Modern management of menorrhagia.
Menorrhagia, defined clinically as menstrual blood loss in excess of 80 ml per cycle, is a common gynaecological complaint that presents both to primary and secondary care. The aim of this review of the literature is to discuss current opinion in the investigation and management of menorrhagia. As menorrhagia is a subjective condition that is difficult and impractical to assess objectively, this review incorporates patient-centred outcomes such as patient satisfaction and continuation with treatment together with more traditional outcomes such as percentage reduction in menstrual loss. As there are many treatment options available, with no one option being superior in all respects, patient choice and treatment preferences should be taken into account when deciding upon management.


Suppression of proinflammatory cytokine production by specific metabolites of Lactobacillus plantarum 10hk2 via inhibiting NF-κB and p38 MAPK expressions.
The objective of this study was to evaluate the immunomodulatory effects of specific bacterial metabolites of Lactobacillus plantarum 10hk2 to induce anti-inflammatory mediators in cell cultures of the murine macrophage cell line, RAW 264.7. The effects of the extracellular metabolites of this bacterial strain were examined by dividing them into protein and polysaccharide fractions. A specific protein fraction (8.7 kDa) was found to be a strong IL-10 inducer in LPS-stimulated RAW 264.7 cells and suppressed LPS-induced NF-κB induction and inhibited LPS-induced phosphorylation of I-κB and p38 MAPK. To the best of our knowledge, this was the first study that investigated the anti-inflammatory effects of an extracellular peptide derived from lactic acid bacteria. In addition, we characterized the inhibitory mode of this molecule in the induction of proinflammatory cytokines. Based on the findings presented in this study, this molecule holds promise for use as an agent to modulate inflammation related diseases.


Variable self-renewal of reconstituting stem cells in long-term bone marrow cultures.
Long-term bone marrow cultures (LTBMC) serve as a valuable in vitro model of the bone marrow microenvironment. The stromal layer supports the growth of immature and mature cell populations through production of colony-stimulating factors and cell:cell interactions. LTBMC are devoid of mature lymphoid cells but contain stem cells capable of restoring lymphoid and myeloid function in suitable recipients. Severe combined immune deficiency (scid) mice provide a useful environment to study lymphocyte development, as their autosomal recessive mutation on chromosome 16 leaves them with a severe deficiency of B and T lymphocytes. To determine the presence of different classes of stem cells in LTBMC, adherent cells from the cultures were grafted into sublethally irradiated scid mice and lineage reconstitution was evaluated 6 weeks to 3 months postengraftment. Self-renewal of donor stem cells was tested by serial transfer of scid bone marrow to donor secondary C.B-17 and scid recipients. Mature lymphoid and myeloid cells were isolated from reconstituted mice and a restriction fragment length polymorphism (RFLP) at the Cmu immunoglobulin locus was used to distinguish donor and host cells. We found that LTBMC contained both long-term and short-term reconstituting stem cells. The long-term stem cells had significant self-renewal potential and fully reconstituted all lineages in both primary and secondary recipients The short-term stem cells produced mostly lymphoid progeny at the time of analysis and their limited self-renewal capacity led to partial reconstitution of only the primary recipients. The short-term reconstituting cells may be lymphoid-restricted stem cells


Solar structure and terrestrial weather.
If there is indeed an effect of the variable sun on the weather, the physical cause for it remains quite elusive (12). We should keep in mind the possibility that there may be several causes and several effects. The situation may change through the 11-year sunspot cycle and the 22-year solar magnetic cycle, as well as on longer time scales. Work is proceeding at a lively pace at the institutions mentioned in this article and at many others around the world. The Soviet Union has long had considerably more workers interested in this field than has any other country. A bilateral agreement between the Soviet Union and the United States has considerably increased the interactions between workers interested in this subject, including an exchange of extended visits between the two countries. A detailed knowledge of solar causes of geomagnetic activity is only now beginning to emerge after many years of scientific efforts. This suggests that a possible successful solution to the sun-weather problem will require a similar magnitude of effort. We look forward with interest and optimism to the results of the next few years.


Ultrasonography of the pediatric hip and spine.
Ultrasonography (US) is a useful screening method for the diagnosis of developmental dysplasia of the hip (DDH) and congenital spinal anomalies in infants. In addition, US is a useful, noninvasive imaging modality for the diagnosis of transient synovitis in children. The early detection of DDH leads to a better prognosis without surgical intervention. Moreover, spinal US allows the detection of congenital malformations and can also demonstrate normal anatomy and normal variants that may resemble disorders. Therefore, radiologists should be familiar with the sonographic anatomy of the normal infant hip, scanning and measurement techniques for DDH, the US features of transient synovitis in children, spinal US techniques, and the US features of normal anatomical structures, normal variants, and congenital spinal anomalies.


Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria.
Mutations in the E-cadherin (CDH1) gene are a well documented cause of hereditary diffuse gastric cancer (HDGC). Development of evidence based guidelines for CDH1 screening for HDGC have been complicated by its rarity, variable penetrance, and lack of founder mutations. Forty three new gastric cancer (GC) families were ascertained from multiple sources. In 42 of these families at least one gastric cancer was pathologically confirmed to be a diffuse gastric cancer (DGC); the other family had intestinal type gastric cancers. Screening of the entire coding region of the CDH1 gene and all intron/exon boundaries was performed by bi-directional sequencing. Novel mutations were found in 13 of the 42 DGC families (31% overall). Twelve of these mutations occur among the 25 families with multiple cases of gastric cancer and with pathologic confirmation of diffuse gastric cancer phenotype in at least one individual under the age of 50 years. The mutations found include small insertions and deletions, splice site mutations, and three non-conservative amino acid substitutions (A298T, W409R, and R732Q). All three missense mutations conferred loss of E-cadherin function in in vitro assays. Multiple cases of breast cancers including pathologically confirmed lobular breast cancers were observed both in mutation positive and negative families. Germline truncating CDH1 mutations are found in 48% of families with multiple cases of gastric cancer and at least one documented case of DGC in an individual under 50 years of age. We recommend that these criteria be used for selecting families for CDH1 mutational analysis.


Significant enhancement of energy storage density and polarization in self-assembled PbZrO3 : NiO nano-columnar composite films.
Self-assembled nanostructures are important for determining the physical properties of epitaxial oxide films. We successfully fabricated perfectly ordered NiO nano-columns embedded in an antiferroelectric (AFE) PbZrO3 (PZO) matrix over large areas. In this system, a giant recoverable energy storage density of Wr = 24.6 J cm-3 and polarization of PS = 91 μC cm-2 were achieved in the structure of PZO : NiO nano-composites. These values are 333% and 253% larger than those of a pure PZO film, respectively. Additionally, the properties could be tuned by gradually changing the volume ratio of the constituents. Hence, we demonstrate a new approach for enhancing the energy storage of AFE materials and exercising control over nano-column-embedded nanocomposites.


Patients with high-risk aggressive lymphoma treated with frontline intensive chemotherapy and autografting: evidence of marked differences in outcome between patients with age-adjusted International Prognostic Index scores 2 and 3.
The goal of the current study was to evaluate the impact of presentation with an age-adjusted International Prognostic Index (aaIPI) score of 2 or 3 on patients with high-risk aggressive lymphoma who are treated with frontline intensive chemotherapy and autografting. Sixty-nine consecutive patients (median age, 40 years) with either B-cell (n = 60) or non-B-cell (n = 9) aggressive lymphoma were treated with high-dose sequential (HDS) chemotherapy and peripheral blood progenitor cell (PBPC) autografting. The patients who were examined had poor prognoses, with aaIPI scores of 2 (n = 37) or 3 (n = 32). The original treatment regimen, sequential delivery of cyclophosphamide, methotrexate, and etoposide, followed by PBPC autografting (o-HDS), was used in the first 32 patients; the program was intensified by the addition of a course of high-dose cytosine arabinoside (C-HDS) in the next 37 patients. There were 4 toxicity-related deaths-2 in each aaIPI subgroup (treatment-related mortality, 5.8%). The complete remission rate was significantly higher among patients with an aaIPI score of 2 (n = 32 [86%]) compared with those with an aaIPI score of 3 (n = 13 [41%]; P < 0.001). Patients with an aaIPI score of 2 had significantly better outcomes than did patients with an aaIPI score of 3 in terms of both overall survival (78% vs. 34% at 8 years; P < 0.001) and event-free survival (72% vs. 28% at 8 years; P < 0.001). Similar results were observed when the analysis was limited to the 60 patients with B-cell-derived lymphoma. No significant differences in outcome between patients receiving o-HDS and patients receiving C-HDS were observed. Multivariate analysis demonstrated that an aaIPI score of 3 was the only parameter that was significantly associated with poor overall and event-free survival. Age-adjusted International Prognostic Index score is applicable to patients with aggressive lymphoma who are treated with frontline intensive chemotherapy and autografting. In addition, upfront use of HDS chemotherapy appears to be beneficial to patients with an aaIPI score of 2 but not to those with an aaIPI score of 3.


Isolation and molecular characterization of methicillin-resistant staphylococci from horses, personnel and environmental sites at an equine hospital in Turkey.
The present study was carried out to assess the frequency of methicillin-resistant staphylococci (MRS) among racehorses (n=209) and veterinary personnel (n=13) as well as environmental surfaces (n=14) at an equine hospital in Adana, Turkey. In addition, species distribution, antimicrobial susceptibility, resistance genes, staphylococcal chromosomal cassette mec (SCCmec) type and clonality of these isolates were also investigated. MRS were identified by 16S rRNA sequencing, and typed by pulsed-field gel electrophoresis (PFGE). As a result, MRS was isolated in horses (48.3%), clinic staff (92.3%) and environmental samples (71.4%). Of the 123 MRS isolates, 118 isolates were identified as Staphylococcus lentus, and the remaining ones were found to be S. sciuri (n=3), S. intermedius (n=1) and S. fleuretti (n=1). All isolates were found to be susceptible against vancomycin, quinupristin-dalfopristin and rifampicin. Additionally, single or various combinations of resistance genes were detected among MRS isolates. SCCmec type II was identified in all isolates. Similar PFGE patterns were observed among MRS isolated from horses, humans, and environmental samples. Since MRS were concurrently isolated from horses and humans it is suggested that cross-transmission of MRS between horses and humans might occur. However, it cannot be ruled out that transmission is human to animal or animal to human.


Longitudinal Study after Sputnik V Vaccination Shows Durable SARS-CoV-2 Neutralizing Antibodies and Reduced Viral Variant Escape to Neutralization over Time.
Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC; Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI; Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (N = 536) collected from 118 volunteers obtained between January and October 2021 were used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity for the Wuhan-related lineages of SARS-CoV-2 and VOC is maintained within 6 months of vaccination. In addition, an improved antibody cross-neutralizing ability for circulating variants of concern (Beta and Gamma) was observed over time postvaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least 6 months and show a reduction of VOC escape to neutralizing antibodies over time after vaccination. IMPORTANCE Vaccines have been produced in record time for SARS-CoV-2, offering the possibility of halting the global pandemic. However, inequalities in vaccine accessibility in different regions of the world create a need to increase international cooperation. Sputnik V is a recombinant adenovirus-based vaccine that has been widely used in Argentina and other developing countries, but limited information is available about its elicited immune responses. Here, we examined longitudinal antibody levels and viral neutralizing capacity elicited by Sputnik V vaccination. Using a cohort of 118 volunteers, we found that while anti-spike antibodies wane over time, the neutralizing capacity to viral variants of concern and local variants of interest is maintained within 4 months of vaccination. In addition, we observed an increased cross-neutralization activity over time for the Beta and Gamma variants. This study provides valuable information about the immune response generated by a vaccine platform used in many parts of the world.


Nanostrontium ranelate incorporated injectable hydrogel enhanced matrix production supporting chondrogenesis in vitro.
An injectable hydrogel, with the advantage of adaptability to defect sites, patient compliance, controlled flowability and high water uptake capability, was explored as a prototype for cartilage tissue regeneration. Chitosan and fibrin are natural biomaterials that are biocompatible, biodegradable, resemble the ECM of the tissues and contain cell adhesion sites thereby providing a support for cell growth. In this study strontium ranelate, a drug recently studied to enhance cartilage regeneration, was encapsulated in chitosan nanoparticles to provide sustained delivery of the drug content within the composite gel (chitosan/alginate/fibrin hydrogel). The developed nanocomposite gel was characterized using SEM, EDS and FTIR. The particle size of the strontium ranelate loaded chitosan nanoparticles was found to be 160 ± 30 nm. The encapsulation and loading efficiency values of strontium ranelate were found to be 40 ± 10% and 36 ± 2% respectively. Rheological data showed a storage modulus of 5.514 ± 0.102 kPa with thermal stability over the studied temperature range, and the gel properties could be restored within 10 s after the application of a high shear rate. The cytocompatibility and chondrogenic potential was analyzed using human mesenchymal stem cells (hMSCs) to evaluate the applicability of the developed hydrogel for cartilage regeneration. hMSCs were found to be viable in the developed hydrogels and chondrogenic differentiation of hMSCs was observed which was confirmed with enhanced proteoglycan and collagen synthesis. These results indicated that the developed injectable nanocomposite gel would be a suitable system for cartilage regeneration.


Convergence of congenic mapping and allele-specific alterations in tumors for the resolution of the Skts1 skin tumor susceptibility locus.
Although several familial cancer genes with high-penetrance mutations have been identified, the major genetic component of susceptibility to sporadic cancers is attributable to low-penetrance alleles. These 'weak' tumor susceptibility genes do not segregate as single Mendelian traits and are therefore difficult to find in studies of human populations. Previously, we have proposed that a combination of germline mapping and analysis of allele-specific imbalance in tumors may be used to refine the locations of susceptibility genes using mouse models of cancer. Here, we have used linkage analysis and congenic mouse strains to map the major skin tumor susceptibility locus Skts1 within a genetic interval of 0.9 cM on proximal chromosome 7. This interval lies in an apparent recombination cold spot, and corresponds to a physical distance of about 15 Mb. We therefore, used patterns of allele-specific imbalances in tumors from backcross and congenic mice to refine the location of Skts1. We demonstrate that this single tumor modifier locus has a dramatic effect on the allelic preference for imbalance on chromosome 7, with at least 90% of tumors from the congenics showing preferential gain of markers on the chromosome carrying the susceptibility variant. Importantly, these alterations enabled us to refine the location of Skts1 at higher resolution than that attained using the congenic mice. We conclude that low-penetrance susceptibility genes can have strong effects on patterns of allele-specific somatic genetic changes in tumors, and that analysis of the directionality of these somatic events provides an important and rapid route to identification of germline genetic variants that confer increased cancer risk.


Some viral and protozool diseases in the European wildcat (Felis silvestris).
Ten European wildcats (Felis silvestris) were examined at necropsy and an additional 23 were examined clinically for evidence of viral diseases in Scotland. Two plasma samples taken from live free-living wildcats showed positive ELISA reactions to feline leukemia antigen. A feline leukemia virus of subgroup A was isolated from one of these samples, taken from a wildcat in north-western Scotland. No antibodies to feline coronavirus or feline immunodeficiency virus were detected in any sample. Three of the live wildcats and one of the dead had chronic mucopurulent rhinotracheitis suggestive of "cat flu." One other dead wildcat had diffuse enlargement of anterior lymph nodes. The findings indicated that feline leukemia virus infection can occur in free-living Felis silvestris. It is possible that the disease exists as a sustained infection in some wildcat populations, although the close interaction between wildcat and the domestic cat means that the latter could act as a continual source of infection.


Hydrogen Peroxide-triggered Chemical Strategy for Controlling CRISPR systems.
The function of the CRISPR system can be conditionally controlled through rationally guided RNA engineering such that the target sequences can be precisely selected and manipulated. In particular, gRNA, as an important component of the CRISPR system, provides a unique tool for multifunctional control of the system based on the structure of the RNA itself. Therefore, we introduced here a protective group on the 2'-OH position of RNA to inhibit RNA-guided nucleic acid cleavage. Next, the modified gRNA can restore its original function under the chemical stimulation of hydrogen peroxide to realize the control of the CRISPR system. The experiment result demonstrated that the operating mechanism of this strategy may be based on chemical modifications that reduce the number of complementary base pairs between RNAs and targets, and the RNA-protein interaction. This further enriches the toolbox of conditional control of CRISPR function and has broad potential for gene editing in living cells and disease treatment using endogenous hydrogen peroxide.


Evaluation of the Impact of Metabolic Syndrome on Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease.
Metabolic syndrome (MS) is a condition that consists of several disorders, and the individual impact of these disorders on metabolic dysfunction-associated fatty liver disease (MAFLD) is still not clear in a combined diagnosis of MS. In this study, we aimed to investigate the effect of MS on advanced fibrosis in patients with MAFLD. We recruited the patients from our gastroenterology out-patient clinic who were being followed up for MAFLD. MAFLD was diagnosed with liver biopsy in all patients. The frequency of MS and other metabolic parameters were also compared between groups with advanced fibrosis and groups in which fibrosis was not as advanced. In total, we enrolled 424 biopsy-proven MAFLD patients to the study. In univariate analysis, individuals with greater age, body mass index (BMI), higher aspartate transaminase (AST), MS, impaired fasting glucose, hypertension, enlarged waist circumference (WC), diabetes mellitus (DM), and women had significantly increased risk for fibrosis. In multivariate analysis, it was found that DM, greater age, higher BMI, and increased AST were seen more commonly in MAFLD patients with advanced fibrosis. Greater age, a higher BMI, higher AST and a diagnosis of diabetes were more commonly associated with advanced fibrosis. However, DM was found to be the strongest predictive factor of advanced fibrosis in our cohort (OR: 2.495). Multivariate analyses did not indicate a significantly common occurrence of MS in the advanced fibrosis group, despite its important role in MAFLD pathophysiology.


Bromodomain Containing Protein 4 (BRD4) Regulates Expression of its Interacting Coactivators in the Innate Response to Respiratory Syncytial Virus.
Bromodomain-containing protein 4 plays a central role in coordinating the complex epigenetic component of the innate immune response. Previous studies implicated BRD4 as a component of a chromatin-modifying complex that is dynamically recruited to a network of protective cytokines by binding activated transcription factors, polymerases, and histones to trigger their rapid expression via transcriptional elongation. Our previous study extended our understanding of the airway epithelial BRD4 interactome by identifying over 100 functionally important coactivators and transcription factors, whose association is induced by respiratory syncytial virus (RSV) infection. RSV is an etiological agent of recurrent respiratory tract infections associated with exacerbations of chronic obstructive pulmonary disease. Using a highly selective small-molecule BRD4 inhibitor (ZL0454) developed by us, we extend these findings to identify the gene regulatory network dependent on BRD4 bromodomain (BD) interactions. Human small airway epithelial cells were infected in the absence or presence of ZL0454, and gene expression profiling was performed. A highly reproducible dataset was obtained which indicated that BRD4 mediates both activation and repression of RSV-inducible gene regulatory networks controlling cytokine expression, interferon (IFN) production, and extracellular matrix remodeling. Index genes of functionally significant clusters were validated independently. We discover that BRD4 regulates the expression of its own gene during the innate immune response. Interestingly, BRD4 activates the expression of NFκB/RelA, a coactivator that binds to BRD4 in a BD-dependent manner. We extend this finding to show that BRD4 also regulates other components of its functional interactome, including the Mediator (Med) coactivator complex and the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin (SMARC) subunits. To provide further insight into mechanisms for BRD4 in RSV expression, we mapped 7,845 RSV-inducible Tn5 transposase peaks onto the BRD4-dependent gene bodies. These were located in promoters and introns of cytostructural and extracellular matrix (ECM) formation genes. These data indicate that BRD4 mediates the dynamic response of airway epithelial cells to RNA infection by modulating the expression of its coactivators, controlling the expression of host defense mechanisms and remodeling genes through changes in promoter accessibility.


Comparison of type 2 diabetes prevalence estimates in Saudi Arabia from a validated Markov model against the International Diabetes Federation and other modelling studies.
To compare the estimates and projections of type 2 diabetes mellitus (T2DM) prevalence in Saudi Arabia from a validated Markov model against other modelling estimates, such as those produced by the International Diabetes Federation (IDF) Diabetes Atlas and the Global Burden of Disease (GBD) project. A discrete-state Markov model was developed and validated that integrates data on population, obesity and smoking prevalence trends in adult Saudis aged ≥25 years to estimate the trends in T2DM prevalence (annually from 1992 to 2022). The model was validated by comparing the age- and sex-specific prevalence estimates against a national survey conducted in 2005. Prevalence estimates from this new Markov model were consistent with the 2005 national survey and very similar to the GBD study estimates. Prevalence in men and women in 2000 was estimated by the GBD model respectively at 17.5% and 17.7%, compared to 17.7% and 16.4% in this study. The IDF estimates of the total diabetes prevalence were considerably lower at 16.7% in 2011 and 20.8% in 2030, compared with 29.2% in 2011 and 44.1% in 2022 in this study. In contrast to other modelling studies, both the Saudi IMPACT Diabetes Forecast Model and the GBD model directly incorporated the trends in obesity prevalence and/or body mass index (BMI) to inform T2DM prevalence estimates. It appears that such a direct incorporation of obesity trends in modelling studies results in higher estimates of the future prevalence of T2DM, at least in countries where obesity has been rapidly increasing.


Pathological changes of distal motor neurons after complete spinal cord injury.
Traumatic spinal cord injury (SCI) causes serious disruption of neuronal circuits that leads to motor functional deficits. Regeneration of disrupted circuits back to their original target is necessary for the restoration of function after SCI, but the pathophysiological condition of the caudal spinal cord has not been sufficiently studied. Here we investigated the histological and biological changes in the distal part of the injured spinal cord, using a mice model of complete thoracic SCI in the chronic stage (3 months after injury). Atrophic changes were widely observed in the injured spinal cord both rostral and caudal to the lesion, but the decrease in area was mainly in the white matter in the rostral spinal cord while both the white and gray matter decreased in the caudal spinal cord. The number of the motor neurons was maintained in the chronic phase of injury, but the number of presynaptic boutons decreased in the lumbar motor neurons caudal to the lesion. Using laser microdissection, to investigate gene expressions in motor neurons caudal to the lesion, we observed a decrease in the expressions of neuronal activity markers. However, we found that the synaptogenic potential of postsynapse molecules was maintained in the motor neurons after SCI with the expression of acetylcholine-related molecules actually higher after SCI. Collectively, our results show that the potential of synaptogenesis is maintained in the motor neurons caudal to the lesion, even though presynaptic input is decreased. Although researches into SCI concentrate their effort on the lesion epicenter, our findings suggest that the area caudal to the lesion could be an original therapeutic target for the chronically injured spinal cord.


Development of new bioactive molecules to treat breast and lung cancer with natural myricetin and its derivatives: A computational and SAR approach.
Each biopharmaceutical research and new drug development investigation is targeted at discovering novel and potent medications for managing specific ailments. Thus, to discover and develop new potent medications, it should be performed sequentially or step by step. This is because drug development is a lengthy and risky work that requires significant money, resources, and labor. Breast and lung cancer contributes to the death of millions of people throughout the world each year, according to the report of the World Health Organization, and has been a public threat worldwide, although the global medical sector is developed and updated day by day. However, no proper treatment has been found until now. Therefore, this research has been conducted to find a new bioactive molecule to treat breast and lung cancer-such as natural myricetin and its derivatives-by using the latest and most authentic computer-aided drug-design approaches. At the beginning of this study, the biological pass prediction spectrum was calculated to select the target protein. It is noted that the probability of active (Pa) score is better in the antineoplastic (Pa: 0.788-0.938) in comparison with antiviral (Pa: 0.236-0.343), antibacterial (Pa: 0.274-0.421), and antifungal (Pa: 0.226-0.508). Thus, cancerous proteins, such as in breast and lung cancer, were picked up, and the computational investigation was continued. Furthermore, the docking score was found to be -7.3 to -10.4 kcal/mol for breast cancer (standard epirubicin hydrochloride, -8.3 kcal/mol), whereas for lung cancer, the score was -8.2 to -9.6 kcal/mol (standard carboplatin, -5.5 kcal/mol). The docking score is the primary concern, revealing that myricetin derivatives have better docking scores than standard chemotherapeutic agents epirubicin hydrochloride and carboplatin. Finally, drug-likeness, ADME, and toxicity prediction were fulfilled in this investigation, and it is noted that all the derivatives were highly soluble in a water medium, whereas they were totally free from AMES toxicity, hepatotoxicity, and skin sensitization, excluding only ligands 1 and 7. Thus, we proposed that the natural myricetin derivatives could be a better inhibitor for treating breast and lung cancer.


Normal and anomalous diffusion in highly confined hard disk fluid mixtures.
Monte Carlo simulation is used to study binary mixtures of two-dimensional hard disks, confined to long, narrow, structureless pores with hard walls, in a regime of pore sizes where the large particles exhibit single file diffusion while the small particles diffuse normally. The dynamics of the small particles can be understood in the context of a hopping time, tau(21), that measures the time it takes for a small particle to escape the single file cage formed by its large particle neighbors, and can be linked to the long time diffusion coefficient. We find that tau(21) follows a power law as a function of the reduced pore radius for a wide range of particle size ratios with an exponent, alpha, that is independent of the size ratio, but linearly dependent on the Monte Carlo step size used in the dynamic scheme. The mean squared displacement of the small particles as a function of time exhibits two dynamic crossovers. The first, from normal to anomalous diffusion, occurs at intermediate times then the system returns to normal diffusion in the long time limit. We also find that the diffusion coefficient is related to tau(21) through a power law with exponent beta=-0.5, as predicted by theory. Finally, we show that particle separation in a binary mixture will be optimal at the pore radius that causes the large particles to undergo their transition from normal to anomalous diffusion.


Fluid supplementation for neonatal unconjugated hyperbilirubinaemia.
Neonatal hyperbilirubinaemia is a common problem which carries a risk of neurotoxicity. Certain infants who have hyperbilirubinaemia develop bilirubin encephalopathy and kernicterus which may lead to long-term disability. Phototherapy is currently the mainstay of treatment for neonatal hyperbilirubinaemia. Among the adjunctive measures to compliment the effects of phototherapy, fluid supplementation has been proposed to reduce serum bilirubin levels. The mechanism of action proposed includes direct dilutional effects of intravenous (IV) fluids, or enhancement of peristalsis to reduce enterohepatic circulation by oral fluid supplementation. To assess the risks and benefits of fluid supplementation compared to standard fluid management in term and preterm newborn infants with unconjugated hyperbilirubinaemia who require phototherapy. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to 7 June 2017), Embase (1980 to 7 June 2017), and CINAHL (1982 to 7 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We included randomised controlled trials that compared fluid supplementation against no fluid supplementation, or one form of fluid supplementation against another. We extracted data using the standard methods of the Cochrane Neonatal Review Group using the Covidence platform. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), risk difference (RD), and risk ratio (RR) with 95% confidence intervals (CIs). Out of 1449 articles screened, seven studies were included. Three articles were awaiting classification, among them, two completed trials identified from the trial registry appeared to be unpublished so far.There were two major comparisons: IV fluid supplementation versus no fluid supplementation (six studies) and IV fluid supplementation versus oral fluid supplementation (one study). A total of 494 term, healthy newborn infants with unconjugated hyperbilirubinaemia were evaluated. All studies were at high risk of bias for blinding of care personnel, five studies had unclear risk of bias for blinding of outcome assessors, and most studies had unclear risk of bias in allocation concealment. There was low- to moderate-quality evidence for all major outcomes.In the comparison between IV fluid supplementation and no supplementation, no infant in either group developed bilirubin encephalopathy in the one study that reported this outcome. Serum bilirubin was lower at four hours postintervention for infants who received IV fluid supplementation (MD -34.00 μmol/L (-1.99 mg/dL), 95% CI -52.29 (3.06) to -15.71 (0.92); participants = 67, study = 1) (low quality of evidence, downgraded one level for indirectness and one level for suspected publication bias). Beyond eight hours postintervention, serum bilirubin was similar between the two groups. Duration of phototherapy was significantly shorter for fluid-supplemented infants, but the estimate was affected by heterogeneity which was not clearly explained (MD -10.70 hours, 95% CI -15.55 to -5.85; participants = 218; studies = 3; I² = 67%). Fluid-supplemented infants were less likely to require exchange transfusion (RR 0.39, 95% CI 0.21 to 0.71; RD -0.01, 95% CI -0.04 to 0.02; participants = 462; studies = 6; I² = 72%) (low quality of evidence, downgraded one level due to inconsistency, and another level due to suspected publication bias), and the estimate was similarly affected by unexplained heterogeneity. The frequencies of breastfeeding were similar between the fluid-supplemented and non-supplemented infants in days one to three based on one study (estimate on day three: MD 0.90 feeds, 95% CI -0.40 to 2.20; participants = 60) (moderate quality of evidence, downgraded one level for imprecision).One study contributed to all outcome data in the comparison of IV versus oral fluid supplementation. In this comparison, no infant in either group developed abnormal neurological signs. Serum bilirubin, as well as the rate of change of serum bilirubin, were similar between the two groups at four hours after phototherapy (serum bilirubin: MD 11.00 μmol/L (0.64 mg/dL), 95% CI -21.58 (-1.26) to 43.58 (2.55); rate of change of serum bilirubin: MD 0.80 μmol/L/hour (0.05 mg/dL/hour), 95% CI -2.55 (-0.15) to 4.15 (0.24); participants = 54 in both outcomes) (moderate quality of evidence for both outcomes, downgraded one level for indirectness). The number of infants who required exchange transfusion was similar between the two groups (RR 1.60, 95% CI 0.60 to 4.27; RD 0.11, 95% CI -0.12 to 0.34; participants = 54). No infant in either group developed adverse effects including vomiting or abdominal distension. There is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy, kernicterus, or cerebral palsy in healthy, term newborn infants with unconjugated hyperbilirubinaemia requiring phototherapy. In this review, no infant developed these bilirubin-associated clinical complications. Low- to moderate-quality evidence shows that there are differences in total serum bilirubin levels between fluid-supplemented and control groups at some time points but not at others, the clinical significance of which is uncertain. There is no evidence of a difference between the effectiveness of IV and oral fluid supplementations in reducing serum bilirubin. Similarly, no infant developed adverse events or complications from fluid supplementation such as vomiting or abdominal distension. This suggests a need for future research to focus on different population groups with possibly higher baseline risks of bilirubin-related neurological complications, such as preterm or low birthweight infants, infants with haemolytic hyperbilirubinaemia, as well as infants with dehydration for comparison of different fluid supplementation regimen.


Constrained least-squares restoration and renogram deconvolution: a comparison with other techniques.
It has previously been shown that an iterative constrained least-squares (CLSR) technique using a noise-based constraint may be superior to other methods of renogram deconvolution analysis. To test this hypothesis on real data, renography was performed on 70 patients with established diagnoses of normal, insufficient or acutely obstructed kidneys. Standard renography parameters were obtained from the time activity curves which were then deconvolved using three techniques. One kidney per patient was chosen at random for analysis resulting in a total of 43 normal and 27 diseased kidneys. The ability of each of the analytical techniques to discriminate between normal and diseased kidneys was assessed using logistic regression. CLSR proved to be robust and provide the best discrimination of the deconvolution techniques. However, the best overall discrimination was provided by a model based on the renography parameters excretion ratio, rate of uptake and time to peak activity which correctly classified 86% of the kidneys. It is possible that the renogram parameters could be used to produce notional probabilities of renal dysfunction which the physician could use as an aid in the interpretation of gamma-camera renography.


Personality traits and self-injurious behaviour in patients with eating disorders.
The interest in different aspects of personality and the neuropsychological basis for behaviour in eating disorder patients has increased over the last decade. The present study aims at exploring personality traits, self-injurious behaviour (SIB) and suicide attempts in a group of severely ill eating disorder patients. Patients with eating disorders (N = 38) and age-matched controls (N = 67) were examined concerning self-reported personality traits by means of the Karolinska scales of personality (KSP). Psychosocial history and SIB was collected from medical records. Depression was rated by means of the Beck Depression Inventory (BDI). Results indicated significantly higher anxiety-related and detachment traits in both anorexia nervosa (AN) and bulimia nervosa (BN) patients and higher hostility in BN patients than controls. No specific personality traits could be defined as typical for self-injurious or suicidal behaviour. The AN group was lower than the BN group on scales measuring impulsivity, guilt and anxiety. Furthermore, presence of SIB and suicide attempts was more frequent among the BN patients.


Effects of a low-fat vegan diet and a Step II diet on macro- and micronutrient intakes in overweight postmenopausal women.
This study investigated the nutrient intake of overweight postmenopausal women assigned to a low-fat vegan diet or a Step II diet. Fifty-nine overweight (body mass index, 26 to 44 kg/m2) postmenopausal women were randomly assigned to a self-selected low-fat vegan or a National Cholesterol Education Program Step II diet in a 14-wk controlled trial on weight loss and metabolism. Nutrient intake, which was measured per 1000 kcal, was the main outcome measure. Statistical analyses included within-group and between-group t tests examining changes associated with each diet. Consumption of a low-fat vegan diet was associated with greater decreases in fat, saturated fat, protein, and cholesterol intakes and greater increases in carbohydrate, fiber, beta-carotene, and total vitamin A intakes than was a Step II diet. The low-fat vegan group also increased thiamin, vitamin B6, and magnesium intakes more than the Step II group, and both groups increased folic acid, vitamin C, and potassium intakes. If considering only food sources of micronutrients, the low-fat vegan group decreased vitamin D, vitamin B12, calcium, selenium, phosphorous, and zinc intakes compared with baseline. However, with incidental supplements included, decreases were evident only in phosphorous and selenium intakes. No micronutrient decreases were found in the Step II group. Individuals on a low-fat vegan or Step II diet should take steps to meet the recommended intakes of vitamin D, vitamin K, folic acid, calcium, magnesium, and zinc. Individuals on a low-fat vegan diet should also ensure adequate intakes of vitamin B12, phosphorous, and selenium.


Giving Voice to Vulnerable Children: Machine Learning Analysis of Speech Detects Anxiety and Depression in Early Childhood.
Childhood anxiety and depression often go undiagnosed. If left untreated these conditions, collectively known as internalizing disorders, are associated with long-term negative outcomes including substance abuse and increased risk for suicide. This paper presents a new approach for identifying young children with internalizing disorders using a 3-min speech task. We show that machine learning analysis of audio data from the task can be used to identify children with an internalizing disorder with 80% accuracy (54% sensitivity, 93% specificity). The speech features most discriminative of internalizing disorder are analyzed in detail, showing that affected children exhibit especially low-pitch voices, with repeatable speech inflections and content, and high-pitched response to surprising stimuli relative to controls. This new tool is shown to outperform clinical thresholds on parent-reported child symptoms, which identify children with an internalizing disorder with lower accuracy (67-77% versus 80%), and similar specificity (85-100% versus 93%), and sensitivity (0-58% versus 54%) in this sample. These results point toward the future use of this approach for screening children for internalizing disorders so that interventions can be deployed when they have the highest chance for long-term success.


Simulation-Based Training in Flexible Bronchoscopy and Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA): A Systematic Review.
The use of simulators in a training programme for technically challenging procedures has the advantages of lowering the risk of patient complications while helping the trainees with the initial part of their learning curve. The aim of this study was to perform a systematic review of simulation-based training in flexible bronchoscopy and endobronchial ultrasound (EBUS). We identified 1,006 publications in the PubMed database and included publications on flexible bronchoscopy below the carina and EBUS involving hands-on simulation-based training. Publications were excluded if they were written in languages other than English, if paediatric airways were involved or if they were not journal articles. The screening process was performed by 2 individuals, and a third reviewer made the final decision in case of disagreement. We included 30 publications. The studies included participants of varying experience and most commonly used a virtual reality simulator as a training modality. Assessment of the participants' skills was based on simulator metrics or on an assessment tool. Some studies included performance on patients for assessment of the operator after training on a simulator. Simulation-based training was demonstrated to be more efficient than the traditional apprenticeship model. Physical models and virtual reality simulators complement each other. Simulation-based education should be based on a mastery learning approach and structured as directed self-regulated learning in a distributed training programme.


A new human Duffy blood group specificity defined by a murine monoclonal antibody. Immunogenetics and association with susceptibility to Plasmodium vivax.
A new Duffy specificity, Fy6, defined by a murine monoclonal antibody of the IgG1 kappa class, is related to susceptibility to malarial invasion. In humans, Fy6 is present on the red cells of all persons except those of the Fy(a-b-) type, a distribution resembling that of Fy3. However proteolytic enzyme treatment of red cells enhances the reactivity of Fy3, whereas Fy6, like Fya and Fyb, is susceptible to degradation by this process. The number of Fy6 sites on human red cells was found to be 12,200 per cell, in close agreement with earlier estimates of the number of Fya sites. Anti-Fy6 reacted in western blots with a membrane glycoprotein of approximately 46,000 Mr, not significantly different from that of a molecule known to bear the Fya determinant. The Fy6 epitope is shown to be present on the red cells of some but not all nonhuman primate species, where it has a distribution not only distinctly different from Fya, Fyb, and Fy3, but in close accordance with susceptibility to penetration by Plasmodium vivax. Thus, the red cells of two species of macaques (Macaca mulatta and M. fascicularis), which are invaded by Plasmodium knowlesi but not by P. vivax are shown to have other Duffy antigens but to be devoid of Fy6. It appears, therefore, that the red cell epitopes used by these closely related species are distinct, and that susceptibility to P. vivax merozoite penetration is dependent on the presence of Fy6.


Identification of the p53 protein domain involved in formation of the simian virus 40 large T-antigen-p53 protein complex.
An expression vector utilizing the enhancer and promoter region of the simian virus 40 (SV40) DNA regulating a murine p53 cDNA clone was constructed. The vector produced murine p53 protein in monkey cells identified by five different monoclonal antibodies, three of which were specific for the murine form of p53. The murine p53 produced in monkey cells formed an oligomeric protein complex with the SV40 large tumor antigen. A large number of deletion mutations, in-frame linker insertion mutations, and linker insertion mutations resulting in a frameshift mutation were constructed in the cDNA coding portion of the p53 protein expression vector. The wild-type and mutant p53 cDNA vectors were expressed in monkey cells producing the SV40 large T antigen. The conformation and levels of p53 protein and its ability to form protein complexes with the SV40 T antigen were determined by using five different monoclonal antibodies with quite distinct epitope recognition sites. Insertion mutations between amino acid residues 123 and 215 (of a total of 390 amino acids) eliminated the ability of murine p53 to bind to the SV40 large T antigen. Deletion (at amino acids 11 through 33) and insertion mutations (amino acids 222 through 344) located on either side of this T-antigen-binding protein domain produced a murine p53 protein that bound to the SV40 large T antigen. The same five insertion mutations that failed to bind with the SV40 large T antigen also failed to react with a specific monoclonal antibody, PAb246. In contrast, six additional deletion and insertion mutations that produced p53 protein that did bind with T antigen were each recognized by PAb246. The proposed epitope for PAb246 has been mapped adjacent (amino acids 88 through 109) to the T-antigen-binding domain (amino acids 123 through 215) localized by the mutations mapped in this study. Finally, some insertion mutations that produced a protein that failed to bind to the SV40 T antigen appeared to have an enhanced ability to complex with a 68-kilodalton cellular protein in monkey cells.


Spinal deformity after combined thoracotomy and sternotomy for congenital heart disease.
Patients with congenital heart disease are at an increased risk to develop scoliosis. The purpose of this study was to determine the incidence of spinal deformity in patients after thoracotomy and sternotomy for congenital heart disease. Sixty-eight patients underwent thoracotomy followed by a sternotomy and met inclusion criteria. The medical records were reviewed to gather demographic data and medical and surgical history. Serial radiographs were reviewed. Scoliosis developed in 26% of the patients (10 boys, 8 girls). The mean Cobb angle was 40 degrees (range, 15-78 degrees). The mean age at diagnosis of scoliosis was 10.7 years (range, 2.9-17 years). The mean follow-up was 14.9 years (range, 5-20 years). Twelve percent (8 patients) required posterior spinal fusion. A kyphotic deformity developed in 21% (14 patients). In patients with scoliosis, the mean kyphosis was 38 degrees (range, 2-88 degrees). Patients with a cyanotic cardiac condition had a 4-fold incidence of scoliosis. There was no correlation between the development of scoliosis or kyphosis and the age at time of procedures, number of surgeries, sex, heart size, or side of the aortic arch. The risk of developing scoliosis in children with congenital heart disease is more than 10 times that of idiopathic scoliosis. Spinal deformities, including scoliosis and/or hyperkyphosis, were found in 38% of the patients. Curves develop at a younger age, which increases the risk of progression. The sagittal alignment in scoliosis patients tends toward hyperkyphosis. The thoracic spine receives a "double hit" when both procedures are combined.


Independent effects of stable and changing body weight on total mortality.
Most studies find that associations between mortality and either body mass index or weight change are U-shaped. Previous studies, however, have not considered independent effects of weight level and weight change while also controlling for confounding by diseases leading to weight change. We used follow-up data on average 10-year total mortality from a Danish population of 15,113 men and women, who had their weight measured at about 5-year intervals. We obtained information on preexisting disease at surveys and by linkage to hospital discharge registers. We defined subclinical disease as incident disease or death during the first 4 years of follow-up. We decomposed the mortality risk associated with weight change into a static effect, corresponding to the difference in mortality at stable weight at the initial and attained weight, and a dynamic effect, estimated as the difference between mortality after weight change and mortality at stable weight at the attained weight. Both weight level and weight change had independent effects on total mortality, with both these associations being U-shaped. Adjustment for smoking and the exclusion of subjects with preexisting and subclinical disease did not alter the associations.


Observational study of subclinical diabetic macular edema.
To determine the rate of progression of eyes with subclinical diabetic macular edema (DME) to clinically apparent DME or DME necessitating treatment during a 2-year period. In all, 43 eyes from 39 study participants with subclinical DME, defined as absence of foveal center edema as determined with slit lamp biomicroscopy but a center point thickness (CPT) between 225 and 299 μm on time domain (Stratus, Carl Zeiss Meditec) optical coherence tomography (OCT) scan, were enrolled from 891 eyes of 582 subjects screened. Eyes were evaluated annually for up to 2 years for the primary outcome, which was an increase in OCT CPT of at least 50 μm from baseline and a CPT of at least 300 μm, or treatment for DME (performed at the discretion of the investigator). The cumulative probability of meeting an increase in OCT CPT of at least 50 μm from baseline and a CPT of at least 300 μm, or treatment for DME was 27% (95% confidence interval (CI): 14%, 38%) by 1 year and 38% (95% CI: 23%, 50%) by 2 years. Although subclinical DME may be uncommon, this study suggests that between approximately one-quarter and one-half of eyes with subclinical DME will progress to more definite thickening or be judged to need treatment for DME within 2 years after its identification.


[Transport of calcium to synaptosomes and subcellular membrane fractions of the brain: effects of opioid peptides].
Highly purified synaptosomal and subcellular fractions identified as mitochondria and microsomes were obtained by fractionation of brain tissues. The greatest Ca-accumulating capacity and the highest rate of Ca2+ accumulation were revealed in the mitochondrial fraction. Upon further fractionation of the synaptosomal fraction the energy-dependent uptake (accumulation) of Ca2+ was revealed only in the mitochondria. It was demonstrated that opioid peptides accelerate Ca2+ uptake by the synaptosomes in a medium with physiological concentration of K+ and inhibit this process during K+-dependent membrane depolarization. It was shown that beta-endorphine, methionine-encephaline and leucine-encephaline (10(-8)-10(-5) M) inhibit the Ca-accumulating capacity of both mitochondria and microsomes from brain. The experimental data suggest that opioid peptides can modulate the release of neurotransmitters and/or neurohormones by inhibiting the potential-dependent Ca2+ influx into the nerve endings and by decreasing the intrasynaptosomal pool of Ca2+.


Advanced buffer materials for indoor air CO2 control in commercial buildings.
In this study, we evaluated solid sorbents for their ability to passively control indoor CO2 concentration in buildings or rooms with cyclic occupancy (eg, offices, bedrooms). Silica supported amines were identified as suitable candidates and systematically evaluated in the removal of CO2 from indoor air by equilibrium and dynamic techniques. In particular, sorbents with various amine loadings were synthesized using tetraethylenepentamine (TEPA), poly(ethyleneimine) (PEI) and a silane coupling agent 3-aminopropyltriethoxysilane (APS). TGA analysis indicates that TEPA impregnated silica not only displays a relatively high adsorption capacity when exposed to ppm level CO2 concentrations, but also is capable of desorbing the majority of CO2 by air flow (eg, by concentration gradient). In 10 L flow-through chamber experiments, TEPA-based sorbents reduced outlet CO2 by up to 5% at 50% RH and up to 93% of CO2 adsorbed over 8 hours was desorbed within 16 hours. In 8 m3 flow-through chamber experiments, 18 g of the sorbent powder spread over a 2 m2 area removed approximately 8% of CO2 injected. By extrapolating these results to real buildings, we estimate that meaningful reductions in the CO2 can be achieved, which may help reduce energy requirements for ventilation and/or improve air quality.


Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ.
Therapies targeting inflammation reveal inconsistent results in idiopathic pulmonary fibrosis (IPF). Aerosolised interferon (IFN)-γ has been proposed as a novel therapy. Changes in the host airway microbiome are associated with the inflammatory milieu and may be associated with disease progression. Here, we evaluate whether treatment with aerosolised IFN-γ in IPF impacts either the lower airway microbiome or the host immune phenotype. Patients with IPF who enrolled in an aerosolised IFN-γ trial underwent bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of bronchoalveolar lavage fluid (BALF) was used to evaluate the lung microbiome. Biomarkers were measured by Luminex assay in plasma, BALF and BAL cell supernatant. The compPLS framework was used to evaluate associations between taxa and biomarkers. IFN-γ treatment did not change α or β diversity of the lung microbiome and few taxonomic changes occurred. While none of the biomarkers changed in plasma, there was an increase in IFN-γ and a decrease in Fit-3 ligand, IFN-α2 and interleukin-5 in BAL cell supernatant, and a decrease in tumour necrosis factor-β in BALF. Multiple correlations between microbial taxa common to the oral mucosa and host inflammatory biomarkers were found. These data suggest that the lung microbiome is independently associated with the host immune tone and may have a potential mechanistic role in IPF.


The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition.
Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.


Antibacterial activity of medicinal plants from The Physicians of Myddvai, a 14th century Welsh medical manuscript.
Antimicrobial drug resistance is a growing threat to global public health. Historical records and herbal texts relating to traditional Celtic medicine indicate an extensive pharmacopeia of plants for treating infections likely caused by microbes. However, a major barrier for successful integration of these remedies into mainstream practice is the current lack of accurate interpretation and scientific validation. We investigated the flora of the Isle of Arran, Scotland, via in situ targeted screening of 83 out of 138 plants identified in Meddygion Myddvai (a 14th century Welsh manuscript) to treat conditions related to microbial infections, and an additional 18 plants from modern ethnobotanical knowledge on the island (Scottish School of Herbal Medicine). In a follow-up proof-of-concept study, bioassay-guided fractionation was performed to identify bioactive constituents from two high scoring hits that inhibited Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacterial growth. 67 historical plants (80.7%) and 14 modern plants (77.8%) were found to have detectable levels of antimicrobial activity when tested using Mobile Discovery kits, with human saliva as a source of bacteria for screening. Sabinene, a natural bicyclic monoterpene from juniper "berries" (Juniperus communis L.) and alliin, a natural sulfoxide from garlic cloves (Allium sativum L.), were isolated and confirmed as primary antibacterial leads. Using historical medical sources such as those associated with traditional Celtic medicine to guide rigorous, evidence-based scientific investigation, provides additional leads for new and alternative bioactive molecules for combating bacterial diseases.


Candidate pathway polymorphisms in one-carbon metabolism and risk of rectal tumor mutations.
We examined candidate polymorphisms in genes involved in the folate-mediated, one-carbon metabolism pathway, DNMT1 1311V, MTHFD1 R134K and R653Q, MTHFR R594Q, MTR D919G, MTRR H595Y and I22M, SHMT1 L474F, SLC19A1 H27R, and TDG G199S, and associations with rectal tumor characteristics. We hypothesized that these candidate genes would influence CpG Island Methylator Phenotype and potentially KRAS2 or TP53 tumors. Data from a population-based study of 747 rectal cases (593 with tumor markers) and 956 controls were evaluated using generalized estimating equations. We observed an increased risk of TP53 tumor mutations in homozygous carriers of the MTHFD1 134K allele (0R=2.0, 95%CI 1.2-3.1, P- trend=0.02). In the presence of low folate intake, the R134K variant was associated with increased risk of CIMP+ tumors (OR=2.8, 95%CI 1.04-7.7). The MTRR I22M variant genotype was associated with a modest increased risk of TP53 mutations (OR=1.7, 95%CI 1.2-2.5, P-trend=0.001). Our findings offer limited support that polymorphisms in one-carbon metabolism genes influence rectal tumor phenotype, and that folate may interact with MTHFD1 to alter CIMP+ risk.


Blood pressure, edema and proteinuria in pregnancy. 3. Study design, population and data characteristics.
1. The mean blood pressure runs a curvilinear pattern during the course of pregnancy, with the lowest reading between 20 and 27 weeks of gestation, a continuous rise from 28 to 36 weeks, followed by a plateau. 2. the mean blood pressure in pregnancies without edema and proteinuria are lowest throughout pregnancy. However, the mean blood pressures in pregnancies complicated by edema, proteinuria, or both, are less than 5 mm. Hg higher after 28 weeks of gestation. 3. The mean blood pressures are lower in black gravidas than in white gravidas throughout pregnancy, independent of the presence or absence of edema, proteinuria, or their combinations. 4. The mean blood pressure is related to age and parity. Median-age gravidas (20-34 years) of parity 1-5 have the lowest mean blood pressures overall at any time during gestation. The mean blood pressure of nulliparas, independent of age, is elevated over the mean blood pressure of comparable multiparas. Independent of parity, maternal age systematically affects the mean blood pressure. 5. The standard deviations for the mean diastolic and systolic blood pressures are approximately 9 and 11 mm. Hg, respectively, independent of the weeks of gestation. They are affected very little by the absence or presence of edema or proteinuria, or both. 6. Edema of hands and/or face occurs more often in black gravidas. 7. The overall perinatal mortality rates in pregnancies complicated by edema are not higher than in pregnancies without edema. Perinatal mortality rates in pregnancies with proteinuria, or edema and proteinuria, on the other hand, are approximately double the rates for pregnancies without edema and proteinuria.


Patterns of early primary school-based literacy interventions among Pacific children from a nationwide health screening programme of 4 year olds.
Literacy success is critical to unlocking a child's potential and enhancing their future wellbeing. Thus, the early identification and redressing of literacy needs is vital. Pacific children have, on average, the lowest literacy achievement levels in New Zealand. However, this population is very diverse. This study sought to determine whether the current national health screening programme of pre-school children could be used as an early detection tool of Pacific children with the greatest literacy needs. Time-to-event analyses of literacy intervention data for Pacific children born in years 2005-2011 were employed. A multivariable Cox proportional hazard model was fitted, and predictive assessment made using training and test datasets. Overall, 59,760 Pacific children were included, with 6,861 (11.5%) receiving at least one literacy intervention. Tongan (hazard ratio [HR]: 1.33; 95% confidence interval [CI]: 1.23, 1.45) and Cook Island Māori (HR: 1.33; 95% CI: 1.21, 1.47) children were more likely to receive an intervention than Samoan children; whereas those children with both Pacific and non-Pacific ethnic identifications were less likely. However, the multivariable model lacked reasonable predictive power (Harrell's c-statistic: 0.592; 95% CI: 0.583, 0.602). Regardless, important Pacific sub-populations emerged who would benefit from targeted literacy intervention or policy implementation.


An analytical model for the design of RF resonators for MR body imaging.
A closed form, analytical solution describing the RF fields generated by an RF body coil resonator for MR imaging at 1.5 and 4.0 T is presented. This solution extends the results of earlier studies of RF penetration in the body by explicitly including the RF coil, the RF shield, and the field variation along the z axis for high-pass bird cage coils. A salient feature of this treatment is the calculation of the axial propagation constant, kz, which determines the z dependence of the RF field. We have determined the relative power deposition in the body, the B1 field homogeneity, and coil losses, which are functions of the coil-to-shield separation and body size. The relative power deposition in the body has been calculated to vary as the 1.58 power of the body radius. The calculations have also predicted that the field homogeneity in the z direction exhibits greater degradation at higher frequencies in a high-pass coil than in a low-pass coil. The model predicts an increase in coil losses by a factor of 2.8 as the coil-to-shield separation is reduced from 5 to 2 cm in a standard body resonator. Although the results for only a homogeneous cylindrical object or body are presented, the theory can be extended to a multilayered heterogeneous object of varying permittivity and conductivity.


The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn.
Human newborns are susceptible to microbial infection and mount poor vaccine responses, yet the mechanisms underlying their susceptibility are incompletely defined. We have previously reported that despite normal basal expression of TLRs and associated signaling intermediates, human neonatal cord blood monocytes demonstrate severe impairment in TNF-alpha production in response to triacylated (TLR 2/1) and diacylated (TLR 2/6) bacterial lipopeptides (BLPs). We now demonstrate that in marked contrast, BLP-induced synthesis of IL-6, a cytokine with anti-inflammatory and Th2-polarizing properties, is actually greater in neonates than adults. Remarkably, newborn blood plasma confers substantially reduced BLP-induced monocyte synthesis of TNF-alpha, while preserving IL-6 synthesis, reflecting the presence in neonatal blood plasma of a soluble, low molecular mass inhibitory factor (<10 kDa) that we identify as adenosine, an endogenous purine metabolite with immunomodulatory properties. The neonatal adenosine system also inhibits TNF-alpha production in response to whole microbial particles known to express TLR2 agonist activity, including Listeria monocytogenes, Escherichia coli (that express BLPs), and zymosan particles. Selective inhibition of neonatal TNF-alpha production is due to the distinct neonatal adenosine system, including relatively high adenosine concentrations in neonatal blood plasma and heightened sensitivity of neonatal mononuclear cells to adenosine A3 receptor-mediated accumulation of cAMP, a second messenger that inhibits TLR-mediated TNF-alpha synthesis but preserves IL-6 production. We conclude that the distinct adenosine system of newborns polarizes TLR-mediated cytokine production during the perinatal period and may thereby modulate their innate and adaptive immune responses.


[Gastrointestinal stromal tumors in the pediatric population. Report of two cases and a review of the literature].
Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal (GI) tract that occur predominantly in adults. GISTs in pediatric patients are rare and not well characterized. We reviewed the presentation, diagnostic work-up, pathological specimens, and outcomes of two children with GIST that originated from the stomach. Literature pertaining to pediatric GISTs was also reviewed. Both patients presented with upper GI bleeding from a gastric tumor. The first patient was a 10-year-old male who underwent partial gastrectomy but had recurrence 26 years later requiring surgical exploration due to extensive infiltration into the surrounding organs; the tumor was not resected. The patient is currently being treated with imatinib mesylate. The second patient was a 12-year-old female who had a pedunculated mass originating from the stomach and requiring resection. She subsequently had a local recurrence 2 years later requiring partial gastrectomy. Adjuvant imatinib mesylate was recommended because of the large size of the tumor (8 cm). Pediatric GISTs represent a distinct subset of sarcomas with a strong predominance for females and gastric location, with 56 cases reported in the English-language literature.


Trends in Occupational Infectious Diseases in South Korea and Classification of Industries According to the Risk of Biological Hazards Using K-Means Clustering.
Against the backdrop of the COVID-19 pandemic, it is necessary to identify these risks and determine whether the current level of management is appropriate to respond to the risk of biological hazards depending on the occupation. In this study, the incidence and fatality rates of occupational diseases were calculated using industrial accident statistics of South Korea, and trends by year using joinpoint regression and relative risk by industry using k-means clustering were evaluated for infectious diseases. We found that infectious diseases had the third highest incidence and fourth highest fatalities among all occupational diseases. In the incidence rate, joinpoints appeared in 2009 and 2018, and the annual percent change changed to 7.79, -16.63, and 82.11. The fatality rate showed a consistent increase with an annual percent change of 4.37, but it was not significant. Industries were classified into five groups according to risk, and the legal control measures of certain industries were not sufficient. Follow-up studies are needed to rectify the structural limitations of industrial accident statistics.


Heparin binding domain of insulin-like growth factor binding protein-5 stimulates mesangial cell migration.
Insulin-like growth factor I (IGF-I) binding protein-5 (IGFBP-5) is produced by mesangial cells (MCs) and likely functions to modulate glomerular IGF-I activity. Although IGFBP-5 may be inhibitory for IGF-stimulated MC activity, preliminary studies suggested that IGFBP-5 acts directly on MCs. To investigate this further, we evaluated the effects of IGFBP-5 on rat MC migration. We found that the carboxytruncated fragment, IGFBP-5-(1-169), inhibited IGF-I-stimulated migration, but intact IGFBP-5 simulated migration when IGF-I was not present. Demonstration that 125I-labeled IGFBP-5 directly binds to MCs further supports an independent role for IGFBP-5. Because heparin inhibited MC binding of 125I-IGFBP-5, we tested the heparin binding peptide, IGFBP-5-(201-218), for stimulatory activity. IGFBP-5-(201-218) stimulated MC migration, and this effect was inhibited by heparin. Because the disintegrin, kistrin, blocked IGF-I-induced migration but not migration induced by IGFBP-5-(201-218), the migratory induction mechanism for the two peptides is different. These data indicate that separate, specific regions of IGFBP-5 are responsible for interactive effects with IGF-I as well as direct effects on MC activity.


Coping with caring for someone with dementia: reviewing the literature about men.
As the demographics of the population change, men are assuming increasingly important roles as caregivers, despite caregiving often being perceived as a feminine activity. Research to date has described sex differences in caregiving and psychological outcomes. However, there appears to be little understanding of varying ways men may cope with the strains of caregiving. To this end, a systematic literature search was carried out to determine what is known about men coping with caring for someone with dementia. The search process elicited 93 articles, reviewed and categorised by their content. The majority of articles reported research and interventions with little detailed analysis of gender as a mediating variable for coping. Four articles reported finding no sex-differences in coping and burden. Of the nine articles that reported exclusively on men caregivers, only one generated quantitative data within an explicit framework of stress, appraisal and coping. Conclusions suggest that future research requires refinement and sophistication to address the role of gender in mediating appraisals of strain and coping responses to familial dementia care. The limitations of gender difference research and self-report methodologies are discussed along with their implications for interventions and suggestions for future research.


Developmental changes in the adhesive disk during Giardia differentiation.
Giardia lamblia is a protozoan parasite infecting the upper mammalian small intestine. Infection relies upon the ability of the parasite to attach to the intestine via a unique cytoskeletal organelle, the ventral disk. We determined the composition and structure of the disk throughout the life cycle of the parasite and identified a new disk protein, SALP-1. SALP-1 is an immunodominant protein related to striated fiber-assemblin (SFA). The disk is disassembled during encystation and stored as four fragments in the immobile cyst. Serial Analysis of Gene Expression (SAGE) showed that the mRNA levels of the disk proteins decreased in encystation but two-dimensional protein gels showed that the protein levels were more constant. The parasite emerges without a functional disk but the four disk fragments are quickly reassembled into two new disks on the dividing, early excysting form. Thus, disk proteins are stored within the cyst, ready to be used in the rapid steps of excystation.


STAT3 and NF-κB cooperatively control in vitro spontaneous apoptosis and poor chemo-responsiveness in patients with chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is an adult disease characterized by in vivo accumulation of mature CD5/CD19/CD23 triple positive B cells and is currently incurable. CLL cells undergo spontaneous apoptosis in response to in vitro cell culture condition but the underlying mechanism is unclear. We hypothesize that the sensitivity of CLL cells to spontaneous apoptosis may be associated with the constitutive activities of transcription factors STAT3 and/or NF-κB. We now show that the sensitivity of fresh CLL cells to spontaneous apoptosis is highly variable among different patients during 48 hours' cell culture and inversely correlated with in vivo constitutively activated STAT3 and NF-κB (p < 0.001). Both activated STAT3 and NF-κB maintain the levels of anti-apoptotic protein Mcl-1/Bcl-xL and autocrine IL-6 production. CLL cells with higher susceptibility to in vitro spontaneous apoptosis show the greatest chemosensitivity (p < 0.001), which is reflected clinically as achieving a complete response (CR) (p < 0.001), longer lymphocyte doubling times (p < 0.01), time to first treatment (p < 0.01), and progression free survival (p < 0.05). Our data suggest that the sensitivity of CLL cells to in vitro spontaneous apoptosis is co-regulated by constitutively activated STAT3 and NF-κB and reflects the in vivo chemo-responsiveness and clinical outcomes.


Crisis intervention: elders awaiting placement in an acute care facility.
1. Awaiting nursing home placement may be viewed as a situational crisis for elders in acute care facilities. 2. Crisis intervention techniques focus on solving the immediate problem in the person's life to re-establish emotional equilibrium in the individual. 3. The more predictable the new nursing home environment is to the elder, the less negative the effects of relocation. 4. Ethically, it must be assumed that cognitively impaired elders will benefit from some form of crisis intervention prior to nursing home relocation.


Insights in Public Health: The University of Hawai'i West O'ahu Undergraduate Health Science Program: Training the Workforce of the Future.
Hawai'i faces a significant healthcare workforce shortage, not only with physicians, but also with health science workers. "Health science" is a hands-on field that combines biomedical and psychosocial aspects of health, disease, and health care. Many of the fastest-growing jobs are in the health sciences, including home health aides, physical therapists, school counselors, and social workers. In Hawai'i, an aging population and the retirement of current health professionals increases the demand for health science workers. Innovative approaches and new care models are essential to meet Hawaii's needs. One promising solution involves creating four-year undergraduate degree concentrations that train students in marketable skills that are projected to be in demand in Hawai'i, such as in long-term care, community health, and health information management. These bachelor-level graduates could serve critical roles in relieving nurses and physicians of administrative, managerial, care coordination, and clinical data analysis duties that hamper their abilities to practice at the top of their licenses and training. The undergraduate health sciences program at the University of Hawai'i West O'ahu supports students who want to enter these career paths. The program's primary goal is to establish multiple pathways that provide opportunities for underserved youth in West O'ahu communities to choose marketable healthcare careers that pay a sustainable and living wage. Support for this innovative initiative will create a stronger, more well-rounded and sustainable health care workforce that meets Hawaii's increasing demand for affordable, accessible and high-quality care. The final measure of success will be the quality and number of our graduates from our communities, serving our communities.


Determination of minimum individual cow colostral immunoglobulin G concentration required to provide adequate total immunoglobulin G mass in pooled colostrum fed to Jersey calves.
Quantify the minimum individual cow colostral immunoglobulin G (IgG) concentration required for pooling to achieve adequate transfer of passive immunity in calves. 201 Jersey cows. Colostrum was collected from 28 pools and heat treated before being fed to calves or stored. Parity, total number of cows contributing to the pool, individual cow colostral volume contributions, and total volume of each colostrum pool were recorded. Colostrum IgG concentrations in individual and pooled (pre- and post-heat treatment) samples were analyzed by radial immunodiffusion and Brix refractometry. Colostral IgG concentration of ≥ 50g/L was considered the current recommended dairy industry standard for acceptable colostrum quality. Multivariable models were performed to determine factors affecting pooled colostral IgG concentrations. The minimum colostral IgG concentration required for pooling to achieve the recommended total mass of at least 200g IgG to be fed to a calf was calculated. Total pool volume and the number of cows contributing to the pool were significant factors affecting IgG concentration. Colostrum pools from ≤ 7 cows, with a minimum pool IgG concentration of 70.4 g/L (22.9% Brix) or colostrum pool volume ≤ 40 L, with a minimum pool IgG concentration of 66.2 g/L (21.8% Brix) achieved the recommended total mass of at least 200g IgG in 4L of colostrum. When feeding pooled colostrum, IgG concentrations higher than the industry standard of 50 g/L is recommended to reduce the risk of failure of transfer of passive immunity in calves.


Neurocutaneous melanosis with transposition of the great arteries and renal agenesis.
Neurocutaneous melanosis (NCM) is rare and is characterized by the proliferation of melanocytes in the central nervous system. A 6-day-old infant boy was referred to our department with giant congenital melanocytic nevi and convulsions. On physical examination the patient had a giant black-brown pigmented nevus covering his face, neck, scalp, shoulders, back, chest, and abdomen. Numerous satellite lesions were noted on the face, neck, and upper extremities. In the right bulbar conjunctiva, a brown plaque was present. Magnetic resonance imaging (MRI) showed hyperintense areas in the brain on short repetition time/short echo time sequences, compatible with intraparenchymal melanin deposits. No leptomeningeal abnormality was seen. Further investigation also revealed agenesis of the right kidney and transposition of the great arteries. Transposition of the great arteries, which has never been reported in NCM, may be an incidental finding. We present a case of NCM associated with agenesis of the right kidney and transposition of the great arteries.


A comparison of peripheral and central effects of CCK8 on water-reinforced operant responding.
Systemic administration of cholecystokinin-octapeptide (CCK8) suppresses operant responding in water deprived rats, but it is unclear whether this effect is centrally or peripherally mediated. Rats were trained to press a lever for water in an operant conditioning chamber under a variable-interval schedule of reinforcement. After response rate stabilized injections were administered, and response suppression was measured by comparing injection response rate to baseline rate. Intracerebroventricular injections of CCK8 reduced lever pressing at relatively high doses (20 and 50 micrograms/rat). But in a direct comparison, the same dose of CCK8 (20 micrograms/rat) given intraperitoneally reduced responding significantly more than when given into the lateral ventricle. The suppressive effects of CCK8 (30 and 300 micrograms/kg i.p.) were significantly reduced by complete abdominal vagotomy. The effects of CCK8 (30 micrograms/kg i.p.) were blocked by pretreatment with the specific competitive CCK8 antagonist dibutyryl cyclic GMP (70 and 140 mg/kg i.p.), but not by the acetylcholine antagonist atropine (0.1 to 10 mg/kg i.p.). These data suggest that suppression by CCK8 of operant lever pressing in water-deprived rats is primarily mediated by vagal afferent fibers.


The mechanisms underlying fructose-induced hypertension: a review.
We are currently in the midst of an epidemic of metabolic disorders, which may, in part, be explained by excess fructose intake. This theory is supported by epidemiological observations as well as experimental studies in animals and humans. Rising consumption of fructose has been matched with growing rates of hypertension, leading to concern from public health experts. At this stage, the mechanisms underlying fructose-induced hypertension have not been fully characterized and the bulk of our knowledge is derived from animal models. Animal studies have shown that high-fructose diets up-regulate sodium and chloride transporters, resulting in a state of salt overload that increases blood pressure. Excess fructose has also been found to activate vasoconstrictors, inactivate vasodilators, and over-stimulate the sympathetic nervous system. Further work is required to determine the relevance of these findings to humans and to establish the level at which dietary fructose increases the risk of developing hypertension.


A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study.
Patients with type 2 diabetes mellitus (T2DM) have reduced platelet inhibition compared with non-diabetics following P2Y(12) receptor blockade. Whether inhibition of P2Y(12) signalling can be enhanced by adjunctive treatment with cilostazol in T2DM patients is unknown. The aim of this pilot study was to assess the functional impact of cilostazol in T2DM patients on standard aspirin and clopidogrel treatment. This was a prospective, double-blind, double-dummy, placebo-controlled, randomized, cross-over platelet function study. T2DM patients on dual antiplatelet therapy were assigned to receive cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment assignments for another 14 days. Platelet function was performed at three time points: at baseline, 14 days after randomization, and 14 days after treatment cross-over. The P2Y(12) reactivity index, determined through flow cytometric assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein, was the primary endpoint measure. In addition to this flow cytometric evaluation, light transmittance aggregometry and VerifyNow testing were performed. A total of 25 T2DM patients were randomized; five patients discontinued treatment due to side effects. The P2Y(12) reactivity index was significantly lower following cilostazol treatment compared with placebo (36.3 +/- 20 vs. 59.9 +/- 16%; P = 0.0002). All other P2Y(12)-specific functional assessments showed enhanced inhibition of this signalling pathway following treatment with cilostazol. Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy enhances inhibition of platelet P2Y(12) signalling.


Distortion product otoacoustic emmissions in Ménière's disease.
Distortion product otoacoustic emissions (DPOAEs) are an objective, non-invasive measure for evaluating outer hair cell (OHC) activity. In this study DPOAEs were measured in 70 patients affected by Meniere's disease (MD). In addition 58 out of 70 patients performed both an audiometric threshold evaluation pre- and postglycerol administration (i.e. glycerol test) and DPOAEs pre- and post-osmotic drug assumption. The purpose of this combined form of testing was to explore the effects of glycerol on the active non-linear mechanisms of the cochlea. More than 60% of the ears with MD emitted DPOAEs despite the presence of an average hearing threshold level above 40 dB (HTL). Changes in the DPOAE baseline measures were observed in 32.4% of cases after glycerol administration. Patients were divided in four groups according to the different pattern of DPOAEs shown after the glycerol test. In particular, three-quarters of cases showed a significant increase in DPOAE amplitude, one-quarter of patients, who initially did not express DPOAEs, eventually did after intake of the osmotic agent, while no decreased DPOAEs were observed in these series. The different expressions of DPOAEs should be associated with the evolutive phases of MD. In addiction, elucidation of the relationship between DPOAEs and the stages of MD was an outcome of this test.


T cell defect in lepromatous leprosy is reversible in vitro in the absence of exogenous growth factors.
T lymphocytes from patients with lepromatous leprosy (LL) characteristically fail to respond to Mycobacterium leprae. This specific immunologic defect is thought to contribute to the aggressive clinical course that typifies patients with LL. We report that although fresh CD4+ (helper) T cells from most LL patients are specifically unresponsive to M. leprae, after culture in medium alone for 48 hr the same cells respond to M. leprae antigens. The recovery of T cell function is specific for M. leprae, occurs at the level of responder CD4+ T cells, and is not affected by monocytes or CD8+ (suppressor) T cells. Recovery of T cell reactivity is blocked by the presence of M. leprae bacilli in the preculture medium. These findings indicate that despite the apparent specific anergy seen in patients with LL, the T cells of most LL patients can respond to M. leprae. Their failure to do so, in vivo, may be due to the persistence of antigen, which renders antigen-reactive T cells nonresponsive either directly or via activation of CD4+ suppressor cells.


Electrolyte ion adsorption and charge blocking effect at the hematite/aqueous solution interface: an electrochemical impedance study using multivariate data analysis.
A model-free multivariate analysis using singular value decomposition is employed to refine an equivalent electrical circuit model in order to probe the electrochemical properties of the hematite/water interface in dilute NaCl and NH4Cl solutions using electrochemical impedance spectroscopy. The result shows that the surface protonation is directly related to the mobility and trapping of charge carriers at the mineral surface. Moreover, the point of zero charge can be found at pH where the charge transfer resistance is the highest, in addition to the minimum double layer capacitance. The inner-sphere interaction of the NH4(+) ion with the surface is indicated by an increase of capacitance for charge carrier trapping from the protonated surface as well as lower double layer capacitance and open circuit potential. It is clear that the intrinsic electrochemical activity of hematite depends on the degree of surface (de)protonation and other inner-sphere adsorption, as these processes affect the charge carrier density in the surface state. This work also highlights an important synergistic effect of the two spectral analyses that enables EIS to be utilized in an in-depth investigation of mineral/water interfaces.


[Internet and mobile phone interventions to decrease alcohol consumption and to support smoking cessation in adolescents: a review].
The aim of this study was to review the published literature on Internet and mobile phone interventions to decrease alcohol consumption and for smoking cessation in adolescents. Electronic searches of PubMed, MEDLINE, Web of Science, PsycINFO, ERIC, and the Cochrane Register of Controlled Trials were conducted in August 2009. Additionally, reference lists of previously published reviews and meta-analyses within this topic were checked. Studies, published in scientific journals, containing English abstracts, and reporting results about the effectiveness of an intervention were included into the review. Initial searches in the literature databases identified 2 263 articles of which 31 were eligible for inclusion in this review: 19 articles address internet interventions to decrease alcohol consumption, 7 Internet interventions for smoking cessation, and 5 mobile phone text messaging interventions for smoking cessation. No articles concerning mobile phone interventions to decrease alcohol consumption in adolescents were identified. 16 out of the 19 studies that aimed at decreasing alcohol consumption by the use of the Internet were conducted in college or university students from the United States or New Zealand and the majority of these studies were based on the social norms approach. Good empirical evidence exists concerning the efficacy of web-based social norms interventions to decrease alcohol consumption in students. In the field of smoking cessation, Internet interventions are much more heterogeneous concerning the target group and the provided interventions. So far, 5 controlled studies concerning Internet interventions for smoking cessation in adolescents are available, 2 of these studies were effective in decreasing the smoking prevalence at the last follow-up. Interventions using mobile phone text messaging for smoking cessation were well accepted and promising; however, they were primarily tested within pilot studies and conclusions about their efficacy are not possible so far. Suggestions for the implementation of certain intervention approaches in Germany could not be derived from the existing studies. For research in Germany, it is suggested to work on the following topics: (1) testing the efficacy of web-based social norms interventions to decrease alcohol consumption in student and non-student samples, (2) testing the efficacy of Internet interventions for smoking cessation, and (3) testing the efficacy of text messaging interventions for smoking cessation.


A Multisystemic Approach Revealed Aminated Polystyrene Nanoparticles-Induced Neurotoxicity.
Exposure to plastic nanoparticles has dramatically increased in the last 50 years, and there is evidence that plastic nanoparticles can be absorbed by organisms and cross the blood-brain-barrier (BBB). However, their toxic effects, especially on the nervous system, have not yet been extensively investigated, and most of the knowledge is based on studies using different conditions and systems, thus hard to compare. In this work, physicochemical properties of non-modified polystyrene (PS) and amine-functionalized PS (PS-NH2 ) nanoparticles are initially characterized. Advantage of a multisystemic approach is then taken to compare plastic nanoparticles effects in vitro, through cytotoxic readouts in mammalian cell culture, and in vivo, through behavioral readouts in the nematode Caenorhabditis elegans (C. elegans), a powerful 3R-complying model organism for toxicology studies. In vitro experiments in neuroblastoma cells indicate a specific cytotoxic effect of PS-NH2 particles, including a decreased neuronal differentiation and an increased Amyloid β (Aβ) secretion, a sensitive readout correlating with Alzheimer's disease pathology. In parallel, only in vivo treatments with PS-NH2 particles affect C. elegans development, decrease lifespan, and reveal higher sensitivity of animals expressing human Aβ compared to wild-type animals. In summary, the multisystemic approach discloses a neurotoxic effect induced by aminated polystyrene nanoparticles.


Performance-based IADL evaluation of older adults with cognitive impairment within a smart home: A feasibility study.
Mild cognitive impairment (MCI) is characterized by subtle deficits that functional assessment via informant-report measures may not detect. Sensors can potentially detect deficits in everyday functioning in MCI. This study aims to establish feasibility and acceptability of using sensors in a smart home for performance-based assessments of two instrumental activities of daily living (IADLs). Thirty-five older adults (>65 years) performed two IADL tasks in a smart home laboratory equipped with sensors and a web camera. Participants' cognitive states were determined using published criteria including measures of global cognition and comprehensive neuropsychological test batteries. Selected subtasks of the IADL assessment were autonomously captured by the sensors. Total time taken for each task and subtask were computed. A point scoring system captured accuracy and number of attempts. Acceptability of the smart home setup was assessed. Participants with MCI (n = 21) took longer to complete both tasks than participants with healthy cognition (HC; n = 14), with significant time differences observed only in "Cost calculation." Completion time for IADL tasks and scores correlated in the expected direction with global cognition. Over 95% of the participants found the smart home assessment acceptable and a positive experience. We demonstrated the feasibility and acceptability of the use of unobtrusive commercially available sensors in a smart home for facilitating parts of the objective assessment of IADL in older adults. Future studies need to identify more IADLs that are suitable for semi-automated or automated assessments through the use of simple, low-cost sensors.


Correlates of outcome and response to IVIg in 88 patients with multifocal motor neuropathy.
Identification and examination of all patients with multifocal motor neuropathy (MMN) in the Netherlands to document the clinical spectrum and response to IV immunoglobulin (IVIg) and to determine correlates of outcome. A national cross-sectional descriptive study was performed. Ninety-seven patients were identified; 88 participated. Logistic regression analysis was used to study determinants of outcome. Age at onset was younger in men than in women (38 vs 45 years, p = 0.05). Onset of weakness was in distal arm (61%) or distal leg (34%), and occasionally in the upper arm (5%). Initial diagnosis was motor neuron disease in one-third of patients. Brisk, but not pathologic, reflexes in weakened muscles were found in 8%. Conduction blocks were most frequently detected in the ulnar (80%) and median (77%) nerves, but occasionally only between Erb and axilla (6%), or in the musculocutaneous nerve (1%). Ninety-four percent responded to IVIg therapy: nonresponders had longer disease duration before the first treatment (p = 0.03). Seventy-six percent received IVIg maintenance treatment at the time of this study (median duration 6 years; range 0-17): the median dose increased over the years from 12 to 17 g per week (p < 0.01). Independent determinants of more severe weakness and disability were axon loss (p < 0.001; p < 0.0001) and longer disease duration without IVIg (p = 0.03; p = 0.07). The results of this study may help aid recognition the clinical picture of MMN. Early IVIg treatment may help to postpone axonal degeneration and permanent deficits. This study provides Class IV evidence that IVIg improves muscle strength of patients with MMN and disability (defined as an increase of >or=1 Medical Research Council grade in at least 2 muscle groups without decrease in other muscle groups) in 94% (95% confidence interval, 86.8%-97.4%) of patients.