[Role of breakfast and its quality in the health of children and adolescents in Spain].
Eating breakfast is a healthy habit that should be encouraged since childhood. When it provides nutritional quality, it is an important daily meal. The consumption of dairy products, cereals, and fruits at breakfast is associated with healthier dietary patterns, with a beneficial impact on the overall quality of the diet. In Spain, as in many other countries, the proportion of children who eat breakfast daily is very high, decreasing somewhat in adolescence. However, the quality of breakfast leaves room for improvement, with a low proportion of children/adolescents with high nutritional quality breakfasts. Children/adolescents who eat breakfast regularly have a higher intake of various nutrients (especially vitamins and minerals) than those who do not eat breakfast. Although the evidence is not entirely conclusive, numerous studies have shown various benefits when comparing the population that eats breakfast regularly versus those who do not, such as cardiometabolic risk parameters (obesity, diabetes, blood pressure and lipid profile) and cognitive functions. Breakfast should be included in healthy eating plans, since it allows incorporating foods that are difficult to consume in other meals and may contribute to reducing the risk of developing cardiometabolic diseases. In order to promote the intake of a healthy breakfast, it is essential to act on the sociodemographic and cultural factors that influence compliance and quality, such as age, nutritional education (mainly parents and children/adolescents, but also other family members, school mates, friends...), carrying it out as a family, adapting it to the tastes of each population and balancing quality and costs.


Impact of Ethnicity and Underlying Comorbidity on COVID-19 Inhospital Mortality: An Observational Study in Abu Dhabi, UAE.
The UAE reported its first cluster of COVID 2019 in a group of returned travellers from Wuhan in January 2020. Various comorbidities are associated with worse disease prognosis. Understanding the impact of ethnicity on the disease outcome is an important public health issue but data from our region is lacking. We aim to identify comorbidities among patients hospitalized for COVID-19 that are associated with inhospital death. Also, to assess if ethnicity is correlated with increased risk of death. Patients and Method. The study is a single-centre, observational study in Shaikh Shakhbout Medical City, Abu Dhabi. Patients admitted with COVID-19, between 1st of March and the end of May, were enrolled. Records were studied for demography, comorbidity, and ethnicity. Ethnicity was divided into Arabs (Gulf, North Africa, and the Levant), South Asia (India, Pakistan, Bangladesh, Nepal, and Afghanistan), Africans, the Philippines, and others. The study was approved by the Department of Health of Abu Dhabi. 1075 patients (972 males) were enrolled. There were 24 nationalities under 5 ethnicity groups. Mean (average) age was 51 years (20-81). 101 (9.4%) died with deceased patients being significantly older. Death risk was not significantly influenced by sex. Duration of hospitalization among survivors was 6.2 days (0.2-40.4) with older patients and men staying longer (P < 0.01). Comorbidities of diabetes, hypertension, cardiovascular disease, chronic renal disease, liver disease, and malignancy were associated with higher risk of mortality univariate, but only liver disease reached statistical significance after adjustment for age. The highest percentage of death was seen in Arab Levant (21.2) followed by the Asian Afghan (18.8); however, differences among ethnicities did not reach statistical significance (P = 0.086). COVID-19 outcome was worse in older people and those with comorbidities. Men and older patients required longer hospitalization. Ethnicity is not seen to impact the risk of mortality.


Cyclic AMP-dependent protein kinases and human trophoblast cell differentiation in vitro.
Human trophoblast cells offer a unique in vitro model for the study of aspects of the dynamic processes occurring during cell fusion and syncytium formation. In the human placenta, mononuclear cytotrophoblasts aggregate and fuse to form a multinucleated syncytiotrophoblast. In vitro, the addition of cyclic AMP analogs, 8-bromo-cyclic-AMP or Sp-8-bromo-cyclic AMPS, promotes syncytiotrophoblast formation, as shown by the disappearance of immunostained E-cadherin and desmoplakin, and increased numbers of nuclei per syncytium. An antagonist of cyclic AMP, Rp-8-bromo-cyclic AMPS, and an inhibitor of the cyclic AMP-dependent protein kinase catalytic subunit, H-89, impair cell fusion. This led us to study the pattern of expression and subcellular localization of cyclic-AMP-dependent protein kinase subunits during syncytium formation. Cytotrophoblasts expressed the RIalpha and RIIalpha regulatory subunits and the Calpha and Cbeta catalytic subunits. RIalpha was down-regulated during syncytium formation. No change in RIIalpha protein levels was observed, but there was a drastic subcellular redistribution. RIIalpha located in the Golgi-centrosomal area of cytotrophoblasts was scattered throughout the cytoplasm of the syncytiotrophoblast. Interestingly, an accumulation of RIIalpha was observed underneath the apical membrane of syncytiotrophoblast in vitro and in situ. This suggests a key role of cyclic AMP-dependent protein kinase type IIalpha during cell fusion and microvilli formation, both of which are essential for the secretory and transfer functions of the syncytiotrophoblast.


Overexpression of c-Met and CD44v6 receptors contributes to autocrine TGF-β1 signaling in interstitial lung disease.
The hepatocyte growth factor (HGF) and the HGF receptor Met pathway are important in the pathogenesis of interstitial lung disease (ILD). Alternatively spliced isoforms of CD44 containing variable exon 6 (CD44v6) and its ligand hyaluronan (HA) alter cellular function in response to interaction between CD44v6 and HGF. TGF-β1 is the crucial cytokine that induces fibrotic action in ILD fibroblasts (ILDFbs). We have identified an autocrine TGF-β1 signaling that up-regulates both Met and CD44v6 mRNA and protein expression. Western blot analysis, flow cytometry, and immunostaining revealed that CD44v6 and Met colocalize in fibroblasts and in tissue sections from ILD patients and in lungs of bleomycin-treated mice. Interestingly, cell proliferation induced by TGF-β1 is mediated through Met and CD44v6. Further, cell proliferation mediated by TGF-β1/CD44v6 is ERK-dependent. In contrast, action of Met on ILDFb proliferation does not require ERK but does require p38(MAPK). ILDFbs were sorted into CD44v6(+)/Met(+) and CD44v6(-)/Met(+) subpopulations. HGF inhibited TGF-β1-stimulated collagen-1 and α-smooth muscle cell actin expression in both of these subpopulations by interfering with TGF-β1 signaling. HGF alone markedly stimulated CD44v6 expression, which in turn regulated collagen-1 synthesis. Our data with primary lung fibroblast cultures with respect to collagen-1, CD44v6, and Met expressions were supported by immunostaining of lung sections from bleomycin-treated mice and from ILD patients. These results define the relationships between CD44v6, Met, and autocrine TGF-β1 signaling and the potential modulating influence of HGF on TGF-β1-induced CD44v6-dependent fibroblast function in ILD fibrosis.


Subcellular, regional and immunohistochemical localization of adenosine deaminase in various species.
Immunohistochemical and subcellular fractionation techniques were employed to compare the cellular and subcellular localization of adenosine deaminase (ADA) in various brain regions of several mammalian species. A relatively restricted distribution of ADA-immunoreactive neurons in rat brain was previously reported. Mouse brain exhibited a pattern similar in many respects to rat and, in addition, contained intensely immunostained neurons in lateral habenula and hippocampus. Glial immunostaining was absent or very light in rat but evident in mouse. Prominent immunoreactive fibers and neurons were observed in hamster spinal cord and anterior hypothalamus, respectively. ADA-immunostaining in guinea-pig was localized to presumptive fibers in the superficial layers of spinal cord dorsal horn and to glial cells throughout the brain. Demonstration of specific immunostaining in rabbit was not possible. ADA activity was far more heterogeneously distributed in rat and most brain areas in guinea-pig and rabbit contained up to 5-fold and 10-fold higher levels of activity, respectively, compared with rat. Crude synaptosomal (P2) fractions of rat cortex contained a greater proportion of ADA activity than those of rabbit cortex. Within rat, relatively high activity was found in P2 fractions of whole hypothalamus, cerebellum, and hippocampus. ADA activity was greater in P2 fractions of rat anterior compared with whole hypothalamus and the greatest proportion of the enzyme in this fraction was localized to purified synaptosomes. The large variations in the activity and cellular location of ADA in the animals examined suggest species differences in mechanisms governing adenosine metabolism in brain and possible differences in the relationships between cellular metabolism, ADA and the neuroregulatory role of adenosine in the CNS.


Molecular cloning of a cDNA encoding the porcine type XVII collagen noncollagenous 16 A domain and localization of the domain to the upper part of porcine skin basement membrane zone.
Bullous pemphigoid is an autoimmune blistering human skin disease mediated by immunoglobulin (Ig)G autoantibodies targeting skin basement membrane component type XVII collagen, a transmembrane protein. Also designated BP180 and BPAG2, type XVII collagen is an extracellular matrix element essential for the connection between the epidermis and the underlying dermis. In addition to being a target antigen in the human disease bullous pemphigoid, type XVII collagen is also targeted by autoantibodies of canine, feline, equine and porcine patients suffering from a similar blistering skin disease. Previously, enzyme-linked immunosorbent assay and Western blot analyses have shown that autoantibodies from pigs affected with bullous pemphigoid recognize the human NC16A domain of type XVII collagen. To facilitate the development of porcine model of bullous pemphigoid, we isolated cDNA encoding the porcine type XVII collagen NC16A domain using a reverse transcription-polymerase chain reaction technique. The amino acids deduced from the NC16A cDNA showed 61% identity with the sequence of human NC16A. An antibody generated against a 20-amino acid peptide within the porcine NC16A localized the NC16A epitope to the upper part of porcine skin basement membrane zone. Our data provide further information of the porcine bullous pemphigoid target antigen and may help investigators for their further studies of this disease.


Measurement of the limiting equivalent conductivities and mobilities of the most prevalent ionic species of EGTA (EGTA2- and EGTA3-) for use in electrophysiological experiments.
In many experimental biological situations, chelating agents like EGTA (ethylene glycol-bis-(beta-amino-ethyl ether) N,N,N',N'-tetra-acetic acid) are commonly used to control or suppress the concentration of divalent ions like Ca2+. The evaluation of liquid junction potentials in electrophysiological measurements, and particularly in patch-clamp situations, requires information about the ions within the solution. Where there is a significant concentration of EGTA present, it is necessary to know the values of the relative mobility of at least the most predominant ionic species of EGTA in order to complete these calculations. EGTA, with four negative charges with different pKas, can therefore exist as four differently charged ions in solution (EGTA-, EGTA2-, EGTA3- and EGTA4-) or as uncharged, although between pH 5.5 and 8 it is almost exclusively EGTA2-. We have measured limiting equivalent conductivities of the most common ionic forms of EGTA (EGTA2- and EGTA3-) encountered at physiological pHs. These were 35.9 +/- 0.7 and 56 +/- 2.5 S cm2 equiv(-1) respectively. Their mobilities relative to K+ were 0.24 +/- 0.01 for EGTA2- and 0.25 +/- 0.01 for EGTA3-. Thus for typical electrophysiological solutions, the contribution of EGTA to the liquid junction potential should be small (e.g. approximately 0.4 mV).


Costimulation through the CD137/4-1BB pathway protects human melanoma tumor-infiltrating lymphocytes from activation-induced cell death and enhances antitumor effector function.
Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose interleukin-2 is a promising form of immunotherapy for stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8(+) T cells to differentiate into effector cells losing key costimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8(+) TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative costimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Postrapid expansion protocol (REP) TIL were found to be highly sensitive to activation-induced cell death when reactivated through the T-cell receptor with low levels of OKT3 antibody. However, coligation of 4-1BB using 2 different agonistic anti-4-1BB antibodies potently prevented activation-induced cell death of post-REP CD8(+) TIL, including those specific for melanoma antigen recognized by T cells, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB costimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced cytotoxic T-cell activity against melanoma cells. Lastly, post-REP CD8(+) TIL were protected from cell death by anti-4-1BB ligation when exposed to human leukocyte antigen-matched melanoma cells. Our results indicate that 4-1BB costimulation may significantly improve TIL survival during melanoma ACT and boost antitumor cytolytic activity.


[The effect of aminostimil on the regulation of sexual function in rats].
The effect of aminostimil: a synthetic drug of the acylhydrazide group, was studied in white rats. Aminostimil decreased the uterus weight but did not interfere with estrogen positive action in ovariectomized (OVX) rats, although it increased the FSH level, abolished the inhibitory effect of estradiol on the FSH secretion and did not change the secretion of the LH. Aminostimil induced accumulation of GnRH in the preoptic area and median eminence area in intact female and male rats, LH concentration in the blood plasma but decreased. The data obtained suggest that the antiestrogenic effect of aminostimil is due to inhibition of the GnRH secretion from the hypothalamus into the portal blood.


The Thumb Domain Mediates Acid-sensing Ion Channel Desensitization.
Acid-sensing ion channels (ASICs) are cation-selective proton-gated channels expressed in neurons that participate in diverse physiological processes, including nociception, synaptic plasticity, learning, and memory. ASIC subunits contain intracellular N and C termini, two transmembrane domains that constitute the pore, and a large extracellular loop with defined domains termed the finger, β-ball, thumb, palm, and knuckle. Here we examined the contribution of the finger, β-ball, and thumb domains to activation and desensitization through the analysis of chimeras and the assessment of the effect of covalent modification of introduced Cys at the domain-domain interfaces. Our studies with ASIC1a-ASIC2a chimeras showed that swapping the thumb domain between subunits results in faster channel desensitization. Likewise, the covalent modification of Cys residues at selected positions in the β-ball-thumb interface accelerates the desensitization of the mutant channels. Studies of accessibility with thiol-reactive reagents revealed that the β-ball and thumb domains reside apart in the resting state but that they become closer to each other in response to extracellular acidification. We propose that the thumb domain moves upon continuous exposure to an acidic extracellular milieu, assisting with the closing of the pore during channel desensitization.


Associations between cancer and Alzheimer's disease in a U.S. Medicare population.
Several studies have reported bidirectional inverse associations between cancer and Alzheimer's disease (AD). This study evaluates these relationships in a Medicare population. Using Surveillance, Epidemiology, and End Results (SEER) linked to Medicare data, 1992-2005, we evaluated cancer risks following AD in a case-control study of 836,947 cancer cases and 142,869 controls as well as AD risk after cancer in 742,809 cancer patients and a non-cancer group of 420,518. We applied unconditional logistic regression to estimate odds ratios (ORs) and Cox proportional hazards models to estimate hazards ratios (HRs). We also evaluated cancer in relation to automobile injuries as a negative control to explore potential study biases. In the case-control analysis, cancer cases were less likely to have a prior diagnosis of AD than controls (OR = 0.86; 95% CI = 0.81-0.92). Cancer cases were also less likely than controls to have prior injuries from automobile accidents to the same degree (OR = 0.83; 95% CI = 0.78-0.88). In the prospective cohort, there was a lower risk observed in cancer survivors, HR = 0.87 (95% CI = 0.84-0.90). In contrast, there was no association between cancer diagnosis and subsequent automobile accident injuries (HR = 1.03; 95% CI = 0.98-1.07). That cancer risks were similarly reduced after both AD and automobile injuries suggest biases against detecting cancer in persons with unrelated medical conditions. The modestly lower AD risk in cancer survivors may reflect underdiagnosis of AD in those with a serious illness. This study does not support a relationship between cancer and AD.


Relationship between homogeneous IgG fractions and measles virus antibody activities in subacute sclerosing panencephalitis brain.
Cellulose acetate and agarose gel electrophoresis of pH 7.4 brain extracts from three patients with subacute sclerosing panencephalitis (SSPE) revealed two to three homogeneous bands in the gamma-globulin region. The IgG concentration in the brain extracts ranged from 6 to 8.5% of the total protein. The IgG was isolated by passing each brain extract twice through gel filtration on Sephadex G-200 column. The Sephadex-isolated IgG preparations, at a concentration of 1 mg/ml, had hemagglutination inhibition (HI) titers ranging from 512 to 800, complement fixation (CF) titers of 64 to 100, and neutralizing titers of 400 to 1024 when tested against envelope, nucleocapsids, and while measles virus, respectively. These IgG preparations were further separated into several fractions by isoelectric focusing (IEF) technique and the reactivities of these eluted fractions were examined against differnt specific measles virus components and against whole virus. The results showed that both slow and fast moving homogeneous IgG had high HI and neutralizing titers. However, CF antibodies were present only in specific IEF-eluted fractions and their profiles differed somewhat from one brain to another. The IgG fractions reacted with both kappa-and gamma-chain antisera, but the reactivity varied from one brain to another. When the polyacrylamide gel electrophoretic (PAGE) patterns of heavy (H) and light (L) chains of SSPE IgG were compared to those of IgG from controls, the H chain patterns of both groups were identical whereas the SSPE brain IgG demonstrated two distinct bands in L chain as compared to a single diffuse band observed in controls. These latter results, in addition to homogeneous bands and selective CF antibody activity in IEF eluted IgG fractions from SSPE brain, fulfill some of the criteria of monoclonality.


Injury severity assessment in tibial plateau fractures.
Assessment of injury severity is an integral component of the care of the patient with a fracture of the tibial plateau. Devising ways to reliably quantify injury severity, and to make predictive links between injury severity and outcome, however, has been difficult. Assessment of patient-related factors, such as age, functional capabilities, and medical comorbidities, are necessarily subjective, but certain of these factors clearly shape the treatment plan for a patient with a tibial plateau fracture. Clinical examination findings, such as extent of soft tissue injury and mediolateral stability of the knee, also play an important role in determining treatment and predicting outcome. Radiographic classification of tibial plateau fractures also is an important determinant of treatment, but current classification systems have suffered from disappointing interobserver reliability. Although the severity of injury to the articular cartilage almost certainly affects outcome, there currently are no validated modalities to measure this important factor. More carefully validated tools are needed in many of these areas if we are to perfect our understanding of injury severity and establish more accurate correlations between injury severity and outcomes.


Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients.
Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC. We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients. We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs. This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.


Comparison of Xpert MTB/RIF with AFB smear and AFB culture in suspected cases of paediatric tuberculosis in a tertiary care hospital, Karachi.
To evaluate the sensitivity, specificity, positive predictive and negative predictive values of Xpert mycobacterium tuberculosis and resistance to rifampicin by comparing it with acid-fast bacilli smear and culture in suspected tuberculosis patients. The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised patient data from January 2013 to December 2016. Data related to children with clinical suspicion of pulmonary and extra-pulmonary tuberculosis based on Modified Kenneth Jones criteria, aged 1 month to 18 years whose samples (respiratory or non-respiratory) were sent for Xpert mycobacterium tuberculosis and resistance to rifampicin and acid-fast bacilli smear and culture con currently. Analysis was carried out by STATA 12 and Med Calc softwares . Of the 91 cases, 50(54.9%) related to females. The overall median age of the patients was 12.5 years (interquartile range: 8 years). Overall, 42(46.2%) cases had extra-pulmonary tuberculosis. The Xpert test had 66.7% sensitivity compared to smear microscopy 47.6%. Overall sensitivity, specificity, positive predictive value and negative predictive value were 95.7%, 72%, 51.2% and 98.3% respectively when the two tests were compared. Xpert mycobacterium tuberculosis was found to be more sensitive than acid-fast bacilli smear and culture in both pulmonary and extra-pulmonar y tuberculosis in children.


Effects of non-aversive versus tail-lift handling on breeding productivity in a C57BL/6J mouse colony.
Non-aversive handling is a well-documented refinement measure for improving rodent welfare. Because maternal stress is related to reduced productivity, we hypothesized that welfare benefits associated with non-aversive handling would translate to higher production and fewer litters lost in a laboratory mouse breeding colony. We performed a randomized controlled trial to examine the effects of a standard method of handling (tail-lift with forceps) versus non-aversive handling with transfer tunnels ('tunnel-handled') on breeding performance in 59 C57BL/6J mouse pairs. Intervention assignments could not be concealed from technicians, but were concealed from assessors and data analyst. An operationally significant effect of tunnel-handling (large enough differences to warrant programmatic change) was defined before study initiation as a 5% increase in productivity, or one extra pup over the reproductive lifetime of each pair. Pairs were randomly allocated to handling intervention and cage rack location, and monitored over an entire 6-month breeding cycle. For each group, we measured number of pups born and weaned, and number of entire litters lost prior to weaning. Differences between transfer methods were estimated by two-level hierarchical mixed models adjusted for parental effects and parity. Compared to tail-lift mice, tunnel-handled mice averaged one extra pup per pair born (+1.0; 95% CI 0.9, 1.1; P = 0.41) and weaned (+1.1, 95% CI 0.9, 1.2; P = 0.33). More tunnel-handled pairs successfully weaned all litters produced (13/29 pairs, 45% vs 4/30 pairs, 13%; P = 0.015), averaged fewer litter losses prior to weaning (11/29 pairs [38%] vs 26/30 pairs [87%]; P <0.001), and had a 20% lower risk of recurrent litter loss. The increase in numbers of pups produced and weaned with tunnel handling met threshold requirement for operational significance. These data and projected cost savings persuaded management to incorporate tunnel handling as standard of care across the institution. These data also suggest that overlooked husbandry practices such as cage transfer may be major confounders in studies of mouse models.


Tissue effects of subclinical diode laser treatment of the retina.
To determine whether consistent tissue effects are obtained when laser lesions are produced with a commercially available diode laser that are near the limit of clinical detection at the time of treatment. Continuous-wave or micropulse diode laser was used to produce clinically undetectable (subthreshold) or barely detectable (threshold) retinal lesions in pigmented rabbits. Tissue effects at intervals after treatment were determined in retinal pigment epithelial (RPE) whole mounts by fluorescence microscopy, and in sections of retina and RPE by light and electron microscopy. Continuous-wave and micropulse laser lesions that were originally clinically undetectable were detectable as zones of pigment mottling after 5 days. By microscopy, compaction and/or swelling was seen in the outer retina, and cells in the RPE monolayer became heterogeneous in size, shape, and pigmentation, but the tissue responses in the outer retina and RPE were variable even within and among lesions in the same eye. Subthreshold energies used to create both continuous-wave and micropulse laser lesions produced variable effects on the RPE and the overlying neurosensory retina. It appears that, near the minimum effective dose of laser irradiation, individual RPE cell heterogeneity becomes detectable as variability in sensitivity to laser injury. As laser energy is reduced to limit collateral tissue damage in clinical applications, it may be difficult to generate reproducible lesions because of heterogeneity among individual cells.


Impairment of Nucleolin Activity and Phosphorylation by a Trachylobane Diterpene from Psiadia punctulata in Cancer Cells.
Human nucleolin (hNcl) is a multifunctional protein involved in the progression of various cancers and plays a key role in other pathologies. Therefore, there is still unsatisfied demand for hNcl modulators. Recently, we demonstrated that the plant ent-kaurane diterpene oridonin inhibits hNcl but, unfortunately, this compound is quite toxic for healthy cells. Trachylobane diterpene 6,19-dihydroxy-ent-trachiloban-17-oic acid (compound 12) extracted from Psiadia punctulata (DC.) Vatke (Asteraceae) emerged as a ligand of hNcl from a cellular thermal shift assay (CETSA)-based screening of a small library of diterpenes. Effective interaction between this compound and the protein was demonstrated to occur both in vitro and inside two different types of cancer cells. Based on the experimental and computational data, a model of the hNcl/compound 12 complex was built. Because of this binding, hNcl mRNA chaperone activity was significantly reduced, and the level of phosphorylation of the protein was affected. At the biological level, cancer cell incubation with compound 12 produced a cell cycle block in the subG0/G1 phase and induced early apoptosis, whereas no cytotoxicity towards healthy cells was observed. Overall, these results suggested that 6,19-dihydroxy-ent-trachiloban-17-oic could represent a selective antitumoral agent and a promising lead for designing innovative hNcl inhibitors also usable for therapeutic purposes.


Systematic review and meta-analysis of remotely delivered interventions using self-monitoring or tailored feedback to change dietary behavior.
Self-monitoring (SM) of diet and tailored feedback (TF) have been suggested as tools for changing dietary behavior. New technologies allow users to monitor behavior remotely, potentially improving reach, adherence, and outcomes. We conducted a systematic literature review and meta-analysis to address the following question: are remotely delivered standalone (i.e., no human contact) interventions that use SM or TF effective in changing eating behaviors? Five databases were searched in October 2016 (updated in September 2017). Only randomized controlled trials published after 1990 were included. Trials could include any adult population with no history of disordered eating which delivered an SM or TF intervention without direct contact and recorded actual dietary consumption as an outcome. Three assessors independently screened the search results. Two reviewers extracted the study characteristics, intervention details, and outcomes, and assessed risk of bias using the Cochrane tool. Results were converted to standardized mean differences and incorporated into a 3-level (individuals and outcomes nested in studies) random effects meta-analysis. Twenty-six studies containing 21,262 participants were identified. The majority of the studies were judged to be unclear or at high risk of bias. The meta-analysis showed dietary improvement in the intervention group compared to the control group with a standardized mean difference of 0.17 (95% CI: 0.10, 0.24; P < 0.0001). The I2 statistic for the meta-analysis was 0.77, indicating substantial heterogeneity in results. A "one study removed" sensitivity analysis showed that no single study excessively influenced the results. Standalone interventions containing self-regulatory methods have a small but significant effect on dietary behavior, and integrating these elements could be important in future interventions. However, there was substantial variation in study results that could not be explained by the characteristics we explored, and there were risk-of-bias concerns with the majority of studies.


Self-reported Exposure to Sexual and Reproductive Health Information among American Indian Youth: Implications for Technology Based Intervention.
While technology-based interventions show promise in certain populations of American youth, the technology may intrinsically widen intergenerational communication chasms associated with youth's increased access to Smartphone technologies. The authors examined self-reported exposure to sexual and reproductive health information and evaluated its relationship with sexual risk behaviors with American Indian youth. Approximately 296 students, ages of 15-18 years old, were surveyed to examine self-reported exposure and attitudes to information received about sexual intercourse, reproduction, and social media use in relation to sexual risk behaviors. Results indicate that information received regarding sexual intercourse and birth control from intra-familial network members was associated with more engagement in sex, and that increased social media use to talk or learn about sex was associated with not using a condom at the last sexual encounter. We advise that researchers and programmers considering technology-based interventions with AI communities carefully consider the gravity of investing preventive resources into technology-based interventions that may further deepen communication gaps that youth experience within their community networks.


Mechanisms involved in the desflurane-induced post-conditioning of isolated human right atria from patients with type 2 diabetes.
Desflurane triggers post-conditioning in the diabetic human myocardium. We determined whether protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels, Akt, and glycogen synthase kinase-3β (GSK-3β) were involved in the in vitro desflurane-induced post-conditioning of human myocardium from patients with type 2 diabetes. The isometric force of contraction (FoC) of human right atrial trabeculae obtained from patients with type 2 diabetes was recorded during 30 min of hypoxia followed by 60 min of reoxygenation. Desflurane (6%) was administered during the first 5 min of reoxygenation either alone or in the presence of calphostin C (PKC inhibitor) or 5-hydroxydecanoate (5-HD) (mitoK(ATP) channel antagonist). Phorbol 12-myristate 13-acetate (PKC activator) and diazoxide (a mitoK(ATP) channel opener) were superfused during early reoxygenation. The FoC at the end of the 60 min reoxygenation period was compared among treatment groups (FoC(60); mean and sd). The phosphorylation of Akt and GSK-3β was studied using western blotting. Desflurane enhanced the recovery of force [FoC(60): 79 (3)% of baseline] after 60 min of reoxygenation when compared with the control group (P>0.0001). Calphostin C and 5-HD abolished the beneficial effect of desflurane-induced post-conditioning (both P<0.0001). Phorbol 12-myristate 13-acetate and diazoxide enhanced the FoC(60) when compared with the control group (both P<0.0001). Desflurane increased the level of phosphorylation of Akt and GSK-3β (P<0.0001). Desflurane-induced post-conditioning in human myocardium from patients with type 2 diabetes was mediated by the activation of PKC, the opening of the mitoK(ATP) channels, and the phosphorylation of Akt and GSK-3β.


Systematics and evolution of ticks with a list of valid genus and species names.
In recent years there has been much progress in our understanding of the phylogeny and evolution of ticks, in particular the hard ticks (Ixodidae). Indeed, a consensus about the phylogeny of the hard ticks has emerged which is quite different to the working hypothesis of 10 years ago. So that the classification reflects our knowledge of ticks, several changes to the nomenclature of ticks are imminent or have been made. One subfamily, the Hyalomminae, should be sunk, while another, the Bothriocrotoninae, has been created (Klompen, Dobson & Barker, 2002). Bothriocrotoninae, and its sole genus Bothriocroton, have been created to house an early-diverging ('basal') lineage of endemic Australian ticks that used to be in the genus Aponomma. The remaining species of the genus Aponomma have been moved to the genus Amblyomma. Thus, the name Aponomma is no longer a valid genus name. The genus Rhipicephalus is paraphyletic with respect to the genus Boophilus. Thus, the genus Boophilus has become a subgenus of the genus Rhipicephalus (Murrell & Barker, 2003). Knowledge of the phylogenetic relationships of ticks has also provided new insights into the evolution of ornateness and of their life cycles, and has allowed the historical zoogeography of ticks to be studied. Finally, we present a list of the 899 valid genus and species names of ticks as of February 2004.


Perspective of adults in Saudi Arabia toward complementary and alternative medicine use for autism spectrum disorder: a cross-sectional study.
Autism Spectrum Disorder (ASD) is a high-prevalence neurodevelopmental disorder characterized by communicational, social, and behavioral challenges. Complementary and alternative medicine (CAM) is a group of practices and products that fall outside the realm of conventional medicine practiced worldwide. Traditional CAM is a health practice that comes from a particular culture, such as the use of Zamzam water and black seeds in Saudi Arabia. CAM comprises widely utilized practices in Saudi Arabia for children of various ages and adults. In many cases, CAM is used to treat ASD. The aim of this study is to investigate the perspectives of adults in Saudi Arabia toward CAM for treating ASD. A cross-sectional study was conducted by distributing an online questionnaire to adults in different regions of Saudi Arabia. A total of 4,311 adults participated in this study; 66.8% were females and 33.2% were male. Half of the participants reported that they knew about ASD (54.7%). More than half of the participants indicated that CAM-including art therapy (69.0%), physical exercise (67.0%), and limiting the use of electronic (55.4%)-could help in ASD management. Around half of the respondents indicated a belief that traditional treatment cannot help in treating ASD (53.9%). Only 20.0% of the respondents thought that ASD could be entirely treated using CAM therapies. The most common source of knowledge about CAM was social media and the internet (58.6%). The majority of participants in this study did not believe that ASD could be treated entirely using CAM. In addition, fewer than half of the participants believed that CAM therapies could improve different aspects of ASD, such as behavioral issues. The study highlighted the need for awareness among residents of Saudi Arabia regarding specific treatments for ASD.


Benchmark study on glyphosate-resistant cropping systems in the United States. Part 5: Effects of glyphosate-based weed management programs on farm-level profitability.
Glyphosate-resistant (GR) crops have changed the way growers manage weeds and implement control strategies. Since the introduction of GR crops, growers in many instances have relied on glyphosate almost exclusively to control a broad spectrum of weeds. This over-reliance on glyphosate has resulted in the evolution of glyphosate resistance in some weed species. Growers and scientists are concerned about the sustainability of GR crops and glyphosate. When a grower is making decisions about weed control strategies, economic costs and benefits of the program are primary criteria for selection and implementation. Studies across six states were initiated in 2006 to compare the economics of using a weed resistance best management practice (BMP) system with a grower's standard production system. Resistance BMP systems recommended by university scientists were more costly but provided similar yields and economic returns. Rotation of GR crops resulted in a higher net return (maize and soybean) compared with continuous GR crop (cotton or soybean) or rotating a GR crop with a non-GR crop (maize). Growers can implement weed resistance BMP systems with the confidence that their net returns will be equivalent in the short run, and, in the long term, resistance BMP systems will prevent or delay the evolution of GR weeds in their fields, resulting in substantial savings.


A small step or a giant leap: Accounting for settlement delay and dispersal in restoration planning.
Understanding larval duration and hence dispersal potential of the European oyster Ostrea edulis is crucial to inform restoration strategies. Laval duration has an obligatory period of maturity to pediveliger (when larvae are ready to settle), but also an unknown period until metamorphosis is triggered by a settlement cue. The extent to which larvae can prolong the pediveliger period and delay metamorphosis has not been studied. Here we show that O. edulis larvae can delay metamorphosis for a period of 11 days, while retaining the capability to settle in high proportions when presented with a suitable settlement cue. O. edulis larvae are likely to be able to delay metamorphosis even further, since 80% of larvae in the control treatment were still alive when the experiment was terminated at day 14. The results indicate the ability of O. edulis larvae to more than double pelagic duration and probably further delay metamorphosis. We discuss these findings in the context of larval mortality, and the importance of O. edulis' larval settlement requirements for dispersal potential, recruitment success and connectivity of restoration sites.


Short Communication: Virion Aggregation by Neutralizing and Nonneutralizing Antibodies to the HIV-1 Envelope Glycoprotein.
We used dynamic light scattering to detect aggregation of HIV-1 virions by antibodies (IgG) to the viral envelope glycoprotein (Env). Virions of different strains were inactivated by 2,2'-dithiodipyridine (AT-2), a procedure that abrogates infectivity but preserves the native antigenic structure of Env. Neutralizing antibodies directed to a V3-base- and glycan-dependent epitope on gp120 and to the apex of the Env trimer, as well as nonneutralizing antibodies to the epitope cluster I on the gp41-ectodomain, aggregated virions, but in markedly narrow concentration ranges. In contrast, the neutralizing antibody 2G12, which is specific for a composite glycan-dependent epitope on gp120 and functionally monovalent because of its unusual domain-swap structure, was nonaggregating. These results have potentially complex implications for vaccine development.


First biologic and genetic characterization of Toxoplasma gondii isolates from chickens from Africa (Democratic Republic of Congo, Mali, Burkina Faso, and Kenya).
The prevalence of Toxoplasma gondii in free-ranging chickens (Gallus domesticus) is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. In the present study, prevalence of T. gondii in chickens from Democratic Republic of Congo, Mali, Burkina Faso, and Kenya is reported. The prevalence of T. gondii antibodies in sera of 50 free-range chickens from Congo was 50% based on the modified agglutination test (MAT); antibody titers were 1:5 in 7, 1:10 in 7, 1:20 in 6, 1:40 in 1, and 1:160 or more in 4 chickens. Hearts, pectoral muscles, and brains of 11 chickens with titers of 1:20 or more were bioassayed individually in mice; T. gondii was isolated from 9, from the hearts of 9, brains of 3, and muscles of 3 chickens. Tissues of each of the 14 chickens with titers of 1:5 or 1:10 were pooled and bioassayed in mice; T. gondii was isolated from 1 chicken with a titer of 1:10. Tissues from the remaining 25 seronegative chickens were pooled and fed to 1 T. gondii-free cat. Feces of the cat were examined for oocysts, but none was seen. The results indicate that T. gondii localizes in the hearts more often than in other tissues of naturally infected chickens. Genotyping of these 10 isolates using the SAG2 locus indicated that 8 were isolates were type III, 1 was type II, and 1 was type I. Two isolates (1 type I and 1 type III) were virulent for mice. Toxoplasma gondii was isolated by mouse bioassay from a pool of brains and hearts of 5 of 48 chickens from Mali and 1 of 40 chickens from Burkina Faso; all 6 isolates were avirulent for mice. Genetically, 4 isolates were type III and 2 were type II. Sera were not available from chickens from Mali and Burkina Faso. Toxoplasma gondii antibodies (MAT 100 or more) were found in 4 of 30 chickens from Kenya, and T. gondii was isolated from the brain of 1 of 4 seropositive chickens; this strain was avirulent for mice and was type II. This is the first report on isolation and genotyping of T. gondii from any source from these 4 countries in Africa.


Astroglial heme oxygenase-1 and the origin of corpora amylacea in aging and degenerating neural tissues.
Corpora amylacea (CA) are glycoproteinaceous (predominantly glial and extracellular) inclusions that accumulate in normal aging brain and, to a greater extent, in Alzheimer disease (AD). Previous pharmacological evidence suggested that up-regulation of endogenous heme oxygenase-1 (HO-1) in astrocytes promotes transformation of normal mitochondria to CA-like inclusions. Here, we determined whether 1) HMOX1 transfection fosters the accumulation of CA-like inclusions in cultured rat astroglia; 2) the HMOX1 transgene promotes CA formation in the brains of aging GFAP.HMOX1 mice; and 3) brain mitochondrial damage and CA biogenesis are augmented in persons with mild cognitive impairment (MCI), a harbinger of AD. CA were ascertained in (i) neonatal rat astroglia transfected with flag-tagged human HO-1 cDNA, (ii) brain sections derived from 19month-old GFAP.HMOX1 and wild-type (WT) mice, and (iii) post-mortem hippocampal sections from individuals with mild (MCI) and no cognitive impairment (NCI) after staining with PAS or antisera against HO-1, ubiquitin (Ub), manganese superoxide dismutase (MnSOD), and α-synuclein or tyrosine hydroxylase (TH). HMOX1 transfection induced cytoplasmic vacuolation and the accumulation of PAS+ inclusions in cultured astroglia. Numerous CA-like inclusions stained with PAS and immunoreactive for HO-1, Ub and MnSOD were observed in the brains of GFAP.HMOX1 mice, but were rarely encountered in age-matched, WT controls. Numbers of HO-1-positive CA were significantly increased in certain hippocampal strata of MCI subjects relative to NCI preparations. MnSOD and Ub proteins co-localized to CA in both the control and MCI specimens. HO-1 promotes mitochondrial damage and CA biogenesis in astrocyte cultures and in the intact aging brain. CA formation is enhanced in the MCI hippocampus and thus occurs relatively early in the pathogenesis of AD. Glial HO-1 suppression may attenuate bioenergetic failure and slow disease progression in AD and other neurodegenerative conditions featuring accelerated accumulation of CA.


Does Pressure Regulating Balloon Location Make a Difference in Functional Outcomes of Artificial Urinary Sphincter?
We compared functional outcomes in patients who received an artificial urinary sphincter in the space of Retzius vs the same device placed at a high submuscular location. We reviewed a prospectively maintained database of patients who received an artificial urinary sphincter between July 2007 and December 2014. After cuff placement was completed via a perineal incision, a 61 to 70 cm H2O pressure regulating balloon was placed through a separate high scrotal incision in the space of Retzius or in a high submuscular tunnel. Demographics, perioperative comorbidities and functional outcomes were compared between the groups. A total of 294 consecutive patients underwent artificial urinary sphincter placement. Mean followup was 23 months. Space of Retzius and high submuscular placement was performed in 140 (48%) and 154 patients (52%), respectively. Functional outcomes were similar between the groups, including the continence rate (defined as 0 or 1 pad daily) in 81% vs 88% (p = 0.11), the erosion rate in 9% vs 8% (p = 0.66) and the explantation rate in 10% vs 11% (p = 0.62). Artificial urinary sphincter revision for persistent incontinence was required in a similar proportion of the 2 groups (13% vs 8%, p = 0.16) with a comparable mean followup (24 vs 23 months, p = 0.30). Kaplan-Meier analysis revealed no difference between the groups in the rate of explantation (p = 0.70) or revision (p = 0.06). High submuscular placement of a pressure regulating balloon at artificial urinary sphincter surgery is a safe, effective alternative with functional outcomes equivalent to those of traditional placement in the space of Retzius.


Indirect growth of mesoporous Bi@C core-shell nanowires for enhanced lithium-ion storage.
In this paper, we propose a facile synthetic strategy for uniform bismuth@carbon (Bi@C) core-shell nanowires, which are prepared via controlled pyrolysis of Bi2S3@glucose-derived carbon-rich polysaccharide (GCP) nanowires under an inert atmosphere. Carbonization of GCP and pyrolysis of Bi2S3 into Bi occur at 500 °C and 600 °C, respectively, which increase the specific surface area and the pore volume of the nanowires, thus allowing accommodation of more lithium ions. Meanwhile, the carbon shell serves as a buffer layer to relieve large volume expansion-contraction during the electrochemical alloy formation, and can also efficiently reduce the aggregation of the nanowires. As a proof-of-concept, the Bi@C core-shell nanowire anodes manifest enhanced cycling stability (408 mA h g(-1) after 100 cycles at a current density of 100 mA g(-1)) and rate capacity (240 mA h g(-1) at a current density of 1 A g(-1)), much higher than pure bismuth microparticles and corresponding Bi2S3@C nanowires.


Prediction of problem gambling by demographics, gaming behavior and psychological correlates among gacha gamers: A cross-sectional online survey in Chinese young adults.
The objective of this study is to explore the association of problem gambling with demographics, psychological distress, and gaming behavior in young adult gacha gamers in Hong Kong. Cross-sectional data was collected in the first and fifth waves of COVID-19 pandemic in Hong Kong online. Participants who aged 18-25 years and had been playing gacha games over the past 12 months were recruited. Stepwise multiple regression was used to explore the association among risk of problem gambling, gaming behavior, participation in gaming activities and psychological distress. A two-sided p-value <0.05 was considered as statistical significance. Three hundred and thirty-seven completed questionnaires were received with no missing data. 34.7% (n = 117) of the participants had non/low-risk of problem gambling. About 40% (n = 136) of them had moderate-risk and the remaining 25% (n = 84) were at high risk of problem gambling. A higher proportion of female participants (78.6%) were found in high-risk group as compared to 39.7% and 55.6% only in the non/low-risk and moderate-risk groups, respectively. The regression model (R 2 = 0.513, F = 71.895, p < 0.001) showed that 51.3% of the variance of the total problem gambling score could be explained by stress, anxiety, monthly expenses on gacha purchases, number of motives for gacha purchase and number of gambling activities engaged. The present study provides empirical evidence to support the association between problem gambling and microtransaction especially for gacha which is the most popular type of video game microtransaction in Asia. The established regression model suggests that gacha gamers with higher risk of problem gambling tend to have greater stress, higher anxiety level, spend more on gacha purchase, have more motives for gacha purchases and engage in more gambling activities. In contrast to the extant literature, higher proportion of female participants in high-risk group indicates that female gacha gamers are also at very high risk of becoming problem gamblers.


[Rare congenital defects of adrenal steroidogenesis].
Congenital defects of adrenal steroidogenesis comprises a group of autosomally recessive disorders, which are usually caused by inactivating mutations in single enzymes involved in adrenal steroid biosynthesis. Each of the defects causes different biochemical consequences and clinical features. A different degree of enzyme dysfunction is responsible for a wide range of phenotypic expression even in the same disorder. The basis for the diagnosis of inborn errors of steroidogenesis are often refined methods for steroid determination. Because these defects may result in life-threatening conditions and, if not treated, lead to serious complications, its is essential to consider their presence in a differential diagnosis of various symptoms. Deficiency of 21-hydroxylase, the most common of these disorders, has been recently extensively reviewed. Therefore, this paper discusses the etiopathogenesis, clinical manifestation, biochemical abnormalities and management of other less frequent defects of adrenal steroidogenesis.


The ratio of the kinetic inductance to the geometric inductance: a key parameter for the frequency tuning of the THz semiconductor split-ring resonator.
By introducing the frequency tuning sensitivity, an analytical model based on equivalent LC circuit is developed for the relative frequency tuning range of THz semiconductor split-ring resonator (SRR). And the model reveals that the relative tuning range is determined by the ratio of the kinetic inductance to the geometric inductance (RKG). The results show that under the same carrier density variation, a larger RKG results in a larger relative tuning range. Based on this model, a stacked SRR-dimer structure with larger RKG compared to the single SRR due to the inductive coupling is proposed, which improves the relative tuning range effectively. And the results obtained by the simple analytical model agree well with the numerical FDTD results. The presented analytical model is robust and can be used to analyze the relative frequency tuning of other tunable THz devices.


Identification of a unique TGF-β-dependent molecular and functional signature in microglia.
Microglia are myeloid cells of the CNS that participate both in normal CNS function and in disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia versus myeloid and other immune cells. Of the 239 genes, 106 were enriched in microglia as compared with astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS, and was also observed in human microglia. We found that TGF-β was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia and that microglia were absent in the CNS of TGF-β1-deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling and provide insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease.


[Prophylaxis of pleurectomy complications].
Basing on the literature and the observations of their own data analysis, the authors suggest, that pleurectomy constitutes a reconstructive-restoration operation. Nevertheless, this procedure, due to its complexity and traumatism, not infrequently is complicated by various intraoperative complications, in particular, the life threatening--in 1.1% observations and dangerous for health--in 13.8%. The methods of prevention and overcoming of possible complications are determined.


Sex determination, longevity, and the birth and death of reptilian species.
Vertebrate sex-determining mechanisms (SDMs) are triggered by the genotype (GSD), by temperature (TSD), or occasionally, by both. The causes and consequences of SDM diversity remain enigmatic. Theory predicts SDM effects on species diversification, and life-span effects on SDM evolutionary turnover. Yet, evidence is conflicting in clades with labile SDMs, such as reptiles. Here, we investigate whether SDM is associated with diversification in turtles and lizards, and whether alterative factors, such as lifespan's effect on transition rates, could explain the relative prevalence of SDMs in turtles and lizards (including and excluding snakes). We assembled a comprehensive dataset of SDM states for squamates and turtles and leveraged large phylogenies for these two groups. We found no evidence that SDMs affect turtle, squamate, or lizard diversification. However, SDM transition rates differ between groups. In lizards TSD-to-GSD surpass GSD-to-TSD transitions, explaining the predominance of GSD lizards in nature. SDM transitions are fewer in turtles and the rates are similar to each other (TSD-to-GSD equals GSD-to-TSD), which, coupled with TSD ancestry, could explain TSD's predominance in turtles. These contrasting patterns can be explained by differences in life history. Namely, our data support the notion that in general, shorter lizard lifespan renders TSD detrimental favoring GSD evolution in squamates, whereas turtle longevity permits TSD retention. Thus, based on the macro-evolutionary evidence we uncovered, we hypothesize that turtles and lizards followed different evolutionary trajectories with respect to SDM, likely mediated by differences in lifespan. Combined, our findings revealed a complex evolutionary interplay between SDMs and life histories that warrants further research that should make use of expanded datasets on unexamined taxa to enable more conclusive analyses.


Gastric outlet obstruction caused by metastatic tumor of the stomach originating from primary breast cancer: A case report.
The most common sites of breast cancer metastasis are the bone, liver, lung and brain, while gastrointestinal metastasis from breast cancer is rare. We herein present the case of a 68-year-old woman who was admitted to our department with nausea and appetite loss. The patient's medical history included right mastectomy with sentinel lymph node biopsy 5 years earlier for invasive lobular carcinoma, measuring 6.2 cm in greatest diameter, without lymphovascular invasion. Two years after the surgery, the patient developed brain metastasis and underwent metastasectomy to control the neurological symptoms, including unsteadiness and asthenia. After the second surgery, the patient received systemic chemotherapy using S-1, followed by bevacizumab plus paclitaxel. However, due to bevacizumab-related cardiotoxicity, the treatment was switched to eribulin. On esophagogastroduodenoscopy, an elevated lesion was identified in the antrum, causing severe narrowing of the gastric outlet. Biopsy and histological examination of the tumor revealed infiltration of the gastric wall by undifferentiated neoplastic cells with poor adhesion, morphologically similar to invasive lobular carcinoma, and immunohistochemical staining was positive for estrogen receptor, mammaglobin and GATA3. Finally, 18F-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography combined with computed tomography imaging revealed FDG uptake across the thickness of the antral wall. The patient was diagnosed with gastric metastasis from the original breast cancer and subsequently underwent endoscopic self-expandable metallic stent (SEMS) placement. There were no procedure-related adverse events, and the patient remained alive under best supportive care 4 months after SEMS placement. To the best of our knowledge, this is the first reported case of gastric outlet obstruction caused by metastatic breast carcinoma managed by SEMS placement. While such a diagnosis is rare, clinicians treating patients with gastric metastases should be aware of possible gastric outlet obstruction and SEMS placement as an effective palliative intervention.


On-Chip Sinusoidal Signal Generators for Electrical Impedance Spectroscopy: Methodological Review.
This paper reviews architectures and circuit implementations of on-chip sinusoidal signal generators (SSGs) for electrical impedance spectroscopy (EIS) applications. In recent years, there have been increasing interests in on-chip EIS systems, which measure a target material's impedance spectrum over a frequency range. The on-chip implementation allows EIS systems to have low power and small form factor, enabling various biomedical applications. One of the key building blocks of on-chip EIS systems is on-chip SSG, which determines the frequency range and the analysis precision of the whole EIS system. On-chip SSGs are generally required to have high linearity, wide frequency range, and high power and area efficiency. They are typically composed of three stages in general: waveform generation, linearity enhancement, and current injection. First, a sinusoidal waveform should be generated in SSGs. The generated waveform's frequency should be accurately adjustable over a wide range. The firstly generated waveform may not be perfectly linear, including unwanted harmonics. In the following linearity-enhancement step, these harmonics are attenuated by using filters typically. As the linearity of the waveform is improved, the precision of the EIS system gets ensured. Lastly, the filtered voltage waveform is now converted to a current by a current driver. Then, the current sinusoidal signal is injected into the target impedance. This review discusses the principles, advantages, and disadvantages of various techniques applied to each step in state-of-the-art on-chip SSGs. In addition, state-of-the-art designs are compared and summarized.


Effects of temperature and SDS on the structure of beta-glycosidase from the thermophilic archaeon Sulfolobus solfataricus.
The effects of temperature and SDS on the three-dimensional organization and secondary structure of beta-glycosidase from the thermophilic archaeon Sulfolobus solfataricus were investigated by CD, IR spectroscopy and differential scanning calorimetry. CD spectra in the near UV region showed that the detergent caused a remarkable change in the protein tertiary structure, and far-UV CD analysis revealed only a slight effect on secondary structure. Infrared spectroscopy showed that low concentrations of the detergent (up to 0.02%) induced slight changes in the enzyme secondary structure, whereas high concentrations caused the alpha-helix content to increase at high temperatures and prevented protein aggregation.


A murine IgM monoclonal antibody binds an antigenic determinant in outer surface protein A, an immunodominant basic protein of the Lyme disease spirochete.
A hybridoma cell line formed by the fusion of the P3x63-Ag8.653 myeloma cell line with splenocytes from BALB/c mice immunized with Borrelia burgdorferi produced an IgM monoclonal antibody (mAb-11G1) with kappa-light chains which detected an antigenic determinant in a major spirochetal protein of m.w. approximately 31,000, also known as outer surface protein A (OSP-A). Apparent saturation was reached in approximately 35 min with 34 ng of mAb-11G1 binding to 5 X 10(7) spirochetes giving an estimated 4.8 X 10(2) IgM molecules per spirochete and thus a minimum of 480 binding sites per organism. Enzymatic digestion studies suggest that the antigenic determinant to mAb-11G1 is contained within the peptide chain of OSP-A as binding could be eliminated by treatment of the spirochetes with proteinase K, Pronase and pepsin (100 to 200 micrograms/ml of enzyme) but not by trypsin or bromelain treatment. Periodate oxidation as well as mixed and endoglycosidase treatment of the spirochetes did not alter the binding of mAb-11G1. Two-dimensional gel electrophoresis of whole spirochetal cell lysates disclosed that OSP-A is a heterogeneously charged basic protein with an apparent isoelectric point range from 8.5 to 9.0. Amino acid analysis of OSP-A showed a 10% lysine component which could provide the basic nature to the protein. OSP-A with the intact antigenic determinant for mAb-11G1 can be found in the urine of hamsters experimentally infected with B. burgdorferi.


Hypoglycaemic constituents of Stachytarpheta cayennensis leaf.
The aqueous infusion (tea) of Stachytarpheta cayennensis leaves is used ethnomedically in Peru, Nigeria and other tropical countries for the management of diabetes. Oral administration (p. o.) of aqueous (125 mg/kg) and methanolic (2000 mg/kg) extracts of the leaves to alloxan-diabetic rats showed significant blood glucose reductions by 43 and 53%, respectively, at the end of a 4 hour period similar to the strong effect of glibenclamide (5 mg/kg, P. O.). The methanolic extract was successively partitioned into ethyl acetate, butanol and water fractions, and the same test showed that the butanol fraction (2000 mg/kg) had the highest (50%) hypoglycaemic activity at 4 hours after oral administration. It was also the most active fraction when tested in vitro [insulin release from an insulin secreting cell line (INS-1)] and was also active in normal rats and rats made hyperglycaemic by a glucose load. Its activity was comparable to that of glibenclamide (positive control) in these models. This active butanol fraction was subjected to chromatographic subfractionation; some subfractions reduced hyperglycaemia in alloxan-diabetic rats to 60 and 78% and induced insulin release from the INS-1 cells; other subfractions, however, gave hyperglycaemic activities IN VIVO and inhibition of insulin release from the INS-1 cells. Three major compounds of the butanol fraction were isolated and characterised as 6beta-hydroxyipolamide, ipolamide and isoverbascoside; they increased insulin secretion from INS-1 cells to 125, 128 and 127%, respectively, whereas glibenclamide increased insulin secretion to 157%. The results justify the ethnomedical use of the plant in the management of diabetes and suggest that the butanol fraction and some of its isolated constituents mediate their actions primarily by stimulating insulin release directly.


Bacteria hold their breath upon surface contact as shown in a strain of Escherichia coli, using dispersed surfaces and flow cytometry analysis.
Bacteria are ubiquitously distributed throughout our planet, mainly in the form of adherent communities in which cells exhibit specific traits. The mechanisms underpinning the physiological shift in surface-attached bacteria are complex, multifactorial and still partially unclear. Here we address the question of the existence of early surface sensing through implementation of a functional response to initial surface contact. For this purpose, we developed a new experimental approach enabling simultaneous monitoring of free-floating, aggregated and adherent cells via the use of dispersed surfaces as adhesive substrates and flow cytometry analysis. With this system, we analyzed, in parallel, the constitutively expressed GFP content of the cells and production of a respiration probe--a fluorescent reduced tetrazolium ion. In an Escherichia coli strain constitutively expressing curli, a major E. coli adhesin, we found that single cell surface contact induced a decrease in the cell respiration level compared to free-floating single cells present in the same sample. Moreover, we show here that cell surface contact with an artificial surface and with another cell caused reduction in respiration. We confirm the existence of a bacterial cell "sense of touch" ensuring early signalling of surface contact formation through respiration down modulation.


Antioxidant activity and polyphenol content in extracts from various parts of fresh and frozen mangosteen.
The search for new sources of natural antioxidants is very important because many diseases are caused by oxidative stress. Fruit which contain antioxidants are an important part of a healthy diet. The aim of this study was to evaluate the antioxidant activity of extracts of both the fresh and frozen peel and the flesh of Garcinia mangostana L. The extracts from the fresh and frozen peel and the flesh of mangosteen were prepared by ultrasound-assisted extraction using 20%, 40%, 70% and 96% (v/v) ethanol for 15, 30 or 60 minutes. The antioxidant potential was evaluated by the DPPH, ABTS, CUPRAC, FRAP and FIC methods, whereas the total phenolic content was measured using the Folin-Ciocalteu (F-C) technique. The contents of anthocyanins and flavonoids in the peel extracts were also determined. In most cases, the highest antioxidant activity was observed in the fresh peel samples. It was higher than the antioxidant potential of the frozen peels and the fresh and frozen flesh. The ultrasound-assisted extraction, in particular those lasting 30 or 60 minutes and using ethanol in concentrations higher than 20% (v/v), seemed to be an effective extraction process. The obtained results suggest that G. mangostana, in particular its peels, could be a valuable source of antioxidants. The extraction parameters, such as the time or solvent concentration, as well as the type of plant material, had an impact on the tested properties of the extracts. However, more detailed studies on the antioxidant activity of the studied plants are required.


The effects of acetaldehyde on nitrogenase, hydrogenase and photosynthesis in the cyanobacterium Anabaena cylindrica.
Acetaldehyde was shown to be an irreversible inhibitor of nitrogenase, hydrogenase, CO2 fixation and growth in the cyanobacterium Anabaena cylindrica, but had no effect on photosynthetic electron flow as measured by Methyl Viologen-dependent O2 uptake. The concentration-dependence of the inhibition of nitrogenase and hydrogenase activities was determined, and it was shown that acetaldehyde inhibition poses problems for anaerobic experiments in which the activities of these enzymes are measured in the presence of the frequently used glucose/glucose oxidase/catalase/ethanol O2 trap. It is suggested that acetaldehyde may find use as an inhibitor in experiments designed to separate electron flow through the photosystems from consequent fixation of CO2 and N2.


Anatomy of word and sentence meaning.
Reading and listening involve complex psychological processes that recruit many brain areas. The anatomy of processing English words has been studied by a variety of imaging methods. Although there is widespread agreement on the general anatomical areas involved in comprehending words, there are still disputes about the computations that go on in these areas. Examination of the time relations (circuitry) among these anatomical areas can aid in understanding their computations. In this paper, we concentrate on tasks that involve obtaining the meaning of a word in isolation or in relation to a sentence. Our current data support a finding in the literature that frontal semantic areas are active well before posterior areas. We use the subject's attention to amplify relevant brain areas involved either in semantic classification or in judging the relation of the word to a sentence to test the hypothesis that frontal areas are concerned with lexical semantics and posterior areas are more involved in comprehension of propositions that involve several words.


; RESULTS OF RESECTION METHODS OF TREATMENT IN PATIENTS WITH GIANT PYLORODUODENAL ULCERS COMPLICATED BY PERFORATION AND BLEEDING.
We studied the immediate and long-term results of various methods of gastric resection in 35 patients operated at the S.S. Yudin State Medical Center in Moscow from 2000 to 2019. 20 (57.1%) patients were operated on for perforation, and 15 (42.6%) patients underwent surgery for ulcerative bleeding. There were 27 (77.2%) males and 8 (22.8%) females. The average age of patients was 48.3±2.3 years. The diagnosis of peptic ulcer disease was previously made in 24 (68.6%) patients, the duration of the disease was 7.7±2.7 years. Of the 35 patients, 29 (82.8%) underwent standard gastric resection without vagotomy with Billroth-II anastomosis in various modifications and 6 (17.2%) underwent pylorobulbar resection with Billroth-I anastomosis with bilateral stem vagotomy. According to the analysis of the results of surgical interventions, gastric resection was accompanied by a significant number of early postoperative complications observed in 18 (51.4% of patients): associated with the nature of the operation, 10 and 5 patients had complications from the cardiovascular and respiratory systems. The most frequent complication due to the nature of surgery was a clinically significant violation of the evacuation function of the stomach stump, which developed in 8 of 35 (22.8%) patients. In 4 patients after pylorobulbar resection, the violation of the evacuation function of the stump was due to its parasympathetic denervation. The remaining 4 patients after standard resection of gastric stasis stump occurred due to maintenance of anastomositis of gastrojejunal anastomosis. Post-vagotomic diarrhea: observed in 3 of 6 patients: 1 patient of moderate severity, and 2 patients-mild. Failure of sutures was observed in 2 out of 35 (5.7%) patients after standard gastric resection: one after resection of Hofmeister Finsterer and the other after resection for PY. Complications from the cardiovascular system were observed in 5 (14.3%) patients. After surgery, 5 (22.7%) patients died: 4 after resection of 2/3 of the stomach and 1 patient after pyloroduodenal resection with stem vagotomy. All the deceased were operated on urgently: 2 patients for perforation of giant ulcers and 3 patients for continuing profuse bleeding. The causes of death of patients operated on for bleeding were: myocardial infarction in 1 patient, pulmonary embolism in 2 patients. Another 2 patients with failure of duodenal stump sutures, operated on for perforation of giant ulcers, died from increasing cardiovascular insufficiency. The analysis of long-term results of surgical interventions showed a steady decrease in the number of post gastric resection and post-vagotomic disorders, as well as the absence of ulcer recurrence. It should be noted that the phenomena of dumping syndrome observed in patients after standard gastric resection were not severe and were corrected by a lax diet. After piloroduodenal resection with anastomosis by Billroth-I and stem vagotomy, manifestations of gastrostasis and diarrhea were stopped in the remote postoperative period. When assessing the quality of life, there were no unsatisfactory results, all previously operated patients led their usual lifestyle, maintained their working capacity, and did not require re-hospitalization.


Phyllocoptes parviflori is a distinct species and a vector of the pervasive blackberry leaf mottle associated virus.
Several viruses are transmitted by eriophyid mites (Acariformes: Eriophyoidea) including blackberry leaf mottle-associated emaravirus (BLMaV) (Emaravirus rubi). BLMaV is transmitted by an unidentified eriophyid species and is involved in blackberry yellow vein, a devastating disease in the southeastern United States. In this study, we assessed the eriophyid mite Phylocoptes parviflori as a vector of BLMaV and clarified its taxonomic status as it was previously synonymized with Phyllocoptes gracilis. P. parviflori can efficiently transmit BLMaV. The virus was found to cause yellow vein disease symptoms on 'Ouachita' blackberry marking a paradigm shift as disease symptoms have always been associated with multiple virus infections. Therefore, we propose renaming the virus to blackberry leaf mottle virus. The occurrence of P. parviflori on wild and cultivated blackberries, as well as its ability to colonize other Rubus species, enhances its importance as a major contributor to the spread of yellow vein disease.


Fine mapping of the major latency-related RNA of herpes simplex virus type 1 in humans.
In situ hybridization with synthetic oligonucleotides was used to fine map the extent and continuity of herpes simplex virus type 1 (HSV-1) latency-related RNA (LR RNA) in trigeminal ganglia of latently infected humans. A series of 34 20 residue oligonucleotides were employed to cover a 3 kb region of the HSV-1 genome to which the latency-related gene had previously been mapped. The 5' end of the main LR RNA transcript began approximately 1210 nucleotides downstream from the 3' end of the mRNA from the immediate early gene ICP0. The 3' end of the LR RNA overlapped the 3' end of the ICP0 mRNA by approximately 1000 nucleotides. A potential small intron was detected near the 3' end of the LR RNA.


Anti-Inflammatory and Antimicrobial Properties of Flavonoids from Heliotropium subulatum Exudate.
Heliotropium subulatum is an erect or procumbent perennial herb; leaves contain foliar trichomes and its resinous exudate is used in traditional medicine. The anti-inflammatory activity of dichloromethane fraction and isolated flavonoids was evaluated by using carrageenan and CFA-induced paw oedema models. Similarly, the disc diffusion and microdilution methods were used for the assessment of antimicrobial activity. Five isolated flavonoids were investigated for their antiinflammatory and antimicrobial activities. Eriodictyol demonstrated maximum anti-inflammatory activity (53.09%) at 30.0 mg/kg dose on 6(th) h and similarly, it inhibited the CFA-induced arthritis swelling (41.84%) with 30.0 mg/kg dose on 8(th) day respectively. As per disc diffusion and microdilution methods used for antimicrobial activity determination, the pinocembrin was found to be most active against Staphylococcus aureus (IZ=27±0.7 mm, 08 μg/ml dose) and Candida albicans (IZ=17±0.9 mm; 12 μg/ml dose). These investigated results revealed that the eriodictyol and pinocembrin showed significant anti-inflammatory and antimicrobial activities. Further studies which aimed to investigate the mechanism of action of these isolated flavonoids in the treatment of inflammations and various types of infections have been initiated.


Genetic variability at the human tumor necrosis factor loci.
Variability in the structure of the human tumor necrosis factor (TNF-alpha) or lymphotoxin (TNF-beta) genes may contribute to the functional polymorphism of the HLA gene complex. We have characterized an allelic restriction fragment length polymorphism (RFLP) of the TNF-beta gene by using the restriction endonuclease NcoI. Digestion of genomic DNA with NcoI and Southern blotting by using TNF-alpha gene probes show 5.4-kb and 10.5-kb hybridizing fragments. In Caucasian populations, the 10.5-kb fragment is present in 64 to 72% of haplotypes. The polymorphic NcoI site is located within the first intron of the TNF-beta gene. Additional restriction fragment variability was demonstrated by digestion with AccI; however, this restriction fragment variability was not allelic in nature. Rather, it was a consequence of variable DNA methylation at AccI sites within and upstream of the TNF-beta gene. In peripheral blood leukocytes, methylation of the TNF-beta AccI sites was greatest in neutrophils (TNF-beta nonproducers), and lowest in T lymphocytes (the major producers of TNF-beta). These results suggest strongly that variation in DNA methylation may play an important role in regulation of the expression of the TNF-beta gene.


Hypoxic activation of ATR and the suppression of the initiation of DNA replication through cdc6 degradation.
Many severely hypoxic cells fail to initiate DNA replication, but the mechanism underlying this observation is unknown. Specifically, although the ataxia-telangiectasia-rad3 related (ATR) kinase has been shown to be activated in hypoxic cells, several studies have not been able to document down-stream consequences of ATR activation in these cells. By clearly defining the DNA replication initiation checkpoint in hypoxic cells, we now demonstrate that ATR is responsible for activating this checkpoint. We show that the hypoxic activation of ATR leads to the phosphorylation-dependent degradation of the cdc25a phosphatase. Downregulation of cdc25a protein by ATR in hypoxic cells decreases CDK2 phosphorylation and activity, which results in the degradation of cdc6 by APC/C(Cdh1). These events do not occur in hypoxic cells when ATR is depleted, and the initiation of DNA replication is maintained. We therefore present a novel mechanism of cdc6 regulation in which ATR can have a central role in inhibiting the initiation of DNA replication by the regulation of cdc6 by APC/C(Cdh1). This model provides insight into the biology and therapy of hypoxic tumors.


Reducing Unplanned Admissions: Focusing on Hospital Admissions and Emergency Department Visits for Patients With Head and Neck Cancer During Radiation Therapy .
Head and neck cancer (HNC) treatments cause severe toxicities, leading to high rates of emergency department (ED) visits and unplanned hospital admissions (UHAs). . The study aimed to evaluate a quality improvement project to reduce ED visits and UHAs. . A weekly nurse/nurse practitioner-led symptom management clinic was created for patients with HNC receiving radiation therapy deemed at high risk for an ED visit or UHA. Primary quality metrics were rate of visits or unplanned admissions. Time-to-event actuarial analysis and log-rank tests (two-tailed) were performed to compare observed to historic rates. . Rates of ED visits and UHAs were 11% and 16%, respectively. Having more symptom management visits marginally correlated with reduction in UHA. The authors estimate six ED visits and four UHAs were prevented, which is a $176,848 cost reduction.


dSTIM- and Ral/Exocyst-Mediated Synaptic Release from Pupal Dopaminergic Neurons Sustains Drosophila Flight.
Manifestation of appropriate behavior in adult animals requires developmental mechanisms that help in the formation of correctly wired neural circuits. Flight circuit development in Drosophila requires store-operated calcium entry (SOCE) through the STIM/Orai pathway. SOCE-associated flight deficits in adult Drosophila derive extensively from regulation of gene expression in pupal neurons, and one such SOCE-regulated gene encodes the small GTPase Ral. The cellular mechanism by which Ral helps in maturation of the flight circuit was not understood. Here, we show that knockdown of components of a Ral effector, the exocyst complex, in pupal neurons also leads to reduced flight bout durations, and this phenotype derives primarily from dopaminergic neurons. Importantly, synaptic release from pupal dopaminergic neurons is abrogated upon knockdown of dSTIM, Ral, or exocyst components. Ral overexpression restores the diminished synaptic release of dStim knockdown neurons as well as flight deficits associated with dSTIM knockdown in dopaminergic neurons. These results identify Ral-mediated vesicular release as an effector mechanism of neuronal SOCE in pupal dopaminergic neurons with functional consequences on flight behavior.


The evolution of optimal female mating rate changes the coevolutionary dynamics of female resistance and male persistence.
Mating decisions usually involve conflict of interests between sexes. Accordingly, males benefit from increased number of matings, whereas costs of mating favour a lower mating rate for females. The resulting sexual conflict underlies the coevolution of male traits that affect male mating success ('persistence') and female traits that affect female mating patterns ('resistance'). Theoretical studies on the coevolutionary dynamics of male persistence and female resistance assumed that costs of mating and, consequently, the optimal female mating rate are evolutionarily constant. Costs of mating, however, are often caused by male 'persistence' traits that determine mating success. Here, we present a model where the magnitude of costs of mating depend on, and evolve with, male persistence. We find that allowing costs of mating to depend on male persistence results in qualitatively different coevolutionary dynamics. Specifically, we find that male traits such as penis spikes that harm females are not predicted to exhibit runaway selection with female resistance, in contrast to previous theory that predicts indefinite escalation. We argue that it is essential to determine when and to what extent costs of mating are caused by male persistence in order to understand and accurately predict coevolutionary dynamics of traits involved in mating decisions.


[Solar cosmic radiation and the radiation hazard of space flight].
Present-day data on the spectrum of solar radiation in the source and near the Earth are discussed as applied to the radiation safety of crewmembers and electronics onboard manned and unmanned spacecraft. It is shown that the slope of the solar radiation spectrum changes (flattens) in the low energy range. Quantitative information about absolute solar radiation fluxes near the Earth is summarized in relation to the most significant flares of 1956--1978. The time-related evolution of the solar radiation spectrum in the interplanetary space is described in quantitative terms (as illustrated by the solar flare of 28 September 1961). It is indicated that the nonmonotonic energy dependence of the transport path of solar radiation in the interplanetary space should be taken into consideration. It is demonstrated that the diffusion model of propagation can be verified using solar radiation measurements in space flights.


Physiotherapists' perceptions of their role in treating and managing people with depression and anxiety disorders: A systematic review.
Despite the prevalence of mental health disorders rising worldwide, physio-therapists' perceptions of their role and ability to holistically treat people with anxiety and depression remain unclear. This research aimed to understand the physiotherapists' perception of their role in treating and managing people with anxiety and depression while revealing barriers and facilitators in practice. PubMed, PsycInfo, CINAHL, EMBASE, Web of Science, and Google Scholar were searched systematically for mixed-method, quantitative, or qualitative designs. Using the Joanna Briggs Institute (JBI) Methodology for Systematic Reviews, data was extracted, critically appraised, assigned quality grades, and synthesized through meta-aggregation. A total of 2991 records were initially sourced, with eleven studies included in the systematic review. The studies were published worldwide between 2016 and 2021, with the majority (n = 8) published in 2020-2021. Participating physiotherapists most frequently had a Bachelor's degree (35.7-62.6%), followed by a Master's degree (28.4-37.4%). Meta-aggregation revealed the synthesized finding that physiotherapists perceived their role to include treating people with anxiety and depression despite feeling underprepared. Physiotherapists perceive many barriers and facilitators, such as education, when treating people with anxiety and depression. Physiotherapists have positive perceptions toward anxiety and depression, despite feeling underprepared in their ability to implement psychosocial strategies.


Activities at Thoracic Aortic Research Center, IRCCS Policlinico San Donato.
The Thoracic Aortic Research Center (TARC) of the IRCCS Policlinico San Donato (PSD) aims to promote research on thoracic aortic diseases, to disclose the scientific knowledge and clinical experience and to develop new scientific paths within the Hospital and the aortic community, in collaboration with other national and international centres. Thoracic Aortic Research Center collaborates with many centres in both Europe (e.g. University of Utrecht, the Netherlands) and the USA (e.g. University of Michigan). This has led to multiple highly regarded publications in respected cardiovascular journals and has led to several PhD programmes resulting in doctorate degrees. Within Italy, in association with the Bioengineering School of the University of Pavia, TARC has founded the "BETA-lab" (Biomechanics for Endovascular Treatment of the Aorta laboratory), where MDs, Bioengineers, and PhD fellows conduct experimental studies using in vitro/ex vivo models of the physiologic aorta and aortic diseases. Furthermore, a database (iCardiocloud) where the medical imaging of cardiovascular patients from the PSD is structured, for in silico analysis utilizing computational fluid dynamics, and in vitro studies using also 3D printed aortic models. With the role of principal investigator or co-investigator, TARC at PSD has been participating in other several projects, including the International Registry of Acute Aortic Dissection, the International Aortic Arch Surgery Study Group, the European Registry of Endovascular Aortic Repair Complications, the ADSORB and ASSIST trials, and the GREAT registry. International collaborations have included also studies on predictors of aortic growth after dissection with the Yale University and University of Virginia, and on aortic biomarkers with the University of Tokyo.


Assessing the capacity of ministries of health to use research in decision-making: conceptual framework and tool.
The capacity to demand and use research is critical for governments if they are to develop policies that are informed by evidence. Existing tools designed to assess how government officials use evidence in decision-making have significant limitations for low- and middle-income countries (LMICs); they are rarely tested in LMICs and focus only on individual capacity. This paper introduces an instrument that was developed to assess Ministry of Health (MoH) capacity to demand and use research evidence for decision-making, which was tested for reliability and validity in eight LMICs (Bangladesh, Fiji, India, Lebanon, Moldova, Pakistan, South Africa, Zambia). Instrument development was based on a new conceptual framework that addresses individual, organisational and systems capacities, and items were drawn from existing instruments and a literature review. After initial item development and pre-testing to address face validity and item phrasing, the instrument was reduced to 54 items for further validation and item reduction. In-country study teams interviewed a systematic sample of 203 MoH officials. Exploratory factor analysis was used in addition to standard reliability and validity measures to further assess the items. Thirty items divided between two factors representing organisational and individual capacity constructs were identified. South Africa and Zambia demonstrated the highest level of organisational capacity to use research, whereas Pakistan and Bangladesh were the lowest two. In contrast, individual capacity was highest in Pakistan, followed by South Africa, whereas Bangladesh and Lebanon were the lowest. The framework and related instrument represent a new opportunity for MoHs to identify ways to understand and improve capacities to incorporate research evidence in decision-making, as well as to provide a basis for tracking change.


[Incidence of nosocomial infections in the Russian Federation].
In the past 5 years, the incidence rates of nosocomial infections (NI) have been steady-state at a relatively low level of 0.8-0.9 per 1,000 patients. However, this apparent well-being is attributable to a significant underestimate of the cases of NI, an attempt to refer these infections to as intrauterine ones the proportion of which has increased by several times for this period. Nosological entities, such as urinary tract infections, postoperative complications, pneumonias, pyoseptic infections in parturients, are being underestimated now as before. To eliminate serious shortcomings in the prevention of NI, the Russian Consumer Inspectorate has proposed a number of measures: further improvement of NI epidemiological surveillance; introduction of a system for monitoring NI pathogens and their antibiotic resistance; staffing therapeutic-and-prophylactic institutions with hospital epidemiologists; a decrease in the number of invasive diagnostic and therapeutic procedures; a reduction in the length of hospital stay; blood quarantinization; expansion of the network of centralized sterilization departments and strengthening of control over their work; general introduction of novel highly effective disinfectants and equipment; implementation of measures to protect medical staff; and fortification of the material-and-technical basis of a therapeutic-and-prophylactic institution. The major tasks of combating infectious diseases for 2007-2010 are as follows: the further development of a standard methodological basis in the prevention of infectious and parasitic diseases, which are to revise the current technical regulations and to prepare new ones, sanitary regulations of activities in the implementation of organizational, prophylactic measures against some infectious diseases; to enhance the efficiency of epidemiological surveillance of infectious diseases, by extensively applying new information telecommunication technologies, diagnostic systems based on proteomic, postgenomic, and nanotechnologies, that of monitoring the environment and herd immunity.


Oxygen-evolving photosystem II preparation from wild type and photosystem II mutants of Synechocystis sp. PCC 6803.
We present here a simple and rapid method which allows relatively large quantities of oxygen-evolving photosystem II- (PS-II-) enriched particles to be obtained from wild-type and mutants of the cyanobacterium Synechocystis 6803. This method is based on that of Burnap et al. [Burnap, R., Koike, H., Sotiropoulou, G., Sherman, L. A., & Inoue, Y. (1989) Photosynth. Res. 22, 123-130] but is modified so that the whole preparation, from cells to PS-II particles, is achieved in 10 h and involves only one purification step. The purified preparation exhibits a 5-6-fold increase of O2-evolution activity on a chlorophyll basis over the thylakoids. The ratio of PS-I to PS-II is about 0.14:1 in the preparation. The secondary quinone electron acceptor, QB, is present in this preparation as demonstrated by thermoluminescence studies. These PS-II particles are well-suited to spectroscopic studies as demonstrated by the range of EPR signals arising from components of PS-II that are easily detectable. Among the EPR signals presented are those from a formal S3-state, attributed to an oxidized amino acid interacting magnetically with the Mn complex in Ca(2+)-deficient PS-II particles, and from S2 modified by the replacement of Ca2+ by Sr2+. Neither of these signals has been previously reported in cyanobacteria. Their detection under these conditions indicates a similar lesion caused by Ca2+ depletion in both plants and cyanobacteria. The protocol has also been applied to mutants which have site-specific changes in PS-II. Data are presented on mutants having changes on the electron donor (Y160F) and electron acceptor (G215W) side of the D2 polypeptide.


Comparison of polysaccharides produced by Myxococcus strains.
Exopolysaccharides were prepared from cultures of four Myxococcus strains grown on solid and in liquid media, and also from the fruiting bodies. Lipopolysaccharides could be extracted with aqueous phenol from the vegetative bacteria, but were absent from microcysts. Mannose and D-glucose were present in all the exopolysaccharides and three of the lipopolysaccharides examined. Other monosaccharides identified in the exopolysaccharides were D-galactose, N-acetylglucosamine and N-acetylgalactosamine. The composition of the lipopolysaccharides was more complex than that of the exopolysaccharides and, in addition to the neutral hexoses and amino sugars, rhamnose was identified in two preparations and ribose in another. No lipopolysaccharide preparations contained O-methyl xylose or heptose. The polysaccharides secreted by the bacillary forms grown on solid or in liquid media closely resembled the polysaccharides isolated from the fruiting bodies, in which they provided a matrix surrounding the microcysts. Each pair of polysaccharides contained the same monosaccharides, although in slightly different proportions. Differences were found in preparations from different strains. These results suggest that in the development cycle of the genus Myxococcus, considerable use is made of pre-existing enzyme systems to synthesize the precursors necessary for polysaccharide synthesis. Any specific difference between the polysaccharide produced by the bacilli and that surrounding the microcysts may lie in the fine structure, rather than in the individual components.


Pediatric Fibrinogen PART I-Pitfalls in Fibrinogen Evaluation and Use of Fibrinogen Replacement Products in Children.
Fibrinogen is a key coagulation protein, playing a critical role in hemostasis. It is the first factor to decrease to critical levels during bleeding. Hypofibrinogenemia is an important risk factor for bleeding in clinical settings, including pediatric surgery. Yet, the optimal measurement of fibrinogen levels is subject to debate, as is the critical threshold for intervention. Fibrinogen replacement may be provided by cryoprecipitate and fibrinogen concentrate. Whilst both products contain fibrinogen, they are not equivalent, each has its own advantages and disadvantages, especially for pediatric use. Unfortunately, medical literature to support fibrinogen replacement in children is limited. In this article we review the current diagnostic tools to measure fibrinogen, with respect to their use in the pediatric critical care setting. Secondly, we evaluate the different fibrinogen replacement therapies, focusing on cryoprecipitate and fibrinogen concentrate and examine their individual product characteristics, associated risks and benefits, different dosing strategies and specific pitfalls for use in children. We summarize by highlighting current knowledge gaps and areas for future research.