Expansion or extinction: deterministic and stochastic two-patch models with Allee effects.
We investigate the impact of Allee effect and dispersal on the long-term evolution of a population in a patchy environment. Our main focus is on whether a population already established in one patch either successfully invades an adjacent empty patch or undergoes a global extinction. Our study is based on the combination of analytical and numerical results for both a deterministic two-patch model and a stochastic counterpart. The deterministic model has either two, three or four attractors. The existence of a regime with exactly three attractors only appears when patches have distinct Allee thresholds. In the presence of weak dispersal, the analysis of the deterministic model shows that a high-density and a low-density populations can coexist at equilibrium in nearby patches, whereas the analysis of the stochastic model indicates that this equilibrium is metastable, thus leading after a large random time to either a global expansion or a global extinction. Up to some critical dispersal, increasing the intensity of the interactions leads to an increase of both the basin of attraction of the global extinction and the basin of attraction of the global expansion. Above this threshold, for both the deterministic and the stochastic models, the patches tend to synchronize as the intensity of the dispersal increases. This results in either a global expansion or a global extinction. For the deterministic model, there are only two attractors, while the stochastic model no longer exhibits a metastable behavior. In the presence of strong dispersal, the limiting behavior is entirely determined by the value of the Allee thresholds as the global population size in the deterministic and the stochastic models evolves as dictated by their single-patch counterparts. For all values of the dispersal parameter, Allee effects promote global extinction in terms of an expansion of the basin of attraction of the extinction equilibrium for the deterministic model and an increase of the probability of extinction for the stochastic model.


Mechanisms of Endothelial Protection by Natural Bioactive Compounds from Fruit and Vegetables.
The endothelium is fundamental for the regulation of vascular tone and structure. Under disease conditions, including the presence of cardiovascular disease risk factors, the endothelium loses its protective role and becomes a proatherosclerotic structure. In this article we searched for strategies from PUBMED and Science Direct databases using the following key words: endothelium, natural bioactive compounds, polyphenols and cardiovascular diseases. The search was restricted to english language papers. Studies have identified the contribution of diet to the risk of developing cardiovascular diseases. In this context, high intakes of fruit and vegetables are associated with the decrease of cardiovascular diseases. Thus the most important fruit/vegetables and bioactive compounds to prevent endothelial diseases are berries, apples, virgin olive oil, tomatoes, soybeans, and polyphenols, carotenoids and unsaturated fatty acids, respectively. The bioactive compounds from fruit and vegetables provide endothelial protection through the following mechanisms: improved eNOS/NO bioavailability, attenuates oxidative stress, inhibited NF-κB pathway and decreased cell adhesion molecules expression. In this article natural bioactive compound mechanisms of endothelium protection are thoroughly reviewed.


Dactylogyrids (Platyhelminthes, Monogenea) from the gill lamellae of doradids (Siluriformes) with description of five new species of Cosmetocleithrum and new geographical distribution for known species from the Neotropical Region, Brazil.
Five new species of Cosmetocleithrum were described parasitizing the gill filaments of neotropical doradid fishes. Cosmetocleithrum undulatum n. sp., Cosmetocleithrum brachylecis n. sp. and Cosmetocleithrum ludovicense n. sp. are described from Platydoras brachylecis from a market-place of São Luís, State of Maranhão, Brazil. Cosmetocleithrum sacciforme n. sp. and Cosmetocleithrum basicomplexum n. sp. are described from Oxydoras niger from Juruá River, State of Acre, Brazil. Cosmetocleithrum undulatum and Cosmetocleithrum brachylecis resemble Cosmetocleithrum falsunilatum Feronato, Razzolini, Morey & Boeger, 2022 mainly by the unique male copulatory organ (MCO) morphology but differ from these and all congeneric species mainly by the morphology of the MCO, accessory piece and hooks pairs. Cosmetocleithrum ludovicense is closer to Cosmetocleithrum confusus Kritsky, Thatcher & Boeger, 1986 and to Cosmetocleithrum akuanduba Soares, Santos Neto & Domingues, 2018 but differs from those mainly by the morphology of the accessory piece. Cosmetocleithrum sacciforme differs from all congeneric species mainly by the morphology of the accessory piece formed by a single plate of saccular appearance. Cosmetocleithrum basicomplexum also shares morphological characters with Cosmetocleithrum gigas Morey, Cachique & Babilonia, 2019 considering the size of the body and shape of the anchors, but differs mainly in the morphology of the bars and hooks. Besides the new species, new data are presented for Cosmetocleithrum leandroi Soares, Neto & Domingues, 2018, C. akuanduba and C. confusus regarding morphological characteristics and biogeography.


Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity.
Hyperglycemia is associated with altered myocardial substrate use, a condition that has been hypothesized to contribute to impaired cardiac performance. The goals of this study were to determine whether changes in cardiac metabolism, gene expression, and function precede or follow the onset of hyperglycemia in two mouse models of obesity, insulin resistance, and diabetes (ob/ob and db/db mice). Ob/ob and db/db mice were studied at 4, 8, and 15 wk of age. Four-week-old mice of both strains were normoglycemic but hyperinsulinemic. Hyperglycemia develops in db/db mice between 4 and 8 wk of age and in ob/ob mice between 8 and 15 wk. In isolated working hearts, rates of glucose oxidation were reduced by 28-37% at 4 wk and declined no further at 15 wk in both strains. Fatty acid oxidation rates and myocardial oxygen consumption were increased in 4-wk-old mice of both strains. Fatty acid oxidation rates progressively increased in db/db mice in parallel with the earlier onset and greater duration of hyperglycemia. In vivo, cardiac catheterization revealed significantly increased left ventricular contractility and relaxation (positive and negative dP/dt) in both strains at 4 wk of age. dP/dt declined over time in db/db mice but remained elevated in ob/ob mice at 15 wk of age. Increased beta-myosin heavy chain isoform expression was present in 4-wk-old mice and persisted in 15-wk-old mice. Increased expression of peroxisomal proliferator-activated receptor-alpha regulated genes was observed only at 15 wk in both strains. These data indicate that altered myocardial substrate use and reduced myocardial efficiency are early abnormalities in the hearts of obese mice and precede the onset of hyperglycemia. Obesity per se does not cause contractile dysfunction in vivo, but loss of the hypercontractile phenotype of obesity and up-regulation of peroxisomal proliferator-activated receptor-alpha regulated genes occur later and are most pronounced in the presence of longstanding hyperglycemia.


Burden of child and adolescent obesity on health services in England.
To assess the numbers of obese children and young people (CYP) eligible for assessment and management at each stage of the childhood obesity pathway in England. Pathway modelling study, operationalising the UK National Institute for Health and Care Excellence guidance on childhood obesity management against national survey data. Data on CYP aged 2-18 years from the Health Survey for England 2006 to 2013. Clinical obesity (body mass index (BMI) >98th centile), extreme obesity (BMI ≥99.86th centile); family history of cardiovascular disease or type 2 diabetes; obesity comorbidities defined as primary care detectable (hypertension, orthopaedic or mobility problems, bullying or psychological distress) or secondary care detectable (dyslipidaemia, hyperinsulinaemia, high glycated haemoglobin, abnormal liver function). 11.2% (1.22 million) of CYP in England were eligible for primary care assessment and for community lifestyle modification. 2.6% (n=283 500) CYP were estimated to be likely to attend primary care. 5.1% (n=556 000) were eligible for secondary care referral. Among those aged 13-18 years, 8.2% (n=309 000) were eligible for antiobesity drug therapy and 2.4% (90 500) of English CYP were eligible for bariatric surgery. CYP from the most deprived quintile were 1.5-fold to 3-fold more likely to be eligible for obesity management. There is a mismatch between population burden and available data on service use for obesity in CYP in England, particularly among deprived young people. There is a need for consistent evidence-based commissioning of services across the childhood obesity pathway based on population burden.


The social networks of older schizophrenia patients. Clinical Research Center on Late Life Psychosis Research Group.
There is a paucity of research that examines the role of family members and friends in the lives of older schizophrenia patients. This study compared 66 middle-aged and elderly outpatients with 31 normal comparison subjects. Five dimensions of social network were assessed: (a) family composition, geographic proximity, and frequency of contact; (b) instrumental support; (c) emotional support and interpersonal difficulties; (d) role of friends; and (e) use of formal service providers as sources of support and assistance. As compared with normal subjects, the schizophrenia patients were less likely to be married, less likely to have children, more likely to live alone, and had fewer friendships. The patients were, however, similar to comparison subjects on the following family-relationship variables: frequency of contact, instrumental support received, presence of a family confidant, and extent of interpersonal difficulties. These findings do not support the stereotype of older schizophrenia patients as being estranged from family members. The need for developing interventions that use key family members to interface with service providers and to monitor treatment compliance and continuity of care is discussed.


Classification and regression of spatio-temporal signals using NeuCube and its realization on SpiNNaker neuromorphic hardware.
The objective of this work is to use the capability of spiking neural networks to capture the spatio-temporal information encoded in time-series signals and decode them without the use of hand-crafted features and vector-based learning and the realization of the spiking model on low-power neuromorphic hardware. The NeuCube spiking model was used to classify different grasp movements directly from raw surface electromyography signals (sEMG), the estimations of the applied finger forces as well as the classification of two motor imagery movements from raw electroencephalography (EEG). In a parallel investigation, the designed spiking decoder was implemented on SpiNNaker neuromorphic hardware, which allows low-energy real-time processing. Experimental results reveal a better classification accuracy using the NeuCube model compared to traditional machine learning methods. For sEMG classification, we reached a training accuracy of 85% and a test accuracy of 84.8%, as well as less than 19% of relative root mean square error (rRMSE) when estimating finger forces from six subjects. For the EEG classification, a mean accuracy of 75% was obtained when tested on raw EEG data from nine subjects from the existing 2b dataset from 'BCI competition IV'. This work provides a proof of concept for a successful implementation of the NeuCube spiking model on the SpiNNaker neuromorphic platform for raw sEMG and EEG decoding, which could chart a route ahead for a new generation of portable closed-loop and low-power neuroprostheses.


Clinical experience with polydioxanone monofilament absorbable sutures in plastic surgery.
Various sizes of undyed monofilament polydioxanone surgical suture were assessed in 52 surgical patients who underwent plastic surgery. With a single exception, follow-up observations were carried out for at least 40 days. Clinical results were judged satisfactory in 13 patients and excellent in 39 patients. The suture was found significantly better than gut in terms of pliability, ease of passage through tissue, ease of tying, strength, fray resistance, and overall handling properties. The undyed suture material tested in this study was rated as having inferior visibility when compared with surgical gut. This new suture material, the first synthetic absorbable available as a monofilament, would appear to be particularly useful in situations requiring extended wound support, in potentially infected wounds in which a monofilament suture would have lessened tendency to harbor pathogenic bacteria, and in cases where ease of passage through tissue, smooth tie-down, and precise knot placement are important.


The Safe Values of Quantitative Perfusion Parameters of ICG Angiography Based on Tissue Oxygenation of Hyperspectral Imaging for Laparoscopic Colorectal Surgery: A Prospective Observational Study.
Safe values for quantitative perfusion parameters of indocyanine green (ICG) angiography have not been fully defined, and interpretation remains at the surgeon's discretion. This prospective observational study aimed to establish the safe values for the quantitative perfusion parameters by comparing tissue oxygenation levels from HSI images in laparoscopic colorectal surgery. ICG angiography was performed using a laparoscopic near-infrared (NIR) camera system with ICG diluted in 10 mL of distilled water. For quantitative perfusion parameters, the changes in fluorescence intensity with perfusion times were analyzed to plot a time-fluorescence intensity graph. To assess real-time tissue oxygen saturation (StO2) in the colon, the TIVITA® Tissue System was utilized for hyperspectral imaging (HSI) acquisition. The StO2 levels were compared with the quantitative perfusion parameters derived from ICG angiography at corresponding points to define the safe range of ICG parameters reflecting good tissue oxygenation. In the regression analysis, T1/2MAX, TMAX, slope, and NIR perfusion index were correlated with tissue oxygen saturation. Using this regression model, the cutoff values of quantitative perfusion parameters were calculated as T1/2MAX ≤ 10 s, TMAX ≤ 30 s, slope ≥ 5, and NIR perfusion index ≥50, which best reflected colon StO2 higher than 60%. Diagnostic values were analyzed to predict colon StO2 of 60% or more, and the ICG perfusion parameters T1/2MAX, TMAX, and perfusion TR showed high sensitivity values of 97% or more, indicating their ability to correctly identify cases with acceptable StO2. The safe values for quantitative perfusion parameters derived from ICG angiography were T1/2MAX ≤ 10 s and TMAX ≤ 30 s, which were associated with colon tissue oxygenation levels higher than 60% in the laparoscopic colorectal surgery.


Gypenosides induce cell death and alter gene expression in human oral cancer HSC-3 cells.
Gypenosides (Gyp), the primary components of Gynostemma pentaphyllum Makino, have long been used as a Chinese herbal medicine. In the present study, the effects of Gyp on cell viability, the cell cycle, cell apoptosis, DNA damage and chromatin condensation were investigated in vitro using human oral cancer HSC-3 cells. The results of the present study indicated that Gyp induces cell death, G2/M phase arrest and apoptosis in HSC-3 cells in a dose-dependent manner. It was also demonstrated that Gyp decreased the depolarization of mitochondrial membrane potential in a time-dependent manner. A cDNA microarray assay was performed and the results indicated that a number of genes were upregulated following Gyp treatment. The greatest increase was a 75.42-fold increase in the expression of GTP binding protein in skeletal muscle. Levels of the following proteins were also increased by Gyp: Serpine peptidase inhibitor, clade E, member 1 by 20.25-fold; ras homolog family member B by 18.04-fold, kelch repeat and BTB domain containing 8 by 15.22-fold; interleukin 11 by 14.96-fold; activating transcription factor 3 by 14.49-fold; cytochrome P450, family 1 by 14.44-fold; ADP-ribosylation factor-like 14 by 13.88-fold; transfer RNA selenocysteine 2 by 13.23-fold; and syntaxin 11 by 13.08-fold. However, the following genes were downregulated by GYP: Six-transmembrane epithelial antigen of prostate family member 4, 14.19-fold; γ-aminobutyric acid A receptor by 14.58-fold; transcriptional-regulating factor 1 by 14.69-fold; serpin peptidase inhibitor, clade B, member 13 by 14.71-fold; apolipoprotein L 1 by 14.85-fold; follistatin by 15.22-fold; uncharacterized LOC100506718; fibronectin leucine rich transmembrane protein 2 by 15.61-fold; microRNA 205 by 16.38-fold; neuregulin 1 by 19.69-fold; and G protein-coupled receptor 110 by 22.05-fold. These changes in gene expression illustrate the effects of Gyp at the genetic level and identify potential targets for oral cancer therapy.


Risk factors for multiple oral premalignant lesions.
Oral leukoplakia, oral submucous fibrosis and erythroplakia are 3 major types of oral premalignant lesions. Multiple oral premalignant lesions may possibly develop due to field cancerization, where carcinogenic exposures can cause simultaneous genetic defects to the upper aerodigestive tract epithelium, putting the epithelium at high risk for development of premalignant lesions at different stages of carcinogenesis. There have been no epidemiological studies on risk or protective factors of the disease. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. A total of 115 subjects with multiple oral premalignant lesions (8-10% of oral premalignant lesions in our case series) were included: 64 subjects with oral leukoplakia and oral submucous fibrosis, 19 subjects with oral leukoplakia and erythroplakia, 22 subjects with oral submucous fibrosis and erythroplakia and 10 subjects with all 3 lesions. Individuals without oral lesions were considered controls (n=47,773). The odds ratio (OR) for ever tobacco chewers was 37.8 (95% confidence interval (CI)=16.2-88.1) when adjusted for age, sex, education, BMI, smoking, drinking and fruit/vegetable intake. Dose-response relationships were seen for the frequency (p<0.0001) and duration of tobacco chewing (p<0.0001) with the risk of multiple oral premalignant lesions. Whereas alcohol drinking may possibly be a risk factor for multiple oral premalignant lesions, smoking was not associated with the risk of multiple oral premalignant lesions (OR=0.9, 95%CI=0.5-1.7). The results suggest that tobacco chewing was the most important risk factor for multiple oral premalignant lesions and may be a major source of field cancerization on the oral epithelium in the Indian population.


Insulin-like growth factor binding proteins-2 to -6 are expressed by human vascular smooth muscle cells.
We have investigated the expression and secretion of insulin-like growth factor binding proteins (IGFBPs-1 to -6) in human vascular smooth muscle cells (hVSMCs) cultured from human renal arteries. Solution hybridization was used to determine IGFBP mRNA levels and Western immunoblot to detect the corresponding peptides. The hVSMCs expressed mRNAs for IGFBPs-2 to -6; IGFBP-1 mRNA was not detected. IGFBPs-3, -4 and -6 mRNAs were the most abundant, IGFBP-5 was also highly expressed, whereas the IGFBP-2 mRNA was just above the limit of detection. Serum starvation for 48 h significantly decreased the mRNA levels of IGFBPs-2 to -5 and tended to decrease IGFBP-6 mRNA also. IGFBPs-2, -4, -5 and -6 peptides could be detected in conditioned medium, but IGFBP-3 peptide was not detected. IGFBP-4 was the only peptide detected without any concentration step. Low-molecular-mass immunoreactive degradation products were found for IGFBPs-2 and -4. Exogenous IGFBPs-1, -3 and -4 in concentrations of 50 ng/ml inhibited DNA synthesis induced by 1 nM IGF-I, whereas IGFBPs-2, -5 and -6 had no significant inhibitory effects at this concentration. We conclude from these results that all IGFBPs except IGFBP-1 are expressed in hVSMC. Our results indicate that locally produced, in addition to circulating, IGFBPs may have an important role in the regulation of hVSMC.


Pawsitively sad: pet-owners are more sensitive to negative emotion in animal distress vocalizations.
Pets have numerous, effective methods to communicate with their human hosts. Perhaps most conspicuous of these are distress vocalizations: in cats, the 'miaow' and in dogs, the 'whine' or 'whimper'. We compared a sample of young adults who owned cats and or dogs ('pet-owners' n = 264) and who did not (n = 297) on their ratings of the valence of animal distress vocalizations, taken from a standardized database of sounds. We also examined these participants' self-reported symptoms of anxiety and depression, and their scores on a measure of interpersonal relationship functioning. Pet-owners rated the animal distress vocalizations as sadder than adults who did not own a pet. Cat-owners specifically gave the most negative ratings of cat miaows compared with other participants, but were no different in their ratings of other sounds. Dog sounds were rated more negatively overall, in fact as negatively as human baby cries. Pet-owning adults (cat only, dog only, both) were not significantly different from adults with no pets on symptoms of depression, anxiety or on self-reported interpersonal relationship functioning. We suggest that pet ownership is associated with greater sensitivity to negative emotion in cat and dog distress vocalizations.


Dynamic Ligand Surface Chemistry of Excited PbS Quantum Dots.
The ligand shell around colloidal quantum dots mediates the electron and energy transfer processes that underpin their use in optoelectronic and photocatalytic applications. Here, we show that the surface chemistry of carboxylate anchoring groups of oleate ligands passivating PbS quantum dots undergoes significant changes when the quantum dots are excited to their excitonic states. We directly probe the changes of surface chemistry using time-resolved mid-infrared spectroscopy that records the evolution of the vibrational frequencies of carboxylate groups following excitation of the electronic states. The data reveal a reduction of the Pb-O coordination of carboxylate anchoring groups to lead atoms at the quantum dot surfaces. The dynamic surface chemistry of the ligands may increase their surface mobility in the excited state and enhance the ability of molecular species to penetrate the ligand shell to undergo energy and charge transfer processes that depend sensitively on distance.


Validation of the Turkish Version of the Montreal Cognitive Assessment Scale (MoCA-TR) in patients with Parkinson's disease.
The study aimed to examine the reliability and validity of the Turkish version of the Montreal Cognitive Assessment Scale (MoCA-TR) as a screening tool for cognitive dysfunction in Parkinson's disease (PD). A total of 50 patients with PD and 50 healthy controls were included. The screening instruments-MoCA-TR followed by the Mini-Mental Status Examination (MMSE-TR) and MoCA-TR retest within 1 month-and detailed neuropsychological testing were administered to the PD patients. MoCA-TR and MMSE-TR were also administered to controls. The discriminant validities of the MoCA-TR and MMSE-TR as screening and diagnostic instruments were ascertained. The concurrent and criterion validity, test-retest reliability, and internal consistency of the MoCA-TR and MMSE-TR were examined. The Cronbach's alpha of the MoCA-TR as an index of internal consistency was 0.664, and the test-retest reliability of MoCA-TR was 0.742. With a cut-off score of < 21 points, the MoCA-TR showed sensitivity of 59% and specificity of 89% in the detection of cognitive dysfunction in PD. The area under the receiver-operating characteristics curve (95% confidence interval) for MoCA-TR was 0.794 (0.670-0.918), p<.001. The present results indicated that the MoCA-TR has acceptable psychometric properties and it should be used to assess mild cognitive impairment and early dementia in PD patients, whereas the MMSE-TR should remain the instrument of choice to assess cognitive impairment in PD dementia.


Older siblings are at increased risk for foreign bodies.
A prospective, case-control study was performed to describe the role that siblings play in foreign bodies of the head and neck and to recognize situations in which children are most at risk for foreign bodies. Any child or adolescent (0 to 17 years old) with a foreign body removed from the head or neck was included. The data collected included location of the foreign body, location of acquisition (e.g., home), and the number of and ages of siblings. Controls were matched by age, sex, and location of removal (clinic, operating room, or emergency department). Thirty-four patients were enrolled (20 male, 14 female). The average age was 5.25 years (range: 10 months to 15 years). The average age of patients with foreign bodies in the ear was 5.98 years (n = 23), esophagus 4.34 years (n = 6), and nose 2.97 years (n = 5). Nineteen (56%) of the foreign bodies were acquired at home and 17 (50%) under supervision by parents. Children with a younger sibling have a significantly increased risk of acquiring a foreign body compared with children without a younger sibling (odds ratio = 4.00, p = 0.04). We conclude that although acquisition of foreign bodies should become less common as children mature, older siblings (i.e., children who have a younger sibling) are at increased risk for foreign body acquisition. Most foreign bodies are acquired at home under supervision by parents. Increased awareness of this finding may help prevent foreign bodies in the head and neck.


Hormonal regulation of protein synthesis in the rat epididymis. Characterization of androgen-dependent and testicular fluid-dependent proteins.
1. Protein synthesis has been investigated in different regions of the rat epididymis by measuring incorporation of [35S]methionine in tissue minces incubated in vitro followed by analysis of labelled proteins on polyacrylamide gels containing sodium dodecyl sulphate. Rates of synthesis were highest in the proximal cauda > distal cauda > initial segment > ductuli efferentes > corpus > distal caput > proximal caput. One protein (mol.wt. 23 000) characterized the initial segment, three proteins (mol.wts. 18 500, 19 000 and 32 000) the caput and one protein (mol.wt. 47 000) the cauda. 2. After castration, [35S]methionine incorporation in all regions of the epididymis was reduced to < 10% of that in normal animals but could be restored to control levels within 5 days by testosterone treatment. Other steroids (corticosterone, oestrogen or progesterone) were ineffective. 3. The synthesis of the 18 500, 19 000, and 32 000 mol.wt. proteins in the caput and the 47 000 mol.wt. protein in the cauda were preferentially regulated by androgens, whilst the synthesis of 23 000 and approx. 80 000 mol.wt. proteins in the initial segment was dependent upon factors present in testicular fluid. 4. The androgen-dependent and testicular fluid-dependent proteins were major components of epididymal secretion. Purification and characterization of the 18 500, 19 000, 23 000 and 32 000 mol.wt. proteins showed them to be acidic glycoproteins with a carbohydrate content of 7.6-13.2%. The 47 000 mol.wt. protein, on the other hand, is highly basic. 5. A possible role for these proteins in the acquisition of motility, fertilizing capacity and storage of spermatozoa in the epididymis is discussed.


Validating a Measure of Numeracy Skill Use in the Workplace for Incarcerated and Household Adults.
The aim of this study is to construct a measure of numeracy skill use in the workplace for incarcerated and household adults. The 2012/2014 Programme for the International Assessment of Adult Competencies (PIAAC) Survey of Adult Skills asked about the type and frequency of numeracy tasks performed as part of one's job to nationally-representative incarcerated and household adult samples. This paper takes these items from this survey and focuses on the validation of a measure of numeracy skill use in the workplace using the principles of the Rasch rating scale model. In the interest of exploring options for strengthened validity, response categories were collapsed to produce an optimal categorization structure. Findings suggest an instrument to measure numeracy skill use in prison and free market workplaces could potentially be improved with fewer response categories and more items that ask about a broader range of numeracy skills.


A young mountaineer surviving sudden cardiac arrest at high altitude.
A young mountaineer suffered from sudden cardiac arrest at high altitude. Cardiopulmonary resuscitation was initiated immediately. After 30 min a rescue team arrived and successfully defibrillated ventricular fibrillation upon which spontaneous circulation returned. The subsequent ECG was suggestive of extensive anterior myocardial infarction. Therefore, the patient was thrombolysed and transferred for primary percutaneous coronary intervention. Echocardiography revealed severely reduced left ventricular function with antero-septo-apical akinesia. However, angiography showed unobstructed coronary arteries. The patient fully recovered and left ventricular function normalised within 2 weeks. It may be speculated that exposure to high altitude resulted in acute coronary thrombosis which dissolved by rapid thrombolysis.


Enhanced nonlinear optical conversion from a periodically nanostructured metal film.
We demonstrate an approximately10(4) increase in conversion efficiency for optical second-harmonic generation (SHG) from a periodically nanostructured metal structure consisting of a single subwavelength aperture in a thin silver film surrounded by a set of concentric surface grooves. The forward-transmitted second-harmonic radiation from this structure is measured relative to that from an identical aperture with no surrounding surface periodicity. We explain the observed SHG enhancement quantitatively in terms of a measured 120x increase in the strength of the fundamental radiation in the vicinity of the aperture resulting from the periodic nanostructuring.


"Death drive" scientifically reconsidered: Not a drive but a collection of trauma-induced auto-addictive diseases.
Over the last 102 years, a lot of discussion was being held about the psychoanalytic conception of the "death drive," but still with inconclusive results. In this paper, we start with a brief review of Freud's conception, followed by a comprised overview of its subsequent support or criticisms. The core of our argument is a systematic review of current biochemical research about two proposed manifestations of the "death drive," which could hopefully move the discussion to the realm of science. It was already established that drive satisfaction leads to the secretion of beta-endorphins, and research evidence also shows that the same biochemical mechanisms get activated in the case of masochism and the gambling disorder but only if they are preceded by chronic frustration of the essential drives. We conclude that the actual situation is more complex than Freud hypothesized, and that a fundamental revision of the psychoanalytic drive theory is necessary.


Dual Polymerization Pathway for Polyolefin-Polar Block Copolymer Synthesis via MILRad: Mechanism and Scope.
This work explores the mechanism whereby a cationic diimine Pd(II) complex combines coordination insertion and radical polymerization to form polyolefin-polar block copolymers. The initial requirement involves the insertion of a single acrylate monomer into the Pd(II)-polyolefin intermediates, which generate a stable polymeric chelate through a chain-walking mechanism. This thermodynamically stable chelate was also found to be photochemically inactive, and a unique mechanism was discovered which allows for radical polymerization. Rate-determining opening of the chelate by an ancillary ligand followed by additional chain walking allows the metal to migrate to the α-carbon of the acrylate moiety. Ultimately, the molecular parameters necessary for blue-light-triggered Pd-C bond homolysis from this α-carbon to form a carbon-centered macroradical species were established. This intermediate is understood to initiate free radical polymerization of acrylic monomers, thereby facilitating block copolymer synthesis from a single Pd(II) complex. Key intermediates were isolated and comprehensively characterized through exhaustive analytical methods which detail the mechanism while confirming the structural integrity of the polyolefin-polar blocks. Chain walking combined with blue-light irradiation functions as the mechanistic switch from coordination insertion to radical polymerization. On the basis of these discoveries, robust di- and triblock copolymer syntheses have been demonstrated with olefins (ethylene and 1-hexene) which produce amorphous or crystalline blocks and acrylics (methyl acrylate, ethyl acrylate, n-butyl acrylate, and methyl methacrylate) in broad molecular weight ranges and compositions, yielding AB diblocks and BAB triblocks.


Development and clinical evaluation of a dried urine spot method for detection of morphine among opioid users.
In recent years, drug testing in body fluids has gained popularity for validating self-reported drug use. The storage and transportation of urine specimens is a major concern for remote areas where the facilities for performing drug abuse testing are lacking. The aim of the present study was to develop an efficient method for testing opiate in dried urine spots (DUS) and to evaluate its clinical applicability. The methodology involved optimization of conditions for extraction, recovery, short-, and long-term stability (room temperature, 4°C,-20°C) for detection of opiate from dried urine spots. Further, the extraction efficiency from dried urine spots was compared with the conventional drug testing methodology. The screening was done by using enzyme-linked immunosorbent assay technique, and confirmation was achieved by gas chromatography equipped with nitrogen phosphorus detector. Deionized water was found to be a suitable extracting solvent compare to bi-carbonate buffer (pH 9.2) and saline. Primary screening was achieved by 2 punches taken from a 20-μl (diameter 1.3 cm) spotted urine samples, whereas confirmation was achieved by 2 complete circles each of 20 μl sample volume. The recovery was found to be 99.41% in water. No sign of significant degradation was seen among all storage conditions. In the current study, DUS has achieved the same level of precision and reproducibility as that of standard methods used for drug testing in urine. Hence, the DUS sampling appears to have potential to detect opiate among drug users in a clinical setting.


Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications.
OCT has revolutionized the practice of ophthalmology over the past 10-20 years. Advances in OCT technology have allowed for the creation of novel OCT-based methods. OCT-Angiography (OCTA) is one such method that has rapidly gained clinical acceptance since it was approved by the FDA in late 2016. OCTA images are based on the variable backscattering of light from the vascular and neurosensory tissue in the retina. Since the intensity and phase of backscattered light from retinal tissue varies based on the intrinsic movement of the tissue (e.g. red blood cells are moving, but neurosensory tissue is static), OCTA images are essentially motion-contrast images. This motion-contrast imaging provides reliable, high resolution, and non-invasive images of the retinal vasculature in an efficient manner. In many cases, these images are approaching histology level resolution. This unprecedented resolution coupled with the simple, fast and non-invasive imaging platform have allowed a host of basic and clinical research applications. OCTA demonstrates many important clinical findings including areas of macular telangiectasia, impaired perfusion, microaneurysms, capillary remodeling, some types of intraretinal fluid, and neovascularization among many others. More importantly, OCTA provides depth-resolved information that has never before been available. Correspondingly, OCTA has been used to evaluate a spectrum of retinal vascular diseases including diabetic retinopathy (DR), retinal venous occlusion (RVO), uveitis, retinal arterial occlusion, and age-related macular degeneration among others. In this review, we will discuss the methods used to create OCTA images, the practical applications of OCTA in light of invasive dye-imaging studies (e.g. fluorescein angiography) and review clinical studies demonstrating the utility of OCTA for research and clinical practice.


The role of CEA and liver function tests in the detection of hepatic metastases from colo-rectal cancer.
Carcinoembryonic antigen and some liver function tests (alkaline phosphatase, gamma-glutamyltranspeptidase, lactic dehydrogenase and cholinesterase) were evaluated in patients with primary colorectal cancer in order to define their role in the pre-operative detection of liver metastases. The records of 278 consecutive patients admitted to the Istituto Nazionale Tumori of Milan between January 1982 and December 1983 who were suffering from primary invasive colo-rectal cancer and who underwent laparotomy were retrospectively analyzed. At laparotomy, liver metastases were found in 38 pts (13.7%). Considering single tests, CEA was the most sensitive (71%); no single test was found to be reliably predictive, when the result was abnormal. On the contrary, the normal value of each test was associated with a good prediction. When we considered all the five tests together in the single patient their predictive value, when abnormal, proved to be quite good only if four or five results were abnormal. On the other hand, liver metastases in the presence of all normal tests were found only in two patients, so giving a negative predictive value of about 97%. So we conclude that, in the lack of an infallible imaging technique for liver evaluation, in the presence of all normal tests any other investigation on the liver could be avoided. However, when liver tests are pathologic, some other imaging technique should be performed in order to supply the surgeon with information about the extent and the spread of the metastases.


Use of deep brain stimulation in treatment-resistant depression.
Deep brain stimulation has emerged as an experimental treatment option for the sizeable proportion of patients with major depression that is refractory to multiple medications and psychotherapy. Chronic stimulation of the ventral internal capsule/ventral striatum has been shown to improve function and mood in patients with severe obsessive-compulsive disorder, and has likewise been applied to patients with treatment-resistant depression. Multicenter experience with chronic deep brain stimulation of the ventral capsule/ventral striatum in 17 patients with severe treatment-resistant depression has demonstrated sustained improvements across multiple scales of depression, anxiety, and global function. Further research on deep brain stimulation in larger populations of patients with treatment-refractory depression is under way. While such research should benefit from the recent US Food and Drug Administration approval of deep brain stimulation for severe obsessive-compulsive disorder, it must adhere to strict principles for appropriate patient selection.


Molecular characterization of a novel 55.1 kb (G)gamma((A)gammadeltabeta)(0)-thalassemia deletion in two Canadian families.
We report two Canadian families in which there are four carriers of a novel (G)gamma((A)gammadeltabeta)(0)-thalassemia deletion. The patients all have mild microcytosis and hypochromia, and elevated levels of Hb F ranging from 9.7 to 17.3%. The precise endpoints of the deletion have been identified and are unique relative to other forms of (G)gamma((A)gammadeltabeta)(0)-thal reported in the literature. The deletion encompasses approximately 55.1 kb, beginning approximately 1.6 kb downstream of the (G)gamma-globin gene and extending approximately 29.0 kb downstream of the beta-globin gene.


Dyspareunia in a Survivor of Childhood Sexual Abuse.
Dyspareunia is a frequent chief concern encountered by midwives and other women's health care providers. There are many possible etiologies for dyspareunia, including a history of childhood sexual abuse, and approaching assessment in a holistic manner is necessary to identify the etiology. This case report presents evidence on the importance of screening a woman who presents with dyspareunia in a therapeutic manner to facilitate disclosure of sexual abuse. Best practices for screening for sexual violence, along with recommendations for providing gynecologic care to survivors, are offered. By understanding the long-term sequelae of sexual abuse and through screening all women, midwives and other women's health care providers can facilitate healing and treatment for survivors.


Caregiver and community insights on coping strategies used by adolescents living in conflict-affected communities.
The aim of this qualitative study was to provide a context-specific understanding of adolescent (10-15 years of age) exposure and coping with trauma from the perspective of mothers/female caregivers and key informants in rural conflict-affected villages. Focus groups were conducted with mothers/female caregivers (4 groups with total participants n = 26) and interviews were conducted with key informants (n = 9) in four villages in the Walungu Territory, Eastern Democratic Republic of Congo. Focus group and interview guides were designed to elicit responses by participants on adolescent exposures to trauma and coping strategies. A grounded theory approach was used to identify emergent themes. Mothers/female caregivers and key informants reported use of both cognitive and behavioural coping strategies by adolescents. Cognitive coping strategies included avoidance and trying to forget. Behavioural strategies included self-imposed isolation, risk-taking and social-support-seeking behaviours. Findings indicated community social support was a critical resource for adolescents, particularly for adolescents that did not have adequate support from their family. Supporting positive peer, family and community relationships can help prevent risk-taking behaviours and teach positive coping strategies to break a cycle of violence reported in these communities. Recommendations for gender-specific intervention programming are highlighted. DRC: Democratic Republic of Congo; PAIDEK: Programme d'Appui aux Initiatives Economiques; PFP: Pigs for Peace; RFR: Rabbits for Resilience.


Controlling mode degeneracy in a photonic crystal nanocavity with infiltrated liquid crystal.
We demonstrate the control of the mode degeneracy when a liquid crystal (LC) is infiltrated into an InGaAsP membrane photonic crystal nanocavity with embedded InAs quantum dots. Mode splitting exists in the anisotropic nematic LC state, and not in the unfilled or isotropic LC state. The degeneracy lifting of the quadrupole mode is attributed to the different interactions of the two orthogonal basis modes of the degenerate mode with the two components of the refractive index of the LC. The interpretation is supported by the quantitative agreement between the experimental results and the three-dimensional finite-difference time-domain computations.


Brazilin from Caesalpinia sappan L. as a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor: Pharmacophore-Based Virtual Screening, In Silico Molecular Docking, and In Vitro Studies.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial regulator of low-density lipoprotein cholesterol (LDL-c) levels, as it binds to and degrades the LDL receptor (LDLR) in the lysosome of hepatocytes. Elevated levels of PCSK9 have been linked to an increased LDL-c plasma levels, thereby increasing the risk of cardiovascular disease (CVD), making it an attractive target for therapeutic interventions. As a way to inhibit PCSK9 action, we searched for naturally derived small molecules which can block the binding of PCSK9 to the LDLR. In this study, we carried out in silico studies which consist of virtual screening using an optimized pharmacophore model and molecular docking studies using Pyrx 0.98. Effects of the candidate compounds were evaluated using in vitro PCSK9-LDLR binding assays kit. Eleven natural compounds that bind to PCSK9 were virtually screened form HerbalDB database, including brazilin. Next, molecular docking studies using Pyrx 0.98 showed that brazilin had the highest binding affinity with PCSK9 at -9.0 (Kcal/mol), which was higher than that of the other ten compounds. Subsequent in vitro PCSK9-LDLR binding assays established that brazilin decreased the binding of PCSK9 to the EGF-A fragment of the LDLR in a dose-dependent manner, with an IC50 value of 2.19 μM. We have identified brazilin, which is derived from the Caesalpinia sappan herb, which can act as a small molecule inhibitor of PCSK9. Our findings suggest that screening for small molecules that can block the interaction between PCSK9 and the LDLR in silico and in vitro may be a promising approach for developing novel lipid-lowering therapy.


Generation and validation of a myoglobin knockout zebrafish model.
Previous studies using myoglobin (Mb) knockout mice and knockdown zebrafish have presented conflicting results about in vivo phenotypes resulting from the loss of this conserved and highly expressed protein, and therefore a new well-characterized knockout model is warranted. We here describe the generation of three distinct zebrafish mb knockout lines using the CRISPR/Cas system. None of the three lines exhibited any morphological phenotypes, changes in length, or lethality during embryonic and larval development. The adult homozygous knockout mb(Auzf13.2) zebrafish line were absent of Mb protein, had an almost complete degradation of mb mRNA, and showed no changes in viability, length, or heart size. Furthermore, transcriptomic analysis of adult heart tissue showed that mb knockout did not cause altered expression of other genes. Lastly, no off-targeting was observed in 36 screened loci. In conclusion, we have generated three mb knockout lines with indistinguishable phenotypes during embryonic and larval development and validated one of these lines, mb(Auzf13.2), to have no signs of genetic compensation or off-target effects in the adult heart. These findings suggests that the mb(Auzf13.2) shows promise as a candidate for investigating the biological role of Mb in zebrafish.


Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications.
CHCHD2 mutations have been identified in various neurological diseases such as Parkinson's disease (PD), frontotemporal dementia (FTD), and Alzheimer's disease (AD). It is also the first mitochondrial gene whose mutations lead to PD. CHCHD10 is a homolog of CHCHD2; similar to CHCHD2, various mutations of CHCHD10 have been identified in a broad spectrum of neurological disorders, including FTD and AD, with a high frequency of CHCHD10 mutations found in motor neuron diseases. Functionally, CHCHD2 and CHCHD10 have been demonstrated to interact with each other in mitochondria. Recent studies link the biological functions of CHCHD2 to the MICOS complex (mitochondrial inner membrane organizing system). Multiple experimental models suggest that CHCHD2 maintains mitochondrial cristae and disease-associated CHCHD2 mutations function in a loss-of-function manner. However, both CHCHD2 and CHCHD10 knockout mouse models appear phenotypically normal, with no obvious mitochondrial defects. Strategies to maintain or enhance mitochondria cristae could provide opportunities to correct the associated cellular defects in disease state and unravel potential novel targets for CHCHD2-linked neurological conditions.


Human growth hormone promotes corneal epithelial cell migration in vitro.
Corneal wound healing is a highly regulated process that requires the proliferation and migration of epithelial cells and interactions between epithelial cells and stromal fibroblasts. Compounds that can be applied topically to the ocular surface and that have the capability of activating corneal epithelial cells to proliferate and/or migrate would be useful to promote corneal wound healing. We hypothesize that human growth hormone (HGH) will activate signal transducers and activators of transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial cell and fibroblast proliferation and/or migration in vitro. The purpose of this study was to test these hypotheses. We studied cell signaling, proliferation, and migration using an immortalized human corneal epithelial cell line and primary human corneal fibroblasts in vitro. We also examined whether insulin-like growth factor-1 (IGF-1), a hormone known to mediate many of HGH's growth promoting actions, may play a role in this effect. We show that HGH activates STAT5 signaling and promotes corneal epithelial cell migration in vitro. The migratory effect requires an intact communication between corneal epithelia and fibroblasts and is not mediated by IGF-1. HGH may represent a topical therapeutic to promote corneal epithelial wound healing. This warrants further investigation.


Alteration of endothelial cell surface morphology after experimental aortic coarctation.
The aortic arch of normal swine shows areas of enhanced permeability to proteins which take up intravenously-injected Evans blue (Old blue areas) and adjacent areas of lesser permeability which do not take up dye (white areas). Following 4 wk of coarctation at the ductus scar level (60% occlusion), former white areas demonstrate Evans blue uptake (New blue areas). Microscopic quantitation showed that endothelial cells in new blue areas had a significantly (p less than .001) altered axial ratio (cell length to width) of 1.41 +/- .04 and mean surface area of 704 +/- 35 mu2 compared to the same area in controls (axial ratio 3.30 +/- .09, mean area 545 +/- 38), but were not significantly different from old blue areas (axial ratio 1.39 +/- .03, area 741 +/- 40). Both new and old blue areas contained three times as many dead or injured cells as white areas in controls. Electron microscopy revealed that New blue area endothelium was similar to that of old blue areas, and that focal denudation and platelet adherence was sometimes present in both areas. The results support the belief that the altered characteristics of spontaneous blue areas are due to hemodynamics effects, and demonstrate that arterial occlusion increases endothelial cell surface area and alters cell orientation relative to blood flow, as well as enhancing injury. Such endothelial alterations could potentiate the disease process in partially-occluded arteries.


Men's use of sexual health services.
Previous research on users of sexual health services has focused primarily on women. However, a focus on men also is needed to address sexual ill-health. This paper uses various data sources to describe the level of, and trends in, men's use of sexual health services in England. Routine data are presented on clients of family planning clinics (FPCs), Brook Advisory Centres and attendances at genitourinary medicine (GUM) clinics. Cross-sectional surveys used include the National Survey of Sexual Attitudes and Lifestyles, Morbidity Statistics from General Practice and the National Gay Men's Sex Survey. The number of male clients attending FPCs has increased by 160% over the 1990s. Most of this increase is due to more men obtaining condoms. The ages of these clients are unknown, but data from Brook Advisory Centres show an increase among younger men. The one service for which male and female use is approximately equal is GUM. Male cases of sexually transmitted infections and other treatments have increased over the 1990s, although not at the same rate as female cases. Use of GUM clinics by homosexually active men is much greater than by all men. Recent data on men's use of general practice for sexual health are lacking. While overall service use among men is still at a comparatively low level, it has increased over the 1990s for some services. Further in-depth research should question men's wants and demands from sexual health services.


Performance evaluation of two multiplexes used in fluorescent short tandem repeat DNA analysis.
The performance of two commercial multiplex kits that together amplify the 13 core short tandem repeat (STR) loci currently in use by forensic laboratories and the U.S. national Combined DNA Indexing System (CODIS) were evaluated. The typing systems examined were AmpFlSTR Profiler Plus and AmpFlSTR COfiler (PE Applied Biosystems, Foster City, CA). Electrophoretic separation and detection of the fluorescent PCR products was achieved by capillary electrophoresis (CE) using an ABI Prism 310 Genetic Analyzer. The studies addressed the on-site validation of the instrument, the software, and each typing system. These studies included instrument sensitivity, resolution, precision, binning, peak height ratios, mixtures, stutter, and the amplification of non-probative and simulated forensic samples. Other additional developmental-type work is also reported herein, such as species specificity testing and amplification of environmentally insulted samples. Amplification conditions were found to be robust and the primer sets shown to be specific to human DNA. Stutter and peak height ratios fell within limits published by the manufacturer and other laboratories. The data demonstrate that the CE instrument can consistently resolve fragments differing in length by one base and that the +/-0.5 base bin used by the Genotyper software is acceptable for making accurate allele calls. Correct typing results were obtained from non-probative and simulated case samples, as well as samples exposed to outdoor environmental conditions. The results support the conclusion that DNA extracted from biological samples routinely encountered in the forensic laboratory can be reliably analyzed with AmpFlSTR Profiler Plus and COfiler using CE.


Chlamydia pneumoniae infection induces vascular smooth muscle cell migration via Rac1 activation.
Chlamydia pneumoniae infection has been shown to be associated with the development of atherosclerosis by promoting the migration of vascular smooth muscle cells (VSMCs). However, how C. pneumoniae infection induces VSMC migration is not fully understood. A primary role of Ras-related C3 botulinum toxin substrate 1 (Rac1) is to generate a protrusive force at the leading edge that contributes to cell migration. Whether Rac1 activation plays a role in C. pneumoniae infection-induced VSMC migration is not well defined. In the present study, we therefore examined Rac1 activation in C. pneumoniae-infected rat primary VSMCs and the role of Rac1 activation in C. pneumoniae infection-induced VSMC migration. Glutathione S-transferase pull-down assay results showed that Rac1 was activated in C. pneumoniae-infected rat primary VSMCs. A Rac1 inhibitor, NSC23766 (50 µM,) suppressed Rac1 activation stimulated by C. pneumoniae infection, and thereby inhibited C. pneumoniae infection-induced VSMC migration. In addition, C. pneumoniae infection-induced Rac1 activation in the VSMCs was blocked by LY294002 (25 µM), an inhibitor of phosphatidylinositol 3-kinase (PI3K). Taken together, these data suggest that C. pneumoniae infection promotes VSMC migration, possibly through activating Rac1 via PI3K.


A randomized controlled trial on the efficiency of free-handed, pilot-drill guided and fully guided implant surgery in partially edentulous patients.
To compare the effectiveness of free-handed (FH), pilot-drill guided (PG) and fully guided (FG) implant surgery by means of the apical global deviation (AGD) in relation to the additional financial cost and time spent. Thirty-three partially edentulous patients in need of ≥2 implants in the posterior maxilla were randomly allocated to one of the following treatment groups: FH, PG and FG. Eleven patients (mean age 57; eight females; altogether 26 implants) were treated by FH surgery, 11 (mean age 53; seven females; altogether 24 implants) by PG surgery and 10 (mean age 60; six females; altogether 21 implants) by FG surgery. The accuracy in implant positioning was assessed by comparing the actual implant position to its planned position with the AGD as the main measure of effectiveness. Cost analysis included data on time investment (pre- and per-operative) and operational cost. The efficiency of PG and FG surgery was assessed by means of the incremental cost-effectiveness ratio (ICER), defined as the extra investment that is needed per unit reduction in AGD when compared to FH surgery. FG surgery was most effective (mean AGD: 0.97 mm) and FH surgery was least effective (mean AGD: 2.11 mm) in terms of surgical accuracy. As a result, 5/26 implants had to be restored with a cement-retained restoration following FH surgery, although screw-retention was planned for all implants in every group. The total time investment did not differ significantly between the 3 groups (p = 0.811). A significant additional cost per implant was found for PG and FG as compared to FH surgery pointing to 8.29% (€176.54) and 10.45% (€222.52), respectively (p < 0.001). The ICER revealed an additional cost of €5.48 and €4.12 per per cent reduction in AGD for PG and FG surgery, respectively. The extra operational cost for guided implant surgery is acceptable and clinically justified since cementation can be avoided. FG surgery is the most efficient surgical approach, even though the absolute operational cost is higher when compared to PG and FH surgery.


The effect of consanguinity on the gestation period and anthropometric traits of the new-born in Southern India.
The effect of consanguinity on the period of gestation and the anthropometric characteristics at birth was studied in a southern Indian population. A total of 1000 new-born babies, born without undue birth trauma, developmental anomalies or acute illness were measured on the first day of their life. They were divided into four groups according to the relationship of their parents as uncle-niece, first cousins, beyond first cousins and unrelated. Birth weight, length and head and chest circumferences of both male and female infants were almost equal in consanguineous and non-consanguineous groups. Neither was the period of gestation significantly different. It is therefore concluded that in this population there is no significant effect of consanguinity on the anthropometric characteristics at birth as well as on the gestation period.


Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase.
An avidin-biotin enhanced immunoperoxidase procedure using monoclonal antibodies (AA1, AA3, and AA5) prepared against human mast cell tryptase resulted in intense staining of mast cells in paraffin-embedded tissue. The distribution of mast cells observed was similar to that seen when adjacent serial sections were stained using a standard procedure with toluidine blue, though the immunoperoxidase technique permitted the identification of significantly more mast cells. With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary. There was no staining of antibody on basophils or on any other normal blood leukocyte. The technique was effective with tissue fixed in either Carnoy's or neutral buffered formalin, though the internal mast cell structure was better preserved with formaldehyde fixation. The immunoperoxidase staining procedure with monoclonal antibody AA1 is a highly specific and sensitive means for the detection of mast cells in routinely processed tissues.


Consequences of noncompliance for therapy efficacy and emergence of resistance in murine tuberculosis caused by the Beijing genotype of Mycobacterium tuberculosis.
Despite great effort by health organizations worldwide in fighting tuberculosis (TB), morbidity and mortality are not declining as expected. One of the reasons is related to the evolutionary development of Mycobacterium tuberculosis, in particular the Beijing genotype strains. In a previous study, we showed the association between the Beijing genotype and an increased mutation frequency for rifampin resistance. In this study, we use a Beijing genotype strain and an East-African/Indian genotype strain to investigate with our mouse TB model whether the higher mutation frequency observed in a Beijing genotype strain is associated with treatment failure particularly during noncompliance therapy. Both genotype strains showed high virulence in comparison to that of M. tuberculosis strain H37Rv, resulting in a highly progressive infection with a rapid lethal outcome in untreated mice. Compliance treatment was effective without relapse of TB irrespective of the infecting strain, showing similar decreases in the mycobacterial load in infected organs and similar histopathological changes. Noncompliance treatment, simulated by a reduced duration and dosing frequency, resulted in a relapse of infection. Relapse rates were correlated with the level of noncompliance and were identical for Beijing infection and East African/Indian infection. However, only in Beijing-infected mice, isoniazid-resistant mutants were selected at the highest level of noncompliance. This is in line with the substantial selection of isoniazid-resistant mutants in vitro in a wide isoniazid concentration window observed for the Beijing strain and not for the EAI strain. These results suggest that genotype diversity of M. tuberculosis may be involved in emergence of resistance and indicates that genotype-tailor-made treatment should be investigated.


Establishing a colorectal cancer liver metastasis patient-derived tumor xenograft model for the evaluation of personalized chemotherapy.
In order to suggest optimal anticancer drugs for patient-tailored chemotherapy, we developed a colorectal cancer (CRC)-liver metastasis patient-derived tumor xenograft (PDTX) model. Tissue obtained from a patient with CRC-liver metastasis (F0) was transplanted in a nonobese female mouse with diabetic/severe combined immune deficiency (F1) and the tumor tissue was retransplanted into nude mice (F2). When tumor volumes reached ~500 mm3, the F2 mice were randomly divided into 4 groups (n = 4/group) of doxorubicin, cisplatin, docetaxel, and nontreated control groups. The tumor tissues were investigated using H&E staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunohistochemistry. To determine where the mutant allele frequencies varied across the different passages, we isolated genomic DNA from the primary tumor, liver metastasis, and PDTX models (F1/F2). The physiological properties of the tumor were in accord with those of the patient's tumors. Anticancer drugs delayed tumor growth, inhibited proliferation, and caused apoptosis. Histological assessments revealed no observable heterogeneity among the intragenerational PDTX models. Target exon sequencing analysis without high-quality filter conditions revealed some genetic variations in the 83 cancer-related genes across the generations. However, when de novo mutations were defined as a total count of zero in F0 and ≥5 in F2, exactly prognostic impact of clone cancer profiling (EGFR, KRAS, BRAF, PIK3CA, NRAS, APC and TP53) were detected in the paired. A CRC liver metastasis PDTX model was established for the evaluation of chemotherapeutic efficacy. This model retained the physiological characters of the patient tumors and potentially provides a powerful means of assessing chemotherapeutic efficacy.


Severe obsessive-compulsive disorder with and without body dysmorphic disorder: clinical correlates and implications.
Body Dysmorphic Disorder is a putative obsessive-compulsive spectrum disorder. This exploratory study systematically examined prevalence and clinical correlates of Body Dysmorphic Disorder (BDD) comorbidity in an inpatient Obsessive-Compulsive Disorder (OCD) population. Consecutive patients from an OCD Intensive Residential Treatment program were included (N = 275). Clinician-rated and patient-rated measures were administered at baseline and repeated at discharge. The prevalence of BDD was determined and clinical characteristics were statistically compared between groups with (N = 42) and without (N = 233) comorbid BDD. The prevalence of BDD among residential patients with OCD was 15.3% (N = 42). Those with comorbid BDD were younger (p = 0.007) and more predominantly female (p = 0.02), with lower marriage rates (p = 0.006), more severe depression (p = 0.003) and increased self-reported illicit substance use histories (p = 0.003) versus those without BDD. This cohort also had earlier onset OCD (p = 0.02) and more severe hoarding (p = 0.01), symmetry (p = 0.01), reassurance-seeking (p = 0.01) and checking symptoms (p = 0.01) than patients without comorbid BDD. OCD treatment response was unaffected by the presence of BDD. BDD is a common comorbidity in severe OCD. Younger women and those with early-onset OCD appear more likely to have BDD. OCD patients with BDD also have increased hoarding, symmetry, reassurance-seeking and checking severity, which requires consideration in treatment planning.


Myocardin expression is regulated by Nkx2.5, and its function is required for cardiomyogenesis.
Nkx2.5 (also known as Csx) is an evolutionarily conserved cardiac transcription factor of the homeobox gene family. Nkx2.5 is required for early heart development, since Nkx2.5-null mice die before completion of cardiac looping. To identify genes regulated by Nkx2.5 in the developing heart, we performed subtractive hybridization by using RNA isolated from wild-type and Nkx2.5-null hearts at embryonic day 8.5. We isolated a mouse cDNA encoding myocardin A, which is an alternative spliced isoform of myocardin and the most abundant isoform in the heart from embryo to adult. The expression of myocardin A and myocardin was markedly downregulated in Nkx2.5-null mouse hearts. Transient-cotransfection analysis showed that Nkx2.5 transactivates the myocardin promoter. Inhibition of myocardin function in the teratocarcinoma cell line P19CL6 prevented differentiation into cardiac myocytes after dimethyl sulfoxide treatment. Myocardin A transactivated the promoter of the atrial natriuretic factor gene through the serum response element, which was augmented by bone morphogenetic protein 2 and transforming growth factor beta-activated kinase 1. These results suggest that myocardin expression is regulated by Nkx2.5 and that its function is required for cardiomyogenesis.


Functional brain-imaging correlates of negative affectivity and the onset of first-episode depression.
The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala-sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression. Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala-sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression. The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala-sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala-sACC connectivity at follow-up. Amygdala-sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological 'scar' hypothesis of depression.


Cluster headache prevalence in the Italian general population.
Prevalence of cluster headache (CH) is estimated at 56 to 69 per 100,000. To calculate the CH lifetime prevalence in a sample representative of the Italian general population over age 14 years. Possible CH cases according to the diagnostic criteria of the 1988 International Headache Society classification were screened from a sample of 10,071 patients (5,311 women and 4,760 men; mean age 50.4 years, SD 19.7 years) registered in the lists of seven Parma-based general practitioners (GPs), using a previously validated, specially designed, self-administered questionnaire. Seven thousand five hundred twenty-two subjects (74.7%; 3,971 women and 3,551 men; mean age 50.8 years, SD 19.0 years) responded to the questionnaire in their GP's office (n = 3,338; 1,885 women and 1,453 men) or at home by mail (n = 1,914; 1,030 women and 884 men) or by phone (n = 2,270; 1,056 women and 1,214 men). Of the 111 suspected cases (76 women and 35 men), 105 were seen by a neurologist and 6 were contacted on the phone. The diagnosis of CH was confirmed in 21 (9 women and 12 men), including 7 already followed at the authors' center for CH. Seventeen patients had episodic CH, and four (all men) had chronic CH. The estimated prevalence rate was 279 per 100,000 (95% CI 173 to 427), 227 per 100,000 (95% CI 104 to 431) in women, and 338 per 100,000 (95% CI 175 to 592) in men. These results point to a higher cluster headache lifetime prevalence than previous reports.


Effects of whole-body vibration on spinal reflexes in man.
Recent studies have described sensory-motor function alterations resulting from vibrations applied to various parts of the body. The present work describes the effects produced at the myotatic loop level by long-term vibration. Hoffmann and Tendon reflexes as well as tendon vibration response were substantially depressed by 18 Hz, +/- 0.25 G vibration applied to the whole body or to the legs of seated human subjects. The reflex inhibition lasted throughout the 15-min vibration period and persisted minutes after stimulus cessation. In contrast, vibration limited to the S's head and trunk showed much weaker effects. This suggests that the vibration acts mainly upon extero- and proprioceptive receptors rather than upon the vestibular organs. The results are discussed in relation to findings derived from experiments involving locally applied short-duration vibration.


Early Detection of Bilateral Testicular Metastases From Prostatic Adenocarcinoma Using 68Ga-PSMA Ligand PET/CT.
We present the case of a 76-year-old man with biochemical relapse after primary therapy for prostate cancer. Ga prostate-specific membrane antigen (PSMA) ligand PET/CT performed for localization of recurrent disease revealed bilateral metastases to the testes. Histopathologic evaluation after bilateral orchiectomy revealed testicular metastases. Metastases to the testes are rare and usually seen in advanced stages. Ga-PSMA ligand PET/CT is a highly sensitive and specific imaging method for the detection of primary and metastatic prostate cancer and has refined diagnostic approaches. This case highlights the potential of PSMA-targeted PET/CT for detection of prostate cancer metastases, even in very unusual localizations.


Uncertainty in urban flood damage assessment due to urban drainage modelling and depth-damage curve estimation.
Due to the increased occurrence of flooding events in urban areas, many procedures for flood damage quantification have been defined in recent decades. The lack of large databases in most cases is overcome by combining the output of urban drainage models and damage curves linking flooding to expected damage. The application of advanced hydraulic models as diagnostic, design and decision-making support tools has become a standard practice in hydraulic research and application. Flooding damage functions are usually evaluated by a priori estimation of potential damage (based on the value of exposed goods) or by interpolating real damage data (recorded during historical flooding events). Hydraulic models have undergone continuous advancements, pushed forward by increasing computer capacity. The details of the flooding propagation process on the surface and the details of the interconnections between underground and surface drainage systems have been studied extensively in recent years, resulting in progressively more reliable models. The same level of was advancement has not been reached with regard to damage curves, for which improvements are highly connected to data availability; this remains the main bottleneck in the expected flooding damage estimation. Such functions are usually affected by significant uncertainty intrinsically related to the collected data and to the simplified structure of the adopted functional relationships. The present paper aimed to evaluate this uncertainty by comparing the intrinsic uncertainty connected to the construction of the damage-depth function to the hydraulic model uncertainty. In this way, the paper sought to evaluate the role of hydraulic model detail level in the wider context of flood damage estimation. This paper demonstrated that the use of detailed hydraulic models might not be justified because of the higher computational cost and the significant uncertainty in damage estimation curves. This uncertainty occurs mainly because a large part of the total uncertainty is dependent on depth-damage curves. Improving the estimation of these curves may provide better results in term of uncertainty reduction than the adoption of detailed hydraulic models.


Harvesting cells under anchorage-independent cell transformation conditions for biochemical analyses.
Most molecular biology and biochemical analyses use cultured cells grown in anchorage-dependent monolayer conditions. The standard oncogenic transformation assay for cell lines is usually performed in soft agar rather than in monolayers because of the higher transformation efficiency of cells in soft agar. However, cells suspended in soft agar cannot be readily recovered for studying inducible biochemical and molecular events. We developed an over-agar assay that enables us to study tumor promoter-induced cell transformation and the associated biochemical or molecular events under anchorage-independent conditions.


A Retrospective Analysis of Reporting of Adverse Drug Reactions in a Tertiary Care Teaching Hospital: One Year Survey.
Pharmacovigilance (PV) is related to detection, assessment, understanding and prevention of Adverse Drug Reactions (ADRs) which are incurred when drug is made available in the market and used in different physiological conditions. In many countries, ADRs ranks among the top ten leading cause of morbidity and mortality. There is a lack of formal culture for monitoring and reporting of ADRs in India, with ADR reporting rate being only 1% as compared to 5% in world. This type of academic detailing activity helps to create awareness of ADR reporting in the institutions. This study was planned to evaluate and analyse the incidence and patterns of ADRs in various inpatient and outpatient departments of hospital. This was an observational, retrospective and record based study conducted by analysing the spontaneous ADR forms, collected over a period of 12 months (September 2014 to August 2015) at Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. During the period of one year, 292 ADR forms were collected from 4,34,965 patients attending OPD and inpatients of the hospital. Incidence of ADR was 0.67 per thousand patients and average of around 24 ADR collected per month. Male:Female ratio was 1.30. Adolescent (16-30 yr) was the most common age group affected. Department of Skin and VD reported the maximum number of ADRs (33.22%), followed by the Departments of Oncology (18.84%). Antibiotics were the most common drug implicated followed by anticancer drugs. ADR reporting is an ongoing and continuous process. Studies from the institute helps to identify and rectify the problems related to ADR reporting. Pitfalls can be addressed by creating awareness among physicians and the patients to achieve finally the goal of Pharmacovigilant India.


Grapevine aquaporins: gating of a tonoplast intrinsic protein (TIP2;1) by cytosolic pH.
Grapevine (Vitis vinifera L.) is one of the oldest and most important perennial crops being considered as a fruit ligneous tree model system in which the water status appears crucial for high fruit and wine quality, controlling productivity and alcohol level. V. vinifera genome contains 28 genes coding for aquaporins, which acting in a concerted and regulated manner appear relevant for plant withstanding extremely unfavorable drought conditions essential for the quality of berries and wine. Several Vv aquaporins have been reported to be expressed in roots, shoots, berries and leaves with clear cultivar differences in their expression level, making their in vivo biochemical characterization a difficult task. In this work V. vinifera cv. Touriga nacional VvTnPIP1;1, VvTnPIP2;2 and VvTnTIP2;1 were expressed in yeast and water transport activity was characterized in intact cells of the transformants. The three aquaporins were localized in the yeast plasma membrane but only VvTnTIP2;1 expression enhanced the water permeability with a concomitant decrease of the activation energy of water transport. Acidification of yeast cytosol resulted in loss of VvTnTIP2;1 activity. Sequence analysis revealed the presence of a His(131) residue, unusual in TIPs. By site directed mutagenesis, replacement of this residue by aspartic acid or alanine resulted in loss of pH(in) dependence while replacement by lysine resulted in total loss of activity. In addition to characterization of VvTn aquaporins, these results shed light on the gating of a specific tonoplast aquaporin by cytosolic pH.


Chronically ill adolescents' experiences of communicating with doctors: a qualitative study.
To explore the experiences of chronically ill adolescents in communicating with health professionals, including the identification of factors which hinder or facilitate their use of health professionals as an information source. 63 adolescents (11-16 years) with a chronic condition (cystic fibrosis, diabetes, epilepsy, juvenile chronic arthritis, or Duchenne muscular dystrophy) were interviewed, and subsequently took part in two group discussion meetings with other adolescents of a similar age with the same condition. Data were analyzed using the framework method involving data reduction, data display, and conclusion-drawing and verification. Factors affecting the openness and effectiveness of communication included: duration and frequency of contact; gender; perceived attitudes towards adolescents; the communication skills of the adolescent and health professional; and the presence of parents and medical students/trainee doctors. The type of information needed also affected whether the adolescents felt able to discuss an issue with a health professional. Adolescents were reluctant to raise personal or sensitive issues or to ask questions that revealed poor adherence. A perceived lack of interest in the wider impacts of having a chronic condition on day-to-day life was also a barrier to adolescents discussing difficulties at school and socio-emotional problems. Communication and information provision are key roles for health professionals, yet this study highlights a population with potentially high levels of information need who are facing considerable barriers to addressing these needs. Steps taken to improve adolescent-health professional communication need to address a range of practical, attitudinal and behavioral factors.


Influenza in the emergency department: 2020 update
Emergency clinicians must be aware of the current diagnostic and therapeutic recommendations for influenza and the available resources to guide management. This comprehensive review outlines the classification of influenza viruses, influenza pathophysiology, the identification of high-risk patients, and the importance of vaccination, with an update on the 2019-2020 influenza season. Seasonal variations of influenza are discussed, as well as the rationale for limiting testing during periods of high prevalence. Differences between strains of influenza are discussed, as well as the challenges in achieving optimal vaccine effectiveness. Recommendations for use of the currently available oral, intranasal, and intravenous antiviral treatments are provided, as well as utilizing shared decision-making with patients regarding risks and benefits of treatment.


Rapid evidence synthesis approach for limits on the search date: How rapid could it be?
Rapid reviews have been widely employed to support timely decision-making, and limiting the search date is the most popular approach in published rapid reviews. We assessed the accuracy and workload of search date limits on the meta-analytical results to determine the best rapid strategy. The meta-analyses data were collected from the Cochrane Database of Systematic Reviews (CDSR). We emulated the rapid reviews by limiting the search date of the original CDSR to the recent 40, 35, 30, 25, 20, 15, 10, 7, 5, and 3 years, and their results were compared to the full meta-analyses. A random sample of 10% was drawn to repeat the literature search by the same timeframe limits to measure the relative workload reduction (RWR). The relationship between accuracy and RWR was established. We identified 21,363 meta-analyses of binary outcomes and 7683 meta-analyses of continuous outcomes from 2693 CDSRs. Our results suggested that under a maximum tolerance of 5% and 10% on the bias of magnitude, a limit on the recent 20 years can achieve good accuracy and at the same time save the most workload. Under the tolerance of 15% and 20% on the bias, a limit on the recent 10 years and 15 years could be considered. Limiting the search date is a valid rapid method to produce credible evidence for timely decisions. When conducting rapid reviews, researchers should consider both the accuracy and workload to make an appropriate decision.


Complication of polymethylmethacrylate bone cement in the mandible.
Polymethylmethacrylate bone cements have been widely used in orthopedic surgery as well as in maxillofacial area. Despite the advantages, it is well known that acrylic bone cements may cause bone or soft tissue necrosis because of the properties of its components and polymerization. This clinical report presents an extensive necrosis of the mandible after the use of the acrylic bone cement to fill the cyst cavity. The purpose of this article was to alert the clinicians about the complications that may occur after the use of the polymethylmethacrylate-based bone cements.


Crystallin-αB regulates skeletal muscle homeostasis via modulation of argonaute2 activity.
The core functional machinery of the RNAi pathway is the RNA-induced silencing complex (RISC), wherein Argonaute2 (Ago2) is essential for siRNA-directed endonuclease activity and RNAi/microRNA-mediated gene silencing. Crystallin-αB (CryAB) is a small heat shock protein involved in preventing protein aggregation. We demonstrate that CryAB interacts with the N and C termini of Ago2, not the catalytic site defined by the convergence of the PAZ, MID, and PIWI domains. We further demonstrate significantly reduced Ago2 activity in the absence of CryAB, highlighting a novel role of CryAB in the mammalian RNAi/microRNA pathway. In skeletal muscle of CryAB null mice, we observe a shift in the hypertrophy-atrophy signaling axis toward atrophy under basal conditions. Moreover, loss of CryAB altered the capability of satellite cells to regenerate skeletal muscle. These studies establish that CryAB is necessary for normal Ago2/RISC activity and cellular homeostasis in skeletal muscle.


Development of a novel chloramphenicol resistance expression plasmid used for genetic complementation of a fliG deletion mutant in Treponema denticola.
A new expression plasmid containing the fla operon promoter and a staphylococcal chloramphenicol resistance gene, was constructed to help assess the role of fliG in Treponema denticola motility. Deletion of fliG resulted in a nonmotile mutant with a markedly decreased number of flagellar filaments. Wild-type fliG genes from T. denticola and from Treponema pallidum were cloned into this expression plasmid. In both cases, the gene restored the ability of the mutant to gyrate its cell ends and enabled colony spreading in agarose. This shuttle plasmid enables high-level expression of genes in T. denticola and possesses an efficient selectable marker that provides a new tool for treponemal genetics.


Red fluorescent protein-aequorin fusions as improved bioluminescent Ca2+ reporters in single cells and mice.
Bioluminescence recording of Ca(2+) signals with the photoprotein aequorin does not require radiative energy input and can be measured with a low background and good temporal resolution. Shifting aequorin emission to longer wavelengths occurs naturally in the jellyfish Aequorea victoria by bioluminescence resonance energy transfer (BRET) to the green fluorescent protein (GFP). This process has been reproduced in the molecular fusions GFP-aequorin and monomeric red fluorescent protein (mRFP)-aequorin, but the latter showed limited transfer efficiency. Fusions with strong red emission would facilitate the simultaneous imaging of Ca(2+) in various cell compartments. In addition, they would also serve to monitor Ca(2+) in living organisms since red light is able to cross animal tissues with less scattering. In this study, aequorin was fused to orange and various red fluorescent proteins to identify the best acceptor in red emission bands. Tandem-dimer Tomato-aequorin (tdTA) showed the highest BRET efficiency (largest energy transfer critical distance R(0)) and percentage of counts in the red band of all the fusions studied. In addition, red fluorophore maturation of tdTA within cells was faster than that of other fusions. Light output was sufficient to image ATP-induced Ca(2+) oscillations in single HeLa cells expressing tdTA. Ca(2+) rises caused by depolarization of mouse neuronal cells in primary culture were also recorded, and changes in fine neuronal projections were spatially resolved. Finally, it was also possible to visualize the Ca(2+) activity of HeLa cells injected subcutaneously into mice, and Ca(2+) signals after depositing recombinant tdTA in muscle or the peritoneal cavity. Here we report that tdTA is the brightest red bioluminescent Ca(2+) sensor reported to date and is, therefore, a promising probe to study Ca(2+) dynamics in whole organisms or tissues expressing the transgene.


Preparation and Activity of Hemostatic and Antibacterial Dressings with Greige Cotton/Zeolite Formularies Having Silver and Ascorbic Acid Finishes.
The need for prehospital hemostatic dressings that exert an antibacterial effect is of interest for prolonged field care. Here, we consider a series of antibacterial and zeolite formulary treatment approaches applied to a cotton-based dressing. The design of the fabric formulations was based on the hemostatic dressing TACGauze with zeolite Y incorporated as a procoagulant with calcium and pectin to facilitate fiber adherence utilizing silver nanoparticles, and cellulose-crosslinked ascorbic acid to confer antibacterial activity. Infra-red spectra were employed to characterize the chemical modifications on the dressings. Contact angle measurements were employed to document the surface hydrophobicity of the cotton fabric which plays a role in the contact activation of the coagulation cascade. Ammonium Y zeolite-treated dressings initiated fibrin equal to the accepted standard hemorrhage control dressing and showed similar improvement with antibacterial finishes. The antibacterial activity of cotton-based technology utilizing both citrate-linked ascorbate-cellulose conjugate analogs and silver nanoparticle-embedded cotton fibers was observed against Staphylococcus aureus and Klebsiella pneumoniae at a level of 99.99 percent in the AATCC 100 assay. The hydrogen peroxide levels of the ascorbic acid-based fabrics, measured over a time period from zero up to forty-eight hours, were in line with the antibacterial activities.


Cellular compartmentation of cadmium and zinc in relation to other elements in the hyperaccumulator Arabidopsis halleri.
The cellular compartmentation of elements was analysed in the Zn hyperaccumulator Arabidopsis halleri (L.) O'Kane & Al-Shehbaz (=Cardaminopsis halleri) using energy-dispersive X-ray microanalysis of frozen-hydrated tissues. Quantitative data were obtained using oxygen as an internal standard in the analyses of vacuoles, whereas a peak/background ratio method was used for quantification of elements in pollen and dehydrated trichomes. Arabidopsis halleri was found to hyperaccumulate not only Zn but also Cd in the shoot biomass. While large concentrations of Zn and Cd were found in the leaves and roots, flowers contained very little. In roots grown hydroponically, Zn and Cd accumulated in the cell wall of the rhizodermis (root epidermis), mainly due to precipitation of Zn/Cd phosphates. In leaves, the trichomes had by far the largest concentrations of Zn and Cd. Inside the trichomes there was a striking sub-cellular compartmentation, with almost all the Zn and Cd being accumulated in a narrow ring in the trichome base. This distribution pattern was very different from that for Ca and P. The epidermal cells other than trichomes were very small and contained lower concentrations of Zn and Cd than mesophyll cells. In particular, the concentrations of Cd and Zn in the mesophyll cells increased markedly in response to increasing Zn and Cd concentrations in the nutrient solution. This indicates that the mesophyll cells in the leaves of A. halleri are the major storage site for Zn and Cd, and play an important role in their hyperaccumulation.


Microfluidic long DNA sample preparation from cells.
A number of outstanding problems in genomics, such as identifying structural variations and sequencing through centromeres and telomeres, stand poised to benefit tremendously from emerging long-read genomics technologies such as nanopore sequencing and genome mapping in nanochannels. However, optimal application of these new genomics technologies requires facile methods for extracting long DNA from cells. These sample preparation tools should be amenable to automation and minimize fragmentation of the long DNA molecules by shear. We present one such approach in a poly(dimethylsiloxane) device, where gel-based high molecular weight DNA extraction and continuous flow purification in a 3D cell culture-inspired geometry is followed by electrophoretic extraction of the long DNA from the miniaturized gel. Molecular combing reveals that the device produces molecules that are typically in excess of 100 kilobase pairs in size, with the longest molecule extending up to 4 megabase pairs. The microfluidic format reduces the standard day-long and labor-intensive DNA extraction process to 4 hours, making it a promising prototype platform for routine long DNA sample preparation.


Localization of the lectin reactive sites in adult and prepubertal horse testes.
The testes of prepubertal and adult horses were investigated using 10 horseradish peroxidase conjugated lectins combined with sialidase digestion and potassium hydroxide treatment, to localise the oligosaccharide sequences of glycoconjugates during spermatid maturation. In adult animals, the lectins showed a variable affinity for spermatids and Sertoli cell apical extensions. Soybean agglutinin (SBA), peanut agglutinin (PNA), Ricinus communis agglutinin (RCA-I) and wheat germ agglutinin (WGA) bound to the acrosomal structures of spermatids, whereas Griffonia simplicifolia agglutinin (GSA-II) labelled these structures only during Golgi and cap phases. These results suggested that glycoproteins of mature acrosomes contain both N- and O-linked oligosaccharides and that these carbohydrate chains undergo modifications during spermiogenesis. Sialic acid residues were not detected throughout the acrosomal development. The lectin binding pattern of Sertoli cells was very similar to that of acrosome of spermatids during the maturation phase. In sexually immature horses, only the degenerated germinal cells and the Leydig cells showed reactivity towards lectins. The first cells reacted with SBA and Dolichos biflorus agglutinin (DBA), the latter with SBA, PNA, WGA, GSA-II, Canavalia ensiformis agglutinin (ConA), Lens culinaris agglutinin (LCA) and also with DBA after sialidase digestion.


Ebola Virus Inclusion Body Formation and RNA Synthesis Are Controlled by a Novel Domain of Nucleoprotein Interacting with VP35.
Ebola virus (EBOV) inclusion bodies (IBs) are cytoplasmic sites of nucleocapsid formation and RNA replication, housing key steps in the virus life cycle that warrant further investigation. During infection, IBs display dynamic properties regarding their size and location. The contents of IBs also must transition prior to further viral maturation, assembly, and release, implying additional steps in IB function. Interestingly, the expression of the viral nucleoprotein (NP) alone is sufficient for the generation of IBs, indicating that it plays an important role in IB formation during infection. In addition to NP, other components of the nucleocapsid localize to IBs, including VP35, VP24, VP30, and the RNA polymerase L. We previously defined and solved the crystal structure of the C-terminal domain of NP (NP-Ct), but its role in virus replication remained unclear. Here, we show that NP-Ct is necessary for IB formation when NP is expressed alone. Interestingly, we find that NP-Ct is also required for the production of infectious virus-like particles (VLPs), and that defective VLPs with NP-Ct deletions are significantly reduced in viral RNA content. Furthermore, coexpression of the nucleocapsid component VP35 overcomes deletion of NP-Ct in triggering IB formation, demonstrating a functional interaction between the two proteins. Of all the EBOV proteins, only VP35 is able to overcome the defect in IB formation caused by the deletion of NP-Ct. This effect is mediated by a novel protein-protein interaction between VP35 and NP that controls both regulation of IB formation and RNA replication itself and that is mediated by a newly identified functional domain of NP, the central domain.IMPORTANCE Inclusion bodies (IBs) are cytoplasmic sites of RNA synthesis for a variety of negative-sense RNA viruses, including Ebola virus. In addition to housing important steps in the viral life cycle, IBs protect new viral RNA from innate immune attack and contain specific host proteins whose function is under study. A key viral factor in Ebola virus IB formation is the nucleoprotein, NP, which also is important in RNA encapsidation and synthesis. In this study, we have identified two domains of NP that control inclusion body formation. One of these, the central domain (CD), interacts with viral protein VP35 to control both inclusion body formation and RNA synthesis. The other is the NP C-terminal domain (NP-Ct), whose function has not previously been reported. These findings contribute to a model in which NP and its interactions with VP35 link the establishment of IBs to the synthesis of viral RNA.


Identity-linked perceptions of the police among African American juvenile offenders: a developmental perspective.
Ethnic identity development can play a role in youths' perceptions and attitudes concerning police, but this process has not been explored in delinquent samples. In this article, we examine how youths' perceptions of police legitimacy and levels of legal cynicism are related to processes of ethnic identity development. Participants were 561 black youth ages 14-18 (12% female) who were adjudicated of a felony or serious misdemeanor. Data were taken from semi-annual interviews conducted over 3 years. Increased ethnic identity exploration was related to positive perceptions of police legitimacy and lower legal cynicism. Higher ethnic identity affirmation predicted higher perceived legitimacy over time, but affirmation was not related to legal cynicism after accounting for psychosocial maturity. This study provides evidence that ethnic identity development operates similarly among high risk youth as in non-delinquent samples, and that it is connected to beliefs that can have implications for juvenile offenders' future compliance with the law.