Why may allopregnanolone help alleviate loneliness?
Impaired biosynthesis of Allopregnanolone (ALLO), a brain endogenous neurosteroid, has been associated with numerous behavioral dysfunctions, which range from anxiety- and depressive-like behaviors to aggressive behavior and changes in responses to contextual fear conditioning in rodent models of emotional dysfunction. Recent animal research also demonstrates a critical role of ALLO in social isolation. Although there are likely aspects of perceived social isolation that are uniquely human, there is also continuity across species. Both human and animal research show that perceived social isolation (which can be defined behaviorally in animals and humans) has detrimental effects on physical health, such as increased hypothalamic pituitary adrenal (HPA) activity, decreased brain-derived neurotrophic factor (BDNF) expression, and increased depressive behavior. The similarities between animal and human research suggest that perceived social isolation (loneliness) may also be associated with a reduction in the synthesis of ALLO, potentially by reducing BDNF regulation and increasing HPA activity through the hippocampus, amygdala, and bed nucleus of the stria terminalis (BNST), especially during social threat processing. Accordingly, exogenous administration of ALLO (or ALLO precursor, such as pregnenolone), in humans may help alleviate loneliness. Congruent with our hypothesis, exogenous administration of ALLO (or ALLO precursors) in humans has been shown to improve various stress-related disorders that show similarities between animals and humans i.e., post-traumatic stress disorders, traumatic brain injuries. Because a growing body of evidence demonstrates the benefits of ALLO in socially isolated animals, we believe our ALLO hypothesis can be applied to loneliness in humans, as well.


Hepatitis C virus (HCV) genotyping by annealing reverse transcription-PCR products with genotype-specific capture probes.
The genotype of the hepatitis C virus (HCV) strain infecting a given patient is an important predictive factor for the clinical outcome of chronic liver disease and its response to anti-viral therapeutic agents. We herein sought to develop a new easy, sensitive and accurate HCV genotyping method using annealing genotype-specific capture probes (AGSCP) in an automation-friendly 96-well plate format. The validation of our new AGSCP was performed using the Standard HCV Genotype Panel. We then used both our AGSCP and the commercially available INNO-LiPA assay to analyze the HCV genotypes from 111 Korean patients. Discordant results were analyzed by direct sequencing. AGSCP successfully genotyped the standard panel. The genotypes of 111 patient samples were also obtained successfully by AGSCP and INNO-LiPA. We observed a high concordance rate (93 matched samples, 83.8%) between the two assays. Sequencing analysis of the 18 discordant results revealed that the AGSCP had correctly identified 12 samples, whereas the INNO-LiPA had correctly identified only 6. These results collectively indicate that AGSCP assay is a convenient and sensitive method for large-scale genotyping, and it may be a promising tool for the determination of HCV and other genotypes in clinical settings.


Heterogeneity of specific-IgE responses in workers sensitized to acid anhydride compounds.
Acid anhydride compounds cause IgE-mediated respiratory sensitization in the workplace. In this study reaginic responses in four workers sensitized to phthalic anhydride (PA), hexahydrophthalic (HHPA), or himic anhydride (HA) were determined by direct RAST by use of PA-human serum albumin (HSA), HPPA-HSA, and HA-HSA methylcellulose disc substrates. RAST inhibition of binding to anhydride-HSA substrates was done with various concentrations of sodium salts, lysine, and HSA conjugates of PA, HHPA, HA, and trimellitic anhydride (TMA) in order to characterize cross-reactivity and specificity of humoral responses in these workers. Molar concentrations of anhydride bound to lysine and HSA carriers were assayed by protein hydrolysis followed by gas chromatographic analysis. Significant direct RAST binding against PA-HSA, HHPA-HSA, and HA-HSA was found in all four workers. PA-HSA-IgE binding in one PA-sensitive worker (no. 1) was inhibited significantly by PA-HSA alone and not by sodium PA or PA lysine. In contrast, another PA-sensitized worker (no. 2) exhibited 50% inhibition of PA-HSA binding by PA-HSA (1 X 10(-9) M), PA-lysine (7 X 10(-8) M), and NaPA (1 X 10(-7) M); no inhibition of PA-HSA by heterologous HHPA-, HA-, or TMA-inhibitory reagents was found in either of the PA workers. RAST binding to HHPA-HSA in the HHPA-sensitive worker was inhibited by HHPA-HSA alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Schistosoma mansoni: development of the cercarial glycocalyx.
The development of the cercarial glycocalyx of Schistosoma mansoni was studied by transmission electron microscopy and immunofluorescence light microscopy employing antibodies raised against extracted and chromatographed glycocalyx. By electron microscopy, cercariae present in the brood chamber of daughter sporocysts were surrounded by an electron-dense granular and fibrillar matrix. This material appeared structurally distinct from the glycocalyx which was coarsely fibrillar and located only on the surface of organisms that had developed a final tegument. The thickness of the glycocalyx apparently increased with the maturation of the tegument, since teguments that had many spines also had the thickest glycocalyx. Immunofluorescent staining of frozen sections of infected snail hepatopancreas showed that glycocalyx antigens were present on the surface of the cercariae and not in the matrix within the brood chamber or in snail tissues. Immunofluorescent staining of isolated larval cercariae showed staining of some but not all parasites with partially elongated tails. These studies suggest that the glycocalyx develops late in cercarial development (late in Stage 6 or in Stage 7 of Cheng and Bier), is made by the cercariae themselves, and is not a product of either the sporocyst wall cells or snail hepatopancreas.


NuBBEDB: an updated database to uncover chemical and biological information from Brazilian biodiversity.
The intrinsic value of biodiversity extends beyond species diversity, genetic heritage, ecosystem variability and ecological services, such as climate regulation, water quality, nutrient cycling and the provision of reproductive habitats it is also an inexhaustible source of molecules and products beneficial to human well-being. To uncover the chemistry of Brazilian natural products, the Nuclei of Bioassays, Ecophysiology and Biosynthesis of Natural Products Database (NuBBEDB) was created as the first natural product library from Brazilian biodiversity. Since its launch in 2013, the NuBBEDB has proven to be an important resource for new drug design and dereplication studies. Consequently, continuous efforts have been made to expand its contents and include a greater diversity of natural sources to establish it as a comprehensive compendium of available biogeochemical information about Brazilian biodiversity. The content in the NuBBEDB is freely accessible online (https://nubbe.iq.unesp.br/portal/nubbedb.html) and provides validated multidisciplinary information, chemical descriptors, species sources, geographic locations, spectroscopic data (NMR) and pharmacological properties. Herein, we report the latest advancements concerning the interface, content and functionality of the NuBBEDB. We also present a preliminary study on the current profile of the compounds present in Brazilian territory.


Parietal motor syndrome: a clinical description in 32 patients in the acute phase of pure parietal strokes studied prospectively.
We prospectively studied motor symptoms in 32 patients with CT- or MRI-proven acute pure parietal stroke. A transient, mild, 'pseudoparesis' of the hand (90%), was noted, improved by visual attention and prompting, associated with non-awareness of muscle power (53%), transient soft pyramidal signs (50%), unilateral akinesia (100%) and motor hemineglect (37%) in non-dominant lesions. Lower motoneurone-type atrophy was not observed in this acute phase. We called 'poikilotonia' the striking unpredictable variations in muscle tone, ranging from extreme hypertonia to hypotonia, found in all patients. When maintaining postures, patients showed large oscillations (100%), laterodeviation or levitation of the arm (60%), especially in the case of large or posterior lesions, or, occasionally (3%), motor persistence or even hemicatalepsy (3%). Limb kinetic and manipulatory apraxia, with inadequate organization and anticipation of motor sequences and synergies, motor arrests, perplexity, unrecognizable gestures and loss of bimanual coordination, was a constant finding (100%). Other apraxias (62%) and difficulty in copying intransitive gestures of the hand (84%) were associated with posterior lesions involving the supramarginal gyrus. When reaching towards objects, all patients showed abnormal anticipatory hand shaping, but visuomotor ataxia (3%) was only seen with bilateral posterior stroke. Sensory (70%) or pseudocerebellar (4%) ataxia, was seen in both anterior and posterior lesions. Avoidance behaviors (34%) were not uncommon, but had no localizing value. Of the dyskinesias, hand dystonia (84%) was frequent, but athetosis (16%), asterixis (15%), postural tremor (15%), myoclonus (9%) and stereotypia (9%), were uncommon. The abnormal eye movements were unilateral hypo-akinesia of exploratory saccades (43%), abnormal ipsilateral pursuit and contralateral optokinetic nystagmus in the case of posterior lesions, and oculomotor apraxia with bilateral posterior lesions. In conclusion, parietal motor syndrome can be recognized during bedside examination, and probably reflects the loss of multiple sensory feedback to motor programs, especially those directed to the extrapersonal space.


Cyclic AMP-dependent protein kinase phosphorylation facilitates GABA(B) receptor-effector coupling.
GABA (gamma-aminobutyric acid)(B) receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. Here we show that the functional coupling of GABA(B)R1/GABA(B)R2 receptors to inwardly rectifying K(+) channels rapidly desensitizes. This effect is alleviated after direct phosphorylation of a single serine residue (Ser892) in the cytoplasmic tail of GABA(B)R2 by cyclic AMP (cAMP)-dependent protein kinase (PKA). Basal phosphorylation of this residue is evident in rat brain membranes and in cultured neurons. Phosphorylation of Ser892 is modulated positively by pathways that elevate cAMP concentration, such as those involving forskolin and beta-adrenergic receptors. GABA(B) receptor agonists reduce receptor phosphorylation, which is consistent with PKA functioning in the control of GABA(B)-activated currents. Mechanistically, phosphorylation of Ser892 specifically enhances the membrane stability of GABA(B) receptors. We conclude that signaling pathways that activate PKA may have profound effects on GABA(B) receptor-mediated synaptic inhibition. These results also challenge the accepted view that phosphorylation is a universal negative modulator of G protein-coupled receptors.


The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation.
Mycophenolate mofetil, a pro-drug for mycophenolic acid, reduces the likelihood of allograft rejection after renal transplantation. We studied the relationship between mycophenolic acid pharmacokinetics and the likelihood of rejection in a randomized concentration-controlled trial. Under double-blind conditions, recipients of kidney transplants were followed for evidence of allograft rejection for 6 months. In addition to mycophenolate mofetil, patients received usual doses of cyclosporine (INN, ciclosporin) and corticosteroids. The dose of mycophenolate mofetil (given twice daily) was controlled by feedback, with mycophenolic acid area under the concentration-time curve (AUC) as the controlled variable. Patients were randomly assigned to 1 of 3 target AUC groups. Logistic regression analysis showed a significant (P < .0001) relationship between mycophenolic acid AUC and the likelihood of rejection. High mycophenolic acid values were associated with a very low probability of rejection. An AUC of 15 micrograms.h/mL yielded 50% of maximal achievable efficacy with a 4% change of efficacy for a 1 microgram.h/mL change in AUC at the midpoint of the logistic curve. Exploratory analyses showed other variables (e.g., the maximum observed plasma concentration, predose plasma concentration, and drug dose) had poorer predictive power for the rejection outcome. Bivariate regression confirmed the importance of AUC as a highly predictive variable and showed low predictive value of other variables, once the contribution of AUC had been considered. The characteristic side effects of mycophenolate mofetil therapy appeared related to drug dose but not to mycophenolic acid concentration. The AUC of mycophenolic acid is predictive of the likelihood of allograft rejection after renal transplantation in patients receiving mycophenolate mofetil.


Heterologous expression of polygalacturonase genes isolated from Galactomyces citri-aurantii IJ-1 in Pichia pastoris.
ABSTACT: The objective of this work was to isolate the polygalacturonase genes of Galactomyces citri-aurantii IJ-1 harvested from rotten citrus peels and to heterologously express these genes in Pichia pastoris. Two polygalacturonase (PG) genes from G. citri-aurantii IJ-1 were obtained and tentatively named PG1 and PG2. The genes were cloned into pPICZαC, and expressed in Pichia pastoris strain GS115 with a native signal peptide or the α-factor secretion signal peptide of Saccharomyces cerevisiae. All of the recombinant proteins were successfully secreted into the culture media and confirmed as a single band with a molecular weight of 35 to 38 kDa by SDS-PAGE. The specific enzyme activities of recombinant PG1 and PG2 purified by His-tag affinity resin were 4,749 and 6,719 U/mg, respectively, with an optimal pH and temperature of pH 4.0 and 50°C. The Michaelis-Menten kinetic constants for PG1 and PG2, K (m), were confirmed to be 0.94 and 0.84 mM, respectively. In the presence of Mn(2+), the activity of PG1 and PG2 were increased to 160.8 and 146.4% of normal levels, respectively. In contrast, Cu(2+) and Fe(3+) acted as strong inhibitors to the PGs.


Diabetes mellitus and risk factors in human immunodeficiency virus-infected individuals at Jimma University Specialized Hospital, Southwest Ethiopia.
Globally, diabetes is rising dramatically causing high health burden in low- and middle-income countries. It is estimated that about 382 million people had diabetes in 2013. In 2013, diabetes caused 5.1 million deaths globally. Almost 80% of diabetes deaths occur in low- and middle-income countries. To assess the magnitude of diabetes mellitus (DM) and associated risk factors in human immunodeficiency virus (HIV)-infected individuals. An institution-based cross-sectional study was conducted from April to May 2014 at Jimma University Specialized Hospital. Convenient sampling technique was implemented. Sociodemographic and anthropometric data were collected by senior clinical nurses. Venous blood was collected from each study participant. Serum glucose and lipid profile of the study participants was measured using HumaStar 80 spectrophotometer. Data were analyzed using SPSS version 20. Bivariate and multivariate logistic regressions were utilized. A total of 393 HIV-infected individuals of age ranging from 21 years to 75 years had enrolled in this study. The overall prevalence of DM in this study was 6.4% (n=25). Two hundred and ninety-one (74%) and 77 (19.6%) of the study participants had normal (70-110 mg/dL) and impaired (111-125 mg/dL) fasting blood glucose values, respectively. After adjusting for the other variables, age (adjusted odds ratio [AOR] =4.812, 95% confidence interval [CI]: 1.668-13.881, P=0.004), duration of highly active antiretroviral therapy (HAART) (AOR =26.928, 95% CI: 3.722-194.822, P=0.001), hypertension (AOR =4.779, 95% CI: 1.646-13.874, P=0.004), and low-density lipoprotein cholesterol (AOR =5.669, 95% CI: 1.849-17.382, P=0.004) were significantly associated with DM. HAART may have an impact on the cause of diabetes. Hence, HIV-infected individuals should be screened for diabetes, both before and after initiation of HAART.


Generic equivalence of dermatologic products. How equivalent is equivalent?
More and more pharmaceutical products are becoming available under the generic designation as patents for their brand-name counterparts expire. Although some generic products are exact duplicates of the brand-name drug, others may vary with regard to their inactive ingredients or in other ways. Sometimes these allowable variations in product formulation are clinically significant for certain individuals. Therefore it is important for both the prescriber and the dispenser of medication to recognize potential differences in marketed products so that a truly equivalent preparation can be provided when a generic substitution is made. This article chronicles a case in which miscommunication and noncommunication led to the suboptimal treatment of a skin disease with a generic "equivalent." Suggestions are made for improving interprofessional communication so that the patient's needs are served to the maximum degree.


Verruciform xanthoma in close association with isolated epidermolytic acanthoma: a case report and review of the Japanese dermatological literature.
A 52-year-old man presented to our department with a scrotal skin nodule, first noted as a papule two to three years previously. The nodule was red and pedunculated with a granular surface and a diameter of 10 mm. Three red papules were scattered around the nodule. Histopathologic examination of the nodule showed epidermal papillary hyperplasia, collections of foam cells in the papillary dermis, and a dense infiltration of inflammatory cells into all dermal layers. In addition, granular degeneration was seen in the pedunculated lesion of the nodule free from the foam cells. Microscopic examination of the red papules also showed granular degeneration. The patient was diagnosed with verruciform xanthoma associated with isolated epidermolytic acanthoma. This is the first report of these two lesions occurring at the same site on the scrotum.


Criteria for the evaluation of a cloud-based hospital information system outsourcing provider.
As cloud computing technology has proliferated rapidly worldwide, there has been a trend toward adopting cloud-based hospital information systems (CHISs). This study examines the critical criteria for selecting the CHISs outsourcing provider. The fuzzy Delphi method (FDM) is used to evaluate the primary indicator collected from 188 useable responses at a working hospital in Taiwan. Moreover, the fuzzy analytic hierarchy process (FAHP) is employed to calculate the weights of these criteria and establish a fuzzy multi-criteria model of CHISs outsourcing provider selection from 42 experts. The results indicate that the five most critical criteria related to CHISs outsourcing provider selection are (1) system function, (2) service quality, (3) integration, (4) professionalism, and (5) economics. This study may contribute to understanding how cloud-based hospital systems can reinforce content design and offer a way to compete in the field by developing more appropriate systems.


Surface fluid absorption and secretion in small airways.
Native small airways must remain wet enough to be pliable and support ciliary clearance, but dry enough to remain patent for gas flow. The airway epithelial lining must both absorb and secrete ions to maintain a critical level of fluid on its surface. Despite frequent involvement in lung diseases, the minuscule size has limited studies of peripheral airways. To meet this challenge, we used a capillary to construct an Ussing chamber (area <1 mm(2)) to measure electrolyte transport across small native airways (∼1 mm ø) from pig lung. Transepithelial potentials (V(t)) were recorded in open circuit conditions while applying constant current pulses across the luminal surface of dissected airways to calculate transepithelial electrical conductance (G(t)) and equivalent short circuit current (I(eq)(sc)) in the presence and absence of selected Na(+) and Cl(-) transport inhibitors (amiloride, GlyH-101, Niflumic acid) and agonists (Forskolin + IBMX, UTP). Considered together the responses suggest an organ composed of both secreting and absorbing epithelia that constitutively and concurrently transport fluids into and out of the airway, i.e. in opposite directions. Since the epithelial lining of small airways is arranged in long, accordion-like rows of pleats and folds that run axially down the lumen, we surmise that cells within the pleats are mainly secretory while the cells of the folds are principally absorptive. This structural arrangement could provide local fluid transport from within the pleats toward the luminal folds that may autonomously regulate the local surface fluid volume for homeostasis while permitting acute responses to maintain clearance.


CT-guided Transgluteal Prostate Fiducial Marker Insertion for Localized Radiation Therapy.
To Evaluate the safety and technical success of transgluteal CT-guided fiducial marker implantation into the prostate as an alternative method to transperineal and transrectal approaches. We retrospectively identified all patients who had undergone CT-guided transgluteal fiducial marker insertion between 2020 and 2022. Four patients with confirmed prostate cancer were identified. One radiologist performed all procedures via a bilateral transgluteal approach under the guidance of real-time CT-fluoroscopy. Twenty cm long pre-waxed 18G guiding needles, preloaded with smooth gold fiducial markers, were used to implant markers. Technical success was defined as the successful placement of the fiducial markers into the planned positions. The mean age of patients was 70 years. The mean procedure time was 19.25 (SD: 6.75) min, and the mean total dose length product (DLP) was 801.75 (SD: 291.17) mGycm, which is compatible with the 12 mSv estimated effective dose. All procedures were technically successful (100%). All patients tolerated the procedure and did not require any analgesia for pain, and there were no requests to stop or pause the procedure. Only one patient reported hematuria one day after the procedure, which required no treatment. Transgluteal CT-guided fiducial marker implantation into the prostate is an alternative method to transperineal and transrectal approaches. In this technique, the risk of septic complications is minor, and general anesthesia is not required. Thus, transgluteal CT-guided marker insertion is a feasible and well-tolerated method for image-guided radiation therapy (IGRT) in patients with prostate cancer.


Dinuclear zinc catalyzed asymmetric spirannulation reaction: an umpolung strategy for formation of α-alkylated-α-hydroxyoxindoles.
A highly diastereo- and enantioselective formal [3 + 2] cycloaddition of α,β-unsaturated esters and 3-hydroxyoxindoles catalyzed by a dinuclear zinc-ProPhenol complex is reported. The stereoselective Michael additions of 3-hydroxyoxindoles and the subsequent transesterifications afford spirocyclic δ-lactones.


Non-invasive caries detection and delineation via novel laser-induced fluorescence with hyperspectral imaging.
Carious is a global chronic disease; 2 billion people and 520 million children suffer from permanent and primary teeth caries respectively. Early caries detection via precise, non-invasive, non-ionizing radiation is highly appreciated. Carious deteriorate the chemical structure of sound tooth tissues, with variation in its optical properties. In this study, customized laser-induced fluorescence system consists of non-ionizing laser light source and hyperspectral camera was developed for early caries detection. Tested tooth sample was illuminated with laser source of 385 nm and 5 mW power. The emitted spectrum signature for main tooth elements including enamel, dentin, stain, and caries were captured. Logarithmic scale of spectrum signature was applied in an attempt to enhance system sensitivity to fluorescent signal. Fluorescence signature at 500 nm secured the maximum fluorescence intensity difference for different tooth elements. Consequently 2D hyperspectral image at 500 nm was constructed. Enhanced 2D image was accomplished via nonlinear filter to enhance contrast. Segmentation via K mean clustering was adopted for precise caries delineation. This narrative, facile, non-invasive, non-ionizing technique experienced precise and accurate delineation of different caries stages (normal, moderate, and severe).


Antimicrobial and antibiofilm activities of nanoemulsions containing Eucalyptus globulus oil against Pseudomonas aeruginosa and Candida spp.
Candida species are the main responsible microorganisms for causing fungal infections worldwide, and Candida albicans is most frequently associated with infectious processes. Pseudomonas aeruginosa is a gram-negative bacterium commonly found in immunocompromised patients. The infection persistence caused by these microorganisms is often related to antimicrobial resistance and biofilm formation. In this context, the objective of the present study was to prepare and characterize nanoemulsions containing Eucalyptus globulus oil and to verify its antimicrobial and antibiofilm activities against P. aeruginosa and Candida spp. The nanoemulsions had a size of approximately 76 nm, a polydispersity index of 0.22, a zeta potential of - 9,42 mV and a pH of approximately 5.0. The E. globulus oil was characterized by gas chromatography, being possible to observe its main components, such as 1-8-Cineol (75.8%), p- Cymene (7.5%), α-Pinene (7.4%) and Limonene (6.4%). The antimicrobial activity of the nanoemulsion was determined from the macrodilution tests and the cell viability curve, where the minimum fungicidal concentration of 0.7 mg/mL for C. albicans and 1.4 mg/mL for C. tropicalis and C. glabrata were obtained. However, the nanoemulsions did not present antimicrobial activity against P. aeruginosa, since it contains only 5% of the oil, being ineffective for this microorganism. The nanoencapsulated oil action against the formed biofilm was evaluated by atomic force microscopy and calcofluor staining, and the nanoemulsion was more efficient for two of the three Candida species when compared to free oil.


Binding characterization of the interleukin-13 signaling complex and development of a ternary time-resolved fluorescence resonance energy transfer assay.
Interleukin-13 (IL-13) is a critical mediator of pulmonary pathology associated with asthma. Drugs that block the biological function of IL-13 may be an effective treatment for asthma. IL-13 signals by forming a ternary complex with IL-13Ralpha1 and IL-4R. Genetic variants of IL-13 and of its receptor components have been linked to asthma. One in particular, IL-13R110Q, is associated with increased IgE levels and asthma. We characterized the interactions of the binary complexes composed of IL-13 or IL-13R110Q with IL-13Ralpha1 and the ternary complexes composed of IL-13 or IL-13R110Q and IL-13Ralpha1 with IL-4R using surface plasmon resonance and time-resolved fluorescence resonance energy transfer (TR-FRET). By both biophysical methods, we found no differences between IL-13 and IL-13R110Q binding in either the binary or the ternary complex. IL-4R bound to the IL-13/IL-13Ralpha1 complex with slow on and off rates, resulting in a relatively weak affinity of about 100nM. We developed a TR-FRET assay targeting the interaction between the IL-4R and the binary complex. Two antibodies with known binding epitopes to IL-13 that block binding to either IL-13Ralpha1 or IL-4R inhibited the TR-FRET signal formed by the ternary complex. This assay will be useful to identify and characterize inhibitory molecules of IL-13 function.


Platelet deposition in remote cardiac regions after coronary occlusion.
Activated platelets might contribute to endothelial dysfunction in non-ischaemic territories during acute myocardial infarction. We assessed platelet deposition, coronary flow reserve and contractile function in remote cardiac regions after transient coronary occlusion and their association with systemic platelet activation. In 10 pigs (series A) subjected to 48-min occlusion of the left anterior descending coronary artery (LAD), 99mTc-platelet content in the right coronary artery (RCA) and its dependent myocardium was counted after reflow. In 10 pigs (series B) receiving the same occlusion of the RCA, the hyperaemic response at the LAD and systolic shortening in LAD-dependent myocardium were monitored after reperfusion. P-selectin expression on circulating platelets was assessed in both series by flow cytometry. In series A, platelet counts in the RCA and non-ischaemic myocardium were correlated with platelet content, polymorphonuclear leukocyte infiltration and infarct size in the reperfused zone, as well as with the percentage of P-selectin-positive platelets after reflow. In series B, a transient reduction in peak hyperaemic response in the LAD and sustained contractile dysfunction in non-ischemic myocardium were observed after releasing the RCA occlusion, these changes being also correlated with platelet activation status. Ischaemic injury triggers macro- and microvascular platelet deposition and causes an impairment in coronary flow reserve and contractile function in distant regions of the heart, which are related to activation of circulating platelets.


3-Methylglutaconic aciduria in two infants.
We studied two children who developed normally for the first 3-4 months of life and then displayed a failure-to-thrive syndrome, regression in psychomotor development, pronounced muscular hypotonia, and liver damage. At the age of about 1-2 years, optic atrophy and spastic parapareses were evident. One child died at the age of 2.5 years the other at an age of 4 years. Both children excreted 3-methylglutaconic acid, 0.1-0.4 mol/mol creatinine and 3-methylglutaric acid, 0.02-0.05 mol/mol creatinine. The excretion of 3-hydroxy-3-methylglutaric acid was not increased. One of the children was available for further biochemical studies. The activity of hydroxymethylglutaryl-CoA lyase (EC 220.127.116.11) was moderately reduced in leucocytes and fibroblasts. During a 21-h fast there was a normal formation of ketone bodies and we conclude that the cause of the syndrome is not a deficiency of hydroxymethylglutaryl-CoA lyase. Normal formation of 14CO2 from [1-14C]isovaleric acid and [2-14C]leucine in fibroblasts and leucocytes apparently excludes a deficiency of methylglutaconyl CoA-hydratase (EC 220.127.116.11).


[Long-term course of patients in neurological rehabilitation Phase B. Results of the 6-year follow-up in a multicenter study].
After conclusion of emergency care for severe neurological diseases patients in Germany are admitted at an early stage to so-called Phase B rehabilitation. No studies have been carried out on the long-term course of these patients. In a prospective study in 2002 patients in Phase B from 9 centers were included and follow-up investigations were carried out after 5 and 6 years. Assessment instruments used were the Barthel index, the Rankin scale and the EQ-5D. Factors for the risk of a poor outcome and the chances for a good outcome were evaluated using multivariate logistic regression. A total of 1,280 patients were included in the study. A high age increased the risk of dying with a hazard quotient (HQ) of 1.05 (95% CI: 1.04-1.06) and high point counts in the coma remission scale (HQ 0.93; 95% CI: 0.92-0.96) and Barthel index (HQ 0.97; 95% CI: 0.97-0.98) on discharge reduced the risk of dying after 5 years. The factors swallowing impairment (OR 3.1; 95% CI: 1.7-5.5) and obligatory surveillance at the end of rehabilitation (OR 3.2; 95% CI: 1.2-8.6) increased the risk of a poor result in the Rankin scale 2-4 and the factors communication disorder (OR 5.0; 95% CI: 2.0-12.8) and PEG (percutaneous endoscopic gastrostomy) (OR 19.7; 95% CI: 2.7-144.4) on discharge increased the risk of a reduced health-related quality of life (defined as EQ-5D VAS <70) after 6 years. If support for bodily functions can be successfully reduced during Phase B rehabilitation, the patients will have a good outcome with respect to 5-year survival. If this is not successful the outcome is unfavorable with respect to survival and with respect to achieving self-sufficiency and health-related quality of life after 6 years.


A functional SNP rs895819 on pre-miR-27a is associated with bipolar disorder by targeting NCAM1.
The aberrant expression or genomic mutations of microRNA are associated with several human diseases. This study analyzes the relationship between genetic variations of miRNA and schizophrenia or bipolar disorder. We performed case-control studies for ten SNPs in a total sample of 1584 subjects. All these ten SNPs were on or near mature microRNAs. We identified the association between bipolar disorder and the T/C polymorphism at rs895819. To illustrate the function of miR-27a, we constructed several miR-27a knockout (KO) cell lines, determined candidates of miR-27a, and then verified NCAM1 as a target gene of miR-27a. Further studies revealed that the T/C polymorphism on miR-27a led to the differential expression of mature and precursor miR-27a without affecting the expression of primary miR-27a. Furthermore, the C mutation on pre-miR-27a suppresses cell migration and dopamine expression levels. Our study highlights the importance of miR-27a and its polymorphism at rs895819 in bipolar disorder.


Ultrasound and dual X-ray absorptiometry measurement of the calcaneus: influence of region of interest location.
Ultrasound measurements of the calcaneus are related to incidence of osteoporotic fracture. Such measurements are generally made at fixed coordinates relative to a footplate. This study compares measurements at an anatomically located region of interest (ROIanat) and at fixed coordinates (ROIfixed), with bone mineral density measurements, in 84 postmenopausal women. Bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry at both ROIs as well as at lumbar spine and femoral neck. Broadband ultrasound attenuation and velocity of sound were measured using a CUBA system at ROIanat and ROIfixed. Additionally, broadband ultrasound attenuation at ROIfixed was measured using a Walker Sonix instrument. Mean bone mineral density, broadband ultrasound attenuation and velocity of sound did not differ significantly between ROIfixed and ROIanat, although broadband ultrasound attenuation by Walker Sonix (81.4 +/- 14.6 dBMHz-1) was significantly (P < 0.001) greater than that by CUBA (63.7 +/- 14.2 dBMHz-1). The relationship between broadband ultrasound attenuation and BMD differed significantly between the 2 ROIs and the correlation of this relationship was significantly greater at ROIfixed than at ROIanat(r = 0.74 versus 0.46, P < 0.01). The differing relationship may reflect structural variation at different regions. ROI selection may thus be a possible confounding factor in ultrasound measurement.


Salicylhydroxamic acid (SHAM) inhibits O(2) photoreduction which protects nitrogenase activity in the cyanobacterium Synechococcus sp. RF-1.
Synechococcus sp. RF-1, a unicellular N(2)-fixing cyanobacterium, can grow photosynthetically and diazotrophically in continuous light. How the organism protects its nitrogenase from damage by oxygen is unclear. In cyanobacerial cells, electron transport carriers associated with photosynthesis and respiration are all on the thylakoid membranes and share some common components, including plastoquinone pool and cytochrome b (6) f complex, and the pathways are interacting with each other. In this work, a pulse amplitude modulation (PAM) fluorometer (PAM-101) and an O(2) electrode are used simultaneously to study the chlorophyll a fluorescence and to monitor O(2) exchanges in Synechococcus sp. RF-1 cells. At the CO(2) compensation point, the photochemical quenching activity remained high unless the O(2) was exhausted by the glucose oxidase system (GOS). It indicates that in addition to CO(2), O(2) can also act as electron acceptor to receive electrons derived from Q(A). Studies with various inhibitors of the electron transport chain demonstrated that 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB) and salicylhydroxamic acid (SHAM) inhibited the photoreduction of O(2), while glycolaldehyde, disalicylidenepropanediamine (DSPD), methyl viologen (MV) and KCN did not. These results imply that a KCN-resistant and SHAM-sensitive oxidase transfers electrons generated from Photosystem II to O(2) between cytochrome b (6) f complex and ferredoxin. When SHAM blocked this alternative electron transport pathway, the dinitrogen-fixing activity decreased significantly. The results indicate that a novel oxidase may function as an intracellular O(2)-scavenger in Synechococcus sp. RF-1 cells.


Determination of 12 urinary phthalate metabolites in Norwegian pregnant women by core-shell high performance liquid chromatography with on-line solid-phase extraction, column switching and tandem mass spectrometry.
Phthalates (dialkyl or alkyl phenyl esters of phthalic acid, benzene-1.2-dicarboxylic acid) are a group of industrial chemicals that have been used for more than 50 years. Phthalates are ubiquitous and can potentially have adverse effects on humans. The present study presents an accurate, sensitive and automated analytical method for measuring 12 phthalate metabolites (free and conjugated) in human urine using on-line solid phase extraction coupled to high performance liquid chromatography - electrospray ionization - tandem mass spectrometry. A small volume of urine sample (300μL) is required. Glucoronidated phthalate metabolites are deconjugated by incubation with glucoronidase enzyme (Escherihia coli-K 12) and the reaction is stopped by adding formic acid. This is the only sample preparation needed prior to injection into the column switching system. Thus, the method involves minimal sample handling and minimizes possible contaminations from the surroundings. The method was validated by spiking synthetic urine at 5-8 levels in the range of 0.1-500ng phthalate metabolites/mL synthetic urine. The method is sensitive with limits of detection in the low nanogram range, and rapid with a total run time about 25min. The accuracy was between 90 and 120 % and the intermediate precision was given as relative standard deviation was below 20% for most of the compounds. The high sensitivity, high throughput and minimal manual handling make the method suitable for large-scale biomonitoring studies. The present method was applied for the determination of phthalate metabolites in urine samples from 116 pregnant women, a subproject within the Norwegian Mother and Child Cohort Study. Concentrations of all the twelve phthalate metabolites was >LOQ in 100% of the samples analysed. Mean urinary concentrations for different phthalate metabolites ranged from 1 to 100ng/mL, the highest concentrations were observed for di-2-ethylhexyl phthalate (DEHP) metabolites and lowest for di-iso-nonyl phthalate (DiNP) metabolites. The urinary concentrations for most of the phthalate metabolites in the present study were found to be in the same range as found in other studies of pregnant women.


General dental practitioners' approach to caries prevention in high-caries-risk children.
To evaluate the advice and preventive care provided by General Dental Practitioners (GDPs) to high-caries-risk children in Jordan. A cross-sectional study using an open-ended questionnaire. GDPs were presented with a high-caries-risk child scenario and asked regarding: (1) oral hygiene and dietary advice they would give; (2) preventive-care they would offer; (3) barriers they face in prevention delivery. Answers were compared to an evidence-based guideline. Data were input into SPSS-20 and analysed using descriptive statistics and frequencies. Chi-square test was used to compare results by age, gender, practice location and type. One-hundred and sixty GDPs were approached and 128 agreed to participate (80%), of whom 87 (69%) were female. The average age was 31 years [range 22-50]. Sixty-nine percent practiced in the capital, Amman. Sixty-five percent gave advice on tooth-brushing frequency, but only 23% suggested brushing at bed-time and 24% recommended parental supervision. None provided advice on toothpaste fluoride content. Seventy-one percent advised reducing sugary-food amounts, but only 21% focused on frequency and 2% suggested using diet diaries. Most knew about fissure-sealants (77%) and fluoride-varnish (80%). Forty-two percent reported barriers to delivering preventive-care, including parental attitudes (36%), child cooperation (30%), financial reward (19%), and training (6%). Participants practicing outside of the capital were less likely to use fluoride-varnish [P = 0.002] and more likely to report barriers [P = 0.001]. Advice delivered by GDPs to high-caries-risk children in Jordan does not meet the standards of an evidence-based guideline. Future initiatives for oral-health-promotion should aim to address the barriers reported, especially outside the capital.


Improving blood flow in occluded veins to reduce anti-vascular endothelial growth factor injections for branch retinal vein occlusion.
To assess the relationship between improving blood flow via arteriovenous (AV) sheathotomy without vitrectomy and the total number of anti-vascular endothelial growth factor injections (VEGF) required to treat branch retinal vein occlusion (BRVO). In this prospective, clinical case series, 16 eyes of 16 patients at the Toho University Sakura Medical Center with best-corrected visual acuity (BCVA) of 20/40 or worse due to macular edema associated with BRVO were analyzed for 12 months. AV sheathotomy was performed without vitrectomy for all cases. On the second day after surgery, anti-VEGF was injected into the operated eye. During the 12-month follow-up after surgery, pro re nata injections were administered when changes in foveal exudation and BCVA were evident. The blood flow of the occluded vein was assessed before and after AV sheathotomy during the operation using laser speckle flowgraphy. The total number of anti-VEGF injections, central retinal thickness (CRT), and BCVA 12 months after surgery were examined. The changes in CRT and BCVA from baseline to month 12 were statistically significant (P < 0.01). No additional anti-VEGF injections were required for nine of 16 eyes (56.3%) during the 12 months. The total number of anti-VEGF injections for 12 months correlated with the change rate of blood flow in an occluded vein before and after AV sheathotomy (r = -2.816, P = 0.022). Improved blood flow in occluded vein may reduce the need for anti-VEGF injections in BRVO.


Differences in the Clinical Presentation and Biochemical Profile of the Patients with Primary Hyperparathyroidism with regard to their Serum Vitamin D Levels: a Single-center Experience.
The association between vitamin D deficiency and primary hyperparathyroidism (PHPT) is common and has clear implications. Vitamin D deficiency is commonly seen in PHPT population and exacerbates its severity with skeletal and metabolic effects. Retrospective data collection and review were done in patients who underwent surgery for PHPT at a tertiary care hospital in India between January 2011 and December 2020. A total of 150 subjects were included in the study and were divided into group 1 (vitamin D < 20 ng/ml, deficient), group 2 (vitamin D 21-29 ng/ml, insufficient), and group 3 (vitamin D > 30 ng/ml, sufficient). There was no difference in the duration of symptoms or the symptomatology between the three groups. Mean pre-operative serum calcium and serum phosphorous levels were also comparable in all the three groups. Mean pre-operative parathyroid hormone (PTH) levels in the three groups were 703 ± 996 vs 343.6 ± 396 vs 343.6 ± 396 pg/ml, respectively (P = 0.009). There was a statistically significant difference in group 1 vs groups 2 and 3 in their mean weight of the parathyroid gland (P = 0.018) and high alkaline phosphatase (ALP) levels (P = 0.047). Post-operative symptomatic hypocalcemia was observed in 17.3% of patients. Post-operative hungry bone syndrome occurred in 4 patients, all in group 1. PHPT in patients with low serum vitamin D was associated with higher serum PTH levels, increased frequency of high serum ALP levels, and higher weight of the excised gland, with no difference in the serum calcium and phosphorous.


Site matters in metastatic melanoma.
Metastasis and cross-therapy resistance to mitogen-activated protein kinase (MAPK) inhibition and immune checkpoint blockade (ICB) are significant clinical issues in melanoma. A new study in NatureMedicine by Liu et al. utilizes metastatic melanoma (MM) tumors from a rapid autopsy cohort to dissect genomic and transcriptomic features of therapy resistance, organ-specific gene signatures, and crosstalk between MM and organ sites.


Sacral anterior root stimulation for bladder control in patients with a complete lesion of the spinal cord.
A Finetech-Brindley bladder controller was implanted in 17 patients with a complete lesion of the spinal cord. During a microscopic procedure in the cauda equina, the sacral roots were identified and the posterior components of the S2, S3 and S4 roots were cut. The stimulator was placed intradurally around the anterior components of the S2, S3, S4 roots and the S5 root. Our patients have now been followed-up for periods varying between 1 and 6 years. In all 17 patients, the bladder capacity has been increased; 16 patients have a residual volume of less than 30 ml, urinary tract infection is rare; 12 patients are fully continent. All male patients can achieve a full sustained erection by means of the implant and 13 patients are using the implant for bowel function. The method has no significant harmful effects or complications.


Protein-membrane interactions: specific vs. non-specific adsorption and binding of proteins and polyamino acids on erythroblasts transformed by Friend virus.
Friend-virus transformed erythroblasts (HFL cells) were incubated in solutions containing up to 3 different proteinaceous compounds at pH 7.2 or 5.5 at 5 degrees C. The specificity of interaction of each compound with the cell surface was determined by comparing the amounts of each compound adsorbed and bound in the presence of 2 or 3 different compounds or after prior binding of another compound to the amounts when the individual compounds alone interacted with the cells. At pH 7.2, ovalbumin and gelatin apparently interacted with cell surface components common to both proteins, as indicated by a decrease (up to 80%) in the amount of each compound adsorbed and bound in the presence, or after the binding, of the other compound. The relative amounts of each compound that interacted were different at pH 5.5 and pH 7.2. Gelatin and poly-L-lysine interacted mainly with different components at pH 7.2, whereas common components appeared to be involved at pH 5.5. Concanavalin A interacted preferentially with components that it shared with lysozyme at both pH values. In addition to variations in interactions with changes in pH and type of compound, variations occurred with changes in concentration of the compounds and with their sequence of addition to the cells. Comparative studies with horse red blood cells showed that the interactions differed markedly with cell type.


Venous drainage of the soleus muscle.
Soleus veins have been implicated as the site for deep venous thrombosis initiation. Detailed anatomic knowledge is required for the early diagnosis using non-invasive ultrasound techniques. In the present work, we describe the anatomy of the veins that emerge from the ventral face of the soleus muscle. Twenty-eight soleus muscles were dissected and 543 veins were found. The number of veins per leg ranged from 7 to 38. The distribution of these veins per quadrant ranged from 0 to 12. The greatest number of veins occurred at the superior lateral quadrant. Most soleus veins mainly drained into the posterior tibial and fibular veins. The mean length of the soleus veins ranged from 0.907 to 2.804 cm. We conclude that there is a wide variability in the distribution of soleus veins through the soleus muscle and their quadrants. The majority of the soleus veins drain into the tibial and fibular veins.


Investigating the role of a Verticillium fungicola beta-1,6-glucanase during infection of Agaricus bisporus using targeted gene disruption.
Studies on the mycopathogen Verticillium fungicola have shown the up-regulation of beta-1,6-glucanases when grown in the presence of host cell walls and host cell wall components including chitin. These cell-wall-degrading enzymes are hypothesized to contribute to the pathogenic ability of mycopathogens. A beta-1,6-glucanase gene, VfGlu1, showing high similarity to beta-1,6-glucanase genes from Hypocrea virens, Neotyphodium sp., and Trichoderma harzianum, was isolated using degenerate PCR from V. fungicola, a serious mycopathogen of the cultivated mushroom Agaricus bisporus. Agrobacterium-mediated transformation of V. fungicola using homologous DNA from VfGlu1 resulted in homologous integration at the VfGlu1 locus in 75% of transformants, generating mutants disrupted in the VfGlu1 gene. VfGlu1 mutants displayed reduced virulence and diminished ability to utilize chitin as a carbon source, implicating VfGlu1 in the disease process. Agrobacterium-mediated transformation affords an efficient technique for the disruption of genes associated with disease symptom development in the complex V. fungicola-A. bisporus interaction.


Identification and genetic characterization of Anisakis larvae from marine fishes in the South China Sea using an electrophoretic-guided approach.
From 35 species of marine fishes (n = 327) from the South China Sea, 237 nematode larvae were collected and identified morphologically as Anisakis. Genomic DNA was isolated from each larva and subjected to PCR-based RFLP and targeted sequencing of a nuclear ribosomal DNA region between the 3'-end of the small subunit and 5'-end of the large subunit of the rRNA genes (= internal transcribed spacers, ITS+). Four different RFLP profile combinations (sets) were detected for all restriction endonucleases (HinfI, HhaI, and TaqI), of which three were characteristic of Anisakis typica, A. pegreffii, and A. physeteris, respectively. One profile set (for sample CA-2012) was linked to an ITS+ sequence that was identical to a previously published sequence of Anisakis sp. (sample HC-2005; originating from the African shelf) and another sequence (PH-2010; Madeira, Portugal). Phylogenetic analysis was carried out using the ITS+ sequence data from this study and reference sequences from the GenBank database. Neighbor joining and maximum parsimony trees displayed three clades. Clades I and II included nine described species of Anisakis, including all type I and type II larvae; clade III represented some undescribed species of Anisakis. Morphological comparison showed that Anisakis sp. CA-2012 was distinct from type I and type II larvae based on its tail shape and ratio of tail length to body length. The phylogenetic analysis and morphological characters suggest that Anisakis sp. CA-2012 represents a new record, now called Anisakis type III larvae.


Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis.
To compare pro-inflammatory cytokine profiles and kinetics in patients with adult-onset Still's disease (AOSD) to those in patients with systemic juvenile idiopathic arthritis (s-JIA), we analyzed serum cytokine concentrations in 33 patients with AOSD and 77 patients with s-JIA and compared them with clinical features. Patients with AOSD and s-JIA shared a common cytokine profile pattern of a significant increase in IL-18. Patients with AOSD were classified into two subgroups based on serum IL-6 and IL-18 levels. The number of patients with arthritis was significantly higher in the IL-6-dominant subgroup. The cytokine patterns associated with s-JIA and AOSD share common features, such as a significant and predominant increase in IL-18. Distinct IL-6- and IL-18-based cytokine profiles might be responsible for distinct clinical manifestations. The presence of two distinct subgroups in patients with both diseases further supports the view that s-JIA and AOSD share a disease category.


Molecular localization of regions in the L-type calcium channel critical for dihydropyridine action.
Sensitivity to dihydropyridines (DHPs) is a distinct characteristic that differentiates L-type Ca2+ channels from T-, N-, and P-type Ca2+ channels. To identify regions necessary for the functional effects of DHPs, chimeric Ca2+ channels were constructed in which portions of motif III or motif IV of a DHP-insensitive brain Ca2+ channel, BI-2, were introduced into the DHP-sensitive cardiac L-type Ca2+ channel. The resultant chimeric Ca2+ channels were expressed in Xenopus oocytes, and the effects of a DHP agonist and antagonist were studied. The results show that the linker region between S5 and S6 in motif IV of the L-type Ca2+ channel is a major site for DHP action. The DHP agonist and antagonist molecules interact with distinct sites on the alpha 1 subunit of the L-type Ca2+ channel. The data further show that the SS2-S6 region of motif III is not involved in DHP action but may be an important structural component of inactivation.


Occurrence, Risk Factors, Serotypes, and Antimicrobial Resistance of Salmonella Strains Isolated from Imported Fertile Hatching Eggs, Hatcheries, and Broiler Farms in Trinidad and Tobago.
This cross-sectional study was conducted to determine the occurrence, risk factors, and characteristics of Salmonella isolates recovered from imported fertile broiler hatching eggs, hatcheries, and broiler farms in Trinidad and Tobago. Standard methods were used to isolate and characterize Salmonella isolates from two broiler hatcheries and 27 broiler farms in the country. The frequency of isolation of Salmonella was 0.0% for imported fertile hatching eggs (0 of 45 pools of 10 eggs each, i.e., 450 eggs), 7.6% for hatcheries (12 of 158 samples), and 2.8% for broiler farms (24 of 866 samples) (P = 0.006). Stillborn chicks at hatcheries had the highest prevalence of Salmonella (7 of 28 samples, 28.0%), whereas on broiler farms the cloacal swabs had the highest prevalence of Salmonella (15 of 675 samples, 2.2%). None of the 15 farm management and production practices investigated were significantly associated (P > 0.05) with the isolation of Salmonella. The predominant Salmonella serotypes were Kentucky (83.3%) and Infantis (62.5%) among hatchery and farm isolates, respectively. The disk diffusion method revealed frequencies of antimicrobial resistance (i.e., resistance to one or more agents) of 44.0% (11 of 25 isolates) and 87.5% (35 of 40 isolates) at hatcheries and broiler farms, respectively (P = 0.0002). Antimicrobial resistance among hatchery isolates was highest (28.0%) to doxycycline and kanamycin and was very high (>65%) among farm isolates to sulfamethoxazole-trimethoprim, gentamicin, ceftriaxone, kanamycin, and doxycycline. Multidrug resistance (MDR; i.e., resistance to antimicrobial agents from three or more classes) was exhibited by 4.0 and 85.7% of Salmonella isolates recovered from several environmental and animal sources at the hatcheries and farms, respectively (P < 0.0001). The high level of antimicrobial resistance and the presence of MDR among Salmonella isolates from broiler farms highlight the therapeutic implications and the potential for MDR strains to enter the food chain.


Improving oral health with the new dental contract.
The challenge for the twenty-first century for oral health is to reduce the social inequality observed in populations. This challenge has been made explicit by the Department of Health (DH) in England. Turning rhetoric into reality is difficult for all concerned whatever field or profession. A cohesive model that embraces philosophical ideals can help individuals achieve change as it provides structure on which to develop ideas. This paper describes a model of care in general dental practice that fits the requirements of the DoH in addressing social inequalities, in the context of developing general dental services.


The orthotropic viscoelastic characterisation of sub-zero 3D-printed poly(vinyl alcohol) cryogel.
Poly(vinyl alcohol) cryogel (PVA) is a versatile biomaterial used to replicate the biomechanics of tissues. Additive manufacture (AM) at sub-zero (°C) temperatures enables the manufacture of PVA with complex geometry; however, the effect of processing parameters on the mechanical properties of PVA has not been evaluated. The aim of this study is to understand the impact of print nozzle diameter and orientation on the viscoelastic mechanical properties of PVA. Samples of sub-zero AM PVA, with different filament thicknesses, were tested under tension relative to the print direction, to calculate the storage and loss moduli. As the nozzle size was decreased, AM PVA exhibited more pronounced orthotropic properties; the smallest size showed a 33% decrease in storage moduli when tested perpendicular to the print direction, as opposed to parallel. This study has demonstrated the ability of sub-zero AM to tailor the orthotropic properties of PVA. The online version contains supplementary material available at 10.1557/s43580-021-00086-1.


Luminophore Formation in Various Conformations of Bovine Serum Albumin by Binding of Gold(III).
The purpose of the presented protocols is to study the process of Au(III) binding to BSA, yielding conformation change-induced red fluorescence (λem = 640 nm) of BSA-Au(III) complexes. The method adjusts the pH to show that the emergence of the red fluorescence is correlated with the pH-induced equilibrium transitions of the BSA conformations. Red fluorescent BSA-Au(III) complexes can only be formed with an adjustment of pH at or above 9.7, which corresponds to the "A-form" conformation of BSA. The protocol to adjust the BSA to Au molar ratio and to monitor the time-course of the process of Au(III) binding is described. The minimum number of Au(III) per BSA, to produce the red fluorescence, is less than seven. We describe the protocol in steps to illustrate the presence of multiple Au(III) binding sites in BSA. First, by adding copper (Cu(II)) or nickel (Ni(II)) cations followed by Au(III), this method reveals a binding site for Au(III) that is not the red fluorophore. Second, by modifying BSA by thiol capping agents, another nonfluorophore-forming Au(III) binding site is revealed. Third, changing the BSA conformation by cleaving and capping of the disulfide bonds, the possible Au(III) binding site(s) are illustrated. The protocol described, to control the BSA conformations and Au(III) binding, can be generally applied to study the interactions of other proteins and metal cations.


Interleukin-17 enhances the production of interferon-γ and tumour necrosis factor-α by bone marrow T lymphocytes from patients with lower risk myelodysplastic syndromes.
Lower risk myelodysplastic syndromes (MDSs) are characterised by increased apoptosis of haematopoietic cells in the bone marrow (BM). The mechanism driving this excessive apoptosis involves multiple immune molecules, including inflammatory cytokines such as interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukins (ILs). Interleukin-17 (IL-17) is the hallmark cytokine produced by CD4(+) Th17 cells, and IL-17 mediates activation of the adaptive T-cell response inducing an inflammatory cytokine environment. However, little is known about the role of IL-17 in MDS-associated immune dysfunction. A total of 47 patients with myelodysplastic syndromes were enrolled in this study, and the levels of IL-17 and IL-17 receptor (IL-17R) in BM mononuclear cells (BMNCs) were detected by real-time polymerase chain reaction (RQ-PCR) and enzyme-linked immunosorbent assay (ELISA). Then, BMNCs were stimulated with recombinant human IL-17 (rhIL-17), and flow cytometry was used to analyse the production of IFN-γ and TNF-α by CD4(+) and CD(+) T lymphocytes from patients with lower-risk MDS. Characterisation of IL-17 expression in patients with the HLA-DR15 allele or hypocellularity was also performed. mRNA levels for both IL-17 and the IL-17R subunits in BMNCs and for IL-17 in the BM and plasma were higher in patients with lower-risk MDS as compared to patients with higher-risk MDS and normal controls. The production of IFN-γ and TNF-α by CD4(+) and CD8(+) T lymphocytes from patients with lower-risk MDS could be enhanced by recombinant human IL-17 (rhIL-17) treatment. Furthermore, increased IL-17 expression was associated with more severe anaemia in with patients with MDS. Elevated IL-17 levels and IL-17-induced IFN-γ and TNF-α overproduction may be involved in the pathogenesis of lower risk MDS.


Optimization of the azo dye Procion Red H-EXL degradation by Fenton's reagent using experimental design.
Chemical oxidation by Fenton's reagent of a reactive azo dye (Procion Deep Red H-EXL gran) solution has been optimized making use of the experimental design methodology. The variables considered for the oxidative process optimization were the temperature and the initial concentrations of hydrogen peroxide and ferrous ion, for a dye concentration of 100mg/L at pH 3.5, the latter being fixed after some preliminary runs. Experiments were carried out according to a central composite design approach. The methodology employed allowed to evaluate and identify the effects and interactions of the considered variables with statistical meaning in the process response, i.e., in the total organic carbon (TOC) reduction after 120 min of reaction. A quadratic model with good adherence to the experimental data in the domain analysed was developed, which was used to plot the response surface curves and to perform process optimization. It was concluded that temperature and ferrous ion concentration are the only variables that affect TOC removal, and due to the cross-interactions, the effect of each variable depends on the value of the other one, thus affecting positively or negatively the process response.


31P NMR investigations on free and enzyme bound thiamine pyrophosphate.
Pyruvate decarboxylase (PDC) contains thiamine pyrophosphate (TPP) and Mg2+ as cofactors. 31P NMR studies with PDC in the presence of added Mn2+ reveal the pyrophosphate moiety of TPP to be a nonaccessible area for the external Mn2+ and thus proving the Mg-P-complex (taking part in the binding of the coenzyme to the protein) to be a nonaccessible area for the medium. Glyoxylic acid, acting as an inhibitor of PDC by forming a noncleavable bond with the catalytic center of TPP causes a steric immobilization of the coenzyme indicated by a line broadening of the pyrophosphate moiety.


The impact of transoesophageal echocardiography in elderly patients with infective endocarditis.
Infective endocarditis (IE) increasingly involves older patients. Geriatric status may influence diagnostic and therapeutic decisions. To describe transoesophageal echocardiography (TEE) use in elderly IE patients, and its impact on therapeutic management and mortality. A multicentre prospective observational study (ELDERL-IE) included 120 patients aged ≥75 years with definite or possible IE: mean age 83.1±5.0; range 75-101 years; 56 females (46.7%). Patients had an initial comprehensive geriatric assessment, and 3-month and 1-year follow-up. Comparisons were made between patients who did or did not undergo TEE. Transthoracic echocardiography revealed IE-related abnormalities in 85 patients (70.8%). Only 77 patients (64.2%) had TEE. Patients without TEE were older (85.4±6.0 vs. 81.9±3.9 years; P=0.0011), had more comorbidities (Cumulative Illness Rating Scale-Geriatric score 17.9±7.8 vs. 12.8±6.7; P=0.0005), more often had no history of valvular disease (60.5% vs. 37.7%; P=0.0363), had a trend toward a higher Staphylococcus aureus infection rate (34.9% vs. 22.1%; P=0.13) and less often an abscess (4.7% vs. 22.1%; P=0.0122). Regarding the comprehensive geriatric assessment, patients without TEE had poorer functional, nutritional and cognitive statuses. Surgery was performed in 19 (15.8%) patients, all with TEE, was theoretically indicated but not performed in 15 (19.5%) patients with and 6 (14.0%) without TEE, and was not indicated in 43 (55.8%) patients with and 37 (86.0%) without TEE (P=0.0006). Mortality was significantly higher in patients without TEE. Despite similar IE features, surgical indication was less frequently recognized in patients without TEE, who less often had surgery and had a poorer prognosis. Cardiac lesions might have been underdiagnosed in the absence of TEE, hampering optimal therapeutic management. Advice of geriatricians should help cardiologists to better use TEE in elderly patients with suspected IE.


Treatment outcome in a drinking-decisions program.
Of 98 alcoholics who were free to decide whether or not to drink during a 6-week inpatient treatment program, 55 chose to drink. The nondrinkers tended to show more improvement at a 6-month follow-up than did the drinkers.


Synaptic activation of metabotropic glutamate receptors regulates dendritic outputs of thalamic interneurons.
Information gating through the thalamus is dependent on the output of thalamic relay neurons. These relay neurons receive convergent innervation from a number of sources, including GABA-containing interneurons that provide feed-forward inhibition. These interneurons are unique in that they have two distinct outputs: axonal and dendritic. In addition to conventional axonal outputs, these interneurons have presynaptic dendrites that may provide localized inhibitory influences. Our study indicates that synaptic activation of metabotropic glutamate receptors (mGluRs) increases inhibitory activity in relay neurons by increasing output of presynaptic dendrites of interneurons. Optic tract stimulation increases inhibitory activity in thalamic relay neurons in a frequency- and intensity-dependent manner and is attenuated by mGluR antagonists. Our data suggest that synaptic activation of mGluRs selectively alters dendritic output but not axonal output of thalamic interneurons. This mechanism could serve an important role in focal, feed-forward information processing in addition to dynamic information processing in thalamocortical circuits.


A plasmonic colorimetric strategy for biosensing through enzyme guided growth of silver nanoparticles on gold nanostars.
A plasmonic colorimetric strategy was designed for sensitive detection of biomolecules through enzyme guided silver nanoparticles (AgNPs) growth on gold nanostars (AuNS). The growth of AgNPs on AuNS led to a substantial blue shift of the localized surface plasmon resonance (LSPR) peak and the color change of AuNS from blue to dark blue, purple and ultimately orange. Both the LSPR blueshift wavelength and the color of detection solution containing AuNS, Ag(+) and ascorbic acid 2-phosphate (AAP) depend on the amount of enzyme that catalyzed the dephosphorylation of AAP to reduce Ag(+) on AuNS surface. Thus this strategy could be used for LSPR and naked-eye detections of both the enzyme such as alkaline phosphatase (ALP) and other biomolecules involved in biorecognition events using ALP as a tag. The LSPR detection method for ALP showed a linear range from 1.0 pM to 25 nM with a detection limit of 0.5 pM. Using DNA as a mode target molecule, this technique showed a detection range from 10 fM to 50 pM DNA with a detection limit of 2.6 fM through the convenient combination with hybridization chain reaction amplification. The proposed plasmonic colorimetric strategy could be extended as a general analytical platform for design of immunosensors and aptasensors with ALP as a label.


Nonalcoholic Fatty liver disease, diabetes, obesity, and hepatocellular carcinoma.
Diabetes and obesity are associated with nonalcoholic fatty liver disease (NAFLD) and an increased incidence of hepatocellular carcinoma (HCC). NAFLD is the commonest cause of chronic liver disease. HCC can develop in NAFLD patients even without cirrhosis, suggesting an association between the metabolic process and HCC and raising a concern that many cancers could be missed given high NAFLD prevalence and screening limitations. The increasing prevalence of these conditions and lack of effective treatments necessitate a better understanding of their connection. This article defines the known interrelationships and common pathways between NAFLD, diabetes, obesity and HCC and possible chemoprevention strategies.


Psychosocial factors associated with physical activity in patients who have undergone bariatric surgery.
Identifying psychosocial variables associated with physical activity may lead to the development of interventions that better address the challenges to participating in physical activity experienced by postbariatric surgery patients. To examine associations between select psychosocial variables and physical activity in patients who had undergone bariatric surgery within the past 2 years. Bariatric surgery candidates were recruited from the Greater Pittsburgh region. Eighty-three patients who had undergone bariatric surgery self-reported current physical activity and select psychosocial constructs. In addition, participants provided retrospective information on physical activity and psychosocial constructs before surgery. Patients increased physical activity from baseline (median = 156.00 [25th, 75th percentiles: 53.00, 600.00] kcal/week) to post surgery (median = 976.00 [25th, 75th percentiles: 344.00, 1832.00] kcal/week) (P < .001). A number of pre- to postsurgery changes in psychosocial variables were associated with change in physical activity; however, only change in fitness orientation (P = .001), change in social support from friends (P = .005), and change in self-reported weight (P = .012) emerged as predictors of change in physical activity from pre- to postsurgery. Several postsurgery psychosocial factors were also significantly associated with postsurgery physical activity, but only postsurgery fitness orientation (P < .001), social support from co-workers (P = .002), and physical function (P = .023) emerged as predictive of the amount of postsurgical PA. Pre- and postbariatric surgery interventions aimed at increasing physical activity participation may need to target important constructs that include the encouragement of social support and strategies to enhance the effort individuals put forward to engage in physical activity, as well as a focus on enhancing physical function and awareness of weight status.


Somatostatin desensitization in rat anterior pituitary cells.
The possibility that desensitization to the inhibitory effects of somatostatin (SS) might develop following chronic exposure to this tetradecapeptide was examined in cultured rat anterior pituitary cells. Pretreatment with 1 microM SS for 48 h caused a shift in the IC50 of SS to inhibit 3-isobutyl-1-methylxanthine (IBMX) or growth hormone-releasing factor (GRF)-induced growth hormone (GH) and TRH + IBMX-induced thyroid-stimulating hormone (TSH) release by more than 2 orders of magnitude. Refractoriness developed after 12 h of exposure to doses of SS of 10 nM or more and became maximal at 48 h. Restoration of SS responsiveness followed a similar time-course upon removal of the peptide. In superfused cells, 10 nM SS lowered GH secretion rates to less than 5 ng/min within 2 h, but GH release began to rise after 16 h despite the continued presence of SS. However, when somatostatin was delivered in pulses, it remained fully effective for more than 36 h. Somatostatin-28 was also capable of inducing refractoriness in cultured pituitary cells. However, cells made refractory to either SS-14 or SS-28 were not made refractory to the same extent to the other form of somatostatin. These results indicate that the pituitary can become desensitized to the inhibitory actions of somatostatin just as it does to the stimulatory actions of the other hypothalamic releasing hormones.


Some observations concerning 200 stapedectomies: fifteen years postoperatively.
In this study, a statistical evaluation of the hearing improvement, the incidence of postoperative tinnitus and vertigo, and the permanency of the surgically restored hearing of 120 women and 80 men operated on for otosclerosis between 1970 and 1971 was undertaken. The standardized operating procedure in all of these cases involved the use of a Gelfoam and wire prosthesis (Schuknecht 3). All patients underwent normal audiological examinations, including determination of bone and air conduction values. Pure tone thresholds were determined by averaging the values for 500, 1,000, 2,000 and 4,000 Hz. The incidence (10%) of severe sensorineural loss in regard to age, preoperative bone conduction, and oval window pathology was examined. Severe sensorineural losses had occurred immediately postoperatively in 14 of the ears. In the remaining ears, losses were gradual in the course of 15 years. Hearing thresholds in ears not subjected to operation were also determined.


Carcinoembryonic antigen levels in cervico-vaginal fluid from patients with intra-epithelial and invasive carcinoma of the cervix.
Carcinoembryonic antigen (CEA) levels have been measured in cervico-vaginal washout fluid using the direct CEA Roche radioimmunoassay. Raised CEA levels were found associated with cervical intra-epithelial neoplasia and invasive carcinoma (85% above 300 ng/ml) compared with benign cervical lesions (29% above 300 ng/ml), suggesting that estimation of local CEA levels might be a useful adjunct to cytology and biopsy in the investigation of cervical neoplasia.


Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum.
Proplasmepsin II is the zymogen of plasmepsin II, an aspartic proteinase used by Plasmodiumfalciparum to digest hemoglobin during the blood stage of malaria. A large shift between the N-domain and the central and C-domains of proplasmepsin II opens the active site cleft, preventing the formation of a functional aspartic proteinase active site. This mode of inhibition of catalytic activity has not been observed in any other aspartic proteinase zymogen. Instead of occluding a pre-formed active site, as in the gastric aspartic proteinase zymogens, the prosegment of proplasmepsin II interacts extensively with the C-domain and serves as a 'harness' to keep the domains apart. Disruption of key salt bridges at low pH may be important in activation.


Association for Bariatric Endoscopy systematic review and meta-analysis assessing the American Society for Gastrointestinal Endoscopy Preservation and Incorporation of Valuable Endoscopic Innovations thresholds for aspiration therapy.
A subcommittee of the Association for Bariatric Endoscopy, a division of the American Society for Gastrointestinal Endoscopy (ASGE) comprising experts in the subject area, performed this systematic review and meta-analysis. The systematic review and meta-analysis was reviewed by the ASGE Technology Committee and was ultimately submitted to the ASGE Governing Board for approval. The systematic review and meta-analysis underwent peer review by outside experts in statistics and meta-analysis before receiving final ASGE Governing Board approval. The Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) initiative is an ASGE program whose objectives are to identify important clinical questions related to endoscopy and to establish a priori diagnostic and/or therapeutic thresholds for endoscopic technologies designed to resolve these clinical questions. Once endoscopic technologies meet an established PIVI threshold, those technologies are appropriate to incorporate into clinical practice, presuming the appropriate training in that endoscopic technology has been achieved. ASGE encourages and supports the appropriate use of technologies that meet its established PIVI thresholds.


Discussion of development processes in insect-fungus association derived from the shaggy parasol fruiting on the nests of hairy wood ants.
Chlorophyllum rhacodes, typically regarded as a rich grassland or open forest "mushroom" species, was found fruiting abundantly on nests of Formica lugubris, occurring in a Pinus silvestris plantation. Fruiting was absent from the rest of the woodland.Research focussed on the activities in the nests that could explain this. Within nests, there was a spatial relationship between C. rhacodes mycelium, insect cadavers, fruitbody initiation, and roots of adjacent trees.In vitro experiments found that C. rhacodes was not mycorrhizal with P. silvestris, but that it had qualities which rendered it suitable for colonization of the rhizosphere in the conditions of the nest mound and for further niche development.Implications of the unusual presence of fruit-bodies and the distribution of associated hyphae are discussed in relation to the nutritional biology (and recent taxonomical reassignment) of the fungus. This includes reference to the relevant physiology of insects and to the accepted evolution of mutualistic symbioses between fungi and the Attini and Termitidae.An argument is presented that the situation observed in vivo provides evidence of a degree of facultative association and what could be tangible support for the theory for the developmental origin of mutualistic fungus cultivation by insects. It is presented as a context for continued experimental research.


Elastic behavior of the lungs in healthy children determined by means of an exponential function.
In order to evaluate the elastic properties of the lungs in children, a new exponential sigmoid curve fitting model was developed with the function VL = Vm + (Vm/1 + b X e-K X Pst), where VL is the lung volume, Pst the static recoil pressure, VM and Vm the upper and the lower asymptotes (limits of lung volume) and K and b are specific constants. Pressure-volume (PV) data obtained from tidal breathing cycles at different inflation and deflation levels from functional residual capacity (FRC) up to approximately 90% total lung capacity (TLC) in 16 healthy children have been evaluated by this model. K in relation to age, calculated by the least square nonlinear regression analysis decreased during childhood, whereas in b increased. It seems that K (a volume-independent index of compliance and alveolar distensibility) is influenced by the increasing number of elastic fiber bundles, changes in the surface/volume ratio and finally by changes in the composition of the surfactant. It can be seen that this model is not only restricted to higher lung volumes, the lower limb of the S-shaped curve is also represented.


Dispersion of graphene in ethanol using a simple solvent exchange method.
A dispersion of graphene in ethanol was achieved using solvent exchange from N-methyl-2-pyrrolidone (NMP) that enables broader application of dispersed graphene.


Manipulating ionic strength to improve single cell electrophoretic separations.
A capillary electrophoresis system with ultrasensitive two-color laser-induced fluorescence detection was used to probe the effect of ionic strength on single cell separations of glycosphingolipids. Differentiated PC12 cells were incubated with two ganglioside substrates tagged with different fluorophores within the BODIPY family such that two distinct metabolic patterns could be simultaneously monitored. Aspiration of single differentiated PC12 cells suspended in a phosphate-buffered saline solution showed excessive peak dispersion, poor resolution, and peak efficiencies below 100,000 theoretical plates. Aspiration of single differentiated PC12 cells suspended in deionized water corrected peak dispersion. Average peak efficiencies ranged between 400,000 and 600,000 theoretical plates. Improved performance was due to the dilution of the high salt concentrations inside of single neuronal-like cells to produce field amplified sample stacking. Single cell separations showed the highest resolution when aspiration of single differentiated PC12 cells suspended in deionized water were separated using a running buffer of high ionic strength. The improvement in resolution allowed for the identification of analytes not previously detected in single cell metabolism studies.


Anchoring structure of the calvarial periosteum revealed by focused ion beam/scanning electron microscope tomography.
An important consideration in regeneration therapy is the fact that the tissue surrounding an organ supports its function. Understanding the structure of the periosteum can contribute to more effective bone regeneration therapy. As a cellular source, the periosteum also assists bone growth and fracture healing; this further necessitates its direct contact with the bone. However, its anchoring strength appears to be inexplicably stronger than expected. In this study, we used focused ion beam/scanning electron microscope tomography to investigate ultrathin serial sections as well as the three dimensional ultrastructure of the periosteum to clarify the architecture of its anchoring strength, as such assessments are challenging using conventional methods. We discovered perforating fibres that arise from the bone surface at 30 degree angles. Additionally, the fibres across the osteoblast layer were frequently interconnected to form a net-like structure. Fibroblast processes were observed extending into the perforating fibres; their morphologies were distinct from those of typical fibroblasts. Thus, our study revealed novel ultrastructures of the periosteum that support anchorage and serve as a cellular source as well as a mechanical stress transmitter.


Early abortion. Update and implications for midwifery practice.
Medical abortion using methotrexate and misoprostol and manual vacuum aspiration are two new methods for pregnancy termination during the first 8 weeks of gestation. Compared to the regimen of mifepristone (RU 486) and misoprostol, both methods offer high rates of complete abortion and acceptability to users. Limitations of the new two-drug regimen compared with mifepristone include a longer time to effect abortion, transient gastrointestinal side effects, and risk of potential teratogenicity from methotrexate's cytotoxicity. Compared to standard surgical abortion, both methods allow women to avoid surgery, are more privately performed, and may be more easily accessible. The safety of first-trimester abortion provided by nurse practitioners and physician assistants has been established. Whether midwives and either new method to their practices depends on several factors. These include obtaining appropriate training, overcoming legal restrictions, and meeting professional and personal challenges inherent in providing early abortion care.


5-HT2A receptor SPECT imaging with [¹²³I]R91150 under P-gp inhibition with tariquidar: More is better?
Pharmacological P-glycoprotein (P-gp) inhibition with tariquidar (TQD) is considered a promising strategy for the augmentation of radiotracer brain uptake. However, a region-dependent effect may compromise the robustness of quantitative studies. For this reason, we studied the effect of a TQD pretreatment on 5-HT2A imaging with [(123)I]R91150 and compared results with those obtained in Mdr1a knock-out (KO) rats. Ex vivo autoradiography was performed in TQD (15 mg/kg) pretreated wild-type (WT-TQD), Mdr1a knock-out (KO) and untreated WT rats for Specific Binding Ratio (SBR) estimation. In vivo dynamic SPECT imaging with serial arterial blood sampling was performed in the former two groups of rats and kinetic analysis was performed with a one tissue-compartment (1TC) model and the Specific Uptake Ratio (SUR). Results were analyzed statistically using repeated measures ANOVA. SBR values differed between WT-TQD, Mdr1a KO and WT rats in a region-dependent manner (p<0.0001). In vivo brain uptake of radiotracer did not differ between groups. Similarly, kinetic analysis provided distribution volume (V(T)) values that did not differ significantly between groups. SUR binding potential (BPND) values from both groups highly correlated with corresponding V(T) (r=0.970, p<0.0001 and r=0.962, p<0.0001, respectively). However, SUR measured over averaged images between 100 and 120 min, using cerebellum as reference region, demonstrated values that were, by average, 2.99±0.53 times higher in the WT-TQD group, with the difference between groups being region-dependent (p<0.001). In addition, coefficient of variation of the SUR BPND values across brain regions was significantly higher in the WT-TQD rats (41.25%±9.63% versus 11.13%±5.59%, p<0.0001). P-gp inhibition with TQD leads to region-dependent effect in the rat brain, with probably sub-optimal effect in cerebellum. This warrants attention when it is used as a reference region for quantitative studies.


Prey selectivity of Piona exigua, a planktonic water mite.
Females, males and nymphs of Piona exigua were observed during prey capture and ingestion. The encounter radius of the mite was very small, allowing the escape of some crustaceans, such as the calanoid copepod Boeckella. Cladocerans, such as Bosmina or Chydorus, with little or no pre-contact escape response were the most vulnerable to mite predation. Preference values in size-selection experiments varied widely between individual mites. Adult mites presented with two sizes of Daphnia carinata generally preferred the smaller prey. When four sizes were presented simultaneously, however, the preferences of female mites for each size were not significantly different. Patterns of prey selection varied with predator age and sex; for example, female mites preferred Daphnia to Simocephalus, Ceriodaphnia and Chydorus, while nymphs showed a strong preference for Chydorus over Ceriodaphnia. When two prey types were present in equal proportions, differences in total prey density (range 5 or 10/1 - 30 or 50/1) did not alter preferences between the prey species. The preference of female mites for a particular prey type generally increased with increasing relative abundance of the prey type in each of three experiments (Daphnia: Ceriodaphnia, Ceriodaphnia: Chydorus, and Daphnia: Simocephalus). These results imply switching behaviour in these mites. Our results indicate the value of direct observation of predatory behaviour as an adjunct to prey selection experiments. It is also apparent that predatory behaviour in the presence of more than one prey type may not be predictable from that observed in single-prey situations. Predation rates on particular prey species were sometimes reduced in the presence of another species. The relative proportions of prey eaten when two species were present could not be predicted from the number of each species eaten when they were presented separately.


Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung.
1. During fetal life the lung develops as a liquid-filled organ. This liquid is produced by the fetal lung and leaves via the trachea from where it is either swallowed or enters the amniotic sac. Fetal lung liquid plays a crucial role in the growth and development of the lungs by maintaining them in a distended state. It is now recognized that the retention of liquid within the future airways is required to maintain the lungs at an appropriate level of expansion in order to stimulate their growth. Indeed, it is likely that most, if not all, of the conditions and malformations that lead to inadequate growth of the fetal lung do so by reducing the volume of lung liquid and hence the degree of lung expansion. 2. The volume of fetal lung liquid is principally regulated by the resistance to lung liquid efflux through the fetal upper airway and by the presence of diaphragmatic activity associated with fetal breathing movements (FBM). During non-breathing periods, the relatively high resistance offered by the upper airway to the efflux of lung liquid opposes the loss of liquid from the lung, thereby maintaining fetal lung expansion. During episodes of FBM, when the larynx is actively dilated and the resistance to lung liquid efflux is reduced, lung liquid leaves the lungs at an increased rate. However, selective inhibition of diaphragmatic muscle activity in the foetus leads to a reduction in lung liquid volume, rather than an increase. This finding indicates that during periods of FBM, rhythmical contractions of the diaphragm retard the loss of lung liquid and help to maintain lung expansion when the upper airway resistance is reduced. It is now apparent that the maintenance of lung expansion by FBM is the basis for their role in promoting fetal lung growth. 3. Successful transition from intra-uterine to extra-uterine life is dependent upon the clearance of liquid from the fetal lungs at the time of birth so that the lungs may effectively function as an organ of gas exchange.(ABSTRACT TRUNCATED AT 400 WORDS)


Experimental observation of cumulative second-harmonic generation of lamb waves propagating in long bones.
The experimental observation of cumulative second-harmonic generation of fundamental Lamb waves in long bones is reported. Based on the modal expansion approach to waveguide excitation and the dispersion characteristics of Lamb waves in long bones, the mechanism underlying the generation and accumulation of second harmonics by propagation of the fundamental Lamb waves was investigated. An experimental setup was established to detect the second-harmonic signals of Lamb wave propagation in long bones in vitro. Through analysis of the group velocities of the received signals, the appropriate fundamental Lamb wave modes and the duration of the second-harmonic signals could be identified. The integrated amplitude of the time-domain second-harmonic signal was introduced and used to characterize the efficiency of second-harmonic generation by fundamental Lamb wave propagation. The results indicate that the second-harmonic signal generated by fundamental Lamb waves propagating in long bones can be observed clearly, and the effect was cumulative with propagation distance when the fundamental Lamb wave mode and the double-frequency Lamb wave mode had the same phase velocities. The present results may be important in the development of a new method to evaluate the status of long bones using the cumulative second harmonic of ultrasonic Lamb waves.


Evidence for a cytoplasmic factor regulating murine leukemia virus DNA synthesis and its preliminary characterization.
Postmitochondrial cytoplasmic extracts, prepared from uninfected NIH/3T3 cells as well as from chronically or exogenously infected with murine leukemia virus (MLV), were found to stimulate the endogenous reaction of purified MLV reverse transcriptase. No such stimulation was observed with the exogenous reaction of this enzyme, using poly (rA) oligo (dT) as an exogenous template-primer. While the stimulatory capacity of extracts from uninfected and chronically infected cells was comparable, that of the exogenously infected cells was much more powerful in this respect. The stimulatory activity could be destroyed by trypsin, indicating that it was excerted by a protein. In uninfected and chronically infected cells this protein was found to be of a short functional life time under conditions blocking continuous protein synthesis. However the mRNA coding for this factor was found in these cells to be stable. On the other hand, the increased stimulatory activity, observed in extract of exogenously infected cells, was independent on protein synthesis and therefore was attributed to a protein apparently introduced into the cells by the penetrating virions. Experiments with monospecific antibodies against MLV proteins suggested that p30 is an important accessory for reverse transcriptase activity and that the cytoplasmic stimulatory factor might be also related to p 30.


Retracted: Applying Lightweight Deep Learning-Based Virtual Vision Sensing Technology to Realize and Develop New Media Interactive Art Installation.
[This retracts the article DOI: 10.1155/2022/9119316.].


Decellularization reduces the immune response to aortic valve allografts in the rat.
Cryopreserved valve allografts used in congenital cardiac surgery are associated with a significant cellular and humoral immune response. This might be reduced by removal of antigenic cellular elements (decellularization). The aim of this study was to determine the immunologic effect of decellularization in a rat allograft valve model. Brown Norway and Lewis rat aortic valves were decellularized with a series of hypotonic and hypertonic buffers, protease inhibitors, gentle detergents (Triton X-100), and phosphate-buffered saline. Valves were implanted into Lewis rats in syngeneic and allogeneic combinations. Cellular (CD3 and CD8) infiltrates were assessed with morphometric analysis, and the humoral response was assessed with flow cytometry. Morphometric analysis identified a significant reduction in CD3 + cell infiltrates (cells per square millimeter of leaflet tissue) in decellularized allografts compared with that seen in nondecellularized allografts at 1 (79 +/- 29 vs 3310 +/- 223, P < .001), 2 (26 +/- 11 vs 109 +/- 20, P = .004), and 4 weeks (283 +/- 122 vs 984 +/- 145, P < .001). Anti-CD8 staining confirmed the majority of infiltrates were cytotoxic T cells. Flow cytometric mean channel fluorescence intensity identified a negative shift (abrogated antibody formation) for decellularized allografts compared with nondecellularized allografts at 2 (19 +/- 1 vs 27 +/- 3, P = .033), 4 (35 +/- 2 vs 133 +/- 29, P = .001), and 16 weeks (28 +/- 2 vs 166 +/- 54, P = .017). Decellularization significantly reduces the cellular and humoral immune response to allograft tissue. This could prolong the durability of valve allografts and might prevent immunologic sensitization of allograft recipients.


Strong second-harmonic generation by sublattice polarization in non-uniformly strained monolayer graphene.
Despite the potential of graphene for building a variety of quantum photonic devices, its centrosymmetric nature forbids the observation of second harmonic generation (SHG) for developing second-order nonlinear devices. To activate SHG in graphene, extensive research efforts have been directed towards disrupting graphene's inversion symmetry using external stimuli like electric fields. However, these methods fail to engineer graphene's lattice symmetry, which is the root cause of the forbidden SHG. Here, we harness strain engineering to directly manipulate graphene's lattice arrangement and induce sublattice polarization to activate SHG. Surprisingly, the SHG signal is boosted 50-fold at low temperatures, which can be explained by resonant transitions between strain-induced pseudo-Landau levels. The second-order susceptibility of strained graphene is found to be larger than that of hexagonal boron nitride with intrinsic broken inversion symmetry. Our demonstration of strong SHG in strained graphene offers promising possibilities for developing high-efficiency nonlinear devices for integrated quantum circuits.


The value of coupling thin-layer chromatography to mass spectrometry in lipid research - a review.
Mass spectrometry has emerged as an extremely powerful analytical tool, which is widely used in many fields. This broad application range became possible with the invention of MALDI and ESI as "soft ionization" techniques that keep fragmentation of the analyte to a minimum. However, when these techniques are applied to mixture analysis, less-sensitively detectable compounds may be suppressed by more sensitively detectable compounds, a process called "ion suppression". Thus, previous separation of the mixture into the individual lipid classes is necessary to be able to detect all compounds. This review summarizes the current knowledge in the field of combined TLC/MS and discusses the most important strengths and weaknesses of the different MS (particularly ionization) techniques with respect to phospholipids. This comprises techniques such as MALDI and ESI, but less established approaches such as plasma desorption will be also discussed.


Study of the antifungal capacity by means of the contact test.
The antifungal activity of econazole nitrate (Pevaryl) can be demonstrated by means of a new test -- called contact test -- developed by the authors. This method of assessing the fungicidal activity was tested in nine patients and found to be satisfactory.


Treatment of congenital clubfoot with the Ponseti method: the parents' perspective.
This study aimed to analyze the perceptions of parents of children with clubfoot regarding the Ponseti method of treatment, and identify aspects of treatment that families found most difficult. Thirty families of children with clubfoot were treated with the Ponseti method over a 4-year period, and questionnaires were distributed at the conclusion of treatment. The most difficult components of treatment were identified. However, these challenges did not impact treatment outcome negatively. We hypothesize that a strong physician-patient relationship and high levels of parental education may decrease perceived difficulties of treatment with the Ponseti method.


Effects of sulthiame upon intellectual, neuropsychological, and social functioning abilities among adult epileptics: comparison with diphenylhydantoin.
This report presented results of psychological studies done during a double-blind study which compared sulthiame with diphenylhydantoin as primary agents in the treatment of uncontrolled epileptics. Assessments of intellectual, neuropsychological, and social functioning abilities were made with 22 adult epileptic patients. The results showed significantly less impairment with treatment by diphenylhydantoin than by sulthiame, and substantial differences were revealed on intellectual tasks, on tasks calling for sustained concentration and attention, and on psychomotor problem-solving tasks. The results could not be explained on the basis of increased tonic-clonic seizures while on sulthiame. However, an increase in other types of seizures was noted, as was an increase in EEG epileptiform discharges. Possible mechanisms for the decrement in performance were discussed, and the value of an objective assessment of the psychological effects of anticonvulsant agents was noted.