Range and stability of cell fate determination in isolated sea urchin blastomeres.
We have examined the developmental potential of blastomeres isolated from either the animal (mesomeres) or vegetal (macromeres-micromeres) half of 16-cell embryos of the sea urchin Lytechinus pictus. We have also examined the effects of two known vegetalizing agents on the development of isolated mesomeres; LiCl treatment and combination with micromeres, the small blastomeres found at the vegetal pole of the 16-cell embryo. The markers for differentiation used were both morphological (invaginations, spicules and pigment cells) and molecular (gut-specific alkaline phosphatase activity, and monoclonal antibodies against antigens specific for gut and oral ectoderm). Embryoids derived from isolated mesomeres expressed markers characteristic of vegetal differentiation only at very low levels. They did express an antigen characteristic of animal development, the oral ectoderm antigen, but with an altered pattern. Isolated macromere-micromere pairs expressed all markers characteristic of vegetal development, but did not express the marker characteristic of animal development. Increasing concentrations of LiCl caused isolated mesomeres to give rise to embryoids with an increasing tendency to express vegetal markers of differentiation, and it was found that expression of different vegetal markers begin to appear at different concentrations of LiCl. LiCl also caused the marker for oral ectoderm to be expressed in a more normal pattern. Combining micromeres with mesomeres also induced mesomere derivatives to differentiate in a vegetal manner. Micromeres were not completely effective in inducing a more normal pattern of expression of the marker for oral ectoderm. The treatment of isolated mesomeres with both LiCl and micromeres produces a synergistic effect resulting in embryoids expressing markers not induced by either treatment alone.


[Hyalinizing intravascular bronchioloalveolar tumor--a rare form of diffuse lung lesions].
A rare, badly known diffuse pulmonary lesion--multifocal hyalinizing intravascular "bronchiolo-alveolar" tumour in a woman of 22, is described. The lesion was revealed at fluorography, diagnosed by means of mediastinopleuroscopy, in lung biopsy; there were no clinical manifestations. A hyalinized compact and branching node, poor in cells, intruding at the periphery into the alveolar septa in the form of micropolyps was found histologically.


3D organotypic cultures of human HepaRG cells: a tool for in vitro toxicity studies.
Drug-induced human hepatotoxicity is difficult to predict using the current in vitro systems. In this study, long-term 3D organotypic cultures of the human hepatoma HepaRG cell line were prepared using a high-throughput hanging drop method. The organotypic cultures were maintained for 3 weeks and assessed for (1) liver specific functions, including phase I enzyme and transporter activities, (2) expression of liver-specific proteins, and (3) responses to three drugs (acetaminophen, troglitazone, and rosiglitazone). Our results show that the organotypic cultures maintain high liver-specific functionality during 3 weeks of culture. The immunohistochemistry analyses illustrate that the organotypic cultures express liver-specific markers such as albumin, CYP3A4, CYP2E1, and MRP-2 throughout the cultivation period. Accordingly, the production rates of albumin and glucose, as well as CYP2E1 activity, were significantly higher in the 3D versus the 2D cultures. Toxicity studies show that the organotypic cultures are more sensitive to acetaminophen- and rosiglitazone-induced toxicity but less sensitive to troglitazone-induced toxicity than the 2D cultures. Furthermore, the EC50 value (2.7mM) for acetaminophen on the 3D cultures was similar to in vivo toxicity. In summary, the results from our study suggest that the 3D organotypic HepaRG culture is a promising in vitro tool for more accurate assessment of acute and also possibly for chronic drug-induced hepatotoxicity.


The influence of induced hypocapnia and sleep on the endogenous respiratory rhythm in humans.
1. Ventilation has been studied during hypocapnia produced by passive mechanical ventilation in ten normal human subjects. 2. During wakefulness, disconnection of the ventilator led to inconsistent apnoea of only brief duration. During sleep, at a similar degree of hypocapnia, disconnection of the ventilator led more consistently to apnoea which was also of much longer duration; the deeper the sleep stage, the longer the apnoea. 3. The resumption of breathing during sleep could precede or follow arousal or be unaccompanied by arousal; in the absence of prior arousal, the evidence suggests that a starting end-tidal CO2 pressure (PET, CO2) less than 41 mmHg could result in an apnoea during sleep stages I and II. 4. Subjects did not report any common sensation which led them to breathe following an apnoea whilst awake. 5. Prior hyperoxia in one subject prolonged the apnoea duration in both slow-wave sleep and rapid eye movement sleep. 6. The results are interpreted as showing that even during light sleep, the maintenance of the respiratory rhythm is critically dependent on the arterial CO2 and O2 tensions. During wakefulness, other behavioural drives, which may not reach consciousness, supervene.


Multi-Site Spinal Cord Transcutaneous Stimulation Facilitates Upper Limb Sensory and Motor Recovery in Severe Cervical Spinal Cord Injury: A Case Study.
Individuals with cervical spinal cord injury (SCI) rank regaining arm and hand function as their top rehabilitation priority post-injury. Cervical spinal cord transcutaneous stimulation (scTS) combined with activity-based recovery training (ABRT) is known to effectively facilitate upper extremity sensorimotor recovery in individuals with residual arm and hand function post SCI. However, scTS effectiveness in facilitating upper extremity recovery in individuals with severe SCI with minimal to no sensory and motor preservation below injury level remains largely unknown. We herein introduced a multimodal neuro-rehabilitative approach involving scTS targeting systematically identified various spinal segments combined with ABRT. We hypothesized that multi-site scTS combined with ABRT will effectively neuromodulate the spinal networks, resulting in improved integration of ascending and descending neural information required for sensory and motor recovery in individuals with severe cervical SCI. To test the hypothesis, a 53-year-old male (C2, AIS A, 8 years post-injury) received 60 ABRT sessions combined with continuous multi-site scTS. Post-training assessments revealed improved activation of previously paralyzed upper extremity muscles and sensory improvements over the dorsal and volar aspects of the hand. Most likely, altered spinal cord excitability and improved muscle activation and sensations resulted in observed sensorimotor recovery. However, despite promising neurophysiological evidence pertaining to motor re-activation, we did not observe visually appreciable functional recovery on obtained upper extremity motor assessments.


Arabidopsis-Based Dual-Layered Biological Network Analysis Elucidates Fully Modulated Pathways Related to Sugarcane Resistance on Biotrophic Pathogen Infection.
We assembled a dual-layered biological network to study the roles of resistance gene analogs (RGAs) in the resistance of sugarcane to infection by the biotrophic fungus causing smut disease. Based on sugarcane-Arabidopsis orthology, the modeling used metabolic and protein-protein interaction (PPI) data from Arabidopsis thaliana (from Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioGRID databases) and plant resistance curated knowledge for Viridiplantae obtained through text mining of the UniProt/SwissProt database. With the network, we integrated functional annotations and transcriptome data from two sugarcane genotypes that differ significantly in resistance to smut and applied a series of analyses to compare the transcriptomes and understand both signal perception and transduction in plant resistance. We show that the smut-resistant sugarcane has a larger arsenal of RGAs encompassing transcriptionally modulated subnetworks with other resistance elements, reaching hub proteins of primary metabolism. This approach may benefit molecular breeders in search of markers associated with quantitative resistance to diseases in non-model systems.


Glomerular Microangiopathy with Cellular Crescent-like Formation and Endotheliopathy Due to Ramucirumab Treatment for Metastatic Sigmoid Colon Cancer.
We encountered a 77-year-old Japanese man who presented with nephrotic-range proteinuria 20 days after receiving ramucirumab treatment for metastatic sigmoid colon cancer. A kidney biopsy showed two characteristic histological findings. The first finding was podocyte injury with cellular crescent-like formation, although focal segmental glomerulosclerosis (FSGS) (collapsing variant) according to the Columbia classification may have been a more appropriate name for this injury, as hypertrophy and hyperplasia of epithelial cells, presumably resulting from podocyte injury, were seen between Bowman's capsule and the glomerular basement membrane (GBM); these changes appeared to be due to the collapse of the GBM rather than to GBM destruction with fibrinoid necrosis. The second finding was endotheliopathy characterized by prominent mesangial interposition via enlargement of the mesangial matrix with mesangiolysis. Proteinuria and renal dysfunction subsided after discontinuation of ramucirumab. Bevacizumab has been reported to induce glomerular microangiopathy with endothelial damage and swelling six months after treatment, but in this case, ramucirumab may have induced focal segmental glomerulosclerosis (FSGS) collapsing variant and glomerular microangiopathy with endotheliopathy via mesangial damage within 1 month. We believe that the damage to the glomerular podocyte and endothelial cells via mesangial damage secondary to ramucirumab in our patient was a different type of glomerular microangiopathy than the endothelial cell damage with enlargement of the subendothelial space caused by bevacizumab.


A meta-analysis of the relationship between early maladaptive schemas and depression in adolescence and young adulthood.
Early maladaptive schemas (EMS) are broad, pervasive themes and patterns of emotions, memories, cognition and physical sensations that impede the goal of individuals. Maladaptive behaviours can occur as a response to maladaptive or negative schemas, often culminating in depression or anxiety. The current meta-analysis integrates the existing literature to estimate the magnitude of effect of association between EMS and depression among adolescents and young adults. A systematic search of seven different databases including Embase, CINAHL, Medline, ASSIA, Psych INFO, Scopus and Web of Science was carried out identifying 24 relevant studies of adolescents (10-18 years) and young adults (19-29 years). The random-effect model estimate for association between overall EMS and depression was r = 0.56 (95% CI 0.49-0.63, Z = 12.88, p ≤ 0.0001), suggesting higher predominant EMS significantly linked to higher levels of depressive symptoms, with a large effect size. Separate meta-analytical results with schema domains indicated moderately stronger associations between schemas of disconnection/rejection, impaired autonomy/performance and other-directedness with depression. Age and gender were not found to have any significant moderating effect on the associations. The findings suggest that it is vital for clinicians to identify specific maladaptive schemas contributing towards depression, to have a better understanding of underlying cognitive processes and in turn promote psychological health, well-being and resilience in adolescents and young adults. Furthermore, findings will also assist clinicians to focus more on the content of three significant schema domains, which emerged as particularly salient factors underlying adolescent depression.


Interaction of phenytoin with chloramphenicol or pentobarbital in the dog.
Two dogs that had been given phenytoin for control of seizures for approximately 1 year developed signs of phenytoin toxicosis (postural ataxia an d a hypermetric gait) when chloramphenicol was added to the therapeutic regimen. The signs of toxicosis disappeared within 24 hours after cessation of chloramphenicol treatment. Oral treatment of laboratory dogs with chloramphenicol (50 mg/kg, TID for 3 days) prior to intravenous injection of phenytoin increased the half-life of phenytoin from 3 hours to 15 hours. Dogs infused with phenytoin during pentobarbital anesthesia had little or no change in serum phenytoin concentration during a 2-hour postinfusion observation period, which was unexpected for the intravenous route of administration.


Simultaneous detection of the genus Brucella by combinatorial PCR.
We have developed a combinatorial polymerase chain reaction (PCR) procedure to identify four major species of the genus Brucella simultaneously. Four pairs of primers targeting the genes encoding a cell surface protein (BCSP31) and outer membrane proteins (omp2b, omp2a and omp31) were prepared. PCR using these primers gave rise to specific patterns of amplification for each Brucella spp. examined in this study. B. abortus could be identified when fragments of BCSP31 and omp2b/2a were amplified by B. abortus-specific primers. B. melitensis could be identified by the amplification of fragments of BCSP31, omp2b/2a and omp31 using pair of primers B4/B5, JRF/JPR-ab and omp31. Identification of B. canis could be achieved when the amplicons of omp2b/2a were detected by B. canis-specific primers, as could the identification of BCSP31 and omp31. If specific amplifications occurred using all pairs of primers, the strain was identified as B. suis. Combinatorial PCR reported here thus appeared to be an ideal method of identifying Brucella spp., the causative pathogen of human brucellosis.


Are Roma People Descended from the Punjab Region of Pakistan: A Y-Chromosomal Perspective.
Gypsies are a separate ethnic group living in Pakistan and some other countries as well. They are mostly known as 'Roma' and 'untouchables'. They have different types of lifestyles as compared to other common people, as they always keep migrating from one place to another. They do not have proper houses; they live in tent houses and most probably work on daily wages to earn their living. Gypsies cannot be specified according to the place of residence and can only be classified according to their migration route. Previous historical and linguistic research showed the north Indian origin of Roma people. The present study collected 285 unrelated Roma individuals living in Punjab and typed with the Goldeneye Y20 system. Allelic frequencies ranged between 0.0035 and 0.5266, with haplotype diversity (HD) of 0.9999 and discrimination capacity (DC) of 0.8790. Gene diversity (GD) ranged from 0.6489 (DYS391) to 0.9764 (DYS391) (DY385ab). A total of 223 unique alleles were observed. Interestingly, the haplogroup R accounted for 40.56% and J for 22.06%. In MDS analysis, Pakistani Roma formed a close cluster with Roma from Constanta, Romania. The migration pattern of the Roma population from Pakistan, India and Europe was inferred using coalescence theory in the Migrate-n program. Overlapping Y-STR data were used to test different migration models. These migration models showed us the dominant gene flow from Pakistan to India and Europe to Pakistan. The results of our study showed that Y STRs provided substantially stronger discriminatory power in the Pakistani Roma population.


Effects of paeonol on anti-neuroinflammatory responses in microglial cells.
Increasing studies suggest that inflammatory processes in the central nervous system mediated by microglial activation plays an important role in numerous neurodegenerative diseases. Development of planning for microglial suppression is considered a key strategy in the search for neuroprotection. Paeonol is a major phenolic component of Moutan Cortex, widely used as a nutrient supplement in Chinese medicine. In this study, we investigated the effects of paeonol on microglial cells stimulated by inflammagens. Paeonol significantly inhibited the release of nitric oxide (NO) and the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Treatment with paeonol also reduced reactive oxygen species (ROS) production and inhibited an ATP-induced increased cell migratory activity. Furthermore, the inhibitory effects of neuroinflammation by paeonol were found to be regulated by phosphorylated adenosine monophosphate-activated protein kinase-α (AMPK-α) and glycogen synthase kinase 3 α/β (GSK 3α/β). Treatment with AMPK or GSK3 inhibitors reverse the inhibitory effect of neuroinflammation by paeonol in microglial cells. Furthermore, paeonol treatment also showed significant improvement in the rotarod performance and microglial activation in the mouse model as well. The present study is the first to report a novel inhibitory role of paeonol on neuroinflammation, and presents a new candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.


Long-term results using local excision after preoperative chemoradiation among selected T3 rectal cancer patients.
To assess the pelvic failure among patients with T3 rectal cancer treated with local excision after preoperative chemoradiation. Between January 1990 and June 2002, 431 patients with clinically staged T3 rectal cancer were treated with preoperative chemoradiation followed by surgical resection. Full-thickness local excision [Kraske (n = 3) or a transanal excision (n = 23)] was performed in 26 patients because of patient refusal of abdominoperineal resection (APR) (n = 13), medical comorbidity (n = 4), physician preference after a complete clinical response (n = 6), and other reasons (n = 3). All patients were treated with continuous-infusion 5-fluorouracil (5-FU) (300 mg/m(2) Monday to Friday) and concomitant pelvic radiation (45 Gy in 25 fractions with a 3-field belly board technique). Ten local-excision patients received a concomitant boost during the last week of therapy (1.5-Gy second daily fractions) for a total dose of 52.5 Gy. Similar preoperative treatment was followed by total mesorectal excision in 405 patients. Among the local-excision patients, the median tumor size was 3.5 cm (range, 0.5-7 cm). Well-differentiated or moderately-differentiated histology was present in all but 3 cases, and endoscopic ultrasound staging examination was performed in 25 of 26 patients. Based on CT findings, 1 patient was node positive. The median circumference involved by tumor was 33%, (20%-75%). The median distance from the anal verge was 3 cm (range, 1-8 cm). The mean follow-up was 46 months (range, 5-109 months) in the local-excision group. In the local-excision group, 19 of 26 patients had only residual scarring noted on digital rectal examination and rigid proctoscopy before surgery. Fourteen patients (54%) had a complete histologic response to chemoradiation, 9 patients (35%) had microscopic residual disease, and 3 patients (12%) had gross residual disease. Two intrapelvic recurrences occurred at 76 and 20 months among the 26 patients treated with local excision (6% 5-year actuarial pelvic recurrence rate). This rate compared with an 8% 5-year actuarial pelvic recurrence rate among T3 patients treated with mesorectal excision and a 6% pelvic recurrence rate in the subgroup of mesorectal-excision patients with a complete clinical response to preoperative chemoradiation. One additional local-excision patient recurred in an inguinal lymph node after local excision and subsequently died of metastatic disease. A total of 2 local-excision patients died of metastatic rectal cancer. Actuarial overall survival at 5 years was 86% in the local-excision group compared with 81% among mesorectal-excision patients (p = NS), and 85% in patients with a complete clinical response to chemoradiation followed by mesorectal excision by APR or LAR (p = NS). In an experience stimulated by patient refusal of APR, highly selected patients who responded well to conventional external-beam radiotherapy (CXRT) were selected to undergo local excision. Most of these patients had pathologic complete response. Local control and survival rates are comparable to those achieved with chemoradiation followed by mesorectal excision. This strategy should be prospectively studied in a group of patients with low rectal cancer who have no clinical evidence of tumor after chemoradiation.


Natural variation in host-specific nodulation of pea is associated with a haplotype of the SYM37 LysM-type receptor-like kinase.
Rhizobium leguminosarum bv. viciae, which nodulates pea and vetch, makes a mixture of secreted nodulation signals (Nod factors) carrying either a C18:4 or a C18:1 N-linked acyl chain. Mutation of nodE blocks the formation of the C18:4 acyl chain, and nodE mutants, which produce only C18:1-containing Nod factors, are less efficient at nodulating pea. However, there is significant natural variation in the levels of nodulation of different pea cultivars by a nodE mutant of R. leguminosarum bv. viciae. Using recombinant inbred lines from two pea cultivars, one which nodulated relatively well and one very poorly by the nodE mutant, we mapped the nodE-dependent nodulation phenotype to a locus on pea linkage group I. This was close to Sym37 and PsK1, predicted to encode LysM-domain Nod-factor receptor-like proteins; the Sym2 locus that confers Nod-factor-specific nodulation is also in this region. We confirmed the map location using an introgression line carrying this region. Our data indicate that the nodE-dependent nodulation is not determined by the Sym2 locus. We identified several pea lines that are nodulated very poorly by the R. leguminosarum bv. viciae nodE mutant, sequenced the DNA of the predicted LysM-receptor domains of Sym37 and PsK1, and compared the sequences with those derived from pea cultivars that were relatively well nodulated by the nodE mutant. This revealed that one haplotype (encoding six conserved polymorphisms) of Sym37 is associated with very poor nodulation by the nodE mutant. There was no such correlation with polymorphisms at the PsK1 locus. We conclude that the natural variation in nodE-dependent nodulation in pea is most probably determined by the Sym37 haplotype.


Educating workers about tuberculosis.
At a state penitentiary, workers are told that the communicable disease unit is a safe environment in which to work due to the negative air pressure in the isolation rooms and the improved ventilation system. However, nobody is trained to monitor the system or understands the role of negative air pressure, and isolation room doors are occasionally left open. As a result, workers are reluctant to work in the unit. At a soup kitchen, workers refuse to serve people with HIV due to fear of tuberculosis transmission. They have heard that people infected with HIV are likely to have TB and, therefore, to protect themselves, they feel the soup kitchen should not serve people with HIV. In a large, urban social service agency, workers buy masks and begin wearing them to work when they hear a coworker has tuberculosis. Pictures of them in the newspaper instigate a string of similar actions in other agencies. Emergency room workers in a city hospital have been told they are not at increased risk of contracting TB, because they do not have prolonged contact with infectious patients. However, when they discover that several coworkers tested positive on PPD screening tests, they go to their union demanding action.


The novel adenosine A(2A) antagonist prodrug MSX-4 is effective in animal models related to motivational and motor functions.
Adenosine A(2A) and dopamine D2 receptors interact to regulate diverse aspects of ventral and dorsal striatal functions related to motivational and motor processes, and it has been suggested that adenosine A(2A) antagonists could be useful for the treatment of depression, parkinsonism and other disorders. The present experiments were performed to characterize the effects of MSX-4, which is an amino acid ester prodrug of the potent and selective adenosine A(2A) receptor antagonist MSX-2, by assessing its ability to reverse pharmacologically induced motivational and motor impairments. In the first group of studies, MSX-4 reversed the effects of the D2 antagonist eticlopride on a concurrent lever pressing/chow feeding task that is used as a measure of effort-related choice behavior. MSX-4 was less potent after intraperitoneal administration than the comparison compound, MSX-3, though both were equally efficacious. With this task, MSX-4 was orally active in the same dose range as MSX-3. MSX-4 also reversed the locomotor suppression induced by eticlopride in the open field, but did not induce anxiogenic effects as measured by the relative amount of interior activity. Behaviorally active doses of MSX-4 also attenuated the increase in c-Fos and pDARPP-32(Thr34) expression in nucleus accumbens core that was induced by injections of eticlopride. In addition, MSX-4 suppressed the oral tremor induced by the anticholinesterase galantamine, which is consistent with an antiparkinsonian profile. These actions of MSX-4 indicate that this compound could have potential utility as a treatment for parkinsonism, as well as some of the motivational symptoms of depression and other disorders.


An updated evolutionary classification of CRISPR-Cas systems.
The evolution of CRISPR-cas loci, which encode adaptive immune systems in archaea and bacteria, involves rapid changes, in particular numerous rearrangements of the locus architecture and horizontal transfer of complete loci or individual modules. These dynamics complicate straightforward phylogenetic classification, but here we present an approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR-cas loci into distinct classes, types and subtypes. The new classification retains the overall structure of the previous version but is expanded to now encompass two classes, five types and 16 subtypes. The relative stability of the classification suggests that the most prevalent variants of CRISPR-Cas systems are already known. However, the existence of rare, currently unclassifiable variants implies that additional types and subtypes remain to be characterized.


Is sildenafil citrate affect endometrial receptivity? An immunohistochemical study.
The authors aimed to investigate the effect of sildenafil citrate (Sc) on expressions of β(3) integrin and vascular endothelial growth factor (VEGF), which is taking part in endometrium receptivity in implantation window period in controlled ovarian hyperstimulation (COH) performed rats. In this study, Wistar albino female rats were used and were divided into four groups as control, COH, Sc, and COH + Sc groups. They were sacrificed on the third, fourth, and fifth day of pregnancy, uteruses were resected, and uteri sections were stained with immunohistochemical method and evaluated. β(3) integrin immunoreactivity was most intensely observed in the endometrial glandular epithelium (GE) and stromal cells in the Sc group on the third day, whereas immunoreactivity was most intensely detected in the luminal epithelium (LE), GE, and stromal cells in the Sc group on the fourth day. VEGF immunoreactivity was most intensely observed in the endometrial LE in the Sc group on the third day, in the Sc and COH + Sc groups on the fourth day, and in the COH + Sc group on the fifth day. Our results indicated that Sc plays a role in both implantation and decidualization by affecting β(3) integrin and VEGF expressions in implantation window period in rats.


Free will from the viewpoint of teleological behaviorism.
A teleological and behavioral view is presented of the concept of free will. Free will is not something people essentially have or do not have. Instead, the following question is asked: Why does society find it useful to label some actions free and some actions not free? It is argued that the function of such labels is to aid in assigning responsibility to people for their actions. Responsibility in turn is useful in assigning rewards and punishments. The sort of actions that are typically seen as free are the same as those seen as self-controlled. Such actions are responsive to environmental contingencies of relatively wide temporal extent.


In-situ fabrication of NixSey/MoSe2 hollow rod array for enhanced catalysts for efficient hydrogen evolution reaction.
Alkaline water electrocatalysis is considered as one of the most reliable method to prepare the stable, inexpensive, and sustainable water splitting catalyst in large-scale. Recently, MoSe2 attracted great attention as a promising catalyst because of its high electrochemical activity and earth-abundant nature. In this paper, bionic NixSey/MoSe2 coralline-liked heterogeneous structures were successfully prepared on 3D nickel foam (NF) via a simple solvothermal process complemented by hydrothermal strategy with selenization and alkali treatment. Furthermore, to overcome the less active sites and poor electrical conductivity of MoSe2, we learned from the coral structure for the inspiration, and reported a novel hollow rod-like structure with increased active sites. Also, 1 T-2H MoSe2 improved the electrical conductivity of single phase MoSe2. We first confirmed the multi-phase of catalyst by XPS analysis with Mo 3d5/2 splited into two independent regions with the 2H and 1 T phase transition. The optimal ratio of NixSey/MoSe2/NF-5 exhibited excellent electrocatalytic activity towards HER in 1 M KOH, driving current densities of 10, 100 and 200 mA cm-2 at only 76, 165 and 194 mV with stability over 24 h. The work provides new ideas for the construction of transition metal selenides hollow rod array structures of efficient HER electrocatalysts.


Thermodynamics of Malonamide Aggregation Deduced from Molecular Dynamics Simulations.
The aggregation of malonamide extractants diluted in an aliphatic solvent phase has been studied in the presence of water by molecular dynamics simulation. Using association criteria based on distances between molecules and graphs theory, the aggregate distribution has been computed and the corresponding Gibbs energy of aggregates and mass action law constants have been determined. Finally, a model allowing us to the compute critical micelle concentration and osmotic data for a variable concentration of extractants, with or without a correction of the organic phase activity, was developed. It appears however that the accurate depiction of the aggregation allows modeling the thermodynamics of the solution even without an explicit calculation of the activity: both models give results in good agreement with the experiments.


Dynamic molecular exchange and conformational transitions of alpha-synuclein at the nano-bio interface.
The notion that nanoscale surfaces influence protein conformational transitions stimulates the investigation of fibrillogenic polypeptides adsorbing to nanomaterials. Alpha-synuclein (αS) is a prototypical amyloidogenic protein whose aggregation is associated with severe neurodegenerative disorders. We explored the interaction of αS with silica nanoparticles (SNPs) in diverse solution conditions, ranging from protein-free to protein-rich media. We found that the SNP-binding region of αS, determined by site-resolved NMR spectroscopy, was similar in simple buffer and blood serum. Competition binding experiments with isotopic homologues and different proteins showed that cosolutes elicited molecular exchange in a protein-specific manner. The interaction of an oxidized, fibrillation-resistant protein form with SNPs was similar to that of unmodified αS. SNPs, however, did not stimulate fibrillation of the oxidized protein, which remained fibrillation incompetent. CD experiments revealed SNP-induced perturbations of the structural properties of oxidized and non-oxidized αS. Thus, while αS binding to SNPs is essentially orthogonal to fibril formation, the interaction perturbs the distribution of conformational states populated by the protein in the colloidal suspension. This study sheds light on the dynamic nature of αS interactions with NPs, an aspect that crucially impacts on our ability to control aggregation of αS.


Sex bias in ability to cope with cancer: Tasmanian devils and facial tumour disease.
Knowledge of the ecological dynamics between hosts and pathogens during the initial stages of disease emergence is crucial to understanding the potential for evolution of new interspecific interactions. Tasmanian devil (Sarcophilus harrisii) populations have declined precipitously owing to infection by a transmissible cancer (devil facial tumour disease, DFTD) that emerged approximately 20 years ago. Since the emergence of DFTD, and as the disease spreads across Tasmania, the number of devils has dropped up to 90% across 80% of the species's distributional range. As a result, the disease is expected to act as a strong selective force on hosts to develop mechanisms of tolerance and/or resistance to the infection. We assessed the ability of infected devils to cope with infection, which translates into host tolerance to the cancer, by using the reaction norm of the individual body condition by tumour burden. We found that body condition of infected hosts is negatively affected by cancer progression. Males and females presented significant differences in their tolerance levels to infection, with males suffering declines of up to 25% of their body condition, in contrast to less than 5% in females. Sex-related differences in tolerance to cancer progression may select for changes in life-history strategies of the host and could also alter the selective environment for the tumours.


Dual function of fish hepcidin: response to experimental iron overload and bacterial infection in sea bass (Dicentrarchus labrax).
The role of hepcidin in iron metabolism regulation and bacterial infection has been the focus of recent attention. However, in spite of the growing number of hepcidin genes known from different organisms, little is known about its putative dual function in fish. The aim of this study was to characterize the sea bass hepcidin gene and to study its role in iron metabolism and infection. The novel sea bass hepcidin gene was found to be organized into two introns and three exons with several copies present in the genome. The transcript showed a constitutive low basal expression being mainly expressed in liver and encoding a putative 85 residues long peptide. Fish were submitted either to iron status modulation or bacterial infection and the hepcidin transcript levels were analysed along with a number of other parameters. Liver hepcidin expression was found to increase in both the iron-overloaded and infected fish, while in the iron-deficient fish no alteration in expression levels was detected. These results point to the evolutionary conservation of hepcidin's dual functions.


Biomarker support for ADHD diagnosis based on Event Related Potentials and scores from an attention test.
ADHD is a heterogeneous neurodevelopmental disorder associated with dysfunctions in several brain systems. Objective markers of brain dysfunction for clinical assessment are lacking. Many studies applying electroencephalography (EEG) and neuropsychological tests find significant differences between ADHD and controls, but the effect sizes (ES) are often too small for diagnostic purposes. This study aimed to compute a diagnostic index for ADHD by combining behavioral test scores from a cued visual go/no-go task and Event Related Potentials (ERPs). Sixty-one children (age 9-12 years) diagnosed with ADHD and 69 age- and gender-matched typically developing children (TDC) underwent EEG-recording while tested on a go/no-go task. Based on comparisons of ERP group-means and task-performance, variables that differed significantly between the groups with at least moderate ES were converted to a five points percentile scale and multiplied by the ES of the variable. The sum-scores of the variables constituted the diagnostic index. The index discriminated significantly between patients and TDC with a large ES. This index was applied to an independent sample (20 ADHD, 21 TDC), distinguishing the groups with an even larger ES. The diagnostic index described has the potential to support assessment. Further research establishing diagnostic indexes for differential diagnoses is needed.


Intensity of occupational physical activity in blue-collar workers: do self-reported rating and device-worn measurements agree?
High intensity occupational physical activity (OPA) seem to aggravate health and increase risk of sick leave and early retirement. Most intensity of OPA monitoring has been self-reported, e.g. by rating of perceived exertion (RPE). However, no studies have investigated the precision and risk of bias in RPE reporting during free-living OPA. This study investigated the agreement between OPA intensity in percentage of the heart rate reserve (%HRR) estimated from RPE and device-measured heart rate (HR), and potential bias factors on this agreement. The CR10 scale measured RPE at work. The Actiheart monitor measured HR during 24-h a day for 2-4 days. Both RPE and device-worn HR were converted to %HRR. The difference between both %HRR and their limits of agreement was determined in a Bland Altman plot. To detect bias factors, the difference between both %HRR was regressed on age, sex, cardiorespiratory fitness, occupational lifting, medication, consequences of musculoskeletal disorders and the interactions between these factors with device-work %HRR. Six hundred and twenty-three participants were included in the analysis. Mean difference between RPE-based and device-worn %HRR was 54.6% (SD 19.5). The limits of agreement were wide (11.6-90.1%HRR). Age (0.48%HRR, 95% CI 0.18-0.79) occupational lifting (9.84%HRR, 95% CI 3.85-15.83) and cardiorespiratory fitness (0.41%HRR, 95% CI 0.03-0.79) significantly biased the agreement between the estimations of OPA intensity. RPE overestimated OPA intensity, and was biased by several factors. Device-worn %HRR should be preferred when evaluating OPA intensity among workers with physically demanding jobs.


A recombinant IgG3-(IL-2) fusion protein for the treatment of human HER2/neu expressing tumors.
Anti-HER2/neu therapy of human HER2/neu expressing malignancies such as breast cancer has shown only partial success in clinical trials. To expand the clinical potential of this approach, we have genetically engineered an anti-HER2/neu human IgG3 fusion protein containing interleukin-2 (IL-2) fused at its carboxyl terminus. Anti-Her2/neu IgG3-(IL-2) retained antibody and cytokine related activity. Treatment of immunocompentent mice with this antibody fusion protein resulted in significant retardation in the subcutaneous (s.c.) growth of CT26-HER2/neu tumors suggesting that anti-HER2/neu IgG3-(IL-2) fusion protein will be useful in the treatment of HER2/neu expressing tumors. We also found that fusing IL-2 to human IgG3 results in a significant enhancement of the murine anti-human antibody (MAHA) response.


Fossil Atmospheres: a case study of citizen science in question-driven palaeontological research.
Palaeontologists increasingly use large datasets of observations collected from museum specimens to address broad-scale questions about evolution and ecology on geological timescales. One such question is whether information from fossil organisms can be used as a robust proxy for atmospheric carbon dioxide through time. Here, we present the citizen science branch of 'Fossil Atmospheres', a project designed to refine stomatal index of Ginkgo leaves as a palaeo-CO2 proxy by involving citizen scientists in data collection through the Zooniverse website. Citizen science helped to overcome a barrier presented by the time taken to count cells in Ginkgo samples; however, a new set of challenges arose as a result. A beta-testing phase with Zooniverse volunteers provided an opportunity to improve instructions to ensure high fidelity data. Exploration of citizen scientists' estimates shows that volunteer counts of stomata are accurate with respect to counts made by the project's lead scientist. However, counts of epidermal cells have a wide range, and mean values tend to underestimate expert counts. We demonstrate a variety of approaches to reducing the inaccuracy in the calculated stomatal index that this variation causes. Zooniverse serves as an ideal tool for collection of palaeontological data where the distribution of fossils would be impossible, but where specimens can be easily imaged. Such an approach facilitates the collection of a large palaeontological dataset, as well as providing an opportunity for citizens to engage with climate research.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.


Exploiting heterogeneous features to improve in silico prediction of peptide status - amyloidogenic or non-amyloidogenic.
Prediction of short stretches in protein sequences capable of forming amyloid-like fibrils is important in understanding the underlying cause of amyloid illnesses thereby aiding in the discovery of sequence-targeted anti-aggregation pharmaceuticals. Due to the constraints of experimental molecular techniques in identifying such motif segments, it is highly desirable to develop computational methods to provide better and affordable in silico predictions. Accurate in silico prediction techniques of amyloidogenic peptide regions rely on the cooperation between informative features and classifier design. In this research article, we propose one such efficient fibril prediction implementation exploiting heterogeneous features based on bio-physio-chemical (BPC) properties, auto-correlation function of carefully selected amino acid indices and atomic composition within a protein fragment of amino acids in a window. In an attempt to get an optimal number of BPC features, an evolutionary Support Vector Machine (SVM) integrating a novel implementation of hybrid Genetic Algorithm termed Memetic Algorithm and SVM is utilized. Five prediction modules designed using Artificial Neural Network (ANN) models are trained with independent and integrated features in order to validate the fibril forming motifs. The results provide evidence that incorporating new feature namely auto-correlation function besides BPC, attempt to strengthen the sequence interaction effect in forming the feature vector thereby obtaining better prediction quality in terms of sensitivity, specificity, Mathews Correlation Coefficient and Area under the Receiver Operating Characteristics curve. A significant improvement in performance is observed by introducing features like auto-correlation function that maintains sequence order effect, in addition to the conventional BPC properties selected through a novel optimization strategy to predict the peptide status - amyloidogenic or non-amyloidogenic. The proposed approach achieves acceptable results, comparable to most online predictors. Besides, it compensates the lacuna in existing amyloid fibril prediction tools by maintaining equilibrium between sensitivity and specificity.


Regulation of mating in the cell cycle of Saccharomyces cerevisiae.
The capacity of haploid a yeast cells to mate (fuse with a haploid strain of alpha mating type followed by nuclear fusion to produce a diploid cell) was assessed for a variety of temperature-sensitive cell division cycle (cdc) mutants at the permissive and restrictive temperatures. Asynchronous populations of some mutants do not mate at the restrictive temperature, and these mutants define genes (cdc 1, 4, 24, and 33) that are essential both for the cell cycle and for mating. For most cdc mutants, asynchronous populations mate well at the restrictive temperature while populations synchronized at the cdc block do not. Populations of a mutant carrying the cdc 28 mutation mate well at the restrictive temperature after synchronization at the cdc 28 step. These results suggest that mating can occur from the cdc 28 step, the same step at which mating factors arrest cell cycle progress. The cell cycle interval in which mating can occur may or may not extend to the immediately succeeding and diverging steps (cdc 4 and cdc 24). High frequency mating does not occur in the interval of the cell cycle extending from the step before the initiation of DNA synthesis (cdc 7) through DNA synthesis (cdc 2, 8, and 21), medial nuclear division (cdc 13), and late nuclear division (cdc 14 and 15).


Effectiveness of Distance Technology in Promoting Physical Activity in Cardiovascular Disease Rehabilitation: Cluster Randomized Controlled Trial, A Pilot Study.
Physical activity is beneficial for cardiovascular rehabilitation. Digitalization suggests using technology in the promotion of physical activity and lifestyle changes. The effectiveness of distance technology interventions has previously been found to be similar to that of conventional treatment, but the added value of the technology has not been frequently studied. The aim of this pilot study was to investigate whether additional distance technology intervention is more effective in promoting physical activity than non-technology-based treatment in 12 months of cardiac rehabilitation. The cardiovascular disease rehabilitation intervention consisted of three 5-day inpatient periods in a rehabilitation center and two 6-month self-exercise periods at home in between. Participants were recruited from among cardiac patients who attended the rehabilitation program and were cluster-randomized into unblinded groups: conventional rehabilitation control clusters (n=3) and similar rehabilitation with additional distance technology experimental group clusters (n=3). Experimental groups used Fitbit Charge HR for self-monitoring, and they set goals and reported their activity using Movendos mCoach, through which they received monthly automated and in-person feedback. Physical activity outcomes for all participants were measured using the Fitbit Zip accelerometer and the International Physical Activity Questionnaire. During the first 6 months, the experimental group (n=29) engaged in light physical activity more often than the control group (n=30; mean difference [MD] 324.2 minutes per week, 95% CI 77.4 to 571.0; P=.01). There were no group differences in the duration of moderate to vigorous physical activity (MD 12.6 minutes per week, 95% CI -90.5 to 115.7; P=.82) or steps per day (MD 1084.0, 95% CI -585.0 to 2752.9; P=.20). During the following 6 months, no differences between the groups were observed in light physical activity (MD -87.9 minutes per week, 95% CI -379.2 to 203.3; P=.54), moderate to vigorous physical activity (MD 70.9 minutes per week, 95% CI -75.7 to 217.6; P=.33), or steps per day (MD 867.1, 95% CI -2099.6 to 3833.9; P=.55). The use of additional distance technology increased the duration of light physical activity at the beginning of cardiac rehabilitation (for the first 6 months), but statistically significant differences were not observed between the two groups for moderate or vigorous physical activity or steps per day for both 6-month self-exercise periods. ISRCTN Registry ISRCTN61225589; https://doi.org/10.1186/ISRCTN61225589.


Potential laboratory misdiagnosis of hemophilia and von Willebrand disorder owing to cold activation of blood samples for testing.
To assess the potential for misdiagnosis of von Willebrand disorder (vWD) and hemophilia A while following current National Committee for Clinical Laboratory Standards (NCCLS) guidelines and consequent to a poorly recognized cold-activation phenomenon, we processed 39 normal citrate-anticoagulated samples by standard procedures (reference) or stored at low (approximately 4 degrees C) or ambient (approximately 22 degrees C) temperature for 3.5 hours before centrifugation and processing. Samples were tested in parallel for several hemostasis factors, including von Willebrand factor (vWF). Similar results were obtained for all samples for factors II, V, VII, IX, X, XI, and XII. For factor VIII (FVIII) and vWF, only samples stored at ambient temperature had results comparable to reference sample results. In most cases, low temperature storage led to much lower results. Taking the lower reference limit as 50%, most would have been defined as "abnormal," and a misdiagnosis of vWD or hemophilia A could easily arise. ABO classification and age were associated with FVIII and vWF levels, but neither was associated conclusively with relative loss of plasma FVIII coagulant and vWF caused by the cold-activation phenomenon. We advise laboratories following current NCCLS guidelines not to store or transport whole blood samples for FVIII and vWF testing at 2 degrees C to 4 degrees C because of the risk of misdiagnosing vWD or hemophilia A. Storage and transport at ambient temperature seem acceptable and provide results comparable to freshly centrifuged samples.


AutophagyNet: high-resolution data source for the analysis of autophagy and its regulation.
Macroautophagy/autophagy is a highly-conserved catabolic procss eliminating dysfunctional cellular components and invading pathogens. Autophagy malfunction contributes to disorders such as cancer, neurodegenerative and inflammatory diseases. Understanding autophagy regulation in health and disease has been the focus of the last decades. We previously provided an integrated database for autophagy research, the Autophagy Regulatory Network (ARN). For the last eight years, this resource has been used by thousands of users. Here, we present a new and upgraded resource, AutophagyNet. It builds on the previous database but contains major improvements to address user feedback and novel needs due to the advancement in omics data availability. AutophagyNet contains updated interaction curation and integration of over 280,000 experimentally verified interactions between core autophagy proteins and their protein, transcriptional and post-transcriptional regulators as well as their potential upstream pathway connections. AutophagyNet provides annotations for each core protein about their role: 1) in different types of autophagy (mitophagy, xenophagy, etc.); 2) in distinct stages of autophagy (initiation, expansion, termination, etc.); 3) with subcellular and tissue-specific localization. These annotations can be used to filter the dataset, providing customizable download options tailored to the user's needs. The resource is available in various file formats (e.g. CSV, BioPAX and PSI-MI), and data can be analyzed and visualized directly in Cytoscape. The multi-layered regulation of autophagy can be analyzed by combining AutophagyNet with tissue- or cell type-specific (multi-)omics datasets (e.g. transcriptomic or proteomic data). The resource is publicly accessible at http://autophagynet.org.Abbreviations: ARN: Autophagy Regulatory Network; ATG: autophagy related; BCR: B cell receptor pathway; BECN1: beclin 1; GABARAP: GABA type A receptor-associated protein; IIP: innate immune pathway; LIR: LC3-interacting region; lncRNA: long non-coding RNA; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; miRNA: microRNA; NHR: nuclear hormone receptor; PTM: post-translational modification; RTK: receptor tyrosine kinase; TCR: T cell receptor; TLR: toll like receptor.


Newborn clavicle fractures.
A prospective screening program of 9106 newborns identified 43 infants with clavicle fractures for a prevalence of 1 fracture in every 213 live births (0.5%). The fractures were equally distributed by right and left side involvement, and male and female sex. All fractures occurred during vaginal deliveries. None were breech presentation. Risk factors for fracture included large birth-weight, shoulder dystocia, mechanically assisted delivery, and prolonged gestational age. One in 11 newborns with a clavicle fracture also had a brachial plexus palsy.


Modified neck dissection for metastatic testicular carcinoma.
Carcinoma of the testicle is a unique clinicopathologic entity in that an optimistic attitude toward cure can be entertained even in the presence of distant metastasis. Chemotherapy, followed by an aggressive surgical resection of residual disease, can result in eradication of this neoplasm. This tumor is capable of being monitored by the use of serum markers, namely, human chorionic gonadotropin and alpha-fetoprotein. After induction chemotherapy, the transition of elevated serum tumor markers to normal levels suggests that malignant disease has been eliminated or converted to teratoma. Elevated markers indicate persistent or recurrent carcinoma and mandate further chemotherapy. If normalization of tumor markers occurs, any residual mass in the abdomen, chest, or neck should be surgically resected. The otolaryngologist plays a role in the diagnosis and the resection of residual neck disease. Metastatic testicular carcinoma can present as a supraclavicular neck mass and must be considered in the differential diagnosis of a mass in this area. Large residual neck lesions are best removed through the exposure afforded by modified neck dissection.


Optimization of immobilized enzyme hydrolysis combined with high-performance liquid chromatography/thermospray mass spectrometry for the determination of neuropeptides.
Peptidases, including chymotrypsin, thermolysin, trypsin, V8 protease, and carboxypeptidases A, B, and Y, were immobilized for use in conjunction with HPLC/thermospray MS for the analysis of neuropeptides. The optimal operating conditions for each immobilized enzyme bioreactor were determined. Optimal hydrolysis usually occurred at the highest percentage of aqueous solution in the mobile phase at pH 7-8 and 40-50 degrees C. Often post-HPLC column addition of aqueous solutions before the bioreactor could improve activity and thermospray sensitivity without changing the HPLC separation. Enzymatic hydrolysis requirements were compatible under conditions for HPLC separation and thermospray MS detection of the selected neuropeptides. Synthetic alpha-, beta-, and gamma-endorphins were the primary neuropeptides used to evaluate on-line immobilized enzyme bioreactor/MS. HPLC followed by peptidase hydrolysis produced characteristic hydrolysis products for confirming the peptides' identity using thermospray MS detection. Furthermore, the peptide formed from enzymatic hydrolysis resulted in a MS ion current 10-40 times higher than that of the [M + 2H]2+ ion for unhydrolyzed beta-endorphin. The increased sensitivity achieved for detecting the hydrolysis products permits detection and quantitation of synthetic peptides down to 800 fmol.


Plasmon-Triggered Ultrafast Operation of Color Centers in Hexagonal Boron Nitride Layers.
High-quality emission centers in two-dimensional materials are promising components for future photonic and optoelectronic applications. Carbon-enriched hexagonal boron nitride (hBN:C) layers host atom-like color-center (CC) defects with strong and robust photoemission up to room temperature. Placing the hBN:C layers on top of Ag triangle nanoparticles (NPs) accelerates the decay of the CC defects down to 46 ps from their reference bulk value of 350 ps. The ultrafast decay is achieved due to the efficient excitation of the plasmon modes of the Ag NPs by the near field of the CCs. Simulations of the CC/Ag NP interaction show that higher Purcell values are expected, although the measured decay of the CCs is limited by the instrument response. The influence of the NP thickness on the Purcell factor of the CCs is analyzed. The ultrafast operation of the CCs in hBN:C layers paves the way for their use in demanding applications, such as single-photon emitters and quantum devices.


Occurrence and Phenotypes of Pyrimethanil Resistance in Penicillium expansum from Apple in Washington State.
Penicillium expansum is the cause of blue mold in stored apple fruit. In 2010-11, 779 isolates of P. expansum were collected from decayed apple fruit from five packinghouses, tested for resistance to the postharvest fungicide pyrimethanil, and phenotyped based on the level of resistance. In 2010, 85 and 7% of the isolates were resistant to pyrimethanil in packinghouse A and B, respectively, where pyrimethanil had been used for four to five consecutive years. In 2011, pyrimethanil or fludioxonil was used in packinghouse A, and 96% of the isolates from the fruit treated with pyrimethanil were resistant but only 4% of the isolates from the fruit treated with fludioxonil were resistant to pyrimethanil, suggesting that fungicide rotation substantially reduced the frequency of pyrimethanil resistance. No pyrimethanil-resistant isolates were detected in 2010 in the three other packinghouses where the fungicide had been used recently on a small scale. However 1.8% of the isolates from one of the three packinghouses in 2011 were resistant to pyrimethanil. A significantly higher percentage of thiabendazole-resistant than thiabendazole-sensitive isolates were resistant to pyrimethanil. Of the pyrimethanil-resistant isolates, 37 to 52, 4 to 5, and 44 to 58% were phenotyped as having low, moderate, and high resistance to pyrimethanil, respectively. Fludioxonil effectively controlled pyrimethanil-resistant phenotypes on apple fruit but pyrimethanil failed to control phenotypes with moderate or high resistance to pyrimethanil and only partially controlled the low-resistance phenotype.


Investigating Complex Samples with Molograms of Low-Affinity Binders.
In vitro diagnostics relies on the quantification of minute amounts of a specific biomolecule, called biomarker, from a biological sample. The majority of clinically relevant biomarkers for conditions beyond infectious diseases are detected by means of binding assays, where target biomarkers bind to a solid phase and are detected by biochemical or physical means. Nonspecifically bound biomolecules, the main source of variation in such assays, need to be washed away in a laborious process, restricting the development of widespread point-of-care diagnostics. Here, we show that a diffractometric assay provides a new, label-free possibility to investigate complex samples, such as blood plasma. A coherently arranged sub-micron pattern, that is, a peptide mologram, is created to demonstrate the insensitivity of this diffractometric assay to the unwanted masking effect of nonspecific interactions. In addition, using an array of low-affinity binders, we also demonstrate the feasibility of molecular profiling of blood plasma in real time and show that individual patients can be differentiated based on the binding kinetics of circulating proteins.


Angiographic disappearance of multiple dural arteriovenous malformations. Case report.
Angiographic disappearance of two dural arteriovenous malformations (AVM's) in different locations in one case is reported. One of the AVM's involved the right transverse sinus, and the other involved the superior sagittal sinus. The patient's presenting symptoms were due to obstructive hydrocephalus resulting from a small intraventricular hemorrhage that was diagnosed by computerized tomography on admission. The symptoms cleared 25 hours after the ictus in conjunction with improvement of hydrocephalus. The AVM involving the right transverse sinus was supplied by the occipital artery, but ligation of that artery was not successful in eliminating the anomaly. One year later, follow-up angiography revealed disappearance of both dural AVM's.


Neuroleptic malignant syndrome in a patient with neurosyphilis.
Neuroleptic malignant syndrome (NMS) is a catatonic-like syndrome of uncertain etiology occurring in patients taking dopamine blocking medications. The paper describes how NMS presents and is treated and reports the case of a patient with undetected neurosyphilis who developed NMS. The case highlights the need for a thorough organic evaluation of all patients with initial-onset psychotic features and suggests the possibility of a CNS cofactor--neurosyphilis--initiating the NMS as proposed by other researchers.


Effects of propranolol in chronic two-kidney Goldblatt hypertension in rats.
Propranolol administered subcutaneously in a dise of 30 mg/kg twice a day for 3 weeks did not significantly lower systolic tail blood pressure (STBP) in chronic two-kidney Goldblatt hypertension in rats. Plasma renin activity (PRA) measured at the end of the treatment was not significantly different in propranolol treated and dextrose treated rats, although there was marked bradycardia in propranolol treated rats. However, 3 out of 10 propranolol treated hypertensive rats had pressures in the normotensive range during the last week of therapy. PRA values in these three rats were significantly lower than those in dextrose treated hypertensive rats. STBP on day 20 showed a positive correlation with PRA in both propranolol (r = 0.90, p less than 0.01) and dextrose (r = 0.85, p less than 0.01) treated hypertensive rats. Hypertension was associated with an increase in heart weight, which was significantly blunted but not abolished by propranolol treatment. Thus, propranolol did not decrease blood pressure in most rats with chronic two-kidney Goldblatt hypertension; when it did lower blood pressure, its antihypertensive effect appeared related to its renin suppression effect. Furthermore, propranolol mitigated hypertension induced cardiac hypertrophy, independently of its antihypertensive effect.


Menarcheal age for Norwegian women born 1830-1960.
Data from birth records from the maternity hospitals in the three main cities in Norway have been used to study the trend in menarcheal age for women born from about 1830 to about 1960. The investigation is based on a sample of 200-300 records around every 10th year from each of the three clinics in partly overlapping time periods relating to a total of 9152 women. The recollected age at menarche fell from just above 16 years for women born around 1830 to just above 13 years for those born around 1960, the decrease being not totally linear. These results correspond closely with a previously published investigation from Oslo from about the same period of time (Brudevoll, Liestøl and Walløe, 1979), but our results, which cover more of Norway, show a more linearily shaped curve than the results covering only Oslo. We have also analysed the relationships of several independent variables to menarcheal age, using multivariate linear regression methods. Besides the woman's year of birth, which was the most important variable throughout the whole period of time, various geographical variables were found to be of moderate importance. Being born in the countryside and in towns other than Oslo and Bergen led to a slightly higher age at menarche. No significant difference between Oslo, Bergen and Trondheim was detected except for the period up to about 1880 where the Bergen women had about 2.6 months earlier menarche than the Oslo women. Married women amongst the sample had experienced menarche a little earlier than the unmarried, and among married women there was an association between occupation and menarcheal age, women from the lowest social classes having the latest ages at menarche. The importance of these socially related parameters declined with time, and for women born after 1945 the difference seemed to have disappeared. The age at menarche was found to be positively related to a woman's age at first birth; the further back in time the stronger the relation. In addition, delayed age at menarche was also found to be associated with irregularities in the menstrual cycles in later life.


Transcriptional control by two leucine-responsive regulatory proteins in Halobacterium salinarum R1.
Archaea combine bacterial-as well as eukaryotic-like features to regulate cellular processes. Halobacterium salinarum R1 encodes eight leucine-responsive regulatory protein (Lrp)-homologues. The function of two of them, Irp (OE3923F) and lrpA1 (OE2621R), were analyzed by gene deletion and overexpression, including genome scale impacts using microarrays. It was shown that Lrp affects the transcription of multiple target genes, including those encoding enzymes involved in amino acid synthesis, central metabolism, transport processes and other regulators of transcription. In contrast, LrpA1 regulates transcription in a more specific manner. The aspB3 gene, coding for an aspartate transaminase, was repressed by LrpA1 in the presence of L-aspartate. Analytical DNA-affinity chromatography was adapted to high salt, and demonstrated binding of LrpA1 to its own promoter, as well as L-aspartate dependent binding to the aspB3 promoter. The gene expression profiles of two archaeal Lrp-homologues report in detail their role in H. salinarum R1. LrpA1 and Lrp show similar functions to those already described in bacteria, but in addition they play a key role in regulatory networks, such as controlling the transcription of other regulators. In a more detailed analysis ligand dependent binding of LrpA1 was demonstrated to its target gene aspB3.


Exacerbation rates and adherence to disease type in a prospectively followed-up population with multiple sclerosis. Implications for clinical trials.
Two hundred fifty-four patients with definite multiple sclerosis were followed up prospectively for 1 to 5 years (mean, 2.6 years). None of the patients received immunosuppressive medication. Yearly exacerbation rates and each patient's adherence to initial disease type were determined. Disease type was defined at entry and prospectively each subsequent year as stable, relapsing remitting stable, relapsing remitting progressive, or chronic progressive. Exacerbation rates determined prospectively did not decline significantly during 3 years of follow-up, even if patients were stratified by disease duration. Adherence to the initially assigned disease type was highly variable. When followed up for 2 years, 30% of patients with chronic progressive disease had conditions become stable, 32% of patients with stable disease had conditions become chronic progressive, 20% of patients with relapsing remitting disease had conditions become stable, and 20% of patients with relapsing remitting disease had conditions become chronic progressive. Patients with stable or relapsing remitting stable disease switched to one of the progressive categories as frequently (44%) as patients with progressive disease stabilized (46%). Progression of disease measured by changes in Kurtzke Expanded Disability Status Scores did not differ between the different disease types. The results challenge dogma regarding the natural history of exacerbation rates and the assumption that we can reliably assign patients to a specific disease type. The findings have important implications for understanding the natural history of multiple sclerosis and designing clinical trials.


Community-based screening to determine the prevalence, health and nutritional status of patients with CKD in rural and peri-urban Bangladesh.
Studies have labelled chronic kidney disease (CKD) among the adult population in urban Bangladesh. To address knowledge gaps on CKD, we aimed to generate data on prevalence, health and nutrition of CKD individuals living in rural and peri-urban Bangladesh. Participants were recruited from the Mirzapur Demographic Surveillance System by age-stratified random sampling. We screened participants by measuring serum creatinine and urine albumin to creatinine ratio, and collected socio-demographic, lifestyles and health information (phase I). After 3 months (phase II), we repeated the urine and blood tests as per the Kidney Disease Outcomes Quality Initiative guidelines. The glomerular filtration rate was calculated using the CKD Epidemiology Collaboration equation. Among 928 participants, 872 completed the study. In phase I, probable CKD cases were 281 (32.2%); in phase II, confirmed cases were 192 (22.0%) (stage 1, 4.0%; stage 2, 11.8%; stage 3, 5.5%; stage 4, 0.6%; stage 5, 0.1%). In multivariable analysis, associated factors for prevalent CKD included aged ⩾60 years [adjusted odds ratio (aOR) 5.02; 95% confidence interval (CI) 1.85-13.65], hypertension (aOR 3.08; 95% CI 2.07-4.59), diabetes (aOR 2.52; 95% CI 1.60-3.96), presence of red blood cell in urine (aOR 3.20; 95% CI 1.71-5.98) and anemia (aOR 2.50; 95% CI 1.63-3.84). This is the first ever research on CKD prevalence in rural and peri-urban Bangladesh and recorded about 22%, which is higher than urban settings. Monitoring systems are needed to evaluate the overall burden and to mitigate risk factors with an emphasis on the rural and peri-urban population.


Incidence of acute pulmonary embolism in COVID-19 patients: Systematic review and meta-analysis.
Acute pulmonary embolism (PE) has been described as a frequent and prognostically relevant complication of COVID-19 infection. We performed a systematic review and meta-analysis of the in-hospital incidence of acute PE among COVID-19 patients based on studies published within four months of COVID-19 outbreak. Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. We searched Medline, Scopus and Web of Science to locate all articles published up to August 1, 2020 reporting the incidence of acute PE (or lung thrombosis) in COVID-19 patients. The pooled in-hospital incidence of acute PE among COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. We analysed data from 7178 COVID-19 patients [mean age 60.4 years] included in twenty-three studies. Among patients hospitalized in general wards and intensive care unit (ICU), the pooled in-hospital incidence of PE (or lung thrombosis) was 14.7% of cases (95% CI: 9.9-21.3%, I2=95.0%, p<0.0001) and 23.4% (95% CI:16.7-31.8%, I2=88.7%, p<0.0001), respectively. Segmental/sub-segmental pulmonary arteries were more frequently involved compared to main/lobar arteries (6.8% vs18.8%, p<0.001). Computer tomography pulmonary angiogram (CTPA) was used only in 35.3% of patients with COVID-19 infection across six studies. The in-hospital incidence of acute PE among COVID-19 patients is higher in ICU patients compared to those hospitalized in general wards. CTPA was rarely used suggesting a potential underestimation of PE cases.


Clinicopathological Characteristics and Prognosis of Lupus Nephritis Patients with Acute Kidney Injury.
Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for chronic kidney failure. Here, we aimed to assess the characteristics and prognosis of LN patients with AKI. AKI and AKI severity stages in LN patients were defined by the Kidney Disease Improving Global Outcomes (KDIGO) classification. Long-term renal outcomes and patient mortality between different stages of AKI were compared by Cox regression analysis. Of 1272 LN patients, 225 (17.69%) had AKI and 72 (5.66%) were AKI stage 3. Compared with the non-AKI group, the proportion of male patients was significantly higher in the AKI group (p = 0.002). In addition, there were markedly higher proportions of hematologic system damage, more severe renal manifestations, and higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores in the AKI group than in the non-AKI group. The active and chronic lesions in renal biopsy were significantly higher in LN patients with AKI than those without AKI. During a median follow-up of 53 months, Kaplan-Meier curve showed that LN patients with AKI stage 3 had significantly poorer long-term renal outcomes (p = 0.002) and patient survival (p < 0.001) than those without AKI. Furthermore, AKI stage 3, but not stage 1 or 2 was significantly associated with adverse renal outcomes (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.01-6.28, p = 0.048) and all-cause mortality (HR = 2.80, 95% CI: 1.18-6.61, p = 0.019) in LN patients. In patients with AKI, increased baseline serum creatinine and severe glomerular sclerosis were independent risk factors for worse renal outcomes, while higher blood pressure, increased baseline serum creatinine, and anti-Sjogren's syndrome A positivity could indicate poor survival. LN patients with AKI stage 3, but not stages 1 and 2, have poorer long-term renal outcomes and patient survival. Our study demonstrates the importance of early identification and management of AKI in LN patients.


Diametral tensile strength of dual-curing resin cements submitted exclusively to autopolymerization.
To evaluate, at different times, the diametral tensile strength (DTS) of dual-curing resin cements that were not photopolymerized. Equal amounts of base and catalyst pastes of Panavia F (Kuraray), Variolink II (Vivadent), Rely X (3M ESPE), and Enforce (Dentsply) were mixed and inserted into cylindrical molds (4 x 2 mm) (n = 10). Cements were not photopolymerized. DTS test was performed in a testing machine at 30 minutes, 1 hour, 24 hours, and 7 days. The specimens were stored in light-proof containers with distilled water at 37 degrees C until the time of assay. An autopolymerizing resin cement (Cement-It, Jeneric Pentron) and a zinc phosphate cement served as controls. One-way analysis of variance (ANOVA) and Tukey test were performed separately for each cement and for each time (P <.05). All cements showed an increase in DTS when tested at 1 and 24 hours. Tests at 24 hours and 7 days revealed no statistically significant differences. In all groups, the zinc phosphate cement had the lowest DTS mean values (2.1 MPa, 3.6 MPa, 6.5 MPa, and 6.9 MPa), while Cement-It (35.1 MPa, 33.6 MPa, 46.9 MPa, and 46.3 MPa) and Enforce (31.9 MPa, 31.7 MPa, 43.4 MPa, and 47.6 MPa) presented the highest DTS mean values. All cements presented maximal strength at 24 hours. The dual-curing resin cements, even when nonphotopolymerized, demonstrated higher DTS than the zinc phosphate cement and similar or lower values than the autopolymerizing resin cement.


Racial and Ethnic Differences in Mental Health among Asian Americans and Non-Hispanic Whites: Based on California Health Interview Survey.
While Asians are becoming the largest ethnic group in the United States, studies have focused on Asians as a single population. The purpose of this study was to explore the racial and ethnic mental health differences between non-Hispanic Whites and Asians, with an emphasis on understudied subgroups, from the California Health Interview Survey 2011/2012. In this dataset Asians had significantly lower adjusted odds ratios for both mental distress and serious mental illness. However, when Asians were divided into subgroups and compared to Whites, Vietnamese and Japanese subgroups were significantly lower than Whites for mental distress while Koreans were significantly higher. Vietnamese and Chinese were found to have significantly less serious mental illness than Whites in the subgroup analyses. Our results underscore the importance of recognizing that Asian subgroups should not be overlooked, and all Asians should not automatically be treated as a homogenous group.


Secondary cleft-lip rhinoplasty utilizing porous high-density polyethylene.
Secondary nasal deformity associated with cleft lip is a difficult surgical task. For more than 100 years, numerous surgical methods have been created to address the structural changes that occur over time after the primary surgery. Although early surgical methods have relied on various rotational flaps and local tissue manipulation, the recent advent of synthetic materials has provided facial plastic surgeons with more tools to correct the structural and supportive deficiencies. In this article, we describe our 10-year experience with porous high-density polyethylene (PHDPE) implants in secondary cleft-lip rhinoplasty. PHDPE implants have been well tolerated and achieved excellent long-term aesthetic results through fibrovascular ingrowth to the surrounding tissue.


Retinal receptor potentials and their linear relationship to light intensity.
After treatment of the isolated retina of a fish (Centropomus) with ammonia (NH(3)), the electrical responses to light are confined to the receptor layer. These receptor responses are fast in light adaptation and very slow in dark adaptation. The light-adapted responses have thresholds 3 to 4 logarithmic units of light intensity higher than the dark- adapted ones. Both kinds of responses are linearly related to light intensity up to the appearance of saturation. Interactions between receptors and adjacent glia cells appear to be involved in adaptation.


CRASY: mass- or electron-correlated rotational alignment spectroscopy.
Rotational spectra have traditionally been measured without a concurrent means of differentiating the molecular constituents of the sample. Here, we present an all-optical multipulse experiment that allows the correlated measurement of rotational and mass or photoelectron spectra by combining Fourier transform rotational coherence spectroscopy with resonance-enhanced multiphoton ionization. We demonstrate the power of this method with the determination of ground-state rotational constants and fragmentation channels for 10 different isotopes in a natural carbon disulfide sample. Three of the reported rotational constants were previously inaccessible by conventional spectroscopic techniques.


Variability of the immunoglobulin heavy chain constant region locus: a population study.
The Immunoglobulin Heavy chain Constant region (IGHC) locus is a multigene family composed of highly homologous segments often involved in unequal crossings over that lead to deleted and duplicated haplotypes. The frequencies of these haplotypes in 558 individuals from Lombardy, Veneto, Puglia and Sardinia were determined by Pulsed Field Gel Electrophoresis (PFGE), followed by Southern blotting with four IGHC probes, and compared with those observed in 110 subjects from Piedmont. Twenty deletions and 60 duplications were characterized, all in heterozygous individuals except for 2 homozygous deletions. The differences in frequency between the five populations were not significant. The deletions/duplications involved one or more genes: GP-A2, A1-E and G4 duplications, and A1-E and GP-A2 deletions were the most common. Four new duplications are described: three, involving the genes from GP to A2, from G2 to G4, and G4, are counterparts of known deletions. The fourth duplication spans from GP to G2. A G1 deleted heterozygous individual never previously described in Italy is reported. All the rearranged haplotypes seem to be the result of unequal crossing over. The difference between the number of duplications and deletions was significant in Sardinia, Lombardy, Puglia and in the total of 668 subjects (P < 0.001). This may be due to selection or genetic drift.


In Vitro Tests for a Rapid Evaluation of Antidiabetic Potential of Plant Species Containing Caffeic Acid Derivatives: A Validation by Two Well-Known Antidiabetic Plants, Ocimum gratissimum L. Leaf and Musanga cecropioides R. Br. ex Tedlie (Mu) Stem Bark.
Plant bioactive extracts represent a major resource for identifying drugs and adjuvant therapy for type 2 diabetes. To promote early screening of plants' antidiabetic potential, we designed a four in vitro tests strategy to anticipate in vivo bioactivity. Two antidiabetic plants were studied: Ocimum gratissimum L. (Oc) leaf extract and Musanga cecropoides R. Br. ex Tedlie (Mu) stem bark extract. Chemical compositions were analyzed by LCMS and HPLC. Antidiabetic properties were measured based on (1) INS-1 cells for insulin secretion, (2) L6 myoblast cells for insulin sensitization (Glut-4 translocation), (3) L6 myoblast cells for protection against hydrogen peroxide (H2O2) oxidative stress (cell mortality), and (4) liver microsomial fraction for glucose-6-phosphastase activity (G6P). Oc extract increased insulin secretion and insulin sensitivity, whereas it decreased oxidative stress-induced cell mortality and G6P activity. Mu extract decreased insulin secretion and had no effect on insulin sensitivity or G6P activity, but it increased oxidative stress-induced cell mortality. Results were compared with NCRAE, an antidiabetic plant extract used as reference, previously characterized and reported with increased insulin secretion and insulin sensitivity, protection against oxidative stress, and decreased G6P activity. The proposed set of four in vitro tests combined with chemical analysis provided insight into the interest in rapid early screening of plant extract antidiabetic potential to anticipate pharmaco-toxicological in vivo effects.


Prognostic significance of cell kinetics in laryngeal squamous cell carcinoma: clinicopathological associations.
A consecutive series of 99 untreated patients undergoing radical surgical resection for stage I-IV laryngeal carcinomas has been studied prospectively. Our purpose was to analyze the predictive relevance of proliferative variables studied [proliferating cell nuclear antigen (PCNA) expression, volume-corrected mitotic (M/V) index, and S-phase fraction (SPF)] on clinical outcome in relation to DNA ploidy and clinicopathological features. All of the patients were followed up for a median of 32 months (range, 5-58 months). A weak, but significant, positive correlation was found between M/V and PCNA indices (except the PCNA weighted mean index:labeling index ratio) or these indices and SPF. At univariate analysis, node positivity (P < 0.05), poor histological grade (P < 0.01), DNA aneuploidy (P < 0.01), a high SPF (P < 0.01), and a high M/V index (P < 0.05) proved to be related significantly to quicker relapse, whereas T4 (P < 0.05), subglottic site (P < 0.05), DNA aneuploidy (P < 0.01) and a high SPF (P < 0.01) were related significantly to shorter overall survival. With multivariate analysis, a high SPF (> 12.1%) and histological grade (G3) were related to the risk of relapse (relative risk, 8.65 and 5.45, respectively), whereas only a high SPF was related independently to the risk of death (relative risk, 7.30). Our study has identified SPF, in addition to histological grade, as an important biological indicator in laryngeal carcinomas.


Time to onset of action of vardenafil: a retrospective analysis of the pivotal trials for the orodispersible and film-coated tablet formulations.
Patients and physicians consider a rapid onset of action to be an important attribute of oral pharmacotherapy for erectile dysfunction. To investigate the time to onset of action of a new orodispersible tablet (ODT) formulation of vardenafil. A post hoc integrated analysis was performed on data from two 12-week, double-blind, multicenter, randomized, parallel-group, placebo-controlled phase III trials of 10 mg vardenafil ODT. Data for the vardenafil film-coated tablet were generated from a retrospective integrated analysis at week 12 of four double-blind, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled phase III trials. Time intervals (in 15-, 30-, and 60-minute increments, up to ≥6 hours after study medication intake) were determined for the period between dosing and start of sexual activity (with the intention of intercourse). The total number of sexual intercourse attempts and Sexual Encounter Profile question 3 (SEP3) success rates were calculated per time interval. Within 15 minutes postdosing, mean per-patient SEP3 success rates were 62.5% (vardenafil ODT) vs. 29.4% (placebo), with corresponding overall SEP3 success rates of 59.8% and 38.2%. In this time interval, 5.3% vs. 2.8% of all sexual activity attempts were initiated by subjects taking vardenafil ODT (n = 89) or placebo (n = 62), respectively. At 16-30 minutes postdosing, SEP3 success rates were 65.3% and 32.6% (mean per-patient) and 70.2% and 51.0% (overall) for vardenafil ODT vs. placebo, respectively, with a corresponding 10.4% and 8.7% of all sexual activity attempts being made by subjects taking vardenafil ODT (n = 170) or placebo (n = 118). Comparable results were observed for vardenafil 10 and 20 mg film-coated tablet at corresponding time intervals. Vardenafil ODT shows a rapid onset of action comparable with that of vardenafil film-coated tablet. In those men who begin sexual activity within 30 minutes after dosing, the majority of sexual attempts lead to successful intercourse.


Feasibility assessment of a chemoresponse assay to predict pathologic response in neoadjuvant chemotherapy for breast cancer patients.
For chemosensitivity and resistance assays to be clinically useful in predicting patient outcome, they should require small amounts of tissue and be highly reproducible and reliable. Expanded tumor cells from transcutaneous biopsies of breast lesions (n=62) were tested for chemoresponse using the cell-based ChemoFx assay. Pathologic complete response (pCR) was determined on a subset of patients (n=34). Assay score and pCR were determined independently in a blinded manner. Logistic regression models were used to select predictors for response. Tumor cells were successfully isolated from 83.9% of patients. Chemoresponse profiles were robust and reproducible with coefficient of variance of <3%. In a limited initial patient outcome correlation, assay score of docetaxel/capecitabine significantly predicted pCR; the cross-validated model was 75% accurate. It is feasible to assess the chemoresponsiveness of small breast lesions using the ChemoFx assay to assist in choosing neoadjuvant chemotherapy for breast cancer patients.


Purification and characterization of Clostridium sordellii lethal toxin and cross-reactivity with Clostridium difficile cytotoxin.
Lethal toxin (LT) was purified from Clostridium sordellii IP82 by DEAE-Trisacryl, Ultrogel AcA3-4 gel filtration, and hydroxyapatite column chromatography. The molecular weight of purified LT was estimated to be 240,000 to 250,000, and the pI was at pH 4.55. LT was lethal for mice by intraperitoneal injection (3.4 X 10(5) mouse lethal doses per mg of protein), cytotoxic for Vero cells (6.1 X 10(4) cytotoxic units per mg of protein), erythematous and edematous by intradermal injection in guinea pigs, and induced a moderate fluid accumulation in the guinea pig intestinal loop test. The lethal activity was inactivated by N-bromosuccinimide, N-chlorosuccinimide, chloramine-T, and sodium dodecyl sulfate. The data suggest that tryptophan and methionine residues present in the toxin are important for lethal activity. Furthermore, LT was inactivated by oxidized glutathione and activated by dithiothreitol. Inactivation by sulfhydryl-group reagents 5,5'-dithiobis(2-nitrobenzoic acid) and iodoacetamide was only obtained with dithiothreitol-treated LT. Thiol groups which are protected as a disulfide bond(s) seem to be essential for the LT activity. A specific antiserum against LT neutralized the biological activities of LT and also cytotoxic activity and lethal activity of Clostridium difficile toxin B but not of C. difficile toxin A. However, this serum did not recognize antigen from C. difficile culture supernatant by immunoblotting. It was concluded that antibodies prepared from C. sordellii LT that neutralized C. difficile cytotoxic activity recognized a low number of epitopes or tertiary structures of C. difficile cytotoxin.


Primary bacterial pyomyositis associated with septic arthritis caused by Streptococcus pyogenes: a case report.
Pyomyositis is relatively rare in temperate climates. This is the first report of a case of calf pyomyositis associated with septic arthritis of the knee. This case illustrates that pyomyositis should be included in the differential diagnosis of a swollen, tender calf in an emergency setting. The other notable feature of this case is that the infective organism was not the usual Staphylococcus aureus but rather the relatively rarely involved Streptococcus pyogenes.


Quantitative culture of Helicobacter pylori from gastric juice: the potential for transmission.
The transmission of Helicobacter pylori may occur by spread of organisms from gastric juice which has been introduced into the mouth by gastro-oesophageal reflux. The aim of this study was to quantify the load of H. pylori present in gastric juice available for transmission. Gastric antral biopsy and gastric juice samples were collected from 108 adult dyspeptic patients undergoing routine upper gastroscopy and the presence of H. pylori was determined. In all, 54 (50%) of 108 patients gave positive results in the gastric antral biopsy rapid urease test and for H. pylori histology. The gastric juice of 40 (37%) of patients gave positive results for the urease A gene by PCR assay; 34 (31%) of patients were positive by these three tests and H. pylori was cultured from the gastric juice of 13 (38%) of these patients. The median count of H. pylori in gastric juice was 1.75 x 10(1) cfu/ml. Viable organisms in gastric juice may lead to transmission of H. pylori when refluxed or vomited into the mouth.


Collaboration: a concept analysis.
Collaboration is a complex phenomenon, yet one that is of significance to nursing. This concept analysis presents definitions and defining characteristics of collaboration so that the concept may be used in the creation of operational definitions, or to develop and evaluate tools for measuring collaboration. Antecedents, consequences and empirical referents of collaboration are explored. Model, contrary and related cases are presented to clarify this concept further.


Inferiorly based nasolabial flap for reconstruction of full-thickness medium-sized lower lip and commissural defects following ablative cancer surgery.
Information regarding the design and usage of inferiorly based nasolabial flap for lower lip and commissural defect reconstruction following ablative cancer surgery remains limited. This study aimed to provide our design and experiences for such reconstructive purpose. Patients with lower lip or oral commissural cancer who received curative surgery involving reconstruction with inferiorly based nasolabial flap were included. The demographic data and clinical outcomes of these patients were obtained by retrospective chart review. A total of eight patients were enrolled in this study. All patients received ablative surgery at the National Cheng Kung University Hospital during May 2019 to May 2021, with their surgical defects reconstructed with unilateral inferiorly based nasolabial flap successfully. Among the five patients with lower lip cancer, one had a limited area of necrosis at flap tip. Another patient had a small orocutaneous fistula that healed spontaneously. No trismus or oral incompetence was noted following recovery. For the three patients with commissural cancer, a second stage commisuroplasy was needed after primary reconstruction. One patient had limited wound dehiscence at mouth angle following surgery, resulting in mild oral incompetence. Although mild trismus was noted in these three commissural cancer patients, all patients resumed normal diet during follow-up. Inferiorly based nasolabial flap is an excellent local flap for lower lip reconstruction following cancer ablative surgery. It is also a viable option for reconstruction of oral commissural defects. Minimal donor side morbidity, good functional recovery, and esthetic outcomes can be achieved with meticulous flap design.


Photosynthetic acclimation and resource use by the C3 and C4 subspecies of Alloteropsis semialata in low CO2 atmospheres.
During the past 25 Myr, partial pressures of atmospheric CO2 (Ca ) imposed a greater limitation on C3 than C4 photosynthesis. This could have important downstream consequences for plant nitrogen economy and biomass allocation. Here, we report the first phylogenetically controlled comparison of the integrated effects of subambient Ca on photosynthesis, growth and nitrogen allocation patterns, comparing the C3 and C4 subspecies of Alloteropsis semialata. Plant size decreased more in the C3 than C4 subspecies at low Ca , but nitrogen pool sizes were unchanged, and nitrogen concentrations increased across all plant partitions. The C3, but not C4 subspecies, preferentially allocated biomass to leaves and increased specific leaf area at low Ca . In the C3 subspecies, increased leaf nitrogen was linked to photosynthetic acclimation at the interglacial Ca , mediated via higher photosynthetic capacity combined with greater stomatal conductance. Glacial Ca further increased the biochemical acclimation and nitrogen concentrations in the C3 subspecies, but these were insufficient to maintain photosynthetic rates. In contrast, the C4 subspecies maintained photosynthetic rates, nitrogen- and water-use efficiencies and plant biomass at interglacial and glacial Ca with minimal physiological adjustment. At low Ca , the C4 carbon-concentrating mechanism therefore offered a significant advantage over the C3 type for carbon acquisition at the whole-plant scale, apparently mediated via nitrogen economy and water loss. A limiting nutrient supply damped the biomass responses to Ca and increased the C4 advantage across all Ca treatments. Findings highlight the importance of considering leaf responses in the context of the whole plant, and show that carbon limitation may be offset at the expense of greater plant demand for soil resources such as nitrogen and water. Results show that the combined effects of low CO2 and resource limitation benefit C4 plants over C3 plants in glacial-interglacial environments, but that this advantage is lessened under anthropogenic conditions.


Is there a role for mitochondrial genes in carcinogenesis?
Although defective respriration is not characteristic of all tumors, recent comparative studies on the ultrastructure of normal and tumor cell mitochondria indicate that in malignant cells mitochondria deviate from normal not only in relative abundance but also in the size, form, density, and frequency of appearance of lesions. Normal and abnormal mitochondria may populate the same cell, suggesting that there may be a gradation in respiratory deficiency depending on the proportion of normal to abnormal forms. Recent advances in mitochondrial genetics suggest that aberrant mitochondria may be formed as a result of the presence of an abnormal mitochondrial genome. In analogy with the petite mutant of certain strains of yeast, animal cells may be transformed by treatment with dyes that alter the structure of their mitochondrial DNA, so that their mitochondria also become deficient in enzymes of the respiratory chain. Whether nutritional or other deficiencies are mutagenic with respect to mitochondrial DNA of animal cells is not known; nor is it known whether mitochondrial mutagenesis is causally involved in carcinogenesis. New knowledge of cytoplasmic genetics and of mitochondrial DNA and membrane structure and dynamics should encourage investigations aimed at examining the possible role of mitochondrial genes in neoplastic transformation.


Protein-carbohydrate interaction effects on energy balance, FGF21, IGF-1, and hypothalamic gene expression in rats.
Amino acids are involved in energy homeostasis, just as are carbohydrates and lipids. Therefore, mechanisms controlling protein intake should operate independently and in combination with systems controlling overall energy intake to coordinate appropriate metabolic and behavioral responses. The objective of this study was to quantify the respective roles of dietary protein and carbohydrate levels on energy balance, plasma fibroblast growth factor 21 (FGF21) and insulin growth factor 1 (IGF-1) concentrations, and hypothalamic neurotransmitters (POMC, NPY, AgRP, and CART). In a simplified geometric framework, 7-wk-old male Wistar rats were fed 12 diets containing 3%-30% protein for 3 wk, in which carbohydrates accounted for 30%-75% of the carbohydrate and fat part of the diet. As a result of this study, most of the studied parameters (body composition, energy expenditure, plasma FGF21 and IGF-1 concentrations, and Pomc/Agrp ratio) responded mainly to the protein content and to a lesser extent to the carbohydrate content in the diet.NEW & NOTEWORTHY As mechanisms controlling protein intake can operate independently and in combination with those controlling energy intakes, we investigated the metabolic and behavioral effects of the protein-carbohydrate interaction. With a simplified geometric framework, we showed that body composition, energy balance, plasma FGF21 and IGF-1 concentrations, and hypothalamic Pomc/Agrp ratio were primarily responsive to protein content and, to a lesser extent, to carbohydrate content of the diet.


[Psychiatric and Psychotherapeutic Care of Refugees by Reference of a Large Psychiatric Care Hospital in Western Germany].
Medical and psychological care of refugees is among the most important current challenges in German health politics. Work with patients from this heterogeneous group who have often faced severe stress before, during and after their migration is currently based on a thin data foundation. Based on introductory information on current knowledge concerning psychiatric morbidity of refugees this article presents the psychiatric care of refugees at LVR Clinics Cologne - a psychiatric specialty hospital situated in North Rhine-Westphalia, Germany. A sample of 239 cases of refugee patients who were referred to in- and outpatient departments of the LVR Clinics Cologne between April 2015 and March 2016 are evaluated in respect of diagnoses, admission modalities and socio-demographic variables. The majority of principal diagnoses (40.2%) belong to the group of stress-related and somatoform disorders (F4 in ICD-10). Mood disorders (F3 in ICD-10) represented 31.0%, followed by mental and behavioral disorders due to psychoactive substance use (F1 in ICD-10) with 15.1%. Posttraumatic Stress Disorder (PTSD) was the most prevalent diagnose (13.0%). Among the 29 countries of the patients' origin Afghanistan (10,0%), Serbia (9.6%) and Kosovo (8.8%) were the most abundant. The diagnoses and the high rate of acute psychiatric events reflect the massive psychological pressure of the patients. The important role of interpreters and mediators specialized in language and integration in the treatment process is emphasized.