REDUCED HAND GRIP STRENGTH IN OVERWEIGHT AND OBESE CHRONIC HEPATITIS C PATIENTS.
Hepatitis C is a liver disease that causes significant changes in metabolism, and also has an impact on nutritional status. To evaluate the nutritional status and cardiovascular risk in patients with chronic hepatitis C. This cross-sectional study investigated 58 patients with chronic hepatitis C, non-cirrhotic and were not under active pharmacological treatment. Patients with significant alcohol consumption (greater than 10 g ethanol/day) were excluded. Patients underwent nutritional assessment through anthropometric measurements and functional assessment using hand grip strength by dynamometry. The physical activity was assessed using the International Physical Activity Questionnaire. Patients also underwent clinical and laboratory evaluation. Cardiovascular risk was calculated by the Framingham score. The mean age of patients was 51.6±9.7 years, 55.2% were female, and 79.3% had genotype 1. The most prevalent degree of fibrosis was F1 (37.9%) followed by F2 (27.6%) and F3 (1.7%). The prevalence of overweight/obesity considering the body mass index was 70.7%. However, 57.7% of men and 68.8% of women were considered malnourished according to hand grip strength. These patients also had waist circumference (93.5±10.7 cm) and neck circumference (37.0±3.6 cm) high. Almost 60% of patients were considered sedentary or irregularly active. In relation to cardiovascular risk, 50% of patients had high risk of suffering a cardiovascular event within 10 years. Although most patients with hepatitis C presented overweight, associated with high cardiovascular risk, they also have reduced functional capacity, indicative of protein-caloric commitment. Therefore, body mass index can not be considered the only method of assessment for nutritional diagnosis of patients with liver disease. Adopting methods such as hand grip strength can be important for a better understanding of nutritional status of these patients.


BMP-7 attenuates TGF-β1-induced fibroblast-like differentiation of rat dermal papilla cells.
Dermal papilla cells (DPCs) show phenotypic plasticity during wound healing. The multipotency of DPCs is well recognized, but the signaling pathways that regulate the differentiation of these cells into fibroblasts are poorly understood. A preliminary experiment showed that transforming growth factor beta1 (TGF-β1) can induce DPCs to differentiate into fibroblast-like cells, which suggests that DPCs may be a source of wound-healing fibroblasts. Bone morphogenetic protein-7 (BMP-7), a member of the TGF-β superfamily, can prevent and reverse fibrosis by counteracting the TGF-β1-mediated profibrotic effect. To determine whether BMP-7 attenuates the TGF-β1-induced differentiation of DPCs into fibroblasts, we established an in vitro system for DPC differentiation and recorded the gene expression patterns that distinguished DPCs from fibroblasts. The proportion of fibroblast-like cells was significantly enhanced in DPCs treated with TGF-β1, as evidenced by immunocytochemistry, flow cytometry, quantitative real-time reverse transcriptase polymerase chain reaction, and Western blot analysis. BMP-7 and TGF-β1 administration substantially decreased fibroblast-like differentiation, indicating inhibition of TGF-β1-induced differentiation. The antagonistic BMP-7- and TGF-β1-activated signaling pathways can be used to promote wound healing or suppress hypertrophic scarring.


Successful arterial embolization of a giant pseudoaneurysm of the gastroduodenal artery secondary to chronic pancreatitis with literature review.
We report a case of an uncommon giant pseudoaneurysm of the gastroduodenal artery secondary to chronic pancreatitis. It presented with a perfused volume of 17.3 cm(3) close to the branch-off of the right hepatic artery. Superselective transcatheter embolization including interlocking detachable coils and a mixture of Ethibloc and Lipiodol was our technique of choice. Following the procedure, the patient was in hemodynamically stable condition. At that time, he was free of any clinical symptoms and showed no further signs of bleeding or ischaemia. Additionally, we present an overview of the relevant literature.


A comprehensive model for sub-10 nm electron-beam patterning through the short-time and cold development.
In this study, we propose a set of single-spot experiment to construct a comprehensive model of electron-beam lithography to describe the relation among the incident electrons, resist, and the development conditions such as durations and temperatures. Through the experiments, small feature can be achieved by performing a short-time development due to the high acceleration voltage and large depth of focus of electron-beam system. The singular point in the beginning of the development is also observed in our model and supported by the experimental data. In addition, we verify the characteristic region of each incident spot induced by the point spread function of the electron-beam system. We further fabricate the single line with narrow groove width by utilizing the results from single-spot experiment at low developing temperatures. The line is formed by arranging a series of incident points with a distance close to the characteristic radius. This method can eliminate the proximity effect effectively and thus the groove width is scaled down to 8 nm. By adopting the successful experience in the single line formation, dense array with narrow linewidth is also demonstrated under well suppression of the proximity effect. The minimum groove width of 9 nm with 30 nm pitch is achieved with 5 s development time at -10 °C. Finally, the exceptional capability of pattern transfer is presented due to the high aspect ratio of the resist.


Role modeling excellence in clinical nursing practice.
Role modeling excellence in clinical nursing practice is the focus of this paper. The phenomenological research study reported involved a group of 8 nurses identified by their colleagues as exemplary. The major theme revealed in this study was that these exemplary nurses were also excellent role models in the clinical setting. This paper details approaches used by these nurses that made them excellent role models. Specifically, the themes of attending to the little things, making connections, maintaining a light-hearted attitude, modeling, and affirming others are presented. These themes are discussed within the framework of Watson [Watson, J., 1989. Human caring and suffering: a subjective model for health services. In: Watson, J., Taylor, R. (Eds.), They Shall Not Hurt: Human Suffering and Human Caring. Colorado University, Boulder, CO] "transpersonal caring" and [Bandura, A., 1997. Social Learning Theory. Prentice Hall, Englewood Cliffs, NJ] "Social Learning Theory." Particular emphasis in the discussion is on how positive role modeling by exemplary practitioners can contribute to the education of clinical nurses in the practice setting.


[Late development of congestive heart failure in interventricular communication caused by penetrating wound, with pulmonary hypertension resolution after surgical correction].
Male, 33 years-old, with onset of heart failure and edema; he used to be completely asymptomatic but mentioned he underwent previously a pleural drainage, after a hemothorax provoked by a stab wound. His physical examination confirmed he was in heart failure and showed a harsh holosystolic murmur between mitral and tricuspid areas. Cardiac catheterization demonstrated a large apical ventricular septal defect (VSD) and systemic pulmonary arterial pressures. With oxygen there was an increase in the left to right shunt and normal pulmonary vascular resistance. The clinical diagnosis was that of a traumatic VSD provoking pulmonary hypertension although a congenital etiology could not be completely ruled out. At surgery there was a sharp cut at the pericardium and an apical epicardial lesion; the VSD was patch sutured and the patient did well with control of his heart failure. A control hemodynamic study performed within the first postoperative month showed no residual shunt and complete normalization of the pulmonary pressures and resistance.


New 2-Oxoindolin Phosphonates as Novel Agents to Treat Cancer: A Green Synthesis and Molecular Modeling.
The work reports the facile synthesis of novel α-aminophosphonate derivatives coupled with indole-2,3-dione moieties, namely the diethyl(substituted phenyl/heteroaryl)(2-(2-oxoindolin-3-ylidene)hydrazinyl)methylphosphonates derivatives 4(a⁻n). One-pot three component Kabachnik-Fields reactions were used to synthesize these derivatives. The reaction was carried out at room temperature by stirring in presence of ceric ammonium nitrate (CAN) as a green catalyst. The structures of the synthesized compounds were established by spectral studies. The synthesized derivatives 4(a⁻n) were evaluated for their in vitro anticancer activity against six human cancer cell lines by the SRB assay method. The cancer cell lines used in this research work are SK-MEL-2 (melanoma), MCF-7 (breast cancer), IMR-32 (neuroblastoma) MG-63 (human osteosarcoma), HT-29 (human colon cancer) and Hep-G2 (human hepatoma). All the synthesized derivatives inhibited the cell proliferation. Importantly, all the target compounds showed no cytotoxicity towards normal tissue cells (GI50 > 250 µM). A docking study was performed to predict the mode of action. Docking results indicate that the compounds have good binding with the enzyme tyrosine kinase as well as with microtubules, which makes them dual inhibitors. The result of in-silico bioavailability studies suggests that the compounds from the present series have good oral drug-like properties and are non-toxic in nature. In vivo acute oral toxicity study results indicate that the compounds can be considered safe, and therefore could be developed in the future as good anticancer agents or as leads for the design and synthesis of novel anticancer agents.


Tricks for improving compliance with acne therapy.
Adherence to a medical regimen is the most important aspect of therapeutic efficacy. It goes without saying that a drug that is not used will not be effective. Reasons for noncompliance can be related to the specific disease state, to characteristics of the drugs chosen, to patient personality traits, and to effectiveness of the clinician in dealing with the individual patient. Recognizing, confronting, and improving noncompliant behavior are all part of an effective doctor-patient relationship.


Elegant design of electrode and electrode/electrolyte interface in lithium-ion batteries by atomic layer deposition.
Lithium-ion batteries (LIBs) are very promising power supply systems for a variety of applications, such as electric vehicles, plug-in hybrid electric vehicles, grid energy storage, and microelectronics. However, to realize these practical applications, many challenges need to be addressed in LIBs, such as power and energy density, cycling lifetime, safety, and cost. Atomic layer deposition (ALD) is emerging as a powerful technique for solving these problems due to its exclusive advantages over other film deposition counterparts. In this review, we summarize the state-of-the-art progresses of employing ALD to design novel nanostructured electrode materials and solid-state electrolytes and to tailor electrode/electrolyte interface by surface coatings in order to prevent unfavorable side reactions and achieve optimal performance of the electrode. Insights into the future research and development of the ALD technique for LIB applications are also discussed. We expect that this review article will provide resourceful information to researchers in both fields of LIBs and ALD and also will stimulate more insightful studies of using ALD for the development of next-generation LIBs.


Foraging for Information in the EHR: The Search for Adherence Related Information by Mental Health Clinicians.
In this project we sought to qualitatively describe clinician's search for information related to the complex construct of adherence. Nineteen think aloud observations and semi-structured interviews were conducted with mental health providers as they prepared for a patient visit. The transcripts were coded according to constructs from information foraging theory (information goal, patch, scent, enrichment, and opportunity cost). The search strategies uncovered were complicated: provider's searches were sometimes multi-staged (e.g. a search of the EHR led to further enquiry when interviewing the patient), and involved multiple 'patches' (i.e. data from the EHR, the patient and other providers were all sought out). In addition, some information that providers considered relevant to understand adherence related questions was non-obvious (e.g. the absence of specific information was considered a useful cue). Providers' information search strategies for complex constructs are at times non-intuitive; implications for the design of EHR summarization tools are discussed.


Direct composite coronal reconstruction of two fractured incisors: an 8-year follow-up.
Dental fractures of the anterior teeth are a relatively frequent accident during childhood. However until maxillary maturation is completed, the employment of porcelain crowns is not recommended, the treatment of choice, instead, would be direct composite restoration. The procedure for restoration of two extensive superior central incisor fractures is presented. Composite crowns were customized directly over the teeth. Root canal treatment was performed in one of the pieces and subsequently a post was cemented, around which a composite core was constructed. Acetate crowns were filled with composite, adapted to the dental contour and photo cured before removal to reproduce the anatomy. After follow-up of 8 years restorations remained esthetic and fully functional.


Cytoplasmic lipid droplets: rediscovery of an old structure as a unique platform.
Cytoplasmic lipid droplets (LDs) exist in virtually any kind of cell. They have a core of lipid esters covered by the surface phospholipid monolayer. A number of proteins related to various cell functions are present in LDs and/or LD-rich subcellular fractions, suggesting that LDs are an independent organelle that is engaged in various cellular activities. Furthermore, a recent study suggested that LDs are a platform where the proteasomal and autophagic pathways converge. The molecular composition and architecture of LDs are discussed here, with special reference to the technical difficulties encountered when analyzing this unique organelle.


Nonfatal instances of intoxication with gamma-hydroxybutyrate in the United Kingdom.
There has been much publicity regarding the use and abuse of gamma-hydroxybutyrate (GHB, "liquid ecstasy," or "GBH"). GHB has been found to be an endogenous compound but has also been used for various therapeutic applications in addition to illicit use, particularly as a dietary supplement, sexual adjunct, and "party drug." Toxicological analysis was performed using urine and/or plasma specimens from 27 nonfatal instances of suspected GHB intoxication in the United Kingdom between May 1998 and May 2003. GHB was detected in the plasma and urine, invariably with the additional presence of ethanol and other drugs of abuse (eg, amphetamines, cocaine, and morphine). GBL was also detected in the majority of urine specimens analyzed but was not detected in the plasma samples (<10 mg/L). The mean plasma and urine concentrations measured as "total GBL" were found to be 245 mg/L (range 86-551 mg/L) and 1732 mg/L (range 5-5581 mg/L), respectively. This is believed to be the largest compilation of nonfatal cases from the United Kingdom.


Ultrawide Spectral Response of CIGS Solar Cells Integrated with Luminescent Down-Shifting Quantum Dots.
Conventional Cu(In1-x,Gax)Se2 (CIGS) solar cells exhibit poor spectral response due to parasitic light absorption in the window and buffer layers at the short wavelength range between 300 and 520 nm. In this study, the CdSe/CdZnS core/shell quantum dots (QDs) acting as a luminescent down-shifting (LDS) layer were inserted between the MgF2 antireflection coating and the window layer of the CIGS solar cell to improve light harvesting in the short wavelength range. The LDS layer absorbs photons in the short wavelength range and re-emits photons in the 609 nm range, which are transmitted through the window and buffer layer and absorbed in the CIGS layer. The average external quantum efficiency in the parasitic light absorption region (300-520 nm) was enhanced by 51%. The resulting short circuit current density of 34.04 mA/cm2 and power conversion efficiency of 14.29% of the CIGS solar cell with the CdSe/CdZnS QDs were improved by 4.35 and 3.85%, respectively, compared with those of the conventional solar cells without QDs.


Arterial obliteration in POEMS syndrome: possible role of vascular endothelial growth factor.
Acute arterial obliteration is a newly acknowledged manifestation of the POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes), in which overproduction of proinflammatory cytokines has been implicated. We describe a case in which serum levels of proinflammatory cytokines were normal or slightly raised. In contrast, vascular endothelial growth factor (VEGF) was greatly increased. This angiogenic and vascular permeability factor is involved in the development of atheromatous and thrombotic lesions and may be responsible for the arterial complications of the disorder.


The relationship between serum enalaprilat concentration and the hypotensive effect in man.
The relationship between serum concentrations of the angiotensin converting enzyme inhibitor, enalaprilat, and its antihypertensive action was investigated using integrated pharmacokinetic-dynamic modelling techniques. The model was parameterized in terms of slope "m", describing the sensitivity to the fall of blood pressure, and an intercept term "i". A linear pharmacodynamic model: E = m. ce(t) + i, adequately characterized the concentration-effect relationship in most of the young (aged 22-30 years) and elderly normotensive subjects (aged 65-73 years). However, no age-related differences were seen, indicating that angiotensin II vasoconstrictor action is unaltered by senescence.


[Application of nerve block in total knee arthroplasty under general anesthesia].
To evaluate the effect of femoral and sciatic nerve block in total knee replacement of elderly patients under general anesthesia. From July 2017 to July 2019, 60 patients with unilateral total knee replacement were selected, including 35 males and 25 females; aged 66 to 74(70.2±10.3) years;BMI 18 to 25 (21.3 ± 3.5) kg /m2;course 2 to 3 (1.2±0.3) days. The patients were divided into general anesthesia group (G group) 30 cases and general anesthesia plus nerve block group(GNB group) 30 cases. In GNB group, the femoral nerve sciatic nerve block was guided by ultrasound before anesthesia induction, 20 to 25 ml was injected into the femoral nerve puncture point with 0.5% ropivacaine, 15 to 20 ml was injected into the sciaticnerve puncture point, and the total volume was no more than 40 ml. Postoperative intravenous analgesia (PCIA) was performed in two groups. The dosage of propofol and remifentanil was recorded. Forty-eight hours after operation, the incidence of postoperative nausea and vomiting (PONV) and postoperative farsightedness were recorded. When VAS>3, tramadol 2 mg / kg was injected intravenously, and the additional times of tramadol were recorded. Forty-eight hours after operation, patients' satisfaction score was used to record the length of stay. Compared with group G, the dosage of propofol and remifentanil decreased, the incidence of PONV and the number of additional tramadol decreased, and the patients' satisfaction increased (P<0.05). There was no significant difference in the length of stay between two groups (P>0.05). The ROM and HSS scores of two groups after treatment were higher than those before treatment (P<0.05), and the VAS scores were lower than those before treatment (P<0.05). There was no significantdifference in ROM, VAS scores and HSS scores between two groups before treatment (P>0.05). The ROM and HSS scores of the GNB group after treatment were higher than those of the G group (P<0.05), and the VAS scores were lower than those of the G group (P<0.05). The application of femoral sciatic nerve block in total knee replacement under general anesthesia in elderly patients has good postoperative analgesic effect, and can reduce the dosage of general anesthesia, reduce PONV, and increase patient satisfaction.


Expression of a P-selectin ligand in zona pellucida of porcine oocytes and P-selectin on acrosomal membrane of porcine sperm cells. Potential implications for their involvement in sperm-egg interactions.
The selectin family of cell adhesion molecules mediates initial leukocyte adhesion to vascular endothelial cells at sites of inflammation. O-glycan structural similarities between oligosaccharides from human leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) and from zona pellucida glycoproteins of porcine oocytes indicate the possible existence of a P-selectin ligand in the zona pellucida. Here, using biochemical as well as morphological approaches, we demonstrate that a P-selectin ligand is expressed in the porcine zona pellucida. In addition, a search for a specific receptor for this ligand leads to the identification of P-selectin on the acrosomal membrane of porcine sperm cells. In vitro binding of porcine acrosome-reacted sperm cells to oocytes was found to be Ca2+ dependent and inhibitable with either P-selectin, P-selectin receptor-globulin, or leukocyte adhesion blocking antibodies against P-selectin and PSGL-1. Moreover, porcine sperm cells were found to be capable of binding to human promyeloid cell line HL-60. Taken together, our findings implicate a potential role for the oocyte P-selectin ligand and the sperm P-selectin in porcine sperm-egg interactions.


Electroacupuncture for post-thoracotomy pain: A systematic review and meta-analysis.
Thoracotomy is an invasive surgical procedure that produces intense postoperative pain. Electroacupuncture has been used to induce analgesia in various situations, including after surgery. The aim of the following systematic review and meta-analysis was to evaluate the effect of electroacupuncture on post-thoracotomy pain. The studies for the systematic review were searched using the following 9 databases: PubMed, Cochrane Library, EMBASE, MEDLINE Complete, Google Scholar, China National Knowledge Infrastructure (CNKI), Korean Medical Database (KMBASE), Koreanstudies Information Service System (KISS), and OASIS, without language restriction. Randomized controlled trials (RCTs) that met the inclusion criteria were selected. The quality assessment was performed using the Cochrane risk-of-bias tool, and RevMan 5.3 was used for meta-analysis. The review protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42019142157. Eleven randomized controlled trials were included in the systematic review. The meta-analysis was performed for two outcome measures: pain score 24 hours after surgery and total dose of opioid analgesics. A subgroup analysis was performed according to the control group: sham acupuncture and conventional analgesia group. Pain score 24 hours after surgery of electroacupuncture group showed a standard mean difference of -0.98 (95% CI: -1.62 to -0.35) compared to sham acupuncture. The standard mean difference was -0.94 (95% CI: -1.33 to -0.55) compared to conventional analgesia. The total dose of opioid analgesics of electroacupuncture group showed a standard mean difference values of -0.95 (95% CI: -1.42 to -0.47) compared to sham acupuncture. The standard mean difference was -1.96 (95% CI: -2.82 to -1.10) compared to conventional analgesia. Current evidence suggests that electroacupuncture might provide useful pain relieving effect on post-thoracotomy patients. However, due to low quality and high heterogeneity of existing data, further rigorously designed studies should be performed to confirm the safety and efficacy.


Antimicrobial action of thymol-camphor compared with 20 pharmaceutical preparations. 1. Staphylococcus aureus.
The antimicrobial action of 21 pharmaceutical preparations has been compared in vitro by testing them against Staph. aureus (Oxford strain) in an identical environment. While a number of chemicals produced a degree of action, which can be considered adequate for clinical purposes, the combination thymol-camphor gave the best results.


[Sterility of immunologic origin].
Antispermatozoal antibodies in the woman, the man, or both, may be the cause of nonorganic infertility in a small number of couples. The antibodies are most often found in the serum or in the genital fluids. Diagnosis is based on the postcoital test and on various laboratory tests to assess sperm-cervical mucous compatibility and to detect antispermatozoal antibodies. In women the strongest relation between results of laboratory tests and infertility is between the presence of serum antispermatozoal antibodies and infertility of more than 3 years' duration. In men there is a relation between high levels of these antibodies in the semen and infertility. Various treatments have been proposed, but further prospective studies are needed. However, promising results have been reported with homologous intrauterine insemination and with immunosuppression in men.


Loss of PML nuclear bodies in familial amyotrophic lateral sclerosis-frontotemporal dementia.
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share genetic causes and pathogenic mechanisms. The critical genetic players of ALS and FTD are the TARDBP, FUS and C9orf72 genes, whose protein products, TDP-43, FUS and the C9orf72-dipeptide repeat proteins, accumulate in form of cytoplasmic inclusions. The majority of the studies focus on the understanding of how cells control TDP-43 and FUS aggregation in the cytoplasm, overlooking how dysfunctions occurring at the nuclear level may influence the maintenance of protein solubility outside of the nucleus. However, protein quality control (PQC) systems that maintain protein homeostasis comprise a cytoplasmic and a nuclear arm that are interconnected and share key players. It is thus conceivable that impairment of the nuclear arm of the PQC may have a negative impact on the cytoplasmic arm of the PQC, contributing to the formation of the cytoplasmic pathological inclusions. Here we focused on two stress-inducible condensates that act as transient deposition sites for misfolding-prone proteins: Promyelocytic leukemia protein (PML) nuclear bodies (PML-NBs) and cytoplasmic stress granules (SGs). Upon stress, PML-NBs compartmentalize misfolded proteins, including defective ribosomal products (DRiPs), and recruit chaperones and proteasomes to promote their nuclear clearance. SGs transiently sequester aggregation-prone RNA-binding proteins linked to ALS-FTD and mRNAs to attenuate their translation. We report that PML assembly is impaired in the human brain and spinal cord of familial C9orf72 and FUS ALS-FTD cases. We also show that defective PML-NB assembly impairs the compartmentalization of DRiPs in the nucleus, leading to their accumulation inside cytoplasmic SGs, negatively influencing SG dynamics. Although it is currently unclear what causes the decrease of PML-NBs in ALS-FTD, our data highlight the existence of a cross-talk between the cytoplasmic and nuclear PQC systems, whose alteration can contribute to SG accumulation and cytoplasmic protein aggregation in ALS-FTD.


Determinants of Stunting, Wasting, and Anemia in Guinean Preschool-Age Children: An Analysis of DHS Data From 1999, 2005, and 2012.
Wasting, stunting, and anemia are persistent and important forms of malnutrition in preschool-age children in the less developed world, in particular the Republic of Guinea, which was the site of a large outbreak of Ebola virus disease in 2014 to 2015. We analyzed data from 3 Demographic and Health Surveys done in Guinea in 1999, 2005, and 2012 to identify possible determinants of wasting, stunting, and anemia. All analyses, both bivariate and multivariate, were carried out separately for each of 3 age groups: less than 6 months, 6 to 23 months, and 24 to 59 months. Variables found statistically significantly associated with stunting, wasting, or anemia in bivariate analysis were placed in an age-specific logistic regression model for that outcome. Overall, anthropometric indices were available for 9228 children and hemoglobin concentrations were available for 5681 children. Logistic regression found relatively few variables associated with nutrition outcomes in children younger than 6 months. More variables were associated with nutrition outcomes in children aged 6 to 23 months. Such variables measured a wide variety of conditions, including estimated birth size, child health and nutritional status, child caring practices, mother's nutritional and health status, and household water source and sanitation. A similarly broad range of variables was statistically significantly associated with one or more nutrition outcomes in children aged 24 to 59 months. Few of the standard infant and young child feeding indicators were associated with any nutrition outcome. Improvement in the nutritional status of young children in Guinea may require a broad range of nutrition and health interventions.


Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis.
Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy. Retrospectively collected serum from 11 "poor" (<6 months progression free interval [PFI]) and 22 "favorable" (>24 months PFI) prognosis patients, were evaluated using circulating cell-free DNA (cfDNA). DNA from both groups showed 50 to 10 000 bp fragments. Pairwise analysis of sequenced cfDNA from patients showed that gene dosages were higher for 29 genes and lower for 64 genes in poor than favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins, while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2, and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Our results indicate that the cfDNA gene dosage combined with protein expression in tumor samples can serve as gene signature panel for prognosis determination amongst ovarian cancer patients.


Kinetically Controlled Coassembly of Multichromophoric Peptide Hydrogelators and the Impacts on Energy Transport.
We report a peptide-based multichromophoric hydrogelator system, wherein π-electron units with different inherent spectral energies are spatially controlled within peptidic 1-D nanostructures to create localized energy gradients in aqueous environments. This is accomplished by mixing different π-conjugated peptides prior to initiating self-assembly through solution acidification. We can vary the kinetics of the assembly and the degree of self-sorting through the choice of the assembly trigger, which changes the kinetics of acidification. The hydrolysis of glucono-δ-lactone (GdL) provides a slow pH drop that allows for stepwise triggering of peptide components into essentially self-sorted nanostructures based on subtle pKa differences, whereas HCl addition leads to a rapid formation of mixed components within a nanostructure. Using 1H NMR spectroscopy and fiber X-ray diffraction, we determine the conditions and peptide mixtures that favor self-sorting or intimate comixing. Photophysical investigations in the solution phase provide insight into the correlation of energy-transport processes occurring within the assemblies to the structural organization of the π-systems.


Malnourishment and length of hospital stay among paediatric cancer patients with febrile neutropaenia: a developing country perspective.
The prevalence of malnourishment among paediatric cancer patients undergoing chemotherapy in developing countries is poorly documented despite greater potential for malnourishment in such settings. We aimed to estimate the prevalence of malnourishment among paediatric cancer patients in Mexico City, and assess the association between malnourishment and length of hospital stay. Individuals eligible for this study were paediatric cancer patients (aged <18 years) admitted to Hospital Infantil de Mexico Federico Gomez (Mexico City) with febrile neutropaenia. Our exposure of interest, malnourishment, was defined as an age-adjusted and sex-adjusted z-score<-2 (ie, 2 SDs below the expected mean of the WHO reference population). We estimated time ratios (TRs) and 95% confidence limits (CLs) for the association between malnourishment and length of hospital stay. Our study population comprised 111 paediatric cancer patients with febrile neutropaenia, of whom 71% were aged <10 years and 52% were males. The prevalence of malnourishment was 14%, equal to a 530% (standardised morbidity ratio=6.3; 95% CL 3.7, 10) excess of malnourishment compared with the world reference population. The median length of hospital stay for malnourished patients was 15 days, which corresponded with a 50% (TR=1.5, 95% CL 1.0, 2.3) relative increase in length of stay compared with patients who were not malnourished. Patients with body mass indices equal to the mean of the world reference population had the shortest length of stay. Future studies should explore potential interventions for malnourishment to reduce the length of hospital stay or other established adverse consequences of malnourishment.


Bladder and rectal toxicity of BeamCath application in radiotherapy of prostate cancer.
Patient-reported toxicity in two radiotherapy regimens for early stage prostate cancer was investigated. In 2003, the Swedish BeamCath technique was adapted for Northern Norway. Ninety men underwent radiotherapy for early-stage prostate cancer in February 2002 to March 2005. They were invited to participate in a telephone interview employing a questionnaire guide focusing on bladder, intestinal and sexual function. Eighty patients responded, which represents 89% of all patients. The treatment group (23 patients) had received 76 Gy with the BeamCath technique and the control group (57 patients) received 70 Gy employing a conformal technique. The BeamCath technique was associated with a lower median rectal (p=0.004; 50.6 Gy versus 56.2 Gy) and bladder dose (p=0.017; 48.5 Gy versus 61.5 Gy). There were no differences in scores on masculinity and sexual function. In conclusion, the BeamCath technique did not increase rectal or bladder toxicity.


Questionable Reliability of Homocysteine as the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease.
An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients. A group of 50 COPD patients (28 males/22 females, age (χ̄±SD=49.0±14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) μg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cutoff used for classification (4.4, 6.6 and 8.0 μg/L - folate; 203 and 473 ng/L - vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.


A generalized modified-chi2 analysis of categorical bacteria survival data from a complex dilution experiment.
A well-known method of estimation for the density of bacteria in a sample solution is the most probable number (MPN) procedure. This paper considers the change in density through time of bacteria populations which are undergoing extinction. The MPN with its estimated variance for a fixed time point is a basic module of these investigations and is treated as a general implicit function of the cell proportions in linear categorical data analysis. These quantities are then used to fit exponential decay models over time by weighted least squares. When such models are supported by the data, comparisons of decay rates between populations under possibly different experimental conditions can be undertaken. This methodology is illustrated with an example pertaining to the survival experience of Leptospira autumnalis.


EVIDENCE FOR GENETIC DIFFERENTIATION BETWEEN CHOKE-INDUCING AND ASYMPTOMATIC STRAINS OF THE EPICHLOË GRASS ENDOPHYTE FROM BRACHYPODIUM SYLVATICUM.
Life cycle and breeding system variation in Epichloë grass endophytes (choke disease) is tightly linked to the degree of stroma formation. It is not known whether this variation results from differences in host resistance, fungal virulence, or environmental conditions. We found genetic differentiation between 173 asymptomatic (NS) and 93 stromata-forming (S) Epichloë strains isolated from one grass species, Brachypodium sylvaticum, based on 13 presumed allozyme loci, of which six were variable. The fungal strains originated from 10 sites in Switzerland, three sites of which were represented by both NS and S subpopulations. In total, 19 allozyme genotypes, that were nonrandomly distributed among S and NS were detected. Genetic variation measured as GST between S and NS strains isolated from the same site ranged from 0.73 to 0.98. Clonality, measured as linkage disequilibrium at one site, was significant in the NS subpopulation (P ≪ 0.001), but not in the S subpopulation (P = 0.21), implying asexual reproduction by NS strains as well as successful horizontal transmission of S strains. Since all seeds are usually infected vegetatively, horizontal transmission implies the occurrence of multiple host infections. Altogether, these results provide indirect evidence that NS and S strains do not belong to one panmictic population and that differentiation patterns of stroma formation found in nature are due to genetic differences among fungi in associations with their host plants. We discuss the direction of evolution of disease expression in this system. The distribution of genetic variability suggests that the asymptomatic strains were derived from stromata-forming populations.


Epidemiologic and clinical features of Bell's palsy among children in Northern California.
Bell's palsy (BP) is an acute, idiopathic, and usually unilateral paralysis of the facial nerve. Large population-based studies of BP among children are lacking. We determined epidemiologic and clinical features of BP among children enrolled in a large integrated health care delivery system. From 2001 through 2006, all children ≤18 years of age diagnosed with BP within the population of Kaiser Permanente Northern California were identified using the International Classification of Diseases, 9th Revision, code 351.0. All cases were adjudicated by an otolaryngologist and categorized as definite, probable, or rejected. Using chart abstraction forms, epidemiologic and clinical features of BP were determined. Of a total of 977 cases initially identified, 822 (84.1%) were adjudicated as a definite or probable case. The overall incidence rate of BP during the study period was 18.8 (95% CI 17.6-20.2) per 100,000 person-years. The incidence rate increased by age and was higher in females than males across all age strata. There was no evidence for a seasonal pattern in the occurrence of BP (p for trend = 0.81). BP among children may be more common than previously recognized.


The interrelationship between bleeding, perforation, and stenosis in duodenal ulceration.
The interrelationship of gastrointestinal bleeding, acute perforation, and pyloroduodenal stenosis was examined in a hospital series of 1,457 patients with duodenal ulcers. The proportion of each complication among the total number of ulcer patients after various periods of ulcer symptoms was determined. There was little variation in the proportion with bleeding as the duration of symptoms increased, whereas the proportion with perforation decreased and the proportion with stenosis increased with increasing duration of ulcer dyspepsia. The association of bleeding with perforation (26 patients) was more common than the association of bleeding with stenosis (12 patients), and more so than the association of perforation with stenosis (4 patients). To explain the paradoxical relationship of perforation and stenosis it was proposed that perforation occurred when the pathological process in ulceration was such that there was more tissue destruction. than tissue repair, and that stenosis would result if there was more tissue repair than tissue destruction


Diffusion Kurtosis Imaging: A Possible MRI Biomarker for AD Diagnosis?
The purpose of this explorative study was to investigate whether diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) parameter changes are reliable measures of white matter integrity changes in Alzheimer's disease (AD) patients using a whole brain voxel-based analysis (VBA). Therefore, age- and gender-matched patients with mild cognitive impairment (MCI) due to AD (n = 18), dementia due to AD (n = 19), and age-matched cognitively healthy controls (n = 14) were prospectively included. The magnetic resonance imaging protocol included routine structural brain imaging and DKI. Datasets were transformed to a population-specific atlas space. Groups were compared using VBA. Differences in diffusion and mean kurtosis measures between MCI and AD patients and controls were shown, and were mainly found in the splenium of the corpus callosum and the corona radiata. Hence, DTI and DKI parameter changes are suggestive of white matter changes in AD.


Predictors of early initiation of breastfeeding among Zimbabwean women: secondary analysis of ZDHS 2015.
The World Health Organization recommends initiation of breastfeeding within the first hour of delivery. Early initiation is beneficial for both mother and baby. Previous Zimbabwe Demographic and Health Surveys (ZDHS) have shown reduction in early initiation of breast feeding from 68% (2005/06) to 58% (2015). This study sought to investigate factors associated with early initiation of breast feeding among women aged 15-49 years in Zimbabwe. Secondary analysis of ZDHS 2015 data was done to investigate the association between early initiation of breast feeding and maternal, provider and neonatal factors using multivariate logistic regression (n = 2192). The majority of the study sample (78%) reported having practised early initiation of breastfeeding during their most recent delivery (preceding 24 months).Children who were put on skin to skin contact (AOR = 1.51, 95% CI 1.13-2.02) and those delivered by skilled attendants (AOR = 4.36, 95% CI 1.07-17.77) had greater odds of early initiation compared to those who were not. Other factors associated with early initiation were multiparity (AOR 1.82 95% CI 1.33-2.49) and rural residence (AOR 2.10 95% 1.12-3.93). However, having an abnormal birth weight, i.e. low birth weight (AOR 0.60 95% CI 0.36-0.99) and macrosomia (AOR = 0.42, CI 0.22-0.79) as well as delivery by caesarean section (AOR 0.1195% CI 0.06-0.19) were associated with reduced odds of early initiation. Early initiation of breast feeding in Zimbabwe is mainly associated with residing in the rural areas and multiparity. The 78% rate of early initiation of breastfeeding was contrary to the 58% reported in the ZDHS findings. Interventions targeting an improvement in early initiation of breastfeeding must aim at women who deliver by caesarean section, women with babies of abnormal birth weight, primi-parous women and women residing in rural areas.


Reconstitution of Saccharomyces cerevisiae DNA polymerase ε-dependent mismatch repair with purified proteins.
Mammalian and Saccharomyces cerevisiae mismatch repair (MMR) proteins catalyze two MMR reactions in vitro. In one, mispair binding by either the MutS homolog 2 (Msh2)-MutS homolog 6 (Msh6) or the Msh2-MutS homolog 3 (Msh3) stimulates 5' to 3' excision by exonuclease 1 (Exo1) from a single-strand break 5' to the mispair, excising the mispair. In the other, Msh2-Msh6 or Msh2-Msh3 activate the MutL homolog 1 (Mlh1)-postmeiotic segregation 1 (Pms1) endonuclease in the presence of a mispair and a nick 3' to the mispair, to make nicks 5' to the mispair, allowing Exo1 to excise the mispair. DNA polymerase δ (Pol δ) is thought to catalyze DNA synthesis to fill in the gaps resulting from mispair excision. However, colocalization of the S. cerevisiae mispair recognition proteins with the replicative DNA polymerases during DNA replication has suggested that DNA polymerase ε (Pol ε) may also play a role in MMR. Here we describe the reconstitution of Pol ε-dependent MMR using S. cerevisiae proteins. A mixture of Msh2-Msh6 (or Msh2-Msh3), Exo1, RPA, RFC-Δ1N, PCNA, and Pol ε was found to catalyze both short-patch and long-patch 5' nick-directed MMR of a substrate containing a +1 (+T) mispair. When the substrate contained a nick 3' to the mispair, a mixture of Msh2-Msh6 (or Msh2-Msh3), Exo1, RPA, RFC-Δ1N, PCNA, and Pol ε was found to catalyze an MMR reaction that required Mlh1-Pms1. These results demonstrate that Pol ε can act in eukaryotic MMR in vitro.


Barriers to physical activity among women in the rural midwest.
Physical activity is an important factor in chronic disease control and prevention. Yet women and rural residents consistently report lower rates of physical activity than their male and urban/suburban counterparts. The objective of this study was to assess the relationship between personal, social, and environmental barriers and meeting moderate physical activity recommendations in a sample of rural women. Data were obtained from a telephone survey of 2,510 residents of rural southeastern Missouri, Tennessee, and Arkansas. After adjusting for age and income, women who identified personal barriers, such as lack of time, no motivation, disinterest in exercise, and having no one to exercise with were less likely to meet physical activity recommendations. There was evidence of a dose-response relationship between the number of barriers identified and meeting moderate physical activity recommendations among women with higher incomes and women with lower incomes; however, this relationship was most striking among women with annual household incomes of 25,000 US Dollar or more. These findings may be used to tailor physical activity interventions to women in rural communities.


Expert's comment concerning Grand Rounds case entitled "Minimal access bilateral transforaminal lumbar interbody fusion for high-grade isthmic spondylolisthesis" (by Nasir A. Quraishi and Y. Raja Rampersaud; doi:10.1007/s00586-012-2623-2).
This Expert's Comment discusses the Grand Rounds Case entitled "Minimal Access Bilateral Transforaminal Lumbar Interbody Fusion for High-Grade Isthmic Spondylolisthesis" by Nasir A Quraishi and Raja Y Rampersaud. It puts a technically elegant surgical method for minimally invasive reduction and arthrodesis of isthmic spondylolistheses into the context of short and long term outcomes and questions the motivations for performing such minimally invasive procedures in the absence of any proven mid or long term advantages over more traditional techniques. In addition, the use of BMP in spinal arthrodesis is discussed on the background of recently published IPD metaanalyses from the Infuse spinal FDA trials.


The contribution of remifentanil to middle latency auditory evoked potentials during induction of propofol anesthesia.
There is a debate regarding whether opioids, as a component of general anesthesia, are adequately reflected in the assessment of anesthesia based on derivatives of the electroencephalogram. To test the hypothesis of a possible quantitative contribution of remifentanil on middle latency auditory evoked potentials, we studied its interaction with propofol anesthesia in 45 unpremedicated male patients undergoing elective lower limb orthopedic surgery. They were allocated randomly to three groups. The first two groups received remifentanil either with a high (8 ng mL(-1)) or a low (3 ng mL(-1) target concentration using target-controlled infusion (TCI). The third group received spinal anesthesia instead of remifentanil. Anesthesia was induced by a stepwise increase in propofol concentration using TCI. The auditory evoked potential index (AEPex) and calculated propofol effect site concentrations were determined at loss of consciousness and the reaction to laryngeal mask airway insertion was noted. The propofol infusion was then converted to a closed-loop TCI using an AEPex value of 40 as the target. We found no significant contribution of remifentanil alone on the auditory evoked response, whereas increasing concentrations of remifentanil led to a significant decrease of the calculated propofol effect site concentrations (P = 0.023) necessary for unconsciousness. Prediction probability for AEPex was inversely related to the remifentanil concentration and was best for the control group, which received propofol alone. These results support previous findings of a quantitative interaction between remifentanil and propofol for loss of consciousness but question the specific contribution of remifentanil to auditory evoked potentials.


Exploration of the Effect of Blue Light on Functional Metabolite Accumulation in Longan Embryonic Calli via RNA Sequencing.
Light is an important factor that affects the synthesis of functional metabolites in longan embryogenic calli (ECs). However, analysis of the effect of light on functional metabolites in longan ECs via RNA sequencing has rarely been reported and their light regulation network is unclear. The contents of various functional metabolites as well as the enzymatic activities of superoxide dismutase and peroxidase and the level of H₂O₂ in longan ECs were significantly higher under blue light treatment than under the other treatments (dark, white). In this study, we sequenced three mRNA libraries constructed from longan ECs subjected to different treatments. A total of 4463, 1639 and 1806 genes were differentially expressed in the dark versus blue (DB), dark versus white (DW) and white versus blue (WB) combinations, respectively. According to GO and KEGG analyses, most of the differentially expressed genes (DEGs) identified were involved in transmembrane transport, taurine and hypotaurine metabolism, calcium transport and so forth. Mapman analysis revealed that more DEGs were identified in each DB combination pathway than in DW combination pathways, indicating that blue light exerts a significantly stronger regulatory effect on longan EC metabolism than the other treatments. Based on previous research and transcriptome data mining, a blue light signaling network of genes that affect longan functional metabolites was constructed and HY5, PIF4 and MYC2 were shown to be the key regulatory genes in the network. The results of this study demonstrate that the expression levels of phase-specific genes vary with changes in longan EC functional metabolites.


Pattern of injuries in fatal falls from buildings.
When bodies are brought for autopsy it is sometimes unclear whether the injuries are due to a fall from a height or due to blunt trauma from other causes, especially when the bodies are found near buildings with no eyewitnesses available. Studies discussing the injury patterns in adults after falls exclusively from buildings are rare. A five-year retrospective study was carried out on 151 cases of fatal falls from buildings brought for autopsy. The aim was to assess the pattern of these injuries and identify features helpful in discriminating between these and injuries due to blunt trauma from other causes. The majority of cases comprised subjects who fell from heights of 10-20 feet (3-6m) with most falls occurring late at night or in the early morning. The pattern that emerged is quite distinct from ground level falls and pedestrian injuries. Abrasions are the commonest injury and bruises very rare. Lacerations are mostly on the head and skull fractures are evenly distributed between the vertex, base and vertex plus base. Subarachnoid haemorrhage is the commonest intracranial lesion. Extradural haemorrhage alone is rare. Fractures of ribs and cervical vertebrae are common and fractures of thoracic vertebrae and long bones are uncommon. Safety measures to prevent such falls have been suggested.


A randomized controlled crossover trial evaluating differential responses to antihypertensive drugs (used as mono- or dual therapy) on the basis of ethnicity: The comparIsoN oF Optimal Hypertension RegiMens; part of the Ancestry Informative Markers in HYpertension program-AIM-HY INFORM trial.
Ethnicity, along with a variety of genetic and environmental factors, is thought to influence the efficacy of antihypertensive therapies. Current UK guidelines use a "black versus white" approach; in doing so, they ignore the United Kingdom's largest ethnic minority: Asians from South Asia. The primary purpose of the AIM-HY INFORM trial is to identify potential differences in response to antihypertensive drugs used as mono- or dual therapy on the basis of self-defined ethnicity. A multicenter, prospective, open-label, randomized study with 2 parallel, independent trial arms (mono- and dual therapy), AIM-HY INFORM plans to enroll a total of 1,320 patients from across the United Kingdom. Those receiving monotherapy (n = 660) will enter a 3-treatment (amlodipine 10 mg od; lisinopril 20 mg od; chlorthalidone 25 mg od), 3-period crossover, lasting 24 weeks, whereas those receiving dual therapy (n = 660) will enter a 4-treatment (amlodipine 5 mg od and lisinopril 20 mg od; amlodipine 5 mg od and chlorthalidone 25 mg od; lisinopril 20 mg od and chlorthalidone 25 mg od; amiloride 10 mg od and chlorthalidone 25 mg od), 4-period crossover, lasting 32 weeks. Equal numbers of 3 ethnic groups (white, black/black British, and Asian/Asian British) will ultimately be recruited to each of the trial arms (ie, 220 participants per ethnic group per arm). Seated, automated, unattended, office, systolic blood pressure measured 8 weeks after each treatment period begins will serve as the primary outcome measure. AIM-HY INFORM is a prospective, open-label, randomized trial which aims to evaluate first- and second-line antihypertensive therapies for multiethnic populations.


Effects of ICV administration of the alpha1A-adrenoceptor antagonist 5-methylurapidil on concurrent measures of eating and locomotion after cocaine in the rat.
Psychostimulants including amphetamine and cocaine induce locomotion and stereotypy and suppress eating. Although the capacity of cocaine to alter locomotion is usually viewed as related to dopamine neurotransmission, recent studies suggest that norepinephrine, acting through alpha1-adrenergic receptors (alpha1-ARs) can facilitate cocaine-stimulated locomotion. Of the three alpha1-AR subtypes (alpha(1A), alpha(1B), and alpha(1D)) identified to date, inactivation of the alpha(1B)-AR subtype diminishes cocaine-stimulated locomotion, whereas the impact of inactivation of the alpha(1A)-AR subtype on either eating or locomotion is unknown. In the present study, we assessed the relative impact of ICV administration of the alpha(1B)-AR antagonist 5-methylurapidil (5-MU) on cocaine-stimulated hyperlocomotion and hypophagia, using a concurrent method [Wellman, P.J., Ho, D.H., Davis, K.W., 2005. Concurrent measures of feeding and locomotion in rats. Physiology of Behavior 84 (5), 769-774.]. Rats were infused ICV with one of 3 doses of 5-MU (0, 3, or 30 nmol) and then injected (i.p.) with 0, 2.5, 5.0, 10.0, or 20.0 mg/kg cocaine HCl on each of five tests. Rats always received the same 5-MU dose, but a different cocaine dose on each trial. Feeding and locomotion were assessed concurrently during a 45-min postinjection period. Significant suppression of eating was noted at 2.5 mg/kg cocaine, a dose that does not alter forward locomotion in the rat. Administration of 5-MU did not alter locomotion in rats treated with saline, but did significantly increase baseline food intake. Neither cocaine-induced hypophagia nor hyperlocomotion was altered by ICV administration of 5-MU. These results suggest that the capacity of alpha1-AR agonists (e.g. phenylpropanolamine) to suppress eating may be related to activation of the alpha(1A)-AR subtype, whereas cocaine does not act through the alpha(1A)-AR subtype to suppress eating nor does this subtype modulate cocaine-induced hyperlocomotion.


Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts.
Prostacyclin and its mimetics are used therapeutically for the treatment of pulmonary hypertension. These drugs act via cell surface prostacyclin receptors (IP receptors); however, some of them can also activate the nuclear receptor peroxisome proliferator-activated receptor beta (PPARbeta). We examined the possibility that PPARbeta is a therapeutic target for the treatment of pulmonary hypertension. Using the newly approved (for pulmonary hypertension) prostacyclin mimetic treprostinil sodium, reporter gene assays for PPARbeta activation and measurement of lung fibroblast proliferation were analyzed. Treprostinil sodium was found to activate PPARbeta in reporter gene assays and to inhibit proliferation of human lung fibroblasts at concentrations consistent with an effect on PPARs but not on IP receptors. The effects of treprostinil sodium on human lung cell proliferation are mimicked by those of the highly selective PPARbeta ligand GW0742. There are no receptor antagonists for PPARbeta or for IP receptors, but by using lung fibroblasts cultured from mice lacking PPARbeta (PPARbeta-/-) or IP (IP-/-), we demonstrate that the antiproliferative effects of treprostinil sodium are mediated by PPARbeta and not IP in lung fibroblasts. These observations suggest that some of the local, longer-term benefits of treprostinil sodium on reducing the remodeling associated with pulmonary hypertension may be mediated by PPARbeta. This study is the first to identify PPARbeta as a potential therapeutic target for the treatment of pulmonary hypertension, which is important because orally active PPARbeta ligands have been developed for the treatment of dyslipidemia.


Association between the 8-item Morisky Medication Adherence Scale (MMAS-8) and blood pressure control.
Non-adherence to treatment is an important and often unrecognized risk factor that contributes to reduced control of blood pressure (BP). To determine the association between treatment adherence measured by a validated version in Portuguese of the 8-item Morisky Medication Adherence Scale (MMAS-8) and BP control in hypertensive outpatients. A cross-sectional study was carried out with hypertensive patients older than 18 years, treated at six of the Family Health Strategy Units in Maceió (AL), through interviews and home blood pressure measurements, between January and April 2011. Adherence was determined by MMAS-8 version translated for this study. The patients were considered adherent when they had a score equal to 8 at the MMAS-8. The prevalence of adherence among the 223 patients studied was 19.7%, while 34% had controlled BP (> 140/90 mmHg). The average adherence value according to the MMAS-8 was 5.8 (± 1.8). Adherent patients showed to be more prone (OR = 6.1, CI [95%] = 3.0 to 12.0) to have blood pressure control than those who reached mean (6 to <8) or low values (<6) at the adherence score. The Portuguese version of MMAS-8 was showed a significant association with BP control (p = 0.000). The diagnosis of non-adherent behavior through the application of MMAS-8 in patients using of antihypertensive medications was predictive of elevated systolic and diastolic BP.


Long-Term Surgical Outcome of 1057 Gastric GISTs According to 7th UICC/AJCC TNM System: Multicenter Observational Study From Korea and Japan.
The aim of this study was to evaluate the treatment and prognosis of gastric gastrointestinal stromal tumors (GISTs) according to the 7th UICC/AJCC tumor-node-metastasis (TNM) system and the modified National Institutes of Health (NIH) risk classification. The study cohort consisted of 1057 patients with gastric GIST who underwent surgery between January 2000 and December 2007 from 13 institutions in Korea and 2 in Japan. Clinicopathologic characteristics, surgical outcomes, recurrence, and 5-year recurrence-free survival were evaluated.The mean age of the patients was 58.6 years. Thirty patients (2.8%) had distant metastasis preoperatively. Median tumor size was 4.0 cm. Complete resection (R0 resection) was achieved in 1018 patients (96.3%). Eighty-six patients (8.1%) had postoperative complications, and 2 patients (0.2%) died within 30 days after surgery. According to the 7th UICC/AJCC TNM system, 5-year recurrence-free survival rates were 95% to 99% in stage I, 94.1% in stage II, 74.1% in stage IIIA, 48.6% in stage IIIB, and 50.0% in stage IV patients. On survival analysis of high-risk patients according to the TNM system, the 5-year recurrence-free survival rates were 91.6% in stage II, 74.1% in stage IIIA, and 48.6% in stage IIIB patients. Independent factors of recurrence following surgery for gastric GIST were gender, tumor size, mitotic count, and radicality on multivariate analysis.The treatment outcome and prognosis of gastric GIST in Korea and Japan seem more favorable compared to those in Western countries. Compared to the modified NIH risk classification, the 7th UICC/AJCC TNM system is more reflective of the 5-year recurrence-free survival of patients with gastric GIST.


The effect of physiotherapy on post-temporomandibular joint surgery patients.
The purpose of this study was to investigate the effect of physiotherapy on rehabilitation of patients who had temporomandibular joint (TMJ) surgery. The treatment group consisted of 22 post-surgical patients who were treated with physiotherapy, and the non-treatment group consisted of 22 post-surgical patients who received no physiotherapy. The assessment tools were made using visual analogue scale (VAS) and craniomandibular index (CMI) which consisted of dysfunction index (DI) and palpation index (PI). All patients received follow-up for 7 months. The subjects were measured three times; before surgery, 6 weeks after surgery and 7 months after surgery. On the 6 week post-surgery assessment, DI and total CMI scores of the treatment group were significantly lower (P < 0.05) than those of the non-treatment group. On the assessment performed 7 months after surgery, all variables were significantly lower (P < 0.05) for the treatment group compared with those of the non-treatment group. The findings of the study indicate that physiotherapy has a positive effect in relieving pain and restoring TMJ function after surgery.


[Intravenous injection of coenzyme Q10 increases its level in rat brain].
It is established that intravenous injection of solubilized coenzyme Q10 provides quick and lasting increase in its level in the brain as compared to control intact rats and those with cerebral ischemia. These new data provide a basis for studying the efficacy of coenzyme Q10 as a neuroprotective agent in ischemic stroke.


Inadequate Dietary Phosphorus Levels Cause Skeletal Anomalies and Alter Osteocalcin Gene Expression in Zebrafish.
Phosphorus (P) is an essential mineral for the development and maintenance of the vertebrate skeletal system. Modulation of P levels is believed to influence metabolism and the physiological responses of gene expression. In this study, we investigated the influence of dietary P on skeletal deformities and osteocalcin gene expression in zebrafish (Danio rerio), and sought to determine appropriate levels in a diet. We analyzed a total of 450 zebrafish within 31 days of hatching. Animals were distributed in a completely randomized experimental design that consisted of five replications. After an eight-week experiment, fish were diaphanized to evaluate cranial and spinal bone deformities. Increases in dietary phosphorus were inversely proportional to the occurrence of partial spine fusions, the absence of spine fusions, absence of parallelism between spines, intervertebral spacing, vertebral compression, scoliosis, lordosis, ankylosis, fin caudal insertion, and craniofacial deformities. Additionally, osteocalcin expression was inversely correlated to P levels, suggesting a physiological recovery response for bone mineralization deficiency. Our data showed that dietary P concentration was a critical factor in the occurrence of zebrafish skeletal abnormalities. We concluded that 1.55% P in the diet significantly reduces the appearance of skeletal deformities and favors adequate bone mineralization through the adjustment of osteocalcin expression.


[When health makes the headlines. Press, elite complicities and health globalisation in Bamako, Mali].
To overcome the socio-medical failures observed in Africa's health services, researchers and practitioners of public health often mention the necessity to resort to counter-powers. But, what are precisely these counter-powers? To analyse the problem, we describe the treatment of health issues in the Bamako press during one year. The analysis of various processes (external references, lack of training, insufficient deontological standards, "elite" complicity among journalists and health directors) allows us to underline the complexity of the links between the press and health. The economic flows related to the economy of development "projects" in particular with AIDS, encourage the journalists to see themselves as "educationalists" of populations rather than spokesmen for their claims or difficulties. Two consequences follow. First of all the press counter-power has to be developed in the case one wishes to see it as the expression of "the voice of the voiceless" and a good help to make an "informal" evaluation of the quality of health cares by users. But, more generally within this context of globalisation of health, instead of encouraging the expression of a "popular" criticism, newspapers work out a system of mutual legitimacies and social connivances among local "elites". Far from contributing to the improvement of the health system by looking actively into the problem leading to a modernity under control, health journalism disconnects the discourse from its referent and contributes to discredit "political" language. This journalistic construction of the insignificance is one of the principal political effects of this medical journalism instrumentalized by institutions of development.


Strategies for improved rhamnolipid production by Pseudomonas aeruginosa PA1.
Rhamnolipids are biosurfactants with potential for diversified industrial and environmental uses. The present study evaluated three strategies for increasing the production of rhamnolipid-type biosurfactants produced by Pseudomonas aeruginosa strain PA1. The influence of pH, the addition of P. aeruginosa spent culture medium and the use of a fed-batch process were examined. The culture medium adjusted to pH 7.0 was the most productive. Furthermore, the pH of the culture medium had a measurable effect on the ratio of synthesized mono- and dirhamnolipids. At pH values below 7.3, the proportion of monorhamnolipids decreased from 45 to 24%. The recycling of 20% of the spent culture medium in where P. aeruginosa was grown up to the later stationary phase was responsible for a 100% increase in rhamnolipid volumetric productivity in the new culture medium. Finally, the use of fed-batch operation under conditions of limited nitrogen resulted in a 3.8-fold increase in the amount of rhamnolipids produced (2.9 g L(-1)-10.9 g L(-1)). These results offer promising pathways for the optimization of processes for the production of rhamnolipids.


Effects of branching and molecular weight of surface-bound poly(ethylene oxide) on protein rejection.
To understand better the origin of protein rejection observed with surface-bound poly(ethylene oxide) (or PEO), we have measured fibrinogen adsorption for a series of linear and branched, low-molecular-weight PEOs bound to solid polystyrene surfaces. The results show that a dependence on molecular weight is found below 1500 g mol-1 for linear PEO. Branched PEOs are less effective at protein rejection than linear PEOs. The branched PEOs have smaller exclusion volumes (from GPC) than the corresponding linear PEOs, consistent with restriction in conformational freedom for the branched compounds. The protein rejection results are interpreted in terms of entropy changes that result upon protein adsorption. In addition, some practical problems in preparation of PEO glycidyl ethers have been clarified, thus making these PEO derivatives more useful for surface modification.


Criminal responsibility and mental health experts: the A,B,Cs of cross-examination.
Experts from the field of behavioral sciences are regularly called upon in criminal prosecutions to offer an opinion as to an accused person's mental state at the time an alleged crime was committed. Within the confines of a criminal courtroom, perception often becomes reality. From a lawyer's perspective, the author attempts to reveal how the optics of a trial can become better aligned with actual fact through the adversarial process. Although written by a prosecutor, the upcoming commentary on the A,B,Cs of cross-examination should equally assist the defence counsel who must prepare his/her expert, the judge who must decide what weight to put on the testimony and the mental health expert who ultimately will be obliged to answer the questions.


The effect of H2 partial pressure on the reaction progression and reversibility of lithium-containing multicomponent destabilized hydrogen storage systems.
It is known that the reaction path for the decomposition of LiBH(4):MgH(2) systems is dependent on whether decomposition is performed under vacuum or under a hydrogen pressure (typically 1-5 bar). However, the sensitivity of this multicomponent hydride system to partial pressures of H(2) has not been investigated previously. A combination of in situ powder neutron and X-ray diffraction (deuterides were used for the neutron experiments) have shed light on the effect of low partial pressures of hydrogen on the decomposition of these materials. Different partial pressures have been achieved through the use of different vacuum systems. It was found that all the samples decomposed to form Li-Mg alloys regardless of the vacuum system used or sample stoichiometry of the multicomponent system. However, upon cooling the reaction products, the alloys showed phase instability in all but the highest efficiency pumps (i.e., lowest base pressures), with the alloys reacting to form LiH and Mg. This work has significant impact on the investigation of Li-containing multicomponent systems and the reproducibility of results if different dynamic vacuum conditions are used, as this affects the apparent amount of hydrogen evolved (as determined by ex situ experiments). These results have also helped to explain differences in the reported reversibility of the systems, with Li-rich samples forming a passivating hydride layer, hindering further hydrogenation.


Xylobiose Prevents High-Fat Diet Induced Mice Obesity by Suppressing Mesenteric Fat Deposition and Metabolic Dysregulation.
Obesity is a public concern and is responsible for various metabolic diseases. Xylobiose (XB), an alternative sweetener, is a major component of xylo-oligosaccharide. The purpose of this study was to investigate the effects of XB on obesity and its associated metabolic changes in related organs. For these studies, mice received a 60% high-fat diet supplemented with 15% d-xylose, 10% XB, or 15% XB as part of the total sucrose content of the diet for ten weeks. Body weight, fat and liver weights, fasting blood glucose, and blood lipids levels were significantly reduced with XB supplementation. Levels of leptin and adipokine were also improved and lipogenic and adipogenic genes in mesenteric fat and liver were down-regulated with XB supplementation. Furthermore, pro-inflammatory cytokines, fatty acid uptake, lipolysis, and β-oxidation-related gene expression levels in mesenteric fat were down-regulated with XB supplementation. Thus, XB exhibited therapeutic potential for treating obesity which involved suppression of fat deposition and obesity-related metabolic disorders.


Effects of soil mineral matrix on the analysis of plant- and soil-derived polysaccharides after acid hydrolysis.
The efficiency of extraction procedures for the determination of organic compounds in soil may be affected by the presence of the mineral phase. Our aim was to analyse the magnitude of such an effect on both total polysaccharide content and (13)C-isotopic signature of the polysaccharides. After acid hydrolysis of (13)C-labelled wheat, soil and a mixture of these, sugars were quantified and analysed isotopically. Measured values were compared with theoretical contents. No matrix effect was apparent for total sugar-C content of the mixture. However, a matrix effect was observed for the contribution of (13)C-labelled wheat sugars. For the soil+plant mixture (13)C-labelled wheat sugar contribution was overestimated. Soil-derived sugar-C contribution to the mixture was underestimated. Studies using stable isotopes to follow the fate of added plant-derived compounds in soil need to take into account matrix effects. Further studies have to elaborate on correction procedures and/or the development of extraction procedures to overcome the influence of matrix effects and/or acid hydrolysis extraction on sugar-C contents.


The impact of weight normalization on quality of recovery in anorexia nervosa.
There is little agreement on what constitutes remission in anorexia nervosa. This study compared the medical, psychological, and social status of 2 female populations previously treated for anorexia nervosa and differing in their achievement of normal weight. One hundred forty-one patients responded to a questionnaire documenting morphometric parameters, subjective perception of outcome, concerns about body shape and diet, and quality of familial, emotional, and professional life. Two groups were defined according to body mass index (BMI): normal (n = 69) with BMI > or = 18.5 kg/m(2), and subnormal (n = 72) with BMI < 18.5 kg/m(2). In addition, subgroups (21 in each category) were interviewed. An age-matched control population composed of 156 women, either students or Health Services employees, responded to a similar questionnaire. Only a minority of patients assessed themselves as recovered, and there was no statistically significant difference in perception of recovery between normal BMI and subnormal BMI groups (27.5% and 15.3%, respectively). As expected, underweight patients reported significantly more frequent purging behaviors, amenorrhea, recent hospitalization, and prolonged student status. In contrast, there were no significant differences in terms of pregnancy rate, psychiatric comorbidities, social integration, sexual activity, and self-assessment of professional and familial life. In comparison to control subjects, former anorexia patients with normalized BMI more frequently reported vomiting, fear of high-calorie foods, and treatment for depression. These few long-term advantages observed after BMI normalization suggest that normalization of nutritional status remains an important target in anorexia nervosa. However, the persistence of psychological distress after nutritional recovery confirms that more effective treatments are needed that target long-term psychological recovery.


Geodesics-based image registration: applications to biological and medical images depicting concentric ring patterns.
In many biological or medical applications, images that contain sequences of shapes are common. The existence of high inter-individual variability makes their interpretation complex. In this paper, we address the computer-assisted interpretation of such images and we investigate how we can remove or reduce these image variabilities. The proposed approach relies on the development of an efficient image registration technique. We first show the inadequacy of state-of-the-art intensity-based and feature-based registration techniques for the considered image datasets. Then, we propose a robust variational method which benefits from the geometrical information present in this type of images. In the proposed non-rigid geodesics-based registration, the successive shapes are represented by a level-set representation, which we rely on to carry out the registration. The successive level sets are regarded as elements in a shape space and the corresponding matching is that of the optimal geodesic path. The proposed registration scheme is tested on synthetic and real images. The comparison against results of state-of-the-art methods proves the relevance of the proposed method for this type of images.


How the C-O bond breaks during methanol decomposition on nanocrystallites of palladium catalysts.
Experimental findings imply that edge sites (and other defects) on Pd nanocrystallites exposing mainly (111) facets in supported model catalysts are crucial for catalyst modification via deposition of CH(x) (x = 0-3) byproducts of methanol decomposition. To explore this problem computationally, we applied our recently developed approach to model realistically metal catalyst particles as moderately large three-dimensional crystallites. We present here the first results of this advanced approach where we comprehensively quantify the reactivity of a metal catalyst in an important chemical process. In particular, to unravel the mechanism of how CH(x) species are formed, we carried out density functional calculations of C-O bond scission in methanol and various dehydrogenated intermediates (CH3O, CH2OH, CH2O, CHO, CO), deposited on the cuboctahedron model particle Pd79. We calculated the lowest activation barriers, approximately 130 kJ mol(-1), of C-O bond breaking and the most favorable thermodynamics for the adsorbed species CH3O and CH2OH which feature a C-O single bond. In contrast, dissociation of adsorbed CO was characterized as negligibly slow. From the computational result that the decomposition products CH3 and CH2 preferentially adsorb at edge sites of nanoparticles, we rationalize experimental data on catalyst poisoning.


Secretomic profiling of cells from hollow fiber bioreactor reveals PSMA3 as a potential cholangiocarcinoma biomarker.
Cholangiocarcinoma (CCA), derived from the bile duct, occurs with a relatively high incidence in Northeast Thailand. Early diagnosis is still hampered by the lack of sufficient biomarkers. In recent years, biomarker discovery using secretomes has provided interesting results, including our studies on CCA secretomes, especially with three-dimensional cell cultures. Thus, cells cultured using the hollow fiber bioreactor (HFB) with 20 kDa molecular weight cut-off (MWCO) yielded higher quality and quantity of secretomes than those from conditioned media of the monolayer culture (MNC) system. In this study, we employed the HFB culture system with 5 kDa MWCO and compared conditioned media from the HFB and MNC systems using two-dimensional gel electrophoresis, followed by identifying proteins of interest by liquid chromatography and mass spectrometry (LC/MS/MS). Two out of 4 spots of NGAL or lipocalin-2 were found to show highest increase in expression of 19.93-fold and 18.79-fold in HFB compared to MNC. Interestingly, all 14 proteasome subunits including proteasome subunit α type-1 to type-7 and β type-1 to type-7 showed 2.92-fold to 12.13-fold increased expression in HFB. The protein-protein interactions of upregulated proteins were predicted, and one of the main interaction clusters involved 20S proteasome subunits. Proteasome activity in the HFB conditioned media was also found to be higher than that in MNC conditioned media. Three types of proteasome subunit were also validated by immunoblotting and showed higher expression in the HFB system compared to MNC system. Proteasome subunit α type-3 (PSMA3) showed the highest level in plasma of cholangiocarcinoma patients compared to normal and hepatocellular carcinoma patients by immunodetection, and is of interest as a potential biomarker for cholangiocarcinoma.


Tunable Thermo-Responsive Properties of Hydroxybutyl Chitosan Oligosaccharide.
In this study, a simple method was used to synthesize novel thermosensitive hydroxybutyl chitosan oligosaccharide (HBCOS) by introducing hydroxybutyl groups to C6-OH of chitosan oligosaccharide (COS) chain. The variation in light scattering demonstrated that HBCOS had good thermosensitive properties and the particle size of HBCOS changed from 2.21-3.58 to 281.23-4,162.40 nm as the temperature increased to a critical temperature (LCST). The LCST of HBCOS (10 mg/ml) decreased from 56.25°C to 40.2°C as the degrees of substitution (DSs) increased from 2.96 to 4.66. The LCST of HBCOS with a DS of 4.66 decreased to 33.5°C and 30°C as the HBCOS and NaCl concentrations increased to 50 mg/ml and 4% (w/v), respectively. Variable-temperature FTIR spectroscopy confirmed that dehydration of hydrophobic chains and the transition of hydrogen bonds were the driving forces for the phase transition of HBCOS. Moreover, HBCOS was not cytotoxic at different concentrations. This work generated a novel thermosensitive HBCOS with tunable thermoresponsive properties and excellent biocompatibility, which may be a potential nanocarrier for the biomedical application.


A novel epithelial keratin, hK6irs1, is expressed differentially in all layers of the inner root sheath, including specialized huxley cells (Flügelzellen) of the human hair follicle.
In this study we have characterized a novel human type II keratin, hK6irs1, which is specifically expressed in the inner root sheath of the hair follicle. This keratin represents the ortholog of the recently described mouse inner root sheath keratin mK6irs. The two keratins were highly related and migrated at the same height as keratin 6 in two-dimensional gel electrophoresis. Both RNA in situ hybridization and indirect immunofluorescence studies of human hair follicles demonstrated hK6irs1 expression in the Henle and Huxley layers as well as in the cuticle of the inner root sheath. In all three layers, the expression of hK6irs1 mRNA and protein began simultaneously in adjacent cells of the lowermost bulb above the germinative cell pool. Higher up in the follicle, the detection limits for both hK6irs1 mRNA and protein precisely coincided with the asynchronous onset of abrupt terminal differentiation of the Henle layer, inner root sheath cuticle, and Huxley layer. Mainly above the level of terminal Henle cell differentiation, both indirect immunofluorescence and immunoelectron microscopy revealed the occurrence of distinct Huxley cells that developed pseudopodal hK6irs1-positive extensions passing through the fully keratinized Henle layer. These outwardly protruding foot processes abutted upon cells of the companion layer, with which they were connected by numerous desmosomes. These specialized Huxley cells have previously been termed "Flügelzellen", which means "winged cells", with reference to their characteristic foot processes. We provide evidence that, together with Henle cells, Flügelzellen ensure the maintenance of a continuous desmosomal anchorage of the companion layer along the entire inner root sheath. This tightly connected companion layer/inner root sheath unit provides an optimal molding and guidance of the growing hair shaft.


Chromogenic indicator for anion reporting based on an N-substituted oxoporphyrinogen.
5,10,15,20-Tetrakis-3,5-di-tert-butyl-4-oxocyclohexadienylidene porphyrinogen and its di-N-benzylated derivative are solvatochromic dyes capable of binding anionic species. The influence of solvent polarity and hydrogen bonding on their electronic absorption spectra was observed. Hydrogen bonding by the porphyrinogen amine protons of acetone solvent molecules could be observed in the solid state. The acetone solvate of N21N23-dibenzyl-5,10,15,20-tetrakis-3,5-di-tert-butyl-4-oxocyclohexadienylidene porphyrinogen crystallized under anhydrous conditions in the space group P with cell dimensions a = 12.1693(11) A, b = 17.5849(13) A, c = 21.0965(17) A, alpha = 69.870(4) degrees , beta = 78.140(4) degrees , gamma = 82.865(5) degrees . These porphyrinogens are capable of binding a variety of anions and can be used to distinguish fluoride chromogenically from the other halide anions. Solvatochromism was combined with anion binding in an attempt to provide more selective tests for anions. The anion binding properties were investigated using UV/vis spectrophotometry and 1H NMR spectroscopy.


Perspectives on the geographic stability and mobility of people in cities.
A class of questions in the human environment sciences focuses on the relationship between individual or household behavior and local geographic context. Central to these questions is the nature of people's geographic mobility as well as the duration of their locational stability at varying spatial and temporal scales. The problem for researchers is that the processes of mobility/stability are temporally and spatially dynamic and therefore difficult to measure. Whereas time and space are continuous, analysts must select levels of aggregation for both length of time in place and spatial scale of place that fit with the problem in question. Previous work has emphasized mobility and suppressed stability as an analytic category. I focus here on stability and show how analyzing individuals' stability requires also analyzing their mobility. Through an empirical example centered on the relationship between entrepreneurship and place, I demonstrate how a spotlight on stability illuminates a resolution to the measurement problem by highlighting the interdependence between the time and space dimensions of stability/mobility.


LRP-1 Binds Fibrinogen in a Sialylation-Dependent Manner: A Quartz Crystal Microbalance Study.
Cardiovascular disease (CVD) is the leading cause of mortality in the United States. Atherosclerosis, the dominant condition leading to CVD, is characterized by fibrofatty plaque formation. Fibrinogen, an important clotting factor, has been known to promote atherogenesis as it retains the ability to trigger smooth muscle cell proliferation, localize in areas crucial to plaque progression, and bind both platelets and leukocytes. Yet, these consequences can be suppressed through anti-inflammatory receptors like LRP-1─an endocytic receptor part of the LDLR family responsible for the endocytosis of cell debris and protein degradation products. However, the continual progression of atherosclerosis in many patients indicates that such clearance mechanisms, deemed efferocytosis, are impaired during atherosclerosis. Using the quartz crystal microbalance with dissipation monitoring (QCM-D) as a platform to investigate receptor-ligand interactions, we identify fibrinogen to be a ligand of LRP-1 and characterize its binding with LRP-1. By examining a key player in atherosclerosis development─the effect of sialidase on receptor efficacy─we found that the desialylation of LRP-1 reduces its ability to bind fibrinogen. Protein docking simulations highlighted the N-terminus portion of fibrinogen's α domain as the LRP-1 docking site. The sialylated O-linked glycans at T894 and T935 have the potential to mediate direct binding of LRP-1 to fibrinogen and support the tertiary structure of LRP-1. These phenomena are important in showing a probable cause of defective efferocytosis that occurs readily during atherosclerosis.


Proliferation of anchorage-dependent contact-inhibited cells: I. Development of theoretical models based on cellular automata.
We report the development of new class of discrete models that can accurately describe the contact-inhibited proliferation of anchorage-dependent cells. The models are based on cellular automata, and they quantitatively account for contact inhibition phenomena occurring during all stages of the proliferation process: (a) the initial stage of "exponential" growth of cells without contact inhibition; (b) the second stage where cell colonies form and grow with few colony mergings; and (c) the final stage where proliferation rates are dominated by colony merging events. Model prediction are presented and analyzed to study the complicated dynamics of large cell populations and determine how the initial spatial cell distribution, the seeding density, and the geometry of the growth surface affect the observed proliferation rates. Finally, we present a model variant that can simulate contact-inhibited proliferation of asynchronous cell populations with arbitrary cell cycle-time distribution. The latter model can also compute the percentage of cells that are in a specific phase of their division cycle at a given time.


Measurements of interstitial muscle glycerol in normal and insulin-resistant subjects.
The aim of this project was to study the regulation of interstitial glycerol levels in muscle in normal subjects, and to estimate interstitial muscle glycerol in obese subjects and patients with type 2 diabetes. In healthy lean subjects, microdialysis of forearm sc and muscle tissue were combined with arterial and deep venous catheterization, as well as blood flow registrations during oral glucose ingestion. In two other separate studies, obese (n = 9) vs. lean (n = 10) subjects and type 2 diabetes patients (n = 8) vs. weight-matched control subjects (n = 8) were investigated by means of muscle microdialysis during a euglycemic hyperinsulinemic clamp. Oral glucose ingestion suppressed the interstitial sc glycerol concentration by approximately 40% (P < 0.05), whereas no significant reduction of muscle interstitial glycerol was found. In contrast to the significant muscle interstitial-arterial (I-A) glycerol difference, the venous-arterial difference was small and varying throughout the oral glucose tolerance test. At steady-state hyperinsulinemia, obese subjects' interstitial muscle glycerol and I-A glycerol difference were both significantly higher than lean controls, whereas type 2 diabetes patient had interstitial muscle glycerol concentrations and I-A glycerol differences similar to those found in weight-matched controls. A significant and marked I-A glycerol difference exists in the absence of a significant venous-arterial difference, indicating that muscle glycerol cannot be taken as a marker of intramyocellular lipolysis because local turnover of muscle glycerol might be significant. The present data also suggest that, in contrast to sc tissue, muscle tissue lacks a clear antilipolytic effect of insulin. Moreover, the muscle interstitial glycerol concentration is elevated in obese patients but does not precipitate insulin resistance and type 2 diabetes.


Development of enzyme immunoassay for endogenous ouabain-like compound in human plasma.
Widespread evidence supports the existence of an endogenous digitalis-like compound in mammals. We report here the development of a novel enzyme immunoassay for ouabain that, in conjunction with a detailed HPLC study, identifies a ouabain-like compound (OLC) in extracted human plasma. The assay is sensitive-minimum detection limit for OLC 37 pmol/L (11 pmol/L in plasma)-and has a working range (between-assay CV < 10%) of 180-10000 pmol/L (54-3000 pmol/L in plasma). Mean recoveries of ouabain added to plasma ranged from 90% to 100%, and plasma extracts diluted in parallel to the standard curve. Plasma OLC concentrations in 10 healthy volunteers averaged 92 pmol/L (range 55-168), assuming 100% cross-reactivity of OLC in the ouabain assay. HPLC analysis with two distinct chromatographic conditions demonstrated that endogenous human plasma OLC co-eluted with authentic ouabain. The enzyme immunoassay is rapid and easy to perform and will support further investigation of the nature of this controversial endogenous steroid.


Meningococcal disease outbreak related to the World Scout Jamboree in Japan, 2015.
Six invasive meningococcal disease cases occurred among Scottish and Swedish nationals associated with the World Scout Jamboree (WSJ), an international mass gathering, held in Japan. The index case developed symptoms while returning home. The strains from all six cases were identical and seldom seen in Japan. Over 33 000 participants from 155 countries attended WSJ. At the Jamboree site, participants of the North of Scotland's and Sweden's units camped within the same subcamp and kept the same schedule of events. No information was available about the Swedish and Scottish cases' close personal contact history. Health Protection Scotland investigated Scottish cases, conducted active case finding, provided chemoprophylaxis, vaccinated close contacts and advised Scottish WSJ participants and contacts to seek medical care if they developed symptoms. The Public Health Agency of Sweden recommended chemoprophylaxis to all participants in Sweden. In Japan, the Ministry of Health, Labour and Welfare (MHLW) requested the Scout Association of Japan advise all participants to seek medical attention if they developed symptoms. MHLW shared information about the event with local authorities, medical associations, and the Ministry of Education, Culture, Sports, Science and Technology. No additional case related to WSJ has been reported. This outbreak highlighted the risk for international spread of invasive meningococcal disease at international mass gatherings. Assessing risk, educating participants, enhancing surveillance and sharing timely information among related countries are significant for prevention and response against invasive meningococcal disease outbreaks at mass gatherings.


Identification of a new all-trans-retinol metabolite produced through a new retinol metabolic pathway.
In vitro incubation of all-trans-retinol (atROL) with kidney homogenate from vitamin A-deficient and retinoic acid-supplemented (VAD-RAS) female rats produces a new retinol metabolite. Reverse-phase (RP) and normal-phase (NP) high-performance liquid chromatography (HPLC) analysis showed that this metabolite coelutes with the unknown all-trans-retinol (atROL) metabolite previously found in the day 10 conceptus and kidneys of vitamin A-deficient rats maintained on all-trans-retinoic acid (VAD-RA) and given 2 microg of [3H]atROL. Normal-phase (NP) HPLC purification of the metabolite collected from a RP HPLC column further separated the radiolabeled material into two components. The two isolated compounds have identical or very similar spectroscopic properties. Their nuclear magnetic resonance (1H NMR) and mass spectra (MS) indicated that they are isomers. Spectroscopic studies of the metabolites and their derivatives showed that they are nine-carbon fragments resulting from an oxidative cleavage of the side chain of atROL. The cleavage occurs at C-9, and the product is then oxidized to a keto group. The primary hydroxy group from atROL is preserved in the metabolite. A sulfide bridge is formed between C-11 and C-14, which interrupts the conjugation. The formation of the new metabolites, possessing a 2,5-dihydrothiophene ring, is catalyzed by an enzyme(s) located in the cytosolic fraction of kidneys. The process represents a new retinol metabolic pathway; however, its biological significance is unknown.


CENTRAL RETINAL VEIN OCCLUSION IN GATA2 DEFICIENCY.
To examine the association between GATA2 deficiency-related myelodysplastic syndrome (MDS) and central retinal vein occlusion (CRVO). Clinical ophthalmologic examination and laboratory work-up was performed for a patient with GATA2 deficiency-related MDS who experienced a unilateral CRVO. The literature was reviewed for reports of CRVO in the setting of MDS and allogeneic hematopoietic stem cell transplantation. Ophthalmologic examination revealed findings consistent with unilateral CRVO. Typical hypercoagulable work-up did not reveal an identifiable cause. A review of the patient's medical history revealed multiple potential causes of CRVO, including drug-induced and/or related to her history of MDS and hematopoietic stem cell transplantation. The literature was reviewed for reports of CRVO in association with her risk factors. On review of the literature, we determined that GATA2 deficiency-related MDS was a possible cause of this patient's CRVO although it is likely that her multiple risk factors worked synergistically to create a prothrombotic state. This case and review of the literature serve as an important reminder of the long and ever-evolving list of risk factors for the development of CRVO.