Patient and informal carer experience of hip fracture: a qualitative study using interviews and observation in acute orthopaedic trauma.
The time taken for older people to recover from hip fracture can be extensive. The aim of this study was to gain an understanding of patient and informal carer experience of recovery in the early stage, while in acute care. A phenomenological (lived experience) approach was used to guide the design of the study. Interviews and observation took place between March 2016 and December 2016 in acute care. Trauma wards in a National Health Service Foundation Trust in the South West of England. A purposive sample of 25 patients were interviewed and observation taking 52 hours was undertaken with 13 patients and 12 staff. 11 patients had memory loss, 2 patients chose to take part in an interview and observation. The age range was 63-91 years (median 83), 10 were men. A purposive sample of 25 informal carers were also interviewed, the age range was 42-95 years (mean 64), 11 were men. The results identified how participants moved forward together after injury by sharing the journey. This was conveyed through three themes: (1) sustaining relationships while experiencing strong emotions and actively helping, (2) becoming aware of uncertainty about the future and working through possible outcomes, (3) being changed, visibly looking different, not being able to walk, and enduring indignity and pain. This study identified the experience of patients and informal carers as they shared the journey during a challenging life transition. Strategies that support well-being and enable successful negotiation of the emotional and practical challenges of acute care may help with longer term recovery. Research should focus on developing interventions that promote well-being during this transition to help provide the foundation for patients and carers to live fulfilled lives.


Breaking Mass Transport Limitations by Iodized Polyacrylonitrile Anodes for Extremely Fast-Charging Lithium-Ion Batteries.
The fast-charging capability of rechargeable batteries is greatly limited by the sluggish ion transport kinetics in anode materials. Here we develop an iodized polyacrylonitrile (I-PAN) anode that can boost the bulk/interphase lithium (Li)-ion diffusion kinetics and accelerate Li-ion desolvation process to realize high-performance fast-charging Li-ion batteries. The iodine immobilized in I-PAN framework expands ion transport channels, compresses the electric double layer, and changes the inner Helmholtz plane to form LiF/LiI-rich solid electrolyte interphase layer. The dissolved iodine ions in the electrolyte self-induced by the interfacial nucleophilic substitution of PF6 - not only promote the Li-ion desolvation process, but also reuse the plated/dead Li formed on the anode under fast-charging conditions. Consequently, the I-PAN anode exhibits a high capacity of 228.5 mAh g-1 (39 % of capacity at 0.5 A g-1 delivered in 18 seconds) and negligible capacity decay for 10000 cycles at 20 A g-1 . The I-PAN||LiNi0.8 Co0.1 Mn0.1 O2 full cell shows excellent fast-charging performance with attractive capacities and negligible capacity decay for 1000 cycles at extremely high rates of 5 C and 10 C (1 C=180 mA g-1 ). We also demonstrate high-performance fast-charging sodium-ion batteries using I-PAN anodes.


Cloning and characterization of novel human SLC4A8 gene products encoding Na+-driven Cl-/HCO3(-) exchanger variants NDCBE-A, -C, and -D.
The reported sequences of the human and mouse Na+-driven Cl-/HCO3(-) exchangers (NDCBEs) differ greatly in their extreme cytosolic COOH termini (Ct). In human NDCBE (NDCBE-B), a 17-amino acid (aa) sequence replaces 66 aa at the equivalent position in mouse NDCBE (NDCBE-A). We performed 5'- and 3'-rapid amplification of cDNA ends (RACE) on human brain cDNA, followed by PCR of full-length cDNAs to determine whether the human SLC4A8 gene was capable of producing the mouselike Ct sequence. Our study confirmed the presence in human cDNA of mouse NDCBE-like transcripts (human NDCBE-A) and also disclosed the existence of three further novel NDCBE transcripts that we have called NDCBE-C, NDCBE-D, and NDCBE-D'. The novel NDCBE-C/D/D' transcripts initiate at a novel "exon 0" positioned approximately 35 kb upstream of the first exon of NDCBE-A/B. NDCBE-C/D/D' protein products are predicted to be truncated by 54 aa in the cytosolic NH(2) terminus (Nt) compared with NDCBE-A/B. Our data, combined with a new in silico analysis of partial transcripts reported by others in the region of the human SLC4A8 gene, increase the known extent of the SLC4A8 gene by 49 kb, to 124 kb. A functional comparison of NDCBE-A/B/C/D expressed in Xenopus oocytes demonstrates that the Nt variation does not affect the basal functional expression of NDCBE, but those with the shorter Ct have a 25-50% reduced functional expression compared with those with the longer Ct. By comparison with an artificially truncated NDCBE that contains neither 17-aa nor 66-aa Ct cassette, we determined that the functional difference is unrelated to the 66-aa cassette of NDCBE-A/C, but is instead due to an inhibitory effect of the 17-aa cassette of NDCBE-B/D.


Autism spectrum disorder symptoms in juvenile suspects of sex offenses.
To investigate autism spectrum disorder (ASD) symptoms in juvenile suspects of sex offenses. A group of 175 juvenile suspected sex offenders (all males, mean +/- SD age = 14.9 +/- 1.4 years) was compared with a matched healthy control group (N = 500, mean +/- SD age = 14.0 +/- 1.4 years) and a group of children with DSM-IV-diagnosed ASD (N = 114, mean +/- SD age = 14.2 +/- 1.9 years) with respect to autistic symptoms as measured by means of a standardized questionnaire, the Children's Social Behavior Questionnaire. Furthermore, specific subgroups of sexual offenders, i.e., child molesters, solo peer offenders, and group offenders, were compared with regard to levels of ASD symptoms. The study was conducted from May 2003 to December 2006. Significantly higher levels of ASD symptoms were found in juvenile sex offenders than in healthy controls, while levels were lower than in the ASD group (F = 148.259, p < .05). Solo peer offenders and child molesters scored higher on several subscales as well as on core autistic symptoms than group offenders (F = 5.127, p < .05). Levels of ASD symptoms are higher in juvenile suspects of sex offenses as compared to the healthy population, which argues for considering specific diagnostic assessment in this population, especially in solo offenders and child molesters.


Integrin activation promotes axon growth on inhibitory chondroitin sulfate proteoglycans by enhancing integrin signaling.
Chondroitin sulfate proteoglycans (CSPGs) are upregulated after CNS lesions, where they inhibit axon regeneration. In order for axon growth and regeneration to occur, surface integrin receptors must interact with surrounding extracellular matrix molecules. We have explored the hypothesis that CSPGs inhibit regeneration by inactivating integrins and that forcing integrins into an active state might overcome this inhibition. Using cultured rat sensory neurons, we show that the CSPG aggrecan inhibits laminin-mediated axon growth by impairing integrin signaling via decreasing phosphorylated FAK (pFAK) and pSrc levels, without affecting surface integrin levels. Forcing integrin activation and signaling by manganese or an activating antibody TS2/16 reversed the inhibitory effect of aggrecan on mixed aggrecan/laminin surfaces, and enhanced axon growth from cultured rat sensory neurons (manganese) and human embryonic stem cell-derived motoneurons (TS2/16). The inhibitory effect of Nogo-A can also be reversed by integrin activation. These results suggest that inhibition by CSPGs can act via inactivation of integrins, and that activation of integrins is a potential method for improving axon regeneration after injury.


Application of proteomics to identify the target molecules involved in Lonicera japonica-induced photokilling in human lung cancer CH27 cells.
The Lonicera japonica has been used as natural and healthy drink for its anti-inflammatory effect and pleasant odor in China and Taiwan. 2D electrophoresis was used to analyze the proteins involved in photoactivated Lonicera japonica-induced CH27 cell apoptosis. The fluorescent dyes MitoTracker Red CMXRos, calcein AM and JC-1 were used to elucidate mitochondrial function. The protein expression was performed by Western blotting. Fluorescent image of endoplasmic reticulum was accomplished by using ER-Tracker Green. This study used fluorescent dye CM-H2DCFDA to detect intracellular generation of reactive oxygen species. The identified proteins can be classified into three major groups, which include proteins involved in mitochondrial function, cytoskeleton-related proteins and proteins associated with endoplasmic reticulum (ER) stress. Photoactivated Lonicera japonica caused a significant effect on the mitochondrial function and ER stress in CH27 cells. The reactive oxygen species producing was found to be involved in photoactivated Lonicera japonica-induced CH27 cell apoptosis. Mitochondria and endoplasmic reticulum are the integral targets in photoactivated Lonicera japonica-induced CH27 cell apoptosis. We also demonstrated that ethyl acetate fraction of Lonicera japonica extracts caused photocytotoxicity in a dose-dependent manner in CH27 cells. This could explain the fact that the ethyl acetate fraction of Lonicera japonica extracts may contain compounds which exhibit the photosensitizing activity in CH27 cells.


Living in a box or call of the wild? Revisiting lifetime inactivity and sarcopenia.
The accepted effects of aging in mammalian skeletal muscle are progressive atrophy and weakening, or sarcopenia. Canonical hallmarks of aging in skeletal muscle include a reduction in muscle fiber cross-sectional area, a loss in muscle fibers through apoptosis and denervation, and infiltration of connective tissue or fibrosis. Emerging thought suggests that pro-inflammatory signaling and oxidative stress may contribute to sarcopenia. Unfortunately, most of the mammalian models used to examine and understand sarcopenia are confounded by the pervasive influence of prolonged physical inactivity. Further, the potential for underlying metabolic disorder and chronic disease (e.g., type II diabetes and cardiovascular disease) may accelerate skeletal muscle wasting. Because physical inactivity may share elevated pro-inflammatory (tumor necrosis factor-alpha and inducible nitric oxide synthase) and insufficient stress response (insulin-like growth factor-1 [IGF-1], heat-shock protein 25 [HSP25], NAD-dependent deacetylase sirtuin-3 [SIRT-3], and peroxisome proliferator-activated receptor-gamma coactivator 1[PGC-1α]) signaling with aging and chronic disease, it is critical to distinguish true aging from chronic inactivity or underlying disease. Conversely, the efficacy of exercise and caloric restrictive interventions against sarcopenia in aging populations appears highly effective when (a) conducted across the lifespan, or (b) at higher intensities when commenced in middle age or later. While the prospective mechanisms by which exercise or daily activity provide have not been elucidated, upregulation of HSPs, PGC-1α, and IGF-1 may ameliorate inflammatory signaling, apoptosis, and sarcopenia. Limited data indicate that the aging phenotype exhibited by mammals living in their natural habitat (Weddell seal and shrews) express limited apoptosis and fiber atrophy, whereas significant collagen accumulation remains. In addition, aging shrews displayed a remarkable ability to upregulate antioxidant enzymes (copper, zinc isoform of superoxide dismutase, manganese isoform of superoxide dismutase, catalase, and glutathione peroxidase). It is possible that in healthy populations requiring daily activity to thrive, fibrosis and weakness, more than atrophy, may be the predominant phenotype of muscle aging until senescence. Elucidating the molecular mechanisms by which lifetime inactivity contributes to sarcopenia and chronic disease will be critical in managing the quality of life and health costs associated with our aging population.


Lysine and arginine side chains in glycosaminoglycan-protein complexes investigated by NMR, cross-linking, and mass spectrometry: a case study of the factor H-heparin interaction.
We have used the interaction between module 7 of complement factor H (CFH approximately 7) and a fully sulfated heparin tetrasaccharide to exemplify a new approach for studying contributions of basic side chains to the formation of glycosaminoglycan (GAG)-protein complexes. We first employed HISQC and H(2)CN NMR experiments to monitor the side-chain resonances of lysines and arginines in (15)N, (13)C-labeled protein during titrations with a fully sulfated heparin tetrasaccharide under physiological conditions. Under identical conditions and using (15)N-labeled protein, we then cross-linked tetrasaccharide to CFH approximately 7 and confirmed the 1:1 stoichiometry by FT-ICR-MS. We subsequently characterized this covalent protein-GAG conjugate by NMR and further MS techniques. MALDI-TOF MS identified protein fragments obtained via trypsin digestion or chemical fragmentation, yielding information concerning the site of GAG attachment. Combining MS and NMR data allowed us to identify the side chain of K405 as the point of attachment of the cross-linked heparin oligosaccharide to CFH approximately 7. On the basis of the analysis of NMR and MS data of the noncovalent and cross-linked CFH approximately 7-tetrasaccharide complexes, we conclude that the K446 side chain is not essential for binding the tetrasaccharide, despite the large chemical shift perturbations of its backbone amide (15)N and (1)H resonances during titrations. We show that R444 provides the most important charge-charge interaction within a C-terminal heparin-binding subsite of CFH approximately 7 whereas side chains of R404, K405, and K388 are the predominant contributors to an N-terminal binding subsite located in the immediate vicinity of residue 402, which is implicated in age-related macular degeneration (AMD).


Role of Ser(289) in RARgamma and its homologous amino acid residue of RARalpha and RARbeta in the binding of retinoic acid.
The biological actions of retinoic acid (RA) are mediated by retinoic acid receptors (RARalpha, -beta, and -gamma) and retinoid X receptors (RXRalpha, -beta, and -gamma). Although the ligand-binding domains of RARs and RXRs have been suggested to share the same novel folding pattern, the ligand-binding pockets of each of the retinoid receptors must have unique structural features since it has been possible to develop RAR subtype-selective and RXR-selective retinoids. We have previously demonstrated the importance for RA binding and RA-dependent transactivation of Arg(276) in RARalpha and Arg(278) in RARgamma; however, in RARbeta Arg(269) functions in conjunction with Lys(220). Here we have examined the role of the hydroxyl group of RARgamma Ser(289) and its homologous amino acid residues in RARalpha (Ser(287)) and RARbeta (Ser(280)) alone and in conjunction with their respective RARgamma Arg(278) homologs for RA binding and RA-dependent transactivation activity. The hydroxyl group of this Ser in all three RARs was found by itself not to be important for RA binding and RA-dependent transactivation activity. However, in RARalpha and RARgamma this Ser appears to play a small role in conjunction with Arg(276) and Arg(278), respectively, for these activities. Alternatively, strong synergism was observed in RARbeta between Ser(280) and Arg(269) for RA-binding and RA-dependent transactivation activity. This provides further evidence that the mechanism of interaction between the carboxylate group of retinoids and the amino acid residues in the ligand binding pocket of RARbeta is different from that of RARalpha and RARgamma.


Treatment seeking behaviour in hypertension: factors associated with awareness and medication among socioeconomically disadvantaged migrants in Delhi, India.
The present study is apart of a cross-sectional prevalence study. Descriptive statistics were used to present the awareness, treatment and control of hypertension. Multiple logistic regression analyses were performed to examine the influence of socio-demographic and other variables on awareness and on current medication use. The results reveal that only 41% of the total hypertensive persons were aware of their hypertension status, and only 59% of them were on medication. Of those treated, only 5% had controlled hypertension. Multiple logistic regression analyses reveal that gender, age, pulse rate and education were significantly associated with awareness of hypertension whereas age is the only significant factor associated with medication use. The Hosmer and Lemeshow tests for goodness of fit reveal that these regression models are a good fit. The study concludes that undiagnosed hypertension is considerable. Awareness, treatment and control of hypertension are not adequate among socioeconomically disadvantaged migrants. Since hypertension has become a common problem, the health education and awareness campaigns along with facilities such as blood pressure screening and hypertension treatment through primary health care system are essential.


Studies on the cell surface of zoospores and cysts of the fungus Phytophthora cinnamomi: nature of the surface saccharides as determined by quantitative lectin binding studies.
The nature of the surface saccharides of zoospores, "partially encysted zoospores" and cysts of the root-rotting fungus Phytophthora cinnamomi, has been examined by quantitative lectin binding studies. Zoospores bound concanavalin A (Con A), but did not bind any of a variety of other lectins tested. In contrast, both cysts and "partially encysted zoospores" bound soybean agglutinin (SBA) as well as Con A. This indicates that accessible alpha-D-glucosyl/alpha-D-mannosyl-containing glycoconjugates predominate at the zoospore surface, whereas both alpha-D-glucosyl/alpha-D-mannosyl and galactosyl and/or N-acetyl-D-galactosaminosyl residues are accessible at the surface of cysts and "partially encysted zoospores." Neither Ulex europeus lectin nor wheat germ agglutinin (WGA) bound to any of the three cell preparations, indicating the absence of accessible alpha-L-fucosyl and N-acetyl-D-glucosaminosyl residues.


Negative hyper-selection of metastatic colorectal cancer patients for anti-EGFR monoclonal antibodies: the PRESSING case-control study.
Refining the selection of metastatic colorectal cancer patients candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies. We conducted this multicentre, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations. Hypothesizing a prevalence of candidate alterations of 15% and 0% in resistant and sensitive RAS and BRAF wild-type patients, respectively, with two-sided α and β errors of 0.05 and 0.20, 47 patients per group were needed. Forty-seven patients per group were included. PRESSING panel alterations were significantly more frequent in resistant (24 out of 47, 51.1%) than in sensitive (1 out of 47, 2.1%) patients (P < 0.001) and in right- (12 out of 29, 41.4%) than left-sided (13 out of 65, 20.0%) tumours (P = 0.03). The predictive accuracy of PRESSING panel and sidedness was 75.3% and 70.2%, respectively. Among hyper-selected patients, right-sidedness was still associated with resistance (P = 0.002). The predictive accuracy of the combined evaluation of PRESSING panel and sidedness was 80.4%. As a secondary analysis, 8 (17.0%) resistant and 0 sensitive patients showed microsatellite instability (P < 0.001). The investigated panel of genomic alterations allows refining the selection of RAS and BRAF wild-type metastatic colorectal cancer patients candidates for anti-EGFRs, partially explaining and further corroborating the predictive ability of primary tumour sidedness.


Properties of strains of Escherichia coli carried in different phases of ulcerative colitis.
Strains of E. coli from the faeces of patients with active ulcerative colitis and with colitis in remission were examined for haemolysin and necrotoxin production. Cultures from 63 patients with active colitis grew haemolytic E. coli in 23 (37%) as compared with 24 (21%) from 115 patients whose disease was in remission (p < 0.05). The corresponding proportions for necrotoxin-producing strains were 22% and 12%. Of 35 patients investigated both in relapse and remission of the colitis, 14 changed their carriage of haemolytic E. coli. Thirteen of these carried haemolytic organisms in relapse but not in remission, and one carried haemolytic organisms in remission but not in relapse (p < 0.01). Strains of E. coli were also examined from specimens of faeces obtained at weekly intervals for 28 weeks from 19 patients. The acquisition of haemolytic or necrotoxic E. coli strains tended to follow rather than precede the onset of the attack in the four patients who developed a relapse of the disease during this period. Among these 19 patients haemolytic and necrotoxic strains were found most commonly when blood was regularly present in the faeces. These facts suggest that conditions in the bowel during a relapse of colitis tend to favour the presence of haemolysin- and necrotoxin-producing organisms, rather than that these organisms cause the relapse. Of 50 strains of E. coli from patients treated with sulphasalazine tested for sensitivity to sulphapyridine 49 were resistant. There was no clear relation between the activity of the colitis and the presence of any of the 27 serotypes of E. coli examined.


Pulmonary nodule characterization, including computer analysis and quantitative features.
Pulmonary nodules are commonly detected in computed tomography (CT) chest screening of a high-risk population. The specific visual or quantitative features on CT or other modalities can be used to characterize the likelihood that a nodule is benign or malignant. Visual features on CT such as size, attenuation, location, morphology, edge characteristics, and other distinctive "signs" can be highly suggestive of a specific diagnosis and, in general, be used to determine the probability that a specific nodule is benign or malignant. Change in size, attenuation, and morphology on serial follow-up CT, or features on other modalities such as nuclear medicine studies or MRI, can also contribute to the characterization of lung nodules. Imaging analytics can objectively and reproducibly quantify nodule features on CT, nuclear medicine, and magnetic resonance imaging. Some quantitative techniques show great promise in helping to differentiate benign from malignant lesions or to stratify the risk of aggressive versus indolent neoplasm. In this article, we (1) summarize the visual characteristics, descriptors, and signs that may be helpful in management of nodules identified on screening CT, (2) discuss current quantitative and multimodality techniques that aid in the differentiation of nodules, and (3) highlight the power, pitfalls, and limitations of these various techniques.


Increased susceptibility to hypoxia of prolonged action potential duration in ventricular papillary muscles from diabetic rats.
The action potential duration (APD) of ventricular muscles obtained from diabetic animals is reported to be prolonged. We studied the effect of varied periods of diabetes on APD prolongation using isolated ventricular papillary muscles from streptozocin-injected rats. We found that a diabetic period greater than 30 wk was necessary for the evolution of significant prolongation of APD. We then studied the effect of repeated hypoxia (PO2 40 mmHg) and normoxia (PO2 300 mmHg) on prolonged APD of diabetic muscles and compared the findings with those from control rats. Transmembrane potentials were recorded with conventional glass microelectrodes. Under normoxic conditions, the APDs of diabetic muscles were significantly prolonged, the maximum upstroke velocity of action potentials tended to be decreased, and the resting membrane potential was not changed significantly compared with controls. The first hypoxia (20 min) shortened the APD in both diabetic and control rats but more so in diabetic rats, thereby making the APD of diabetic rats virtually identical to the control rat APD during the hypoxia. On subsequent reoxygenation (30 min), these hypoxia-induced changes were almost recovered. The second hypoxia (20 min) produced more severe shortening of the APD in both muscle types, and the effect was again far greater in diabetic rats than controls, ending with a reversed sequence of APDs and the APD of diabetic muscles much shorter than the controls. Excessive shortening of APD in diabetic muscles during hypoxic conditions was speculated to be due to greater increases in the outward K+ current through ATP-regulated K+ channels that may be secondary to the more severe reduction of intracellular ATP concentrations in diabetic versus control hearts.


Effects of Acute Normobaric Hypoxia on Non-linear Dynamics of Cardiac Autonomic Activity During Constant Workload Cycling Exercise.
Measurements of Non-linear dynamics of heart rate variability (HRV) provide new possibilities to monitor cardiac autonomic activity during exercise under different environmental conditions. Using detrended fluctuation analysis (DFA) technique to assess correlation properties of heart rate (HR) dynamics, the present study examines the influence of normobaric hypoxic conditions (HC) in comparison to normoxic conditions (NC) during a constant workload exercise. Nine well trained cyclists performed a continuous workload exercise on a cycle ergometer with an intensity corresponding to the individual anaerobic threshold until voluntary exhaustion under both NC and HC (15% O2). The individual exercise duration was normalized to 10% sections (10-100%). During exercise HR and RR-intervals were continuously-recorded. Besides HRV time-domain measurements (meanRR, SDNN), fractal correlation properties using short-term scaling exponent alpha1 of DFA were calculated. Additionally, blood lactate (La), oxygen saturation of the blood (SpO2), and rating of perceived exertion (RPE) were recorded in regular time intervals. We observed significant changes under NC and HC for all parameters from the beginning to the end of the exercise (10% vs. 100%) except for SpO2 and SDNN during NC: increases for HR, La, and RPE in both conditions; decreases for SpO2 and SDNN during HC, meanRR and DFA-alpha1 during both conditions. Under HC HR (40-70%), La (10-90%), and RPE (50-90%) were significantly-higher, SpO2 (10-100%), meanRR (40-70%), and DFA-alpha1 (20-60%) were significantly-lower than under NC. Under both conditions, prolonged exercise until voluntary exhaustion provokes a lower total variability combined with a reduction in the amplitude and correlation properties of RR fluctuations which may be attributed to increased organismic demands. Additionally, HC provoked higher demands and loss of correlation properties at an earlier stage during the exercise regime, implying an accelerated alteration of cardiac autonomic regulation.


Purification and characterization of the active-site-mutated recombinant human mu-calpain expressed in baculovirus-infected insect cells.
Recombinant human mu-calpain whose active site Cys-115 was substituted with Ser was expressed in insect cells using baculovirus system. The mutant mu-calpain, purified using an affinity-column of calpastatin oligopeptides, had no proteolytic activities of autolysis and caseinolysis. The large subunit of the mutant mu-calpain was processed from the 80 kDa form to the 76 kDa form by the wild type calpain, supporting the intermolecular cleavage mechanism of procalpain during activation. Fluorescence polarization analysis revealed that the mutant mu-calpain retained high affinity toward fluorescein-labeled calpastatin domain 1. Fragmentation of the full-length calpastatin by the wild type calpain was enhanced by pre-incubating the inhibitor with the mutant calpain. The recombinant mutant calpain was suggested to retain the integrity of the high ordered structure of the wild type calpain.


The effect of dry heat and dry cold application on pain, anxiety and fear levels before blood sample collection in school age children (7-12 years): A randomized controlled study.
Blood sampling, which is frequently performed on children admitted to hospital, causes them pain, anxiety and fear. The study was carried out to determine the effects of dry heat and dry cold application before blood sampling on pain, anxiety and fear levels in school age children. The study was conducted between June and January 2021 with a parallel-group randomized controlled experimental design. It was carried out with 117 children who applied to the Pediatric Blood Collection Polyclinic of a training and research hospital. The children were assigned to dry heat application, dry cold application and control group by simple randomization. Data were collected using the Child-Family Introductory Information Form, Wong Baker Faces Pain Rating Scale (WBFPS), Child Fear Anxiety Scale (CFAS) and Medical Procedure Fear Scale (MPFS). In the data analysis, descriptive statistics, the Kruskal-Wallis H test, the Dunn test, Yates correction and the Pearson Chi-Square test were used. A level of p < 0.05 was considered statistically significant. It was found that children who were treated with dry heat and dry cold before blood sampling experienced less pain. The anxiety of the children in the dry heat treatment group was lower than the control group. According to the children's MPFS Operational Fear sub-dimension median scores, procedural fear was found to be lower in the dry heat application group. Pediatric nurses can safely use dry heat and dry cold application in the management of invasive procedure-related pain, and dry heat application in the management of anxiety. This trial is registered with the US National Institutes of Health (ClinicalTrials.gov) under the number NCT05974319.


Systematic review of the influence of chemotherapy-associated liver injury on outcome after partial hepatectomy for colorectal liver metastases.
The impact of chemotherapy-associated liver injury (CALI) on postoperative outcome in patients undergoing partial hepatectomy for colorectal liver metastases (CRLM) remains controversial. The objective of this study was to clarify the effect of CALI (sinusoidal dilatation (SD), steatosis and steatohepatitis) on postoperative morbidity and mortality by investigating a large data set from multiple international centres. PubMed and Embase were searched for studies published between 1 January 2004 and 31 December 2013 with keywords 'chemotherapy', 'liver resection', 'outcome' and 'colorectal metastases' to identify potential collaborating centres. Univariable and multivariable analyses were performed using binary logistic regression models, with results presented as odds ratios (ORs) with 95 per cent confidence intervals. A consolidated database comprising 788 patients who underwent hepatectomy for CRLM in eight centres was obtained. In multivariable analyses, severe SD was associated with increased major morbidity (Dindo-Clavien grade III-V; OR 1·73, 95 per cent c.i. 1·02 to 2·95; P = 0·043). Severe steatosis was associated with decreased liver surgery-specific complications (OR 0·52, 95 per cent c.i. 0·27 to 1·00; P = 0·049), whereas steatohepatitis was linked to an increase in these complications (OR 2·08, 1·18 to 3·66; P = 0·012). Subgroup analysis showed that lobular inflammation was the sole component associated with increased overall morbidity (OR 2·22, 1·48 to 3·34; P = 0·001) and liver surgery-specific complications (OR 3·35, 2·11 to 5·32; P < 0·001). Finally, oxaliplatin treatment was linked to severe SD (OR 2·74, 1·67 to 4·49; P < 0·001). An increase in postoperative major morbidity and liver surgery-specific complications was observed after partial hepatectomy in patients with severe SD and steatohepatitis. Postoperative liver failure occurred more often in patients with severe SD.


Domestication via the commensal pathway in a fish-invertebrate mutualism.
Domesticator-domesticate relationships are specialized mutualisms where one species provides multigenerational support to another in exchange for a resource or service, and through which both partners gain an advantage over individuals outside the relationship. While this ecological innovation has profoundly reshaped the world's landscapes and biodiversity, the ecological circumstances that facilitate domestication remain uncertain. Here, we show that longfin damselfish (Stegastes diencaeus) aggressively defend algae farms on which they feed, and this protective refuge selects a domesticator-domesticate relationship with planktonic mysid shrimps (Mysidium integrum). Mysids passively excrete nutrients onto farms, which is associated with enriched algal composition, and damselfish that host mysids exhibit better body condition compared to those without. Our results suggest that the refuge damselfish create as a byproduct of algal tending and the mutual habituation that damselfish and mysids exhibit towards one another were instrumental in subsequent mysid domestication. These results are consistent with domestication via the commensal pathway, by which many common examples of animal domestication are hypothesized to have evolved.


Endocrinological disorders and inflammatory skin diseases during COVID-19 outbreak: a review of the literature.
In the next future, dermatologists, endocrinologist and physicians may cope with the impact of extent SARS-CoV-2 (COVID-19) infection over chronic inflammatory skin diseases and their treatment. COVID-19 pandemic obliged many countries to impose social restrictions, resulting in the need to adapt daily lifestyle habits and working activities. These changes have drastically reduced physical activity and social interactions, with the possible increase of anxiety, eating disorders and weight gain. We searched for relevant studies (trials, real-life studies and case reports, meta-analysis, pooled data analysis, reviews) on endocrine disorders and inflammatory skin diseases. The database used was PubMed. The studies included were those published in the English language between January 1, 2018 and May 5, 2020. Several studies have been previously showed the association of overweight and obesity, with the metabolic syndrome and insulin-resistance. It has been demonstrated how these conditions correlate with the worsening of such chronic inflammatory skin diseases, such as psoriasis, hidradenitis suppurativa and acne. Many evidences suggest an important role of adipose tissue in the production of pro-inflammatory cytokines (Leptin, adiponectin, TNFα, IL-6, MCP-1, PAI-1), involved in the pathogenesis and the exacerbations of these skin diseases. In addition, we should expect an increasing incidence rate of hypovitaminosis D in the next future due to reduced sun exposure caused by isolation at home and missed holidays. Scientific evidences already show the important immunomodulating role of vitamin D in inflammatory skin diseases. Our study pays attention on medium-long term effects of COVID-19 outbreak on inflammatory skin disorders, due to the lifestyle changes. In such context this review considers how a multidisciplinary approach, involving dermatologists, nutritionists and endocrinologists, may lead to a better management of dermatologic patients.


Demonstration of a landscape-scale approach for predicting acute copper toxicity to larval fathead minnows (Pimephales promelas) in surface waters.
Watersheds have historically been used as the appropriate spatial classification unit for managing water resources. However, geology, soil type, predominant vegetation, and climate have obvious influences on water quality and are not constrained by watercourses or political boundaries. This concept has evolved for several decades and developed the concept of ecoregions and other spatial schemes. While this approach to water resource management has considered the interaction between water quality and biological integrity (aquatic community structure and assemblage), it has not been applied in the context of predicting aquatic toxicity. As such, a previously published study providing a chemical and toxicological data set consisting of 24 sampling sites in South Carolina, USA, and was used to develop empirical models for predicting acute copper (Cu) toxicity to larval fathead minnows (Pimephales promelas). Moreover, numerous spatial classifications (hydrologic units, ecoregions, stream order, adjacent land use, and proximity to certain land uses) and seasonality were used to delineate sites and develop empirical models based on these different classifications. An independent sampling and testing regime was implemented to determine the performance of the empirical models and whether certain classifications could be used to extrapolate toxicity data across spatial landscapes. Additionally, a computational model (biotic ligand model [BLM]) for deriving site-specific water quality criteria for Cu also was used as a reference for current regulatory application. Empirical models based on delineations of stream order, hydrologic unit, and downstream distance to urbanization accurately predicted at least 60% of the observed Cu toxicity values within the supplemental data set. Delineations based on adjacent land use, ecoregions, and seasons were not as useful for predicting acute Cu toxicity but demonstrated better performance than the BLM.


Survey of laboratory practices for diagnosis of fungal infection in seven Asian countries: An Asia Fungal Working Group (AFWG) initiative.
An online survey of mycology laboratories in seven Asian countries was conducted to assess the status, competence, and services available. Country representatives from the Asia Fungal Working Group (AFWG) contacted as many laboratories performing mycology diagnosis as possible in their respective countries, requesting that the laboratory heads complete the online survey. In total, 241 laboratories responded, including 71 in China, 104 in India, 11 in Indonesia, 26 in the Philippines, four in Singapore, 18 in Taiwan, and seven in Thailand. Overall, 129/241 (53.5%) surveyed mycology laboratories operate as separate designated mycology laboratories, 75/241 (31.1%) conduct regular formal staff training, 103/241 (42.7%) are accredited, and 88/157 (56.1%) participate in external quality assurance scheme (EQAS) programs. Microscopy and culture methods are available in nearly all laboratories, although few perform DNA sequencing (37/219; 16.9%) or use matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) (27/219; 12.3%) for isolate identification. Antifungal susceptibility testing is performed in 142/241 (58.9%) laboratories, mainly for yeasts. The most commonly performed nonculture diagnostic is cryptococcal antigen testing (66 laboratories), followed by galactomannan testing (55), polymerase chain reaction (PCR) diagnosis (37), and beta-D-glucan testing (24). Therapeutic drug monitoring is conducted in 21 laboratories. There is almost no access to advanced diagnostic tests, like galactomannan, β-D-glucan, and PCR, in the surveyed laboratories in Indonesia, the Philippines, and Thailand. These results highlight the need for development of quality laboratories, accreditation and training of manpower in existing laboratories, and access to advanced non-culture-based diagnostic tests to facilitate the diagnosis of fungal infections in Asia.


Homeostatic responses of colonic LGR5+ stem cells following acute in vivo exposure to a genotoxic carcinogen.
Perturbations in DNA damage, DNA repair, apoptosis and cell proliferation in the base of the crypt where stem cells reside are associated with colorectal cancer (CRC) initiation and progression. Although the transformation of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5)(+) cells is an extremely efficient route towards initiating small intestinal adenomas, the role of Lgr5(+) cells in CRC pathogenesis has not been well investigated. Therefore, we further characterized the properties of colonic Lgr5(+) cells compared to differentiated cells in Lgr5-EGFP-IRES-creER(T2) knock-in mice at the initiation stage of carcinogen azoxymethane (AOM)-induced tumorigenesis using a quantitative immunofluorescence microscopy approach. At 12 and 24h post-AOM treatment, colonic Lgr5(+) stem cells (GFP(high)) were preferentially damaged by carcinogen, exhibiting a 4.7-fold induction of apoptosis compared to differentiated (GFP(neg)) cells. Furthermore, with respect to DNA repair, O(6)-methylguanine DNA methyltransferase (MGMT) expression was preferentially induced (by 18.5-fold) in GFP(high) cells at 24h post-AOM treatment compared to GFP(neg) differentiated cells. This corresponded with a 4.3-fold increase in cell proliferation in GFP(high) cells. These data suggest that Lgr5(+) stem cells uniquely respond to alkylation-induced DNA damage by upregulating DNA damage repair, apoptosis and cell proliferation compared to differentiated cells in order to maintain genomic integrity. These findings highlight the mechanisms by which colonic Lgr5(+) stem cells respond to cancer-causing environmental factors.


99mTc-HMPAO brain single photon emission computerized tomography in mitochondrial encephalomyopathies.
Mitochondrial encephalomyopathies are heterogeneous diseases with common clinical features of muscle and/or the central nervous system. Although molecular and histological diagnoses have been established, imaging modalities for the functioning evaluation of these patients are still obscure. In this study, we tried to use 99mTc-HMPAO brain SPECT images to analyze various mitochondrial encephalomyopathies. We examined 99mTc-HMPAO Brain SPECT studies of 15 patients with various types of mitochondrial encephalomyopathy (3 Leber's hereditary optic neuropathy (LHON), 4 Kearns-Sayre syndrome (KSS), 4 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), 3 myoclonic epilepsy and ragged-red fiber disease (MERRF), and 1 Leigh syndrome), diagnosed by molecular studies. The results of our studies show obviously decreased radiotracer accumulation in the parieto-temporal regions after stroke-like episodes in patients with MELAS and MERRF: Relatively diminished brain perfusion in patients with KSS is noted, probably secondary to severe encephalomyopathy or subdural effusion. However, there seems to be no significant correlation between the clinical manifestations and the imaging findings in LHON and Leigh. 99mTc-HMPAO Brain SPECT is useful in the diagnosing and assessment of the progress of MERRF, MELAS and KSS. However, its role in LHON and Leigh syndrome seems to be debatable.


Common fate, different experience: gender-specific aspects of the Armenian Genocide, 1915-1917.
Violence against women was a central feature of the Armenian Genocide. Even before the mass killings, sexual humiliation was used to intimidate the Armenian community. After the murder of the Armenian leadership and men of military age, Ottoman authorities and Ittihadist supporters deported surviving Armenians from Anatolia into the Syrian desert. During this ethnic cleansing, rape, kidnapping, sex slavery, and forced re-marriage became de facto instruments of genocide. Eyewitness accounts and diplomatic reports shed light on the place of gender during genocidal persecution. Although scholarship has only recently begun to explore the issue, the Armenian Genocide offers opportunities for comparative gender studies.


[Clinical chemical diagnosis of affective diseases by means of a neuroendocrine function test (author's transl)].
The stimulation of pituitary hormone secretion with thyroliberin and by insulin-induced hypoglycemia was investigated on 52 depressive patients and 12 postdepressive, lithiumtreated subjects. The serum concentrations of somatotropin, cortisol, prolactin, thyrotropin and glucose were followed for 2 hours. Differences in the neuroendocrine response between endogenous and reactive (neurotic) depressive patients were observed, and changes during the course of the diseases were also recorded. 1. Stimulation of somatotropin and cortisol secretion, and the decrease of glucose are diminished in endogenous depressive patients, as compared to those of reactive depressive patients and healthy controls. 2. Somatotropin stimulation maxima below 40 mU/l in depressive phase are indicative of endogenous depression, rather than the reactive form, with a confidence probability of 0.9. 3. An increase in the stimulation of somatotropin and cortisol secretion can be shown after termination of endogenous depression. However, the somatotropin maxima are then also lower than those found in reactive depression. 4. The stimulation of somatotropin secretion in lithiumtreated psychosis-free subjects shows no difference from that of healthy controls; thyrotropin secretion increase. The weak, insulin-induced hypoglycemia, observed in these subjects, is higher (66%) than in the healthy controls. 5. Fear and agitation have an inhibitory effect on the stimulation of the prolactin secretion during the depressive phase. The pituitary stimulation test offers a means of ascertaining the disturbed neuroendocrine function in affective diseases and objectifying the differential diagnosis of depressive syndromes.


Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K+ current.
To define how insulin acts in hypokalemic periodic paralysis (HypoPP). HypoPP results from point mutations of the skeletal muscle L-type Ca2+ channel. Attacks of flaccid paralysis are associated with hypokalemia and triggered by insulin. A persistent inward current causes depolarization-induced paralysis. The relationships of the Ca2+ channel mutations to the persistent inward current and how insulin triggers paralytic attacks are not yet known. Intercostal muscle fibers from HypoPP and normal subjects were studied in vitro at 37 degrees C using two electrodes to determine action potential thresholds and a three-electrode voltage clamp to study membrane currents. HypoPP fibers were depolarized in bathing solution with 4 mM K+. Reducing K+ from 4.0 mM to 2.5 or 1.0 mM depolarized HypoPP fibers but hyperpolarized normal fibers. Adding 12 mU/mL of insulin to bathing fluids increased the depolarization of HypoPP fibers and increased the hyperpolarization of normal fibers. Depolarized HypoPP had increased action potential thresholds. The fraction of excitable muscle fibers decreased with increasing fiber depolarization. Blocking Na+ channels or L-type Ca2+ channels did not prevent depolarization induced by hypokalemia or by insulin. Insulin reduced the conductance of the inward rectifier K+ channel for outward-flowing currents. Insulin potentiates depolarization of hypokalemic periodic paralysis (HypoPP) fibers by reducing inward rectifier K+ conductance. The Ca2+ mutations in HypoPP indirectly derange membrane excitability by altering the function of other membrane channels.


Histophysiology of the microvascular bed in experimental trauma.
1. Morphohistological changes in a focus of spinal cord trauma have a phasic character, with a period of primary lesions (5-30 min after traumatization) and a period of secondary lesions (1-23 h after traumatization). 2. Variation of transport enzyme activities in the walls of the microvessels of the traumatized spinal cord is characterized by an undulating course and by asynchrony of the peaks of Mg-dependent ATPase and alkaline phosphatase activity. 3. With reference to the rapid drop in the given enzyme activities and to progressive necrotic changes in the traumatized spinal cord, it is desirable that the cord circulation should be corrected within the first few hours after traumatization.


[Quality assurance by improved cooperation?--Results of a study of prenatal care in Berlin].
Cooperation between the various participants of Public Health services is now recognised as a significant factor to ensure quality in health services. The German system of prenatal care is, because of its heterogenic structure, particularly dependent on a functioning co-ordination between the individual providers of services to pregnant women. However, cooperation between gynaecologists, midwives, social workers and others working in this field in Germany has proved considerably deficient. Within the framework of a qualitative study on the situation of services available to pregnant women in four selected districts of Berlin, a number of decisive barriers to cooperation could be identified, e.g. deficient mutual information among providers, differing concepts of care, as well as different structural and economic conditions of the various members within the health system. On the other hand, a number of different approaches at different levels were perceived which may allow for a better cooperation between the various participants. The results of the study were discussed at conferences attended by regional experts. As a pragmatic aid for the advancement of cooperation, community guides orientated around the needs of pregnant women were drafted for each of the four districts.


Wearing face masks in public during the influenza season may reflect other positive hygiene practices in Japan.
Although the wearing of face masks in public has not been recommended for preventing influenza, these devices are often worn in many Asian countries during the influenza season. In Japan, it is thought that such behavior may be an indicator of other positive hygiene practices. The aim of this study, therefore, was to determine if wearing a face mask in public is associated with other positive hygiene practices and health behaviors among Japanese adults. We initially recruited around 3,000 Japanese individuals ranging from 20 to 69 years of age who were registered with a web survey company. Participants were asked to recall their personal hygiene practices during the influenza season of the previous year. Logistic regression analysis was then used to examine the associations between wearing a face mask in public and personal hygiene practices and health behaviors. A total of 3,129 persons responded to the survey, among whom 38% reported that they had worn a face mask in public during the previous influenza season. Wearing a face mask in public was associated with various self-reported hygiene practices including: frequent hand washing (adjusted Odds Ratio [OR]: 1.67; 95% Confidence Interval [95%CI]: 1.34-1.96), occasional hand washing (OR: 1.43; 95%CI: 1.10-1.75), frequently avoiding crowds (OR: 1.85; 95%CI: 1.70-1.98), occasionally avoiding crowds (OR: 1.65; 95%CI: 1.53-1.76), frequent gargling (OR: 1.68; 95%CI: 1.51-1.84), occasional gargling (OR: 1.46; 95%CI: 1.29-1.62), regularly avoiding close contact with an infected person (OR: 1.50; 95%CI: 1.33-1.67), occasionally avoiding close contact with an infected person (OR: 1.31; 95%CI: 1.16-1.46), and being vaccinated of influenza in the last season (OR: 1.31; 95%CI: 1.17-1.45). Overall, this study suggests that wearing a face mask in public may be associated with other personal hygiene practices and health behaviors among Japanese adults. Rather than preventing influenza itself, face mask use might instead be a marker of additional, positive hygiene practices and other favorable health behaviors in the same individuals.


[Malignant tumors of extrahepatic bile ducts].
In connection with increased incidence of extrahepatic bile duct cancer, clinicalpathological characteristics, treatment and prognosis of this particular tumor are revised on the basis of data obtained from patients series observed by the authors and from those of the reference.


Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma.
Glioblastoma (GBM) is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq) on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor's genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration.


Exponential growth using the internet and your web site.
Developing a successful Internet strategy can help attract new patients and take your practice to the next level. Today, as the Internet has evolved, it is more important than ever, especially as your competitors are likely pursuing more aggressive strategies themselves. There are several important components involved, and maximizing your efforts with each can help create a comprehensive and sound strategy that achieves significant results. Behind such a strategy you will find a strong focus in many areas, including Web site development, search engine optimization, link building, content creation, blogs, video, choosing a vendor, patient conversion, Web 2.0, social networking, reputation management, and more. Understanding each of these areas, and the efforts required to tackle each effectively, can help you ensure that your own Internet strategy is functioning well and reaching its true potential.


Peripheral mitochondrial dysfunction in Alzheimer's disease: focus on lymphocytes.
Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. Today, AD affects millions of people worldwide and the number of AD cases will increase with increased life expectancy. The AD brain is marked by severe neurodegeneration like the loss of synapses and neurons, atrophy and depletion of neurotransmitter systems in the hippocampus and cerebral cortex. Recent findings suggest that these pathological changes are causally induced by mitochondrial dysfunction and increased oxidative stress. These changes are not only observed in the brain of AD patients but also in the periphery. In this review, we discuss the potential role of elevated apoptosis, increased oxidative stress and especially mitochondrial dysfunction as peripheral markers for the detection of AD in blood cells especially in lymphocytes. We discuss recent not otherwise published findings on the level of complex activities of the respiratory chain comprising mitochondrial respiration and the mitochondrial membrane potential (MMP). We obtained decreased basal MMP levels in lymphocytes from AD patients as well as enhanced sensitivity to different complex inhibitors of the respiratory chain. These changes are in line with mitochondrial defects obtained in AD cell and animal models, and in post-mortem AD tissue. Importantly, these mitochondrial alterations where not only found in AD patients but also in patients with mild cognitive impairment (MCI). These new findings point to a relevance of mitochondrial function as an early peripheral marker for the detection of AD and MCI.


Consumers' Suggestions for Improving the Mental Healthcare System: Options, Autonomy, and Respect.
While the mental healthcare-consumer voice has gained in legitimacy and perceived value, policy initiatives and system improvements still lack input from consumers. This study explores consumers' suggestions for improving the mental healthcare system. Participants (N = 46) were conveniently recruited and responded to an online survey asking: "What are your suggestions for improving the mental healthcare system?" Eight themes were identified using iterative, inductive and deductive coding. Themes included treatment options, autonomy and empowerment, respect and relationships, medication management, peer support, insurance and access, funding and government support, and treatment environment. Theoretically, there is interdependence among themes where five of the themes are foundational for the three main themes (i.e. treatment options, autonomy and empowerment, respect and relationships). Findings suggest that consumers see the need for improvement in patient-centered care. While access is the focus of much mental healthcare policy discussions, the ultimate goal should be provisioning person-centered mental healthcare.


Urodynamic effects of terazosin treatment for Japanese patients with symptomatic benign prostatic hyperplasia.
For treating benign prostatic hyperplasia (BPH) 5 or 10 mg. terazosin hydrochloride daily has been routinely used in North America and Europe. We investigated the urodynamic effects of 2 mg. terazosin daily on Japanese patients with symptomatic BPH using pressure flow study. A total of 20 Japanese patients 50 years old or older with symptomatic BPH underwent symptomatic and urodynamic evaluations, including pressure flow study, before and after terazosin treatment. Patients were given 1 mg. terazosin once daily for the first 7 days and they continued to receive 1 mg. terazosin twice daily for the following 3 weeks. At 4 weeks after terazosin treatment the International Prostate Symptom Score, quality of life index and maximum and average flow rates were significantly improved. Pressure flow study demonstrated decreased detrusor pressure at maximum flow, and minimum detrusor pressure during voiding and urethral resistance factor after terazosin treatment. Of the 20 patients 13 (65%) showed improvement in the linear passive urethral resistance relation. There was no significant difference in the maximum W. factor before and after terazosin treatment. Terazosin treatment, even 2 mg. daily, urodynamically relieved bladder outlet obstruction in Japanese patients with symptomatic BPH without any changes in detrusor contractility.


What Is Nonconsensual Sex? Young Women Identify Sources of Coerced Sex.
Extending the American Psychological Association (APA) report on the Sexualization of Girls, this study investigated how young women identified sources of coerced sex. Findings from three focus groups with 25 Black and White adolescent women uncovered a perceived overarching force that "pushed" them to have sex before they felt ready. Participants identified four domains of coerced sex: (a) Sociocultural Context, (b) Internalized Sexual Scripts, (c) Partner Manipulation of Sexual Scripts, and (d) Developmental Status. Coerced sex was a complex system consisting of cultural, peer, and internal messages that create pressures to engage in sexual activities. Future implications for research and practice are presented.


Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol: Longitudinal Data from a 7-Year Study in Crohn's Disease.
Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease. PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. Of the CZP-ADAb-positive patients, 40 (22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.


[Quantitative analysis of differential proteins in renal tissues of rats with chronic intermittent hypoxic exposure based on TMT and PRM technology].
To screen the differentially expressed proteins in the kidneys of rats exposed to chronic intermittent hypoxia (CIH) based on TMT-PRM technology to identify the potential biomarkers of renal injuries induced by CIH. Twenty SD rats were randomized into two groups (n=10) and exposed to CIH or normoxia. After 12 weeks of exposure, the kidneys of the rats were collected for observing pathological changes. The renal proteins were extracted, enzymatically digested and labelled with TMT, and LC-MS/MS was used to identify the proteins. The data were processed using Proteome Discoverer2.4 for bioinformatic analysis of the differentially expressed proteins. PRM technology was used to verify the expression of the candidate proteins. CIH induced obvious renal injury in the rats, manifested by irregular glomerulus and swelling of the epithelial cells of the renal tubules. A total of 31 differentially expressed proteins were identified in CIH rats, including 22 up-regulated and 9 down-regulated proteins. Enrichment analysis of GO function and KEGG pathway analysis showed that the differentially expressed proteins participated mainly in the biological processes of cell adhesion, hypoxic stress, and calcium ions and were involved in the PPAR, AMPK, and metabolic pathways. In PRM quantitative analysis, 3 proteins, namely P07379 (PCK1), P19132 (Fth1) and Q5XI79 (Ndufaf7), showed results consistent with those of TMT-quantitative proteomic analysis. Thirty-one differentially expressed proteins were identified in the renal tissues of rats with CIH exposure, and among them P07379 (PCK1), P19132 (Fth1), and Q5XI79 (Ndufaf7) may be the key proteins closely related to the renal injury in induced by CIH.


Genome-wide analysis of histone modifications in human pancreatic islets.
The global diabetes epidemic poses a major challenge. Epigenetic events contribute to the etiology of diabetes; however, the lack of epigenomic analysis has limited the elucidation of the mechanistic basis for this link. To determine the epigenetic architecture of human pancreatic islets we mapped the genome-wide locations of four histone marks: three associated with gene activation-H3K4me1, H3K4me2, and H3K4me3-and one associated with gene repression, H3K27me3. Interestingly, the promoters of the highly transcribed insulin and glucagon genes are occupied only sparsely by H3K4me2 and H3K4me3. Globally, we identified important relationships between promoter structure, histone modification, and gene expression. We demonstrated co-occurrences of histone modifications including bivalent marks in mature islets. Furthermore, we found a set of promoters that is differentially modified between islets and other cell types. We also use our histone marks to determine which of the known diabetes-associated single-nucleotide polymorphisms are likely to be part of regulatory elements. Our global map of histone marks will serve as an important resource for understanding the epigenetic basis of type 2 diabetes.


A role for Tau protein in maintaining ribosomal DNA stability and cytidine deaminase-deficient cell survival.
Cells from Bloom's syndrome patients display genome instability due to a defective BLM and the downregulation of cytidine deaminase. Here, we use a genome-wide RNAi-synthetic lethal screen and transcriptomic profiling to identify genes enabling BLM-deficient and/or cytidine deaminase-deficient cells to tolerate constitutive DNA damage and replication stress. We found a synthetic lethal interaction between cytidine deaminase and microtubule-associated protein Tau deficiencies. Tau is overexpressed in cytidine deaminase-deficient cells, and its depletion worsens genome instability, compromising cell survival. Tau is recruited, along with upstream-binding factor, to ribosomal DNA loci. Tau downregulation decreases upstream binding factor recruitment, ribosomal RNA synthesis, ribonucleotide levels, and affects ribosomal DNA stability, leading to the formation of a new subclass of human ribosomal ultrafine anaphase bridges. We describe here Tau functions in maintaining survival of cytidine deaminase-deficient cells, and ribosomal DNA transcription and stability. Moreover, our findings for cancer tissues presenting concomitant cytidine deaminase underexpression and Tau upregulation open up new possibilities for anti-cancer treatment.Cytidine deaminase (CDA) deficiency leads to genome instability. Here the authors find a synthetic lethal interaction between CDA and the microtubule-associated protein Tau deficiencies, and report that Tau depletion affects rRNA synthesis, ribonucleotide pool balance, and rDNA stability.


The political economy of sugar-sweetened beverage taxation in Latin America: lessons from Mexico, Chile and Colombia.
In Latin America, total sales of sugar-sweetened beverages (SSBs) continue to rise at an alarming rate. Consumption of added sugar is a leading cause of diet-related non-communicable diseases (NCDs). Coalitions of stakeholders have formed in several countries in the region to address this public health challenge including participation of civil society organizations and transnational corporations. Little is currently known about these coalitions - what interests they represent, what goals they pursue and how they operate. Ensuring the primacy of public health goals is a particular governance challenge. This paper comparatively analyses governance challenges involved in the adoption of taxation of sugar-sweetened beverages in Mexico, Chile and Colombia. The three countries have similar political and economic systems, institutional arrangements and regulatory instruments but differing policy outcomes. We analysed the political economy of SSB taxation based on a qualitative synthesis of existing empirical evidence. We identify the key stakeholders involved in the policy process, identified their interests, and assess how they influenced adoption and implementation of the tax. Coalitions for and against the SSB taxation formed the basis of policy debates in all three countries. Intergovernmental support was critical to framing the SSB tax aims, benefits and implementation; and for countries to adopt it. A major constraint to implementation was the strong influence of transnational corporations (TNCs) in the policy process. A lack of transparency during agenda setting was notably enhanced by the powerful presence of TNCs. NCDs prevention policies need to be supported across government, alongside grassroots organizations, policy champions and civil society groups to enhance their success. However, governance arrangements involving coalitions between public and private sector actors need to recognize power asymmetries among different actors and mitigate their potentially negative consequences. Such arrangements should include clear mechanisms to ensure transparency and accountability of all partners, and prevent undue influence by industry interests associated with unhealthy products.


The Role of Hemoglobin A1C in Diabetes Screening and Diabetic Retinopathy.
Hemoglobin A1C (A1C) is used in various settings. Its performance has not been evaluated systemically. We compared A1C in diagnosis of diabetes with fasting plasma glucose (FPG) and 2-h postchallenged plasma glucose (2hPG) parameters in a cross-sectional cohort in the United Stated. Adult subjects (≥20 years) were identified from the National Health and Nutrition Examination Survey 2005-2016 without a history of diabetes who had BMI, A1C, FPG, and 2hPG (n = 10,416). For comparisons, we calculated the sample weighted prevalence, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with subgroup analyses. For the retinopathy study, diabetic subjects with established diabetes who responded to the question of diabetic retinopathy were evaluated (n = 3907). Compared to the FPG/2hPG criteria, A1C ≥ 48 mmol/mol (6.5%) had a low sensitivity at 25.90%, with specificity 99.70%, PPV 84.70%, and NPV 95.70%. Subgroup analyses revealed a lower sensitivity in males (24.52%); the lowest in non-Hispanic White (21.35%), in the third decade (14.32%), and in the BMI < 22.50 kg/m2 group (7.21%). The prevalence of self-reported diabetic retinopathy increased drastically with an inflection point at A1C 48 mmol/mol (6.5%) from 11.52% to 18.32% (p < 0.0001). A1C ≥ 48 mmol/mol (6.5%) should be cautiously used to diagnose diabetes in certain subgroups due to very low sensitivity in certain groups. With the confirmation of the association of increasing self-reported diabetic retinopathy with A1C ≥ 48 mmol/mol (6.5%), the current A1C cutoff is an acceptable value with the understanding of especially low sensitivity in certain subgroups.


Impact of male-partner-focused interventions on breastfeeding initiation, exclusivity, and continuation.
Informal sources of support, particularly the male partner, have more influence on breastfeeding behaviors than formal support from health care providers. This systematic review examined the impact of male-partner-focused breastfeeding interventions on breastfeeding initiation, exclusivity, and continuation. Four unique interventions were identified that were tested through randomized controlled studies or quasi-experimental design. These 4 provided breastfeeding education to fathers, with breastfeeding outcomes reported by the mother. Three of the 4 studies compared initiation rates between intervention and control conditions, and 2 showed significantly higher rates of breastfeeding initiation in the intervention group. Although studies were inconsistent in their categorization and reporting of full, partial, or no breastfeeding, significantly higher rates of breastfeeding initiation, exclusivity, and/or continuation were seen for 2 interventions. Because all 4 interventions found at least 1 breastfeeding outcome to be superior in the treatment group, breastfeeding education should be offered to male partners. Future studies should test if intervention effectiveness can be increased if education is supplemented with other activities. Future studies also should use controlled designs and validated outcome measures.


p53-Ubl fusions as models of ubiquitination, sumoylation and neddylation of p53.
The tumour suppressor p53 has been shown to be modified at its C-terminus with ubiquitin and the ubiquitin-like proteins SUMO and NEDD8. Whereas monoubiquitination of p53 is strongly associated with nuclear export, the effects of sumoylation and neddylation remain unclear. In this study we have generated p53-Ub, p53-SUMO-1 and p53-NEDD8 fusion proteins as models for the effect of these modifications on the localization and function of p53. As shown before, the ubiquitin fusion clearly drives nuclear export of p53 and we now find that this is also partially the case for a SUMO-1 fusion, which does not localise to PML bodies. In contrast a NEDD8 fusion has little effect on nuclear export, and mutating NEDD8 to more closely resemble ubiquitin did not restore nuclear export. Despite their differing subcellular localization, we find that both p53-ubiquitin and p53-NEDD8 retain similar transcriptional activity and both induce apoptosis at a similar level to unfused p53. The p53-ubiquitin fusion protein is potentially a good model for studying the role of p53 outside the nucleus. However, in our experiments we find that the export of p53 from the nucleus is not sufficient to activate its cytoplasmic apoptotic function which may depend on the ability to deubiquitinate cytoplasmic p53.


An integrated 16/spl times/16 PVDF pyroelectric sensor array.
This paper presents a fully integrated PVDF-on-silicon pyroelectric sensor array. The pyroelectric sensor has two main features: a subpixel low noise charge amplifier and a self-absorbing layered structure. The integrated low noise charge amplifier is implemented in a standard CMOS process technology. It is located directly under the sensing structure, maximizing the pixel fill factor. The self-absorbing pyroelectric sensor is a three-layer stack, consisting of a conductive polymer as an absorber layer and front electrode, a thin PVDF film as the pyroelectric material, and a rear metal layer acting as a reflector layer and rear electrode. The manufacture of the pyroelectric sensor array requires five maskless post-CMOS processing steps and is compatible with any n-well, double metal, double polysilicon, CMOS process. The array has an average pixel voltage sensitivity of 2200 V/W at 100 Hz, an NEP of 2.4/spl times/10/sup -11/ W//spl radic/Hz at 100 Hz, and a specific detectivity of 4.4/spl times/10/sup 8/ cm /spl radic/Hz/W at 100 Hz.


[Hypernatremia as a predictor of poor outcomes in children with severe brain injury].
The aim of the study was to elucidate a relationship between the development of hypernatremia and the frequency of poor outcomes in children with severe brain injury (SBI). The retrospective study enrolled 77 children (54 boys and 23 girls) aged 1 month to 18 years, who had SBI in the period of January 2008 to September 2009, and were divided into 3 groups after treatment termination. The admission injury severity criterion was Glasgow coma scale (8 scores or less) rating. Group A comprised 51 children with SBI without hypernatremia; Group B included 14 children with SBI and hypernatremia. Group C consisted of 12 children with SBI, hypernatremia, and polyuremia. The latter group was appraised as a group with evolving central diabetes insipidus. A total of 26 (33.8%) patients had hypernatremia. Poor outcomes (Glasgow outcome scores of 1-3) at 30 days were noted in only Groups B and C: comparison of outcomes in Groups B and C showed the higher incidence of poor outcomes in 10 (84%) Group C patients (with hypernatremia and polyuria) and 4 (28%) children in Group B. Comparison of Groups B and C children indicated that the hazard ratio was 0.3. Therefore, the risk of poor outcomes is much higher in the development of central diabetes insipidous in the presence of hypernatremia.


Generation of iPSC lines with SLC16A2:G401R or SLC16A2 knock out.
The X-linked Allan-Herndon-Dudley syndrome (AHDS) is characterized by severely impaired psychomotor development and is caused by mutations in the SLC16A2 gene encoding the thyroid hormone transporter MCT8 (monocarboxylate transporter 8). By targeting exon 3 of SLC16A2 using CRISPR/Cas9 with single-stranded oligodeoxynucleotides as homology-directed repair templates, we introduced the AHDS patient missense variant G401R and a novel knock-out deletion variant (F400Sfs*17) into the male healthy donor hiPSC line BIHi001-B. We successfully generated cerebral organoids from these genome-edited lines, demonstrating the utility of the novel lines for modelling the effects of MCT8-deficency on human neurodevelopment.


Accurate long-term prediction of height during the first four years of growth hormone treatment in prepubertal children with growth hormone deficiency or Turner Syndrome.
The study aim was to develop and validate models for long-term prediction of growth in prepubertal children with idiopathic growth hormone deficiency (GHD) or Turner syndrome (TS) for optimal, cost-effective growth hormone (GH) therapy. Height was predicted by sequential application of annual prediction algorithms for height velocity in cohorts of GHD (n = 664) and TS (n = 607) as documented within KIGS (Pfizer International Growth Database). As height prediction models also require an estimate of weight, new algorithms for weight increase during the first to fourth prepubertal years on GH were developed. When height was predicted from the start of GH treatment, the predicted and observed mean (SD) gain over 4 years was 30.4 (3.4) cm and 30.1 (4.9) cm, respectively, in GHD patients, and 27.2 (2.2) cm and 26.6 (3.5) cm, respectively, in TS patients. For all 4 years, gains of weight SD scores (SDS) were accurately described as a function of weight SDS and observed gain in height SDS (R(2) > 0.89). In GHD and TS patients treated with GH, an accurate prepubertal long-term prediction of height development in groups is possible. Based on this, an optimal individual height outcome could be simulated.


Temperature dependence of the benzodiazepine-receptor interaction.
The temperature dependence of the interaction of three benzodiazepines with their receptors in rat brain membranes containing about 2 microM (endogenous) gamma-aminobutyric acid was investigated. van't Hoff plots of the equilibrium dissociation constants were linear for [3H]diazepam and its N-desmethyl derivative (N-desmethyldiazepam, NDz), whereas for [3H]flunitrazepam a break between two linear portions occurred at about 10 degrees. Binding of diazepam, NDz, and flunitrazepam (for the latter, at temperature greater than 10 degrees) is enthalpy-driven (delta H approximately -40 to -50 kJ/mole with a negligible contribution from delta S. The latter result indicates that the interaction is not a simple hydrophobic association, but that it may be more complex in nature, possibly involving a conformational transition of the receptor-ligand complex. The activation energy for dissociation of the [3H]flunitrazepam- and [3H]diazepam-receptor complexes is about 100 kJ/mole. Consequently, the complexes dissociate about 100 times faster on changing temperature from 0 degrees to 37 degrees.


Incentive and Reminder Strategies to Improve Response Rate for Internet-Based Physician Surveys: A Randomized Experiment.
Most research on how to enhance response rates in physician surveys has been done using paper surveys. Uncertainties remain regarding how to enhance response rates in Internet-based surveys. To evaluate the impact of a low-cost nonmonetary incentive and paper mail reminders (formal letter and postcard) on response rates in Internet-based physician surveys. We executed a factorial-design randomized experiment while conducting a nationally representative Internet-based physician survey. We invited 3966 physicians (randomly selected from a commercial database of all licensed US physicians) via email to complete an Internet-based survey. We used 2 randomly assigned email messages: one message offered a book upon survey completion, whereas the other did not mention the book but was otherwise identical. All nonrespondents received several email reminders. Some physicians were further assigned at random to receive 1 reminder via paper mail (either a postcard or a letter) or no paper reminder. The primary outcome of this study was the survey response rate. Of the 3966 physicians who were invited, 451 (11.4%) responded to at least one survey question and 336 (8.5%) completed the entire survey. Of those who were offered a book, 345/2973 (11.6%) responded compared with 106/993 (10.7%) who were not offered a book (odds ratio 1.10, 95% CI 0.87-1.38, P=.42). Regarding the paper mail reminder, 168/1572 (10.7%) letter recipients, 148/1561 (9.5%) postcard recipients, and 69/767 (9.0%) email-only recipients responded (P=.35). The response rate for those receiving letters or postcards was similar (odds ratio 1.14, 95% CI 0.91-1.44, P=.26). Offering a modest nonmonetary incentive and sending a paper reminder did not improve survey response rate. Further research on how to enhance response rates in Internet-based physician surveys is needed.


Berry fruits modulated endothelial cell migration and angiogenesis via phosphoinositide-3 kinase/protein kinase B pathway in vitro in endothelial cells.
Polyphenolic-rich berry fruits are known to activate redox-sensitive cellular signaling molecules such as phosphatidylinositol-3-kinase (PI3 kinase)/kinase B (Akt), resulting in a cascade of downstream signaling pathways. This study investigated the ability of strawberry (SB), wild blueberry (WBB), and cranberry (CB) extracts to induce the activation of PI3 kinase/Akt signaling in vitro in human umbilical endothelial cells (HUVECs) and whether this activation would enhance cell migration and angiogenesis. Anthocyanin profiles of the extracts were characterized using HPLC-ESI/MS, and Akt activation was investigated using the Alpha Screen SureFire assay. The total anthocyanin contents of SB, WBB, and CB extracts were 81.7, 82.5, and 83.0 mg/100 g fresh weight, respectively. SB, WBB, and CB extracts activated Akt in a dose-dependent manner via PI3 kinase and induced cell migration and angiogenesis in vitro in HUVECs. The results from this study suggest that polyphenolics in berry fruits may play a role in promoting vascular health.


A contact anti-aphrodisiac pheromone supplied by the spermatophore in the rove beetle Aleochara curtula: mode of transfer and evolutionary significance.
By reducing the attractiveness of their mating partner via an anti-aphrodisiac pheromone, males can prevent a remating of the female and thus reduce the risk of sperm competition. For females, the main benefit from allowing the chemical manipulation of their attractiveness is probably the avoidance of sexual harassments from rival males. While mating plugs generally constitute a physical barrier which hinders male mating attempts, chemical manipulations must trustfully inform the responding male of the female's reluctance to mate; otherwise, it would be beneficial to ignore the repellent information. In our experiments, males of the polyandrous rove beetle Aleochara curtula chemically manipulated the attractiveness of their mating partner. Coincident with the deposition of a spermatophore into the female genital chamber, an anti-aphrodisiac pheromone was transferred and readily spread onto the female surface, where it was subsequently perceived by rival males via parameres, the claspers of the male genitalia. Males aborted contact with the mated female to avoid further time- and energy-consuming elements of the mating sequence. The chemical mode of action was demonstrated inter alia by spicing virgin females with spermatophore extracts. The action of the anti-aphrodisiac correlated with the persistence of the spermatophore in the female genital chamber and corresponded to the length of stay of the mated female at a carcass, where the density of rival males is highest. The ensuing benefits for all three parties involved in this communication system, which render this post-copulatory mate guarding strategy evolutionary stable, are discussed.


Helical tomotherapy planning for lung cancer based on ventilation magnetic resonance imaging.
To investigate the feasibility of lung ventilation-based treatment planning, computed tomography and hyperpolarized (HP) helium-3 (He-3) magnetic resonance imaging (MRI) ventilation images of 6 subjects were coregistered for intensity-modulated radiation therapy planning in Tomotherapy. Highly-functional lungs (HFL) and less-functional lungs (LFL) were contoured based on their ventilation image intensities, and a cylindrical planning-target-volume was simulated at locations adjacent to both HFL and LFL. Annals of an anatomy-based plan (Plan 1) and a ventilation-based plan (Plan 2) were generated. The following dosimetric parameters were determined and compared between the 2 plans: percentage of total/HFL volume receiving ≥20 Gy, 15 Gy, 10 Gy, and 5 Gy (TLV(20), HFLV(20), TLV(15), HFLV(15), TLV(10), HFLV(10), TLV(5), HFLV(5)), mean total/HFL dose (MTLD/HFLD), maximum doses to all organs at risk (OARs), and target dose conformality. Compared with Plan 1, Plan 2 reduced mean HFLD (mean reduction, 0.8 Gy), MTLD (mean reduction, 0.6 Gy), HFLV(20) (mean reduction, 1.9%), TLV(20) (mean reduction, 1.5%), TLV(15) (mean reduction, 1.7%), and TLV(10) (mean reduction, 2.1%). P-values of the above comparisons are less than 0.05 using the Wilcoxon signed rank test. For HFLV(15), HFLV(10), TLV(5), and HTLV(5), Plan 2 resulted in lower values than plan 1 but the differences are not significant (P-value range, 0.063-0.219). Plan 2 did not significantly change maximum doses to OARs (P-value range, 0.063-0.563) and target conformality (P = 1.000). HP He-3 MRI of patients with lung disease shows a highly heterogeneous ventilation capacity that can be utilized for functional treatment planning. Moderate but statistically significant improvements in sparing functional lungs were achieved using helical tomotherapy plans.


[Caregivers of dependent elderly at home: changes in family relationships].
The study aimed to identify, in the view of the caretaker, the changes that happened in the family relationships after a dependence generator event on aged person, and the factors that provoked it. It is a field study with a qualitative approach. It was carried out recorded interviews with eight family caregivers, during home visits, with guiding questions and observations being recorded in a field diary. The content analysis of Bardin was applied, being constructed categories and subcategories. The familiar union preexisting to the dependence situation predisposes positive changes, favored with formal and informal support. The family caregiver burden due to lack of support, age and activities of caregiving, leads to negative situations in the family. The effectiveness of public policies to provide formal support for the elderly and their caregivers, and the creation of support groups, may contribute to the family wellbeing.


[Use of a new biological factor--exogenous nitric oxide--during surgical treatment of periodontitis].
In order to improve the efficiency of surgical treatment of periodontitis, the operative wound was exposed to nitrogen oxide (NO) during osteogingivoplasty and on days 3, 5, and 6 after it. Clinical and laboratory data making use of the cytomorphometrical method indicate that NO exposure decreased and maybe prevented secondary injury to the operation wound in up to 46.6% patients, which was confirmed by decrease and even normalization of destruction index and inflammatory destructive index on days 7 and 14, which was not observed in the reference group patients not exposed to NO.


Designing Hybrid Chiral Photonic Films with Circularly Polarized Room-Temperature Phosphorescence.
Circular polarized luminescence (CPL) is essential to chiral sciences and photonic technologies, but the achievement of circular polarized room-temperature phosphorescence (CPRTP) remains a great challenge due to the instability of triplet state excitons. Herein, we found that dual CPL and CPRTP were demonstrated by hybrid chiral photonic films designed by the coassembly of cellulose nanocrystals (CNCs), poly(vinyl alcohol) (PVA), and carbon dots (CDs). Tunable photonic band gaps were achieved by regulating the ratio of CNC/PVA in the hybrid films, leading to tunable CPL with invertible handedness, tunable wavelengths, and considerable dissymmetric factors (glum) up to -0.27. In particularly, triplet excitons produced by CDs were stable in the chiral photonic crystal environment, resulting in tunable right-handed CPRTP with long lifetimes up to 103 ms and large RTP dissymmetric factors (gRTP) up to -0.47. Moreover, patterned films with multiple polarized features were demonstrated by a mold technique.


In vitro antiproliferative and antioxidant effects of urolithin A, the colonic metabolite of ellagic acid, on hepatocellular carcinomas HepG2 cells.
The intestinal metabolites of ellagic acid (EA), urolithins are known to effectively inhibit cancer cell proliferation. This study investigates antiproliferative and antioxidant effects of urolithin A (UA) on cell survival of the HepG2 hepatic carcinomas cell line. The antiproliferative effects of UA (0-500 μM) on HepG2 cells were determined using a CCK assay following 12-36 h exposure. Effects on β-catenin and other factors of expression were assessed by using real-time PCR and Western blot. We found that UA showed potent antiproliferative activity on HepG2 cells. When cell death was induced by UA, it was found that the expression of β-catenin, c-Myc and Cyclin D1 were decreased and TCF/LEF transcriptional activation was notably down-regulated. UA also increased protein expression of p53, p38-MAPK and caspase-3, but suppressed expression of NF-κB p65 and other inflammatory mediators. Furthermore, the antioxidant assay afforded by UA and EA treatments was associated with decreases in intracellular ROS levels, and increases in intracellular SOD and GSH-Px activity. These results suggested that UA could inhibit cell proliferation and reduce oxidative stress status in liver cancer, thus acting as a viably effective constituent for HCC prevention and treatment.


[Palliative care for patients with advanced dementia: Evidence-based practice replaced by values-based practice].
For the treatment of patients with advanced dementia, we could not find any evidence based guidelines to help in decision making. Individual values and expected quality of life must be the leading goals of any intervention. Symptom control and relieving suffering are core values of palliative care, but the recognition of discomfort needs qualified assessment skills. Pain assessment with common tools like the VAS fails in patients with cognitive impairment and inability to communicate; instruments like Doloplus and ECPA can be helpful to assess behavioral changes as expression of pain. The treatment of acute and chronic pain in advanced dementia is still not sufficient and needs improvement. Oral feeding in advanced dementia becomes more and more difficult. No randomized controlled study has found evidence that tube feeding will reduce the risk of aspiration or prolong life expectancy. Eating may be the only meaningful activity that remains for the patient; artificial feeding cannot serve the same function. All final complications, like pneumonia, call for a decision making process. Those who care for and care about these patients must make decisions. The feelings of the family have to be considered, but the probable will of the patient, his dignity and quality of life must not be overridden.


Asc1 supports cell-wall integrity near bud sites by a Pkc1 independent mechanism.
The yeast ribosomal protein Asc1 is a WD-protein family member. Its mammalian ortholog, RACK1 was initially discovered as a receptor for activated protein C kinase (PKC) that functions to maintain the active conformation of PKC and to support its movement to target sites. In the budding yeast though, a connection between Asc1p and the PKC signaling pathway has never been reported. In the present study we found that asc1-deletion mutant (asc1Delta) presents some of the hallmarks of PKC signaling mutants. These include an increased sensitivity to staurosporine, a specific Pkc1p inhibitor, and susceptibility to cell-wall perturbing treatments such as hypotonic- and heat shock conditions and zymolase treatment. Microscopic analysis of asc1Delta cells revealed cell-wall invaginations near bud sites after exposure to hypotonic conditions, and the dynamic of cells' survival after this stress further supports the involvement of Asc1p in maintaining the cell-wall integrity during the mid-to late stages of bud formation. Genetic interactions between asc1 and pkc1 reveal synergistic sensitivities of a double-knock out mutant (asc1Delta/pkc1Delta) to cell-wall stress conditions, and high basal level of PKC signaling in asc1Delta. Furthermore, Asc1p has no effect on the cellular distribution or redistribution of Pkc1p at optimal or at cell-wall stress conditions. Taken together, our data support the idea that unlike its mammalian orthologs, Asc1p acts remotely from Pkc1p, to regulate the integrity of the cell-wall. We speculate that its role is exerted through translation regulation of bud-site related mRNAs during cells' growth.


Gonadotrophin levels and morphological testicular features in rats after different doses of the phytoestrogen coumestrol.
Phytoestrogens are a wide variety of chemical compounds, mainly isoflavonoids, from a vegetable source. Their name makes reference to their ability to induce estrogenic responses in mammals. Coumestrol is a phytoestrogen that can be found in high concentrations in the dietary elements of cattle. Some endocrine alterations have been reported for cows and ewes after ingestion of vegetables with high concentrations of coumestrol. However, these studies have been made mainly in females. To analyze some features of the masculine endocrine response in rats after several doses of the phytoestrogen coumestrol. Adult male rats were injected with several doses of coumestrol. Plasma gonadotrophins (LH/FSH) and testosterone levels were assessed. In addition, morphology of the testicles was analyzed. Experiments were done in the facilities of the neurosciences area at the University. No significant changes were observed in gonadotrophin levels after the administration of coumestrol. Testosterone levels showed a significant decrease with the higher doses. Morphological analysis showed an inhibitory effect on spermatogenesis expressed mainly in the right testicle. Testicular volume decreased and the tubular area increased significantly after coumestrol treatment. These results suggest that the endocrine effect of coumestrol is mainly expressed in peripheral targets in male rats. In addition, the possible mediation of estrogen beta receptors is discussed.


Mucus glycoproteins secreted by respiratory epithelial tissue from cystic fibrosis patients.
Tracheae, bronchi, nasal epithelial, and nasal polyp tissue slices were incubated in tissue culture with [3H]-glucosamine, and the rate of secretion of labeled mucus glycoproteins was measured. Secretion rates were at least 3- to 6-fold higher for all of the samples from nine patients with cystic fibrosis (CF) who were studied, as compared with values for tissue slices from eight young subjects not affected with this disease. The secreted glycoproteins were further purified into one neutral and three acidic fractions by ion-exchange chromatography on DEAE-cellulose. The glycoproteins secreted by respiratory epithelial tissue from cystic fibrosis subjects contained relatively more of two acidic glycoprotein fractions. Double-label experiments with both [3H]-glucosamine and [35S]-sulfate as mucus glycoprotein precursors further substantiated the shift to more acidic components in the purified mucus glycoproteins and, in addition, suggested a higher level of sulfation of these same two acidic glycoprotein fractions. All four of the labeled glycoprotein fractions secreted by cultured human bronchi cochromatographed with authentic mucus glycoproteins purified from sputum of cystic fibrosis subjects by the same techniques. The differences between mucus glycoproteins from cultured CF airway tissue and mucus glycoproteins from other patients' tissue included relatively increased rates of production, level of sulfation, and greater acidity. Further applications of these in vitro techniques should allow the determination of the enzymatic and biochemical causes of these observed differences in the absence of such potentially confounding variables as concurrent airway infection or of oropharyngeal secretions.


Circular RNA Circ-ZNF609 Promotes Lung Adenocarcinoma Proliferation by Modulating miR-1224-3p/ETV1 Signaling.
Circ-ZNF609 has been shown to modulate cancer progression in several kinds of cancer. However, the role of circ-ZNF609 played in lung adenocarcinoma (LAUD) remains unclear. In this study, we investigated the role of circ-ZNF609 in regulating LAUD cancer progression. Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circ-ZNF609 expression in 52 LAUD tissues and 52 matched adjacent normal tissues, LAUD cell lines and bronchial epithelial cell line (HBE). The direct interaction between miR-1224-3p and circ-ZNF609 or EVT1 was verified using luciferase reporter assay and RNA immunoprecipitation assay. Cell Counting Kit-8, colony formation assay, cell-cycle analysis were utilized to examine the effect of circ-ZNF609 or miR-1224-3p on cell proliferation. Circ-ZNF609 was significantly upregulated in LAUD tissues and cell lines, and its inhibition induced reduced cell proliferation of LAUD cells. Mechanistically, we demonstrated that circ-ZNF609 sponged miR-1224-3p to promote EVT1 expression. More importantly, miR-1224-3p overexpression strongly suppressed circZNF609-induced malignant phenotype of LAUD cells. Circ-ZNF609 enhances LAUD progression by increasing oncogenic EVT1 expression via sponging miR-1224-3p, revealing that circ-ZNF609/miR-1224-3p/ETV1 axis may be a promising therapeutic target for LAUD treatment.