intervention studies in critical care have been emerging since 2015, they are limited and so there is much to learn about the type, the delivery and the intensity of treatments in this setting to inform future clinical trials. The aim of this systematic review is to summarise the evidence regarding the relationship between dysphagia interventions and clinically important patient outcomes in acute and critical care settings. We will search MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL and clinical trial registries from inception to the present. We will include studies conducted with adults in acute care settings such as acute hospital wards or units or intensive care units and critical care settings. Studies will be restricted to randomised controlled trials and quasi-randomised controlled trials comparing a new dysphagia intervention with usual care or another intervention. The main outcomes that will be collected include length of time taken to return to oral intake, change in incidence of aspiration and pneumonia, nutritional status, length of hospital stay and quality of life. Key intervention components such as delivery, intensity, acceptability, fidelity and adverse events associated with such interventions will be collected to inform future clinical trials. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. A meta-analysis will be conducted as appropriate. No systematic review has attempted to summarise the evidence for oropharyngeal dysphagia interventions in acute and critical care. Results of the proposed systematic review will inform practice and the design of future clinical trials. PROSPERO CRD 42018116849 (http://www.crd.york.ac.uk/PROSPERO/).


Combined measles-mumps-rubella-varicella vaccine and febrile convulsions: the risk considered in the broad context.
Studies on quadrivalent measles, mumps, rubella, and varicella (MMRV) vaccines have indicated a twofold increased relative risk of febrile convulsion (FC) after the first dose compared to MMR and V administered at the same medical visit (MMR+V). This narrative review contextualizes FC occurrence after the first MMRV vaccine dose from a clinical perspective and outlines approaches to attenuate FC occurrence post-vaccination. While the relative FC risk increases after the first dose of MMRV compared to MMR+V vaccine in measles-naïve infants, the attributable risk is low versus the overall FC risk in the pediatric population triggered by other causes, like natural exposure to pathogens or routine vaccination. No increased risk of FC has been reported after MMRV co-administration with other routine vaccines compared to MMRV alone. Based on our findings and considering the MMRV vaccination benefits (fewer injections, higher coverage, better vaccination compliance), the overall benefit-risk profile of MMRV vaccine is considered to remain positive. Potential occurrence of FC in predisposed children (e.g. with personal/family history of FC) may be attenuated if they receive MMR+V instead of MMRV as the first dose. It is also important to monitor vaccinees for fever during the first 2 weeks post-vaccination.


Systematic Review of mHealth Applications That Interface with Inhaler Sensors in Asthma.
A better understanding of outcomes associated with mobile health (mHealth) applications (apps) for asthma self-management that pair with inhaler sensor technology is needed for clinicians to practice evidence-based medicine. To evaluate the effects of mHealth apps that integrate with an inhaler-based sensor on outcomes of patients with asthma. We performed a systematic review in GooglePlay and Apple App stores for consumer-facing mHealth apps for asthma management that pair with an inhaler-based sensor. We then searched for evidence evaluating these apps via PubMed and Cochrane Central (January 2007-May 2020), bibliographies on product websites, and www.clinicaltrials.gov. We included studies in patients with asthma evaluating apps discovered in the app stores on adherence or a health outcome of interest, and qualitatively summarized evidence. We identified 6 mHealth apps and screened 2594 citations for evidence on these apps; 7 studies of 2 apps were included. Interventions modestly improved maintenance inhaler adherence and reduced rescue inhaler use but did not impact Asthma Control Test scores. Effects on exacerbations, quality of life, and pulmonary function were not evaluated in these studies. The current literature evaluating mHealth apps paired with inhaler-based sensors focuses on a small number of available products and has limitations in quality. Positive effects on rescue inhaler use, inhaler adherence, and patient satisfaction were found. However, more comprehensive evaluation of products and their impact on health outcomes is needed before clinicians and patients can weigh the benefits against resources needed to adopt these technologies.


Specific characteristics of spontaneous movements in preterm infants at term age are associated with developmental delays at age 3 years.
The aim of this study was to investigate the relationship between the characteristics of spontaneous movements in preterm infants at term age and developmental delay at 3 years of age. We analysed video recordings of the spontaneous movements in the supine position of 124 preterm infants (44 males, 80 females) at 36 to 44 weeks postmenstrual age (PMA). The infants were born preterm (22-36wks PMA; birthweight 489-1696g) and had not received a diagnosis of a neurological or developmental disorder by the age of 3 years. The recorded spontaneous movements were quantified using six movement indices, which were calculated from two-dimensional trajectories of all limbs. The infants were divided into three developmental groups, normal, borderline, or delayed, based on their developmental quotient as calculated using the Kyoto Scale of Psychological Development 2001 (Kyoto Scale) at 3 years of age. Group differences in the movement indices were analysed. In the delayed group, average velocity of arms and legs were significantly lower (p<0.05 and p<0.01 respectively), the numbers of movement units of arms and legs were significantly lower (p<0.05 and p<0.01 respectively), kurtosis of acceleration of arms and legs was significantly higher (p<0.05 in each case), and correlation between limb velocities was higher (p<0.05) than in the normal group. In children who exhibited developmental delay at 3 years of age, the spontaneous movements at term age can be described as less active with intermittent occurrences of abrupt and synchronized movements of the limbs. Recognition of these characteristics of spontaneous movements at term age may be used as a predictor for subsequent cognitive and behavioural development in preterm infants.


Association between pregnancy and pregnancy loss with COPD in Chinese women: The China Kadoorie Biobank study.
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by airflow blockage. Pregnancy and pregnancy loss may be related to an elevated risk of COPD, although studies have yet to report on this association. Hence, this study aims to investigate the association between pregnancy and pregnancy loss with the risk of COPD among Chinese women. Data on 302,510 female participants from the China Kadoorie Biobank were utilized for this study. Multivariable logistic regression, stratified by sociodemographic and lifestyle factors, was employed to obtain the odds ratio (ORs) and 95% confidence intervals (CIs) for the association between pregnancy and pregnancy loss with COPD. Pregnancy loss was significantly associated with increased risk of COPD (OR 1.19, 95% CI 1.13-1.25), specifically, spontaneous (OR 1.19, 95% CI 1.11-1.29) and induced abortion (OR 1.18, 95% CI 1.12-1.25). Stillbirth, however, was not significantly associated with the risk of COPD (OR 1.09, 95% CI 0.99-1.20). Increasing number of pregnancy losses was associated with increasing risk of COPD (one pregnancy loss: OR 1.14, 95% CI 1.07-1.21, two or more pregnancy loss: OR 1.25, 95% CI 1.17-1.32, and each additional pregnancy loss: OR 1.06, 95% CI 1.03-1.09). A single pregnancy was significantly associated with reduced risk of COPD (OR 0.75, 95% CI 0.59-0.97), although each additional pregnancy was significantly associated with increased risk of COPD (OR 1.03, 95% CI 1.01-1.04). Pregnancy loss, in particular, spontaneous and induced abortions are associated with increased risk of COPD among Chinese women. A single pregnancy, however, demonstrated protective effects.


Heavy drinking in a population of methadone-maintained clients.
The purpose of this study was to clarify the relationship between heavy use of alcohol and response to methadone treatment. A sample of clients showing three or more DSM-III-R symptoms (n = 79) were identified and compared with a sample of heavy-drinking clients (n = 108) with less than three alcohol dependency symptoms on admitting characteristics and on tenure in treatment. As expected, clients meeting DSM-III-R dependency criteria were significantly more likely to show evidence of psychological problems and dysfunction of family and peer relations at admission. An unexpected finding was that they were also more likely to remain in treatment longer than drinking clients who did not report dependency. Alcohol dependent clients were significantly more likely to have prior experience with self-help groups, which may reflect less denial and therefore relatively better ability to focus on opiate dependency problems. Failure to differentiate between alcohol dependent and nondependent groups of drinkers enrolled in methadone treatment may help account for reported differences in treatment outcome studies. Recognizing these different types of drinkers also may help clinicians plan more effective treatments.


Naidispora caidianensis n. gen. n. sp. infecting coelomocytes of oligochaete Branchiura sowerbyi (Oligochaeta: Naididae) in China.
A new microsporidian parasite, Naidispora caidianensis n. gen. n. sp. was found in coelomocytes of oligochaete Branchiura sowerbyi Beddard, 1892 from Wuhan city, Hubei Province, China. Opaque, hypertrophied coelomocytes (0.17-0.24 mm in diameter) depicted clinical signs of infection. Electron microscopy revealed a microsporidian with monokaryotic life stages. Rounded uninucleate meronts subsequently transformed into multinucleate merogonial plasmodia with masses of electron-dense projections on their plasma membrane. Electron-dense sporogonial plasmodia separated into uninucleate sporonts through rosette-like budding, and further developed into sporoblasts, enclosed by a sporophorous vesicle. Uninucleate mature spores were pyriform, measured 4.1 ± 0.1 (3.9-4.3) μm × 2.1 ± 0.07 (1.9-2.2) μm (average ± SE, range, n = 50), and contained a mushroom-like anchoring disk, bipartite polaroplast, electron-lucent posterior vacuole, trilaminar spore wall and 12-14 turns of an isofilar polar filament arranged in 2-3 ranks. The 1542 bp sequence from B. soweryi showed the highest similarity (below 80 %) with Nematocenator marisprofundi (accession number: JX463178). SSU rRNA gene-based phylogenetic analysis demonstrated that the novel taxon formed an independent clade from known microsporidian parasites. Based on the ultrastructural features and SSU rRNA gene sequence, we propose the establishment of a novel genus (Naidispora n. gen.) and species (Naidispora caidianensis n. sp.) to contain this parasite.


Differences in cardio-respiratory responses to exhaustive exercise between athletes and non-athletes.
To study the factors limiting the O2 supply in heavy exercise, O2 uptake at exhaustion was determined by progressive loading method with a bicycle ergometer in 33 well-trained male runners and 34 male sedentary adults. Pulmonary ventilation, oxygen removal, respiratory rate, tidal volume, pulmonary diffusing capacity, alveolar-capillary oxygen difference, cardiac output, arterial-venous oxygen difference, stroke volume and heart rate were measured. It was found that pulmonary diffusing capacity, cardiac output and stroke volume were correlated with the difference in O2 uptake at exhaustion between athletes and non-athletes.


Internalization of triiodothyronine-bovine serum albumin-colloidal gold complexes in human peripheral leukocytes.
Complexes of triiodothyronine-bovine serum albumin-colloidal gold were specifically internalized in human peripheral leukocytes after 5 min of incubation. The specificity was partially lost after a longer incubation.


Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) As a Biomarker for Lymphoid Malignancy with HCV Infection.
The hepatitis C virus (HCV) is potentially associated with liver cancer, and advances in various drugs have led to progress in the treatment of hepatitis C and attempts to prevent its transition to liver cancer. Furthermore, reactivation of HCV has been observed in the treatment of lymphoma, during which the immortalization and proliferation of lymphocytes occur, which leads to the possibility of further stimulating cytokines and the like and possibly to the development of lymphoid malignancy. There are also cases in which the disappearance of lymphoid malignancy has been observed by treating HCV and suppressing HCV-Ribonucleic acid (RNA), as well as cases of recurrence with an increase in HCV-RNA. While HCV-associated lymphoma has a poor prognosis, improving the prognosis with Direct Acting Antivirals (DAA) has recently been reported. The reduction and eradication of HCV-RNA by means of DAA is thus important for the treatment of lymphoid malignancy associated with HCV infection, and HCV-RNA can presumably play a role as a biomarker. This review provides an overview of what is currently known about HCV-associated lymphoma, its epidemiology, the mechanisms underlying the progression to lymphoma, its treatment, the potential and limits of HCV-RNA as a therapeutic biomarker, and biomarkers that are expected now that DAA therapy has been developed.


PHA-543613 preserves blood-brain barrier integrity after intracerebral hemorrhage in mice.
Blood-brain barrier disruption and consequent vasogenic edema formation codetermine the clinical course of intracerebral hemorrhage (ICH). This study examined the effect of PHA-543613, a novel α7 nicotinic acetylcholine receptor agonist, on blood-brain barrier preservation after ICH. Male CD-1 mice, subjected to intrastriatal blood infusion, received PHA-543613 alone or in combination with α7 nicotinic acetylcholine receptor antagonist methyllycaconitine or phosphatidylinositol 3-kinase inhibitor wortmannin. PHA-543613 alone, but not in combination with methyllycaconitine or wortmannin, inhibited glycogen synthase kinase-3β, thus, stabilizing β-catenin and tight junction proteins, which was paralleled by improved blood-brain barrier stability and ameliorated neurofunctional deficits in ICH animals. PHA-543613 preserved blood-brain barrier integrity after ICH, possibly through phosphatidylinositol 3-kinase-Akt-induced inhibition of glycogen synthase kinase-3β and β-catenin stabilization.


Isoelectric focusing and hybridisation experiments on creatine kinase (EC 18.104.22.168).
In the case of increased creatine kinase levels, the MM isozyme in human serum can often be subdivided by electrophoresis into three isozymes: MM1, MM2 and MM3. This paper presents the results of hybridisation experiments, which prove the existence of two different M-subunits. The MM isozyme fractions used in the hybridisation experiments were isolated by isoelectric focusing of human sera. The experiments were completed by hybridisation of mixtures of BB and MM isozymes, leading to the formation of two MB isozymes.


Identification of functional bradykinin B(2) receptors endogenously expressed in HEK293 cells.
The human embryonic kidney (HEK) 293 cell line is widely used in cell biology research. Although HEK293 cells have been meticulously studied, our knowledge about endogenous G protein-coupled receptors (GPCR) in these cells is incomplete. While studying the effects of bradykinin (BK), a potent growth factor for renal cells, we unexpectedly discovered that BK activates extracellular signal-regulated protein kinase 1 and 2 (ERK) in HEK293 cells. Thus, we hypothesized that HEK293 cells possess endogenous BK receptors. RT-PCR demonstrated the presence of mRNAs for BK B(1) and BK B(2) receptors in HEK293 cells. Western blotting with BK B(1) and BK B(2) receptor antibodies confirmed this result at the protein level. To establish that BK receptors are functional, we employed fluorescent measurements of intracellular Ca(2+), measured changes in extracellular acidification rate (ECAR) as a reflection of the Na(+)/H(+) exchange (NHE) with a Cytosensortrade microphysiometer, and assessed ERK activation by Western blotting with a phospho-specific ERK antibody. Exposure of HEK293 cells to BK produced a concentration-dependent rise in intracellular Ca(2+) (EC(50)=36.5+/-8.0 x 10(-9)M), a rapid increase in tyrosine phosphorylation of ERK (EC(50)=9.8+/-0.4 x 10(-9)M), and elevation in ECAR by approximately 20%. All of these signals were blocked by HOE-140 (B(2) receptor antagonist) but not by des-Arg(10)-HOE-140 (B(1) receptor antagonist). We conclude that HEK293 cells express endogenous functional BK B(2) receptors, which couple to the mobilization of intracellular Ca(2+), increases in ECAR and increases in ERK phosphorylation.


TP53-altered chronic lymphocytic leukemia treated with firstline Bruton's tyrosine kinase inhibitor-based therapy: A retrospective analysis.
Long-term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53-altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53-m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients had del(17p). TP53-m was noted in 89/110 (81%) patients tested; there were 101 unique TP53-m with an available VAF. The 4-year progression-free survival (PFS) and overall survival (OS) rates were 72.9% and 83.6%. No baseline characteristics including IGHV mutation status and number of TP53 alterations were associated with significant differences in PFS or OS, though a trend toward shorter PFS with increasing karyotypic complexity (hazard ratio 1.08, p = .066) was observed. Del(17p) was identified in <25% of cells in 26/104 (25%) of patients, and 28/101 (28%) of TP53-m were low-burden with a VAF of <10%; outcomes of these patients were similar to those with high-burden lesions. This study suggests that low-burden TP53 alterations should not be ignored when assessing genomic risk in CLL in the era of targeted therapy.


Health Inequalities in the South African elderly: The Importance of the Measure of Social-Economic Status.
A common approach when studying inequalities in health is to use a wealth index based on household durable goods as a proxy for socio-economic status. We test this approach for elderly health using data from an aging survey in a rural area of South Africa and find much steeper gradients for health with consumption adjusted for household size than with the wealth index. These results highlight the importance of the measure of socioeconomic status used when measuring health gradients, and the need for direct measures of household consumption or income in ageing studies.


Clinical and Instrumental Objective Evidence of the Efficacy of a New Water-Based Nail-Strengthening Solution Containing Pistacia lentiscus and Hyaluronic Acid Applied for Up to 6 Months to Improve the Appearance of Weak, Brittle Nails.
Brittle nails are fragile or split nails; they affect 20% of the population and may be primary or secondary to different conditions. The aim of our studies was to evaluate the efficacy and tolerability of a new water-based nail-strengthening treatment containing hyaluronic acid and Pistacia lentiscus with daily application for a period of 1-3 months for one study (n = 30) and up to 6 months for a second study (n = 30). In total, we enrolled 60 patients of both sexes with brittle and weak nails due to primary or secondary causes and evaluated the efficacy of this new product using subjective and objective methods: clinical evaluation, assessment of photographs, onychoscopy evaluation, investigator and patient global assessment, dynamic optical coherence tomography (D-OCT) and reflectance confocal microscopy (RCM). Studies subjects presented a statistically significant improvement in global assessment scale (GAS) scores at 14 days (GAS = 1.7 ± 0.6), 1 month (GAS = 1.4 ± 0.7) and at 3 months (GAS = 1±0.7) versus the GAS score obtained before treatment (1.9 ± 0.5) (p < 0.0001). From the Italian study at 6 months (n = 30) 76% of the patients had an improvement in their nail appearance. Reduction in nail plate roughness with improved nail resistance and decreased distal breakage were the most evident benefits, demonstrated on clinical and instrumental evaluations. No side effects were reported. All patients reported an improvement in nail appearance after using the product for 1 month, 3 months and 6 months, and had a positive opinion on the product. This new product is an effective, safe, and easy-to-use option for topical treatment of brittle nails and primary nail fragility and an adjuvant therapy in secondary nail fragility. Moreover, its ease of application and cosmetic qualities allow good compliance. ISDIN.


Effects on lipid profile of supplementation with vitamin D in type 2 diabetic patients with vitamin D deficiency.
Epidemiological studies suggest that vitamin D status may have an influence on lipid profile. We studied consecutive type 2 diabetic patients with vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) lower than 20 ng/ml). They were treated with 16,000 IU of calcifediol orally once a week for a minimum of 8 weeks. A total of 28 patients were treated for a mean time of 84.1 days (range 56-120 days). All patients achieved serum levels of 25(OH)D higher than 20 ng/ml. There was significant reduction in total cholesterol (172.1 ± 32.4 versus 164.4 ± 27.3 mg/dl, p = 0.04). There were nonsignificant reductions in low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and triglycerides. There was no change in HDL cholesterol. Correction of vitamin D deficiency in type 2 diabetic patients decreases total cholesterol. Our results do not rule out reductions in LDL cholesterol, non-HDL cholesterol and triglycerides.


[Anthrax].
Anthrax is a serious bacterial infection sustained by Bacillus anthracis and occurring in most mammals, especially grazing herbivors, but it can also involve humans when bacterial endospores enter the body through abrasions in the skin or by inhalation or ingestion. Human disease results from contact with infected animals or contaminated animal products, while there are no known cases of human-to-human transmission. The most common form of human anthrax is the cutaneous infection, usually curable with antimicrobial therapy and rarely leading to systemic and fatal disease; on the other hand, gastrointestinal and inhalatory forms (resulting from inhalation or ingestion of endospores) are very uncommon, but they show a mortality rate approaching 100 percent, usually related to septic and toxic shock. For centuries, anthrax has caused disease in animals and only a few cases in humans, with some outbreaks in developing countries. Today, after the new events in the United States, at least 17 nations are believed to have offensive biological weapon programs, and this old bacterial infection became a modern menace to world safety.


Nucleosides and nucleotides. 176. 2'-Deoxy-2'-hydroxylaminocytidine: a new antitumor nucleoside that inhibits DNA synthesis although it has a ribonucleoside structure.
The design and synthesis of potential antitumor antimetabolites 2'-deoxy-2'-hydroxylaminouridine (2'-DHAU) and -cytidine (2'-DHAC) are described. We found that 2'-DHAC in neutral solution generated 2'-aminoxy radicals at room temperature. 2'-DHAC inhibited the growth of L1210 and KB cells, with IC50 values of 1.58 and 1.99 microM, respectively, more potently than 2'-DHAU, with IC50 values of 34.5 and 27.3 microM, respectively. 2'-DHAC was effective against 9 human cell lines, with IC50 values of in the micromolar range. The in vivo antitumor activity of 2'-DHAC was also examined using the mouse leukemia P388 model, which gave a T/C value 167%. Phosphorylation of 2'-DHAC by uridine/cytidine kinase was essential for its cytotoxicity, as suggested by a competition experiment using several common nucleosides. Inhibition of DNA synthesis was the predominant mechanism of action of 2'-DHAC, although it has a ribo-configuration.


Transformation Pathway upon Heating of Metastable β Titanium Alloy Ti-15Mo Investigated by Neutron Diffraction.
A transformation pathway during thermal treatment of metastable β Ti-15Mo alloy was investigated by in situ neutron diffraction. The evolution of individual phases α , β , and ω was investigated during linear heating with two heating rates of 1.9 ∘ C / min and 5 ∘ C / min and during aging at 450 ∘ C . The results showed that with a sufficient heating rate (5 ∘ C / min in this case), the ω phase dissolves before the α phase forms. On the other hand, for the slower heating rate of 1.9 ∘ C / min , a small temperature interval of the coexistence of the α and ω phases was detected. Volume fractions and lattice parameters of all phases were also determined.


A case of primary B-cell type non-Hodgkin lymphoma originating in the iris.
To report a case of primary malignant B-cell type non-Hodgkin lymphoma originating in the iris. Interventional case report. An 83-year-old woman presented with anterior uveitis resulting from primary malignant lymphoma in the iris. Ultrasound biomicroscopy and indocyanine green angiography using a scanning laser ophthalmoscope showed abnormalities in the iris. Diagnostic biopsy of the iris revealed B-cell type non-Hodgkin lymphoma. The patient was treated with radiotherapy, and the tumorous lesion resolved. Primary lymphoma localized in the iris only is rare. In this case, diagnostic biopsy and radiotherapy of the iris lymphoma provided good results.


Superior mesenteric artery injury during nephrectomy for Wilms' tumor.
Iatrogenic injury to the aorta or its major branches during nephrectomy for Wilms' tumor in children is rarely reported but may be more common than is currently acknowledged. We identified four patients with ligation of the superior mesenteric artery (SMA) that occurred during nephrectomy for nephroblastoma and another child in whom SMA thrombosis developed postoperatively. All of the tumors were on the left side. Interruption of the SMA was recognized intraoperatively in all four children, and primary repair was done. In three patients, appearance of the bowel remained normal before repair of the injury. Three of the arteries were repaired by primary reanastomosis, and one was joined with an interpositioned hypogastric artery graft. None of these patients had gastrointestinal complications postoperatively. In the fifth patient, SMA thrombosis developed after repair of an aortic tear during nephrectomy. This patient required subsequent small bowel resection for bowel infarction and died in the perioperative period. Every surgeon treating children with Wilms' tumor should be aware of the possibly distorted vascular anatomy and take precautions to avoid such a significant injury. Attempts at early ligation of the vessels may not be justified until the renal vasculature is clearly identified.


The novel axis of YAP1, transcription enhancer factor 3 and Down Syndrome Candidate Region 1 isoform 1L is a common signaling pathway downstream of several angiogenic factors.
Angiogenesis is a hallmark of many diseases. Previously, we found that Down Syndrome Candidate Region 1 Isoform 1L (DSCR1-1L) was expressed in human tumor vessels, but was not detectable in normal tissues, and played important roles in angiogenesis induced by vascular endothelial growth factor (VEGF-A165). The expressions of DSCR1-1L mRNA and protein induced by VEGF-A165 were regulated via the direct interaction of transcription enhancer factor 3 (TEF3) with DSCR1-1L promoter. However, the function and the regulation of DSCR1-1L in angiogenesis had not been completely understood. In this study, we found that the expressions of DSCR1-1L mRNA and proteins were upregulated by other angiogenic factors, including VEGF-A121, VEGF-E, histamine, PAF, the endothelial cell (EC) growth medium, and the conditional medium obtained from cancer cells, but not by PlGF, bFGF, PDGF, and serotonin. The EC proliferation, migration and elongation induced by histamine and EC growth medium were inhibited by knocking down the mRNA and protein expressions of DSCR1-1L and TEF3. The TEF3 activation was regulated by its interaction with YAP1, and translocation from cytosol to nuclei, but not by increase of protein expression, after the stimulation of VEGF, histamine and EC growth medium. YAP1 regulated the protein expression of DSCR1-1L, the proliferation, migration and elongation of ECs induced by VEGF, histamine and EC growth medium. Taken together, this study identified a novel axis of YAP1, TEF3 and DSCR1-1L that was a common signaling pathway downstream of several angiogenic factors to regulate angiogenesis, suggesting that this pathway is an excellent therapeutic target for angiogenic diseases and cancers. Our results contribute significantly to the field of mechanistic studies.


Triose phosphate use limitation of photosynthesis: short-term and long-term effects.
The triose phosphate use limitation was studied using long-term and short term changes in capacity. The TPU limitation caused increased proton motive force; long-term TPU limitation additionally reduced other photosynthetic components. Photosynthetic responses to CO2 can be interpreted primarily as being limited by the amount or activity of Rubisco or the capacity for ribulose bisphosphate regeneration, but at high rates of photosynthesis a third response is often seen. Photosynthesis becomes insensitive to CO2 or even declines with increasing CO2, and this behavior has been associated with a limitation of export of carbon from the Calvin-Benson cycle. It is often called the triose phosphate use (TPU) limitation. We studied the long-term consequences of this limitation using plants engineered to have reduced capacity for starch or sucrose synthesis. We studied short-term consequences using temperature as a method for changing the balance of carbon fixation capacity and TPU. A long-term and short-term TPU limitation resulted in an increase in proton motive force (PMF) in the thylakoids. Once a TPU limitation was reached, any further increases in CO2 was met with a further increase in the PMF but no increase or little increase in net assimilation of CO2. A long-term TPU limitation resulted in reduced Rubisco and RuBP regeneration capacity. We hypothesize that TPU, Rubisco activity, and RuBP regeneration are regulated so that TPU is normally in slight excess of what is required, and that this results in more effective regulation than if TPU were in large excess.


A novel triazole derivative of betulinic acid induces extrinsic and intrinsic apoptosis in human leukemia HL-60 cells.
In an attempt to arrive at more potent cytotoxic agent than the bioactive natural product betulinic acid, influence of small structural modifications of its 1, 2, 3 triazole derivatives tethered at C-28 and both C3, C-28 using click chemistry approach has been studied. The chemically characterized triazoles have been screened for in vitro cytotoxicity against four human cancer cell lines HL-60, MiaPaCa-2, PC-3 and A549 which has allowed to identify triazole derivative 28{1N (4-fluoro phenyl)-1H-1, 2, 3-triazol-4-yl} methyloxy betulinic ester having better potency profile than the parent compound with IC50 values in the range of 5-7 μM. It caused disruption of mitochondrial membrane potential, rendered Bcl-2 cleavage, Bax translocation and decrease Bcl-2/Bax ratio. These events are accompanied by activation of caspases -9, -3, which cleave the PARP-1. It also induces caspase-8, which is involved in extrinsic apoptotic pathway. Therefore, it induces apoptosis through both intrinsic and extrinsic pathways in human leukemia HL-60 cells.


Cloning and functional analysis of c/ebpα as negative regulator of dmrt1 in Chinese tongue sole (Cynoglossus semilaevis).
c/ebpα is a member of the C/EBP family of transcription factors, which are involved in cell growth and differentiation and have a conserved basic leucine zipper (bZIP) domain. However, little is known about its function in sex determination and differentiation. In the present study, c/ebpα was cloned from the gonads of Chinese tongue sole (Cynoglossus semilaevis). The full-length cDNA of c/ebpα was 1583 bp, with a 198-bp 5' UTR, a 446-bp 3' UTR, and a 939-bp open reading frame encoding a 312-amino acid peptide. qRT-PCR revealed that c/ebpα was predominantly expressed in undifferentiated gonads of male C. semilaevis at 30 dpf and 60 dpf and peaked at 60 dpf. Expression levels of c/ebpα in the testis were constantly higher than those in ovaries at all developmental stages. Moreover, a dual-luciferase assay revealed that c/ebpα could negatively regulate the male-determining gene dmrt1 in vitro. These results provide fundamental information indicating that C. semilaevis c/ebpa might be involved in early gonadal differentiation and functions as a negative regulator of dmrt1 by repressing its transcription.


Acetylene Semi-Hydrogenation at Room Temperature over Pd-Zn Nanocatalyst.
A reaction of fundamental and commercial importance is acetylene semi-hydrogenation. Acetylene impurity in the ethylene feedstock used in the polyethylene industry poisons the Ziegler-Natta catalyst which adversely affects the polymer quality. Pd based catalysts are most often employed for converting acetylene into the main reactant, ethylene, however, it often involves a tradeoff between the conversion and the selectivity and generally requires high temperatures. In this work, bimetallic Pd-Zn nanoparticles capped by hexadecylamine (HDA) have been synthesized by co-digestive ripening of Pd and Zn nanoparticles and studied for semi-hydrogenation of acetylene. The catalyst showed a high selectivity of ~85 % towards ethylene with a high ethylene productivity to the tune of ~4341 μmol g-1 min-1 , at room temperature and atmospheric pressure. It also exhibited excellent stability with ethylene selectivity remaining greater than 85 % even after 70 h on stream. To the best of the authors' knowledge, this is the first report of room temperature acetylene semi-hydrogenation, with the catalyst effecting high amount of acetylene conversion to ethylene retaining excellent selectivity and stability among all the reported catalysts thus far. DFT calculations show that the disordered Pd-Zn nanocatalyst prepared by a low temperature route exhibits a change in the d-band center of Pd and Zn which in turn enhances the selectivity towards ethylene. TPD, XPS and a range of catalysis experiments provided in-depth insights into the reaction mechanism, indicating the key role of particle size, surface area, Pd-Zn interactions, and the capping agent.


Effectiveness of BNT162b2 and ChAdOx1 Vaccines against Symptomatic COVID-19 among Healthcare Workers in Kuwait: A Retrospective Cohort Study.
Estimating vaccine effectiveness (VE) against severe, acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) is necessary to demonstrate protection from the disease. Between 24 December 2020 and 15 June 2021, we determined the factors associated with vaccine coverage and estimated VE against SARS-CoV-2 infection in HCWs at a secondary hospital in Kuwait. We extracted sociodemographic, occupational, SARS-CoV-2 infection, and vaccination data for eligible HCWs from the hospital records. Vaccine coverage percentages were cross-tabulated with the HCW factors. Cox regression was used to estimate hazard ratios in vaccinated versus unvaccinated. 3246 HCWs were included in the analysis, of which 82.1% received at least one vaccine dose (50.4% only one dose of ChAdOx1, 3.3% only one dose of BNT162b2, and 28.3% two doses of BNT162b2). However, 17.9% of HCWs were unvaccinated. A significantly lower vaccination coverage was reported amongst female HCWs, younger age group (20-30 years), and administrative/executive staff. The adjusted VE of fully vaccinated HCWs was 94.5% (95% CI = 89.4-97.2%), while it was 75.4% (95% CI = 67.2-81.6%) and 91.4% (95% CI = 65.1-97.9%) in partially vaccinated for ChAdOx1 and BNT162b2, respectively. BNT162b2 and ChAdOx1 vaccines prevented most symptomatic infections in HCWs across age groups, nationalities, and occupations.


Antidiabetic Effects of Vigna nakashimae Extract in Humans: A Preliminary Study.
Vigna nakashimae (VN) extract has been shown to have antidiabetic and antiobesity effects in various animal studies; however, to our knowledge, no data on such effects exist in humans. We performed a randomized placebo-controlled study to investigate the antidiabetic effects of VN extract treatment for 12 weeks in humans. A total of 18 Korean patients with type 2 diabetes were enrolled in this study and were allocated randomly to either the VN extract group (1 g thrice daily) or control group (placebo tablets) for 12 weeks. We investigated blood glucose levels, body weight, lipid profiles, and adverse events after 12 weeks of treatment. Fifteen subjects were included in the final analysis. There was no difference in age, sex, fasting glucose levels, or lipid profiles between the VN extract and control groups at baseline. However, the baseline glycosylated hemoglobin (HbA1c) levels of the control group were lower than those of the VN extract group. After treatment with VN extract for 12 weeks, the body weight and lipid profile of the VN extract group remained unchanged; however, the HbA1C levels decreased by 0.36% ± 0.33% (p = 0.027). In contrast, the HbA1C levels of the control group did not change after 12 weeks (p = 0.228). During the 12-week treatment with VN extract, no serious adverse events were reported. Our data indicate that VN extract has implications for glucose lowering in type 2 diabetic patients.


[Dynamics of the antihemagglutinin level in annual human immunization with inactivated influenza vaccines].
Inactivated influenza vaccines are classified according to the types of antihemagglutinin response after annual revaccination of people with inactivated influenza vaccines carried out for 3 successive years. The results of analysis show that in response to annual revaccination with inactivated vaccine up to 80% of the vaccinees develop no positive changes in antihemagglutinin titres. An experiment using a liver moderately attenuated vaccine after a single immunization with an inactivated vaccine demonstrated that 64.7% vaccinees would not be involved in the epidemic process at all and 11.5% would be involved at the level of asymptomatic infection. The remaining portion (23.8%), also involved in the epidemic process after immunization with inactivated vaccine, apparently requires additional immunological protection. The results of the above study indicate the inefficacy of annual vaccination of the same subjects with the same inactivated influenza vaccine.


Pseudopotential theory of Auger processes in CdSe quantum dots.
Auger rates are calculated for CdSe colloidal quantum dots using atomistic empirical pseudopotential wave functions. We predict the dependence of Auger electron cooling on size, on correlation effects (included via configuration interaction), and on the presence of a spectator exciton. Auger multiexciton recombination rates are predicted for biexcitons as well as for triexcitons. The results agree quantitatively with recent measurements and offer new predictions.


Evidence for the involvement of superoxide in vitamin K-dependent carboxylation of glutamic acid residues of prothrombin.
The formation of vitamin K epoxide and the vitamin K-dependent carboxylation of glutamic acid residues present in synthetic substrates and decarboxyprothrombin are both inhibited by superoxide dismutase. Catalase only inhibits the generation of vitamin K epoxide, suggesting that the carboxylation and epoxidation reactions are not inter-dependent.


Optimal transfer learning based nutrient deficiency classification model in ridge gourd (Luffa acutangula).
The efficient detection of nutrient deficiency and proper fertilizer for that deficiency becomes the critical challenges various farmers face. The family Cucurbitaceae includes members cultivated globally as a source of indigenous medicines, food, and fiber. Luffa acutangula (L.) Roxb, generally called Ridge gourd, belongs to the Cucurbitaceae family and is an annual herb originating in several areas of India, particularly in the coastal regions. Nutrient deficiency detection in ridge gourd is essential to improve crop productivity. In agricultural practises, the early identification and categorization of nutrient deficiencies in crops is essential for sustaining optimal growth and production. Addressing these nutrient deficiencies, we applied the Ring Toss Game Optimization with a Deep Transfer Learning-based Nutrient Deficiency Classification (RTGODTL-NDC) to Ridge Gourd (Luffa acutangula). This research proposes a new ring toss game optimization with a deep transfer learning-based nutrient deficiency classification (RTGODTL-NDC) method. The RTGODTL-NDC technique uses pre-processing, segmentation, feature extraction, hyperparameter tuning, and classification. The Gabor filter (GF) is mainly used for image pre-processing, and the Adam optimizer with SqueezeNet model is utilized for feature extraction. Finally, the RTGO algorithm with the deep hybrid learning (HDL) model is applied to classify nutrient deficiencies. The suggested framework has the potential to improve crop management practises by allowing for proactive and targeted interventions, which will result in improved agricultural health, production, and resource utilisation. The outcomes represented by the RTGODTL-NDC method have resulted in improved performance. For example, based on accuracy and specificity, the RTGODTL-NDC methodology rendered maximum [Formula: see text] of 97.16% and specificity of 98.29%. The outcomes show how effective the transfer learning-based model is in identifying nutrient deficits in ridge gourd plants, as seen by its high level of accuracy.


[The effect of transcardiac galvanization on the course of the physical rehabilitation of patients with an acute myocardial infarct based on the data from a measured loading test].
Transcardiac galvanization effect was assessed in 76 patients with primary noncomplicated macrofocal anterior myocardial infarction admitted to hospital within initial 6 hours of the disease. As shown by the evidence obtained at bicycle ergometry, tetrapolar rheography and clinical examination, transcardiac galvanization within 3 days of the infarction enhances hospital physical rehabilitation course, increases exercise tolerance by the disease month 6, promotes an increase in myocardial maximal oxygen consumption, increases coronary reserve and improves cardiac contractility.


Ultrafast optical switching to a metallic state by photoinduced mott transition in a halogen-bridged nickel-chain compound.
We demonstrate the ultrafast photoinduced Mott transition from a charge transfer insulator to a metal in a halogen-bridged Ni-chain compound by pump-probe reflection spectroscopy. Upon the irradiation of a 130-femtosecond laser pulse, the spectral weight of the gap transition is transferred to the inner-gap region. When the photoexcitation density exceeds 0.1/Ni site, the Drude-like high-reflection band appears in the infrared region, signaling the formation of a metallic state. The photogeneration of the metallic state and the subsequent recovery to the original gapped state occur within a few picoseconds.


Peptidase Inhibitor 16 Attenuates Left Ventricular Injury and Remodeling After Myocardial Infarction by Inhibiting the HDAC1-Wnt3a-β-Catenin Signaling Axis.
Background Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. PI16 (peptidase inhibitor 16), as a secreted protein, is highly expressed in heart diseases such as heart failure. However, the functional role of PI16 in MI is unknown. This study aimed to investigate the role of PI16 after MI and its underlying mechanisms. Methods and Results PI16 levels after MI were measured by enzyme-linked immunosorbent assay and immunofluorescence staining, which showed that PI16 was upregulated in the plasma of patients with acute MI and in the infarct zone of murine hearts. PI16 gain- and loss-of-function experiments were used to investigate the potential role of PI16 after MI. In vitro, PI16 overexpression inhibited oxygen-glucose deprivation-induced apoptosis in neonatal rat cardiomyocytes, whereas knockdown of PI16 exacerbated neonatal rat cardiomyocyte apoptosis. In vivo, left anterior descending coronary artery ligation was performed on PI16 transgenic mice, PI16 knockout mice, and their littermates. PI16 transgenic mice showed decreased cardiomyocyte apoptosis at 24 hours after MI and improved left ventricular remodeling at 28 days after MI. Conversely, PI16 knockout mice showed aggravated infract size and remodeling. Mechanistically, PI16 downregulated Wnt3a (wingless-type MMTV integration site family, member 3a)/β-catenin pathways, and the antiapoptotic role of PI16 was reversed by recombinant Wnt3a in oxygen-glucose deprivation-induced neonatal rat cardiomyocytes. PI16 also inhibited HDAC1 (class I histone deacetylase) expression, and overexpression HDAC1 abolished the inhibition of apoptosis and Wnt signaling of PI16. Conclusions In summary, PI16 protects against cardiomyocyte apoptosis and left ventricular remodeling after MI through the HDAC1-Wnt3a-β-catenin axis.


The value of a new prognostic model developed by lymphocyte-monocyte ratio and platelet-monocyte ratio in peripheral T-cell lymphoma.
Peripheral T-cell lymphoma(PTCL) is a group of lymphoproliferative tumors originated from post-thymic T cells or mature natural killer (NK) cells. It shows highly aggressive clinical behaviour, resistance to conventional chemotherapy, and a poor prognosis. Although a few prognostic models of PTCL have been established in retrospective studies, some high-risk patients still can not be screened out. Therefor we retrospectively studied 347 newly diagnosed PTCL patients and assessed the prognostic role of lymphocyte-monocyte ratio (LMR) and platelet-monocyte ratio (PMR) in the complete response (CR) and survival of PTCL patients. Patients with LMR ≤ 1.68 and PMR ≤ 300 achieved a lower CR rate and a poor survival. In multivariate analysis, LMR ≤ 1.68 (HR = 1.751, 95% CI 1.158-2.647, p < 0.05) and PMR ≤ 300 (HR = 1.762, 95% CI 1.201-2.586, p < 0.05) were independently associated with short survival. On this basis, a new prognostic model of PTCL was established to screen out high-risk patients. In our "Peripheral Blood Score (PBS)" model, three groups were identified at low risk (178 patients, 51.3%, score 0), intermediate risk (85 patients, 24.5%, score 1), and high risk (84 patients, 24.2%, score 2), having a 1-year OS of 86%, 55.3% and 22.6% (p < 0.05), and a 3-year OS of 43.4%, 20% and 13.1% (p < 0.05), respectively. Optimal strategies for identifying high-risk patients with PTCL are urgently needed. Our new PBS model is simple, inexpensive and widely available to screen out the high risk patients.


Cathepsin B inhibitory activities of three new phthalate derivatives isolated from seahorse, Hippocampus Kuda Bleeler.
Three new phthalate acid derivatives, 2,12-diethyl-11-methylhexadecyl 2-ethyl-11-methylhexadecyl phthalate (1), 2-ethyldecyl 2-ethylundecyl phthalate (2), and bis(2-ethyldodecyl) phthalate (3), were isolated from seahorse, Hippocampus Kuda Bleeler, together with a known natural analog bis(2-ethylheptyl) phthalate (4). The structures of these compounds were elucidated mainly by means of the comprehensive analysis of their NMR spectroscopic data. The four phthalate derivatives showed dose-dependent cathepsin B inhibitions activities with IC(50) values of 0.13 mM (1), 0.21 mM (2), 0.18 mM (3), and 0.29 mM (4), respectively.


Fabrication of an ultrasensitive ibuprofen nanoaptasensor based on covalent attachment of aptamer to electrochemically deposited gold-nanoparticles on glassy carbon electrode.
The paper reports the development of an ultrasensitive nanoaptasensor based on the covalent attachment of an aptamer (Apt) to gold-nanoparticles (AuNPs) deposited on the surface of a glassy carbon electrode (GCE) as the unique platform. The developed nanoaptasensor was utilized to assay the anti-inflammatory drug, ibuprofen (IBP). The sensing platform was fabricated using a single-stage electrodeposite approach. It is worth noting that the proposed nanoaptasensor combines the advantages of the deposition of neatly arranged AuNPs (enlarged active surface area and strengthened electrochemical signal) and the elimination of enzymes or antibodies for the amplified detection of IBP, with the covalent attachment of the Apt to the surface of the modified electrode. Moreover, the newly developed nanoaptasensor embraces a number of attractive features such as ease of fabrication, low detection limit, excellent selectivity, good stability and a wide linear range with respect to IBP. Meanwhile, interference of common interfering analgesic drugs was effectively avoided. In optimized empirical conditions, the response current of the nanoaptasensor is linear to IBP concentrations from 0.005 nmol(-1) to 7 nmol(-1) with the detection limit (LOD) as accurate as 0.5 pmol(-1). This LOD value proves more sensitive in comparison with previously reported methods. Thus, the fabricated nanoaptasensor can serve as a powerful sensor for rapid diagnosis of IBP in human blood samples and shows great potential for practical bioapplication.


miRNAs orchestration of testicular germ cell tumors - Particular emphasis on diagnosis, progression and drug resistance.
Testicular cancer (TC) is one of the most frequently incident solid tumors in males. A growing prevalence has been documented in developed countries. Although recent advances have made TC an exceedingly treatable cancer, numerous zones in TC care still have divisive treatment decisions. In addition to physical examination and imaging techniques, conventional serum tumor markers have been traditionally used for the diagnosis of testicular germ cell tumors (TGCT). Unlike other genital and urinary tract tumors, recent research methods have not been broadly used in TGCTs. Even though several challenges in TC care must be addressed, a dedicated group of biomarkers could be particularly beneficial to help classify patient risk, detect relapse early, guide surgery decisions, and tailor follow-up. Existing tumor markers (Alpha-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have limited accuracy and sensitivity when used as diagnostic, prognostic, or predictive markers. At present, microRNAs (miRNA or miR) play a crucial role in the process of several malignancies. The miRNAs exhibit pronounced potential as novel biomarkers since they reveal high stability in body fluids, are easily detected, and are relatively inexpensive in quantitative assays. In this review, we aimed to shed light on the recent novelties in developing microRNAs as diagnostic and prognostic markers in TC and discuss their clinical applications in TC management.


[Smoke-free Germany 2040: a discussion paper].
A "smoke-free" society is assumed if less than 5 % of a population smoke. We predict when this goal could be reached in Germany. To reduce the proportion of smokers in the population, the World Health Organization recommends a bundle of measures (MPOWER) that should minimize both the supply of and the demand for tobacco. The current level of implementation of these recommendations in Germany is presented. A total of 21 representative cross-sectional surveys of the Drug Affinity Study and the Epidemiological Survey of Substance Abuse since 2000/2001 with adolescents and adults show the smoking behavior of the population until 2018. Per capita consumption of factory-built and self-made cigarettes during the same period is used as an objective data basis. Regression analyses are used to model the date at which less than 5 % of the German population smoke. A selective literature review is carried out to describe the implementation of the MPOWER program. Before 2000 there was no trend in Germany towards non-smoking. After the implementation of various preventive measures such as price increases for tobacco products and the introduction of non-smoking protection laws, the spread of smoking among the population has steadily decreased since 2000. By 2018, the 5 % prevalence target among adolescents had almost been reached, as the relative proportion of adolescents who smoked fell by 20.9 percentage points to 6.6 %. The relative proportion of smoking in adult women fell by 12.1 percentage points to 18.5 %, the relative proportion of smoking in men by 14.8 percentage points to 24.2 %. Assuming a linear trend, the prevalence target of less than 5 % smoking adults can be reached by around 2043. Of the six recommended measures of the MPOWER program, Germany is currently only implementing the monitoring of tobacco consumption in society without compromises. After various tobacco prevention measures were implemented, a trend towards non-smoking began in Germany. The continual price increase recommended by the World Health Organization, the further restriction of availability, the ban on all tobacco advertising and promotion, the support of smoking cessation as well as the education of the population appear to be necessary to reinforce this trend and to achieve the health policy goal of a smoke-free society in 2040.


Loss of hemolysin expression in Staphylococcus aureus agr mutants correlates with selective survival during mixed infections in murine abscesses and wounds.
During the screening of a Staphylococcus aureus signature-tagged mutagenesis library, it was noted that nonhemolytic bacteria became more abundant as time passed in murine abscess and wound models, but not within organ tissues associated with systemic infections. To examine this further, a mixed population of hyperhemolytic, hemolytic, and nonhemolytic S. aureus strain RN6390 cells were inoculated into mice using abscess, wound, and systemic models of infection. After 7 days in the abscess, the hyperhemolytic group markedly declined, whereas the nonhemolytic population increased significantly. A similar phenomenon occurred in murine wounds, but not during the systemic infection. Sequencing of several of the signature-tagged mutants indicated mutations in the agrC gene or within the agrA-agrC intergenic region. Both alpha-hemolysin and delta-hemolysin activity was curtailed in these mutants, but beta-hemolysin activity was unaffected. Single strain comparisons between wild-type strain 8325-4 and strain DU1090 (hla-) as well as between strain RN6911 (agr) and wild-type strain RN6390 were performed using the same three animal models of infection. The agr mutant strain and the hla mutant strain showed no difference in bacterial counts in murine wounds compared to their respective parent strains. The same held true in murine abscesses at day 4, but strain RN6911 counts then declined at day 7. Considerable clearing of the hla mutant strain and the agr mutant strain occurred in the systemic model of infection. Mixed infections with the DU1090 and 8325-4 strains in the abscess model showed a slight advantage given to the DU1090 population, but a distinct selection for the parental 8325-4 strain in the liver. These results suggest that agr mutations cause reductions in the expression of several secreted proteins, including alpha- and delta-hemolysin, which in turn contribute to a growth advantage of this agr mutant group within a mixed population of S. aureus cells residing in abscesses and wounds.


Performance of decellularized xenogeneic tissue in heart valve replacement.
Due to human valve (allograft) scarcity, the concept of decellularization of xenogeneic valves is currently pursued. The two current concepts of guided tissue regeneration and tissue engineering are critically discussed. While guided tissue regeneration shows promising results in animal experiments, there is no scientific evidence that the obtained results might be transferred to the human. The approach of tissue engineering using decellularized xenogeneic heart valves bears enormous potential, however, numerous issues need to be studied and clarified prior potential clinical application.


Course of recovery for whiplash associated disorders in a compensation setting.
The detailed course of recovery following compensable whiplash associated disorders (WAD) is not well understood. Some people recover within months and others report symptoms for extended periods. Recent research identified distinct recovery pathways. Identifying recovery pathways for people with this condition in compensable settings could assist clinical and claim management. This study aimed to identify recovery trajectories based on disability, pain catastrophising and mental health and, secondly, to examine developmental linkages between the trajectories. A cohort of 246 people with compensable WAD were followed for 24 months after a motor vehicle related injury. Functional Rating Index (FRI), Pain Catastrophising Scale (PCS) and the SF36 Mental Component Score (SF 36 MCS). Group-based trajectory analytical techniques were used to identify distinct post-injury profiles. Multinominal logistic regression modelling identified factors associated with membership of different trajectories. 246 people were enrolled a median of 72 days after injury. Three trajectories were identified for the measures used and their prevalences, respectively, were: for disability (FRI) they were mild (47%), moderate (31%), and severe (22%); for pain catastrophising (PCS) they were non-catastrophisers (55%), moderate-low catastrophisers (32%) and clinically significant catastrophisers (13%); and, for mental health (SF36 MCS) they were good mental health (40%), moderately low mental health (42%) and severely low mental health (18%). All groups showed no further recovery beyond 12 months after injury. The significant baseline predictors of the severe disability trajectory were: lower (that means worse) bodily pain scores (SF 36 BPS) (p≤0.01); high pain catastrophising (p≤0.01); and, self-reported fair or poor general health (p=0.03). Conditional probabilities for group membership showed that the three trajectories for both PCS and FRI were linked. Dual membership was high for the mild disability and mild pain catastrophising trajectories and, for the severe disability and clinically significant pain catastrophising trajectories. There is a strong and plausible association between severe disability, clinical levels of pain catastrophising and low mental health. Claimants can be identified at claim notification based on three estimated recovery trajectories. Claim and clinical interventions can be targeted to the profile within each recovery trajectory.


Apical extrusion of debris with different rotary and reciprocating single-file endodontic instrumentation systems: a systematic review and meta-analysis protocol.
Root canal treatment is one of the oldest dental procedures for the treatment of endodontic infection. Extrusion of debris beyond the root apex during root canal instrumentation and subsequent persistence of pain are common complications. A systematic review of the evidence on reciprocating single-file instrumentation systems and their comparison with rotary single-file systems, with apical extrusion of debris as primary outcome, will be done through this study. Published ex vivo and in vitro studies with no language restriction will be included. We will search MEDLINE (Ovid), EMBASE (Ovid), Web of Science, Cochrane and Google Scholar. Strategies will be incorporated to search grey literature also. Thorough evaluation of search results, completion of data abstraction and assessment of quality will be done by two reviewers independent from each other. Assessment of included studies will be done by utilising an evidence model developed on the basis of standards of quality reported in guidelines to document ex vivo and in vitro studies regarding dental materials and pertained for extrusion of debris apically and has been already used in quality assessment of studies involving quantification of debris extrusion apically. We will calculate the standardised mean differences for apically extruded debris, with congruent 95% CIs. We will measure the statistical heterogeneity by applying the Cochrane Q test and quantify using the I2 statistic. Existence of covariates and any potential heterogeneity will be explored through prespecified subgroup and sensitivity analyses. Approval from an ethical research committee is not required because it will be done using data that have been already published and have no concerns related to the privacy of patients. Extensive dissemination of results from this review will be done through submission to a peer-reviewed journal for publication and conferences. CRD42019151804.


Genetic analysis of ryanodine receptor function in Caenorhabditis elegans based on unc-68 revertants.
The Caenorhabditis elegans ryanodine receptor is encoded by the unc-68 gene, and functions as a Ca2+-induced Ca2+ release channel during muscle contraction. To investigate the factors that suppress calcium release and identify molecules that interact with the ryanodine receptor, we isolated revertants from two unc-68 mutants. Three of the revertants obtained from the null allele unc-68(e540), which displayed normal motility, had intragenic mutations that resulted in failure to splice out intron 21. The other two, kh53 and kh55, had amino acid insertions in the third of the four RyR domains. The brood size and the egg laying rate remain abnormal in these revertants. This suggests the third RyR domain may be required for egg laying and embryogenesis, although we can not determine a molecular mechanism. Five ketamine sensitive revertants recovered from the missense mutant unc-68(kh30) showed altered responses to caffeine, ryanodine, levamisole and ouabain relative to those of the unc-68(kh30) animals. These may carry second-site suppressor mutations, which may define genes for proteins that regulate the Ca2+ concentration in body-wall muscle. One of these mutants, kh52, shows lower motility and higher sensitivity to drugs, and this mutation was mapped to chromosome X. These observations provide a basis for the study of ryanodine receptor functions in embryogenesis and in calcium-mediated regulation of muscle contraction in C. elegans. This is the first study to show that the conserved RyR domain of the receptor acts in egg laying and embryogenesis.


Dietary intake of concentrated gamma-linolenic acid (GLA)-enriched oil suppresses cutaneous level of dihomo-gamma-linolenic acid (DGLA): possible in vivo inhibition of microsomal elongation of GLA to DGLA.
The dietary supplementation of normal guinea-pig diet with moderate levels of vegetable oils containing gamma-linolenic acid (GLA) is associated with elevation of epidermal levels of dihomo-gamma-linolenic acid (DGLA) and 15-hydroxyeicosatrienoic acid (15-lipoxygenase product of DGLA). However, supplementation of diet with higher level (70%) of GLA (GLA-70) resulted in marked decrease of epidermal level of DGLA. This nutritional observation prompted us to investigate in vitro the effects of varying concentrations of polyunsaturated fatty acids (PUFAs) on rat liver microsomal chain elongation of GLA into DGLA. Our data revealed that low concentrations of GLA (less than 100 microM) are stimulatory on the chain elongation while higher concentrations (greater than 100 microM) are inhibitory. The 18-carbon linoleic acid (precursor of GLA) was also markedly inhibitory at high concentrations. Interestingly, the longer chain 20-carbon n-3 PUFAs: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exerted negligible effect. The results suggest that increased systemic presence of free PUFAs, such as may occur in vivo after dietary intake of high n-6 PUFA-containing vegetable oils, may explain the decreased level of DGLA in the epidermal tissue.


Safety and efficacy of tubeless percutaneous nephrostolithotomy.
The experience at this institution with tubeless percutaneous nephrostolithotomy was reviewed to determine its safety and efficacy. Between April 1997 and June 1998, 33 "tubeless" percutaneous nephrostolithotomies were performed. All procedures were performed by a single surgeon (R.W.W). All patients had an internal ureteral stent placed at the time of surgery, and a Foley catheter remained in place overnight. All patients had their nephrostomy tube removed in the OR at the end of their surgery. The length of hospitalization, operative time, patients' comorbid conditions, pre- and postoperative hematocrits, transfusion requirements, reasons for a stay of longer than 24 h, complications, stone burdens treated, residual stone disease, any additional procedures required, and postoperative analgesia requirements were reviewed. All 33 percutaneous procedures were performed without significant complication. No transfusion was required. The average length of hospital stay was 1.5 days, with two-thirds of patients staying less than 24 h. A 94% stone-free rate was achieved, and patients had minimal analgesia requirements. This experience with the "tubeless" percutaneous nephrostolithotomy indicates that it is a safe and effective means of stone management. It will likely have an expanding role in the treatment of stone disease and other urologic problems of the upper urinary tract.


Nonisothermal kinetics using a microcomputer: a derivative approach to the prediction of the stability of penicillin formulations.
A procedure is described for the determination of the shelf-life of pharmaceutical preparations using nonisothermal kinetics. A BASIC computer program, which enables the data analysis to be undertaken rapidly and automatically on a microcomputer, is presented.


Application of principal component analysis for the optimisation of lead(II) biosorption.
Current study was focused on optimising lead(II) biosorption carried out by living cells of Arthrospira platensis using Principal Component Analysis. Various experimental conditions were considered: initial metal concentration (50 and 100 mg/l), solution pH (4.0, 4.5, 5.0, 5.5) and contact time (10, 20, 30, 40, 50 and 60 min) at constant rotary speed 200 rpm. It was found that when the biomass was separated from experimental solutions by the filtration, almost 50% of initial metal dose was removed by the filter paper. Moreover, pH was the most important parameter influencing examined processes. The Principal Component Analysis indicated that the most optimum conditions for lead(II) biosorption were metal initial concentration 100 mg/l, pH 4.5 and time 60 min. According to the analysis of the first component it might be stated that the lead(II) uptake increases in time. In overall, it was found to be useful for analysing data obtained in biosorption experiments and eliminating insignificant experimental conditions. Experimental data fitted Langmuir and Dubinin-Radushkevich models indicating that physical and chemical absorption take place at the same time. Further studies are necessary to verify how sorption-desorption cycles affect A. platensis cells.


Effect of shutdown on styrene removal in a biofilter inoculated with Pseudomonas sp. SR-5.
Styrene gas removal was carried out in a biofilter inoculated with a styrene-degrading Pseudomonas sp. SR-5 using a mixed packing material of peat and ceramic under the non-sterile condition. More than 86% removal efficiency was obtained at styrene load of 5-93 g m(-3) h(-1) for 62 days operation period and 78% carbon of removed styrene was converted to CO2. Thereafter, three kinds of styrene shutdown experiments were conducted: (i) air and mineral medium were supplied for 4 days, (ii) complete shutdown, namely no styrene, air and moisture supply was conducted for 3 days, and (iii) only air was supplied for 11 days. When styrene gas was re-supplied after (i) and (iii) shutdown experiments, styrene removal efficiency rapidly recovered, but after (ii) shutdown, recovery of styrene removal was significantly delayed. Supply of air during shutdown period was found to be enough to resume microbial activity to degrade styrene.


Experimental murine IgA nephropathy following passive administration of vomitoxin-induced IgA monoclonal antibodies.
Oral exposure of mice to vomitoxin (VT) induces elevated levels of serum IgA, circulating IgA immune complexes (IgA-IC), mesangial IgA deposition and haematuria, which all mimic the clinical signs of human IgA nephropathy (IgAN). To further assess the effects of VT-induced IgA in the murine model, B6C3F1 and BALB/C mice were injected intraperitoneally with affinity-purified monoclonal IgA derived from Peyer's patch hybridomas of VT-exposed mice. In B6C3F1 mice, serum IgA, IgM and IgA-IC levels were increased two- to fivefold in treatment groups after 4 and 6 wk compared with controls, whereas increases in serum IgG as high as 18-fold were observed. Urinary erythrocyte counts were also significantly elevated in treatment groups after 2, 4 and 6 wk compared with controls. Concurrent increases in IgA and IgG complexes containing casein, the dietary protein source, occurred in treatment mice. Mesangial IgA, IgG, IgM and C3 deposition were significantly increased in all treatment mice after 6 wk. Electron-dense deposits occurred in the glomeruli of IgA-injected mice after 6 wk. All the above parameters were similarly affected in BALB/C mice. Injection of IgA-secreting hybridoma cells into BALB/C mice increased serum IgA, IgA-IC and IgG levels as well as elevated mesangial IgA, IgG and C3 deposition and haematuria after 2-3 weeks compared with controls. In total, these data indicate that passive administration of VT-induced IgAs can induce the hallmarks of IgA nephropathy. Casein, an antigen found in the diet used for these mice, appeared to form IC with IgA or IgG and these IC may participate in the pathogenesis of this nephropathy.


Taurine, glutamate and GABA modulate the outgrowth from goldfish retinal explants and its concentrations are affected by the crush of the optic nerve.
The amino acid taurine plays an important trophic role during development and regeneration of the central nervous system. Other amino acid systems, such as those for glutamate and gamma-aminobutyric acid (GABA), are modified during the same physiological and pathological processes. After crushing the optic nerve, goldfish retinal explants were plated in the absence and in the presence of different amino acids and amino acid receptor agonists. The length and the density of the neurites were measured at 5 days in culture. Taurine increased the length and the density of neurites. Glutamate and glycine increased them at low concentration, but were inhibitors at higher concentration. The combination of N-methyl-D-aspartate (NMDA) and glycine produced a greater inhibitory effect than NMDA alone. NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) added simultaneously with taurine impaired the stimulatory effect of the latter. GABA stimulated the emission of neurites in a concentration dependent manner. Hypotaurine also elevated the length of neurites, but cysteinsesulfinic acid did not produce a significant effect. The concentrations of taurine, glutamate and GABA were determined by HPLC with fluorescent detection in the retina of goldfish at various days post-crushing the optic nerve. The levels of taurine were significantly increased at 48h after the crush, and were elevated up to 20 days. Glutamate level decreased after the lesion of the optic nerve and was still low at 20 days. GABA concentration was not significantly different from the control. The interaction of these amino acids during the regenerative period, especially the balance between taurine and glutamate, may be a determinant in restoring vision after the crush.


Correlation of antistaphylococcal antibody titers with severity of staphylococcal disease.
Counterimmunoelectrophoresis (CIE) was utilized to determine antistaphylococcal precipitin antibody titers in patients with various staphylococcal diseases and in control subjects. Patients with staphylococcal disease comprised five cases of endocarditis, 22 of deep tissue infection (including seven cases of osteomyelitis), six of bacteremia and six of skin infection. Control subjects consisted of 31 patients with nonstaphylococcal bacteremias, 29 hospitalized patients without infection and 30 healthy subjects. Antistaphylococcal antibodies were present in all patients with staphylococcal endocarditis and deep tissue staphylococcal infection, and all but three had titers greater than or equal to 1:4. No significant difference in titers was found between these two groups of patients. Antibodies, although present in some patients in the other categories, were detected less frequently; only two patients had titers greater than or equal to 1:4. Thus, an antistaphylococcal antibody titer by CIE of 1:4 or greater may be an additional diagnostic parameter helpful in distinguishing patients with staphylococcal endocarditis or deep tissue infection from those with other forms of staphylococcal infection and from noninfected subjects.


Assessing suitability for long-term colorectal cancer shared care: a scenario-based qualitative study.
Shared care is the preferred model for long-term survivorship care by cancer survivors, general practitioners and specialists. However, survivorship care remains specialist-led. A risk-stratified approach has been proposed to select suitable patients for long-term shared care after survivors have completed adjuvant cancer treatment. This study aims to use patient scenarios to explore views on patient suitability for long-term colorectal cancer shared care across the risk spectrum from survivors, general practitioners and specialists. Participants completed a brief questionnaire assessing demographics and clinical issues before a semi-structured in-depth interview. The interviews focused on the participant's view on suitability for long term cancer shared care, challenges and facilitators in delivering it and resources that would be helpful. We conducted thematic analysis using an inductive approach to discover new concepts and themes. Interviews were conducted with 10 cancer survivors, 6 general practitioners and 9 cancer specialists. The main themes that emerged were patient-centredness, team resilience underlined by mutual trust and stronger system supports by way of cancer-specific training, survivorship care protocols, shared information systems, care coordination and navigational supports. Decisions on the appropriateness of this model for patients need to be made collaboratively with cancer survivors, considering their trust and relationship with their general practitioners and the support they need. Further research on improving mutual trust and operationalising support systems would assist in the integration of shared survivorship care.


Routine biliary sphincterotomy may not be indispensable for endoscopic pancreatic sphincterotomy.
It is generally accepted that biliary sphincterotomy is mandatory to avoid possible cholestasis and infection due to edema after pancreatic sphincterotomy. However, biliary sphincterotomy is an invasive procedure and the above claim on dual sphincterotomy has not been proven by a prospective randomized study. The aim of our study was to determine whether cholangitis develops more frequently when the patients have not undergone concomitant biliary sphincterotomy during the endoscopic pancreatic sphincterotomy. From January 1990 to November 1997, 60 patients (38 men, 22 women, age range 19-45 years) with non-alcoholic chronic calcifying pancreatitis were prospectively enrolled. The patients with jaundice (bilirubin > or = 3 mg/dl), cholangitis, or parenchymal liver disease were excluded. The patients were randomly subjected either to dual sphincterotomy (group I, n = 30) or to pancreatic sphincterotomy alone (group II, n = 30). Groups I and II were further classified as IA (or IIA) and IB (or IIB), according to the level of serum alkaline phosphatase (sALP) and the diameter of the common bile duct (CBD). Group IA (or IIA) was defined when abnormal in both sALP (> or = 2 times the upper limit of normal) and CBD diameter (> or = 12 mm), whereas group IB (or IIB) was defined when normal, or solely abnormal in sALP or CBD diameter. As a complication after sphincterotomy, pancreatitis developed in one of eight patients (12.5%) in group IA, whereas cholangitis occurred in one of 22 (4.5%) and hemorrhage in one of 22 (4.5%) cases in group IB. By contrast, in group IIA, the cholangitis developed in 56% (five of nine patients), which was significantly more frequent than in any other groups (P < 0.05). Hemorrhage (one of 21, 4.8%) and pancreatitis (one of 21, 4.8%) occurred in group IIB. Our results suggest that dual sphincterotomy may be indicated only in patients who have both dilated choledochus and elevated alkaline phosphatase in chronic pancreatitis. Routine biliary sphincterotomy may not be indispensable for pancreatic sphincterotomy.


Comparative MR imaging study of brain maturation in kittens with T1, T2, and the trace of the diffusion tensor.
To assess the time-course of the relaxation times and the orientationally averaged water diffusion coefficient Doav in postnatal brain development. Multisection maps of T1, T2, and the trace of the diffusion tensor (Trace[D] = 3 x Doav) were obtained in four kittens at eight time points. In the adult, Doav was about 700 micron 2/sec in both white and gray matter. In the newborn, Doav was 1,100-1,350 micron 2/sec in white matter and 1,000 micron 2/sec in gray matter. For all anatomic regions and time points, the correlation between Doav and 1/T2 was high (R2 = 0.87, P << .001). T1 showed a lower correlation with Doav and a higher sensitivity to myelinization than did T2. Although Doav shows dramatic changes in the maturing brain, the high correlation between Doav and T2 indicates that little additional information can be obtained by measuring this diffusion parameter during normal brain development. This contrasts with previous findings in brain ischemia, where Doav and T2 appear to be uncorrelated. After including the authors' data and published iontophoretic measurements in a simple model of diffusion in tissues, the authors suggest that the underlying mechanisms of Doav reduction in brain maturation and ischemia are different. Doav changes during development are mainly affected by events occurring in the cellular compartment, while changes in extracellular volume fraction and tortuosity, which are thought to determine the reduction in Doav during ischemia, are probably of secondary importance.


Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents.
The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac-superior mesenteric ganglionectomy (CGX). Irrespective of the operational procedure, rimonabant (10mg/kg) effectively reduced standard chow as well as palatable diet (ensure) intake. In conclusion, the data clearly demonstrate that neither vagal gut afferents, nor gut afferents traveling via the sympathetic nervous system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia.