HCl emission characteristics and BP neural networks prediction in MSW/coal co-fired fluidized beds.
The HCl emission characteristics of typical municipal solid waste (MSW) components and their mixtures have been investigated in a phi 150 mm fluidized bed. Some influencing factors of HCl emission in MSW fluidized bed incinerator was found in this study. The HCl emission is increasing with the growth of bed temperature, while it is decreasing with the increment of oxygen concentration at furnace exit. When the weight percentage of auxiliary coal is increased, the conversion rate of Cl to HCl is increasing. The HCl emission is decreased, if the sorbent (CaO) is added during the incineration process. Based on these experimental results, a 14 x 6 x 1 three-layer BP neural networks prediction model of HCl emission in MSW/coal co-fired fluidized bed incinerator was built. The numbers of input nodes and hidden nodes were fixed on by canonical correlation analysis technique and dynamic construction method respectively. The prediction results of this model gave good agreement with the experimental results, which indicates that the model has relatively high accuracy and good generalization ability. It was found that BP neural network is an effectual method used to predict the HCl emission of MSW/coal co-fired fluidized bed incinerator.


Synthesis of α-Keto Acids via Oxidation of Alkenes Catalyzed by a Bifunctional Iron Nanocomposite.
An efficient methodology for synthesis of α-keto acids via oxidation of alkenes using TBHP as oxidant catalyzed by a bifunctional iron nanocomposite has been established. A variety of alkenes with different functional groups were smoothly oxidized into their corresponding α-keto acids in up to 80% yield. Moreover, the bifunctional iron nanocomposite catalyst showed outstanding catalytic stability for successive recycles without appreciable loss of activity.


Podocalyxin-like protein 1 expression and correlation with clinical characteristics in epithelial serous and mucinous ovarian carcinoma and tumor-like lesions.
Podocalyxin-like protein 1 (PCLP1) may be involved in the invasion and metastasis of tumors. However, to date the role of PCLP1 in the progression of epithelial ovarian carcinoma has not been investigated. PCLP1 expression was examined by immunohistochemistry in 471 cases with various degrees of ovarian epithelial lesions, including 46 cases of normal ovarian epithelial tissue, 105 benign serous tumors, 74 borderline serous tumors, 94 serous carcinomas, 58 benign mucinous tumors, 50 borderline mucinous tumors and 44 mucinous carcinomas. Associations between PCLP1 expression and various clinical characteristics were analyzed. PCLP1 expression in mucinous carcinoma and borderline mucinous tumor tissues was found to be significantly lower than that observed in normal and benign mucinous tumor tissue. In addition, PCLP1 expression was significantly lower in mucinous carcinoma patients in advanced clinical stage and with poor differentiation of tumor cells. No positive results were observed in serous carcinomas. Our findings suggest that PCLP1 may be involved in the progression of ovarian mucinous lesions but not in serous lesions. Low PCLP1 expression may be a potential predictor of a poor prognosis in mucinous carcinomas.


Amyloid Beta Peptides and Th1 Cytokines Modulate Human Brain Vascular Smooth Muscle Tonic Contractile Capacity In Vitro: Relevance to Alzheimer's Disease?
Alzheimer's Disease (AD) is a neurodegenerative condition characterized both by the presence of tau protein neurofibrillary tangles and amyloid beta (Aβ) containing extracellular "plaques". The cleavage of amyloid precursor protein (APP) yields several Aβ peptides. Although Aβ toxicity to neurons has been described extensively, its effects on other components of the neurovasculature such as vascular smooth muscle cells have been less well characterized. AD is now also recognized as a neurovascular disease characterized by cerebral microbleeds and disturbances in autoregulation. AD is also a neuroinflammatory condition in which several proinflammatory cytokines are elevated and may contribute to the intensification of AD severity. Cerebral autoregulation (the mechanism by which brain blood flow is maintained despite changes in perfusion pressure) is extremely tightly controlled in the brain and shows disturbances in AD. The failure of autoregulation in AD may make the brain susceptible to cerebral microbleeds through a reduced capacity to limit blood flow when pressure is increased. Conversely, reduced vasodilation during low flow might could also exacerbate tissue hypoxia. Currently, whether and how Aβ peptides and inflammatory cytokines depress brain smooth muscle cell tonic contraction is not known, but could reveal important targets in the preservation of autoregulation which is disturbed in AD. We used a collagen gel contractility assay to evaluate the influence of Aβ25-35, Aβ1-40 and Aβ1-42 peptides and inflammatory cytokines on the tonic contractility of human brain vascular smooth muscle cells (HBVSMC) as an in vitro model of cerebral autoregulation. We found that 5 and 10 μM Aβ1-42 significantly depressed HBVSM contractility, while Aβ1-40 5-20 μM had no effect on contractility. Conversely, Aβ25-35 (1-50 μM) increased contractility. Interestingly, the inflammatory cytokines TNF-α (20 ng/mL), IL-1β (20 ng/mL) and IFN-γ (1000 U/mL) also depressed HBVSM tonic contractility alone and in combination. These data suggest that both the inflammatory milieu in AD as well as the abundance of Aβ peptides may promote autoregulatory failure and increase brain susceptibility to dysregulated perfusion and microbleeds which are an important and devastating characteristic of AD.


An open-label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn's disease.
Infliximab, a chimeric monoclonal antibody to tumour necrosis factor-alpha, is a new potent therapy for active Crohn's disease, but induces short-lived improvements. To evaluate the efficacy of thalidomide, a drug with anti-tumour necrosis factor-alpha activity, for the maintenance of infliximab-induced response in refractory Crohn's disease. Fifteen patients with severe, refractory disease (10 females, five males; mean age, 40 years; eight with luminal disease, two with fistulizing disease and five with both luminal and fistulizing disease) were started on thalidomide (100 mg daily), 29 +/- 10 days after they had responded to infliximab (5 mg/kg infusions). The median follow-up period was 238 days (range, 10-458 days) from the initiation of thalidomide and 265 days (range, 10-537 days) from the last infliximab infusion. The median Crohn's disease activity indices were 322 (range, 170-525), 119 (range, 24-503) and 35 (range, -60-360) before infliximab, at the initiation of thalidomide and at the end of follow-up, respectively. Remission rates on thalidomide were 92%, 83% and 83% at 3, 6 and 12 months, respectively, after the last infliximab infusion (Kaplan-Meier). Four patients (two in remission) stopped thalidomide for suspected adverse effects. Side-effects (drowsiness, rash and peripheral neuropathy) were mild and mostly transient. Thalidomide appears to be an effective and relatively safe drug to maintain response to infliximab in chronically active and fistulizing refractory Crohn's disease.


Extracts of Selected South African Medicinal Plants Mitigate Virulence Factors in Multidrug-Resistant Strains of Klebsiella pneumoniae.
The emergence of multidrug-resistant (MDR) Klebsiella pneumoniae remains a global health threat due to its alarming rates of becoming resistant to antibiotics. Therefore, identifying plant-based treatment options to target this pathogen's virulence factors is a priority. This study examined the antivirulence activities of twelve plant extracts obtained from three South African medicinal plants (Lippia javanica, Carpobrotus dimidiatus, and Helichrysum populifolium) against carbapenem-resistant (CBR) and extended-spectrum beta-lactamase (ESBL) positive K. pneumoniae strains. The plant extracts (ethyl acetate, dichloromethane, methanol, and water) were validated for their inhibitory activities against bacterial growth and virulence factors such as biofilm formation, exopolysaccharide (EPS) production, curli expression, and hypermucoviscosity. The potent extract on K. pneumoniae biofilm was observed with a scanning electron microscope (SEM), while exopolysaccharide topography and surface parameters were observed using atomic force microscopy (AFM). Chemical profiling of the potent extract in vitro was analysed using liquid chromatography-mass spectrometry (LC-MS). Results revealed a noteworthy minimum inhibitory concentration (MIC) value for the C. dimidiatus dichloromethane extract at 0.78 mg/mL on CBR- K. pneumoniae. L. javanica (ethyl acetate) showed the highest cell attachment inhibition (67.25%) for CBR- K. pneumoniae. SEM correlated the in-vitro findings, evidenced by a significant alteration of the biofilm architecture. The highest EPS reduction of 34.18% was also noted for L. javanica (ethyl acetate) and correlated by noticeable changes observed using AFM. L. javanica (ethyl acetate) further reduced hypermucoviscosity to the least length mucoid string (1 mm-2 mm) at 1.00 mg/mL on both strains. C. dimidiatus (aqueous) showed biofilm inhibition of 45.91% for the ESBL-positive K. pneumoniae and inhibited curli expression at 0.50 mg/mL in both K. pneumoniae strains as observed for H. populifolium (aqueous) extract. Chemical profiling of L. javanica (ethyl acetate), C. dimidiatus (aqueous), and H. populifolium (aqueous) identified diterpene (10.29%), hydroxy-dimethoxyflavone (10.24%), and 4,5-dicaffeoylquinic acid (13.41%), respectively, as dominant compounds. Overall, the ethyl acetate extract of L. javanica revealed potent antivirulence properties against the studied MDR K. pneumoniae strains. Hence, it is a promising medicinal plant that can be investigated further to develop alternative therapy for managing K. pneumoniae-associated infections.


Detection and levels of androgen receptor messenger ribonucleic acid in the rat brain by means of reverse transcription-polymerase chain reaction.
In order to examine the existence and level of androgen receptor messenger ribonucleic acid (ARmRNA) in the rat brain, reverse transcription-polymerase chain reaction (RT-PCR)-Southern blot analysis was carried out. Total RNA extracted from each tissue was reverse transcribed, followed by PCR with two oligonucleotide primers specific for a part (458 bp) of the androgen binding domain of the rat ARcDNA. It was confirmed by direct nucleotide sequencing that the amplified fragment corresponded to part of the rat ARcDNA. To detect and quantify the amplified fragments, a Southern blot analysis was carried out. The levels of amplified fragments were calculated from the standard curve obtained from graded diluted adrenal total RNAs. In the present study, it was revealed that the RT-PCR-Southern blot analysis possessed a high-degree of sensitivity and allowed the quantitative estimation of mRNA. With this method, amplified fragments were obtained from all five brain regions examined. The results indicate that ARmRNA is widely distributed in the whole brain. Moreover, since the ARmRNA level roughly paralleled the AR protein level, it seems that the AR protein level in the brain may be primarily regulated by the ARmRNA level.


Inhibition of CBP-mediated protein acetylation by the Ets family oncoprotein PU.1.
Aberrant expression of PU.1 inhibits erythroid cell differentiation and contributes to the formation of murine erythroleukemias (MEL). The molecular mechanism by which this occurs is poorly understood. Here we show that PU.1 specifically and efficiently inhibits CBP-mediated acetylation of several nuclear proteins, including the hematopoietic transcription factors GATA-1, NF-E2, and erythroid Krüppel-like factor. In addition, PU.1 blocks acetylation of histones and interferes with acetylation-dependent transcriptional events. CBP acetyltransferase activity increases during MEL cell differentiation as PU.1 levels decline and is inhibited by sustained PU.1 expression. Finally, PU.1 inhibits the differentiation-associated increase in histone acetylation at an erythroid-specific gene locus in vivo. Together, these findings suggest that aberrant expression of PU.1 and possibly other members of the Ets family of oncoproteins subverts normal cellular differentiation in part by inhibiting the acetylation of critical nuclear factors involved in balancing cellular proliferation and maturation.


Classification of Different Degrees of Disability Following Intracerebral Hemorrhage: A Decision Tree Analysis from VISTA-ICH Collaboration.
Prognostication following intracerebral hemorrhage (ICH) has focused on poor outcome at the expense of lumping together mild and moderate disability. We aimed to develop a novel approach at classifying a range of disability following ICH. The Virtual International Stroke Trial Archive collaboration database was searched for patients with ICH and known volume of ICH on baseline CT scans. Disability was partitioned into mild [modified Rankin Scale (mRS) at 90 days of 0-2], moderate (mRS = 3-4), and severe disabilities (mRS = 5-6). We used binary and trichotomy decision tree methodology. The data were randomly divided into training (2/3 of data) and validation (1/3 data) datasets. The area under the receiver operating characteristic curve (AUC) was used to calculate the accuracy of the decision tree model. We identified 957 patients, age 65.9 ± 12.3 years, 63.7% males, and ICH volume 22.6 ± 22.1 ml. The binary tree showed that lower ICH volume (<13.7 ml), age (<66.5 years), serum glucose (<8.95 mmol/l), and systolic blood pressure (<170 mm Hg) discriminate between mild versus moderate-to-severe disabilities with AUC of 0.79 (95% CI 0.73-0.85). Large ICH volume (>27.9 ml), older age (>69.5 years), and low Glasgow Coma Scale (<15) classify severe disability with AUC of 0.80 (95% CI 0.75-0.86). The trichotomy tree showed that ICH volume, age, and serum glucose can separate mild, moderate, and severe disability groups with AUC 0.79 (95% CI 0.71-0.87). Both the binary and trichotomy methods provide equivalent discrimination of disability outcome after ICH. The trichotomy method can classify three categories at once, whereas this action was not possible with the binary method. The trichotomy method may be of use to clinicians and trialists for classifying a range of disability in ICH.


Epstein - Barr virus epidemiology in HIV infected transsexuals.
To molecularly characterise the relationship between Epstein-Barr virus (EBV) genotypes and Pashtun ethnicity. The cross-sectional study was conducted from November 2018 to December 2019 after approval from the Gomal University, Dera Ismail Khan, Pakistan, and comprised blood samples from transgender sex workers who were seropositive for human immunodeficiency virus-1 and seronegative for human immunodeficiency virus residing in two cities of Khyber Pakhtunkhwa province and Islamabad, the federal capital. Formalin-fixed paraffin-embedded (FFPE). Samples were collected from the partner institute along with the patients data, but without any follow-up from the study subjects which was purely on the basis of physical availability. β-globin gene and EBER-1(EBV encoded small RNA-1) were amplified for qualitative assessment and existence of Epstein-Barr virus. Characterisation of EBNA-2 (EBV Nuclear Antigen-2 was done through nested polymerase chain reaction. Of the 80 subjects, 40(50%) each were seropositive and seronegative individuals. The overall mean age was 28±6.917 years. Among the seropositive group, 38(95%) were homosexual and 2(5%) were heterosexual. Among the seropositive group, 16(40%) had Epstein-Barr virus genotype 1 and 6(15%) had genotype 2, while co-infections were found in 2(5%) subjects. In the seronegative group, 36(90%) subjects had Epstein-Barr virus genotype 1, while there was no case of genotype 2 or co-infection. EBV-2 genotypes with HIV seropositivity showed strong association (p=0.005). Amplification for the EBER-1 gene was done in all the 80(100%) samples. Epstein-Barr virus EBV genotype 1 was found to be the most frequent type, while genotype 2 and co-infections were detected in only seropositive samples.


Effects of oleic acid on SP-B expression and release in A549 cells.
Pulmonary surfactant-associated protein B (SP-B), which is synthesized and secreted by alveolar epithelial type II cells, is crucial for normal functioning of pulmonary surfactant. Degeneration of pulmonary surfactant is the essential cause of acute lung injury (ALI). ALI is often studied in animal models using oleic acid, and the effects of oleic acid on pulmonary surfactant and SP-B are not clear. In this study, we examined the effects of oleic acid on the A549 cell line which resembles the alveolar epithelial type II cells. A549 cells were exposed for 24 hours to 300, 400, 500 or 600 µM of oleic acid. Cell morphological changes were observed using an inverted microscope, and cell proliferation was quantified with the Cell Counting Kit-8. Extracellular SP-B levels were assessed by ELISA, whereas intracellular SP-B expression by Western blot. Oleic acid caused dose-dependent changes in cell morphology of A549 cells and decreased their proliferation. This was accompanied by release of SP-B into extracellular supernatants and corresponding decrease of intracellular levels of this protein. Oleic acid causes a dose-dependent injury to A549 cells, release of SP-B into extracellular compartment, and decrease of intracellular SP-B expression. Our findings provide mechanistic insights into animal modeling of ALI with oleic acid.


Phase I dose-escalating study of S-1 in combination with oxaliplatin for patients with advanced and/or metastatic colorectal cancer.
The purpose of this study was to determine the optimal dose of oxaliplatin, when combined with a fixed dose of S-1 (40 mg/m twice daily on days 1-14) on a 3-week schedule, for patients with advanced and/or metastatic colorectal cancer. Patients were required to have a histologically proven advanced or metastatic colorectal cancer for which they had received no previous chemotherapy. Oxaliplatin was administered intravenously on day 1 every 3 weeks. Patients were divided into two groups to receive two doses of oxaliplatin - 100 mg/m or 130 mg/m. Ten patients were enrolled in the study between March 2006 and July 2006, and were followed up until 50% of the patients progressed. All patients were evaluated for chemotherapy-related toxicity. The maximum tolerated dose was not reached during the first course. One of six patients experienced grade 3 thrombocytopenia at dose level 2 of oxaliplatin. Nonhematological toxicity was mild and tolerable. During the full course of treatment, complete response was achieved in two of the nine evaluated patients and partial response was achieved in one patient. The remaining six patients achieved stable disease during first two courses of therapy, and four patients remained stable at the time of the last follow-up. The median time to progression-free survival was 8.3 months. When combined with a fixed dose of S-1 80 mg/m, oxaliplatin administered at a dose of 130 mg/m is tolerable and recommended for phase II study.


Effects of Meglumine Antimoniate Treatment on Cytokine Production in a Patient with Mucosal Leishmaniasis and Chagas Diseases Co-Infection.
The influence of antimoniate treatment on specific anti-protozoan T-cell responses was evaluated in a 48-year-old male patient diagnosed with mucosal leishmaniasis and Chagas disease infection. Before and after treatment, PBMC (peripheral blood mononuclear cells) were cultured in the absence or presence of Leishmania braziliensis or Trypanosoma cruzi live parasites, their soluble antigens, or PHA (phytohaemagglutinin). Cytokines were measured and Treg (T regulatory) cell percentages were quantified. Before treatment, PBMC were able to produce higher amounts of TNF-α, IL-6 (Interleukin-6), and IL-10 (Interleukin-10) but lower amounts of IL-12 (Interleukin-12) in response to culture stimulation. However, after treatment, there was a down-modulation of TNF-α, IL-6, and IL-10 cytokines but an up-modulation in IL-12 production. PBMC had the ability to produce TNF-α only against live parasites or PHA. There was an overall decrease of circulating Treg cells after treatment. In mixed Leishmaniasis and Chagas disease infection, treatment with antimoniate could modulate immune responses toward a more protective profile to both diseases.


Expression of mucin-2 and correlation with PAS-alcian blue stain in Barrett's esophagus.
Hematoxylin-eosin stain may fail to show intestinal metaplasia in Barrett's esophagus, and PAS-alcian blue may present difficulties of interpretation due to its more heterogeneous staining. We investigated whether Mucin-2 is a good substitute for PAS-alcian blue in the detection of goblet cells. Biopsy specimens from 47 Barrett's esophagus patients were stained with hematoxylineosin and PAS-alcian blue. Mucin-2 expression was evaluated with monoclonal antibody. The intra- and interobserver agreements about the expression of Mucin-2 and PAS-alcian blue stain were determined by kappa statistics. PAS-alcian blue and Mucin-2 were positive in all cases. Mucin expression was positive in goblet cells and few columnar cells. PAS-alcian blue showed heterogeneous staining. The columnar epithelium and the submucosal glands were also stained. Intra- and interobserver agreement in the identification of intestinal metaplasia was 100%. Mucin-2 agreed fully with PAS-alcian blue. The intra- and interobserver agreement was perfect, justifying its use in the diagnosis of Barrett's esophagus.


Machine learning-guided evolution of BMP-2 knuckle Epitope-Derived osteogenic peptides to target BMP receptor II.
Bone morphogenetic protein-2 (BMP-2) is a key regulator of bone formation, growth and regeneration, which contains a conformational wrist epitope and a linear knuckle epitope that are functionally responsible for the protein by mediating its interaction with type-I and type-II receptors, respectively. Previously, a long (19-mer) knuckle peptide derived from the knuckle epitope region (residues 73-92) has been found to promote osteogenesis and bone repair. Here, we attempt to rationally redesign the knuckle peptide by using bioinformatics and machine learning-guided evolution to obtain structurally simplified, potent osteogenic peptides that are capable of targeting type-II receptor. Complex analysis reveals that only a fraction of the epitope region can directly interact with type-II receptor, which represents a small (12-mer) knuckle-derived peptide (KDP0 peptide). Glycine scanning further identifies three KDP0 anchor residues Ser88, Leu90 and Tyr91 that are fundamentally important in the peptide-receptor binding. Systematic mutation, amino acid combination and uniform design of other nine KDP0 non-anchor residues generate 32 new knuckle-derived peptides (KDP1-KDP32); their binding affinities to recombinant protein of human type-II receptor are determined using fluorescence spectroscopy assay. The resulting affinity values (Kd) are used to train six regression models developed by combination of two machine learning methods and three amino acids descriptors. The best SVM/VHSE predictor is then utilised to guide the genetic evolution of a knuckle-derived peptide population. Eight peptides (KDP33-KDP40) with high affinity scores are selected from the improved population, and their osteogenic activities on bone marrow stromal cells are measured using alkaline phosphatase assay. Consequently, six out of the 8 tested peptides exhibit increased activity relative to KDP0 peptide. The KDP34 (DFQTWSFLYVEN) is found as the most potent peptide with APL activities of 195% and 279% at 0.01 and 0.1 µg/ml, respectively, which shares a similar binding mode with the native knuckle epitope and can form diverse nonbonded interactions of hydrogen bond, hydrophobic contact, cation-π/π-π stacking and salt bridge with type-II receptor.


Transcriptomic Responses of Two Ecologically Divergent Populations of Japanese Mantis Shrimp (Oratosquilla oratoria) under Thermal Stress.
Crustaceans are generally considered more sensitive to ocean warming due to their lack of certain efficient regulators. However, the alterations in the physiology and behavior of crustaceans in response to thermal stress differ vastly even among the infraspecific populations of heterogeneous landscapes. Consequently, understanding the impact of temperature fluctuation on crustacean infraspecific populations might be essential for maintaining a sustainable persistence of populations at existing locations. In the present study, we chose the Japanese mantis shrimp (Oratosquilla oratoria) as the representative crustacean population, and conducted transcriptome analyses in two divergent O. oratoria populations (the Zhoushan and Qingdao populations) under same thermal stress (20-28 °C) to identify the population-specific expression response to thermal stress. The results showed significant differences in gene expressions, GO terms and metabolic pathways between the two populations. We hypothesized that intraspecific mutations in the same or different genes might lead to thermal adaptive divergences. Temperature increases from 20-28 °C produced significant enrichment in GO terms and altered the metabolic pathways in the Zhoushan population despite the lack of differentially expressed unigenes. Therefore, several functional genes with large pleiotropic effects may underlie the response to thermal stress in the Zhoushan population. Furthermore, the most significantly enriched biological processes of the Qingdao population were associated with the state or activity of cells and its significant enriched pathways with genetic information processing as well as immune and environmental information processing. In contrast, the differentially regulated unigenes of the Zhoushan population were primarily involved in the regulatory cellular and transcription processes and the most significant pathways found were metabolic and digestive. Consequently, the regulatory mechanisms of the Zhoushan population are probably more efficient than those of the Qingdao population under the same thermal stress.


Pharmacogenetics of cardiovascular drugs.
Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted.


The pattern of brain metabolism in chronic steno-occlusive cerebral artery disease.
Dispersion of gray matter and white matter and abnormal hemodynamic changes are common in patients with chronic stenosis cerebral artery disease. It is not easy to capture these abnormal changes with conventional magnetic resonance imaging (MRI). Magnetic resonance spectroscopy (MRS) is useful for obtaining metabolic information in either preclinical or clinical applications. The aim of our study was to apply MRS to non-invasively investigate changes in brain metabolism in MRI-negative patients with chronic cerebral artery steno-occlusive disease. We performed MRS examinations with 3.0T MRI on 34 patients with severe unilateral middle cerebral artery (MCA) stenosis or occlusion without parenchymal abnormalities. Additionally, N-acetylaspartic acid (NAA), creatine (Cr), choline (Cho), NAA/Cr, and Cho/Cr in the coronal, parenchymal, and thalamic regions of the affected brain and contralateral brain were determined. The mean concentrations of NAA, Cr, Cho, NAA/Cr, and Cho/Cr in the coronal, parenchymal, and thalamic regions of the ipsilateral and contralateral brains were compared using the 2-tailed paired t-test. At the ipsilateral corona radiata and lenticular nucleus, the mean NAA was significantly lower, whereas the Cho and Cho/Cr were significantly higher than the contralateral corona radiata and lentiform nucleus (P<0.05). In addition, the creatine and NAA/Cr values in the coronal region of the affected side were significantly lower than those in the opposite side (P<0.05), but there was no significant difference between the pectin nuclei on both sides. No metabolic changes were found at the ipsilateral thalamus. In this study, we demonstrated that MRS could reveal metabolic changes and that the NAA, NAA/Cr, Cho, and Cho/Cr concentration might be used as indexes for evaluating neuronal damage in the chronic steno-occlusive cerebral artery disease, treatment strategies, and treatment effectiveness.


Antiresorptive therapy in asthmatic patients receiving high-dose inhaled steroids: a prospective study for 18 months.
Inhaled steroid therapy is an effective and well tolerated mode of therapy for asthma. Although systemic side-effects of inhaled steroids are much less common than those found with systemic steroids, the drugs may be absorbed through mucosal surfaces. Inhaled steroids have been reported to disturb normal bone metabolism, and they are associated with a decrease in bone mineral density. We conducted this study to investigate bone density in asthmatic subjects receiving long-term high-dose inhaled steroids and the effects of supplementation with oral calcium with or without etidronate. We evaluated thirty-eight Chinese subjects (24 men and 14 premenopausal women; 28 patients and 10 healthy control subjects) in this prospective study. Patients were randomized into three arms: those receiving no supplement, those receiving 1000 mg/day calcium supplement, and those receiving 400 mg/day cyclical sodium etidronate with 1000 mg/day calcium, respectively. The patients and control subjects were matched for age, sex, and dose of inhaled steroids. Bone density at lumbar spine and hip region was measured by dual energy x-ray absorptiometry with a densitometer at baseline and at 6, 12, and 18 months for the asthmatic groups and at baseline and at 12 and 18 months for the control group. Serum calcium, phosphate, alkaline phosphatase, osteocalcin, parathyroid hormone, 25-hydroxyvitamin D, and urinary hydroxyproline/creatine were measured simultaneous to bone density assessments. There were 10 control subjects, 10 asthmatic subjects receiving no supplement, eight asthmatic subjects receiving calcium supplement, and 10 asthmatic subjects receiving calcium and etidronate therapy, respectively. The mean (+/- SEM) dosages of beclomethasone or budesonide for the three groups of asthmatic subjects were 2.2 +/- 0.3, 2.0 +/- 0.2, and 2.0 +/- 0.2 mg/day, respectively. Mean dietary calcium intake of the study subjects was 766 +/- 39 mg/day. At baseline, bone mineral density of the spine in the group receiving no supplement was significantly lower than that found in the control group (p < 0.05). At 18 months, patients receiving no supplement had significantly greater bone loss at the lumbar spine than patients receiving etidronate plus calcium lactate-gluconate (CaLG) or CaLG alone (p < 0.05). The increase in bone mineral density versus baseline observed in patients receiving CaLG with or without etidronate (p < 0.05) probably did not result from increased bone formation because serum osteocalcin levels showed a significant reduction in all three groups of patients (p < 0.05). An increase in mean serum calcium (p < 0.05) was seen in patients receiving CaLG with or without etidronate. Our results suggest that long-term administration of high-dose inhaled steroid (>1.5 mg/day) induces bone loss that is preventable with calcium supplementation with or without cyclical etidronate. Long-term studies involving more patients should follow to confirm these preliminary findings.


[Genodermatoses - pathogenesis and molecular diagnostics].
Genetically determined skin diseases, genodermatoses, are a group of rare disorders characterized by heterogeneous clinical course, prognosis and complex molecular pathology. In Epidermolysis Bullosa (EB) and Mendelian disorders of cornification (MeDOC) epidermal dysfunction occurs. Mutations in several dozen genes have been identified to be responsible for clinical symptoms of EB and MeDOC, which, in general, include: tendency to blister formation with skin fragility and abnormal keratinization, respectively. However, clinical symptoms of these diseases can be variable and genotype-phenotype correlations are only partially determined. Molecular diagnostics aimed at identification of mutations in affected individuals enables verification of clinical diagnosis, calculation of disease recurrence risk in other family members and, gradually, is also the basis for new therapies development. Nevertheless, even modern molecular technologies allow mutation detection in 80% of patients only. Hence, further, interdisciplinary scientific research are needed in order to increase detection rate and develop effective therapies.


Transient left ventricular apical ballooning developing after the Central Niigata Prefecture Earthquake: two case reports.
Two patients presented with transient left ventricular apical ballooning (takotsubo cardiomyopathy) induced by emotional stress caused by the Central Niigata Prefecture Earthquake in 2004. These patients complained of chest pain immediately after the earthquake. In patient 1, electrocardiography (ECG) showed slight ST elevation in leads V5 to V6 and 1 mm ST depression in lead III. Serial ECG revealed inverted giant T waves in leads V3 to V6 and inverted T waves in leads I, II, aVL and aVF 13 days after the earthquake occurred. Patient 2 also complained of chest pain right after the earthquake, but consulted a doctor 15 days after the earthquake occurred. ECG showed inverted giant T wave in leads V1 to V6 and inverted T waves in leads I, II and aVL. Transthoracic echocardiography showed hypokinesis of the apical area of the left ventricle with normokinesis in the basal area in both patients. Coronary angiography showed no stenotic segments and coronary spasms were not induced by provocative testing. Serial cardiac radionuclide single photon emission computed tomography of myocardial functional sympathetic innervation using iodine-123-metaiodobenzyl-guanidine (MIBG) and thiallium-201 (201Tl) showed an MIBG uptake defect and increased wash-out in the apical area, but only mild decrease of apical 201Tl uptake. Due to strong emotional stress, earthquakes may induce transient left ventricular apical ballooning (takotsubo cardiomyopathy).


Physical Effort Exertion for Peer Feedback Reveals Evolving Social Motivations From Adolescence to Young Adulthood.
Peer relationships and social belonging are particularly important during adolescence. Using a willingness-to-work paradigm to quantify incentive motivation, we examined whether evaluative information holds unique value for adolescents. Participants (N = 102; 12-23 years old) rated peers, predicted how peers rated them, and exerted physical effort to view each peer's rating. We measured grip force, speed, and opt-out behavior to examine the motivational value of peer feedback, relative to money in a control condition, and to assess how peer desirability and participants' expectations modulated motivated effort across age. Overall, when compared with adolescents, adults were relatively less motivated for feedback than money. Whereas adults exerted less force and speed for feedback when expecting rejection, adolescents exerted greater force and speed when expecting to be more strongly liked or disliked. These findings suggest that the transition into adulthood is accompanied by a self-protective focus, whereas adolescents are motivated to consume highly informative feedback, even if negative.


Toxic exposure to ethylene dibromide and mercuric chloride: effects on laboratory-reared octopuses.
The effects of acute and chronic exposure to either ethylene dibromide (EDB) or mercuric chloride (MC) were studied in laboratory-reared Octopus joubini, O. maya and O. bimaculoides. The advantages of using octopuses were that the responses were immediate, highly visible and sensitive. All species demonstrated signs of toxicity to acute and chronic exposure to EDB and to MC. A dosage-sensitive relationship for the loss and subsequent recovery of locomotor response and of chromatophore expansion was found for each species after acute exposure. For each species the LC50 for chronic exposure occurred within 12 hr at 100 mg/l for EDB and within 3 hr at 1,000 mg/l for MC. This study demonstrated the potential usefulness of laboratory-reared octopuses in evaluating the toxicity of marine environmental pollutants.


Heat shock protein 27 mediates the effect of 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone on mitochondrial apoptosis in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a global public health problem which causes approximately 500,000 deaths annually. Considering that the limited therapeutic options for HCC, novel therapeutic targets and drugs are urgently needed. In this study, we discovered that 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone (TDP), isolated from the traditional Chinese medicinal herb, Garcinia oblongifolia, effectively inhibited cell growth and induced the caspase-dependent mitochondrial apoptosis in HCC. A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were performed to find the molecular targets of TDP in HCC cells. Eighteen proteins were identified as differently expressed, with Hsp27 protein being one of the most significantly down-regulated proteins induced by TDP. In addition, the following gain- and loss-of-function studies indicated that Hsp27 mediates mitochondrial apoptosis induced by TDP. Furthermore, a nude mice model also demonstrated the suppressive effect of TDP on HCC. Our study suggests that TDP plays apoptosis-inducing roles by strongly suppressing the Hsp27 expression that is specifically associated with the mitochondrial death of the caspase-dependent pathway. In conclusion, TDP may be a potential anti-cancer drug candidate, especially to cancers with an abnormally high expression of Hsp27.


Symptoms and sites of pain experienced by AIDS patients.
HIV/AIDS is the top single cause of mortality burden in South Africa and patients with AIDS present with unique and challenging symptoms and pain syndromes. To identify and increase awareness of the 10 most prevalent symptoms and 5 most common sites of pain in patients with advanced AIDS. A nurse-led questionnaire was used to collect data, and a descriptive, quantitative analysis was done. Subjects included 103 adult patients with World Health Organisation (WHO) stage 4 AIDS. Patients with impaired cognitive function were excluded. The main outcome measures included a list of 30 symptoms, 13 site-specific pains, age, gender, worst overall symptom and access to antiretroviral therapy (ART). Results were based on review of data collected between May 2002 and February 2003. Results showed the mean age of patients to be 35.4 years, with females an average of 4.4 years younger than males. There were a higher number of female respondents (62.6%) than males (37.4%). The 10 most common symptoms in order of prevalence were pain (98%), weight loss (81%), loss of appetite (70.9%), low mood (69.9%), weakness (66%), dry skin (56.3%), diarrhoea (53.4%), nausea and vomiting (44.7%), cough (44.7%) and fatigue (42.7%). Of the of respondents 34.4% mentioned pain as the worst overall symptom. The average number of pains experienced was 2.91. Females reported significantly more anxiety, genital sores and pain than males. Of the patients 3.9% had had access to ART. Lower limb pain was the most prevalent pain (66%) followed by mouth pain (50.5%), headache (42.3%), throat pain (39.8%) and chest pain (17.5%). Patients with advanced AIDS in South Africa suffer significantly from pain and many distressing symptoms. In the light of the HIV/AIDS pandemic in South Africa reforms are needed to increase knowledge and education in the palliative management of AIDS.


Partial nodular transformation of the liver presenting with ascites.
Partial nodular transformation of the liver is a rare condition. Only six cases have been reported previously, all of which presented with bleeding from oesophageal varices. A further example of the disorder is recorded differing in the mode of onset with ascites. The total duration of the illness was eight weeks. Necropsy showed widespread evidence of liver cell damage with nodule formation around the hilum. These nodules had caused portal venous obstruction and ascites.


Nanocluster Transformation Induced by SbF6- Anions toward Boosting Photochemical Activities.
The interactions between SbF6- and metal nanoclusters are of significance for customizing clusters from both structure and property aspects; however, the whole-segment monitoring of this customization remains challenging. In this work, by controlling the amount of introduced SbF6- anions, the step-by-step nanocluster evolutions from [Pt1Ag28(S-Adm)18(PPh3)4]Cl2 (Pt1Ag28-Cl) to [Pt1Ag28(S-Adm)18(PPh3)4](SbF6)2 (Pt1Ag28-SbF6) and then to [Pt1Ag30Cl1(S-Adm)18(PPh3)3](SbF6)3 (Pt1Ag30-SbF6) have been mapped out with X-ray crystallography, with which atomic-level SbF6- counterion effects in reconstructing and rearranging nanoclusters are determined. The structure-dependent optical properties, including optical absorption, photoluminescence, and electrochemiluminescence (ECL), of these nanoclusters are then explored. Notably, the Pt1Ag30-SbF6 nanocluster was ultrabright with a high phosphorescence quantum yield of 85% in N2-purged solutions, while Pt1Ag28 nanoclusters were fluorescent with weaker emission intensities. Furthermore, Pt1Ag30-SbF6 displayed superior ECL efficiency over Pt1Ag28-SbF6, which was rationalized by its increased effectively exposed reactive facets. Both Pt1Ag30-SbF6 and Pt1Ag28-SbF6 demonstrated unprecedented high absolute ECL quantum efficiencies at sub-micromolar concentrations. This work is of great significance for revealing the SbF6- counterion effects on the control of both structures and luminescent properties.


A Perspective on the Role of Point-of-Care "Immuno-Triaging" to Optimize COVID-19 Vaccination Distribution in a Time of Scarcity.
Vaccine bears hope to bring COVID-19 pandemic under control. With limited supply, vaccines must be utilized efficiently to provide protection to those who need it most. Currently, no practical framework has been proposed to ensure fair vaccine allocation at individual level, which is a recognized problem. We propose here an evidence-based decision-making framework for COVID-19 vaccine appropriation that prioritizes vaccine doses to individuals based on their immunological status, or immuno-triaging. To ensure successful implementation of the proposed framework, point-of-care (POC) immunodiagnostic testing is needed to quickly ramp up the testing capability. Considerations for deploying POC immunodiagnostic testing at such a large scale are discussed. We hope that the proposed immunological decision-making framework for evidence-based COVID-19 vaccine appropriation provides an objective approach to ensure fair and efficient utilization of the scarce vaccine resource at the individual level that also maximizes the collective societal benefit.


SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies.
The SOX2 transcription factor is expressed early in the embryonic stem cells of the blastocyst and later in the neural stem cells. It is a member of the SOX family of proteins that carry a DNA-binding high-mobility group domain and additional domains that regulate embryonic development and cell fate determinations. We surveyed 93 patients with severe eye malformations for mutations in SOX2. Here, we report a novel nonsense mutation in one female patient with bilateral clinical anophthalmia, absence of all optic pathways, and other neurological abnormalities. The mutation, Q155X, creates a premature termination codon early in the transcriptional activation domain and is likely to be a null allele. Our data show that mutations in SOX2 can cause not only anophthalmia, but also aplasia of the optic nerve, chiasm and optic tract, as well as modest bilateral sensorineural hearing loss, and global developmental delay, underscoring the importance of SOX2 in early human eye and brain development.


The G(1) cyclin Cln3 promotes cell cycle entry via the transcription factor Swi6.
In Saccharomyces cerevisiae (budding yeast), commitment to cell division in late G(1) is promoted by the G(1) cyclin Cln3 and its associated cyclin-dependent kinase, Cdc28. We show here that all known aspects of the function of Cln3 in G(1) phase, including control of cell size, pheromone sensitivity, cell cycle progress, and transcription, require the protein Swi6. Swi6 is a component of two related transcription factors, SBF and MBF, which are known to regulate many genes at the G(1)-S transition. The Cln3-Cdc28 complex somehow activates SBF and MBF, but there was no evidence for direct phosphorylation of SBF/MBF by Cln3-Cdc28 or for a stable complex between SBF/MBF and Cln3-Cdc28. The activation also does not depend on the ability of Cln3 to activate transcription when artificially recruited directly to a promoter. The amino terminus and the leucine zipper of Swi6 are important for the ability of Swi6 to respond to Cln3 but are not essential for the basal transcriptional activity of Swi6. Cln3-Cdc28 may activate SBF and MBF indirectly, perhaps by phosphorylating some intermediary protein.


Properties and active center of the thermostable branching enzyme from Bacillus stearothermophilus.
Although the branching enzyme (EC 188.8.131.52) is a member of the alpha-amylase family, the characteristics are not understood. The thermostable branching enzyme gene from Bacillus stearothermophilus TRBE14 was cloned and expressed in Escherichia coli. The branching enzyme was purified to homogeneity, and various enzymatic properties were analyzed by our improved assay method. About 80% of activity was retained when the enzyme was heated at 60 degrees C for 30 min, and the optimum temperature for activity was around 50 degrees C. The enzyme was stable in the range of pH 7.5 to 9.5, and the optimum pH was 7.5. The nucleotide sequence of the gene was determined, and the active center of the enzyme was analyzed by means of site-directed mutagenesis. The catalytic residues were tentatively identified as two Asp residues and a Glu residue by comparison of the amino acid sequences of various branching enzymes from different sources and enzymes of the alpha-amylase family. When the Asp residues and Glu were replaced by Asn and Gln, respectively, the branching enzyme activities disappeared. The results suggested that these three residues are the catalytic residues and that the catalytic mechanism of the branching enzyme is basically identical to that of alpha-amylase. On the basis of these results, four conserved regions including catalytic residues and most of the substrate-binding residues of various branching enzymes are proposed.


Wheat kernel black point and fumonisin contamination by Fusarium proliferatum.
Fusarium proliferatum is a major cause of maize ear rot and fumonisin contamination and also can cause wheat kernel black point disease. The primary objective of this study was to determine whether nine F. proliferatum strains from wheat from Nepal can cause black point and fumonisin contamination in wheat kernels. For comparison, the study included three Fusarium strains from US maize. In test 1, all the strains but one produced significant symptoms of kernel black point; two strains decreased kernel yield; and four strains contaminated kernels with fumonisins B(1), B(2) and B(3) as determined by liquid chromatography-mass spectroscopy. Strain Ggm202 from Nepal, which produced the highest levels of fumonisins (mean = 49 microg g(-1)) on five wheat cultivars in test 1, was confirmed to produce fumonisins (mean = 38 microg g(-1)) on two cultivars in test 2. The data indicate a potential for fumonisin contamination of wheat infected with F. proliferatum.


[Effects of infrasound therapy on proliferation, apoptosis and ultrastructure of human B lymphoma Raji cells].
To investigate the effect of infrasound therapy on the proliferation, apoptosis and ultrastructure of human B lymphoma Raji cells. Human B lymphoma Raji cells were exposed to infrasound treatment for 15, 30, 60, 90 and 120 min and cultured subsequently for 24 or 48 h. MTT assay, flow cytometry analysis, and electron microscopy were performed to examine the proliferative status, cell apoptosis and ultrastructural changes of the exposed cells, respectively. MTT assay revealed no significant changes in the proliferation of the cells exposed to infrasound treatment (P>0.05), nor did flow cytometry analysis identified significant variation in the cell apoptosis (P>0.05). Scanning electron microscopy, however, identified shortened or reduced cell processes and microvilli on the surface of the cells with infrasound exposure and a subsequent 24-hour culture, and the cell membrane surface became smooth. Under transmission electron microscope, the cells with infrasound treatment presented with significantly reduced microvilli, and the cell nuclei appeared homogeneous, with cytoplasmic budding and losses after a 48-hour culture. Infrasound less than 90 dB does not obviously affect the proliferation and apoptosis of Raji cells, but may directly cause cell ultrastructural changes such as reduction of the cell processes.


Interplay between heat shock proteins HSP101 and HSA32 prolongs heat acclimation memory posttranscriptionally in Arabidopsis.
Heat acclimation improves the tolerance of organisms to severe heat stress. Our previous work showed that in Arabidopsis (Arabidopsis thaliana), the "memory" of heat acclimation treatment decayed faster in the absence of the heat-stress-associated 32-kD protein HSA32, a heat-induced protein predominantly found in plants. The HSA32 null mutant attains normal short-term acquired thermotolerance but is defective in long-term acquired thermotolerance. To further explore this phenomenon, we isolated Arabidopsis defective in long-term acquired thermotolerance (dlt) mutants using a forward genetic screen. Two recessive missense alleles, dlt1-1 and dlt1-2, encode the molecular chaperone heat shock protein101 (HSP101). Results of immunoblot analyses suggest that HSP101 enhances the translation of HSA32 during recovery after heat treatment, and in turn, HSA32 retards the decay of HSP101. The dlt1-1 mutation has little effect on HSP101 chaperone activity and thermotolerance function but compromises the regulation of HSA32. In contrast, dlt1-2 impairs the chaperone activity and thermotolerance function of HSP101 but not the regulation of HSA32. These results suggest that HSP101 has a dual function, which could be decoupled by the mutations. Pulse-chase analysis showed that HSP101 degraded faster in the absence of HSA32. The autophagic proteolysis inhibitor E-64d, but not the proteasome inhibitor MG132, inhibited the degradation of HSP101. Ectopic expression of HSA32 confirmed its effect on the decay of HSP101 at the posttranscriptional level and showed that HSA32 was not sufficient to confer long-term acquired thermotolerance when the HSP101 level was low. Taken together, we propose that a positive feedback loop between HSP101 and HSA32 at the protein level is a novel mechanism for prolonging the memory of heat acclimation.


Mobile lipids and metabolic heterogeneity of brain tumours as detectable by ex vivo 1H MR spectroscopy.
To examine metabolic heterogeneity in primary brain tumour, multiple biopsies (one to five per tumour) from four benign meningiomas, five acoustic schwannomas, eleven glial tumours and five medulloblastomas were each subdivided into one to five samples (total = 194) and investigated using ex vivo 360 MHz 1H MR spectroscopy with histopathological correlation. Low amounts of mobile lipids were detected in meningothelial meningiomas and medulloblastomas, high amounts in some or all samples of all other tumours. The differences in non-lipid metabolites between different tumour types were less marked, with the exception of the medulloblastomas, which had high amounts of N-acetyl aspartate and cholines. The amount of mobile lipid correlated with Antoni type B areas in schwannomas and necrosis in a high grade giant cell tumour. The amount of lipid varied significantly from sample to sample in a grade 2 astrocytoma and grade 4 astrocytoma samples with 0-5% necrosis but did not correlate with the site in the tumour or histopathological characteristics. The metabolic heterogeneity occurred on a spatial scale at least as small as the size of the MR samples, i.e., < or = 60 mg. These results suggest that the detection of metabolic heterogeneity and mobile lipids may have importance for the design of clinical studies.


Implementing a Skin Cancer Prevention Lesson to Enact Institutional Change: A Schoolwide Survey.
Schools can play a major role in protecting students from skin cancer by instituting preventive policies and educational programs. A high school-wide study was conducted to assess students' current understanding of skin cancer prevention, provide an up-to-date instruction lesson, and evaluate changes in students' knowledge and behaviors. Written surveys were distributed to 2,688 high school students with a return rate of 38.1% (n = 1,025). Surveys were administered prior to (survey 1), immediately after (survey 2), and 1 month after (survey 3) presenting a video lesson. Significant changes in knowledge gain (an increase from survey 1 to survey 2), knowledge decay (a decrease from survey 2 to survey 3), and knowledge persistence (an increase from survey 1 to survey 3) throughout all grade levels were found. Behavioral changes included an increase in students wearing sunscreen 5-7 days per week (p < 0.001) and students examining themselves for changing moles (p = 0.10). With this survey, the Health Education Framework for California Public Schools was revised to include updated recommendations regarding skin cancer prevention efforts in schools. A skin cancer video lesson given to high school students effectively increased students' knowledge and promoted healthy behaviors.


Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities.
Papillary renal cell carcinoma (pRCC) is the second most common renal cell carcinoma (RCC) subtype and accounts for 10-15% of all RCCs. Despite clinical need, few pharmacogenomics studies in pRCC have been performed. Moreover, current research fails to adequately include pRCC laboratory models, such as the ACHN or Caki-2 pRCC cell lines. The molecular mechanisms involved in pRCC development and drug resistance are more diverse than in clear-cell RCC, in which inactivation of VHL occurs in the majority of tumours. Drug resistance to multiple therapies in pRCC occurs via genetic alteration (such as mutations resulting in abnormal receptor tyrosine kinase activation or RALBP1 inhibition), dysregulation of signalling pathways (such as GSK3β-EIF4EBP1, PI3K-AKT and the MAPK or interleukin signalling pathways), deregulation of cellular processes (such as resistance to apoptosis or epithelial-to-mesenchymal transition) and interactions between the cell and its environment (for example, through activation of matrix metalloproteinases). Improved understanding of resistance mechanisms will facilitate drug discovery and provide new effective therapies. Further studies on novel resistance biomarkers are needed to improve patient prognosis and stratification as well as drug development.


Cast-model and scanning electron microscopy of the rat brain ventricular system.
In order to establish a good experimental model for comparative studies of the brain ventricular system in mammals, a resin-cast model and scanning electron microscopy were employed to examine the rat brain ventricular system. From the resin-cast model, we found that the gross morphology of the brain ventricular systems of rats is simpler than that of humans. From scanning electron microscopy, local variations of ependymal cells lining the rat brain ventricle were noted. Most areas of the ventricles were lined by ciliated ependymal cells arranged in regular rows, whereas in some other areas non-ciliated ependymal cells were also observed. Epiplexus cells and supraependymal cells were also encountered on the top surface of the choroid epithelium, and ependymal cells in certain area such as the pineal recess.


Interaction of mant-adenosine nucleotides and magnesium with kinesin.
Displacement of the fluorescent substrate analogue methylanthraniloyl ADP (mant-ADP) from kinesin by excess ATP results in a biphasic fluorescent transient. The pH and microtubule dependence of the rates and amplitudes indicates that the two phases are produced by release of bound mant-ADP, with an excess of the 3'-isomer, followed by the subsequent relaxation of the free 2'- and 3'-isomers to their equilibrium distribution. The first phase for release of mant-ADP is accelerated by microtubules and occurs at the same rate as ADP release measured using [32P]ADP. The second phase is subject to base catalysis and occurs at the same rate as the isomerization of isolated 2'- or 3'-mant-ATP over a 100-fold range of rates. The bound mant-ADP isomers undergo isomerization rapidly when bound to kinesin at pH 8.2, whereas mant-ADP isomers interconvert only slowly when bound to myosin. No fluorescence resonance energy transfer occurs between the single tryptophan in the kinesin neck domain and bound mant-ADP, but efficient energy transfer does occur from protein tyrosine groups. The rate of mant-ADP release in the absence of microtubules is minimal (0.005 s-1) at pH 7-8, 2 mM Mg2+, and 25 mM KCl but is accelerated at lower pH (0.04 s-1 at pH 5.5) and either lower or higher [KCl] (0.01 and 0. 06 s-1 at 0 and 800 mM KCl, respectively). The microtubule-stimulated rate of ADP release is accelerated at low pH and inhibited by high concentrations of monovalent salts. Reduction of the free Mg2+ by addition of excess EDTA increases the release of mant-ADP from E.MgADP to 0.03 s-1. This acceleration at low Mg2+ likely represents sequential release of Mg2+ at 0.03 s-1 followed by rapid release of ADP, as the rate of ADP release from Mg-free E.ADP is fast (>0.5 s-1). At high Mg2+, rebinding of Mg2+ to E.ADP forces release of ADP from the E.MgADP complex at 0.005 s-1.


Hypoxic Gene Expression of Donor Bronchi Linked to Airway Complications after Lung Transplantation.
Central airway stenosis (CAS) after lung transplantation has been attributed in part to chronic airway ischemia; however, little is known about the time course or significance of large airway hypoxia early after transplantation. To evaluate large airway oxygenation and hypoxic gene expression during the first month after lung transplantation and their relation to airway complications. Subjects who underwent lung transplantation underwent endobronchial tissue oximetry of native and donor bronchi at 0, 3, and 30 days after transplantation (n = 11) and/or endobronchial biopsies (n = 14) at 30 days for real-time polymerase chain reaction of hypoxia-inducible genes. Patients were monitored for 6 months for the development of transplant-related complications. Compared with native endobronchial tissues, donor tissue oxygen saturations (Sto2) were reduced in the upper lobes (74.1 ± 1.8% vs. 68.8 ± 1.7%; P < 0.05) and lower lobes (75.6 ± 1.6% vs. 71.5 ± 1.8%; P = 0.065) at 30 days post-transplantation. Donor upper lobe and subcarina Sto2 levels were also lower than the main carina (difference of -3.9 ± 1.5 and -4.8 ± 2.1, respectively; P < 0.05) at 30 days. Up-regulation of hypoxia-inducible genes VEGFA, FLT1, VEGFC, HMOX1, and TIE2 was significant in donor airways relative to native airways (all P < 0.05). VEGFA, KDR, and HMOX1 were associated with prolonged respiratory failure, prolonged hospitalization, extensive airway necrosis, and CAS (P < 0.05). These findings implicate donor bronchial hypoxia as a driving factor for post-transplantation airway complications. Strategies to improve airway oxygenation, such as bronchial artery re-anastomosis and hyperbaric oxygen therapy merit clinical investigation.


Buildup region of high-energy x-ray beams in radiosurgery.
The depths of dose maxima of radiosurgical x-ray beams increase with the field diameter in the range from 10-30 mm. Furthermore, the degree of the increase is proportional to the photon beam energy. This behavior is in contrast to that of large radiotherapeutic fields, where the depths of dose maxima decrease with increasing field size. The surface doses, depths of dose maxima, and collimator scatter factors for radiosurgical beams with energies between 6 and 18 MV are presented. It is shown that the change in dmax for radiosurgical beams is a result of photon scatter in the phantom rather than in the collimator. Monte Carlo simulations of the radiosurgical beams are used to separate the total dose into two components: the primary dose and the scattered dose. Calculations indicate that buildup region characteristics are governed by the primary dose deposition in the medium. The scattered dose has a minimal effect on the total dose deposited in media by radiosurgical beams.


Apoptosis plays a distinct role in the loss of precursor lymphocytes during zinc deficiency in mice.
Lymphopenia is a characteristic of zinc deficiency, which is associated with massive loss of pre-B and pre-T cells from the primary lymphoid organs of zinc-deficient mice that have elevated serum corticosterone (CS). We examined whether this naturally elevated glucocorticoid level is associated with increased apoptotic loss of pre-T cells in the thymus of A/J and CAF1/J mice. In three experiments, partially atrophied thymuses were removed from 20 marginally zinc-deficient (ZD) young adult mice and cultured for 6 h in parallel with thymocytes prepared from 17 adequately fed mice. Thymocyte immunophenotyping combined with flow cytometric cell cycle analysis was used to identify the degree of apoptotic cell death among thymocytes of the two dietary groups, which were compared in the absence of in vivo phagocytosis. Apoptosis was enhanced 50-300% among pre-T cells (CD4+CD8+) prepared from ZD mice. This resulted in a 38% shrinkage of the thymic pre-T cell compartment, which was associated with an 80% decrease in thymic cell number. Pro-T cells (CD4-CD8-) and mature T cells (CD4+CD8-, CD4-CD8+), which express higher levels of Bcl-2 protein, survived ZD to a greater extent and formed a greater proportion of the remaining thymocyte population in ZD mice. Collectively, these data show that heightened degrees of apoptotic cell death induced in vivo by CS-disrupted thymic T cell lymphopoiesis, identifies the means of disruption of marrow B cell lymphopoiesis and explains the appearance of lymphopenia.


Effects of Flash Glucose Monitoring on Dietary Variety, Physical Activity, and Self-Care Behaviors in Patients with Diabetes.
The aim of this study was to evaluate the effects of flash glucose monitoring on dietary variety, physical activity, and self-care behavior in patients with diabetes. This study included outpatients with diabetes using insulin who presented at the Department of Diabetes and Metabolism of the Ise Red Cross Hospital. Before initiating flash glucose monitoring and 12 weeks after its initiation, blood glucose-related parameters were assessed and self-administered questionnaires were completed (Dietary Variety Score (DVS), the International Physical Activity Questionnaire (IPAQ), the Summary of Diabetes Self-Care Activities Measure (SDSCA), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ)) and compared between the two time points. We analyzed 42 patients with type 1 diabetes mellitus and 48 patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus, but not type 1 diabetes mellitus, there was an increase in moderate/high category scores for IPAQ (P < 0.001) and for treatment satisfaction reported via DTSQ. Furthermore, in patients with type 2 diabetes mellitus, the glycemic excursion index improved significantly and HbA1c decreased significantly (from 7.7 (1.2) to 7.4 (0.8), P = 0.025). Results showed that standard deviation and mean amplitude of glycemic excursions significantly decreased in patients with type 1 diabetes mellitus (from 71.2 (20.4) to 66.2 (17.5), P = 0.033 and from 124.6 (31.9) to 108.1 (28.4), P < 0.001, respectively). Flash glucose monitoring is a useful tool to improve physical activity in patients with type 2 diabetes.


Mesenchymal stem cell secretome decreases the inflammatory response in annulus fibrosus organ cultures.
Mesenchymal stem/stromal cell (MSC)-based therapies have been proposed for back pain and disc degeneration, despite limited knowledge on their mechanism of action. The impact of MSCs/their secretome on annulus fibrosus (AF) cells and tissue was analysed in bovine AF organ cultures (AF-OCs) exposed to upper-physiological cyclic tensile strain (CTS, 9 %, 1 Hz, 3 h/d) and interleukin (IL)-1β in a custom-made device. A 4 d treatment of the CTS + IL-1β-stimulated AF-OCs with MSC secretome downregulated the expression of inflammation markers [IL-6, IL-8, prostaglandin-endoperoxide synthase 2 (PTGS2)], complement system regulators [cluster of differentiation (CD)46, CD55, CD59] and matrix metalloproteinase 1 but also of tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and collagen type I. At the protein level, it was confirmed that IL-6, MMP-3 and collagen content was decreased in AF-OCs treated with the MSC secretome compared to the CTS + IL-1β stimulation alone. 9 d after treatment, a biomechanical peel-force test showed that the annular adhesive strength was significantly decreased by the MSC secretome treatment. Overall, MSC secretome had a stronger impact on AF tissue than MSCs in co-culture. The secretome contributed to a decrease in the inflammatory and catabolic status of AF cells activated by CTS + IL-1β and played a role in the regulation of the complement system. However, it also contributed to a decrease in collagen at the gene/protein level and in AF mechanical strength compared to the CTS + IL-1β stimulation alone. Therefore, the use of MSC secretome requires further investigation regarding its influence on disc matrix properties.


Novel Score-based Decision Approach in Chronic Myeloid Leukemia Patients After Acute Toxic Imatinib-induced Liver Injury.
The tyrosine kinase inhibitor (TKI) imatinib in rare cases can cause acute toxic hepatitis, hepatic failure, and death. Currently, the choice of further chronic myeloid leukemia (CML) therapy in patients after acute hepatotoxicity is still a difficult question, which requires a complex individual approach based on the clinical guidelines of adverse event management. Data about the further follow-up strategy approach in patients with CML after acute toxic imatinib-induced liver injury are of concern, and at times controversial. In addition, one of the questions is about the necessity and safety of the imatinib therapy resumption after acute hepatotoxicity. In some publications, imatinib resumption without the recurrence of hepatotoxicity has been discussed; in others, imatinib resumption with the recurrence of imatinib hepatotoxicity has been mentioned. There are a few publications about the experience of administration of the second-line TKIs after acute imatinib hepatotoxicity. There are no clear data on which factors the physician's decision should be based on in patients with CML after acute toxic imatinib-induced liver injury. Imatinib should be restarted or withdrawn, when and for whom second-line therapy should be started. The physician's decision is usually based on the published data of similar cases, personal experience, and the severity of hepatotoxicity. We have discussed the clinical guidelines devoted to the peculiarities of the patient's management after acute toxic imatinib-induced hepatitis and main strategy approaches. A complex score-based decision algorithm for choosing the further strategy approach after acute toxic imatinib-induced hepatitis in patients with CML has been presented. The following parameters should be assessed: the grade of hepatotoxicity reaction, the presence of liver transplantation or imatinib-induced liver cirrhosis and its possible pathogenetic mechanism, the presence of early molecular response (EMR) to imatinib therapy defined as three-month BCR-ABL1 ≤10% according to the international scale (BCR-ABL1IS ) or/and six-month BCR-ABL1 IS <1%; and the presence of the offender concomitant drug that probably caused the drug interaction with imatinib and the presence of viral hepatitis reactivation identified by polymerase chain reaction (PCR).


Effects of frequency modulation (FM) transmitter microphone directivity on speech perception in noise.
Frequency modulation (FM) technology can significantly improve the speech perception ability of individuals with sensorineural hearing loss (SNHL) in background noise. Previous investigations have demonstrated that the microphone design of the FM transmitter can have a significant impact on this improved speech perception. The purpose of this investigation was to compare 3 types of FM transmitter microphone designs: (a) wide angle (omnidirectional microphone), which amplifies sounds coming from all directions around the microphone equally; (b) zoom (1 directional microphone), which provides less amplification to signals coming from the rear, and (c) superzoom (2 directional microphones), which provides less amplification to signals originating from the rear and the sides. Fifteen adults with bilateral slight to moderately severe SNHL participated. Speech perception was assessed using the Hearing in Noise Test (M. Nilsson, S. Soli, and J. Sullivan, 1994). Speech spectrum shaped noise served as the noise competition. Results revealed that the best speech perception in noise was obtained when the FM transmitter was used in the zoom setting. The poorest performance was obtained when the FM transmitter was in the wide-angle mode. The clinical implications of these results are discussed.


Modulation of Iron Availability at the Host-Pathogen Interface in Phagocytic Cells.
This review summarizes recent data on iron metabolism in macrophages, with a special emphasis on possible bacteriostatic and bactericidal consequences for intracellular pathogens. It includes the role of biological chelators and transporters in normal macrophage physiology and antimicrobial defense. Iron is an essential metal cofactor for many biochemical pathways in mammals. However, excess iron promotes the formation of cytotoxic oxygen derivatives so that systemic iron levels must be tightly regulated. The mechanism of iron recycling by macrophages including iron efflux from erythrocyte-containing phagosomes, iron release from macrophages, and entry into the transferrin (Tf) cycle remain poorly understood. Ferroportin expression in the liver, spleen, and bone marrow cells appears to be restricted to macrophages. Mutant mice bearing a conditional deletion of the ferroportin gene in macrophages show retention of iron by hepatic Kupffer cells and splenic macrophages. Hepcidin is induced by lipopolysaccharide (LPS) in mouse spleens and splenic macrophage in vitro and appears to mediate the LPS-induced down-regulation of ferroportin in the intestine and in splenic macrophages, suggesting that inflammatory agents may regulate iron metabolism through modulation of ferroportin expression. The host transporter Nramp1 may compete directly with bacterial divalent-metal transport systems for the acquisition of divalent metals within the phagosomal space. The ultimate outcome of these competing interactions influences the ability of pathogens to survive and replicate intracellularly. This seems particularly relevant to the Salmonella, Leishmania, and Mycobacterium spp., in which inactivating mutations in Nramp1 abrogate the natural resistance of macrophages to these pathogens.


Variations in the adenohypophysis of the expression of proliferating cellular nuclear antigen, oestrogen and androgen receptors in relation to gonadal steroids during pregnancy of viscachas (Lagostomus maximus maximus).
Viscachas are native rodents of South America that present a long pregnancy of ~154 days. In this work, we analysed variations in the expression of proliferating cellular nuclear antigen, oestrogen and androgen receptors (ERα and AR) in pituitary pars distalis (PD) and pars tuberalis (PT) in relation to oestradiol and testosterone serum levels in non-pregnant and pregnant viscachas. In PD, cell proliferation increased with pregnancy and lactotrophs proliferated during mid-pregnancy (MP). ERα nuclear-immunoreactive cells (ERαn-ir) were maximal in late pregnancy and AR expression did not vary during pregnancy. In PT, cell proliferation and AR expression increased during pregnancy, but ERα expression was very scarce. The immunostaining pattern of receptors was different in PD and PT. The peak of serum oestradiol and testosterone occurred during MP. Our results suggest that cell proliferation and gonadal receptors might be differentially regulated in the pituitary by oestradiol and testosterone during viscacha pregnancy.


Association between HCO3(-) absorption and K+ uptake by Amphiuma jejunum: relations among HCO3(-) absorption, luminal K+, and intracellular K+ activity.
Titration techniques and K+- sensitive microelectrodes have been used to investigate the relations among HCO3(-) absorption, luminal K+, and intracellular K+ activity in in vitro Amphiuma jejunum. The HCO3(-) absorptive flux (JHCO3(-] measured by pH-stat under short circuit was reduced by removal of K+ from the medium but not by replacement of Na+ with choline. JHCO3(-) exhibited a seasonal variation when K+ was absent from the media and was increased to a maximum when K+ equaled 5 mM. Addition of K+ to a K+-free luminal medium stimulated JHCO3(-) much more than addition to the serosal medium. Acetazolamide (10(-4) M) blocked K+-stimulated HCO3(-) absorption while benzolamide reduced the short-circuit current associated with HCO3(-) absorption much more rapidly when added to the mucosal bathing medium. Intracellular K+ activity (aik) and mucosal membrane potential (psi m) of jejunal villus cells were measured with double-barreled microelectrodes. When bathed bilaterally with HCO3(-)-containing media, K+ was actively accumulated for many hours (aik = 58.5 mM) but in the presence of ouabain fell to equilibrium (16 mM) after 2 h. In contrast, when HCO3(-) absorption was induced by removal of serosal HCO3(-), aik was elevated to 83.6 mM and, after 4-h exposure to ouabain cell K+, remained far above electrochemical equilibrium at 33 mM. Tissues bathed in Na+-free (Tris) media containing ouabain retained cell K+ after 4 h at even higher levels (46 mM). Cell K+ activity was reduced by removal of K+ from either the mucosal or serosal medium. Acetazolamide reduced aik over 2 h in Na+-free media from 66 to 42 mM. The decline in aik was associated with a concomitant decline in the HCO3(-) absorptive current. It is concluded that K+ is actively accumulated across both luminal and serosal membranes of the jejunal absorptive cell and that the luminal uptake mechanism is linked to HCO3(-) absorption or an equivalent process.


International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.
The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.


Lessons from SARS: control of acute lung failure by the SARS receptor ACE2.
Angiotensin-converting enzyme 2 (ACE2), a second angiotensin-converting enzyme (ACE), regulates the renin-angiotensin system by counterbalancing ACE activity. Accumulating evidence in recent years has demonstrated a physiological and pathological role of ACE2 in the cardiovascular systems. Recently, it has been shown that severe acute respiratory syndrome (SARS) coronavirus, the cause of SARS, utilizes ACE2 as an essential receptor for cell fusion and in vivo infections in mice. Intriguingly, ACE2 acts as a protective factor in various experimental models of acute lung failure and, therefore, acts not only as a key determinant for SARS virus entry into cells but also contributes to SARS pathogenesis. Here we review the role of ACE2 in disease pathogenesis, including lung diseases and cardiovascular diseases.


Distribution of blood group antigens A, B and H in human fetal oral mucosal and odontogenic epithelium.
The distribution of blood group antigens A, B and H was examined in human fetal oral mucosal and odontogenic epithelium. Tissue from 19 fetuses with crown-rump lengths of 57 mm to 189 mm, corresponding to a fertilization age of 10-20 weeks, was included in the study. The distribution of blood group antigens was studied by immunofluorescence methods on tissue sections. Cell membrane bound blood group antigen A or B was demonstrated in the oral mucosal epithelium of 10 fetuses whereas blood group antigen H was found in all fetuses. All the epithelial cell layers of the tooth germs were devoid of the blood group antigens A, b and H independent of the age of the fetus. The blood group antigens A, B and H were located on the cell membranes of the upper cell layers of the oral epithelium, whereas the basal cells showed no reaction even in the youngest fetuses. Following the differentiation of the epithelial cells, changes were seen in the distribution of the blood group antigens.


Socioeconomic differences in the cost, availability and quality of healthy food in Sydney.
To compare the cost of a basket of staple foods, together with the availability and quality of fresh fruit and vegetables, by supermarket store type in high and low socioeconomic suburbs of Sydney. A food basket survey was undertaken in 100 supermarkets in the 20 highest and 20 lowest socioeconomic suburbs of Sydney. We assessed the cost of 46 foods, the range of 30 fresh fruit and vegetables and the quality of ten fresh fruit and vegetables. Two major supermarket retailers, a discount supermarket chain and independent grocery stores were surveyed. The food basket was significantly cheaper in low compared to high socioeconomic suburbs ($177 vs $189, p<0.01). Discount supermarkets were at least 30% cheaper than other supermarket stores. There were fewer varieties and poorer quality fruit and vegetables in stores in low socioeconomic suburbs. Food basket prices and the availability and quality of fruit and vegetables varied significantly by store type and socioeconomic status of suburb. Implications for public health: A nationwide food and nutrition surveillance system is required to inform public health policy and practice initiatives. In addition to the food retail environment, these initiatives must address the underlying contributors to inequity and food insecurity for disadvantaged groups.


Cd(II)-terpyridine-based complex as a ratiometric fluorescent probe for pyrophosphate detection in solution and as an imaging agent in living cells.
The terpyridine anthracene ligand was synthesized and characterized. is a ratiometric fluorescent probe for Cd(2+) with a recognition mechanism based on intramolecular charge transfer (ICT). An complex was isolated, and its structure was established using single-crystal XRD. The complex was able to serve as a novel reversible chemosensing ensemble to allow ratiometric response to pyrophosphate (PPi) in aqueous media. Moreover, the fluorescence imaging in living cells from these two emission channels suggested that was a ratiometric probe for Cd(2+), and the in situ generated complex was also a ratiometric ensemble for PPi detection in living cells.


Static and fatigue resistance of two types of implant/abutment connectors.
The aim of this study is to determine in an experimental way through mechanical tests the static, fatigue and torque resistance of two types of implant/abutment connectors with diameters of 3.4–5.2 mm.


Factors influencing the implementation of the Becoming Breastfeeding Friendly initiative in Ghana.
Becoming Breastfeeding Friendly (BBF) is an initiative designed to help countries assess their readiness to scale-up breastfeeding programs and develop key recommendations to strengthen their breastfeeding environment. In 2016, Ghana was one of two countries to first pilot BBF. In applying BBF, a committee of 15 Ghanaian nutrition, health, and breastfeeding experts implemented the BBF toolbox over 8 months. Following implementation, semistructured interviews were conducted with 12 committee members (CMs) to (a) identify facilitators and barriers to implement BBF and (b) determine factors needed to strengthen the breastfeeding environment in Ghana. Using a grounded theory approach, five domains were identified. First, a dynamic committee of key stakeholders drove the implementation of BBF. Second, CMs faced some logistical and methodological challenges, including difficulty accessing data and the need for strong in-country technical support for adhering to the BBF process. Third, CMs felt well positioned to facilitate and lead the dissemination and implementation of recommendations. Fourth, accountability would be essential to properly translate recommendations. Fifth, to move recommendations to action, advocacy would be a required first step, and BBF was proposed to facilitate this step. BBF provided an in-depth analysis of Ghana's current breastfeeding environment to help Ghana strengthen its breastfeeding governance, policies, and programs while informing CMs' government and non-governmental organizations' breastfeeding efforts.


Diversity and taxonomy of endophytes from Leymus chinensis in the Inner Mongolia steppe of China.
Epichloë species and their anamorphic relatives in genus Neotyphodium are fungal symbionts of grasses ubiquitously existing in temperate regions all over the world. To date, 13 Epichloë species and 22 Neotyphodium species have been formally described, based on morphological characters and phylogenetic analyses. Leymus chinensis (Poaceae) is a dominant grass native to the Inner Mongolia steppe of China. Previously, it was reported to harbor endophytes, but little was known about these endophytes. To investigate their diversity and taxonomy, 96 fungal isolates were obtained from three field populations of L. chinensis. The isolates were classified into three morphotypes based on morphological characters and phylogenetic analyses of sequences of genes for β-tubulin (tubB), translation elongation factor 1-α (tefA), and actin (actG). The dominant morphotype, morphotype I, was identified as a choke disease endophyte, Epichloë bromicola. This broadened the host range and phylogenetic definition of E. bromicola.


Bacterial endophytes of sugar maple leaves vary more idiosyncratically than epiphytes across a large geographic area.
Bacteria from the leaf surface and the leaf tissue have been attributed with several beneficial properties for their plant host. Though physically connected, the microbial ecology of these compartments has mostly been studied separately such that we lack an integrated understanding of the processes shaping their assembly. We sampled leaf epiphytes and endophytes from the same individuals of sugar maple across the northern portion of its range to evaluate if their community composition was driven by similar processes within and across populations differing in plant traits and overall abiotic environment. Leaf compartment explained most of the variation in community diversity and composition across samples. Leaf epiphytic communities were driven more by host and site characteristics than endophytic communities, whose community composition was more idiosyncratic across samples. Our results suggest a greater importance of priority effects and opportunistic colonization in driving community assembly of leaf endophytes. Understanding the comparative assembly of bacterial communities at the surface and inside plant leaves may be particularly useful for leveraging their respective potential for improving the health of plants in natural and anthropized ecosystems.


Genetic Characteristics and Transcriptional Regulation of Sodium Channel Related Genes in Chinese Patients With Brugada Syndrome.
Objective: To investigate the genetic characteristics and transcriptional regulation of the SCN5A gene of Brugada syndrome (BrS) patients in China. Methods: Using PubMed, Medline, China National Knowledge Internet (CNKI), and Wanfang Database, Chinese patients with BrS who underwent SCN5A gene testing were studied. Results: A total of 27 suitable studies involving Chinese BrS patients who underwent the SCN5A gene test were included. A total of 55 SCN5A gene mutations/variations were reported in Chinese BrS patients, including 10 from southern China and 45 from northern China. Mutations/variations of BrS patients from southern China mostly occurred in the regions of the α-subunit of Nav1.5, including DIII (Domain III), DIV, DIII-DIV, C-terminus regions, and the 3'UTR region. Furthermore, we analyzed the post-transcriptional modifications (PTMs) throughout the Nav1.5 protein encoded by SCN5A and found that the PTM changes happened in 72.7% of BrS patients from southern China and 26.7% from northern China. Conclusions: SCN5A mutations/variations of BrS patients in southern China mostly occurred in the DIII-DIV to C-terminus region and the 3'-UTR region of the SCN5A gene, different from northern China. PTM changes were consistent with the mutation/variation distribution of SCN5A, which might be involved in the regulation of the pathogenesis of BrS patients.


Adhesion mechanisms in embryogenesis and in cancer invasion and metastasis.
Cell-substratum and cell-cell adhesion mechanisms contribute to the development of animal form. The adhesive status of embryonic cells has been analysed during epithelial-mesenchymal cell interconversion and in cell migrations. Clear-cut examples of the modulation of cell adhesion molecules (CAMs) have been described at critical periods of morphogenesis. In chick embryos the three primary CAMs (N-CAM. L-CAM and N-cadherin) present early in embryogenesis are expressed later in a defined pattern during morphogenesis and histogenesis. The axial mesoderm derived from gastrulating cells expresses increasing amounts of N-cadherin and N-CAM. During metamerization these two adhesion molecules become abundant at somitic cell surfaces. Both CAMs are functional in an in vitro aggregation assay; however, the calcium-dependent adhesion molecule N-cadherin is more sensitive to perturbation by specific antibodies. Neural crest cells which separate from the neural epithelium lose their primary CAMs in a defined time-sequence. Adhesion to fibronectins via specific surface receptors becomes a predominant interaction during the migratory process, while some primary and secondary CAMs are expressed de novo during the ontogeny of the peripheral nervous system. In vitro, different fibronectin functional domains have been identified in the attachment, spreading and migration of neural crest cells. The fibronectin receptors which transduce the adhesive signals play a key role in the control of cell movement. All these results have prompted us to examine whether similar mechanisms operate in carcinoma cell invasion and metastasis. In vitro, rat bladder transitional carcinoma cells convert reversibly into invasive mesenchymal cells. A rapid modulation of adhesive properties is found during the epithelial-mesenchymal carcinoma cell interconversion. The different model systems analysed demonstrate that a limited repertoire of adhesion molecules, expressed in a well-defined spatiotemporal pattern, is involved in tissue formation and in key processes of tumour spread.


Upregulation of FoxM1 protects against ischemia/reperfusion-induced myocardial injury.
Ischemia/reperfusion (I/R) induced lethal tissue injury in myocardium. FoxM1 (Forkhead Box M1), expressed in proliferating cardiac progenitor cells, could regulate myocardial development. However, the role of FoxM1 in I/R-induced myocardial injury has not been reported yet. Rats were conducted with regional ischemia followed by reperfusion in myocardium through ligation of the left anterior descending coronary artery. Triphenyl-tetrazolium chloride staining was utilized to assess the infarct size. ELISA was performed to detect activities of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Protein expression of FoxM1 in heart tissues and H9c2 were determined by western blot. H9c2 cells were used to establish a hypoxia/reoxygenation cell model, and the cell viability, proliferation and apoptosis were evaluated by MTT, EdU (5-ethynyl-2'-deoxyuridine) staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, respectively. Adenovirus (Ad)-mediated over-expression of FoxM1 was injected into the anterior wall of the left ventricle of rats to evaluate the role of FoxM1 on in vivo I/R-induced myocardial injury. FoxM1 was reduced in heart tissues isolated from rats post myocardial I/R injury. Forced FoxM1 expression increased cell viability and proliferation of hypoxia/reoxygenation-induced H9c2, while repressed the cell apoptosis with increased Bcl-2 and decreased Bax and cleaved caspase-3. Injection of Ad-FoxM1 suppressed infarct size of the heart and decreased activities of CK-MB and LDH. FoxM1 attenuated I/R-induced myocardial injury, providing potential therapeutic target for the disease.


Drug use and suicidal ideation in the daily lives of individuals in a dialectical behavior therapy program.
Substance use disorders and borderline personality disorders (BPD) often co-occur and may be concurrently treated by Dialectical Behavior Therapy (DBT). However, there is limited information on how drug use and suicidal ideation may interact in the daily lives of individuals receiving DBT treatment. This study examined the DBT diary cards of 47 individuals in a community mental health center's partial hospital and intensive outpatient program. Multilevel modeling techniques were used to examine the moderating effects of BPD symptom severity on the relationship between same day, 1-, 2-, and 3-day lagged drug use and suicidal ideation. Results indicated a significant relationship between same-day, 1-day lagged, 2-day lagged drug use and suicidal ideation. BPD was a moderator for the relationship between 1-day lagged drug use and suicidal ideation. Limitations of the study include the measure for BPD symptom severity was only collected pretreatment and the results are likely limited to the effects of cannabis use on suicidal ideation. Clinicians may need to consider the prolonged effects of drug use on suicidal ideation when conducting chain analyses on suicidal behaviors.


Haloperidol, but not olanzapine, impairs cognitive performance after traumatic brain injury in rats.
Traumatic brain injury can cause a variety of impairments, including persistent alterations in personality, mood, and cognition. Antipsychotic agents are frequently used to treat pathologic behaviors in traumatic brain injury patients, but the influence of prolonged administration of such drugs on cognition after injury is unknown. The effects of two antipsychotic drugs on cognitive recovery after traumatic brain injury were assessed using the fluid percussion model in rats. The typical antipsychotic, haloperidol, and the third-generation antipsychotic, olanzapine, were administered via intraperitoneal injection beginning 24 hr after injury and continuing daily for the duration of the study. Morris water maze performance was assessed on days 11-15 postinjury. Haloperidol, an antagonist acting on D2-like dopamine receptors, exacerbated the cognitive deficits induced by injury, as injured rats treated with 0.30 mg/kg haloperidol performed worse in the Morris water maze than injured rats treated with vehicle. Our results demonstrate the importance of the D2 receptor in cognitive recovery after traumatic brain injury. Also, the data illustrate that some classes of antipsychotic drugs may influence cognitive recovery, and further research is needed to determine the optimal pharmacologic treatment of aggression, agitation, and other pathologic behaviors in patients with traumatic brain injury.


Mice cloned by nuclear transfer from somatic and ntES cells derived from the same individuals.
The current success rate of cloned mice from adult somatic cell nuclei is very low, whereas it is relatively high for cloned mice from ES cell nuclei. In this experiment, we examined whether the success rate of cloning from somatic cells could be improved via nuclear transfer embryonic stem cells (ntES cells) established from somatic cell nuclei. We obtained 11 cloned mice and 68 ntES cell lines from the somatic cell nuclei of 7 mice, and cloned 41 mice were cloned from the ntES cell nuclei. Unexpectedly, the overall success rate of cloning from ntES cell nuclei in this series was no better than when using somatic cell nuclei. Interestingly, full-term cloned mice were produced only via ntES cells from two individuals, but not by direct nuclear transfer from the somatic cells, and vice versa. Ultimately, we were able to obtain clone mice from 6 out of 7 individuals using either somatic cells or ntES cells. Thus, although ntES cells as donor nuclei do not absolutely assure a better success rate for mouse cloning than somatic cells, to preserve and clone valuable individuals, we recommend that ntES cell lines be established. These can then be used as an unlimited source of donor nuclei for nuclear transfer, and thus complement conventional somatic cell nuclear transfer cloning approaches.


Left coronary ostial stenosis after the modified bentall using a long interposed coronary graft in a patient with pectus excavatum.
A 26-year-old man presented chest oppression. He had pectus excavatum associated with Loeys-Dietz syndrome and a history of redo aortic root replacement with the modified Bentall technique using an 8-mm long interposed graft to the left coronary ostium. Coronary angiography revealed severe stenosis of both left coronary ostium and proximal left anterior descending artery, which was supposed to be resulted from thrombosis in the interposed graft. The left coronary system was bypassed through a left thoracotomy, which was suitable in this patient because the pectus excavatum would prevent harvest of the left internal thoracic artery through re-median sternotomy and to avoid potential sternal reentry injury of the heart. Although the left anterior descending artery was easily accessed under off-pump technique, exposure and anastomosis of the circumflex coronary artery was more difficult than expected without cardiopulmonary bypass as the pectus excavatum and adhesion of the heart prevented anterior shift and rotation of the heart.