Steady-state nucleation rate and flux of composite nucleus at saddle point.
The steady-state nucleation rate and flux of composite nucleus at the saddle point is studied by extending the theory of binary nucleation. The Fokker-Planck equation that describes the nucleation flux is derived using the Master equation for the growth of the composite nucleus, which consists of the core of the final stable phase surrounded by a wetting layer of the intermediate metastable phase nucleated from a metastable parent phase recently evaluated by Iwamatsu [J. Chem. Phys. 134, 164508 (2011)]. The Fokker-Planck equation is similar to that used in the theory of binary nucleation, but the non-diagonal elements exist in the reaction rate matrix. First, the general solution for the steady-state nucleation rate and the direction of nucleation flux is derived. Next, this information is then used to study the nucleation of composite nucleus at the saddle point. The dependence of steady-state nucleation rate as well as the direction of nucleation flux on the reaction rate in addition to the free-energy surface is studied using a model free-energy surface. The direction of nucleation current deviates from the steepest-descent direction of the free-energy surface. The results show the importance of two reaction rate constants: one from the metastable environment to the intermediate metastable phase and the other from the metastable intermediate phase to the stable new phase. On the other hand, the gradient of the potential Φ or the Kramers crossover function (the commitment or splitting probability) is relatively insensitive to reaction rates or free-energy surface.


Postoperative intracerebral haemorrhages remote from the site of the initial operation.
Two cases of postoperative intracerebral haemorrhages remote from the site of the initial craniotomy for saccular aneurysms are reported and the other cases from the literature are reviewed. Lack of a good postoperative recovery and the appearance of neurological signs not related to the site of the operation may suggest this complication, which is associated with high mortality and disability rate. The possible pathogeness of those postoperative haemorrhages is discussed.


Global drivers and tradeoffs of three urban vegetation ecosystem services.
Our world is increasingly urbanizing which is highlighting that sustainable cities are essential for maintaining human well-being. This research is one of the first attempts to globally synthesize the effects of urbanization on ecosystem services and how these relate to governance, social development and climate. Three urban vegetation ecosystem services (carbon storage, recreation potential and habitat potential) were quantified for a selection of a hundred cities. Estimates of ecosystem services were obtained from the analysis of satellite imagery and the use of well-known carbon and structural habitat models. We found relationships between ecosystem services, social development, climate and governance, however these varied according to the service studied. Recreation potential was positively related to democracy and negatively related to population. Carbon storage was weakly related to temperature and democracy, while habitat potential was negatively related to democracy. We found that cities under 1 million inhabitants tended to have higher levels of recreation potential than larger cities and that democratic countries have higher recreation potential, especially if located in a continental climate. Carbon storage was higher in full democracies, especially in a continental climate, while habitat potential tended to be higher in authoritarian and hybrid regimes. Similar to other regional or city studies we found that the combination of environment conditions, socioeconomics, demographics and politics determines the provision of ecosystem services. Results from this study showed the existence of environmental injustice in the developing world.


Theoretical identification of the superior anchoring effect and electrochemical performance of Ti2CS2 by single atom Zn doping for lithium-sulfur batteries.
As one of the promising next-generation energy storage systems, lithium-sulfur (Li-S) batteries have been the subject of much recent attention. However, the polysulfide shuttle effect remains problematic owing to the dissolution of intermediate polysulfide species in the electrolyte and the sluggish reaction dynamics in Li-S batteries. To overcome these issues, this work reports an effective strategy for enhancing the electrochemical performance of Li-S batteries using single atom Zn doping on the S-terminated Ti2C MXenes (Ti2-xZnxCS2). Spin-polarized density functional theory (DFT) calculations were performed to elucidate the interactions of lithium polysulfides (LiPSs) and the Ti2-xZnxCS2 surface in terms of geometric and electronic properties, as well as the delithiation process of Li2S on the Ti2-xZnxCS2 surface. It is found that doping single atom Zn could induce a new Lewis acid-based sites, which could provide proper affinity toward LiPSs. Combined with the metallic character, a low Li diffusion barrier and high catalytic activity for the delithiation process of Li2S, makes Ti2-xZnxCS2 a promising cathode material for Li-S batteries. The results demonstrate the importance of surface chemistry and the electronic structure of MXenes in LiPSs' adsorption and catalysis capability. We believe that our findings provide insights into the recent experimental results and guidance for the preparation and practical application of MXenes in Li-S batteries.


In vivo evaluation of the interaction between the Escherichia coli IGP synthase subunits using the Bacterial Two-Hybrid system.
Histidine biosynthesis is one of the most characterized metabolic routes for its antiquity and its central role in cellular metabolism; indeed, it represents a cross-road between nitrogen metabolism and de novo synthesis of purines. This interconnection is due to the activity of imidazole glycerol phosphate synthase, a heterodimeric enzyme constituted by the products of two his genes, hisH and hisF, encoding a glutamine amidotransferase and a cyclase, respectively. Despite their interaction was suggested by several in vitro experiments, their in vivo complex formation has not been demonstrated. On the contrary, the analysis of the entire Escherichia coli interactome performed using the yeast two hybrid system did not suggest the in vivo interaction of the two IGP synthase subunits. The aim of this study was to demonstrate the interaction of the two proteins using the Bacterial Adenylate Cyclase Two-Hybrid (BACTH) system. Data obtained demonstrated the in vivo interaction occurring between the proteins encoded by the E. coli hisH and hisF genes; this finding might also open the way to pharmaceutical applications through the design of selective drugs toward this enzyme.


[Safety and efficacy of inhaled ciclesonide in asthma].
Poor adherence to medications and other aspects of the treatment plan are described in patients with asthma, especially with adverse events concerning the upper respiratory and digestive tracts. Against this background a review is presented of current knowledge about the new class of glucocorticoids (ciclesonide).


Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value.
Tumor markers were studied in the sera of 883 untreated patients with primary breast cancer diagnosed between 1989 and 2007. Abnormal human epidermal growth factor receptor 2 (HER-2)/neu levels (>15 ng/mL) were found in 9.5%, carcinoembryonic antigen (CEA) in 15.9%, and cancer antigen (CA) 15.3 in 19.7% of the patients. One or more tumor markers were abnormal in 305 (34.5%) of the 883 studied patients. Significantly higher serum HER-2/neu levels were found in patients with tissue overexpression of this oncoprotein (p < 0.0001). CEA, CA 15.3, and HER-2/neu (only in those patients with tissue overexpression) serum levels were related with tumor stage (tumor size and nodal involvement) and steroid receptors (higher values in estrogen receptor-negative (ER-) tumors). Univariate analysis showed that HER-2/neu serum levels were prognostic factors in disease-free survival (DFS) and overall survival (OS) only in patients with tissue overexpression. Multivariate analysis in 834 patients show that nodal involvement, tumor size, ER, CEA, and adjuvant treatment were independent prognostic factors in DFS and OS. When only patients with HER-2/neu overexpression in tissue were studied, tumor size, nodal involvement, and tumor markers (one or another positive) were independent prognostic factors for both DFS and OS. HER-2/neu serum levels were also an independent prognostic factor, with CEA, ER, and nodes in 106 patients treated with neoadjuvant treatment. In summary, serum HER-2/neu, CEA, and CA 15.3 are useful tools in the prognostic evaluation of patients with primary breast cancer.


Characterization of muscarinic receptor subtype mediating contraction and relaxation in equine coronary artery in vitro.
In coronary arterial rings isolated from horses, 10(-8)-10(-6) mol/l acetylcholine (ACh) induced concentration-dependent contractions which were potentiated by the removal of endothelium and by pretreatment with L-nitro-arginine (LNAG) or methylene blue (MB). Relatively lower concentrations of ACh (10(-14)-10(-8) mol/l) induced relaxation when the coronary rings were contracted by phenylephrine (PE). ACh-induced contractions in the coronary rings without endothelium were competitively inhibited by each muscarinic subtype selective antagonist in the following order of potency: 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > pirenzepine > or = parafluoro-hexahydrosiladiphenidol (pFHHSiD) > methoctramine. ACh-induced relaxation in the rings with endothelium was inhibited by LNAG or MB, and by each selective antagonist in the following order of potency: 4-DAMP > pFHHSiD > pirenzepine > methoctramine. These results suggest that the ACh-induced contraction and relaxation in equine coronary arteries are mediated mainly by an M3-receptor located on the smooth muscle cells and endothelial cells, respectively, and that the stimulation of the M3-receptor on the endothelial cells liberates nitric oxide.


Effects of lung recruitment maneuvers on splanchnic organ perfusion during endotoxin-induced pulmonary arterial hypertension.
Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin-induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 ± 2 mmHg (mean ± SD) to 31 ± 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 ± 14 mmHg to 27 ± 13 mmHg (mean ± SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% ± 21%, 69% ± 20%, 76% ± 16%, 79% ± 18%, and 81% ± 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% ± 19%, 77% ± 13%, 66% ± 26%, and 71% ± 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows.


Ocular fluorophotometry using high S-N ratio fluorophotometer.
fluorophotometer was remolded to improve S-N (Sensitivity-Noise) ratio by means of photomultiplier cooling system, and ocular fluorophotometry was performed in 13 subjects aged from 20 to 40 (mean 32.5) years old and 13 subjects aged from 55 to 62 (mean 59.2) years old to assess aging effect on the blood-ocular barrier. The results revealed that the fluorescence value at the midvitreous, lenticular autofluorescence, and the anterior chamber of older group is higher than that of the younger group (p less than 0.05). The higher value of midvitreous may be derived from increase of diffusion rate due to vitreous liqueation rather than the blood-retinal barrier abnormalities.


The major isozyme of rat cardiac glutathione transferases. Its correspondence to hepatic transferase X.
A major isozyme of rat heart glutathione transferase was purified to homogeneity by Sephadex G-200 gel filtration, ammonium sulfate precipitation, CM-cellulose chromatography and affinity chromatography on S-hexylglutathione-linked Sepharose 6B. The purified isozyme was a dimer with an apparent relative molecular mass of 50 000 composed of two Yb-size subunits (Mr = 26 500). The isozyme is immunologically related to rat liver glutathione transferase X and 3-3, especially closely to transferase X, and no immunological cross-reactivity with subunits 1 and 2 of hepatic glutathione transferases was observed. The isoelectric point (pI = 6.9) of the isozyme was identical with and the substrate specificity was very similar to transferase X. Thus, the cardiac near-neutral isozyme is considered to be identical to glutathione transferase X recognized in rat liver. The amount of this near-neutral isozyme estimated to be present in heart tissue is 70 micrograms/g. The isozyme has relatively high activities towards alpha, beta-unsaturated carbonyl compounds such as trans-4-phenyl-3-buten-2-one and trans-4-hydroxynon-2-enal. The latter is a cytotoxic product resulting from lipid peroxidation of polyunsaturated fatty acids, and the cardiac isozyme may play a physiologically significant role with glutathione conjugation of this compound. In addition to the near-neutral isozyme, acidic forms with isoelectric points of 4.9, 5.2 and 5.5 were partially purified; some of them are considered to consist of subunits immunologically related to transferase X.


Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite.
Ticks are hematophagous arthropods that use a complex mixture of salivary proteins to evade host defenses while taking a blood meal. Little is known about the immunological and physiological consequences of tick feeding on humans. Here, we performed the first bulk and single-nucleus RNA sequencing (snRNA-seq) of skin and blood of four persons presenting with naturally acquired, attached Ixodes scapularis ticks. Pathways and individual genes associated with innate and adaptive immunity were identified based on bulk RNA sequencing, including interleukin-17 signaling and platelet activation pathways at the site of tick attachment or in peripheral blood. snRNA-seq further revealed that the Hippo signaling, cell adhesion, and axon guidance pathways were involved in the response to an I. scapularis bite in humans. Features of the host response in these individuals also overlapped with that of laboratory guinea pigs exposed to I. scapularis and which acquired resistance to ticks. These findings offer novel insights for the development of new biomarkers for I. scapularis exposure and anti-tick vaccines for human use.


Spotlight on brodalumab in the treatment of moderate-to-severe plaque psoriasis: design, development, and potential place in therapy.
Brodalumab is a novel fully human immunoglobulin G2 monoclonal antibody that antagonizes the interleukin (IL)-17 pathway by binding with high affinity to human IL-17RA. The role of IL-17A in the pathogenesis of psoriasis, as well as the remarkable effectiveness of IL-17 inhibitors in the treatment of moderate-to-severe plaque psoriasis, is well established. The mechanism of action of brodalumab is unique in that it inhibits the IL-17 receptor compared to the two other currently FDA-approved IL-17 inhibitors, secukinumab and ixekizumab, which inhibit the IL-17A molecule itself. The efficacy of brodalumab in the treatment of moderate-to-severe plaque psoriasis has been demonstrated in phase 2 and 3 trials, and subsequently the FDA approved this medication in February 2017. Brodalumab was approved in Japan in July 2016 and approval is pending in Europe. The safety and adverse effects of brodalumab were reviewed across several clinical trials, which, similar to other IL-17 inhibitors, demonstrated increased rates of neutropenia and Candida infections. Brodalumab treatment, similar to ixekizumab and secukinumab, showed no improvement in inflammatory bowel disease patients, and on the contrary, more exacerbations were encountered. Suicidal ideation and behavior events have been reported with brodalumab treatment and are of significant concern. Brodalumab provides another highly effective treatment option for moderate-to-severe plaque psoriasis.


Effect of exogenous nerve growth factor on neurotoxicity of and neuronal gene delivery by a herpes simplex amplicon vector in the rat brain.
We have previously shown that local destruction of neural tissue by wild-type herpes simplex virus type 1 (HSV-1) is attenuated by intracerebral infusion of nerve growth factor (NGF). To investigate the effect of NGF on the extent of neurolysis and efficacy of neuronal gene transfer mediated by an HSV-1 amplicon vector system in vivo, rats were stereotaxically injected in the striatum with an amplicon preparation, pHSVlac. This amplicon contains the Escherichia coli lacZ gene under the transcriptional control of the HSV-1 immediate early 4/5 promoter and is packaged by an HSV-1 helper virus carrying a deletion in the immediate early 3 gene. Vector injection was followed by continuous intracerebral infusion of NGF-beta (total dose 5 micrograms) or vehicle solution over 7 days. Animals were sacrificed at the end of the 7-day infusion period for histological analysis of the brains. A distinct zone of inflammation and necrosis surrounded the injection site in all vector-inoculated animals. The volume of striatal tissue destruction was significantly smaller in NGF-treated animals (1.27 +/- 0.19 mm3; mean +/- SEM) than in the vehicle-treated controls (2.16 +/- 0.37 mm3; P < 0.05 by t-test). Immunohistochemical staining for HSV and beta-galactosidase (beta-Gal) in vehicle-treated animals revealed that many striatal cells harbored HSV antigens (3,678 +/- 636), but only a small number expressed the reporter gene at 7 days post-injection (294 +/- 60). NGF infusion did not significantly affect the number of HSV-immunoreactive cells (4,224 +/- 618), or the number of cells expressing beta-Gal (330 +/- 72) at this time.(ABSTRACT TRUNCATED AT 250 WORDS)


Rifampicin-associated acute renal failure and hemolysis: a rather uncommon but severe complication.
Rifampicin is a widely used anti-tuberculosis agent. Apart from hepatotoxicity, rifampicin can rarely lead to adverse reactions of immunologic nature such as acute renal failure (ARF). We report the case of 57-year-old previously healthy man under treatment for pulmonary tuberculosis who presented with hemolysis and severe ARF. Rifampicin was discontinued and the patient was treated with fluid repletion, iv furosemide and dialysis therapy. Kidney biopsy revealed acute tubulointerstitial nephritis with no evidence of granulomas. The patient significantly improved and was discharged after 51 days of hospitalization. Clinicians using rifampicin should be aware of this rather uncommon but severe complication.


[The G/C polymorphism of RAD51 gene in breast cancer].
The development of breast cancer is associated with an accumulation of specific genetic alterations. The aim. In this study the distribution of G/G, G/C and C/C genotype and frequencies of the G and C allele of RAD51 G/C polymorphism in women with breast cancer was examined. 85 breast cancer samples were included in this study. They were categorised according to Scarf-Bloom-Richardson criteria in women with breast cancer. Blood samples age matched healthy individuals (n = 91) served as control. The distribution of the genotypes of the G/C polymorphism RAD51 in both control and patients did not differ significantly (p>0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences in the genotype distributions and allele frequencies between node-positive and node-negative patients. Our study implies that it is possible that the G/C polymorphism of the RAD51 gene may not be directly involved in the development and/or progression of breast cancer but further researches, conducted on larger population, are needed to clarify this point.


Artifact correction of the ongoing EEG using spatial filters based on artifact and brain signal topographies.
Review and analysis of continuous EEG recordings may be impeded by physiological artifacts such as blinks, eye movements, or cardiac activity. Spatial filters based on artifact and brain signal topographies can remove artifacts completely without distortion of relevant brain activity. The authors describe the basic principle of artifact correction by spatial filtering and they review different approaches to estimate artifact and brain signal topographies. The main focus is on the preselection approach, which is fast enough to be applied while paging through the segments of a digital EEG recording. Examples of real EEG segments, containing epileptic seizure activity or interictal spikes contaminated by artifacts, show that spatial filtering by preselection can be a useful tool during EEG review. Advantages and disadvantages of the different spatial filter approaches are discussed.


Hybrid procedure for a Kommerell's diverticulum in a right-sided aortic arch.
A rare case of an aneurysmal Kommerell's diverticulum in a right-sided aortic arch was successfully treated using a hybrid procedure comprising total arch replacement and percutaneous stent grafting. A 65-year-old man with dysphagia was diagnosed with an ectatic right-sided aortic arch and a saccular aneurysm of the Kommerell's diverticulum. Since its radical resection during a single surgery was unfeasible because of its complex configuration, a 2-stage procedure was adopted.


[Irradiation in radiodiagnosis: recent possibilities of decreasing the doses (author's transl)].
Depending on the film used, the new super-fast re-enforcing screens enable a four to six fold reduction in diagnosis cutaneous irradiation. This diagnosis irradiation which remains rather considerable under classical techniques, is frequently injustly neglected: the distribution of this new type of material seems desireable. On the contrary, the use of xeroradiography leads to an irradiation which is three times greater than in conventional techniques and fifteen times greater than in these new techniques: xeroradiography must therefore be reserved for very specific problems.


Association of the apolipoprotein A-IV: 360 Gln/His polymorphism with cerebrovascular disease, obesity, and depression in a Brazilian elderly population.
The identification of genetic polymorphisms as risk factors for complex diseases can be relevant for their prevention, diagnosis, and prognosis. The apolipoprotein A-IV: 360 Gln/His polymorphism was investigated in 383 elderly individuals, who were participants of a longitudinal study commenced in 1991. The major morbidities that affect elderly people, such as cardiovascular diseases, diabetes, low cognitive function, depression, and obesity, were extensively investigated. DNA was isolated from blood cells, amplified by PCR, and digested with Fnu4HI. In this population the frequency of the His allele was 0.056 and the genotypes were distributed according to Hardy-Weinberg equilibrium. Logistic regression analysis showed a significant association between the presence of His allele and cerebrovascular disease and/or transitory ischemic attack (odds ratio) (OR = 3.070, P = 0.027), obesity (OR = 2.241, P = 0.047), and depression (OR = 2.879, P = 0.005). This study indicates that the presence of the rare allele in elderly people can play a significant role in the occurrence of multifactorial diseases. This is the first study analyzing this polymorphism in elderly people in Brazil. More studies should be encouraged to elucidate the mechanisms involved in these diseases.


Two efficiency elements flanking the editing site of cytidine 6666 in the apolipoprotein B mRNA support mooring-dependent editing.
Normally, apolipoprotein B (apoB) mRNA editing deaminates a single cytidine (C6666) in apoB mRNA. However, when the catalytic subunit of the editing enzyme complex, APOBEC-1, was overexpressed in transgenic mice and rabbits, numerous cytidines in the apoB mRNA and in a novel mRNA, NAT1, were aberrantly hyperedited, and the animals developed liver dysplasia and hepatocellular carcinomas. To identify the RNA motifs in the apoB mRNA that support physiological editing and those that support aberrant hyperediting, we constructed rabbit apoB RNA substrates and tested them in vitro for physiological editing and hyperediting. Three previously unrecognized RNA elements that are critical for efficient physiological editing at C6666 were identified. In concert with the mooring sequence (6671-6681), the 5' efficiency element (6609-6628), an A-rich region (6629-6640), and the 3' efficiency element (6717-6747) increased editing at C6666. The 5' efficiency element was the most potent, elevating physiological editing to wild-type levels in combination with the mooring sequence. The 3' efficiency element was somewhat less important but increased physiological editing to levels approaching wild type. These elements encompass 139 nucleotides on the apoB RNA transcript and are sufficient for editing with the efficiency of full-length apoB mRNA. Furthermore, a distal downstream apoB region (6747-6824) may function as a recognition element in the apoB mRNA. Hyperediting at C6802 in the rabbit apoB mRNA is mediated by RNA elements similar to those required for normal physiological editing at C6666. Similarly sized upstream and downstream flanking regions of C6802 are necessary for hyperediting in combination with a degenerate mooring sequence.


Antibiotic residues in milk and dairy products in China: occurrence and human health concerns.
Although veterinary antibiotics are essential in preventing and treating clinical diseases in cattle, the frequent use of antibiotics leads to antibiotic residues in milk and dairy products, consequently threatening human health. The massive milk consumption makes it necessary to assess antibiotic pollution and health impact comprehensively. Hence, we conducted a systematic review to evaluate antibiotics in milk and dairy products and their potential health risk. We searched four databases using multiple keyword combinations to retrieve 1582 pieces of literature and finally included eighteen articles to analyze antibiotic residues in milk and dairy products. These studies detected seven antibiotics in different regions of China. Quinolones and β-lactam antibiotics exceeded the MRL for raw and commercial milk. The maximum levels of sulfonamides and tetracyclines were detected in the same raw milk sample, exceeding the MRL. The estimated THQ and HI values in milk and dairy products are less than 1 for adults, indicating negligible noncarcinogenic health risk of antibiotics through consuming milk and dairy products. Children face higher health risks than adults, with the HI and THQ of quinolones exceeding 1. It is worth noting that quinolones accounted for nearly 89% of health risks associated with all antibiotics. Finally, we put forward possible research directions in the future, such as specific health effects of total dietary exposure to low levels of antibiotics. In addition, policymakers should effectively improve this problem from the perspectives of antibiotic use supervision, antibiotic residue analysis in food, and continuous environmental monitoring and control.


Challenges for Insured Patients in Accessing Behavioral Health Care.
The Patient Protection and Affordable Care Act (ACA) mandates that health insurance plans include sufficient access to behavioral health providers, but lacks specific guidelines to define sufficient access Using a secret shopper methodology, we called behavioral health providers in the Denver metropolitan area networked with 3 large insurance companies. We found that, depending on insurance company and level of training, 9.8% to 59% of providers could offer a new patient appointment, with psychiatry appointments being particularly difficult to schedule. These findings are consistent with similar studies conducted in other regions, suggesting that access to outpatient behavioral health care is limited despite existing ACA regulations.


Characterization of porcine leptin receptor polymorphisms and their association with reproduction and production traits.
Fatness in pigs is of prime economic importance due to market incentives for production of lean pork and elevated fatness increasing the feed costs. Leptin (LEP) action, mediated through its specific receptors (LEPR), was reported to be involved in the regulation of fatness via feed intake, energy expenditure, and whole-body energy balance in pigs. In this study, we have designed 17 primer sets based on the human and mouse LEPR sequences and successfully amplified coding regions of 15 porcine LEPR exon fragments by polymerase chain reactions (PCR). Four single nucleotide polymorphisms (SNP) of Intron 2, Exons 2, 6, and 18 were found in Landrace, Yorkshire, and Duroc by mutagenetically separated-PCR (MS-PCR) and PCR-restriction fragment length polymorphisms (PCR-RFLP). Chi-square statistics was used to calculate homogeneity of genotypic frequencies of 4 gene polymorphisms for three breeds of animals. Effects of Intron 2, Exon 2, and Exon 18 polymorphisms on the reproduction trait such as litter sizes of sows were evident (p < 0.05) in Duroc and Yorkshire. There was no (p > 0.05) significant influence on the production trait of average daily gain due to four candidate gene polymorphisms in three porcine breeds. However, effects of Exon 6 and 18 polymorphisms on the production trait of backfat thickness were significant (p < 0.05) in Landrace and Yorkshire, respectively. Effects of Exon 18 polymorphisms on feed efficiency were also evident (p < 0.05) in Duroc.


Efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn: a Metaanalysis.
To systematically evaluate the efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn (PPHN). Chinese Journal Full-text Database, Weipu Database, Wanfang Data, China Biology Medicine disc, PubMed, Web of Science, Embase, and Cochrane Library were searched for literature on bosentan in the treatment of PPHN published up to August 31, 2021. A total of 8 randomized controlled trials were included for Meta analysis. The results of the Meta analysis showed that compared with the control group, the bosentan treatment group had a significantly lower treatment failure rate (RR=0.23, P<0.001), a significantly greater reduction in pulmonary artery pressure [mean difference (MD)=-11.79, P<0.001)], significantly greater increases in oxygen partial pressure (MD=10.21, P=0.006) and blood oxygen saturation (MD=8.30, P<0.001), and a significantly shorter length of hospital stay (MD=-1.35, P<0.001). The descriptive analysis showed that the bosentan treatment group had a lower degree of tricuspid regurgitation than the control group after treatment. The main adverse reactions of bosentan treatment included abnormal liver function, anemia and edema. The results of subgroup analysis based on treatment regimen, research area, and drug dose were consistent with those before stratification. Bosentan is effective in the treatment of PPHN. However, when using bosentan, attention should be paid to adverse reactions such as abnormal liver function.


Soluble fms-Like Tyrosine Kinase 1 as a Link Between Angiogenesis and Endothelial Dysfunction in Pediatric Patients With β-Thalassemia Intermedia.
Endothelial damage has been implicated in the pathogenesis of vascular complications in β-thalassemia intermedia (β-TI). Soluble fms-like tyrosine kinase 1 (sFLT-1) is a member of the vascular endothelial growth factor receptor (VEGFR) family. Soluble fms-like tyrosine kinase 1 is an antiangiogenic protein that induces endothelial dysfunction by adhering to and inhibiting VEGF and placenta growth factor. The aim of this study was to assess the level of sFLT-1 in 35 children and adolescents with β-TI, correlating it with markers of hemolysis and iron overload as well as cardiopulmonary complications. Patients were studied focusing on the history of cardiac disease, splenectomy, transfusion, chelation/hydroxyurea therapy, serum ferritin, and sFLT-1 levels. Echocardiography and measurement of carotid intima-media thickness (CIMT) were done for all participants. Soluble fms-like tyrosine kinase 1 was significantly higher in TI patients compared to the control group (median [interquartile range], 110 [80-155] pg/mL versus 70 [60-90] pg/mL; P < .001). Splenectomized patients and those who had pulmonary hypertension risk or heart disease had higher sFLT-1 levels than those without ( P < .001). The sFLT-1 cutoff value that differentiates patients with and without pulmonary hypertension risk or heart disease was determined. Soluble fms-like tyrosine kinase 1 was lower among patients who received chelation therapy and/or hydroxyurea. Significant positive relations were observed between sFLT-1 and lactate dehydrogenase, serum ferritin, liver iron concentration, tricuspid regurgitant jet velocity, and CIMT. We suggest that sFLT-1 represents a link between angiogenesis, endothelial dysfunction, and subclinical atherosclerosis. Measurement of sFLT-1 as a marker of vascular dysfunction in β-TI may provide utility for early identification of patients at increased risk of cardiopulmonary complications.


The Influence of the Apolipoprotein E (APOE) Gene on Subacute Post-Concussion Neurocognitive Performance in College Athletes.
The purpose of this study was to determine whether the ε4 allele of the APOE gene influences neurocognitive outcome following sports-related concussion. It was hypothesized that participants with an ε4 allele would show poorer neurocognitive performance and greater neurocognitive variability than those without an ε4 allele. Participants included 57 concussed collegiate athletes (77.2% male) who participated in a concussion management program at a large university. All athletes underwent a comprehensive neuropsychological assessment and provided a DNA sample for determination of their APOE genotype. The test battery included measures sensitive to concussion, covering the broad domains of learning and memory, attention, processing speed, and executive functions. The sample was divided into ε4 + (n = 20) and ε4 - (n = 37) groups. No significant differences were found between athletes with and without an ε4 allele when examining mean neurocognitive standardized scores (all p > .05; d = 0.16-0.18). However, athletes with an ε4 allele were more likely to show a greater number of impaired neurocognitive scores post-injury compared to athletes without an ε4 allele, χ2(1, N = 57) = 3.96, p = < .05, φ = 0.26. Additionally, athletes with an ε4 allele demonstrated greater neurocognitive variability than athletes without an ε4 allele, t(55) = -2.04, p < .05, d = 0.53. This research furthers our understanding of how genetic factors uniquely contribute to neurocognitive performance differences following concussion. Our findings suggest a possible relationship between the ε4 allele and post-concussion impairment, as well as between the ε4 allele and neurocognitive performance variability, suggesting that the ε4 genotype may be a risk factor for less efficient cognitive processing in concussed athletes.


Positive determinations of tricyclic antidepressant drugs in the material of toxicological laboratory--analysis of trends.
This paper presents the analysis of trends in a number of cases and an average age of patients for whom determination of tricyclic antidepressants (TCA) showed positive results. The studied data were gathered in toxicological laboratory of Dept. of Analytical Toxicology and Therapeutic Drug, CM UJ in Kraków. The data were collected in period December 2001 August 2004. The main findings of this study are: The number of cases is exponentially increasing at the rate of 0.068% per day (p = 0.0165). No statistically significant correlation between the number of cases and: (a) day-length (p = 0.9819), (b) day-length change (p = 0.2312), (c) direction of change of day-length (p = 0.4640), d) day of the week (p = 0.7588) has been found, so periodicity of this phenomenon is questionable. It has been observed that the average age of patients is decreasing and the estimated rate of this decrease equals 0.0092-years per day (p = 0.0555). TCA positive patients treated in the Clinic on different days of the week differ in average age (p = 0.0016). From Tuesday till Friday the average age of patients is increasing. In the middle of the studied period the increase started from 30-year-olds on Mondays and ended with 48-year-old patients on Friday. At weekends the average dropped to 38 and stayed constant. On Mondays the average was about 46.


Cervical analgesic discography. A new test for the definitive diagnosis of the painful-disk syndrome.
The cervical discogenic (painful-disk) syndrome consists of scapular pain radiating into the head, shoulder, and upper arm, often associated with paresthesias but without neurologic deficit. Plain roentgenograms or myelograms are normal or show degenerative changes. Positive-contrast discography has been useful but is subject to a high percentage of false-positive results roentgenographically and nonspecific pain patterns clinically. Analgesic discography more precisely confirms the diagnosis and more accurately locates the pain-producing disk. Injection of a local anesthetic into a painful disk produces transient symptomatic relief and full neck mobility. Its use during a two-year period in 71 consecutive discogenic patients followed by anterior cervical fusion resulted in a 93% excellent or good recovery rate. Analgesic discography is the most effective test for diagnosis and location in the painful-disk syndrome.


Analysis of phthalate esters in soils near an electronics manufacturing facility and from a non-industrialized area by gas purge microsyringe extraction and gas chromatography.
Here, a novel technique is described for the extraction and quantitative determination of six phthalate esters (PAEs) from soils by gas purge microsyringe extraction and gas chromatography. Recovery of PAEs ranged from 81.4% to 120.3%, and the relative standard deviation (n=6) ranged from 5.3% to 10.5%. Soil samples were collected from roadsides, farmlands, residential areas, and non-cultivated areas in a non-industrialized region, and from the same land-use types within 1 km of an electronics manufacturing facility (n=142). Total PAEs varied from 2.21 to 157.62 mg kg(-1) in non-industrialized areas and from 8.63 to 171.64 mg kg(-1) in the electronics manufacturing area. PAE concentrations in the non-industrialized area were highest in farmland, followed (in decreasing order) by roadsides, residential areas, and non-cultivated soil. In the electronics manufacturing area, PAE concentrations were highest in roadside soils, followed by residential areas, farmland, and non-cultivated soils. Concentrations of dimethyl phthalate (DMP), diethyl phthalate (DEP), and di-n-butyl phthalate (DnBP) differed significantly (P<0.01) between the industrial and non-industrialized areas. Principal component analysis indicated that the strongest explanatory factor was related to DMP and DnBP in non-industrialized soils and to butyl benzyl phthalate (BBP) and DMP in soils near the electronics manufacturing facility. Congener-specific analysis confirmed that diethylhexyl phthalate (DEHP) was a predictive indication both in the non-industrialized area (r(2)=0.944, P<0.01) and the industrialized area (r(2)=0.860, P<0.01). The higher PAE contents in soils near the electronics manufacturing facility are of concern, considering the large quantities of electronic wastes generated with ongoing industrialization.


Alkyl Amine Bevirimat Derivatives Are Potent and Broadly Active HIV-1 Maturation Inhibitors.
Concomitant with the release of human immunodeficiency virus type 1 (HIV-1) particles from the infected cell, the viral protease cleaves the Gag polyprotein precursor at a number of sites to trigger virus maturation. We previously reported that a betulinic acid-derived compound, bevirimat (BVM), blocks HIV-1 maturation by disrupting a late step in protease-mediated Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA. BVM was shown in multiple clinical trials to be safe and effective in reducing viral loads in HIV-1-infected patients. However, naturally occurring polymorphisms in the SP1 region of Gag (e.g., SP1-V7A) led to a variable response in some BVM-treated patients. The reduced susceptibility of SP1-polymorphic HIV-1 to BVM resulted in the discontinuation of its clinical development. To overcome the loss of BVM activity induced by polymorphisms in SP1, we carried out an extensive medicinal chemistry campaign to develop novel maturation inhibitors. In this study, we focused on alkyl amine derivatives modified at the C-28 position of the BVM scaffold. We identified a set of derivatives that are markedly more potent than BVM against an HIV-1 clade B clone (NL4-3) and show robust antiviral activity against a variant of NL4-3 containing the V7A polymorphism in SP1. One of the most potent of these compounds also strongly inhibited a multiclade panel of primary HIV-1 isolates. These data demonstrate that C-28 alkyl amine derivatives of BVM can, to a large extent, overcome the loss of susceptibility imposed by polymorphisms in SP1.


Clonal distribution of Streptococcus suis isolated from diseased pigs in the central region of Chile.
The characteristics of 29 Chilean field strains of Streptococcus suis recovered between 2007 and 2011 from pigs with clinical signs at different farms were studied. Serotyping with use of the coagglutination test revealed that all but 1 strain belonged to serotype 6; the remaining strain was serotype 22. All the serotype-6 strains were suilysin (hemolysin)-negative; in addition, they were found to be genotypically homogeneous by enterobacterial repetitive intergenic consensus sequence-based polymerase chain reaction (ERIC-PCR) and sensitive to ampicillin, ceftiofur, penicillin, and trimethoprim/sulfamethoxazole. The results indicate that, in contrast to what is generally observed in other countries, a single clone of S. suis was isolated from diseased pigs in the central region of Chile.


INTRASPECIFIC PHYLOGEOGRAPHY ACROSS THE POINT CONCEPTION BIOGEOGRAPHIC BOUNDARY.
Recent studies of intraspecific phylogeography have suggested that the geographic location of genetic discontinuities, or phylogeographic breaks, may frequently coincide with biogeographic boundaries. The concordance is hypothesized to reflect similarity in the processes governing species boundaries and intraspecific lineage boundaries. This concordance has not, however, been widely tested. In the case of the Point Conception biogeographic boundary between the Oregonian and Californian marine biotas, only the supralittoral copepod Tigriopus californicus has been found to have a coincident phylogeographic break. Here I show that the apparent relationship between this break and Point Conception was, in fact, an artifact of insufficient geographic sampling. Mitochondrial DNA analyses of T. californicus populations between Morro Bay and San Diego reveal at least five equally deep phylogeographic breaks in the region (where only one biogeographic boundary is recognized). Limited nuclear DNA sequence data and allozyme data also support the occurrence of multiple genetic discontinuities along this geographic range. Lack of one-to-one correspondence between intraspecific phylogeography and biogeographic boundaries indicates that the processes affecting the genetic differentiation of populations of T. californicus differ from those responsible for determining species distributional limits at the Point Conception biogeographic boundary. A review of genetic data from other species also fails to provide evidence for concordance of biogeography and intraspecific phylogeography across Point Conception. I suggest that the concordance of phylogeography with biogeography will only be pronounced where the biogeographic boundary separates biotas that are phylogenetically related. The numerous cases of interspecific hybrid zones in the region of Cape Canaveral, for example, indicate that many sister-species pairs occur across this biogeographic boundary. Such hybrid zones are not common at Point Conception, and there appears to be no cases of intraspecific phylogeographic breaks associated with this well-recognized biogeographic boundary.


Understanding and applying a resource-based relative value system to your neurosurgical practice.
The payment policy for United States physicians was formerly based on determination of customary and prevailing charges from their fee schedules. Rapidly growing health care expenditures in the 1980s led to a fundamental change in payment reimbursement in which the new system was based on the resource costs to the physician for providing health care services. This reform highlights the significant regulatory morass that has come to burden the health care industry. One of the most critical changes in physician reimbursement was caused by the Congressional mandate that led to the development of a resource-based relative value scale (RBRVS) for the creation of the Medicare physician fee schedule. Most physicians, however, have limited familiarity with the RBRVS system, which now serves as the basis for Medicare-related physician reimbursement as well as many third-party payers. A historical review of the development of the RBRVS will serve as the basis for applying the methodology to improve the effectiveness of the neurosurgeon's practice.


Structure of the 4-hydroxy-tetrahydrodipicolinate synthase from the thermoacidophilic methanotroph Methylacidiphilum fumariolicum SolV and the phylogeny of the aminotransferase pathway.
The enzyme 4-hydroxy-tetrahydrodipicolinate synthase (DapA) is involved in the production of lysine and precursor molecules for peptidoglycan synthesis. In a multistep reaction, DapA converts pyruvate and L-aspartate-4-semialdehyde to 4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid. In many organisms, lysine binds allosterically to DapA, causing negative feedback, thus making the enzyme an important regulatory component of the pathway. Here, the 2.1 Å resolution crystal structure of DapA from the thermoacidophilic methanotroph Methylacidiphilum fumariolicum SolV is reported. The enzyme crystallized as a contaminant of a protein preparation from native biomass. Genome analysis reveals that M. fumariolicum SolV utilizes the recently discovered aminotransferase pathway for lysine biosynthesis. Phylogenetic analyses of the genes involved in this pathway shed new light on the distribution of this pathway across the three domains of life.


Long-Life Nickel-Rich Layered Oxide Cathodes with a Uniform Li2ZrO3 Surface Coating for Lithium-Ion Batteries.
As nickel-rich layered oxide cathodes start to attract worldwide interest for the next-generation lithium-ion batteries, their long-term cyclability in full cells remains a challenge for electric vehicles. Here we report a long-life Ni-rich layered oxide cathode (LiNi0.7Co0.15Mn0.15O2) with a uniform surface coating of the cathode particles with Li2ZrO3. A pouch-type full cell fabricated with the Li2ZrO3-coated cathode and a graphite anode displays 73.3% capacity retention after 1500 cycles at a C/3 rate. The Li2ZrO3 coating has been optimized by a systematic study with different synthesis approaches, annealing temperatures, and coating amounts. The complex relationship among the coating conditions, uniformity, and morphology of the coating layer and their impacts on the electrochemical properties are discussed in detail.


Saccharomyces boulardii and bacillus cereus var. Toyoi influence the morphology and the mucins of the intestine of pigs.
The mode of action of probiotics is still incompletely understood. To study the interactions between probiotic micro-organisms and the host their effects on morphology and mucins of the intestinal mucosa were investigated. Fifteen clinically healthy weaned pigs were divided into three groups and received either Saccharomyces boulardii or Bacillus cereus var. toyoi or were left untreated. Sections of duodenum, proximal and mid jejunum, ileum, caecum, and colon were examined. An increase of villus length in the small intestine and a decrease in the number of goblet cells with 2.6-sialylated mucins in the large intestine were observed in both treatment groups. There were no differences in crypt morphology, number of Ki67-positive cells, total number of goblet cells and number of goblet cells with acidic, neutral, sulphated, or 2.3-sialylated mucins between groups. The results indicate an effect of Saccharomyces boulardii and Bacillus cereus var. toyoi on the intestinal architecture of pigs.


ECG-Guided Surveillance Technique in Cryoballoon Ablation for Paroxysmal and Persistent Atrial Fibrillation: A Strategy to Prevent From Phrenic Nerve Palsy.
Phrenic nerve palsy (PNP) is still a cause for concern in Cryoballoon ablation (CBA) procedures. New surveillance techniques, such as invasive registration of the compound motor action potential (CMAP), have been thought to prevent the occurrence of PNP. The present study investigates the impact of CMAP surveillance via an alternative and non-invasive ECG-conduction technique during CBA. PVI with CBA was performed in 166 patients suffering from AF. Diaphragmal contraction was monitored by abdominal hands-on observation in Observation Group I; Observation Group II was treated using additional ECG-conduction, as a means of modified CMAP surveillance method. During the ablation of the right superior and inferior pulmonary veins, the upper extremities lead I was newly adjusted between the inferior sternum and the right chest, thereby recording the maximum CMAP. The CMAP in the above-mentioned ECG leads was continuously observed in a semi-quantitative manner. PNP was observed in 10 (6%) patients in total. In Observation Group I, 6 out of 61 (9.8%) demonstrated PNP. In Observation Group II a significant decrease of PNP could be demonstrated (p <0,001) and occurred in 4 out of 105 patients (3.8%). While three patients from Observation Group I left the EP lap with an ongoing PNP, none of the patients in Observation Group II had persistent PNP outside of the EP lab. The present study demonstrates that additional ECG-conduction, used as modified CMAP surveillance, is an easy, effective and helpful additional safety measure to prevent PNP in CBA.


Cytological development of yolk sac endoderm and protein-absorptive mesothelium in the little brown bat, Myotis lucifugus.
The yolk sac of the little brown bat is unusual in that during the course of gestation both the inner endodermal cells (bordering the yolk sac cavity) and outer mesothelium (facing the exocelom) form simple columnar epithelia which persist throughout gestation. These endodermal cells develop an extensive system of agranular endoplasmic reticulum, numerous lipid droplets and unusual "giant" mitochondria. During development the Golgi apparatus changes position from the apical to the basal side of the nucleus, reversing the polarity of the cells. In general, the endodermal cells have cytological features suggestive of synthetic or secretory activity. The mesothelial cells develop an extensive "absorptive apparatus" in their apices, while large crystalloid-containing granules become numerous in their basal cytoplasm. The mesothelial cells have large deposits of glycogen, especially during mid-gestation, but few mitochondria and little granular endoplasmic reticulum. Endodermal cells do not absorb exogenous protein (peroxidase) even if it is injected directly into the yolk sac cavity. However, placement of peroxidase either in the exocelom or in the maternal vascular system results in the appearance of this protein in the "absorptive apparatus" of mesothelial cells as well as in macrophages in the stroma of the yolk sac. While evidence of absorption was clear, no direct evidence of transport of tracer to fetal blood vascular system was obtained. It is postulated that a major function of the hypertrophied mesothelial cells during gestation is the absorption of proteins and possibly other substances from the exocelomic fluid. The major function of the hypertrophied endodermal cells may be synthesis and secretion of substances into the fetal circulation.


Systemic administration of a cyclic signal transducer and activator of transcription 3 (STAT3) decoy oligonucleotide inhibits tumor growth without inducing toxicological effects.
Hyperactivation of signal transducer and activator of transcription 3 (STAT3) has been linked to tumorigenesis in most malignancies, including head and neck squamous cell carcinoma. Intravenous delivery of a chemically modified cyclic STAT3 decoy oligonucleotide with improved serum and thermal stability demonstrated antitumor efficacy in conjunction with downmodulation of STAT3 target gene expression such as cyclin D1 and Bcl-X(L) in a mouse model of head and neck squamous cell carcinoma. The purpose of the present study was to determine the toxicity and dose-dependent antitumor efficacy of the cyclic STAT3 decoy after multiple intravenous doses in Foxn1 nu mice in anticipation of clinical translation. The two doses (5 and 10 mg/kg) of cyclic STAT3 decoy demonstrated a significant decrease in tumor volume compared with the control groups (mutant cyclic STAT3 decoy or saline) in conjunction with downmodulation of STAT3 target gene expression. There was no dose-dependent effect of cyclic STAT3 decoy on tumor volume or STAT3 target gene expression. There were no significant changes in body weights between the groups during the dosing period, after the dosing interval or on the day of euthanasia. No hematology or clinical chemistry parameters suggested toxicity of the cyclic STAT3 decoy compared with saline control. No gross or histological pathological abnormalities were noted at necropsy in any of the animals. These findings suggest a lack of toxicity of intravenous administration of a cyclic STAT3 decoy oligonucleotide. In addition, comparable antitumor effects indicate a lack of dose response at the two dose levels investigated.


Response regulator GacA and transcriptional activator RhlR proteins involved in biofilm formation of Pseudomonas aeruginosa are prospective targets for natural lead molecules: Computational modelling, molecular docking and dynamic simulation studies.
Pseudomonas aeruginosa has become a global concern due to its extreme resistance to most of the last resort antibiotics. Present study focuses on the screening of potential molecular targets involved in regulation of biofilm formation in P. aeruginosa and identification of potential natural lead molecules against these targets by molecular modelling, docking and simulation studies. Response regulator (GacA) and transcriptional activator (RhlR) involved in biofilm formation in P. aeruginosa were identified as molecular targets by metabolic pathway analysis and the three dimensional structures of these proteins were predicted by homology modelling and validated. By thorough literature survey, 78 lead molecules were screened and their pharmacokinetic profiles were determined and best two of them selected. The binding potential of selected lead molecules against GacA and RhlR were predicted by molecular docking and their binding energy was compared with the interaction of meropenem and its usual target penicillin binding protein-3. The stabilities of best docked complex were studied by molecular dynamic (MD) simulation. This study showed that Celastrol present in Celastrus paniculatus and Rotiorinol present in Chaetomium cupreum showed better binding affinities with GacA (binding energy -7.2 kcal/mol) and RhlR (binding energy -8.0 kcal/mol) respectively in comparison with the binding of Meropenem and its target (binding energy -6.2 kcal/mol). MD simulation studies showed that GacA-Celastrol and RhlR-Rotiorinol complexes demonstrated conformational stability throughout the simulation. This study highlights the application of GacA and RhlR as prospective targets and Celastrol and Rotiorinol are the potential lead molecules towards biofilm producing drug resistant P. aeruginosa.


Synthesis and in vitro pharmacology of substituted quinoline-2,4-dicarboxylic acids as inhibitors of vesicular glutamate transport.
The vesicular glutamate transport (VGLUT) system selectively mediates the uptake of L-glutamate into synaptic vesicles. Uptake is linked to an H+-ATPase that provides coupling among ATP hydrolysis, an electrochemical proton gradient, and glutamate transport. Substituted quinoline-2,4-dicarboxylic acids (QDCs), prepared by condensation of dimethyl ketoglutaconate (DKG) with substituted anilines and subsequent hydrolysis, were investigated as potential VGLUT inhibitors in synaptic vesicles. A brief panel of substituted QDCs was previously reported (Carrigan et al. Bioorg. Med. Chem. Lett. 1999, 9, 2607-2612)(1) and showed that certain substituents led to more potent competitive inhibitors of VGLUT. Using these compounds as leads, an expanded series of QDC analogues were prepared either by condensation of DKG with novel anilines or via aryl-coupling (Suzuki or Heck) to dimethyl 6-bromoquinolinedicarboxylate. From the panel of almost 50 substituted QDCs tested as inhibitors of the VGLUT system, the 6-PhCH=CH-QDC (K(i) = 167 microM), 6-PhCH2CH2-QDC (K(i) = 143 microM), 6-(4'-phenylstyryl)-QDC (K(i) = 64 microM), and 6-biphenyl-4-yl-QDC (K(i) = 41 microM) were found to be the most potent blockers. A preliminary assessment of the key elements needed for binding to the VGLUT protein based on the structure-activity relationships for the panel of substituted QDCs is discussed herein. The substituted QDCs represent the first synthetically derived VGLUT inhibitors and are promising templates for the development of selective transporter inhibitors.


Experimental approaches to therapy and prophylaxis for heat stress and heatstroke.
New developments in the fields of biochemistry, physiology, sepsis, cancer therapy, and molecular genetics have led to opportunities for the development of new therapies and prophylaxes for heat illnesses and for improving human performance during conditions of environmental stress. These include antilipopolysaccharide agents, anticytokines, potassium channel agents, a diet rich in omega-3 fatty acids, and psychological conditioning. This review summarizes the backgrounds and recent findings in the above fields and provides specific suggestions for potential therapy and prophylaxis for classic and exertional heatstroke and for improving athletic performance.


Trade-off between Plasticity and Velocity in Mycelial Growth.
Tip-growing fungal cells maintain cell polarity at the apical regions and elongate by de novo synthesis of the cell wall. Cell polarity and tip growth rate affect mycelial morphology. However, it remains unclear how both features act cooperatively to determine cell shape. Here, we investigated this relationship by analyzing hyphal tip growth of filamentous fungi growing inside extremely narrow 1 μm-width channels of microfluidic devices. Since the channels are much narrower than the diameter of hyphae, any hypha growing through the channel must adapt its morphology. Live-cell imaging analyses revealed that hyphae of some species continued growing through the channels, whereas hyphae of other species often ceased growing when passing through the channels, or had lost apical polarity after emerging from the other end of the channel. Fluorescence live-cell imaging analyses of the Spitzenkörper, a collection of secretory vesicles and polarity-related proteins at the hyphal tip, in Neurospora crassa indicates that hyphal tip growth requires a very delicate balance of ordered exocytosis to maintain polarity in spatially confined environments. We analyzed the mycelial growth of seven fungal species from different lineages, including phytopathogenic fungi. This comparative approach revealed that the growth defects induced by the channels were not correlated with their taxonomic classification or with the width of hyphae, but, rather, correlated with the hyphal elongation rate. This report indicates a trade-off between morphological plasticity and velocity in mycelial growth and serves to help understand fungal invasive growth into substrates or plant/animal cells, with direct impact on fungal biotechnology, ecology, and pathogenicity.IMPORTANCE Cell morphology, which is controlled by polarity and growth, is fundamental for all cellular functions. However how polarity and growth act cooperatively to control cell shape remains unclear. Here we investigated their relationship by analyzing hyphal tip growth of filamentous fungi growing inside extremely narrow 1 μm-width channels of microfluidic devices. We found that most fast growing hyphae often lost the cell polarity after emerging from the channels, whereas slow growing hyphae retained polarity and continued growing, indicating a trade-off between plasticity and velocity in mycelial growth. These results serve to understand fungal invasive growth into substrates or plant/animal cells, with direct impact on fungal biotechnology, ecology and pathogenicity.


Correlated Wishart ensembles and chaotic time series.
We study the correlated Wishart ensembles in the context of time series analysis. We are interested in the statistics of eigenlevels, viz. variables associated with independent eigenmodes in the system. The motivation of this work is to study the effect of time series correlations on the Wishart ensembles. In this connection, we derive the level density and the two-point function for the correlated Wishart ensembles by using the binary correlation method. Using our analytic results we analyze spectra of autocovariance matrices derived from single variable stationary time series. We consider the stochastic time series of Gaussian variables with exponentially decaying correlations and time series of chaotic maps, viz. the Arnold map, the Standard map and the stadium billiard map. In both cases, correlated time series are encountered and analyzed under the framework of random matrix theory. It is shown that the eigenlevel statistics for the chaotic maps follow closely those of correlated Wishart ensembles. It is indicated that the presence of collective modes in the spectra of autocovariance matrices is related to the integrability of the system.


A miniature cesium iodide-photodiode detector for ambulatory monitoring of left ventricular function.
The physical characteristics of a portable nonimaging scintillation probe system for continuous ambulatory monitoring of the left ventricular function are described. The detector of the equilibrium radionuclide labeled blood pool is a single cesium iodide (CsI) crystal coupled to a silicium photodiode and interfaced to a microcomputer. The spatial properties of this small CsI crystal (1 x 1 x 1 cm3) were evaluated with various single-hole collimators. Linearity was studied in nonattenuating medium. Saturation began at 3000 cps, count loss was 10% at 4000 cps, maximal count rate was 24,000 cps. In attenuating medium, isocount curve of 5% of the maximal count rate was 100 mm deep and 160 mm wide. The most appropriate tested lead collimator to record the global ejection fraction of the left ventricle was a disc-shaped (thickness 5 mm, diameter 41 mm) single-hole (proximal aperture 8 mm, distal aperture 18 mm) collimator. Sensitivity was similar to the sensitivity of a sodium iodide nuclear probe. The detection performance appeared comparable to other available detector systems. Our results indicate that such a CsI-photodiode probe is a promising candidate for left ventricular function monitoring. The application to an ambulatory multicrystal detector system is presented and discussed.


Expression and purification of the h1 and h2 isoforms of calponin.
Three homologous calponin isoforms, named h1, h2, and acidic calponins, have been found in birds and mammals. Based primarily on studies of chicken gizzard smooth muscle (h1) calponin, calponin has been identified as a family of actin-associated proteins that inhibit actomyosin ATPase activity. Evolutionary divergence of the calponin isoforms suggests differentiated function. While the role of h1 calponin in smooth muscle contraction is under investigation, h2 calponin has been shown regulating the function of actin cytoskeleton. Using cloned cDNA, we expressed mammalian h1 and h2 calponins in Escherichia coli. We have developed effective methods to purify biologically active h1 and h2 calponin proteins from transformed bacterial culture. The purified calponin isoform proteins were used to generate monoclonal antibodies that reveal epitopic structure difference between h1 and h2 calponins. Together with their differential expression in tissues and during development, the structural diversity of h1 and h2 calponins suggests non-redundant physiological function. Nevertheless, h1 and h2 calponins bind F-actin with similar affinity, indicating a conserved mechanism for their role in regulating actin filaments in smooth muscle and non-muscle cells.


Estimation of the minimum detectable activity of preclinical PET imaging systems with an analytical method.
The traditional figures of merit used in the evaluation of positron emission tomography (PET) systems, including system sensitivity and spatial resolution, do not directly reflect the minimum detectable activity (MDA) performance, despite the fact that it is one of the most important tasks for a PET system. MDA, as a combination of the more traditional PET system parameters, is directly related to lesion detection. However, MDA evaluation is task specific and cannot be done by a single measurement. Therefore, a simple method to evaluate system detectability needs to be developed. In this work, an analytical method of MDA estimation was developed, taking into account system sensitivity, spatial resolution, source properties, and noise propagation in image reconstruction by using the Rose criterion and/or the Curie equation as the detection standard. In the implementation, the source background, as well as the intrinsic activity background from the scintillation material of the system, was also taken into consideration. The accuracy of this method was evaluated in two commercially available preclinical PET systems, with phantom experiments that were designed to closely mimic in vivo tumor uptake without introducing finite boundaries between the source and the background. The lesion contrast-to-noise ratio calculated by the analytical evaluation showed good agreement with that obtained from the experiments. Visual assessment of the reconstructed images at the detection limit (based on analytical evaluation) also was in agreement with the Rose criterion. The MDA performance was quantitatively compared between the two preclinical PET systems and showed different detection limits under different imaging conditions, suggesting that the detection limit of a PET system strongly depends on the lesion properties and acquisition settings. An analytical method of evaluating the PET system detectability was developed and validated by experiments. Overall, the analytical MDA calculation provides a simple way to evaluate the signal detectability of a PET system and can be used for comparing different systems. It also provides guidelines for designing new PET tomographs as well as optimizing data acquisition protocols.


From the voices of supervisees: A theoretical model of reflective supervision (Part II).
Empirical study of reflective supervision/consultation (RS/C) has been gaining ground over the past decade. However, much of this literature is focused on the supervisor perspective of what RS/C is, what makes it effective, and how it impacts the work of the supervisee. This paper, Part II of a two-part series, presents a theoretical model of RS/C that was developed from the perspectives and experiences of supervisees who work with infants, young children, and families and participate in either group or individual RS/C. This qualitative study built upon themes that emerged from data obtained from 50 IECMH professionals in the United States who participated in focus groups or individual interviews aimed at investigating their experiences of RS/C. Data were analyzed using a Grounded Theory approach. A developmental and ecological theoretical model of RS/C emerged from the data that includes three domains of influence - individual, relational, and contextual - on the supervisee's capacity to understand and use their experience of RS/C in their work. These novel data contribute to our understanding of RS/C from the supervisee perspective. The theoretical model provides a framework from which to investigate outcomes, train supervisors and supervisees, and advocate for RS/C within agencies and programs.


Intraosseous dural arteriovenous fistula of the skull base associated with hearing loss. Case report.
The most common clinical presentations of dural arteriovenous fistulas (DAVFs) are bruit, headache, increased intracranial pressure, and intracranial hemorrhage. In particular locations, such as the cavernous sinus or middle cranial fossa, cranial nerve involvement due to dural arterial steal or venous occlusion may develop. A case in which a DAVF is associated with hearing loss, however, has not previously been reported. The authors report a case in which an intraosseous DAVF and associated hearing loss probably resulted from cochlear nerve or vascular compression caused by the draining vein or nidus of the DAVF.


Steroid hormones in bovine oviductal fluid during the estrous cycle.
Ovarian steroid hormones are major regulators of the physiology of the oviduct and reproductive events occurring within the oviduct. To establish a whole steroid profiling of the bovine oviductal fluid (OF) during the estrous cycle, contralateral and ipsilateral (to the corpus luteum or preovulatory follicle) oviducts were classified into four stages of the estrous cycle (n = 18-27 cows per stage): postovulatory (Post-ov), mid-luteal (Mid-lut), late luteal (Late-lut), and preovulatory on the basis of the ovarian morphology and intrafollicular steroid concentrations. Steroids were extracted from pools of 150 to 200 μL OF (three to 10 cows per pool; three to four pools per "stage × side" group), purified, fractioned by high-performance liquid chromatography, and analyzed by gas chromatography coupled with tandem mass spectrometry. The concentrations of progesterone (P4) in ipsilateral OF increased from Post-ov (56.9 ± 13.4 ng/mL) to Mid-lut (120.3 ± 34.3 ng/mL), then decreased from Late-lut (76.7 ± 1.8 ng/mL) to Pre-ov (6.3 ± 1.7 ng/mL), and were four to 16 times higher than in contralateral OF. Most P4 metabolites followed similar patterns of variation. Concentrations of 17beta-estradiol (E2) were significantly higher at Pre-ov (290.5 ± 63.2 pg/mL) compared with all other stages (<118.3 pg/mL), with no difference regarding the side of ovulation. Concentrations of androstenedione displayed a pattern similar to that of E2, whereas other androgens, estrone, and corticoids did not vary between stages or sides. In conclusion, a highly concentrated and fluctuating hormonal environment was evidenced in the bovine OF. These results could be useful to improve media for IVF, embryo development, and culture of oviductal cells.


Are adults content or continent after repair for high anal atresia? A long-term follow-up study in patients 18 years of age and older.
This study investigated the current state of fecal and urinary continence in an extensive group of adults after operative correction for high anorectal malformations and how they cope with their incontinence. Normal fecal continence is hardly to be expected after correction for high anorectal malformation; despite this, it is commonly accepted that for most patients fecal continence improves with growing age and that most adult patients have no problems. Until now, however, few long-term follow-up studies in small groups of adults have been performed to assess continence after operative repair for high anorectal malformation. Fifty-eight adult patients (median age, 26.0 years; range, 18.1 to 56.9 years) with an operatively corrected high anorectal malformation were evaluated by questionnaire with respect to their current state of fecal and urinary continence and mode of control of defecation. Seven patients have a permanent ileostoma or colostoma. Of the 51 patients with anal defecation, 61% control defecation by themselves, whereas 35% control defecation by using enemas or bowel irrigations, and 4% do not have any control at all. Besides medical therapy, 65% take dietary measures to influence defecation. According to existing scoring methods, 41% reached good and 49% fair control of defecation, whereas only 10% had poor control. Current control of defecation was reached from a median age of 15.0 years (range, 5 to 31 years). Conclusively, the authors can say that after correction for high anorectal malformation nobody reached normal fecal continence. Most patients with anal defecation reached good and fair control of defecation, however. Of all 58 patients, 84% are satisfied with their level of cleanliness.


Squaraine-linked zwitterionic COF modified LLZTO nanoparticles for high performance polymer composite electrolytes in Li-S batteries.
Lithium-sulfur (Li-S) batteries are severely restricted for practical application due to the polysulfide shuttle effect, Li dendrites and thermal runaway. The use of PEO-based polymer composite electrolytes (PCEs) as an alternative strategy suffers from limited lithium-ion conductivity with deficient long-range transfer route. Herein, Li6.4La3Zr1.4Ta0.6O12 (LLZTO) nanoparticles modified with an in situ-synthesized zwitterionic covalent organic framework layer (denoted as LLZTO@HUT4) were introduced into PEO-based PCEs. Zwitterionic HUT4 modified the lithiophobic LiOH/Li2CO3 layer on the surface of LLZTO nanoparticles, which could notably promote Li+ ion transport for superior electrochemical performance of PCEs. Additionally, the intermediate layer HUT4 located between LLZTO and PEO could further improve the mechanical properties of electrolytes due to the enhanced inorganic/organic interface compatibility and intermolecular interaction. As a result, the obtained LLZTO@HUT4-15%/PEO electrolyte exhibited a competent ionic conductivity of 0.73 mS cm-1 with a Li+ transference number of up to 0.74 at 60 °C. The assembled S@CNT|LLZTO@HUT4-15%/PEO|Li coin cell delivered a considerable initial discharge capacity of 1018 mA h g-1 at 0.2 C, with approximately 92.1% capacity retention after 100 cycles, elucidating an obviously suppressed shuttle effect.


A ternary membrane protein complex anchors the spindle pole body in the nuclear envelope in budding yeast.
In budding yeast (Saccharomyces cerevisiae) the multilayered spindle pole body (SPB) is embedded in the nuclear envelope (NE) at fusion sites of the inner and outer nuclear membrane. The SPB is built from 18 different proteins, including the three integral membrane proteins Mps3, Ndc1, and Mps2. These membrane proteins play an essential role in the insertion of the new SPB into the NE. How the huge core structure of the SPB is anchored in the NE has not been investigated thoroughly until now. The present model suggests that the NE protein Mps2 interacts via Bbp1 with Spc29, one of the coiled-coil proteins forming the central plaque of the SPB. To test this model, we purified and reconstituted the Mps2-Bbp1 complex from yeast and incorporated the complex into liposomes. We also demonstrated that Mps2-Bbp1 directly interacts with Mps3 and Ndc1. We then purified Spc29 and reconstituted the ternary Mps2-Bbp1-Spc29 complex, proving that Bbp1 can simultaneously interact with Mps2 and Spc29 and in this way link the central plaque of the SPB to the nuclear envelope. Interestingly, Bbp1 induced oligomerization of Spc29, which may represent an early step in SPB duplication. Together, this analysis provides important insights into the interaction network that inserts the new SPB into the NE and indicates that the Mps2-Bbp1 complex is the central unit of the SPB membrane anchor.


The ability to concentrate iodide as a marker of hormone dependence in GR mouse mammary tumors.
We have previously shown that hormone-dependent (HD) but not hormone-independent (HI) mammary tumors of GR mice concentrate iodide. Since hormone dependence is lost during serial transplantation of the tumors, we have investigated whether the ability to concentrate iodide is lost simultaneously. All tumors progressing to hormone independence lost the ability to concentrate iodide at the time of transition from the HD to the HI state. We believe, therefore, that the ability to concentrate iodide is a marker of hormone dependence in GR mouse mammary tumors.


2:1 multiplexing function in a simple molecular system.
1-[(Anthracen-9-yl)methylene] thiosemicarbazide shows weak fluorescence due to a photo-induced electron transfer (PET) process from the thiosemicarbazide moiety to the excited anthracene. The anthracene emission can be recovered via protonation of the amine as the protonated aminomethylene as an electron-withdrawing group that suppresses the PET process. Similarly, chelation between the ligand and the metal ions can also suppress the PET process and results in a fluorescence enhancement (CHEF). When solvents are introduced as the third control, a molecular 2:1 multiplexer is constructed to report selectively the inputs. Therefore, a molecular 2:1 multiplexer is realized in a simple molecular system.


[Isoenzymic spectra of lactate dehydrogenase and malate dehydrogenase in the loach unfertilized eggs and embryos].
Isoenzymic spectra of lactate dehydrogenase and malate dehydrogenase were detected in unfertilized eggs of Misgurnus fossilis. They do not change significantly in the embryos during blastula, gastrula and early organogenesis stages of development. The intraspecific polymorphism of one lactate dehydrogenase subunit was found in the unfertilized eggs and embryos. The polymorphism is pronounced in the existence of three types of isoenzymic spectra of different frequencies in the given population of the loach.


The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype.
Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA) DR and DQ haplotypes in a cohort with early-onset (age < 5 years), long term type 1 diabetes (T1D) and explored their influence on clinical and laboratory parameters. Intermediate resolution HLA-DRB1, DQA1 and DQB1 typing was performed in 233 samples from the German Paediatric Diabetes Biobank and compared with a local control cohort of 19,544 cases. Clinical follow-up data of 195 patients (diabetes duration 14.2 ± 2.9 years) and residual C-peptide levels were compared between three HLA risk groups using multiple linear regression analysis. Genetic variability was low, 44.6% (104/233) of early-onset T1D patients carried the highest-risk genotype HLA-DRB1*03:01-DQA1*05:01-DQB1*02:01/DRB1*04-DQA1*03:01-DQB1*03:02 (HLA-DRB1*04 denoting 04:01/02/04/05), and 231 of 233 individuals carried at least one of six risk haplotypes. Comparing clinical data between the highest (n = 83), moderate (n = 106) and low risk (n = 6) genotypes, we found no difference in age at diagnosis (mean age 2.8 ± 1.1 vs. 2.8 ± 1.2 vs. 3.2 ± 1.5 years), metabolic control, or frequency of associated autoimmune diseases between HLA risk groups (each p > 0.05). Residual C-peptide was detectable in 23.5% and C-peptide levels in the highest-risk group were comparable to levels in moderate to high risk genotypes. In this study, we saw no evidence for a different clinical course of early-onset T1D based on the HLA genotype within the first ten years after manifestation.


Psychological factors and consumer behavior during the COVID-19 pandemic.
The COVID-19 pandemic is far more than a health crisis: it has unpredictably changed our whole way of life. As suggested by the analysis of economic data on sales, this dramatic scenario has also heavily impacted individuals' spending levels. To better understand these changes, the present study focused on consumer behavior and its psychological antecedents. Previous studies found that crises differently affect people's willingness to buy necessities products (i.e., utilitarian shopping) and non-necessities products (i.e., hedonic shopping). Therefore, in examining whether changes in spending levels were associated with changes in consumer behavior, we adopted a fine-grained approach disentangling between necessities and non-necessities. We administered an online survey to 3833 participants (age range 18-64) during the first peak period of the contagion in Italy. Consumer behavior toward necessities was predicted by anxiety and COVID-related fear, whereas consumer behavior toward non-necessities was predicted by depression. Furthermore, consumer behavior toward necessities and non-necessities was predicted by personality traits, perceived economic stability, and self-justifications for purchasing. The present study extended our understanding of consumer behavior changes during the COVID-19 pandemic. Results could be helpful to develop marketing strategies that consider psychological factors to meet actual consumers' needs and feelings.


[Obstructive sleep apnea in the child: an interdisciplinary treatment concept with special reference to craniofacial changes].
Diagnosis and therapy of obstructive sleep-related breathing disturbances SRBD in adults may not be applied without hesitation to children. SRBD in newborn and infants are often due to craniofacial disturbances (Pierre Robin syndrome, Goldenhars syndrome etc.), obesity is of minor importance. More than 30 infants with SRBD and craniofacial changes have been diagnosed and successfully treated over a 2-year period. Conservative therapy starts immediately after birth. The first step in newborn with Pierre Robin syndrome, for instance, is prone position for protrusion of tongue and mandible and mandibular growth stimulation. Intermediate nightly nasopharyngeal tubes are an alternative to nCPAP-/BiPAP treatment. Conventional orthopaedic/orthodontic treatment should not be neglected, even if it takes years to become effective. Surgical therapies are able to support, sometimes to replace or at least to shorten conservative methods. In rare cases when prone position in combination with palatal plates in cases of Robin syndrome, for instance, are not fully effective, mandibular extension is indicated. Aplasia or defects demand adequate surgical reconstruction, even if this does not necessarily mean abolishment of SRBD. In contrast to adults adenotonsillectomy is highly effective in infants and does not only reduce SRBD, but also improves nasal breathing and thus positively influences facial growth. A relatively new method is gradual mandibular distraction osteogenesis according to Ilizarov, which also enhances soft tissue growth. Maxillary and mandibular advancement osteotomies should not be considered before the termination of facial growth. Thanks to this refined treatment concept we were able to avoid tracheotomies in children during the past few years.


Coronavirus (COVID-19) in the United Kingdom: A personality-based perspective on concerns and intention to self-isolate.
Objectives Public behaviour change is necessary to contain the spread of coronavirus (COVID-19). Based on the reinforcement sensitivity theory (RST) framework, this study presents an examination of individual differences in some relevant psychological factors. Design Cross-sectional psychometric. Methods UK respondents (N = 202) completed a personality questionnaire (RST-PQ), measures of illness attitudes, concerns about the impact of coronavirus on health services and socio-economic infrastructures, personal safety, and likelihood of voluntary self-isolation. Results Respondents most concerned were older, had negative illness attitudes, and scored higher on reward reactivity (RR), indicating the motivation to take positive approach action despite prevailing worry/anxiety. Personal safety concerns were highest in those with negative illness attitudes and higher fight-flight-freeze system (FFFS, reflecting fear/avoidance) scores. Results suggest people are experiencing psychological conflict: between the urge to stay safe (FFFF-related) and the desire to maintain a normal, pleasurable (RR-related) life. Ways of ameliorating conflict may include maladaptive behaviours (panic buying), reflecting reward-related displacement activity. Intended self-isolation related to FFFS, but also low behavioural inhibition system (related to anxiety) scores. Older people reported themselves less likely to self-isolate. Conclusions Interventions need to consider individual differences in psychological factors in behaviour change, and we discuss relevant literature to inform policy makers and communicators. Statement of contribution What is already known on this subject? Reinforcement sensitivity theory (RST) personality systems can influence perception of persuasive health messages. However, there is limited evidence for their direct effects on health concerns and behaviours, and none relating to specific infectious diseases. What does this study add? Reward reactivity (RR) is associated with concern about impact of coronavirus on the NHS and other social infrastructures, indicating the motivation to take positive-approach action despite worry/anxiety. Personal safety concerns are related to fight-flight-freeze system traits (FFFS, reflecting fear/avoidance). Intended self-isolation related to FFFS, but also low behavioural inhibition system (related to anxiety) scores. Older people reported themselves less likely to self-isolate. Results suggest psychological conflict: between the urge to stay safe (FFFF-related) and the desire to maintain a normal, pleasurable life (RR-related). Ways of ameliorating conflict may include maladaptive behaviours (panic buying), reflecting reward-related displacement activity.


Clinical significance of psychotic-like experiences in children and adolescents.
Psychotic-like experiences (PLEs) are subtle, subclinical hallucinations and delusions which are quite common in general population. In children and youth prevalence rate is probably age-dependent with higher rate in younger population. PLEs are suggested to be a form of extended psychosis phenotype. Similar demographic, genetic and environmental risk factors observed for PLEs and schizophrenia support this hypothesis. Other mental health problems associated with PLEs include depression, suicidality, low functioning and psychiatric comorbidity. PLEs may be a risk factor for psychosis, but probably only for a minor subgroup of population. It is possible however, that PLEs are a risk factor for different psychiatric disorders. In the majority of children and adolescents PLEs disappear over time. PLEs are supposed to be a heterogenic phenomenon with different subtypes: associated with psychosis risk, associated with other psychiatric disorders and being within the normal range of experiences. Due to lack of widely acknowledged PLEs definition and because of substantial diversity of research methodology interpretation of the previous research should be made with caution.


Causes and effects of zygomatico-orbital and zygomatico-maxillo-orbital fractures managed by open reduction and rigid internal fixation.
Progressive violence, the quickening pace of life and transport facilities' development have as a consequence an increased number of traumas. Midface fractures involving zygomatic bone fractures take one of the leading positions in the total number of traumas. It seems appropriate to study the causes and the effects of zygomatico-orbital and zygomatico-maxillo-orbital fractures managed by open reduction and rigid internal fixation at the present time of the medical service being reformed and economic rules being included in the treatment. The analysis of the economic consequences of midface traumas and their causes as well as the search for the influence of social and cultural changes on fracture management was the aim of the study. Histories of 61 injured patients treated by open reduction and rigid internal fixation in 1st Department of Maxillofacial Surgery of the Silesian Medical University in Zabrze between 1996 and 2001 were studied. Patients' sex, the most frequent trauma causes and their disposition in different age groups were taken into consideration. It was observed that certain symptoms of the fracture tend to coexist with high energy traumas (traffic accidents, violent assaults). The influence of injury's extension on the prolongation of hospitalization time was emphasized. It was concluded that assaults and traffic accidents are the most frequent and devastating causes of zygomatico-orbital and zygomatico-maxillo-orbital fractures. The fractures usually involve men aged from 21 to 40 years. The rapid growth of violence and the pace of life have in recent times necessitated the general use of advanced and expensive operating techniques in injured patients recently. The break in social and professional activity of injured individuals and the scale of the problem indicate the necessity of change in medical service financing.


Electron-immunocytochemical localization of calcitonin and calcitonin-gene-related peptide in human c cells of the thyroid.
A preembedding immunocytochemical technique enabled us to demonstrate normal human parafollicular (C) cells at the electron-microscopic level. The normal human C cells had numerous large secretory granules with a diameter of approximately 200 nm, well-developed rough endoplasmic reticulum and Golgi complex in their cytoplasm. Calcitonin immunoreactivity and calcitonin-gene-related peptide (CGRP) immunoreactivity were present only in the C cells whose secretory granules were heavily labeled. Both calcitonin and CGRP immunoreaction deposits were seen in the cytosol but not in the cisterna of endoplasmic reticulum, Golgi apparatus or mitochondrial matrix. The two peptides produced from a single calcitonin gene were stored in the secretory granules of the C cells.


The study on the application of solid-state method for synthesizing the polyaniline/noble metal (Au or Pt) hybrid materials.
The solid-state method was applied for synthesizing polyaniline (PANI)/noble metal hybrid materials with the presence of HAuCl4·4H2O or H2PtCl6·6H2O in the reaction medium. The structure, morphology, and electrochemical activity of the composites were characterized by Fourier transform infrared (FTIR) spectra, UV-visible (vis) absorption spectra, energy dispersive spectrum (EDS), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and cyclic voltammetry. The results from FTIR and UV-vis spectra showed that the oxidation degree and doping level of the PANI in composites can be influenced by HAuCl4·4H2O and H2PtCl6·6H2O. The EDS data demonstrated that the composites contain a certain amount of Au (or Pt) element. XRD analysis indicated the presence of crystalline-state Au particles in PANI matrix prepared from the presence of HAuCl4·4H2O and revealed that the H2PtCl6·6H2O cannot be converted into metal Pt. The TEM and SEM images implied that the Au particles did exist in the polymer matrix with the size of about 20 nm. The enzymeless H2O2 sensor constructed with PANI/Au composite from the presence of HAuCl4·4H2O showed a short response time (within 5 s) and displayed an excellent performance in wide linear range.


Ankyrin and beta-spectrin accumulate independently of alpha-spectrin in Drosophila.
We report the identification and initial characterization of Drosophila melanogaster ankyrin. Oligonucleotide primers based on the spectrin-binding domain of human brain ankyrin were used to amplify Drosophila genomic DNA. A cloned 184-bp PCR product was used to isolate Drosophila ankyrin cDNAs. Ankyrin cDNA probes detected a 5.5-kb transcript from embryonic poly(A)+ RNA and a single polytene chromosome locus (101F-102A). The cDNA sequence encodes a 170-kDa protein that is 53% identical to human brain ankyrin (Ank2). Antibodies directed against a recombinant fragment of Drosophila ankyrin reacted with a 170-kDa polypeptide from Drosophila embryos, larvae, S2 cells, and adult flies. The ankyrin antibody coimmunoprecipitated alpha- and beta-spectrin with ankyrin in detergent extracts of Drosophila embryo membranes. Antibodies against Drosophila ankyrin, alpha-spectrin and beta-spectrin were used to detect these proteins in wild-type and alpha-spectrin-mutant larvae. alpha-Spectrin levels were greatly diminished in mutant larvae, but levels of ankyrin and beta-spectrin were indistinguishable from wild type. The persistence of ankyrin and beta-spectrin may explain the relatively mild phenotype of alpha-spectrin mutants during early Drosophila development.


Diagnosing recurring headaches: IHS criteria and beyond.
Current classification systems for diagnosing recurring headaches utilize sets of specific criteria. To determine the usefulness of these criteria in the practical application of diagnosing headache patients, 698 headache specialists were asked to review four case vignettes of headache patients and assign a diagnosis. They also ranked International Headache Society (IHS) criteria along with other features commonly used in the diagnosis of headaches in order of importance. There was no difference in ranked importance for the specific criteria posed by the IHS compared with commonly used criteria not included within the IHS system. A large majority of the respondents combined IHS features with other associated features not used in the IHS system as the basis of diagnostic assignment. These results raise a question about the acceptance and utilization of the IHS system as a basis for diagnoses. They also suggest that there is a need to educate health care providers about the appropriate use of the current IHS criteria to increase reliability of headache diagnosis.


A λ Cro-Like Repressor Is Essential for the Induction of Conjugative Transfer of SXT/R391 Elements in Response to DNA Damage.
Integrative and conjugative elements (ICEs) of the SXT/R391 family are the main contributors to acquired multidrug resistance in the seventh pandemic lineage of Vibrio cholerae, the etiological agent of the diarrheal disease cholera. Conjugative transfer of SXT/R391 ICEs is triggered by antibiotics and agents promoting DNA damage through RecA-dependent autoproteolysis of SetR, an ICE-encoded λ CI-like repressor. Here, we describe the role of CroS, a distant λ Cro homolog, as a key component contributing to the regulation of expression of the activator SetCD that orchestrates the expression of the conjugative transfer genes. We show that deletion of croS abolishes the SOS response-dependent induction of SXT despite the presence of a functional setR gene. Using quantitative reverse transcription-PCR and lacZ reporter assays, we also show that CroS represses setR and setCD expression by binding to operator sites shared with SetR. Furthermore, we provide evidence of an additional operator site bound by SetR and CroS. Finally, we show that SetCD expression generates a positive feedback loop due to SXT excision and replication in a fraction of the cell population. Together, these results refine our understanding of the genetic regulation governing the propagation of major vectors of multidrug resistance. Healthcare systems worldwide are challenged by an alarming drug resistance crisis caused by the massive and rapid propagation of antibiotic resistance genes and the associated emergence of multidrug-resistant pathogenic bacteria. SXT/R391 ICEs contribute to this phenomenon not only in clinical and environmental vibrios but also in several members of the family Enterobacteriaceae. We have identified and characterized here the regulator CroS as a key factor in the stimulation of conjugative transfer of these ICEs in response to DNA-damaging agents. We have also untangled conflicting evidence regarding autoactivation of transfer by the master activator of SXT/R391 ICEs, SetCD. Discovery of CroS provides a clearer and more complete understanding of the regulatory network that governs the dissemination of SXT/R391 ICEs in bacterial populations.