Psychiatric and behavioral disorders in persons with Down syndrome.
Similar to the state of the broader intellectual disabilities field, many gaps exist in the research and treatment of mental health concerns in people with Down syndrome. This review summarizes key findings on the type and prevalence of behavior and emotional problems in children, adolescents, and adults with Down syndrome. Such findings include relatively low rates of severe problems in children, and well-documented risks of depression and Alzheimer's disease in older adults. The review also considers emerging data on autism, and the paucity of studies on adolescents. Three next steps for research are highlighted, including a need to: (1) connect research on psychiatric status and diagnoses across developmental periods, including adolescence, and to examine such associated processes as sociability, anxiety and attention; (2) unravel complicated biopsycho-social risk and protective factors that serve to increase or diminish psychopathology; and (3) identify evidence-based treatments that both reduce distressful symptoms and enhance well-being in individuals with Down syndrome.


Controllable synthesis, magnetic properties, and enhanced photocatalytic activity of spindlelike mesoporous α-Fe(2)O(3)/ZnO core-shell heterostructures.
Mesoporous spindlelike iron oxide/ZnO core-shell heterostructures are successfully fabricated by a low-cost, surfactant-free, and environmentally friendly seed-mediate strategy with the help of postannealing treatment. The material composition and stoichiometry, as well as these magnetic and optical properties, have been examined and verified by means of high-resolution transmission electron microscopy and X-ray diffraction, the thickness of ZnO layer can be simply tailored by the concentration of zinc precursor. Considering that both α-Fe2O3 and ZnO are good photocatalytic materials, we have investigated the photodegradation performances of the core-shell heterostructures using organic dyes Rhodamin B (RhB). It is interesting to find that the as-obtained iron oxides/ZnO core-shell heterostructures exhibited enhanced visible light or UV photocatalytic abilities, remarkably superior to the as-used α-Fe2O3 seeds and commercial TiO2 products (P25), mainly owing to the synergistic effect between the narrow and wide bandgap semiconductors and effective electron-hole separation at the interfaces of iron oxides/ZnO.


[Molecular mechanism of the stress induction of MDR1 gene].
MDR1 promoter activity increases in response to various environmental stimuli, including anticancer drugs and in a manner that is dependent on the inverted CCAAT box. The binding activity of a nuclear factor MDR-NF1 that interacts with this promoter region was augmented when the nuclear extract was prepared from cells that had been treated with either UV or anticancer drugs. In an attempt to understand the molecular basis for the stress-dependent induction of MDR1 promoter activity, the cDNA for MDR-NF1 have been cloned. The amino acid sequence encoded by the cloned cDNA was identical to that of YB-1. The human Y-Box binding protein (YB-1) is a member of a DNA-binding protein family with a structurally and functionally conserved cold shock domain. YB-1 was found to be much higher in all cisplatin-resistant cell lines than that in the respective drug-sensitive parental counterparts. Two transfectants with a YB-1 antisense construct showed increased sensitivity to cisplatin, mitomycin C and UV irradiation, but not to vincristine, doxorubicin, camptothecin or etoposide. Thus, YB-1 may protect cells from the cytotoxic effects of agents that induce cross-linking of DNA, suggesting a novel function of this ancestor DNA binding protein. Regulatory mechanism of the YB-1 gene expression and the cellular functions of YB-1 are currently under investigation in relation to drug resistance.


Investigating the effective factors in creatinine changes among hemodialysis patients using the linear random effects model.
Background and objectives:Out of 10 apparently healthy humans, one was somewhat suffering from one of the types of renal disease. Hemodialysis is known as the most applicable method of taking care of this group of patients. In addition, serum creatinine is an important mark in the performance of kidneys. The aim of the present study was to investigate the effective factors in creatinine and its effect on the performance of kidneys. Materials and methods: The present study is a longitudinal experiment in which 500 participants were randomly selected from the hemodialysis patients in Mazandaran Province. Creatinine variable was considered as the longitudinal responding variable, which was measured 3 times per year over a period of 6 years. The random effects model was also considered the most appropriate model for the collected data. Results:The total mean value of creatinine was 1.62 ± 0.49, among men 1.69 ± 0.46 and among women 35.1 ± 0.49. Variables of weight (p<0.001), age of disease diagnosis (p<0.001), time (p<0.001), gender (p<0.005), and cardiovascular diseases were significant and had effects on the trend of creatinine changes among the hemodialysis patients. Creatinine mean value had an increasing trend. Conclusion:Blood creatinine had a significant effect on the performance of kidneys, and the identification of variables that affected the creatinine level was highly helpful in controlling the performance of the kidneys. The results of most studies conducted on hemodialysis patients indicated that by measuring and controlling variables like weight, tobacco consumption, and control of related diseases like blood pressure could predict and control creatinine changes precisely.


Intraoperative ultrasonography in cystic brain lesions.
Four neurosurgical patients were operated on under real-time ultrasonographic guidance. Two had cystic tumors which were drained through the unincised dura. In one patient a brain abscess was located intraoperatively by ultrasound after a small craniotomy. In a fourth patient with multiple abscesses, one abscess was drained under ultrasonographic guidance through a previous craniotomy. Using intraoperative ultrasonography the length of the operation can be shortened and normal brain tissue spared. Intraoperative ultrasonography is of special value in cystic lesions which can be drained under ultrasonographic guidance.


Thermodynamics and kinetics of an A-U RNA base pair under force studied by molecular dynamics simulations.
Mechanical force has been widely used to study RNA folding and unfolding. Understanding how the force affects the opening and closing of a single base pair, which is a basic step for RNA folding and unfolding and a fundamental behavior in some important biological activities, is crucial to understanding the mechanism of RNA folding and unfolding under mechanical force. In this work, we investigated the opening and closing process of an RNA base pair under mechanical force with constant-force stretching molecular dynamics simulations. It was found that high mechanical force results in overstretching, and the open state is a high-energy state. The enthalpy and entropy change of the base-pair opening-closing transition were obtained and the results at low forces were in good agreement with the nearest-neighbor model. The temperature and force dependence of the opening and closing rates were also obtained. The position of the transition state for the base-pair opening-closing transition under mechanical force was determined. The free energy barrier of opening a base pair without force is the enthalpy increase, and the work done by the force from the closed state to the transition state decreases the barrier and increases the opening rate. The free energy barrier of closing the base pair without force results from the entropy loss, and the work done by the force from the open state to the transition state increases the barrier and decreases the closing rate. The transition rates are strongly dependent on the temperature and force, while the transition path times are weakly dependent on force and temperature.


Mutation spectrum revealed by breakpoint sequencing of human germline CNVs.
Precisely characterizing the breakpoints of copy number variants (CNVs) is crucial for assessing their functional impact. However, fewer than 10% of known germline CNVs have been mapped to the single-nucleotide level. We characterized the sequence breakpoints from a dataset of all CNVs detected in three unrelated individuals in previous array-based CNV discovery experiments. We used targeted hybridization-based DNA capture and 454 sequencing to sequence 324 CNV breakpoints, including 315 deletions. We observed two major breakpoint signatures: 70% of the deletion breakpoints have 1-30 bp of microhomology, whereas 33% of deletion breakpoints contain 1-367 bp of inserted sequence. The co-occurrence of microhomology and inserted sequence is low (10%), suggesting that there are at least two different mutational mechanisms. Approximately 5% of the breakpoints represent more complex rearrangements, including local microinversions, suggesting a replication-based strand switching mechanism. Despite a rich literature on DNA repair processes, reconstruction of the molecular events generating each of these mutations is not yet possible.


Haemodynamic and humoral reaction in arterial hypertension during acute blood pressure lowering induced by nitroglycerin.
The aim of the study was to test whether there are typical changes in haemodynamics and humoral regulation in untreated hypertensives compared to normotensives with acute lowering of blood pressure (and venous return) induced by nitroglycerin (NTG). 23 hypertensives were investigated by radiocardiography and microcatheterization of the pulmonary artery as well as by means of humoral analyses in comparison to 10 normotensives. After performing the studies at rest and during exercise, 0.8 mg NTG was given and the investigations were repeated. There were only insignificant differences in cardiac output and left ventricular filling pressure (PAEDP) at rest and during exercise between both groups. The pressure reductions due to NTG were also similar. Plasma renin activity and plasma kallikrein did not differ in hypertensives and normotensives either at rest and during exercise or after NTG. The prostaglandins (PgE, PgF2-alpha, PgI) were extremely variable. In hypertensives, only PgI was decreased, with increase after NTG, at rest. Thus, PgI is the only humoral indicator participating in blood pressure lowering induced by NTG.


Multigene phylogeny, phylogenetic network, and morphological characterizations reveal four new arthropod-associated Simplicillium species and their evolutional relationship.
Simplicillium species are widely distributed and commonly found on various substrates. A minority of species are associated with arthropods. A spider-associated species Simplicillium araneae, and three insect-associated species, Simplicillium coleopterorum, Simplicillium guizhouense, and Simplicillium larvatum, are proposed as novel species based on a multi-locus phylogenetic analysis and morphological characteristics. These Simplicillium species completely fit the nutritional model of Hypocreales fungi and could be used as a model to study their evolutionary relationship. A phylogenetic network analysis based on ITS sequences suggests that a host jump was common among Simplicillium species, and S. araneae may have originally come from an insect host and then jumped to a spider host. However, the evolutionary relationship of S. coleopterorum, S. guizhouense, and S. larvatum was not clear in the phylogenetic network and more sequencing information should be added to the network. In addition, strain CBS 101267 was identified as Simplicillium subtropicum.


Spectrum-Effect Relationship between HPLC Fingerprints and Antioxidant Activity of Yangyin Tongnao Prescription.
Yangyin Tongnao (YYTN) prescription is used as a traditional Chinese herbal formula, and it has antioxidant activity that mainly contributes in the treatment of cardiovascular and cerebrovascular diseases. However, the compounds related to its antioxidant activity are still unknown. In the present study, the fingerprints of YYTN extracts under different extraction conditions were obtained by high performance liquid chromatography (HPLC) to identify the common peaks to all the samples processed. A 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay and ferric reducing antioxidant power (FRAP) assay were carried out to evaluate the antioxidant activity of the extracts. Spectrum-effect relationship between HPLC fingerprints and antioxidant activity of YYTN was assessed by Pearson product-moment correlation coefficient (PPMCC) and multiple linear regression analysis (MLRA). The results showed that peaks 5, 6, 13, 15, and 24 of the fingerprints were closely connected to antioxidant activity. Five peaks were identified: vanillic acid (P5), puerarin (P7), ferulic acid (P13), daidzein (P21), and formononetin (P23). Our study successfully established the spectrum-effect relationship between HPLC fingerprints and antioxidant activity of YYTN, which provided a general method for establishing quality standards with a combination of chromatography and antioxidant activity.


Genital fistula--our experience.
Genital fistulas cause immense physical and psychosocial problem in women's life. The present study was conducted to note the varieties of genital fistula as well as their causative factors and the results of the operative corrections. Altogether 42 patients with different varieties of genital fistula were enrolled in the study. The causative factors of the genital fistulas, specially, that of vesicovaginal fistulas were thoroughly enquired. After confirming the diagnosis, the operative corrections were undertaken. Among the varieties of genital fistula, 76.19% were vesicovaginal fistula, 11.90% were rectovaginal fistula and 4.76%, 4.76% and 2.38% cases of ureterovaginal, urethrovaginal and vesicocervical fistulas respectively. The primipara women were the major sufferers of genital fistulas due to obstetric grounds. Regarding aetiologies of vesicovaginal fistulas, 71.87% patients had obstetric reasons, after prolonged labour, instrumental delivery and after caesarean section due to obstructed labour. Abdominal hysterectomy (44.44%) topped the list of the gynaecological causes of vesicovaginal fistulas. The cases of ureterovaginal fistulas were after abdominal hysterectomy. One case of urethrovaginal fistula was due to some chemical application for correction of genital prolapses. The rectovaginal fistulas were mostly due to obstetric reasons. The success rate after the first attempt of repair of vesicovaginal fistula was 82.75% and overall failure was 10.34%. The other varieties of fistulas were repaired with 100% success rate. The incidence of genital fistulas can be reduced by vigilant obstetric care and meticulous surgery.


Wandering along the epigenetic timeline.
Increasing life expectancy but also healthspan seems inaccessible as of yet but it may become a reality in the foreseeable future. To extend lifespan, it is essential to unveil molecular mechanisms involved in ageing. As for healthspan, a better understanding of the mechanisms involved in age-related pathologies is crucial. We focus on the epigenetic side of ageing as ageing is traced by specific epigenetic patterns and can be measured by epigenetic clocks. We discuss to what extent exposure to environmental factor, such as alcohol use, unhealthy diet, tobacco and stress, promotes age-related conditions. We focused on inflammation, cancer and Alzheimer's disease. Finally, we discuss strategies to reverse time based on epigenetic reprogramming. Reversibility of the epigenetic marks makes them promising targets for rejuvenation. For this purpose, a better understanding of the epigenetic mechanisms underlying ageing is essential. Epigenetic clocks were successfully designed to monitor these mechanisms and the influence of environmental factors. Further studies on age-related diseases should be conducted to determine their epigenetic signature, but also to pinpoint the defect in the epigenetic machinery and thereby identify potential therapeutic targets. As for rejuvenation, epigenetic reprogramming is still at an early stage.


Spectrum of congenital heart disease in Malta. An excess of lesions causing right ventricular outflow tract obstruction in a population-base study.
To quantify birth prevalence and spectrum of congenital heart disease in the Island population of Malta, and compare these rates with previous studies. All patients diagnosed as having congenital heart disease by echocardiography, cardiac catheterization, surgery or post-mortem by 1 year of age between 1990-1994 were included. There were 231 cases of live born congenital heart disease with a birth prevalence of 8.8/1000 live births. The commonest lesions were ventricular septal defect, pulmonary stenosis and tetralogy of Fallot. The rates of individual lesions were compared with two recent epidemiological studies with similar methodologies. Although the overall birth prevalence of congenital heart disease was similar in three studies, significantly higher rates of pulmonary stenosis, tetralogy of Fallot and double outlet right ventricle were found in Malta, all of which predispose to right ventricular outflow tract obstruction. In contrast, there were lower rates of lesions causing left ventricular outflow tract obstruction. A higher rate of ventricular septal defect was also found. The Maltese gene pool may contain an inherent predisposition towards lesions causing right ventricular outflow tract obstruction.


Review of species of the genus Nicotikis Marseul, 1883 (Coleoptera: Histeridae) from Southeast Asia.
A study of specimens of family Histeridae from Southeast Asia yielded two species of the genus Nicotikis, which are here described: Nicotikis kabakovi sp. n. (Thailand and Vietnam) and N. korshunovi sp. n. (Thailand). Both species are illustrated and a key to species of Nicotikis from Southeast Asia is provided.


Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy.
To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response. Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values. Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy.


The rhabdomyoblast in mixed Müllerian tumors of the uterus and ovary. An immunohistochemical study of myoglobin in 25 cases.
Forty per cent of 25 uterine and ovarian mixed müllerian tumors contained stainable myoglobin that was present in the abundant cytoplasm of large rounded tumor cells. Intracytoplasmic cross striations identified rhabdomyoblasts in 32% of the cases, but were difficult to find. The authors believe that the immunoperoxidase technic successfully demonstrates skeletal muscle differentiation in a high proportion of mixed müllerian tumors and may be employed as a suitable diagnostic aid. However, the nonspecific staining of benign and malignant squamous elements should be interpreted with caution.


Interaction between resting pulmonary ventilation function and cardiac autonomic function assessed by heart rate variability in young adults.
An association between ambient air pollution and reduced cardiac autonomic function assessed by heart rate variability (HRV) mainly in elderly persons has been suggested by a number of epidemiological studies, but the link between the HRV and pulmonary function in humans remains unknown although such air pollution should primarily affect pulmonary function. To clarify this link, pulmonary ventilation parameters such as oxygen uptake (V(O(2))) and carbon dioxide output (V(CO(2))), as well as the HRV with spectral analysis (high- and low-frequency components of HRV, i.e., CCV(HF) and CCV(LF), reflecting cardiac parasympathetic and sympathetic activities, respectively), were measured in 66 healthy women aged 19-20 years after an overnight fast of 12 h. Significant correlations were found between the CCV(HF) of HRV and both the end-tidal carbon dioxide concentration (FET(CO(2))) and gas exchange ratio (V(CO(2))/V(O(2))) in the subjects (partial correlation coefficients r = 0.354 and 0.320, respectively), whereas there was no significant connection between the FET(CO(2)) and the V(CO(2))/V(O(2)). Similarly, the CCV(LF) correlated significantly with the resting tidal volume of lung (r = 0.364). These findings suggest that resting pulmonary ventilation function interacts with cardiac autonomic function assessed by the HRV, at least in healthy young adults, which may be useful for explaining the pathophysiology concerning the short-term effect of air pollution such as fine particulate matter on cardiovascular function.


Recent strategy for the management of advanced testicular cancer.
Testicular cancer is the most common cancer in young men and the cure rate has been approximately 80% since the introduction of cisplatin in the 1970s. BEP therapy (including bleomycin, etoposide and cisplatin) has become a standard induction therapy instead of PVB therapy (cisplatin, vinblastin and bleomycin). However, the patients with incomplete responses to cisplatin-based first-line therapy or with relapsed disease have an extremely poor prognosis. For such difficult-to-treat patients, there are some proposed treatment options such as ifosfamide-containing salvage chemotherapy or high-dose chemotherapy (HDCT). HDCT with bone marrow rescue has been carried out as salvage or induction chemotherapy. However, a randomized control trial did not show the superiority to conventional first line therapy or salvage therapy. Therefore, a new anticancer agent was tested for cisplatin-refractory or resistant testicular cancer. The development of combination therapy with new anticancer agents such as paclitaxel and irinotecan seems to be effective for these patients. TIP therapy including paclitaxel, ifosfamide and cisplatin would be a standard second line therapy for the patients with BEP failure. Residual tumor resection including retroperitoneal lymph node dissection integrated with induction and salvage chemotherapy still remains to play an important role to achieving a cure for advanced testicular cancer because there is no modality to predict residual viable cancer cells or teratoma element in the residual tumors. In the present review, we discuss and focus on the recent treatment strategy of advanced testicular cancer.


Energy alignment induced negative differential resistance: the role of hybrid states in aromatic molecular devices.
Hybridization in aromatic molecules plays an important role in determining their electron transport properties. When an sp(2) bonded aromatic ring hybridizes with a carbon pair in either sp(3), sp(2), or sp form, only sp(2) and sp result in a delocalized state across the whole molecule, opening a channel for transport. At the same time negative differential resistance (NDR) is found only in the sp(2) and sp cases. An energy alignment scheme is adopted to elucidate the NDR process. This is constructed by comparing the positions of frontier molecular levels and the states of leads. It is revealed that the alignment between lead states located around the Fermi energy with the lowest unoccupied molecular orbital of the central molecule is the main cause of the NDR.


Anticalculus effect of a cetylpyridinium chloride/zinc gluconate mucoadhesive gel: results of a randomized, double-blind, controlled clinical trial.
This randomized, double-blind, controlled clinical trial investigated the anticalculus effect of a cetylpyridinium chloride/ zinc gluconate (CPC/ZG) mucoadhesive gel. The 80 adults from the San Francisco area who fulfilled the enrollment criteria were stratified based on total Volpe-Manhold Index (VMI) scores (low, medium, or high), gender, and other demographic data. Within these strata, they were randomly assigned to the CPC/ZG gel group or the placebo gel group, and underwent a baseline oral soft tissue (OST) examination. Subjects were dispensed Oral-B Indicator 35 Compact Head soft toothbrushes and Colgate Cavity Protection MFP toothpaste, and instructed to brush twice daily using these products. Every night for three months, following the nighttime brushing and just before retiring, subjects applied their assigned treatment gel to the lingual surfaces of the six mandibular anterior teeth. They were instructed not to eat or drink until morning and to avoid using other methods of interdental cleaning between the treated teeth, except to remove impacted food. Total VMI scores and OST examination findings obtained at three months were compared with baseline findings. Seventy-eight (78) of the 80 subjects complied with the protocol and completed the study. After three months of treatment, the CPC/ZG group showed a 30% decrease in mean VMI score compared with a 0% decrease in the placebo group. OST examination at three months revealed no serious adverse events in either group. Results of this clinical trial indicate that regular use of the CPC/ZG gel, with or without the use of floss or other interdental cleaning products, yields a statistically significant reduction in calculus.


The effect of anesthetic technique on survival in human cancers: a meta-analysis of retrospective and prospective studies.
Animal models have shown that regional anesthesia (combined with or without general anesthesia) would attenuate the surgical stress response by preserving immune function and result in better long-term outcome. In order to test the hypothesis that cancer patients who had surgery with epidural anesthesia (EA) would have better outcome (either overall survival [OS] or recurrence-free survival [RFS]) than those who were general anesthesia (GA), we performed this meta-analysis. By searching relevant literature, a total of 14 studies containing 18 sub-studies (seven in OS analysis and eleven in RFS analysis) were identified and meta-analyzed. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the strength of association. For OS, the random-effects model was used to analyze the data and demonstrated an OS benefit in favor of EA compared with GA alone (HR = 0.84, 95% CI 0.74-0.96, P = 0.013). The influence analysis showed the robustness of the results. Specifically, a significantly positive association between EA and improved OS was observed in colorectal cancer (HR = 0.65, 95% CI 0.43-0.99, P = 0.045). For RFS, the random-effects model was used to analyze the data and no significant relationship between RFS benefit and EA (HR = 0.88, 95% CI 0.64-1.22, P = 0.457) was detected. In conclusion, our meta-analysis suggests that epidural anesthesia and/or analgesia might be associated with improved overall survival in patients with operable cancer undergoing surgery (especially in colorectal cancer), but it does not support an association between epidural anesthesia and cancer control. Prospective studies are needed to determine whether the association between epidural use and survival is causative.


A turnstile mechanism for fronts propagating in fluid flows.
We consider the propagation of fronts in a periodically driven flowing medium. It is shown that the progress of fronts in these systems may be mediated by a turnstile mechanism akin to that found in chaotic advection. We first define the modified ("active") turnstile lobes according to the evolution of point sources across a transport boundary. We then show that the lobe boundaries may be constructed from stable and unstable burning invariant manifolds (BIMs)--one-way barriers to front propagation analogous to traditional invariant manifolds for passive advection. Because the BIMs are one-dimensional curves in a three-dimensional (xyθ) phase space, their projection into xy-space exhibits several key differences from their advective counterparts: (lobe) areas are not preserved, BIMs may self-intersect, and an intersection between stable and unstable BIMs does not map to another such intersection. These differences must be accommodated in the correct construction of the new turnstile. As an application, we consider a lobe-based treatment protocol for protecting an ocean bay from an invading algae bloom.


[Ketotifen in the treatment of chronic urticaria and angioneurotic edema].
26 male and female patients, suffering chronic idiopathic urticaria and angioneurotic edema, are treated with a new synthase molecule, Ketotifen, which offers a polivalent action. Among the patients there was a great majority of females (61,5%) their mean age being 35 years. The mean duration of this urticaria was 57,3 months, being even longer in male patients. In eleven of these cases there was a previous history of atopy in their families, and sixteen patients had some episodes of atopy in the past. All the patients were treated with ketotifen, in 1 mg. tablets, usually administered before meals, with partial doses no higher than 1 mg. 3 times a day, and a total dosage ranging from 28 to 180 mg. With this dosage we attained satisfactory results in 80,8% of the cases, with complete curation in 16 patients and a remarkable improvement of symptoms in 5 patients. In only two of the cases there was no response to the treatment. Tolerance to this drug was excellent in 88,6% of the patients. For all these reasons we consider ketotifen as an excellent therapeutic agent in Chronic Idiopathic Urticaria and Angioneurotic Edema, especially in those cases in which traditional therapies have failed. We also think that ketotifen, in association with other drugs, for example, terbutaline ( SAIHAN ) may solve, at least in some patients, the therapeutical problem that these conditions present. Furthermore, the nearly complete absence of important secondary effects, as observed in our study, makes it the treatment of choice in patients with gastric intolerance to drugs, or in those patients that, owing to their occupational activities, might be exposed to a high risk of laboral accidents.


Disseminated protothecosis causing acute blindness and deafness in a dog.
A 3-year-old Collie bitch was euthanatized two weeks after the onset of blindness and deafness. The hearing deficit had been localized by clinical signs, brain stem auditory evoked responses, and impedance audiometry. Protothecosis was diagnosed by cytologic and histologic examinations. The organism was identified as Prototheca zopfii . Organisms and granulomatous lesions were found in kidney, heart, liver, skeletal muscle, thyroid gland, colon, bronchial lymph node, brain, and cochlea.


Mass vaccination against poliomyelitis in Mexico.
In 1959, oral poliovirus vaccine ( OPV ) was introduced as an antiepidemic measure in Mexico. As in many other developing countries, the vaccine was misused, coverages achieved were often poor, and an adequate cold chain was lacking. However, in 1972 a mass campaign reached 70% of children younger than five years of age, and consequently the reported cases declined sharply from 1.9 to 0.4 per 100,000 population. Due to economic restrictions, only single doses of monovalent type 1 OPV were administered to 80% of the target population in 1981, 1982, and 1983. The present incidence of poliomyelitis of 0.1 per 100,000 population represents a 96.7% reduction from the rate during the prevaccine era, when the annual average rate was 4.26 per 100,000. The present aim of poliomyelitis control is to maintain and decrease the present incidence of disease. Future plans are to continue mass vaccination in an attempt to reach small and isolated villages that have been without vaccination and limit possible rural foci of wild poliovirus.


The mediating role of negative emotions in the relationship between smoking and health-related quality of life among Chinese individuals: A cross-sectional study.
Although the negative impact of smoking on health has been confirmed in various studies, few have explored psychological factors mediating the relationship between smoking and health-related quality of life (HRQOL). This study aimed to investigate the relationship between smoking and HRQOL in the Chinese population and the mediating role of negative emotions (NEs). Survey data were derived from a cross-sectional study conducted in China from 20 June to 31 August 2022. We recruited participants from 148 cities across the country using a stratified multistage sampling method. The HRQOL of the dependent variable was measured using the Chinese version of European Quality of Life-5 Dimensions (EQ-5D-5L). The Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), and Perceived Stress Scale (PSS-4) were used to measure NE parameters including depression, anxiety, and perceived stress, as the intermediate variables. A multiple parallel mediation model was used to analyze the mediating role of NEs in smoking and HRQOL. A total of 21916 valid questionnaires were collected, of which 3010 (13.7%) and 18906 (86.3%) were categorized into smokers and non-smokers, respectively. The HRQOL (EQ-VAS score) of smokers (71.70 ± 23.08) was lower than that of non-smokers (73.69 ± 21.32), whereas the depression and anxiety levels of smokers were higher than those of non-smokers (all p<0.001). Moreover, smoking, NEs (depression and anxiety), and HRQOL showed pairwise correlations. According to the mediation analysis, depression (β= -0.461; 95% BCa CI: -0.664 - -0.268) and anxiety (β= -0.279; 95% BCa CI: -0.435 - -0.138) mediated the relationship between smoking and HRQOL after adjusting for demographic and life factors. These findings emphasize the necessity of studying the interaction between smoking, HRQOL, and Nes, and complementing the research on the impact of psychological factors on the HRQOL of smokers. Public health activities should focus on mental health and take targeted measures for the prevention, treatment, and rehabilitation of smokers.


Drug resistance among HIV-infected pregnant women receiving antiretrovirals for prophylaxis.
To quantify primary resistance mutations (PRMs) among HIV-1-infected women receiving antiretroviral therapy (ART) for prevention of mother-to-child transmission (MTCT). Peripheral blood mononuclear cell samples from HIV-1-infected women enrolled in a prospective cohort study in Argentina, the Bahamas, Brazil, and Mexico (NISDI Perinatal Study) were assayed for PRMs. Eligible women were those enrolled by March 2005 and diagnosed with HIV-1 infection during the current pregnancy, and who received ART for MTCT prophylaxis and were followed for 6-12 weeks postpartum. Of 819 women, 198 met the eligibility criteria. At enrollment, 98% were asymptomatic, 62% had plasma viral load < 1000 copies/ml, 53% had CD4+ cell count > or = 500 cells/microl, and 78% were ART-exposed (mean duration, 8.0 weeks; 95% confidence interval, 7.1-8.9). The most complex ART regimen during pregnancy was usually (81%) a three-drug regimen [two nucleoside reverse transcriptase inhibitors (NRTIs) + one protease inhibitor or two NRTIs + one non-nucleoside reverse transcriptase inhibitor). PRMs were observed in samples from 19 (16%) of 118 women that were amplifiable at one or both time points [11/76 (14%) at enrollment; 14/97 (14%) at 6-12 weeks]. The occurrence of PRMs was not associated with clinical, immunological, or virological disease stage at either time point, whether ART-naive versus exposed at enrollment, or the most complex or number of antiretroviral drug regimens received during pregnancy (P > 0.1). Of 55 women with amplifiable samples at both time points, PRMs were detected in 11 samples (20%). PRMs occurred among 16.1% of relatively healthy HIV-1-infected mothers from Latin American and Caribbean countries receiving MTCT prophylaxis.


TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts.
Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-β (TGF-β), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-κB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1α (IL-1α) signaling and non-COX-2/PGE2 pathway through TGF-β receptor signaling. TGF-β1 and IL-1α produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma.


The domed architecture of Giardias ventral disc is necessary for attachment and host pathogenesis.
After ingestion of dormant cysts, the widespread protozoan parasite Giardia lamblia colonizes the host gastrointestinal tract via direct and reversible attachment using a novel microtubule organelle, the ventral disc. Extracellular attachment to the host allows the parasite to resist peristaltic flow, facilitates colonization and is proposed to cause damage to the microvilli of host enterocytes as well as disrupt host barrier integrity. The 9 um in diameter ventral disc is defined by a highly complex architecture of unique protein complexes scaffolded onto a spiral microtubule (MT) array of one hundred parallel, uniformly spaced MT polymers that bend approximately one and a quarter turns to form a domed structure. To investigate the role of disc-mediated attachment in causing epithelial cell damage, we used a new approach to rapidly create a stable quadruple knockout of Giardia of an essential ventral disc protein, MBP, using a new method of CRISPR-mediated gene disruption with multiple positive selectable markers. MBP quadruple KO mutant discs lack the characteristic domed architecture and possess a flattened crescent or horseshoe-shaped conformation that lacks the overlapping region, with severe defects in the microribbon-crossbridge (MR-CB) complex structure. MBP KO mutants are also unable to resist fluid flow required for attachment to inert surfaces. Importantly, MBP KO mutants have 100% penetrance off positive selection, which is essential for quantification of in vivo impacts of disc and attachment mutants with host cells. Using a new gastrointestinal organoid model of pathogenesis, we found that MBP KO infections had a significantly reduced ability to cause the barrier breakdown characteristic of wild-type infections. Overall, this work provides direct evidence of the role of MBP in creating the domed disc, as well as the first direct evidence that parasite attachment is necessary for host pathology, specifically epithelial barrier breakdown.


Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin.
Transient receptor potential (TRP) channels are a superfamily of ion channels termed after the trp gene in Drosophila that are diverse in structure and control a wide range of biological functions including cell development and growth, thermal regulation, and vascular physiology. Of significant interest is the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, also known as the capsaicin receptor and the vanilloid receptor 1, that is a non-selective cation channel sensitive to a host of external stimuli including capsaicin and camphor, venoms, acid/basic pH changes, and temperature. Given the multiple modalities that TRPV1 receptors impact in the body, we examined and discussed the role of these receptors in vasomotor control, metabolic disorders, cellular injury, oxidative stress, apoptosis, autophagy, and neurodegenerative disorders and their overlap with other signal transduction pathways that impact trophic factors. Surprisingly, TRPV1 receptors do not rely entirely upon calcium signaling to affect cellular biology, but also have a close relationship with the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and protein kinase B (Akt) that have roles in pain sensitivity, stem cell development, cellular survival, and cellular metabolism. These pathways with TRPV1 converge in the signaling of growth factors with recent work highlighting a relationship with erythropoietin (EPO). Angiogenesis and endothelial tube formation controlled by EPO requires, in part, the activation of TRPV1 receptors in conjunction with Akt and AMPK pathways. TRPV1 receptors could prove to become vital to target disorders of vascular origin and neurodegeneration. Broader and currently unrealized implementations for both EPO and TRPV1 receptors can be envisioned for for the development of novel therapeutic strategies in multiple systems of the body.


Neurochemical and behavioral responses to stress.
The relationship between the hypothalamic - pituitary - adrenocortical (HPA) and the sympathetic - adrenomedullary (SA) systems is discussed by considering their role at the central and peripheral level. HPA and SA responses are not independent of each other, which indicates a number of hormonal, monoaminergic and peptidergic reactions at the brain level. It is demonstrated that a number of interacting systems and feedback mechanisms take part in stress responses.


'Death is the cure of all diseases': using the General Register Office cause of death statistics for 1837-1920.
The series of cause of death statistics for England and Wales published by the General Register Office between 1837 and 1920 are a fundamental source for historians studying death and disease in this period. Attention was first drawn to the historical importance of this source, and to its principal shortcomings, by Bill Luckin in 1980. Research by a number of scholars in recent years on mortality and morbidity in the nineteenth century has uncovered further problems, which are outlined in this essay under two heads: general problems, and problems relating to specific cause of death categories.


Niche partitioning and the storage effect facilitate coexistence in an amphibian community.
Virtually all natural community assemblages are dominated by a handful of common species. Dominant species can exert negative impacts on biodiversity through competitive exclusion, and thus there is a strong incentive to understand imbalances in community composition, changes in dominance hierarchies through time, and mechanisms of coexistence. Pond-breeding amphibians that utilize ephemeral wetlands provide an excellent opportunity to evaluate theoretical predictions of community composition in stochastic environments. One of the most striking features of pond-breeding amphibians is the marked stochastic fluctuations in abundance across years. Given strong theoretical and empirical links between evenness and biomass, one would expect community evenness to change from year to year. Moreover, if different species exhibit different boom-and-bust reproductive cycles, then a storage effect may help to explain why one species does not outcompete all others. Here, we explore the interplay between biotic and abiotic conditions in shaping amphibian communities at two ephemeral wetlands on Eglin Air Force Base, Florida. We document consistent community composition over 6 years of monitoring, resulting from a lack of species turnover and similar responses of all community members to environmental conditions. The similar dynamics of species argues against a storage effect as the sole mechanism for coexistence and instead points to niche partitioning as a more important factor. In support of this conclusion, we show that the degree of synchrony in breeding migrations only correlates with environmental conditions within species, not between species. The lack of pattern seen between species implies that individuals are somewhat constrained in the timing of breeding migrations, perhaps owing in part to competition with other community members. We hope that our work reinvigorates interest in amphibian communities and highlights ephemeral wetlands as model systems to study community dynamics in stochastic environments.


miR‑132 in atrial fibrillation directly targets connective tissue growth factor.
Atrial fibrillation (AF) is the most frequently occurring, persistent cardiac arrhythmia, and the hallmark of AF‑dependent structural remodeling is atrial fibrosis. Connective tissue growth factor (CTGF) is important in the process of fibrosis. The association between miRNA and CTGF in AF‑dependent fibrosis remains to be elucidated. The present study aimed to determine if microRNA (miR)‑132 was able to regulate CTGF with an anti‑fibrotic effect in AF. A total of ten dogs or patients were assigned to control (n=4) and AF groups (n=6). The left atrium of dogs or right atrial appendage of patients was observed. Following this, cardiac fibroblasts of adult rats were treated with or without angiotensin II (Ang II). Furthermore, cardiac fibroblasts were transfected with miR‑132 mimics, inhibitor or negative control. The expression of miR‑132 and CTGF were analyzed by reverse transcription‑quantitative polymerase chain reaction or western blotting. These analyses demonstrated that miR‑132 expression was decreased and CTGF increased in the human and canine models with AF. The expression of miR‑132 and CTGF protein levels were upregulated in Ang II stimulated cardiac fibroblasts of adult rats. Furthermore, when miR‑132 was introduced into cardiac fibroblasts, the expression of miR‑132 increased significantly whereas the expression of CTGF decreased. Inverse results were observed when cardiac fibroblasts were transfected with miR‑132 inhibitor. The luciferase reporter assay was then performed to confirm that miR‑132 may suppress CTGF expression by binding to its 3'‑untranslated region. In conclusion, miR‑132 may target CTGF in regulating fibrosis in Ang II‑treated cardiac fibroblasts. These findings may aid in providing potential therapeutic targets in the treatment of AF.


Asymptomatic anorectal Chlamydia trachomatis and Neisseria gonorrhoeae infections are associated with systemic CD8+ T-cell activation.
Oral preexposure prophylaxis (PrEP) has been established as a pivotal strategy in HIV prevention. However, bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis and Neisseria gonorrhoeae, are also highly prevalent. Although the presence of STI-related mucosal lesions is a known risk factor for HIV acquisition, the potential increase in risk associated with asymptomatic STIs is not completely understood. Recent data demonstrated higher T-cell activation is a risk factor for sexually acquired HIV-1 infection. We examined the effect of asymptomatic C. trachomatis and N. gonorrhoeae anorectal infection on systemic immune activation, potentially increasing the risk of HIV acquisition. We analyzed samples from participants of PrEP Brasil, a demonstration study of daily oral emtricitabine/tenofovir disoproxil fumarate HIV PrEP among healthy MSM, for T-cell activation by flow cytometry. We included 34 asymptomatic participants with anorectal swab for C. trachomatis and/or N. gonorrhoeae infection, whereas negative for other STIs, and 35 controls. We found a higher frequency of human leukocyte antigen DRCD38 CD8 T cells (1.5 vs. 0.9%, P < 0.005) and with memory phenotype in the group with asymptomatic C. trachomatis and/or N. gonorrhoeae infection. Exhaustion and senescence markers were also significant higher in this group. No difference was observed in the soluble CD14 levels. Our findings suggest asymptomatic anorectal C. trachomatis and/or N. gonorrhoeae increase systemic immune activation, potentially increasing the risk of HIV acquisition. Regular screening and treatment of asymptomatic STIs should be explored as adjuvant tools for HIV prevention.


Preferred delivery method and acceptability of Wheat-Soy Blend (WSB++) as a daily complementary food supplement in northwest Bangladesh.
Fortified blended foods (FBFs) are widely used to prevent undernutrition in early childhood in food-insecure settings. We field tested enhanced Wheat Soy Blend (WSB++)-a FBF fortified with micronutrients, milk powder, sugar, and oil-in preparation for a complementary food supplement (CFS) trial in rural northwestern Bangladesh. Formative work was conducted to determine the optimal delivery method (cooked vs. not) for this CFS, to examine mothers' child feeding practices with and acceptance of the WSB++, and to identify potential barriers to adherence. Our results suggest WSB++ is an acceptable CFS in rural Bangladesh and the requirement for mothers to cook WSB++ at home is unlikely to be a barrier to its daily use as a CFS in this population.


Changes in appetite, energy intake, body composition, and circulating ghrelin constituents during an incremental trekking ascent to high altitude.
Circulating acylated ghrelin concentrations are associated with altitude-induced anorexia in laboratory environments, but have never been measured at terrestrial altitude. This study examined time course changes in appetite, energy intake, body composition, and ghrelin constituents during a high-altitude trek. Twelve participants [age: 28(4) years, BMI 23.0(2.1) kg m-2] completed a 14-day trek in the Himalayas. Energy intake, appetite perceptions, body composition, and circulating acylated, des-acylated, and total ghrelin concentrations were assessed at baseline (113 m, 12 days prior to departure) and at three fixed research camps during the trek (3619 m, day 7; 4600 m, day 10; 5140 m, day 12). Relative to baseline, energy intake was lower at 3619 m (P = 0.038) and 5140 m (P = 0.016) and tended to be lower at 4600 m (P = 0.056). Appetite perceptions were lower at 5140 m (P = 0.027) compared with baseline. Acylated ghrelin concentrations were lower at 3619 m (P = 0.046) and 4600 m (P = 0.038), and tended to be lower at 5140 m (P = 0.070), compared with baseline. Des-acylated ghrelin concentrations did not significantly change during the trek (P = 0.177). Total ghrelin concentrations decreased from baseline to 4600 m (P = 0.045). Skinfold thickness was lower at all points during the trek compared with baseline (P ≤ 0.001) and calf girth decreased incrementally during the trek (P = 0.010). Changes in plasma acylated and total ghrelin concentrations may contribute to the suppression of appetite and energy intake at altitude, but differences in the time course of these responses suggest that additional factors are also involved. Interventions are required to maintain appetite and energy balance during trekking at terrestrial altitudes.


Characterization and application of monoclonal antibodies against turbot (Scophthalmus maximus) Rhabdovirus.
Five monoclonal antibodies (mAbs), 1G8, 1H9, 2D2, 2D3, and 2F5, against Scophthalmus maximus rhabdovirus (SMRV) were prepared. Characterization of the mAbs included indirect enzyme-linked immunosorbent assay, isotyping, viral inhibition assay, immunofluorescence staining of virus-infected cell cultures, and Western blot analysis. Isotyping revealed that 1G8 and 1H9 were of the IgG2b subclass and that the other three were IgM. 2D2, 2D3, and 2F5 partially inhibited SMRV infection in epithelioma papulosum cyprinid (EPC) cell culture. Western blotting showed that all five mAbs could react with two SMRV proteins with molecular masses of approximately 30 kDa (P) and 26 kDa (M). These two proteins were localized within the cytoplasm of SMRV-infected EPC cells by immunofluorescence assay. Also, progressive foci of viral replication in cell cultures were monitored from 6 to 24 h, using mAb 2D3 as the primary antibody. A flow cytometry procedure was used to detect and quantify SMRV-infected (0.01 PFU/cell) EPC cells with mAb 2D3, and 10.8% of cells could be distinguished as infected 36 h postinfection. Moreover, mAb 2D3 was successfully applied for the detection of viral antigen in cryosections from flounder tissues by immunohistochemistry tests.


Treating adolescent obesity: a pilot project in a school.
A weight control program for junior high school students was developed to change eating, exercise and habit patterns. The course included dietary management, physical activity and behavior modification techniques. Classes were structured to emphasize peer group involvement and daily practical application. The curriculum was compiled in a book for educational personnel. The program was tested as a pilot project with a selected group of eighth grade obese adolescent girls and a comparison group. Immediately after the course, the subjects' percent of overweight had decreased; at a subsequent eight-month follow-up, additional losses were noted. The percent of overweight of the girls in the comparison group remained relatively unchanged. While the program was successful with this particular group of students, several key questions, requiring further study, were defined.


Self-Assembly of Silver Metal Clusters of Small Atomicity on Cyclic Peptide Nanotubes.
Subnanometric noble metal clusters, composed by only a few atoms, behave like molecular entities and display magnetic, luminescent and catalytic activities. However, noncovalent interactions of molecular metal clusters, lacking of any ligand or surfactant, have not been seen at work. Theoretically attractive and experimentally discernible, van der Waals forces and noncovalent interactions at the metal/organic interfaces will be crucial to understand and develop the next generation of hybrid nanomaterials. Here, we present experimental and theoretical evidence of noncovalent interactions between subnanometric metal (0) silver clusters and aromatic rings and their application in the preparation of 1D self-assembled hybrid architectures with ditopic peptide nanotubes. Atomic force microscopy, fluorescence experiments, circular dichroism and computational simulations verified the occurrence of these interactions in the clean and mild formation of a novel peptide nanotube and metal cluster hybrid material. The findings reported here confirmed the sensitivity of silver metal clusters of small atomicity toward noncovalent interactions, a concept that could find multiple applications in nanotechnology. We conclude that induced supramolecular forces are optimal candidates for the precise spatial positioning and properties modulation of molecular metal clusters. The reported results herein outline and generalize the possibilities that noncovalent interactions will have in this emerging field.


In vitro interactions of micafungin with amphotericin B, itraconazole or fluconazole against the pathogenic phase of Penicillium marneffei.
Penicillium marneffei infection is an important disease among human immunodeficiency virus patients in south-east Asia, including southern China. However, therapeutic strategies are limited. Combination regimens with synergistic drugs could provide additional options for treating penicilliosis. We evaluated the in vitro efficacy of combining micafungin with amphotericin B, itraconazole or fluconazole against the pathogenic yeast form of P. marneffei. Twenty isolates of P. marneffei were assayed. Drug interactions were assessed with the chequerboard technique using the CLSI (formerly the NCCLS) microdilution method (M27-A2) with minor modifications. The fractional inhibitory concentration index (FICI) was used to classify drug interactions. Results were interpreted as follows: synergy, FICI < or =0.5; no interaction, FICI >0.5 and < or =4.0; or antagonism, FICI >4.0. The in vitro interactions of micafungin combined with itraconazole showed the highest percentage of synergic interaction (65%); for the micafungin/amphotericin B combination, 50% of the isolates had synergic interaction. Micafungin significantly enhanced the antifungal activity of amphotericin B and itraconazole against P. marneffei. Micafungin, however, did not enhance the activity of fluconazole and no synergism was observed with this combination. Antagonism was not detected for any of the antifungal combinations assayed. The results of this study suggest that micafungin enhances the efficacy of itraconazole or amphotericin B in vitro and indicate that an echinocandin, such as micafungin, might have a potential role in combination therapy among patients infected with P. marneffei.


Hereditary keratosis palmoplantaris varians of Wachters (keratosis palmoplantaris striata et areata).
Keratosis palmoplantaris varians of Wachters is a rare autosomal dominant disorder. A 17-year-old boy with characteristic clinical and histopathologic findings of 10 years' duration is described. He displayed yellowish patchy and linear hyperkeratoses of the palms and nummular keratoses on the soles that were symmetrical and often confluent, specifically on the pressure points. Because there was no family history of a similar pattern, he probably represented an isolated case in his family. The typical clinical presentation, differential diagnosis, and classification of hereditary palmoplantar keratoses are discussed.


Modulation of voltage-dependent Ca2+ conductance by changing Cl- concentration in rat lactotrophs.
In pituitary cells, voltage-dependent Ca2+ channels play an important role in such physiological processes as exocytosis, secretion, the cell cycle, and proliferation. Thus mechanisms that modulate voltage-dependent Ca2+ channel activity participate indirectly in regulating intracellular Ca2+ concentration. We have shown a new modulating mechanism for voltage-dependent Ca2+ channels by demonstrating that Ca2+ influx is influenced by Cl-. To evaluate the role of Cl- on Ca2+ conductance coupling, we first measured the intracellular Cl- concentration of rat lactotrophs using the Cl(-)-sensitive fluorescence probe sulfopropylquinolinium by simple microspectrofluorometry or combined with electrophysiology. We found an average intracellular Cl- concentration of rat lactotrophs of approximately 60 mM (n = 39). Using the whole cell tight-seal recording technique, we showed that a reduction in external Cl- concentration ([Cl-]o) and a decrease in Cl- conductances affected Ca2+ conductance as measured by Ba2+ movement through the Ca2+ channels (I(Ba)). Low [Cl-]o (39 mM) induced a decrease in Ca2+ entry via voltage-gated Ca2+ channels (-27.75 +/- 4% of normalized I(Ba)). Similarly, blockade of the Cl- conductance by 1 mM 9-anthracene carboxylic acid induced a decrease in I(Ba) (-26 +/- 6% of normalized I(Ba)). This modulation of I(Ba) was inhibited by 24-h pretreatment of the cells with pertussis toxin (1 microg/ml), suggesting that changes in Cl- concentration induced by low [Cl-]o and 9-anthracene carboxylic acid interfered with the phosphorylation of G proteins involved in Ca2+ channel activation. These results suggest a feedback mechanism based on constant interaction between Ca2+ and Cl-. Finally, they also emphasize the physiological role of Cl- in rat lactotrophs.


[Gene expression, metabolic regulation and aging].
The biological ageing comprises changes of of structure and function depending on time with the beginning of the autonomy of a living being up to death. On the one hand, the causes of this process are genetically fixed, on the other hand they depend on environmental factors and are not programmed. In the course of life the total genome and also the nucleic acid underlie influences, which must have consequences on the gene expression. In these cases the changed sensitivity of the genetic apparatus in comparison to hormones is impressionably changed. The decreased protein biosynthesis may be stimulated by increased amino acid concentrations and by SH-substances, Age-depending changes are also observed for enzymatically catalyzed reactions and in the regulation of chains of metabolism. At first the biologic ageing appears as a complex multiform process, which reaches the simplest integration level in the cellular metabolism.


Extended gene expression by medium exchange and repeated transient transfection for recombinant protein production enhancement.
Production of recombinant products in mammalian cell cultures can be achieved by stable gene expression (SGE) or transient gene expression (TGE). The former is based on the integration of a plasmid DNA into the host cell genome allowing continuous gene expression. The latter is based on episomal plasmid DNA expression. Conventional TGE is limited to a short production period of usually about 96 h, therefore limiting productivity. A novel gene expression approach termed extended gene expression (EGE) is explored in this study. The aim of EGE is to prolong the production period by the combination of medium exchange and repeated transfection of cell cultures with plasmid DNA to improve overall protein production. The benefit of this methodology was evaluated for the production of three model recombinant products: intracellular GFP, secreted GFP, and a Gag-GFP virus-like particles (VLPs). Productions were carried out in HEK 293 cell suspension cultures grown in animal-derived component free media using polyethylenimine (PEI) as transfection reagent. Transfections were repeated throughout the production process using different plasmid DNA concentrations, intervals of time, and culture feeding conditions in order to identify the best approach to achieve sustained high-level gene expression. Using this novel EGE strategy, the production period was prolonged between 192 and 240 h with a 4-12-fold increase in production levels, depending on the product type considered.


Systematic review of aspirin for thromboprophylaxis in modern elective total hip and knee arthroplasty.
There is uncertainty regarding the optimal means of thromboprophylaxis following total hip and knee arthroplasty (THA, TKA). This systematic review presents the evidence for acetylsalicylic acid (aspirin) as a thromboprophylactic agent in THA and TKA and compares it with other chemoprophylactic agents. A search of literature published between 2004 and 2014 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 13 studies were eligible for inclusion. Evidence from one good quality randomised controlled trial (RCT) showed no difference in rates of venous thrombo-embolism (VTE) in patients given aspirin or low molecular weight heparin (LMWH) following TKA. There was insufficient evidence from trials with moderate to severe risk of bias being present to suggest aspirin is more or less effective than LMWH, warfarin or dabigatran for the prevention of VTE in TKA or THA. Compared with aspirin, rates of asymptomatic deep vein thrombosis (DVT) in TKA may be reduced with rivaroxaban but insufficient evidence exists to demonstrate an effect on incidence of symptomatic DVT. Compared with aspirin there is evidence of more wound complications following THA and TKA with dabigatran and in TKA with rivaroxaban. Some studies highlighted concerns over bleeding complications and efficacy of aspirin. The results suggest aspirin may be considered a suitable alternative to other thromboprophylactic agents following THA and TKA. Further investigation is required to fully evaluate the safety and efficacy of aspirin. Cite this article: Bone Joint J 2016;98-B:1056-61.


Generation of reactive oxygen species in blood platelets.
The generation of superoxide anion radicals (O2*-) and the other reactive oxygen species (ROS) was estimated by means of cytochrome c reduction and chemiluminescence, as well in resting blood platelets and in platelets stimulated by thrombin in the presence or absence of some inhibitors of pathways involved in platelet activation. We used allopurinol (xanthine oxidase inhibitor), wortmannin (PI 3-kinase inhibitor) and staurosporine (protein kinase C inhibitor). To determine the involvement of the glutathione in ROS generation, we used L-buthionine sulfoximine (BSO) which blocks GSH synthesis. Our results confirmed that thrombin stimulates the production of ROS concomitant with metabolism of arachidonate and production of malonyldialdehyde (MDA) in blood platelets (P < 0.05) and showed that, in the presence of inhibitors, the generation of ROS in platelets (resting and stimulated) was reduced. This indicates that xanthine oxidase, PI 3-kinase or protein kinase C take part in the formation of ROS in blood platelets. Moreover, adhesion of platelets to fibrinogen and secretion of adenine nucleotides from platelets after wortmannin and staurosporine action was also inhibited. BSO not only decreased GSH level, but also reduced the amount of ROS; a correlation between the depletion of GSH and the decrease of ROS was observed (R = -0.987; P < 0.02). It is concluded that in blood platelets, ROS are produced in the receptor-mediated signaling pathways and platelet activation (arachidonic acid metabolism, the glutathione cycle, metabolism of phosphoinositoides and due to xanthine oxidase). Our results support the importance of ROS in platelet function.


Vascular thrombin receptor regulation in hypertensive rats.
Thrombin has been implicated as an important mediator of vascular lesion formation in atherosclerosis and restenosis. To investigate a potential role for thrombin signaling in the vascular response to hypertension, we have studied thrombin receptor (TR) expression and regulation in hypertensive rats. Aortic TR mRNA was upregulated by angiotensin II (Ang II)-induced hypertension (10.7 +/- 2.5 times control, P < .02), which correlated with a 4-fold increase in thrombin-induced constriction in isolated endothelium-denuded aortic rings. The AT1 receptor antagonist losartan normalized blood pressure and TR mRNA. Conversely, lowering blood pressure to the same degree with hydralazine did not abolish the upregulation of TR mRNA expression. When low-renin low-Ang II hypertension was induced in Dahl salt-sensitive rats, there was no detectable increase in the expression of aortic thrombin receptor mRNA. Finally, treatment with a chimeric heparin-binding form of the recombinant human Cu/Zn superoxide dismutase caused complete inhibition of TR mRNA upregulation, suggesting that an increased rate of superoxide anion production is an important signaling mechanism. Thus, increased TR expression via a redox-sensitive mechanism in the aortic smooth muscle of rats treated with Ang II represents a novel in vivo mechanism through which the hypertensive effects of Ang II are mediated.


Paenibacillus lacus sp. nov., isolated from a water reservoir.
A bacterial strain, designated Agd-32T, was isolated from a water sample taken from the Agongdian Reservoir in Taiwan and characterized using a polyphasic taxonomy approach. Cells of strain Agd-32T were Gram-stain-variable, aerobic, motile by means of peritrichous flagella, endospore-forming, rod-shaped and surrounded by a thick capsule. Strain Agd-32T contained anteiso-C15 : 0 and C16 : 0 as the predominant fatty acids. The major isoprenoid quinone was MK-7, and the polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophosphoglycolipid, one unidentified glycolipid, one unidentified phospholipid and one unidentified lipid. The DNA G+C content of the genomic DNA was 56.0 mol%. Strain Agd-32T contained meso-diaminopimelic acid in the cell-wall peptidoglycan. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Agd-32T belonged to the genus Paenibacillus and was most closely related to Paenibacillus tarimensis with sequence similarity of 96.1 % and less than 95.9 % sequence similarity with other members of the genus. On the basis of the phylogenetic inference and phenotypic data, strain Agd-32T should be classified as a representative of a novel species, for which the name Paenibacillus lacus sp. nov. is proposed. The type strain is Agd-32T (=BCRC 80902T=LMG 28836T=KCTC 33691T).


A rare case of monozygotic iniodymic diprosopiasis in a German Holstein calf.
Craniofacial duplication abnormity is a rare phenomenon in buiatric practice. This report attends to a male German Holstein calf which could be classified as a diprosopic iniodymus. A fetus exhibiting a doubled face was delivered after fetotomy. To our knowledge, this is the first description of diprosopiasis with two cranial cavities as well as two separate encephala in a calf showing the potential extent of duplication. Throughout this work also the question is answered of whether this malformation in a bovine species arose from one embryo or rather, there is a dizygotic background by genotyping of tissue samples from both parts of the diprosopus. Regarding etiology, not only hereditary dispositions including among others a failed function of the signaling molecule Sonic hedgehog mediating regulation of craniofacial morphogenesis, but also incompletely separated monozygotic twins are discussed.


Closed-loop automated reaching apparatus (CLARA) for interrogating complex motor behaviors.
Objective.Closed-loop neuromodulation technology is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. To address this need, we developed CLARA, a closed-loop automated reaching apparatus.Approach.Using breakthroughs in computer vision, CLARA integrates fully-automated, markerless kinematic tracking of multiple features to classify animal behavior and precisely deliver neural stimulation based on behavioral outcomes. CLARA is compatible with advanced neurophysiological tools, enabling the testing of neurostimulation devices and identification of novel neurological biomarkers.Results.The CLARA system tracks unconstrained skilled reach behavior in 3D at 150 Hz without physical markers. The system fully automates trial initiation and pellet delivery and is capable of accurately delivering stimulation in response to trial outcome with short latency. Kinematic data from the CLARA system provided novel insights into the dynamics of reach consistency over the course of learning, suggesting that learning selectively improves reach failures but does not alter the kinematics of successful reaches. Additionally, using the closed-loop capabilities of CLARA, we demonstrate that vagus nerve stimulation (VNS) improves skilled reach performance and increases reach trajectory consistency in healthy animals.Significance.The CLARA system is the first mouse behavior apparatus that uses markerless pose tracking to provide real-time closed-loop stimulation in response to the outcome of an unconstrained motor task. Additionally, we demonstrate that the CLARA system was essential for our investigating the role of closed-loop VNS stimulation on motor performance in healthy animals. This approach has high translational relevance for developing neurostimulation technology based on complex human behavior.


Preduodenal Portal Vein Associated With Intestinal Malrotation and Jejunal Atresia.
Preduodenal portal vein (PDPV) is a rare congenital anomaly commonly associated with other gastrointestinal abnormalities. We report the case of a female neonate with a PDPV, intestinal malrotation and jejunal atresia. This is the second account of this association reported in the literature. The previously reported case underwent a gastroduodenostomy to correct the presumed duodenal obstruction caused by the PDPV. In our case, the PDPV was not corrected and the child remains well and asymptomatic. We propose that in this rare association, the PDPV is not a cause of obstruction and does not need correction.


[Hormonal investigation in the diagnosis of anorchia in childhood].
We have stimulated seventeen children (4-12 years old) with bilateral non palpable testes with LH-RH and HCG. The differential diagnosis between anorchia (5 patients) and bilateral cryptorchidism (12 patients) was possible with evaluation of FSH and Testosterone plasma levels before and after hormonic stimulation.


Optic axons ignore denervated foreign territory in goldfish tectum.
Ultrastructural morphometry was used to test firstly, whether regenerating optic axons in goldfish tectum will form connections in adjacent denervated foreign territory and secondly, whether intact optic axons will collaterally sprout to innervate this territory. The stratum fibrosum marginale of the tectum was partially denervated by removing the torus longitudinalis and cutting the tectal commissure. Optic axons do not normally synapse in this layer. Thirty days after partial denervation and optic tract section the numbers of normal synapses in a micron 2 column through the stratum fibrosum marginale reached a minimum and then started to increase so that by 159-173 days after the operation they had returned to control levels. Optic terminals, recognised by their degeneration after optic nerve section, did not contribute to these increasing numbers of synapses. Instead, optic axons preferentially reinnervated their normal tectal layers. Similarly, there was no evidence of collateral sprouting of intact optic axons into the partially denervated stratum fibrosum marginale and numbers of normal synapses in the layer also returned to control levels. These probably arose from collateral sprouting of terminals remaining after the partial denervation, raising the possibility that optic axons were prevented from synapsing there by the rapid occupation of vacant sites by other axons. However, delaying the partial denervation with respect to the tract section did not alter the result. These results support the idea of a specific affinity between optic axons and their postsynaptic targets.


Epithelial cell-fibroblast interactions in lung injury and repair.
Although direct intercellular contacts between alveolar epithelial cells and fibroblasts have been described in developing and adult lung, the frequency of such contacts and their relationship to type 2 cell division and differentiation in normal and abnormal repair is not known. The authors now correlate measurements of type 2 cell basal surface, basement membrane continuity, and the incidence of epithelial-interstitial cell contacts with the proliferative index of type 2 cells and fibroblasts in normal repair (after hyperoxia) and in abnormal repair with fibrosis (after bleomycin or butylated hydroxytoluene). In each case, type 1 cell necrosis was followed by an increase in type 2 cell basal surface as the cells spread over the denuded capillary wall before dividing. After hyperoxia, a high but short-lived peak in type 2 cell division was not accompanied by fibrosis. After more severe drug-induced injury, the type 2 proliferative phase was extended and was accompanied by prolonged fibroblast growth. Type 2 cells persisted where they covered a thick interstitium of fibroblasts and fibrillar collagen. The incidence of epithelial-interstitial cell contacts decreased at the time of maximal type 2 cell division, then increased immediately after the peak. The results suggest a reciprocal epithelial-fibroblast control system whereby 1) epithelial necrosis and delayed repair promotes fibroblast growth, and 2) direct contact of epithelial cells with fibroblasts or fibrillar collagen may provide a factor important for the regulation of type 2 cell growth and differentiation.


Artemisia umbelliformis Lam. and Génépi Liqueur: Volatile Profile as Diagnostic Marker for Geographic Origin and To Predict Liqueur Safety.
Artemisia umbelliformis, commonly known as "white génépi", is characterized by a volatile fraction rich in α- and β-thujones, two monoterpenoids; under European Union (EU) regulations these are limited to 35 mg/L in Artemisia-based beverages because of their recognized activity on the human central nervous system. This study reports the results of an investigation to define the geographical origin and thujone content of individual plants of A. umbelliformis from different geographical sites, cultivated experimentally at a single site, and to predict the thujone content in the resulting liqueurs through their volatile fraction. Headspace solid phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) and non-separative HS-SPME-MS were used as analytical platforms to create a database suitable for chemometric description and prediction through linear discriminant analysis (LDA). HS-SPME-MS was applied to shorten analysis time. With both approaches, a diagnostic prediction of (i) plant geographical origin and (ii) thujone content of plant-related liqueurs could be made.


Rechargeable Aluminum-Ion Batteries Based on an Open-Tunnel Framework.
Rechargeable batteries based on an abundant metal such as aluminum with a three-electron transfer per atom are promising for large-scale electrochemical energy storage. Aluminum can be handled in air, thus offering superior safety, easy fabrication, and low cost. However, the development of Al-ion batteries has been challenging due to the difficulties in identifying suitable cathode materials. This study presents the use of a highly open framework Mo2.5 + y VO9 + z as a cathode for Al-ion batteries. The open-tunnel oxide allows a facile diffusion of the guest species and provides sufficient redox centers to help redistribute the charge within the local host lattice during the multivalent-ion insertion, thus leading to good rate capability with a specific capacity among the highest reported in the literature for Al-based batteries. This study also presents the use of Mo2.5 + y VO9 + z as a model host to develop a novel ultrafast technique for chemical insertion of Al ions into host structures. The microwave-assisted method employing diethylene glycol and aluminum diacetate (Al(OH)(C2 H3 O2 )2 ) can be performed in air in as little as 30 min, which is far superior to the traditional chemical insertion techniques involving moisture-sensitive organometallic reagents. The Al-inserted Al x Mo2.5 + y VO9 + z obtained by the microwave-assisted chemical insertion can be used in Al-based rechargeable batteries.


Long noncoding RNA NEAT1-modulated miR-506 regulates gastric cancer development through targeting STAT3.
Accumulating evidence has indicated that long noncoding RNA NEAT1 exerts critical roles in cancers. So far, the detailed biological role and mechanisms of NEAT1, which are responsible for human gastric cancer (GC), are still largely unknown. Here, we observed that NEAT1 and STAT3 expressions were significantly upregulated in human GC cells including BGC823, SGC-7901, AGS, MGC803, and MKN28 cells compared with normal gastric epithelial cells GES-1, while miR-506 was downregulated. We inhibited NEAT1 and observed that NEAT1 inhibition was able to repress the growth, migration, and invasion of GC cells. Conversely, overexpression of NEAT1 exhibited an increased ability of GC progression in BGC823 and SGC-7901 cells. Bioinformatics analysis, dual luciferase reporter assays, RIP assays, and RNA pull-down tests validated the negative binding correlation between NEAT1 and miR-506. In addition, it was found that miR-506 can modulate the expression of NEAT1 in vitro. STAT3 was predicted as a messenger RNA (mRNA) target of miR-506, and miR-506 mimics can suppress STAT3 mRNA expression. Subsequently, it was observed that downregulation of NEAT1 can restrain GC development by decreasing STAT3, which can be reversed by miR-506 inhibitors. Therefore, it was hypothesized in our study that NEAT1 can be recognized as a competing endogenous RNA to modulate STAT3 by sponging miR-506 in GC. In conclusion, we implied that NEAT1 can serve as an important biomarker in GC diagnosis and treatment.


Agrobacterium tumefaciens iron superoxide dismutases have protective roles against singlet oxygen toxicity generated from illuminated Rose Bengal.
Singlet oxygen is a highly reactive form of molecular oxygen that is harmful to biological systems. Here, the role of three iron-containing superoxide dismutase (sodB) genes is clearly shown in protecting Agrobacterium tumefaciens against singlet oxygen toxicity. A sodBI mutant was more sensitive to singlet oxygen than both wild-type bacteria and a double sodBII-sodBIII mutant strain. Moreover, a sodBI-sodBII double mutant had higher sensitivity to singlet oxygen than a single sodBI mutant, although the double mutant was comparable to a sodB null mutant. High-level expression of sodBI and sodBII fully complemented the singlet oxygen hypersensitivity phenotype of the sodB null mutant, while high-level expression of sodBIII encoding a periplasmic SOD only partially restored the phenotype. Taken together, our data suggest that SodBI and SodBII have novel protective roles against singlet oxygen toxicity through unknown mechanisms.


Effect of MicroRNA-21 Transfection on In-vitro Differentiation of Human Naive CD4+ T Cells to Regulatory T Cells.
Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group. We showed that expression of Foxp3, transforming growth factor beta (TGF-β), and interleukin-10 (IL-10) are increased in iTregs generated after miR-21 transfection in comparison with cytokine-differentiated iTregs and control group. Our findings demonstrate that miR-21 has positive role in in-vitro generation of induced regulatory T-cells (iTregs).


Modeling the temporal dynamics of the gut microbial community in adults and infants.
Given the highly dynamic and complex nature of the human gut microbial community, the ability to identify and predict time-dependent compositional patterns of microbes is crucial to our understanding of the structure and functions of this ecosystem. One factor that could affect such time-dependent patterns is microbial interactions, wherein community composition at a given time point affects the microbial composition at a later time point. However, the field has not yet settled on the degree of this effect. Specifically, it has been recently suggested that only a minority of taxa depend on the microbial composition in earlier times. To address the issue of identifying and predicting temporal microbial patterns we developed a new model, MTV-LMM (Microbial Temporal Variability Linear Mixed Model), a linear mixed model for the prediction of microbial community temporal dynamics. MTV-LMM can identify time-dependent microbes (i.e., microbes whose abundance can be predicted based on the previous microbial composition) in longitudinal studies, which can then be used to analyze the trajectory of the microbiome over time. We evaluated the performance of MTV-LMM on real and synthetic time series datasets, and found that MTV-LMM outperforms commonly used methods for microbiome time series modeling. Particularly, we demonstrate that the effect of the microbial composition in previous time points on the abundance of taxa at later time points is underestimated by a factor of at least 10 when applying previous approaches. Using MTV-LMM, we demonstrate that a considerable portion of the human gut microbiome, both in infants and adults, has a significant time-dependent component that can be predicted based on microbiome composition in earlier time points. This suggests that microbiome composition at a given time point is a major factor in defining future microbiome composition and that this phenomenon is considerably more common than previously reported for the human gut microbiome.


Regional differences in dendritic spine density confer resilience to chronic social defeat stress.
Although alterations in the dendritic spine density in the brain regions may play a role in the stress-induced depression-like phenotype, the precise mechanisms are unknown. The aim was to investigate the role of spine density in the brain regions after chronic social defeat stress (CSDS). We examined dendritic spine density in the medial prefrontal cortex (mPFC), CA1, CA3, dentate gyrus (DG) of hippocampus, nucleus accumbens (NAc), and ventral tegmental area (VTA) of susceptible and resilient mice after CSDS. Spine density in the prelimbic area of mPFC, CA3, and DG in the susceptible group, but not resilient group, was significantly lower than control group. In contrast, spine density in the NAc and VTA in the susceptible group, but not resilient group, was significantly higher than control group. The results suggest that regional differences in spine density may contribute to resilience versus susceptibility in mice subjected to CSDS.


Three-dimensional Pentagon Carbon with a genesis of emergent fermions.
Carbon, the basic building block of our universe, enjoys a vast number of allotropic structures. Owing to its bonding characteristic, most carbon allotropes possess the motif of hexagonal rings. Here, with first-principles calculations, we discover a new metastable three-dimensional carbon allotrope entirely composed of pentagon rings. The unique structure of this Pentagon Carbon leads to extraordinary electronic properties, making it a cornucopia of emergent topological fermions. Under lattice strain, Pentagon Carbon exhibits topological phase transitions, generating a series of novel quasiparticles, from isospin-1 triplet fermions to triply degenerate fermions and further to Hopf-link Weyl-loop fermions. Its Landau level spectrum also exhibits distinct features, including a huge number of almost degenerate chiral Landau bands, implying pronounced magneto-transport signals. Our work not only discovers a remarkable carbon allotrope with highly rare structural motifs, it also reveals a fascinating hierarchical particle genesis with novel topological fermions beyond the Dirac and Weyl paradigm.


Erectogenic Effects of Clerodendron capitatum: Involvement of Phosphodiesterase Type-5 Inhibition.
Clerodendron capitatum (Willd) (family: verbenaceae) is locally named as Gung and used traditionally to treat erectile dysfunction. Therefore, the current study was designed to investigate the erectogenic properties of C. capitatum. The relaxation effect of this plant was tested on phenylephrine precontracted rabbit corpus cavernosum smooth muscle (CCSM). The effects of C. capitatum were also examined on isolated Guinea pig atria alone, in the presence of calcium chloride (Ca(2+) channel blocker), atropine (cholinergic blocker), and glibenclamide (ATP-sensitive K(+) channel blocker). These effects were confirmed on isolated rabbit aortic strips. The extract, when tested colorimetrically for its inhibitory activities on phosphordiesterase-5 (PDE-5) in vitro towards p-nitrophenyl phenyl phosphate (PNPPP), was observed to induce significant dose-dependent inhibition of PDE-5, with an ID(50) of 0.161 mg/ml (P < .05). In conclusion, our results suggest that C. capitatum possesses a relaxant effect on CCSM, which is attributable to the inhibition of PDE-5, but not mediated by the release calcium, activation of adrenergic or cholinergic receptors, or the activation of potassium channels.


Quantification of polyacrylamide gel electrophoresis for analysis of whey proteins.
Polyacrylamide gel electrophoresis of whey proteins has been quantified by standardization of the separation and staining procedure. During each electrophoresis experiment, a standard solution of whey proteins was separated and stained under the same conditions as the test material. In this way, proteins in the standard solution were subjected to identical processing conditions as the test samples. Densitometric scanning of the stained protein-containing gels followed by peak area determinations was carried out. By comparison with the standard peak areas, individual protein concentrations of the test samples were determined.


Impact of Venous Thromboembolism on the Formation and Progression of Carotid Atherosclerosis: The Tromsø Study.
Venous thromboembolism (VTE) is associated with increased risk of arterial cardiovascular diseases (CVD), and development of atherosclerosis secondary to VTE may be an intermediate between VTE and CVD. Therefore, we aimed to investigate whether incident VTE was associated with subsequent carotid atherosclerosis formation and progression in a population-based observational study. Subjects attending two or more ultrasound examinations of the right carotid artery, with measurement of total plaque area (TPA), in the Tromsø Study in 1994-1995, 2001-2002, and/or 2007-2008 were eligible. We identified 150 subjects diagnosed with first-lifetime VTE between the initial and follow-up visit, and randomly selected 600 age- and sex-matched subjects without VTE between the visits. Subjects with VTE and carotid plaque(s) at the first visit had 4.1 mm 2 (β: 4.13, 95% CI: -1.72 to 9.98) larger change in TPA between the first and second visit compared with subjects without VTE after adjustment for change in high-sensitivity C-reactive protein (hs-CRP) and traditional atherosclerotic risk factors. The association remained after restricting the analyses to VTE events diagnosed in the first half of the time interval between the carotid ultrasounds (β: 4.02, 95% CI: -3.66 to 11.70), supporting that the change in TPA occurred subsequent to the VTE. No association was found between VTE and novel carotid plaque formation. In conclusion, we found a possible association between VTE and atherosclerosis progression in those with already established carotid plaques, but not between VTE and novel plaque formation. The association between VTE and carotid plaque progression was not mediated by low-grade inflammation assessed by hs-CRP.


Quantitative nanoorganized structural evolution for a high efficiency bulk heterojunction polymer solar cell.
We have developed an improved small-angle X-ray scattering (SAXS) model and analysis methodology to quantitatively evaluate the nanostructures of a blend system. This method has been applied to resolve the various structures of self-organized poly(3-hexylthiophene)/C61-butyric acid methyl ester (P3HT/PCBM) thin active layer in a solar cell from the studies of both grazing-incidence small-angle X-ray scattering (GISAXS) and grazing-incidence X-ray diffraction (GIXRD). Tuning the various length scales of PCBM-related structures by a different annealing process can provide a flexible approach and better understanding to enhance the power conversion of the P3HT/PCBM solar cell. The quantitative structural characterization by this method includes (1) the mean size, volume fraction, and size distribution of aggregated PCBM clusters, (2) the specific interface area between PCBM and P3HT, (3) the local cluster agglomeration, and (4) the correlation length of the PCBM molecular network within the P3HT phase. The above terms are correlated well with the device performance. The various structural evolutions and transformations (growth and dissolution) between PCBM and P3HT with the variation of annealing history are demonstrated here. This work established a useful SAXS approach to present insight into the modeling of the morphology of P3HT/PCBM film. In situ GISAXS measurements were also conducted to provide informative details of thermal behavior and temporal evolution of PCBM-related structures during phase separation. The results of this investigation significantly extend the current knowledge of the relationship of bulk heterojunction morphology to device performance.


"Locked" cancer cells are more sensitive to chemotherapy.
The treatment of metastatic cancer is a great challenging issue throughout the world. Conventional chemotherapy can kill the cancer cells and, whereas, would exacerbate the metastasis and induce drug resistance. Here, a new combinatorial treatment strategy of metastatic cancer was probed via subsequentially dosing dual nanomedicines, marimastat-loaded thermosensitive liposomes (MATT-LTSLs) and paclitaxel nanocrystals (PTX-Ns), via intravenous and intratumoral injection. First, the metastasis was blocked and cancer cells were locked in the tumor microenvironment (TME) by delivering the matrix metalloproteinase (MMP) inhibitor, MATT, to the tumor with LTSLs, downregulating the MMPs by threefold and reducing the degradation of the extracellular matrix. And then, the "locked" cancer cells were efficiently killed via intratumoral injection of the other cytotoxic nanomedicine, PTX-Ns, along with no metastasis and 100% inhibition of tumor growth. This work highlights the importance of the TME's integrity in the chemotherapy duration. We believe this is a generalized strategy for cancer treatment and has potential guidance for the clinical administration.


[Recent progress in image analysis of rheumatoid arthritis].
The establishment of better methods than the conventional radiological examination in the management of rheumatoid arthritis is one of the key issues to be achieved in near future. The conventional X-ray examinations are not so sensitive or specific to early pathologies of inflammation and subtle changes. However, from the economical and clinical point of view, still plane X-ray images have several advantage. Several grading system including Steinbrocker, Larsen grade and Sharp score had been developed. Magnetic resonance image offers improved sensitivity to early inflammation of synovial tissue and bone destructive changes in the joints in RA patients. There are clear evidence for MRI synovitis representing true synovial inflammation. The clinician who intends to manage the inflammatory joint diseases should have the knowledge of these evaluation systems.


Do adolescent inpatient wards make a difference? Findings from a national young patient survey.
There is little evidence to support the effectiveness of adolescent inpatient wards. These analyses test the hypotheses that nursing young people in adolescent wards improves aspects of quality of care and patient satisfaction compared with child or adult wards. Secondary analyses of the national English Young Patient Survey 2004 were weighted to take account of variations in hospital size and response rate. Participants included 8855 subjects aged 12 to 17 years. Ward types (adolescent, child, and adult) were compared. Patient-reported quality-of-care indicators included rating by young people of overall care, respect, safety, confidentiality, communication, team-working, noise, and leisure facilities. Logistic regression models were adjusted for gender, disability, and previous hospital admissions. Ten percent of 12- to 14-year-olds and 18% of 15- to 17-year-olds were nursed in an adolescent ward, 0.4% of 12- to 15-year-olds and 16% of 15- to 17-year-olds in an adult ward, with the remainder in a child ward. Compared with being in an adolescent ward, 15- to 17-year-olds were less likely to report excellent overall care in an adult ward and less likely to report feeling secure, having confidentiality maintained, feeling treated with respect, confidence in staff, appropriate information transmission, appropriate involvement in own care, and appropriate leisure facilities. Compared with being in an adolescent ward, 12- to 14-year-olds were less likely to report excellent overall care in a child ward and less likely to report feeling involved in their own care. Dedicated adolescent inpatient wards improve aspects of quality of care for young people compared with child or adult wards, particularly for older adolescents. These data support the continued development of adolescent wards in larger general hospitals and children's hospitals.


Variations in the branching pattern of the celiac trunk and its clinical significance.
Celiac trunk is the artery of foregut, arising from the abdominal aorta at the level of T12/L1 vertebral body. It extends approximately 1.5 to 2 cm horizontally forwards before dividing into three branches: left gastric, common hepatic, and splenic arteries. Out of the three ventral branches of abdominal aorta, celiac trunk is more prone to have variations. During routine dissection of abdomen for undergraduate students we found some rare variations in the branching pattern of the celiac trunk. Absence of celiac trunk with hepatomesenteric trunk, quadrifurcation with dorsal pancreatic artery arising from it, quadrifurcation with middle colic artery arising from it, left inferior phrenic artery arising from celiac trunk, highly tortuous splenic artery supplying distal 1/3rd of transverse colon and hepatosplenic trunk. Knowledge of such variations is essential for liver and pancreas transplantations, pancreaticoduodenectomy, radiological abdominal interventions, laproscopic surgeries, and in trauma of the abdomen.