Clinical validation of software for a versatile variability analyzer: Assessment of autonomic function.
Study of physiological variability is an upcoming area of research having manifold clinical applications. Considerable work has been done on heart rate variability and blood pressure variability during the past four decades. Electronics division, Bhabha Atomic Research Centre, has developed an instrument called medical analyzer, which can be used to study several variabilities simultaneously. This instrument has been used to collect data from control subjects and patients with established diagnosis. The data has been analyzed with the help of a software package developed for this purpose and has been found to be consistent with expected manifestations of the disease on the autonomic nervous system. The description of the software package and results of the study are briefly described in this paper.


Effect of sludge water distribution on the liquid-solid separation of a biological sludge.
Water distribution in sludge is worthy of investigation due to its importance in the liquid-solid separation of sludge. Biological sludge contains different physical states of water, including free water, interstitial water, vicinal water, and water of hydration, associated with sludge solids. Conventional dewatering processes can remove only the free water and a part of the interstitial water. Release of interstitial water held inside the cell structure requires the disruption of sludge cells. This study investigates the effect of water distribution on the liquid-solid separation of a biological sludge. Sludge cells were disrupted by alkali treatment, NaCl treatment, heat treatment, and sonication. Water distribution in sludge was determined by differential scanning calorimetry (DSC) and centrifugation. The results of this study indicated that the sludge cell disruption changed the water distribution in sludge and improved its compactibility (as a measure for liquid solid separation). It released a considerable amount of interstitial water trapped inside the cells. Cell disruption created extra surfaces for water binding and increased the unfreezable water content (mostly vicinal water, water of hydration, and a fraction of interstitial water). Compactibility (liquid-solid separation property) of the sludge in terms of cake solids content was improved to about 2-7.5 folds depending on the disruption method used.


Acquired aphasia with convulsive disorder: a pervasive developmental disorder variant.
A 5 1/2-year-old boy with language delay and behavioral problems was evaluated. His symptoms were consistent with pervasive developmental disorder, and electroencephalography showed frequent generalized spike and polyspike activity. After therapeutic levels of anticonvulsant medication were achieved, improvement was noted in communication skills and behavior, as well as on the electroencephalogram. Although the response of language dysfunction to these drugs has been generally disappointing in previously reported cases of communication disorders associated with electroencephalographic abnormalities, a trial of anticonvulsant medication is probably warranted.


Diagnosis and treatment of depression in Alzheimer's disease: impact on mood and cognition.
Depression, a common neuropsychiatric syndrome associated with lower quality of life (QOL), higher mortality, and higher caregiver burden, is estimated to occur in 20-50% of Alzheimer's disease (AD) patients. Recent research suggests that depression in AD (dAD) may differ from major depression phenomenologically and etiologically. Treatment options for dAD include behavioral modifications, pharmacotherapy, and electroconvulsive therapy. Successful treatment of dAD has been reported to improve patients' mood and QOL, as well as lower caregiver burden. Further research is needed in therapeutics of dAD to enhance treatment options and effectiveness.


Lateral patellar luxation in miniature horses.
Bilateral luxation of the patella in four Miniature Horses was corrected by a lateral release incision and medial imbrication of the parapatellar fascia to the tendon of the sartorius muscle. Before surgery, the four horses had a grade 3 to 4 lateral patellar luxation bilaterally and had difficulty walking. Trochlear ridge hypoplasia was evident on radiographs in each horse. Follow-up information varied from 11 months to 4 years after surgery. Three horses had no patellar luxation or lameness. The other horse had a normal right stifle, but patellar luxation (grade 3) had recurred on the left.


[Surgical and nonsurgical treatment of clavicular midpiece fracture in adults: a case-control study].
To compared surgical and nonsurgical treatment of clavicular midpiece fracture. From September 2002 to September 2011, 254 adult cases of displaced midshaft clavicle fractures were retrospective analyzed, including 188 males and 66 females who ranged in age from 19 to 62 years (mean 39.3 years). There were 38 cases of transverse fracture, 71 cases of oblique fracture,and 145 cases of comminuted fracture. All cases were fresh single fractures. According to the treatment methods, these patients were divided into conservative group and surgical group. In conservative group, 127 patients (96 male and 31 female; mean age 40.1 +/- 6.02) were treated by manipulative reduction and fixation with "infinity" shaped bandage. In surgical group, .96 patients (92 male and 35 female; mean age 39.0 +/- 5.11) were treated by open reduction and internal fixation with reconstruction plates. Appearance satisfaction, the cost of treatment and the incidence of complications were compared between the two groups. Therapeutic efficacy was evaluated according to Han's standard. All patients of both groups were followed up for 8-10 months (mean 9.8 months). In surgical group,the curative effect was excellent in 110 cases, good in 12 cases and fair in 3 cases; in conservative group, the curative effect was excellent in 62 cases,good in 28 cases and fair in 37 cases. The therapeutic efficacy in surgical group was better than that in conservative group. The appearance satisfaction of conservative group was higher than that of surgical group. The cost of treatment and complications were lower in conservative group than those in surgical group. Treatment modalities for adult clavicle fractures should be selected on the basis of comprehensive analysis. Non-surgical treatment should be the treatment of choice, and indication for surgical treatment should be controlled strictly.


MOPAT: a graph-based method to predict recurrent cis-regulatory modules from known motifs.
The identification of cis-regulatory modules (CRMs) can greatly advance our understanding of eukaryotic regulatory mechanism. Current methods to predict CRMs from known motifs either depend on multiple alignments or can only deal with a small number of known motifs provided by users. These methods are problematic when binding sites are not well aligned in multiple alignments or when the number of input known motifs is large. We thus developed a new CRM identification method MOPAT (motif pair tree), which identifies CRMs through the identification of motif modules, groups of motifs co-occurring in multiple CRMs. It can identify 'orthologous' CRMs without multiple alignments. It can also find CRMs given a large number of known motifs. We have applied this method to mouse developmental genes, and have evaluated the predicted CRMs and motif modules by microarray expression data and known interacting motif pairs. We show that the expression profiles of the genes containing CRMs of the same motif module correlate significantly better than those of a random set of genes do. We also show that the known interacting motif pairs are significantly included in our predictions. Compared with several current methods, our method shows better performance in identifying meaningful CRMs.


Causes of gastrointestinal colic in horses in western Canada: 604 cases (1992 to 2002).
The medical records of equine gastrointestinal colic cases presented to the Western College of Veterinary Medicine between 1992 and 2002 are reviewed. There was no breed predisposition to colic. Geldings were more prone to colic than females and stallions. Overall, the 3 most common causes of colic were large colon impaction (20.8%), large colon displacement (16.5%), and spasmodic colic (11.7%), after excluding the 13% of cases in which the diagnosis was undetermined. Of the medical cases, large colon impaction (38.4%) and spasmodic colic (22.5%) were the most common. Of the surgical cases, large colon displacement (24.5%), large colon torsion (14.3%), and strangulating lipoma (13.5%) were the most common. Recovery rate for the medical cases was 93.6%. Recovery rate for surgical cases was 73.5%. In conclusion, most of the equine colic cases were medical, and the recovery rates for both surgical and medical cases were comparable with those of other studies.


Alterations in multipotent mesenchymal stromal cells from the bone marrow of acute myeloid leukemia patients at diagnosis and during treatment.
We analyzed multipotent mesenchymal stromal cells (MMSCs) from the bone marrow (BM) of 33 acute myeloid leukemia (AML) patients at diagnosis, after the first course of chemotherapy (day 37), and at days 100 and 180 after diagnosis. All patients were treated according to the AML 01.10 protocol. Cumulative production of MMSCs from AML patients at diagnosis was normal but increased during treatment. Most of the studied genes were upregulated at AML diagnosis, some (IL6, IL1B, LIF) remained upregulated during treatment, and others were downregulated (FGFR1, ICAM1) or normalized. A few genes were normal at diagnosis but decreased during treatment (FGF2, FGFR2, VEGF, SDF1, SOX9, TGFB1). The upregulation of proinflammatory genes both at diagnosis and during remission reflects ongoing inflammation. PDGFRB expression was upregulated in MMSCs from patients in relapse versus those in remission. The AML 01.10 protocol downregulates the expression of genes related to proliferation, differentiation and niche formation.


Cementless total hip arthroplasty for haemophilic arthropathy: follow-up result of more than 10 years.
The improvement of prophylaxis and adequate replacement of clotting factors, the quality of life and natural history of haemophilia have been significantly improved. However, significant functional impairment is inevitable. This study was performed to evaluate over 10 years clinical and radiographic outcomes of cementless total hip arthroplasty (THA) for treatment of haemophilic hip arthropathy. Between 1995 and 2003, 27 cases of cementless total hip arthroplasties were performed in 23 haemophilic patients. A total of 21 cases from 17 patients were available for follow-up analysis over 10 years. Modified Harris hip score, the range of motion of the hip joint, perioperative coagulation factor requirements and complications associated with bleeding were evaluated as part of the clinical assessment. For the radiographic assessment, fixation of component, osteolysis, loosening and other complications were evaluated. Clinically, the mean Harris hip score improved from 57 points before the operation to 94 points at the last follow-up. The mean flexion contracture was 10° preoperatively and 0.9° at the final follow-up. The further flexion improved from 68.4° to 90.5° after surgery. The mean monthly requirement of factor VIII reduced from 3150 units before surgery to 1800 units at the time of the last follow-up. There were three cases of rebleeding. In one case, a progressive haemophilic pseudotumour was found. Reoperation for any reason including revision was performed in three cases. We believe that cementless THA in patient with haemophilic hip arthropathy can bring reliable pain relief and functional improvement for longer than 10 years.


Effect of preliminary irradiation on the bond strength between a veneering composite and alloy.
The shear bond strength of a veneering composite (Solidex) and silver-palladium-copper-gold alloy (Castwell M.C.12) was evaluated for different duration times and irradiance for preliminary photo-polymerization. A veneering composite was applied onto a cast disk. Preliminary photo irradiation was performed using different duration times or irradiance. After final polymerization, the bond strength and the spectral distribution of each curing unit were determined. Shear bond strength was significantly higher for 90 s (12.4 MPa), than that for 0 s (8.3 MPa). With regard to the effect of irradiance, that from Solidilite (11.4 MPa) was significantly higher than that from Sublite S at 3 cm (8.7 MPa). The irradiance of Hyper LII and Sublite S at 3 cm was higher than Sublite S at 15 cm or Solidilite unit. Long time irradiation and low intensity is effective for preliminary irradiation in order to enhance the bond strength.


Primary cilium-dependent mechanosensing is mediated by adenylyl cyclase 6 and cyclic AMP in bone cells.
Primary cilia are chemosensing and mechanosensing organelles that regulate remarkably diverse processes in a variety of cells. We previously showed that primary cilia play a role in mediating mechanosensing in bone cells through an unknown mechanism that does not involve extracellular Ca(2+)-dependent intracellular Ca(2+) release, which has been implicated in all other cells that transduce mechanical signals via the cilium. Here, we identify a molecular mechanism linking primary cilia and bone cell mechanotransduction that involves adenylyl cyclase 6 (AC6) and cAMP. Intracellular cAMP was quantified in MLO-Y4 cells exposed to dynamic flow, and AC6 and primary cilia were inhibited using RNA interference. When exposed to flow, cells rapidly (<2 min) and transiently decreased cAMP production in a primary cilium-dependent manner. RT-PCR revealed differential expression of the membrane-bound isoforms of adenylyl cyclase, while immunostaining revealed one, AC6, preferentially localized to the cilium. Further studies showed that decreases in cAMP in response to flow were dependent on AC6 and Gd(3+)-sensitive channels but not intracellular Ca(2+) release and that this response mediated flow-induced COX-2 gene expression. The signaling events identified provide important details of a novel early mechanosensing mechanism in bone and advances our understanding of how signal transduction occurs at the primary cilium.


A Cross-Sectional Study on Self-Medication Prevalence and Usage Patterns: An Alarming Concept Among the Saudi Population.
Self-medication (SM) has many potential drawbacks, including toxicity, drug resistance, severe adverse effects, drug interactions, drug abuse, and drug dependence, but it is still widely used for a variety of reasons, including time and money savings, symptom prevention or treatment of minor illnesses, a lack of access to doctors, etc. This study aimed to describe and analyse the usage of antibiotics without a prescription, self-medication practises, and patterns of using them among Saudis. In 13 provinces of Saudi Arabia, a community-based cross-sectional study was done. After gaining consent, data were gathered from 420 adults during face-to-face interviews using a questionnaire. SPSS was used to analyse the data once it had been entered into Microsoft Excel (Microsoft® Corp., Redmond, WA). Regarding self-medication, among 208 participants, there was a male predominance and among upper lower class with respect to socioeconomic status. The self-medication rate was found to be higher among graduates and professionals with respect to education and occupation. Self-medication was discovered to be more prevalent among metropolitan residents. The majority of those who started using self-medication got their knowledge from various advertisements. The most frequent symptom of self-medication was fever, followed by a common cold. The most commonly used medication was paracetamol, followed by cough syrups. Weight loss advertisements influence participants the most for self-medication, followed by hair loss and diabetes. TV advertisements have the highest influence on people practising self-medication. The study calls for greater knowledge of the impacts of antibiotic self-medication, which can be accomplished through efficient measures including behaviour change communication and encouraging more research into its causes and effects.


The role of intrinsically photosensitive retinal ganglion cells in nonimage-forming responses to light.
Light exerts many effects on behavior and physiology. These effects can be characterized as either image-forming or nonimage-forming (NIF) visual processes. Image-forming vision refers to the process of detecting objects and organisms in the environment and distinguishing their physical characteristics, such as size, shape, and direction of motion. NIF vision, in contrast, refers to effects of light that are independent of fine spatiotemporal vision. NIF effects are many and varied, ranging from modulation of basal physiology, such as heart rate and body temperature, to changes in higher functions, such as mood and cognitive performance. In mammals, many NIF effects of light are dependent upon the inner retinal photopigment melanopsin and the cells in which melanopsin is expressed, the intrinsically photosensitive retinal ganglion cells (ipRGCs). The ipRGCs project broadly throughout the brain. Many of these projections terminate in areas known to mediate NIF effects, while others terminate in regions whose link to photoreception remains to be established. Additionally, the presence of ipRGC projections to areas of the brain with no known link to photoreception suggests the existence of additional ipRGC-mediated NIF effects. This review summarizes the known NIF effects of light and the role of melanopsin and ipRGCs in driving these effects, with an eye toward stimulating further investigation of the many and varied effects of light on physiology and behavior.


Spontaneous thrombosis of a giant cerebral aneurysm in five days. Report of a case.
This single case report describes a large (giant) left internal carotid aneurysm that showed a very marked decrease in the size of its lumen on reevaluation 5 days after the initial arteriogram. A review of the literature found only 5 cases of spontaneous thrombosis documented by arteriography and only one involved a giant aneurysm. Follow-up arteriography however, may show this rare occurrence and eliminate unwarranted surgery.


Natural history of untreated otitis media.
Data from cohort studies and untreated groups in randomized controlled trials can be identified through systematic literature review and synthesized with meta-analysis to estimate natural history of acute otitis media (AOM) and otitis media with effusion (OME). Systematic literature review and meta-analysis. Source articles were identified by MEDLINE search through August 2002 plus manual crosschecks of bibliographies and published meta-analyses. Data were abstracted independently by two investigators and combined with random effects meta-analysis to estimate spontaneous resolution, 95% confidence intervals (CI), and heterogeneity. Sensitivity analysis was performed. Sixty-three articles met inclusion criteria. AOM symptoms improved within 24 hours without antibiotics in 61% of children (95% CI, 50-72%), rising to 80% by 2 to 3 days (95% CI, 69-90%). Suppurative complications were comparable if antibiotics were withheld (0.12%) or provided (0.24%). Children entered recurrent AOM trials with a mean rate of 5.5 or more annual episodes but averaged only 2.8 annual episodes while on placebo (95% CI, 2.2-3.4). No AOM episodes occurred in 41%, and only 17% remained otitis prone (3 or more episodes). OME after untreated AOM had 59% resolution by 1 month (95% CI, 50-68%) and 74% resolution by 3 months (95% CI, 68-80%). OME of unknown duration had 28% spontaneous resolution by 3 months (95%, CI 14-41%), rising to 42% by 6 months (95% CI, 35-49%). In contrast, chronic OME had only 26% resolution by 6 months and 33% resolution by 1 year. The natural history of otitis media is very favorable. Combined estimates of spontaneous resolution provide a benchmark against which to judge new or established interventions. The need for surgery in children with recurrent AOM or chronic OME should be balanced against the likelihood of timely spontaneous resolution and the potential risk of learning, language, or other adverse sequelae from persistent middle ear effusion. Further research is needed to identify prognostic factors that can target children unlikely to improve spontaneously for earlier intervention.


Climate variability, animal reservoir and transmission of scrub typhus in Southern China.
We aimed to evaluate the relationships between climate variability, animal reservoirs and scrub typhus incidence in Southern China. We obtained data on scrub typhus cases in Guangzhou every month from 2006 to 2014 from the Chinese communicable disease network. Time-series Poisson regression models and distributed lag nonlinear models (DLNM) were used to evaluate the relationship between risk factors and scrub typhus. Wavelet analysis found the incidence of scrub typhus cycled with a period of approximately 8-12 months and long-term trends with a period of approximately 24-36 months. The DLNM model shows that relative humidity, rainfall, DTR, MEI and rodent density were associated with the incidence of scrub typhus. Our findings suggest that the incidence scrub typhus has two main temporal cycles. Determining the reason for this trend and how it can be used for disease control and prevention requires additional research. The transmission of scrub typhus is highly dependent on climate factors and rodent density, both of which should be considered in prevention and control strategies for scrub typhus.


Influencing factors of carbonyl compounds and other VOCs in commercial airliner cabins: On-board investigation of 56 flights.
Volatile organic compounds (VOCs) as a non-negligible aircraft cabin air quality (CAQ) factor influence the health and comfort of passengers and crew members. On-board measurements of carbonyls (short-chain (C1 -C6 )) and other volatile organic compounds (VOCs, long-chain (C6 -C16 )) with a total of 350 samples were conducted in 56 commercial airliner cabins covering 8 aircraft models in this study. The mean concentration for each individual carbonyl compound was between 0.3 and 8.3 μg/m3 (except for acrolein & acetone, average = 20.7 μg/m3 ) similar to the mean concentrations of other highly detected VOCs (long-chain (C6 -C16 ), 97% of which ranged in 0-10 μg/m3 ) in aircraft cabins. Formaldehyde concentrations in flights were significantly lower than in residential buildings, where construction materials are known formaldehyde sources. Acetone is a VOC emitted by humans, and its concentration in flights was similar to that in other high-occupant density transportation vehicles. The variation of VOC concentrations in different flight phases of long-haul flights was the same as that of CO2 concentration except for the meal phase, which indicates the importance of cabin ventilation in diluting the gaseous contaminants, while the sustained and slow growth of the VOC concentrations during the cruising phase in short-haul flights indicated that the ventilation could not adequately dilute the emission of VOCs. For the different categories of VOCs, the mean concentration during the cruising phase of benzene series, aldehydes, alkanes, other VOCs (detection rate > 50%), and carbonyls in long-haul flights was 44.2 µg/m3 , 17.9 µg/m3 , 18.6 µg/m3 , 31.5 µg/m3 , and 20.4 µg/m3 lower than those in short-haul flights, respectively. Carbonyls and d-limonene showed a significant correlation with meal service (p < 0.05). Unlike the newly decorated rooms or new vehicles, the inner materials were not the major emission sources in aircraft cabins. Practical Implications. The on-board measurements of 56 flights enrich the VOC database of cabin environment, especially for carbonyls. The literature review of carbonyls in the past 20 years contributes to the understanding the current status of cabin air quality (CAQ). The analysis of VOC concentration variation for different flight phases, flight duration, and aircraft age lays a foundation for exploring effective control methods, including ventilation and purification for cabin VOC pollution. The enriched VOC data is helpful to explore the key VOCs of aircraft cabin environment and to evaluate the acute/chronic health exposure risk of pollutants for passengers and crew members.


Differences in the organization of interface residues tunes the stability of the SARS-CoV-2 spike-ACE2 complex.
The continuous emergence of novel variants represents one of the major problems in dealing with the SARS-CoV-2 virus. Indeed, also due to its prolonged circulation, more than ten variants of concern emerged, each time rapidly overgrowing the current viral version due to improved spreading features. As, up to now, all variants carry at least one mutation on the spike Receptor Binding Domain, the stability of the binding between the SARS-CoV-2 spike protein and the human ACE2 receptor seems one of the molecular determinants behind the viral spreading potential. In this framework, a better understanding of the interplay between spike mutations and complex stability can help to assess the impact of novel variants. Here, we characterize the peculiarities of the most representative variants of concern in terms of the molecular interactions taking place between the residues of the spike RBD and those of the ACE2 receptor. To do so, we performed molecular dynamics simulations of the RBD-ACE2 complexes of the seven variants of concern in comparison with a large set of complexes with different single mutations taking place on the RBD solvent-exposed residues and for which the experimental binding affinity was available. Analyzing the strength and spatial organization of the intermolecular interactions of the binding region residues, we found that (i) mutations producing an increase of the complex stability mainly rely on instaurating more favorable van der Waals optimization at the cost of Coulombic ones. In particular, (ii) an anti-correlation is observed between the shape and electrostatic complementarities of the binding regions. Finally, (iii) we showed that combining a set of dynamical descriptors is possible to estimate the outcome of point mutations on the complex binding region with a performance of 0.7. Overall, our results introduce a set of dynamical observables that can be rapidly evaluated to probe the effects of novel isolated variants or different molecular systems.


From metal-organic framework to nanoporous carbon: toward a very high surface area and hydrogen uptake.
In this work, with a zeolite-type metal-organic framework as both a precursor and a template and furfuryl alcohol as a second precursor, nanoporous carbon material has been prepared with an unexpectedly high surface area (3405 m(2)/g, BET method) and considerable hydrogen storage capacity (2.77 wt % at 77 K and 1 atm) as well as good electrochemical properties as an electrode material for electric double layer capacitors. The pore structure and surface area of the resultant carbon materials can be tuned simply by changing the calcination temperature.


Serum gastrin in canine chronic lymphocytic-plasmacytic enteritis.
This study evaluates serum gastrin concentrations in dogs with chronic lymphocytic-plasmacytic enteritis, as well as its possible relationship with the severity of lesions present in the stomach. To achieve this aim, 5 dogs without gastrointestinal disease and 15 dogs with chronic lymphocytic-plasmacytic enteritis were included. Serum gastrin concentrations were significantly increased in dogs with chronic lymphocytic-plasmacytic enteritis compared with those in dogs without gastrointestinal disease. Also, there was a positive correlation between the severity of the gastric lesion and the serum gastrin concentration. Our findings indicate the possibility that gastrin plays a role in the etiology of an accompanying chronic antral gastritis in canine chronic lymphocytic-plasmacytic enteritis.


Triterpenoid saponin, oleanolic acid 3-O-beta-d-glucopyranosyl(1-->3)-alpha-l-rhamnopyranosyl(1-->2)-alpha-l-arabinopyranoside (OA) from Aralia elata inhibits LPS-induced nitric oxide production by down-regulated NF-kappaB in raw 264.7 cells.
It is well known that the pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin (PG)E(2) are involved in several inflammatory diseases and lipopolysaccharide (LPS) can stimulate these inflammatory responses. Oleanolic acid 3-O-beta-d-glucopyranosyl(1-->3)-alpha-l-rhamnopyranosyl(1-->2)-alpha-l-arabinopyranoside (OA) was purified from edible plant Aralia elata. OA inhibited LPS-induced NO and PGE(2) production in raw 264.7 murine macrophages in a dose-dependent manner and RT-PCR analysis indicated OA inhibited mRNA transcriptions of iNOS and COX-2 genes in LPS-induced cells. EMSA and Western blot analysis revealed that OA drastically reduced NF-kappaB translocation by the inhibition effects of LPS-induced phosphorylation of IkappaBalpha. In addition, it was found that OA inhibited the phosphorylation of ERK1/2, p38 and JNK MAPK, and the treatment of U0126 in LPS-induced raw 264.7 cells showed significant inhibition activity on the NO production and the phosphorylation of IkappaBalpha. Taken together, it is suggested that OA from A. elata has an anti-inflammatory activity via down-regulation of NF-kappaB.


Discovery of a Novel Linoleate Dioxygenase of Fusarium oxysporum and Linoleate Diol Synthase of Colletotrichum graminicola.
Fungal pathogens constitute serious threats for many forms of life. The pathogenic fungi Fusarium and Colletotrichum and their formae speciales (f. spp.) infect many types of crops with severe consequences and Fusarium oxysporum can also induce keratitis and allergic conditions in humans. These fungi code for homologues of dioxygenase-cytochrome P450 (DOX-CYP) fusion proteins of the animal heme peroxidase (cyclooxygenase) superfamily. The objective was to characterize the enzymatic activities of the DOX-CYP homologue of Colletotrichum graminicola (EFQ34869) and the DOX homologue of F. oxysporum (EGU79548). The former oxidized oleic and linoleic acids in analogy with 7,8-linoleate diol synthases (LDSs), but with the additional biosynthesis of 8,11-dihydroxylinoleic acid. The latter metabolized fatty acids to hydroperoxides with broad substrate specificity. It oxidized 20:4n-6 and 18:2n-6 to hydroperoxides with an R configuration at the (n-10) positions, and other n-6 fatty acids in the same way. [11S-(2)H]18:2n-6 was oxidized with retention and [11R-(2)H]18:2n-6 with loss of deuterium, suggesting suprafacial hydrogen abstraction and oxygen insertion. Fatty acids of the n-3 series were oxidized less efficiently and often to hydroperoxides with an R configuration at both (n-10) and (n-7) positions. The enzyme spans 1426 amino acids with about 825 residues in the N-terminal domain with DOX homology and 600 residues at the C-terminal domain without homology to other enzymes. We conclude that fungal oxylipins can be formed by two novel subfamilies of cyclooxygenase-related DOX.


[The contribution of inflammatory process in pathogenesis and natural history of atrial fibrillation].
The inflammatory process plays important role in pathogenesis of some cardiovascular diseases. Atrial fibrillation is atrial arrhythmia with rapid, asynchronous activation of atrial myocytes. The inflammatory process can be responsible for atrial electrical and anatomical remodeling and therefore shifts towards arrhythmia persistence. The presence of systemic inflammation may be assessed by means of C-reactive protein (CRP) measurement. Maximal concentration of CRP coincidences with the peak of paroxysmal atrial fibrillation occurrence in patients after cardiac surgery. In patients with sinus rhythm the concentration of CRP is a risk factor for this arrhythmia in long-term follow-up. In patients with atrial fibrillation mean CRP concentration is 2-fold higher comparing to control group. CRP concentration is higher in patients with chronic than paroxysmal form of this arrhythmia. High CRP level predicts worse results of direct current cardioversion and more frequent paroxysms of atrial fibrillation during follow-up. Besides of, the patients with echocardiographic signs of thromboembolic risk have higher CRP levels than control subjects. There is no data about the influence of anti-inflammatory therapy on atrial fibrillation or its recurrences.


Synthesis and characterization of radioiodinated MD-230254: a new ligand for potential imaging of monoamine oxidase B activity by single photon emission computed tomography.
A series of iodinated analogues of MD-230254 was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase B (MAO-B). Among them, 5-[4-(2-iodobenzyloxy)phenyl]-3-(cyanoethyl)-1,3,4-oxadiazole-2(3H)one (2-IBPO) was found to have high inhibitory potency and selectivity toward MAO-B (IC50=2.0 nM, MAO-A/MAO-B >50000). Analysis of the inhibition kinetics indicated that 2-IBPO acts in a two-step mechanism as a competitive, slow, and tight-binding inhibitor of MAO-B with a Ki value of 2.4 nM and an overall Ki* value at an equilibrium of 3.8 nM. The new radioligand for MAO-B, [125I]2-IBPO was conveniently synthesized from a tributylstannyl precursor by an iododestannylation reaction using sodium [125I]iodide and hydrogen peroxide with high radiochemical yield. The in vivo tissue distribution studies of [125I]2-IBPO demonstrated its high initial uptake and prolonged retention in the brain. A selective interaction of [125I]2-IBPO with MAO-B was confirmed by the pretreatment experiment with well known MAO specific inhibitors, l-deprenyl, Ro-16-6491, clorgyline, and Ro-41-1049. These very desirable characteristics of [125I]2-IBPO suggested that a 123I-labeled counterpart, [123I]2-IBPO, would have great potential in in vivo studies of MAO-B in the human brain with single photon emission computed tomography (SPECT).


Characterization of the membrane ion currents of a model molluscan muscle, the accessory radula closer muscle of Aplysia californica. II. Depolarization-activated K currents.
1. The accessory radula closer (ARC) muscle of Aplysia californica and its innervation is a model preparation for the study of the neural and cellular mechanisms of behavioral plasticity. Much of the plasticity is mediated by release of neurotransmitters and peptide cotransmitters that modulate contractions of the muscle. Preliminary to investigating the cellular mechanisms of action of these modulators, we have characterized the major membrane ion currents present in the unmodulated ARC muscle and their likely roles in normal contraction. We have studied single dissociated but functionally intact ARC muscle fibers under voltage clamp. This is the second of three papers describing this work. In the preceding paper we described the electrophysiological properties of the fibers at hyperpolarized voltages, and characterized the two major hyperpolarized-activated currents present, a classical inwardly rectifying K current and a Cl current induced by elevated intracellular Cl-. 2. In this paper we dissect the large outward current that becomes activated when the fibers are depolarized above -50 or -40 mV. We find that this current consists of two major depolarization-activated K currents, a fast transient "A"-type current and a slower maintained delayed rectifier, with perhaps a small component of Ca(2+)-activated K current. 3. The A current begins to activate with voltage steps above -50 or -40 mV. It activates in milliseconds, then inactivates virtually completely within 100-200 ms. It is fully available for activation below -80 mV, and almost completely inactivated above -40 mV. It is Ca2+ independent, half-maximally blocked by approximately 3 mM 4-aminopyridine (4-AP) but only 460 mM tetraethylammonium (TEA). 4. The delayed rectifier both activates and inactivates more slowly and more positive than the A current. Thus it begins to activate only above -30 or -20 mV; it activates in tens of milliseconds, then inactivates incompletely over several seconds; it is fully available below -70 mV and inactivated above 0 mV. It is Ca2+ independent, half-maximally blocked by 10 mM TEA and 3-10 mM 4-AP. 5. In the following paper we describe a depolarization-activated Ca current that underlies the K currents and most likely provides Ca2+ necessary for contraction of the muscle. By activating simultaneously with the Ca current, the K currents serve to prevent spikes, so that the depolarization is confined to a range where small voltage changes provide fine control over a wide range of contraction strengths.


Models of change.
Implementing change in organizations is a key nursing leadership competency. At the same time, it is a daunting responsibility. Fortunately, models of successful change illustrate useful concepts for leaders. Change concepts embedded in successful models include careful use of power, reason, reeducation, structure, behavior, and technology. This article discusses models of change. Learning from models may help nurse executives avoid perils such as change fatigue and may promote smoother movement toward safer systems of care.


Promoting fruit and vegetable consumption among students: a randomized controlled trial based on social cognitive theory.
To assess the effectiveness of an educational intervention based on social cognitive theory on increasing consumption of fruit and vegetable among Grade 4 students. The randomised study was conducted in Isfahan, Iran, during 2011 and comprised 138 students, who were randomly divided into intervention and control groups. Data was collected at the beginning and three months after the intervention. A self-administered questionnaire based on constructs of social cognitive theory and food consumption was used. Theory-based nutrition education was imparted on the intervention group. Data was analysed using SPSS 15 and appropriate statistical tests. The intervention group had 68 (49.27%) subjects, while there were 70 (50.72%) controls. After the intervention, mean scores of behavioural capability (p < 0.001), self-efficacy in difficult situations (p = 0.04), self-efficacy in selecting fruits and vegetables (p = 0.01), social support (p = 0.03), and observational learning (p = 0.002) had significantly improved in the intervention group. Nutritional behaviour also showed significant improvement on mean daily intake of fruits and vegetables in the intervention group (p < 0.001). Intervention based on social cognitive theory led to increase in the consumption of fruits and vegetables among students, which confirmed the efficiency of social cognitive theory for such interventions.


Atmospheric Concentrations and Wet/Dry Loadings of Mercury at the Remote Experimental Lakes Area, Northwestern Ontario, Canada.
Mercury (Hg) is a global pollutant released from both natural and human sources. Here we compare long-term records of wet deposition loadings of total Hg (THg) in the open to dry deposition loadings of THg in throughfall and litterfall under four boreal mixedwood canopy types at the remote Experimental Lakes Area (ELA) in Northwestern Ontario, Canada. We also present long-term records of atmospheric concentrations of gaseous elemental (GEM), gaseous oxidized (GOM), and particle bound (PBM) Hg measured at the ELA. We show that dry THg loadings in throughfall and litterfall are 2.7 to 6.1 times greater than wet THg loadings in the open. GEM concentrations showed distinct monthly and daily patterns, correlating positively in spring and summer with rates of gross ecosystem productivity and respiration. GOM and PBM concentrations were less variable throughout the year but were highest in the winter, when concentrations of anthropogenically sourced particles and gases were also high. Forest fires, Arctic air masses, and road salt also impacted GEM, GOM, and PBM concentrations at the ELA. A nested GEOS-Chem simulation for the ELA region produced a dry/wet deposition ratio of >5, suggesting that the importance of dry deposition in forested regions can be reasonably modeled by existing schemes for trace gases.


Motor Imagery EEG Classification Using Capsule Networks.
Various convolutional neural network (CNN)-based approaches have been recently proposed to improve the performance of motor imagery based-brain-computer interfaces (BCIs). However, the classification accuracy of CNNs is compromised when target data are distorted. Specifically for motor imagery electroencephalogram (EEG), the measured signals, even from the same person, are not consistent and can be significantly distorted. To overcome these limitations, we propose to apply a capsule network (CapsNet) for learning various properties of EEG signals, thereby achieving better and more robust performance than previous CNN methods. The proposed CapsNet-based framework classifies the two-class motor imagery, namely right-hand and left-hand movements. The motor imagery EEG signals are first transformed into 2D images using the short-time Fourier transform (STFT) algorithm and then used for training and testing the capsule network. The performance of the proposed framework was evaluated on the BCI competition IV 2b dataset. The proposed framework outperformed state-of-the-art CNN-based methods and various conventional machine learning approaches. The experimental results demonstrate the feasibility of the proposed approach for classification of motor imagery EEG signals.


A homolog of mammalian PRL-releasing peptide (fish arginyl-phenylalanyl-amide peptide) is a major hypothalamic peptide of PRL release in teleost fish.
Two PRL-releasing peptides (PrRP20 and PrRP31) were recently identified from mammalian hypothalamus by an orphan receptor strategy, and a C-terminal RF (arginyl-phenylalamyl-) amide peptide (RFa), structurally related to mammalian PrRP, was also identified from the brain of the Japanese crucian carp (C-RFa) by an intestine-contracting assay. However, to date there have been no reported studies that have examined the PRL-releasing effects of RFa in fish. In the present study we determined the cDNA, primary structure, and function of a homolog of the mammalian PrRP20 in the chum salmon, Oncorhynchus keta. An RFa cDNA encoding a preprohormone of 155 amino acids was cloned from the hypothalamus of chum salmon by 3'- and 5'-rapid amplification of cDNA ends. A native RFa was purified from an acid extract of salmon hypothalami by a Sep-Pak C(18) cartridge, affinity chromatography using anti-synthetic C-RFa, and reverse phase HPLC on an ODS-120T column. The salmon RFa proved to be identical with C-RFa on the basis of elution position on reverse phase HPLC. Immunocytochemical staining in rainbow trout, Oncorhynchus mykiss, revealed that C-RFa-immunoreactive cell bodies were located in the posterior part of hypothalamus and C-RFa-immunoreactive fibers were abundant from the hypothalamus to the ventral telencephalon. A small number of immunoreactive fibers were projected to the pituitary and terminated close to the PRL cells in the rostral pars distalis and to the somatolactin (SL) cells in the pars intermedia. The hypophysiotropic effects of the fish homolog were determined on the release of PRL, SL, and GH from the pituitary of the rainbow trout. Plasma PRL and SL levels were increased at 3 and 9 h, respectively, after ip injection of the synthetic C-RFa into the rainbow trout at doses of 50 and 500 ng/g body weight. In contrast, plasma GH levels were decreased after 1 h at 500 ng/g body weight. Perifusion of the trout pituitaries with synthetic C-RFa at concentrations of 10 pM to 100 nM demonstrated maximum PRL release at 100 pM and maximum SL release at 10 and 100 nM. However, GH release was not affected. These data are the first to demonstrate that a homolog of mammalian PrRP (fish RFa) is a major hypothalamic peptide of PRL release in teleost fish.


Systemic factors are trophic in Thiry-Vella loop in the absence of luminal contents.
Mucosal histology, crypt cell proliferation and brush border enzymes were measured in rats with varying degrees of Thiry-Vella fistulas, in order to compare the effect of systemic and luminal factors on adaptive growth and differentiation (brush border enzymes) in small intestinal epithelium. Twenty-four male Wistar rats (300-350 g) were divided with three groups of eight which underwent the following operations: 20% Thiry-Vella fistula, 80% Thiry-Vella fistula and sham operation. 80% Thirty-Vella fistulas caused a functional short gut; in intestine remaining in continuity there were significant increases in segmental weight, protein, Alp activity and villus height, compared with sham-operated controls and 20% Thiry-Vella fistulas. There was a significant fall in villus height, crypt cell production in loops of 20% Thiry-Vella fistula rats not exposed to luminal contents compared with control segments of sham-operated rats. In contrast, loops of the 80% Thiry-Vella fistula rats were not atrophied despite the much greater distance from luminal nutrients; the villus height and PCNA-LI were higher than in 20% Thiry-Vella fistula rats, and at least as great as in sham-operated rats. This study indicates that atrophy does not occur in loops after 80% Thiry-Vella fistula because crypt cell proliferation is maintained in Thiry-Vella fistulas. Thus, the atrophic effect of diversion of luminal nutrients can be counteracted by systemic growth factors released as part of the adaptive response; luminal factors are not essential for maintenance of normal cellular turnover when there is a powerful stimulus to cell proliferation.


Type-specific antigens of Neisseria meningitidis serogroup A.
By using Ouchterlony immunodiffusion techniques, we defined three unique antigenic determinants (A1, A2, and A3) among six isolates of Neisseria meningitidis serogroup A. Two of these determinants (A2 and A3) were identified as lipopolysaccharides in nature and were not found to occur on the serogroup B strains of N. meningitidis that we examined. The A1 determinant commonly occurred among the serogroup B strains and was identified as a protein determinant.


Distal hereditary motor neuropathy in Korean patients with a small heat shock protein 27 mutation.
Distal hereditary motor neuropathy (dHMN) is a heterogeneous disorder characterized by degeneration of motor nerves in the absence of sensory abnormalities. Recently, mutations in the small heat shock protein 27 (HSP27) gene were found to cause dHMN type II or Charcot-Marie-Tooth disease type 2F (CMT2F). The authors studied 151 Korean axonal CMT or dHMN families, and found a large Korean dHMN type II family with the Ser135Phe mutation in HSP27. This mutation was inherited in an autosomal dominant manner, and was well associated with familial members with the dHMN phenotype. This mutation site is located in the alpha-crystallin domain and is highly conserved between different species. The frequency of this HSP27 mutation in Koreans was 0.6%. Magnetic resonance imaging analysis revealed that fatty infiltrations tended to progressively extend distal to proximal muscles in lower extremities. In addition, fatty infiltrations in thigh muscles progressed to affect posterior and anterior compartments but to lesser extents in medial compartment, which differs from CMT1A patients presenting with severe involvements of posterior and medial compartments but less involvement of anterior compartment. The authors describe the clinical and neuroimaging findings of the first Korean dHMN patients with the HSP27 Ser135Phe mutation. To our knowledge, this is the first report of the neuroimaging findings of dHMN type II.


Expression of NF2 Modulates the Progression of BRAFV600E Mutated Thyroid Cancer Cells.
We previously reported the frequent neurofibromatosis 2 (NF2) gene mutations in anaplastic thyroid cancers in association with the BRAFV600E mutation. We aimed to investigate the role of NF2 in thyroid cancer with BRAF mutation. To identify the function of NF2 in thyroid cancers, we investigated the changes in cell proliferation, colon formation, migration and invasion of thyroid cancer cells (8505C, BHT101, and KTC-1) with BRAFV600E mutation after overexpression and knock-down of NF2. We also examined how cell proliferation changed when NF2 was mutagenized. Human NF2 expression in papillary thyroid carcinoma (PTC) was analyzed using the The Cancer Genome Atlas (TCGA) data. First, NF2 was overexpressed in 8505C and KTC-1 cells. Compared to control, NF2 overexpressed group of both thyroid cancer cells showed significant inhibition in cell proliferation and colony formation. These results were also confirmed by cell migration and invasion assay. After knock-down of NF2 in 8505C cells, there were no significant changes in cell proliferation and colony formation, compared with the control group. However, after mutagenized S288* and Q470* sites of NF2 gene, the cell proliferation increased compared to NF2 overexpression group. In the analysis of TCGA data, the mRNA expression of NF2 was significantly decreased in PTCs with lateral cervical lymph node (LN) metastasis compared with PTCs without LN metastasis. Our study suggests that NF2 might play a role as a tumor suppressor in thyroid cancer with BRAF mutation. More studies are needed to elucidate the mechanism how NF2 acts in thyroid cancer with BRAF mutation.


[The role of bcl-2 family proteins in psoriasis].
Apoptosis is a physiological process of programmed cell death responsible for homeostasis in the body. In skin, apoptotic process regulates keratinocyte proliferation and differentiation in that way maintaining homeostasis of epidermal compartment. The process of apoptosis is controlled by proteins of the Bcl-2 family, several proapoptotic (Bax, Bak, Bad) and antiapoptotic (Bcl-2, Bcl-x(L)) proteins. Nowadays, it seems that dysfunctional apoptosis has an important role in the pathogenesis of several skin diseases. Psoriasis is a chronic hypeproliferative inflammatory skin disease characterized by abnormal keratinocyte hyperproliferation and differentiation as well as by decreased keratinocyte apoptosis. Based on recent studies, it is likely that apoptosis has an important role in epidermal hyperproliferation of psoriatic lesion. Having in mind the significance of Bcl-2 family proteins in apoptosis, it is important to elucidate their role in psoriasis pathogenesis. Observed upregulation of antiapoptotic and downregulation of proapoptotic Bcl-2 family molecules in psoriatic skin implies their significance in psoriasis development.


Ulcerating necrobiosis lipoidica resolving in response to cyclosporine-A.
Necrobiosis lipoidica often fails to respond adequately to therapy with topical and intralesional corticosteroids, or to systemic medications like niacinamide and pentoxifylline (Trental). On the basis of unpublished work which showed a predominance of T helper cells in lesions of necrobiosis lipoidica, and recalling the case of a woman whose necrobiosis lipoidica improved after she was started on cyclosporine for a renal transplant, systemic cyclosporine was successfully used in the cases of two young women who had insulin-dependent diabetes and were disfigured by severe, ulcerating necrobiosis lipoidica on the anterior lower legs. Response to treatment was monitored with photographs. In both cases the ulcers resolved, and remained in remission after cyclosporine was stopped.


[The policy and role of government in community dental health care in the twenty-first century].
The level of dental treatment in Japan is highly rated in the world. However, Japanese prevalence of dental caries in children is relatively high for industrialized countries. The purpose of this paper is to suggest some strategies for community-based dental health promotion in Japan for the twenty-first century, based on a review of the results of an evaluation in Niigata prefecture. The suggestions are as follows; 1. Legislation shoulde be adopted for community-based dental health promotion. 2. Adoption of fluoride usage as an effective preventive method for dental caries should be given priority. 3. Primary dental health services should be provided by municipalities to its inhabitants, and the role for such services by the health center and prefectural government should be clearly defined. 4. Adequate staffing-dental personnel, dentists and dental hygienists-should be secured by municipal governments. 5. A system for evaluation of efficacy of preventive services should be established.


Effects of cast-bracing of the knee on physical performance in healthy subjects.
Effects of application of a hinged cast-brace on thigh muscle strength and physical performance tests were studied in eight healthy volunteers. The cast-brace was applied to one leg for four weeks. The subjects were free to move around. The extra loading by the cast-brace was determined in a progressive uphill walk test on a treadmill with measurements of oxygen uptake, heart rate and plasma lactate concentration. Submaximal oxygen uptake in the uphill walk test was raised significantly (average 9%) on the day after application. After four weeks of cast-brace wearing the submaximal oxygen uptake in the uphill walk test had decreased, but remained elevated (average 4%) even one day after removal. Heart rate was significantly higher (average 7%) during cast application and after removal. Plasma lactate concentration, however, was not influenced. To investigate the effect of four weeks cast-bracing various performance tests to judge the thigh muscle function were taken before application and after removal. No significant changes in peak torque of knee flexion and extension, in physiologic variables at submaximal running pace during treadmill exercise, maximal running speed, 60 m dash, or in jump height were found. In conclusion, cast-bracing of a healthy knee for four weeks has no significant effects on physical performance after removal.


Effect of CT screening on smoking habits at 1-year follow-up in the Danish Lung Cancer Screening Trial (DLCST).
The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large randomised controlled trials. This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial (DLCST), a 5-year randomised controlled trial comprising 4104 subjects; 2052 subjects received annual low-dose CT scan (CT group) and 2052 received no intervention (control group). Participants were healthy current and former smokers (>4 weeks since smoking cessation) with a tobacco consumption of >20 pack years. Smoking habits were determined at baseline and at annual screening. Smoking status was verified using exhaled carbon monoxide levels. Lung function tests, nicotine dependency and motivation to quit smoking were assessed. Quit rates and relapse rates were determined at 1-year follow-up for all subjects. At 1 year the quit rates among smokers were 11.9% in the CT group and 11.8% in the control group (p = 0.95). Relapse rates for former smokers were 10.0% and 10.5% in the CT and control groups, respectively (p = 0.81). Significant predictors (p<0.05) for smoking cessation were: high motivation to quit, low dependency, low ratio of forced expiratory volume in 1 s to forced vital capacity, low pack years, higher age, longer period of abstinence and CT findings necessitating 3-month repeat CT scans. Overall, quit rates were similar in the CT and control group at 1-year follow-up, with a net quit rate of 6.0%. Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later.


[Construction, expression and purification of UreB-Omp11 fusion protein of Helicobacter pylori and its immunocompetence].
To construct H.pylori vaccine candidate strain expressing UreB-Omp11 recombinant fusion protein of H.pylori. To express and purify the fusion protein UreB-Omp11 and to determine its immunocompetence. The two genes were amplified by PCR, and the fusion gene ureB-omp11 was amplified by over lap extension PCR and then cloned into the fusion expression vector pET30a(+), pET28a(+) and pMAL-c2X. The appropriate expression system was selected, and the recombinant UreB-Omp11 fusion protein was expressed and indentfied by SDS-PAGE and Western blot analysis. Then the fusion protein was purified by MBP affinity chromatography and the purity was indentfied by SDS-PAGE. Then the fusion protein was immunized to mice. The immunized mice sera were analyzed by Western blot with purified fusion protein. The ureB-omp11 fusion gene was correctly insected into pET30a(+) and confirmed by Enzyme digestion and sequencing analysis; Results in SDS-PAGE and optical density scanning demonstrated that this fusion protein MBP-UreB-Omp11 was expressed in the recombinant strain of E.coli TB1(pMAL-ureB-omp11). The fusion protein UreB-Omp11 was recognized by the mice sera immunized by H.pylori, the human sera infected with H.pylori and The purity of fusion protein was 90% after purification. The fusion protein purified could be recognized by corresponding antibody of mice sera immunized by this fusion piotein, This fusion protein has strong immunoantigenicity and immunoreactivity. The prokaryotic expression system TB1 (pMAL-c2X-ureB-omp11) was successfully constructed and selected. The results obtained lay the foundation for research on development of protein and DNA vaccine of Hp.


Root canal obturation: experimental study on the thermafil system related to different irrigation protocols.
The aim of this study was to stress the ability of a specific obturation technique (thermafil technique) to seal root canal system in presence or absence of smear layer. Sixteen monoradicular teeth, extracted for periodontal reasons, were collected for this study. All specimens were prepared with nickel-titanium rotary files, and then divided into two groups: for each group was applied a different kind of irrigation method, verifying the effectiveness in removing the smear layer, thus rendering the dentinal tubules more permeable for penetration of softened gutta-percha. Thermafil system was used to fill the root canals, and then all the specimens were observed under scanning electron microscope (SEM). The results showed that the Group which followed irrigation only with sodium hypochlorite exhibited significantly less gutta-percha tags when compared to the second Group, which was irrigated with sodium hypochlorite and EDTA. The thermafil systems have a very good quality of compression and fluency that permit to gain a good seal of endodontic space; furthermore it allows the penetration of gutta-percha with the formation of numerous of gutta-percha tags inside the dentinal tubules above all when smear layer is reduced or eliminated.


Phase transitions in semiflexible-rod diblock copolymers: a self-consistent field theory.
We investigate the phase behavior of semiflexible-rod diblock copolymers in a parameter range where the system displays columnar and lamella structures, using a self-consistent field theory based on the wormlike-chain model. Both Flory-Huggins and Maier-Saupe orientational interactions are incorporated in the formalism, which allows us to explore microphase separation and liquid-crystal ordering simultaneously. Order-to-order phase transitions induced by chain rigidity and orientational interaction are both reported and analyzed. Coupled orientational ordering and spatial inhomogeneity of the four microphase-separated states are discussed in this work: hexagonal column, ellipse column, smectic-A, and smectic-C.


Echinococcus granulosus: characterization of the Spanish strains using in vitro vesicular development.
Differences in in vitro vesicular development (microcyst formation) in three Spanish strains of Echinococcus granulosus (sheep-cattle, horse and pig-goat) are reported. Microcyst formation occurred in 19-37 days (sheep strain), 9-18 days (pig strain) and 35-47 days (horse strain). Comparing these results with those from human samples (microcyst formation in 24-38 days), it is possible to consider the sheep strain as the most likely source of human infections in Spain.


Evaluation of a novel line probe assay to detect resistance to pyrazinamide, a key drug used for tuberculosis treatment.
The development of rapid molecular diagnostic assays for pyrazinamide (PZA) resistance is considered technically challenging as mutations are highly diverse, scattered along the full length of the pncA gene and not all are associated with PZA resistance. We evaluated the performance of the novel Genoscholar PZA-TB II line probe assay (PZA-LPA2; NIPRO Corporation, Japan). To evaluate the applicability of the PZA-LPA2 in clinical settings, we compared the performance of the PZA-LPA2 to a composite reference standard pncA Sanger and Illumina sequencing plus phenotypic susceptibility testing on a panel of 87 Mycobacterium tuberculosis isolates from World Health Organization (WHO) drug resistance surveys, harbouring mutations previously classified as associated or not associated with resistance according to data from peer-reviewed literature. In addition, the PZA-LPA2 was challenged against a selection of isolates with lineage-specific and non-resistance-associated mutations, for which the frequency among clinical isolates is unknown, and tested directly on 59 sputum extracts. For the survey isolates, the PZA-LPA2 reached an overall agreement with the composite reference of 97.6% (80/82) or 94.3% (82/87) excluding or including heteroresistance, respectively. The PZA-LPA2 failed on 8.5% (5/59) of clinical samples; among valid results, 100% (14/14) sensitivity and 100% (7/7) specificity was reached relative to pncA Sanger sequencing. The PZA-LPA2 represents a valid and rapid alternative for indirect PZA susceptibility testing. Preliminary findings on clinical samples show promise for direct testing. Further studies are needed to assess the clinical risk of missing heteroresistance and falsely detecting lineage-specific, silent and nonassociated mutations.


Efficient synthesis of nonnatural mutants in Escherichia coli S30 in vitro protein synthesizing system.
Factors that affect the efficiency of in vitro synthesis of mutant proteins that contain nonnatural amino acids were investigated. The process of the nonnatural mutagenesis consists of chemical aminoacylation of a tRNA that contains a 4-base anticodon, followed by in vitro synthesis in the presence of an mRNA that contains the corresponding 4-base codon. Detailed studies on the time courses of the synthesis revealed two major factors that suppress the yield of nonnatural mutants compared with the wild-type protein. First, a cyclic tRNA that exists as a by-product of the chemical aminoacylation inhibits the protein synthesis. Second, the very short lifetime of a tRNA aminoacylated with a nonnatural amino acid limits the protein yield. As a simple and practical way of surmounting these factors, aminoacyl tRNA was added into the in vitro system at 5 min after the start of the synthesis. The addition increased the protein yield up to the level of conventional proteins in the in vitro system.


Robustness of mode-locking in harmonic cavity nanolasers subjected to potential distortions.
We theoretically analyze the robustness to potential distortion of mode-locking in a harmonic cavity nanolaser sustaining oscillation of Hermite-Gaussian modes. Different types of imperfections of the harmonic potential that create the Hermite-Gaussian modes are considered: the non-parabolicity of the potential and the possible random errors in the shape of the potential. The influence of the different laser parameters, including the Henry factors of the gain medium and the saturable absorber, on the robustness of the mode-locked regime is discussed in detail.


The role of polyhedral oligomeric silsesquioxane on the thermo-mechanical properties of polyoxymethylene copolymer based nanocomposites.
Hybrid nanocomposites formed with polyoxymethylene copolymer (POM) and different types of polyhedral oligomeric silsesquioxane (POSS) nanoparticles have been investigated. Four types of POSS have been studied in contents of 2.5% and 5% wt. The POSS were incorporated by direct melt-mixing. Traditionally copolymerization has been the preferred approach used to form polymer-POSS nanocomposites because the possibility of immiscibility with the polymer matrix is reduced. However, melt-blended POSS nanoparticles can also improve the thermo-mechanical properties of some polymers. Different morphologies were obtained depending on the type of POSS used. GI-POSS and O-POSS exhibit sub-micron or micron-sized inclusions which size increased with increasing percentages of POSS added. On the other hand, both G-POSS and T-POSS appeared to be uniformly dispersed in the POM matrix probably at a molecular level. This is a clear indication of miscibility between these systems and also that POSS solubility in POM is higher than 5 wt%. G-POSS improved the thermal stability of the systems. However, the melting temperature and the modulus of elasticity were found to slightly decrease. On the other hand, the O-POSS produced the opposite effect in the matrix. Finally T-POSS filled systems do not yield important variations in regard to polymethylene oxide properties although interaction between T-POSS and the matrix was detected.


[Proteasomes and their role in the extracellular space].
The presented review concerns the intracellular proteasome and their possible functions. The ubiquitin-proteasome system (UPS) is responsible for the common regulated proteolysis in the cell. 26S proteasome is a central proteolytic unit of UPS and is a multisubunit protein complex consisting of a core catalytic complex, called 20S proteasome, capped at one or both ends by 19S regulatory complex. Proteasomes have been shown in the extracellular space: in alveolar and cerebrospinal fluids, blood plasma. Extracellular proteasomes are intact intracellular particles that exhibit three types of specific peptidase activity. Extracellular proteasomes have been detected in both healthy people and patients with different diseases. Its concentration has been found to be increased in patients suffering from autoimmune diseases, malignant tumors, trauma or sepsis and to correlate with the disease progression, which has both diagnostic and prognostic value.


Evidence for the hallmarks of human aging in replicatively aging yeast.
Recently, efforts have been made to characterize the hallmarks that accompany and contribute to the phenomenon of aging, as most relevant for humans 1. Remarkably, studying the finite lifespan of the single cell eukaryote budding yeast (recently reviewed in 2 and 3) has been paramount for our understanding of aging. Here, we compile observations from literature over the past decades of research on replicatively aging yeast to highlight how the hallmarks of aging in humans are present in yeast. We find strong evidence for the majority of these, and summarize how yeast aging is especially characterized by the hallmarks of genomic instability, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, and mitochondrial dysfunction.


The Spatial and Temporal Characters of Demyelination and Remyelination in the Cuprizone Animal Model.
Multiple sclerosis (MS) is the most common central nervous system disease due to demyelination in young adults, and currently, there is no cure. Some experimental animal models were generated to mimic specific aspects of MS pathological characteristics. Among them, the cuprizone (CPZ)-induced mouse demyelination model presents heterogeneous pathologies with both focal and diffuse lesions. Considering that MS is a progressive disease, it is important to study the spatial and temporal characters of de- and remyelination in MS animal models. However, such data especially in some brain regions such as lateral septal area, fimbria of hippocampus, and hippocampus are still lacking. In this study, we investigated the alterations of myelin in these areas in parallel to the changes in corpus callosum using coronal sections. We found that the progression of demyelinating varied in different brain regions in C57BL/6J mice treated with CPZ for 1 to 5 weeks. This result suggests that each brain region has a distinct sensitivity to CPZ intoxication. Interestingly, activated microglia appeared not only in the active demyelinating areas but also in the non-myelinolysis regions. After CPZ withdrawal, significant remyelination was started in corpus callosum as early as 3 days. The completion of remyelination in the entire brain regions took 3 weeks. Our study detailed characterized the dynamics of myelin alterations and microglial status in the brain of the CPZ model. This information is valuable to facilitate further MS studies utilizing the CPZ model. Anat Rec, 302:2020-2029, 2019. © 2019 American Association for Anatomy.


Do extremely preterm infants need retinopathy of prematurity screening earlier than 31 weeks postmenstrual age?
To evaluate the utility of screening all extremely preterm infants for retinopathy of prematurity (ROP) at 4 weeks chronologic age, which is earlier than recommended by the 2018 AAP guidelines. Retrospective analysis of infants <27 weeks gestation from two tertiary NICUs between 2006 and 2018 who survived until first eye examination. 550 infants (gestational age 25.1 ± 1.2 weeks and birth weight 758 ± 323 g) had 1310 examinations performed by 32 weeks postmenstrual age (PMA), and 676 (51.6%) of these were prior to 31 weeks PMA. No examinations in infants prior to 31 weeks PMA met the criteria for laser therapy. Of 87/550 infants (15.8%) who required laser therapy, none did so prior to 32 weeks PMA. No infants born <27 weeks gestation were found to have severe ROP prior to 31 weeks PMA, supporting the most recent AAP recommendation of initiating ROP screening at 31 weeks PMA for extremely preterm infants.


Study on the epigenetic methylation modification of bipolar disorder major genes.
We aimed to study changes and possible roles of epigenetic modification of candidate genes in the pathogenesis of bipolar disorder, and provide the basis for clinical diagnosis and analysis. A total of 150 patients with bipolar disorder were enrolled in this study from January 2014 to June 2015; also, 50 healthy subjects were enrolled as control group. The patients were followed up for 18 months and followed up once every 3 months to review the methylation status. The methylation status was examined before and after treatment, and the patients were followed up every 3 months after treatment, and the follow-up period was 18 months. Compared with the healthy control group, there were 2075 CpG island aberrant methylation points in patients with bipolar disorder, which can be divided into 24 categories. Log-Ratio > 0.5 was used as the positive criteria, and COMT and PPIEL were identified as the genes associated with bipolar disorder. Compared with the control group, the levels of COMT and PPIEL gene methylation in the observation group were significantly higher (p < 0.05). There was no significant difference in the methylation level of COMT and PPIEL gene between the two groups (p > 0.05) after 12 months of treatment. The methylation level of COMT and PPIEL gene is closely related to bipolar disorder.


Urinary calcium to creatinine ratio: a potential marker of secondary hyperparathyroidism in patients with vitamin D-dependent rickets type 1A.
Patients with vitamin D-dependent rickets type 1A (VDDR1A) are usually treated with alfacalcidol, an analog of vitamin D. Around puberty, an increased dose of alfacalcidol is recommended for these patients to avoid hypocalcemia and secondary hyperparathyroidism. However, no indicators of secondary hyperparathyroidism except for PTH are presently known. The aim of this study is to evaluate whether urinary calcium to creatinine ratio (U-Ca/Cr) is useful as a biomarker of secondary hyperparathyroidism in VDDR1A patients in order to determine the proper dose of alfacalcidol. Two brothers with VDDR1A were recruited who had null mutations of CYP27B1 which encodes 1-alpha-hydroxylase of vitamin D. We investigated the relationship between U-Ca/Cr and intact-PTH around puberty when the brothers showed hypocalcemia with secondary hyperparathyroidism. The results were compared to those of five patients with vitamin D deficiency (VDD). As a result, high intact-PTH levels were observed when U-Ca/Cr decreased to less than 0.1 (mg/mg) in both VDDR1A brothers. This relationship was also observed in the VDD patients. However, it is necessary to take into account body calcium status, either in depletion or in excess, to accurately evaluate the relationship between U-Ca/Cr and secondary hyperparathyroidism. First, low U-Ca/Cr was detected in situations with calcium depletion without hyperparathyroidism in the VDDR1A patients. Second, high U-Ca/Cr with hyperparathyroidism could be detected theoretically in a condition of excess calcium supply. In conclusion, a U-Ca/Cr ratio of less than 0.1 (mg/mg) in VDDR1A patients is useful to accurately evaluate calcium depletion and secondary hyperparathyroidism.


Transcervical uniportal pulmonary lobectomy.
The aim of the study is a description of surgical technique of uniportal transcervical video-assisted thoracoscopic surgery (VATS) for pulmonary lobectomy. We used a collar neck incision (transcervical) of an average length 5-8 centimeters. The manubrium of the sternum is elevated with a hook connected to the Zakopane II frame (Aesculap-Chifa, B. Braun, Nowy Tomyśl, Poland). The first step is a transcervical extended mediastinal lymphadenectomy (TEMLA), for improved staging and possible improved survival. The nodes removed during TEMLA undergo intraoperative imprint cytology examination. In case of no metastasis a uniportal VATS lobectomy through the neck follows. Ventilation of the operated lung is disconnected and the pleural cavity is entered by opening of the mediastinal pleura. Pleural adhesions, if present are managed with electrocautery. The branches of the pulmonary artery and vein are sequentially dissected and managed with endostaplers or vascular clips. The lobar bronchus and the fissures are divided with endostaplers and the resected lobe is removed in an endobag. There were 16 patients operated on in the period 1.2.2016-30.7.2016. There were two conversions-in one patient with left lower lobe tumor we had to convert to uniportal VATS left lower lobectomy due to extensive adhesions. In the other patient undergoing right lower lobectomy there was a conversion to right thoracotomy because of the bleeding from the pulmonary artery. There was no mortality and complications occurred in three patients. The mean operative time was 245.6 min (range, 145-385 min) for the whole TEMLA procedure with imprint cytology and lobectomy and 175.6 min (range, 75-295 min) for a lobectomy solely. A uniportal transcervical VATS approach for pulmonary lobectomy combined with transcervical extended mediastinal lobectomy (TEMLA) provides an opportunity for radical pulmonary resection and superradical extensive mediastinal lymphadenectomy.


Permanent Education in BLS and ACLS: impact on the knowledge of nursing professionals.
The theoretical knowledge and practical skills of the Basic Life Support (BLS) and the Advanced Life Support (ALS) are among the most important determining factors of the cardiopulmonary reanimation success rates. Assess the impact of a permanent training program in BLS and ALS on the knowledge of nursing professionals. Cross-sectional study. Population was made of nursing professionals of a tertiary level hospital. Assessments were carried out before and after training. The critical points of the International Liaison Committee on Resuscitation (ILCOR) analysis were addressed. 213 professionals were assessed (76 nurses, 35.7%; 38 assistants, 17.8%; and 99 technicians, 46.7%). Pre-course assessment average grades were statistically different (p<0.001) among assistants (3.25), technicians (3.96) and nurses (4.69). Single professional without kids showed performance significantly superior to married professional with kids (p=0.02 and 0.004 respectively). Pre-training level of knowledge was inversely proportional to the time elapsed since the completion of undergraduate course or technical course. Main deficiencies were related to the initial approach of airways, to post-resuscitation cares and to the external cardiac massage technique. The post-course general average grade was 7.26. Assistants achieved a performance of 131.2%, technicians, of 78.9% and the nurses, of 85%, with no significant statistic difference (p=0.43). The permanent training program in BLS and ALS resulted in important increment in the level of knowledge of nursing professionals.


Influenza A whole virion vaccine induces a rapid reduction of peripheral blood leukocytes via interferon-α-dependent apoptosis.
Infection with single strand RNA (ssRNA) viruses, such as influenza A virus, is known to induce protective acquired immune responses, including the production of neutralizing antibodies. Vaccination also causes a reduction in the number of peripheral blood leukocytes (PBL) shortly after inoculation, a result which may have undesirable adverse effects. The cellular mechanisms for this response have not been elucidated so far. Here we report that formalin-inactivated influenza A whole virus vaccine (whole virion) induces a significant decrease in PBL in mice 5-16 h after administration, whereas an ether-split vaccine (HA split) made from the same influenza virus strain does not induce a similar loss of PBL. Concordant with this reduction in the number of PBL, a rapidly induced and massive production of interferon (IFN)-α is observed when mice are injected with whole virion, but not with HA split vaccines. The role of Toll-like receptors (TLR), which are involved in signal transduction of influenza virus, and the subsequent induction of IFNα were confirmed using mice lacking TLR7, MyD-88, or IFNα/β receptor. We further demonstrated that the observed PBL loss is caused by apoptosis in an IFNα-dependent manner, and not by leukocyte redistribution due to chemokine signaling failure. These findings indicate that RNA-encapsulated whole virion vaccines can rapidly induce a loss of leukocytes from peripheral blood by apoptosis, which may modulate the subsequent immune response.


Using Natural Language Processing and Network Analysis to Develop a Conceptual Framework for Medication Therapy Management Research.
This paper describes a theory derivation process used to develop a conceptual framework for medication therapy management (MTM) research. The MTM service model and chronic care model were selected as parent theories. Review article abstracts targeting medication therapy management in chronic disease care were retrieved from Ovid Medline (2000-2016). Unique concepts in each abstract were extracted using MetaMap and their pairwise cooccurrence determined. The information was used to construct a network graph of concept co-occurrence that was analyzed to identify content for the new conceptual model. 142 abstracts were analyzed. Medication adherence is the most studied drug therapy problem and co-occurred with concepts related to patient-centered interventions targeting self-management. The enhanced model consists of 65 concepts clustered into 14 constructs. The framework requires additional refinement and evaluation to determine its relevance and applicability across a broad audience including underserved settings.


The clavulanic acid biosynthetic cluster of Streptomyces clavuligerus: genetic organization of the region upstream of the car gene.
The genetic organization of the region upstream of the car gene of the clavulanic acid biosynthetic gene cluster of Streptomyces clavuligerus has been determined. Sequence analysis of a 12.1 kb region revealed the presence of 10 ORFs whose putative functions, according to database searches, are discussed. Three co-transcriptional units are proposed: ORF10-11, ORF12-13 and ORF15-16-17-18. Potential transcriptional terminators were identified downstream of ORF11 (fd) and ORF15. Targeted disruption of ORF10 (cyp) gave rise to transformants unable to produce clavulanic acid, but with a considerably higher production of cephamycin C. Transformants inactivated at ORF14 had a remarkably lower production of clavulanic acid and similar production of cephamycin C. Significant improvements of clavulanic acid production, associated with a drop in cephamycin C biosynthesis, were obtained with transformants of S. clavuligerus harbouring multiple copies of plasmids carrying different constructions from the ORF10-14 region. This information can be used to guide strain improvement programs, blending random mutagenesis and molecular cloning, to optimize the yield of clavulanic acid.


Histiocytosis X characterized by marked elevation of serum alkaline phosphatase and rapid destructive changes in the lung parenchyma.
A 23 yr old man was admitted suspected of having a liver disease because of marked elevation of the serum alkaline phosphatase. A biopsy of the liver was without cholestasis. A skin biopsy of a papule was compatible with eosinophilic granuloma. Over a few months the patient developed severe restrictive lung disease. The elevation of the serum alkaline phosphatase was probably due to diffuse bone affection.


Lack of validity of standard corrections for white blood cell counts of blood-contaminated cerebrospinal fluid in infants.
An evaluation of the validity in infants of standard computations for the correction of white cell counts in blood-contaminated cerebrospinal fluid (traumatic lumbar puncture) was undertaken. In 39 infants with significant blood contamination (greater than 10(4) red blood cells/microL) and no evidence of bacterial meningitis, both calculated corrections based on simultaneously obtained complete blood counts and estimated corrections based on average values resulted in overcorrection in a majority of cases (33 of 39 and 25 of 39, respectively). The mechanism of this overcorrection could not be defined. In eight infants with significant blood contamination and proven bacterial meningitis, correction computations normalized or overcorrected the white cell count in one case. It appears that standard computations frequently overcorrect white cell counts in blood-contaminated cerebrospinal fluid and that the magnitude of the overcorrection may obscure pathologic states in some cases.


A methodology for evaluating organizational change in community-based chronic disease interventions.
In 2003, the Monterey County Health Department, serving Salinas, California, was awarded one of 12 grants from the Steps to a HealthierUS Program to implement a 5-year, multiple-intervention community approach to reduce diabetes, asthma, and obesity. National adult and youth surveys to assess long-term outcomes are required by all Steps sites; however, site-specific surveys to assess intermediate outcomes are not required. Salinas is a medically underserved community of primarily Mexican American residents with high obesity rates and other poor health outcomes. The health department's Steps program has partnered with traditional organizations such as schools, senior centers, clinics, and faith-based organizations as well as novel organizations such as employers of agricultural workers and owners of taquerias. The health department and the Stanford Prevention Research Center developed new site-specific, community-focused partner surveys to assess intermediate outcomes to augment the nationally mandated surveys. These site-specific surveys will evaluate changes in organizational practices, policies, or both following the socioecological model, specifically the Spectrum of Prevention. Our site-specific partner surveys helped to 1) identify promising new partners, select initial partners from neighborhoods with the greatest financial need, and identify potentially successful community approaches; and 2) provide data for evaluating intermediate outcomes matched to national long-term outcomes so that policy and organizational level changes could be assessed. These quantitative surveys also provide important context-specific qualitative data, identifying opportunities for strengthening community partnerships. Developing site-specific partner surveys in multisite intervention studies can provide important data to guide local program efforts and assess progress toward intermediate outcomes matched to long-term outcomes from nationally mandated surveys.


Quantification and characterization of maize lipid transfer protein, a food allergen, by liquid chromatography with ultraviolet and mass spectrometric detection.
Maize (Zea mays) is not considered a major allergenic food; however, when food induced allergenic and immunologic reactions have been implicated to maize, lipid transfer proteins (LTPs) have been identified as major allergens. LTP is an extremely stable protein that is resistant to both proteolytic attack and food processing, which permits the allergen to reach the gastrointestinal immune system in an immunogenic and allergenic conformation, allowing sensitization and induction of systemic symptoms. They are considered a complete food allergen in that they are capable of inducing specific IgE as well as eliciting severe symptoms. We have purified and characterized an endogenous ~9 kDa LTP from maize kernels. The maize LTP consists of 93 amino acid residues and has a M(r) of 9046.1 Da, determined by electrospray ionization mass spectrometry. Following accurate identification and characterization of maize LTP, a highly specific and quantitative assay using liquid chromatography with ultraviolet and mass spectrometric detection was developed. The present assay enables determination of LTP over a concentration range from 29 to 1030 μg/g in maize kernel samples. Assay recovery (percent relative error, % RE) was measured at 11 different concentrations ranging from 4 to 147 μg/mL and did not exceed 5.1%. The precision (percent coefficient of variation, % CV) was measured at 3 concentrations on each of 4 days and did not exceed 14.4%. The method was applied to evaluate the levels of LTP in 14 different maize lines. To our knowledge, this represents the first quantitative liquid chromatography-ultraviolet/mass spectrometry (LC-UV/MS) assay for the determination of LTP for the assessment of a food allergen.


Genetic manipulation of proline accumulation influences the concentrations of other amino acids in soybean subjected to simultaneous drought and heat stress.
The effect of simultaneous drought and heat stress on free amino acid levels was compared in wild type and transgenic soybean (Glycine max (L.) Merr cv Ibis) plants transformed with the cDNA coding for the last enzyme of Pro biosynthesis, l-Delta(1)-pyrroline-5-carboxylate reductase (EC 184.108.40.206), in sense and antisense directions. The most rapid increase in Pro content was found in the sense transformants that exhibited the least water loss, while the slowest elevation of Pro levels was detected in the antisense transformants that exhibited the greatest water loss during stress. Correspondingly, the level of the Pro precursors Glu and Arg was higher in sense transformants and lower in antisense ones compared to the wild type plants during the initial part of the stress. Interestingly, genetic manipulation of Pro levels also affected the stress-induced changes in the concentration of several other amino acids, which indicates the coordinated regulation of their metabolic pathways.


Clinical study monitoring the pH on tooth surfaces in patients with and without erosion.
The aim of this study was to compare tooth surface pH after drinking orange juice or water in 39 patients with dental erosion and in 17 controls. The following investigations were carried out: measurement of pH values on selected tooth surfaces after ingestion of orange juice followed by ingestion of water (acid clearance), measurement of salivary flow rate and buffering capacity. Compared with the controls, patients with erosion showed significantly greater decreases in pH after drinking orange juice, and the pH stayed lower for a longer period of time (p < 0.05). Saliva parameters showed no significant differences between the two patient groups except for a lower buffering capacity at pH 5.5 in the erosion group.


Endothelial von Willebrand factor release due to eNOS deficiency predisposes to thrombotic microangiopathy in mouse aging kidney.
Endothelial dysfunction is critical in the decline of renal function with. By using endothelial nitric oxide synthase knockout (eNOSKO) mice, we tested the hypothesis that a lack of endothelial nitric oxide synthase accelerates renal injury in the aging kidney. In contrast to control mice and young eNOSKO mice, aging eNOSKO mice showed greater renal injury and in particular developed a thrombotic microangiopathy, with mesangiolysis, endothelial swelling, endothelial cell loss, double-contour appearance of glomerular basement membrane (GBM), and thrombus formation. Thrombi, which were composed of fibrin, platelets, and von Willebrand factor (vWF), were identified predominantly in glomerular capillaries and rarely in arterioles, but not in larger vessels. In the tubulointerstitium, tubular degeneration and macrophage infiltration were also prominent in aging eNOSKO mice. Intraluminal vWF deposition was accompanied with thrombus formation, whereas mesangial deposition of vWF was associated with mesangial matrix expansion. Furthermore, the mesangial vWF deposition was detectable in young eNOSKO mice in which severe glomerular injury had not yet developed. Finally, a higher level of serum P-selectin in eNOSKO mice was consistent with the vWF behavior and suggested exocytosis of the Weibel-Palade body by the endothelium. In conclusion, a lack of endothelial nitric oxide synthase resulted in the development of glomerular thrombotic microangiopathy. A lack of nitric oxide likely contributed to the release of vWF, leading to thrombus formation in this model.


Survival trends of metastatic small intestinal neuroendocrine tumor: a population-based analysis of SEER database.
Incidence of small intestinal neuroendocrine tumors (SNETs) is increasing and they now comprise the most common types of small intestinal cancer. SNETs frequently present with distant metastasis. Significant uncertainty prevails with regards to the surgical management strategies in metastatic SNETs. Therefore, we aim to analyze survival trends in metastatic SNET patients stratified by type of surgical treatment. We analyzed the data from the SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2016 Sub (1973-2014 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with metastatic SNET between 2000 and 2014. Treatment received was divided into two broad categories; surgical resection and no surgery and further subcategorized into local resection (LR) (surgery of the primary tumor only) and radical resection (RR) (surgery for primary tumor and metastasectomy). We identified 1,138 metastatic SNET cases. Median age was 61 years. Median survival was 41 months and 5 year RSR was 72%. Age >50 years (HR 2.10, P<0.001), poorly differentiated histology (HR 3.50, P<0.001) and tumor size >2 cm (HR 1.27, P=0.07), showed poor outcome. The group which did not receive any tumor directed surgery showed the worst survival (5 years RSR 45.30% vs. 76%, respectively for no surgery vs. surgery group, P<0.001). We found no significant difference in survival between LR and RR (HR 1.01, 95% CI: 0.73-1.40, P=0.92). Upon further stratification, surgery significantly improved survival on patients who were >50 years (HR 0.37), and for primary tumor location in the duodenum (HR 0.13). Surgery for the primary tumor (LR or RR) significantly improved 5-year survival even in the presence of distant metastasis irrespective of primary tumor size, grade, or histology. Poor prognostic factors include, age >50 years, duodenal primary, tumor size >2 cm, and poorly differentiated histology.


Excited state gradients for a state-specific continuum solvation approach: The vertical excitation model within a Lagrangian TDDFT formulation.
The accurate modeling of the environment response is a fundamental challenge for accurately describing the photophysics and photochemistry of molecules both in solution and in more complex embeddings. When large rearrangements of the electron density occur after an electronic transition, state-specific formulations, such as the vertical excitation model, are necessary to achieve a proper modeling of the processes. Such a state-specific model is fundamental not only to obtain accurate energies, but also to follow the geometrical relaxation accompanying the evolution of the excited-states. This study presents the analytical expression of the gradients of the vertical excitation model approach by a Lagrangian formulation in the time dependent density functional theory framework. Representative organic chromophores in solution are used to test the reliability of the implementation and provide comparisons with the linear response description.


[The Derosne, Parisian pharmacists from 1779 to 1855].
The pharmacy of the 115 Saint Honoré street was successively kept by François, by his two sons Jean-François and Louis-Charles, and by the son-in-law of the elder, François-Bernard who took the Bernard-Derosne family name. The two brothers made many chemical studies, among which the "essential salt" of the opium extract, and the sugar purification. Louis-Charles had many industrial activities, in Chaillot, where he made vapor engines. The two brothers were members of the Académie Royale de Médecine, and Jean-François was twice the President of the Société de Pharmacie de Paris.


Redefining venereology practice in Tamil Nadu, South India - Nakshatra Health - A networking model.
Accessing care for sexual health has always been a challenge in our Indian context. The primary reason is a lack of awareness of modes of transmission of sexually transmitted diseases (STD), appropriate testing, and treatment options. The second is taboo associated with the morality of the individual. The third is the accessibility and availability of Quality STD care by allopathic specialists in comparison to the demand. This has paved way for lots of myths and misconceptions among the general public regarding STDs and HIV disease. Compounding it is the mushrooming of nonqualified practitioners and healers who claim to cure all STDs and HIV has led to poor treatment outcomes. Several methods of partnership with qualified allopathic practitioners have been tried for the provision of quality STD care by various donor-funded, HIV and STD prevention programs in the country. The key reasons for the nonsustainability of these clinics were the lack of technical capability to handle the sexual health and STD clinical cases and the huge cost involved in the advertisement and maintenance of the clinics. Seven clinicians from different geographical locations in Tamil Nadu, who were exclusively qualified in Venereology, conceived the idea of provision of comprehensive clinical care cum counseling and testing services through a networking model from December 01, 2020. The model comprised the following: (1) Dedicated YouTube channel (Nakshatra Health) to provide scientific information on STD and HIV, modes of transmission, clinical symptoms, lab testing, interpretation of results, clinical treatment options, and counseling on prevention, (2) Dedicated telephone helpline was established with WhatsApp to answer the queries of clients by the network venereologists, (3) Dedicated website (www.nakshatra.health) was developed to provide information on STD and HIV and options to clarify doubts and fix appointments online, (4) Clinical consultations were done in a hybrid mode with an option for direct clinic and online consultation. Prescriptions were provided using dedicated software instantly, (5) Networking was done with NABL-accredited labs and collection centers for performing STD and HIV tests with e-test request forms, (6) Networking was done with pharma companies to provide pre- and postexposure prophylaxis (PEP) services to clients through e-prescriptions. Cross referrals were made across the network members to facilitate easy access to clinical services by clients from different parts of Tamil Nadu. The entire concept was branded as "Nakshatra health" with a tagline - "Your sparkling solution for safe sexual health care." Quality STD care and ethical practice were the underlying motos of this concept. During the 20 months (December 2020 to July 2022), 6442 phone calls and 9328 WhatsApp messages were received. 82.3% of the calls and messages were queries from clients related to their sexual exposures, and 16.4% were general information seekers. During this period, the Nakshatra Health YouTube channel had 1590 subscribers and nearly 2.4 lakh views of all its 24 videos. Among the viewers, 92.4% were male. 52.29% of viewers were between the ages of 25 and 34 years, 28.25% were between the ages of 18 and 24 years, and 17.25% viewers were between the ages of 35 and 44 years. 86% of the viewers were from India and 13% were Tamil-speaking viewers from Middle East, Southeast Asian countries and 1% were from European, African, and American countries. The most commonly watched videos were related to HIV symptoms and lab tests for STD and HIV. 16% of the viewers repeatedly watched the various videos in the series. The network laboratories provided testing services for 1082 clients with 2423 various STD/HIV tests. Totally 3328 clients availed of online consultation and 924 clients accessed clinic-based services across the network members. Among these cases, 18 cases of Syphilis (primary and secondary) and 12 cases of acute gonococcal urethritis, and 10 cases of genital warts were diagnosed and treated. 12 cases of phimosis and 4 cases of anal warts were surgically treated in collaboration with a surgeon. Through this initiative, PEP and PreP services were provided to 228 and 8 individuals. Designing a comprehensive sexual health service package is crucial to ensure the availability and ease of access to services to the general public. Provision of correct scientific information, networking and cross-referral of cases with like-minded dermatovenereologists/clinicians interested in venereology sexually transmitted infections, easily accessible clinical, laboratory, and treatment services including PreP and PEP medications, and ethical practice are the key factors for scaling this concept.