The Relation between Media Literacy and COVID-19 Vaccination.
Background: Media literacy refers to a set of skills designed specially to help people make better health decisions while dealing with media tasks. The present study was conducted to investigate the relationship between media literacy and willingness to be vaccinated among medical students. Methods: This is a descriptive cross-sectional study. The statistical population consisted of all students at Iran University of Medical Sciences, among whom, 389 samples were recruited. Two questionnaires were used: (1) Media Literacy and (2) Willingness to be Vaccinated. The validity of these questionnaires was confirmed by the content validity method and consultation with experts. Data were analyzed using Pearson correlation, t test, and one-way analysis of variance using SPSS v. 20 (SPSS Inc). Results: The willingness to be vaccinated was higher in men (23.04 ± 5.59) than in women (21.07 ± 3.77) and this difference was significant (P<.001). However, there was no significant difference between willingness to be vaccinated and marital status, educational level, and age. The findings showed a significant relationship between media literacy and willingness to be vaccinated. Conclusion The effect of media literacy on retrieving and recognizing accurate information is one of the crucial results of the present study. This skill affects an individual's willingness to make the right decision on timely COVID-19 vaccination.


Approval process for devices and mesh for surgical treatment of pelvic organ prolapse and urinary incontinence.
Most marketed devices in the United States, including most used to treat prolapse and incontinence, are marketed without FDA approval; instead, they gain "clearance" as a class II device through premarket notification [also known as the 510(k) process]. Under this process, the manufacturer states that the device is substantially equivalent to one already on the market. Thus, mesh kits for prolapse and incontinence were not required to undergo clinical testing before reaching the market. In January 2012, the FDA announced that it would require postmarket surveillance studies to address safety and effectiveness of mesh kits for prolapse and for single-incision slings.


The Effect of Alkali Treatment on Properties of Dopamine Modification of Bamboo Fiber/Polylactic Acid Composites.
In this study, a synergistic treatment including dopamine (DA) modification and alkali pretreatment on bamboo fiber (BF) was used as reinforcement in a polylactic acid (PLA) matrix to improve the mechanical and thermal properties of BF/PLA composites. The effects of the sodium hydroxide loading rate on the performance of mussel-inspired dopamine-modified bamboo fiber and the BF/PLA composites were evaluated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), mechanical testing (examining flexural, tensile, and impact properties), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). Analysis of the composites suggested that the optimal condition was treatment with a 4 wt % solution of NaOH and a 1 wt % concentration of dopamine. Compared with the untreated bamboo fiber/polylactic acid composites, the synergistic treatment improved the thermal properties and mechanical properties; flexural, tensile, and impact strengths increased by 16.1%, 34.4%, and 3.7%, respectively. It was further verified that appropriate alkali treatment was a promising approach in promoting the effect of dopamine-modified coating while maintaining the crystal structure of the cellulose.


Meta-analysis of the efficacy and safety of intradiscal electrothermal therapy (IDET).
The objective of this study was to determine the representative outcomes of the intradiscal electrothermal therapy (IDET) procedure in terms of pain relief, reduction of disability, and risk of complications. Meta-analysis, using a random-effects model. A Medline literature search was conducted using search terms associated with the IDET procedure including IDET, intradiscal electrothermal therapy, intervertebral disk, and annuloplasty. The outcomes analyzed were the visual analog scale (VAS) assessment of pain, the bodily pain, and physical functioning subscales of the SF-36 health survey, and the Oswestry disability index. From 1998 to March 2005, 62 peer-reviewed articles were identified regarding the IDET procedure. Forty-five articles were excluded, leaving a total of 17 unique published reports included in this review. The overall mean improvement in pain intensity was 2.9 points as measured by the VAS. The overall mean improvement in physical function was 21.1 points as measured by the SF-36. The overall mean improvement in bodily pain was 18.0 points as measured by the SF-36. The overall mean improvement in disability was 7.0 points as measured by the Oswestry disability index. The overall incidence of complications was 0.8%. Although variation exists in the reported outcomes among the various studies of the IDET procedure, the pooled results of the published studies provide compelling evidence of the relative efficacy and safety of the IDET procedure.


Expression of integrin subunit beta1B in integrin beta1-deficient GD25 cells does not interfere with alphaVbeta3 functions.
We have expressed the beta1B integrin subunit in beta1-deficient GD25 cells to examine beta1B functions without the interference of endogenous beta1A expression. As previously reported [Retta et al., 1998, Mol. Biol. Cell 9, 715-731], the beta1B integrins did not mediate cell adhesion under normal culture conditions, while the presence of 0.3 mM Mn(2+) allowed beta1B integrins to support adhesion. Mn(2+), as well as the small soluble peptide GRGDS, induced a beta1B conformation, which was recognized by the mAb 9EG7, a marker for active or ligand-bound integrins. beta1B integrins were found to localize to a subset of focal contacts in a ligand-independent manner on fibronectin, but not on vitronectin. However, clustering of beta1B did not induce tyrosine phosphorylation of FAK, p130(Cas), or paxillin, as studied by beta1B-mediated adhesion, to fibronectin in the presence of Mn(2+) or to anti-beta1 antibody in DMEM. Induction of ligand-occupied conformation by the GRGDS peptide during the adhesion to anti-beta1 antibody also failed to trigger FAK phosphorylation. Stimulation of tyrosine phosphorylation on FAK, p130(Cas), and paxillin by adhesion via integrin alphaVbeta3 to fibronectin or vitronectin was not disturbed in GD25-beta1B cells compared to the untransfected GD25 cells, nor were any negative effects of beta1B observed on alphaVbeta3-mediated cell attachment, spreading, and actin organization, or on the cell proliferation rate. These results show that the reported negative effects of beta1B on adhesive events do not apply to alphaVbeta3-dependent interactions and suggest that they may specifically act on beta1 integrins.


Hemiarthroplasty and total hip arthroplasty for treating primary intracapsular fracture of the hip: a systematic review and cost-effectiveness analysis.
Hip fracture is a common problem in people aged > 60 years. The treatment options for individuals with high pre-fracture mobility, function and independence are hemiarthroplasty (HA) and total hip arthroplasty (THA). The aim of this report is to assess the clinical effectiveness and cost-effectiveness evidence of THA compared with HA in patients with displaced intracapsular fracture who are cognitively intact with high pre-fracture mobility or function. A systematic search was made of 11 databases of published and unpublished literature from their inception to december 2010: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, Biological Science Citation Index, Social Science Citation Index, Conference Proceedings Citation Index - Science, UK Clinical Trials Research Network and the National Research Register archive, Current Controlled Trials and ClinicalTrials.gov. A systematic review of randomised controlled trials (RCTs) to assess the effectiveness of THA compared with HA in terms of dislocations, revisions, pain and function, and quality of life. Meta-analysis, independent subgroup analyses and exploratory cost-effectiveness modelling were performed. The literature search identified 532 unique citations, of which eight RCTs with almost 1000 participants satisfied the criteria for the effectiveness review. Meta-analysis found a statistically significant increased risk of dislocation for patients treated with THA compared with HA (p = 0.01), but a reduced risk of revision (p = 0.0003). There were no differences in terms of mortality. In all trials, individuals treated with THA reported better function and mobility and less pain than those treated with HA. Four trials reporting utility data found similar trends. Sensitivity analyses indicated that there were no statistically significant differences in outcomes based on follow-up, study quality, surgical approach taken, type of head or the use of cement. Four papers reported a cost-utility analysis or the cost-effectiveness of THA compared with HA. Exploratory modelling was undertaken that showed that THA is likely to be cost-effective compared with HA even when the limitations of the data and methodology are considered. The costs and disutilities associated with revisions and dislocations were not included in the economic evaluation. THA appears to be more cost-effective than HA. It is likely that THA will be associated with increased costs in the initial 2-year period, but lower longer-term costs, owing to potentially lower revision rates. However, these longer-term costs have not been modelled. The capacity and experience of surgeons to perform THA have not been explored and these would need to be addressed at local level were THA to become recommended for active, elderly patients in whom THA is not contraindicated. Further studies examining the impact of surgeon experience on performing the two procedures may offer more robust evidence on outcomes. The National Institute for Health Research Health Technology Assessment programme.


Diet and resource partitioning among anurans in irrigated rice fields in Pantanal, Brazil.
Artificial ponds or irrigated systems scattered throughout farmlands can offer important habitats for anurans and can be interesting sites for research on species resources use in a changing landscape. This study describes the diet and resource partitioning among anurans inhabiting irrigated rice fields in the Pantanal region. Twenty categories of prey were found in the stomachs of Leptodactylus chaquensis, L. elenae, L. podicipinus and Rhinella bergi, the most frequent being Coleoptera, Hymenoptera, larvae of Hexapoda, Hemiptera, Diptera and Orthoptera. The great differences found in the diet of these species in rice fields compared to other locations, according to available records in the literature, was the increased importance of Hemipitera and Orthoptera and the decrease in importance of Hymenoptera in the diet of leptodactylids. These differences might be attributed to changes in the availability of resources in response to habitat modification. Although diet composition was very similar among species, niche overlap was larger than expected by chance, suggesting that the competition for food resources is not, or has not been, a significant force in determining the structure of this frog community. Two non-exclusive hypotheses could be considered as a justification for this result: 1) the high niche overlap could result from resource availability, which is sufficient to satisfy all species without any strong competition; 2) or the high values of niche overlap could be a selective force driving species to compete, but there has not been enough time to express a significant divergence in the species diet because the study area is characterised as a dynamic habitat influenced by frequent and cyclical changes.


Eosinophilic peritonitis in a patient with continuous ambulatory peritoneal dialysis (CAPD).
Eosinophilic peritonitis is defined as when there are more than 100 eosinophils present per milliliter of peritoneal effluent, of which eosinophils constitute more than 10% of its total WBC count. Most cases occur within the first 4 weeks of peritoneal catheter insertion and they usually have a benign and self-limited course. We report a patient of eosinophilic peritonitis that was successfully resolved without special treatment. An 84-year-old man with end stage renal disease secondary to diabetic nephropathy was admitted for dyspnea and poor oral intake. Allergic history was negative. and physical examination was unremarkable. Complete blood count showed a hemoglobin level of 11.1 g/dL, WBC count was 24,500/mm3 (neutrophil, 93%; lymphocyte, 5%; monocyte, 2%), platelet count was 216,000/mm3, serum BUN was 143 mg/dL, Cr was 5.7 mg/dL and albumin was 3.5 g/dL. Creatinine clearance was 5.4 mL/min. Three weeks after peritoneal catheter insertion, he was started on peritoneal dialysis with a 6-hour exchange of 2L 1.5% peritoneal dialysate. After nine days, he developed turbid peritoneal effluents with fever (38.4 degrees C), abdominal pain and tenderness. Dialysate WBC count was 180/mm3 (neutrophil, 20%; lymphocyte, 4%; eosinophil, 76% [eosinophil count: 136/mm3]). Cultures of peritoneal fluid showed no growth of aerobic or anaerobic bacteria, or of fungus. Continuous ambulatory peritoneal dialysis (CAPD) was commenced, and he was started on intraperitoneal ceftazidime (1.0 g/day) and cefazolin (1.0 g/day). After two weeksr, the dialysate had cleared up and clinical symptoms were improved. Dialysate WBC count decreased to 8/mm3 and eosinophils were not detected in peritoneal fluid. There was no recurrence of eosinophilic peritonitis on follow-up evaluation, but he died of sepsis and pneumonia fifteen weeks after admission.


The conquest of 'river blindness'.
Studies carried out at the WHO/OCP Onchocerciasis Chemotherapeutic Centre in Tamale, Ghana, are reported, culminating in the clinical trials of ivermectin (Mectizan), which has revolutionized our approach to the treatment of the disease. It is concluded that the conquest of 'river blindness' is an eminently achievable goal.


Evidence for epigenetic mechanisms that silence both basal and immune-stimulated transcription of the IL-8 gene.
It is becoming increasingly clear that epigenetic silencing of gene transcription plays a critical role in the regulation of gene expression in many biological processes. Tight regulation of immunomodulatory substances that are important for the initiation of the inflammatory cascade, such as chemoattractive cytokines, is essential to prevent initiation of unrestrained immune activation. Using the Caco-2 intestinal cell line as a model, we reveal two distinctly different mechanisms by which the gene for the neutrophil chemoattractive cytokine IL-8 is silenced. Nuclear run-on studies, as well as stably transfected reporter and marked minigene constructs, demonstrate that cellular differentiation inhibits immune-activated transcription of the IL-8 gene, a mechanism that is dependent on histone deacetylase activity. Unexpectedly, this silencing mechanism does not involve previously described regulatory elements in the IL-8 promoter but rather cis-acting regions located at a distance from the IL-8 gene locus. Genomic elements distant to the immediate IL-8 locus are also required to silence aberrant basal transcriptional activity of the IL-8 promoter in the absence of immune activation. However, in this case, silencing occurs in a histone deacetylase-independent fashion. These findings were confirmed in transgenic mice in which, in the absence of these elements, aberrant IL-8 gene activity was present primarily in the intestinal tract. Epigenetic silencing of cytokine gene transcription through distant genomic elements is an important level of gene regulation that may be relevant to the pathogenesis of immunologic disease states.


Differentiation of aspartic and isoaspartic acids using electron transfer dissociation.
Electron-transfer dissociation allows differentiation of isoaspartic acid and aspartic acid residues using the same c + 57 and z - 57 peaks that were previously observed with electron capture dissociation. These peaks clearly define both the presence and the position of isoaspartic acid residues and they are relatively abundant. The lower resolution of the ion trap instrument makes detection of the aspartic acid residue's diagnostic peak difficult because of interference with side-chain fragment ions from arginine residues, but the aspartic acid residues are still clearly observed in the backbone cleavages and can be inferred from the absence of the isoaspartic acid diagnostic ions.


[Electrocorticographic evaluation of the neurologic tolerability of iobitridol (Xenetix), a new non-ionic contrast medium in rabbits].
Electro-corticographic tracings (two longitudinal leads, bipolar assembly) were recorded from curarized rabbits (5/group) receiving selective internal carotid artery injections of either iobitridol, a new non-ionic contrast medium, or iohexol, the high osmolar diatrizoate or hypertonic mannitol (isotonic to the non-ionic agents). A further group was submitted to the surgical preparation but was not injected. The solutions were injected at a dose of 2.5 ml during 30 seconds. The animals were anaesthetized (halothane) during the surgical period. The permeability of the blood-brain barrier was assessed by means of the extravasation of Evans'blue. Tracings were visually assessed and a semi-quantitative method for blind evaluation of fast/slow rhythms was used. This method was pharmacologically validated by the use of pentobarbital and pentylenetetrazole. Diatrizoate and iohexol induced respectively 3 and 2 paroxystic tracings during or immediately after the injection period. Iobitridol and hypertonic mannitol did not cause such effect. Paroxystic tracings in the iohexol group were not associated with extravasation of Evans'blue in the cerebral parenchyma. Blood brain barrier was disrupted in all rabbits receiving the high osmolar agent diatrizoate. Tracings of the control group were characterized by a progressive increase of fast rhythms, as those of the iobitridol and mannitol groups. On the contrary, iohexol and especially diatrizoate induced an increase in the proportion of slow waves. Taken together, these data suggest that iobitridol shows an excellent tolerability potential for clinical use.


Effect of an aerobic exercise training program on resting metabolic rate in chronically beta-adrenergic blocked hypertensive patients.
There is substantial evidence that the use of beta-adrenergic receptor blockers (beta-blockers) is associated with a reduction in resting metabolic rate (RMR) and that a weight gain usually occurs in the first few months of treatment. The purpose of this study was to determine if RMR of overweight and sedentary subjects consuming beta-blockers can be increased following an aerobic exercise training program. Twenty-four subjects participated in the study; 11 (6 women, 5 men) were treated with beta-blockers for hypertension and 13 (9 women, 4 men) were nonmedicated (control group). Body composition, RMR, and peak oxygen uptake (VO2peak) were assessed for all subjects before and after a 12-week aerobic exercise training program. Weekly exercise energy expenditure equaled 83.68 kJ (20 kcal) per kg of body weight while exercise intensity was maintained between 60% and 70% of the VO2 reserve. Body composition, RMR, and VO2peak did not differ among groups at the beginning of the study. Body weight (-1.4 kg for beta-blockers, P < .05; -2.5 kg for control, P < .05) and VO2peak (+2.2 mL x kg(-1) x min(-1) for beta-blockers, P < .05; +4.1 mL x kg(-1) x min(-1) for control, P < .001) were significantly improved in both groups, whereas RMR (-272 kJ x day(-1) for beta-blockers, NS; +573 kJ x day(-1) for control, P < .05) was increased only in the control group after the aerobic exercise training program. These results suggest that beta-blockers limit the increase in RMR normally observed following an aerobic exercise training program. Consequently, obtaining a negative energy balance in an attempt to lose weight may be more difficult.


Inhaled steroids in the treatment of asthma.
The authors present a review of recent data that is relevant to the effects of inhaled steroids on the bone growth of asthma patients. The authors recommend appropriate treatment plans based on this review and the NHBLI/NIH guidelines for the management of asthma.


Modulating Nanoparticle Size to Understand Factors Affecting Hemostatic Efficacy and Maximize Survival in a Lethal Inferior Vena Cava Injury Model.
Intravenous nanoparticle hemostats offer a potentially attractive approach to promote hemostasis, in particular for inaccessible wounds such as noncompressible torso hemorrhage (NCTH). In this work, particle size was tuned over a range of <100-500 nm, and its effect on nanoparticle-platelet interactions was systematically assessed using in vitro and in vivo experiments. Smaller particles bound a larger percentage of platelets per mass of particle delivered, while larger particles resulted in higher particle accumulation on a surface of platelets and collagen. Intermediate particles led to the greatest platelet content in platelet-nanoparticle aggregates, indicating that they may be able to recruit more platelets to the wound. In biodistribution studies, smaller and intermediate nanoparticles exhibited longer circulation lifetimes, while larger nanoparticles resulted in higher pulmonary accumulation. The particles were then challenged in a 2 h lethal inferior vena cava (IVC) puncture model, where intermediate nanoparticles significantly increased both survival and injury-specific targeting relative to saline and unfunctionalized particle controls. An increase in survival in the second hour was likewise observed in the smaller nanoparticles relative to saline controls, though no significant increase in survival was observed in the larger nanoparticle size. In conjunction with prior in vitro and in vivo experiments, these results suggest that platelet content in aggregates and extended nanoparticle circulation lifetimes are instrumental to enhancing hemostasis. Ultimately, this study elucidates the role of particle size in platelet-particle interactions, which can be a useful tool for engineering the performance of particulate hemostats and improving the design of these materials.


[Potentially inappropriate prescribing: Usefulness of STOPP/START criteria version 2 in Catalonian elderly population].
To measure the prevalence of potentially inappropriate prescribing (PIP) among the elderly population in Catalonia using criteria Screening Tool of Older Person's Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) version 2. In addition, to evaluate the association between PIP and several factors (polypharmacy, gender, age and sociodemographic conditions). Design: Retrospective cross sectional population study. Primary Health Care, Catalonia, Spain. The study population comprised of participants 70 years old and over, who attended primary health care centres in Catalonia in 2014 (700.058 patients). 55 STOPP and 19 START criteria are applied to analyse PIP prevalence. Logistic regression models are adjusted to determine PIP association with several factors. The mean age is 79. 2±6.5. 58.5% being female. 38.7% of patients have 7 or more prescribed drugs, whereas 50% go to a primary care centre 10 or more times during one year. The most frequent PIP among STOPP criteria are related to nonsteroidal anti-inflammatory drug intake, antiplatelet and anticoagulants use, and benzodiazepines. According to START, the most frequent omissions are vitamin D and calcium supplements, antidepressants, and cardiovascular medications. Factors that increase PIP are: female gender, living in a nursing home, receiving home health care, polypharmacy and frequent visits to primary care centres. The overall prevalence of PIP is 89.6%. PPI is significantly related to certain drugs and patient's conditions. The knowledge of this association is important for the implementation of security measures for medical prescription.


[From program to metaphor--managing the needs of children in a separation or divorce process involving their parents].
In German-speaking regions there are several independent intervention programs, derived from concepts originating in the USA, which are designed to assist children whose parents are separated or divorced. Two of these programs will be presented here. Consistent with the thematic implication that divorce entails trauma and stress, the childrens' need of advice and help is placed at the conceptual center of the intervention. This results in a behavioral-cognitive training program, which should enable children to overcome the stress of their situation. In contrast to these two programs, an understanding of divorce may be achieved, through phenomenological analysis, which gives due consideration to the various aspects and meanings of the divorce process. The concept of intervention derived from this approach is to assist children in further developing their own search for solutions, focused on the parents-child-relation. The primary emphasis of this approach is not the childrens' difficulty in dealing with their parents' separation and divorce, but rather their own attempt to deal with the problem, as is visible in the metaphor of their spontaneous descriptions and images of experiences and events. The central concept of the proposed course is the further development of this creative process in the form of a dynamic-communicative group happening. Furthermore it is shown how children can be assisted in a practical way, and encouraged to create their individual and personally adequate solution to the experience of divorce.


[The role of gallium scintigraphy in the diagnosis of sarcoidosis and in monitoring treatment effectiveness].
Sarcoidosis is an inflammatory disorder of unclear origin that can affect many organs. The hallmark of sarcoidosis is formation non-caseating epithelioid cell granulomas. The aetiology and the pathogenesis of the disease are not well understood, therefore in the absence of specific histopathology distinguishing marks the diagnosis is established by exclusion. In this case, the authors present a unique case of Boeck sarcoidosis with pulmonary manifestation and pleural involvement. They would like to draw attention to the importance of gallium scintigraphy in the diagnostic workup of the disease. During the diagnostic process, the exact diagnosis could be established with the help of gallium scintigraphy. Gallium scan also played an important role in identifying extrapulmonary manifestations. Serial control examinations--as being the only sensitive non invasive diagnostic test method- provided valuable help in estimating the activity of the inflammatory process and monitoring therapeutic efficacy.


[Anti-allergy therapy in children].
The discovery of the physiopathological mechanisms of asthma and the diseases of allergy has allowed the development of many symptomatic therapeutical perspectives. We review below the mechanisms of actions, routes of administration, secondary effects, dosages and indications for different commercialised anti-allergy medications. A better understanding of the pharmacology of the different medications should produce optimisation of the treatment of the allergic child.


Health Equity Demands Health Literacy: Ethics in the Pediatric Emergency Department.
The ability of the patient or the parent, in pediatrics, to read, understand, and act upon health information is termed health literacy. Health literacy has been shown to be of primary importance when determining a patient's ability to achieve optimal health. As physicians, we often fail to recognize the enormous obstacles facing our patients. In the pediatric emergency department (PED), communication is complicated. Physicians must be able to effectively relay information to the patient's caregiver while still not forgetting to provide developmentally appropriate instructions to the child. Individuals who do not have a good understanding of what is needed to properly care for themselves or their children are at a disadvantage, and it is therefore the responsibility of the pediatric provider to do all they can to identify gaps in health literacy. As providers, we need to always be questioning as to whether we properly conveyed the information to our patients. Teaching which results in good understanding is the ultimate goal when treating and releasing our patients in the pediatric emergency department. Matching the method of delivery of information and education to the family's health literacy will help the care team deliver effective information so that it is applied at home hopefully preventing a rapid revisit.


Developmental changes in the nicotinic responses of ciliary ganglion neurons.
The accumulation of functional neurotransmitter receptors by neurons during development is an essential part of synapse formation. Chick ciliary ganglion neurons express two kinds of nicotinic receptors. One is abundant, contains the alpha7 gene product, rapidly desensitizes, and binds alpha-bungarotoxin. The other is less abundant, contains multiple gene products (alpha3, beta4, alpha5, and beta2 subunits), slowly desensitizes, and binds the monoclonal antibody mAb 35. Rapid application of agonist to freshly dissociated neurons elicits responses from both classes of receptors. Between embryonic days 8 and 15, the whole cell response of alpha3-containing receptors increases fivefold in peak amplitude and, normalized for cell growth, 1.7-fold in current density. In addition, the response decays more slowly in older neurons, suggesting a developmental decrease in the rate of desensitization. The whole cell response of alpha7-containing receptors increases 10-fold in peak amplitude over the same period and 3-fold in current density. No change in the rate of desensitization was apparent for alpha7-containing receptors with developmental age, but analysis was limited by overlap in responses from the two kinds of receptors. Indirect immunofluorescence measurements on dissociated neurons showed that the relative levels of alpha7-containing receptors on the soma increased during development to the same extent as the whole cell response attributed to them. In contrast, the relative levels of alpha3-containing receptors increased more during the same time period than did the whole cell response they generated. The immunofluorescence analysis also showed that both classes of receptors become distributed in prominent clusters on the cell surface as a function of developmental age. The results indicate that during this period of synaptic consolidation on the neurons, the two major classes of functional nicotinic receptors undergo substantial upregulation; alpha3-containing receptors as a class may undergo changes in receptor properties as well.


Vitamin D and calcium status and appropriate recommendations in bariatric surgery patients.
Bariatric surgery is becoming an increasingly common procedure performed to achieve long-term weight loss in morbidly obese patients. Bariatric surgery may cause long-term morbidity because of vitamin and mineral deficiencies. This review synthesizes the research on vitamin D and calcium status in obese patients before and after bariatric surgery. The literature shows that morbidly obese patients are likely deficient in vitamin D prior to surgery because of poor sunlight exposure, less bioavailability of the vitamin when sequestered in fat cells, and inhibited hepatic vitamin activation. Gastric bypass surgery may further exacerbate vitamin D and calcium deficiencies secondary to poor compliance, loss to follow-up, reduced food intake, and malabsorption. It is imperative that research be conducted to determine adequate supplementation regimens for vitamin D and calcium in bariatric surgery patients.


A mechanical non-enzymatic method for isolation of mouse embryonic fibroblasts.
Mouse embryonic fibroblasts (MEFs) accessibility coupled with their simple generation make them as a typical embryonic cell model and feeder layer for in vitro expansion of pluripotent stem cells (PSCs). In this study, a mechanical isolation technique was adopted to isolate MEFs and the efficiency of this technique was compared with enzymatic digestion method. The suspended MEFs were prepared either by mechanical method or 0.25% trypsin enzymatic digestion. The effect of tissue processing on cell apoptosis/necrosis, morphology, viable cell yield, population doubling time, surface marker expression, and the capacity to support PSCs were determined. The mechanical method yielded a significantly higher number of viable cells. However, it showed similar morphology and proliferation characteristics as compared to enzymatic digestion. The mechanical method induced slight apoptosis in MEFs; however, it did not exert the necrotic effect of trypsinization. Treatment of tissue slurry with trypsin solution caused cell lysis and subsequently cell clump formation. Mechanically isolated cells exhibited a higher expression of the MEF surface antigens Sca1, CD106, and CD105. The PSCs on mechanically isolated MEFs displayed a higher expression of pluripotency genes, and formed more compact colonies with a stronger tendency to crowding compared with those cultured on cells isolated by enzymatic digestion. The mechanical method based on tissue inter-syringe processing is relatively a rapid and simple method for MEF isolation. Compared to the enzymatic digestion, the cells obtained from this method show higher expression of embryonic fibroblasts markers and a more functional capacity in supporting PSCs culture.


Human in-stent restenosis tissue obtained by means of coronary atherectomy consists of an abundant proteoglycan matrix with a paucity of cell proliferation.
In-stent restenosis (ISR) is a shortcoming of percutaneous coronary revascularization. Although neointimal cell proliferation is suspected to be the cause of this problem, little histological characterization of this tissue or data on cell replication exist. The purpose of this study was to examine the histologic features and proliferation profile of coronary ISR tissue derived from atherectomy procedures performed on patients with clinical evidence of ISR. ISR tissue retrieved by means of atherectomy from 20 coronary lesions was subjected to histomorphological analyses and immunocytochemistry as a means of examining proteoglycan expression. Cell proliferation was assessed with 2 sensitive markers of replication, in situ hybridization for histone 3 messenger RNA expression and immunocytochemistry for Ki-67 expression. The ISR atherectomy specimens consisted primarily of smooth muscle cells, with occasional focal collections of inflammatory cells and organizing thrombus. All specimens had low levels of interstitial collagen and an abundant proteoglycan matrix, with biglycan being overexpressed more commonly than decorin. Cell proliferation was found in only 1 of 20 specimens (2 cells). Established ISR lesions contained an abundant proteoglycan matrix and a paucity of proliferating cells. Future therapeutic strategies for ISR should include targeting extracellular matrix production.


Sequencing of peptides containing alanine, asparagine, histidine, isoleucine and tryptophan by partial methanolysis and fast atom bombardment mass spectrometry.
Five peptides containing the amino acids alanine, asparagine, histidine, isoleucine and tryptophan were investigated by partial methanolysis and fast atom bombardment mass spectrometry in order to examine the behaviour of these amino acid residues under the conditions employed in the methanolytic step. The results obtained confirm that partial methanolysis prior to mass analysis increases considerably the content of sequence information in the mass spectra and that no secondary reactions occur in the residues of the amino acids now investigated, with the exception of the esterification of the glutamic acid carboxyl group and partial conversion of the asparagine amide group in the corresponding methyl ester.


Structural and functional changes to lymph nodes in ageing mice.
Lymph nodes (LN) are secondary lymphoid organs spread throughout the lymphatic system. They function to filter pathogenic material from the lymphatic fluid to maintain the health of the organism. Subcapsular sinus macrophages (SCSM) are among the first-responders within the LN due to their strategic location within the subcapsular sinus region. These macrophages aid the delivery of immune complexes to B cells and follicular dendritic cells (FDC) within the LN. Here we show an increase in SCSM and other macrophage populations within aged LN. However, immune complex uptake by macrophages within LN was not altered with age, nor was immune complex uptake by B cells. LN stromal cell populations, important in immune responses and the localization and survival of leucocytes, were altered in their representation and distribution in aged LN. In particular, FDC regions were decreased in size and had decreased chemokine CXCL13 expression. Furthermore, the retention of immune complexes by FDC was decreased in aged LN at 24 hr post-injection. As FDC are important in the maintenance of germinal centre responses, the decreased retention of immune complex in aged LN may contribute to the reduced germinal centre responses observed in aged mice.


Rapid and Sensitive Analytical Method for the Determination of Insulin in Liposomes by Reversed-Phase HPLC.
Insulin is an important anabolic hormone that regulates the metabolism of carbohydrates, lipids and proteins. In this study, a reverse-phase liquid chromatography (RP-LC) method was successfully validated and tested for the encapsulation efficiency assay of insulin and in vitro release studies. HPLC analyses were carried out using a RP C18- Luna® Phenomenex (4.6 × 250 mm, 5 ?m particle size) column maintained at room temperature, using a mobile phase constituted by a mixture of acetonitrile and 0.1% TFA aqueous solution (60:40, v/v), in an isocratic mode with a flow rate of 1.0 mL/ min, with ultraviolet detection at 214 nm and 20 ?L of injection volume. Method validation was performed according recognized guidelines for system suitability, specificity, linearity, precision, accuracy, LOD, LOQ and robustness. The method was shown to be linear in the range of 0.5-100 ?g/mL (r2 = 0.9993) selective, precise, robust, accurate with LOD and LOQ values were 0.097 ?g/mL and 0.294 ?g/mL, respectively. The developed method proved to be adequate to analyze the encapsulation efficiency and the profile of insulin release from liposomes.


Cumulative effect of depression on dementia risk.
Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer's disease (AD), with control of vascular factors (VFs). Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES) study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (nD), past depression (pD), present depression (prD), and present and past depression (prpD). Logistic regression was used. Results. Data of 1,807 subjects were investigated at baseline (mean age 74.3, 59.3% women), and 1,376 (81.6%) subjects were evaluated after three years. The prevalence of dementia at baseline was 6.7%, and dementia incidence was 6.3%. An effect of depression was observed on dementia prevalence (OR [CI 95%] 1.84 [1.01-3.35] for prD and 2.73 [1.08-6.87] for prpD), and on dementia due to AD (OR 1.98 [0.98-3.99] for prD and OR 3.98 [1.48-10.71] for prpD) (fully adjusted models, nD as reference). Depression did not influence dementia incidence. Conclusions. Present depression and, particularly, present and past depression are associated with dementia at old age. Multiple mechanisms, including toxic effect of depression on hippocampal neurons, plausibly explain these associations.


Relationships between pulmonary inflammation, plasma transudation, and oxygen metabolite secretion by alveolar macrophages.
We have previously shown that alveolar macrophages from normal rabbit lungs do not synthesize reactive oxygen intermediates unless first conditioned by culture in vitro in the presence of serum for 24 to 48 hr. This conditioning process is mediated by a serum constituent that partitions on gel exclusion columns with an apparent m.w. of 30,000 to 50,000 daltons. Alveolar macrophage conditioning in vitro requires protein synthesis, is associated with the generation of membrane NADPH oxidase activity, and is reversible. We have predicted therefore that during the course of pulmonary inflammation, as observed 3 wk after i.v. injection of M. butyricum in oil, alveolar macrophages might similarly become conditioned in vivo through exposure to plasma protein transudates reaching the alveolus. In support of this hypothesis we show that after experimental production of granulomatous pulmonary inflammation in rabbits, alveolar macrophages showed an augmented capacity to secrete superoxide anion when stimulated with phorbol ester, and this enhancement increases exponentially with increased plasma transudation. This augmented enhancement was reversible, and decreased after culture in vitro in the absence of serum. Mature alveolar macrophages were responsible for this enhanced superoxide anion production rather than freshly emigrated monocytes. Moreover, superoxide anion production in this model of pulmonary inflammation appears to be an "all-or-none" phenomenon, with superoxide anion production associated with a subpopulation of optimally conditioned alveolar macrophages, whereas the remaining unconditioned alveolar macrophages produce little or none. We feel that these two classes of alveolar macrophages may be derived from inflamed and noninflamed regions of the lung, respectively, thereby reflecting the discontinuous nature of the inflammatory lesions themselves. Thus we propose that measurements of reactive oxygen intermediate production by lavaged alveolar macrophages may provide a semi-quantitative measure of chronic pulmonary inflammation.


Interictal Epileptiform Activity in the Foramen Ovale Electrodes of a Frontotemporal Dementia Patient.
Frontotemporal dementia (FTD) is a frequent cause of cognitive decline. While epilepsy is an important comorbidity of Alzheimer's disease, we lack studies on its presence in FTD. We report on an FTD patient with transient, short-term changes of behavior and cognitive performance suggesting non-convulsive epilepsy. Video-EEG recording with foramen ovale (FO) electrodes revealed mesio-temporal epileptiform potentials, undetectable by scalp leads. We also found beta spindles in the FO electrodes, not described in the literature. We conclude that video-EEG monitoring with FO electrodes might usefully complement the assessment of dementia-associated epilepsy opening new perspectives in dementia-research.


The role of persistent foramen ovale and other shunts in decompression illness.
A persistent foramen ovale (PFO) and other types of right-to-left shunts are associated with neurological, cutaneous and cardiovascular decompression illness (DCI). A right-to-left shunt is particularly likely to be implicated in causation when these types of DCI occur after dives that are not provocative. It is believed that venous nitrogen bubbles that form after decompression pass through the shunt to circumvent the lung filter and invade systemic tissues supersaturated with nitrogen (or other inert gas) and as a result there is peripheral amplification of bubble emboli in those tissues. Approximately a quarter of the population have a PFO, but only a small proportion of the population with the largest right-to-left shunts are at high risk of shunt-mediated DCI. The increased risk of DCI in people with migraine with aura is because migraine with aura is also associated with right-to-left shunts and this increased risk of DCI appears to be confi ned to those with a large PFO or other large shunt. Various ultrasound techniques can be used to detect and assess the size of right-to-left shunts by imaging the appearance of bubble contrast in the systemic circulation after intravenous injection. In divers with a history of shunt-mediated DCI, methods to reduce the risk of recurrence include cessation of diving, modification of future dives to prevent venous bubble liberation and transcatheter closure of a PFO.


Trajectory of smoking behavior change among Chinese immigrant smokers.
The incidence and mortality rates of smoking-associated lung cancer are high among Chinese immigrant smokers. Coming from a country with different smoking policies, culture, and economic background than the U.S., Chinese smokers may change their smoking behaviors after immigrating to the U.S. This study aims to explore the trajectory of smoking behavior change among Chinese immigrant smokers migrating to the U.S. This qualitative study was guided by the Grounded theory. Semi-structured intensive individual interviews were conducted among 10 eligible participants. A purposive theoretical sampling method was used to recruit participants through a website. Individual interviews were conducted online, via telephone, or in-person in Mandarin. Data were transcribed verbatim in Mandarin, translated into English, and triangulated with follow-up interviews and dialogues among authors to enhance trustworthiness and consistency of the study. Process coding and content analysis were used to analyze data. A total of 10 participants, 7 males and 3 females, were interviewed. Results showed the trajectory of smoking behavior change among Chinese immigrant smokers went through three phases: 1) Beginning to smoke, which included learning to smoke from others, trying to smoke and learning to smoke, and hiding their smoking behaviors from others; 2) maintaining smoking, which included setting boundary around smoking, smoking as a facilitator or barrier to social interaction, feeling pressures related to smoking behavior, and making others happy: Collective smoking and controlling smoking desire; and 3) changing smoking behaviors, which included experiencing life events that were triggers to changing smoking behavior, boredom as a reason for relapses, personal will as a key to quitting smoking, and quitting smoking for a loved one. Although some differences existed between male and female Chinese immigrant smokers' smoking behaviors, their trajectories of smoking behavior change were generally similar. Findings from this study can help health care providers to extend their understanding toward smoking behavior change among Chinese immigrant smokers across different socio-cultural contexts.


Associations of Low-Intensity Resistance Training with Body Composition and Lipid Profile in Obese Patients with Type 2 Diabetes.
Resistance training to increase muscle mass and functional capacity is an integral part of diet and exercise programs for the management of obesity and type 2 diabetes. Low-intensity resistance training with slow movement and tonic force generation (LST) may be a practical and safe regimen for elderly obese individuals but the health benefits are uncertain. This study investigated the effects of LST on body composition and metabolic parameters in obese patients with type 2 diabetes. Twenty-six obese patients with type 2 diabetes engaged in LST training during hospitalization and were advised to maintain this regimen for 12 weeks after discharge. We compared lipid profile, arterial stiffness, and body composition before and after LST training. After 12 weeks of LST training, the ratio of lower extremity muscle mass to body weight increased significantly (0.176 ± 0.028 to 0.184 ± 0.023, mean ± SD), while body fat mass and body fat percentage decreased significantly (36.2 ± 10.9 kg to 34.3 ± 9.4 kg and 41.2 ± 8.6% to 40.1 ± 7.7%, respectively). Moreover, high-density lipoprotein cholesterol was significantly increased (42.2 ± 14 mg/dl to 46.3 ± 12.4 mg/dl) and both free fatty acids and lipoprotein(a) were decreased (665.2 ± 212.1 μEq/l to 525.4 ± 231.3 μEq/l and 15.4 ± 18 mg/dl to 13.8 ± 18 mg/dl, respectively). No significant change was observed in arterial stiffness. Although this study was a non-controlled investigation and some confounding factors including dietary intake, medication and compliance with training might affect the study result, a brief (12-week) LST training program may be a safe and effective strategy for the management of obesity and type 2 diabetes.


Infrared refractive index of germanium-silicon alloy crystals.
The relationship between infrared refractive index and near-infrared, visible, and ultraviolet absorption spectra is examined. The long-wavelength limit and dispersion are determined as simple functions of composition. The computed results are compared with infrared ellipsometric measurements.


[Update on spinal muscular atrophy treatment].
Spinal muscular atrophy (SMA) has been known as a clinical entity for 130 yearsis still recognized today as the most severe autosomal recessive neuromuscular disease (5q,13,2) in pediatrics. Until 2015, SMA treatment was limited to ventilatory, nutritional, and physical therapy support. Currently, the existence of genetic treatments: gene modification by inclusion of exon 7 to the SMN2 gene (nusinersen and risdiplam) or insertion of the SMN1 gene through the adeno-associated viral transporter (onasemnogene) have radically modified the clinical evolution of children with SMA,especially if they are treated early. This review details the effects of the 3 treatments currently in use worldwide.


Effects of Salmonella enterica serovar Enteritidis on cellular recruitment and cytokine gene expression in caecum of vaccinated chickens.
Although vaccination of poultry is a suitable method to limit human food borne gastroenteritis caused by Salmonella (S.), the immune mechanisms responsible for a longer lasting protection against Salmonella infection in birds are not completely understood. To reveal unique protection-related immune parameters, day-old chicks were vaccinated with a commercial live S. Enteritidis vaccine and challenged with wild-type S. Enteritidis 147N at day 56 of life. The bacterial cell count was determined in gut and liver, while the immune cell composition and cytokine gene expression patterns were analysed by immunohistochemistry and quantitative real-time RT-PCR in caecum samples. The presented data suggest that the vaccine-elicited immune protection against the Salmonella wild-type infection was rather related to the bacterial count in gut mucosa and liver than to the colonisation in gut lumen. The higher number of Salmonella wild-type organisms found in caecal wall and liver of the non-immunised compared to immunised birds after challenge correlated with a more pronounced gene expression rate for IL-8, LITAF, iNOS, IL-12 and IFN-gamma. In contrast, immunised birds exhibited higher amounts of CD8(+) T cells as well as IgA than the non-immunised chickens after S. Enteritidis 147N infection in caecum. The results demonstrated a distinctive immune reaction pattern of previously vaccinated compared to non-vaccinated chickens upon S. Enteritidis wild-type challenge.


Direct and indirect effects of demographic, medical, and psychological variables on neuropsychological performance in normal geriatric persons: a structural equation model.
The direct and indirect effects of demographic, medical, and psychological variables on neuropsychological performance in elderly individuals were examined using a LISREL structural equation model. One-hundred fifty-six geriatric subjects were individually administered a comprehensive neuropsychological battery, an extensive medical history and demographics questionnaire, and the Neuropsychology Behavior and Affect Profile (a psychological assessment instrument). The model assessed the effects of five independent latent variables (medical history, psychological functioning, global mental status, education, and gender-related functioning) on two dependent latent variables (nonverbal and verbal neuropsychological functioning). The best fitting model revealed that three latent variables (medical history, global mental status, and gender-related functioning) had direct effects on neuropsychological functioning and that all five independent variables exhibited indirect effects. These findings suggest that the influence of demographic variables on neuropsychological functioning for geriatric persons is complex and that certain variables should not be interpreted independently of each other due to their significant moderating influences.


Adsorption Removal of 17β-Estradiol from Water by Rice Straw-Derived Biochar with Special Attention to Pyrolysis Temperature and Background Chemistry.
Rice straw biochar that produced at three pyrolysis temperatures (400, 500 and 600 °C) were used to investigate the adsorption properties of 17β-estradiol (E2). The biochar samples were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), elemental analysis and BET surface area measurements. The influences of pyrolysis temperature, E2 concentration, pH, ionic strength, background electrolyte and humic acid were studied. Kinetic and isotherm results illustrated that the adsorption process could be well described by pseudo-second-order and Freundlich models. Experimental results showed that ionic strength had less influence on the adsorption of E2 by 500 and 600 °C rice straw biochar. Further, multivalent ions had positive impact on E2 removal than monovalent ions and the influence of the pyrolysis temperature was unremarkable when background electrolyte existed in solutions. The adsorption capacity of E2 decreased with the pH ranged from 3.0 to 12.0 and the humic acid concentration from 2 to 10 mg L-1. Electrostatic attractions and π-π interaction were involved in the adsorption mechanisms. Compared to low-temperature biochar, high-temperature biochar exhibited a better adsorption capacity for E2 in aqueous solution, indicated it had a greater potential for E2 pollution control.


New strategies of diagnostic and therapeutic approach to emergencies in the evolution of patients with diabetes mellitus (Review).
Diabetes mellitus, known as the most widespread disease in the world, along with four other chronic diseases, involves major expenditures and significant human resources for care, thus representing a burden on any type of health care system especially due to its rapid evolution of acute and chronic complications. For the emergency department (ED), the requirements of patients with acute complications of diabetes, determine expenses which are three times higher than those for non-diabetic patients and their hospitalizations are four times more frequent. The acute complications for which patients with diabetes most frequently require the ED are hypoglycemic, hyperosmolar, or ketoacidosis coma as well as alterations of the general condition that is typical of hypoglycemia, diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state and new-onset hyperglycemia. Hypoglycemia and the Somogyi phenomenon are the most common complications of type 1 diabetes but they can also occur in patients with type 2 diabetes who are treated with insulin through its overdose. DKA can occur in type 1 and 2 diabetes either by administering inadequate doses of insulin or due to the existence of precipitating factors such as stress, acute myocardial infarction, infections, sepsis, and/or gastrointestinal bleeding. Hyperosmolar hyperglycemic status is the most common complication in patients with type 2 diabetes and DKA. Treating the acute complications of diabetes in the ED involves, besides taking immediate measures to assess and maintain vital functions, monitoring patients, assessing blood sugar, electrolytes, urea, creatinine, and bicarbonate, and applying appropriate immediate therapeutic measures for each type of acute diabetes complication.


B-type natriuretic peptide following thoracic surgery: a predictor of postoperative cardiopulmonary complications.
B-type natriuretic peptides (BNPs) are secreted by the human heart in response to ventricular wall stretch or myocardial ischaemia, and predict adverse cardiovascular events and death in the general population. Following non-cardiac surgical procedures, there is growing evidence supporting BNP measurement as a powerful independent predictor of death and perioperative complications. However, the clinical implication of elevated BNP measurements after pulmonary resection has not been completely defined. This study aimed to evaluate the role of BNP in predicting adverse cardiopulmonary events after thoracic surgery. A prospective, short-term, observational cohort study was conducted in a tertiary care hospital, including consecutive patients undergoing scheduled pulmonary resection between April 2012 and October 2013. Baseline clinical details were obtained; serum BNP levels were measured at baseline and on postoperative days 1 and 4. We enrolled 294 consecutive patients, median age 66 [interquartile range (IQR): 57-73], 67% male. There were 2 perioperative deaths, and 52 patients experienced one or more cardiopulmonary complications. The baseline median BNP value was normal (29.5 pg/ml, IQR: 16-57.2), and showed significant postoperative increase, peaking on day 1. Patients who developed postoperative complications had a significantly greater BNP increase (P < 0.0001) when compared with those without complications. A postoperative day 1 BNP measurement of ≥118.5 [receiver operating characteristic area: 0.654; 95% confidence interval (CI): 0.57-0.74; P = 0.001] was associated with a 3-fold risk of developing postoperative cardiopulmonary complications [odds ratio (OR): 2.94; 95% CI: 1.32-6.57; P = 0.008]. Logistic regression analysis showed major pulmonary resections (lobectomies or pneumonectomies), BNP ≥ 118.5 and age ≥ 65 to be the only independent predictive variables. In the subset of patients undergoing lobectomy or pneumonectomy (n = 226), BNP was the strongest independent predictor of complications (OR: 3.49; 95% CI: 1.51-8.04). Our results show that BNP elevation, measured in the first days after thoracic surgery, is independently associated with postoperative adverse events. In patients undergoing major pulmonary resections, a postoperative BNP elevation is the strongest independent predictor of cardiopulmonary complications.


Internal dynamics of human ubiquitin revealed by 13C-relaxation studies of randomly fractionally labeled protein.
The use of random, fractional 13C-enrichment combined with low pass filtration has allowed the determination of NMR relaxation parameters at an unprecedented number of sites within recombinant human ubiquitin. Essentially complete 1H, 13C, and 15N resonance assignments for the protein are reported. Carbon spin lattice and heteronuclear NOE relaxation data have been analyzed in the context of the Lipari-Szabo "model free" formalism. The generalized order parameters for 56 main chain alpha C-H vectors have been determined and are found to correspond to the highly restricted motion seen in previous studies of the motion of amide N-H vectors. In distinct contrast, the analysis presented here indicates an unexpected range of dynamics within the interior of the protein. The generalized order parameters of 45 methyl groups of human ubiquitin have been determined. The methyl groups of Thr and Ala residues show generalized order parameters ranging from the Woessner limit (0.111) to below 0.01. Generalized order parameters for all methyl groups of the seven isoleucine residues were determined. With one exception, the generalized order parameters of the gamma methyls were equal to or greater than the corresponding delta methyls, indicating higher mobility away from the main chain. Generalized order parameters for 11 methyl groups of leucine residues were also determined. In six of the seven cases where the generalized order parameters of both prochiral methyl groups were determined, the pro-R methyl consistently shows a higher value than the pro-S methyl group. Generalized order parameters for seven methyl groups of four valines were also determined. There is no apparent correlation of methyl group prochirality with the value of the generalized order parameter. These data have several implications and generally indicate that the interior of the protein is heterogeneously dynamic.


[Advances in studies on chemical components and pharmacology of epiphytic type medicinal plants in the Orohid family].
Many of the epiphytic Orchids are used as traditional Chinese medicine. The chemical components and pharmacology have been studied in recent 15 years. This article reviewed the studies which will be beneficial to reveal the relatives among these medicinal plants in the Orchid Family and be helpful to develop new drugs.


Functional status and co-morbidities are associated with in-hospital mortality among older patients with acute decompensated heart failure: a multicentre prospective cohort study.
Among patients admitted for acute decompensated heart failure (ADHF), half are aged 75 years or over. The high prevalence of co-morbidities and functional impairments in this age group may affect patient outcomes. To assess the association between co-morbidities, functional status and in-hospital mortality in patients with ADHF aged ≥75 years. A prospective, multicentre cohort study. Five French hospitals. Five hundred and fifty-five patients aged ≥75 years admitted to the emergency department with ADHF. Baseline clinical data and co-morbidities were recorded at admission. Functional status and cognition were assessed using the Katz index and Mini-Mental Status Examination score, respectively. The primary outcome was in-hospital mortality. We found high prevalences of co-morbidities and functional impairments including hypertension (74.0%), atrial fibrillation (40.2%), prior acute coronary syndrome (32.3%) and diabetes (18.2%). The average creatinine clearance was 56.3 ml/min/1.73 m(2) (interquartile range, 39.2-77.0). In-hospital mortality was 67/555 (12.1%; 95% confidence interval, 9.4-14.8). In multivariate analysis, in-hospital mortality showed a statistically positive association with prior loss of self-sufficiency (Odds ratio [OR]: 5.85 [2.25-12.19]), hyperglycaemia (OR: 1.80 [1.26-2.54] per 1 SD increase), prior cerebral ischaemic event (OR: 3.56 [1.51-8.44]) and troponin I elevation above upper limit of normal (OR: 2.81 [1.37-5.77]). In addition, systolic blood pressure (OR: 0.98 [0.97-0.99] per 1 mmHg increase) and creatinine clearance (OR: 0.72 [0.51-1.00] per 1 SD increase) were negatively associated with in-hospital mortality. Co-morbidities and functional impairments are associated with a worse short-term prognosis in patients aged ≥75 years admitted for ADHF. Assessing these parameters at admission may improve patient management.


Ex vivo culture of oral keratinocytes using direct explant cell culture technique.
Culture of cells and tissues is a standard research method practiced in many laboratories. In most of the cases, these cultures are being used as substrates for cell products or as investigative tools for delving the mechanism of gene expression, cell proliferation and transformation. Primary monolayer cell culture has been beneficial to study the general biology of both oral and skin keratinocytes. There are two different techniques of primary cell cultures followed, which include direct explant and enzymatic techniques. The aim of the study was to optimize the culture of keratinocytes obtained from patients with normal oral mucosa by direct explant technique. Keratinocytes were isolated from 15 patients and were cultured in vitro and observed under an inverted microscope. The cultured cells were characterized by immunocytochemistry method using pan-cytokeratin. The total success rate of primary culture of the oral epithelial cells by direct explant technique was 88.6%. No contamination of microorganisms in the primary cell cultures was obtained. Within the limited numbers of samples used in the current pilot study, we conclude that the direct explant technique appears to be a simple and successful technique for the isolation of oral mucosal keratinocytes if we follow the appropriate protocol.


Photoinduced amino-imino tautomerism: an infrared study of 2-amino-5-methylpyridine in a low-temperature argon matrix.
The photoreaction of 2-amino-5-methylpyridine was investigated by matrix-isolation infrared spectroscopy and DFT calculation. Photoinduced reversible amino (N=C-NH(2))-imino (NH-C=NH) tautomerism was found between 2-amino-5-methylpyridine and 5-methyl-2(1H)-pyridinimine; the amino tautomer changes to the imino tautomer by UV irradiation (340>lambda>or= 300 nm) and the reverse change occurs by longer-wavelength light irradiation (420>lambda>or= 340 nm). The results of the CASSCF calculation revealed that the amino-imino tautomerism proceeds in vibrational relaxation process from electronic excited state to the ground state. The IR spectra of 2-amino-5-methylpyridine in the T(1) state and 5-methyl-2-pyridinamino radical were also obtained by UV irradiation (lambda>or= 300 nm).


Universality classes for self-avoiding walks in a strongly disordered system.
We study the behavior of self-avoiding walks (SAWs) on square and cubic lattices in the presence of strong disorder. We simulate the disorder by assigning random energy epsilon taken from a probability distribution P(epsilon) to each site (or bond) of the lattice. We study the strong disorder limit for an extremely broad range of energies with P(epsilon) is proportional to 1/epsilon. For each configuration of disorder, we find by exact enumeration the optimal SAW of fixed length N and fixed origin that minimizes the sum of the energies of the visited sites (or bonds). We find the fractal dimension of the optimal path to be d(opt)=1.52+/-0.10 in two dimensions (2D) and d(opt)=1.82+/-0.08 in 3D. Our results imply that SAWs in strong disorder with fixed N are much more compact than SAWs in disordered media with a uniform distribution of energies, optimal paths in strong disorder with fixed end-to-end distance R, and SAWs on a percolation cluster. Our results are also consistent with the possibility that SAWs in strong disorder belong to the same universality class as the maximal SAW on a percolation cluster at criticality, for which we calculate the fractal dimension d(max)=1.64+/-0.02 for 2D and d(max)=1.87+/-0.05 for 3D, values very close to the fractal dimensions of the percolation backbone in 2D and 3D.


Effects of brief cognitive-behavioral interventions on confidence to resist the urges to use heroin and methamphetamine in relapse-related situations.
The aim of this study was to examine the effect of brief cognitive-behavioral (C-B) intervention on improving confidence in managing situations related to heroin and methamphetamine (MAMP) use in drug users. The subjects in the intervention group received a five-session C-B intervention, which focused on the acquisition of skills aimed at helping the subject to reduce drug use. The subjects in the intervention and control groups completed pretest and posttest assessments to determine the changes of confidence in managing situations related to drug use. A total of 70 subjects (40 heroin and 30 MAMP users) and 75 subjects (38 heroin and 37 MAMP users) in the control group completed pretest and posttest assessments. The results revealed that among heroin users, the intervention group had greater improvement in confidence to manage interpersonal situations related to heroin use than did the control group, but there was no difference in the improvement in confidence to manage intrapersonal situations between the two groups. Furthermore, MAMP users in the intervention group showed greater improvement in confidence to manage both intrapersonal and interpersonal situations related to MAMP use than the control group. The present study confirmed the efficacy of brief C-B interventions in improving confidence in ability to resist urges to use heroin and MAMP in stressful interpersonal situations and to use MAMP in intrapersonal situations. The possible explanations for the ineffectiveness of brief C-B interventions to improve confidence in managing intrapersonal situations related to heroin use are discussed.


[Erlotinib as the Second-line Treatment for NSCLC Patients of Stage IIIb/IV.].
Erlotinib has begun to show its unique advantage in the past several years. The aim of this study was to evaluate the efficacy and adverse reactions of erlotinib on patients with advanced non-small cell lung cancer (NSCLC) of stage IIIb/IV. Patients with advanced NSCLC ( IIIb/IV stage) were recruited in this study. They had recurrence after receiving at least one or two regimens of platinum-based chemotherapy from March 2007 to January 2009. Erlotinib was given orally to the patients at dose of 150 mg/d, once daily until disease progression. The clinical outcomes and adverse reactions were observed. Patients were followed up. Kaplan-Meier method was used to perform survival analysis. Among the 16 patients, 0 patients got complete response (0%); 2 patients got partial response (12.5%); 5 stable disease (31.2%) and 9 progressive disease (56.2%). The total response rate (CR+PR) was 12.5% and the disease control rate (including tumor response and stable disease) was 43.7%. All patients were followed up for 1-22 months; 2 cases are still alive until January 2009; the follow-up ratio was 100%. The average survival time could reach 10.25 (3-22) months. The median overall survival period were 9 months and one year progression free survival rate were 13.3%. The main toxicities were rash (93.7%), diarrhea (68.7%), reduced appetite (43.7%) and liver dysfunction (18.7%). Erlotnib demonstrated significant anti-tumor activity and a favorable tolerability profile in this series of NSCLC patients.


Changes in fibroblast growth factor 9 mRNA in granulosa and theca cells during ovarian follicular growth in dairy cattle.
Fibroblast growth factor 9 (FGF9) has been suggested to act as an antidifferentiation factor in cattle by reducing steroidogenesis and increasing cell proliferation in granulosa (GC) and theca (TC) cells. The objective of this study was to characterize FGF9 mRNA abundance in GC and TC during development of dominant follicles in dairy cattle. Estrous cycles of nonlactating dairy cattle were synchronized, and ovaries were collected on either d 3 to 4 (n=8) or 5 to 6 (n=8) postovulation for GC and TC RNA extraction from small (1-5mm), medium (5.1-8mm), and large (8.1-18mm) follicles for PCR analysis. The FGF9 mRNA abundance was greater in GC than in TC. In GC, FGF9 mRNA abundance was greater in small, medium, and large estrogen-inactive [i.e., concentrations of estradiol (E2)<progesterone (P4)] follicles than in large E2-active (i.e., concentrations of E2>P4) follicles at both early (d 3-4) and late (d 5-6) growing phases of first dominant follicle. Abundance of FGF9 mRNA increased in medium-sized follicles from early to late growing phase of the dominant follicle. In TC, FGF9 mRNA abundance was greater in large E2-inactive follicles than in large E2-active follicles on d 3 to 4 postovulation; no significant differences in TC FGF9 mRNA existed among follicle types on d 5 to 6 postovulation. Correlations among levels of follicular fluid hormones and FGF9 mRNA levels revealed significant negative correlations between GC FGF9 mRNA abundance and follicular fluid E2 (r=-0.68), free IGF-1 (r=-0.63), and E2-to-P4 ratio (r=-0.58). In summary, abundance of FGF9 mRNA in GC and TC increases in medium-sized follicles during development of dominant follicles and is less in dominant E2-active than subordinate E2-inactive follicles, suggesting that FGF9 signaling could contribute to normal follicle development and steroidogenesis in dairy cattle.


Potassium channel expression in human CD4+ regulatory and naïve T cells from healthy subjects and multiple sclerosis patients.
The membrane potential of human T cells is regulated by two potassium channels: the voltage-gated K(V)1.3 and the Ca2+-activated K(Ca)3.1. These two channels are essential for efficient antigenic activation and proliferation of T cells and are expressed at different levels in naïve, central memory and effector memory T cells. This provides the opportunity to inhibit the proliferation of the targeted subtype by channel-specific blocking compounds. Regulatory T cells (Tregs) also represent a unique subtype of T cells that perform highly specialized tasks in controlling immune responses, which raises the possibility that they too have a distinctive channel expression pattern. Using whole-cell patch-clamp we tested this hypothesis and determined the ion channel expression of CD4+CD25(hi)CD127(lo) regulatory and CD4+CD25(lo)CD127(hi) naïve T cells from the peripheral blood of healthy volunteers and multiple sclerosis (MS) patients sorted by flow cytometry. We have found that naïve and Treg cells from healthy controls expressed equal numbers of K(V)1.3 channels, while Tregs had a greater membrane surface as assessed by capacitance measurements, and consequentially lower channel density than naïve cells, indicating an "incomplete activation state" of Tregs. In contrast, Tregs from MS patients had fewer K(V)1.3 channels than naïve cells and there was no difference in the membrane capacitance or channel density between the two subtypes of cells. The expression level of K(Ca)3.1 channels was similar in all cell subsets. The observed differences in K(V)1.3 channel expression density may contribute to the varying responses upon antigenic stimulation by these cell types in health and disease.


Prevalence of and rationale for antimicrobial prescription during ambulatory care visits in Japan: a prospective, multicentre, cross-sectional study.
To determine the rate of outpatient antimicrobial use and the rationale for antimicrobial prescription. A prospective, multicentre, cross-sectional study. Ambulatory care settings at community general hospitals. A total of 1972 consecutive ambulatory visits by 1952 patients were included from 2 February 2020 to 13 February 2020. Visits resulting in hospital admission and regularly scheduled visits were excluded. The primary outcome was the proportion of ambulatory visits resulting in antimicrobial drug prescriptions. The secondary outcomes were the reasons for antimicrobial drug prescription and the proportion of unnecessary antimicrobial prescriptions among all antimicrobial drugs used for treatment. The mean patient age was 53.8 (SD 25.8) years old, and the proportion of women was 52.6%. A total of 162 antimicrobial drugs were prescribed in 153 (7.8%) visits. The most common antimicrobial drugs were penicillins (n=48, 29.6%), followed by third-generation cephalosporins (n=35, 21.6%) and quinolones (n=20, 12.4%). Among all the antimicrobial drugs prescribed, 125 (77.2%), 18 (11.1%) and 11 (6.8%) were used for infection treatment, wound prophylaxis and surgical prophylaxis, respectively. Of the 125 antimicrobial drugs used for infection treatment, 60 (48.0%) were judged to be unnecessary. One in every 13 ambulatory visits resulted in antimicrobial use in Japan. Three-fourths of the prescribed antimicrobial drugs were used for infection treatment, but approximately half of those drugs may have been unnecessary. Further efforts to reduce unnecessary antimicrobial drug use are needed. UMIN000039360.


A two-state model for the multilamellar structure of a DNA/cationic lipid complex in the bulk.
Polyanionic DNA can bind electrostatically with cationic lipids to form a complex used for gene delivery and nanostructure construction. Here, we reveal two multilamellar phases, L(I) and L(II), characterized by distinct states of lipid packing and DNA conformation in a DNA/cationic lipid complex in the bulk state. The L(II) phase, formed when the lipids are in excess of DNA in terms of overall ionic charge, is composed of B-DNA confined between the bilayers with the lipid tails aligning normal to the lamellar interface. When DNA becomes in excess of the lipids, the L(I) phase in which the DNA is bound with the tilted lipid chains adopting the A conformation is favored because this configuration offers more economical electrostatic binding between these two components.


The effects of language used by caregivers on agitation in residents with dementia.
In this study, We addressed the problem of whether residents with a diagnosis of dementia would become agitated if given verbal commands at a level of language complexity above their comprehension ability. The study used an A-B-A research design. The convenience sample of 15 subjects was comprised of 11 men and 4 women who resided in a long-term care institution. Their mean age was 86.6 years, and their average length of stay in the institution was 317.3 days. The results lent support to the hypothesis that exposing residents with dementia to language beyond their comprehension ability could result in agitated behavior. The predominant manifestations of agitation were general restlessness, strange noises, and negativism. An important implication for nursing practice is that the language used by caregivers should match the comprehension ability of residents. Caregiving can thereby facilitate communication and, potentially, prevent agitation.


The StepOne real-time polymerase chain reaction detection of Salmonella sp., Salmonella enterica ser. typhimurium and enteritidis in milk and meat.
The aim of this study was to follow contamination of ready to eat milk and meat products with Salmonella spp. by using the StepOne real-time polymerase chain reaction (PCR). Classical microbiological methods for detection of foodborne bacteria involve the use of pre-enrichment and/or specific enrichment, following isolation of bacteria in solid media and the final confirmation by biochemical and/or serological tests. We used the PrepSEQ Rapid Spin Sample Preparation Kit for isolation of DNA and MicroSEQ® Salmonella spp. Detection Kit for pursuance of the real-time PCR (Applied Biosystems). In samples without incubation we detected strain of Salmonella sp. in 5 out of 25 samples (swabs), as well as in the internal positive control (IPC), which was positive in all samples. This StepOne real-time PCR assay is extremely useful for any laboratory equipped by real-time PCR. It is a fast, reproducible, simple, specific and sensitive way to detect nucleic acids, which could be used in clinical diagnostic tests in the future. Our results indicated that real-time PCR assay developed in this study could sensitively detect Salmonella spp. in ready-to-eat food. This could prevent infection caused by Salmonella, and also could benefit food manufacturing companies by extending their product's shelf-life as well as saving the cost of warehousing their food products while awaiting pathogen testing results.


Four-Corner Arthrodesis Using a Dedicated Dorsal Circular Plate.
Scaphoid excision and 4-corner fusion is a standard procedure for advanced carpal collapse. The purpose of this study was to evaluate its effectiveness using a specific designed locking plate of the latest generation. Between October 2012 and December 2015, 12 patients underwent this procedure using the Flower (KLS Martin Group, Tuttlingen, Germany) circular locking plate. The surgical technique is standardized. Three patients were affected by a scapholunate advanced collapse and 9 patients by a scaphoid nonunion advanced collapse. All patients underwent a computed tomographic scan to study the real achievement of the fusion. Only 2 patients did not show complete fusion. All the patients with successful fusion returned to previous work and manual activities. Four-corner arthrodesis with circular locking plate is an alternative surgical treatment for carpal arthritic collapse.


Ultraviolet matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for phosphopeptide analysis with a solidified ionic liquid matrix.
A solidified ionic liquid matrix (SILM) consisting of 3-aminoquinoline, α-cyano-4- hydroxycinnamic acid and ammonium dihydrogen phosphate combines the benefits of liquid and solid MALDI matrices and proves to be well suitable for phosphopeptide analysis using MALDI-MS in the low femtomole range. Desalting and buffer exchange that typically follow after phosphopeptide elution from metal oxide affinity chromatography (MOAC) materials can be omitted. Shifting the pH from acidic to basic during target preparation causes slow matrix crystallization and homogeneous embedding of the analyte molecules, forming a uniform preparation from which (phospho)peptides can be ionized in high yields over long periods of time. The novel combination of MOAC-based phosphopeptide enrichment with SILM preparation has been developed with commercially available standard phosphopeptides and with α-casein as phosphorylated standard protein. The applicability of the streamlined phosphopeptide analysis procedure to cell biological and clinical samples has been tested (i) using affinity-enriched endogenous TRIM28 from cell cultures and (ii) by analysis of a two-dimensional gel-separated protein spot from a bladder cancer sample.


Proteolytic activity of the purified hormone-binding subunit in the estrogen receptor.
The hormone-binding subunit of the calf uterus estradiol receptor was purified as a hormone-free molecule. Immunoaffinity chromatography with a specific monoclonal antibody was used as the final step. The purified subunit was specifically labeled by radioactive diisopropyl fluorophosphate. The diisopropyl fluorophosphate-labeled amino acid was serine. The purified receptor was able to release the fluorogenic or chromogenic group from synthetic peptides containing phenylalanine at the carboxyl terminus. This occurred only in the presence of estradiol and was hampered by aprotinin and diisopropyl fluorophosphate. Estradiol-dependent hydrolytic activity was also found in the eluate from gel slices after SDS/PAGE of purified receptor. This activity comigrated with the renaturable estradiol-binding activity. The estradiol antagonists 4-hydroxytamoxifen and ICI 164,384 as well as other steroid hormones were unable to activate this hydrolytic activity.


The effects of n-3 fatty acids on atherosclerosis and the vascular response to injury.
The potentially beneficial effects of dietary fatty acids on vascular disease continues to generate intense clinical and investigative interest throughout the world. In particular, attention has focused on the highly unsaturated n-3 fatty acids found in marine and certain plant oils in the prevention of atherosclerosis and thrombosis. This article will review the impact of these fatty acids on vascular disease in epidemiologic studies, in animal models of atherosclerosis and vascular injury, and in human clinical trials of restenosis following angioplasty. Some of the more specific cellular effects of n-3 fatty acids will also be discussed. The data accumulated in the last 15 years suggest that additional prospective clinical trials of n-3 fatty acids in the prevention or treatment of vascular disease are warranted in humans.


Inducible and cell type-specific expression of VL30 U3 subgroups correlate with their enhancer design.
The murine VL30 elements constitute one family of retrotransposons represented in 100 to 200 copies that are dispersed among the mouse chromosomes. On the basis of sequence homology, we have subdivided mouse VL30 members into four distinct U3 subgroups. The use of subgroup-specific probes in Northern (RNA) blot analyses shows that individual VL30 U3 subgroups are expressed in a tissue-specific manner. We show by in situ hybridization of mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) that VL30 expression is induced in epidermal keratinocytes but not in dermal fibroblasts. Transient transfections of reporter gene plasmids together with in vitro binding analysis indicate that TPA-induced VL30 transcription specific for keratinocytes is mediated by two cooperating sequence motifs in juxtaposed position. One sequence motif is shown to constitutively bind CREB- and Jun-related proteins in both keratinocytes and fibroblasts, whereas the other is a target for TPA-induced c-Rel/p65(NF-kappa B)-binding activity specifically in keratinocytes. These binding sites are found to be conserved within U3 subgroups and individual U3 regions showing induced expression in TPA-treated mouse epidermis. These results together with a sequence comparison between different U3 subgroups indicate that cell type-specific activity of transcription factors known to regulate VL30 transcription and the presence or absence of their cognate binding sites within individual U3 regions determine inducible and cell type-specific VL30 expression. The variable VL30 U3 regions might thus be useful tools to study inducible and cell type-specific transcription in many different cell systems.


Catching the Conformational Wave: Measuring the Working Strokes of Protofilaments as They Curl Outward from Disassembling Microtubule Tips.
Optical traps have enabled foundational studies of how mechanoenzymes such as kinesins and dynein motors walk along microtubules, how myosins move along F-actin, and how nucleic acid enzymes move along DNA or RNA. Often the filamentous substrates serve merely as passive tracks for mechanoenzymes but microtubules and F-actin are themselves dynamic protein polymers, capable of generating movement and force independently of conventional motors. Microtubule-driven forces are particularly important during mitosis, when they align duplicated chromosomes at the metaphase plate and then pull them apart during anaphase. These vital movements depend on specialized protein assemblies called kinetochores that couple the chromosomes to the tips of dynamic microtubule filaments, thereby allowing filament shortening to produce pulling forces. Although great strides have been made toward understanding the structures and functions of many kinetochore subcomplexes, the biophysical basis for their coupling to microtubule tips remains unclear. During tip disassembly, strain energy is released when straight protofilaments in the microtubule lattice curl outward, creating a conformational wave that propagates down the microtubule. A popular viewpoint is that the protofilaments as they curl outward hook elements of the kinetochore and tug on them, transferring some of their curvature strain energy to the kinetochore. As a first step toward testing this idea, we recently developed a laser trap assay to directly measure the working strokes generated by curling protofilaments. Our "wave" assay is based on an earlier pioneering study, with improvements that allow measurement of curl-driven movements as functions of force and quantification of their conformational strain energy. In this chapter, we provide a detailed protocol for our assay and describe briefly our instrument setup and data analysis methods.


Cutting edge technologies in chronic inflammation research.
This concise review provides the broad background and selection from the literature for a Keynote lecture at EHSF 2022 on state of the art technologies in inflammation research, with an emphasis on disease of the skin and the nervous system. The value of ex vivo skin explant models is discussed, as well as the innovative use of animal models, wherein the crucial roles of antigen experience and "wild" microbiota are emphasized. Spectral flow cytometry allowing large surface marker panels to be explored is touched upon, as well as multiplex technology for cytokines and other analytes important for inflammation and tissue damage. Single-cell sequencing and in situ transcriptomics (spatial profiling) now provide exciting granular information on functional cell subsets, interactions and plasticity. A selection of novel research and diagnostic tools for antibodies against linear peptides or gangliosides is presented. Finally, the review discusses a new anti-inflammatory strategy against skin inflammation with a panel of protease inhibitors derived from the protein fraction of industrial starch potatoes.


Heating temperature dependence of Cr(III) oxidation in the presence of alkali and alkaline earth salts and subsequent Cr(VI) leaching behavior.
In this paper, the temperature dependence of Cr(III) oxidation in high temperature processes and the subsequent Cr(VI) leaching was studied using synthetic mixtures. It was experimentally shown that in the presence of alkali and alkaline earth salts, oxidation of Cr(III) takes place, consistent with thermodynamic calculations. Heating of synthetic mixtures of Cr2O3 and Na, K, or Ca salts led to elevated leaching of Cr(VI); in the presence of Na, more than 80% of the initial Cr(III) amount was converted to Cr(VI) at 600-800 °C. Kinetic experiments allowed explanation of the increase in Cr(VI) leaching for increasing temperatures up to 600-800 °C. After reaching a maximum in Cr(VI) leaching at temperatures around 600-800 °C, the leaching decreased again, which could be explained by the formation of a glassy phase that prevents leaching of the formed Cr(VI). By way of illustration, Cr(VI) formation and leaching was evaluated for a case study, the fabrication of ceramic material from contaminated sludge. Based on the proposed reaction mechanisms, countermeasures to prevent Cr oxidation (addition of NH4H2PO4, heating under inert atmosphere) were proposed and successfully tested for synthetic mixtures and for the case study.


[Evaluation for druggability of traditional Chinese medicine preparations in medical institutions based on human use experience].
Traditional Chinese medicine(TCM) preparations in medical institutions are an important source of research and development(R&D) of TCM new drug. With years of usage in therapy, these preparations' safety and effectiveness have generally been validated in clinic. However, there are still a few disadvantages in TCM new medicine development, such as similar prescriptions, excessive prescription ingredients, too broad clinical orientation, lack of solid clinical data, issue in pharmaceutical quality control, and intellectual property disputes. Nowadays, the Three-Combined Evaluation System has strengthened policy support for the new TCM R&D. In order to improve the success rate of TCM R&D, due to the difficulties within, this paper proposes the process of transforming TCM preparations in medical institutions into new TCM and advocates the evaluation for druggability based on Human Use Experience(HUE). The potencial preparations ought to follow traditional Chinese Medical theory, sufficient HUE data in indication, syndrome type of TCM, target population, usage, dosage, and course of treatment are required. Particular attention should be paid to the source, evolution, and improvement process of prescription, and evaluate the dosage, ingredients, and herb resources of prescription. To assess the feasibility of mass production, it is necessary to determine whether the pharmaceutical process is mostly consistent with the new drug and whether the dosage form is reasonable. By summarizing the clinical application of the preparations, the whole picture of its clinical application would be reveal as much as possible. It is beneficial to evaluate its clinical value and R&D prospect. In consideration of the lack of clinical safety data of preparations, safety profile needs to be collected according to the prescription. The quality of clinical data needs to be evaluated by focusing on the integrity and accuracy of data to reduce bias and confusion. Significant care should be paid to intellectual property protection to avoid legal disputes.


Indirect injury of the optic nerve.
Visual loss due to optic nerve injury after closed head trauma constitutes a formidable diagnostic and therapeutic challenge for the clinician. Assessment must be made of the site of optic nerve injury, and this is often difficult in the patient with an altered level of consciousness. A decision regarding optic nerve decompression must be formulated, yet the literature is confusing with regard to operative indications. In reviewing current pathogenetic theories, clinicopathological data, and therapeutic options, this report attempts to clarify the role of surgical intervention in indirect optic nerve injury.


Impulse control disorders and compulsive behaviors associated with dopaminergic therapies in Parkinson disease.
Impulse control disorders (ICD) (most commonly pathologic gambling, hypersexuality, and uncontrollable spending) and compulsive behaviors can be triggered by dopaminergic therapies in Parkinson disease (PD). ICD are especially prevalent in patients receiving a dopamine agonist as part of their treatment regimen for PD, and have also been reported when dopamine agonists are used for other indications (e.g., restless legs syndrome). Although these iatrogenic disorders are common, affecting 1 in 7 patients with PD on dopamine agonists, they often elude detection by the treating physician. ICD lead to serious consequences, causing significant financial loss and psychosocial morbidity for many patients and families. ICD can appear at any time during treatment with dopamine agonists, sometimes within the first few months, but most often after years of treatment, particularly when patients receive dopamine agonists and levodopa together. In most cases ICD resolve if the dopamine agonist is withdrawn, and PD motor symptoms are managed with levodopa monotherapy. Familiarity with the clinical aspects, risk factors, pathophysiology, and management of ICD is essential for physicians using dopaminergic therapies to treat PD and other disorders.


Treatment strategies in patients with rheumatoid arthritis for whom methotrexate monotherapy has failed: data from the NOR-DMARD register.
To compare the effectiveness of adding synthetic disease-modifying antirheumatic drugs (sDMARDs) versus tumour necrosis factor α inhibitors (TNFi) to methotrexate (MTX) in patients with rheumatoid arthritis (RA) who were MTX inadequate responders (IR). Second, to examine outcomes in patients receiving MTX+TNFi for whom the MTX+sDMARD combination had also failed. Patients with RA (disease duration ≤ 5 years, MTX IR and naïve to other DMARDs) starting treatment with MTX+TNFi or MTX+sDMARDs were included. From the latter group a subgroup of patients who went on to receive MTX+TNFi was identified. Patients receiving MTX+TNFi (n=98) and MTX+sDMARDs (n=129) had similar baseline disease activity when starting combination therapy (mean Disease Activity Score 28 (DAS28) = 4.90 and 4.96, respectively). Three- and 6-month effectiveness and 2-year drug survival were better for MTX+TNFi than for MTX+sDMARDs: mean DAS28 was -1.61 versus -0.85 after 3 months (p<0.001) and -1.91 versus -1.03 after 6 months (p=0.01); DAS28<2.6 was reached by 29.0% versus 11.6% after 3 and 34.5% versus 12.9% after 6 months. Effectiveness was somewhat better with triple therapy than other MTX+sDMARD combinations but was generally inferior compared with MTX+TNFi. For the patients who received MTX+TNFi as a third step after MTX+sDMARDs had failed (n=38) there was a tendency towards lower remission rates, worse disease activity states and inferior drug survival compared with patients who received MTX+TNFi directly after the failure of MTX. Effectiveness was better for MTX+TNFi than for MTX+sDMARDs. Patients who started MTX+TNFi after two synthetic DMARD regimens had failed had a tendency to less favourable disease states after 3 months than patients who switched directly from MTX to MTX+TNFi.


Ganciclovir transiently attenuates murine cytomegalovirus-associated renal allograft inflammation.
Prophylactic ganciclovir (GCV) is used in high-risk renal transplant patients to prevent acute cytomegalovirus (CMV) disease, but its impact on inflammation within the allograft itself remains undefined. To study the effect of GCV prophylaxis on allograft inflammation, murine CMV (MCMV)-infected allografts were analyzed in a murine donor positive/recipient negative allogeneic renal transplantation model by flow cytometry and immunofluorescent staining. By flow cytometry, CD45+ leukocyte infiltrates were more abundant in MCMV-infected allografts at 14 days posttransplant compared with uninfected grafts (P<0.01) and decreased in the presence of GCV (P<0.05). CD11c+ dendritic cells, Gr-1+ myeloid cells, CD204+ macrophages, and CD49b+ natural killer cells were reduced in GCV-treated allografts compared with MCMV-infected grafts without GCV treatment (P<0.05). However, GCV failed to reduce these cell types to levels found in MCMV-uninfected allografts. By day 7 after cessation of GCV prophylaxis, dendritic cells, macrophages, and natural killer cells increased in number and became statistically indistinguishable from numbers of cells found in MCMV-infected allografts without GCV. GCV treatment did not affect the numbers of CD4+, CD8+, or CD19+/B220+ lymphocytes infiltrating the allografts. Infiltrates were confirmed histologically by immunofluorescent staining for CD3+ and CD11b+ cells. In this model, MCMV-infected allografts developed significantly greater innate and adaptive leukocytic infiltrates compared with uninfected grafts. GCV attenuated the MCMV-associated innate leukocyte infiltrates in infected allografts but not the lymphocytic infiltrates. The attenuated innate response was limited to the period of GCV prophylaxis.