Stress, anxiety, depression, and health-related quality of life in caregivers of children with intestinal failure receiving parenteral nutrition: A cross-sectional survey study.
Improved survival rates for children with intestinal failure (IF) have resulted in an increased population of children receiving long-term parenteral nutrition (PN). Our objective was to determine burden on caregivers of children with IF receiving long-term PN. We performed a cross-sectional study of caregivers of children with IF receiving long-term PN in our intestinal rehabilitation program. A healthy comparison group matched on age of the child was enrolled. All participants completed standardized questionnaires, including the Parental Stress Index - Short Form (PSI-SF), Hospital Anxiety and Depression Scale (HADS), and PedsQL Family Impact Module (PedsQL FIM). Univariate analysis was completed using a Student t test and chi-square, with an alpha value of <0.05 considered significant. Thirty-eight caregivers of children with IF and 29 caregivers of healthy children consented, with response rates of 89% and 96.5%, respectively. Our study demonstrated increased stress for caregivers compared with comparison parents (PSI-SF total score of 83 [SD = 26.8] vs 62.9 [SD = 13.5]; P < 0.01). Caregivers had increased anxiety (HADS anxiety score of 9.3 [SD = 4.8] vs 6.7 [SD = 3.2]; P = 0.02) and higher depression scores (HADS depression score of 6.3 [SD = 4.3] vs 4.1 [SD = 2.6]; P = 0.02) compared with the comparison group. Caregivers of children with IF demonstrated decreased health-related quality of life (HRQoL) (reduced PedsQL FIM total score of 50.6 [SD = 18.2] vs 84.1 [SD = 20.5]; P < 0.01). Our results demonstrated significant burden of care in caregivers of children with IF receiving long-term PN, with elevated stress, anxiety, and depression and decreased HRQoL.


Field experiments on the ability of Arthrobotrys oligospora (Hyphomycetales) to reduce the number of larvae of Cooperia oncophora (Trichostrongylidae) in cow pats and surrounding grass.
In field experiments, conducted on parasite-free grass plots in two consecutive summers, artificially prepared cow pats containing Cooperia oncophora eggs were inoculated with the nematode-trapping fungus Arthrobotrys oligospora. Numbers of infective C. oncophora larvae isolated from the pats as well as from the surrounding herbage were subject to an approximately ten-fold reduction as compared with numbers in fungus-free pats and herbage surrounding these. This reduction was undoubtedly a result of entrapment of the parasite larvae within the faecal pats.


Beta-D-xylosidase from Selenomonas ruminantium of glycoside hydrolase family 43.
Beta-D-xylosidase from the ruminal anaerobic bacterium, Selenomonas ruminantium (SXA), catalyzes hydrolysis of beta-1,4-xylooligosacharides and has potential utility in saccharification processes. The enzyme, heterologously produced in Escherichia coli and purified to homogeneity, has an isoelectric point of approx 4.4, an intact N terminus, and a Stokes radius that defines a homotetramer. SXA denatures between pH 4.0 and 4.3 at 25 degrees C and between 50 and 60 degrees C at pH 5.3. Following heat or acid treatment, partially inactivated SXA exhibits lower k(cat) values, but similar K(m) values as untreated SXA. D-glucose and D-xylose protect SXA from inactivation at high temperature and low pH.


Integration of metabolomics and proteomics analysis to explore the mechanism of neurotoxicity induced by receipt of isoniazid and rifampicin in mice.
Isoniazid (INH) and rifampicin (RIF) are co-administered in tuberculosis treatment but can cause neurotoxicity, and the mechanism is not known. To explore this mechanism, we employed an integrated approach using metabolomics analysis (MA) and proteomics analysis (PA). Male mice were divided into three groups and administered vehicle (control group), or co-administered INH (120 mg/kg) and RIF (240 mg/kg), for 7 or 14 days. Mice brains were collected for mass spectrometry-based PA and MA plus lipidomics analysis. Measurement of brain levels of malondialdehyde and superoxide dismutase revealed time-dependent brain injury after exposure to INH+RIF for 7 and 14 days. Also, 422 proteins, 35 metabolites, and 21 lipids were dysregulated and identified. MA demonstrated "purine metabolism," "phenylalanine, tyrosine and tryptophan biosynthesis," "biosynthesis of unsaturated fatty acids," "phenylalanine metabolism," and "arginine biosynthesis" to be disturbed significantly. PA demonstrated pathways such as "lipids," "amino acids," and "energy metabolism" to be disrupted. Peroxisome proliferator-activated receptor (PPAR) pathways were changed in energy metabolism, which led to the neurotoxicity induced by INH+RIF. Immunohistochemical analyses of PPARs in mice brains verified that PPAR-α and -γ expression was downregulated. PPAR-α and -γ activation might be a key target for alleviating INH+RIF-induced neurotoxicity.


Placenta previa may acquire invasive nature by factors associated with epithelial-mesenchymal transition and matrix metalloproteinases.
To investigate the differences in epithelial-mesenchymal transition (EMT)- and matrix metalloproteinases (MMP)-related factors among placenta previa with and without placenta accreta spectrum (PAS) (n = 69), and normal placenta (n = 51). The women diagnosed with placenta previa with or without PAS, and normal placentas, who delivered at our institution between 2006 and 2016, were enrolled. The difference of EMT-related factors' expression by immunochemical analysis in chorionic villi and decidual cells between the normal placenta and placenta previa with or without PAS were evaluated. In chorionic villi of placenta previa with and without PAS, E-cadherin expression decreased, while that of ZEB1, SNAIL2 and MMP-9 increased than that in normal placenta. In decidual cells of placenta previa with and without PAS, expression of vimentin, ZEB1 and MMP-9 increased than that in normal placenta. In placenta previa with and without PAS, there was strong co-expression of ZEB1 and vimentin in chorionic villi, of ZEB1 and MMP-2 or MMP-9 in decidual cells, and of SNAIL2 and vimentin or MMP-9 in both chorionic villi and decidual cell. Vimentin expression in both chorionic villi and decidual cells was higher in placenta previa with PAS (n = 18) than in placenta previa without PAS (n = 51). MMP-2 expression in decidual cells was higher in placenta previa with PAS than in placenta previa without PAS. This study revealed that EMT- and MMP-associated factors may be related to placenta previa with and without PAS. Furthermore, placenta previa without PAS may acquire invasive nature.


A stable reagent system for screening and identifying red blood cell irregular antibodies: application to commercial antibodies.
Development of a new solid-phase system for screening and identifying irregular red cell antibodies. Red blood cell membranes were prepared by a semi-automated procedure in which the hemolysate solution was passed through a hollow-fiber system. The membranes were fixed to the solid phase (microtiter plates) by centrifugation and incubated with 8% fat-free milk. Antibodies added to the microtiter plate were detected by anti-human antibodies adsorbed onto yellow latex particles. The system had good sensitivity (titer <1); 97% of anti-D samples were detected. The detection system was stable for 6 months at 4 degrees C. This stable-antigen solid-phase system readily detects and identifies red cell antibodies that are important in transfusion.


A combination Verhoeff's elastic and Masson's trichrome stain for routine histology.
A method for the combined staining of elastic, muscle and connective tissue for routine use in histopathology is described. The elastica, stained black by Verhoeff's technique, is contrasted with the muscle and connective tissue stained red and green or blue respectively by a modification of Masson's trichrome. Cell nuclei stain blue-black with Weigert's iron hematoxylin. The procedure takes approximately two hours and is most suitable for the study of vascular pathology in surgical and autopsy sections.


Glutathione biosynthesis in Escherichia coli K 12. Properties of the enzymes and regulation.
The synthesis of glutathione in Escherichia coli K 12 was studied in crude, cell-free extracts. The pH optima and the apparent Km values for the substrates have been determined for both synthesizing enzymes, gamma-glutamylcysteine synthetase and glutathione synthetase. gamma-Glutamylcysteine synthetase was found to be approximately twice as active as glutathione synthetase. In a growing culture, the cellular level of GSH showed a considerable increase up to 6.6 mumol per ml cell pellet in the stationary growth phase. GSSG was not detectable. The levels of the enzymes remained constant, indicating that glutathione biosynthesis depends at least in the beginning on the availability of the component amino acids. The pathway is controlled by feedback inhibition and not by repression.


Role of angiotensin II in ischemia/reperfusion-induced leukocyte-endothelium interactions in the colon.
The aims of the present study were to determine the effects and mechanisms of angiotensin II (Ang II) on leukocyte-endothelium interactions and the role of Ang II in a novel model of ischemia/reperfusion (I/R) in the mouse colon. Ang II dose-dependently increased leukocyte rolling and adhesion in colonic venules. Importantly, Ang II-induced leukocyte rolling was completely inhibited by immunoneutralization of P-selectin, and leukocyte adhesion was abolished in lymphocyte function antigen-1 (LFA-1)-deficient mice. The P-selectin-dependent rolling was found to be a precondition for the subsequent LFA-1-dependent leukocyte adhesion. Moreover, Ang II-induced leukocyte responses involved generation of reactive oxygen species and up-regulation of CXC chemokines. Notably, CXC chemokines, but not Ang II, stimulated leukocyte chemotaxis in vitro. I/R increased gene expression of angiotensin converting enzyme (ACE) in the colon and plasma concentrations of Ang II. Inhibition of ACE and the type 1 angiotensin (AT1) receptor significantly decreased the I/R-induced leukocyte adhesion. Taken together, these novel findings demonstrate that Ang II exerts potent pro-inflammatory effects in the colonic microcirculation and that inhibition of Ang II expression or function protects against I/R-induced leukocyte responses in the colon. Thus, it is suggested that Ang II is a major target to control pathological inflammation in the colon.


Dehydration, lens movement and dryness ratings of hydrogel contact lenses.
Previous studies have shown that soft lenses dehydrate during lens wear. The purpose of this study was to determine the dehydration time course of 38% water content non-ionic Medalist, 58% ionic Acuvue and 74% non-ionic Permaflex lenses, and the relationship between dehydration and in vivo diameter, movement and symptoms of dryness. Nineteen subjects randomly wore three pairs of lenses, each for 7 h. Lens movement and diameter were measured in vivo and hydration after lens removal at 1, 3 and 7 h. Dryness was rated by the subjects using a visual analogue scale. A separate experiment was conducted to measure hydration changes after 7 continuous hours of lens wear. The water content of all three lens types decreased significantly over 7 h with Acuvue decreasing more than the Permaflex and Medalist lenses in the interrupted and continuous experiments (ANOVA P < 0.05). Dehydration of Acuvue was significantly greater in the 7 h continuous experiment (9.0 +/- 2.6% H2O, ANOVA P = 0.0062) compared to the interrupted experiment. Hydration levels measured for Acuvue lenses on subjects for control purposes at 0, 1, 3 and 7 h showed no difference over time (ANOVA P = 0.0711). Movement of Permaflex lenses decreased 0.60 +/- 0.57 mm (ANOVA P = 0.0005) over 7 h and the in vivo diameter of Acuvue lenses decreased by 0.12 +/- 0.16 mm (ANOVA P = 0.0569). Dryness ratings increased significantly and equally for all three lenses over 7 h (ANOVA P = 0.9833).(ABSTRACT TRUNCATED AT 250 WORDS)


Enantioselective column coupled electrophoresis employing large bore capillaries hyphenated with tandem mass spectrometry for ultra-trace determination of chiral compounds in complex real samples.
A new multidimensional analytical approach for the ultra-trace determination of target chiral compounds in unpretreated complex real samples was developed in this work. The proposed analytical system provided high orthogonality due to on-line combination of three different methods (separation mechanisms), i.e. (1) isotachophoresis (ITP), (2) chiral capillary zone electrophoresis (chiral CZE), and (3) triple quadrupole mass spectrometry (QqQ MS). The ITP step, performed in a large bore capillary (800 μm), was utilized for the effective sample pretreatment (preconcentration and matrix clean-up) in a large injection volume (1-10 μL) enabling to obtain as low as ca. 80 pg/mL limits of detection for the target enantiomers in urine matrices. In the chiral CZE step, the different chiral selectors (neutral, ionizable, and permanently charged cyclodextrins) and buffer systems were tested in terms of enantioselectivity and influence on the MS detection response. The performance parameters of the optimized ITP - chiral CZE-QqQ MS method were evaluated according to the FDA guidance for bioanalytical method validation. Successful validation and application (enantioselective monitoring of renally eliminated pheniramine and its metabolite in human urine) highlighted great potential of this chiral approach in advanced enantioselective biomedical applications.


Role of MUC1 and MUC5AC expressions as prognostic indicators in gastric carcinomas.
The aim of this study is to clarify the relationship between the expression of MUC1 and MUC5AC mucins and the clinicopathological features in human gastric carcinomas using the mouse monoclonal antibodies VU-4H5 and Clone 45M1, respectively. Furthermore, the possibility of using phenotypes (MUC1+/MUC5AC+, MUC1+/MUC5AC-, MUC1-/MUC5AC-, MUC1-/MUC5AC+) to predict prognosis of the patients is evaluated. Formalin-fixed, paraffin wax-embedded tissues from 76 cases of gastric cancer were examined for the expression of MUC1 and MUC5AC mucin antigens immunohistochemically using the avidin-biotin-peroxidase method. Of the 76 cases, MUC1 and MUC5AC immunoreactivities were observed in 49 (64.5%) and in 32 (42.1%) of gastric carcinoma tissues, respectively. MUC1 expression was significantly correlated to the depth of invasion, lymph node metastasis, peritoneal dissemination, and tumor stage. On the other hand, MUC5AC was inversely associated with depth of invasion, lymph node metastasis, liver metastasis, and tumor stage. Multivariate analyses indicated that tumor stage and MUC1 mucin expression were independently correlated with overall survival. The patients with MUC1+/MUC5AC- antigen staining in carcinoma tissues showed the lowest survival rate among four phenotypes. In contrast, the patients with MUC1-/MUC5AC+ antigen staining in carcinoma tissues showed the highest survival rate. Altogether these data suggest that combined evaluation of MUC1 and MUC5AC mucin staining may be clinically helpful to predict outcome in patients with gastric cancer.


Overdiagnosis of scabies and overprescribing of scabies treatment in a scabies-endemic region.
To assess the objective evidence upon which diagnosis of scabies and subsequent prescription of permethrin cream or oral ivermectin is based at a tertiary referral hospital in the Northern Territory. A retrospective cohort study of inpatients who were prescribed permethrin or ivermectin between July and September 2017 at a single tertiary referral hospital. Eighty-eight inpatient admissions, belonging to 77 unique patients, were included. This list was generated with the hospital's electronic prescribing software. Age, ethnicity, skin diagnosis on admission, which anti-scabies medications were prescribed, which concurrent medications were prescribed to treat a rash or pruritus, which differential or concurrent skin diagnoses were made, whether the dermatology department had seen the patient during their admission, and what evidence was documented as reason for diagnosis of scabies. In the cases in which scabies treatment was prescribed, less than one quarter had positive skin scrapings for scabies, and few had documentation of burrows, and documentation of a contact history combined with clinical lesions. Most cases met none of these diagnostic criteria. Very few were reviewed by the dermatology department as an inpatient. There were likely high rates of diagnostic uncertainty among the cases in which scabies treatment was prescribed. It is possible that anti-scabies medications are being prescribed empirically in this hospital.


Association of intra-tumoral tumour-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio is an independent prognostic factor in non-small cell lung cancer.
Studies suggest that tumour-infiltrating lymphocytes (TILs) and inflammation markers have independent roles in non-small cell lung cancer (NSCLC), but the relationship between the two pronostic factors remains unclear. In this study, we investigated TILs and inflammation markers in with patients advanced stage NSCLC and assessed the association of their levels with prognosis. TILs were evaluated by immunohistochemical staining for cluster of differentiation 3 (CD3) and cluster of differentiation 5 (CD5) and by hematoxylin and eosin staining for non-specific lymphocyte. We investigated the localisation pattern of TILs in advanced stage NSCLC. We divided all cases into two groups: TILs-high and TILs-low groups, by 75th percentile of the population of. In our study, inflammation markers were assessed by C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR). The results showed that the presence of intra-tumoral high CD3+ and low CD5+ were an independent prognostic factor for overall survival (respectively, P = 0.022 and P = 0.025). Moreover, the high NLR and serum high CRP levels were associated with poor survival (respectively, P = 0.008; P = 0.027). In multi-variate survival analysis, the high CD3+ , low CD5+ , high NLR, tumour node metastasis (TNM) stage, depth of tumour invasion and lymph node metastasis remained independent prognostic factors (respectively, P = 0.018, P = 0.020, P = 0.024, P = 0.038, P = 0.020 and P = 0.047).The high NLR was detected negative correlation with intra-tumoral CD3+ and positive correlation with intra-tumoral CD5+ (respectively, r = -0.623, P = 0.012; r = 0.628, P = 0.028). This study is first report demonstrating the prognostic value of intra-tumoral low CD5+ with NSCLC. Increased CD3+ and low CD5+ was observed in patients with poor prognosis; the two molecules were correlated with NLR, suggesting that inflammation might be used as improve therapeutic efficacy to immunotherapy for advanced NSCLC.


Timely Wound Healing Is Dependent on Endothelial but Not on Hair Follicle Stem Cell Toll-Like Receptor 2 Signaling.
As a part of innate immunity, toll-like receptor 2 (TLR2) plays an important function in most defensive responses of the organism, including but not limited to infections. Cutaneous injury, one of the most common challenges for mammals, mobilizes a number of cell types, including epithelial, immune, and vascular cells, for timely tissue repair. However, in contrast to immune cells, little is known about TLR2 function on nonimmune cells during skin regeneration. In this study, we used two tissue-specific conditional Tlr2-knockout mouse lines to address the effects of TLR2 in endothelial and hair follicle stem cells (HFSCs) on cutaneous wound healing. The loss of TLR2 on endothelial cells diminishes their ability to migrate, sprout, and proliferate in response to specific TLR2 ligands and also reduces the secretion of key proangiogenic factors. Lack of TLR2 on endothelial cells prolongs wound healing owing to diminished angiogenesis. TLR2 is expressed in key structures of hair follicles, including HFSCs, secondary hair germ, and dermal papilla. Despite the prominent role of HFSCs in skin regeneration, excision of TLR2 from HFSCs has no effects on their proliferation or wound healing potential. Our study shows that timely tissue regeneration after skin injury is dependent on endothelial TLR2 for robust angiogenesis, whereas HFSC TLR2 is dispensable.


Characterizing classes of antiretroviral drugs by genotype.
This paper develops methods for using HIV-1 genotypic information to group patients who are expected to have similar patterns of sensitivity or resistance to two or more drugs. The methods presented are an extension of prediction based classification to handle multiple drug responses. Here, the goal is to determine the probability that one antiretroviral therapy will be more favourable than another for an individual given the specific genotypic or other characteristics of the infecting viral population. This approach requires a model relating genotype to a vector of drug specific phenotypic responses. A comparison of Nelfinavir and Indinavir is provided using 2746 protease sequences and corresponding in vitro sensitivity assays provided to us by the Virco Group.


Chromatographic parameters: Characteristic parameters of solute retention - an insightful description of column properties.
Previously introduced characteristic parameters of solute retention - the solute characteristic temperature (Tchar) and thermal constant (θ) in GC as well as the characteristic solvent composition (ϕchar) and the composition-constant (Φ) in LC - are described herein from a single perspective. Unlike conventional thermodynamic parameters, e.g., entropy and enthalpy of solute evaporation from stationary phase in GC that do not have a direct chromatographic meaning, the characteristic parameters do. Thus, Tchar and ϕchar are the column temperature and the solvent composition in GC and LC, respectively, at which the solute retention factor (k) is equal to 1. Quantities θ and Φ in GC and LC, respectively, are analogous to the time-constant in scientific and technical fields. Thus, e.g., Φ is the increase in the solvent composition leading to e-fold reduction (e ≈ 2.72) in k. Properties of characteristic parameters illustrating intuitive nature and simplicity of based on them concepts and equations are described.


A hand research fellowship training programme.
There are currently 68 hand surgery fellowship programmes known to the authors in the United States and many more throughout the world. To our knowledge, there are no hand fellowships which focus on research. Such a hand surgery research fellowship is being developed to provide this training. This paper outlines the goals and objectives of the intended 2 year training programme and includes a description of the fellowship. The first year would be mostly committed to learning research methods and the second would be a clinical hand fellowship. This will combine clinical expertise in hand surgery, practical research experience and formal research training. Hand researchers would learn research methods, develop innovative research ideas and begin an active research and academic career.


A multivariate analysis of the risk of iron deficiency in plateletpheresis donors based on logistic regression.
The purpose of this study was to analyze the application of individual factors, blood cell related indicators, and blood donation frequency in predicting the risk of iron deficiency of plateletpheresis donors. A total of 801 plateletpheresis donors were included in this study. The relationship between risk factors and iron deficiency was retrospectively analyzed by univariate analysis and logistic regression analysis. The application of Hb, MCHC, RDW-CV and blood donation frequency combined prediction of iron deficiency risk among plateletpheresis donors was evaluated. The rate of iron deficiency in this study was 31.5 % (241/766). The age, gender (the ratio of male donors), red blood cell related indicators, blood donation frequency were statistically different between the normal and iron deficiency group (all P < 0.05). Age, gender, the reciprocal of Hb and MCHC, RDW-CV, total number of blood donation and number of plateletpheresis donation in the past year, these indicators to predict the risk of iron deficiency area under the curve (AUC) were 0.558, 0.672, 0.785, 0.717, 0.599, 0.621, 0.646, respectively. The AUC of these indicators combined to predict the risk of iron deficiency was 0.877, higher than all single indicators. The sensitivity and specificity of these indicators combined in prediction of iron deficiency were 88.89 % and 81.57 %, respectively. Age, gender, the reciprocal of Hb and MCHC, RDV-CV, blood donation frequency are associated with the risk of iron deficiency in plateletpheresis donors. The combination of these indicators has high value in predicting the risk of iron deficiency.


Kinetics of somatostatin inhibition of pentagastrin-stimualted gastric acid secretion.
Dogs with gastric fistulae and denervated gastric pouches received graded doses of pentagastrin with and without a background infusion of somatostatin (1 microgram kg-1 h-1). Similarly, graded doses of somatostatin (0.25, 0.5, 1, 2 and 4 microgram kg-1 h-1) were infused after a steady state gastric secretion had been achieved with pentagastrin (1.5 microgram kg-1 h-1), about twice the dose required to produce half maximal (D50) response. Somatostatin inhibited pentagastrin-stimulated gastric acid secretion with competitive inhibition kinetics, but its precise site of action remains uncertain. The minimum effective dose of somatostatin on a twice D50 dose of pentagastrin was 0.25 microgram kg-1 h-1.


Determination of triazine herbicides and their metabolites in multiple medicinal parts of traditional Chinese medicines using streamlined pretreatment and UFLC-ESI-MS/MS.
A rapid, sensitive, and reliable ultra-fast liquid chromatography combined with electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) method was established and applied to simultaneous determination of 31 triazine herbicides and their metabolites in multiple medicinal parts of traditional Chinese medicines (TCMs). A streamlined pretreatment approach using one-step extraction and dilution was proposed, which provided high-throughput processing, excellent recovery, and negligible interference. Afterwards, multiple-reaction monitoring (MRM) and information-dependent acquisition (IDA) triggered enhanced product ion spectra (EPI) was adopted to identify and quantify the targets in a single analysis. The optimized method was then validated according to the guidelines of the European Commission for the following parameters: Matrix effects, specificity, accuracy, precision, linearity, range, and stability. The LOD and LOQ for the 31 triazine herbicides were 0.1-10 μg kg-1 and 0.5-25 μg kg-1, respectively. Recoveries at three concentration levels were within 67.9-120.3% with an associated precision RSD <20%. Using the proposed approach, trazines herbicides were determined from 44 commercially available TCMs. The detection rate of triazine herbicides residues was 15.9% of the total samples. Among them, atrazine, simeton, and simetryn were found in the radix, herba, and seed TCMs with values far below the referenced maximum residue limits (MRLs), but no residues were detected in either the flos or fructus. Taken together, this method has the potential to provide a means for triazines screening in extensive matrices, thereby laying the foundation for pesticide registration on TCMs. Moreover, it has the potential to guide further triazine residue control in TCMs.


[Managing warfarin treatment in a small Icelandic rural practice in Húsavík].
To investigate the efficiency of warfarin management in Húsavík Health Care Center. All patients receiving warfarin treatment managed in Húsavík in the years 2001 and 2003 were included in the study. Main outcome measures were the percentage time within INR target range (Rosendaal) and whether the management was deemed satisfactory or unsatisfactory (defined as <3 measurements per year). In 2001 there were 34 patients receiving warfarin treatment in Húsavík but 57 in 2003. Median age was 71.5 and 76 years, 65% and 67% were males, indication for treatment was atrial fibrillation in 53% and 73% and INR target range was 2.0-3.0 in 74% and 86% respectively. The management was deemed unsatisfactory in 38.2% in 2001 but 10.5% in 2003 (27.7% absolute reduction, p=0.0017). Percentage time spent within target range was 61.2% and 63.1% respectively. These findings suggest that the quality of anticoagulant control in Húsavík is adequate and fully comparable with that shown in previous studies from our neighbouring countries.


Climate attribution of interpersonal violence: International evidence.
Anthropogenic climate change is increasingly threatening interpersonal violence, yet global evidence for related impacts and potential transmission mechanisms remains limited. We examine whether and how climate change, particularly climate extremes, affects interpersonal violence. Using the panel data of 140 countries and regions from 2000 to 2019, we find that hot and wet extremes precipitated increase in homicide rates globally. Economic level, inequality, and resources scarcity were important intermediaries through which climate extremes affected homicide, while the direct effects still dominated the total effects. We then reveal the heterogeneous effects of climate extremes, further suggesting that poor countries and regions with relatively small contributions to climate change were particularly sensitive to climate extremes. These findings elucidate a strong climate-violence link, helping explain implications of facilitating violence prevention and mitigating climate change.


Oil wastes as unconventional substrates for rhamnolipid biosurfactant production by Pseudomonas aeruginosa LBI.
Oil wastes were evaluated as alternative low-cost substrates for the production of rhamnolipids by Pseudomonas aeruginosa LBI strain. Wastes obtained from soybean, cottonseed, babassu, palm, and corn oil refinery were tested. The soybean soapstock waste was the best substrate, generating 11.7 g/L of rhamnolipids with a surface tension of 26.9 mN/m, a critical micelle concentration of 51.5 mg/L, and a production yield of 75%. The monorhamnolipid RhaC(10)C(10) predominates when P. aeruginosa LBI was cultivated on hydrophobic substrates, whereas hydrophilic carbon sources form the dirhamnolipid Rha(2)C(10)C(10) predominantly.


Older Age as a Predictive Risk Factor for Acute Mountain Sickness.
Older populations are increasing and comprise a substantial portion of high-altitude travelers. Aging physiology may influence susceptibility to acute mountain sickness, though prior research remains inconclusive. The goal of this study was to investigate the relationship between increasing age and acute mountain sickness. This study was a pooled analysis of 5 prospective randomized controlled trials conducted at White Mountain, California from 2010, 2016-2019 with identical 4-hour rapid ascent from 1242 m to overnight sojourn at 3810 m. Acute mountain sickness was defined by the 2018 Lake Louise Questionnaire criteria. There were 491 participants analyzed, 234 (48%) diagnosed with acute mountain sickness and 71 (14%) with moderate acute mountain sickness. Mean age was 37 years (±13). There was no significant correlation between Lake Louise Questionnaire severity and age (r = -0.02; 95% confidence interval [CI], -0.11-0.07, P = .7), 40-year-old dichotomy (t = -0.6; 95% CI, -0.53-0.28, P = .6), or decade of life (P = .4). Logistic regression found no increased odds of acute mountain sickness for increasing age by decade of life (odds ratio [OR] 1.0; 95% CI, 0.97-1.0) or 40-year-old dichotomy (OR 1.4; 95% CI, 0.97-2.1). A history of acute mountain sickness increased odds of acute mountain sickness (OR 3.2; 95% CI, 1.5-7.7). Older age was not associated with incidence nor severity of acute mountain sickness. A history of altitude illness increased odds of acute mountain sickness and should be used for pre-ascent risk stratification.


A Prospective Study of Cyclosporine A 0.1% Combined with Loteprednol 0.2% vs Cyclosporine A 0.05% Alone in the Treatment of Dry Eye.
To examine the efficacy and tolerability of a combination of cyclosporine 0.1% and loteprednol 0.2% (CsA-LE; Klarity CL) in comparison to commercially available cyclosporine 0.05% (CsA; Restasis) in improving signs and symptoms of dry eye. This multicenter, prospective, randomized, controlled, open-label study evaluated 60 patients randomized to a single treatment for 4 weeks and evaluated at day 0, day 14, and day 28. Comparison was made of corneal higher-order aberrations (HOAs), dry-eye symptoms (SPEED score), tear-breakup time (TBUT), corneal staining, and ocular hyperemia, as well as tolerability of each medication with the validated COMTOL instrument. A total of 56 patients completed enrollment. Corneal HOAs improved significantly with CsA-LE, but not CsA alone. Both groups showed significant improvement (with no significant differences between groups) in SPEED scores, corneal staining, TBUT, and conjunctival hyperemia. Tolerability was similar between the drugs, and no significant safety issues were identified. The combination of CsA 0.1%-LE 0.2% provided significant improvement in corneal HOAs, while CsA 0.05% did not. For all other measures of ocular surface improvement, both medications showed similar benefits. Tolerability was comparable between the formulations. When rapid rehabilitation of the ocular surface is needed to reduce aberrations, CsA-LE is an appropriate choice.


Atherosclerosis precursors in Finnish children and adolescents. III. Blood pressure.
In connection with the Finnish Multicentre Study on the precursors of atherosclerosis in 3-, 6-, 9-, 12-, 15- and 18-year-old children and adolescents, blood pressure was measured in 3,596 subjects in the five university hospital areas. Blood pressure was measured with an ultrasound device (Arteriosonde 1020, Roche) in the 3-year-old children, and an ordinary mercury sphygmomanometer was used in the rest of the subjects. The systolic and diastolic values increased with age as has been shown earlier. There were no significant differences in the values between boys and girls except that the 15- and 18-year-old boys had values a little higher than girls of the same age. Weight and height correlated well to both systolic and diastolic blood pressures. Physical maturation also correlated to blood pressure.


Enzymatic preparation of prostaglandin endoperoxides.
A simple and reliable method is described for the preparation of the endoperoxide intermediates (PGG2 and PGH2) in the biosynthesis of prostaglandins. The endoperoxides are thermolabile and easily decomposed by water (t 1/2 congruent to 5 min at 37 degrees C). Because of this, special precautions must be taken to work at low temperature and to minimize contact with moisture. Milligram quantities of PGG2 and PGH2 were obtained by running several reactions successively and pooling the extracts before chromatographic fractionation. The method is now being developed further to scale up the procedure.


The effects of self-control on cognitive resource allocation during sustained attention: a transcranial Doppler investigation.
Vigilance, or sustained attention, is a required ability in many operational professions. While past research has consistently indicated that vigilance performance declines over time, referred to as the vigilance decrement, the theoretical mechanisms underlying the decrement continue to be explored. In the current study, trait self-control was examined to determine how this individual differences measure may contribute to the theoretical explanation of vigilance decrement. Transcranial Doppler sonography (TCD) was used as a measure of cerebral blood flow velocity (CBFV), as previous research has indicated that CBFV may index attentional resource allocation during vigilance (e.g., Shaw et al. in Hum Factors Ergon Soc 50:1619-1623, 2009). Participants performed a demanding 12-min computer-based vigilance task. Prior to the task, a validated self-report measure was used to determine trait-level self-control, and subjective workload was measured after the task was completed. Participants were divided, based upon survey responses, as either low- or high-trait self-control. Performance results showed a significant decrement across participants, but no significant main effect or interaction relating to the self-control measure was observed. Results relating to the TCD measure showed a significant decline in CBFV in the low self-control group, but no CBFV decrement was observed in the high self-control group. The subjective workload results revealed a nonsignificant trend of the low self-control group becoming more frustrated after the task. These results suggest that there are differences in the resource allocation strategies between low and high self-control participants. How trait self-control can add to an understanding of the theoretical underpinnings of sustained attention performance is discussed.


[Changes in the distance between carina and orotracheal tube during open or videolaparoscopic bariatric surgery].
To examine whether there are changes in the distance between the orotracheal tubeand carina induced by orthostatic retractor placement or by pneumoperitoneum insufflation in obese patients undergoing gastroplasty. 60 patients undergoing bariatric surgery by two techniques: open (G1) or videola-paroscopic (G2) gastroplasty were studied. After tracheal intubation, adequate ventilation of both hemitoraxes was confirmed by lung auscultation. The distance orotracheal tube-carina was estimated with the use of a fiber bronchoscope before and after installation of orthostatic retractors in G1 or before and after insufflation of pneumoperitoneum in patients in G2. G1 was composed of 22 and G2 of 38 patients. No cases of endobronchial intubationwere detected in either group. The mean orotracheal tube-carina distance variation was estimated in -0.03 cm (95% CI 0.06 to -0.13) in the group of patients undergoing open gastroplastyand in -0.42 cm (95% CI -0.56 to -1.4) in the group of patients undergoing videolaparoscopic gastroplasty. The extremes of variation in each group were: 0.5 cm to -1.6 cm in patients under-going open surgery and 0.1 cm to -2.2 cm in patients undergoing videolaparoscopic surgery. There was no significant change in orotracheal tube-CA distance after placementof orthostatic retractors in patients undergoing open gastroplasty. There was a reduction inorotracheal tube-CA distance after insufflation of pneumoperitoneum in patients undergoing videolaparoscopic gastroplasty. We recommend attention to lung auscultation and to signals of ventilation monitoring and reevaluation of orotracheal tube placement after peritoneal insufflation.


Problems of continuous Pa, O2 monitoring by means of indwelling intra-arterial electrodes.
Continuous monitoring of intra-arterial PO2 has many advantages in intensive care. However, there are some problems which have prevented the routine use of this method until now. A commercially available polarographic oxygen electrode was tested in vitro. Continuous PO2 monitoring was performed in vivo in 63 adult patients. The electrode is suitable for intensive care with regard to handling, dimensions, biocompatibility, mechanical stability, electrical safety, sensitivity, flow dependency, response time and costs. It should be improved with regard to the instability of the measuring properties and its non-linearity in hyperoxia. Serious complications of continuous PO2 monitoring were not observed. In view of the specific properties of the polarographic electrode and the contraindications of arterial cannulation, the continuous intra-arterial PO2 measurement has proved to be a valuable, safe and simple technique of monitoring, especially for short-term changes of arterial PO2.


Polymorphism 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene is associated with IgE-mediated allergic diseases and asthma in the Czech population.
Plasminogen activator inhibitor type 1 (PAI-1) is a glycoprotein that belongs to the serine protease inhibitor superfamily and has an essential role in tissue remodeling after inflammation. Recently, a single base pair deletion/insertion (4G/5G) polymorphism of the PAI-1 gene has been associated with an increased risk of asthma in nuclear families from the UK. The present study was thus conducted to determine the association of this polymorphism with the development of IgE-mediated asthma and other allergic diseases in the Czech population. A case-control approach was used in our study. DNA taken from subjects with clinically manifested asthma and other allergic diseases (n = 207) and from reference ethnically age-gender-matched unrelated subjects (n = 186) was examined for base deletions/insertions in the PAI-1 gene. A significant association (P = 0.0035) was observed between the PAI-1 promoter polymorphism and IgE-mediated allergic diseases altogether. Furthermore, the 4G allele frequency was also significantly higher in the asthmatic patients than in the control group (P = 0.0148). Our findings support the idea that the 4G allele of the 4G/5G polymorphism in the PAI-1 gene may be a risk factor for IgE-mediated asthma and allergic diseases.


Late-onset rectal bleeding with hemorrhagic shock after transrectal prostate needle biopsy.
Late-onset rectal bleeding after transrectal prostate needle biopsy is potentially life-threatening. We report the case of a 75-year-old male who presented with severe rectal bleeding 3 days after transrectal prostate needle biopsy. Because the bleeding could not be arrested by conservative treatment, emergent colorectal endoscopic clipping (twice) and elective angiography were performed. Packed red blood cell transfusion (14 units in total) was required to treat the developed hemorrhagic shock. Colorectal endoscopy and arterial embolization are effective treatments for severe rectal bleeding after transrectal prostate needle biopsy and should be performed without hesitation.


The interplay between microalgae and toxic metal(loid)s: mechanisms and implications in AMD phycoremediation coupled with Fe/Mn mineralization.
Acid mine drainage (AMD) is low-pH with high concentration of sulfates and toxic metal(loid)s (e.g. As, Cd, Pb, Cu, Zn), thereby posing a global environmental problem. For decades, microalgae have been used to remediate metal(loid)s in AMD, as they have various adaptive mechanisms for tolerating extreme environmental stress. Their main phycoremediation mechanisms are biosorption, bioaccumulation, coupling with sulfate-reducing bacteria, alkalization, biotransformation, and Fe/Mn mineral formation. This review summarizes how microalgae cope with metal(loid) stress and their specific mechanisms of phycoremediation in AMD. Based on the universal physiological characteristics of microalgae and the properties of their secretions, several Fe/Mn mineralization mechanisms induced by photosynthesis, free radicals, microalgal-bacterial reciprocity, and algal organic matter are proposed. Notably, microalgae can also reduce Fe(III) and inhibit mineralization, which is environmentally unfavorable. Therefore, the comprehensive environmental effects of microalgal co-occurring and cyclical opposing processes must be carefully considered. Using chemical and biological perspectives, this review innovatively proposes several specific processes and mechanisms of Fe/Mn mineralization that are mediated by microalgae, providing a theoretical basis for the geochemistry of metal(loid)s and natural attenuation of pollutants in AMD.


A behavioural method for accelerating re-entrainment of rhythms to new light-dark cycles.
The idea of ameliorating jetlag with drugs has received considerable attention. Melatonin has been found to reduce feelings of jetlag in people after transatlantic flights. In hamsters, injections of triazolam, a benzodiazepine, increase the rate of adjustment of activity rhythms to an 8 h advance of the light-dark (LD) cycle. But melatonin can make people drowsy and triazolam often induces hamsters to run in their wheels. Therefore, it is not clear whether these chemicals exert their chronotypic effects by acting directly on circadian pacemakers or because they first alter behavioural states. Non-photic behavioural events (for instance, social interactions) are capable of entraining rhythms and causing phase shifts. Thus, it is possible that behavioural events alone could alter the rate of adjustment to new LD cycles. To investigate this possibility, we studied the rate of re-entrainment of hamsters in a testing paradigm similar to that used with triazolam. We found that the rate of adjustment could be more than doubled simply by making the animals active on a single occasion in the middle of their normal rest period, immediately after the shift in the LD cycle.


Metagenomic insights into comparative study of nitrogen metabolic potential and microbial community between primitive and urban river sediments.
As a result of anthropogenic pollution, the nitrogen nutrients load in urban rivers has increased, potentially raising the risk of river eutrophication. Here, we studied how anthropogenic impacts alter nitrogen metabolism in river sediments by comparing the metagenomic function of microbial communities between relatively primitive and human-disturbed sediments. The contents of organic matter (OM), total nitrogen (TN), NO3--N and NO2--N were higher in primitive site than in polluted sites, which might be due to vegetation density, sediment type, hydrology, etc. Whereas, NH4+-N content was higher in midstream and downstream, indicating that nitrogen loading increased in the anthropogenic regions and subsequently leading higher NH4+-N. Hierarchical cluster analyses revealed significant changes in the community structure and functional potential between the primitive and human-affected sites. Metagenomic analysis demonstrated that Demequina, Streptomyces, Rubrobacter and Dechloromonas were the predominant denitrifiers. Ardenticatena and Dechloromonas species were the most important contributors to dissimilatory nitrate reduction. Furthermore, anthropogenic pollution significantly increased their abundance, and resulting in a decrease in NO3-, NO2--N and an increase in NH4+-N contents. Additionally, the SOX metabolism of Dechloromonas and Sulfuritalea may involve in the sulfur-dependent autotrophic denitrification process by coupling the conversion of thiosulfate to sulfate with the reduction of NO3--N to N2. From pristine to anthropogenic pollution sediments, the major nitrifying bacteria harboring Hao transitioned from Nitrospira to Nitrosomonas. This study sheds light on the consequences of anthropogenic activities on nitrogen metabolism in river sediments, allowing for better management of nitrogen pollution and eutrophication in river.


Licensing web-based nursing programs, courses, and course materials.
With the advent of the digital information age, schools of nursing are developing and using web-based programs, courses, and course materials to meet students' needs for access and high-quality learning experiences. In an attempt to maximize scant resources, including faculty, many schools are seeking grant funding, joining consortia, or forming partnerships that require sharing of web-based course materials. Entering such collaborative arrangements usually requires licensing agreements to transfer intellectual capital. This article explains licensing and the related concepts of intellectual property, copyright, and technology transfer. It also identifies the advantages and disadvantages of licensing and describes a licensing process.


Classification of functional near-infrared spectroscopy signals corresponding to the right- and left-wrist motor imagery for development of a brain-computer interface.
This paper presents a study on functional near-infrared spectroscopy (fNIRS) indicating that the hemodynamic responses of the right- and left-wrist motor imageries have distinct patterns that can be classified using a linear classifier for the purpose of developing a brain-computer interface (BCI). Ten healthy participants were instructed to imagine kinesthetically the right- or left-wrist flexion indicated on a computer screen. Signals from the right and left primary motor cortices were acquired simultaneously using a multi-channel continuous-wave fNIRS system. Using two distinct features (the mean and the slope of change in the oxygenated hemoglobin concentration), the linear discriminant analysis classifier was used to classify the right- and left-wrist motor imageries resulting in average classification accuracies of 73.35% and 83.0%, respectively, during the 10s task period. Moreover, when the analysis time was confined to the 2-7s span within the overall 10s task period, the average classification accuracies were improved to 77.56% and 87.28%, respectively. These results demonstrate the feasibility of an fNIRS-based BCI and the enhanced performance of the classifier by removing the initial 2s span and/or the time span after the peak value.


Experiences in the Family Health Strategy: demands and vulnerabilities in the territory.
To understand the daily demands of Family Health Strategy in clinical practice of the team and social vulnerabilities of community territory. Research with qualitative approach, in a critical-reflexive perspective, held with two teams of the Family Health Strategy, in the city of Fortaleza, State of Ceará, Brazil. The participants were 22 users and 19 health professionals from the basic health network. Data from the interviews and observation were analyzed under the assumptions of critical hermeneutics. We highlight the unveiling of sufferings and daily clashes, the influence of social determinants on health and psychosocial demands, limits and possibilities of everyday clinical practice. The clinic attention must recognize the perceptions and living conditions by listening and promoting health in the community. Compreender as demandas cotidianas da Estratégia Saúde da Família na prática clínica da equipe e as vulnerabilidades sociais do território comunitário. Pesquisa com abordagem qualitativa, numa perspectiva crítico-reflexiva, realizada com duas equipes da Estratégia Saúde da Família, no município de Fortaleza, Estado do Ceará, Brasil. Os participantes foram 22 usuários e 19 profissionais de saúde da rede básica de saúde. Os dados das entrevistas e observação foram analisados sob os pressupostos da hermenêutica crítica. Evidenciam-se o desvelamento de sofrimentos e enfrentamentos cotidianos, a influência dos determinantes sociais na saúde e as demandas psicossociais, limites e possibilidades da prática clínica cotidiana. Considera-se que a atenção clínica deve reconhecer as percepções e condições de vida pela escuta e ações de promoção de saúde na comunidade.


Core decompression in early stages of femoral head osteonecrosis--an MRI-controlled study.
We treated 45 hips with idiopathic necrosis of the femoral head stages I-III with core decompression. Average age of patients was 41 (27-68) years and average follow-up 68.9 (31-120) months. In 30 hip joints in stage I, 29 showed no radiographic progression and a complete remission of the changes consistent with necrosis on MRI at the last follow-up. In 27 patients the clinical result based on the Harris Hip Score (HHS) assessment--was excellent (average HHS 91.9 points). Of nine hips in stage II, four had received a total hip arthroplasty, one had deteriorated to stage IV, and four were still classified as stage II (average HHS 95 points). Of six hips in stage III, three had received a total hip arthroplasty and three had deteriorated to stage IV (average HHS 73 points).


Comparison of radiographic joint space width and magnetic resonance imaging for prediction of knee replacement: A longitudinal case-control study from the Osteoarthritis Initiative.
To evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement. Knees replaced between 36 and 60 months' follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI. Changes between the annual visit before replacement (T0) and 2 years before T0 (T-2) were compared using conditional logistic regression. One hundred and nineteen knees from 102 participants (55.5 % women; age 64.2 ± 8.7 [mean ± SD] years) were studied. Fixed-location JSW change at 22.5 % from medial to lateral differed more between replaced and control knees (case-control [cc] OR = 1.57; 95 % CI: 1.23-2.01) than minimum medial JSW change (ccOR = 1.38; 95 % CI: 1.11-1.71). Medial femorotibial cartilage loss displayed discrimination similar to minimum JSW, and central tibial cartilage loss similar to fixed-location JSW. Location-independent thinning and thickening scores were elevated prior to knee replacement. Discrimination of structural progression between knee pre-placement cases versus controls was stronger for fixed-location than minimum radiographic JSW. MRI displayed similar discrimination to radiography and suggested greater simultaneous cartilage thickening and loss prior to knee replacement. • Fixed-location JSW predicts surgical knee replacement more strongly than minimum JSW. • MRI predicts knee replacement with similar accuracy to radiographic JSW. • MRI reveals greater cartilage thinning and thickening prior to knee replacement.


Differential expression of RDC1/CXCR7 in the human placenta.
Chemokine receptor expression by human trophoblast and other placental cells have important implications for understanding the regulation of placental growth, development, and their role in maternofetal HIV transmission. CXCR7, now a deorphanized G protein coupled receptor that has been recently shown to bind to the ligands ITAC and CXCL12 has been proposed to act as a co-receptor for HIV-1, HIV-2, and SIV strains. The differential expression of CXCR7 in the human placenta is not yet reported. The expression of CXCR7 was studied in 45 different human placental tissues, of which 20 were from early placental tissues (8-10 week old) obtained from medically terminated pregnancies and 25 were placenta from normal term deliveries. Immunohistochemistry and RT-PCR analysis revealed a greater expression of CXCR7 in term human placenta as compared to the early stage. This was further confirmed by real-time PCR. Our study reveals, for the first time, the differential expression of CXCR7 in early (8-10 weeks) and term human placenta. The precise role of CXCR7 in the human placenta needs to be determined. HIV vertical transmission is reported to occur mainly during the end stages of pregnancy. Our finding of increased CXCR7 expression in the term human placenta therefore warrants future studies to assess its role in the vertical transmission of HIV-1.


Management of injection pain in children.
Researchers have come to understand a great deal about pain mechanisms, especially in the past 30 years. This understanding has spawned the development of a number of psychological pain control strategies which have been extensively assessed for use with adults. Less is known about pain control strategies in children. The purpose of this study was to assess the value of 2 cognitive strategies (suggestion and music distraction) in reducing pain in children. Two hundred children, aged 4.5-6.5 years, receiving routine immunization injections were randomly assigned to one of the intervention groups in this factorial study. The groups were designated as: distraction, distraction with suggestion, suggestion and control. Subjects reported their pain using a 4-point pain scale. Distraction was found to significantly decrease pain whereas suggestion did not. Combining suggestion and distraction did not further enhance pain relief compared to use of distraction alone. Age was found to be an important determinant of the success of distraction. Furthermore, age was found to be related to amount of pain reported by children regardless of type of treatment. The results of this study support the use of music distraction in the reduction of injection pain in children.


Dispensing practices for psychotropic medications amongst pharmacists in Karachi, Pakistan.
Uninformed use of medications can be dangerous especially those medications that require some level of monitoring to ensure safety and tolerability and prevent misuse, such as benzodiazepines and other psychotropic medications. In most developed countries, medications (except over-the-counter medications) are not dispensed without a physician's script. This may not be true for developing countries, like Pakistan, where nearly all medications are dispensed without a script. However, the extent and nature of script-less dispensing has never been studied. This study was designed to investigate the extent and prevalence of dispensing psychotropic medications without physicians' prescriptions, and the pharmacy practices, including the staff qualifications, to not only dispense but also recommend psychotropic medications, in Karachi, Pakistan. A Cross-sectional study was conducted in Karachi over three months (September 2021 to November 2021) with 200 pharmacists in various pharmacies, using a structured questionnaire in a convenient study sample. Pharmacists from registered pharmacies were included in the study. Statistical analysis was done using the Chi-Square test of association. Out of 200 pharmacists working at various locations, 89.0% did not required prescriptions to dispense medications, with benzodiazepines being the most frequently dispensed medication. Surprisingly, only 9.0% had a bachelor's in pharmacy and were qualified enough to legally dispense medications. 76.0% admitted to recommending medications to the patients. Since many of the pharmacists were not qualified enough to dispense medications, 78.5% mentioned that they did not had awareness regarding the abuse potential of psychotropic medications. Dispensing of psychotropic medications without prescriptions and recommending such medications has been a significant issue in the past. Our study reveals this practice to be prevalent in this part of the world, posing a serious threat to the patients. Steps should be taken by the government to ensure proper dispensing of these medications having an abuse potential to prevent harm.


Effects of long-term treatment with mizoribine in patients with proliferative lupus nephritis.
Mizoribine (MZR) is a purine antimetabolic immunosuppressant agent that has few little severe adverse events. We studied whether maintenance therapy with MZR and prednisolone (PSL) in severe proliferative lupus nephritis patients could improve immunity, reduce proteinuria, prevent renal relapse, and reduce steroid dose. Long-term maintenance therapy with MZR and PSL was evaluated in ten patients with biopsy-proven proliferative lupus nephritis. Patients with severe lupus nephritis, who had proteinuria of 0.5 g or more even after treatments with plasma exchange and/or pulse methyl prednisolone, were recruited. MZR at an average dose of 140 +/- 10 (100 - 200) mg was administered two to three times/day in combination with PSL. The average period for the MZR maintenance therapy was 89.7 +/- 5.5 (70 - 126) months. Urine protein excretion, serum hemolytic complement activity (CH50), C3, serum creatinine, general and biochemical blood examinations, anti-ds-DNA antibody were collected at each monthly medical examination. All patients were females, mean age 43.0 +/- 3.3 years. A significant decrease in proteinuria was noted two years after the combination therapy (p = 0.0016). Five patients experienced lupus nephritis relapse. Patients who did not experience relapses had their MZR combination therapy initiated earlier (p = 0.037) when compared with the patients who experienced relapses. Serum creatinine levels remained unchanged in all patients throughout treatment and follow-up, even during renal relapses. Levels of C3 and CH50 normalized as proteinuria decreased. None of the patients developed serious side effects during MZR treatment. A significant steroid-sparing effect was observed three years after initiating MZR (p = 0.0025). From our long-term observation, maintenance therapy with low-dose PSL combined with MZR can eliminate proteinuria and have steroid-sparing effect. Early initiation of the therapy can protect against renal relapses among severe proliferative lupus nephritis patients without serious side effects.


Therapy of sinuorbital aspergillosis with amphotericin B colloidal dispersion.
Invasive aspergillosis is a feared complication in the management of patients with malignancies. We report a 13-year-old boy with acute myelogenous leukaemia and chronic sinusitis who developed a sinuorbital fungal infection during cytostatic and prolonged antibiotic treatment. The clinical findings, diagnostic measures and treatment and its adverse effects are described and discussed. Special emphasis is given to our experience of the use of colloidal dispersed amphotericin B (Amphocil).


Two-year drinking-water study of formaldehyde in rats.
Formaldehyde was administered in the drinking-water to groups of 70 male and 70 female Wistar rats for up to 24 months. Survivors of subgroups of ten rats/sex/group each were killed after 12 or 18 months. The mean formaldehyde doses administered were 0, 1.2, 15 or 82 mg/kg body weight/day for males, and 0, 1.8, 21 or 109 mg/kg/day for females. There were no adverse effects on general health, survival or haematological or clinical chemistry parameters. Body weight and food intake were decreased in the high-dose group. Liquid intake was decreased by 40% in the high-dose group in both sexes in comparison with the controls. There was a slight temporary increase in the density of urine, whereas there was a tendency towards lower urine production in the high-dose group. The relative kidney weights were increased in the high-dose females. Gross examination at autopsy revealed a raised and thickened limiting ridge of the forestomach in most high-dose rats. In addition, several rats in the high-dose group showed irregular mucosal thickenings in the fore- and/or glandular stomach. Treatment-related histopathological gastric changes seen in most of the animals of the high-dose group included papillary epithelial hyperplasia frequently accompanied by hyperkeratosis and focal ulceration in the forestomach and focal chronic atrophic gastritis, occasionally accompanied by ulceration and/or glandular hyperplasia, in the glandular stomach. A higher incidence and/or degree of renal papillary necrosis occurred in the high-dose rats. From this study it appeared that the 'no-observed-adverse-effect level' of formaldehyde was 15 and 21 mg/kg body weight/day for male and female rats, respectively. Oral administration of formaldehyde at doses of 82 and 109 mg/kg/day to male and female rats, respectively, caused severe damage to the gastric mucosa but did not result in gastric tumours or tumours at other sites. The study did not provide any evidence of carcinogenicity of formaldehyde after oral administration.


Vasopressin-neurophysin and DST in major depression: relationship with suicidal behavior.
The purpose of the present study was to assess if AVP-neurophysin is associated with hypercortisolemia and suicidal behaviour in depressed patients. The study included 28 patients subgrouped into suicide attempters (n=13) and nonattempters (n=15). We assessed basal AVP-neurophysins concentrations and post-dexamethasone (DST) cortisol levels. Concentrations of AVP-neurophysins did not differ between DST suppressors and nonsuppressors: 0.29+/-0.13 ng/ml vs 0.36+/-0.21 ng/ml, (F=1.1, df=1, 27, p=0.30). Suicide attempters did not differ from nonattempters for AVP-neurophysins levels. Our results fail to support a role of AVP in the early cortisol escape.


Are Eating Disorders Related to Attention Deficit/Hyperactivity Disorder?
Attention deficit/hyperactivity disorder (ADHD) is a disorder characterized by impulsivity, hyperactivity, and inattention. Binge-eating behavior is often impulsive and is the hallmark of the two eating disorders, binge-eating disorder (BED) and bulimia nervosa (BN), both of which are associated with significant health impairment. Bingeing behavior is also seen in the binge purge subtype of anorexia nervosa. Individuals with AN of the binge purge subtypes, BN and BED, have been found to exhibit impulsive behaviors that are often not limited to binge eating alone. There is preliminary evidence linking ADHD to BN and to BED in both adults and children. The neurobiological mechanisms behind these associations are only beginning to emerge; however, they suggest that impulse control deficits may play a role in these eating disorders. Additionally, although they may not meet full criteria for one of these eating disorders, some adults and children with ADHD present with dysregulated, impulsive eating disorder behaviors and there is a growing association between ADHD, obesity, and binge-eating behavior in both children and adults. The relationship between ADHD and binge eating is novel, supported by growing evidence and worthy of further research. We will review the underlying neurobiological underpinnings, neuroimaging data, and possible psychopharmacological treatment options, which target both ADHD and binge-eating behaviors as well as future research and treatment directions.


External food cue responsiveness and emotional eating in adolescents: A multimethod study.
Eating in response to external food cues (i.e., external eating) and internal emotional experiences (i.e., emotional eating) are associated with obesity. While external and emotional eating co-occur, little is known about how external food cue responsiveness may interact with internal emotional cues to influence eating episodes in adolescents. The current study examined how trait-level external food cue responsiveness modulates momentary associations between affective states and eating in adolescents. Participants were drawn from a prior study of siblings (N = 78; ages 13-17) who completed an ecological momentary assessment protocol to assess eating episodes and affective states. External food cue responsiveness was determined by comparing energy consumption following presentation of an appetizing food (pizza) on one day and a control activity (reading) on another day. Generalized linear mixed models examined positive and negative affective states, cue responsiveness, and their interactions as predictors of the likelihood of eating. The relationship between affective states and likelihood of eating was stronger among adolescents with higher versus lower external food cue responsiveness. Among adolescents with higher cue responsiveness, endorsing negative affect was associated with a lower likelihood of eating, whereas endorsing positive affect was associated with a higher likelihood of eating (within-person effects). Findings suggest that high sensitivity to external food cues and greater proclivity for emotional eating may be likely to coincide such that any cue, internal or external, is likely to disrupt sensitivity to internal hunger and satiety signals. Future studies are needed to elucidate how sensitivities to internal and external cues may interact to influence obesity risk.


Risk factors for recollapse of new vertebral compression fractures after percutaneous kyphoplasty in geriatric patients: establishment of a nomogram.
The main objective of this study was to investigate the risk factors for recollapse of new vertebral compression fractures (NVCFs) after percutaneous kyphoplasty (PKP) treatment for osteoporotic vertebral compression fracture (OVCF) and to construct a new nomogram model. We retrospectively analysed single-level OVCFs from January 2017 to June 2020, randomizing patients to a training set and a testing set. In the training set, independent risk factors for NVCFs in OVCF patients treated with PKP were obtained by univariate and multivariate regression analyses. These risk factors were then used as the basis for constructing a nomogram model. Finally, internal validation of the built model was performed in the testing set using the consistency index (C-index), receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). In total, 371 patients were included in this study. NVCFs occurred in 21.7% of the training set patients, and multivariate regression analysis showed that a low Hounsfield unit (HU) value, cement leakage, and thoracolumbar (TL) junction fracture were independent risk factors for NVCF after PKP. The C-index was 0.81 (95% CI: 0.74-0.81), and the validation showed that the predicted values of the established model were in good agreement with the actual values. In this study, three independent risk factors were obtained by regression analysis. A nomogram model was constructed to guide clinical work and to make clinical decisions relatively accurately to prevent the occurrence of vertebral recollapse fractures.


Breast cancer stem cells and tumor suppressor genes.
Studies of breast cancer stem cells are in their infancy and many fundamental questions have yet to be fully addressed. The molecular distinction between normal and cancerous breast stem cells is not clear. While there have been recent breakthroughs in mouse mammary stem cells and lineage determination in mammary glands, little has been determined in human cells. Microarray analyses have provided molecular categorization of breast cancer. However, the cellular origin of different types of breast cancer is largely unknown. In addition, the relationship between breast cancer stem cells and mammary progenitor cells has yet to be clarified. One of the key questions is how a normal mammary stem cell becomes a breast cancer stem cell. Importantly, the existence of different types of human breast cancers with distinct pathologic and molecular signatures suggests the possibility that different types of breast cancer stem cells may exist. Here, we aim to review the current evidence for the existence of different subtypes of breast cancer stem cells and provide further insight into how tumor suppressors might be involved in the initiation of breast cancer stem cells.


Double network oleogels co-stabilized by hydroxypropyl methylcellulose and monoglyceride crystals: Baking applications.
Edible double network oleogels were prepared by hydroxypropyl methylcellulose (HPMC) and glyceryl monostearate (GMS) by the cryogel-templated method. Hot GMS soybean oil solutions were absorbed by HPMC cryogels, which were further homogenized and cooled to form oleogels containing both the HPMC network and GMS network. The crystal network constructed by GMS crystal clusters significantly enhanced the mechanical and rheological attributes of oleogels. Both the HPMC network and the GMS network were built up due to hydrogen bonds. According to the normalization analysis of FTIR and the deepening of the shift of the absorption peak, hydrogen bonds could also be formed between HPMC and GMS to connect the two independent networks. Double network oleogels were further used to fabricate cookies and cakes, assessed by the texture profile analysis. The combination of the HPMC network and GMS network in preparing oleogels will promote the application of oleogels as the fat replacer.


Influence of multi valent states of vanadium ions in ZnO doped novel calcium fluoro phosphate bio glasses.
ZnO-CaF2-P2O5 glasses doped with different concentrations of V2O5 (ranging from 0 to 1.0 mol %) were prepared. The prepared bio glasses are soaked in SBF for duration of 2, 3, 7 and 10 days in separate plastic containers and then kept in incubator maintained at body temperature 36.5 °C. The influence of valence states of vanadium ions (V4+/V5+) with respect to the structural aspects by means of FTIR and Raman Spectra, elastic properties by means of relevant parameters, the thermal stability by means of DTA studies and other spectroscopic properties by using OA and ESR studies are studied. The raise in wavenumber and comparative areas of the two absorption bands corresponding to electronic transitions 2B2g → E2g, 2B2g → 2B1g respectively in optical absorption spectra of these CZPV glasses clearly indicate that vanadium ions have octahedral co-ordination with tetragonal compression due to modifier action of V2O5in the glass network. The optical absorption and ESR studies have revealed that vanadium ions exist in V4+ states. The characteristic temperatures of these prepared glasses obtained from DTA curves explain modifications taking place in the structure of glass network. The structural changes are explained with the aid of FTIR and Raman studies. The bio active nature of the titled glasses is evident from dissociation and pH studies by SEM &EDS of these glasses before and after immersion into SBF.


Identification of clandestine groundwater pollution sources using heuristics optimization algorithms: a comparison between simulated annealing and particle swarm optimization.
Groundwater pollution is the biggest threat to sustainability of groundwater resources and even more difficult to detect in case of clandestine sources. At the time when pollution is first detected in randomly located sparse wells, very little is known about the pollution sources. Finding the precise locations of clandestine sources of pollution and their release flux history is the biggest challenge and often termed as a problem belonging to the class of environmental forensics. In this study, two linked simulation optimization-based novel techniques are developed to estimate locations and release flux history from clandestine point sources of groundwater pollution. Simulation model is clubbed with optimization solver to determine the locations and release flux histories of groundwater pollution sources by minimizing the residual error between observed and simulated concentration values. Simulated annealing (SA) and particle swarm optimization (PSO) are used as optimization algorithms. A detailed comparative analysis of these two meta-heuristic optimization algorithms in minimizing the residual error is presented in this study. The performance evaluation of both the algorithms in identifying the sources locations and release flux history is carried out for two synthetic cases and a real-life scenario of groundwater pollution in an aquifer in New South Wales, Australia, which has not been attempted in the past. The results of source location identification and release flux history show the selective applicability of each algorithm in solving real-life scenarios of groundwater pollution.


Complete Genome Sequence and Methylome of Staphylococcus schleiferi, an Important Cause of Skin and Ear Infections in Veterinary Medicine.
Staphylococcus schleiferi, a Gram-positive and coagulase-variable organism, is an opportunistic human pathogen and a major cause of skin and soft tissue infections in dogs. Here, we report the first S. schleiferi genome sequence and methylome from four canine clinical isolates.


Linear and whorled naevoid hypermelanosis: a case with systemic involvement and trisomy 18 mosaicism.
We describe a 20-year-old woman with trisomy 18 mosaicism, who presented with skeletal anomalies, epilepsy, mental retardation, and linear and whorled naevoid hypermelanosis.


Sustained benefits of autologous serum eye drops on self-reported ocular symptoms and vision-related quality of life in Australian patients with dry eye and corneal epithelial defects.
This research examined the effect of autologous serum eye drops (ASED) on ocular symptoms, visual-related functioning and quality of life for patients failing other therapies. Patients (N = 77) were asked to complete a survey prior to ASED use, and 2 and 12 months post-treatment. Significant improvements in symptom frequency and severity were documented for dryness, ocular pain and grittiness at 2 and 12 months. Patients felt more in control and required less help from others at 12 months. ASED produce sustained benefits to dry eye symptoms, improve feelings of control and reduce requirements for assistance from others.


The Role of Topiramate in the Management of Cocaine Addiction: a Possible Therapeutic Option.
Topiramate (TPM) is an antiepileptic drug able to play a role in both neurological and psychiatric disorders. TPM facilitates gamma-aminobutyric acid (GABA) transmission and inhibits glutamatergic transmission (i.e. AMPA/kainate receptors). Several studies reported that the modulation of GABAergic and glutamatergic synaptic transmission may reduce cocaine reinforcement. Therefore, TPM could be used in the management of cocaine dependence.


Efficacy of Percutaneous Coronary Intervention With Synergy Stents in Patients Aged ≥75 Years: 1-Year Clinical Outcomes from the Synergy Elderly Registry.
Data regarding the clinical outcomes of older patients after Synergy everolimus-eluting stent (S-EES) implantation are limited. This study investigated the 12-month clinical outcomes of older patients who underwent percutaneous coronary intervention with new-generation drug-eluting stents according to ischemic risks. This prospective multicenter study targeted patients aged ≥75 years who underwent S-EES implantation. The primary and secondary end points included 12-month device-oriented composite end point (DOCE) (cardiovascular death, target vessel myocardial infarction, or target lesion revascularization) and major adverse cardiac and cerebrovascular events (MACCEs; all-cause death, myocardial infarction, target vessel revascularization, stent thrombosis, or stroke), respectively. A stratified analysis was conducted according to high-ischemic risk (HIR), defined as complex coronary intervention (number of stents implanted ≥3, total stented length >60 mm, chronic total occlusion, left main, or bifurcation), diabetes, or chronic kidney disease. In total, 650 enrolled patients aged ≥75 years were categorized into HIR (n = 425) and non-HIR groups (n = 225). In the total population, the 1-year incidence of DOCEs was 2.5%. The rates of DOCEs were not significantly different between the HIR and the non-HIR groups, whereas the MACCE rate was higher in the HIR (9.4%) than the non-HIR group (4.9%, p = 0.035), and the DOCE and MACCE components did not differ significantly in the occurrence between the groups. The independent predictors for the DOCEs or MACCEs included age, anemia, or left ventricular ejection fraction <40%. In conclusion, in older patients, S-EES implantation demonstrated favorable device-related outcomes, regardless of procedural complexity or co-morbidities. However, it requires careful attention because older patients with HIR are associated with worse clinical outcomes.


Acid-base and hematological regulation in chicken embryos during internal progressive hypercapnic hypoxia.
Development of the capacity to mitigate potential disturbances to blood physiology in bird embryos is incompletely understood. We investigated regulation of acid-base and hematology in day 15 chicken embryos exposed to graded intrinsic hypercapnic hypoxia created by varying degrees of water submersion. Metabolic acidosis with additional respiratory or metabolic acidosis occurred at 2 h according to magnitude of submersion. Acid-base disturbance was partially compensated by metabolic alkalosis at 6 h, but compensatory metabolic alkalosis was absent at 24 h. Following submersion with only air cell exposed to air, both hypercapnic respiratory acidosis and metabolic acidosis occurred within 10 min. Subsequently, both forms of acidosis created lethal levels of [HCO3-] at ∼120 min. Blood hematology showed small but significant effects associated with induced acid-base disturbance. Increased Hct occurring during partial egg submersion lasting 24 h was attributed to an increase in MCV. By day 15 of development chicken embryos are able to partially compensate for and withstand all but severe induced internal hypoxic hypercapnia.


Biowaste upcycling into second-generation microbial protein through mixed-culture fermentation.
Securing a sustainable protein supply at the global level is among the greatest challenges currently faced by humanity. Alternative protein sources, such as second-generation microbial protein (MP), could give rise to innovative circular bioeconomy practices, synthesizing high-value bioproducts through the recovery and upcycling of resources from overabundant biowastes and residues. Within such a multi-feedstock biorefinery scenario, the wide range of microbial pathways and networks that characterize mixed microbial cultures, offers interesting and not yet fully explored advantages over conventional monoculture-based processes. In this review, we combine a comprehensive analysis of waste recovery platforms for second-generation MP production with a critical evaluation of the research gaps and potentials offered by mixed culture-based MP fermentation processes.


Abemaciclib does not increase the corrected QT interval in healthy participants.
Abemaciclib is an orally administered, potent, and selective small molecule inhibitor of cyclin-dependent kinases 4 and 6, approved for advanced or metastatic breast cancer. This study aimed to use an exposure-response approach to investigate the effect of abemaciclib and its active metabolites (M2 and M20) on QTc interval and delay in cardiac repolarization at clinically relevant exposures. This was a single-blind, randomized, and placebo-controlled study of ascending doses of abemaciclib. Thirty-five healthy participants were administered a single dose of 200-600 mg abemaciclib. Twelve-lead electrocardiogram tracings and pharmacokinetic samples were collected serially pre- and post-dose. The primary objective was to study the relationship between abemaciclib and its active metabolites (M2 and M20) and QTc interval following ascending oral doses of abemaciclib. The secondary objective included evaluating the safety and tolerability of single ascending doses of abemaciclib in healthy participants. Exposure-response analysis demonstrated that there was no significant relationship between placebo-corrected change from baseline QTcF (ΔΔQTcF), abemaciclib, and metabolite plasma concentrations. Additionally, the ΔΔQTcF slopes of abemaciclib, its metabolites, and total analyte concentrations were not statistically different from zero. Single doses of abemaciclib, up to 400 mg, were well-tolerated by healthy participants; however, at the 600 mg dose (three times the highest registered dose), the frequency and severity of treatment-related gastrointestinal events (primarily diarrhea, nausea, and vomiting) increased. In conclusion, single doses of abemaciclib, up to 400 mg, had no statistically or clinically relevant effects on QTc, and abemaciclib was well tolerated up to a dose of 400 mg in this study.


Grin1 deletion in CRF neurons sex-dependently enhances fear, sociability, and social stress responsivity.
The corticotropin releasing factor (CRF) system plays a critical role in responses to stressful stimuli, and is expressed in many areas of the brain involved in processing fear, anxiety, and social behaviors. To better understand the mechanisms by which the CRF system modulates responses to stressful events and social stimuli, we employed a mouse model that selectively disrupts NMDA receptor function via NMDA receptor subunit NR1 (Grin1) knockout specifically in Cre-expressing CRF neurons. These animals (Cre+/(fGrin1+)) were compared with littermates lacking Cre expression (Cre-/(fGrin1+)). Following cue discrimination fear conditioning, male Cre+/(fGrin1+) mice showed increased fear expression to the tone paired with a foot shock (CS+) while still discriminating the CS+ from a tone never paired with a foot shock (CS-). In contrast to males, female mice learned and discriminated fear cues equivalently across the genotypes. Similarly, no genotype differences in sociability or social novelty were observed in female mice, but Cre+/(fGrin1+) males displayed greater naive sociability and preference for social novelty than Cre-/(fGrin1+) littermates. Furthermore, the level of social withdrawal exhibited by male Cre+/(fGrin1+) mice susceptible to social defeat stress relative to same genotype controls was significantly more pronounced than that displayed by susceptible Cre-/(fGrin1+) mice compared to control Cre-/(fGrin1+) mice. Together, these results demonstrate increased fear, social, and stress responsiveness specifically in male Cre+/(fGrin1+) mice. Our findings indicate that NMDA-mediated glutamatergic regulation of CRF neurons is important for appropriately regulating fear and social responses, likely functioning to promote survival under aversive circumstances.


Efficiency and limits of the Serial Analysis of Gene Expression (SAGE) method: discussions based on first results in bovine trypanotolerance.
Post genomic biotechnologies, such as transcriptome analysis, are now efficient enough to characterize the full complement of genes involved in the expression of specific biological functions. One of them is the Serial Analysis of Gene Expression (SAGE) technique. SAGE involves the construction of transcript libraries for a quantitative analysis of the entire set of genes expressed or inactivated at particular stages of cellular activation. Bioinformatic comparisons in hosts and pathogens genomic databases allow the identification of several up- and down-regulated genes, ESTs and unknown transcripts directly involved in the host-pathogen immunological interaction mechanisms. Based on the first results obtained during an experimental Trypanosoma congolense infection in trypanotolerant cattle, the efficiency and limits of such a technique, from the data acquisition level to the data analysis level, is discussed in this analysis.


Lower Rates of Femoral Fracture and Subsidence with a Morphometric Stem in Cementless Total Hip Arthroplasty.
A "morphometric" tapered femoral stem with size-specific medial curvatures and proportional neck lengths was introduced, attempting to improve fixation and biomechanics in cementless total hip arthroplasty (THA) across a range of femoral sizes and morphotypes. We investigated whether this design reduced complications and better restored anatomy (e.g., limb length and offset) compared to a traditional tapered stem with consistent neck lengths across sizes. We reviewed 389 THAs (340 patients) performed using either of two cementless femoral implants. Records were reviewed for demographics, surgical details, complications, and reoperations. Radiographs were examined for subsidence, biologic fixation, leg lengths, offset, and proximal femoral morphology. The intraoperative fracture rate was lower with this morphometric stem compared to this traditional stem (0 vs. 3.4%), as was the incidence of postoperative subsidence ≥3mm (4.7 vs. 19.2%). With the numbers available, no differences were identified regarding rates of reoperation for periprosthetic femur fracture (0 vs. 1.0%) and femoral fixation failure without fracture (1.1 vs. 0%), or all-cause reoperations (2.7 vs. 2.4%). Limb length and offset restoration were similar with the two implants, but the shortest available femoral head was used less frequently with this morphometric stem compared to this traditional stem (22 vs. 54%). This morphometric stem was associated with decreased rates of intraoperative fracture and postoperative subsidence, along with decreased use of the shortest available head. Nevertheless, both implants demonstrated clinical success, allowing reconstruction of limb length and offset with low rates of femoral fixation failure.


On generalized photocurrent spectral moments and the recovery of speed distribution in laser Doppler flowmetry.
Laser Doppler flowmetry (LDF) is a noninvasive method to assess tissue blood flow. By calculating the first moment of the Doppler signal power spectral density, a real-time output is generated that scales linearly with the perfusion flux defined as the product of average speed and concentration of moving blood cells (MBC's) if multiple scattering is negligible. However, this first spectral moment alone is apparently deficient to provide further information about the MBC's under study and therefore unable to answer more intricate questions in LDF. Without assuming any specific MBC speed or scattering vector distribution, a generalized formula for photocurrent spectral moments is first derived in the case of low and moderate MBC concentration. Then as a direct and important use of the formula, the speed distribution of MBC's is obtained via Henyey-Greenstein phase function and a Fourier inversion. The important implications and applications of this formulation in extracting more MBC information are discussed together with some other related issues.


Factors influencing healthy aging with multiple sclerosis: a qualitative study.
The purpose of this study was to describe the factors influencing healthy aging from the perspective of the older person with multiple sclerosis (MS) in order to build curricula for MS self-management programs. We sourced participants, older than 55 years with MS for more than 20 years, from a database of MS clinic and outpatient rehabilitation visits. Recruitment continued until data saturation was reached (n = 18). Semi-structured interviews explored perspectives on aging and health and lifestyle habits. Demographic, lifestyle and perceived health status information was also gathered. We analyzed the transcribed text for themes and theme relationships. Work and social engagement, effective and accessible health care, healthy lifestyle habits, and maintaining independence at home were found to be critical proximal factors for healthy aging. The presence of financial flexibility, social support, cognitive and mental health, and resilience provided a supporting foundation to these critical proximal factors. These factors comprised a two-tiered model of healthy aging with MS. This two-tiered conceptual model of health aging, based on the perspectives of older persons with MS, provides a potential framework for the development of MS self-management program curricula aimed at optimizing quality of life. Further empirical testing may validate its utility in predicting healthy aging with MS.


Effect of phosphate on the kinetics and specificity of glycation of protein.
The glycation (nonenzymatic glycosylation) of several proteins was studied in various buffers in order to assess the effects of buffering ions on the kinetics and specificity of glycation of protein. Incubation of RNase with glucose in phosphate buffer resulted in inactivation of the enzyme because of preferential modification of lysine residues in or near the active site. In contrast, in the cationic buffers, 3-(N-morpholino)propane-sulfonic acid and 3-(N-tris(hydroxymethyl)methyl-amino)-2-hydroxypropanesulfonic acid, the kinetics of glycation of RNase were decreased 2- to 3-fold, there was a decrease in glycation of active site versus peripheral lysines, and the enzyme was resistant to inactivation by glucose. The extent of Schiff base formation on RNAse was comparable in the three buffers, suggesting that phosphate, bound in the active site of RNase, catalyzed the Amadori rearrangement at active site lysines, leading to the enhanced rate of inactivation of the enzyme. Phosphate catalysis of glycation was concentration-dependent and could be mimicked by arsenate. Phosphate also stimulated the rate of glycation of other proteins, such as lysozyme, cytochrome c, albumin, and hemoglobin. As with RNase, phosphate affected the specificity of glycation of hemoglobin, resulting in increased glycation of amino-terminal valine versus intrachain lysine residues. 2,3-Diphosphoglycerate exerted similar effects on the glycation of hemoglobin, suggesting that inorganic and organic phosphates may play an important role in determining the kinetics and specificity of glycation of hemoglobin in the red cell. Overall, these studies establish that buffering ions or ligands can exert significant effects on the kinetics and specificity of glycation of proteins.


Patch clamp experiments on nicotinic acetylcholine receptor-ion channels in bullfrog sympathetic ganglion cells.
Nicotinic acetylcholine-receptor ion channels (AChR channels) were studied in bullfrog sympathetic ganglion cells cultured for 1 day to 3 weeks, using a patch clamp technique. Microsuperfusion of ACh (2-10 microM) to the ganglion cell under the whole cell clamp produced an inward current at membrane potentials negative to -60 mV, which had a fast onset and decay. This rapid ACh-induced current was accompanied by a large current fluctuation, decreased and increased in amplitude by membrane depolarization and hyperpolarization, respectively, and blocked by d-tubocurarine. Thus, this current must be induced by the nicotinic action of ACh, but not by a muscarinic effect to activate a slow cation-selective current. At depolarized levels more than -50 mV, ACh induced an additional inward current which was slow in time course, accompanied by no or decreased current fluctuation and increased in amplitude by membrane depolarization. Accordingly, this slow ACh-induced current could result from the suppression of a voltage-dependent K+ current (M-current: Brown and Adams 1980) by the muscarinic action of ACh. Fluctuation analysis of the rapid ACh-induced current at potentials negative to -50 mV revealed the elementary conductance of 14 pS and a power spectral density distribution of the double Lorentzian function which yielded the time constants of 5.4 and 62.5 ms at -60 to -80 mV. The variance of either component was independent of the mean current.


Changes in expression of a synaptic vesicle antigen in aging sympathetic neurons.
The effects of altering synaptic activity of sympathetic neurons on the expression of a synaptic vesicle protein (p65) were studied by deafferentation of the superior cervical ganglion (SCG) in adult and aged Fischer-344 rats. Levels of p65, an integral membrane protein of synaptic vesicles, were assayed by radioimmunoassay. After deafferentation, a transient increase in p65 levels is observed in the SCG of adult rats. In aged animals, the response to deafferentation is delayed and enhanced, and levels do not drop to values observed in operated adults. After SCG deafferentation, p65 levels in the iris, an SCG target, initially are depressed below control levels; p65 levels return to control values in adult animals after 14 days, but remain depressed in aged animals. In contrast, a transient increase in p65 levels is observed in the pineal of both adult and aged animals. These results suggest that while the aged sympathetic nervous system retains the ability to respond to alterations in synaptic activity, it is unable to reregulate once a response is initiated.


Recombinant truncated tilapia growth hormone enhances growth and innate immunity in tilapia fry (Oreochromis sp.).
Pichia pastoris cells transformed with a plasmid engineered for the expression of tilapia growth hormone as a secreted product produced a proteolytically cleaved form of the recombinant protein. The sequence of this truncated variant was obtained by mass spectrometry analysis. The cleavage site was determined to be between residues Tyr 158 and Tyr 159. The resulting truncated tilapia growth hormone was a single chain protein lacking 46 amino acids of the C-terminal portion. In this study, we showed that the truncated growth hormone produced in the P. pastoris culture supernatant has growth promoting effects and stimulates innate immune parameters (lysozyme and lectins) in tilapia larvae. These results suggest that the C-terminal portion of growth hormone is not required for its growth promoting activity and the innate immune functions studied herein in fish. In addition, we found that the culture supernatant containing truncated tilapia growth hormone has a stronger effect over growth and immune system than cells lysate containing intact tilapia growth hormone expressed in P. pastoris.


[Changes in pelvic organ mobility and ligamentous laxity during pregnancy and postpartum. Review of literature and prospects].
The role of pregnancy in pelvic floor disorders occurrence remains poorly known. It might exist a link between changes in ligamentous laxity and changes in pelvic organ mobility during this period. Our objective was to conduct a non-systematic review of literature about changes in pelvic organ mobility as well as in ligamentous laxity during pregnancy and postpartum. From the PubMed, Medline, Cochrane Library and Web of Science database we have selected works which pertains clinical assessment of pelvic organ mobility (pelvic organ prolapse quantification), ultrasound assessment of levator hiatus and urethral mobility, ligamentous laxity assessment during pregnancy and postpartum. Clinical assessments performed in these works show an increase of pelvic organ mobility and perineal distension during pregnancy followed by a recovery phase during postpartum. Pelvic floor imaging shows an increase of levator hiatus area and urethral mobility during pregnancy then a recovery phase in postpartum. Different authors also report an increase of ligamentous laxity (upper and lower limbs) during pregnancy followed by a decrease phase in postpartum. Pelvic organ mobility, ligamentous laxity, levator hiatus and urethral mobility change in a similarly way during pregnancy (increase of mobility or distension) and postpartum (recovery). 3.


6,6'-Di-tert-butyl-4,4'-dimethyl-2,2'-[1,2-phenyl-enebis(nitrilo-methanylyl-idene)]diphenol.
In the title mol-ecule, C(30)H(36)N(2)O(2), the dihedral angles between the central benzene ring and the two benzene rings of the butyl-salicylaldimine groups are 14.3 (2) and 40.6 (2)°. There are two strong intra-molecular O-H⋯N hydrogen bonds which form S(6) rings. The crystal studied was a non-merohedral twin with refined components of 0.270 (4) and 0.730 (4).