Self-assembly of the hydrophobin SC3 proceeds via two structural intermediates.
Hydrophobins self assemble into amphipathic films at hydrophobic-hydrophilic interfaces. These proteins are involved in a broad range of processes in fungal development. We have studied the conformational changes that accompany the self-assembly of the hydrophobin SC3 with polarization-modulation infrared reflection absorption spectroscopy, attenuated total reflection Fourier transform infrared spectroscopy, and circular dichroism, and related them to changes in morphology as observed by electron microcopy. Three states of SC3 have been spectroscopically identified previously as follows: the monomeric state, the alpha-helical state that is formed upon binding to a hydrophobic solid, and the beta-sheet state, which is formed at the air-water interface. Here, we show that the formation of the beta-sheet state of SC3 proceeds via two intermediates. The first intermediate has an infrared spectrum indistinguishable from that of the alpha-helical state of SC3. The second intermediate is rich in beta-sheet structure and has a featureless appearance under the electron microscope. The end state has the same secondary structure, but is characterized by the familiar 10-nm-wide rodlets.


Association between metabolic effects and tobacco use in 60-year-old Swedish men.
There is a controversy whether use of smokeless tobacco is associated with an increased risk of diabetes. A population-based cross-sectional study was undertaken of 1,859 men, aged 60 years, in Stockholm County. No significant association was found between risk of diabetes and any use of tobacco, even if an association between snuff and risk of diabetes could not be excluded.


The Drosophila homologue of the dystrophin gene - introns containing promoters are the major contributors to the large size of the gene.
We show that the drosophila gene encoding the dystrophin-like protein (DLP) is as complex as the mammalian dystrophin gene. Three 5' promoters and three internal promoters regulate the expression of three full-length and three truncated products, respectively. The existence of this complex gene structure in such evolutionary remote organisms suggests that both types of products have diverse important functions. The promoters of both the DLP gene and the mammalian dystrophin gene are located in very large introns. These introns contribute significantly to the large size of the genes. The possible relevance of the conservation of the large size of introns containing promoters to the regulation of promoter activity is discussed.


A recessive X-linked mutation causes a threefold reduction of total body zinc accumulation in Drosophila melanogaster laboratory strains.
A newly identified human locus on chromosome 15 was recently associated with zinc accumulation. Based on a prior report of a threefold difference in zinc accumulation between fumble(1) heterozygous mutants and control fly strains, it was suggested that phosphopantothenoylcysteine decarboxylase might affect zinc status through its effects on vitamin B5 (pantothenate) metabolism. We report here that outcrossed fumble(1) heterozygous mutant flies with low zinc content have been recovered, suggesting that pantothenate metabolism did not alter zinc homeostasis in fumble(1) heterozygous flies. We show instead that the Drosophila condition of low body zinc accumulation is an X-chromosome-linked recessive trait.


Is there a serious risk of resistance development to azoles among fungi due to the widespread use and long-term application of azole antifungals in medicine?
It is well known that development of antibiotic resistance in bacteria is not a matter of if but of when. Recently, azoles have been recommended for long-term prophylaxis of invasive fungal infections; hence, it could be argued that fungi also will become resistant to these agents. However, fungi are different from bacteria in several critical points. Bacteria display several resistance mechanisms: alteration of the target, limited access to the target and modification/inactivation of the antibacterial compound. In fungi some mechanisms of resistance to azoles are also known; with azoles for example, alterations of the 14alpha-demethylase target, as well as efflux pumps. It has been observed that these phenotypes develop in yeast populations either due to mutations or to selection processes. However, enzymes which destroy azoles are not found. Furthermore, a horizontal transfer of genes coding resistance traits does not occur in fungi, which means that an explosive expansion of resistances is unlikely to occur, especially in moulds. Indeed, in epidemiologic studies on human and environmental isolates there is convincing evidence that azole resistance is quite uncommon.


Facial changes related to brachycephaly in Cavalier King Charles Spaniels with Chiari-like malformation associated pain and secondary syringomyelia.
Recent studies including an innovative machine learning technique indicated Chiari-like malformation (CM) is influenced by brachycephalic features. Morphometric analysis of facial anatomy and dysmorphia in CM-associated pain (CM-P) and syringomyelia (SM) in the Cavalier King Charles Spaniel (CKCS). Sixty-six client-owned CKCS. Retrospective study of anonymized T2W sagittal magnetic resonance imaging of 3 clinical groups: (1) 11 without central canal dilation (ccd) or SM (CM-N), (2) 15 with CM-P with no SM or <2 mm ccd (CM-P), and (3) 40 with syrinx width ≥4 mm (SM-S). Morphometric analysis assessed rostral skull flattening and position of the hard and soft palate relative to the cranial base in each clinical group and compared CKCS with and without SM-S. Sixteen of 28 measured variables were associated to SM-S compared to CM-N and CM-P. Of these 6 were common to both groups. Predictive variables determined by discriminant analysis were (1) the ratio of cranial height with cranial length (P < .001 between SM-S and CM-N) and (2) the distance between the cerebrum and the frontal bone (P < .001 between SM-S and CM-P). CM-P had the lowest mean height of the maxillary area. CKCS with CM-P and SM-S have cranial brachycephaly with osseous insufficiency in the skull with rostral flattening and increased proximity of the hard and soft palate to the cranial base. Changes are greatest with CM-P. These findings have relevance for understanding disease pathogenesis and for selection of head conformation for breeding purposes.


[Pericarditis at the Internal Disease Clinic of the Institute of Tuberculosis and Lung Diseases (1981-1987)].
Causes, symptoms, clinical forms, and methods of diagnosis of pericarditis were analysed in a group of 30 patients. Chest pain, dyspnea, and tachycardia were prevailing clinical symptoms of the disease. Particularly useful diagnostic technique is ultrasound, being a method of choice in the diagnosis of the most frequent exudative pericarditis. The most frequent cause of cardiac tamponade was malignant pericarditis. Diagnostic problems with particular reference to tuberculous etiology of pericarditis have also been discussed.


An overview of safety and regulatory aspects of the new biotechnology.
New technology is producing new drugs and biologic products that present novel safety issues for the regulatory agencies. These products are produced using recombinant DNA or hybridoma techniques. Examples are growth hormone, antihemophilic factor, and interferon, produced by recombinant DNA. Very special proteins, namely, monoclonal antibodies, can be made by hybridoma technology that are extremely pure and potent. At present over two dozen in vitro monoclonal antibody products are approved by FDA and many more are expected. Regulating these products posed some new questions for the FDA, regarding the kinds of safety tests that should be done to establish reasonable levels of safety before clinical trials or marketing of these agents. The production methods are novel and thus require careful consideration to ensure that risks inherent in those methods do not cause disease when these products are administered to human subjects. A general overview of the regulatory safety issues of these new products is given.


Childhood abuse, left-behind status and mental health among lesbian, gay, and bisexual young adults in China.
Lesbian, gay, and bisexual (LGB) young adults are at increased risk of mental distress in China. To better carry out psychological intervention, it is essential to understand unique patterns of mental distress and their association with childhood abuse/neglect, including experiencing being left behind by migrating parents. In a sample of Chinese LGB young adults, we examined: (1) associations between childhood abuse and left-behind status and mental distress; (2) latent profiles of mental distress; and (3) associations between childhood abuse and left-behind status and latent profiles of mental distress. A sample of 630 Chinese LGB young adults aged 18-30 years was recruited to complete an online survey. Participants provided demographic information and completed validated measures of childhood abuse experience and mental distress. Latent profile analysis (LPA) was used to identify patterns of mental distress, and logistic regression analysis was used to examine the relationships among these variables. Results showed that all forms of childhood abuse and left-behind status were associated with all dimensions of adulthood mental distress. The LPA suggested a 3-group solution as optimal (no mental distress, mild mental distress, and moderate/severe mental distress). Participants who experienced any forms of childhood abuse were more likely to be members of both the mild mental distress and moderate/severe mental distress groups (all p's < 0.001). Also, participants who had left-behind status were more likely to be in the moderate/severe mental distress group (AOR = 1.61, p < .05). Our findings highlight the need for interventions aimed at addressing childhood abuse/neglect among Chinese LGB young adults, as these experiences increase the risk for mental health issues in adulthood.


Contacts between receptors and electrophysiologically identified neurones in the retina of the larval tiger salamander.
1. Following the intracellular recording of bipolar and horizontal cell responses, each unit was injected with horseradish peroxidase and a histochemical staining used to identify it at the level of the light and electron microscopes.2. Centre-depolarizing bipolar cells made contact with rods and cones at basal and ribbon junctions, the latter being fewer. Centre-hyperpolarizing bipolar cells made the same types of contacts with the receptors, but ribbon junctions predominated.3. It appears, therefore, that there is no fixed relationship between the sign of synaptic transmission from receptors to bipolar cells and the junctional features revealed by present methods for electron microscopy of tissue sections. Accordingly, the reason for the existence of more than one type of contact between receptors and bipolar cells remains to be determined.4. Light microscopy of the peroxidase-injected horizontal cells gave further support to the notion that type B responses are recorded from the cell body, and type A responses from the axon terminal, of a single type of horizontal cell. Electron microscopy showed that the processes (dendrites) originating from the cell body make ribbon and distal junctions with rods and cones, just as shown before for the axon terminals.5. As a result of these observations, it is possible to exclude one of two alternative hypotheses previously proposed to account for the properties of the surround responses recorded from the horizontal cell bodies.


Schwann cells, neurotrophic factors, and peripheral nerve regeneration.
The peripheral nervous system retains a considerable capacity for regeneration. However, functional recovery rarely returns to the preinjury level no matter how accurate the nerve repair is, and the more proximal the injury the worse the recovery. Among a variety of approaches being used to enhance peripheral nerve regeneration are the manipulation of Schwann cells and the use of neurotrophic factors. Such factors include, first, nerve growth factor (NGF) and the other recently identified members of the neurotrophin family, namely, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5); second, the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF); and third, the transforming growth factors (TGFs)-beta and their distant relative, glial cell line-derived neurotrophic factor (GDNF). In this review article we focus on the roles in peripheral nerve regeneration of Schwann cells and of the neurotrophin family, CNTF and GDNF, and the relationship between these. Finally, we discuss what remains to be understood about the possible clinical use of neurotrophic factors.


Association of different iron deficiency cutoffs with adverse outcomes in chronic kidney disease.
Iron deficiency is highly prevalent in chronic kidney disease (CKD) patients. In clinical practice, iron deficiency is defined based on a combination of two commonly used markers, ferritin and transferrin saturation (TSAT). However, no consensus has been reached which cutoffs of these parameters should be applied to define iron deficiency. Hence, we aimed to assess prospectively which cutoffs of ferritin and TSAT performed optimally for outcomes in CKD patients. We meticulously analyzed 975 CKD community dwelling patients of the Prevention of Renal and Vascular Endstage Disease prospective study based on an estimated glomerular filtration rate < 60 ml/min/1.73m2, albuminuria > 30 mg/24 h, or albumin-to-creatinine ratio ≥ 30 mg/g. Cox proportional hazard regression analyses using different sets and combinations of cutoffs of ferritin and TSAT were performed to assess prospective associations with all-cause mortality, cardiovascular mortality, and development of anemia. Of the included 975 CKD patients (62 ± 12 years, 64% male with an estimated glomerular filtration rate of 77 ± 23 ml/min/1.73m2), 173 CKD patients died during a median follow-up of 8.0 (interquartile range 7.5-8.7) years of which 70 from a cardiovascular cause. Furthermore, 164 CKD patients developed anemia. The highest risk for all-cause mortality (hazard ratio, 2.83; 95% confidence interval, 1.53-5.24), cardiovascular mortality (4.15; 1.78-9.66), and developing anemia (3.07; 1.69-5.57) was uniformly observed for a TSAT< 10%, independent of serum ferritin level. In this study, we have shown that of the traditionally used markers of iron status, reduced TSAT, especially TSAT< 10%, is most strongly associated with the risk of adverse outcomes in CKD patients irrespective of serum ferritin level, suggesting that clinicians should focus more on TSAT rather than ferritin in this patient setting. Specific attention to iron levels below this cutoff seems warranted in CKD patients.


Stimulation of adrenergic nerve fibres to the urinary bladder of the rat.
The contraction of the rat detrusor muscle caused by electrical stimulation of the hypogastric or pelvic nerves was followed by relaxation when the nerves were stimulated for a short period. The relaxation was more pronounced when the initial contraction was reduced by atropine. It was found to be mediated by adrenergic fibres acting on inhibitory beta2-receptors. Stimulation of the hypogastric or pelvic nerves at high frequencies increased the contractile response probably via adrenergic fibres activating excitatory alpha-receptors.


OPG/RANK/RANKL axis relation to cardiac iron-overload in children with transfusion-dependent thalassemia.
OPG/RANK/RANKL axis was reportedly involved in initiating various diseases, especially bone and cardiovascular diseases. This study aimed to assess the relationship between some OPG, RANK, and RANKL polymorphisms and alleles and iron-overload-induced cardiomyopathy in children with transfusion-dependent thalassemia (TDT). This study included 80 TDT children and 80 age and sex-matched controls. Real-time PCR was done for rs207318 polymorphism for the OPG gene and rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, and rs9594782 and rs2277438 polymorphisms for the RANKL gene. Cardiac T2* MRI and ejection fraction (EF) were done to assess the myocardial iron status and cardiac function. In this study, there were no significant differences in frequencies of the studied polymorphisms between cases and controls (p > 0.05 in all). In TDT children, OPG rs2073618 (G > C) had a significant relation to myocardial iron overload (p = 0.02). Its C allele had significantly more frequent normal EF than its G allele (p = 0.04). RANK rs75404403 (C > DEL) had a significant relation to cardiac dysfunction (p = 0.02). Moreover, the C allele of that gene had significantly more frequent affected EF than its DEL allele (p = 0.02). The A allele of RANKL rs2277438 (G > A) had significantly less frequent severe cardiac iron overload than the G allele (p = 0.04). In conclusion, the OPG/ RANK/RANKL genes may act as genetic markers for iron-induced cardiomyopathy in TDT children. Some of the studied genes' polymorphisms and alleles were significantly related to myocardial iron overload and cardiac dysfunction in TDT children.


Cystic fibrosis-adapted Pseudomonas aeruginosa quorum sensing lasR mutants cause hyperinflammatory responses.
Cystic fibrosis lung disease is characterized by chronic airway infections with the opportunistic pathogen Pseudomonas aeruginosa and severe neutrophilic pulmonary inflammation. P. aeruginosa undergoes extensive genetic adaptation to the cystic fibrosis (CF) lung environment, and adaptive mutations in the quorum sensing regulator gene lasR commonly arise. We sought to define how mutations in lasR alter host-pathogen relationships. We demonstrate that lasR mutants induce exaggerated host inflammatory responses in respiratory epithelial cells, with increased accumulation of proinflammatory cytokines and neutrophil recruitment due to the loss of bacterial protease- dependent cytokine degradation. In subacute pulmonary infections, lasR mutant-infected mice show greater neutrophilic inflammation and immunopathology compared with wild-type infections. Finally, we observed that CF patients infected with lasR mutants have increased plasma interleukin-8 (IL-8), a marker of inflammation. These findings suggest that bacterial adaptive changes may worsen pulmonary inflammation and directly contribute to the pathogenesis and progression of chronic lung disease in CF patients.


Characteristic fungi observed in the fermentation process for Puer tea.
The fermentation process for Puer tea, a unique Chinese tea produced by microbial activities, was investigated by physicochemical and microbial analyses. The temperature of a windrow-shaped pile of tea leaves increased instantly at the beginning of fermentation and stayed at around 50 degrees C until day 35, then decreased gradually to room temperature at the end of fermentation, at day 50. Water content was approximately 30% or less, and pH value was maintained at a weakly acidic level of 5 to 6 throughout the fermentation, conditions that are favorable for propagation of fungi including yeasts. Polyphenol, the characteristic component of tea leaves, decreased continually from day 10 to day 50 of fermentation, corresponding well with the fact that the total concentration of fungi steadily increased during the same period. PCR followed by denaturing gradient gel electrophoresis (DGGE) analysis revealed that there were at least two major fungi: Aspergillus niger, which has been well known among Puer tea manufacturers, and Blastobotrys adeninivorans, which is newly recognized in the present study. Furthermore, both of these fungi were observed in the DGGE fingerprint when other commercial Puer tea products were analyzed. These results prompted us to deduce that both A. niger and B. adeninivorans play important roles in the nutritional enhancement of tea leaves during Puer tea fermentation.


Psychosocial factors and shoulder symptom development among workers.
Shoulder injuries are a common cause of pain and discomfort. Many work-related factors have been associated with the onset of shoulder symptoms. The psychosocial concepts in the demand-control model have been studied in association with musculoskeletal symptoms but with heterogeneous findings. The purpose of this study was to assess the relationship between the psychosocial concepts of the demand-control model and the incidence of shoulder symptoms in a working population. After following 424 subjects for approximately 1 year, 85 incident cases were identified from self-reported data. Cox proportional hazards modeling was used to assess the associations between shoulder symptoms and demand-control model quadrants. Cases were more likely to be female and report other upper extremity symptoms at baseline (P < 0.05). From the hazard models, being in either a passive or high strain job quadrant was associated with the incidence of shoulder symptoms. Hazard ratios were 2.17, 95% CI 1.02-4.66 and 2.19, 95% CI 1.08-4.42, respectively. Using self-reporting to determine demand-control quadrants was successful in identifying subjects at risk of developing work-related shoulder symptoms. Research is needed to determine if this relationship holds with clinically diagnosed shoulder and other upper extremity musculoskeletal disorders. This may be part of a simple tool for assessing risk of developing these UEMSDs.


The diabetic alcoholic: characteristics and treatment outcome.
We had previously found a correlation between a recovering alcoholic's propensity to choose free sugar in his diet and his ability to remain sober. To determine if chronic hyperglycemia in itself is a predictor of sobriety, we examined the outcome of alcoholism treatment in 138 diabetics we could identify among 9000 alcoholism treatment outpatients. In general, the diabetics did no better or worse in alcoholism treatment than the whole clinic population, but a subset of the diabetics, those whose diabetes resulted from pancreatitis or pancreatectomy, did very badly. The implications of these findings for future research are discussed.


Impairments in life quality among clients in geriatric home care: associations with depressive and anxiety symptoms.
The aim of this study was to determine the independent contributions of depressive and anxiety symptoms to quality of life among older adults who were receiving services through a home care program. The study sample consisted of 66 community-dwelling older adults (ages 65 years and older), who were experiencing chronic medical illness and concomitant functional disability necessitating home care. Participants completed self-report measures of depression, anxiety, and health-related quality of life. Additional data on cognitive, health, and functional status were collected to be used as covariates. The associations of depressive symptoms with quality of life impairments in home care were substantial and pervasive. Depressive symptoms were significantly associated with quality of life impairments in nearly all domains. After controlling for depressive symptoms, anxiety symptoms accounted for additional and statistically significant variance in impaired life quality in the domains of mental health, role emotional functioning, and bodily pain. These results indicate that depressive and anxiety symptoms demonstrate negative associations with life quality among older adults in home care and highlight the importance of developing community-based programs to assess and treat depressive and anxiety symptoms among home care clients.


Body temperature and heart rate rhythms in acutely head-injured patients.
This descriptive pilot study investigated the circadian (24-hour) rhythms of heart rate and temperature in acutely head-injured patients and the relationships between these variables. The convenience sample consisted of 10 patients who were admitted to the hospital with the diagnosis of acute head injury. Patel's Method of Partition was used to estimate rhythmicity. Only one patient demonstrated circadian rhythms for body temperature and heart rate with the peaks occurring at appropriate times. While three other patients had significant rhythms for these variables, the rhythms had cycles of less than 24 hours and peaks occurring at inappropriate times. Although significant correlations were found between body temperature and heart rate rhythms, they were low.


Study on the pathogenesis of pathophysiological changes of burn systemic infection.
The present prospective study showed that incidence of systemic infection in severe burn patients was 30.9%. Toxic shock and multiple organ failure (MOF) developed in all patients with uncontrolled systemic infection. Both morbidity and mortality of MOF were 76.5%. In the infection group, plasma TXB(2) and TXB(2)/6-keto-PGF(1alpha) ratio increased markedly. Their changes were closely correlated with the clinical course and deterioration of systemic infection. Circulatory platelet aggregate ratio decreased significantly, while myocardiac enzyme spectrum greatly increased. Thrombi were observed in visceral tissues from patients dying of systemic infection. These suggested that TXA(2)/PGI(2). imbalance promoting microaggregate and thrombus formation may be one of the pathogenic effects of toxic shock and MOF in burn patients.


Evaluation of a Lay First Responder Program in Sierra Leone as a Scalable Model for Prehospital Trauma Care.
Few countries in Sub-Saharan Africa have robust emergency medical services (EMS). The World Health Organization (WHO) recommends scaling-up lay first responder programs as the first step toward formal EMS development. We trained and equipped 4,529 lay first responders (LFRs) between June-December 2019 in Bombali District, Sierra Leone, with a 5-hour hands-on, contextually-adapted prehospital trauma course to cover 535,000 people. Instructors trained 1,029 LFRs and 50 local trainers in a training-of-trainers (TOT) model, who then trained an additional 3,500 LFRs. A validated, 23-question pre-/post-test measured knowledge improvement, while six- and nine-month follow-up tests measured knowledge retention. Incident reports tracked patient encounters to assess longitudinal impact. Median pre-/post-test scores improved by 43.5 percentage points (34.8% vs. 78.3%, p<0.0001). Knowledge retention was assessed at six months, with median score dropping to 60.9%, while at nine months, median score dropped to 43.5%. Lay first responders participating in courses led by TOT trainers had a pre-/post-test median score improvement of 30.4 percentage points (21.7% vs. 52.2%, p<0.0001). LFRs treated 1,850 patients over six months, most frequently utilizing hemorrhage control skills in 61.2% of encounters (1,133/1,850). The plurality of patients were young adult males (36.8%) and 48.7% of encounters were motorcycle injury-related. A 5-hour first responder course targeting laypeople demonstrates significant emergency care knowledge improvement and retention. By training networks of transportation providers, lay first responder programs represent a robust and scalable prehospital emergency care alternative for low-resource settings.


V-Set Immunoglobulin Domain-Containing Protein 4 as a Novel Serum Biomarker of Lupus Nephritis and Renal Pathology Activity.
To discover novel serum biomarkers that have diagnostic or predictive value in lupus nephritis (LN). Using a quantitative protein microarray, we screened for high-abundant proteome expression in the serum of patients with LN compared to healthy controls. Top candidates from this screening were validated using a larger cohort of patients with LN compared to a disease control cohort (subjects with other chronic kidney diseases) and a healthy control cohort. Promising markers were then selected using a machine-learning model and further validated with a larger patient cohort. The corresponding autoantibodies and immune complexes containing these proteins were also examined. In total, 13 proteins were found to be significantly elevated in LN patient serum in the screening, among which 8 proteins were validated by enzyme-linked immunosorbent assay using 81 serum samples from LN patients and control subjects. Three serum markers with LN diagnostic potential were identified using feature importance analysis and further validated using 155 serum samples from LN patients and control subjects. V-set immunoglobulin domain-containing protein 4 (VSIG4) appeared to be the most promising marker in distinguishing LN from healthy controls, with an area under the curve of 0.93. VSIG4 could also discriminate active LN from inactive LN. Furthermore, serum VSIG4 levels were positively correlated with all of the following clinical parameters: the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (Spearman's rank correlation rs = 0.42, P < 0.001), the renal domain score of the SLEDAI (rs = 0.46, P < 0.001), the urinary protein-to-creatinine ratio (rs = 0.56, P < 0.001), and the serum creatinine level (rs = 0.41, P < 0.001). Importantly, we found that serum VSIG4 levels tracked with LN disease activity longitudinally, and that serum VSIG4 levels reflected the renal pathology activity index (AI), particularly the AI components of crescent formation and hyaline deposits. VSIG4 may be a promising novel serum biomarker and therapeutic target in patients with LN.


A novel noble-metal-free Mo2C-In2S3 heterojunction photocatalyst with efficient charge separation for enhanced photocatalytic H2 evolution under visible light.
Currently, designing novel noble-metal-free photocatalysts with efficient carriers migration and catalytically active sites have been a researching hotspot in photocatalytic hydrogen evolution. In this paper, a novel noble-metal-free Mo2C-In2S3 heterojunction was synthesized by a simple hydrothermal method. Morphology characterization revealed In2S3 was attached to Mo2C. Electrochemical results showed Mo2C improved the interface conductivity, and promoted the transportation of photogenerated carriers. Under visible light, the optimal Mo2C-In2S3 composite achieved a H2 generation rate of 535.58 μmol h-1 g-1, which was 175.6 and 25.8 times higher than pristine In2S3 (3.05 μmol h-1 g-1) and In2S3-1% Pt (20.73 μmol h-1 g-1). In addition, a reasonable mechanism of the elevated photocatalytic activity was also discussed. This study demonstrates commercial Mo2C has an important effect of separating carriers and replacing Pt as co-catalyst in heterojunctions. This research also provides a method to design and synthesize new noble-metal-free photocatalysts for excellent hydrogen production activity.


Genetic diversity and molecular evolution of Plasmodium vivax Duffy Binding Protein and Merozoite Surface Protein-1 in northwestern Thailand.
The local diversity and population structure of malaria parasites vary across different regions of the world, reflecting variations in transmission intensity, host immunity, and vector species. This study aimed to use amplicon sequencing to investigate the genotypic patterns and population structure of P. vivax isolates from a highly endemic province of Thailand in recent years. Amplicon deep sequencing was performed on 70 samples for the 42-kDa region of pvmsp1 and domain II of pvdbp. Unique haplotypes were identified and a network constructed to illustrate genetic relatedness in northwestern Thailand. Based on this dataset of 70 samples collected between 2015 and 2021, 16 and 40 unique haplotypes were identified in pvdbpII and pvmsp142kDa, respectively. Nucleotide diversity was higher in pvmsp142kDa than in pvdbpII (π = 0.027 and 0.012), as was haplotype diversity (Hd = 0.962 and 0.849). pvmsp142kDa also showed a higher recombination rate and higher levels of genetic differentiation (Fst) in northwestern Thailand versus other regions (0.2761-0.4881). These data together suggested that the genetic diversity of P. vivax in northwestern Thailand at these two studied loci evolved under a balancing selection, most likely host immunity. The lower genetic diversity of pvdbpII may reflect its stronger functional constrain. In addition, despite the balancing selection, a decrease in genetic diversity was observed. Hd of pvdbpII decreased from 0.874 in 2015-2016 to 0.778 in 2018-2021; π of pvmsp142kDa decreased from 0.030 to 0.022 over the same period. Thus, the control activities must have had a strong impact on the parasite population size. The findings from this study provide an understanding of P. vivax population structure and the evolutionary force on vaccine candidates. They also established a new baseline for tracking future changes in P. vivax diversity in the most malarious area of Thailand.


Prediction model of RSV-hospitalization in late preterm infants: An update and validation study.
New vaccines and RSV therapeutics have been developed in the past decade. With approval of these new pharmaceuticals on the horizon, new challenges lie ahead in selecting the appropriate target population. We aimed to improve a previously published prediction model for prediction of RSV-hospitalization within the first year of life. Two consecutive prospective multicenter birth cohort studies were performed from June 2008 until February 2015. The first cohort (RISK-I, n=2524, 2008-2011) was used to update the existing model. The updated model was subsequently validated in the RISK-II cohort (n=1564, 2011-2015). We used the TRIPOD criteria for transparent reporting. 181 infants (n=127 in RISK-I, n=54 in RISK-II) were hospitalized for RSV within their first year of life. The updated model included the following predictors; day care attendance and/or siblings (OR: 5.3; 95% CI 2.8-10.1), birth between Aug. 14th and Dec. 1st (OR: 2.4; 1.8-3.2), neonatal respiratory support (OR 2.2; 1.6-3.0), breastfeeding ≤4 months (OR 1.6; 1.2-2.2) and maternal atopic constitution (OR 1.5; 1.1-2.1). The updated models' discrimination was superior to the original model in the RISK-II cohort (AUROC 0.72 95% CI 0.65-0.78 versus AUROC 0.66, 95% CI 0.60-0.73, respectively). The updated model was translated into a simple nomogram to be able to distinguish infants with high versus low risk of RSV-hospitalization. We developed and validated a clinical prediction model to be able to predict RSV-hospitalization in preterm infants born within 32-35 weeks gestational age. A simple nomogram was developed to target RSV therapeutics to those children who will benefit the most.


Two types of liver-specific F antigen are encoded by a locus located on chromosome 5 in mice.
Two types of liver-specific F antigen in mice were distinguished by an immunoblotting technique after IEF of liver extracts. The IEF banding patterns consist of several bands whose pI vary from 7.57 to 8.15. One type of antigen (designated F2 antigen) showed a pattern that lacked some basic bands which are present in the pattern of the other type of antigen (designated F1 antigen). The latter type was found in AKR, CBA, C3H, DBA/2, and SM strains, while the former type was found in A, C57BL, and many other strains. Breeding experiments indicated that this variation is controlled by a single autosomal locus designated Laf (liver antigen F). Linkage analysis showed that the Laf locus is linked to the Pgm-1 locus on chromosome 5. The recombination frequency between these two loci is estimated to be 0.173 +/- 0.037. The distribution of F1 and F2 antigen types among inbred strains is concordant with that of type 1 and type 2 F antigens, which have been previously distinguished by their immunogenic differences, i.e., whether alloimmunization with the liver extracts from a given strain of mice can produce the antibody to F antigen in certain strains of mice. It is suggested, therefore, that the Laf locus may encode an allogeneic moiety of F antigen molecules.


The role of structured Antenatal Risk Management (sARM) on experiences with antenatal care by vulnerable clients.
Vulnerable clients (i.e. clients reporting psychopathology, psychosocial problems, or substance use, and/or features of deprivation) represent a challenge in perinatal care, both in term of care process and outcome. Adhering to a structured care process (i.e. structured Antenatal Risk Management [sARM]) has shown to benefit professionals in supporting vulnerable clients, but its effect on client experiences is yet to be determined. As better processes are assumed to benefit outcome, we investigated the relationship between vulnerable clients' experiences with antenatal care in perinatal units adhering to differing degrees of sARM. We combined data from two sources: on the client level antenatal collected survey data from which vulnerability status (Mind2Care instrument) and client experiences (ReproQ questionnaire) were derived, and on the unit level interview data from healthcare providers from which the unit degree of sARM was ascertained. A total of N = 1.176 clients from N = 38 units were included in the study. Vulnerable clients with psychosocial problems reported more negative experiences than non-vulnerable clients. In high sARM units, vulnerable clients, regardless of type of problems, reported more negative experiences than non-vulnerable clients. In multiple regression analysis this effect disappeared and only vulnerability defined as psychosocial problems remained predictive for negative experiences. Vulnerable clients, specifically those with psychosocial problems, present a challenge in perinatal healthcare. Negative appraisal of care might be an unavoidable drawback of adhering to sARM. It also stresses the need for improving caregiver-client expectations and system side improvements.


The problem of carcinoma developing in a fibroadenoma: recent experience at Memorial Hospital.
Fourteen new cases of unsuspected carcinoma developing in fibroadenomas are reported with a detailed analysis of their preoperative findings; histopathology, the results of varying surgical procedures and a three month to twenty-six year follow-up. The majority of lesions were lobular carcinoma in situ (71%) and 29% of all cases were found to have carcinoma of the contralateral breast. Our study suggests that for invasive carcinoma within a fibroadenoma complete mastectomy is warranted in virtually all instances while noninvasive disease treated by complete mastectomy is essentially curative. Contralateral breast biopsy at the time of diagnosis with a careful life-time follow-up are appropriate because of the high risk of contralateral invasive coarcinoma. There seemed to be no evidence of striking or unusual epithelial hyperplasia in the breast tissue adjacent to fibroadenomas that contained carcinoma suggesting that the carcinomas are not intrinsically different from those not related to fibroadenomas.


Serendipitous detection of an errant central venous catheter.
The inappropriate placement of a patient's central venous catheter in the pleural space by the serendipitous injection of Tc-99m labeled red blood cells through the catheter during a GI bleeding study was discovered. Position and patency of central venous lines can be incidentally evaluated by using existing central venous catheters for administration of radiopharmaceuticals during radionuclide imaging studies.


CP/MAS spectroscopy in the determination of the tautomeric forms of gossypol, its Schiff bases and hydrazones in the solid state.
New Schiff bases and new hydrazones were synthesized and studied by (13)C and (15)N CP/MAS spectroscopy and by (1)H--(1)H COSY, (1)H--(13)C HMBC, (1)H--(13)C HSQC, (1)H--(15)N HMQC and (1)H--(15)N HSQC correlations. The CP/MAS investigation of gossypol has demonstrated that in the solid state it exists exclusively in the aldehyde-aldehyde tautomeric form. In contrast, CP/MAS studies of hydrazones and Schiff bases reveal that these compounds occur in the solid state in the N-imine-N-imine and enamine-enamine tautomeric forms, respectively. It is shown that the (13)C resonances of C-6, C-7 and C-11 carbon atoms are suitable for distinguishing between the tautomeric forms of aza-derivatives of gossypol in the solid state. Furthermore, we have proved that the (15)N CP/MAS spectra can be used to identify these tautomeric forms.


Trauma-associated growth of suspected dormant micrometastasis.
Cancer patients may harbor micrometastases that remain dormant, clinically undetectable during a variable period of time. A traumatic event or surgery may trigger the balance towards tumor growth as a result of associated angiogenesis, cytokine and growth factors release. We describe a patient with non-small lung cancer who had a rapid tumor growth and recurrence at a minor trauma site of his skull bone. This case is an illustration of the phenomenon of tumor growth after trauma or surgery and its associated cellular mechanisms. This phenomenon deserves further investigation and study.


Convulsions induced by lindane and the involvement of the GABAergic system.
The neurochemical changes underlying the convulsant effects of Lindane, an organochlorinated insecticide, are not known. Since electrophysiological and pharmacological data suggest the view that gamma-aminobutyric acid (GABA) plays an important role in controlling convulsive seizures, the effect of lindane on the GABAergic system, on different areas of the rat brain, has been evaluated. Lindane (100 mg/kg i.p.) induces a selective increase of GABA levels in the cerebellum after the onset of seizures. Non-significant increases were observed in the cortex and hippocampus. GABA turnover, as measured by the accumulation rate of GABA after blockade of its catabolism, was increased in all the brain areas examined. On the other hand, lindane does not significantly displace from their binding sites in vitro either 3H-GABA or 3H-Flunitrazepam. These findings show that convulsions elicited by lindane are not due to an impairment of the GABAergic system. Moreover, an increase of GABA functional activity takes place, in all brain areas examined, probably as a protective mechanism to counteract the seizures.


Possible involvement of the spinal substance P system in pilocarpine-induced scratching in mice.
IT administration of pilocarpine in the spinal subarachnoid space of mice produced a dose-related hindlimb scratching. When coadministered with substance P IT, the pilocarpine-induced scratches were enhanced by high doses of substance P but not by subthreshold doses. This characteristic behavioral response was inhibited dose dependently by IT coadministration of spantide [D-Arg1, D-Trp7,9,Leu11] substance P. Significant antagonistic effects of [D-Phe7,D-His9] substance P (6-11), a selective antagonist for substance P receptors, and substance P (1-7), a substance P N-terminal fragment, were observed against the pilocarpine-induced scratching. Pretreatment with substance P antiserum resulted in the reduction of the response to pilocarpine. When coadministered IT with pilocarpine, atropine potently inhibited pilocarpine-induced scratching. These results demonstrate that not only muscarinic receptors but also substance P-containing neurons in the mouse spinal cord may be involved in elicitation of the scratching behavior following IT injection of pilocarpine.


The effect of spinal cord stimulation on idiopathic detrusor instability and incontinence: a case report.
A patient with long-standing symptoms of detrusor instability has been treated by electrical stimulation of the spinal cord. Stimulation abolished all symptoms and unequivocally inhibited episodes of instability.


L-carnitine inhibits hypoglycemia-induced brain damage in the rat.
Hypoglycemia sometimes occurs in patients with diabetes mellitus who receive excessive doses of insulin. Severe hypoglycemia has been known to induce mitochondrial swelling followed by neuronal death in the brain. Since L-carnitine effectively preserves mitochondrial function in various cells both in vitro and in vivo, we investigated its effects on the neuronal damage induced by hypoglycemic insult in male Wistar rats. Animals were given L-carnitine-containing water (0.1%) for 1 week and then received insulin (20 U/kg, i.p.) to induce hypoglycemia. Although L-carnitine did not affect the mortality of animals that developed hypoglycemic shock, it improved the cognitive function of the survived animals as assessed by the Morris water-maze test. L-carnitine effectively inhibited the increase in oxidized glutathione and mitochondrial dysfunction in the hippocampus and prevented neuronal injury. L-carnitine also inhibited the decrease in mitochondrial membrane potential and the generation of reactive oxygen species in hippocampal neuronal cells cultured in glucose-deprived medium. These results suggest that L-carnitine prevents hypoglycemia-induced neuronal damage in the hippocampus, presumably by preserving mitochondrial functions. Thus, L-carnitine may have therapeutic potential in patients with hypoglycemia induced by insulin overdose.


Principles for consistent value assessment and sustainable funding of orphan drugs in Europe.
The European Orphan Medicinal Products (OMP) Regulation has successfully encouraged research to develop treatments for rare diseases resulting in the authorisation of new OMPs in Europe. While decisions on OMP designation and marketing authorisation are made at the European Union level, reimbursement decisions are made at the national level. OMP value and affordability are high priority issues for policymakers and decisions regarding their pricing and funding are highly complex. There is currently no European consensus on how OMP value should be assessed and inequalities of access to OMPs have previously been observed. Against this background, policy makers in many countries are considering reforms to improve access to OMPs. This paper proposes ten principles to be considered when undertaking such reforms, from the perspective of an OMP manufacturer. We recommend the continued prioritisation of rare diseases by policymakers, an increased alignment between payer and regulatory frameworks, pricing centred on OMP value, and mechanisms to ensure long-term financial sustainability allowing a continuous and virtuous development of OMPs. Our recommendations support the development of more consistent frameworks and encourage collaboration between all stakeholders, including research-based industry, payers, clinicians, and patients.


Asparaginyl-rhamnose: a novel type of protein-carbohydrate linkage in a eubacterial surface-layer glycoprotein.
The subunits of the crystalline surface layer of Bacillus stearothermophilus, strain NRS 2004/3a contain carbohydrates covalently linked to protein. Hydrolysis of a glycopeptide obtained by pronase digestion of the glycoprotein and analysis of the fragments revealed that rhamnose is N-glycosidically linked to the amide nitrogen of an asparaginyl residue.


Potentiating effect of glabridin on GABAA receptor-mediated responses in dorsal raphe neurons.
Flavonoid-rich ethanol extracts of licorice root have sedative and anxiolytic effects. Glabridin is a major flavonoid component from licorice which we evaluated by examining GABA responses in acutely isolated dorsal raphe neurons of the rat. Neurons were recorded with patch-clamp methods at a holding potential of - 50 mV. Glabridin potentiated GABA-induced responses by positively modulating GABAA receptor responses with different concentration range. GABA (2 × 10(-6) M)-evoked currents were potentiated in a stepwise pattern increasing glabridin concentration. Between 10(-12) and 10(-8) M glabridin increased GABA responses by about 140 % of the control. At concentrations above 10(-7) M, a much larger, dose-dependent potentiation occurred before reaching a plateau at 3 × 10-6 M glabridin. A hypnotic drug, zolpidem, also induced biphasic concentration-potentiation relationship. The glabridin potentiation ratio was 2.2 times larger than the maximum potentiation to the benzodiazepine receptor full agonist diazepam. Benzodiazepine receptor antagonist, flumazenil (3 × 10(-7) M), failed to inhibit glabridin (3 × 10(-7) M)-induced potentiation. This result implies that glabridin may exhibit sedative and hypnotic effects by potentiating GABAergic inhibition in dorsal raphe neurons by GABAA receptor actions.


Gamma Radiation Sterilization Reduces the High-cycle Fatigue Life of Allograft Bone.
Sterilization by gamma radiation impairs the mechanical properties of bone allografts. Previous work related to radiation-induced embrittlement of bone tissue has been limited mostly to monotonic testing which does not necessarily predict the high-cycle fatigue life of allografts in vivo. We designed a custom rotating-bending fatigue device to answer the following questions: (1) Does gamma radiation sterilization affect the high-cycle fatigue behavior of cortical bone; and (2) how does the fatigue life change with cyclic stress level? The high-cycle fatigue behavior of human cortical bone specimens was examined at stress levels related to physiologic levels using a custom-designed rotating-bending fatigue device. Test specimens were distributed among two treatment groups (n = 6/group); control and irradiated. Samples were tested until failure at stress levels of 25, 35, and 45 MPa. At 25 MPa, 83% of control samples survived 30 million cycles (run-out) whereas 83% of irradiated samples survived only 0.5 million cycles. At 35 MPa, irradiated samples showed an approximately 19-fold reduction in fatigue life compared with control samples (12.2 × 10(6) ± 12.3 × 10(6) versus 6.38 × 10(5) ± 6.81 × 10(5); p = 0.046), and in the case of 45 MPa, this reduction was approximately 17.5-fold (7.31 × 10(5) ± 6.39 × 10(5) versus 4.17 × 10(4) ± 1.91 × 10(4); p = 0.025). Equations to estimate high-cycle fatigue life of irradiated and control cortical bone allograft at a certain stress level were derived. Gamma radiation sterilization severely impairs the high cycle fatigue life of structural allograft bone tissues, more so than the decline that has been reported for monotonic mechanical properties. Therefore, clinicians need to be conservative in the expectation of the fatigue life of structural allograft bone tissues. Methods to preserve the fatigue strength of nonirradiated allograft bone tissue are needed. As opposed to what monotonic tests might suggest, the cyclic fatigue life of radiation-sterilized structural allografts is likely severely compromised relative to the nonirradiated condition and therefore should be taken into consideration. Methods to reduce the effect of irradiation or to recover structural allograft bone tissue fatigue strength are important to pursue.


Objective Gait Analysis: Review and Clinical Applications.
Objective kinetic and kinematic data can be used as an objective measure of treatment intervention over time but can also be used to evaluate progress of clinical patients. Force plate and pressure sensitive walkway systems both offer the clinician the ability to obtain useful kinetic data, whereas additional equipment is required to obtain kinematic data. Which system is preferred depends on what specific data the researcher or clinician hopes to acquire; both are accurate and consistent, and each offers pros and cons compared with the other that must be considered.


Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: A (31)P MRS study.
Impaired homeostasis of hepatic ATP has been associated with NAFLD. An intravenous fructose infusion has been shown to be an effective challenge to monitor the depletion and subsequent recovery of hepatic ATP reserves using (31)P MRS. The purpose of this study was to evaluate the effects of an oral rather than intravenous fructose challenge on hepatic ATP reserves in healthy subjects. Self-reported healthy males were recruited. Following an overnight fast, baseline liver glycogen and lipid levels were measured using Magnetic Resonance Spectroscopy (MRS). Immediately after consuming a 500 ml 75 g fructose drink (1275 kJ) subjects were scanned continuously for 90 min to acquire dynamic (31)P MRS measurements of liver ATP reserves. A significant effect on ATP reserves was observed across the time course (P < 0.05). Mean ATP levels reached a minimum at 50 min which was markedly lower than baseline (80 ± 17% baseline, P < 0.05). Subsequently, mean values tended to rise but did not reach statistical significance above minimum. The time to minimum ATP levels across subjects was negatively correlated with BMI (R(2) = 0.74, P < 0.005). Rates of ATP recovery were not significantly correlated with BMI or liver fat levels, but were negatively correlated with baseline glycogen levels (R(2) = 0.7, P < 0.05). Depletion of ATP reserves can be measured non-invasively following an oral fructose challenge using (31)P MRS. BMI is the best predictor of postprandial ATP homeostasis following fructose consumption.


The ultra-slow NAT2*6A haplotype is associated with reduced higher cognitive functions in an elderly study group.
N-Acetyltransferase 2 (NAT2) genotype is associated with age-related declines in basic sensory hearing functions. However, the possible modulatory role of NAT2 for higher cognitive functions has not yet been studied. We tested auditory goal-directed behavior and attentional control in 120 NAT2 genotyped subjects (63-88 years), using an auditory distraction paradigm in which participants responded to the duration of long and short tone stimuli. We studied involuntary shifts in attention to task-irrelevant deviant stimuli and applied event-related potentials (ERPs) to examine which cognitive subprocesses are affected by NAT2 status on a neurophysiological level. Relative to the standard stimuli, deviant stimuli decreased performance in the recently described ultra-slow acetylators (NAT2*6A and *7B): The increase in error-corrected reaction times (a combined measure of response speed and accuracy) in ultra-slow acetylators (254 ms increase) was more than twice as high as in the rapid acetylator reference group (111 ms increase; p < 0.01). The increase was still higher than in the other slow acetylators (149 ms increase, p < 0.05). In addition, clear differences were found in the ERP results: Ultra-slow acetylators showed deficits specifically in the automatic detection of changes in the acoustic environment as evidenced by reduced mismatch negativity (MMN, p < 0.005 compared to rapid acetylators). Refocussing of attention after a distracting event was also impaired in the ultra-slow acetylators as evidenced by a reduced re-orienting negativity (RON, p < 0.01 compared to rapid acetylators). In conclusion, the ultra-slow acetylation status was associated with reduced higher cognitive functions.


Developing a clinical trial unit to advance research in an academic institution.
Research, clinical care, and education are the three cornerstones of academic health centers in the United States. The research climate has always been riddled with ebbs and flows, depending on funding availability. During a time of reduced funding, the number and scope of research studies have been reduced, and in some instances, a field of study has been eliminated. Recent reductions in the research funding landscape have led institutions to explore new ways to continue supporting research. Mayo Clinic in Rochester, MN has developed a clinical trial unit within the Department of Medicine, which provides shared resources for many researchers and serves as a solution for training and mentoring new investigators and study teams. By building on existing infrastructure and providing supplemental resources to existing research, the Department of Medicine clinical trial unit has evolved into an effective mechanism for conducting research. This article discusses the creation of a central unit to provide research support in clinical trials and presents the advantages, disadvantages, and required building blocks for such a unit.


Characterization of the glutamate-specific endopeptidase from Bacillus licheniformis expressed in Escherichia coli.
Glutamate-specific endopeptidase from Bacillus licheniformis (GSE-BL) is widely used in peptide recovery and synthesis because of its unique substrate specificity. However, the mechanism underlying its specificity is still not thoroughly understood. In this study, the roles of the prosegment and key amino acids involved in the proteolytic activity of GSE-BL were investigated. Loss of the GSE-BL prosegment severely restricted enzymatic activity toward Z-Phe-Leu-Glu-pNA. A homologous model of GSE-BL revealed that it contains the catalytic triad "His47, Asp96 and Ser 167", which was further confirmed by site-directed mutagenesis. In vitro mutagenesis further indicated that Val2, Arg89 and His190 are essential for enzymatic activity toward Z-Phe-Leu-Glu-pNA. Moreover, the catalytic efficiency of Phe57Ala GSE-BL toward Z-Phe-Leu-Glu-pNA was 50% higher than that of the native mature GSE-BL. This is the first study to fully elucidate the key amino acids for proteolytic activity of GSE-BL. Mature GSE-BL could be obtained through self-cleavage alone when Lys at -1 position was replaced by Glu, providing a new strategy for the preparation of mature GSE-BL. This study yielded some valuable insights into the substrate specificity of glutamate-specific endopeptidase, establishing a foundation for broadening the applications of GSE-BL.


Ethanol attenuates the response of locus coeruleus neurons to excitatory amino acid agonists in vivo.
Recent in vitro electrophysiological studies have revealed that ethanol specifically reduces N-methyl-D-aspartate (NMDA)-activated ion currents, e.g. in hippocampal slices. In the present study, utilizing extracellular recording techniques, the effect of ethanol on excitatory amino acid induced excitability of rat locus coeruleus noradrenergic neurons was investigated in vivo. Administration of ethanol (2 g/kg, i.p.) significantly inhibited the excitation of the locus coeruleus neurons as produced by microiontophoretic application of glutamate, NMDA or quisqualate, but not that of kainate. In contrast, the locus coeruleus response to similarly applied acetylcholine was unaffected by the ethanol treatment. Although ethanol did not alter the basal firing rate of locus coeruleus neurons, the drug significantly changed the firing pattern of the neurons into a more regularized rhythm. It is proposed that the presently observed attenuation of glutamate excitation of locus coeruleus by ethanol may constitute part of the underlaying mechanism for ethanol intoxication in man.


Electricity production and microbial community in psychrophilic microbial fuel cells at 10 °C.
Psychrophilic microbial fuel cell (PMFC) offers an alternative method for low temperature wastewater treatment, but is seldom reported. In this study, the two-chamber PMFC was constructed at 10 °C using acetate as an electron donor. The maximum voltage under external resistance of 1000 Ω was around 550 mV. The columbic efficiency (CE) was 82.4% under external resistance of 100 Ω and the max power density was 582.4 mW/m2. After temperature decreasing to 4 °C, the maximum voltage also reached 530 mV and CE was 38.4%. The direct electron transfer was proposed in PMFC according to cyclic voltammetry curves. The short enriching time (~30 days) of biofilm in the anodic electrode may be due to the high activity of enriched novel exoelectrogens of M. fermentans (46.2%) and E. lemanii (15.4%). The development of PMFC involved biotechnologies in low temperature regions shall benefit for valuable chemicals production and energy generation in the future.


Clock drawing in Alzheimer's disease. A novel measure of dementia severity.
We have tested a simple and reliable measure of visuospatial ability in Alzheimer patients--the Clock Drawing Test. To determine the usefulness of this measure, we asked 67 Alzheimer patients and 83 normal controls to draw the face of a clock reading the time of 2:45. Six independent observers blindly evaluated the results with ratings from 10 (best) to 1 (worst). The mean performance score of Alzheimer subjects was 4.9 +/- 2.7 compared to 8.7 +/- 1.1 for normal controls (P less than .001). Inter-rater reliability for the clocks drawn by Alzheimer patients was highly significant (r = 0.86; P less than .001), and there was relatively little overlap between ratings for Alzheimer patients and normal controls. Furthermore, correlations were highly significant (P less than .001) between the mean score of clock drawings and three independent global measures of dementia severity. Although the Clock Drawing Test is certainly not a definitive indicator of Alzheimer's disease, the test is easy to administer and provides a useful measure of dementia severity for both research and office settings where sophisticated neuropsychological testing is not available.


European Human Rights Dimension of the Online Access to Cultural Heritage in Times of the COVID-19 Outbreak.
The 1948 Universal Declaration of Human Rights recognized that "everyone has the right freely to participate in the cultural life of the community, to enjoy the arts and to share in scientific advancement and its benefits". As a result, cultural rights have been understood as inseparable from human rights and require protection mechanisms within particular international (including regional) legal systems. The European continent is proud to have developed one of the most effective mechanisms of the human rights protection by establishing the Council of Europe and adopting the European Court of Human Rights. The recent outbreak of the COVID-19 reformulated many concepts of access to human rights and possibilities to enjoy freedoms. Even if access to culture (access to cultural heritage) has been available online for many years, it is the time of globally occurring lockdowns that forced people to stay home and found themselves in a situation when all of a sudden online access to culture became the only way of access to culture. The article aims to analyze the current situation in Europe by asking questions if and how online access to culture is recognized and protected under the Council of Europe's mechanisms with special emphasis on the case-law of the European Court of Human Rights in this field.


Catabolite repression in Escherichia coli mutants lacking cyclic AMP.
The regulation of catabolite repression of beta-galactosidase has been studied in Escherichia coli mutants deleted for the adenyl cyclase gene (cya delta), and thus unable to synthesize cyclic AMP. It has been found that, provided a second mutation occurs either in the crp gene coding for the catabolite gene activator protein (CAP) or in the Lactose region, these mutants exhibit catabolite repression. If the catabolite repression seen in the mutant strains corresponds to the mechanism operating in wild-type cells the results would suggest that the intracellular concentration of cyclic AMP cannot be the unique regulator of catabolite repression.


Gastric microbleeding following single and repeated dosing with naproxen.
Adaptation to gastric damage from nonsteroidal anti-inflammatory drugs (NSAID) has been observed during ongoing dosage in rats and humans. However, this does not always occur, and our previous data suggest that NSAID half-life may be a determining factor. To investigate whether adaptation occurs during 1 week of naproxen administration in humans. Thirteen healthy volunteers were studied at baseline, and after one or seven daily doses of naproxen 750 mg. Gastric microbleeding was measured 4 h after naproxen in gastric washings collected during a 30-min period. Serum thromboxane B concentrations were also assayed, as a marker of cyclo-oxygenase inhibition. Mean blood loss after placebo was 0.60 microL/10 min (95% CI: 0.21-0.98). This rose to 2.15 (0.73-3.57) and 1.75 (0.74-2.76) microL/10 min after one and seven daily doses of naproxen, respectively (P < 0.05 vs. baseline; day 1 vs. 7 not significant). Thromboxane B concentrations were < 10% of control at both day 1 and 7 of dosing. In accord with our findings in rats, adaptation to this moderately long acting NSAID in humans was not apparent. We conclude that any adaptation to naproxen is unlikely to be clinically important.


Intracellular thiol redox status of macrophages directs the Th1 skewing in thioredoxin transgenic mice during aging.
We have been proposing the functional distinction of two classes of macrophages (Mp), namely the reductive macrophages (RMp) with high intracellular content of glutathione (GSH) and the oxidative macrophages (OMp) with reduced content. At the same time we have been investigating the variation of RMp/OMp balance during aging of mice, especially in relation to the age related onset of autoimmune diseases. In this paper we have investigated the Th1/Th2 balance of thioredoxin (TRX) transgenic (Tg) mice, with prolonged life longevity, during aging in the context of the intracellular redox status of Mp, which has been hypothesized to be crucial in regulating the Th1/Th2 balance. It was confirmed that peritoneal resident Mp of Tg mice showed the higher GSH/GSSG ratios compared with that of age matched wild type (WT) mice. The predominance of RMp was associated with the sustained maintenance of Th1 prevalence during aging until 2 years in Tg mice, whereas WT littermates showed rapid polarization to Th2 around the age of 8 months. The Tg mice showed elevation of IFN-gamma and reduction of IL-10 with moderate change of IL-4 produced by CD4+ T cells. The WT mice showed inverse changes of IFN-gamma/IL-4 and IFN-gamma/IL-10 ratios during aging. In addition, IL-10 production by Mp was dramatically reduced in aged Tg mice. Thus, TRX Tg mice may be useful to investigate the contribution of the anti-oxidant defense mechanism during aging accompanied with increasing oxidative stress.


Correlation detection as a general mechanism for multisensory integration.
The brain efficiently processes multisensory information by selectively combining related signals across the continuous stream of multisensory inputs. To do so, it needs to detect correlation, lag and synchrony across the senses; optimally integrate related information; and dynamically adapt to spatiotemporal conflicts across the senses. Here we show that all these aspects of multisensory perception can be jointly explained by postulating an elementary processing unit akin to the Hassenstein-Reichardt detector-a model originally developed for visual motion perception. This unit, termed the multisensory correlation detector (MCD), integrates related multisensory signals through a set of temporal filters followed by linear combination. Our model can tightly replicate human perception as measured in a series of empirical studies, both novel and previously published. MCDs provide a unified general theory of multisensory processing, which simultaneously explains a wide spectrum of phenomena with a simple, yet physiologically plausible model.


[The incidence and progression of lymphoma of the cavum in AIDS].
A clinical case of a woman with AIDS who developed lymphoma of the nasopharynx and paralysis of the VII, IX and XII cranial nerves is reported. The probable origin of the paralysis in relation to AIDS and lymphoma is discussed.


Family well-being and disabled children: a psychosocial model of disability-related child behaviour problems.
When parents receive a diagnosis that their child is disabled, many families adjust to this healthily and cope well, but others do not. Feelings of hopelessness, social isolation of the family within the community and child behaviour problems have all been reported. While utilization of social support systems is well documented in the literature as being a significant factor in family coping and adjustment to the child's disability, less attention has been focused on the role of psychological factors. This theoretical study aims to address this inbalance by integrating perspectives from a social model of disability with psychological research on the role of cognitive change in families' coping and adjustment to having a disabled child, and thus to produce a new psychosocial model of disability-related child behaviour problems. Negative societal attitudes to disability identified by a social model of disability are interpreted with respect to how they might translate to parent views of their disabled child within the family. Resultant parenting beliefs and their possible implications for family interaction, child behaviour and family health and well-being are explored within this new framework. The psychosocial model of disability-related child behaviour problems provides a useful conceptual framework that has both clinical and research implications for professionals working with families with disabled children.


Adsorption and desorption of Cd(II) onto titanate nanotubes and efficient regeneration of tubular structures.
Efficient regeneration of desorbed titanate nanotubes (TNTs) was investigated with cycled Cd(II) adsorption and desorption processes. After desorption of Cd (II) from TNTs using 0.1M HNO3, regeneration could be simply achieved with only 0.2M NaOH at ambient temperature, i.e. 2% of the NaOH needed for virgin TNTs preparation at 130°C. The regenerated TNTs displayed similar adsorption capacity of Cd(II) even after six recycles, while significant reduction could be detected for desorbed TNTs without regeneration. The virgin TNTs, absorbed TNTs, desorbed TNTs and regenerated TNTs were systematically characterized. As results, the ion-exchange mechanism with Na(+) in TNTs was convinced with obvious change of -TiO(ONa)2 by FTIR spectroscopy. The easy recovery of the damaged tubular structures proved by TEM and XRD was ascribed to asymmetric distribution of H(+) and Na(+) on the surface side and interlayer region of TNTs. More importantly, the cost-effective regeneration was found possibly related to complex form of TNTs-OCd(+)OH(-) onto the adsorbed TNTs, which was identified with help of X-ray photoelectron spectroscopy, and further indicated due to high relevance to an unexpected mole ratio of 1:1 between exchanged Na(+) and absorbed Cd(II).


Polychlorinated Biphenyl Quinone Promotes Macrophage-Derived Foam Cell Formation.
Polychlorinated biphenyls (PCBs) are organic environmental pollutants that are accused of various toxic effects. PCB exposure is widely believed to be associated with atherosclerosis, but the underlying mechanisms are unclear. Although PCBs are easily metabolized, there is rarely information on the effects of their metabolites on atherosclerosis. Currently, we evaluate the effect of 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ) on the critical phase of atherosclerosis development, that is, the formation of macrophage-derived foam cells. We exposed Ox-LDL-induced RAW264.7 cells to 2.5 μM and 5 μM PCB29-pQ. Varieties of evidence have demonstrated that PCB29-pQ promotes foam cell formation and develops proinflammatory cascade and cell necroptosis. In detail, we observed that PCB29-pQ increased levels of total cholesterol (TC), free cholesterol (FC), triglyceride (TG), and cholesteryl ester (CE) by increasing the cholesterol influx and reducing the cholesterol efflux. Moreover, we found that PCB29-pQ induced inflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and IL-1β, released by activating the mitogen-activated protein kinase (MAPK)-nuclear factor kappa B (NF-κB) inflammatory pathway. In addition, we demonstrated that PCB29-pQ induced cell necroptosis via receptor interacting protein kinases 1 and 3 (RIPK1/3) and a mixed-lineage kinase domain-like (MLKL) pathway. Finally, the overproduction of reactive oxygen species (ROS) by PCB29-pQ played significant roles in these processes, which could be reversed with an antioxidant. Overall, our results indicated that PCB29-pQ promoted the macrophage formation of foam cells, inflammation, and cell necroptosis.


A framework for the atrial fibrillation prediction in electrophysiological studies.
Cardiac arrhythmias are disorders in terms of speed or rhythm in the heart's electrical system. Atrial fibrillation (AFib) is the most common sustained arrhythmia that affects a large number of persons. Electrophysiologic study (EPS) procedures are used to study fibrillation in patients; they consist of inducing a controlled fibrillation in surgical room to analyze electrical heart reactions or to decide for implanting medical devices (i.e., pacemaker). Nevertheless, the spontaneous induction may generate an undesired AFib, which may induce risk for patient and thus a critical issue for physicians. We study the unexpected AFib onset, aiming to identify signal patterns occurring in time interval preceding an event of spontaneous (i.e., not inducted) fibrillation. Profiling such signal patterns allowed to design and implement an AFib prediction algorithm able to early identify a spontaneous fibrillation. The objective is to increase the reliability of EPS procedures. We gathered data signals collected by a General Electric Healthcare's CardioLab electrophysiology recording system (i.e., a polygraph). We extracted superficial and intracavitary cardiac signals regarding 50 different patients studied at the University Magna Graecia Cardiology Department. By studying waveform (i.e., amplitude and energy) of intracavitary signals before the onset of the arrhythmia, we were able to define patterns related to AFib onsets that are side effects of an inducted fibrillation. A framework for atrial fibrillation prediction during electrophysiological studies has been developed. It includes a prediction algorithm to alert an upcoming AFib onset. Tests have been performed on an intracavitary cardiac signals data set, related to patients studied in electrophysiological room. Also, results have been validated by the clinicians, proving that the framework can be useful in case of integration with the polygraph, helping physicians in managing and controlling of patient status during EPS.


Ff1b is required for the development of steroidogenic component of the zebrafish interrenal organ.
The zebrafish ftz-f1 gene, ff1b, is activated in two cell clusters lateral to the midline in the trunk during late embryogenesis. These cell clusters coalesce to form a discrete organ at around 30 hpf, which then begins to acquire a steroidogenic identity as evidenced by the expression of the steroidogenic enzyme genes, cyp11a and 3beta-hsd. The migration of the cell clusters to the midline is impaired in zebrafish midline signaling mutants. Knockdown of Ff1b activity by antisense ff1b morpholino oligonucleotide (ff1bMO) leads to phenotypes that are consistent with impaired osmoregulation. Injection of ff1bMO was also shown to downregulate the expression of cyp11a and 3beta-hsd. Histological comparison of wild-type and ff1b morphants at various embryonic and juvenile stages revealed the absence of interrenal tissue development in ff1b morphants. The morphological defects of ff1b morphants could be mimicked by treatment with aminoglutethimide, an inhibitor of de novo steroid synthesis. Based on these data, we propose that ff1b is required for the development of the steroidogenic tissue of the interrenal organ.


Prevention of injuries at work: the role of the occupational physician.
To highlight the role of occupational physician (OP) in occupational injuries (OI) prevention and management. To suggest an approach beyond traditional focus on descriptive epidemiology, engineering interventions, administrative aspects of OI prevention. To promote a person- and enterprise-tailored approach, entailing greater attention to human factors and to practical problems of the specific workplace, with a call to a leading role played by OP. Analysis of the literature on the broader topic of OI prevention revealed thousands of publications; however, only a handful of them mention or describe the participation of OP in OI prevention. While recognizing that literature search is not the proper and only way to appreciate the current role of OP in this field, therefore, it seems necessary to call OP to a stronger effort in prevention and management of OI, through the context of a comprehensive intervention in cooperation with managers, supervisors, safety personnel and workers, focusing on specific needs of each enterprise. The following areas of OP intervention were examined: risk assessment, health surveillance, management, scientific research and health education. Within each of these topics, possible contributions, methodologies, instruments available for the OP were discussed, taking into account the relevant literature. Pathways for practical applications were illustrated, e.g., OI data generation and analyses, predictors of OI, fitness for work, case management, team work, educational issues, first aid, suggestion for OP contribution in specific research questions. OI continue to take a remarkable toll from individuals and society. New multidisciplinary interventions are needed to prevent OI. Focused activities at the single worksite with a central role from OP are definite options. OP is an effective interface between workforce and management and may offer, through a proactive approach, valuable practical and cultural contributions, while respecting technical and ethical guidelines of occupational health professionals.


Age and responding-hand related changes in performance of neurologically normal subjects on the line-bisection and chimeric-faces tasks.
This study investigated age and responding-hand (left, right, and bimanual) related changes in visuospatial attention. Two tasks were completed by 107 neurologically normal right-handed subjects ranging in age from 5 to 70 years and distributed across four age groups. Task-specific differences between groups were apparent. In the line-bisection task, the younger and older groups displayed symmetrical neglect while the young and middle groups displayed pseudoneglect. In the chimeric-faces task the leftward bias was less pronounced in the older group and more susceptible to responding-hand effects in the middle and older groups. Whilst results, especially those of the bimanual method, provided strong support for an activation model, they imposed an age limitation on its appropriateness as an explanation for performance on the chimeric-faces task. Results are discussed as reflecting changes in the corpus callosum and right hemisphere.


Depression in epilepsy: prevalence, clinical semiology, pathogenic mechanisms, and treatment.
Depression is the most frequent comorbid psychiatric disorder in epilepsy. Its lifetime prevalence has been estimated at between 6% and 30% in population-based studies and up to 50% among patients followed in tertiary centers. The risk of suicide has been estimated to be 10 times higher than that in the general population. Although no one questions that epilepsy is a risk for depression, recent studies have also revealed that a history of depression is associated with a 4- to 6-fold greater risk of developing epilepsy. These data suggest either a possible "bi-directional" relationship between these two disorders or the presence of common pathogenic mechanisms that facilitate the occurrence of one in the presence of the other. The clinical presentation of depressive disorders in epilepsy can be identical to that of nonepileptic patients and can include major depression, bipolar and dysthymic disorders, and minor depression. In a significant percentage of cases, however, the clinical features of depression in epilepsy fail to meet any of the DSM-IV Axis I categories. Depression in epilepsy may be iatrogenically induced with various antiepileptic drugs used to treat the seizure disorder or after surgical treatment of intractable epilepsy. Despite its relatively high prevalence, depression remains unrecognized and untreated, and unfortunately its treatment is based on empirical and uncontrolled data.


Loss of Notch2 and Notch3 in vascular smooth muscle causes patent ductus arteriosus.
The overlapping roles of the predominant Notch receptors in vascular smooth muscle cells, Notch2 and Notch3, have not been clearly defined in vivo. In this study, we use a smooth muscle-specific deletion of Notch2 together with a global Notch3 deletion to produce mice with combinations of mutant and wild-type Notch2/3 alleles in vascular smooth muscle cells. Mice with complete loss of Notch3 and smooth muscle-expressed Notch2 display late embryonic lethality and subcutaneous hemorrhage. Mice without smooth muscle-Notch2 and only one wild-type copy of Notch3 die within one day of birth and present with vascular defects, most notably patent ductus arteriosus (DA) and aortic dilation. These defects were associated with decreased expression of contractile markers in both the DA and aorta. These results demonstrate that Notch2 and Notch3 have overlapping roles in promoting development of vascular smooth muscle cells, and together contribute to functional closure of the DA.


Jumping translocations originate clonal rearrangements in SV40-transformed human fibroblasts.
A comparative study of chromosomal rearrangements occurring in 4 independent clones obtained from SV40-transformed cornea and skin human fibroblasts was performed. Rearrangements principally affect some constitutive heterochromatin and, to a lesser degree, telomeric regions. This results in multiple exchanges between a limited number of chromosome structures, i.e., in jumping translocations. Such rearrangements occur even at early passages and some of them give rise to clonal rearrangements that accumulate at late passages. This process is responsible for progressive modification of the karyotypes, principally characterized by deletion of a number of chromosome segments. Thus, clonal rearrangements are selected among many others not occurring at random. The selective pressure retaining clonal rearrangement seems to be similar for the 4 independent clones, since selection of the derivative chromosomes leads to the same imbalances, whatever the origin of the clone. This sequence of events recalls that of human solid tumors, since jumping rearrangements are generally observed in pre-malignant conditions or in low-grade malignancies, whereas clonal rearrangements leading to typical imbalances are detected in more advanced malignant tumors.


Sisomicin treatment of serious neonatal infections. A clinical and pharmacokinetic study.
23 infants, 20 of which had verified or clinically highly suspected serious infections in the neonatal period, were treated with a new antibiotic aminoglycoside, sisomicin, i.m. in doses from 2.8 to 6.6 mg/kg/24 h. Clinical cure was obtained in 18 of 20 caes, and marked improvement in one case. Adverse effects were only observed in two infants with tenderness at the injection sites. Serum concentrations and half-life estimations showed that the concentrations were similar to those obtained for gentamicin, and that half-life was independent of postnatal age, but highly correlated to the gestational age and to body weight. Consideration should therefore be given to the prolonged half-life of the drug in immature and low birth weight infants.


Low-intensity pulsed ultrasound promotes aggrecan expression via ZNT-9 in temporomandibular joint chondrocytes.
Temporomandibular joint osteoarthritis (TMJ-OA) is one of the most common joint diseases. It causes severe pain and poor quality of life. One key feature of TMJ-OA is degeneration of the chondrocyte extracellular matrix (ECM). Low-intensity pulsed ultrasound (LIPUS) can promote the synthesis of ECM in cartilage. However, the exact mechanism is still unclear. We aimed to explore the mechanism by which LIPUS promotes the expression of aggrecan in chondrocytes. In vivo, TMJ-OA rats established by unilateral occlusal trauma were treated with LIPUS. In our RNA sequencing data, we found that ADAMTS-8 was downregulated by LIPUS. In vitro, chondrocytes were treated with IL-1β and LIPUS. Among Zn2+ exporters, ZNT-9 was specifically upregulated by LIPUS. Activation of ZNT-9 by LIPUS downregulated ECM-degrading enzymes (MMP-3, ADAMTS-5 and ADAMTS-8) and metal regulatory transcription factor-1 (MTF-1) and upregulated aggrecan in chondrocytes. Furthermore, ZNT-9 knockdown caused upregulation of MMP-3, ADAMTS-5, ADAMTS-8 and MTF-1, with concomitant downregulation of aggrecan. The opposite results were obtained after ZNT-9 overexpression. Our experiments demonstrate that LIPUS protects chondrocytes by increasing the expression of aggrecan through ZNT-9.


Cost-effectiveness and diagnostic accuracy of telemedicine in macular disease and diabetic retinopathy: A systematic review and meta-analysis.
To determine cost-effectiveness and the diagnostic accuracy of teleophthalmology (TO) in the detection of macular edema (ME) and various grades of diabetic retinopathy (DR). MEDLINE, EMBASE, and Cochrane databases were searched for TO, ME, and DR on May 25, 2016. The search was updated on April 2, 2019. Pooled sensitivity and specificity for ME and various grades of DR were determined using Meta-Disc software. A systematic review of the articles discussing the cost-effectiveness of TO screening was also performed. Thirty-three articles on the diagnostic accuracy and 28 articles on the cost-effectiveness were selected. Telescreening is moderately sensitive but very specific for the diagnosis of diabetic retinopathy. Non-mydriatic Teleretinal screening services are cost-effective, decrease clinics workload, and increase patient compliance if provided free of cost in remote low socioeconomic regions.


Environmental dust exposure as a factor contributing to an increase in Escherichia coli O157 and Salmonella populations on cattle hides in feedyards.
A study was conducted to determine the impact of exposure to dust in the cattle load-out area in feedyards on pathogen contamination of cattle hides. A total of 250 cattle hides were sampled during summer and fall months, which are associated with elevated prevalence of Escherichia coli O157 in West Texas. Animals were removed from their home pens and restrained in a chute and sampled prior to exposure to dust generated as a result of a simulated loading exercise. The cattle hides were sampled again after exposure to the loading dust to determine total numbers of pathogens on cattle hides on leaving their home pen (before loading) and on cattle hides after exposure to the dust in the loading area. Air and dirt samples from the home pens and the cattle load-out area were also collected. The presence of E. coli O157 and Salmonella was determined in all the samples, and when a positive sample was identified, the total numbers of these bacteria present were enumerated. The total numbers of pathogens increased after dust exposure; Salmonella counts increased from 1.09 log most probable number (MPN)/cm2 to 1.74 log MPN/cm2 after exposure, and E. coli O157 counts increased from 0.80 to 2.35 log MPN/cm2 after sampling. E. coli O157 and Salmonella were recovered from the air samples during dust generation at 6.66 and 11.1%, respectively. Salmonella and E. coli O157 prevalence was not changed and was not associated with the exposure to the dust. Results indicate airborne dust generated as a result of cattle movement and loading could be an important determining factor in total numbers of pathogens recovered on cattle hides.


Reproductive performance, semen quality, and fatty acid profile of spermatozoa in senescent broiler breeder roosters as enhanced by the long-term feeding of dried apple pomace.
Avian spermatozoa are characteristically high in polyunsaturated fatty acids which predispose them to lipoperoxidation, thereby diminishing their fertility. As a by-product, well-known for antioxidative properties, dried apple pomace (AP) was fed to aging Ross 308 breeder roosters (n=80) at the dietary inclusion levels of 0 (AP0), 10 (AP10), 20 (AP20), or 25 (AP25) percent for 14 consecutive weeks. Seminal traits were studied every other week. At the end of the trial, sperm fatty acids profile, seminal plasma total antioxidant capacity (TAC), fertility, hatchability, and hatchling quality were evaluated, using 240 artificially-inseminated young hens. Dietary AP increased sperm motility and livability and decreased the seminal content of thiobarbituric acid reactive species. Dietary treatment and age interacted to positively affect sperm concentration and sperm membrane integrity. Feeding AP was associated with an increase in C20:4(n-6), C22:4(n-6), and total unsaturated fatty acids percentages. Birds in the AP25 and AP20 treatment groups respectively showed 6 and 7% increases in fertility rate. Interestingly, a higher hatchability rate was found for AP20 group, associated with a higher number of sperm penetration holes in the perivitelline membrane and a lower rate of early embryonic mortality. However, hatchling quality was not affected by dietary AP. Overall, these data suggest that AP could remarkably improve several sperm characteristics, seminal TAC, fertility, and hatchability rate in aging breeder roosters. These improvements were also associated with a higher content of total unsaturated FA in the sperm plasma membrane. Future studies are needed to disclose the causal mechanisms involved.


Depletion of hypothalamic norepinephrine reduces the fever induced by polyriboinosinic acid: polyribocytidylic acid (Poly I:Poly C) in rats.
Administration of either Poly I:Poly C (0.05-0.50 micrograms) or norepinephrine (2-8 micrograms) into the anterior hypothalamic area produced a dose-related fever in rats. The fever induced by Poly I:Poly C was attenuated after selective depletion of norepinephrine in the hypothalamus. However, selective depletion of hypothalamic norepinephrine did not affect the fever induced by intrahypothalamic norepinephrine. The data indicate that Poly I:Poly C may act to induce fever through the endogenous release of norepinephrine from the rat's hypothalamus.


Estrogen deficiency reduces the dentinogenic capacity of rat lower incisors.
Endogenous estrogen deficiency usually causes the systemic osteoporosis including the jaw bones. However, it remains unclear whether estrogen deficiency can affect the tooth mineralization. In this study, the classical osteoporotic rat model was established via the ovariectomy, which was subsequently confirmed by the detection of serum estradiol levels and body weights. The mineralization-related assays were performed to observe the potential changes in mineralized tissues of rat lower incisors. The clinical crown length, compressive strength, radiodensity, and calcium content in the ovariectomy group (OVX) were significantly downregulated (P < 0.01), as compared with the sham operation group (Sham). Histological results revealed that OVX incisors presented the thinner predentin structures than Sham incisors. Immunohistochemical staining and western blot assay further demonstrated that the odonto/osteoblast specific proteins (e.g., dentin sialoprotein, runt-related transcription factor 2, osterix, and osteocalcin) in the dentin-pulp complex of OVX incisors were significantly decreased in comparison with Sham counterparts. Together, estrogen deficiency reduces the dentinogenic capacity and calcium deposition in rat incisors, indicating that estrogen plays an important role in the dentinogenesis.


How to do things with metaphors: engineering life as hodgepodge.
This paper presents a collaboration between social scientists and a chemist exploring the promises for new therapy development at the intersection between synthetic biology and nanotechnology. Drawing from ethnographic studies of laboratories and a recorded discussion between the three authors, we interrogate the metaphors that underpin what Mackenzie (Futures 48:5-12 2013) has identified as a recursive relationship in the iconography of the life sciences and its infrastructure. Focusing specifically on the use of gene editing techniques in synthetic biology and bio-nanotechnology, we focus our analysis on the key metaphors of 'evolutionary life as hodge-podge' within which 'cutting' of DNA and the 'sticking' and 'binding' of engineered particles to proteins can be performed by researchers in laboratory settings. Taken together, we argue that these metaphors are consequential for understanding metaphors of life-as-machine and the prevalence of notions of 'engineering life'. Exploring the ways in which notions of cutting, targeting and life as an evolutionary hodgepodge prefigure a more contingent notion of engineering and synthesis we close by considering the interpretive implications for ethnomethodological approaches to contemporary life science research.


Pyridaben induces mitochondrial dysfunction and leads to latent male reproductive abnormalities.
As an organochloride pesticide, pyridaben (PDB) has been used on various plants, including fruiting plants and other crops. Because of emerging concerns regarding exposure to pesticides, the deleterious effects of PDB, including neuronal disease and reproductive abnormalities, have been determined. However, the intracellular mechanisms that contribute to the effects of PDB on the male reproductive system are still unknown. Therefore, we investigated the effects of PDB on the male reproductive organ, focusing on the testes using mouse testicular cells. We demonstrated that PDB suppressed cellular proliferation of mouse Leydig (TM3) and Sertoli (TM4) cells. Additionally, PDB disturbed calcium homeostasis via mitochondrial dysfunction and activation of endoplasmic reticulum stress. Furthermore, PDB inhibited transcriptional gene expression regarding the cell cycle, as well as steroidogenesis and spermatogenesis, which are the primary functions of TM3 and TM4 cells. Moreover, we verified via western blot analysis that PDB dysregulated the intracellular cell signaling pathways in mitochondrial-associated membranes and the Mapk/Pi3k pathway. Lastly, we confirmed that PDB efficiently suppressed the spheroid formation of TM3 and TM4 cells mimicking an in vivo environment. Collectively, the current results indicate that PDB induces testicular toxicity and male reproductive abnormalities by inducing mitochondrial dysfunction, endoplasmic reticulum stress and calcium imbalance.


Double-lumen tube placement with the patient in the supine position without a headrest minimizes displacement during lateral positioning.
The correct position of double-lumen tubes (DLTs) is customarily confirmed after tracheal intubation by bronchoscopy with the patient supine on a headrest. However, displacement of DLTs usually occurs during lateral positioning because of neck extension. This study was undertaken to determine whether displacement of DLTs could be minimized during lateral positioning if DLTs were positioned without a headrest. One hundred patients scheduled for thoracic surgery were randomized into two groups (n = 50 each). After tracheal intubation using a headrest, adjustment of DLT position was performed according to group assignment, i.e., either with the headrest in place or without the headrest. Using a bronchoscope, distances from the tracheal opening to the main carina and from the bronchial opening to the left bronchial carina were measured in both the supine and lateral positions. Displacement of DLTs [mean (standard deviation)] during lateral positioning was greater in the headrest group than in the no-headrest group [12.3 (6.5) mm vs 6.8 (5.5) mm, respectively, in the trachea; 11.6 (6.7) mm vs 6.0 (4.6) mm, respectively, in the bronchus; P < 0.001]. The incidence of significant displacement, defined as > 10 mm from initial correct position, was greater in the headrest group than in the no-headrest group (64% vs 28%, respectively, in the trachea; 58% vs 20%, respectively, in the bronchus; P < 0.001). Displacement of DLTs during lateral positioning appears to be caused primarily by extension of the neck. Correct adjustment of DLT position without a headrest in the supine position is an easy and effective method to minimize DLT displacement during lateral positioning.


The bold and the beautiful. Influence of body size of televised media models on body dissatisfaction and actual food intake.
The effects of exposure to televised thin and average size models on body dissatisfaction and actual food intake were examined. Normal weight female students (N=104) were exposed to a 30-min movie clip featuring beautiful girls. Half of them viewed the movie clip in normal screen size (4:3) and the other half viewed the same movie clip in broad screen size (16:9), in which the body size of the actresses was slightly stretched breadthways. Actual food intake while watching and body dissatisfaction afterwards was examined. Additionally, restrained eating was assessed as a possible moderating variable. Two interaction effects were found between screen size and restrained eating on body dissatisfaction and actual food intake. Restrained eaters tended to feel worse and eat less in the average size condition compared to the thin model condition, whereas unrestrained eaters felt worse and ate less in the thin model condition compared to the average size condition. So, body size of televised images affected body dissatisfaction and food intake, differentially for restrained and unrestrained eaters. The screen sizes used correspond with widely used screen sizes nowadays enhancing the practical relevance of the study, since screen size might affect body dissatisfaction and food intake in daily life as well.


Tacrolimus effects and side effects after liver transplantation: is there a difference between immediate and extended release?
Immunosuppressive therapy after orthotopic liver transplantation (OLT) requires a high degree of patient compliance to guarantee safety and avoid side effects. In 2007, prolonged-release tacrolimus was launched in Europe to improve compliance. In this prospective observational crossover single-center trial, we analyzed effects and side effects of prolonged-release tacrolimus in OLT patients. LT patients at our center were included if they were older than l8 years of age, had had the procedure at least 6 months prior, and were outpatients currently on twice-daily tacrolimus. Patients were observed for 6 months before switching to once-daily tacrolimus. Patient history, clinical examination, and laboratory examinations were recorded on inclusion as well as after 3, 6, 9, 12, and 18 months. The rates of rejection, hypertension, hypercholesterolemia, and diabetes mellitus were compared during twice-daily and once-daily tacrolimus. Similarly, laboratory parameters were identical during both periods with the exception of glycated hemoglobin, which was significantly elevated under once-daily tacrolimus (P = .00l). Converting patients to extended-release tacrolimus with was safe in terms of rejection, hypertension, and hypercholesterolemia as well as renal and liver functions. Further investigations concerning pharmacokinetics and glucose metabolism will be needed to evaluate prolonged-release tacrolimus.