Changes in the prescribed daily doses of transdermal fentanyl and transdermal buprenorphine during treatment of patients with cancer and noncancer pain in Germany: results of a retrospective cohort study.
During long-term therapy with strong opioids (step III opioids according to the World Health Organization [WHO] analgesic ladder), dose increases are often necessary because of deterioration of the primary disease or development of tolerance. The purpose of this study was to compare changes in dosages of transdermal (TD) fentanyl and TD buprenorphine in patients with cancer and non-cancer pain. In a retrospective study, patients with cancer and noncancer pain being treated with TD fentanyl or TD buprenorphine for at least 3 months between January 2001 and December 2003 were identified from the IMS Disease Analyzer-mediplus database, which contains all patient-related data documented from 400 medical practices in Germany. The indications for treatment were defined according to the International Classification of Diseases, 10th Revision, and included neoplasm (cancer groups), and osteoarthritis, low back pain, and osteoporosis (noncancer groups). The cohort patients were considered to have comparable pain intensity because they had received similar analgesic premedication classified according to steps I to III of the WHO analgesic ladder (cohort groups). The mean prescribed daily doses on first and last prescription were documented, and the mean percentile increases were calculated over the whole treatment duration and per day. Additionally, the mean percentile intraindividual increases (on a per-patient basis) were estimated. The cohort groups consisted of 448 patients with noncancer pain and 446 patients with cancer pain (552 women and 342 men; mean age, 74 years; range, 25-101 years). The mean percentile increases in dosages over the whole treatment duration and adjusted per day were significantly higher in patients taking TD fentanyl (P < 0.05). Differences were even greater for the mean percentile intraindividual increases per day, which totaled 0.42%and 0.17% for cancer patients taking TD fentanyl and TD buprenorphine, respectively; corresponding values were 0.25% and 0.09%in noncancer patients (P < 0.001). This retrospective analysis showed a significantly higher increase in the mean daily doses of TD fentanyl as compared with TD buprenorphine. The results must be verified in prospective, randomized clinical studies.


Applied tissue engineering in the closure of severe burns and chronic wounds using cultured human autologous keratinocytes in a natural fibrin matrix.
Whereas in severe burns cultured human epithelial cells may well serve as a life saving method, the true value of tissue-engineered skin products in chronic wound care has yet to be clearly defined. Among other well-known clinical problems, the engraftment rate of commercially available multilayered "sheet grafts" has been shown to vary extremely. Adherence of transplanted cells to the wound bed--especially in the presence of potential wound contamination-- is one of the crucial aspects of this technique. Keratinocyte suspensions in a natural fibrin sealant matrix can potentially treat a variety of skin defects. In acute burn wounds, as well as in chronic wounds the clinical application of this type of tissue-engineered skin substitute demonstrates the capacity of cultured human autologous keratinocytes in a fibrin sealant matrix to adhere to wound beds, attach and spread over the wound resulting in reepithelialization of both acute and chronic wounds. In full thickness burns the combination of this new tool with allogenic dermis is a promising option to achieve complete dermal-epidermal reconstitution by means of tissue engineering and guided tissue repair. When transferring this technique into the treatment of chronic wounds we found an optimal preparation of such recipient wound beds to be crucial to the success. The additional application of continuous negative pressure (vacuum therapy) and preliminary chip skin grafting to optimally prepare the recipient site may be helpful tools to achieve such well-prepared and graftable surfaces. Prospective controlled comparative studies should be designed to further assess the clinical efficacy of this technique.


A computer programme for the calculation of the results of amino acid analysis.
1. An ALGOL computer programme is presented for the calculation of the results of amino acid analysis. 2. The suggestion is made that a similar approach could be made to other tedious and repetitive biochemical calculations.


A Comparative View on Human Somatic Cell Sources for iPSC Generation.
The breakthrough of reprogramming human somatic cells was achieved in 2006 by the work of Yamanaka and Takahashi. From this point, fibroblasts are the most commonly used primary somatic cell type for the generation of induced pluripotent stem cells (iPSCs). Various characteristics of fibroblasts supported their utilization for the groundbreaking experiments of iPSC generation. One major advantage is the high availability of fibroblasts which can be easily isolated from skin biopsies. Furthermore, their cultivation, propagation, and cryoconservation properties are uncomplicated with respect to nutritional requirements and viability in culture. However, the required skin biopsy remains an invasive approach, representing a major drawback for using fibroblasts as the starting material. More and more studies appeared over the last years, describing the reprogramming of other human somatic cell types. Cells isolated from blood samples or urine, as well as more unexpected cell types, like pancreatic islet beta cells, synovial cells, or mesenchymal stromal cells from wisdom teeth, show promising characteristics for a reprogramming strategy. Here, we want to highlight the advantages of keratinocytes from human plucked hair as a widely usable, noninvasive harvesting method for primary material in comparison with other commonly used cell types.


Splenic accumulation of interleukin-3-dependent hematopoietic cells in Friend erythroleukemia.
Interleukin-3-dependent hematopoietic stem cells commonly accumulate in spleens of mice infected with leukemia viruses. To study their origins, a molecularly tagged helper-free Friend spleen focus-forming virus was used to produce erythroleukemias. Uninfected interleukin-3-dependent basophil-mast cell progenitors coproliferated amidst the spleen focus-forming virus-infected leukemic cells. Splenic proliferation of normal stem cells is apparently a host response to leukemogenesis, and we propose that it may contribute to certain retroviral diseases.


Borderline susceptibility to methicillin in Staphylococcus aureus: a new mechanism of resistance?
Staphylococcus aureus strains with borderline levels of susceptibility or resistance to antistaphylococcal penicillinase-resistant penicillins (PRPs) were initially reported as neither heteroresistant nor multiply resistant organisms, producing large amounts of beta-lactamase, and becoming fully susceptible to PRPs in the presence of beta-lactamase inhibitors. This borderline susceptibility or low-level resistance was suggested to be due to beta-lactamase hyperproduction: according to this hypothesis, the staphylococcal beta-lactamase, when hyperproduced, would succeed in partially hydrolyzing methicillin and related PRPs. However, later studies demonstrated that borderline PRP susceptibility cannot be explained soley on this basis, beta-lactamase hyperproduction being neither sufficient nor necessary to determine the borderline phenotype. Intrinsic mechanisms have also been reported to be associated with some borderline PRP susceptible S. aureus strains. The more recent discovery of a PRP-hydrolyzing beta-lactamase (methicillinase) produced, in addition to the conventional penicillinase, by borderline S. aureus strains suggests that this second, more specific beta-lactamase is more likely to be responsible for the borderline phenotype than an increased amount of the penicillinase. The slow kinetics of PRP hydrolysis by methicillinase is consistent with its association with reduced susceptibility rather than true resistance to PRPs. The combined effect of methicillinase plus penicillinase on some common substrates might explain the increased beta-lactamase activity often observed in borderline S. aureus strains.


The phase problem for one-dimensional crystals.
The phase problem for diffraction amplitudes measured from a one-dimensional crystal is examined. In the absence of any a priori information, the solution to this problem is shown to be unique up to a parameterized, low-dimensional set of solutions. Minimal additional a priori information is expected to render the solution unique. The effects of additional information such as positivity, molecular envelope and helical symmetry on uniqueness are characterized. The results are pertinent to structural studies of polymeric and rod-like biomolecular assemblies that form one-dimensional, rather than three-dimensional, crystals. This shows the potential for ab initio phasing of diffraction data from single such assemblies measured using new X-ray free-electron laser sources. Such an approach would circumvent the complicated inversion of cylindrically averaged diffraction that is necessary in traditional X-ray fibre diffraction analysis.


Pathogenesis and management of Candida infection syndromes in non-neutropenic patients.
Infections due to Candida spp. are increasingly common. Despite a number of studies examining the characteristics of fungemic (non-neutropenic) patients, there are no prospective studies defining indications for therapy before the appearance of fungemia. This article reviews the potential pathways for dissemination of Candida from the gastrointestinal tract, believed to be the primary entry route for yeast. Particular attention is focused on mucosal shedding at the villous tip and the potential role of microfold cells in this process. Therapeutic usage of amphotericin B, the agent of choice for serious Candida infection, is reviewed, along with usage of 5-flucytosine and fluconazole.


Detection of eight foodborne bacterial pathogens by oligonucleotide array hybridization.
Simultaneous and rapid detection of multiple foodborne bacterial pathogens is important for the prevention of foodborne illnesses. The aim of this study was to evaluate the use of 16S rDNA and 23S rDNA sequences as targets for simultaneous detection of eight foodborne bacterial pathogens. Nineteen bacterial oligonucleotide probes were synthesized and applied to nylon membranes. Digoxygenin labeled 16S rDNA and 23S rDNA from bacteria were amplified by PCR using universal primers, and the amplicons were hybridized to the membrane array. Hybridization signals were visualized by NBT/BCIP color development. The eight intestinal bacterial pathogens including Salmonella enterica, Escherichia coli, Bacillus cereus, Vibrio cholerae, Shigella dysenteriae, Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis were appropriately detected in a panel of oligonucleotide array hybridization. The experimental results showed that the method could discriminate the bacterial pathogens successfully. The sensitivity of oligonucleotide array was 103 CFU/ml. This study showed that 16S rDNA and 23S rDNA genes had sufficient sequence diversity for species identification and were useful for monitoring the populations of foodborne pathogenic bacteria. Furthermore, results obtained in this study revealed that oligonucleotide array hybridization had a powerful capability to detect and identify the bacterial pathogens simultaneously.


Regulation of cholecystokinin release and transcription in a rat without gene expression of cholecystokinin-A receptor.
An Otsuka Long-Evans Tokushima Fatty (OLETF) rat does not possess cholecystokinin (CKK)-A receptor gene expression because of a genetic abnormality. We examined the CCK release and its transcription in OLETF rats in comparison with control (Long-Evans-Tokushima-LETO) rats. Animals at 5-6 and 24-25 weeks of age were used. The level of CCK mRNA and CCK concentration in the small intestinal mucosa, and the level of CCK-A receptor mRNA in the pancreas were examined. To examine CCK release, rats were prepared with external bile and pancreatic fistulae. The basal plasma levels of CCK and those at 2 h after bile-pancreatic juice diversion were measured by radioimmunoassay. The levels of CCK mRNA, and tissue CCK concentration increased significantly with age in both strains, but the values in OLETF rats were significantly lower than those in LETO rats. The CCK-A receptor mRNA level also increased with age in LETO rats. The plasma CCK concentration was significantly increased by bile-pancreatic juice diversion regardless of age and strain; however, the level of plasma CCK in OLETF rats at 24-25 weeks of age was significantly lower than that of LETO rats. It is suggested that the long-term defect of CCK-A receptor may decrease CCK release and transcription.


Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin.
Protease-activated receptor-2 (PAR-2) plays a role in inflammatory reactions in airway physiology. Proteases cleaving the extracellular NH(2) terminus of receptors activate or inactivate PAR, thus possessing a therapeutic potential. Using RT-PCR and immunocytochemistry, we show PAR-2 in human airway epithelial cell lines human bronchial epithelial (HBE) and A549. Functional expression of PAR-2 was confirmed by Ca(2+) imaging studies using the receptor agonist protease trypsin. The effect was abolished by soybean trypsin inhibitor and mimicked by the specific PAR-2 peptide agonist SLIGKV. Amplitude and duration of PAR-2-elicited Ca(2+) response in HBE and A549 cells depend on concentration and time of agonist superfusion. The response is partially pertussis toxin (PTX) insensitive, abolished by the phospholipase C inhibitor U-73122, and diminished by the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Cathepsin G altered neither the resting Ca(2+) level nor PAR-2-elicited Ca(2+) response. Thermolysin, a prototypic bacterial metalloprotease, induced a dose-dependent Ca(2+) response in HBE, but not A549, cells. In both cell lines, thermolysin abolished the response to a subsequent trypsin challenge but not to SLIGKV. Thus different epithelial cell types express different PAR-2 with identical responses to physiological stimuli (trypsin, SLIGKV) but different sensitivity to modifying proteases, such as thermolysin.


Outcomes of percutaneous zygapophysial and sacroiliac joint neurotomy in a community setting.
To evaluate the analgesic, physical, and psychological outcomes of percutaneous radiofrequency neurotomy for persistent zygapophysial and sacroiliac joint pain in a community setting. A prospective evaluation of 379 consecutive neurotomies in a single specialist practice over an extended period 2001-2010. A provincial community environment in Australia. All patients who had positive responses to diagnostic blocks, performed according to the guidelines of the International Spine Intervention Society by three trained specialists, underwent percutaneous radiofrequency thermal neurotomies performed by the author. Radiofrequency neurotomies to denervate the zygapophysial or sacroiliac joints according to the standards of the International Spine Intervention Society. Numerical Rating Scale for Pain, Functional Rating Index, 4-Activities of Daily Living Scale, General Health Questionnaire, Depression Anxiety Stress Scale, duration of pain relief, "whether they would do it again," and overall amount of pain relief. Of 379 procedures, 272 (72%) were regarded as successful by the patients. Irrespective of region treated. The results were highly significant by t-test, and the effect size was large as determined by the Cohen's d. Adverse events were infrequent and relatively minor. Repetitions of the procedure were highly successful. Neurotomy of the cervical, thoracic, lumbar, and sacroiliac joints were uniformly successful with 72% recipients obtaining an average of 86% reduction in pain for a period of 12 months.


A case of primary oncocytic adenocarcinoma of the lacrimal sac.
Lacrimal sac tumours are rare entities. Patients often present with epiphora, recurrent dacryocystitis, and/or a lacrimal sac mass. Neoplasms of the lacrimal system may conveniently be grouped into epithelial and non-epithelial types: papillomas are the most common benign epithelial tumours, while oncocytic adenocarcinomas are extremely rare. Here we report a case of primary oncocytic adenocarcinoma of the lacrimal sac in a 56-year-old man.


Characteristics of and risk factors for compensated occupational injury and disease claims in dairy farmers: a case-control study.
Research indicates that dairy farmers have an elevated risk of work-related adverse health outcomes. This case-control study evaluated the characteristics of and risk factors for compensated occupational injury and disease claims among Finnish dairy farmers. The cases consisted of 19 farm couples in which both spouses had a history of multiple claims. There were 283 claims in total, a rate of 26.6 claims per 100 person-years. The controls consisted of 12 couples in which neither spouse had compensated or rejected claims during their work history as insured farmers. A combined mail/telephone survey charted potential risk factors for compensated claims. These claims frequently involved work tasks and causes related to animal husbandry. Cattle were the most common cause for injuries in general and for serious injuries in particular. Gender differences in farm work and claims were observed. Using logistic regression analyses, we identified personal and work-related risk factors including long work history, small-scale dairy farm operation, and conventional stanchion barn for dairy cattle. Outdated working conditions, while not statistically significant, were positively associated with claims as well. Declined current work ability and musculoskeletal or respiratory conditions were significantly associated with claims where each of these outcomes may contribute to the other. Identified factors could be used to select subgroups of dairy farmers with either elevated or reduced risk of claims. Prevention of adverse health outcomes could be most effective when targeted to farmers at highest risk of occupational injury and disease.


The impact of gender on the outcomes of invasive versus conservative management of patients with non-ST-segment elevation myocardial infarction.
Studies have suggested that women who present with non-ST-segment elevation myocardial infarction (NSTEMI) may differ in their clinical response to early invasive strategy compared to male patients. We examined the impact of gender difference in NSTEMI patients on outcomes following invasive versus conservative treatment. Patients enrolled in our national myocardial infarction (MI) registry between January 2000 and September 2005 with diagnosis of NSTEMI were retrospectively analysed. The study endpoint was the occurrence of major adverse cardiac events (MACE) in the patients at 1 year. A total of 1353 patients (62.2% male) with NSTEMI were studied. The mean age of men was 62 +/- 14 versus 72 +/- 12 years in women in the cohort (P <0.001). The prevalence of hypertension and diabetes mellitus were significantly higher in women. Men were more likely to undergo revascularisation than women (OR, 2.97; 95% CI, 2.18-3.89, P <0.001). Among those who were revascularised, there was no gender difference in survival or recurrent MI rates during hospitalisation and at 1 year. Compared to medical therapy, percutaneous coronary intervention (PCI) was associated with a significant reduction in MACE in both women (OR, 0.44; 95% CI, 0.20-0.95) and men (OR, 0.40; 95% CI, 4.79-12.75). The most important predictor of MACE for females was diabetes mellitus (HR, 1.98; 95% CI, 1.17-3.33). There is a gender-based difference in the rate of revascularisation among patients with NSTEMI. Women benefit from an invasive approach as much as men, despite their advanced age, with similar rates of mortality and recurrent MI at 1-year follow-up.


Characterization of the virome associated with Haemagogus mosquitoes in Trinidad, West Indies.
Currently, there are increasing concerns about the possibility of a new epidemic due to emerging reports of Mayaro virus (MAYV) fever outbreaks in areas of South and Central America. Haemagogus mosquitoes, the primary sylvan vectors of MAYV are poorly characterized and a better understanding of the mosquito's viral transmission dynamics and interactions with MAYV and other microorganisms would be important in devising effective control strategies. In this study, a metatranscriptomic based approach was utilized to determine the prevalence of RNA viruses in field-caught mosquitoes morphologically identified as Haemagogus janthinomys from twelve (12) forest locations in Trinidad, West Indies. Known insect specific viruses including the Phasi Charoen-like and Humaiata-Tubiacanga virus dominated the virome of the mosquitoes throughout sampling locations while other viruses such as the avian leukosis virus, MAYV and several unclassified viruses had a narrower distribution. Additionally, assembled contigs from the Ecclesville location suggests the presence of a unique uncharacterized picorna-like virus. Mapping of RNA sequencing reads to reference mitochondrial sequences of potential feeding host animals showed hits against avian and rodent sequences, which putatively adds to the growing body of evidence of a potentially wide feeding host-range for the Haemagogus mosquito vector.


Role of immunotherapy in metastatic EGFRm NSCLC: Is it relevant?
EGFR-TKIs have changed the landscape of metastatic NSCLC treatment with a significant improvement in survival of EGFRm patients compared to wild-type EGFR. Even with the newer third generation EGFR TKIs like, Osimertinib, which has proven efficacy against the resistance mutation of EGFRm T790M, progression eventually occurs. There are limited treatment options for patients with metastatic EGFRm NSCLC with other acquired resistance. Therefore, novel therapeutic combination strategies are being researched to overcome potential resistance to EGFR-TKI-targeted therapy. The ICIs targeting the programmed cell death-1 pathway in patients with EGFRm NSCLC were greatly anticipated based on preclinical studies showing increased PD-L1 expression. In clinical settings, this increased expression did not translate into a survival benefit. Treatment with ICIs failed to positively affect EGFRm patients because of multiple reasons: nonsynonymous tumor mutational burden, lower PD-L1 expression in tumors, and cancer cells utilizing alternate immune escape mechanisms. The NCCN guidelines currently do not recommend immunotherapy in patients with metastatic EGFRm NSCLC. Recently, a subgroup analysis in the IMpower150 study provided a signal for overall survival of atezolizumab with bevacizumab plus chemotherapy in EGFRm-TKI progressed patients. Based on these encouraging findings, several combinations of ICIs and EGFR-TKIs are being evaluated in TKI-failed EGFRm patients. These regimens might provide a favorable therapeutic effect by combining higher response rates of TKIs and durable disease control of ICIs. However, further research is warranted to understand the exact underlying molecular and cellular mechanisms responsible for the clinical benefits. In this article, we explored the TKI failed metastatic EGFRm NSCLC, reviewed the available clinical data of ICI use in metastatic EGFRm NSCLC, and discussed its emerging role as a combination regimen in this patient population.


Driving anger and factors related to aggressive driving among Serbian drivers.
Objective: Driving anger has been found to be a motivational determinant of risky and aggressive driving. The study reported in this article focused on research questions concerning the conceptualization of driving anger and relationships between driving anger and aggressive driving.Methods: In a cross-sectional survey study, 1,020 regular Serbian drivers completed a web-based online questionnaire. Exploratory Factor Analysis and Confirmatory Factor Analysis were used to assess the factor structure and psychometric properties of the Driving Anger Scale.Results: The results showed that the adapted DAS was a valid and reliable instrument divided into five subscales such as discourteous behavior, illegal behavior, slow driving, hostile gestures and traffic obstructions. The robustness of the five-factor model obtained from the EFA was confirmed by the CFA. The study provided evidence supporting the predictive validity of the adapted DAS and revealed that the dimensions of driving anger are differently associated with prosocial and aggressive driving behaviors.Conclusions: The study supports the adapted DAS validity and produces evidence that driving anger is associated with driving outcomes.


Pathogenic mechanisms involved in the hematological alterations of arenavirus-induced hemorrhagic fevers.
Viral hemorrhagic fevers (VHFs) caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.


Risk Factors Associated with Keratoconus in an Iranian Population.
To determine associated factors for keratoconus (KCN) in the Iranian population. In this retrospective case-control study, 100 KCN patients and 200 age- and sex-matched individuals, who were either candidates for photorefractive keratectomy or healthy referrals from the Torfeh Eye Hospital, were included as the case and control groups, respectively. KCN patients were all registered at the Iranian National Registry of Keratoconus (KCNRegⓇ). Demographic characteristics, patients' symptoms and their habits, as well as systemic and ocular disorders were documented. Clinical examinations included best corrected visual acuity (BCVA) and refractive error measurements, biomicroscopic examination, and corneal imaging. In this case group, the frequency of mild, moderate, and severe KCN was 38%, 28%, and 34%, respectively. Parental consanguinity (odds ratio [OR] = 1.758, P = 0.029), positive familial history in patients' first degree (OR = 12.533, P < 0.001) and second degree (OR = 7.52, P < 0.001) relatives, vernal keratoconjunctivitis (OR = 7.510, P = 0.003), severe eye rubbing (OR = 10.625, P < 0.001), and systemic diseases including migraine, hypertension, and thyroid disease (OR = 6.828, P = 0.021) were found as associated factors for KCN. Lesser frequency of KCN was observed in patients with Fars ethnicity (OR = 0.583, P = 0.042), with higher levels of wealth indices (OR = 0.31, P < 0.001) and higher levels of education (OR = 0.18, P = 0.024). Severe eye rubbing, vernal keratoconjunctivitis, parental consanguinity and positive familial history of KCN, low socioeconomic status, and low levels of education were significantly associated with KCN in our study population.


Neural response telemetry in 12- to 24-month-old children.
The minimum age for cochlear implantation has been reduced to 12 months in an effort to provide auditory stimulation to children with hearing loss during early development. Because behavioral measures in such young children are limited, objective measures such as the electrically evoked compound action potential (EAP) from the auditory nerve are needed to facilitate measurement of stimulation level requirements. We assessed EAPs recorded by the Nucleus 24 neural response telemetry (NRT) system in children who underwent implantation between 12 and 24 months of age. We recorded EAPs in 37 such children (mean age at implantation, 18.1+/-3.6 months). The EAPs were of large amplitude, and thresholds fell between behavioral T and C levels. A correction factor applied to EAP thresholds provided useful predictions of T levels. The EAPs can be used to ensure that even very young children receive auditory stimulation with their cochlear implants upon device activation.


Use of polarography as a quality-control method for determining diacetyl in citrus and vegetable juices, yoghurt and butter.
The determination of diacetyl permits the detection of microbial growth in the processing of citrus fruit before the appearance of other organoleptic, chemical or microbiological changes. It also makes it possible to detect a break in the cold chain during distribution and sale. The study proposed a polarographic method for the determination of diacetyl that allowed routine analysis with the aim of detecting possible contamination in the citrus juice manufacturing chain (orange and orange-carrot). The analytical performance of the method in terms of a linearity from 0 to 960 microg ml(-1), a recovery of 97 to 98%, a precision of 3.2 to 4.8%, and a sensitivity of 0.2 ng ml(-1) for juices indicated the robustness of the method. The same method was also applied to butter and yoghurt with detection limits of and 0.4 ng g(-1).


Beta(2)-microglobulin removal by extracorporeal renal replacement therapies.
There is increasing evidence that end-stage renal disease patients with lower beta(2)-microglobulin plasma levels and patients on convective renal replacement therapy are at lower mortality risk. Therefore, an enhanced beta(2)-microglobulin removal by renal replacement procedures has to be regarded as a contribution to a more adequate dialysis therapy. In contrast to high-flux dialysis, low-flux hemodialysis is not qualified to eliminate substantial amounts of beta(2)-microglobulin. In hemodialysis using modern high-flux dialysis membranes, a beta(2)-microglobulin removal similar to that obtained in hemofiltration or hemodiafiltration can be achieved. Several of these high-flux membranes are protein-leaking, making them suitable only for hemodialysis due to a high albumin loss when used in more convective therapy procedures. On-line hemodiafiltration infusing large substitution fluid volumes represents the most efficient and innovative renal replacement therapy form. To maximize beta(2)-microglobulin removal, modifications of this procedure have been proposed. These modifications ensure safer operating conditions, such as mixed hemodiafiltration, or control albumin loss at maximum purification from beta(2)-microglobulin, such as mid-dilution hemodiafiltration, push/pull hemodiafiltration or programmed filtration. Whether these innovative hemodiafiltration options will become accepted in clinical routine use needs to be proven in future.


Surface modification of polypropylene nonwovens with LDV peptidomimetics and their application in the leukodepletion of blood products.
For clinical indications and according to European standards, a depletion of the leukocytes from whole blood has to be realized before transfusion to a patient. In this study, the surface of a layer of meltblown oxygen-plasma treated polypropylene nonwoven (O(2)-PP), making part of the composition of leukodepletion filters, was modified with bioactive molecules to enhance the adhesion of leukocytes. These synthetic small molecules (called peptidomimetics) mimic the "Leu-Asp-Val" (LDV) tripeptide sequence recognized by the α(4)β(1) integrin, a receptor expressed on leukocytes. Their activity, as ligands of the α(4)β(1) integrin, was confirmed through cell adhesion assays. The peptidomimetics were covalently immobilized on O(2)-PP nonwoven via activation of the hydroxyl- and carboxyl-functions displayed on the polymer surface with trifluoro-triazine reagent, or were simply deposited on the O(2)-PP surface. The treated materials were characterized by X-ray photoelectron spectroscopy, wettability, and morphological analyses, before and after steam sterilization. Experimental filters composed of 10 layers of O(2)-PP nonwovens and a last layer modified with the peptidomimetics were evaluated, using whole blood filtration assays, for their leukodepletion efficiency, the recovery of red cells and platelets and the waste of blood, with an objective to design new filters fulfilling practical and medical criteria.


Tailored Engineering of an Unusual (C4 H9 NH3 )2 (CH3 NH3 )2 Pb3 Br10 Two-Dimensional Multilayered Perovskite Ferroelectric for a High-Performance Photodetector.
Two-dimensional (2D) layered hybrid perovskites have shown great potential in optoelectronics, owing to their unique physical attributes. However, 2D hybrid perovskite ferroelectrics remain rare. The first hybrid ferroelectric with unusual 2D multilayered perovskite framework, (C4 H9 NH3 )2 (CH3 NH3 )2 Pb3 Br10 (1), has been constructed by tailored alloying of the mixed organic cations into 3D prototype of CH3 NH3 PbBr3 . Ferroelectricity is created through molecular reorientation and synergic ordering of organic moieties, which are unprecedented for the known 2D multilayered hybrid perovskites. Single-crystal photodetectors of 1 exhibit fascinating performances, including extremely low dark currents (ca. 10-12 A), large on/off current ratios (ca. 2.5×103 ), and very fast response rate (ca. 150 μs). These merits are superior to integrated detectors of other 2D perovskites, and compete with the most active CH3 NH3 PbI3 .


Inhibition of MMP-2 gene expression with small interfering RNA in rabbit vascular smooth muscle cells.
Matrix metalloproteinase-2 (MMP-2) is constitutively expressed in vascular smooth muscle cells (VSMCs). Using small interfering RNA (siRNA), we evaluated the effect of MMP-2 inhibition in VSMCs in vitro and ex vivo. Rabbit VSMCs were transfected in vitro with 50 nmol/l MMP-2 siRNA or scramble siRNA. Flow cytometry and confocal microscopy showed cellular uptake of siRNA in approximately 80% of VSMCs. MMP-2 mRNA levels evaluated by real-time RT-PCR, pro-MMP-2 activity from conditioned culture media evaluated by gelatin zymography, and VSMC migration were reduced by 44 +/- 19%, 43 +/- 14%, and 36 +/- 14%, respectively, in MMP-2 siRNA-transfected compared with scramble siRNA-transfected VSMCs (P < 0.005 for all). Ex vivo MMP-2 siRNA transfection was performed 2 wk after balloon injury of hypercholesterolemic rabbit carotid arteries. Fluorescence microscopy showed circumferential siRNA uptake in neointimal cells. Gelatin zymography of carotid artery culture medium demonstrated a significant decrease of pro-MMP-2 activity in MMP-2 siRNA-transfected compared with scramble siRNA-transfected arteries (P < 0.01). Overall, our results demonstrate that in vitro MMP-2 siRNA transfection in VSMCs markedly inhibits MMP-2 gene expression and VSMC migration and that ex vivo delivery of MMP-2 siRNA in balloon-injured arteries reduces pro-MMP-2 activity in neointimal cells, suggesting that siRNA could be used to modify arterial biology in vivo.


A Robust Metal-Organic Framework for Dynamic Light-Induced Swing Adsorption of Carbon Dioxide.
Adsorbents for CO2 capture need to demonstrate efficient release. Light-induced swing adsorption (LISA) is an attractive new method to release captured CO2 that utilizes solar energy rather than electricity. MOFs, which can be tailored for use in LISA owing to their chemical functionality, are often unstable in moist atmospheres, precluding their use. A MOF is used that can release large quantities of CO2 via LISA and is resistant to moisture across a large pH range. PCN-250 undergoes LISA, with UV flux regulating the CO2 desorption capacity. Furthermore, under UV light, the azo residues within PCN-250 have constrained, local, structural flexibility. This is dynamic, rapidly switching back to the native state. Reusability tests demonstrate a 7.3 % and 4.9 % loss in both adsorption and LISA capacity after exposure to water for five cycles. These minimal changes confirm the structural robustness of PCN-250 and its great potential for triggered release applications.


Proximity to a tobacco store and smoking cessation: a cohort study.
It is not clear whether the availability of tobacco affects the likelihood of smoking cessation. We examined whether the proximity to a tobacco store and the number of stores were associated with smoking cessation, and compared results for proximity variables based on walking and straight-line (as the crow flies) distance. The study population consisted of 8751 baseline smokers from the Finnish Public Sector study in 1997-2005. Smoking intensity (cigarettes/day) was determined at baseline and smoking cessation was determined from a follow-up survey in 2008-2009. Proximity was measured using straight-line and walking distance from home to the nearest tobacco store, and another exposure variable was the number of stores within 0.50 km from home. We calculated associations with log-binomial regression models, adjusting for individual-level and area-level confounders. Of the participants, 3482 (39.8%) quit smoking during the follow-up (mean follow-up 5.5 years, SD 2.3 years). Among men who were moderate/heavy smokers at baseline and lived <0.50 km walking distance from the nearest tobacco store, the likelihood of smoking cessation was 27% (95% CI 12% to 40%) lower compared with those living ≥0.50 km from a store. Having even one store within 0.50 km walking distance from home decreased cessation in men who were moderate/heavy smokers by 37% (95% CI 19% to 51%). No decrease was found for men who were light smokers at baseline or for women. Living within walking distance of a tobacco store reduced the likelihood of smoking cessation among men who were moderate/heavy smokers.


Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure.
Cardiac hypertrophy is a mechanism to compensate for increased cardiac work load, that is, after myocardial infarction or upon pressure overload. However, in the long run cardiac hypertrophy is a prevailing risk factor for the development of heart failure. During pathological remodelling processes leading to heart failure, decompensated hypertrophy, death of cardiomyocytes by apoptosis or necroptosis and fibrosis as well as a progressive dysfunction of cardiomyocytes are apparent. Interestingly, the induction of hypertrophy, cell death or fibrosis is mediated by similar signalling pathways. Therefore, tiny changes in the signalling cascade are able to switch physiological cardiac remodelling to the development of heart failure. In the present review, we will describe examples of these molecular switches that change compensated hypertrophy to the development of heart failure and will focus on the importance of the signalling cascades of the TGFβ superfamily in this process. In this context, potential therapeutic targets for pharmacological interventions that could attenuate the progression of heart failure will be discussed.


PEO-b-PPO star-shaped polymers enhance the structural stability of electrostatically coupled liposome/polyelectrolyte complexes.
We propose a strategy to counteract the salt-driven disassembly of multiliposomal complexes made by electrostatic co-assembly of anionic small unilamellar liposomes and cationic star-shaped polyelectrolytes (made of quaternized poly(dimethylaminoethyl methacrylate) (qPDMAEMA100)3.1). The combined action of (qPDMAEMA100)3.1 and a nonionic star-shaped polymer (PEO12-b-PPO45)4, which comprises diblock copolymer arms uniting a poly(ethylene oxide) PEO inner block and a poly(propylene oxide) PPO terminal block, leads to a stabilization of these complexes against disintegration in saline solutions. Hereby, the anchoring of the PPO terminal blocks to the lipid bilayer and the bridging between several liposomes are at the origin of the promoted structural stability. Two-focus fluorescence correlation spectroscopy verifies the formation of multiliposomal complexes with (PEO12-b-PPO45)4. The polyelectrolyte and the amphiphilic polymer work synergistically, as the joint action still assures some membrane integrity, which is not seen for the mere (PEO12-b-PPO45)4-liposome interaction alone.


Proton Conduction of an Acid-Resistant Open-Framework Chalcogenidometalate Hybrid in Anhydrous versus Humid Environments.
Solid proton conductors are broadly applicable to various electrochemical devices; therefore, it is highly desirable to develop robust materials with high proton conductivity under both anhydrous and humid environments within a wide temperature range. In this work, we investigated the proton conducting properties of a 3D open-framework chalcogenidometalate hybrid, [CH3NH3]2[H3O]Ag5Sn4Se12·C2H5OH (1), which exhibited both anhydrous and water-assisted proton conduction. Importantly, the excellent thermal and chemical stabilities of hybrid 1 are superior to many MOF-based proton conducting materials. This present study proved to be a considerable advance based on open-framework chalcogenidometalates in the design of robust solid proton conducting materials that are capable of operating under humid and anhydrous environments in a wide temperature range.


Effects of cocaine on responding for ethanol or sucrose under a progressive ratio schedule.
Progressive ratio (PR) schedules have been increasingly used to study motivation for self-administered drugs of abuse, such as psychostimulants and ethanol. In these and other studies, the breaking point (BP) is thought to be a measure of the motivation of the animal to work for a particular reward. Ethanol, a highly abused drug, maintains only low BPs. The present experiment was designed to examine if the low BP achieved by animals working for ethanol could be increased by the administration of a psychostimulant. A group working for a sucrose reinforcer was included for comparison. Rats previously trained to lever press under a PR schedule for 0.1 ml aliquots of 10% ethanol or 5% sucrose reinforcers were dosed once a week with cocaine (0, 5 and 15 mg/kg intraperitoneally) 30 min prior to their daily operant session using a Latin square design. Vehicle and 5 mg/kg cocaine had no effect on BP for any reinforcer, but 15 mg/kg cocaine produced a significantly higher BP (P<0.05) for animals working for either ethanol or sucrose. The same doses of cocaine decreased consumption of, and preference for, a 5% sucrose solution. These results indicate that, although cocaine administration does not increase sucrose preference, it may increase BP values in PR schedules. It is therefore unlikely that the increases in BP reflect cocaine-induced increased motivation, and they may be due to cocaine's stimulant or other properties. These data reinforce opinions that PR schedules may be unsuitable for assessing the effects of experimental manipulations on motivation for drugs with stimulant actions.


Childbearing experiences of abused Hispanic women.
Previous research has documented that abused childbearing women have longer and more difficult labors than non-abused women. Prevalence of abuse differs depending on the ethnic group involved. Hispanic women experience higher rates of abuse and endure higher rates before reporting abuse than do Caucasian women. The purpose of this study was to explore the experience of childbearing for abused Hispanic women to provide guidance for clinical practice and further research. Cognitive dissonance theory guided the study. A sample of seven abused Hispanic women was recruited from a rural prenatal clinic. Criteria for selection of subjects included self-identification as Hispanic, less than 24 months postpartum, disclosure of abuse status, and willingness to be interviewed in English or Spanish. An acculturation scale and demographic form were completed. Interviews were conducted individually, and data were analyzed by using Van Kaam's 12-step psychophenomenologic technique. Findings indicated that subjects experienced the normal responses associated with having a baby. However, the women also demonstrated a kindled neuroendocrine trauma response that was based on, and often similar to, their prior abuse experiences. The kindled emotional response was triggered by the normative events of childbearing. Understanding of the childbearing experiences of abused Hispanic women will facilitate the development of cultural-specific interventions that may ease the difficulties associated with birth for these women.


Molecular authentication of Radix Puerariae Lobatae and Radix Puerariae Thomsonii by ITS and 5S rRNA spacer sequencing.
In the present study, we examined nuclear DNA sequences in an attempt to reveal the relationships between Pueraria lobata (Willd). Ohwi, P. thomsonii Benth., and P. montana (Lour.) Merr. We found that internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA are highly divergent in P. lobata and P. thomsonii, and four types of ITS with different length are found in the two species. On the other hand, DNA sequences of 5S rRNA gene spacer are highly conserved across multiple copies in P. lobata and P. thomsonii, they could be used to identify P. lobata, P. thomsonii, and P. montana of this complex, and may serve as a useful tool in medical authentication of Radix Puerariae Lobatae and Radix Puerariae Thomsonii.


Assessment of different manufacturing techniques for the production of bioartificial scaffolds as soft organ transplant substitutes.
Introduction: The problem of organs' shortage for transplantation is widely known: different manufacturing techniques such as Solvent casting, Electrospinning and 3D Printing were considered to produce bioartificial scaffolds for tissue engineering purposes and possible transplantation substitutes. The advantages of manufacturing techniques' combination to develop hybrid scaffolds with increased performing properties was also evaluated. Methods: Scaffolds were produced using poly-L-lactide-co-caprolactone (PLA-PCL) copolymer and characterized for their morphological, biological, and mechanical features. Results: Hybrid scaffolds showed the best properties in terms of viability (>100%) and cell adhesion. Furthermore, their mechanical properties were found to be comparable with the reference values for soft tissues (range 1-10 MPa). Discussion: The created hybrid scaffolds pave the way for the future development of more complex systems capable of supporting, from a morphological, mechanical, and biological standpoint, the physiological needs of the tissues/organs to be transplanted.


Identification of large genomic rearrangement of BRCA1/2 in high risk patients in Korea.
While the majority of germline inactivating mutations in BRCA1/2 are small-scale mutations, large genomic rearrangements (LGRs) are also detected in a variable proportion of patients. However, routine genetic methods are incapable of detecting LGRs, and comprehensive genetic testing algorithm is necessary. We performed multiplex ligation-dependent probe amplification assay for small-scale mutation negative patients at high-risk for LGR, based on previously published LGR risk criteria. The inclusion criteria for the high-risk subgroup were personal history of 1) early-onset breast cancer (diagnosed at ≤36 years); 2) two breast primaries; 3) breast cancer diagnosed at any age, with ≥1 close blood relatives (includes first-, second-, or third-degree) with breast and/or epithelial ovarian cancer; 4) both breast and epithelial ovarian cancer diagnosed at any age; and 5) epithelial ovarian cancer with ≥1 close blood relatives with breast and/or epithelial ovarian cancer. Two LGRs were identified. One was a heterozygous deletion of exon 19 and the other was a heterozygous duplication of exon 4-6. The prevalence of LGRs was 7% among Sanger-negative, high-risk patients, and accounted for 13% of all BRCA1 mutations and 2% of all patients. Moreover, LGRs reported in Korean patients, including our 2 newly identified cases, were found exclusively in families with at least one high-risk feature. Our result suggests that selective LGR screening for Sanger-negative, high-risk patients is necessary for Korean patients.


Can pirfenidone prevent tendon adhesions? An experimental study in rats.
In this experimental study, we aimed to investigate the effectiveness of oral pirfenidone (PFD) treatment on preventing tendon adhesion and tendon healing in rats. A total of 21 rats were assigned into three groups including seven rats in each group. In Group 1 (sham group), no surgical procedure was performed. In Group 2 (control group), tendon repair was performed following right achillotomy. In Group 3 (treatment group), the rats also underwent tendon repair after right achillotomy. Additionally, 30 mg/kg of oral PFD was initiated from the postoperative Day 1 and administered via gavage for 28 days. At the end of the study, tendon healing and fibrosis levels in the tendon repair site were compared macroscopically, histopathologically, and immunohistochemically among the groups. Macroscopically, moderate and severe adhesions were observed in four and three rats, respectively in the control group, while no adhesion was found in four rats and filmy adhesions were observed in three rats in the treatment group (p<0.01). Microscopically, there was moderate adhesions in three rats and severe adhesions in four rats in the control group, while three rats had no adhesions and four rats had slight adhesions in the treatment group (p<0.01). Microscopically, tendon healing was good in six rats and fair in one rat in the control group, while five rats showed excellent tendon healing and two rats showed good tendon healing in the treatment group (p<0.01). Immunohistochemically, expressions of collagen I (p<0.01), collagen III (p<0.001), vascular endothelial growth factor (VEGF) (p<0.001), and proliferating cell nuclear antigen (PCNA) (p<0.001) significantly decreased in the treatment group compared to the control group. Our study results indicated that PFD decreased collagen synthesis and prevented the formation of peritendinous adhesion in rats; however, it did not impair tendon healing.


Structural investigation of a high-affinity MnII binding site in the hammerhead ribozyme by EPR spectroscopy and DFT calculations. Effects of neomycin B on metal-ion binding.
Electron paramagnetic resonance spectroscopy and density functional theory methods were used to study the structure of a single, high-affinity Mn(II) binding site in the hammerhead ribozyme. This binding site exhibits a dissociation constant Ke of 4.4 microM in buffer solutions containing 1 M NaCl, as shown by titrations monitored by continuous wave (cw) EPR. A combination of electron spin echo envelope modulation (ESEEM) and hyperfine sublevel correlation (HYSCORE) experiments revealed that the paramagnetic manganese(II) ion in this binding site is coupled to a single nitrogen atom with a quadrupole coupling constant kappa of 0.7 MHz, an asymmetry parameter eta of 0.4, and an isotropic hyperfine coupling constant of Aiso(14N)=2.3 MHz. All three EPR parameters are sensitive to the arrangement of the Mn(II) ligand sphere and can therefore be used to determine the structure of the binding site. A possible location for this binding site may be at the G10.1, A9 site found to be occupied by Mn(II) in crystals (MacKay et al., Nature 1994, 372, 68 and Scott et al., Science 1996, 274, 2065). To determine whether the structure of the binding site is the same in frozen solution, we performed DFT calculations for the EPR parameters, based on the structure of the Mn(II) site in the crystal. Computations with the BHPW91 density function in combination with a 9s7p4d basis set for the manganese(II) center and the Iglo-II basis set for all other atoms yielded values of kappa(14N)=+0.80 MHz, eta=0.324, and Aiso(14N)=+2.7 MHz, in excellent agreement with the experimentally obtained EPR parameters, which suggests that the binding site found in the crystal and in frozen solution are the same. In addition, we demonstrated by EPR that Mn(II) is released from this site upon binding of the aminoglycoside antibiotic neomycin B (Kd=1.2 microM) to the hammerhead ribozyme. Neomycin B has previously been shown to inhibit the catalytic activity of this ribozyme (Uhlenbeck et al., Biochemistry 1995, 34, 11 186).


Concomitant endosome-phagosome fusion and lysis of endosomal membranes account for Pseudomonas aeruginosa survival in human endothelial cells.
P. aeruginosa is selectively internalized by human endothelial cells but is not efficiently killed in the intracellular (IC) compartment. To investigate whether IC survival is associated with failure in bacteria-containing endosome-lysosome (E-L) fusion, endothelial cells were exposed to albumin-colloidal gold complex and to bacterial suspension and submitted to transmission electron microscopy (TEM). Gold granules were detected in P. aeruginosa-containing vacuoles, indicating that E-L fusion had occurred. Bacteria were also seen apparently free in the cell cytoplasm, suggesting disruption of endosome membranes. To ascertain whether phospholipase C (PLC) could account for vacuolar lysis, PLC producing PAO1 and PAK strains were compared with a PLC deficient mutant (PLCN) in their IC survival. All three strains were equally uptaken by the endothelial cells, as determined by the gentamicin exclusion assay. After 3 h of infection, the IC concentration of PAK and PAO1 increased significantly while the concentration of the mutant decreased to 56.8 +/- 18.2% of the viable counts at 1 h of infection. After 5 h, the IC concentration of P. aeruginosa corresponded to 83.1 +/- 34.6%, 109 +/- 22.6% and 26.2 +/- 14.7% of the viable counts detected at 1 h, for PAK, PAO1 and the mutant, respectively. By TEM, while most PAO1-containing vacuoles presented partially lysed membranes, in cells infected with the PLCN mutant bacteria were most often observed in vacuoles with intact membranes. These observations suggest that the IC survival of P. aeruginosa results from a competition between the microbicidal activity of endothelial cells following E-L fusion and the capacity of bacteria to escape from endosomes.


The moderation of elastase-induced emphysema in the hamster by intratracheal pretreatment or post-treatment with succinyl alanyl alanyl prolyl valine chloromethyl ketone.
The capacity of the synthetic elastase inhibitor, succinyl alanyl alanyl prolyl valine chloromethyl ketone (CMK), to moderate elastase-induced emphysema in hamsters was examined using morphometric and physiologic measurements. When 0.5 mg of CMK in saline was injected intratracheally 1 h before the intratracheal injection of 0.1 mg of porcine pancreatic elastase, the hamsters did not develop emphysema. When CMK was injected intratracheally 1 h after elastase, the severity of emphysema was reduced by approximately 50% compared with control animals receiving saline 1 h after elastase. The CMK was ineffective when administered intratracheally 4 h after elastase.


Peripheral lymphoid development and function in TCR mutant mice.
We describe the development and function of the peripheral lymphoid system of mutant mice rendered deficient in either alpha beta or gamma delta T cells via targeting of TCR genes in embryonic stem cells. In the spleen of alpha beta T cell-deficient mice, gamma delta T cells do not compensate in numbers for the lack of alpha beta T cells, but B cells do. alpha beta T cell-deficient mice are unable to mount an antibody response to ovalbumin and do not reject skin allografts. Natural killer cell function is not impaired in any of the mutant mice. TCR mutant mice will prove useful in dissecting differential functions of alpha beta and gamma delta T cells in vivo.


Interactional effects of marital status and physical abuse on adolescent psychopathology.
The purpose of this study was to explore the interactional effects of parental marital disruption and physical abuse on risk for adolescent psychopathology in a nonclinical sample with a randomly selected control group. The sample was drawn from 99 community-based adolescents indicated as physically abused by Child Protective Services and 99 randomly selected controls. Nonabused adolescents whose parents were married, abused adolescents whose parents were married, nonabused adolescents with a parental marital disruption, and abused adolescents with a parental marital disruption were compared. Outcome was psychopathology as measured by psychiatric diagnosis based on a best-estimate procedure subsequent to semistructured diagnostic interviewing. Interactional effects of marital disruption and abuse were found for risk for lifetime Attention Deficit Hyperactivity Disorder (ADHD), with parental marital disruption and having been physically abused combining to increase the risk 15 times for diagnosis of lifetime ADHD. Parental marital status alone was not a significant risk factor for adolescent psychopathology, but physical abuse was a significant risk factor for several diagnostic categories. Future divorce research should include abuse history as a possible confounding variable. Possible reasons for the findings are reviewed and clinical implications are discussed.


GaAs nanowire growth on polycrystalline silicon thin films using selective-area MOVPE.
The growth mechanism of GaAs nanowires (NWs) grown on polycrystalline silicon (poly-Si) thin films using selective-area metalorganic vapor-phase epitaxy was investigated. Wire structures were selectively grown in the mask openings on a poly-Si substrate. The appearance ratio of wire structures strongly depended on the growth conditions and deposition temperature of the poly-Si substrate. Evaluation of the grown shapes and growth characteristics revealed that GaAs NWs grown on a poly-Si substrate have the same growth mechanism as conventional GaAs NWs grown on a single-crystalline GaAs or Si substrate. Experiments showed that the wire structure yield can be improved by increasing the Si grain size and/or increasing the Si deposition temperature. The growth model proposed for understanding NW growth on poly-Si is based on the mask opening size, the Si grain size, and the growth conditions. The ability to control the growth mode is promising for the formation of NWs with complex structures on poly-Si thin layers.


Surgical management of thyroid cancer.
Thyroid cancer is the most common endocrine neoplasm; however, it only accounts for less than 1% of all human malignances. Thyroid cancers are divided into well differentiated and non-well differentiated cancers, according to their histology and behavior. The surgical management options of well-differentiated thyroid cancer include total or near-total thyroidectomy, subtotal thyroidectomy and lobectomy plus isthmusectomy. The extent of surgery for thyroid cancer continues to be an area of controversy. Complications associated with thyroid surgery are directly proportional to the extent of thyroidectomy and inversely proportional to the experience of the operating surgeon. They occur less frequently with good surgical technique and better understanding of surgical anatomy, and include wound healing and infections (seroma, hematoma and wound infection), nerve injury, hypoparathyroidism, hypothyroidism, postoperative hemorrhage and respiratory obstruction.


Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study.
To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ARDS treated (N = 7) with the novel combination of ruxolitinib, a JAK1/2 inhibitor, 10 mg/twice daily for 14 days and eculizumab, an anti-C5a complement monoclonal antibody, 900 mg IV/weekly for a maximum of three weeks, or with the best available therapy (N = 10). Patients treated with the combination showed significant improvements in respiratory symptoms and radiographic pulmonary lesions and decrease in circulating D-dimer levels compared to the best available therapy group. Our results support the use of combined ruxolitinib and eculizumab for treatment of severe SARS-CoV-2-related ARDS by simultaneously turning off abnormal innate and adaptive immune responses.


The Inhibition of Phosphoinositide-3 Kinases Induce Resolution of Inflammation in a Gout Model.
Phosphoinositide-3 kinases (PI3Ks) are central signaling enzymes that are involved in many aspects of immune cell function. PI3Kγ and PI3Kδ are the major isoforms expressed in leukocytes. The role of PI3K isoforms in the resolution of inflammation is still poorly understood. Here, we investigated the contribution of PI3Kγ and PI3Kδ to the resolution of inflammation in a model of gout in mice. Methods and Results: Experiments were performed in wild-type male C57/Bl6 mice. Selective inhibitors of PI3K-γ (AS605240) or PI3Kδ (GSK045) were injected in the joint 12 h after injection of MSU crystals, hence at the peak of inflammation. Inhibition of either PI3K isoform decreased number of neutrophils that migrated in response to the injection of MSU crystals. This was associated with reduction of myeloperoxidase activity and IL-1β levels in periarticular tissues and reduction of histological score. Joint dysfunction, as seen by reduced mechanical hypernociception, was improved by treatment with either inhibitor. The decrease in neutrophil numbers was associated with enhanced apoptosis and efferocytosis of these cells. There was shortening of resolution intervals, suggesting inhibition of either isoform induced the resolution of neutrophilic inflammation. Blockade of PI3Kγ or PI3Kδ reduced Nuclear Factor kappa B (NF-κB) activation. A pan-PI3K inhibitor (CL27c) reduced inflammation induced by MSU crystals by a magnitude that was similar to that attained by the PI3Kγ or PI3Kδ selective inhibitors alone. Conclusion: Taken together, these results suggest that neutrophils can use PI3Kγ or PI3Kδ to remain in the cavity and blockade of either isoenzyme is sufficient to induce their apoptosis and resolve inflammation in a murine model of gout.


Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia.
Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing. Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20 minutes over two weeks using anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0-10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS. Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported. Anodal tDCS over two weeks ameliorates intensity of pain in TN. It may become a valuable treatment option for patients unresponsive to conventional treatment.


[Prognosis of embolization of internal iliac artery during the endovascular repair for abdominal aortic aneurysm].
To study the importance of the internal iliac artery (IIA) during the endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). Forty-six consecutive cases of AAA treated by EVAR were retrospectively analyzed. The complications after exclusion of the IIA were analyzed. The bilateral IIAs were reserved in 18 cases, in which the follow-up was achieved in 16 cases and no complication was observed. The IIAs were excluded in 28 (60.9%) cases, in which the bilateral, right and left IIAs were excluded in 7 (15.2%), 14 (30.4%) and 7 (15.2%) cases respectively. The follow-up was achieved in 26 cases. Buttock claudication was observed in 12 (46.2%) cases, altered bowel habit was observed in 8 (32.0%) cases, erectile dysfunction was observed in 3 (12.0%) cases, and bloody stool was observed in 2 (8.0%) cases. Comparing the bilateral and unilateral IIA exclusions, the rates of buttock claudication were 50.0% vs. 45.0%, altered bowel habit 33.3% vs. 31.6%, and erectile dysfunction 33.3% vs. 5.3% respectively. And the average duration of buttock claudication of bilateral IIAs exclusion (8.3 months) was longer than that of unilateral exclusion (4.7 months). Moreover, comparing the left and right IIA exclusions, the rates of buttock claudication were 57.1% vs. 38.5%, altered bowel habit 57.1% vs. 16.7%, and bloody stool 28.6% vs. 0 respectively. And the average duration of buttock claudication of left IIA exclusion (6.0 months) was longer than that of right exclusion (3.7 months). The IIAs, especially the left IIA, should be reserved during the EVAR for AAA.


Melatonin Inhibits CXCL10 and MMP-1 Production in IL-1β-Stimulated Human Periodontal Ligament Cells.
Melatonin is a hormone that is mainly secreted by the pineal gland and exhibits a wide spectrum of activities, including antioxidant functions. Melatonin has been detected in gingival crevicular fluid. However, the role of melatonin in periodontal tissue is still uncertain. The aim of this study was to examine the effects of melatonin on inflammatory mediator expression in human periodontal ligament cells (HPDLC). Interleukin (IL)-1β induced CXC chemokine ligand (CXCL)10, matrix metalloproteinase (MMP)-1, and tissue inhibitors of metalloproteinase (TIMP)-1 production in HPDLC. Melatonin decreased CXCL10 and MMP-1 production and increased TIMP-1 production in IL-1β-stimulated HPDLC. Western blot analysis showed that melatonin inhibited p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) phosphorylation, and IkB-α degradation and phosphorylation in IL-1β-stimulated HPDLC. These results suggest that melatonin might inhibit Th1 cell migration by reducing CXCL10 production. Moreover, melatonin might inhibit soft tissue destruction by decreasing MMP-1 production in periodontal lesions.


Asna1/TRC40 Controls β-Cell Function and Endoplasmic Reticulum Homeostasis by Ensuring Retrograde Transport.
Type 2 diabetes (T2D) is characterized by insulin resistance and β-cell failure. Insulin resistance per se, however, does not provoke overt diabetes as long as compensatory β-cell function is maintained. The increased demand for insulin stresses the β-cell endoplasmic reticulum (ER) and secretory pathway, and ER stress is associated with β-cell failure in T2D. The tail recognition complex (TRC) pathway, including Asna1/TRC40, is implicated in the maintenance of endomembrane trafficking and ER homeostasis. To gain insight into the role of Asna1/TRC40 in maintaining endomembrane homeostasis and β-cell function, we inactivated Asna1 in β-cells of mice. We show that Asna1(β-/-) mice develop hypoinsulinemia, impaired insulin secretion, and glucose intolerance that rapidly progresses to overt diabetes. Loss of Asna1 function leads to perturbed plasma membrane-to-trans Golgi network and Golgi-to-ER retrograde transport as well as to ER stress in β-cells. Of note, pharmacological inhibition of retrograde transport in isolated islets and insulinoma cells mimicked the phenotype of Asna1(β-/-) β-cells and resulted in reduced insulin content and ER stress. These data support a model where Asna1 ensures retrograde transport and, hence, ER and insulin homeostasis in β-cells.


Allelic variants between mouse substrains BALB/cJ and BALB/cByJ influence mononuclear cardiomyocyte composition and cardiomyocyte nuclear ploidy.
Most mouse cardiomyocytes (CMs) become multinucleated shortly after birth via endoreplication and interrupted mitosis, which persists through adulthood. The very closely related inbred mouse strains BALB/cJ and BALB/cByJ differ substantially (6.6% vs. 14.3%) in adult mononuclear CM level. This difference is the likely outcome of a single X-linked polymorphic gene that functions in a CM-nonautonomous manner, and for which the BALB/cByJ allele is recessive to that of BALB/cJ. From whole exome sequence we identified two new X-linked protein coding variants that arose de novo in BALB/cByJ, in the genes Gdi1 (R276C) and Irs4 (L683F), but show that neither affects mononuclear CM level individually. No BALB/cJ-specific X-linked protein coding variants were found, implicating instead a variant that influences gene expression rather than encoded protein function. A substantially higher percentage of mononuclear CMs in BALB/cByJ are tetraploid (66.7% vs. 37.6% in BALB/cJ), such that the overall level of mononuclear diploid CMs between the two strains is similar. The difference in nuclear ploidy is the likely result of an autosomal polymorphism, for which the BALB/cByJ allele is recessive to that of BALB/cJ. The X-linked and autosomal genes independently influence mitosis such that their phenotypic consequences can be combined or segregated by appropriate breeding, implying distinct functions in karyokinesis and cytokinesis.


Investigation of the Changes in Refractive Surgery Trends in Korea.
To evaluate changes in clinical practice in the field of refractive surgery in Korea over the past 10 years. A survey consisting of 59 multiple-choice questions regarding the preferred types of refractive surgery, excimer laser machine, and presbyopia surgery was mailed to 742 members of the Korean Society of Cataract and Refractive Surgery in January 2016, and 50 members responded to the survey. These data were compared with the 2005 or 2007 survey results. The majority of respondents were in their 40s (54%), and the average number of refractive surgeries performed in one month was 53. The most commonly used excimer laser machine was the VISX S4 in both 2005 (32%) and 2015 (25%); however, a greater variety of machines (EX500 [18%], Allegretto wave Eye-Q [13%], AMARIS 750 [10%]) were used in 2015. The preferred corneal refractive surgery in 2015 was surface ablation (40%), representing a significant increase in its popularity compared to 2005 (15%) (p < 0.001). The popularity of laser in situ keratomileusis (LASIK) surgery decreased to 20% in 2015 compared to 48% in 2005 (p < 0.001). Eighty percent of LASIK procedures in 2015 were performed using femtosecond laser. In 2015, surface ablation and phakic intraocular lens implantation were preferred for the treatment of myopia less than -8 diopters and more than -8 diopters, respectively. The proportion of respondents performing presbyopia surgery in 2015 (76%) was significantly increased from 2007 (30%) (p < 0.001). Over the past decade, the most commonly performed corneal refractive surgery has changed from LASIK to surface ablation, and there has been a significant increase in the popularity of presbyopia surgery.


Effect of High VEGF-C mRNA Expression on Achievement of Complete Remission in Adult Acute Myeloid Leukemia.
Although vascular endothelial growth factor-C (VEGF-C) is known to be expressed in acute myeloid leukemia (AML) blasts, the relevance of VEGF-C in the clinical setting remains to be fully explored. We examined the effect of VEGF-C on achievement of complete remission (CR) in adult de novo AML and immune cell population profiles according to VEGF-C mRNA expression. In comparison of VEGF-C expression between the no-CR and CR groups, the CR group showed a trend toward higher levels of plasma VEGF-C (P = .088), whereas mRNA expression of VEGF-C was downregulated (P = .008). Next, patients with continuous data for VEGF-C were divided into two groups (low vs. high) by a ROC curve analysis. The low- versus high-level groups for plasma VEGF-C (RR of 0.20, P = .030), mRNA expression of VEGF-C (RR of 18.75, P = .003), and the ratio of plasma level to mRNA expression (RR of 0.05, P = .007) were potential predictors of CR on univariate analysis. After adjusting for potential clinical factors including genetic group, multivariate analyses revealed that high VEGF-C mRNA expression was an independent risk factor for failure of induction chemotherapy. Furthermore, patients with high VEGF-C mRNA expression had a lower frequency of NKT and CD8+ cells and showed a trend for a lower frequency of NK cells. These results suggest that interruption of VEGF-C signaling might be a potential therapeutic target for antileukemic treatment in AML patients.


An Advanced Group Contribution Method for High-Dimensional, Sparse Data Sets.
Today's chemical processes involve many components, and it is necessary to know their basic physical properties for process design and operation. However, it is not always possible to find the property information of all components in the literature. Generally, there are two ways to evaluate properties of chemical compounds when they do not exist in the literature: the experimental measurement and predictive approaches based on empirical models. The latter is called the group contribution method (GCM), and its basic concept is that specific functional groups or fragments of a molecule contribute to the value of its physical property. The advantage of the GCMs is that they reduce the effort and cost compared to experiments. This study proposes a novel GCM method suitable for high-dimensional, sparse data sets. In order to improve its applicability and accuracy, the database is extended and divided into non-ring group compounds and ring group ones. Support vector regression (SVR) is adopted as the regression model, and a derivative-free optimization approach, referred to as particle swarm optimization, is incorporated into the parameter optimization step in learning the SVM model to avoid local optimality. Performance of the proposed model is compared to those of other GCMs.


Oral cancer via the bargain bin: The risk of oral cancer associated with a smokeless tobacco product (Naswar).
In the wake of smokeless tobacco (SLT) being advocated as a mean of tobacco harm reduction, it is pertinent to establish individual health risks associated with each SLT product. This case-control study was aimed at assessing the risk of oral cancer associated with a smokeless tobacco product (Naswar). The study was conducted from September 2014 till May 2015 in Khyber Pakhtunkhwa, Pakistan. Exposure and covariate information was collected through a structured questionnaire. Conditional logistic regression was used to calculate odds ratios (OR) along with their 95% confidence intervals (CI). 84 oral cancer cases (62% males) and 174 age- and sex-matched controls were recruited. Ever users of Naswar had more than a 20-fold higher risk of oral cancer compared to never-users (OR 21.2, 95% CI 8.4-53.8). Females had a higher risk of oral cancer with the use of Naswar (OR 29.0, 95% CI 5.4-153.9) as compared to males (OR 21.0, 95% CI 6.1-72.1). Based on this result, 68% (men) and 38% (women) of the oral cancer burden in Pakistan is attributable to Naswar. The risk estimates observed in this study are comparable to risk estimates reported by previous studies on other forms of SLT use and the risk of oral cancer in Pakistan. The exposure-response relationship also supports a strong role of Naswar in the etiology of oral cancer in Pakistan. Although still requiring further validation through independent studies, these findings may be used for smokeless tobacco control in countries where Naswar use is common.


Microengineered Hollow Graphene Tube Systems Generate Conductive Hydrogels with Extremely Low Filler Concentration.
The fabrication of electrically conductive hydrogels is challenging as the introduction of an electrically conductive filler often changes mechanical hydrogel matrix properties. Here, we present an approach for the preparation of hydrogel composites with outstanding electrical conductivity at extremely low filler loadings (0.34 S m-1, 0.16 vol %). Exfoliated graphene and polyacrylamide are microengineered to 3D composites such that conductive graphene pathways pervade the hydrogel matrix similar to an artificial nervous system. This makes it possible to combine both the exceptional conductivity of exfoliated graphene and the adaptable mechanical properties of polyacrylamide. The demonstrated approach is highly versatile regarding porosity, filler material, as well as hydrogel system. The important difference to other approaches is that we keep the original properties of the matrix, while ensuring conductivity through graphene-coated microchannels. This novel approach of generating conductive hydrogels is very promising, with particular applications in the fields of bioelectronics and biohybrid robotics.


Negatively charged metal-organic hosts with cobalt dithiolene species: improving PET processes for light-driven proton reduction through host-guest electrostatic interactions.
By incorporating 1,2-benzenedithiol as a chelator to construct cobalt dithiolene species, two negatively charged redox-active metal-organic hosts were obtained. By taking advantage of electrostatic interactions, cationic Ru-based photosensitizers were constrained to improve photoinduced electron transfer processes for efficient photocatalytic proton reduction.


Modeling the T-cell dynamics and pathogenesis of HTLV-I infection.
Human T-cell lymphotropic virus type I (HTLV-I) infection in humans causes a chronic infection of CD4+ T cells, and is associated with various disease outcomes, among them with the development of adult T-cell leukemia (ATL). The T-cell dynamics after HTLV-I infection can be described in a mathematical model with coupled differential equations. The infection process is modeled assuming cell-to-cell infection of CD4+ T cells. The model allows for CD4+ T cell subsets of susceptible, latently infected and actively infected cells as well as for leukemia cells. Latently infected T cells may harbor the virus for several years until they become activated and able to infect susceptible T cells. Uncontrolled proliferation of CD4+ T cells with monoclonal DNA-integration of HTLV-I results in the development of ATL. The model describes basic features that characterize HTLV-I infection; the chronic infection of CD4+ T cells, the increasing number of abnormal cells and the possible progression to ATL.


Pentafluorophenyl Ester-based Polymersomes as Nanosized Drug-Delivery Vehicles.
In this work, activated ester chemistry is employed to synthesize biocompatible and readily functionalizable polymersomes. Via aminolysis of pentafluorophenyl methacrylate-based precursor polymers, an N-(2-hydroxypropyl) methacrylamide (HPMA)-analog hydrophilic block is obtained. The precursor polymers can be versatile functionalized by simple addition of suitable primary amines during aminolysis as demonstrated using a fluorescent dye. Vesicle formation is proven by cryoTEM and light scattering. High encapsulation efficiencies for hydrophilic cargo like siRNA are achieved using dual centrifugation and safe encapsulation is demonstrated by gel electrophoresis. In vitro studies reveal low cytotoxicity and no protein adsorption-induced aggregation in human blood serum occurs, making the vesicles interesting candidates as nanosized drug carriers.


In aqua structuralization of a three-dimensional configuration using biomolecules.
Ferritin nanoparticles ornamented with a Ti-binding peptide are versatile nanoscaled building blocks. Their specific binding ability is strong enough to position them on nanopatterned Ti regions on a Pt substrate. Furthermore, the peptides mineralization activity enables the formation of titania on the outer side of the particle, and the particle's inner nanospaces can serve as a carrier for inorganic nanodots. Making use of all these properties, here we show controlled in aqua fabrication of three-dimensional nanoscale structures. The X-Y positioning obeyed the specific binding of the peptide, while fabrication in the Z-dimension entailed stepwise formation of titania and ferritin layers by alternately applying the binding and mineralization abilities of the Ti-binding peptide. This method paves the way for in aqua fabrication of nanodevices having complicated structures and functions.


Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition.
Chromatin is reprogrammed after fertilization to produce a totipotent zygote with the potential to generate a new organism. The maternal genome inherited from the oocyte and the paternal genome provided by sperm coexist as separate haploid nuclei in the zygote. How these two epigenetically distinct genomes are spatially organized is poorly understood. Existing chromosome conformation capture-based methods are not applicable to oocytes and zygotes owing to a paucity of material. To study three-dimensional chromatin organization in rare cell types, we developed a single-nucleus Hi-C (high-resolution chromosome conformation capture) protocol that provides greater than tenfold more contacts per cell than the previous method. Here we show that chromatin architecture is uniquely reorganized during the oocyte-to-zygote transition in mice and is distinct in paternal and maternal nuclei within single-cell zygotes. Features of genomic organization including compartments, topologically associating domains (TADs) and loops are present in individual oocytes when averaged over the genome, but the presence of each feature at a locus varies between cells. At the sub-megabase level, we observed stochastic clusters of contacts that can occur across TAD boundaries but average into TADs. Notably, we found that TADs and loops, but not compartments, are present in zygotic maternal chromatin, suggesting that these are generated by different mechanisms. Our results demonstrate that the global chromatin organization of zygote nuclei is fundamentally different from that of other interphase cells. An understanding of this zygotic chromatin 'ground state' could potentially provide insights into reprogramming cells to a state of totipotency.


Effects of Low-Dose Gamma-Ray Radiation on Apoptosis and Development of Zebrafish Embryo Brain.
To investigate the effects of low-dose γ irradiation on apoptosis and development of the brain in zebrafish embryos, cumulative 15 mGy doses of γ rays from a 137Cs source were used to irradiate zebrafish embryos at 2 h post-fertilization (hpf) for 120 h. Apoptosis of the brain, brain morphological development, cell submicroscopic structure and mRNA expression were analyzed, respectively. Results indicate that after 15 mGy exposure, the apoptosis of zebrafish brain increased, vacuoles appeared in brain tissue, some organelles were damaged and vacuoles appeared locally in brain cells. The mRNA expression level of axin2 was significantly upregulated, and those of frizzled, β-catenin, camk2, TCF/ LEF and bcl9 were significantly downregulated in brain tissue. These genes are involved in the Wnt signaling pathway. The findings of this work suggest that low-dose radiation may influence the apoptosis and development of the brain in the zebrafish embryo by inhibiting the Wnt signaling pathway.


Evidence accumulation in the integrated and primed Stroop tasks.
We report distributional analyses of response times (RT) in two variants of the color-word Stroop task using manual keypress responses. In the classic Stroop task, in which the color and word dimensions are integrated into a single stimulus, the Stroop congruence effect increased across the quantiles. In contrast, in the primed Stroop task, in which the distractor word is presented ahead of colored symbols, the Stroop congruence effect was manifested solely as a distributional shift, remaining constant across the quantiles. The distributional-shift pattern mirrors the semantic-priming effect that has been reported in semantic categorization tasks. The results are interpreted within the framework of evidence accumulation, and implications for the roles of task conflict and informational conflict are discussed.


Decision-making on shared sanitation in the informal settlements of Kisumu, Kenya.
Unlike most quantitative studies that investigate decision-making on investing in sanitation, this study adopted a qualitative approach to investigate decision-making on shared sanitation in the informal settlements of Kisumu city, in Kenya. Using a grounded theory approach, landlords and tenants were interviewed to identify sanitation decisions, individuals involved in decision-making and factors influencing decision-making. The results indicate that the main sanitation decisions are on investment, emptying, repair and cleaning. Landlords make investment, emptying and repair decisions, while tenants make cleaning decisions. Absentee landlords are less involved in most decision-making compared to live-in landlords, who rarely consult tenants in decision-making. Tenants make decisions after consultations with a third party and often collectively with other tenants. Sanitation interventions in informal settlements should thus, target landlords and tenants, with investment efforts being directed at landlords and maintenance efforts at tenants.


The Relationship of Astrocytes and Microglia with Different Stages of Ischemic Stroke.
Ischemic stroke is the predominant cause of severe morbidity and mortality worldwide. Post-stroke neuroinflammation has recently received increasing attention with the aim of providing a new effective treatment strategy for ischemic stroke. Microglia and astrocytes are major components of the innate immune system of the central nervous system. They can be involved in all phases of ischemic stroke, from the early stage, contributing to the first wave of neuronal cell death, to the late stage involving phagocytosis and repair. In the early stage of ischemic stroke, a vicious cycle exists between the activation of microglia and astrocytes (through astrocytic connexin 43 hemichannels), aggravating neuroinflammatory injury post-stroke. However, in the late stage of ischemic stroke, repeatedly activated microglia can induce the formation of glial scars by triggering reactive astrogliosis in the peri-infarct regions, which may limit the movement of activated microglia in reverse and restrict the diffusion of inflammation to healthy brain tissues, alleviating the neuroinflammatory injury poststroke. In this review, we elucidated the various roles of astrocytes and microglia and summarized their relationship with neuroinflammation. We also examined how astrocytes and microglia influence each other at different stages of ischemic stroke. Several potential therapeutic approaches targeting astrocytes and microglia in ischemic stroke have been reviewed. Understanding the details of astrocytemicroglia interaction processes will contribute to a better understanding of the mechanisms underlying ischemic stroke, contributing to the identification of new therapeutic interventions.


Combining polymers with the functionality of proteins: new concepts for atom transfer radical polymerization, nanoreactors and damage self-reporting materials.
Proteins are macromolecules with a great diversity of functions. By combining these biomolecules with polymers, exciting opportunities for new concepts in polymer sciences arise. This highlight exemplifies the aforementioned with current research results of our group. We review our discovery that the proteins horseradish peroxidase and hemoglobin possess ATRPase activity, i.e. they catalyze atom transfer radical polymerizations. Moreover, a permeabilization method for polymersomes is presented, where the photo-reaction of an α-hydroxyalkylphenone with block copolymer vesicles yields enzyme-containing nanoreactors. A further intriguing possibility to obtain functional nanoreactors is to enclose a polymerization catalyst into the thermosome, a protein cage from the family of chaperonins. Last but not least, fluorescent proteins are discussed as mechanoresponsive molecular sensors that report microdamages within fiber-reinforced composite materials.


Grazing and climate effects on soil organic carbon concentration and particle-size association in northern grasslands.
Grasslands cover more than 40% of the terrestrial surface of Earth and provide a range of ecological goods and services, including serving as one of the largest reservoirs for terrestrial carbon. An understanding of how livestock grazing, influences grassland soil organic carbon (SOC), including its concentration, vertical distribution and association among soil-particle sizes is unclear. We quantified SOC concentrations in the upper 30 cm of mineral soil, together with SOC particle-size association, within 108 pairs of long-term grazed and non-grazed grassland study sites spanning six distinct climate subregions across a 5.7 M ha area of Alberta, Canada. Moderate grazing enhanced SOC concentration by 12% in the upper 15 cm of soil. Moreover, SOC concentrations in mineral layers were associated with regional climate, such that SOC increased from dry to mesic subregions. Our results also indicate that C concentrations in each of 2000-250, 250-53, < 53 μm soil particle-size fractions were consistent with total SOC concentrations, increasing from semi-arid to more mesic subregions. We conclude that long-term livestock grazing may enhance SOC concentrations in shallow mineral soil and affirm that climate rather than grazing is the key modulator of soil C storage across northern grasslands.


A Novel Treatment to Selectively Harden Ti6Al4V Surfaces.
Various surface treatments have been developed on titanium and its alloy to improve their tribological properties. However, for some components, only specific surfaces need to be hardened rather than the whole surfaces. This study develops a duplex heat treatment including selective surface hardening by prepainting TiO2 powders and thermal oxidation. It is found that the TiO2 powder layer can be used as an oxygen reservoir for boosting diffusion treatment at temperatures of 800-900 °C. The abundance of oxygen provides high potential and accelerates the diffusion process, deeply hardening the surface case. Moreover, the duplex treatment is optimal for selectively hardened surfaces with high load-bearing capacity and much improved tribological properties. Prepainting the surfaces that need to be hardened is easy to operate and has good potential to be applied in industry.


Enhanced catalytic activity of gold nanoparticles doped in a mesoporous organic gel based on polymeric phloroglucinol carboxylic acid-formaldehyde.
Gold nanoparticles were supported by a phloroglucinolcarboxylic acid-formaldehyde (PF) gel, a new organic gel with a 30 nm spheroid-like structure. The surface area of the PF gel with gold nanoparticles was 550 m(2)/g. Gold nanoparticles supported on a PF gel exhibited catalytic activity in the reduction of 4-nitrophenol with a reaction rate constant of 7.4 x 10(-3) s(-1), which is high in the reported heterogeneous reaction system. The adsorption behavior of 4-nitrophenol into the gel support was observed by ultraviolet-visible absorption spectroscopy. Gold nanoparticles in the PF network were characterized by scanning electron microscopy, atomic force microscopy, and transmission electron microscopy observation. The high reduction rate would be attributed to the extraction and diffusion of the reactant through the pores of a PF gel support to encounter the highly dispersed gold nanoparticles on the surface and inside the material.


Special Issue: Antimicrobial Resistance in Livestock.
Antimicrobial resistance threatens the health of both humans and livestock as antimicrobials become continually less effective for controlling infectious disease [...].


Lagerstroemia speciosa Ameliorated Blood Pressure in LNAME Induced Hypertension in Experimental Rats through NO/cGMP and Oxidative Stress Modulation.
Cardiovascular disease is the primary reason for chronic heart diseases and mortality worldwide. Hypertension (HTN) is the utmost dominant risk factor for the evolution of several diseases. Herbal medicines, traditional medicinal herbs, and their extracts are widely utilized to treat and monitor HTN. Herbal components have been shown to help relax arteries and lower oxidative stress. The current study assesses the probable role of herbal plant extract Lagerstroemia speciosa (LS) in the LNAME induced HTN in rats. LNAME (50 mg/100 mL) in drinkable water was given to rats for five weeks. There was a significant upsurge in LNAME-treated hypertensive rats' blood pressure (BP). On treatment with LS, it ameliorates blood pressure. Further, LS also improved body weight, reduced heart weight, and heart hypertrophy. The NO/cGMP concentration was lowered along with a substantial upsurge in the level of glutathione and a decline in MDA level. The LS extract also reduced the inflammatory cytokine markers in the systemic circulation. In conclusion, thus, the extract of LS treatment can efficiently alleviate the BP, oxidative stress markers, and inflammation and improve NO/cGMP concentration in LNAME induced HTN in rats.


The SEARCH for Diabetes in Youth study: rationale, findings, and future directions.
The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions.


Perinatal vs genetic programming of serotonin states associated with anxiety.
Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior.


The Weight of Evidence Does Not Support the Listing of Styrene as "Reasonably Anticipated to be a Human Carcinogen" in NTP's Twelfth Report on Carcinogens.
Styrene was listed as "reasonably anticipated to be a human carcinogen" in the twelfth edition of the National Toxicology Program's Report on Carcinogens based on what we contend are erroneous findings of limited evidence of carcinogenicity in humans, sufficient evidence of carcinogenicity in experimental animals, and supporting mechanistic data. The epidemiology studies show no consistent increased incidence of, or mortality from, any type of cancer. In animal studies, increased incidence rates of mostly benign tumors have been observed only in certain strains of one species (mice) and at one tissue site (lung). The lack of concordance of tumor incidence and tumor type among animals (even within the same species) and humans indicates that there has been no particular cancer consistently observed among all available studies. The only plausible mechanism for styrene-induced carcinogenesis-a non-genotoxic mode of action that is specific to the mouse lung-is not relevant to humans. As a whole, the evidence does not support the characterization of styrene as "reasonably anticipated to be a human carcinogen," and styrene should not be listed in the Report on Carcinogens.


Isolation of bluetongue virus from sheep in Rajasthan State, India.
A cytopathic agent was isolated in a baby hamster kidney (BHK)-21 cell-line from blood samples of cross-bred sheep showing typical bluetongue symptoms at Avikanagar in Rajasthan State, India. The cytopathic agent was identified as a bluetongue virus (BTV) by immunofluorescence, the immunoperoxidase test and electron microscopy of BHK-21 cells infected with the new isolate. The new isolate was typed as BTV serotype 1.