C5a-inhibitor deficiency in peritoneal fluids from patients with familial Mediterranean fever.
Normal peritoneal fluid contains an inhibitor of neutrophil chemotaxis that acts by antagonizing the complement-derived chemotactic anaphyllatoxin C5a. The inhibitor resembles a substance previously described in synovial fluids and is a protein with a molecular weight of approximately 40,000 as determined by gel filtration. In contrast, levels of inhibitory activity in peritoneal fluids from five patients with familial Mediterranean fever were decreased to less than 10 per cent of those found in normal subjects. Gel filtration of peritoneal and synovial fluids from these patients did not yield any fraction with inhibitory activity. We suggest that C5a-inhibitor deficiency in joint and peritoneal fluids from patients with familial Mediterranean fever may have a role in the pathogenesis of the inflammatory attacks characteristic of this disease.


Spectrophotometric estimation of risperidone in tablets.
A simple, rapid and highly sensitive spectrophotometric method is developed for the determination of risperidone in tablet formulation. The method is based on the oxidation of drug using potassium permanganate in alkaline medium and excess potassium permanganate oxidizes 1,10-phenanthroline Fe(II). The measurement of decrease in absorbance of 1,10-phenanthroline Fe (II) was done at 415 nm. The beer's law is obeyed in the concentration range of 5.0 to 40.0 μg/ml and molar absorptivity is found to be 7.3932 × 10(4) l/mol/cm. The proposed method is well suited for the pharmaceutical formulations.


A reduction in serum cytokine levels parallels healing of venous ulcers in patients undergoing compression therapy.
vascular endothelial growth factor (VEGF) and tumour necrosis factor alpha (TNF(alpha)) have been specifically implicated in the tissue damage associated with chronic venous disease (CVD). Furthermore, production of both factors is known to be upregulated in vessel wall cells subject to hypertension. The aim of this study was to determine the local venous levels of VEGF and TNF(alpha) in limbs with venous ulcers before and after treatment with graduated compression. eight patients with venous ulcers and 8 patients with varicose veins only were included in the study. For ulcer patients, serum samples were taken from the superficial veins in lower limbs and repeated after 4 weeks of treatment with 4-layered graduated compression. Serum from the arms of the same patients served as controls. Determination of the concentrations of VEGF and TNF(alpha) proteins were performed with sandwich enzyme-linked immunosorbent assays. both groups of patients had elevated levels of VEGF and TNF(alpha). In patients with venous ulcers there was a reduction in the levels of both cytokines to below control values with treatment. These changes correlated with healing of the ulcers as determined by reduction in ulcer size. these data, for the first time, suggest a central role for both TNF(alpha) and VEGF in the pathogenesis of venous ulceration which may constitute a causative link between venous hypertension and tissue pathology.


Fine needle aspiration cytology in the management ENT of patients.
Aspirates were obtained from 142 masses in 120 patients who presented with palpable swellings in the head and neck region. 120 specimens (84.51 per cent) were adequate for diagnostic purposes and the remaining 22 (15.49 per cent) were unsatisfactory. Final diagnosis was based on resection histology in 87 cases and close clinical follow-up in 55 patients. The overall sensitivity and specificity including unsatisfactory aspirates was 81.37 per cent and 93 per cent respectively (if the technically inadequate specimens were deleted 98.81 per cent and 94.44 per cent). In comparison with the final diagnosis typing of malignant tumours was possible in 58.33 per cent. The correct diagnosis was made in 63.89 per cent of benign lesions.


Apolipoprotein E4 allele is associated with substantial changes in the plasma lipids and hyaluronic acid content in patients with nonalcoholic fatty liver disease.
Fat may affect progression of liver damage in patients with non-alcoholic fatty liver disease (NAFLD). In this study we characterize the state of lipid metabolism in 22 patients with NAFLD and different Apo-E variants. Total concentration of plasma total fatty acids was quantified by gas chromatography, while their derivatives by liquid chromatography/tandem mass spectrometry (LC ESI MS/MS). The ratio of plasma saturated fatty acid to monounsaturated fatty acid increased, whereas the ratio of polyunsaturated fatty acids to saturated fatty acids was reduced in Apo-E4 carriers. Simultaneously, the levels of individual plasma linoleic, arachidonic, and alpha linolenic acids significantly increased in subjects with the Apo-E4 allele. The 15-lipoxygenase metabolite, 13-hydroxyoctadecadienoic acid, was significantly higher in Apo-E3 carriers (p<0.006). 5-oxo-6,8,11,14-eicosatetraenoic acid was significantly elevated in Apo-E4 carriers (p<0.009). A significant difference in hyaluronic acid concentration (p<0.0016) as well as predicted advanced fibrosis (using the BARD scoring system) was found in Apo-E4 carriers (p<0.01). We suggest that a distinct mechanism of fibrosis between Apo E alleles. In Apo-E4 carriers, an elevation in 5-oxo-6,8,11,14-eicosatetraenoic acid synthesis and fatty acid dysfunction may induce fibrosis, while an inflammatory process may be the main cause of fibrosis in Apo-E3 carriers.


[Physical fitness of short children from the rural area].
In past decades we May observe in Poland the secular trend of somatic features as Wall as the phenomenon of maturity processes acceleration. On the other side physical fitness research results are diversified and are the results of multiple factors influence. From population of children, among which appear the effects of secular trend in somatic parameters we may mark the group of children diversified with body build from, as called "evolutionary norm" which may be described as short children. The aim of this work is determining physical fitness characteristics of short children in rural area of Wielkopolska region, in which we conducted wide population research in 2007. For the analyze were used data of 145 females and 140 males at age 7-9, pupils of five basic schools from rural area of Wielkopolska region. For the estimation of physical fitness of children were used test which describe basic motor abilities. For the estimation of speed was used a 5m run. For the estimation of strength was used the dynamometric measurement of hand strength test. Coordination abilities were determined by a run on the figure of eight. Efficiency was determined on the basis of Montoy's step test. 1. The analyze of data shows a lower level of motor development in comparison to children whose body height is placed over 10th centile. 2. Especially important differences were o observed in the case of muscle strength what may be result of low body height, low body mass as well as low muscle mass level. 3. Low quantity of researched ones characterized with short body height (about 17% among girls and about 13% among boys) points towards delicate concluding, concerning great diversity in this group and strong influation on average values of individual fitness tests.


A natural A/T-rich sequence from the yeast FBP1 gene exists as a cruciform in Escherichia coli cells.
Palindromic or semipalindromic sequences can adopt cruciform structures in DNA in vitro. It has been demonstrated in some cases that A/T-rich cruciforms exist also in vivo in Escherichia coli. The biological function of those structures is not understood although putative cruciforms have been found in interesting locations on replication origins, operators, or transcriptional termination regions. Here we show by means of the use of structure-dependent nucleases that the 3' end of the yeast FBP1 gene contains a stable cruciform both in vitro and in E. coli cells and that in both cases, its extrusion depends on the DNA supercoiling state.


Neuromechanism study of insect-machine interface: flight control by neural electrical stimulation.
The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.


A guide to the design and analysis of small clinical studies.
Clinical studies, which have a small number of patients, are conducted by pharmaceutical companies and research institutions. Examples of constraints that lead to a small clinical study include a single investigative site with a highly specialized expertise or equipment, rare diseases, and limited time and budget. We consider the following topics, which we believe will be helpful for the investigator and statistician working together on the design and analysis of small clinical studies: definitions of various types of small studies (exploratory, pilot, proof of concept); bias and ways to mitigate the bias; commonly used study designs for randomized and nonrandomized studies, and some less commonly used designs; potential ethical issues associated with small underpowered clinical studies; sample size for small studies; statistical analysis methods for different types of variables and multiplicity issues. We conclude the paper with recommendations made by an Institute of Medicine committee, which was asked to assess the current methodologies and appropriate situations for conducting small clinical studies.


Population pharmacokinetics analysis of VRC01, an HIV-1 broadly neutralizing monoclonal antibody, in healthy adults.
The monoclonal antibody VRC01 targets the CD4 binding site of the human immunodeficiency virus (HIV)-1 envelope. In the clinical study HVTN 104 (NCT02165267), 84 HIV-uninfected adults received multiple-dose intravenous (IV) VRC01 (10, 20, 30 or 40 mg/kg) every 4 or 8 weeks or subcutaneous (SC) VRC01 (5 mg/kg) every 2 weeks, and were followed for 32 weeks. We conducted a population pharmacokinetics (popPK) analysis based on 1117 VRC01 serum concentrations using a 2-compartment PK model with first-order elimination; for SC VRC01 a depot compartment with a first-order absorption rate constant was also included. All PK parameters were estimated with acceptable precision. Estimated bioavailability of SC VRC01 was 74%, with peak concentrations occurring 2-3 d after administration. For both IV and SC VRC01, population mean estimates for clearance (CL), central volume of distribution (Vc), inter-compartmental distribution clearance (Q) and peripheral volume of distribution (Vp) were 0.40 L/day, 1.94 L, 0.84 L/day and 4.90 L, respectively; the estimated terminal half-life was 15 d and these were independent of VRC01 dose. Body weight significantly influenced CL (1.2% fold/kg), Vc (1.0% fold/kg), Q (0.69 log(L/day)/kg) and Vp (0.82 log(L)/kg). The developed popPK model, supporting weight-dependent dosing regimens, projected positive trough levels, 5.54 (95% prediction interval: 1.69, 14.5) mcg/mL and 15.9 (5.29, 46.63) mcg/mL, respectively, for the 10 mg/kg and 30 mg/kg 8-weekly regimens being evaluated in ongoing HIV prevention efficacy studies of IV VRC01. These results are critical for future dose-regimen selection and modeling research to identify VRC01 serum concentration levels sufficient for protection against HIV infection.


Multiple Trichoepithelioma Syndrome: A Case Report.
Multiple trichoepithelioma syndrome is a rare entity, and little is known about its epidemiological features. Patients usually present with multiple nonsuspicious skin lesions. Surgical excision is the mainstay of treatment, and diagnosis is usually made after the first pathology report. Once the diagnosis is established, patients are kept under clinical surveillance, and surgery is performed again if tumor burden and/or size justifies it. The authors present a male patient who presented to our outpatient clinic for the first time in 36 years without any relevant medical history, medication, or allergies. The patient had complaints of multiple skin lesions spreading across the head and neck regions. Surgical excision of the affected area and resurfacing using local advancement flaps were performed. Pathology reports were always consistent with trichoepitheliomas. No pathology of spiradenoma or cylindroma was ever reported. Usually, tumors are small enough for simple excision and primary closure. However, in the presented case, the size of the tumor and the involvement of central facial aesthetic units demanded a more complex approach.


Rat liver injury induced by hypoxic ischemia and reperfusion: protective action by somatostatins is independent from changes in glucose metabolism.
Changes in glucose metabolism mediated by natural somatostatin and two derivatives (octreotide, 008) were studied in hypoxic ischemic cell injury of the isolated perfused rat liver. The tested somatostatin and its analogues were previously shown to exert protective actions in liver damage induced by hypoxic ischemia and reperfusion. In isolated perfused livers of rats starved for 24 hours and unstarved rats flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. Glucose and lactate concentration, as well as LDH and GLDH activity, were determined in the effluent. In starved and unstarved rat livers hypoxic ischemia resulted in a substantial enzyme release. In livers harvested from unstarved rats hepatic glucose release was noticed which ceased towards prolonged low flow ischemia. In livers harvested from starved rats containing low hepatic glycogen concentration only minimal hepatic glucose release was present. In starved and unstarved rats pretreatment with somatostatin, octreotide, and 008 significantly reduced LDH and GLDH release (p < 0.001). In unstarved rats natural somatostatin and octreotide pretreatment resulted in a substantial output of glucose during the hypoxic ischemic perfusion period (p < 0.001), whereas livers with 008 pretreatment did not show any difference in glucose release compared to controls. In livers harvested from starved rats neither somatostatin nor octreotide nor 008 pretreatment led to a difference in glucose output observed in controls. Natural somatostatin and octreotide cause a strong hepatic glucose release even under hypoxic ischemic conditions in rat livers with filled glycogen stores. The protective action of natural somatostatin, octreotide, and 008 is not mediated by changes in glucose metabolism, and is not related to endocrine activity.


Opioid Treatment Agreements Repurposed-But Who Monitors the Monitors?
In this issue of the Hastings Center Report, Joshua Rager and Peter Schwartz reframe the justification for the use of opioid treatment agreements. Instead of documents used to define the roles and responsibilities of doctors and patients to one another in the course of opioid treatment for chronic pain and to describe the risks and benefits of therapy for the individual, OTAs are now proposed for use as "surveillance and monitoring" instruments. As such, they are specifically meant to disclose the risks of opioid therapy and to describe the other processes and tools used to monitor abuse and diversion of medications. Given the crisis of the opioid overdose and death epidemic, along with this repurposing of OTAs as disclosure documents primarily, Rager and Schwartz argue that patient consent is not needed (although desired) and that OTAs should be universally applied in clinical practices. We can all agree on the big picture goal of limiting the number of opioid prescriptions in order to minimize the tragedy of opioid overdose deaths. We disagree, though, about the acceptable level of collateral damage to people in pain who fall victim to fighting the war against the so-called opioid epidemic.


Treatment of anxiety disorders in primary care practice: a randomised controlled trial.
Anxiety disorders are prevalent in primary care. Psychological treatment is effective but time-consuming, and there are waiting lists for secondary care. Interest has therefore grown in developing guidelines for treatment that would be feasible in primary care. To compare the effectiveness and feasibility of guided self-help, the Anxiety Disorder Guidelines of the Netherlands College of General Practitioners and cognitive behavioural therapy (CBT). Randomised controlled study lasting 12 weeks with follow-up at 3 and 9 months for primary care patients with panic disorder and/or generalised anxiety disorder. The first two forms of treatment were carried out by 46 GPs who were randomly assigned to one or the other form. CBT was carried out by cognitive behaviour therapists in a psychiatric outpatient clinic. Participants (n = 154) were randomly assigned to one of the three forms of treatment. The main outcome measure used was the state subscale of the Spielberger Anxiety Inventory. All three forms of treatment gave significant improvement between pre-test and post-test, and this improvement remained stable between post-test and the follow-ups. The results obtained with the three treatment forms did not differ significantly over time. The feasibility of the Anxiety Disorder Guidelines was low compared with that of guided self-help. Our results indicate that primary care patients with prevalent anxiety disorders for whom the GP does not find referral necessary can be adequately treated by the GP. Psychiatric outpatient clinic referral does not give superior results. Guided self-help is easier for the GP to carry out than a less highly-structured treatment like that laid down in the Anxiety Disorder Guidelines.


Molecular cloning and characterization of a candidate human growth-related and time-keeping constitutive cell surface hydroquinone (NADH) oxidase.
ENOX (ECTO-NOX) proteins are growth-related cell surface proteins that catalyze both hydroquinone or NADH oxidation and protein disulfide-thiol interchange and exhibit both prion-like and time-keeping (clock) properties. The two enzymatic activities they catalyze alternate to generate a regular period of 24 min in length. Here we report the cloning, expression, and characterization of a human candidate constitutive ENOX (CNOX or ENOX1) protein. The gene encoding this 643 amino acid long protein is located on chromosome 13 (13q 14.11). Functional motifs previously identified by site-directed mutagenesis in a cancer-associated ENOX (tNOX or ENOX2) as adenine nucleotide or copper binding along with essential cysteines are present, but the drug-binding motif (EEMTE) sequence of ENOX2 is absent. The activities of the recombinant protein expressed in Escherichia coli were not affected by capsaicin, EGCg, and other ENOX2-inhibiting substances. The purified recombinant protein bound ca. 2 mol of copper/mol of protein. Bound copper was necessary for activity. H260 and H579 were required for copper binding as confirmed by site-directed mutagenesis, loss of copper-binding capacity, and resultant loss of enzymatic activity. Addition of melatonin phased the 24 min period such that the next complete period began exactly 24 min after the melatonin addition as appears to be characteristic of ENOX1 activities in general. Oxidative activity was exhibited with both NAD(P)H and reduced coenzyme Q as substrate. Concentrated solutions of the purified candidate ENOX1 protein irreversibly formed insoluble aggregates, devoid of enzymatic activity, resembling amyloid.


[The blunt open injury to the lower extremities resulting from the overextension of the knee joint].
This article reports a case of the blunt open injury to the lower extremities resulting from the overextension of the knee joint that, despite it severity, turned out to be a mere accompanying event of a more serious condition. This case is of great interest in the context of forensic medical expertise by virtue of the apparent discrepancy between the extent of the injury and the circumstances of the accident. Clearly, such discrepancy may influence the reliability of the expert conclusion as regards the evaluation of such injury.


Adaptive learning and recall of motor-sensory sequences in adult echolocating bats.
Learning to adapt to changes in the environment is highly beneficial. This is especially true for echolocating bats that forage in diverse environments, moving between open spaces to highly complex ones. Bats are known for their ability to rapidly adjust their sensing according to auditory information gathered from the environment within milliseconds but can they also benefit from longer adaptive processes? In this study, we examined adult bats' ability to slowly adapt their sensing strategy to a new type of environment they have never experienced for such long durations, and to then maintain this learned echolocation strategy over time. We show that over a period of weeks, Pipistrellus kuhlii bats gradually adapt their pre-takeoff echolocation sequence when moved to a constantly cluttered environment. After adopting this improved strategy, the bats retained an ability to instantaneously use it when placed back in a similarly cluttered environment, even after spending many months in a significantly less cluttered environment. We demonstrate long-term adaptive flexibility in sensory acquisition in adult animals. Our study also gives further insight into the importance of sensory planning in the initiation of a precise sensorimotor behavior such as approaching for landing.


Omacetaxine mepesuccinate in chronic myeloid leukemia.
Homoharringtonine (HHT) and other alkaloid esters were originally isolated from the Cephalotaxus evergreen tree and have been used in traditional Chinese medicine since the 1970s to treat a variety of malignancies. Although HHT was investigated for the treatment of chronic myeloid leukemia (CML) in the 1990s with good results, the advent of BCR-ABL1 tyrosine kinase inhibitors (TKIs) at that time rapidly established a new standard of care for CML. Omacetaxine mepesuccinate is a semisynthetic derivative of HHT with known clinical activity in relapsed or refractory CML following TKI therapy. In this review, we summarize the biologic effects of HHT and its derivative, omacetaxine, in CML. Additionally, we analyze the concepts learned from the early trials using these drugs. Data from clinical trials resulting in drug approval are also reviewed. Omacetaxine has a clear role in the CML armamentarium for patients in chronic and accelerated phase who have failed or were intolerant to two or more TKIs.


[Effect of nitrogen and phosphorous on the production of microcystin under laboratory conditions].
To explore the effect of phosphorus, nitrogen on the production of microcystin under specific laboratory condition. The microcystis were ampliatively cultured for three times in N and P free culture. Then the microcysitis were inoculated in the culture at the concentrations of 0, 0.5, 1.0, 5.0 and 10.0 mg/L P for 20 days. The microcystis were inoculated in the BG-11 cultures at the concentrations of 0.05 mg/L and 5.0 mg/L P, NaNO3 were added in the culture according to the mol ratios of N/P were 5:1, 10:1, 20:1, 50:1, 100:1 and were cultured for 20 days. The changes of the count of the microcystis were observed. The microcystis cell were breaked at the 8th, 12th, 16th and 20th days after the beginning of culturing, the the microcystin were extracted and detected by HPLC. When the concentrations of phosphorus were lower than 5.0 mg/L, The productions of microcystin increased with the phosphorus concentrations. But when the concentrations of phosphorus were 10.0 mg/L, the productions of microcystin significantly decreased. In the culture at the concentrations of 0.05 mg/L P, the microcystin concentration per cell (MCYST fg/cell) and the microcystin concentrations per milliliter (MCYST microg/ml culture) presented the greatest value when the N/P ratio was 50:1. But, In the culture at the concentrations of 5.0 mg/L P, the microcystin concentrations per cell (MCYST fg/cell) and the microcystin concentrations per milliliter (MCYST microg/ml culture) presented the greatest value when the N/P ratio was 20:1. P concentrations significantly incluence the production of microcystin. The P concentrations in water should be controlled through different way to control the production of microcystins.


[Classification of neuroendocrine tumors of the gastrointestinal tract and pancreas and its therapeutic relevance].
In this review therapeutic strategies for neuroendocrine tumors of the gastrointestinal tract and the pancreas are proposed, based on the recent classification. Generally, for all neuroendocrine tumors even with obvious metastases, surgery is recommended. Particularly for neuroendocrine tumors of the upper intestinal tract and the pancreas as extensive preoperative clinical and histopathological diagnosis is required. We tried to simplify the therapeutic strategies according to the classification; in several cases, however, very close cooperation between gastroenterologists, surgeons and pathologists is necessary to decide on the appropriate therapeutic strategy.


Conductivity and aging behavior of Sr(Ti0.6Fe0.4)1-x O3-δ mixed conductor materials.
Perovskite materials play a significant role in oxygen sensors due to their fascinating electrical and ionic conductivities. The sol-gel technique was employed to prepare various compositions of B-site-deficient Fe-doped SrTiO3 (iron-doped strontium titanate) or Sr(Ti0.6Fe0.4)1-x O3-δ , where x = 0.01, 0.02, and 0.03. The XRD results revealed that the principle crystalline phase of the samples was the cubic perovskite structure. The B-site deficiency improved the ionic and total conductivities of Sr(Ti0.6Fe0.4)1-x O3-δ . A small polaron conduction behavior occurred in the total electrical conductivity. The XPS results showed that the oxygen vacancy value decreased with the rise in the amount of B-site deficiencies. A lower B-site deficiency amount could produce more oxygen vacancies in the lattice but resulted in the ordering of vacancies and then lower ionic conductivity. The aging behavior was caused by the ordering of oxygen vacancies and resulted in a degeneration of electrical features under a long service time. Conversely, augmentation of the B-site deficiency amount inhibited the tendency for the ordering of oxygen vacancies and then promoted the electrical performance under a long usage time. The conduction mechanism of oxygen ions through oxygen vacancies was thoroughly investigated and discussed. The current study presents a feasible approach to ameliorate the physical features of conductors through doping the B-site of the perovskite layer with Fe, which would be a fruitful approach for numerous applications, including oxygen sensors and fuel cells anodes.


[Clinical use of morphine derivatives in neuro-anesthesia].
Narcotics are used in neuro-anesthesiology according to their pharmacology and their effects on cerebral physiology. New narcotics (fentanyl, sufentanil, alfentanil) fulfill the requirements of modern neurosurgical anesthesiology looking for quick awakening.


The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies.
The present review specifies the various chemical and physical factors that can influence drug stability and immunogenicity, and the treatment outcomes of antibody biologicals. Although monoclonal antibodies (mAbs) are known to be more resistant to environmental changes compared with other proteins, the molecules themselves can be subjected to chemical and physical processes that promote their degradation and transformation into their specific amino-acid moieties. With increasing use of medicinal products that contain mAbs, and their self-administration by the patients, the issue of the correct manipulation of these drugs is of increasing importance. This review summarises the correct handling of mAb biologicals from the point of view of the pharmacist, clinical biochemist and patient, as is supported by relevant cases from the literature and our own data and experience. In particular, if there is a break in the cold chain, both healthcare professionals and patients need to be aware of the potential pharmacokinetics and pharmacodynamics alterations to these biologicals. Furthermore, any alterations in the protein structure can induce harmful immune reactions, including anaphylaxis and cytokine storms, or result in the production of neutralising or blocking Abs. Overall, considering also that treatment costs usually remain high, drug stability can have a tremendous effect on the clinical, humanistic and economic outcomes of such treatments.


Interleukin-17 as a molecular target in immune-mediated arthritis: immunoregulatory properties of genetically modified murine dendritic cells that secrete interleukin-4.
Our previous studies have shown that murine dendritic cells (DCs) genetically modified to express interleukin-4 (IL-4) reduce the incidence and severity of murine collagen-induced arthritis. The present studies were performed to assess the immunoregulatory mechanisms underlying this response, by assessing the effects of IL-4 DCs on cytokine production by subsets of T helper cells. Male DBA mice ages 6-8 weeks old were immunized with type II collagen. Splenic T cells obtained during the initiation phase and the end stage of arthritis were cultured with IL-4 DCs or untransduced DCs in the presence of collagen rechallenge. Interferon-gamma (IFNgamma) and IL-17 responses were measured. Antibodies to IL-4, IL-12, and IL-23, and recombinant IL-4, IL-12, and IL-23 were used to further study the regulation of T cell cytokine production by IL-4 DCs. Splenic T cells obtained during the initiation phase of arthritis produced less IL-17 when cultured in the presence of IL-4 DCs, despite their production of increased quantities of other proinflammatory cytokines (IFNgamma and tumor necrosis factor). T cell IL-17 production after collagen rechallenge was not inhibited by a lack of IL-23, since IL-4-mediated suppression of IL-17 was not reconstituted by IL-23, an otherwise potent inducer of IL-17 production by T cells. Although IL-4 DCs can produce increased quantities of IL-12 and IFNgamma, suppression of IL-17 production by IL-4 DCs was independent of both. While IL-17 production by T cells obtained during the initiation phase of arthritis was regulated by IL-4 DCs, IL-17 production by T cells obtained during end-stage arthritis was not altered. Our data suggest that IL-4 DCs exert a therapeutic effect on collagen-induced arthritis by targeting IL-17. IL-17 suppression by IL-4 DCs is robust and is not reversed by IL-23. Timing might be important in IL-17-targeted therapy, since IL-17 production by T cells obtained during end-stage arthritis did not respond to suppression by IL-4 DCs.


[Ligneous conjunctivitis in a patient with plasminogen type I deficiency--case report with review of literature].
Ligneous conjunctivitis is a rare chronic pseudomembranous conjunctivitis. It forms nodular masses on the palpebral conjunctiva. Beside the conjunctival affection pseudomembranes can also be found on other mucosal tissues. We report on a male baby who had a ventriculoperitoneal shunt due to hydrocephalus internus on his fourth day after birth. Recurrent pseudomebranous conjunctivitis started in the first week of life. This was refractory to drug therapy and reoccurred soon after surgical procedure. The analysis of clotting parameters revealed homozygous plasminogen deficiency. Recently type I plasminogen deficiency seems to be a major reason for developing conjunctivitis lignosa. Homozygous and heterozygous mutations in the plasminogen gene are found. At the moment no satisfactory therapy is available. Cases with mild ophthalmological symptoms seem to be positively influenced by a therapy of topical steroids combined with heparin. In severe cases with generalised symptoms systemic therapy with lys-plasminogen is necessary. High costs and poor bioavailability complicate systemic therapy. Improved plasminogen variants for treatment of severe type I plasminogen deficiency would be of great clinical importance.


Women's report of unwanted sexual attention during childhood.
Unwanted Sexual Attention (UWSA) refers to unsolicited verbal comments, gestures, stares, and other non-physical attention toward another's sexuality and physical appearance. The present study describes the occurrence of childhood UWSA and explores its relation to child sexual abuse (CSA). Three hundred fifteen university women (mean age=19.5) completed the Exposure to Sexual Attention Scale, a 200-item inventory which assesses various forms of UWSA received prior to age 18. Findings suggested that non-contact UWSA is a pervasive experience across settings for girls, with 98.7% reporting UWSA during childhood. Those reported most often to perpetrate UWSA (e.g., other students, adult strangers, child strangers, and other children) were also most often reported as sexual abusers. Emotional reactions by women to both UWSA and CSA were predominantly negative. Although significantly greater levels of fear reactions were reported by the CSA group when compared to the UWSA group. No difference was found between the two groups on levels of anger reactions to UWSA and CSA. Overall findings suggest that UWSA is an almost universal experience for girls that causes significant anger and fear. Assessing UWSA will be important from a public health perspective in evaluating if such behaviors pose a risk factor for negative developmental outcomes for girls.


Tumor cell extravasation mediated by leukocyte adhesion is shear rate dependent on IL-8 signaling.
To complete the metastatic journey, cancer cells have to disseminate through the circulation and extravasate to distal organs. However, the extravasation process, by which tumor cells leave a blood vessel and invade the surrounding tissue from the microcirculation, remains poorly understood at the molecular level. In this study, tumor cell adhesion to the endothelium (EC) and subsequent extravasation were investigated under various flow conditions. Results have shown polymorphonuclear neutrophils (PMNs) facilitate melanoma cell adhesion to the EC and subsequent extravasation by a shear-rate dependent mechanism. Melanoma cell-PMN interactions are mediated by the binding between intercellular adhesion molecule-1 (ICAM-1) on melanoma cells and beta2 integrins on PMNs. In addition, the fluid convection affects the extent of activation of beta2 integrins on PMNs by endogenously secreted interleukin 8 (IL-8) within the tumor microenvironment. Results also indicate that shear rate affects the binding kinetics between PMNs and melanoma cells, which may contribute to the shear-rate dependence of melanoma extravasation in a shear flow when mediated by PMNs.


Susceptibility of different leukocyte cell types to Vaccinia virus infection.
Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP), and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1-5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.


Substance abuse and the emergency room: programmatic implications.
A literature review (1984 to 1995) was conducted to identify cost effective policy implications regarding substance use in the emergency room (ER) and trauma unit. Prevalence rates, ranging from 9% to 47%, vary according to where, when and who is tested. Other drugs, most commonly marijuana, benzodiazepines and cocaine, follow a similar pattern to alcohol. The optimal method of measuring substance use depends on the goal of the assessment and a combination of clinical, self-report and biochemical markers is recommended. Simple screening questions such as the TWEAK or AUDIT should be routinely used with all attendants and further assessment provided only when high risk factors have been identified. These include: males, younger patients, metropolitan centres, after midnight and on weekends, injury from violence, accidents including MVAs, high acuity and psychiatric morbidity. Further, this screening should be complimented by an intervention, referral and treatment resource for those in need.


The Use of Intravenous Tranexamic Acid in Patients Undergoing Total Hip or Knee Arthroplasty: A Retrospective Analysis at a Single Military Institution.
To describe a single institution's experience after initiation of a protocol in which all primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients were administered intravenous tranexamic acid (TXA) intraoperatively to decrease perioperative blood loss. A retrospective review of medical records at a single institution from February 2012 to April 2014. The TXA treatment group was compared to a control group. We reviewed intraoperative blood loss, preoperative hemoglobin (Hb) levels, postoperative day 0 to 2 Hb levels, transfusion rates, postoperative venous thromboembolism, and other complication rates. 259 patients underwent either TKA (165) or THA (94). 121 received perioperative intravenous TXA and 138 did not. There was a statistically decreased rate of allogeneic blood transfusion (0 vs. 10, p = 0.003) as well as a higher postoperative day 2 Hb level (10.8 ± 1.1 vs. 10.2 ± 2.6 g/dL, p = 0.02) in the treatment group. There was no statistical difference in any variable measured in the THA group, though there was a trend toward higher postoperative Hb levels at all-time points measured. Intravenous TXA is a safe and effective drug to decrease perioperative blood loss and allogeneic transfusion in THA and TKA. There was no increased risk of venous thromboembolism or other complications in our review.


JNK and ERK signaling pathways in multistage mouse carcinogenesis: studies in the inhibition of signaling cascades as a means to understand their in vivo biological role.
Amplification and mutation of Ha-ras has been shown to correlate with the malignancy of tumors that appear in chemically-induced mouse skin. Cell lines isolated from mouse skin tumors represent the evolutionary stages of tumor development. Due to the high Ha-ras levels the JNK and ERK modules are found elevated, contributing to the enhanced AP-1 activity in the more malignant cells. To examine the role of the transforming Ha-ras in controlling ERK signaling, transfection of an activated Ha-ras allele was tested in a squamous cell carcinoma cell line. The ERK1/2 signaling pathways were blocked pharmacologically by PD98059 MEK inhibitor, which inhibited cell proliferation and anchorage-independent growth of squamous and spindle carcinoma cells. In addition, treatment with PD98059 and introduction of the dominant negative ATF-2 mutant into the spindle carcinoma cells, partially reverted the spindle phenotype to squamous-like. These results suggest that ERK1/2 and A TF-2 play an important role in oncogenicity and in the degree of progression within the mouse skin carcinogenesis system.


[Audits and confidential enquiry: thoughts on the technique used by the French National Committee for the reduction of maternal deaths].
This study demonstrates the need for a confidential approach to medial information when the objective is to improve medical practices, as was the goal of the French National Committee for the reduction of maternal deaths. This approach is the exact opposite of a litigation where the goal is to determine "guilt". Confidential analysis of maternal deaths is not designed to find a guilty person, but rather to identify the mechanisms leading to a maternal death in order to correct the organizational or medical practice leading to failure. We review here similar actions taken to reduce other types of medical accidents such as anesthesia deaths. The confidential approach has been found to be pertinent in the perinatal audit conducted in the Seine-Saint-Denis region, including all fetal and neonatal deaths, that has shown measurable reduction in the number of fetal deaths.


Impact of environmental exposure to persistent organic pollutants on lung cancer risk.
Recent studies suggest that high pre-diagnostic serum concentrations of persistent organic pollutants (POPs) might result in the development of cancers in the general population. However, the association between pre-diagnostic serum POP concentrations and lung cancer risk has not been studied. Here, we evaluated associations between low-dose environmental exposure to POPs and risk of lung cancer using pre-diagnostic serum samples in a case-cohort study based on a population-based prospective cohort. We conducted a case-cohort study based on the Korean National Cancer Center Community Cohort, from which we included 118 lung cancer cases and 252 controls. Serum concentrations of POPs were measured by high resolution gas chromatography/high-resolution mass spectrometry, and data were analyzed using multivariable Cox proportional-hazards regression models. Risk of lung cancer increased per unit increase in the natural log-transformed concentrations of the sum of chlordane congeners, total PCBs, and all PCBs subgrouped by the number of chlorines or ortho- substituted chlorines on the molecules, except for tri/tetrachlorobiphenyls, in all models. Among individual POP analytes with a detection rate >80%, after Bonferroni adjustment, only trans-nonachlor was associated with lung cancer risk. In categorical models, risk of lung cancer was associated with serum concentration of chlordane (4th vs. 1st quartile, hazard ratio [95% confidence interval], 8.79 [2.77-27.97]). Dose-dependent relationships were also found between risk of lung cancer and serum concentrations of PCBs regardless of their degree of chlorination, substitution pattern, or binding affinity to receptors (total PCBs, P = 0.002; mid-chlorinated PCBs, P = 0.004; high-chlorinated PCBs, P < 0.001; non- and mono-ortho PCBs, P = 0.031; di-ortho PCBs, P = 0.003; PCBs with dioxin-like activity, P = 0.011; non-dioxin-like non-/mono-ortho PCBs, P = 0.060). Serum concentrations of chlordane and PCBs are associated with risk of lung cancer in the general population, even decades after the ban on their production and use.


Temporal relationship between postural and focal components of a whole-body reaching movement: a study case of short-term adaptation in microgravity condition.
In this study, the question of postural and focal components integration by the central nervous system (CNS) is investigated through whole body reaching task performance in microgravity. Because of the especially important difficulties suffered by one subject during parabolic flight, observation of temporal relationship evolution was allowed. From these results, short-term adaptation based on the restoration of this relationship could be postulated.


PAXgene-fixed paraffin-embedded sample is applicable to laser capture microdissection with well-balanced RNA quality and tissue morphology.
Assessing how gene expression analysis by RNA sequencing (RNA-Seq) correlates to a unique morphology is increasingly necessary, and laser capture microdissection (LCM) is a critical research tool for discovering the genes responsible in a region of interest (ROI). Because RNA-Seq requires high-quality RNA, a sample preparation procedure that can preserve morphology and give the required quality of RNA is essential. A PAXgene®-fixed paraffin-embedded (XFPE) block can satisfy the need for high-quality RNA, but there are few reports on adapting the method for LCM, such as how small an ROI is analyzable by RNA-Seq. In this study, we confirmed the morphology and preservation of RNA in XFPE and then assessed the relationship between the size of pieces cut by LCM and their RNA quality. In XFPE, the morphology was similar to that in alcohol-based fixed samples, the quality of the RNA extracted from a whole sample was excellent, that is equivalent to that of a fresh frozen sample, and the quality was maintained over one year later. Three sizes of pieces-large (25,000 µm2), medium (5,000 µm2), and small (1,000 µm2)-were cut by LCM so that the total areas of the sections cut per size were the same. RNA quality was found to be best preserved when tissue was cut into pieces of over 5,000 µm2. In summary, XFPE exhibits good morphology and excellent preservation of RNA quality. Furthermore, it can be a good tool when used with LCM and RNA-Seq, giving well-balanced RNA quality and tissue morphology in the ROI.


Involvement of Spt7p in vacuolar polyphosphate level of Saccharomyces cerevisiae.
Saccharomyces cerevisiae became less sensitive to nickel by a defect of the SPT7 gene encoding a transcription factor. Initial rate of nickel uptake by whole cells of a SPT7-negative mutant FY963 was nearly equal to that of the parent strain FY61, and FY963 accumulated nickel about 1.7-fold of the value of FY61 when cultured in medium containing 0.1 mM NiCl2; most of which was sequestered into vacuoles. The pH gradient-driven nickel uptake by vacuolar membrane vesicles was not altered in FY963, but the amount of polyphosphate in vacuoles was highly elevated. Involvement of Spt7p in nickel detoxification through regulation of vacuolar polyphosphate level in S. cerevisiae was discussed.


Influence of Tuning Element Relief Patches on Pain as Analyzed by the Resonant Recognition Model.
Tuning element relief patches (TERPs) are silicon-based titanium salt infused adhesive patches that have been developed by Tuning Element. A number of anecdotal reports have shown that TERPs diffuse pain, including chronic, inflammatory, and neuropathic. Pain is a very complex biochemical and electrical process involving sensory part, nerve transmission, and brain perception of pain. We concentrated our research on nerve transmission, which is electrical signal along the nerve (axon). This electrical signal is created by a complex activity of opening and closing of pain related ion channels and redistribution of electrically charged ions on the nerve cell membrane. Ion channels are made of different proteins, which are involved with the complex processes of opening and closing ion channels. Here, we apply the resonant recognition model to analyze ion channel proteins related to the pain transmission in order to find out, how imprints and particles within TERPs can interfere with pain related activity of ion channels.


Navigating the health-care system in community: Perspectives from Asian immigrant parents of children with special health-care needs.
Children with special health-care needs (CSHCNs) face notable barriers to health-care access and to receiving quality and family-centered care, despite higher health-care utilization rates. Within the population of CSHCNs, there are significant inequities in health-care quality impacting immigrants who have migrated to the United States. However, little is known about the experiences and needs of Asian immigrant families who have CSHCNs. This study aimed to explore how Asian immigrant parents of CSHCNs view their child's health-care access, quality, and utilization. We conducted semi-structured qualitative interviews with 22 Vietnamese- and Cantonese-speaking parents of CSHCNs. Participants were recruited through community partners. Interviews were transcribed, translated, and coded using content analysis. Participants were generally satisfied with their children's care and had strong relationships with their primary care doctors who were often culturally 'matched'. However, participants experienced several important and culturally specific barriers, including gaps in their understanding of the health-care system, language barriers, and a sense of alienation. Parents frequently turned to informal and community supports for assistance in navigating the US health-care system. Further research to understand the drivers of health disparities and policy level solutions is warranted.


The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease.
While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer's disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60+/-10 years, range 36-86) were examined to determine the relationships between CSF measures of total tau (T-tau), hyperphosphorylated tau (P-tau 231), amyloid beta (Abeta42/Abeta40 ratio), and isoprostane (IP) with age and ApoE genotype. The results showed that age by epsilon4 genotype interactions were found for P-tau231 (beta=1.82; p<0.05) and IP (beta=1.6; p<0.05). T-tau CSF concentration increased with age. The increasing CSF concentrations of P-tau and IP in epsilon4 carriers suggest that early tauopathy and oxidative stress may be related to the increased risk for AD. The data also suggest that T-tau changes are more age dependent than Abeta changes. The evidence that P-tau231 and IP are the earliest markers for the neuronal damage related to AD awaits longitudinal study.


Determination of proinsulin intermediates by means of an immunoradiometric method using polyclonal antibodies.
In our endeavour to develop a method for proinsulin determination, an immunoradiometric method was developed. Thereby guinea-pig antibodies to bovine insulin which were purified with an immunoadsorbent, were, in surplus, coupled to polyethylene tubes. These tubes were used to extract proinsulin and insulin from the sample and standard that or was to be determined. The proinsulin adsorbed onto the wall of the tube was distinguished from insulin by incubating, in a second step, a rabbit antibody to human C-peptide with the tubes. In order to render the proinsulin anti-C-peptide complex measurable, a donkey antibody to rabbit IgG was used, which had been purified via an immunoadsorbent and which was labelled with iodine-125. Since proinsulin extracted from human pancreata was available next to biosynthetic human proinsulin, it was striking to note that these substances were very differently recorded by the determination method applied. Thus biosynthetic human proinsulin dissolved in gelatin buffer could not be measured at all. After mild tryptic cleavage of the biosynthetic human proinsulin, a clear increase of the immunoreactivity was seen in this method. Therefore the claim could be made that partially cleaved proinsulin molecules with a retained C-peptide structure had come into existence. This could be verified by application of the proinsulin cleavage products 65/A1 and 32/33, which exhibited a behaviour very similar to that of pancreatic proinsulin in this method. In this way we could demonstrate that the originally planned immunoradiometric determination method for proinsulin, recorded partially hydrolized intermediates of the proinsulin, which represent a large part of the proinsulin immunoreactivity in the serum.


A profile of the adolescent male family planning client.
Family planning programs and policies increasingly focus on the male partner's roles and responsibilities in contraceptive decision-making and use. To effectively tailor services for males, policymakers and providers must refine their understanding of men's psychosocial and reproductive health needs. Using self-administered questionnaires, 1,540 sexually active males aged 19 and younger who attended family planning clinics in California provided information about their sexual behavior, contraceptive use, pregnancy and parenting history, and psychosocial characteristics. Logistic regression was used to examine factors that contributed to effective contraceptive use. Although 73% of participants reported having used a birth control method at first intercourse, only 59% said that they or their partner had used an effective method at last intercourse, and 35% had used no method. If the client was uncomfortable with his method, the odds that he had used an effective method at last intercourse were reduced (odds ratio, 0.4). The likelihood of use at last intercourse was increased among males who agreed with their partner about their method and those who had never impregnated a partner (1.4 and 1.9, respectively). To adequately serve young males, clinics must take into account their sexual and contraceptive histories. But screening should go beyond traditional family planning techniques to discuss how to improve communication with partners and other lifestyle issues that may interfere with consistent use.


Brain tumor imaging: imaging brain metastasis using a brain-metastasizing breast adenocarcinoma.
Brain metastases from primary or secondary breast tumors are difficult to model in the mouse. When metastatic breast cancer cell lines are injected directly into the arterial circulation, only a small fraction of cells enter the brain to form metastatic foci. To study the molecular and cellular mechanisms of brain metastasis, we have transfected MB-231BR, a brain-homing derivative of a human breast adenocarcinoma line MDA-MB-231, with the yellow fluorescent protein (YFP) variant Venus. MB-231BR selectively enters the brain after intracardiac injection into the arterial circulation, resulting in accumulation of fluorescent foci of cells in the brain that can be viewed by standard fluorescence imaging procedures. We describe how to perform the intracardiac injection and the parameters used to quantify brain metastasis in brain sections by standard one-photon fluorescence imaging. The disadvantage of this model is that the kinetics of growth over time cannot be determined in the same animal. In addition, the injection technique does not permit precise placement of tumor cells within the brain. This model is useful for determining the molecular determinants of brain tumor metastasis.


Are interfacility ground transports of patients utilizing intra-aortic balloon pumps safe?
To determine whether the interfacility ground transport of patients with intra-aortic balloon pumps results in morbidity or mortality during transfer. Charts of all intra-aortic balloon pump transports by a private ambulance company occurring from January 1998 through December 1999 (24 months) were reviewed retrospectively. Records were assessed by a single reviewer for adverse events, explicitly defined as any notation on the record describing death, chest pain, dyspnea, altered mental status, device malfunction, bleeding, unstable vital signs (heart rate <50 beats/min or > or = 120 beats/min, respiratory rate <12 breaths/min or > or = 30 breaths/min, systolic blood pressure <90 mm Hg), or hypoxia (oxygen saturation <93%). Unstable vital signs as defined above did not count as adverse events if they represented a patient's baseline condition prior to transport. Thirty-two transports were identified during the study period. Twenty-seven patients (84.4%) had no adverse events. There were no mortalities. Adverse events, none of which resulted in morbidity, were: 1) chest pain and transient paroxysmal atrial tachycardia (relieved with increasing the nitroglycerin infusion); 2) continuous mild chest pain (began during transport and diminished with giving sublingual nitroglycerin and increasing the nitroglycerin infusion); 3) dyspnea and hypoxia (relieved with increased oxygen); 4) transient hypotension (spontaneously resolved); 5) hypotension (resolved by increasing the dopamine infusion). Although a few adverse events occurred, interfacility ground transport of patients with intra-aortic balloon pumps was not associated with morbidity or mortality in this study.


Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound.
In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x107 CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 μg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 μg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models.


Randomized trial comparing two natural surfactants (Survanta vs. bLES) for treatment of neonatal respiratory distress syndrome.
Exogenous surfactants have been used as an effective treatment of neonatal respiratory distress syndrome (RDS). Different preparations of surfactant carry different biophysical and clinical properties. To study the response pattern and treatment outcome of two natural surfactants (bLES and Survanta) for the treatment of RDS, we conducted a randomized clinical trial at the neonatal unit of a university teaching hospital. Premature babies with birth weight between 500-1,800 g who developed RDS requiring mechanical ventilation with an oxygen requirement of more than 30% within 6 hr of life were randomized into two treatment groups. Oxygenation indices (OIs) within 12 hr of treatment were compared as primary outcomes, while neonatal complications were analyzed as secondary outcomes of the study. Sixty babies were recruited, with 29 in the bLES and 31 in the Survanta treatment group. Both groups had significant and sustained improvements in OI after surfactant replacement therapy (SRT), while the bLES group was associated with a significantly lower OI throughout the initial 12 hr after treatment compared with the Survanta group. There was no difference in secondary outcomes including mortality, ventilator days, and occurrence of chronic lung disease. We conclude that infants with RDS respond favorably to both types of surfactant replacement, and that bLES achieved a faster clinical response in terms of improvement in OI than Survanta.


Induction and prevention of virus-associated malignant lymphoma by serial transmission of EBV-related virus from cynomolgus by blood transfusion in rabbits.
Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood transfusion, which subsequently induced virus-associated rabbit lymphomas. The virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was no transmission with transfusion of cell-free plasma (0/6) from the infected rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased during the first 1-2 weeks in the transfused rabbits. The virus-transmitted rabbits showed a gradual increase in antibody titers ranging from peak titers of x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant lymphoma that developed in the first rabbit transfused by infected blood was confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related herpesvirus is serially transmissible by blood transfusion and that transmission can not be completely prevented by irradiation of blood, but removal of blood cells is the best way to prevent transmission of EBV-related virus. Therefore, this animal model provides a convenient in vivo system for studies of the prevention and therapy of transfusion-related transmission of EBV and EBV-associated lymphoproliferative diseases in immunocompromised human beings.


Outcome of acute traumatic extradural hematoma.
To assess the surgical outcome of acute extradural hematoma in terms of neurological recovery and survival. Case series. Postgraduate Medical Institute, Neurosurgery Unit, Hayatabad Medical Complex, Peshawar, from January to October 2006. All patients admitted and operated for acute traumatic extradural hematoma during the study period were included. Demographic data, history, mode of trauma, examination findings, investigations and outcome were recorded. Glasgow coma scale was used for initial assessment and Glasgow outcome scale was applied to assess outcome in terms of neurological recovery in all patients. The follow-up period was 3 months. A total of 30 patients were operated during the period of 10 months including 22 males and 8 females. Patients were in the age range of 20-30 years comprised 30% of all. Most common causes were road traffic accident (50%), fall from height (33%) and assault (17%). Patients were divided according to the initial Glasgow Coma Score (GCS) after resuscitation. The GCS was 3-8 in 6 patients, 9-12 in 7 patients, 13-15 in 17 patients. Twenty-four patients had good outcome, one patient had moderate disability in the form of left sided weakness, one patient remained in vegetative state, while 3 (10%) patients died. Chi-square test was significant for good outcome in patients with GCS 13-15 (p=0.01) and for death in patients with GCS 3-8 (p=0.01). Extradural hematoma in head injuries affected young males more commonly. The outcome was better when the initial GCS was in the higher range.


Sleep at high altitude.
New arrivals to altitude commonly experience poor-quality sleep. These complaints are associated with increased fragmentation of sleep by frequent brief arousals, which are in turn linked to periodic breathing. Changes in sleep architecture include a shift toward lighter sleep stages, with marked decrements in slow-wave sleep and with variable decreases in rapid eye movement (REM) sleep. Respiratory periodicity at altitude reflects alternating respiratory stimulation by hypoxia and subsequent inhibition by hyperventilation-induced hypocapnia. Increased hypoxic ventilatory responsiveness and loss of regularization of breathing during sleep contribute to the occurrence of periodicity. Interventions that improve sleep quality at high altitude include acetazolamide and benzodiazepines.


Loneliness and attachment patterns in young adults.
Loneliness is a pervasive problem for many young adults. How early attachment patterns affect later development of loneliness was investigated in a college sample. Forty-seven young adults residing in Los Angeles were screened for race, disability, age and SES and then administered an attachment history questionnaire and several measures of loneliness, including the Revised UCLA Loneliness Scale. Pearson correlations revealed a moderate to strong relationship between feeling lonely and early disrupted attachment. The results of the study are consistent with Bowlby's notion that underlying attachment disorders may affect subsequent psychological development and social behavior.


Effects of long-term aerobic exercise on EPOC.
This study sought to determine the influence of 16 months of progressive aerobic exercise on excess postexercise oxygen consumption (EPOC) and the extent EPOC contributed to weight management. Twenty-five overweight/obese women and 16 overweight/obese men participated in a 16-month exercise program (moderate-intensity treadmill walking) that progressed across the first 26 weeks to 5 days.wk(-1), 45 min.session(-1), and 75% HRR. Three-hour EPOC was measured at baseline, 9 months, and 16 months by indirect calorimetry in response to an exercise session (treadmill walking), in which energy expenditure (EE) was estimated from the participant's previous 10 exercise sessions. For women, EPOC was 7.5 +/- 4.9, 9.6 +/- 7.6, and 6.5 +/- 6.5 L at baseline, 9 months, and 16 months, respectively (p > 0.05). For men, EPOC increased from baseline (11.8 +/- 6.8 L) to 9 months (13.5 +/- 8.6 L) (p < 0.05) with no further increase at 16 months (13.5 +/- 11.0 L). Change in EPOC was correlated with change in EE at 9 months (r = 0.65; p < 0.05) and 16 months (r = 0.58; p < 0.05) for men but not women. Progressive long-term exercise significantly influenced EPOC in overweight/obese men but not women. Change in volume of exercise likely explained the increase in energy expenditure during EPOC in men. EPOC contributed modestly to EE compared to the exercise itself.


Countertransference : condensed history and personal view of issues with regressed patients.
Freud's ambivalently negative attitude toward countertransference discouraged systematic study until some psychoanalysts, predominantly Kleinians, began to treat patients with narcissistic neuroses. Recognizing the need to understand the unconscious and conscious contribution of the analyst to the therapeutic process, Heimann, Rosenfeld, Balint, and Racker pioneered in serious study of countertransference. Racker and Boyer found that unresolved countertransference problems contributed significantly to unfavorable responses to psychoanalysis in seriously disturbed patients. Searles, Giovacchini, Ogden, and Volkan have like-wise furthered countertransference research. Following a historical review, the author delineates his personal approach to understanding patients, especially seriously disturbed ones, in terms of the ongoing introjection of patient and analyst of each other's projections. This approach stems from Rosenfeld's initial propositions.


Detection of coupling in Duffing oscillator systems.
In complex dynamical systems, the detection of coupling and its direction from observed time series is a challenging task. We study coupling in coupled Duffing oscillator systems in regular and chaotic dynamical regimes. By observing the conditional mutual information (CMI) based on the Shannon entropy, we successfully infer the direction of coupling for different system regimes. Moreover, we show that, in the weak coupling limit, the values of CMI can be used to infer the coupling parameters by computing the derivative of the conditional mutual information with respect to the coupling strength, called the information susceptibility. The complete numerical implementation is available at https://repo.ijs.si/mbresar/duffing-cmi.


Does Continuous Diffusion of Oxygen Improve Diabetic Foot Ulcer Healing?
The objective of this article is to evaluate the study design, rational and results of Continuous Diffusion of Oxygen Therapy (CDOT) to heal diabetic foot ulcers (DFUs). The study was a double-blinded placebo controlled randomized clinical study to evaluate DFUs over a 12-week period. The primary outcome was the proportion of ulcers that healed and the secondary outcome that was reported was the time to ulcer healing. In the per protocol analysis and in the intent to treat analysis, a higher proportion of DFUs healed in the CDOT group (per protocol 46% vs 22%, P = .02, intent to treat 31.5% vs 15.1%, P = .03). CDOT patients healed ulcers faster compared to the in the sham treatment arm ( P = .026).


Dosimetric feasibility of moderately hypofractionated/dose escalated radiation therapy for localised prostate cancer with intensity-modulated proton beam therapy using simultaneous integrated boost (SIB-IMPT) and impact of hydrogel prostate-rectum spacer.
To examine the dosimetric feasibility of hypofractionated/dose escalated radiation therapy in patients with localized prostate carcinoma using simultaneous integrated boost intensity-modulated proton beam therapy (SIB-IMPT) in absence or presence of prostate-rectum spacer. IMPT technique was implemented in 23 patients with intermediate- and high-risk prostate cancer treated at West German Proton Therapy Centre from March 2016 till June 2018, using SIB technique prescribing 60 GyRBE and 72 GyRBE in 30 fractions to PTV1 (prostate and seminal vesicle) and PTV2 boost (prostate and proximal seminal vesicle), respectively. In 15 patients, a transperineal injection of hydrogel was applied prior to radiotherapy to increase the distance between prostate and rectum. Planning and all treatments were performed with a 120 ml fluid-filled endorectal balloon customised daily for each patient. For each patient, 2 lateral IMPT beams were implemented taking a field-specific range uncertainty (RU) into account. Dose volume histograms (DVH) were analyzed for PTV2, PTV2 with range uncertainty margin (PTV2RU), rectum, bladder, right/left femoral heads, and penile bulb. For late rectal toxicities, the normal tissue complication probabilities (NTCP) were calculated using different biological models. A DVH- and NTCP-based dosimetric comparison was carried out between non-spacer and spacer groups. For the 23 patients, high-quality plans could be achieved for target volume and for other organs at risk (OARs). For PTV2, the V107% was 0% and the Dmax did not exceed 106.2% of the prescribed dose. The volume PTV2RU covered by 95% of the dose ranged from 96.16 to 99.95%. The conformality index for PTV2RU was 1.12 ± 0.057 and the homogeneity index (HI) was 1.04 ± 0.014. Rectum Dmax and rectal volume receiving 73-50 Gy could be further reduced for the spacer-group. Significant reductions in mean and median rectal NTCPs (stenosis/necrosis, late rectal bleeding ≥ 2, and late rectal toxicities ≥ 3) were predicted for the spacer group in comparison to the non-spacer group. Hypofractionated/dose escalated radiotherapy with SIB-IMPT is dosimetrically feasible. Further reduction of the rectal volumes receiving high and medium dose levels (73-50 Gy) and rectal NTCP could be achieved through injection of spacers between rectum and prostate.


Anemia and airline flight duties.
This investigation developed and provides guidelines for the determination and medical release of flight crew members for duty with hemoglobin values less than normal. This dilemma occurs commonly to the flight surgeon following blood donation, resolved hemorrhagic disorders, chronic idiopathic blood disorders, and pregnancy. Minimum safe values were computed and tabulated for otherwise healthy individuals at rest and exercise at the routine extremes of the flight environment of present pressurized jet airliners from known physiological parameters. These values were then correlated with the records of 62 pilots and stewardesses with subnormal hemoglobin values to assure the opertional predictive validity.


(Benzene-carbothio-amide-κS)-penta-carbonyl-tungsten(0).
The asymmetric unit of the title complex, [W(C(7)H(7)NS)(CO)(5)], comprises two independent mol-ecules. In each, the W atom is coordinated by five CO groups and the S atom of the benzencarbothioamide ligand in a distorted octa-hedral geometry. The crystal packing can be described as undulating layers of W(CO)(5) and benzene-carbothio-amide parallel to (001). In the crystal, components are linked via inter-molecular N-H⋯O and C-H⋯O hydrogen bonds to form a dimeric chains along the [010] direction. Intra-molecular N-H⋯C inter-actions are also observed.


Role Of Stretching Exercises In The Management Of Constipation In Spastic Cerebral Palsy.
Constipation is considered as one of the most common non-motor manifestations in cerebral palsy (CP). Along with other reasons, spasticity also contributes in developing constipation in CP, by decreasing mobility of trunk and lower extremities and abdominal viscera. Stretching exercises of upper extremities, trunk and lower extremities are routine management of spasticity in CP children. The objective of the study was to determine the role of stretching exercises in improving constipation symptoms in children with spastic cerebral palsy and to explore the association between spasticity and constipation among cerebral palsy children. Single-group Pretest-Posttest Design (Quasi Experimental Study Design). The study was conducted at Physiotherapy Department of National Institute of Rehabilitation Medicine (NIRM) Islamabad. Thirty spastic CP children - both male and female - with complaints of constipation were recruited through non-probability, convenience sampling. The mean age of the children was 7.55±1.33 years. Each child was assessed for defecation frequency (DF), constipation severity by constipation assessment scale (CAS) and level of spasticity by modified ash worth scale for spasticity (MASS) at baseline. Stretching exercises were performed for 30 seconds with five repetitions and at least once a day for six week, followed by positioning of patients in reflex inhibiting posture. Final data was collected using the same tools as done at the baseline. Paired samples t-test was used to analyse the rehabilitation-induced changes after 6 weeks. To determine association between spasticity and constipation Pearson product-moment correlation coefficient was used. The data was analysed through SPSS 20. Significant changes, compared to the baseline scores, were observed after 6 weeks of stretching exercises in MASS (2.53±0.62 Vs 1.53±0.77), DF (2.43±0.67 Vs 3.70±1.02) and CAS (7.23±1.50 Vs 5.43±1.73) with p≤0.05. The results also showed significant correlation between changes in levels of spasticity and severity of constipation (r = 0.37; p=0.04). Finally, significant correlation was present between improvement in spasticity and defecation frequency (r =-0.39; p=0.02). Stretching exercises administered for the management of spasticity in CP can significantly improve the symptoms of constipation in such children. The results of the study showed that constipation is strongly associated with level of spasticity in CP children.


A guide for researchers seeking training in retrospective data harmonization for population neuroscience studies of Alzheimer's disease and related dementias.
Due to needs surrounding rigor and reproducibility, subgroup specific disease knowledge, and questions of external validity, data harmonization is an essential tool in population neuroscience of Alzheimer's disease and related dementias (ADRD). Systematic harmonization of data elements is necessary to pool information from heterogeneous samples, and such pooling allows more expansive evaluations of health disparities, more precise effect estimates, and more opportunities to discover effective prevention or treatment strategies. The key goal of this Tutorial in Population Neuroimaging Curriculum, Instruction, and Pedagogy article is to guide researchers in creating a customized population neuroscience of ADRD harmonization training plan to fit their needs or those of their mentees. We provide brief guidance for retrospective data harmonization of multiple data types in this area, including: (1) clinical and demographic, (2) neuropsychological, and (3) neuroimaging data. Core competencies and skills are reviewed, and resources are provided to fill gaps in training as well as data needs. We close with an example study in which harmonization is a critical tool. While several aspects of this tutorial focus specifically on ADRD, the concepts and resources are likely to benefit population neuroscientists working in a range of research areas.


Metabolic effects of atypical antipsychotics: Molecular targets.
Atypical antipsychotics (AAPs) are commonly prescribed drugs in the treatment of schizophrenia, bipolar disorder and other mental diseases with psychotic traits. Although the use of AAPs is associated with beneficial effects in these patients, they are also associated with undesired metabolic side effects, including metabolic syndrome (MetS). MeS is defined by the presence of metabolic abnormalities such as large waist circumference, dyslipidemia, fasting hyperglycemia and elevated blood pressure, which predispose to type 2 diabetes (T2D) and cardiovascular disease. In this review, the molecular and cellular mechanisms involved in these undesired metabolic abnormalities induced by AAPs are described. These mechanisms are complex as AAPs have multiple cellular targets which significantly affect the activities of several hormones and neuromodulators. Additionally, AAPs affect all the relevant metabolic organs, namely the liver, pancreas, adipose tissue, skeletal muscle and intestine, and the central and peripheral nervous system as well. A better understanding of the molecular targets linking AAPs with MetS and of the mechanisms responsible for clinically different side effects of distinct AAPs is needed. This knowledge will help in the development of novel AAPs with less adverse effects as well as of adjuvant therapies to patients receiving AAPs.


Gastroprotective effect of mangiferin, a xanthonoid from Mangifera indica, against gastric injury induced by ethanol and indomethacin in rodents.
In search of novel gastroprotective agents, mangiferin, a naturally occurring glucosylxanthone from Mangifera indica L. (Anacardiaceae), was evaluated in mice on gastric injury induced by ethanol and indomethacin. The effects of mangiferin on gastric mucosal damage were assessed by determination of changes in mean gastric lesion area or ulcer score in mice and on gastric secretory volume and total acidity in 4-h pylorus-ligated rats. Mangiferin (3, 10 and 30 mg/kg, P. O.) significantly attenuated the gastric damage induced by ethanol by 30, 35, and 63 %, and of indomethacin by 22, 23 and 57 %, respectively. N-Acetylcysteine (750 mg/kg, I. P.) and lansoprazole (30 mg/kg, P. O.) used as positive controls in these ulcerogenic models resulted in 50 % and 76 % suppression of gastric injury, respectively. In 4-h pylorus-ligated rats, intraduodenally applied mangiferin (30 mg/kg) caused significant diminutions in gastric secretory volume and total acidity. In addition, like N-acetylcysteine, a donor of sulfhydryls, mangiferin effectively prevented the ethanol-associated depletion of gastric mucosal non-protein sulfhydryl content in mice, suggesting an antioxidant action. These findings provide evidence that mangiferin affords gastroprotection against gastric injury induced by ethanol and indomethacin most possibly through the antisecretory and antioxidant mechanisms of action.


Anterior cingulate cortex and cerebellar hemisphere neurometabolite changes in depression treatment: A 1H magnetic resonance spectroscopy study.
We utilized single-voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment. Fifteen adult MDD patients and 15 age- and sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment. At baseline, N-acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo-inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas.


Multiunit Activity-Based Real-Time Limb-State Estimation from Dorsal Root Ganglion Recordings.
Proprioceptive afferent activities could be useful for providing sensory feedback signals for closed-loop control during functional electrical stimulation (FES). However, most previous studies have used the single-unit activity of individual neurons to extract sensory information from proprioceptive afferents. This study proposes a new decoding method to estimate ankle and knee joint angles using multiunit activity data. Proprioceptive afferent signals were recorded from a dorsal root ganglion with a single-shank microelectrode during passive movements of the ankle and knee joints, and joint angles were measured as kinematic data. The mean absolute value (MAV) was extracted from the multiunit activity data, and a dynamically driven recurrent neural network (DDRNN) was used to estimate ankle and knee joint angles. The multiunit activity-based MAV feature was sufficiently informative to estimate limb states, and the DDRNN showed a better decoding performance than conventional linear estimators. In addition, processing time delay satisfied real-time constraints. These results demonstrated that the proposed method could be applicable for providing real-time sensory feedback signals in closed-loop FES systems.


Diverse liver morphology in two cases of visceral leishmaniasis: Same face, different expressions.
Two cases of visceral leishmaniasis are presented; one patient was from an endemic region and visceral leishmaniasis was suspected clinically, while the other was from a non-endemic region and it was not suspected clinically. Bone marrow examination was negative in both cases and both showed different morphological pictures in the liver biopsies. These are discussed. Importance of travel history is also highlighted even if it is in distant past.


Effects of supercritical fluid extraction pressure on chemical composition, microbial population, polar lipid profile, and microstructure of goat cheese.
The consumer trend for healthier food choices and preferences for low-fat products has increased the interest in low-fat cheese and nutraceutical dairy products. However, consumer preference is still for delicious food. Low- and reduced-fat cheeses are not completely accepted because of their unappealing properties compared with full-fat cheeses. The method reported here provides another option to the conventional cheese-making process to obtain lower fat cheese. Using CO(2) as a supercritical fluid offers an alternative to reduce fat in cheese after ripening, while maintaining the initial characteristics and flavor. The aim of this experiment was to evaluate the effect of pressure (10, 20, 30, and 40 × 10(6) Pa) of supercritical CO(2) on the amount of fat extracted, microbial population, polar lipid profile, and microstructure of 2 varieties of goat cheese: Majorero, a protected denomination of origin cheese from Spain, and goat Gouda-type cheese. The amount of fat was reduced 50 to 57% and 48 to 55% for Majorero and goat Gouda-type cheeses, respectively. Higher contents (on a fat basis) of sphingomyelin and phosphatidylcholine were found in Majorero cheese compared with control and goat Gouda-type cheeses. The microbial population was reduced after supercritical fluid extraction in both cheeses, and the lethality was higher as pressure increased in Majorero cheese, most noticeably on lactococcus and lactobacillus bacteria. The Gouda-type cheese did not contain any lactobacilli. Micrographs obtained from confocal laser scanning microscopy showed a more open matrix and whey pockets in the Majorero control cheese. This could explain the ease of extracting fat and reducing the microbial counts in this cheese after treatment with supercritical CO(2). Supercritical fluid extraction with CO(2) has great potential in the dairy industry and in commercial applications. The Majorero cheese obtained after the supercritical fluid extraction treatment was an excellent candidate as a low-fat goat cheese, lower in triglycerides and cholesterol but still with all the health benefits inherent in goat milk.


Ionization and collision induced dissociation of steroid bisglucuronides.
Studies on steroid metabolism are of utmost importance to improve the detection capabilities of anabolic androgenic steroids (AASs) misuse in sports drug testing. In humans, glucuronoconjugates are the most abundant phase II metabolites of AAS. Bisglucuronidation is a reaction where two separated functional groups on the same molecule are conjugated with glucuronic acid. These metabolites have not been studied in depth for steroids and could be interesting markers for doping control. The aim of the present work was to study the ionization and collision-induced dissociation of steroid bisglucuronides to be able to develop mass spectrometric analytical strategies for their detection in urine samples after AAS administration. Because steroid bisglucuronides are not commercially available, 19 of them were qualitatively synthesized to study their mass spectrometric behavior. Bisglucuronides ionized as [M+NH4 ]+ in positive mode, and as [M-H]- and [M-2H]2- in negative mode. The most specific product ions of steroid bisglucuronides in positive mode resulted from the neutral losses of 387 and 405 Da (corresponding to [M+NH4 -NH3 -2gluc-H2 O]+ and [M+NH4 -NH3 -2gluc-2H2 O]+ , respectively, being "gluc" a dehydrated glucuronide moiety), and in negative mode, the fragmentation of [M-2H]2- showed ion losses of m/z 175 and 75 (gluc- and HOCH2 CO2- , respectively). On the basis of the common behavior, a selected reaction monitoring method was developed to detect bisglucuronide metabolites in urine samples. As a proof of concept, urines obtained after administration of norandrostenediol were studied, and a bisglucuronide metabolite was detected in those urines. The results demonstrate the usefulness of the analytical strategy to detect bisglucuronide metabolites in urine samples, and the formation of these metabolites after administration of AAS.


Optical and Electrical Characterization of Biocompatible Polymeric Lines for Hemodialysis Applications.
During hemodialysis (HD), blood is circulated through an extracorporeal tubing system (bloodline) made of medical-grade polymeric material. Sensors of various types that do not come into contact with blood (optical, electromagnetic, etc.) are applied directly across the bloodline for clinical purposes and for therapy customization. Thus, a detailed knowledge of the bloodline's physical properties is useful for the development of next-generation HD sensors. In this work, we performed a novel comparative analysis of the materials used by the manufacturers of the bloodlines. We focused on signals and characterization techniques matching those of the abovementioned sensors; consequently, this is an application-specific study of the optical and electrical characterization of bloodline material. Such properties are analyzed and compared for bloodlines from seven different manufacturers by optical absorbance spectroscopy and electrical impedance spectroscopy (EIS). Absorbance spectrum measurements are carried out in the VIS-NIR range. Absorbance spectra are pre-processed and data from both types of analyses are normalized with respect to sample thickness. Optical analysis shows that all bloodlines except one have similarly shaped spectra with slight quantitative differences. In all optical spectra, we find a decreasing trend of specific absorption from 0.14 mm-1 at 400 nm to 0.06 mm-1 at 1000 nm, with an absorption peak at 915 nm. In one case, a large absorption peak centered at ≃600 nm is found. Electrical analysis shows that all bloodlines have the electrical properties of a constant-phase element (CPE), with statistically significant differences in parameters' values. Estimation of electrical CPE parameters for all bloodline returns a range of 0.942-0.957 for parameter n and a range of 12.41-16.64 for parameter Q₀'. In conclusion, we find that, although some statistically significant differences are present, bloodlines from a representative group of manufacturers share similar electrical and optical properties. Therefore, contactless sensing devices developed for HD will work on different bloodlines if a simple recalibration is performed.


Layer-by-layer micromolding of natural biopolymer scaffolds with intrinsic microfluidic networks.
A three-dimensional (3D) microfluidic network plays an important role in engineering thick organs. However, most of the existing methods are limited to mechanically robust synthetic biomaterials and only planar or simple microfluidic networks have been incorporated into soft natural biopolymers. Here we presented an automatic layer-by-layer micromolding strategy to reproducibly fabricate 3D microfluidic porous scaffolds directly from the aqueous solution of soft natural biopolymers. Process parameters such as the liquid volume for each layer and contact displacement were investigated to produce a structurally stable 3D microfluidic scaffold. Microscopic characterization demonstrated that the microfluidic channels were interconnected in 3D and successfully functioned as a convective pathway to transport a polymer solution. Endothelial cells grew relatively well in the porous microfluidic channels. It is envisioned that this method could provide an alternative way to reproducibly build complex 3D microfluidic networks into extracellular matrix-like scaffolds for the fabrication of soft vascularized organs.


Bicuspid aortic valve stenosis with single coronary artery.
A 56-year-old female with congestive heart failure was transferred to our institution. Aortography demonstrated aortic valve stenosis (AS) with a congenitally bicuspid valve and dilatation of the ascending aorta. Preoperative coronary angiography showed a left single coronary artery. Replacement of the aortic valve and ascending aorta was performed. She had an uneventful postoperative course. We report the case of aortic bicuspid valve stenosis with single coronary artery as an extremely rare congenital cardiac anomaly combination.


Accuracy Improvement of a Compact 85Rb Atom Gravimeter by Suppressing Laser Crosstalk and Light Shift.
We design and implement a compact 85Rb atom gravimeter (AG). The diameter of the sensor head is 35 cm and the height is 65 cm; the optical and electronic systems are installed in four standard 3U cabinets. The measurement accuracy of this AG is improved by suppress laser crosstalk and light shift. In addition, the angle of the Raman laser reflector is adjusted and locked, and the attitude of the sensing head is automatically adjusted, and the vibration noise is also compensated. The comparison measurement results between this AG and the superconducting gravimeter indicate that its long-term stability is 0.65 μGal @50000 s.


Looped structure of flowerlike micelles revealed by 1H NMR relaxometry and light scattering.
We present experimental proof that so-called "flowerlike micelles" exist and that they have some distinctly different properties compared to their "starlike" counterparts. Amphiphilic AB diblock and BAB triblock copolymers consisting of poly(ethylene glycol) (PEG) as hydrophilic A block and thermosensitive poly(N-isopropylacrylamide) (pNIPAm) B block(s) were synthesized via atom transfer radical polymerization (ATRP). In aqueous solutions, both block copolymer types form micelles above the cloud point of pNIPAm. Static and dynamic light scattering measurements in combination with NMR relaxation experiments proved the existence of flowerlike micelles based on pNIPAm(16kDa)-PEG(4kDa)-pNIPAm(16kDa) which had a smaller radius and lower mass and aggregation number than starlike micelles based on mPEG(2kDa)-pNIPAm(16kDa). Furthermore, the PEG surface density was much lower for the flowerlike micelles, which we attribute to the looped configuration of the hydrophilic PEG block. (1)H NMR relaxation measurements showed biphasic T(2) relaxation for PEG, indicating rigid PEG segments close to the micelle core and more flexible distal segments. Even the flexible distal segments were shown to have a lower mobility in the flowerlike micelles compared to the starlike micelles, indicating strain due to loop formation. Taken together, it is demonstrated that self-assemblies of BAB triblock copolymers have their hydrophilic block in a looped conformation and thus indeed adopt a flowerlike conformation.


Biodegradable dissolved organic carbon shapes bacterial community structures and co-occurrence patterns in large eutrophic Lake Taihu.
Interactions between dissolved organic matter (DOM) and bacteria are central in the biogeochemical cycles of aquatic ecosystems; however, the relative importance of biodegradable dissolved organic carbon (BDOC) compared with other environmental variables in structuring the bacterial communities needs further investigation. Here, we investigated bacterial communities, chromophoric DOM (CDOM) characteristics and physico-chemical parameters as well as examined BDOC via bioassay incubations in large eutrophic Lake Taihu, China, to explore the importance of BDOC for shaping bacterial community structures and co-occurrence patterns. We found that the proportion of BDOC (%BDOC) correlated significantly and positively with the DOC concentration and the index of the contribution of recent produced autochthonous CDOM (BIX). %BDOC, further correlated positively with the relative abundance of the tryptophan-like component and negatively with CDOM aromaticity, indicating that autochthonous production of protein-like CDOM was an important source of BDOC. The richness of the bacterial communities correlated negatively with %BDOC, indicating an enhanced number of species in the refractory DOC environments. %BDOC was identified as a significant stronger factor than DOC in shaping bacterial community composition and the co-occurrence network, suggesting that substrate biodegradability is more significant than DOC quantity determining the bacterial communities in a eutrophic lake. Environmental factors explained a larger proportion of the variation in the conditionally rare and abundant subcommunity than for the abundant and the rare bacterial subcommunities. Our findings emphasize the importance of considering bacteria with different abundance patterns and DOC biodegradability when studying the interactions between DOM and bacteria in eutrophic lakes.


Tirucallane, apotirucallane, and octanorapotirucallane triterpenes of Simarouba amara.
A chemical investigation of the bark of Simarouba amara, collected in Barbados, resulted in the isolation of six new triterpenes (3-8), in addition to two known compounds, 3-oxatirucalla-7, 24-dien-23-ol (1) and niloticin (2). Compound 3 is a tirucallane triterpene, while compounds 4-7 are apotirucallane derivatives containing an epsilon-lactone in ring A. Compounds 6 and 7 were obtained as a mixture that could not be separated, while compound 8 is an octanorapotirucallane derivative that lacks the C(8) side chain. The structures of all compounds were determined by interpretation of physical data.