Maternal Anxiety and Depression during Late Pregnancy and Newborn Brain White Matter Development.
Anxiety and depression during pregnancy have been associated with an increased risk of adverse neurodevelopmental outcomes in offspring. We aimed to study the in utero effects of maternal anxiety and depression on early brain development. Pregnant women were recruited at ∼36 weeks of gestation for this prospective study. They were assessed for anxiety symptoms by the State-Trait Anxiety Inventory and for depression symptoms by the Beck Depression Inventory, 2nd Edition. After delivery, infant underwent an MR imaging examination of the brain without sedation, including DTI, for evaluation of white matter (WM) development. Infant fractional anisotropy values, a putative marker of WM integrity, were correlated with the mothers' State-Trait Anxiety Inventory and Beck Depression Inventory scores by using both tract-based spatial statistics and ROI methods. Thirty-four infants were included in this study. Both maternal State-Anxiety and Trait-Anxiety scores negatively correlated (P < .05, corrected) with fractional anisotropy values in widespread brain WM regions; Beck Depression Inventory scores also negatively correlated (P < .05) with fractional anisotropy values in one cluster in the brain. Further ROI analyses confirmed significant negative correlations between average fractional anisotropy values in ROIs including left and right prefrontal WM, left and right middle frontal gyrus WM, and the fornix, and State-Anxiety (R values, -0.47 to -0.67; P values, .008 to <.001), Trait-Anxiety (R, -0.37 to -0.59; P, .04 to <.001), and Beck Depression Inventory (R values, -0.36 to -0.55; P, .05 to .002) scores. Higher maternal anxiety and depression symptom scores during late pregnancy were associated with lower estimated infant brain WM development, which indicated in utero influences of maternal mental health during pregnancy on the developing brain.


Posttraumatic stress symptoms and postpartum anxiety among palestinian women: the mediating roles of self-esteem and social support.
Women are estimated to develop several mental disorders during pregnancy and/or for up to a year postpartum, with anxiety and depression being the most common co-morbidities. Postpartum anxiety is less well studied compared with postpartum depression in the Palestinian context in terms of risk factors, mental health outcomes and protective factors. The aim of the current study was to investigate whether self-esteem and social support mediated the association between posttraumatic stress symptoms and postpartum anxiety among Palestinian women. Berlin Social Support Scales, Postpartum Specific Anxiety Scale, Impact of the Event Scale, and Rosenberg self-esteem scale were administered to 408 Palestinian women recruited from health centers in northern of the West Banks/ Palestine using a convenience sample. The findings of our study revealed that postpartum anxiety positively correlated with posttraumatic stress symptoms (r = .56, p < .01), and negatively correlated with social support (r = - .30, p < .01), and self-esteem (r = - .27, p < .05). Moreover, posttraumatic stress symptoms negatively correlated with social support (r = - .24, p < .01), and self-esteem (r = - .25, p < .01). Results of structural equation modeling (SEM) showed a good fit of the hypothesized model. Given this, it is recommended to conduct similar studies with diverse samples in the Palestinian society. It would also be useful for health professionals who work with Palestinian pregnant women (i.e., mental health providers, nurses, midwives, physicians) to assess self-esteem and social support in an effort to identify women who may be at greater risk of developing postpartum anxiety. It may also be worthwhile to develop and implement interventions during pregnancy which serve to enhance a women's sense of self-esteem during this particularly stressful period.


Vav exchange factor counteracts the HIV-1 Nef-mediated decrease of plasma membrane GM1 and NF-AT activity in T cells.
Several findings support the importance of GM1-enriched lipid microdomains of plasma membrane and of Vav, an essential regulator of actin cytoskeletal rearrangement, in the regulation of T cell activation. Moreover, a functional link among lipid microdomains, Vav and the HIV product Nef has been described. These observations suggest that Nef can modify plasma membrane GM1, affecting the behavior of HIV-infected cells towards antigen recognition and Vav towards counteracting such an effect. We observed that Nef expression, either following viral infection or ectopic expression, significantly decreased the level of plasma membrane GM1 in unstimulated T cells. This down-regulation was associated with the inhibition of NF-AT activation, but not with NF-kappaB activation induced by TCR engagement. Dissecting the signaling pathway that regulates NF-AT activation, we found that Nef inhibited exclusively the Ca(2+)/calcineurin cascade, whereas the JNK cascade and AP-1 transcriptional activity were not affected. Our evidence that Vav overexpression counteracted both the Nef-induced decrease of GM1 expression and the inhibition of NF-AT activity, suggests a novel mechanism by which Nef may interfere with TCR-mediated activation through the modulation of intracellular trafficking and clustering of GM1-enriched microdomains at the cell surface.


A Simulation Study to Assess the Effect of Analytic Error on Neonatal Glucose Measurements Using the Canadian Pediatric Society Position Statement Action Thresholds.
The Canadian Pediatric Society (CPS) has endorsed an algorithm for the screening and immediate management of babies at risk of neonatal hypoglycemia that provides time-dependent glucose concentration action thresholds. The objective of this study was to evaluate the impact of glucose analytic error (bias and imprecision) on the misclassification of glucose meter results from a neonatal intensive care unit (NICU) using the CPS guidelines. A simulation dataset of true glucose values (N = 100 000) was derived by finite mixture model analysis of NICU glucose data (N = 23 749). Bias and imprecision were added to create measured glucose values. The percentages of measured glucose values that were misclassified at CPS action thresholds were determined by Monte Carlo simulation. Measurement biases ranging from -20 to +20 mg/dL combined with coefficients of variation 0% to 20% were evaluated to predict misclassification rates at 32, 36, and 47 mg/dL. The models demonstrated low risk of false normoglycemia-at 5% CV and +10 mg/dL bias: 0.8% to 5% misclassification at the 32 and 47 mg/dL thresholds due to bias. The models demonstrated risk of false hypoglycemia-at 5% CV and -10 mg/dL bias: 3% to 12.5% misclassification at 32 and 47 mg/dL thresholds due to both bias and imprecision. Using CPS action thresholds, the simulation model predicted the proportion of neonates at risk of inappropriate clinical action-both of omission or "failure to treat" and commission or "overtreatment" in response to NICU glucose meter results at specific bias and imprecision values.


Evaluation of methods to assess the quality of cryopreserved Solanaceae pollen.
Solanaceae pollen cryopreservation is a common practice in the hybrid seed production industry worldwide, enabling effective hybridization across geographical and seasonal limitations. As pollination with low quality pollen can result in significant seed yield loss, monitoring the pollen quality has become an important risk management tool. In this study, pollen quality analysis methods were evaluated for their suitability for routine quality control of cryopreserved pollen batches. The assessments, including pollen viability, pollen germinability and pollen vigor analysis, were conducted in two locations on a diverse set of cryopreserved tomato and pepper pollen batches. While the viability obtained by Impedance Flow Cytometry (IFC) can be interpreted as the pollen's potential to germinate, the in vitro germination assay directly quantifies this functionality under given assay conditions. A linear correlation was found between pollen viability obtained by IFC and in vitro germinability. In conclusion, IFC is the most suitable tool for applications and industries requiring a high degree of automation, throughput, repeatability, and reproducibility. In vitro germination assays are suitable for studies within certain temporal and geographic limitations, due to difficulties in standardization. On the other hand, vigor assessments are not sufficiently addressing the needs of the industry due to poor reproducibility and low throughput.


Functional, biochemical, and histopathological evidence of airway obstruction in rats following a four-hour acute inhalation exposure to n-butyl isocyanate.
Pulmonary function, arterial blood gases, acid-base status, and bronchoalveolar lavage fluid (BALF) composition were assessed in male Wistar rats after a single 4-h exposure to 0, 7.6, 23.5 or 55.2 mg n-butyl isocyanate (n-BIC)/m3 air. No significant changes other than transient clinical signs were observed in the rats exposed to 7.6 mg/m3 air. Four weeks after exposure the animals of the 55.2 mg/m3 group showed significant effects: those were pronounced histopathological changes of airways and parenchyma, and elevated relative lung weight. The neutrophils, LDH, and protein in BALF were elevated. Quasi-static lung compliance, peak expiratory flow rate, mean mid expiratory flow rate were decreased whereas lung resistance, residual volume, and single breath CO-diffusing capacity were increased. Blood gas measurements revealed an elevation in hemoglobin, pH, arterio-alveolar oxygen difference, and venous admixture. Arterial pO2 and pCO2 were decreased. In animals exposed to 23.5 mg/m3 only marginal effects were detectable.


Lumbar intervertebral thermal therapies.
In hopes of improving outcomes for patients with discogenic pain, less invasive techniques that reduce trauma and shorten the recovery period have been developed. This article attempts to present a comprehensive description of minimally invasive techniques, specifically heat treatments, for lumbar disc disease. The goal is to inform and educate the reader on the various thermal therapies available for lumbar disc disease by evaluating the scientific data in an objective manner.


Allele-specific complementation of an Escherichia coli leuB mutation by a Lactobacillus bulgaricus tRNA gene.
A Lactobacillus bulgaricus gene encoding a serine tRNA with the anticodon CGA was isolated from a L. bulgaricus clone bank and characterized. This gene is expressed and active in Escherichia coli. The wild-type form of the gene allele specifically complements the E. coli leuB6 mutation. This process depends on gene copy number; high copy number restores leucine prototrophy, while low copy number does not. We suggest that restoration of activity of the mutant leuB6 allele occurs by missense suppression. The L. bulgaricus tRNA(CGASer) when overproduced in E. coli is misacylated at a low frequency, leading to the insertion of an amino acid other than serine in response to the presumed mutant codon UCG in the leuB6 gene. Nucleotide (nt) sequences flanking the tRNA coding region are present in the L. bulgaricus tRNA gene, closely resembling E. coli promoter and terminator elements. A noteworthy feature of this tRNA gene is the extreme length (22 nt) of its extra arm. The 3'-terminal CCA of the tRNA is not encoded in this tRNA gene and thus must be added posttranscriptionally.


Hypospadias and the embryogenesis of the penile urethra.
The findings of a histological study of a rare specimen of a human hypospadias penis are presented. These findings suggest that distal pits are due to arrested development of the glandar urethra. The present findings also indicate that accessory urethrae and possibly the ventral position of the urethral meatus are the result of an intrinsic abnormality of the urethral plate.


Distinct binding sites for calcitonin gene-related peptide and salmon calcitonin in rat central nervous system.
Calcitonin gene-related peptide (CGRP) binding sites have been identified in homogenates from the rat brain and spinal cord. Autoradiography with [125I]rat CGRP (rCGRP) revealed high grain density over the lateral hypothalamus, vestibular nuclei, colliculi, medial geniculate body, corpus mamillare and the molecular layer of the cerebellum which lacked binding sites for [125]salmon calcitonin (sCT). In contrast, no rCGRP labeling was seen over the anterior and dorsomedial hypothalamus which showed high sCT binding. The different regional distribution of rCGRP and sCT binding sites indicates that the structurally related peptides interact with separate receptors. The overlap between the localization of CGRP binding sites and endogenous CGRP in many regions of the central nervous system suggests that CGRP exerts unique physiological functions in the central nervous system.


Prevention of posttraumatic stress during inpatient rehabilitation post spinal cord injury: Study protocol for a randomized controlled trial of Brief Prolonged Exposure Therapy (Brief PE).
Scant research has focused on posttraumatic stress disorder (PTSD) in the SCI population, despite high prevalence estimates. Fortunately, prolonged exposure therapy (PE) is a well-researched and highly effective treatment for PTSD. Our recent clinical trial showed that standard 12-session PE was effective for PTSD treatment among inpatients with SCI. Early intervention with brief PE (3-sessions) delivered in the emergency department has also been effective for PTSD prevention, but has not been tested among people post-SCI. Thus, we aim to conduct the first test of the Brief PE intervention to prevent PTSD among patients with SCI. Adults who have experienced a SCI (N = 200) will be randomly assigned during inpatient rehabilitation to either: (a) 3 60-min sessions of Brief PE (intervention group) or (b) treatment as usual (control group). The primary outcome measure (PTSD symptoms measured by the PSSI-5) and secondary outcome measures (depression, anxiety, pain, quality of life, sleep disturbance, and resilience) will be assessed at baseline, 1-month, 3-months, and 6-months. Hierarchical linear modeling (HLM) will be used to evaluate the effectiveness of the PE intervention on PTSD and secondary outcomes. Descriptive statistics will examine feasibility and will include the number of participants enrolled, the number of sessions completed, fidelity of Brief PE delivery, and average scores for difficulty and helpfulness of the intervention scales for those randomized to intervention. Successful completion of this study will provide an evidence-based program to alleviate posttraumatic distress post spinal cord injury and prevent long-term development of PTSD.


Oestrogen-dependent suppression of pulsatile luteinising hormone secretion and kiss1 mRNA expression in the arcuate nucleus during late lactation in rats.
Follicular development and ovulation are strongly suppressed during lactation in mammals via a profound suppression of gonadotrophin secretion. The present study aimed to examine the role of oestrogen feedback action in suppressing luteinising hormone (LH) secretion and hypothalamic kisspeptin expression during the latter half of lactation. Plasma LH concentrations kept at low levels throughout the lactating period in intact and oestrogen-replaced ovariectomised (OVX) lactating rats, whereas plasma LH concentrations gradually elevated from day 10 postpartum in lactating OVX rats. OVX lactating rats showed frequent LH pulses at late lactation, although the LH pulses were significantly inhibited by an oestrogen replacement, which is much less effective on LH release in nonlactating rats. Oestrogen replacement in lactating OVX rats significantly reduced the number of Kiss1 mRNA-expressing cells in the arcuate nucleus (ARC) at late lactation, although the same oestrogen treatment did not affect the number of Kiss1-expressing cells in nonlactating controls. Exogenous kisspeptin challenge (0.2 nmol) into the third cerebroventricle significantly increased LH secretion in lactating OVX, lactating OVX + subcutaneous 17β-oestradiol and intact lactating rats at day 16 postpartum. These results suggest that LH pulse suppression during late lactation could be a result of the enhanced oestrogen-dependent suppression of ARC kisspeptin expression.


Hepatocyte growth factor levels during normal and intra-uterine growth-restricted pregnancies.
Hepatocyte growth factor (HGF), also known as scatter factor, binds the c-met receptor. It has been shown to be involved in mesenchyme-epithelial interactions. HGF is produced by the villous mesenchyme of the placenta throughout pregnancy and its receptor located on the villous cytotrophoblast cells. In this study the levels of HGF were measured in consecutive samples of plasma taken from pregnant women. Normal pregnancies were compared with intrauterine growth restricted (IUGR) pregnancies (below the third centile). In both groups, the levels of HGF were found to increase significantly as pregnancy progressed and then fall post partum. There was a considerable amount of variation found between individual women but no significant difference (P=0.65) between the normal and IUGR pregnancies.


Assessing RNA quality in postmortem human brain tissue.
The development of microarrays for the screening of gene expression has highlighted the importance of obtaining high quality RNA. We have investigated whether it was possible to obtain RNA of sufficiently good quality from postmortem human tissue using samples obtained from the New Zealand Neurological Foundation Human Brain Bank. We have investigated the effect of PM delay, the duration of the agonal state, the tissue pH, the age at death and the sex of the patient on the quality of normal human brain tissue and tissue from patients with various neurodegenerative conditions. Postmortem delay was shown to affect the RNA quality adversely, but the magnitude of the effect was small. While cerebellar RNA quality was not always an exact predictor of the RNA quality in other brain regions of interest, it was shown to have some predictive value and can be used as a preliminary indicator. The principle finding was that RNA quality is most strongly affected by the pH of the tissue, with both the pH and the RNA quality being influenced by the mode of death.


Neuronal pH regulation: constant normal intracellular pH is maintained in brain during low extracellular pH induced by acetazolamide--31P NMR study.
The intracellular pH in the brain was studied in six healthy volunteers before and immediately after the administration of 2 g of acetazolamide. Phosphorus-31 nuclear magnetic resonance spectroscopy by a 1.5 tesla whole-body scanner was used. The chemical shift between the inorganic phosphate and the phosphocreatine resonance frequencies was used for indirect assessment of the intracellular pH. The mean baseline intracellular pH was 7.05 +/- 0.04 (SD). The mean pH changes obtained at 15-min intervals within the first hour of acetazolamide administration were -0.03 +/- 0.04 (SD), -0.02 +/- 0.03 (SD), and 0.00 +/- 0.04 (SD), i.e., no statistically significant pH decrease was observed during the period where extracellular pH is known to drop markedly. Although several factors contribute to the lack of change of the intraneuronal pH, we will discuss that this observation in addition might suggest a direct intracerebral effect of acetazolamide.


Mutagenic activity of some coffee flavor ingredients.
The mutagenicity of 4 coffee flavor ingredients (chlorogenic acid, caffeic acid, pyrazine, and trigonelline) was evaluated in the Salmonella plate incorporation assay and mouse lymphoma L5178Y TK +/- assay. Two of the compounds, pyrazine and trigonelline, were negative in both assays. The other two compounds, caffeic acid and chlorogenic acid, were positive in the mouse lymphoma assay but negative in the Salmonella assay.


[Aplasia of the posterior arches of the atlas: a presentation of 2 cases].
Aplasia of the posterior arches of the atlas is an uncommon condition caused by a defect in their closure. It is usually associated with different syndromes. We present 2 asymptomatic patients with aplasia of C1 posterior bodies. Further studies are required on these lesions in order to take possible protection measures against trauma, and the selection between conservative or surgical treatment.


Role of PI(4,5)P(2) in vesicle exocytosis and membrane fusion.
A role for phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) in membrane fusion was originally identified for regulated dense-core vesicle exocytosis in neuroendocrine cells. Subsequent studies demonstrated essential roles for PI(4,5)P(2) in regulated synaptic vesicle and constitutive vesicle exocytosis. For regulated dense-core vesicle exocytosis, PI(4,5)P(2) appears to be primarily required for priming, a stage in vesicle exocytosis that follows vesicle docking and precedes Ca(2) (+)-triggered fusion. The priming step involves the organization of SNARE protein complexes for fusion. A central issue concerns the mechanisms by which PI(4,5)P(2) exerts an essential role in membrane fusion events at the plasma membrane. The observed microdomains of PI(4,5)P(2) in the plasma membrane of neuroendocrine cells at fusion sites has suggested possible direct effects of the phosphoinositide on membrane curvature and tension. More likely, PI(4,5)P(2) functions in vesicle exocytosis as in other cellular processes to recruit and activate PI(4,5)P(2)-binding proteins. CAPS and Munc13 proteins, which bind PI(4,5)P(2) and function in vesicle priming to organize SNARE proteins, are key candidates as effectors for the role of PI(4,5)P(2) in vesicle priming. Consistent with roles prior to fusion that affect SNARE function, subunits of the exocyst tethering complex involved in constitutive vesicle exocytosis also bind PI(4,5)P(2). Additional roles for PI(4,5)P(2) in fusion pore dilation have been described, which may involve other PI(4,5)P(2)-binding proteins such as synaptotagmin. Lastly, the SNARE proteins that mediate exocytic vesicle fusion contain highly basic membrane-proximal domains that interact with acidic phospholipids that likely affect their function.


Identification of an aspartate transfer RNA gene in maize mitochondrial DNA.
A gene for a transfer RNA (tRNA) specific for aspartic acid was identified in maize mitochondrial DNA. The nucleotide sequence and predicted secondary structure of this tRNA more closely resemble eubacterial and chloroplast aspartate tRNA genes than other mitochondrial aspartate tRNA genes. This gene is located on a 3,123 base pair EcoRI DNA fragment that also contains an elongator methionine tRNA gene. These two tRNA genes are separated by 726 nucleotides and are located on opposite strands of DNA.


Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor.
In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.


Effects of ketamine on neostigmine-induced contractile and phosphatidylinositol responses of the rat trachea.
Neostigmine causes airway smooth muscle contraction through the direct stimulation of muscarinic receptors and the activation of phosphatidylinositol (PI) responses. Ketamine attenuates airway smooth muscle contraction. It is not clear whether ketamine attenuates neostigmine-induced airway smooth muscle contraction by inhibiting the PI response. This study was designed to examine the effects of ketamine on neostigmine-induced contractile and PI responses of the rat trachea. Thirty male Wistar rats weighing 250-350 g were used. In the experiment on the contractile response, active contraction was induced with 1 microM neostigmine in the presence or absence of ketamine. In the experiment on the phosphatidylinositol response, the trachea slices were incubated with [3H]myo-inositol, 1 microM neostigmine, or 100 microM aluminum fluoride, and ketamine. The formation of [3H]inositol monophosphate (IP1), a degradation product of the phosphatidylinositol response, was measured with a liquid scintillation counter. Statistical significance (P < 0.05) was determined by analysis of variance. Neostigmine 1 microM caused tracheal ring contraction. This contraction was attenuated by ketamine dose-dependently and reached resting tension at 100 microM. Neostigmine- and aluminum fluoride-induced IP1, accumulation was also attenuated by ketamine. The results suggest that ketamine attenuates neostigmine-induced contractile responses, at least in part, through the inhibition of phospholipase C coupled with G protein in the PI response.


Health behaviors of Australian colorectal cancer survivors, compared with noncancer population controls.
A better understanding of health behaviors after a cancer diagnosis is important, as these behaviors are related to physical functioning, disease recurrence, development of second primary cancers, and risk of other chronic diseases. Body weight and health behaviors (smoking status, alcohol consumption, and physical activity) were examined in a population-based sample of colorectal cancer survivors and compared to a matched population group. Data were collected by telephone interviews pre-diagnosis (retrospectively reported), 6 and 12 months post-diagnosis for colorectal cancer survivors (n = 1,250). Comparison data were from a population-based cancer risk survey (n = 6,277). Colorectal cancer survivors were most likely to be overweight/obese pre-diagnosis (66%) than at 6 months (54%) or 12 months post-diagnosis (61%). There was little variation from 6 to 12 months in the proportion of current smokers (7% and 8%, respectively) or high-risk drinkers (both 22%). The greatest changes were for physical activity, with 53% of survivor's sufficiently active pre-diagnosis, 32% at 6 months, and 38% at 12 months post-diagnosis. At 12 months, colorectal cancer survivors were more likely than the comparison group to be: underweight (OR = 2.14, 95% CI = 1.38-3.31); a former smoker (OR = 1.44, 95% CI = 1.26-1.63); a low-risk (OR = 1.25, 95% CI = 1.09-1.44) or high-risk drinker (OR = 1.70, 95% CI = 1.43-2.03); and insufficiently active (OR = 1.57, 95% CI = 1.34-1.83) or inactive (OR = 2.76, 95% CI = 2.39-3.19). However, colorectal cancer survivors were significantly less likely to be a current smoker (OR = 0.68, 95% CI = 0.54-0.85). Our findings show particular scope for physical activity interventions for colorectal cancer survivors. Improving the general health of cancer survivors should help to decrease morbidity in this population and associated health system expenditure.


Synthesis and characterization of new and potent alpha-lipoic acid derivatives.
alpha-Lipoic acid [5-[1,2]-dithiolan-3-yl-pentanoic acid (LA)] is a natural antioxidant and cofactor of several enzymes. It increases the glucose transport activity in skeletal muscles and adipocytes in a non-insulin dependent manner. Therefore, LA is widely used in Type 2 diabetic patients as an oral auxiliary drug. However, large doses of LA (0.8-1.8 gr/day p.o.) are required due to its unfavorable pharmacokinetic parameters. In order to improve these parameters, we synthesized ester and amide LA derivates. Two of these newly synthesized compounds, 5-[1,2]-dithiolan-3-yl-pentanoic acid 3-(5-[1,2]dithiolan-3yl-pentanoylamino)-propyl]-amide (AN-7) and 5-[1,2]-dithiolan-3-yl-pentanoic acid 3-(5-[1,2]-dithiolan-3yl-pentanoyloxy)-propyl ester (AN-8) augmented the rate glucose transport in myotubes in culture in the absence or presence of insulin. Their potency was 12-fold higher than that of the parent compound; their maximal stimulatory effect was 1.5-fold higher than that of LA. When tested in vivo in streptozotocin-diabetic C57/Black mice, AN-7 (10 mg/kg/day for 2 weeks, s.c.) reduced blood glucose level by 39% while a higher dose of LA (50 mg/kg/day for 2 weeks, s.c.) lowered it by 30%. These results indicate that AN-7 is more potent than LA in augmenting glucose transport in skeletal muscles and reducing blood glucose in diabetic animals.


Effect of diet on longitudinal bone growth and osteochondrosis in swine.
Weanling gilts were fed either a 12% or 16% protein diet for 10 weeks. Animals fed the 12% protein diet had reduced body weights and reduced longitudinal bone growth as measured in the distal radial growth plate. There was no difference in the growth plate widths between the two animal groups, but there was a significant reduction in the daily rate of cell production in the proliferative zone of animals fed the 12% protein diet. No effect of diet on the rate of expansion of the epiphysis at the articular-epiphyseal junction of the distal femur or humerus could be detected. All animals in both groups had morphologic cartilage lesions consistent with early changes associated with osteochondrosis (OCD), and there was no difference in the lesion morphology between the dietary groups. Areas of disorderly endochondral ossification in the radial growth plate were associated with perpendicular growth cartilage infractions. Growth plate lesions were characterized by increased widths of the maturing cartilage zone without increased width of the proliferative zone or an increase in the daily rate of cell production. Focal growth plate lesions developed because of a transitory inhibition of cartilage mineralization and resorption. Disorderly foci of endochondral ossification beneath articular cartilage were characterized by an area of chondrocyte necrosis which prevented normal cartilage matrix mineralization. Lamellae of cartilage necrosis were also present within the reserve zone of the articular cartilage. These were associated with abnormalities of the cartilage canal vessels, and chondrocyte necrosis was considered to precede degenerative changes in articular cartilage matrix.(ABSTRACT TRUNCATED AT 250 WORDS)


Translation and concurrent validity, sensitivity and specificity of Chinese version of Short Orientation Memory Concentration Test in people with a first cerebral infarction.
This study aimed to translate the English version of the Short Orientation-Memory-Concentration (SOMC) test into a Chinese version, denoted the C-SOMC test, and to investigate the concurrent validity, sensitivity, and specificity of the C-SOMC test against a longer and widely used screening instrument in people with a first cerebral infarction. An expert group translated the SOMC test into Chinese using a forward-backward procedure. Eighty-six participants (67 men and 19 women, mean age = 59.31 ± 11.57 years) with a first cerebral infarction were enrolled in this study. The validity of the C-SOMC test was determined using the Chinese version of Mini Mental State Examination (C-MMSE) as the comparator. Concurrent validity was determined using Spearman's rank correlation coefficients. Univariate linear regression was used to analyze items' abilities to predict the total score on the C-SOMC test and the C-MMSE score. The area under the receiver operating characteristic curve (AUC) was used to demonstrate the sensitivity and specificity of the C-SOMC test at various cut-off values distinguishing cognitive impairment from normal cognition. The total score for the C-SOMC test and the score for item 1 on this test exhibited moderate-to-good correlations with the C-MMSE score, with respective ρ-values of 0.636 and 0.565 (P < 0.001). The scores for each of items 2, 4, 5, 6, and 7 yielded fair correlations with C-MMSE score, with ρ-value from 0.272 to 0.495 (P < 0.05). The total score on the C-SOMC test and the item score were good predictors (adjusted R2 = 0.049 to 0.615) of the C-MMSE score, and six items were good predictors (adjusted R2 = 0.134 to 0.795) of the total score. The AUC was 0.92 for the C-SOMC test. A cut-off of 17/18 on the C-SOMC test gave optimal performance: correct classification of 75% of participants, with 75% sensitivity and 87.9% specificity. The C-SOMC test demonstrated good concurrent validity, sensitivity and specificity in a sample of people with a first cerebral infarction, demonstrating that it could be used to screen for cognitive impairment in stroke patients.


Nickel Nanoparticle Catalyzed Mono- and Di-Reductions of gem-Dibromocyclopropanes Under Mild, Aqueous Micellar Conditions.
Mild mono- and di-hydrodehalogenative reductions of gem-dibromocyclopropanes are described, providing an easy and green approach towards the synthesis of cyclopropanes. The methodology utilizes 0.5-5 mol % TMPhen-nickel as the catalyst, which, when activated with a hydride source such as sodium borohydride, cleanly and selectively dehalogenates dibromocyclopropanes. Double reduction proceeds in a single operation at temperatures between 20-45 °C and at atmospheric pressure in an aqueous designer surfactant medium. At lower loading and either in the absence of ligand or in the presence of 2,2'-bipyridine, this new technology can also be used to gain access to not only monobrominated cyclopropanes, interesting building blocks for further use in synthesis, but also mono- or di-deuterated analogues. Taken together, this base-metal-catalyzed process provides access to cyclopropyl-containing products and is achieved under environmentally responsible conditions.


Potential of Pulsed Electric Fields for the preparation of Spanish dry-cured sausages.
The aim of this investigation was to lay the groundwork of the potential application of Pulsed Electric Fields (PEF) technology for accelerating the drying process of meat and meat products, and specifically in this work of Spanish dry-cured sausages "longaniza". PEF treatments were applied to pork loin samples, and the influence of different PEF parameters on the process were evaluated. An optimal PEF treatment of 1 kV/cm, 200 μs of pulse width and 28 kJ/kg was determined as the most suitable to electroporate meat cells and to improve water transfer by achieving a water content reduction of 60.4% in treated-meat samples dried at 4 °C. The influence of PEF on meat drying rate was also studied on minced pork and the results showed that with a particle size of 4.0 mm higher drying rates were achieved. To validate the results, Spanish cured sausages were prepared from treated and untreated minced pork and stuffed into gauzes and natural pork casings at pilot plant scale. After the curing process, the application of PEF to sausages stuffed into gauze reduced the drying time from 17 to 9-10 days, a reduction of 41-47%, confirming the effects described at lab scale and the potential of PEF for accelerating the sausage-drying process.


Identification of candidate protective variants for common diseases and evaluation of their protective potential.
Human polymorphisms with derived alleles that are protective against disease may provide powerful translational opportunities. Here we report a method to identify such candidate polymorphisms and apply it to common non-synonymous SNPs (nsSNPs) associated with common diseases. Our study also sought to establish which of the identified protective nsSNPs show evidence of positive selection, taking this as indirect evidence that the protective variant has a beneficial effect on phenotype. Further, we performed an analysis to quantify the predicted effect of each protective variant on protein function/structure. An initial analysis of eight SNPs previously identified as associated with age-related macular degeneration (AMD), revealed that two of them have a derived allele that is protective against developing the disease. One is in the complement component 2 gene (C2; E318D) and the other is in the complement factor B gene (CFB; R32Q). Then, combining genomewide ancestral allele information with known common disease-associated nsSNPs from the GWAS catalog, we found 32 additional SNPs which have a derived allele that is disease protective. Out of the total 34 identified candidate protective variants (CPVs), we found that 30 show stronger evidence of positive selection than the protective variant in lipoprotein lipase (LPL; S447X), which has already been translated into gene therapy. Furthermore, 11 of these CPVs have a higher probability of affecting protein structure than the lipoprotein lipase protective variant (LPL; S447X). We identify 34 CPVs from the human genome. Diseases they confer protection against include, but are not limited to, type 2 diabetes, inflammatory bowel disease, age-related macular degeneration, multiple sclerosis and rheumatoid arthritis. We propose that those 30 CPVs with evidence of stronger positive selection than the LPL protective variant, may be considered as priority candidates for therapeutic approaches. The next step towards translation will require testing the hypotheses generated by our analyses, specifically whether the CPV arose from a gain-of-function or a loss-of-function mutation.


Community-initiated screening programme for beta-thalassaemia trait.
Seven hundred and ninety-five people, (96% of whom were of Greek origin) were screened for thalassaemia trait. A prevalence rate of 7.1% for beta-thalassaemia carriers was found. The red cells of individuals with the alpha-1-thalassaemia, beta-thalassaemia, and haemoglobin Lepore traits all had a mean corpuscular volume (MCV) of less than 76 fL and a mean corpuscular haemoglobin (MCH) of less than 25 pg, thus confirming the usefulness of these indices as a preliminary thalassaemia screening test. However, in three of the six people provisionally diagnosed as having delta-beta-thalassaemia trait, an overlap of MCV and MCH values with the normal range occurred. Community attitudes to the survey and its implications are discussed.


Metabolite profiling analysis of plasma, urine, and feces of rats after oral administration of Flos Chrysanthemi Indici preparation through UHPLC-Q-Exactive-MS combined with pharmacokinetic study of markers by UHPLC-QQQ-MS/MS.
Zhenju Antihypertensive Tablet is one of the Flos Chrysanthemi Indici preparations (FCIP) with antihypertensive effect. In order to investigate its process in vivo, a method using ultra-high performance liquid chromatography coupled with quadruple Exactive mass spectrometry (UHPLC-Q-Exactive-MS) was established for comprehensive analysis of the absorbed active component and metabolites in rat plasma, urine, and feces after the oral administration of FCIP. As a result, a total of 61 FCIP-related xenobiotics were identified, including 35 in plasma (25 prototypes, 10 metabolites), 40 in urine (23 prototypes, 17 metabolites), and 25 in feces (12 prototypes, 13 metabolites). The metabolism reactions included phase I reactions (such as oxidation, methylation, and reduction) and phase II reactions (such as sulfate conjugation and glucuronide conjugation). Meanwhile, a verified and optimized ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was developed for the simultaneous investigation of the pharmacokinetic profiles of four markers in FCIP. The results showed that all of the four components had good oral absorption effect. This study simultaneously investigated the comprehensive metabolic profiling of FCIP in rat plasma, urine, and feces after the oral administration as well as the four components pharmacokinetic behavior. The results can provide the therapeutic material basis for FCIP.


lncRNA DLG1-AS1 promotes cervical cancer cell gemcitabine resistance by regulating miR-16-5p/HDGF.
To investigate the long non-coding RNA DLG1 Antisense RNA 1 (lncRNA DLG1-AS1) mechanism in cervical cancer cells with gemcitabine (GEM) resistance. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect DLG1-AS1, miR-16-5p, and hepatoma-derived growth factor (HDGF) expression in cervical cancer cells. The effects of DLG1-AS1 knockdown on cell viability, proliferation, and apoptosis were investigated in GEM-resistant cervical cancer cells. The binding of DLG1-AS1 with miR-16-5p and of miR-16-5p with HDGF was confirmed through dual-luciferase reporter assays. HDGF expression was detected through Western blotting. A xenograft model was established using stably transfected GEM-resistant cervical cancer cells to detect the role of DLG1-AS1 in tumorigenesis in vivo. DLG1-AS1 expression was significantly elevated in HeLa/GEM and SiHa/GEM cells. DLG1-AS1 silencing significantly reduced the viability and proliferation of GEM-resistant cervical cancer cells. DLG1-AS1 also promoted GEM sensitivity in cervical cancer cells by inhibiting miR-16-5p. Moreover, the tumor volume in nude mice in the DLG1-AS1 knockdown group decreased after GEM treatment. In addition, DLG1-AS1 targeted miR-16-5p, and miR-16-5p targeted HDGF. The miR-16-5p inhibitor reversed the DLG1-AS1 knockdown effect in GEM-resistant cervical cancer cells. Knockdown of DLG1-AS1 promoted GEM sensitivity in cervical cancer cells by regulating miR-16-5p/HDGF.


Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users.
TLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection. A total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay. The TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors - 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p=0.037 and 80% vs. 53%; p=0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR=0.29, 95% CI=0.09-0.90). This association remained significant (OR=0.25, 95% CI=0.07-0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use). The TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.


Risk factors for symptomatic urinary tract infections in individuals with chronic neurogenic lower urinary tract dysfunction.
Retrospective investigation. To investigate the association of patient and injury characteristics, as well as bladder management, with the occurrence of patient-reported, symptomatic urinary tract infection(s) UTI(s) in patients with chronic neurogenic lower urinary tract dysfunction (NLUTD). Tertiary urologic referral center. The patient database was screened for patients with chronic (>12 months) NLUTD who had presented between 2008 and 2012. Patient characteristics, bladder evacuation management, the annual number of patient-reported, symptomatic UTIs and the type of prophylactic treatment to prevent UTIs were collected. Binary logistic regression analysis was used to investigate the effects of the investigated risk factors on the occurrence of symptomatic UTI(s) and recurrent symptomatic UTIs (⩾3 annual UTIs). The data of 1104 patients with a mean NLTUD duration of 20.3±11.6 years were investigated. The evacuation method was a significant (P⩽0.004) predictor for the occurrence of symptomatic UTI and recurrent symptomatic UTIs. The greatest annual number of symptomatic UTIs was observed in patients using transurethral indwelling catheters, and the odds of experiencing a UTI and recurrent UTIs were increased more than 10- and 4-fold, respectively. The odds of a UTI or recurrent UTIs were also increased significantly (P⩽0.014) in patients using intermittent catheterization (IC). Botulinum toxin injections into the detrusor increased the odds of a UTI ~10-fold (P=0.03). The bladder evacuation method is the main predictor for symptomatic UTIs in individuals with NLUTD. Transurethral catheters showed the highest odds of symptomatic UTI and should be avoided whenever possible.


Ultrasonography for diagnosing carpal tunnel syndrome: a meta-analysis of diagnostic test accuracy.
Ultrasonography is widely used to diagnose carpal tunnel syndrome (CTS), a common peripheral neuropathy, but the reported diagnostic accuracy varies. This meta-analysis focused on the diagnostic test accuracy of ultrasonography for diagnosing CTS. Structured searches of PubMed for 1990-2010 were done and the data were extracted and meta-analyzed by pooling estimates of sensitivity, specificity, likelihood ratios and diagnostic odds ratios. Diagnostic performance was also judged by using a summary receiver operating characteristic curve. Twenty-eight trials involving 3995 wrists were included. A greater cross-sectional area (CSA) of the median nerve at the carpal tunnel inlet (CSA-I) and a greater flattening ratio at the level of the hamate were seen in CTS wrists than in control wrists. A CSA-I ≥9 mm(2) is the best single diagnostic criterion, with a diagnostic odds ratio of 40.4 (sensitivity 87.3%, specificity 83.3%).


Atomized intranasal vs intravenous fentanyl in severe renal colic pain management: A randomized single-blinded clinical trial.
Renal colic is one of the most common painful disorders in patients referred to the emergency department. The main purpose of this study was to compare the efficiency of two methods of intravenous (IVF) and intranasal (INF) fentanyl administration in pain management in patients with severe renal colic. This was a single-blind randomized clinical trial performed on patients with severe renal colic. The severity of pain was ≥8 based on the Numerical Rating Scale (NRS). The efficacy of pain management was compared within and between the IVF (intramuscular Ketorolac + intravenous fentanyl) and INF (intramuscular Ketorolac + intranasal fentanyl) groups at different times points. Oral consent was obtained from all the patients. Of 220 individuals, 96 (43.60%) were women and 124 (56.40%) were men. There were no significant differences between the two groups regarding the baseline pain severity, age, sex, history of urolithiasis and body mass index (BMI). The pain severity showed a significant reducing trend in both groups (p < 0.0001). There was also a significant difference comparing the mean pain severity between groups at different times (p < 0.0001). In each group, the severity of pain showed significant reduction compared with its prior measurement (P < 0.0001). Fentanyl is highly effective in controlling pain in patients with severe renal colic referring to the emergency department. Intranasal administration of fentanyl combination with ketorolac can be an appropriate, non-invasive, easy-to-use and fast alternative to the intravenous method to manage pain in these patients.


Continuum of care of mothers and immunization status of their children: A secondary analysis of 2015-2016 Myanmar Demographic and Health Survey.
To assess the association between the continuum of care of mothers and the immunization status of their 12-23 months old children. A secondary data analysis using the Myanmar Demographic and Health Survey (2015-16) data, a cross-sectional, household-based, nationally representative survey conducted during 2015-2016. We included 1669 pairs of mothers and their children in this analysis. We categorized the children into fully immunized and no/not fully immunized children and define a continuum of care (CoC) of the mother if women received antenatal care ≥ four times, delivered with skilled birth attendances, and received postnatal care within 48 h after delivery. We used the multivariable binary logistics regression using STATA version 15.1 with the survey command (svy) and reported the results by adjusted odds ratios (aORs) with 95% confidence intervals (CIs). The mother's CoC prevalence was 42.5%, and that of fully immunized children was 33.5%. However, only one-fifth of mothers and their children received the continuum of care services altogether. The children of mothers who received CoC were more likely to be fully vaccinated than those who did not (aOR = 1.60, 95%CI: 1.21, 2.13, P < 0.001). The child's birth order, employment status, and wealth status of the households are independent predictors of the full immunization of children. We concluded that receiving the CoC in mothers influenced their children's vaccination status. Hence, integrating maternal health programs and immunization programs is essential to achieving sustainable development goals in Myanmar.


Well differentiated thyroid carcinoma: current treatment.
Well differentiated thyroid carcinoma (WDTC) is a relatively common malignancy accounting for an estimated 37,000 thousand cases in the United States in 2009 [1]. WDTC also has a generally high 5 year survival rate that correlates with age. Papillary thyroid carcinoma (PTC) greater than 1 cm is best managed by total thyroidectomy. Thyroid lobectomy and isthmusectomy may be adequate for unifocal PTC less than 1 cm in patients without negative prognostic factors. Central compartment and possible lateral neck dissections should be performed when nodal metastases are present in the respective nodal basins. Post-operatively, radioactive iodine ablation with (131)I followed by thyroid stimulating hormone (TSH) suppression is indicated in certain patients to improve locoregional control and reduce recurrence.


Studies into the mechanisms of strain differences in hippocampus-related behaviors.
The heterogeneous mouse stocks HS/Ibg and SABRA/HUC and the inbred strains C57BL/6J, CBA/LAC, and BALB/Crgl were employed in an investigation of strain differences in delayed spontaneous alteration (SA) and eight-arm maze performance (EAM). Intact male mice were tested for SA at age 41 days for 2 consecutive days and for EAM at age 50-54 days, under conditions of water deprivation that commenced on day 43. In SA, BALB mice had a lower score than all other strains on day 1 but differed significantly only from SABRA; performance on day 2 was not consistent with that on day 1. In EAM, HS was first, CBA second, C57 third, SABRA fourth, and BALB fifth. HS was superior to the other strains, while BALB fell far below all other strains in both tests. Except for these two strains, the correlation between the two tests across the other strains was low. A study was undertaken to investigate the role of the hippocampus in the deficits in the performance of BALB mice in the two behaviors. Noradrenergic neurons were transplanted to hippocampus or cortex, and cholinergic neurons to their hippocampus. There were no significant differences in performance between the control and transplanted mice. The possibility was discussed that the behavioral differences are the outcome of variability in the neurotransmitters systems of the hippocampus but probably not the noradrenergic system.


Evaluation of the effectiveness of two Iranian su-strains of Metarhizium anisopliae (ascomycota: hypocreales) on the mortality rate of American cockroach.
The cockroach is one of the most important disease vectors in world. Entomopathogenic fungi, as three concentrations of spores were taken 1.1 × 105, 1.1 × 107, and 1.1 × 109 conidia/mL from two isolates of Nour and Saravan-Iranian. In this study, the immersion method caused about 13% mortality only in isolation (1 × 109 conidia/mL) of Saravan isolates. Inoculation of isolates below the pronotum did not significantly differ the mortality rate between the two genera (P = 0.8), compared to the pathogenicity of three isolates of M. anisopliae (1.1 × 105, 1.1 × 107, and 1.1 × 109 conidia/mL). In total, Saravan and Nour isolates were 66%, 73%, and 93%, respectively, indicating a significant difference (P < 0.001). Mortality of male and female cockroaches with Saravan isolates respectively occurred 3 and 4 days after inoculation (LT50 = 4.3d), while for Nour isolates, in both sexes, mortality was observed within four days after the test (LT50 = 5.5d). Considering the results M. anisopliae can be one benefit methods for control American cockroach in the future. .


Incidence, and natural history of inflammatory bowel disease in Castilla y León: Prospective and multicenter epidemiological study.
The incidence of inflammatory bowel disease (IBD) is increasing worldwide. To evaluate the incidence of IBD in Castilla y León describing clinical characteristics of the patients at diagnosis, the type of treatment received and their clinical course during the first year. Prospective, multicenter and population-based incidence cohort study. Patients aged >18 years diagnosed during 2017 with IBD (Crohn's disease [CD], ulcerative colitis [UC] and indeterminate colitis [IC]) were included from 8 hospitals in Castilla y León. Epidemiological, clinical, and therapeutic variables were registered. The global incidence and disease incidence were calculated. 290 patients were diagnosed with IBD (54.5% UC, 45.2% CD, and 0.3% IC), with a median follow-up of 9 months (range 8-11). The incidence rate of IBD in Castilla y Leon in 2017 was 16.6 cases per 10,000 inhabitants-year (9/105 UC cases and 7.5/105 CD cases), with a UC/CD ratio of 1.2:1. Use of systemic corticosteroids (47% vs 30%; P=.002), immunomodulatory therapy (81% vs 19%; P=.000), biological therapy (29% vs 8%; P=.000), and surgery (11% vs 2%; p=.000) were significatively higher among patients with CD comparing with those with UC. The incidence of patients with UC in our population increases while the incidence of patients with CD remains stable. Patients with CD present a worse natural history of the disease (use of corticosteroids, immunomodulatory therapy, biological therapy and surgery) compared to patients with UC in the first year of follow-up.


E-commerce Policy and the Global Economy: A Path to More Inclusive Development?
The advancement of digitalization is gradually transforming the existing structure of the global economy. According to the McKinsey Global Institute, almost all cross-border transactions had a digital component in 2016. This is also reflected by the growing literature on digitalization and E-commerce. Yet, studies specifically focusing on E-commerce policy are scarce compared with other areas in this domain. By going beyond academic articles and including policy documents in our analysis, this study takes stock of the issues as well as the policy recommendations identified in these publications. Our analysis reveals that to promote an inclusive E-commerce participation, it is imperative to design policies that improve countries' formal institutions, facilitate the inclusion of less-developed countries in the E-commerce space, and enhance E-commerce adoption by small- and medium-sized enterprises. We highlight the significance of collaboration between and solidarity among governments and other stakeholders.


Structure-function relationships of human apolipoprotein D an immunochemical analysis.
Apolipoprotein D (apoD), a 169 amino acid member of the lipocalin family, is thought to be a transporter of small, hydrophobic ligands. A panel of 10 anti-apoD monoclonal antibodies (mAbs) was prepared and characterized in order to define apoD structure-function relationships. An apoD epitope map was constructed based on reactivity of the mAbs with apoD fragments. Three mAbs react with epitopes between apoD residues 7-78, seven mAbs with epitopes between residues 128-169, one mAb recognizes an epitope that straddles residues 99-102 and one mAb is specific for an epitope composed of non-contiguous apoD residues. Several pairs of mAbs whose respective epitopes are widely separated in apoD primary structure can compete for binding to immobilized apoD. This would be consistent with the compact beta-barrel tertiary structure that apoD is thought to adopt. None of the mAbs block the interaction of apoD with pregnenolone, a putative physiological ligand for apoD.


How an American plaintiff's lawyer presents the spinal cord injury resulting from trauma.
The author, a lawyer, describes how he learns the full implications of how spinal cord injury has affected his client. He teaches this to the jury and by describing the economic effects of the injury and its effect of the patient and his family, he obtains the maximum financial compensation.


Immunological detection of mycobacterial antigens in infected fluids, cells and tissues by latex agglutination. Animal model and clinical application.
We devised an immunoassay for the detection of mycobacterial antigens in cell lysates and in tissue extracts which is based on the agglutination of latex particles coated with anti-Mycobacterium bovis F(ab')2, followed by counting of non-agglutinated particles. Mycobacterium bovis cell lysates were tested and a reference curve was established, having a lower limit of detection of 15-20 Mycobacteria. We were able to detect mycobacterial antigens in cell lysates from bronchoalveolar washings and in spleen and liver lysates obtained from experimentally infected rabbits. Antigens were also detected in ten out of 11 samples obtained from patients with proven tuberculous infection. These samples were readily distinguished from 32 negative control samples after pepsin treatment. In contrast, periodate treatment of samples to destroy carbohydrate, abolished all reactivity. Following gel filtration chromatography we identified three peaks with antigenic properties in samples of all types. The detection of mycobacterial carbohydrate antigens by latex agglutination and particle counting should be a useful adjunct in the diagnosis of tuberculosis.


Time course of the use of chromatic and achromatic facial information for sex categorization.
The most useful facial features for sex categorization are the eyes, the eyebrows, and the mouth. Dupuis-Roy et al. reported a large positive correlation between the use of the mouth region and rapid correct answers [Journal of Vision 9 (2009) 1-8]. Given the chromatic information in this region, they hypothesized that the extraction of chromatic and achromatic cues may have different time courses. Here, we tested this hypothesis directly: 110 participants categorized the sex of 300 face images whose chromatic and achromatic content was partially revealed through time (200 ms) and space using randomly located spatio-temporal Gaussian apertures (i.e. the Bubbles technique). This also allowed us to directly compare, for the first time, the relative importance of chromatic and achromatic facial cues for sex categorization. Results showed that face-sex categorization relies mostly on achromatic (luminance) information concentrated in the eye and eyebrow regions, especially the left eye and eyebrow. Additional analyses indicated that chromatic information located in the mouth/philtrum region was used earlier-peaking as early as 35 ms after stimulus onset-than achromatic information in the eye regions-peaking between 165 and 176 ms after stimulus onset-as was speculated by Dupuis-Roy et al. A non-linear analysis failed to support Yip and Sinha's proposal that processing of chromatic variations can improve subsequent processing of achromatic spatial cues, possibly via surface segmentation [Perception 31 (2002) 995-1003]. Instead, we argue that the brain prioritizes chromatic information to compensate for the sluggishness of chromatic processing in early visual areas, and allow chromatic and achromatic information to reach higher-level visual areas simultaneously.


Insulin induced phosphorylation and activation of the cGMP-inhibited cAMP phosphodiesterase in human platelets.
Insulin induced phosphorylation and activation of the cGMP inhibited cAMP phosphodiesterase (cGI-PDE) in human platelets were demonstrated after isolation of the enzyme with specific polyclonal cGI-PDE antibodies. The demonstration of this insulin effect required suppression of basal cGI-PDE phosphorylation, through the use of the protein kinase inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine). The human platelet insulin receptor beta-subunit, previously identified as a 97 kDa polypeptide, was detected with the use of wheat germ agglutinin chromatography and anti-phosphotyrosine antibodies. These results suggest that insulin, through phosphorylation/activation of cGI-PDE, could decrease cAMP/cAMP dependent protein kinase (cAMP-PK) activity and thereby make the platelets more sensitive towards aggregating agents.


Development and Usability Testing of a Mobile Application to Monitor Patient-Reported Outcomes after Stress Urinary Incontinence Surgery.
To develop and perform a usability testing of a mobile application (app) with representative users of surgeons and female patients undergoing stress urinary incontinence (SUI) surgery. A mobile app was developed with the Medical Device Epidemiology Network (MDEpiNet) High-Performance Integrated Virtual Environment (HIVE) to streamline the collection of patient-reported outcomes following SUI surgery using validated questionnaires. It was designed as a collaborative effort with the Women's Health Initiative (WHI), including patient and surgeon involvement. The app evaluation questions addressed the user's rating on the clarity and length of the questions and the comfort level in using the interface for patients to report post-operative outcomes and surgeons to review them. A total of twenty patients and 5 surgeons tested the mobile app and reported their experience and level of satisfaction. The average patient experience score was 9 out of ten, with ten being the best. Eleven patients (55%) were interested in replacing in-person follow-up visits with the app. The surgeons reported an average user experience score of 8.6 out of ten. Four surgeons (80%) were interested in replacing in-person visits with the app. The combined experience score between all users was 8.9 out of ten. Fifteen out of twenty-five users (60%) showed interest in replacing in-person visits with the app. The mobile app for SUI captured important patient-reported outcomes with a high satisfaction reporting from patients and surgeons.


Identification of in vitro metabolites of ethylphenidate by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.
Ethylphenidate is a new potent synthetic psychoactive drug, structurally related to methylphenidate. Using human liver microsomes and cytosol, we have investigated for the first time the Phase-I and Phase-II in vitro metabolism of ethylphenidate. The structure of the metabolites was elucidated by hybrid quadrupole time-of-flight mass spectrometry. Overall, seven Phase-I, but no Phase-II metabolites were detected. Ethylphenidate underwent hydroxylation forming two primary mono-hydroxylated metabolites and, subsequently, dehydration and ring opening with an additional hydroxylation, forming secondary metabolites. The involvement of different human cytochrome P450 (CYP) enzymes in the formation of ethylphenidate metabolites was investigated using a panel of human recombinant CYPs (rCYPs). rCYP2C19 was the most active recombinant enzyme involved in the formation of all seven ethylphenidate metabolites detected, although other rCYPs (rCYP1A2, rCYP2B6, rCYPC9, rCYP2D6, and rCYP3A4, but not rCYP2E1) played a role in the metabolism of ethylphenidate. All metabolites identified in the present study can be considered as potential specific biomarkers of ethylphenidate in toxicological studies. Additionally, ritalinic acid and methylphenidate were formed by non-enzymatic hydrolysis and trans-esterification, and, therefore, they cannot be considered as (oxidative) metabolites of ethylphenidate. The presence of methylphenidate and ritalinic acid cannot be exclusively associated to the use of ethylphenidate, since methylphenidate is a drug itself and ritanilic acid can be formed from both ethylphenidate and methylphenidate.


Potential role of pyridoxal-5'-phosphate phosphatase/chronopin in epilepsy.
Changes in actin dynamics and pyridoxal-5'-phosphate (PLP) metabolisms are closely related to the pathophysiological profiles of the epileptic hippocampus. Recently, it has been reported that PLP phosphatase/chronophin (PLPP/CIN) directly dephosphorylates actin-depolymerizing factor (ADF)/cofilin as well as PLP. In the present study, therefore, we have investigated whether PLPP/CIN is linked to the dynamics of actin filament assembly and the excitability in the rat hippocampus. In control animals, pyridoxine chloride (PNP) treatment increased PLPP/CIN immunoreactivity only in astrocytes, which did not affect electrophysiological properties. Following status epilepticus, the PLPP/CIN protein level increased in granule cells and reactive astrocytes. These changes in PLPP/CIN protein level showed an inverse correlation with phospho-ADF (pADF)/cofilin levels and F-actin content. These changes were also accompanied by alterations in the excitability ratio and paired-pulse inhibition. Transduction of PLPP/CIN by Tat-PLPP/CIN showed similar effects on pADF/cofilin levels, F-actin content and excitability ratio in normal animals. These findings suggest that PLPP/CIN-mediated actin dynamics may play an important role in the changes of morphological properties and excitability of the epileptic hippocampus.


Dermatomyositis and calcific myonecrosis in the leg: ultrasound as an aid in management.
Calcific myonecrosis, often reported in the setting of prior trauma or compartment syndrome, has traditionally been treated with surgical debridement; however, these cases are often complicated by poor wound closure and poor healing. Serial percutaneous aspirations, instead, have been proposed as an alternative treatment option. This is the first report, to our knowledge, of the use of ultrasound guidance in the aspiration of calcific myonecrosis as an aid in management.


[Microspectrophotometric study of the sialomucin content of the glomerular filter in the nephrotic syndrome].
A microspectrophotometric study of sialomucins in human glomerular filter of the kidney in some diseases was carried out. Sialomucins were detected in paraffine sections stained after Haim, and examined on scanning microspectrophotometer. Lipid nephrosis, secondary amyloidosis, membranous-proliferative glomerulonephritis with the nephrotic syndrome were accompanied by a significant decrease in the amount of sialic acid. No reduction of sialomucins occurred in subacute glomerulonephritis with the nephrotic syndrome. A connection between the selective proteinuria and a decrease of the amount of sialomucins in the glomerulus is suggested.


The urinary excretions of iron and chromium by children with burns and scalds.
There is a wide variation in the urinary output of chromium by children who have been burned or scalded. It seems possible that when the excretion of chromium is increased this may be related to an increased plasma concentration of glucose which may follow injury, and when the excretion of chromium is reduced this may be related to a low body content of chromium. During the first seven days after injury there is a significant increase in the excretion of iron. Likewise the iron/chromium ratio is also raised over the first seven days. The overall loss of iron during the first twelve days or thereabouts is probably not sufficient to require nutritional supplements over this period.


Two distinct modes of exocytotic fusion pore expansion in large astrocytic vesicles.
Formation of the fusion pore is a central question for regulated exocytosis by which secretory cells release neurotransmitters or hormones. Here, by dynamically monitoring exocytosis of large vesicles (2-7 μM) in astrocytes with two-photon microscopy imaging, we found that the exocytotic fusion pore was generated from the SNARE-dependent fusion at a ring shape of the docked plasma-vesicular membrane and the movement of a fusion-produced membrane fragment. We observed two modes of fragment movements, 1) a shift fragment that shifted to expand the fusion pore and 2) a fall-in fragment that fell into the collapsed vesicle to expand the fusion pore. Shift and fall-in modes are associated with full and partial collapses of large vesicles, respectively. The astrocytic marker, sulforhodamine 101, stained the fusion-produced membrane fragment more brightly than FM 1-43. Sulforhodamine 101 imaging showed that double fusion pores could simultaneously occur in a single vesicle (16% of large vesicles) to accelerate discharge of vesicular contents. Electron microscopy of large astrocytic vesicles showed shift and fall-in membrane fragments. Two modes of fusion pore formation demonstrate a novel mechanism underlying fusion pore expansion and provide a new explanation for full and partial collapses of large secretory vesicles.


Intraoperative Periprostehtic Femur Fracture - When is the Cerclage Enough?
Intraoperative periprosthetic femoral fractures are among the most serious complications in both primary and revision arthroplasty. They are often not detected, despite intraoperative radiological control. Since an unnoticed intraoperative fracture often requires revision surgery, which has been associated with increased mortality rates, intraoperative diagnosis and corresponding direct and sufficient treatment are crucial. There are patient-, surgery-, and implant-specific risk factors that increase the possibilities of intraoperative fractures. The most common risk factors on the patient side are age, gender, and various pre-existing conditions, such as osteoporosis or rheumatic diseases. A minimally invasive approach and a cementless press-fit fixation are the most significant surgery- and implant-specific risk factors. The Vancouver classification or the modified Mallory classification are available for the classification of intraoperative periprosthetic femoral fractures. Based on these classifications, treatment recommendations can be derived. Different strategies are available for fracture management. Generally, if the stem is stable, osteosynthesis can be performed with preservation of the implant. This procedure can be applied to the majority of cases with non-displaced fractures by using cerclages as fixation. An unstable implant may require replacement of the stem. In higher grade fractures, stabilisation by using plate osteosynthesis may be necessary. The aim is to achieve the most anatomical reposition possible for the best possible bony consolidation. The ultimate goal is high implant stability and restoration of the biomechanics.


Hydrogen sulfide stimulates the catalytic activity of a heme-regulated phosphodiesterase from Escherichia coli (Ec DOS).
Ec DOS, a heme-regulated phosphodiesterase from Escherichia coli, is an oxygen sensor enzyme composed of a heme-bound O(2) sensor domain at the N-terminus and a catalytic domain at the C-terminus. The catalytic activity of Ec DOS is substantially enhanced with the formation of a Fe(II) heme-O(2) complex. The physiological importance of H(2)S as a fourth signaling gas molecule in addition to O(2), CO and NO is an emerging focus of research, since H(2)S participates in various physiological functions. In the present study, we showed that catalysis by Ec DOS is markedly increased by H(2)S under aerobic conditions. Absorption spectral findings suggest that SH(-)-modified heme iron complexes, such as Fe(III)-SH(-) and Fe(II)-O(2) complexes, represent the active species for H(2)S-induced catalysis. We further examined the role of Cys residues in H(2)S-induced catalysis using Cys→Ala mutant enzymes. Based on the collective data, we speculate that H(2)S-induced catalytic enhancement is facilitated by an admixture of Fe(III)-SH(-) and Fe(II)-O(2) complexes formed during catalysis and modification of specific Cys residue(s) in the catalytic domain.


Interleukins 1 and 6 as Main Mediators of Inflammation and Cancer.
The idea of a potential link between cancer and inflammation was first proposed by R. Virchow in the nineteenth century. However, clear evidence regarding a key role of inflammation in oncogenesis appeared only during the last decade. Now the tumor microenvironment is commonly considered as an obligatory and significant component of almost all types of cancer, and the cells infiltrating such microenvironment are a source of inflammatory cytokines. Such cytokines play a key role in regulating inflammation during both normal immune response and developing cancer. In this review, we explore the role of two inflammatory cytokines interleukin 1 and interleukin 6 in cancer development. These cytokines have pleiotropic effects on various cell types in the tumor microenvironment, particularly being able to regulate pro-oncogenic transcription factors NF-κB and STAT3. For this reason, such cytokines influence key parameters of oncogenesis, increasing cell resistance to apoptosis, proliferation of cancer cells, angiogenesis, invasion and malignancy as well as the ability of tumor cells to respond to anticancer therapy. Here we summarize novel experimental data regarding mechanisms underlying the interaction between chronic inflammation and malignant neoplasms.


Selective release of endogenous zinc from the hippocampal mossy fibers in situ.
The release of endogenous zinc was studied in the hippocampus of the anesthetized rat. Push-pull cannulae were bilaterally introduced in the hippocampus and zinc concentrations determined by atomic absorption spectrophotometry. We first studied the regional distribution of K+-evoked release of zinc. A 2 min (30 mM) K+ pulse produced a release of endogenous zinc, when the push-pull cannulae were located in the vicinity of the mossy fibers (CA3 or hilus) but not in other regions (including CA1, fimbria, molecular layer of the fascia dentata, thalamus etc...). In CA3 the maximal release was of 2000 ng/ml (200 times the levels of zinc present in the cerebrospinal fluid (CSF)). Destruction of the mossy fibers by a local unilateral injection of 1.5 micrograms of colchicine dissolved in 0.6 microliter of a saline solution, eliminated this release without affecting the release in the control (contralateral) side. Electrical stimulation of the perforant path at 1 Hz did not evoke a release of zinc. In contrast at 10 Hz this stimulation produced a burst of population spike and a significant release of zinc in the mossy fibers (and not in other regions of the hippocampus). These experiments provide direct evidence that zinc is selectively released from the mossy fibers.


Phytolectin nanoconjugates in combination with standard antifungals curb multi-species biofilms and virulence of vulvovaginal candidiasis (VVC) causing Candida albicans and non-albicans Candida.
Vulvovaginal candidiasis (VVC) is a commonly occurring yeast infection caused by Candida species in women. Among Candida species, C. albicans is the predominant member that causes vaginal candidiasis followed by Candida glabrata. Biofilm formation by Candida albicans on the vaginal mucosal tissue leads to VVC infection and is one of the factors for a commensal organism to get into virulent form leading to disease. In addition to that, morphological switching from yeast to hyphal form increases the risk of pathogenesis as it aids in tissue invasion. In this study, jacalin, a phytolectin complexed copper sulfide nanoparticles (NPs) have been explored to eradicate the mono and mixed species biofilms formed by fluconazole-resistant C. albicans and C. glabrata isolated from VVC patients. NPs along with standard antifungals like micafungin and amphotericin B have been evaluated to explore interaction behavior and we observed synergistic interactions between them. Microscopic techniques like light microscopy, phase contrast microscopy, scanning electron microscopy, confocal laser scanning microscopy were used to visualize the inhibition of biofilm by NPs and in synergistic combinations with standard antifungals. Real-time PCR analysis was carried out to study the expression pattern of the highly virulent genes which are responsible for yeast to hyphal switch, drug resistance and biofilm formation upon treatment with NPs in combination with standard antifungals. The current study shows that lectin-conjugated NPs with standard antifungals might be a different means to disrupt the mixed species population of Candida spp. that causes VVC. The present study focuses on exploiting the high biding affinity between the cell surface glycans present in Candida cells and the plant lectin, Jacalin. Jacalin serves as a 'Trojan Horse' wherein the lectin-coupled nanoparticles show a high efficacy when compared with the unconjugated nanoparticles. The present approach also improves the anti-biofilm activity of the antifungal drugs against drug-resistant Candida strains.


Retracted: Application of Unsupervised Migration Method Based on Deep Learning Model in Basketball Training.
[This retracts the article DOI: 10.1155/2022/6711331.].


A new SOBP-formation method by superposing specially shaped Bragg curves formed by a mini-ridge filter for spot scanning in proton beam therapy.
We propose a new spread-out Bragg peak (SOBP) formation method for low-energy regions of spot-scanning proton therapy in order to reduce the required number of energy layers while maintaining high dose uniformity, while maintaining the distal falloff as sharp as possible. We use only one specially shaped mini-ridge filter (MRF) to create new trapezoidal Bragg curves (TBCs) from very sharp pristine Bragg curves (PBCs) of low-energy proton beams. The TBC has three pre-designed dose regions of proximal, flat-top, and distal components. These components are designed to have nearly equal depth lengths and good linearity. Then, the required SOBP is formed by superposing the TBCs with the correct spacing and beam intensity weights. We then compare the performance of the TBC-based SOBPs with those formed by PBCs. The dose uniformities of the SOBP formed by the proposed method are kept within the design tolerance, and are equivalent to those of conventional SOBPs. The sharpness of the distal falloff is reasonably kept by the deepest TBC. The required number of energy layers is significantly reduced compared with that of conventional PBC-based SOBP. The proposed method enables shortening of the irradiation time of spot-scanning proton beam therapy in low-energy regions with a reduced number of energy layers. It can be realized by using only one specially shaped MRF, which can be easily installed at any facility.


Sympathetic sudomotor and vasoconstrictive neural function in patients with Parkinson's disease.
To evaluate sympathetic sudomotor and vasoconstrictive neural function in Parkinson's disease (PD), we simultaneously recorded sympathetic skin response (SSR) and skin blood flow (SVR; skin vasomotor reflex), as well as skin sympathetic nerve activity (SSNA) measured in peroneal nerves by microneurography, comparing 12 patients with idiopathic PD with 16 healthy controls. Resting SSNA frequency (8.8+/-4.3 bursts/min) was significantly lower in PD patients than in controls (p<0.01). Frequency increases in response to performing mental arithmetic were slightly smaller in PD patients than in controls. PD patients exhibited normal SSNA reflex latencies compared with controls. Although no significant relationship was found between resting SSNA frequency and disease duration or degree of disability, a significantly negative correlation between increases in SSNA with mental arithmetic and PD duration was observed. Occurrence of SSR and SVR following SSNA bursts induced by electrical stimuli was reduced in PD (p<0.05). In patients with PD, sympathetic sudomotor and vasoconstrictive neural function was decreased at rest, but SSNA reflex latencies in the legs were nearly normal. Since responses of peripheral target organs may be impaired, both central and peripheral factors may contribute to autonomic symptoms in PD.


The formation of gap and tight junctions between retinal pigment cells in cell cultures.
The reformation of the junctional complex of retinal pigment cells was studied after trypsin disaggregation and in vitro reaggregation. Control specimens show a zonula occludens (tight junction) with integrated gap junctions and very large macular gap junctions. Isolation after trypsination results in disaggregation of the large gap junctions and fragmentation of the tight junctions with disaggregation of their integrated gap junctions. After two to four days of incubation the restoration of the zonula occludens is complete. After approximately five days of incubation, large gap junctions are found with a patchy arrangement of particles similar to that seen in vivo.


Genetic alterations associated with 18F-fluorodeoxyglucose positron emission tomography/computed tomography in head and neck squamous cell carcinoma.
We investigated the relationship between genetic alterations and 18F-FDG PET/CT findings in head and neck squamous cell carcinoma (HNSC). Using mRNA-sequences of HNSC samples (480 patients) from the Cancer Genome Atlas (TCGA) portal, gene coexpression networks were constructed via a weighted correlation network analysis (WGCNA) algorithm, and their association with the tumor-to-blood signal ratio on 18F-FDG PET/CT data (21 patients) was explored. An elastic-net regression model was developed to estimate the PET tumor-to-blood ratio from the gene networks and to derive an FDG signature score (FDGSS). The FDGSS was evaluated with regard to clinical variables and general mutational profiles, as well as alterations to oncogenic signaling pathways. The FDGSS values differed across clinical stages (p = 0.027), HPV-status (p< 0.001), and molecular subtypes of HNSC (p< 0.001). Multivariate Cox regression demonstrated that FDGSS was an independent predictor for overall (p = 0.019) and progression-free survival (p = 0.024). FDGSS positively correlated with total mutation rate (p = 0.016), aneuploidy (p < 0.001), and somatic copy number alteration scores (p < 0.001). CDKN2A in the cell cycle pathway (q = 0.014) and the TP53 gene in the TP53 pathway (q = 0.005) showed significant differences between high and low FDGSS patients. FDGSS based on the gene coexpression network was associated with the mutational landscape of HNSC. 18F-FDG PET/CT is therefore a valuable tool for the in vivo imaging of these cancers, being able to visualize the glucose metabolism of the tumor and allow inferences to be made on the underlying genetic alterations in the tumor.


Glutamate-induced excitotoxicity in Parkinson's disease: The role of glial cells.
Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamate transmission efficiency depends on the correct functionality and expression of a plethora of receptors and transporters, located both on neurons and glial cells. Of note, glutamate reuptake by dedicated transporters prevents its accumulation at the synapse as well as non-physiological spillover. Indeed, extracellular glutamate increase causes aberrant synaptic signaling leading to neuronal excitotoxicity and death. Moreover, extrasynaptic glutamate diffusion is strongly associated with glia reaction and neuroinflammation. Glutamate-induced excitotoxicity is mainly linked to an impaired ability of glial cells to reuptake and respond to glutamate, then this is considered a common hallmark in many neurodegenerative diseases, including Parkinson's disease (PD). In this review, we discuss the function of astrocytes and microglia in glutamate homeostasis, focusing on how glial dysfunction causes glutamate-induced excitotoxicity leading to neurodegeneration in PD.


A dynamic model for intracellular calcium response in fibroblasts induced by electrical stimulation.
Regulation of intracellular calcium ion concentration ([Ca(2+)]in) in fibroblasts induced by exogenous electrical stimulation could be applied to control gene expressions selectively which in turn modulate the function of the fibroblasts. Regarding the mechanism for electric-field-induced Ca(2+) influx via voltage-gated Ca(2+) channels and/or stretch-activated cation channels in the fibroblasts, a dynamic mathematical model is proposed to quantify the [Ca(2+)]in dynamics in response to direct current or alternating current electric fields. Simulation results demonstrate that the changes in [Ca(2+)]in predicted by our dynamic model are consistent with the experimental data in the literature. The proposed dynamic model could provide not only more insights into the electric-field-induced intracellular Ca(2+) response but also a quantitative way to regulate the [Ca(2+)]in dynamics by controlling the external electrical stimulation.


A symbolic environment for visualizing activated foci in functional neuroimaging datasets.
This paper presents a symbolic visualization environment known as the Corner Cube environment, which was developed to facilitate rapid examination and comparison of activated foci defined by analyses of functional neuroimaging datasets. We have performed a comparative evaluation of this environment against maximum-intensity projection and 'gallery of slices' displays, and the results suggest that the Corner Cube environment has definite advantages over both conventional display techniques. We conclude that the Corner Cube is an effective tool for summarizing the spatial characteristics of activated foci within an easily understood visual context and is especially useful for displaying the similarities and differences in functional neuroimaging datasets.


The role of the anterior and midcingulate cortex in the neurobiology of functional neurologic disorder.
Functional neurologic disorder (FND)/conversion disorder is a prevalent and disabling condition at the intersection of neurology and psychiatry. Clinicians often report feeling ill-equipped treating patients with FND, perpetuated by a historically limited understanding of neurobiologic disease mechanisms. In this review, we summarize the neuroimaging literature across the spectrum of sensorimotor FND, including functional imaging studies during rest, sensorimotor performance, and emotional-processing tasks as well as structural magnetic resonance imaging findings. Particular attention is given to studies implicating the anterior and middle cingulate cortex and related salience network structures (insula, amygdala, and periaqueductal gray) in the neurobiology of FND. Neuroimaging studies identify cingulo-insular functional alterations during rest, motor performance, and emotion processing in FND populations. The literature also supports that patients with FND exhibit heightened amygdalar and periaqueductal gray reactivity to emotionally valenced stimuli, enhanced coupling between amygdalar and motor control areas, and increased amygdalar volumes. The structural neuroimaging literature also implicates cingulo-insular areas in the pathophysiology of FND, though these findings require replication and clarification. While more research is needed to fully elucidate the pathophysiology of FND, salience network alterations appear present in some FND populations and can be contextualized using biopsychosocial models for FND.


Compact electron spin resonance skin oximeter: Properties and initial clinical results.
Skin oxygen level is of significance for the diagnosis and treatment of many clinical problems, such as chronic wounds and diabetic foot ulcers. Furthermore, skin oxygen levels can be correlated to arterial oxygen partial pressure, thereby revealing potentially dangerous conditions such as hyperoxia (too much oxygen), which may occur in ventilated neonates. Traditionally, skin oxygen levels are measured using electrochemical methods and, more recently, also by fluorescence lifetime techniques. These approaches suffer from several drawbacks, rendering them suboptimal. The purpose of this work is to develop an electron spin resonance (ESR) -based method for monitoring oxygen partial pressure (pO2 ) in skin tissue. A compact sensor for pulsed ESR is designed and constructed. Our ESR-based method makes use of a unique exogenous paramagnetic spin probe that is placed on the skin in a special partially sealed sticker, and subsequently measuring its signal with the compact pulsed ESR sensor that includes a miniature magnet and a small S-band (~2.3 GHz) microwave resonator. The inverse of the spin-spin relaxation time (1/T2 ) measured by ESR is shown to be linearly correlated with pO2 levels. The sensor and its matching sticker were tested both in vitro and in vivo (with human subjects). Measured skin pO2 levels reached equilibrium after ~2-3 h and were found to be comparable to those measured by continuous-wave (CW) ESR using a large electromagnet. A compact pulsed ESR sensor with a matching paramagnetic sticker can be used for pO2 monitoring of the skin tissue, similar to large bulky CW ESR systems.


Echo-guided seldinger technique facilitates ascending aorta cannulation in type A aortic dissection.
The ascending aorta is the most simple and rapid arterial access for the establishment of antegrade systemic perfusion. In acute type A aortic dissection, prompt establishment of antegrade central perfusion, especially in unstable hemodynamic emergency operations, help to diminish organ malperfusion and to prevent retrograde embolism. The effectiveness as well as the safety of antegrade perfusion under ultrasonographic guidance through the dissected ascending aorta was evaluated for the repair of type A aortic dissection utilizing a new echo stabilizer. Ascending aortic cannulation was successfully performed in 64 consecutive patients, using the Seldinger technique, with the hands-free continuous-echo monitoring, utilizing a new stabilizer. Epiaortic 2-Dimensional and color Doppler imaging provided real-time monitoring for the placement and proper perfusion of ascending aorta cannulation. Ascending aorta can routinely provide a rapid and reliable route of antegrade central systemic perfusion in type A acute aortic dissection. The echo-guided stabilizer-assisted cannulation method can safely provide a rapid and reliable route for antegrade central perfusion during in type A dissections repair.


Author Response to Comment on: Conventional and Microwave Hydrothermal Synthesis and Application of Functional Materials: A Review.
We recently published an article "Conventional and Microwave Hydrothermal Synthesis and Application of Functional Materials: A Review" on Materials, and we are honored to receive a comment article from Jalouli et al. We will give a detailed explanation for the confusion of the mechanism of crystal nucleation and growth in the comment article.


Simultaneous Detection of Metalloprotease Activities in Complex Biological Samples Using the PrAMA (Proteolytic Activity Matrix Assay) Method.
Proteolytic Activity Matrix Analysis (PrAMA) is a method for simultaneously determining the activities of specific Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinases (ADAMs) in complex biological samples. In mixtures of unknown proteases, PrAMA infers selective metalloproteinase activities by using a panel of moderately specific FRET-based polypeptide protease substrates in parallel, typically monitored by a plate-reader in a 96-well format. Fluorescence measurements are then quantitatively compared to a standard table of catalytic efficiencies measured from purified mixtures of individual metalloproteinases and FRET substrates. Computational inference of specific activities is performed with an easily used Matlab program, which is provided herein. Thus, we describe PrAMA as a combined experimental and mathematical approach to determine real-time metalloproteinase activities, which has previously been applied to live-cell cultures, cellular lysates, cell culture supernatants, and body fluids from patients.


Quality, nutrient and sensory characteristics of aged meat from lambs supplemented with selenomethionine.
Selenium (Se) as a co-factor of antioxidant enzymes is metabolically essential for animals. Its presence in muscle can improve the oxidative stability of meat and is a desirable nutrient for consumers. A novel approach to Se supplementation for meat-producing livestock was demonstrated in a 95-day study of young lambs. DL-selenomethionine (SeMet) was administered by subcutaneous injection at day 0 (3-4 weeks of age) and again at day 54. A Control group (n = 9) received carrier only, whilst Medium and High groups (n = 10) received graded levels of Se. Physicochemical attributes of meat quality and sensory characteristics were measured at 1, 3, 14 and 42 days of ageing (vacuum packaged at -1.5 °C), followed by instrumental colour measurements after 7 days of simulated retail display. There were no significant interactions between SeMet treatment and ageing. Muscle pH, drip and cooking losses, initial display colour and sensory evaluations by trained and consumer panels were unaffected by treatment. Smaller changes in colour during display were observed for the Medium group compared to Control (P < 0.05). The shorter range of ageing times improved meat tenderness however extended ageing decreased colour stability. SeMet markedly increased Se concentrations in muscle, blood, kidney and liver (P < 0.05), resulting in Se enriched meat without appreciable changes in meat quality.


The African enigma: low prevalence of gastric atrophy, high prevalence of chronic inflammation in West African adults and children.
Helicobacter pylori infection is very common in Africa, yet peptic ulcer disease and gastric malignancy are rare. The aim of this study was to quantify mucosal responses to H. pylori in Gambian adults and children and to estimate the prevalence of antibodies to bacterial virulence factors (cagA and vacA) in a symptomatic population. Adults (mean 36 SD 12 years) with dyspepsia and children (mean 1.4 years SD 0.4 years) with malnutrition underwent gastroscopy with biopsy. Blood was simultaneously drawn for cagA and vacA antibody status. Histopathological scoring used the modified Sydney classification. Both adults (n = 45) and children (n = 37) mainly demonstrated chronic mild antral inflammation. Only 2/83 cases of focal atrophy (GA) and 4/83 cases of intestinal metaplasia (IM) were observed. Adults tended to demonstrate more frequent acute (AI) and chronic inflammation (CI) (38% compared with 18% and 85% compared with 72%, respectively). Sixty-seven percent of children were cagA IgG+ and 21% vacA IgG+ and 93% of adults were IgG cagA+ and 86% vacA+. There were no differences in mucosal responses between those who were cagA or vacA positive compared with those who were negative. Gambian adults and children mount a CI response to H. pylori but GA, IM and AI are uncommon. cagA and vacA are commonly expressed in Gambian strains of H. pylori. Further studies are needed in order to confirm that GA and IM are not late findings in old age.


Characteristics of patients attending for cognitive behavioural therapy at one UK specialist unit for dental phobia and outcomes of treatment.
To describe the characteristics of patients attending a psychologist-led cognitive behavioural therapy (CBT) service for individuals with dental phobia and the outcomes of treatment. Analysis of routinely collected assessment and outcome data from 130 patients attending a single secondary service providing CBT for dental phobia. The patients comprised 99 women and 31 men, with an average age of 39.9 years (SD 14.8). Approximately 77% of the patients scored at levels suggestive of dental phobia on the Modified Dental Anxiety Scale (MDAS). Fear of dental injections and the dental drill were the most common high scoring items on the MDAS. Ninety four percent of patients reported one or more impacts of their mouth, teeth and gums on their life using the OHIP-14. A minority of patients had co-morbid psychological conditions - 36.9% had high levels of general anxiety and 12.3% had clinically significant levels of depression. Suicidal ideation was reported by 12% of patients and four (3%) reported recent intent to commit suicide. Of all patients referred 79% went on to have dental treatment without sedation and 6% had their dental treatment under sedation. The average number of CBT appointments required before a patient received dental treatment without sedation was five. CBT offers an effective technique for helping dentally anxious patients receive treatment without sedation. Those interested in running such services should be cognizant of the moderately high level of co-morbid psychological conditions in this group.


Replication banding patterns in the spined loach, Cobitis taenia L. (Pisces, Cobitidae).
The chromosomal complement of Cobitis taenia was analysed by replication banding techniques to determine whether there were specific patterns that could allow distinction of the different chromosomes. The diploid chromosome number of 2n = 48 is diagnostic of this species. In vivo 5-bromodeoxyuridine (5-BrdU) incorporation induced highly reproducible replication bands. Most of the chromosome pairs were distinguishable on the base of their banding patterns. The karyotype, consisting of five pairs of metacentrics, nine pairs of submetacentrics and 10 pairs of subtelocentrics and acrocentrics, was confirmed. C-banding and replication banding patterns were compared, and heterochromatin was both early and later replicating. C-positive heterochromatin in centromeric regions was mainly early replicating, but that located in pericentromeric regions was late replicating. Most of the late-replicating regions found interstitially were C-band negative. The results obtained so far for combined chromosomal staining methods of C. taenia and other Cobitis fish species are discussed.