Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats.
The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may protect GEN-induced acute renal failure (ARF). Therefore, this study was focused on investigating the possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities; glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined using light microscopy. GEN administration to control group rats increased renal MDA and NO levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG administration with GEN injection resulted in significantly decreased MDA, NO generation and increased GSH-Px, SOD, CAT activities and GSH content when compared with GEN alone. Serum levels of Cr and BUN significantly increased as a result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels. Morphological changes in the kidney, including tubular necrosis, intracellular edema, glomerular and basement membrane alterations were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of AG reduced the GEN-induced kidney damage. We propose that AG acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level.


Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression.
Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease. We demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a behavioural phenotype that was distinct from saline-injected wildtype & TgF344 rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the types of errors made, interpolative modeling using logistic exposure-response regression provided an informative analysis of the timing and efficiency of behavioural flexibility. During set-shifting, Tg-ET1 committed fewer perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more regressive errors and had a less efficient strategy change than all other groups. Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in TgF344 rats.


[Vitamin D supplementation for all older people with COVID-19?]
Vitamin D supplementation has been suggested for many diseases and symptoms that are frequent in older people: loss of bone mineral density, falls, loss of muscle mass, infections (including COVID-19) and mortality. In observational studies, vitamin D concentration has been associated with many poor outcomes, but in most Randomized Controlled Trials, there is no beneficial effect of vitamin D supplementation on these outcomes, except for bone mineral density. An alternative explanation of the observed association may be 'confounding': older people with poor mobility have lower vitamin D, and irrespective of that also have poor outcomes. The recent COVIT-TRIAL seems to suggest there is benefit of high dose vitamin D supplementation compared to low dose on mortality in older people with COVID-19, but on closer methodological look this conclusion does not hold. Clinical guidelines rightly do not advise vitamin D supplementation for a whole range of diseases, including COVID-19.


[The lesion of CSF contacting neurons in rat brain parenchyma inhibits the development of morphine dependence and withdrawal].
To investigate the effect of CSF contacting neurons (CSF-CNs) lesion in rat dorsal raphe nucleus (DRN) on the scores of morphine withdrawal symptoms precipitated by naloxone and the nNOS expression in dorsal horn of spinal cord, and study the relationship between the distal CSF-CNs in rat brain parenchyma and the development of morphine dependence and withdrawal. Chemical lesion of neurons the injection of cholera toxin subunit B with horseradish peroxidase (CB-HRP) into one of the rats lateral ventricles, TMBST reaction, nNOS immunohistochemistry and Western blot were used in this study. The withdrawal symptoms by the naloxone precipitated attenuated obviously after the lesion of CSF-CNs in rat DRN, scores of all signs were significantly decreased about 38% compared to that of withdrawal group without lesion (P < 0.05). The withdrawal symptoms scores of vehicle withdrawal group and side lesion withdrawal group were not changed significantly (P > 0.05). Neurons in the location of CSF-CNs concentrated in the rat brain slices of lesion group were damaged obviously, there were only few CB-HRP positive neurons around the lesion location. But the location and the quantity of the CB-HRP positive neurons in the brain slices of the group without lesion was stable relatively, and their appearance was very clear. After the lesion, the nNOS expression and the quantity of the nNOS positive neurons in dorsal horn of spinal cord decreased significantly compared to that of withdrawal group without lesion (P < 0.05), but it also increased significantly compared to that of normal group and dependence group (P < 0.01). The lesion of distal CSF contacting neurons attenuated the scores of morphine withdrawal symptoms precipitated by naloxone and the nNOS expression in dorsal horn of spinal cord. The distal CSF contacting neurons in rat brain parenchyma partly participated in the development of morphine dependence and naloxone precipitated withdrawal possibly by the modulation of NO (nitric oxide).


Regulation of Akt/FoxO3a/Skp2 Axis Is Critically Involved in Berberine-Induced Cell Cycle Arrest in Hepatocellular Carcinoma Cells.
The maintenance of ordinal cell cycle phases is a critical biological process in cancer genesis, which is a crucial target for anti-cancer drugs. As an important natural isoquinoline alkaloid from Chinese herbal medicine, Berberine (BBR) has been reported to possess anti-cancer potentiality to induce cell cycle arrest in hepatocellular carcinoma cells (HCC). However, the underlying mechanism remains to be elucidated. In our present study, G0/G1 phase cell cycle arrest was observed in berberine-treated Huh-7 and HepG2 cells. Mechanically, we observed that BBR could deactivate the Akt pathway, which consequently suppressed the S-phase kinase-associated protein 2 (Skp2) expression and enhanced the expression and translocation of Forkhead box O3a (FoxO3a) into nucleus. The translocated FoxO3a on one hand could directly promote the transcription of cyclin-dependent kinase inhibitors (CDKIs) p21Cip1 and p27Kip1, on the other hand, it could repress Skp2 expression, both of which lead to up-regulation of p21Cip1 and p27Kip1, causing G0/G1 phase cell cycle arrest in HCC. In conclusion, BBR promotes the expression of CDKIs p21Cip1 and p27Kip1 via regulating the Akt/FoxO3a/Skp2 axis and further induces HCC G0/G1 phase cell cycle arrest. This research uncovered a new mechanism of an anti-cancer effect of BBR.


Simulation of intra-ciliary diffusion suggests a novel role of primary cilia as a cell-signaling enhancer.
Besides the role to generate a fluid flow in the surrounding medium, eukaryotic cilia have a crucial function in sensing external signals such as chemical or mechanical stimuli. A large body of work has shown that cilia are frequently found in various types of sensory cells and are closely related to many regulatory mechanisms in differentiation and development. However, we do not yet have a definitive answer to the fundamental question, "why cilia?" It has been a long-standing mystery why cells use cilia for sensing external signals. To shed light on this, we sought to describe the kinetics of signaling with theoretical approaches. Based on the results, here we propose a new role of cilia as a cell-signaling enhancer. The enhancing effect comes from restricted volume for the free intra-ciliary diffusion of molecules due to the cylindrical shape of cilia, which can facilitate quick accumulation of intracellular signaling molecules. Our simulations demonstrate that both the rate and amplitude of response in signal transduction depend on where the membrane receptors or channels are located along the ciliary shaft. In addition, the calculated transfer function of cilia regarded as a transmitter of external signals also suggests the properties of cilia as a signal enhancer. Since such unique composition of receptors and channels in cilia is found in various types of eukaryotic cells, signal enhancing is presumably one of the most essential and conserved roles of cilia.


An ecohydrologic model for a shallow groundwater urban environment.
The urban environment is a patchwork of natural and artificial surfaces that results in complex interactions with and impacts to natural hydrologic cycles. Evapotranspiration is a major hydrologic flow that is often altered through urbanization, although the mechanisms of change are sometimes difficult to tease out due to difficulty in effectively simulating soil-plant-atmosphere interactions. This paper introduces a simplified yet realistic model that is a combination of existing surface runoff and ecohydrology models designed to increase the quantitative understanding of complex urban hydrologic processes. Results demonstrate that the model is capable of simulating the long-term variability of major hydrologic fluxes as a function of impervious surface, temperature, water table elevation, canopy interception, soil characteristics, precipitation and complex mechanisms of plant water uptake. These understandings have potential implications for holistic urban water system management.


Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine.
Shikonin is an anthraquinone derivative extracted from the root of lithospermum. Shikonin is traditionally used in the treatment of inflammatory and infectious diseases such as hepatitis. Shikonin also inhibits proliferation and induces apoptosis in various tumors. However, the effect of shikonin on gliomas has not been fully elucidated. In the present study, we aimed to investigate the effects of shikonin on the migration and invasion of human glioblastoma cells as well as the underlying mechanisms. U87 and U251 human glioblastoma cells were treated with shikonin at 2.5, 5, and 7.5 μmol/L and cell viability, migration and invasiveness were assessed with CCK8, scratch wound healing, in vitro Transwell migration, and invasion assays. The expression and activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) and the expression of phosphorylated β-catenin (p-β-catenin) and phosphorylated PI3K/Akt were also checked. Results showed that shikonin significantly inhibited the cell proliferation, migration, invasion, and expression of MMP-2 and MMP-9 in U87 and U251 cells. The expression of p-β-catenin showed contrary trends in two cell lines. It was significantly inhibited in U87 cells and promoted in U251 cells. Results in this work indicated that shikonin displayed an inhibitory effect on the migration and invasion of glioma cells by inhibiting the expression and activity of MMP-2 and -9. In addition, shikonin also inhibited the expression of p-PI3K and p-Akt to attenuate cell migration and invasion and MMP-2 and MMP-9 expression in both cell lines, which could be reversed by the PI3K/Akt pathway agonist, insulin-like growth factor-1 (IGF-1).


Isolation and characterization of stem cells from the placenta and the umbilical cord.
In addition to its essential role in the development, nutrition and immunological tolerance of the product of conception, human placenta is an important source of stem cells. Over the past years, scientific research has been aimed at isolating and characterizing mesenchymal cells and amniocytes, which show a high plasticity and are found in the chorionic villi and the membranes. At the level of the umbilical cord, two types of stem cells can be found: hematopoietic and mesenchymal. The blood of the umbilical cord is already in the focus of attention of researchers, as an important source of hematopoietic stem cells that can be used for transplantation.


Antifibrogenic effects of vitamin D derivatives on mouse pancreatic stellate cells.
To study the molecular effects of three different D-vitamins, vitamin D2, vitamin D3 and calcipotriol, in pancreatic stellate cells (PSCs). Quiescent PSCs were isolated from mouse pancreas and activated in vitro by seeding on plastic surfaces. The cells were exposed to D-vitamins as primary cultures (early-activated PSCs) and upon re-culturing (fully-activated cells). Exhibition of vitamin A-containing lipid droplets was visualized by oil-red staining. Expression of α-smooth muscle actin (α-SMA), a marker of PSC activation, was monitored by immunofluorescence and immunoblot analysis. The rate of DNA synthesis was quantified by 5-bromo-2'-deoxyuridine (BrdU) incorporation assays. Real-time PCR was employed to monitor gene expression, and protein levels of interleukin-6 (IL-6) were measured by ELISA. Uptake of proline was determined using 18F-proline. Sustained culture of originally quiescent PSCs induced cell proliferation, loss of lipid droplets and exhibition of stress fibers, indicating cell activation. When added to PSCs in primary culture, all three D-vitamins diminished expression of α-SMA (to 32%-39% of the level of control cells; P < 0.05) and increased the storage of lipids (scores from 1.97-2.15 on a scale from 0-3; controls: 1.49; P < 0.05). No such effects were observed when Dvitamins were added to fully-activated cells, while incorporation of BrdU remained unaffected under both experimental conditions. Treatment of re-cultured PSCs with Dvitamins was associated with lower expression of IL-6 (-42% to -49%; P < 0.05; also confirmed at the protein level) and increased expression of the vitamin D receptor gene (209%-321% vs controls; P < 0.05). There was no effect of Dvitamins on the expression of transforming growth factor-β1 and collagen type 1 (chain α1). The lowest uptake of proline, a main component of collagen, was observed in calcipotriol-treated PSCs. The three D-vitamins inhibit, with similar efficiencies, activation of PSCs in vitro, but cannot reverse the phenotype once the cells are fully activated.


Medical management of stable angina pectoris.
The number of drugs available for treatment of angina pectoris has increased dramatically in recent years; new beta and calcium channel blockers are to be introduced; nitrates are now available in transdermal pads and could become released as buccal tablets or aerosol sprays. A broad understanding of the pharmacological principles of their use is necessary to tailor therapy for each patient.


Complex Memory Formation in Frictional Granular Media.
Using numerical simulations it is shown that a jammed, random pack of soft frictional grains can store an arbitrary waveform that is applied as a small time-dependent shear while the system is slowly compressed. When the system is decompressed at a later time, an approximation of the input waveform is recalled in time-reversed order as shear stresses on the system boundaries. This effect depends on friction between the grains, and is independent of some aspects of the friction model. This type of memory could potentially be observable in other types of random media that form internal contacts when compressed.


Conceptual DFT analysis of the regioselectivity of 1,3-dipolar cycloadditions: nitrones as a case of study.
The regioselectivity of the 1,3-dipolar cycloaddition of a model nitrone with a set of dipolarophiles, presenting diverse electronic effects, is analyzed using conceptual density functional theory (DFT) methods. We deviate from standard approaches based on frontier molecular orbitals and formulations of the local hard/soft acid/base principle and use instead the dual descriptor. A detailed analysis is carried out to determine the influence of the way to calculate the dual descriptor, the computational procedure, basis set and choice of method to condensate the values of this descriptor. We show that the qualitative regioselectivity predictions depend on the choice of "computational conditions", something that indicates the danger of using black-box computational set-ups in conceptual DFT studies.


Anxiety and Depression as Predictors of Recurrence in Geriatric Depression: A Preliminary Report.
The authors studied elderly patients with major depression (MDD) who recovered after nortriptyline treatment to determine the relationship of affective symptoms at completion of continuation treatment to eventual MDD recurrence. Independent objective measures of depressive and anxiety symptoms were obtained before and after nortriptyline tapering. Univariate log-rank analysis demonstrated a trend for total post-discontinuation anxiety scores to predict time-to-recurrence in 12 subjects with complete data sets. Items assessing excessive worry and psychic tension (subjective anxiety) were significant predictors. No relationship was found between continuation-phase anxiety or depressive symptoms either immediately preceding or after discontinuation and course.


Mind in the Gap Between Neural and Social Networks - Cyberspace and Virtual Reality in Psychiatry and Healthcare.
In terms of health and healthcare cyberspace and virtual reality can be used differently and for different purposes and consequently create different outcomes. The three main areas which we shall discuss here are: 1) cyberspace as provider of health information and self-help resources, since the anonymity cyberspace provides is particularly important in the highly stigmatized field of psychiatry where a large number of people never seek professional help, which in turn negatively affects not only the person in question, but the family and ultimately the society (work efficiency, disability-adjusted life year - DALY, etc.), 2) cyberspace and virtual reality (VR) as cause of psychopathology, starting from violent behaviour, to addictive behaviour and other, 3) and finally cyberspace and VR as providers of efficient professional therapy in the field of psychiatry.


A syndrome characterized by contractures and pterygia of upper body associated with umbilical hernia, short stature, and distinctive face in an Arabic family.
A large Moslem Arabic family from the North of Israel is presented in which nine individuals are affected with short stature (5th centile and below), variable pterygium of neck or short neck with limited range of motion, pterygium of elbows, short palms, and brachydactyly. Other abnormalities of the fingers include syndactyly, camptodactyly, and/or hypermobility of the small joints. The face typically appeared long and myopathic. Ptosis was present with downslanting palpebral fissures, facial movements were reduced and the midface was flat. Umbilical hernia was present together with hypoplasia of the skin in the periumbilical area. The lower body region was unaffected in this family. The family is characterized by multiple consanguineous marriages, and the pedigree is consistent with autosomal recessive inheritance. The phenotype seems to be distinct from other multiple pterygium syndromes because the lower limbs are spared, and the umbilical hernia with hypoplastic skin has not been described previously.


Effects of Antiretroviral Therapy on CD4+ Cell Count, HIV Viral Load and Death in a South African Cohort: A Modelling Study.
Combination antiretroviral therapy (cART) has improved the survival of HIV infected patients significantly. However, in some patients, survival is not guaranteed due to several factors that are either individual-based or cART based. This study presents an HIV, AIDS, Death (HAD) model to analyse the survival of patients on cART. Continuous-time Markov models are fitted based on the states occupied for an HIV, AIDS and Death (HAD) model. These states are based on CD4 cell count. Factors that affect the survival of HIV-infected patients on cART are also analyzed. These, among others, include age, gender, routinely collected viral load, time on treatment, non-adherence and peripheral neuropathy. Patients with higher viral loads than expected are 11.1 times more likely to be at risk of HIV progression to the AIDS state and 1.1 times more likely to be at risk of mortality from a CD4 cell count state above 200 cell/mm3compared to patients with lower viral loads. Non-adherence to treatment increases the risk of transition from CD4 cell count state above 200 cell/mm3 to the AIDS state by 2.2 folds. Patients who were non-adherent to treatment are 3.8 times more likely to transit from the CD4 state above 200 cell/mm3 to death compared to patients who were adherent to treatment. Patients are expected to recover from the AIDS state after one year of treatment. Recovery from AIDS state by HIV infected patients on cART is likely to occur after one year of cART treatment. However, if the viral load remains higher than expected, this increases risks of immune deterioration even after having achieved normal CD4 cell counts and consequently, mortality risks are increased.


Bond-valence analyses of the crystal structures of FeMo/V cofactors in FeMo/V proteins.
The bond-valence method has been used for valence calculations of FeMo/V cofactors in FeMo/V proteins using 51 crystallographic data sets of FeMo/V proteins from the Protein Data Bank. The calculations show molybdenum(III) to be present in MoFe7S9C(Cys)(HHis)[R-(H)homocit] (where H4homocit is homocitric acid, HCys is cysteine and HHis is histidine) in FeMo cofactors, while vanadium(III) with a more reduced iron complement is obtained for FeV cofactors. Using an error analysis of the calculated valences, it was found that in FeMo cofactors Fe1, Fe6 and Fe7 can be unambiguously assigned as iron(III), while Fe2, Fe3, Fe4 and Fe5 show different degrees of mixed valences for the individual Fe atoms. For the FeV cofactors in PDB entry 5n6y, Fe4, Fe5 and Fe6 correspond to iron(II), iron(II) and iron(III), respectively, while Fe1, Fe2, Fe3 and Fe7 exhibit strongly mixed valences. Special situations such as CO-bound and selenium-substituted FeMo cofactors and O(N)H-bridged FeV cofactors are also discussed and suggest rearrangement of the electron configuration on the substitution of the bridging S atoms.


Bicuspid aortic valve with associated aortopathy, significant left ventricular hypertrophy or concomitant hypertrophic cardiomyopathy: A diagnostic and therapeutic challenge.
Due to its prevalence of 0.5% to 2% in the general population, with a 75% predominance among men, bicuspid aortic valve is the most common congenital heart defect. It is frequently accompanied by other cardiac congenital anomalies, and clinical presentation can vary significantly, with stenosis being the most common manifestation, often resulting in mild to moderate concentric hypertrophy of the left ventricle. Echocardiography is the primary diagnostic modality utilized for establishing the diagnosis, and it is often the sole diagnostic tool relied upon by clinicians. However, due to the heterogeneous clinical presentation and possible associated anomalies (which are often overlooked in clinical practice), it is necessary to employ various diagnostic methods and persist in finding the accurate diagnosis if multiple inconsistencies exist. By employing this approach, we can effectively manage these patients and provide them with appropriate treatment. Through a clinical case from our practice, we provide an overview of the literature on bicuspid aortic valve with aortophaty and the possible association with hypertrophic cardiomyopathy, diagnostic methods, and treatment options. This review article highlights the critical significance of achieving an accurate diagnosis in patients with bicuspid aortic valve and significant left ventricular hypertrophy. It is crucial to exclude other possible causes of left ventricular outflow tract obstruction, such as sub- or supra-aortic obstructions, and hypertrophic cardiomyopathy.


Influence of aeration rate and biodegradability fractionation on composting kinetics.
The influences of aeration rate and biodegradability fractionation on biodegradation kinetics during composting were studied. The first step was the design of a suitable lab-reactor that enabled the simulation of composting. The second step comprised of composting trials of six blends of sludge (originating from a food processing effluent) with wood chips using aeration rates of 1.69, 3.62, 3.25, 8.48, 11.98 and 16.63 L/h/kg DM of mixture. Biodegradation was evaluated by respiration measurements and from the analysis of the substrate (dry matter, organic matter, total carbon and chemical oxygen demand removal). Continuous measurement of oxygen consumption was coupled with the analysis of initial substrate and composted product for chemical oxygen demand (in the soluble and non-soluble fractions), which enabled an evaluation of the organic matter biodegradability. Oxygen requirements to remove both the easily and slowly biodegradable fractions were determined. Dividing the substrate into different parts according to biodegradability allowed explanation of the influence of aeration rate on stabilization kinetics. Considering that the biodegradation kinetics were of the first-order, the kinetic constants of the easily and slowly biodegradable fractions were calculated as a function of temperature. The methodology presented here allows the comparison of organic wastes in terms of their content of easily and slowly biodegradable fractions and the respective biodegradation kinetics.


A Cardiac Troponin T Biosensor Based on Aptamer Self-assembling on Gold.
In this study, a sensitive and accurate aptasensor was designed for early detection of myocardial infarction through the determination of troponin T (TnT). The successful immobilization of a specific aptamer sequence on the surface of gold that had a high affinity toward TnT was accomplished. TnT was electrochemically quantified. The results indicated that the aptasensor detected TnT in a range of 0.05-5 ng mL, and with a detection limit of 0.01 ng/mL. The performance of the aptasensor was investigated by analyzing 99 human serum samples. Both diagnostic specificity and sensitivity of the aptasensor were found to be 95%. The use of the designed aptamer-based biosensor could be an essential achievement in health policy, preventing deaths caused by myocardial infarction, and reducing patients with heart failure. The extensive use of this aptamer-based biosensor can also reduce costs, enhance speed, and improve accuracy in the diagnosis of TnT as an important myocardial infarction biomarker.


Preparation and reactivity of polymer-supported 2-iodylphenol ethers, an efficient recyclable oxidizing system.
Preparation of new recyclable polymer-supported oxidizing reagents based on 2-iodylphenol ethers is described. The synthesis employs commercially available aminomethylated polystyrene or Merrifield resin and affords polymer-supported 2-iodylphenol ethers with loading up to 0.86 mmol/g with respect to IO2 groups. The new reagents effect clean and efficient conversion of a wide range of alcohols, including heteroatomic and unsaturated structures, to the corresponding carbonyl compounds. Recycling of the resins is possible with minimal loss of activity after several reoxidations.


More than just filler: an empirically informed ethical analysis of non-surgical cosmetic procedures in body dysmorphic disorder.
To identify and analyse ethical considerations raised when individuals with body dysmorphic disorder (BDD) consult for non-surgical cosmetic procedures. Ethical analysis was conducted addressing the issues of best interests and capacity to consent for non-surgical cosmetic procedures in individuals with BDD. Analysis was informed by the findings of semistructured interviews with non-surgical cosmetic practitioners and mental health professionals. Non-surgical cosmetic interventions were viewed not to be in the best interests of individuals with BDD, as they fail to address core psychological issues, result in dissatisfaction post-procedure, and risk harm. Referral to mental health services was advocated, however numerous obstacles to this were perceived. The issue of capacity to consent to non-surgical cosmetic procedures raised questions regarding whether standard capacity assessment is sensitive to the manner in which BDD may influence decision-making processes. In addition, concerns were voiced that decisions made by individuals with BDD in this context may be judged foolish, and thus wrongly equated with lack of capacity. Ethical analysis, informed by the available evidence base, suggests that it is generally not in the best interests of individuals with BDD to undergo non-surgical cosmetic intervention, and referral to mental health services is indicated. Analysis of capacity draws parallels between BDD and anorexia nervosa, as decision-making capacity in both conditions can be impaired by pathological values derived from the disorder. Means of differentiating clinical assessment of pathological values from inappropriate value judgements are advocated, in order to safeguard against the latter encroaching into capacity assessment.


Helicobacter pylori risk associated with childhood home environment.
Helicobacter pylori (H. pylori) is considered to be a cause of gastric ulcer, gastric cancer and other diseases. The relationship between infection and the hygiene or housing circumstances of such patients in their childhood was explored. The study subjects were those who applied for a H. pylori antibody test, and were asked to fill out a questionnaire enclosed with a test kit, inquiring as to their hygiene and housing conditions when they were 10 years old. Of 5971 applicants, 5854 agreed to participate in the study. Associations between the six factors in the questionnaire and infection were calculated, and adjusted for sex, age and district. Drinking water, type of toilet, residential area, number of people in the house, and birth order showed significant correlations with H. pylori infection. The odds ratios (95% confidence intervals) were 0.73 (0.55-0.96) for tap water, 0.72 (0.63-0.84) for flush toilets, 0.74 (0.66-0.83) for urban location, 1.34 (1.09-1.64) for 7 or more people in the household, 1.19 (1.00-1.41) for 4th or 5th in birth order, and 1.47 (1.17-1.85) for 6th or more in birth order. No significant association with breast feeding was observed. These results suggest that infection with H. pylori may be associated with water-related sanitary factors in childhood, and that the bacillus may be transmitted within a family.


The Early Detection Research Network: A National Infrastructure to Support the Discovery, Development, and Validation of Cancer Biomarkers.
In 2000, the NCI (Rockville, MD) established the Early Detection Research Network (EDRN) to identify, develop, and validate biomarkers to improve the detection of early-stage cancers and risk assessment. This consortium of more than 300 investigators at academic institutions and in the private sector is working collaboratively to bring biomarkers and imaging methods to clinical fruition. Although significant roadblocks have hindered the field of biomarker discovery and validation, the EDRN has helped overcome many of them by setting well-defined strategies and milestones focused on solving defined unmet clinical needs. The EDRN has implemented measures to improve biomarker discovery and validation, such as data sharing, use of common data elements, generating multidisciplinary and multi-institutional collaborations within a cohesive and productive team environment, and putting emphasis on quality control and data replication for all candidate biomarkers for reaching a "go" or "no go" decision. A measure of the success of the EDRN is the number of biomarkers tests or devices approved by the FDA to which EDRN investigators have made significant contributions and the number of biomarkers tests developed by EDRN investigators that are available in Clinical Laboratory Improvement Amendments laboratories.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."


Building a plant cell wall at a glance.
Plant cells are surrounded by a strong polysaccharide-rich cell wall that aids in determining the overall form, growth and development of the plant body. Indeed, the unique shapes of the 40-odd cell types in plants are determined by their walls, as removal of the cell wall results in spherical protoplasts that are amorphic. Hence, assembly and remodeling of the wall is essential in plant development. Most plant cell walls are composed of a framework of cellulose microfibrils that are cross-linked to each other by heteropolysaccharides. The cell walls are highly dynamic and adapt to the changing requirements of the plant during growth. However, despite the importance of plant cell walls for plant growth and for applications that we use in our daily life such as food, feed and fuel, comparatively little is known about how they are synthesized and modified. In this Cell Science at a Glance article and accompanying poster, we aim to illustrate the underpinning cell biology of the synthesis of wall carbohydrates, and their incorporation into the wall, in the model plant Arabidopsis.


[Factors associated with the efficacy of cardiac resynchronization therapy in patients with chronic heart failure].
To observe the clinical effects of cardiac resynchronization therapy (CRT) in patients with chronic heart failure, and compare the clinical characteristics and outcome between responders and non-responders to define factors related to the efficacy of CRT. We retrospectively analyzed the data of patients underwent CRT-P/D implantation from January 2006 to December 2012 in our Hospital. All patients received long-term follow-up including NYHA classification, left ventricular ejection fraction (LVEF) and left ventricular internal dimension at end diastole (LVIDd). A total of 204 patients were included (130 males, mean age (64.8 ± 11.9) years). The total response rate of CRT was 61.3%. Women, QRS duration ≥ 150 ms, and left bundle branch block (LBBB) were related with better response after CRT (all P < 0.05). Multivariate regression analysis showed that QRS duration was an independent determinant for CRT response. All-cause mortality rate was significantly lower in responder group than in non-responder group (P < 0.001). In patients with chronic heart failure, women, QRS duration ≥ 150 ms, and LBBB are related with better CRT response rate post CRT. QRS duration ≥ 150 ms is an independent predictor of CRT response, and positive response is associated with lower all-cause mortality in this patient cohort.


Massively parallel molecular-dynamics simulation of ice crystallisation and melting: the roles of system size, ensemble, and electrostatics.
Ice crystallisation and melting was studied via massively parallel molecular dynamics under periodic boundary conditions, using approximately spherical ice nano-particles (both "isolated" and as a series of heterogeneous "seeds") of varying size, surrounded by liquid water and at a variety of temperatures. These studies were performed for a series of systems ranging in size from ∼1 × 10(6) to 8.6 × 10(6) molecules, in order to establish system-size effects upon the nano-clusters" crystallisation and dissociation kinetics. Both "traditional" four-site and "single-site" and water models were used, with and without formal point charges, dipoles, and electrostatics, respectively. Simulations were carried out in the microcanonical and isothermal-isobaric ensembles, to assess the influence of "artificial" thermo- and baro-statting, and important disparities were observed, which declined upon using larger systems. It was found that there was a dependence upon system size for both ice growth and dissociation, in that larger systems favoured slower growth and more rapid melting, given the lower extent of "communication" of ice nano-crystallites with their periodic replicae in neighbouring boxes. Although the single-site model exhibited less variation with system size vis-à-vis the multiple-site representation with explicit electrostatics, its crystallisation-dissociation kinetics was artificially fast.


A Comparative Study of Solifenacin, Mirabegron, and Their Combination as Bladder Relaxants in the Management of Overactive Bladder.
Introduction Overactive bladder (OAB) is a medical state that presents as the urgency of urine and increased frequency of micturition and is diagnosed on the basis of the presence of these symptoms in the absence of other explainable diagnoses. The management of this condition includes conservative management, medical management/pharmacotherapy, and surgical management. The overactive bladder has been treated with smooth muscle relaxants, but there are conflicting results. Hence, this study aimed to assess the result of the two smooth muscle relaxants, mirabegron and solifenacin, and their combination to manage an overactive bladder. Methodology A clinical trial was conducted at Swaroop Rani Nehru Hospital, Motilal Nehru Medical College, Prayagraj, India, over the period from November 2019 to December 2020. Ninety patients with OAB were divided into three groups: G1, G2, and G3. These groups were administered solifenacin, mirabegron, and a combination of mirabegron and solifenacin (S+M), respectively. Follow-ups were conducted at 2, 4, 12, and 18 weeks for evaluation. Data were entered into IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States). Appropriate statistical tests, including the chi-square and ANOVA, were employed in this study. Observation The combination of mirabegron and solifenacin was significantly more effective in terms of response compared to solifenacin alone. There was no significant difference between solifenacin versus mirabegron, or between mirabegron (M) and the combination of mirabegron (M) and solifenacin (S). Side effects were more severe in patients taking high doses of solifenacin. Conclusion The S + M combination has higher efficacy than solifenacin and mirabegron when given alone.


Docetaxel/S-1 Versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer: A Retrospective Study.
The treatment efficacy of advanced breast cancer is still not promising. This study aimed to compare the efficacy and safety of docetaxel/S-1 (DS1) versus docetaxel/capecitabine (DX) as the first-line treatment for advanced breast cancer.From June 2008 to June 2013, 22 patients with advanced breast cancer were treated with the DS1 regimen. Another 26 age- and disease status-matched patients treated with the DX regimen served as controls. The 2 groups were compared in terms of time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety profiles.Median TTP did not differ significantly between the DS1 group and the DX group (9.04 vs 10.94 months, P = 0.473). There were no significant differences in objective response rate, disease control rate, and clinical benefit rate between the 2 groups. Both the DS1 and the DX regimens showed good tolerability. The 2 regimens showed no significant difference in adverse events except degree III hand-foot syndrome (DS1 0 vs DX 23.1%, P = 0.025).For the first-line treatment of advanced breast cancer, the DS1 and the DX regimens showed similar efficacy and safety. The DS1 regimen had less severe hand-foot syndrome than the DX regimen.


[Do clinical guidelines and economic restrictions on health care affect the criminal liability of health care professionals?].
Criminal liability in connection with clinical guidelines relates to several different aspects: (1) It refers to the guideline authors' liability under criminal law in the case of faulty guidelines. (2) Guidelines do not constitute legally binding rules. They can only contribute to determining the standard for medical specialists. (3) There can and must not be any reversal in the burden of proof with criminal proceedings. (4) In case of a deviation from guidelines and a related breach of duty, the subjective aspect of negligence (i.e. the recognizability of danger) can often be inferred from the knowledge of the respective guideline that we can reasonably expect of the physician. (5) No physician who has adhered to the guidelines can regularly be accused of (subjective) negligence. (6) Problems may be encountered in cases where the topic in question has not been covered, but only peripherally touched upon by guidelines. For the sake of uniformity in our legal system, the individual physician must not be held criminally responsible for the lack of economic means. Possible solutions include: (1) relating the standard to the practically instead of the theoretically feasible, (2) investigating to what extent criminal liability may be limited by acceptability and possibility. The complete refusal to provide medical care under inadequate conditions may increase the endangerment of legally protected rights and therefore be unacceptable. Attempts to improve structures towards the standard may be regarded as meeting the requirements under criminal law.


Donor quality of life before and after adult-to-adult right liver live donor liver transplantation.
Donor right hepatectomy for adult-to-adult live donor liver transplantation (ALDLT) is a major surgical operation for the benefit of the recipient. Justification of procedure mandates knowledge of the possible physical and psychological negative effects on the donor. We prospectively and longitudinally quantified donor quality of life using generic and condition-specific questionnaires up to 1 year. The generic questionnaires were the Karnofsky Performance Status scale and the Chinese (Hong Kong) version of the Medical Outcomes Study 36-Item Short-Form Survey, which measures 8 health concepts: 4 physical components and 4 mental components. Within 1 year, 30 consecutive donors were included. These 11 male and 19 female donors (36.7% and 63.3%, respectively) had a median age of 35 years (range, 21-56 years). There was no donor mortality or major complications. Donor quality-of-life worsening was most significant in the first 3 postoperative months, particularly among the physical components. The physical and mental components returned to the previous levels in 6 to 12 months' time, though the Karnofsky performance scores were slightly lower at 1 year (P = 0.011). Twenty-six (86.7%) donors declared that they would donate again if there were such a need and it were technically possible. It was noticed that older donors were more likely to express unwillingness to donate again. In conclusion, the temporary worsening of donor quality of life substantiates ALDLT as an acceptable treatment modality.


Behavioral tests for evaluating the characteristics of brain diseases in rodent models: Optimal choices for improved outcomes (Review).
Behavioral assessment is the dominant approach for evaluating whether animal models of brain diseases can successfully mimic the clinical characteristics of diseases. At present, most research regarding brain diseases involves the use of rodent models. While studies have reported numerous methods of behavioral assessments in rodent models of brain diseases, each with different principles, procedures, and assessment criteria, only few reviews have focused on characterizing and differentiating these methods based on applications for which they are most appropriate. Therefore, in the present review, the representative behavioral tests in rodent models of brain diseases were compared and differentiated, aiming to provide convenience for researchers in selecting the optimal methods for their studies.


A Systematic Review of Suture Technologies in Total Knee Arthroplasty.
Over time, various materials and techniques have been developed for superficial and deep wound closure. However, potential complications, such as infections and dehiscences, can still occur, driving the development of new closure modalities. As wound closure technology continues to advance and change, the need to continuously evaluate the current techniques and materials persists. Therefore, the purpose of this systematic review was to evaluate the current literature on the various closure materials and techniques utilized for total knee arthroplasty. Specifically, we evaluated: 1) closure times; 2) infections and complication rates; as well as 3) costs related to superficial and deep wound closures. Based on the findings from the current literature, barbed suture was associated with significantly shorter closing times in all five studies when compared to interrupted sutures (p<0.05). Additionally, the use of barbed sutures may result in similar postoperative complication rates. Although the cost of an individual barbed suture is potentially higher than the cost of an individual conventional suture, a knotless technique can require a shorter suture length, which might also help decrease costs.


Role of dietary antioxidants to protect against DNA damage in adult dogs.
We studied the effects of feeding an antioxidant blend of vitamins, minerals and carotenoids to a mixed adult dog population (n = 40, mean 4.4 +/- 1.85 y) for a 16-wk period. Compared to the control group of dogs (n = 20), the antioxidant (AOX)-supplemented group of dogs (n = 20) demonstrated significant increases in plasma levels of vitamin E and taurine by 4 wk of supplementation (P < 0.01) and total antioxidant activity (as measured by ferric-reducing antioxidant power assay) by 8 wk of supplementation (P < 0.05). Following 8 wk of supplementation, the AOX-supplemented dogs also showed significant reductions in both endogenous and exogenous DNA damage (P < 0.005) compared to that of the control dogs, as measured by the comet assay. Over an 8-wk rabies vaccination course that started at 8 wk supplementation, the AOX-supplemented dogs also demonstrated significantly higher vaccine-specific virus-neutralizing antibody levels at 2, 4 and 6 wk postvaccination (P < 0.05) and a tendency toward establishing a vaccine-specific antibody response quicker than did the control group of dogs. These findings in dogs suggest that antioxidant supplementation can achieve sustained increases in circulating levels of antioxidants that exert a protective effect by a decrease in DNA damage, leading to improved immunological performance. These findings also have implications in a wider context where free-radical damage has been associated with a variety of degenerative disorders and the aging process in general.


An active constraint approach to identify essential spectral information in noisy data.
Multivariate curve resolution (MCR) methods aim at extracting pure component profiles from mixed spectral data and can be applied to high-dimensional data, e.g., from process spectroscopy or hyperspectral imaging techniques. One often observes that some parts of this data, namely certain rows and columns of the data matrix, are considered essential for MCR outcomes, while other parts are of minor importance. Some methods for determining essential data are known, but all have different disadvantages concerning the application for noisy data. This work presents a new approach on how to detect the essential information for noisy, experimental spectral data. Active nonnegativity constraints in combination with duality arguments are the key ingredients for determining essential spectra and frequency channels. The new approach is conceptually simple, computationally cheap and stable with respect to noise. The algorithm is tested for noisy experimental Raman, UV-Vis and FTIR-SEC data.


Septal lines in pure right heart failure.
Two adult patients are described with pure right heart failure and chronically elevated systemic venous pressure. Neither patient had evidence of pulmonary venous hypertension, but both had septal lines. This unusual finding may be the result of impaired centripetal lymph flow in the lungs due to obstruction of the drainage of the thoracic duct by raised systemic venous pressure.


Hydroxystilbenes Are Monomers in Palm Fruit Endocarp Lignins.
Lignin, the plant cell wall polymer that binds fibers together but makes processing difficult, is traditionally formed from three monomers, the so-called monolignols (p-coumaryl, coniferyl, and sinapyl alcohols). Recently, we discovered, in grass lignins, a phenolic monomer that falls outside the canonical lignin biosynthetic pathway, the flavone tricin. As we show here, palm fruit (macaúba [Acrocomia aculeata], carnauba [Copernicia prunifera], and coconut [Cocos nucifera]) endocarps contain lignin polymers derived in part from a previously unconsidered class of lignin monomers, the hydroxystilbenes, including the valuable compounds piceatannol and resveratrol. Piceatannol could be released from these lignins upon derivatization followed by reductive cleavage, a degradative method that cleaves β-ether bonds, indicating that at least a fraction is incorporated through labile ether bonds. Nuclear magnetic resonance spectroscopy of products from the copolymerization of piceatannol and monolignols confirms the structures in the natural polymer and demonstrates that piceatannol acts as an authentic monomer participating in coupling and cross-coupling reactions during lignification. Therefore, palm fruit endocarps contain a new class of stilbenolignin polymers, further expanding the definition of lignin and implying that compounds such as piceatannol and resveratrol are potentially available in what is now essentially a waste product.


Grey matter structural differences in alcohol-dependent individuals with and without comorbid depression/anxiety-an MRI study.
Although depression and anxiety disorders are common comorbid conditions in alcohol dependence, few structural brain imaging studies have compared alcohol-dependent subjects with and without such comorbidity. In the current study, brain scans of 35 alcohol-dependent with and 40 individuals without diagnosis of a comorbid ICD-10 depressive or anxiety disorder receiving detoxification inpatient treatment were evaluated. Thickness and volumes of automatically segmented neuroanatomical structures were measured in FreeSurfer. Furthermore, associations of brain structure with biological markers and clinical severity markers of alcohol dependence were assessed. Despite comparable addiction severity, the non-comorbid group had evidence of higher cytotoxic effects of alcohol use on hepatic and haematological markers, and showed significantly smaller volumes of total cerebral, and cerebellar grey matter. Similarly, they showed unexpected smaller hippocampal and nucleus accumbens volumes, and thinner frontal, temporal and occipital cortices. Smaller brain volumes correlated with increased markers of hepatic and haematological dysfunction, and with longer duration of alcohol dependence in the non-comorbid group. Evidence of higher biomarkers of alcohol use may be indicative of more severe alcohol dependence or higher vulnerability to ethanol toxicity in this group. Furthermore, psychopathology-related drug treatment, which occurred in 53% of the comorbid group over the recent years, or tissue inflammation may have a moderate effect on the grade of cerebral atrophy in alcohol-dependent patients. Longitudinal studies are needed to investigate this issue more fully.


Diversity of Agaricomycetes in southern South America and their bioactive natural products.
Fungi have a unique metabolic plasticity allowing them to produce a wide range of natural products. Since the discovery of penicillin, an antibiotic of fungal origin, substantial efforts have been devoted globally to search for fungal-derived natural bioactive products. Andean region forests represent one of the few undisturbed ecosystems in the world with little human intervention. While these forests display a rich biological diversity, mycological and chemical studies in these environments have been scarce. This review aims to summarise all the efforts regarding the chemical or bioactivity analyses of Agaricomycetes (Basidiomycota) from southern South America environments. Overall, herein we report a total of 147 fungal species, 21 of them showing chemical characterisation and/or biological activity. In terms of chemical cores, furans, chlorinated phenol derivatives, polyenes, lactones, terpenes and himanimides have been reported. These natural products displayed a range of biological activities including antioxidant, antimicrobial, antifungal, neuroprotective and osteoclast-forming suppressing effects.


DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas.
Normal (IMR-90) and simian virus 40-transformed (VA-13) human embryo cells were treated with antitumor nitrosoureas, and the effects on cell viability and cell DNA were compared. All six nitrosoureas tested were more toxic to VA-13 cells than to IMR-90 cells as measured by decrease in cell proliferation or in colony formation. The nitrosoureas capable of generating alkylisocyanates produced a smaller difference between the cell types than did derivatives lacking this capacity. DNA damage was measured by alkaline elution in cells treated with four chloroethylnitrosoureas. Whereas VA-13 cells exhibited dose-dependent interstrand crosslinking, little or none was detected in IMR-90 cells. The IMR-90 cells, however, exhibited at least as much DNA-protein crosslinking as did VA-13 cells. The results can be interpreted in terms of a possible difference in DNA repair between the cell lines.


Evaluation of lipid oxidation after ingestion of bakery products enriched with phytosterols, beta-carotene and alpha-tocopherol.
The aim of this study was to investigate the effect of the consumption of croissants and magdalenas (Spanish muffins), enriched with sterol esters, alpha-tocopherol and beta-carotene, on plasma lipid peroxidation. TBA and conjugated dienes were used as markers of lipid peroxidation. The study was made to a population without changes in their diet or lifestyle, and based on a randomized double-blind controlled repeated measures design. The sample size was 57. During 8 weeks, the subjects of the control group (29) received two daily pieces (standard croissant and muffin), whereas those of the experimental group (28) received the same products, but enriched with sterol-esters, alpha-tocopherol and beta-carotene. The treatment has a positive effect on TBA value for control group and that given to experimental group has negative effect. The mean difference between two groups is 3.16 (P = 0.044). Also TBA was found to be significantly correlated with HDL-, LDL-cholesterol and alpha-tocopherol, both before and after treatment, but TBA was only significantly correlated with beta-carotene before treatment. Finally, the effects on LDL-cholesterol, alpha-tocopherol and TBA presented similar correlation matrices in the two groups, most correlation coefficients being significant at group level, in spite of the low sample sizes, revealing the association between treatment effects.


Inhibition of tumor growth in syngeneic chimeric mice mediated by a depletion of suppressor T cells.
Syngeneic chimeric (lethally irradiated and reconstituted with syngeneic bone marrow cells) mice manifested an increased resistance to the development of Lewis lung carcinoma. In addition, these mice had a higher response to polyvinylpyrrolidone and a reduced reactivity to T mitogens. The present findings suggest that syngeneic chimeric mice lack suppressor T cells shown to regulate the development of Lewis lung tumor and the response to polyvinylpyrrolidone. Other components of the T cell population, such as helper cells responding to sheep red blood cells or cells involved in allograft rejection, assayed in these syngeneic chimeras were found unaffected. The fact that chimeric mice are deficient in a certain suppressor T cell population whereas other T activities are normal suggests the existence of different cell lines within the T cell population.


An automatic patient-adapted ECG heartbeat classifier allowing expert assistance.
In this paper, we present a patient-adaptable algorithm for ECG heartbeat classification, based on a previously developed automatic classifier and a clustering algorithm. Both classifier and clustering algorithms include features from the RR interval series and morphology descriptors calculated from the wavelet transform. Integrating the decisions of both classifiers, the presented algorithm can work either automatically or with several degrees of assistance. The algorithm was comprehensively evaluated in several ECG databases for comparison purposes. Even in the fully automatic mode, the algorithm slightly improved the performance figures of the original automatic classifier; just with less than two manually annotated heartbeats (MAHB) per recording, the algorithm obtained a mean improvement for all databases of 6.9% in accuracy A, of 6.5% in global sensitivity S and of 8.9% in global positive predictive value P(+). An assistance of just 12 MAHB per recording resulted in a mean improvement of 13.1% in A, of 13.9% in S, and of 36.1% in P(+). For the assisted mode, the algorithm outperformed other state-of-the-art classifiers with less expert annotation effort. The results presented in this paper represent an improvement in the field of automatic and patient-adaptable heartbeats classification, concluding that the performance of an automatic classifier can be improved with an efficient handling of the expert assistance.


Diffusing colloidal probes of protein-carbohydrate interactions.
We present diffusing colloidal probe measurements of weak, multivalent, specific protein-polysaccharide interactions mediated by a competing monosaccharide. Specifically, we used integrated evanescent wave and video microscopy methods to monitor the three-dimensional Brownian excursions of conconavilin A (ConA) decorated colloids interacting with dextran-functionalized surfaces in the presence of glucose. Particle trajectories were interpreted as binding lifetime histograms, binding isotherms, and potentials of mean force. Binding lifetimes and isotherms showed clear trends of decreasing ConA-dextran-specific binding with increasing glucose concentration, consistent with expectations. Net potentials were accurately captured by superposition of a short-range, glucose-independent ConA-dextran repulsion and a longer-range, glucose-dependent dextran bridging attraction modeled as a harmonic potential. For glucose concentrations greater than 100 mM, the net ConA-dextran potential was found to have only a nonspecific repulsion, similar to that of bovine serum albumin (BSA) decorated colloids over dextran determined in control experiments. Our results demonstrate the first use of optical microscopy methods to quantify the connections between potentials of mean force and the binding behavior of ConA-decorated colloids on dextran-functionalized surfaces.


Systems Biology for Smart Crops and Agricultural Innovation: Filling the Gaps between Genotype and Phenotype for Complex Traits Linked with Robust Agricultural Productivity and Sustainability.
In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes.


Influence of a Cu-zirconia interface structure on CO2 adsorption and activation.
CO2 adsorption and activation on a catalyst are key elementary steps for CO2 conversion to various valuable products. In the present computational study, we screened different Cu-ZrO2 interface structures and analyzed the influence of the interface structure on CO2 binding strength using density functional theory calculations. Our results demonstrate that a Cu nanorod favors one position on both tetragonal and monoclinic ZrO2 surfaces, where the bottom Cu atoms are placed close to the lattice oxygens. In agreement with previous calculations, we find that CO2 prefers a bent bidentate configuration at the Cu-ZrO2 interface and the molecule is clearly activated being negatively charged. Straining of the Cu nanorod influences CO2 adsorption energy but does not change the preferred nanorod position on zirconia. Altogether, our results highlight that CO2 adsorption and activation depend sensitively on the chemical composition and atomic structure of the interface used in the calculations. This structure sensitivity may potentially impact further catalytic steps and the overall computed reactivity profile.


Real-World Effectiveness of Palbociclib Versus Clinical Trial Results in Patients With Advanced/Metastatic Breast Cancer That Progressed on Previous Endocrine Therapy.
The aim of this study was to assess the real-world effectiveness and tolerability of palbociclib combined with endocrine therapy for the treatment of hormone receptor positive (HR-positive), human epidermal growth factor receptor 2 negative (HER2-negative), advanced/metastatic breast cancer that progressed on previous endocrine therapy, and to compare these results with the outcomes of the PALOMA-3 clinical trial. This study was a retrospective observational cohort study including all patients who started with palbociclib in the St. Antonius Hospital between September 1, 2016 and April 1, 2018 for the treatment of HR-positive, HER2-negative advanced/metastatic breast cancer that progressed on previous endocrine therapy. Individual patient data were collected from electronic medical records. Primary study outcomes were progression-free survival (PFS) and the number of permanent treatment discontinuations before disease progression due to adverse events (AEs). Secondary outcomes were the frequency of all (serious) AEs and the frequency of and reasons for dose reductions, -interruptions and cycle delays. A total of 46 patients were studied with a median follow-up of 13.0 months. Overall, the median PFS in real-world clinical practice was 10.0 months (95% confidence interval (CI) 4.9-15.1), compared with 9.5 months in PALOMA-3 (95% CI 9.2-11.0). Two patients discontinued treatment because of AEs. Neutropenia was the most frequent grade 3-4 AE, but with no febrile neutropenia events. Most AEs were managed with palbociclib dose modifications. Regarding these modifications, more cycle delays, less dose reductions, and less dose interruptions occurred in clinical practice compared with PALOMA-3 (59 vs 36%, 22 vs 34%, and 9 vs 54%, respectively). Patients who did not meet the PALOMA-3 study eligibility criteria (n = 16) showed a lower median PFS of 5.5 months (95% CI 4.7-6.4). The effectiveness and tolerability of palbociclib in real-world clinical practice corresponded well with the results obtained in the PALOMA-3 clinical trial. Despite the differences in dose modifications, this study suggests that there is no efficacy-effectiveness gap in this patient population.


Transdermal oxybutynin in the treatment of adults with overactive bladder: combined results of two randomized clinical trials.
The safety and efficacy of oxybutynin transdermal delivery system (oxybutynin-TDS) versus placebo in adults with urge and mixed urinary incontinence was investigated using combined results from double-blind stages of 2 phase 3 clinical trials. Study 1: placebo-controlled, parallel-group comparison of 3 oxybutynin-TDS doses in 12-week double-blind and open-label periods, followed by a 28-week open-label extension. Study 2 was a 12-week randomized, double-blind, placebo-controlled comparison of oxybutynin-TDS versus long-acting tolterodine and placebo, followed by a 52-week open-label extension. Efficacy analysis included 241 patients receiving oxybutynin-TDS, 244 receiving placebo. Most participants were Caucasian women (92%). Approximately 60% received prior anticholinergic therapy. Primary outcome was determined by changes from baseline to end of treatment in frequency of incontinence episodes, frequency of urination, and void volume. Oxybutynin-TDS was significantly more effective than placebo in reducing median daily incontinence episodes (-3.0 vs placebo -2.0; P=.00004) and daily urinary frequency (-2.0 vs -1.0; P=.0023), and in increasing void volume (25 mL vs 5.5 mL; P<.00001). Overall rates of anticholinergic adverse events (AEs) were 12.8% for oxybutynin-TDS and 11.0% for placebo (P=0.5421). The most common systemic anticholinergic AEs were dry mouth (7.0% for oxybutynin-TDS vs 5.3% for placebo) and constipation (2.1% vs 2.0%). Application site erythema occurred in 7.0% of participants who received oxybutynin-TDS (3.7% discontinuation rate); pruritus occurred in 16.1% (3.3% discontinuation rate). Transdermal oxybutynin was shown to be efficacious, with a proven safety profile. It may be utilized for patients with overactive bladder as a treatment option that could enhance compliance.


Translating pediatric urodynamics from clinic into collaborative research: Lessons and recommendations from the UMPIRE study group.
Pediatric patients present unique challenges in the performance and interpretation of urodynamic studies. Interpretation of urodynamics to guide clinical management at an institutional level is accepted as reliable. Challenges arise however when multi-site collaborations incorporate urodynamics into study design to determine primary or secondary outcomes or to direct decision-making. Although standardized terminology has been established by ICCS, the application of this shared language to performance and interpretation of pediatric urodynamics to across multiple sites may not be intuitive or reliable. With a primary goal of defining the care necessary to protect future renal function, the UMPIRE protocol (Urologic Management to Preserve Initial REnal function) utilizes a urodynamics-based risk stratification to determine medical management for infants with myelomeningocele. Iterative changes in the protocol are based upon the clinical progress of the enrolled children. Despite a team experienced in subtleties of urodynamics and despite efforts to minimize variability across sites, the UMPIRE study group identified several areas in which the language of urodynamics required additional clarification or creation of more explicit definitions to standardize performance and interpretation across sites. This article reviews the foundations of current urodynamics practice, describes limitations and challenges unique to pediatric studies, and the shares the humble lessons learned by the UMPIRE study group on their journey toward standardized urodynamic language for management of infants and children with myelomeningocele.


[Clinical observation of hidden tension suture with absorbable thread].
To observe the operative technique and clinical effects of hidden tension suture after tibiofibular fracture fixation with absorbable thread. From October 2003 to October 2008, 203 patients (220 sides) with tibiofibular fracture underwent hidden tension suture (test group, 102 cases of 112 sides) and the common interrupted suture (control group, 101 cases of 108 sides), including 179 males and 24 females with an median age of 36 years (3-75 years). Fracture was caused by traffic accident in 170 cases, by heavy bruise in 21 cases, and by falling from height in 12 cases. There were 186 cases of single-side fracture, and 17 cases of double-side fracture. Of them, 127 sides were closed fracture, and 93 sides were open fracture (including 38 sides of type I, 45 sides of type II, and 10 sides of type IIIA according to Gustilo classification for the open fracture). The locations were upper tibia in 55 sides, middle tibia in 126 sides, and lower tibia in 39 sides. The X-ray films showed that there were transverse fractures in 65 sides, oblique fractures in 53 sides, spiral fractures in 45 sides, and comminuted fractures in 57 sides. No blood vessel injury, osteofascial compartment syndrome and pressure syndrome were observed. The time from injury to operation was 2 hours to 7 days with an average of 2 days. Of 220 sides, 45 sides were fixed by interlocking nails, others by internal steel plate. In control group, healing by first intention was achieved in 70 cases (69.3%) and healing by secondary intention in 31 cases (30.7%); in test group, healing by first intention was achieved in 93 cases (91.2%) and healing by secondary intention in 9 cases (8.8%); and showing significant difference (P < 0.05). All patients were followed up for 6 months to 2 years (average 9 months). No complication occurred in test group, and scar was obvious in the control group. The hidden tension suture with absorbable thread can be a good alternative for the incision healing after tibiofibular fracture fixation. It deals with the problems of the incision tension and difficult-to-suture, and is good for the incision healing after operation.


Silencing of cyt-c4 led to decrease of biofilm formation in Aeromonas hydrophila.
Aquaculture suffers from a number of diseases caused by Aeromonas hydrophila. Biofilm can protect bacteria from antibiotic therapy. To identify the genes those play crucial roles in A. hydrophila biofilm formation, a library of mini-Tn10 transposon insertion mutants of A. hydrophila B11 has been constructed, and 10 mutants were subjected to biofilm formation assay. The biofilm formation ability of mutant (B188) was significantly decreased compared with B11. The DNA sequence flanking the mini-Tn10 transposon inserted showed that an ORF of approximately 576 bp of the mutant strain B188 was inserted. This ORF putatively displays the highest identity (92%) with the cytochrome c4 gene (cyt-c4) of A. hydrophila subsp. hydrophila ATCC 7966. Silencing cyt-c4 led to deficiencies in biofilm formation, adhesion, drug resistance and pathogenicity of A. hydrophila, which suggests that cyt-c4 plays crucial role in the biofilm formation and virulence mechanisms of A. hydrophila. ABBREVIATIONS: GEN: gentamycin; SDZ: sulfadiazine; AK: amikacin; P: penicillin; CFP: cefoperazone; LEV: levofloxacin; MH: minocycline; FFC: florfenicol; TE: tetracycline; AMP: ampicillin; KAN: kanamycin; STR: streptomycin; SXT: sulfamethoxazole/trimethoprim; DO: doxycycline; OT: Oxytetracycline.


Field evaluations in malaise and canopy traps of selected targets as attractants for tabanid species (Diptera: Tabanidae).
Various configurations of an inflated vinyl beach ball covered with black fabric were evaluated in Malaise and canopy (modified Manitoba) traps for possible use as an insecticide-impregnated visual target (T) for Tabanidae. In Malaise traps, T attracted 2x more flies than no T. When inflated with carbon dioxide, T was not significantly different from T filled with air, no matter which type of trap it was in. In canopy traps, 2 or 4 white spots applied to T did not increase its attractiveness to tabanids. When treated with octenol, T was 2-5x more attractive than an untreated T in canopy traps. However, when an octenol treatment was aged for 48 h, it was less effective than a fresh treatment. Overall, the 3 most frequently collected species, in order of abundance, were: Tabanus lineola hinellus, Hybomitra vicina and Chrysops atlanticus. Significantly more T. l. hinellus and H. vicina were collected at T with octenol than at T without octenol. Attempts to detect an insecticidal effect on flies captured in both types of trap that had been baited with Ts treated with permethrin were unsuccessful.


A pilot study regarding basic knowledge of "cortical visual impairment in children" among ophthalmologists.
A pilot study was done to evaluate knowledge regarding "cortical visual impairment (CVI) in children" among ophthalmologists. This study was conducted during the annual conference of a zonal ophthalmological society. All ophthalmologists who attended the conference were requested to participate in this study. Those who agreed were given a validated questionnaire to assess knowledge regarding CVI. Cronbach's alpha of the questionnaire was 0.6. Participants were asked to respond to multiple choice questions by choosing the single best option. The responses obtained were then evaluated. The total number of registered delegates in the conference was 448. A total of 103 ophthalmologists showed interest to participate in the study with a response rate of 22.9%. Only 89/103 interested delegates were included in the study as remaining were unaware of CVI. No participant gave correct answers to all questions. Although more than 80% of them knew the most common association (87%) and site of pathology (84%), only 52% were sure about clinical features and even lesser respondents (39%) knew that magnetic resonance imaging is the correct investigation of choice. The majority responded correctly that these children need eye examination (89%) and can be managed by rehabilitation through multidisciplinary approach (82%), but only 58% could recognize differential diagnoses and had a correct idea regarding the prognosis of CVI. There was no correlation between the number of patients diagnosed per month by the respondent with knowledge of the disease. In this pilot study, ophthalmologists were found to have limited knowledge regarding clinical features, investigation, differential diagnosis, and visual prognosis of CVI in children. There is a need to improve awareness regarding CVI among ophthalmologists.


Differential diagnosis of purulent and non-purulent acute maxillary sinusitis in young adults.
In acute maxillary sinusitis, purulence could best be assessed from sinus washings, but evaluation based on aspirates was also reliable, provided that the amount of secretion was adequate. Injection-aspirates were of negligible diagnostic value in this respect. Sinus washings and aspirates which were clinically defined as purulent were almost invariably indicative of bacterial infection. The bacterial etiology was most accurately obtained by sinus aspiration. Only 14.5% of cultured specimens were negative for pathogenic bacteria. In maxillary sinusitis, judged to be non-purulent, 52.5% of cultures grew a pathogen. The most common pathogen was Haemophilus influenzae, which accounted for 90% of these isolations. There was a clear correlation between occurrence of many PMNs and pathogen positive culture in non-purulent cases. Thus, antimicrobial therapy which is effective against Haemophilus influenzae seems indicated in most cases of non-purulent maxillary sinusitis.


Macrophage promotes fibroblast activation and kidney fibrosis by assembling a vitronectin-enriched microenvironment.
Background: Renal infiltration of inflammatory cells including macrophages is a crucial event in kidney fibrogenesis. However, how macrophage regulates fibroblast activation in the fibrotic kidney remains elusive. In this study, we show that macrophages promoted fibroblast activation by assembling a vitronectin (Vtn)-enriched, extracellular microenvironment. Methods: We prepared decellularized kidney tissue scaffold (KTS) from normal and fibrotic kidney after unilateral ischemia-reperfusion injury (UIRI) and carried out an unbiased quantitative proteomics analysis. NRK-49F cells were seeded on macrophage-derived extracellular matrix (ECM) scaffold. Genetic Vtn knockout (Vtn-/-) mice and chronic kidney disease (CKD) model with overexpression of Vtn were used to corroborate a role of Vtn/integrin αvβ5/Src in kidney fibrosis. Results: Vtn was identified as one of the most upregulated proteins in the decellularized kidney tissue scaffold from fibrotic kidney by mass spectrometry. Furthermore, Vtn was upregulated in the kidney of mouse models of CKD and primarily expressed and secreted by activated macrophages. Urinary Vtn levels were elevated in CKD patients and inversely correlated with kidney function. Genetic ablation or knockdown of Vtn protected mice from developing kidney fibrosis after injury. Conversely, overexpression of Vtn exacerbated renal fibrotic lesions and aggravated renal insufficiency. We found that macrophage-derived, Vtn-enriched extracellular matrix scaffold promoted fibroblast activation and proliferation. In vitro, Vtn triggered fibroblast activation by stimulating integrin αvβ5 and Src kinase signaling. Either blockade of αvβ5 with neutralizing antibody or pharmacological inhibition of Src by Saracatinib abolished Vtn-induced fibroblast activation. Moreover, Saracatinib dose-dependently ameliorated Vtn-induced kidney fibrosis in vivo. These results demonstrate that macrophage induces fibroblast activation by assembling a Vtn-enriched extracellular microenvironment, which triggers integrin αvβ5 and Src kinase signaling. Conclusion: Our findings uncover a novel mechanism by which macrophages contribute to kidney fibrosis via assembling a Vtn-enriched extracellular niche and suggest that disrupting fibrogenic microenvironment could be a therapeutic strategy for fibrotic CKD.


Should we treat patients with only one set of positive blood cultures for extensively drug-resistant Acinetobacter baumannii the same as multiple sets?
Acinetobacter species are not considered skin commensals and under-treatment is an overriding concern when caring for critically-ill patients who are mostly at risk of extensively drug-resistant Acinetobacter baumannii (XDRAB) infections. Hence even a single blood culture yielding XDRAB will tend to prompt intervention. However, field observations suggest that patients with single-positive blood cultures had milder disease and were more likely to be recruited in interventional studies than those with multiple-positive blood cultures, yet no distinction is made in current clinical or trial recruitment practices. To our knowledge, this is the first study to compare the clinical characteristics and outcomes of patients with single-positive versus multiple-positive blood cultures for XDRAB. In this multicenter prospective cohort study of XDRAB bacteremic patients from July 2010 to June 2015, only patients with at least two simultaneously drawn blood cultures were included. The patients were classified as having single-positive or multiple-positive blood cultures according to the number of positive blood cultures yielding XDRAB. The primary end-point was the 28-day mortality. Of a total of 155 patients enrolled, 69 had a single-positive and 86 had multiple-positive blood cultures. Leukopenia (37.2% vs. 16.2%; P = 0.004), thrombocytopenia (56.0% vs. 26.5%; P < 0.001), higher Pitt bacteremia scores (6.6 vs. 5.5, P = 0.03) and higher 28-day mortality rates (70.9% vs. 43.5%; P = 0.001) distinguished patients with multiple-positive from those with single-positive cultures. Multivariate logistic regression showed that multi-positivity independently predicted 28-day mortality (adjusted odds ratio, 2.34; 95% confidence interval (CI), 1.03-5.28; P = 0.04) and the Cox regression confirmed that multi-positivity (adjusted hazard ratio, 1.80; 95% CI, 1.13-2.85; P = 0.01) predicted rapid mortality. Patients with multiple versus single positive blood cultures yielding XDRAB had greater morbidity and mortality. Investigators and clinicians should be aware that the blood culture positivity rate impacts outcomes of XDRAB bacteremia.


Resveratrol alleviates cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy induction.
Resveratrol has been reported to protect against cerebral ischemia/reperfusion (I/R) injury in rats, but the underlying mechanism is unclear. In the current study, we examined whether resveratrol ameliorates cerebral I/R injury by inhibiting NLRP3 inflammasome-derived inflammation and whether autophagy is involved in this process. In addition, we explored the role of Sirt1 in resveratrol-mediated protective effects. To answer these questions, healthy male Sprague-Dawley rats were exposed to middle cerebral artery occlusion for 1h followed by 24h reperfusion. We found that cerebral I/R increased levels of activated NLRP3 inflammasome, caspase-1, IL-1β, and IL-18 and enhanced autophagy activity (ratio of LC3B-II/LC3B-I and p62/SQSTM1). Treatment with resveratrol, a specific Sirt1 agonist, attenuated I/R-induced NLRP3 inflammasome-derived inflammation but upregulated autophagy. Furthermore, resveratrol treatment clearly reduced cerebral infarct volume, decreased brain water content, and improved neurological scores. In addition, inhibition of autophagy using 3-MA intracerebroventricular injection blocked the inhibitory effect of resveratrol on NLRP3 inflammasome activation. Finally, Sirt1 knockdown with siRNA significantly blocked resveratrol-induced enhancement of autophagy activity and suppression of NLRP3 inflammasome activation. In conclusion, our results demonstrate that resveratrol protects against cerebral I/R injury by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy activity.


Chondroosteogenetic response to crude bone matrix proteins bound to hydroxyapatite.
For the development of a new implantable biomaterial that possesses osteogenetic ability, bone matrix morphogenetic proteins were bound to hydroxyapatite (BMP-HAP). A crude protein extract including the bone morphogenetic protein (BMP) fraction was precipitated in the pores of hydroxyapatite (HAP) inside of a dialysis sac. In tissue culture, BMP-HAP or HAP was used as substratum for rat mesenchymal muscle cell explants. The BMP-HAP and HAP controls were also implanted in the muscle pouches of mice. New cartilage and/or new bone formation was observed on the exterior surface of BMP-HAP but not of HAP controls. Implantation of this HAP into bone marrow cavities of rabbit femoral and tibial condyle produced new bone formation. The deposits extended further inside BMP-HAP than HAP pores. The pore diameters of 90-200 microns produced earlier ingrowth than into larger pore sizes. BMP-HAP should be tested for clinical application as osteogenetic biomaterial for augmentation of bone regeneration.


Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody.
In myasthenia gravis, the neuromuscular junction is impaired by the antibody-mediated loss of postsynaptic acetylcholine receptors (AChRs). Muscle weakness can be improved upon treatment with pyridostigmine, a cholinesterase inhibitor, or with 3,4-diaminopyridine, which increases the release of ACh quanta. The clinical efficacy of pyridostigmine is in doubt for certain forms of myasthenia. Here we formally examined the effects of these compounds in the antibody-induced mouse model of anti-muscle-specific kinase (MuSK) myasthenia gravis. Mice received 14 daily injections of IgG from patients with anti-MuSK myasthenia gravis. This caused reductions in postsynaptic AChR densities and in endplate potential amplitudes. Systemic delivery of pyridostigmine at therapeutically relevant levels from days 7 to 14 exacerbated the anti-MuSK-induced structural alterations and functional impairment at motor endplates in the diaphragm muscle. No such effect of pyridostigmine was found in mice receiving control human IgG. Mice receiving smaller amounts of MuSK autoantibodies did not display overt weakness, but 9 days of pyridostigmine treatment precipitated generalised muscle weakness. In contrast, one week of treatment with 3,4-diaminopyridine enhanced neuromuscular transmission in the diaphragm muscle. Both pyridostigmine and 3,4-diaminopyridine increase ACh in the synaptic cleft yet only pyridostigmine potentiated the anti-MuSK-induced decline in endplate ACh receptor density. These results thus suggest that ongoing pyridostigmine treatment potentiates anti-MuSK-induced AChR loss by prolonging the activity of ACh in the synaptic cleft.


Primary cutaneous amyloidoma: a case report.
Amyloidoma is defined as solitary, localized, tumor-like deposit of amyloid in diverse organs without evidence of systemic amyloidosis. Here we report the case of a 49-year-old male patient with a solitary amyloidoma of the skin seated on the left upper lip. Full medical examination showed no signs of systemic amyloidosis. The mass was removed surgically with tangential shave and so far no signs of recurrence have been found.


Relationship Between Media Coverage and Measles-Mumps-Rubella (MMR) Vaccination Uptake in Denmark: Retrospective Study.
Understanding the influence of media coverage upon vaccination activity is valuable when designing outreach campaigns to increase vaccination uptake. To study the relationship between media coverage and vaccination activity of the measles-mumps-rubella (MMR) vaccine in Denmark. We retrieved data on media coverage (1622 articles), vaccination activity (2 million individual registrations), and incidence of measles for the period 1997-2014. All 1622 news media articles were annotated as being provaccination, antivaccination, or neutral. Seasonal and serial dependencies were removed from the data, after which cross-correlations were analyzed to determine the relationship between the different signals. Most (65%) of the anti-vaccination media coverage was observed in the period 1997-2004, immediately before and following the 1998 publication of the falsely claimed link between autism and the MMR vaccine. There was a statistically significant positive correlation between the first MMR vaccine (targeting children aged 15 months) and provaccination media coverage (r=.49, P=.004) in the period 1998-2004. In this period the first MMR vaccine and neutral media coverage also correlated (r=.45, P=.003). However, looking at the whole period, 1997-2014, we found no significant correlations between vaccination activity and media coverage. Following the falsely claimed link between autism and the MMR vaccine, provaccination and neutral media coverage correlated with vaccination activity. This correlation was only observed during a period of controversy which indicates that the population is more susceptible to media influence when presented with diverging opinions. Additionally, our findings suggest that the influence of media is stronger on parents when they are deciding on the first vaccine of their children, than on the subsequent vaccine because correlations were only found for the first MMR vaccine.


In-depth study of breastfeeding structure: New data from Mali.
A number of variables, including ethnic affiliation, time of day, infant and maternal ages, and infant dietary supplementation, are used to compare their effects on breastfeeding structure of two groups of rural Malian women. The agro-fishing Bozo and the transhumant pastoralist Fulbe live in the Inner Niger Delta of Mali. On-demand breastfeeding is practiced by these groups. Lactation continues throughout the infant's second year of life and often into the third. Comparisons are made with data from other traditional societies to highlight differences in breastfeeding structure and its determinants. Ethnic affiliation does not have any significant effect on nursing variables, and the suckling patterns of the Fulbe and Bozo women are comparable in this study. Suckling activity does not vary according to time of day, although individual women exhibit different temporal patterns of nursing behavior. Infant age is significantly and negatively correlated to session duration. As infants get older and their diets are supplemented with food other than breastmilk, their appetites decrease and, consequently, they suckle less. However, there is much individual variation in this relationship, and it is argued that the decrease in suckling due to supplementation may be offset by an increase in suckling due to infants demanding the breast for physical affection. Maternal age, in contrast, is not correlated with any nursing variable in this study. This indicates that there is no decrease in physiological capacity to provide milk and that access to surrogate caretakers is either not correlated with maternal age, or is not a strategy employed by these women. Am. J. Hum. Biol. 10:179-190, 1998. © 1998 Wiley-Liss, Inc.


Patient Engagement and its Evaluation Tools- Current Challenges and Future Directions Comment on "Metrics and Evaluation Tools for Patient Engagement in Healthcare Organization- and System-Level Decision-Making: A Systematic Review".
Considering the growing recognition of the importance of patient engagement in healthcare decisions, research and delivery systems, it is important to ensure high quality and efficient patient engagement evaluation tools. In this commentary, we will first highlight the definition and importance of patient engagement. Then we discuss the psychometric properties of the patient engagement evaluation tools identified in a recent review on patient engagement in healthcare organization- and system-level decision-making. Lastly, we suggest future directions for patient engagement and its evaluation tools.


Treatment of Infections Associated with Implanted Medical Devices.
The development of an infection in the vicinity of an implanted medical device is a dramatic event in many fields of surgery, especially cardiovascular, orthopedic and neurosurgery. The diagnosis of these infections is usually difficult and their treatment is always complex and represents a challenge for both surgeons and infectious diseases specialists. As foreign materials are used with increased frequency in modern medicine, this problem will probably remain a major one in the future despite the improvement of techniques and the use of new antibiotics. For patients, infection of a prosthetic device often means the loss of its function and. is sometimes associated with a high mortality.


Salmonid alphavirus infection causes skin dysbiosis in Atlantic salmon (Salmo salar L.) post-smolts.
Interactions among host, microbiota and viral pathogens are complex and poorly understood. The goal of the present study is to assess the changes in the skin microbial community of Atlantic salmon (Salmo salar L.) in response to experimental infection with salmonid alphavirus (SAV). The salmon skin microbial community was determined using 16S rDNA pyrosequencing in five different experimental groups: control, 7 days after infection with low-dose SAV, 14 days after infection with low-dose SAV, 7 days after infection with high-dose SAV, and 14 days after infection with high-dose SAV. Both infection treatment and time after infection were strong predictors of the skin microbial community composition. Skin samples from SAV3 infected fish showed an unbalanced microbiota characterized by a decreased abundance of Proteobacteria such as Oleispira sp. and increased abundances of opportunistic taxa including Flavobacteriaceae, Streptococcaceae and Tenacibaculum sp. These results demonstrate that viral infections can result in skin dysbiosis likely rendering the host more susceptible to secondary bacterial infections.


Human fetal weight and placental weight growth curves. A mathematical analysis from a population at sea level.
A mathematical analysis of human fetal and placental growth curves was made on data collected prospectively from a population at sea level. Both the fetal and placental growth curves can best be described by a form of the logistic equation inhibited growth model. The fetal growth rate reaches its maximum approximately 4 weeks after the placental growth rate has reached its maximum. Growth rate constants were calculated for several populations at various altitudes.


Clinical proteomics and biomarker discovery.
Early detection of disease generally provides much-improved outcomes by a definitive medical procedure or through lifestyle modification along with specific medical management strategies. For serum biomarkers, which are central to the diagnosis of many diseases, to become truly useful sentinels of pathogenesis, their sensitivity and specificity in both early detection and recurrence monitoring must be improved. Currently, the detection and monitoring of disease markers is based on solitary proteins, and this approach is not always reliable. New classes of biomarkers derived from mass spectroscopy analysis of the low molecular weight proteome have shown improved abilities in the early detection of disease and hence in patient risk stratification and outcome. The development of a modular platform technology with sufficient flexibility and design abstractions allowing for concurrent experimentation, test, and refinement will help speed the progress of mass spectroscopy-derived proteomic pattern-based diagnostics from the scientific laboratory to the medical clinic. For acceptance by scientists, physicians, and regulatory personnel, new bioinformatic tools are essential system components for data management, analysis, and intuitive display of these new and complex data. Clinically engineered mass spectroscopy systems are essential for the further development and validation of multiplexed biomarkers that have shown tremendous promise for the early detection of disease.


The pathology of bone tissue during peri-implantitis.
Dental implants are one of the most frequently used treatment options for tooth replacement. Approximately 30% of patients with dental implants develop peri-implantitis, which is an oral inflammatory disease that leads to loss of the supporting tissues, predominately the bone. For the development of future therapeutic strategies, it is essential to understand the molecular pathophysiology of human dental peri-implant infections. Here, we describe the gene and protein expression patterns of peri-implantitis bone tissue compared with healthy peri-implant bone tissue. Furthermore, cells from the osteoblastic lineage derived from peri-implantitis samples were immortalized and characterized. We applied microarray, quantitative reverse transcription polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. The levels of typical bone matrix molecules, including SPP1, BGLAP, and COL9A1, in patients with peri-implantitis were reduced, while the inflammation marker interleukin 8 (IL8) was highly expressed. RUNX2, one of the transcription factors of mature osteoblasts, was also decreased in peri-implantitis. Finally, the human telomerase reverse transcriptase immortalized cell line from peri-implantitis exhibited a more fibro-osteoblastic character than did the healthy control.


[Protective effect and mechanism of IPQDS on acute myocardial infarction in rats].
To observe the protective effect of Injection of Panax quinquefolium diolsaponins (IPQDS) and its mechanism on acute myocardial infarction in rats. The acute myocardial infarct model was prepared by left anterior descending coronary occulusion for 24 hours in open chest anesthetized rats. The myocardial infarct size (MIS) was calculated. The activities of serum creatine hosphokinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the contents of malondialdehyde (MDA) and nitric oxide (NO) were determined. Blood was collected to observe low shearing specific viscosity, middle shearing specific viscosity and high shearing specific viscosity of whole blood and plasma viscosity. At the same time, the platelet aggregation rate and platelet adherence rate were also determined. In rats treated by IPQDS (in a dosage of 12.5, 25 and 50 mg x kg(-1) d, i.p. 3d ), the MIS was significantly reduced. The activities of serum CK, LDH and AST, and the content of serum MDA were declined. The activities of SOD and GSH-Px, and the content of NO were increased markedly. In addition, low shearing specific viscosity, middle shearing specific viscosity and high shearing specific viscosity of whole blood and plasma viscosity as well as platelet aggregation rate were also declined significantly. But platelet adherence rate had no significant change. IPQDS has a protective effect on acute myocardial ischemia, which may be related to increasing activity of antioxidase in body, scavenging the damage of peroxidation from oxygen free radicals, decreasing the viscosity of blood and plasma and preventting thrombosis etc.