D2, D3, and D4 dopamine receptors couple to G protein-regulated potassium channels in Xenopus oocytes.
Human D2, D3, D4 and dopamine receptors were individually coexpressed in Xenopus oocytes with a G protein-regulated inwardly rectifying potassium channel (GIRK1). At -100 mV in 96 mM potassium, dopamine (0.1-100 nM) evoked an inward current; the current showed inward rectification, reversed polarity at 0 mV, and was blocked by barium (50% inhibition by 10 microM). The concentrations of dopamine activating 50% of the maximal current (EC50) were not different (2-4 nM) for D2, D3, and D4 receptors, but the maximal current was 3-fold larger for D2 and D4 than for D3 receptors. Dopamine evoked reproducible inward currents at D2 and D4 receptors when applied repeatedly, but second responses could not be observed in oocytes expressing D3 receptors. 7-Hydroxy-N,N-di-n-propyl-2-aminotetralin mimicked the effect of dopamine (EC50 of approximately 2, approximately 3, and approximately 19 nM at D2, D3, and D4, respectively). (-) Sulpiride reversibly blocked the dopamine-induced current with IC50 values of 5, 300, and 2000 nM for D2, D3, and D4 receptors, respectively. Dopamine was ineffective in oocytes injected 2 hr previously with pertussis toxin. We concluded that all three D2-like dopamine receptors share the potential to activate inwardly rectifying potassium channels.


Impact of in situ chemical oxidation on contaminant mass discharge: linking source-zone and plume-scale characterizations of remediation performance.
A large-scale permanganate-based in situ chemical oxidation (ISCO) effort has been conducted over the past ten years at a federal Superfund site in Tucson, AZ, for which trichloroethene (TCE) is the primary contaminant of concern. Remediation performance was assessed by examining the impact of treatment on contaminant mass discharge, an approach that has been used for only a very few prior ISCO projects. Contaminant mass discharge tests were conducted before and after permanganate injection to measure the impact at the source-zone scale. The results indicate that ISCO caused a significant reduction in mass discharge (approximately 75%). The standard approach of characterizing discharge at the source-zone scale was supplemented with additional characterization at the plume scale, which was evaluated by examining the change in contaminant mass discharge associated with the pump-and-treat system. The integrated contaminant mass discharge decreased by approximately 70%, consistent with the source-zone-scale measurements. The integrated mass discharge rebounded from 0.1 to 0.2 kg/d within one year after cessation of permanganate injections, after which it has been stable for several years. Collection of the integrated contaminant mass discharge data throughout the ISCO treatment period provided a high-resolution, real-time analysis of the site-wide impact of ISCO, thereby linking source-zone remediation to impacts on overall risk. The results indicate that ISCO was successful in reducing contaminant mass discharge at this site, which comprises a highly heterogeneous subsurface environment. Analysis of TCE sediment concentration data for core material collected before and after ISCO supports the hypothesis that the remaining mass discharge is associated in part with poorly accessible contaminant mass residing within lower-permeability zones.


Unique inhibitory cascade pattern of molars in canids contributing to their potential to evolutionary plasticity of diet.
Developmental origins that guide the evolution of dental morphology and dental formulae are fundamental subjects in mammalian evolution. In a previous study, a developmental model termed the inhibitory cascade model was established. This model could explain variations in relative molar sizes and loss of the lower third molars, which sometimes reflect diet, in murine rodents and other mammals. Here, I investigated the pattern of relative molar sizes (inhibitory cascade pattern) in canids, a taxon exhibiting a wide range of dietary habits. I found that interspecific variation in canid molars suggests a unique inhibitory cascade pattern that differs from that in murine rodents and other previously reported mammals, and that this variation reflects dietary habits. This unique variability in molars was also observed in individual variation in canid species. According to these observations, canid species have greater variability in the relative sizes of first molars (carnassials), which are functionally important for dietary adaptation in the Carnivora. In conclusion, an inhibitory cascade that differs from that in murine rodents and other mammals may have contributed to diverse dietary patterns and to their parallel evolution in canids.


Comparative transcriptomic and weighted gene co-expression network analysis to identify the core genes in the cultivars of Musa acuminata under both infected and chemical perturbated conditions.
Banana is a high nutrient crop, which ranks fourth in terms of gross value production. Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (FocTR4), is considered the most destructive disease leading to the complete loss of production of the Cavendish cultivars Berangan, Brazilian and Williams, which are vulnerable to the infection of FocTR4. However, the treatment with benzothiadiazole, a synthetic salicylic analog, is aimed to induce resistance in plants. Thus, the treatments pertaining to the banana plants subjected to the Foc infection within the chosen cultivars were compared with chemically treated samples obtained at different time intervals for a short duration (0-4 days). The integrated omics analyses considering the parameters of WGCNA, functional annotation, and protein-protein interactions revealed that many pathways have been negatively influenced in Cavendish bananas under FocTR4 infections and the number of genes influenced also increased over time in Williams cultivar. Furthermore, elevation in immune response and resistance genes were also observed in the roots of the Cavendish banana.


The incidence of infections in compromised patients at Groote Schuur hospital. An autopsy study.
The results of a retrospective autopsy study of 115 adult patients with haematological or lymphoreticular malignancies or who had undergone transplantation procedures, are presented. The overall incidence of infection was 65%, 123 infections being detected in 75 patients. The bulk of the infections involved the gastro-intestinal and respiratory systems, other systems being considerably less frequently affected. Patients who had received allografts and subsequent immunosuppression had the highest incidence of viral inclusions, especially cytomegalovirus. Candida infections were more common than aspergillosis, and severe fungal infections were most frequent in patients with acute leukaemia who had been treated aggressively. The only other mycosis detected was cryptococcosis. Bacterial pneumonia was the most frequent infection over-all (36%). Tuberculosis, pyelonephritis and Pneumocystis pneumonitis were also encountered.


Rapid Metabolic Profiling of 1 μL Crude Cerebrospinal Fluid by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging Can Differentiate De Novo Parkinson's Disease.
Parkinson's disease (PD) is a highly prevalent neurodegenerative disorder affecting the motor system. However, the correct diagnosis of PD and atypical parkinsonism may be difficult with high clinical uncertainty. There is an urgent need to identify reliable biomarkers using high-throughput, molecular-specific methods to improve current diagnostics. Here, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging method that requires minimal sample preparation and only 1 μL of crude cerebrospinal fluid (CSF). The method enables analysis of hundreds of samples in a single experiment while simultaneously detecting numerous metabolites with subppm mass accuracy. To test the method, we analyzed CSF samples from 12 de novo PD patients (that is, newly diagnosed and previously untreated) and 12 age-matched controls. Within the identified molecules, we found neurotransmitters and their metabolites such as γ-aminobutyric acid, 3-methoxytyramine, homovanillic acid, serotonin, histamine, amino acids, and metabolic intermediates. Limits of detection were estimated for multiple neurotransmitters with high linearity (R2 > 0.99) and sensitivity (as low as 16 pg/μL). Application of multivariate classification led to a highly significant (P < 0.001) model of PD prediction with a 100% classification rate, which was further thoroughly validated with a permutation test and univariate analysis. Molecules related to the neuromelanin pathway were found to be significantly increased in the PD group, indicated by their elevated relative intensities compared to the control group. Our method enables rapid detection of PD-related biomarkers in low sample volumes and could serve as a valuable tool in the development of robust PD diagnostics.


Impact of bariatric surgery on cancer risk reduction.
Obesity is second only to tobacco as a preventable cause of cancer in the US. By multifactorial and often additive mechanisms, obesity leads to the development and promotion of 40% of the cancers diagnosed in this country, including post-menopausal breast, endometrial, colorectal, kidney, liver and pancreatic cancers, among others. Though prevention of obesity should be the ultimate goal of thoughtful and effective healthcare practices, it remains a highly prevalent condition, and morbid obesity (BMI ≥40 Kg/m2) can be refractory to lifestyle interventions in many cases. Currently bariatric surgery is an effective treatment strategy for individuals who suffer from morbid obesity or obesity with associated co-morbidities and fail to lose weight under a medically supervised diet and exercise program. The current review addresses seminal studies that have investigated the potential cancer prevention effects of bariatric surgery, demonstrating a positive impact mostly in post-menopausal breast and endometrial cancers. The controversial association between bariatric surgery and increased colorectal cancer (CRC) risk is also recognized and discussed. Finally, while bariatric surgery should not be routinely recommended as a cancer prevention strategy, it has the potential to decrease the risk for certain types of cancers as a collateral beneficial effect.


In-vitro bactericidal activity of cefpirome and cefamandole in combination with glycopeptides against methicillin-resistant Staphylococcus aureus.
The bactericidal activity in vitro of cefpirome plus either vancomycin or teicoplanin was compared with that of a cefamandole-vancomycin combination against ten clinical isolates of homogeneous methicillin-resistant Staphylococcus aureus. Cefpirome (0.125 x MIC) combined with vancomycin (0.5-2 x MIC) or teicoplanin (0.5-4 x MIC) acted synergically against the ten isolates. Similar effects were observed with the cefamandole-vancomycin combination, except that for one isolate, higher cefamandole concentrations (0.25-1 x MIC) were required.


Comparative full genome analysis of four infectious laryngotracheitis virus (Gallid herpesvirus-1) virulent isolates from the United States.
Gallid herpesvirus-1 (GaHV-1), commonly named infectious laryngotracheitis (ILT) virus, causes the respiratory disease in chickens known as ILT. The molecular determinants associated with differences in pathogenicity of GaHV-1 strains are not completely understood, and a comparison of genomic sequences of isolates that belong to different genotypes could help identify genes involved in virulence. Dideoxy sequencing, 454 pyrosequencing and Illumina sequencing-by-synthesis were used to determine the nucleotide sequences of four genotypes of virulent strains from GaHV-1 groups I-VI. Three hundred and twenty-five open reading frames (ORFs) were compared with those of the recently sequenced genome of the Serva vaccine strain. Only four ORFs, ORF C, U(L)37, ICP4 and U(S)2 differed in amino acid (aa) lengths among the newly sequenced genomes. Genome sequence alignments were used to identify two regions (5' terminus and the unique short/repeat short junction) that contained deletions. Seventy-eight synonymous and 118 non-synonymous amino acid substitutions were identified with the examined ORFs. Exclusive to the genome of the Serva vaccine strain, seven non-synonymous mutations were identified in the predicted translation products of the genes encoding glycoproteins gB, gE, gL and gM and three non-structural proteins U(L)28 (DNA packaging protein), U(L)5 (helicase-primase) and the immediate early protein ICP4. Furthermore, our comparative sequence analysis of published and newly sequenced GaHV-1 isolates has provided evidence placing the cleavage/packaging site (a-like sequence) within the inverted repeats instead of its placement at the 3' end of the U(L) region as annotated in the GenBank's entries NC006623 and HQ630064.


[Epidemiology and diagnosis of cervical intraepithelial neoplasia--is the present concept of screening and diagnosis still current?].
Infection with human papillomavirus (HPV) is the major factor in the genesis of cervical intraepithelial (CIN) and invasive neoplasia. However, screening is still based upon cytology and further diagnostic investigation relies on colposcopy with punch biopsy. In this review, recent studies are evaluated with regard to consequences for optimal screening and management strategies of CIN. In summary, exfoliative cytology is still widely considered as the method of choice for population screening. Primary HPV DNA screening proves equivalent or superior to cytology only in populations with a low prevalence of HPV infections. Preliminary data from serological HPV tests are less promising. Cytological diagnosis of HPV infection may be verified by HPV testing. Recognizing high oncogenic risk viruses in CIN 1 may help to reduce the control period from 24 to 12 months and may lead to immediate therapy for CIN 2 lesions. However, further prospective studies evaluating the cost-effectiveness of HPV DNA tests in German-speaking countries are necessary.


Aldehyde dehydrogenase activity and large vessel disease in diabetes mellitus. A preliminary study.
Type II diabetic subjects, 26 with symptoms and/or signs of large vessel disease (LVD group) and 26 free from clinical vascular disease (FVD group), matched for sex, age, body weight, and duration of diabetes after diagnosis, together with 28 healthy controls participated in a preliminary study on new potential risk factors of large vessel disease. The activity of erythrocyte aldehyde dehydrogenase (ALDH) was significantly higher (P less than 0.005) in the LVD than in the FVD group and in the controls, as indicated by a shorter half-life of acetaldehyde in homogenates of erythrocytes and plasma (100 +/- 11, 203 +/- 28, and 180 +/- 21 min, respectively). The results were unaffected by antidiabetes therapy, blood glucose control, alcohol consumption, or by recognized risk factors of angiopathy, such as blood pressure, hyperlipidemia, or smoking. Whether ALDH activity is a primary factor in large vessel disease or is merely a secondary phenomenon is unknown. However, ALDH activity is a critical factor determining chlorpropamide alcohol flush (CPAF), which has been suggested to be an inherited trait in some type II diabetic subjects. In conclusion, high ALDH activity was shown to be associated with an increased risk of large vessel disease in diabetes.


Multifunctional Fe3O4@TiO2@Au magnetic microspheres as recyclable substrates for surface-enhanced Raman scattering.
Herein, we demonstrate the design and fabrication of multifunctional triplex Fe3O4@TiO2@Au core-shell magnetic microspheres (MSs), which show excellent surface enhanced Raman scattering (SERS) activity with high reproducibility and stability. In addition, due to their excellent catalytic properties, the as-prepared Fe3O4@TiO2@Au magnetic MSs can clean themselves by photocatalytic degradation of target molecules adsorbed onto the substrate under irradiation with visible light, and can be re-used for several cycles with convenient magnetic separability. The influence of the size and distribution of Au nanoparticles (NPs) on the Fe3O4@TiO2 beads is investigated. The optimized samples employing Au NPs of 15 nm size and an areal density of about 2120 Au NPs on every MS show the best SERS activity and recyclable performance. The experimental results show that these magnetic MSs indicate a new route in eliminating the 'single-use' problem of traditional SERS substrates and exhibit their applicability as analytical tools for the detection of different molecular species.


Genome-scale models of metabolism and gene expression extend and refine growth phenotype prediction.
Growth is a fundamental process of life. Growth requirements are well-characterized experimentally for many microbes; however, we lack a unified model for cellular growth. Such a model must be predictive of events at the molecular scale and capable of explaining the high-level behavior of the cell as a whole. Here, we construct an ME-Model for Escherichia coli--a genome-scale model that seamlessly integrates metabolic and gene product expression pathways. The model computes ~80% of the functional proteome (by mass), which is used by the cell to support growth under a given condition. Metabolism and gene expression are interdependent processes that affect and constrain each other. We formalize these constraints and apply the principle of growth optimization to enable the accurate prediction of multi-scale phenotypes, ranging from coarse-grained (growth rate, nutrient uptake, by-product secretion) to fine-grained (metabolic fluxes, gene expression levels). Our results unify many existing principles developed to describe bacterial growth.


Effects of different resistance training intensity on indices of oxidative stress.
The purposes of this study were (a) to determine whether acute resistance exercise training (RET) induces oxidative stress, (b) to determine whether chronic RET decreases oxidative stress level at rest condition in previously untrained men, and (c) also to investigate how the RET intensity influences the training-induced oxidative stress response. Sixteen young men who did not have RET experience in the past were randomly divided in 2 groups. Hypertrophy-intensity group (n = 9) performed 3 sets of 12 repetitions at an intensity corresponding to 70% of 1 repetition maximum (1RM), whereas strength-intensity group (n = 7) performed 3 sets of 6 repetitions at an intensity corresponding to 85% of 1RM. Resistance exercise training involved 6 exercises, and it was performed 3 times a week on nonconsecutive days for 6 weeks. Blood samples were obtained just before (pre-RET) and immediately after RET (post-RET) on the first day of the first week, on the last day of the fourth and sixth weeks. The results indicated that malondialdehyde (MDA) significantly decreased (p < 0.05) in both groups immediately after RET; however, there was no significant acute alteration in glutathione (GSH) level in both groups (p > 0.05). After 6 weeks of training, pre-RET values of MDA significantly decreased and pre-RET values of GSH significantly increased in both hypertrophy- and strength-intensity groups (p < 0.05). These alterations occurred independently of training intensity. This study indicated that hypertrophy- and strength-intensity whole-body RET performed regularly for 6 weeks, decreased MDA concentration and increased GSH level in healthy young men. Results suggest that chronic RET has protective effects against oxidative stress similar to aerobic exercises and that these effects seem to be independent of the training intensity.


An introduction to fast dissolving oral thin film drug delivery systems: a review.
Many pharmaceutical companies are switching their products from tablets to fast dissolving oral thin films (OTFs). Films have all the advantages of tablets (precise dosage, easy administration) and those of liquid dosage forms (easy swallowing, rapid bioavailability). Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with Central Nervous System disorders, have difficulty in swallowing or chewing solid dosage forms. Many of these patients are non-compliant in administering solid dosage forms due to fear of choking. OTFs when placed on the tip or the floor of the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and then disintegrate and/or dissolve to release the medication for local and/or systemic absorption. This technology provides a good platform for patent non- infringing product development and for increasing the patent life-cycle of the existing products. The application of fast dissolving oral thin films is not only limited to buccal fast dissolving system, but also expands to other applications like gastroretentive, sublingual delivery systems. This review highlights the composition including the details of various types of polymers both natural and synthetic, the different types of manufacturing techniques, packaging materials and evaluation tests for the OTFs.


Augmentation mentoplasty using a custom-design wire cage.
Mentoplasty is often a complimentary procedure to rhinoplasty. At least 25% of all rhinoplasty patients may need a chin implant to balance facial features better. Augmentation mentoplasty using alloplastic implants such as silicone, rubber, or other materials provides a simple approach to the treatment of the hypoplastic chin. Although these types of implants are readily available in developed countries, there are parts of the world where they are unavailable or quite expensive. The authors have developed a chin implant made of wire that is available throughout the world and is custom designed to the mentum of the patient after a cephalometric evaluation. This technique has been used in 125 patients along with rhinoplasty over the last 20 years at our institution. In an initial series of 8 patients, the prosthesis became displaced and was removed in 2 patients. Since then, a new radiographic technique has been developed to demonstrate the shape of the mentum before surgery and new bone formation after surgery. By using this special radiographic technique, it was possible to detect four types of mentum before surgery and to construct a custom-design wire cage according to this shape. The prosthesis is constructed by an orthodontist according to the cephalometric measurements and shape of the mentum. By using the buccal approach, a pocket is prepared subperiosteally and a wire cage is inserted. In the last 20 cases, the wire cage was filled with diced cartilage wrapped with Surgicel. The results were esthetically satisfactory in most patients. After the shape of the wire prosthesis was modified to conform to the shape of the underlying bone better, no displacement of the prosthesis has been experienced. In 3 patients, it was necessary to remove the prosthesis when new tissue formation began to fill the prosthesis. These specimens were examined histologically, and the regenerating tissue was found to be connective tissue with a thin layer of bone formation. Most patients could be followed up for only 3 to 12 years. In all patients, the results have been consistent and the procedure has been safe.


The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death.
Each cell is under constant surveillance to maintain the integrity of its genome. Genomic lesions in a cell must be repaired before the onset of DNA replication and cell division. In the scenario that the genomic lesion is not repairable, the damaged cells are disposed in an orderly manner known as programmed cell death or apoptosis. Apoptosis and cell cycle progression are two intimately linked phenomena. Uncontrollable cell proliferation perturbs the cellular homeostasis and this can lead to malignancies, as well as organ dysfunction and developmental abnormalities. The biological pathway controlling cell fate is sequentially organized at the molecular level. Recent studies have made important contributions in advancing our knowledge of the mechanisms of cell cycle control and apoptosis regulation. A oncogene-derived protein, Bcl2, confers negative control in the pathway of cellular suicide machinery. A Bcl2-homologous protein, Bax, promotes cell death by competing with Bcl2. While Bax-Bax homodimers act as apoptosis inducers, Bcl2-Bax heterodimer formation evokes a survival signal for the cells. Both Bcl2 and Bax are transcriptional targets for the tumour suppressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. In all, the coordinate performance of these molecules is crucial for controlling life and death of a cell.


Reexamining the effects of gestational age, fetal growth, and maternal smoking on neonatal mortality.
BACKGROUND: Low birth weight (<2,500 g) is a strong predictor of infant mortality. Yet low birth weight, in isolation, is uninformative since it is comprised of two intertwined components: preterm delivery and reduced fetal growth. Through nonparametric logistic regression models, we examine the effects of gestational age, fetal growth, and maternal smoking on neonatal mortality. METHODS: We derived data on over 10 million singleton live births delivered at >/= 24 weeks from the 1998-2000 U.S. natality data files. Nonparametric multivariable logistic regression based on generalized additive models was used to examine neonatal mortality (deaths within the first 28 days) in relation to fetal growth (gestational age-specific standardized birth weight), gestational age, and number of cigarettes smoked per day. All analyses were further adjusted for the confounding effects due to maternal age and gravidity. RESULTS: The relationship between standardized birth weight and neonatal mortality is nonlinear; mortality is high at low z-score birth weights, drops precipitously with increasing z-score birth weight, and begins to flatten for heavier infants. Gestational age is also strongly associated with mortality, with patterns similar to those of z-score birth weight. Although the direct effect of smoking on neonatal mortality is weak, its effects (on mortality) appear to be largely mediated through reduced fetal growth and, to a lesser extent, through shortened gestation. In fact, the association between smoking and reduced fetal growth gets stronger as pregnancies approach term. CONCLUSIONS: Our study provides important insights regarding the combined effects of fetal growth, gestational age, and smoking on neonatal mortality. The findings suggest that the effect of maternal smoking on neonatal mortality is largely mediated through reduced fetal growth.


A systematic review of qualitative research on recently acquired HIV.
Recently acquired HIV is a critical time when people may experience debilitating symptoms and is when they are most likely to pass HIV on. Qualitative research offers insights into lived experiences and a deeper understanding of the contextual factors underlying HIV acquisition. We aimed to synthesize qualitative literature on recently acquired HIV. Systematic review and textual narrative synthesis. We searched MEDLINE, CINAHL Plus, PsycINFO and Sociology Database. Articles were screened, and two authors completed full text review and data extraction. Quality appraisal was conducted (Critical Appraisal Skills Programme Qualitative Studies Checklist) and certainty of findings graded (GRADE-CERQual). We reviewed 1890 articles (1554 following de-duplication), excluding 1539. Fifteen articles were included and an additional article was included after updating the search. We identified 15 themes, three of which we have high confidence in: recent acquisition of HIV facilitates understanding of circumstances of HIV acquisition; indeterminate HIV tests generate uncertainty and anxiety; and people with recently acquired HIV are motivated to reduce risk of onward transmission. Our findings highlight the importance of continued research into recently acquired HIV, as well as the need for support to manage the emotional impact of indeterminate test results and negotiate risk reduction. We found no studies exploring sexual risk in the context of recently acquired HIV, or use of pre-exposure prophylaxis or treatment as prevention. The literature is primarily focused on HIV acquisition from an individual and behavioural perspective, neglecting important aspects of lived experience such as immediate ART, stigma, and health and wellbeing.


Immune complexes and complement abnormalities in patients with cystic fibrosis. Increased mortality associated with circulating immune complexes and decreased function of the alternative complement pathway.
Serum samples from 139 patients with cystic fibrosis (CF) were tested for complement abnormalities and circulating immune complexes (CIC). We found no consistent changes in whole complement activity. However, we found CIC in 29% of these patients and decreased activity of the alternative complement pathway (ACP) in 36%. During 5 yr of observation, mortality was much higher in patients whose sera contained CIC (p less than 0.001) or decreased ACP activity (p less than 0.01). Of patients with both abnormalities, 31% died; however, no deaths occurred in patients with normal ACP activity and negative tests for CIC (p less than 0.001). During a subsequent 2.5-yr period, 55% of patients greater than or equal to 21 yr old with both findings died. In contrast, no deaths occurred in older patients lacking this combination (p = 0.0062). Circulating immune complexes but not decreased ACP activity were an independent risk factor for death. Our findings support the hypothesis that humoral immune mechanisms may contribute to morbidity and mortality in CF.


MUC2 is a highly specific marker of goblet cell metaplasia in the distal esophagus and gastroesophageal junction.
Currently, the American College of Gastroenterology requires identification of goblet cells in mucosal biopsies from the esophagus to diagnose Barrett esophagus (BE). Identification of goblet cells in mucosal biopsies is fraught with limitations such as sampling and interpretation error. One previous study by our group suggested that MUC2 expression in esophageal nongoblet columnar cells represents a late biochemical reaction in the conversion of mucinous columnar cells to goblet cells in BE. We conducted this study to evaluate the prevalence, sensitivity, and specificity of MUC2 positivity in nongoblet columnar epithelium for detection of goblet cells in the distal esophagus and gastroesophageal junction (GEJ) region. We also sought to identify associations between MUC2 positivity and clinical and endoscopic risk factors for BE. This analysis utilized mucosal biopsies of the distal esophagus or GEJ from 100 patients who participated in a community clinic-based study of patients with chronic gastroesophageal reflux disease evaluated prospectively in the western part of Washington state. We randomly selected 50 patients who had columnar epithelium with goblet cells, representing the study group and 50 patients without goblet cells, representing the comparison group. Immunohistochemistry for MUC2 was performed on samples in a blinded manner without knowledge of the clinical or endoscopic features of the patients. The presence of staining was noted in both goblet and nongoblet epithelium, both close to and distant from the mucosa with goblet cells, when the latter were present. All study patients showed MUC2 positivity in goblet cells. MUC2 was present in nongoblet columnar epithelium in 78% of study patients with goblet cells, but in only 4% of controls without goblet cells (P<0.0001) (sensitivity, 78%; specificity, 96% for goblet cell metaplasia). MUC2 was significantly more common in nongoblet columnar cells close to, rather than distant from, the mucosa with goblet cells (P<0.00001). Finally, MUC2 was significantly associated with endoscopic evidence of columnar metaplasia in the distal esophagus, and with known risk factors for BE, such as older age, white race, frequent heartburn, and elevated body mass index. We conclude that goblet cells likely develop from a field of MUC2-positive mucinous columnar cells, and as such, MUC2 represents a late event in the development of goblet cells. MUC2 staining in nongoblet columnar cells is a reasonably sensitive and highly specific marker for goblet cells in the distal esophagus and GEJ, and its presence is predictive of endoscopic columnar metaplasia of the esophagus, even in patients without goblet cells.


[Analysis of comorbid psychiatric disorders in child and adolescent psychiatry using the standardised basic documentation].
A slightly modified version of the basic documentation of the Child and Adolescent Psychiatric Associations is used to record in a standardised way important characteristics of the patients consulting clinics in Munich and Regensburg. The focus of the instrument is on the diagnostic classification of the symptoms according to the multiaxial classification scheme. The data of 5166 patients were analysed for frequency and type of combined psychiatric disorder. The results showed, that more than 60 % of the patients had more than one psychiatric diagnosis. The type of the comorbid disorders are discussed.


The SUMO Pathway in Hematomalignancies and Their Response to Therapies.
SUMO (Small Ubiquitin-related MOdifier) is a post-translational modifier of the ubiquitin family controlling the function and fate of thousands of proteins. SUMOylation is deregulated in various hematological malignancies, where it participates in both tumorigenesis and cancer cell response to therapies. This is the case for Acute Promyelocytic Leukemias (APL) where SUMOylation, and subsequent destruction, of the PML-RARα fusion oncoprotein are triggered by arsenic trioxide, which is used as front-line therapy in combination with retinoic acid to cure APL patients. A similar arsenic-induced SUMO-dependent degradation was also documented for Tax, a human T-cell lymphotropic virus type I (HTLV1) viral protein implicated in Adult T-cell Leukemogenesis. SUMOylation also participates in Acute Myeloid Leukemia (AML) response to both chemo- and differentiation therapies, in particular through its ability to regulate gene expression. In Multiple Myeloma, many enzymes of the SUMO pathway are overexpressed and their high expression correlates with lower response to melphalan-based chemotherapies. B-cell lymphomas overexpressing the c-Myc oncogene also overexpress most components of the SUMO pathway and are highly sensitive to SUMOylation inhibition. Targeting the SUMO pathway with recently discovered pharmacological inhibitors, alone or in combination with current therapies, might therefore constitute a powerful strategy to improve the treatment of these cancers.


An exploration of factors related to deviant sexual arousal among juvenile sex offenders.
To date, there has been limited literature on the measurement of sexual arousal in adolescent sex offenders. The data that exist have been somewhat mixed in terms of factors related to deviant sexual arousal in this group. The present study, with 71 adolescent sex offenders, investigates the relationship between offender and offense characteristics, including gender of victim, history of sexual abuse, history of physical abuse, race, and interactions between these factors in the prediction of physiologically measured sexual arousal to deviant and nondeviant stimulus categories. A number of variables significantly predicted sexual arousal. The most consistent predictors were gender of victim, race, the interaction of race and gender of victim, and to some extent the interaction of offender abuse history and gender of victim. Caucasian subjects tended to respond more than African American subjects did, and this has not been reported previously in the literature. The data are discussed in terms of consistency with other literature, suggesting that those juvenile offenders who target male victims and have been abused themselves may be a high risk group. Limitations of this study are also addressed.


Copper and ceruloplasmin abnormalities in Alzheimer's disease.
The idea that copper may play a role in the pathogenesis of Alzheimer's disease is gaining momentum. Serum copper and ceruloplasmin were measured by both enzymatic (eCp) and immunologic (iCp) methods in 28 patients with Alzheimer's disease and 29 age-matched controls. ''Free copper'' was determined by subtracting copper accounted for in the eCp assay from total serum copper. Percentage free copper, that is the proportion of serum copper not bound to ceruloplasmin, was significantly elevated in patients with Alzheimer's compared to controls. There was significantly more ''defective'' ceruloplasmin, which is apoceruloplamin lacking its copper, in Alzheimer's disease than in normal controls. This abnormality may precede the clinical onset of the disease and help predict risk of disease onset. Increased exposure to environmental copper (eg, the spread of copper plumbing and the use of copper in supplements) and/or defective ceruloplasmin function may play a role in the current epidemic of Alzheimer's disease.


Distribution of D-amino acids in vinegars and involvement of lactic acid bacteria in the production of D-amino acids.
Levels of free D-amino acids were compared in 11 vinegars produced from different sources or through different manufacturing processes. To analyze the D- and L-amino acids, the enantiomers were initially converted into diastereomers using pre-column derivatization with o-phthaldialdehyde plus N-acethyl-L-cysteine or N-tert-butyloxycarbonyl-L-cysteine. This was followed by separation of the resultant fluorescent isoindol derivatives on an octadecylsilyl stationary phase using ultra-performance liquid chromatography. The analyses showed that the total D-amino acid level in lactic fermented tomato vinegar was very high. Furthermore, analysis of the amino acids in tomato juice samples collected after alcoholic, lactic and acetic fermentation during the production of lactic fermented tomato vinegar showed clearly that lactic fermentation is responsible for the D-amino acids production; marked increases in D-amino acids were seen during lactic fermentation, but not during alcoholic or acetic fermentation. This suggests lactic acid bacteria have a greater ability to produce D-amino acids than yeast or acetic acid bacteria.


[Postoperative therapy of an alcoholic patient with an unusually high ethanol metabolic rate].
To avoid alcohol withdrawal syndrome (AWS) a pre-operative withdrawal, post-operative drug therapy or continued substitution of ethanol may be tried. However, substitution of ethanol needs an exact dosage and has to be controlled very carefully. The dose calculation is based on an assumed breakdown rate of 0.15 g%/1000/h, as evaluated in forensic studies. We report on a patient who throws the basis for these calculations into question. The breakdown rate of this 43-year-old man was extraordinary higher than the average turnover. This high level of the turnover rate occurred with no detectable impairment of the liver or other organs. This case demonstrates the importance of a close control of the blood alcohol level during the post-operative administration of ethanol. The individual doses of ethanol to avoid AWS has to be found individually for each patient.


Children can optimally integrate multisensory information after a short action-like mini game training.
Combining information across different sensory modalities is of critical importance for the animal's survival and a core feature of human's everyday life. In adulthood, sensory information is often integrated in a statistically optimal fashion, so that the combined estimates of two or more senses are more reliable than the best single one. Several studies have shown that young children use one sense to calibrate the others, which results in unisensory dominance and undermines their optimal multisensory integration abilities. In this study we trained children aged 4-5 years with action-like mini games, to determine whether it could improve their multisensory as well as their visuo-spatial skills. Multisensory integration abilities were assessed using a visuo-haptic size discrimination task, while visuo-spatial attention skills were investigated using a multiple object tracking task (MOT). We found that 2-weeks training were sufficient to observe both optimal multisensory integration and visuo-spatial enhancements selectively in the group trained with action-like mini games. This plastic change persisted up to 3 months, as assessed in a follow-up. Our novel findings reveal that abilities that are commonly known to emerge in late childhood can be promoted in younger children through action-like mini games and have long-lasting effects. Our data have clinical implications, in that they suggest that specific trainings could potentially help children with multisensory integration deficits.


How respiratory system mechanics may help in minimising ventilator-induced lung injury in ARDS patients.
The main supportive therapy in acute respiratory distress syndrome patients is mechanical ventilation. As with any therapy, mechanical ventilation has side-effects, and may induce lung injury (ventilator-induced lung injury (VILI)/ventilator-associated lung injury). The mechanical factors responsible for VILI are thought to be related to tidal recruitment/derecruitment of previously collapsed alveoli and/or pulmonary overdistension. The volume/pressure (V/P) curve of the respiratory system in patients as well as in animal models of acute lung injury (ALI) has a characteristic sigmoid shape, with a lower inflection point (LIP) corresponding to the pressure/end-expiratory volume required to initiate recruitment of collapsed alveoli, and an upper inflection point (UIP) corresponding to the pressure/end inspiratory volume at which alveolar overdistension occurs. "Protective" ventilatory approaches have therefore set out to minimise mechanical injury by using the V/P curve to individualise positive end-expiratory pressure (PEEP) (PEEP above the LIP) and tidal volume (by setting end-inspiratory V/P below the UIP) since a large number of experimental studies correlate P/V curves to histological and biological manifestations of VILI and two randomised trials showed that protective ventilatory strategy individually tailored to the P/V curve minimised pulmonary and systemic inflammation and decreased mortality in patients with ALI. However, despite the fact that several studies have: 1) proposed new techniques to perform pressure/volume curves at the bedside, 2) confirmed that the lower inflection point and upper inflection point correspond to computed tomography scan evidence of atelectasis and overdistension, and 3) demonstrated the ability of the pressure/volume curve to estimate alveolar recruitment with positive end-expiratory pressure, no large studies have assessed whether such measurement can be performed in all intensive care units as a monitoring tool to orient ventilator therapy. Preliminary experimental and clinical studies show that the shape of the dynamic inspiratory pressure/time profile during constant flow inflation (stress index), allows prediction of a ventilatory strategy that minimises the occurrence of ventilator-induced lung injury.


Network pharmacology combined with metabolomics to explore the mechanism for Lonicerae Japonicae flos against respiratory syncytial virus.
Respiratory Syncytial Virus (RSV) stands out as a primary contributor to lower respiratory tract infections and hospitalizations, particularly in infants. Lonicerae japonicae flos (LJF), a traditional Chinese medicine renowned for its efficacy against various viral infections, including RSV, has been widely employed. Despite its common use, the precise therapeutic mechanism of LJF against RSV remains elusive. This study aimed to investigate the underlying mechanism of LJF against RSV through network pharmacology and metabolomics. In this study, based on network pharmacology, potential targets related to LJF and RSV were obtained from PubChem and Swiss Target Prediction. The core targets and pathways were established and verified by enrichment analysis and molecular docking. The anti-RSV efficacy of LJF was determined by in vitro experiments. Additionally, metabolomics analysis was integrated, allowing for the identification of differential metabolites and their correlation with targets following LJF treatment in the context of RSV infection. A total of 23 active ingredients and 780 targets were obtained, of which 102 targets were associated with LJF anti-RSV. The construction of the corresponding Protein-Protein Interaction (PPI) network unveiled potential core targets, including STAT3, TNF, and AKT1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that LJF's anti-RSV effects primarily involve key pathways such as the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and FoxO signaling pathway. Molecular docking showed that ZINC03978781, 4,5'-Retro-.beta.,.beta.-Carotene -3,3'-dione, 4',5'-didehydro and 7-epi-Vogeloside had better binding ability. The cellular assay showed that the therapeutic index of LJF against RSV was 4.79. Furthermore, 18 metabolites were screened as potential biomarkers of LJF against RSV, and these metabolites were mainly involved in the pathways of purine metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and other related pathways. The intergration of network pharmacology and metabolomics can clarify the active targets and related pathways of LJF against RSV, which could provide a valuable reference for further research and clinical application of LJF.


Syntheses, crystal structures, adsorption properties and visible photocatalytic activities of highly stable Pb-based coordination polymers constructed by 2-(2-carboxyphenyl)imidazo(4,5-f)-(1,10)phenanthroline and bridging linkers.
Five highly stable coordination polymers assembled by 2-(2-carboxyphenyl)imidazo(4,5-f)-(1,10)phenanthroline (2-HNCP) and different aromatic carboxylic acid ligands, namely, [Pb(2-NCP)(L1)]n (1), [Pb2(2-NCP)2(L2)]n·2nH2O (2), [Pb2(2-NCP)2(L2)]n (3), [Pb(2-NCP)(L3)0.5]n (4) and [Pb2(2-NCP)2(L4)]n (5), where HL1 = pyridine-4-carboxylic acid, H2L2 = 2-amino-1,4-benzenedicarboxylic acid, H2L3 = 1,4-benzenedicarboxylic acid and H2L4 = 2-hydroxy-1,4-benzenedicarboxylic acid, have been synthesized under hydrothermal conditions. Their structures have been determined by single crystal X-ray diffraction analyses and further characterized by elemental analyses and infrared spectroscopy. In 1, adjacent ladder-like chains are extended into a three-dimensional (3D) supramolecular architecture by π-π interactions. In 2, the neighboring layers are interconnected by π-π interactions to afford a 3D supramolecular architecture. 3-5 exhibit similar 3D frameworks with a Schläfli symbol of 412·63 topologies. The different auxiliary ligands and the pH value of the reaction system were discussed in regard to the formation of different structures. In addition, these five complexes present high thermal stabilities, the preferential adsorption of CO2 over N2 and excellent photocatalytic activities for dye degradation under visible light irradiation.


Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder.
Disrupted sleep is a major feature in numerous clinical disorders and is related to decrements in affective memory processing. The prevalence of sleep disruption in post-traumatic stress disorder (PTSD) is suggested to be a key feature that exacerbates the impaired ability to recall extinction memories during experimental fear conditioning. We hypothesized that an intervention employing blue-wavelength light therapy (BLT) to regulate sleep and stabilize circadian rhythms in patients with PTSD (i.e., via regulated morning exposure) would be associated with PTSD symptom improvement, decreased sleep-related complaints, as well as improved consolidation and retention of extinction memories relative to a fear conditioning/extinction paradigm. Eighty-two individuals with PTSD underwent a well-validated fear conditioning/extinction protocol with subsequent assignment to receive morning BLUE (BLT) or placebo AMBER (ALT) light therapy daily for 30-min over 6-weeks. Participants returned after the intervention for post-treatment extinction recall, comprised of exposure to the previously conditioned stimuli, with the difference in skin conductance response between the "extinguished" and the "never-extinguished" stimuli at follow-up. Participants also viewed previously conditioned stimuli in a novel context during a functional magnetic resonance imaging (fMRI) scan. BLUE light therapy was associated with improvements relative to correlated decreases between PTSD symptoms and sleep-related complaints. Participants receiving BLT also sustained retention of the extinction memory, while those in the placebo amber light treatment group showed impairment, characterized by the restoration of the extinguished fear response after 6-weeks. Participants in the ALT also demonstrated greater reactivity in the left insula when viewing the previously extinguished fear-conditioned stimuli in a novel context. Daily BLUE-wavelength morning light exposure was associated with greater retention of extinction learning in patients with PTSD when compared to ALT, as supported by both autonomic and neurobiological reactivity. We speculate that improved sleep facilitated by a stabilized circadian rhythm, after fear-learning, led to greater consolidation of the fear extinction memory, decreased PTSD symptom presentation, and associated decreases in sleep-related complaints. Prominent exposure treatments for PTSD incorporate principles of fear extinction, and our findings suggest that blue light treatment may facilitate treatment gains by promoting the consolidation of extinction memories via improved sleep.


Inhibition of glioblastoma cell invasion by hsa-miR-145-5p and hsa-miR-31-5p co-overexpression in human mesenchymal stem cells.
Human bone marrow–derived mesenchymal stem cells (hMSCs) show tropism for brain tumors and may be a useful vehicle for drug or gene delivery to malignant gliomas. Recently, some microRNAs (miRNAs) have been shown to suppress the invasiveness of malignant gliomas. To test their potential to become vehicles for the delivery of miRNA to malignant gliomas, hMSCs were engineered so that hMSC secretion of miRNAs that inhibit glioma cell invasion was enabled without altering the hMSC tropism for glioma cells. In coculture, hMSCs cotransfected with hsa-miR-145-5p and -31-5p miRNAs showed markedly reduced invasion by U87 glioma cells in a contact-dependent manner both in vitro and ex vivo, with invasion of hMSCs cotransfected with these 2 miRNAs by the U87 cells reduced to 60.7% compared with control cells. According to a Matrigel invasion assay, the tropism of the hMSCs for U87 cells was not affected. In glioma cell lines U251 and LN229, hMSCs exhibited tropism in vivo, and invasion of hMSCs cotransfected with hsa-miR-145-5p and -31-5p was also significantly less than that of control cells. When U87 cells were coimplanted into the striatum of organotypic rat brain slices with hMSCs cotransfected with hsa-miR-145 and -31-5p, the relative invasive area decreased by 37.1%; interestingly, these U87 cells showed a change to a rounded morphology that was apparent at the invasion front. Whole-genome microarray analysis of the expression levels of 58,341 genes revealed that the co-overexpression of hsa-miR-145-5p and -31-5p downregulated FSCN1 expression in U87 cells. This study demonstrates that miRNA overexpression in hMSCs can alter the function of glioma cells via contact-dependent transfer. Co-overexpression of multiple miRNAs may be a useful and novel therapeutic strategy. The study results suggest that hMSCs can be applied as a delivery vehicle for miRNAs.


Advancing type 2 diabetes therapy with iGlarLixi in older people: Pooled analysis of four randomized controlled trials.
To assess the efficacy and safety of iGlarLixi in older people (≥65 years) with type 2 diabetes (T2D) advancing or switching from oral agents, a glucagon-like peptide-1 receptor agonist (GLP-1RA), or basal insulin. The data of participants aged <65 years and ≥65 years from four LixiLan trials (LixiLan-O, LixiLan-G, LixiLan-L, SoliMix) were evaluated over 26 or 30 weeks. Participants aged <65/≥65 years (n = 1039/n = 497) had a mean baseline body mass index of 31.4 and 30.7 kg/m2 and glycated haemoglobin (HbA1c) concentration of 66 mmol/mol (8.2%) and 65 mmol/mol (8.1%), respectively. Least squares mean HbA1c change from baseline to end of treatment (EOT) was -14.32 mmol/mol (-1.31%) (95% confidence interval [CI] -14.97, -13.77 [-1.37%, -1.26%]) for those aged <65 years and -13.66 mmol/mol (-1.25%) (95% CI -14.54, -12.79 [-1.33%, -1.17%]) for those aged ≥65 years. At EOT, achievement of HbA1c targets was similar between the group aged <65 years and the group aged ≥65 years: <53 mmol/mol (<7%) (59.0% and 56.5%, respectively), <59 mmol/mol (<7.5%) (75.5% and 73.0%, respectively) and <64 mmol/mol (<8%) (83.8% and 84.1%, respectively). The incidence and event rate of American Diabetes Association Level 1 hypoglycaemia during the studies were also comparable between the two groups: 26.7% and 28.2% and 1.7 and 2.1 events per patient-year for the group aged <65 years and the group aged ≥65 years, respectively. A clinically relevant reduction in HbA1c (>1% from baseline for HbA1c ≥64 mmol/mol [≥8%] or ≥0.5% from baseline for HbA1c <64 mmol/mol [<8%]) without hypoglycaemia was attained by 50.0% and 47.6% of participants aged <65 years and ≥65 years, respectively. Adverse events were similar between the two age groups. iGlarLixi is a simple, well-tolerated, once-daily alternative for treatment advancement in older people with T2D that provides significant improvements in glycaemic control without increasing hypoglycaemia risk, thus reducing the treatment burden.


Salt reduction and hypertension in China: a concise state-of-the-art review.
Hypertension (HTN) and its cardiovascular complications such as stroke and heart failure are a serious public health problem around the world. A growing number of studies confirm that salt plays an important role in the development of HTN. Increasing intake of salt leads to abnormal transport of sodium ions at the cellular level with activation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Studies have shown that salt restriction can reduce blood pressure (BP) in patients with HTN, especially salt-sensitive HTN. Public health interventions to reduce salt intake, with the goal of decreasing adverse outcomes have been launched in numerous countries. In this review we will summarize the epidemiology of cardiovascular diseases and their risk factors, the relationship between salt and HTN, the effect of salt restriction on HTN and the current situation of prevention and treatment of HTN by salt reduction in China.


Democratising "Microscopi": a 3D printed automated XYZT fluorescence imaging system for teaching, outreach and fieldwork.
Commercial fluorescence microscope stands and fully automated XYZt fluorescence imaging systems are generally beyond the limited budgets available for teaching and outreach. We have addressed this problem by developing "Microscopi", an accessible, affordable, DIY automated imaging system that is built from 3D printed and commodity off-the-shelf hardware, including electro-mechanical, computer and optical components. Our design features automated sample navigation and image capture with a simple web-based graphical user interface, accessible with a tablet or other mobile device. The light path can easily be switched between different imaging modalities. The open source Python-based control software allows the hardware to be driven as an integrated imaging system. Furthermore, the microscope is fully customisable, which also enhances its value as a learning tool. Here, we describe the basic design and demonstrate imaging performance for a range of easily sourced specimens.


Neoliberal technocracy: explaining how and why the US Food and Drug Administration has championed pharmacogenomics.
By 2004 the FDA had emerged as a champion of pharmacogenomics as an exemplar for novel approaches to drug development. This was made clear in 2004 when the agency released a wide-ranging report which positioned pharmacogenomics at the heart of a broader regulatory reform agenda. The Critical Path initiative addressed declining productivity of drug development by suggesting that the problem was a mismatch between the rapid pace of discovery in post-genomic biomedicine and the antiquated development process for new drugs. Framing their work in this context, FDA officials reconceptualised their role in the innovation process, in what was the first programmatic statement of a shift from a strictly gate-keeping role to a more collaborative or facilitative role as enablers of innovation. This paper situates the FDA's emergence as a champion of pharmacogenomics in the broader politics of pharmaceutical regulation in the USA. In making a contribution to the pharmaceuticalisation literature this paper will draw on the work of John Abraham who has argued that one of the primary drivers of pharmaceuticalisation has been "deregulatory state policies" and on Williams and colleagues who have argued that the changing relationship between regulatory agencies and the pharmaceutical industry is an important dimension of pharmaceuticalisation. This paper links this to the promotion of pharmaceutical futures such as pharmacogenomics and explores how this shift is also closely related to the trend towards a risk management approach to pharmaceutical regulation. The role of Bush appointees in the development and promotion of the Critical Path agenda is also examined.


Reaction of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) Cu(II) with Ehrlich cells. Binding of copper to metallothionein and its relationship to zinc metabolism and cell proliferation.
The copper complex of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) or CuKTS is reduced and dissociated upon reaction with Ehrlich cells. Titration of the cells with the complex leads to the specific binding of copper to metallothionein with 1 to 1 displacement of its complement of zinc. Under conditions of complete titration of metallothionein, 1.25-2.5 nmol CuKTS/10(7) cells, cellular DNA synthesis is rapidly inhibited but no long term effects on cell proliferation are observed. The kinetics of redistribution of Cu and Zn in Ehrlich cells in culture and in animals were studied after pulse reaction of CuKTS with cells. After exposure of cells to the noncytotoxic concentration of 2.5 nmol of CuKTS/10(7) cells, nonmetallothionein bound copper is lost rapidly from the cells, after which copper in metallothionein decays. New zinc metallothionein is made as soon as exposed cells are placed in culture. New synthesis stops when the level of zinc in metallothionein reaches control levels. A second pulse treatment of cells with CuKTS to displace zinc from metallothionein again stimulates new synthesis of the protein to restore its normal concentration. The kinetics of metal metabolism in Ehrlich cells exposed to 5.5 nmol of CuKTS/10(7) cells, which inhibits cell proliferation, are qualitatively similar except there is a pronounced lag before new zinc metallothionein is synthesized. The Ehrlich ascites tumor in mice responds to CuKTS similarly to cells in culture. It is also shown that cultured Ehrlich cells do not make extra zinc metallothionein in the presence of high levels of ZnCl2, and fail to accumulate copper in the presence of large concentrations of CuCl2.


The use of Erbium:YAG laser for caries removal in paediatric patients following Minimally Invasive Dentistry concepts.
The Er:YAG laser has proven to be effective and efficient in dental hard tissue ablation. The Minimally Invasive Dentistry (MID) approach in caries removal is to stop the disease process and to restore lost tooth structure and function, maximizing the health potential of the tooth. One of the most important concepts of the MID is to preserve as much as possible the dental tissue and this approach is even more important in primary dentition where the dimensions of the crown are smaller and the dimension of the pulp chamber is bigger in relationship to the crown. After treating 30 children's teeth (primary molars and first permanent molars) with the Er:YAG laser, we come to conclusion that laser treatment possesses the requirements of Minimal Invasive Dentistry: the possibility to ablate small area of infected layer guarantees maximum conservation of the tooth structure; using the antibacterial property of the Er:YAG laser we can decontaminate the affected layer that retains its remineralising potential; the lack of smear layer after vaporization with laser assures a better retention of the composite resin to the dentine; preparing the enamel surface with laser before etching gives a better marginal seal of the composite restoration.


Nonsurgical management of advanced hepatocellular carcinoma: a clinical practice guideline.
Practice guidelines based on a systematic review of the literature regarding the nonsurgical management of hepatocellular carcinoma (hcc) in North America are lacking. Resection and transplantation are the foundations for cure of hcc; however, most patients are diagnosed at an advanced stage, precluding those curative treatments. A number of local or regional therapies are used and are followed by systemic therapy for advanced or progressive disease. Other treatments are available, but their efficacy, compared with those standards, is not well known. First, systematic review questions were developed. Literature searches of the medline, embase, and Cochrane library databases (January 2000 to July 2018 or January 2005 to July 2018 depending on the question) were conducted; in addition, abstracts from the 2018 annual meeting of the American Society of Clinical Oncology were reviewed. A practice guideline was drafted that was then scrutinized by internal and external reviewers. Seventy-seven studies were included in the guideline: no guidelines, two systematic reviews, and seventy-five primary studies published in full (including one pooled analysis). Five recommendations were developed. There is no evidence for or against the use of local or regional interventions other than transarterial chemoembolization for the treatment of intermediate- or advanced-stage hcc. Furthermore, there is no evidence to support the addition of sorafenib to any local or regional therapy. Sorafenib or lenvatinib are recommended for first-line systemic treatment of intermediate-stage hcc. Regorafenib or cabozantinib provide survival benefits when given as second-line treatment. Antiviral treatment is recommended in individuals with advanced hcc who are positive for the hepatitis B surface antigen.


Morphology of molecular soy protein fractions in binary composite gels.
We investigate the structural properties of gels of binary mixtures of the three major soy protein fractions: 11S, 7S, and 2S. Gels are formed at 25 degrees C in the presence of glucono-delta-lactone and studied using a combination of dynamic rheology and scanning electron microscopy. The theological data was then modeled using a blending-law approach that yields insights into the solvent distribution between the gelled protein fractions and first-order reaction kinetics that follow the gelation process of the single fractions and their mixtures. Gelled mixtures of 11S and 7S yielded enhanced network strength with increasing solid content; in these gels, 50% more solvent partitioned into the 11S phase as compared to that in the 7S phase. In contrast, the addition of small-molecular-weight counterpart 2S to either 11S or 7S results in a catastrophic drop in the values of the overall strength of the mixture. The unexpected phase behavior has been rationalized on the basis of the high water-holding capacity of 2S; 450% more solvent partitions preferentially into the 2S phase as compared to that in the 11S phase. As the concentration of 2S is increased relative to that of 11S or 7S, it becomes the dominant phase and entraps the polymeric segments of 11S (or 7S), thus preventing them from becoming the structural knots of the gel. In addition to the solvent distribution in the gel, the rates of gelation differ markedly between 11S and 2S (with the 11S rate of gelation being up to 2 orders of magnitude greater); a fixed 11S concentration, the rate of gelation decreases with increasing amounts of 2S, further confirming that the latter essentially becomes the dominant phase in the composite gel.


Biophysical and structural characterization of a multifunctional viral genome packaging motor.
The large dsDNA viruses replicate their DNA as concatemers consisting of multiple covalently linked genomes. Genome packaging is catalyzed by a terminase enzyme that excises individual genomes from concatemers and packages them into preassembled procapsids. These disparate tasks are catalyzed by terminase alternating between two distinct states-a stable nuclease that excises individual genomes and a dynamic motor that translocates DNA into the procapsid. It was proposed that bacteriophage λ terminase assembles as an anti-parallel dimer-of-dimers nuclease complex at the packaging initiation site. In contrast, all characterized packaging motors are composed of five terminase subunits bound to the procapsid in a parallel orientation. Here, we describe biophysical and structural characterization of the λ holoenzyme complex assembled in solution. Analytical ultracentrifugation, small angle X-ray scattering, and native mass spectrometry indicate that 5 subunits assemble a cone-shaped terminase complex. Classification of cryoEM images reveals starfish-like rings with skewed pentameric symmetry and one special subunit. We propose a model wherein nuclease domains of two subunits alternate between a dimeric head-to-head arrangement for genome maturation and a fully parallel arrangement during genome packaging. Given that genome packaging is strongly conserved in both prokaryotic and eukaryotic viruses, the results have broad biological implications.


Cooking outdoors or with cleaner fuels does not increase malarial risk in children under 5 years: a cross-sectional study of 17 sub-Saharan African countries.
Smoke from solid biomass cooking is often stated to reduce household mosquito levels and, therefore, malarial transmission. However, household air pollution (HAP) from solid biomass cooking is estimated to be responsible for 1.67 times more deaths in children aged under 5 years compared to malaria globally. This cross-sectional study investigates the association between malaria and (i) cleaner fuel usage; (ii) wood compared to charcoal fuel; and, (iii) household cooking location, among children aged under 5 years in sub-Saharan Africa (SSA). Population-based data was obtained from Demographic and Health Surveys (DHS) for 85,263 children within 17 malaria-endemic sub-Saharan countries who were who were tested for malaria with a malarial rapid diagnostic test (RDT) or microscopy. To assess the independent association between malarial diagnosis (positive, negative), fuel type and cooking location (outdoor, indoor, attached to house), multivariable logistic regression was used, controlling for individual, household and contextual confounding factors. Household use of solid biomass fuels and kerosene cooking fuels was associated with a 57% increase in the odds ratio of malarial infection after adjusting for confounding factors (RDT adjusted odds ratio (AOR):1.57 [1.30-1.91]; Microscopy AOR: 1.58 [1.23-2.04]) compared to cooking with cleaner fuels. A similar effect was observed when comparing wood to charcoal among solid biomass fuel users (RDT AOR: 1.77 [1.54-2.04]; Microscopy AOR: 1.21 [1.08-1.37]). Cooking in a separate building was associated with a 26% reduction in the odds of malarial infection (RDT AOR: 0.74 [0.66-0.83]; Microscopy AOR: 0.75 [0.67-0.84]) compared to indoor cooking; however no association was observed with outdoor cooking. Similar effects were observed within a sub-analysis of malarial mesoendemic areas only. Cleaner fuels and outdoor cooking practices associated with reduced smoke exposure were not observed to have an adverse effect upon malarial infection among children under 5 years in SSA. Further mixed-methods research will be required to further strengthen the evidence base concerning this risk paradigm and to support appropriate public health messaging in this context.


The Inter-Rater and Intra-Rater Reliability of the Actual Aquatic Skills Test (AAST) for Assessing Young Children's Motor Competence in the Water.
As children's actual aquatic skills are important for the prevention of drowning as well as their engagement in lifelong aquatic physical activity, researchers and practitioners should be able to assess this vital concept accurately and reliably. Therefore, this study aimed to investigate the inter-rater and intra-rater reliability of the Actual Aquatic Skills Test (AAST), consisting of 17 different test items for the assessment of young children's motor competence in the water. Six raters received a training and evaluation session on scoring the AAST, after which five of them assessed four test videos (of various children (n = 38) performing the test items) twice, with one to two weeks in between (i.e., test and re-test). Inter-rater and intra-rater reliability were determined per test video and for the different AAST test items across videos using Gwet's Agreement Coefficient 2 (Gwet's AC2). The Gwet's AC2 for inter-rater reliability at the test varied from 0.414 to 1.000, indicating a moderate to perfect agreement between raters. For intra-rater reliability, it ranged from 0.628 to 1.000, demonstrating a good to perfect agreement between test and re-test scoring. In conclusion, the AAST is a promising tool to reliably assess young children's actual aquatic skills in an indoor swimming pool.


Self versus environment motion in postural control.
To stabilize our position in space we use visual information as well as non-visual physical motion cues. However, visual cues can be ambiguous: visually perceived motion may be caused by self-movement, movement of the environment, or both. The nervous system must combine the ambiguous visual cues with noisy physical motion cues to resolve this ambiguity and control our body posture. Here we have developed a Bayesian model that formalizes how the nervous system could solve this problem. In this model, the nervous system combines the sensory cues to estimate the movement of the body. We analytically demonstrate that, as long as visual stimulation is fast in comparison to the uncertainty in our perception of body movement, the optimal strategy is to weight visually perceived movement velocities proportional to a power law. We find that this model accounts for the nonlinear influence of experimentally induced visual motion on human postural behavior both in our data and in previously published results.


Women's preferences for inpatient and outpatient priming for labour induction: a discrete choice experiment.
In many countries a high proportion of births begin as induced labours. Induction can be lengthy if cervical priming is required prior to induction. This usually occurs as an inpatient, however, an alternative is to allow women to go home after satisfactory fetal monitoring. The aim of this study was to assess the preferences of women for cervical priming for induction of labour in an outpatient or inpatient setting. A discrete choice experiment (DCE) was conducted alongside a randomised trial of inpatient and outpatient cervical priming (the OPRA trial) in two maternity hospitals in South Australia. 362 participants were included, and women's preferences for cervical priming for induction of labour were assessed. Women were willing to accept an extra 1.4 trips to hospital (2.4 trips total) and a total travel time of 73.3 minutes to be able to return to their own home while waiting for the priming to work. For enhanced inpatient services, women were willing to accept a total travel time of 54.7 minutes to have a private room with private bathroom while waiting for the priming to work. The overall benefit score for outpatient priming was 3.63, 3.59 for enhanced inpatient care and 2.89 for basic inpatient care, suggesting slightly greater preferences for outpatient priming. Preferences for outpatient priming increased when women could return to their own home (compared to other offsite accommodation), and decreased with more trips to hospital and longer travel time. Our results suggest that outpatient priming was slightly more preferred than either enhanced inpatient priming or basic care; these results should be confirmed in different clinical settings. There may be merit in providing women information about both options in the future, as preferences varied according to the characteristics of the services on offer and the sociodemographic background of the woman.


Overview of Next-Generation Sequencing Technologies.
High throughput DNA sequencing methodology (next generation sequencing; NGS) has rapidly evolved over the past 15 years and new methods are continually being commercialized. As the technology develops, so do increases in the number of corresponding applications for basic and applied science. The purpose of this review is to provide a compendium of NGS methodologies and associated applications. Each brief discussion is followed by web links to the manufacturer and/or web-based visualizations. Keyword searches, such as with Google, may also provide helpful internet links and information. © 2018 by John Wiley & Sons, Inc.


Drowning related out-of-hospital cardiac arrests: characteristics and outcomes.
There are few studies on drowning-related out-of-hospital cardiac arrest (OHCA) in which patients are followed from the scene through to hospital discharge. This study aims to describe this population and their outcomes in the state of Victoria (Australia). The Victorian Ambulance Cardiac Arrest Registry was searched for all cases of OHCA with a precipitating event of drowning attended by emergency medical services (EMS) between October 1999 and December 2011. EMS attended 336 drowning-related OHCA during the study period. Cases frequently occurred in summer (45%) and the majority of patients were male (70%) and adult (77%). EMS resuscitation was attempted on 154 (46%) patients. Of these patients, 41 (27%) survived to hospital arrival and 12 (8%) survived to hospital discharge (5 adults [6%] and 7 [12%] children). Few patients were found in a shockable rhythm (6%), with the majority presenting in asystole (79%) or pulse-less electrical activity (13%). An initial shockable rhythm was found to positively predict survival (AOR 48.70, 95% CI: 3.80-624.86) while increased EMS response time (AOR 0.73, 95% CI: 0.54-0.98) and salt water drowning (AOR 0.69, 95% CI: 0.01-0.84) were found to negatively predict survival. Rates of survival in OHCA caused by drowning are comparable to other OHCA causes. Patients were more likely to survive if they did not drown in salt water, had a quick EMS response and they were found in a shockable rhythm. Prevention efforts and reducing EMS response time are likely to improve survival of drowning patients.


Joint Optimization of Input Spike Rate and Receiver Decision Threshold to Maximize Achievable Bit Rate of Neuro-Spike Communication Channel.
Nano-networks employ novel nano-scale communication techniques. These techniques are inspired by biological systems. Neuro-spike communication is an example of this communication paradigm. A new example of nano-networks is the artificial neural system where nano-machines are linked to neurons to treat the neurodegenerative diseases. In these networks, nano-machines are used to replace the damaged segments of the nervous system and they behave exactly like biological entities. In this paper, by considering a point-to-point model for the neuro-spike communication which contains several sources of randomness such as the axonal noise, random amplitude, and the synaptic noise, we analyze the achievable bit rate of the neuro-spike communication channel. This model can be divided into two main parts. The first part is the axonal pathway and the second one encompasses the synaptic transmission and the spike generation. First, we focus on the axonal pathway and we model this part as a binary channel through defining the axonal shot noise probability. Next, we investigate the synaptic transmission part to model this part as a binary channel. Then, we consider the neuro-spike communication channel as two cascaded binary channels to obtain its error probability and achievable bit rate. To enhance the achievable bit rate of the neuro-spike communication, we design an optimum spike detection receiver and also we propose an optimum input spike rate. We derive closed-form descriptions for the decision threshold of the optimum receiver and the optimum input spike rate. Since they are coupled, we propose a recursive scheme to derive their optimum values. Finally, simulation results are used to investigate the impact of the axonal noise, the synaptic noise, and modifications of the spikes' shape due to propagation along the axon on the achievable bit rate of the neuro-spike communication channel.


A population-based cohort study of ambulatory care service utilization among older adults.
Age-related effects on ambulatory care service utilization are not well understood. We aim to measure the utilization patterns of ambulatory health care services (i.e. family physician visits, specialist physician visits and emergency room visits) in the late life course (65 years and older). A population-based retrospective cohort study was conducted for the period 1 April 2005 to 31 March 2006. All Ontario, Canada, residents aged 65+ and eligible for government health insurance were included in the analysis. This population-based cohort study demonstrates considerable increase in utilization rates and variability of ambulatory services as age increases. Variations in utilization were observed by gender as overall women were more likely to consult a family physician, and men more likely to visit specialists and the emergency room. A small group of high users, constituting 5.5% of the total population, accounted for 18.7% of total ambulatory visits. Finally, we report socio-economic status (SES) based disparity for specialist services in which high users were more likely to have higher SES. There is increasing utilization and variability in ambulatory service utilization with increase in age. Further research is required to explain the gender and SES differences reported in this study.


Studies on the hormonal regulation of rat liver alcohol dehydrogenase.
These observations have extended and clarified the earlier reports on the effects of thyroid hormone and androgens on liver ADH activity. Thyroid hormone exerts a direct effect on ADH activity, but is not required for the expression of the enzyme. At present, it has not been possible to demonstrate a physiological role for thyroid hormone in determining the developmental and sexual variation in ADH activity. Androgens probably modulate the pattern of secretion of GH, which then determines the level of ADH expression in the liver. We do not understand how GH exerts an effect on liver protein expression in this or other systems. This effect of growth hormone is probably the major controlling factor in the sexual variation in ADH activity. Since the pattern of GH secretion can be influenced by perinatal factors and by stress, it will be of great interest to see if the expression of any of the human ADH isoenzymes is also modified by the pattern of GH secretion.


Epidemiology based etiological study of pediatric cataract in western India.
Cataract is responsible for about 10% blindness among children in India. Etiology of cataract is not well defined especially for childhood cataracts and epidemiological data for Indian population is not available in details. This study was performed to survey the causes of childhood cataracts and to identify the preventable factors in four western states of India. The present study is a hospital-based, prospective study on 172 consecutive pediatric cataract patients. Type of cataract was determined using slit-lamp bio-microscopy or operation microscope after mild general anesthesia especially on very young babies. Other anomalies of eye were determined using appropriate ophthalmic instruments. Parents of the patients were interviewed in their native language using a standardized questionnaire. Biochemical and microbiological tests such as for rubella, reducing sugar and blood glucose were also performed. Out of 172 children, 88.4% had non-traumatic cataract and 11.6% had traumatic cataracts. Among non-traumatic cataracts, 7.2% were hereditary, 4.6% were due to congenital rubella syndrome, 15.1% were secondary and 73.0% were undetermined. In the group of undetermined cases, during pregnancy 67% of the mother had history of illness, and 22% had taken medications during pregnancy. Our study shows that nearly 12% of non-traumatic cataract is due to potentially preventable causes. Health education of women to childbearing age and school children can decrease incidence of pediatric cataracts.


Microstructural white matter changes in cognitively normal individuals at risk of amnestic MCI.
Since Alzheimer disease (AD) is a slowly progressive disorder and its pathologic features are likely to be present for many years before symptoms become manifest, we investigated whether microstructural white matter changes similar to those identified in patients with AD can be detected in cognitively normal individuals without dementia destined to develop amnestic mild cognitive impairment (aMCI). We studied 193 cognitively normal individuals, of whom 173 remained cognitively stable (CN-stable) and 20 were diagnosed with aMCI (CN-aMCI converter) 2 years later. Structural MRI and diffusion tensor imaging were acquired at baseline to assess gray matter atrophy and microstructural white matter changes, respectively. At baseline, compared with CN-stable, CN-aMCI converters had substantial reductions in white matter integrity in the precuneus, parahippocampal cingulum, parahippocampal gyrus white matter, and fornix. Other diffuse white matter changes were observed in the frontal, parietal, and subcortical regions, whereas gray matter structures were relatively intact. The fractional anisotropy (FA) values of the precuneus were found to be a predictor of conversion from cognitively normal to aMCI. In addition, the FA values of the left parahippocampal gyrus white matter were predictive of subsequent episodic memory decline. Microstructural white matter changes are present in cognitively normal individuals in the pre-aMCI stage, and may serve as a potential imaging marker of early AD-related brain changes.


A multi-view assisted registration network for MRI registration pre- and post-therapy.
Image registration of magnetic resonance imaging (MRI) pre- and post-therapy is an important part of evaluating the effect of therapy in tumor patients. The accuracy of evaluation results heavily relies on the alignment of the MRI image after registration. Although recent advancements have been made in medical image registration, applying these methods to MRI registration pre- and post-therapy remains challenging. Existing methods typically utilize single-view data for registration. However, when applied to MRI data where some slices are clear while others are blurred, these methods can be misled by erroneous spatial information in the blurred regions, leading to poor registration outcomes. To mitigate the interference caused by erroneous spatial information in single-view data, this paper proposes a multi-stream fusion-assisted registration network that incorporates different-view MRIs of the same patient at the same site. Additionally, a cross-attention guided fusion module is designed within the network to effectively utilize accurate spatial information from multi-view data. The proposed approach was evaluated on clinical data, and the experimental results demonstrated that incorporating multiple view data as auxiliary information significantly enhances the accuracy of MRI image registration before and after radiotherapy.


Chronic administration of the nitroxyl donor 1-nitrosocyclo hexyl acetate limits left ventricular diastolic dysfunction in a mouse model of diabetes mellitus in vivo.
Nitroxyl (HNO), a redox congener of nitric oxide (NO·), is a novel regulator of cardiovascular function, combining concomitant positive inotropic, lusitropic, and vasodilator properties. Moreover, HNO exhibits myocardial antihypertrophic and superoxide-suppressing actions. Despite these favorable actions, the impact of chronic HNO administration has yet to be reported in the context of cardiomyopathy. Diabetic cardiomyopathy is characterized by early diastolic dysfunction and adverse left ventricular (LV) structural remodeling, with LV superoxide generation playing a major causal role. We tested the hypothesis that the HNO donor 1-nitrosocyclohexylacetate (1-NCA) limits cardiomyocyte hypertrophy and LV diastolic dysfunction in a mouse model of diabetes mellitus in vivo. Diabetes mellitus was induced in male FVB/N mice using streptozotocin. After 4 weeks, diabetic and nondiabetic mice were allocated to 1-NCA therapy (83 mg/kg per day IP) or vehicle and followed up for a further 4 weeks. Diabetes mellitus-induced LV diastolic dysfunction was evident on echocardiography-derived E and A wave velocities, E:A ratio, deceleration, and isovolumic relaxation times; LV systolic function was preserved. Increased LV cardiomyocyte size, hypertrophic and profibrotic gene expression, and upregulation of LV superoxide were also evident. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as an HNO donor was demonstrated by sensitivity of acute 1-NCA to l-cysteine but not to hydroxocobalamin in the normal rat heart ex vivo. Our studies provide the first evidence that HNO donors may represent a promising strategy for treatment of diabetic cardiomyopathy and implies therapeutic efficacy in settings of chronic heart failure.


Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell.
There is increasing interest in deep brain stimulation (DBS) for the treatment of addiction. Initial testing must be conducted in animals, and the alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism. This study is composed of 2 experiments designed to examine the effects of 1) pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on the consumption of alcohol by P rats. In the first experiment, the effects of reversible inactivation of the AcbSh were investigated by administering intracranial injections of γ-aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (8-10 rats/group), after which the animals were placed in operant chambers containing 2 levers--one used to administer water and the other to administer 15% EtOH--to examine the acquisition and maintenance of oral EtOH self-administration. In the second experiment, a DBS electrode was placed in each P rat's left AcbSh. The animals then received 100 or 200 μA (3-4 rats/group) of DBS to examine the effect on daily consumption of oral EtOH in a free-access paradigm. In the first experiment, pharmacological silencing of the AcbSh with GABA agonists did not decrease the acquisition of EtOH drinking behavior but did reduce EtOH consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 μA of DBS consistently reduced EtOH intake by 47% in chronically drinking rats. The amount of EtOH consumption returned to baseline levels following termination of therapy in both experiments. Pharmacological silencing and DBS of the AcbSh reduced EtOH intake after chronic EtOH use had been established in rodents. The AcbSh is a neuroanatomical substrate for the reinforcing effects of alcohol and may be a target for surgical intervention in cases of alcoholism.


Force control in the absence of visual and tactile feedback.
Motor control tasks like stance or object handling require sensory feedback from proprioception, vision and touch. The distinction between tactile and proprioceptive sensors is not frequently made in dynamic motor control tasks, and if so, mostly based on signal latency. We previously found that force control tasks entail more compliant behavior than a passive, relaxed condition and by neuromuscular modeling we were able to attribute this to adaptations in proprioceptive force feedback from Golgi tendon organs. This required the assumption that both tactile and visual feedback are too slow to explain the measured adaptations in face of unpredictable force perturbations. Although this assumption was shown to hold using model simulations, so far no experimental data is available to validate it. Here we applied a systematic approach using continuous perturbations and engineering analyses to provide experimental evidence for the hypothesis that motor control adaptation in force control tasks can be achieved using proprioceptive feedback only. Varying task instruction resulted in substantial adaptations in neuromuscular behavior, which persisted after eliminating visual and/or tactile feedback by a nerve block of the nervus plantaris medialis. It is concluded that proprioception adapts dynamic human ankle motor control even in the absence of visual and tactile feedback.


Correlates of maternal depression, anxiety and functioning across an urban-rural gradient in northern Ecuador.
Maternal depression remains under characterised in many low- and middle-income countries, especially in rural settings. We aimed to describe maternal depression and anxiety symptoms in rural and urban communities in northern Ecuador and to identify socioeconomic and demographic factors associated with these symptoms. Data from 508 mothers participating in a longitudinal cohort study were included. Depression and anxiety symptoms were assessed using the Hopkins Symptom Checklist (HSCL-25), and maternal psychological functioning was assessed using a checklist of daily activities. Tobit regression models were used to examine associations with sociodemographic variables and urbanicity. The median HSCL-25 score was 1.2 (IQR: 0.4) and 14% of women scored above the threshold for clinically relevant symptoms. Rural women reported similar food insecurity, less education, younger age of first pregnancy, and lower socio-economic status compared to their urban counterparts. After adjusting for these factors, rural women reported lower HSCL-25 scores compared to women lin urban areas (β = -0.48, 95%CI:0.65, -0.31). Rural residence was also associated with lower depression and anxiety HSCL-25 sub-scale scores, and similar levels of maternal functioning, compared to urban residence. Our results suggest that both household and community-level factors are risk factors for maternal depression and anxiety in this context.


Impact of a Gender-Transformative HIV and Antiviolence Program on Gender Ideologies and Masculinities in Two Rural, South African Communities.
"One Man Can" (OMC) is a rights-based gender equality and health program implemented by Sonke Gender Justice Network (Sonke) in South Africa. The program seeks to reduce the spread and impact of HIV and AIDS and reduce violence against women and men. To understand how OMC workshops impact masculinities, gender norms, and perceptions of women's rights, an academic/non-governmental organization (NGO) partnership was carried out with the University of Cape Town, the University of California at San Francisco, and Sonke. Sixty qualitative, in-depth interviews were carried out with men who had completed OMC workshops and who were recruited from Sonke's partner organizations that were focused on gender and/or health-related services. Men were recruited who were over age 18 and who participated in OMC workshops in Limpopo and Eastern Cape Provinces, South Africa. Results reveal how men reconfigured notions of hegemonic masculinity both in terms of beliefs and practices in relationships, households, and in terms of women's rights. In the conclusions, we consider the ways in which the OMC program extends public health research focused on masculinities, violence, and HIV/AIDS. We then critically assess the ways in which health researchers and practitioners can bolster men's engagement within programs focused on gender equality and health.


Fluid and hemodynamic management in hemodialysis patients: challenges and opportunities.
Fluid volume and hemodynamic management in hemodialysis patients is an essential component of dialysis adequacy. Restoring salt and water homeostasis in hemodialysis patients has been a permanent quest by nephrologists summarized by the 'dry weight' probing approach. Although this clinical approach has been associated with benefits on cardiovascular outcome, it is now challenged by recent studies showing that intensity or aggressiveness to remove fluid during intermittent dialysis is associated with cardiovascular stress and potential organ damage. A more precise approach is required to improve cardiovascular outcome in this high-risk population. Fluid status assessment and monitoring rely on four components: clinical assessment, non-invasive instrumental tools (e.g., US, bioimpedance, blood volume monitoring), cardiac biomarkers (e.g. natriuretic peptides), and algorithm and sodium modeling to estimate mass transfer. Optimal management of fluid and sodium imbalance in dialysis patients consist in adjusting salt and fluid removal by dialysis (ultrafiltration, dialysate sodium) and by restricting salt intake and fluid gain between dialysis sessions. Modern technology using biosensors and feedback control tools embarked on dialysis machine, with sophisticated analytics will provide direct handling of sodium and water in a more precise and personalized way. It is envisaged in the near future that these tools will support physician decision making with high potential of improving cardiovascular outcome.


Left ventricular hypertrophy among predialysis chronic kidney disease patients: Sindh institute of urology and transplantation experience.
Left ventricular hypertrophy (LVH) is an independent predictor of mortality and its prevention can decrease cardiovascular mortality among predialysis chronic kidney disease (CKD) patients. This cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from March 2013 to October 2013 to determine the frequency of LVH and its risk factors in patients with CKD. A total of 135 outpatients with CKD duration longer than three months, were included in this study. All patients underwent laboratory investigations which included serum creatinine, blood counts, serum calcium, phosphate and uric acid, and parathormone. M-mode, two-dimensional echocardiogram in the left decubitus position was performed to document LVH. LVH was labeled when the left ventricular mass index was >131 g/m2 in men and >100 g/m2 in women on echocardiogram. LVH was found in 76 study patients (56.3%). The frequency of LVH was significantly high in patients with stage-4 CKD and those with duration of CKD above 12 months. Other risk factors included low hemoglobin, high serum calcium and phosphate levels, and decreasing estimated glomerular filtration rate. In conclusion, early detection of LVH and control of risk factors may help to achieve a decrease in cardiovascular morbidity and mortality in patients with CKD.


Responses of vasoactive hormones in congestive cardiac failure.
Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin-angiotensin-aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin-angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.