Amniotic fluid ionic concentration in response to chronic fetal vasopressin infusion.
Chronically prepared, third trimester fetal lambs were administered 72-h intravenous infusions of arginine vasopressin (AVP) (65 or 130 mU/kg h) or 0.9% saline. Saline infusion preceding the AVP infusion did not change amniotic fluid (AF) composition. During the AVP infusion, there were significant increases in amniotic fluid osmolality (278.8 +/- 4.9 to 302.1 +/- 4.5 mosm) and in sodium (122.7 +/- 3.3 to 135.3 +/- 3.6 meq/l) and potassium (9.7 +/- 2.6 to 13.8 +/- 1.3 meq/l) concentrations. Saline infusion after the AVP infusion resulted in return of AF osmolality, sodium, and potassium toward normal levels. Fetal plasma and amniotic fluid AVP levels measured by radioimmunoassay significantly increased during AVP infusion and decreased during the subsequent saline infusion. There were no changes in maternal or fetal plasma osmolality in response to AVP. These results suggest that fetal AVP released in response to intrauterine stress may alter the composition and osmolality of amniotic fluid in a reversible manner.


Dual-targeted nanoparticles with removing ROS inside and outside mitochondria for acute kidney injury treatment.
Mitochondrial oxidative stress and inflammation are the main pathological features of acute kidney injury (AKI). However, systemic toxicity of anti-inflammatory drugs and low bioavailability of antioxidants limit the treatment of AKI. Here, the lipid micelle nanosystem modified with l-serine was designed to improve treatment of AKI. The micelle kernels coating the antioxidant drug 4-carboxybutyl triphenylph-osphine bromide-modified curcumin (Cur-TPP) and quercetin (Que). In the cisplatin (CDDP)-induced AKI model, the nanosystem protected mitochondrial structure and improved renal function. Compared to mono-targeted group, the mitochondrial ROS content of renal tubular epithelial cells acting in the dual-target group decreased about 1.66-fold in vitro, serum creatinine (Scr) and urea nitrogen (BUN) levels were reduced by 1.5 and 1.2 mmol/L in vivo, respectively. Mechanistic studies indicated that the nanosystem inhibited the inflammatory response by interfering with the NF-κB and Nrf2 pathways. This study provides an efficient and low-toxicity strategy for AKI therapy.


From congenital microcephaly to adult onset cerebellar ataxia: Distinct and overlapping phenotypes in patients with PNKP gene mutations.
Pathogenic variants in polynucleotide kinase 3'-phosphatase (PNKP) gene have been associated with two distinct clinical presentations: autosomal recessive microcephaly, seizures, and developmental delay (MCSZ; MIM 613402) and ataxia with oculomotor apraxia type 4 (AOA4; MIM 616267). More than 40 patients have been reported so far, and their clinical presentations revealed a continuum phenotypic spectrum ranging from congenital microcephaly and early-onset intractable seizures, to adult onset slowly progressive sensory-motor neuropathy and cerebellar ataxia. We describe three unrelated Italian patients with different phenotypes and novel or recurrent pathogenic variants in PNKP gene. Patient 1, homozygous for the recurrent frameshift variant (p.Thr424Glyfs*49), had an early-onset MCSZ phenotype. Late in the disease progression, cerebellar ataxia and peripheral neuropathy were recognized. Patient 2, homozygous for a frameshift variant (p.Ala429Thrfs*42), presented a phenotype partially consistent with MCSZ including microcephaly and developmental delay, but without seizures. Patient 3 is one of the oldest patients described to date and presented polyneuropathy, and cerebellar signs. Biochemical tests showed abnormalities of cholesterol, albumin, or alpha-fetoprotein plasma levels. The clinical presentation of our patients encompassed early-to-adult-onset manifestations. For these cases, the long clinical follow-up allowed an in-depth phenotypic characterization and a better delineation of the natural history of patients carrying PNKP pathogenic variants.


Red cell membrane and cation deficiency in Rh null syndrome.
A 52-yr-old multiparous white female was found to have Rh null blood type. She had macrocytic anemia, with reticulocytosis (15%-20%), of long duration. Although stomatocytes in peripheral blood were numerous and osmotic fragility was increased, suggesting increased cell water, the RBC cation content, and thus cell water, was decreased. Cell dehydration was confirmed by an increased proportion of high density RBC on Stractan density gradients. The deformability of RBC from four gradient subpopulations was measured in the ektacytometer as a function of suspending medium osmolality. Analysis of these measurements showed an abnormal reduction in cell surface area with increasing cell density, thus explaining the increased osmotic fragility of whole blood. This was confirmed by a density-dependent reduction in cell cholesterol content, suggesting membrane instability in vivo. Rh null subpopulations showed a twofold increase in both ouabain-sensitive and -insensitive Na-K ATPase activity and 86Rb transport, even in the dense fraction with the fewest reticulocytes. No membrane protein or glycoprotein abnormality was detected by SDS-PAGE. The associated deficiencies of both membrane surface area and cation content in Rh null cells, as well as increased Na-K pump activity, suggest a pleiotropic functional interrelationship among Rh antigen, membrane stability, and cation regulation.


Measurement of ventricular function by ECG gating during atrial fibrillation.
The assumptions necessary to perform ECG-gated cardiac studies are seemingly not valid for patients in atrial fibrillation (AF). To evaluate the effect of AF on equilibrium gated scintigraphy, beat-by-beat measurements of left-ventricular function were made on seven subjects in AF (mean heart rate 64 bpm), using a high-efficiency nonimaging detector. The parameters evaluated were ejection fraction (EF), time to end-systole (TES), peak rates of ejection and filling (PER,PFR), and their times of occurrence (TPER,TPFR). By averaging together single-beat values of EF, PER, etc., it was possible to determine the true mean values of these parameters. The single-beat mean values were compared with the corresponding parameters calculated from one ECG-gated time-activity curve (TAC) obtained by superimposing all the single-beat TACs irrespective of their length. For this population with slow heart rates, we find that the values for EF, etc., produced from ECG-gated time-activity curves, are very similar to those obtained from the single-beat data. Thus use of ECG gating at low heart rates may allow reliable estimation of average cardiac function even in subjects with AF.


Quality of life of rural menopausal women in response to a customized exercise programme.
This paper reports a study examining the effects of physical exercise on the quality of life of menopausal women. People who perform no type of physical activity have poorer physical and mental health. Despite the well-documented benefits of exercise, ageing women remain largely sedentary, and interventions designed to help them to maintain exercise programmes may prove particularly valuable. Measures should focus on increasing women's confidence so that they can overcome barriers to exercise. Conflicting results have been reported in intervention studies to promote exercise in postmenopausal women. Forty-eight menopausal women aged 55-72 years were recruited at a primary care centre as voluntary participants in a quasi-experimental study. They were randomly assigned to one of two groups: control (n = 24) and experimental (n = 24). The experimental group participated in a 12-month programme of cardiorespiratory, stretching, muscle-strengthening and relaxation exercises carried out during two fully supervised exercise sessions per week (total of 3 hours weekly). Health-related quality of life was assessed by using the Quality of Life Profile for Chronically Ill Patients, a generic questionnaire widely used in epidemiological and clinical studies to measure well-being and function, incorporating as an optional module the Kupperman Index of Menopausal Symptomatology. There was a statistically significant improvement in the health-related quality of life of the experimental group, whereas the health-related quality of life of the control group significantly worsened. Menopausal symptoms also significantly improved in the experimental group and significantly worsened in the control group over the 12-month study period. A customized exercise programme is valuable for improving the health-related quality of life of menopausal women.


Evaluation of the Quadrox-I neonatal oxygenator with an integrated arterial filter.
Cardiopulmonary bypass (CPB) can be a potential cause of morbidity in patients for several reasons, including significantly higher gaseous microemboli (GME) formation than extracorporeal life support (ECLS) and physiological circulation, diverted blood flow from the patient via an open purge line of the arterial filter, and pressure drop across the oxygenator that is used in the circuit. Using a combined oxygenator and arterial filter may minimize these harmful factors and can effectively reduce the chances for postoperative morbidity. This study investigated the new QUADROX-i Neonatal Oxygenator (D-72145, Maquet, Hirrlingen, Germany) with an integrated arterial filter in terms of the hemodynamic properties and ability to clear GME in response to hypothermic versus normothermic conditions, open versus closed arterial filter purge line, and varying flow rates in a simulated CPB circuit identical to that of the clinical setting. A flow probe, pressure transducer, and Emboli Detection and Classification (EDAC) quantifier transducer were placed upstream and downstream to the oxygenator to measure changes in each parameter. The circuit was primed with fresh human blood with an hematocrit (Hct) of 26% diluted with Ringer's lactate solution. Five milliliters of air were injected proximal to the venous cardiotomy reservoir, under non-pulsatile perfusion, with flow rates of 500 ml/min, 750 ml/min, and 1000 ml/min. A total of 8 air bolus injections were made at each individual set of conditions for a total of 96 injections. Results showed that the QUADROX-i Neonatal Oxygenator with an integrated filter has excellent hemodynamic properties with extremely low pressure drops and blood flow diverted from the patient, as well as high rates of GME capturing. The arterial filter purge line has a significant effect on the degree of blood flow diverted from the patient (p < 0.001), but does not affect pressure drop across the oxygenator.


AUTONOMY AND RELATEDNESS IN MOTHER-TEEN INTERACTIONS AS PREDICTORS OF INVOLVEMENT IN ADOLESCENT DATING AGGRESSION.
This multi-method, longitudinal study examines the negotiation of autonomy and relatedness between teens and their mothers as etiologic predictors of perpetration and victimization of dating aggression two years later. Observations of 88 mid-adolescents and their mothers discussing a topic of disagreement were coded for each individual's demonstrations of autonomy and relatedness using a validated coding system. Adolescents self-reported on perpetration and victimization of physical and psychological dating aggression two years later. We hypothesized that mother's and adolescents' behaviors supporting autonomy and relatedness would longitudinally predict lower reporting of dating aggression, and that their behaviors inhibiting autonomy and relatedness would predict higher reporting of dating aggression. Hypotheses were not supported; main findings were characterized by interactions of sex and risk status with autonomy. Maternal behaviors supporting autonomy predicted higher reports of perpetration and victimization of physical dating aggression for girls, but not for boys. Adolescent behaviors supporting autonomy predicted higher reports of perpetration of physical dating aggression for high-risk adolescents, but not for low-risk adolescents. Results indicate that autonomy is a dynamic developmental process, operating differently as a function of social contexts in predicting dating aggression. Examination of these and other developmental processes within parent-child relationships is important in predicting dating aggression, but may depend on social context.


Tungsten(VI)-Copper(I)-Sulfur Cluster-Supported Metal-Organic Frameworks Bridged by in Situ Click-Formed Tetrazolate Ligands.
Six analogous two-dimensional (2D) [Tp*WS3Cu3]-based (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate) networks, namely, {[(Tp*WS3Cu3)2L3](μ3-N3)}n (2: L = 5-methyltetrazolate (Mtta); 3a: L = 5-ethyltetrazolate (Etta)) and {[(Tp*WS3Cu3)2L3]BF4}n (3b: L = Etta; 4: L = 5-propyltetrazolate (Ptta); 5: L = 5-butyltetrazolate (Btta); 6: L = 5-pentyltetrazolate (Petta)) were synthesized by reactions of [Et4N][Tp*WS3] (1), [Cu(CH3CN)4]BF4, NaN3, and NH4BF4 in different nitrile solvents (CH3(CH2)nCN, n = 0, 1, 2, 3, and 4) under solvothermal conditions. In the structures of 2-6, each alkyl tetrazolate L as a bridging ligand was generated in situ from the "click" reaction between azide and nitrile. These 2D (6,3) networks support two types of voids wherein the pendant alkyl groups are accommodated. A tetrahedron cage-like cluster [Tp*W(μ3-S)3(μ3-S')Cu3]4 (7) was also formed in some of the above reactions and can be readily separated by solvent extraction. The proportion of 7 increased with the elongation of the alkyl chains and finally became the exclusive product when heptylnitrile was employed. Further use of CuCN as a surrogate for [Cu(CH3CN)4]BF4 with the aim of introducing additional CN bridges into the network led us to isolate a tetrazolate-free compound, {[Et4N]{(Tp*WS3Cu3)[Cu2(CN)4.5]}2·2PhCH2CN}n (8·2PhCH2CN), a unique 2D network that features {(Tp*WS3Cu3)[Cu2(CN)5]}22-, {(Tp*WS3Cu3)3[Cu3(CN)7]2[Cu(CN)3]}4-, and {(Tp*WS3Cu3)[Cu4(CN)9]}26- ring subunits. Compounds 5-8 are soluble in DMF and exhibit a reverse saturable absorption and self-focusing third-order nonlinear optical (NLO) effect at 532 nm with hyperpolarizability γ values in the range of 4.43 × 10-30 to 5.40 × 10-30 esu, which are 400-500 times larger than that of their precursor 1. The results provide an interesting insight into the synergetic synthetic strategy related to the assembly of the [Tp*WS3Cu3]2+ cluster core, the "click" formation of the tetrazolate ligands, and the construction of the [Tp*WS3Cu3]2+ cluster-based 2D networks.


Sympathetic nervous system and adrenal medullary responses to ischemic injury in mice.
Acute, severe injury is frequently attended by hypotension, hypothermia, and decreased metabolic rate despite elevated urine and plasma catecholamine levels. Because the combination of sympathetic nervous system (SNS) suppression and adrenal medullary stimulation documented in several other situations could account for these observations, SNS and adrenal medullary function were examined independently in mice in the hindlimb ischemia model of acute injury. SNS activity was assessed by the measurement of [3H]norepinephrine (NE) turnover in heart and adrenal medullary secretion by depletion of adrenal catecholamine content. In nine separate experiments during the first 10 h after termination of a 2.5-h period of hindlimb ischemia, cardiac NE turnover was reduced an average of 23% (P less than 0.05) in injured mice. At the same time, adrenal catecholamine content fell 37% (P less than 0.05) in injured animals but not in controls. In contrast to the acute reaction, SNS activity in mice surviving 3 days was 59% greater than in controls. Thus, the reduction in NE turnover and depletion of adrenal catecholamine content suggest that SNS suppression and adrenal medullary stimulation constitute the acute sympathoadrenal response in this model of severe injury. Because survival within the first 24 h after injury was decreased in adrenalectomized mice despite glucocorticoid treatment, adrenal medullary catecholamines may contribute to survival in severely injured animals. Furthermore, because the SNS plays an important role in the regulation of blood pressure and heat production, the diminution in SNS activity in the hours after injury may contribute to posttraumatic hypotension and hypometabolism.


A "One-Health" approach for diagnosis and molecular characterization of SARS-CoV-2 in Italy.
The current pandemic is caused by a novel coronavirus (CoV) called SARS-CoV-2 (species Severe acute respiratory syndrome-related coronavirus, subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae). In Italy, up to the 2nd of April 2020, overall 139,422 confirmed cases and 17,669 deaths have been notified, while 26,491 people have recovered. Besides the overloading of hospitals, another issue to face was the capacity to perform thousands of tests per day. In this perspective, to support the National Health Care System and to minimize the impact of this rapidly spreading virus, the Italian Ministry of Health involved the Istituti Zooprofilattici Sperimentali (IZSs), Veterinary Public Health Institutes, in the diagnosis of SARS-CoV-2 by testing human samples. The Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise is currently testing more than 600 samples per day and performing whole genome sequencing from positive samples. Sequence analysis of these samples suggested that different viral variants may be circulating in Italy, and so in Abruzzo region. CoVs, and related diseases, are well known to veterinarians since decades. The experience that veterinarians operating within the Public Health system gained in the control and characterization of previous health issues of livestock and poultry including avian flu, bluetongue, foot and mouth disease, responsible for huge economic losses, is certainly of great help to minimize the impact of this global crisis.


Prevalence of hearing loss and health vulnerability in children aged 25 to 36 months: an analysis of spatial distribution.
To analyze the association between hearing loss and health vulnerability in children aged 25 to 36 months. Analytical observational cross-sectional study conducted through child hearing screening in nine day-care centers. The screening consisted of anamnesis, otoscopy, tympanometry, transient otoacoustic emissions, and pure tone audiometry. For each exam performed, the 'pass' and 'fail' criteria were established. The children's residential addresses were georeferenced and a choropleth map of the spatial distribution was built, considering the Health Vulnerability Index (HVI). The analysis of the association between the HVI and the variables sex, auditory assessment, and region area of the household was performed using Pearson's Chi-square and Fisher's Exact tests. Ninety-five children of both sexes were evaluated, of which 44.7% presented alterations in at least one of the exams performed, being referred for otorhinolaryngological evaluation and subsequent auditory assessment. Of the observed changes, 36.9% occurred in the tympanometry and 7.8% in the transient otoacoustic emissions. Among children referred for reassessment, 9.7% were diagnosed with conductive hearing loss, 13.6% results within normal limits and 21.4% did not attend for assessment. Of the children who presented the final diagnosis of conductive hearing loss (9.7%), 1.9% were classified as low-risk HVI and 6.8% as medium-risk HVI. There was statistical significance between HVI and the child's place of residence. The association between hearing loss and HIV was not statistically significant; however, it was possible to observe that 77.7% of the children with hearing loss resided in sectors with medium- risk HIV.


Evidence relating sodium intake to blood pressure and CVD.
Sodium is an essential nutrient, mostly ingested as salt (sodium chloride). Average sodium intake ranges from 3 to 6 g per day (7.5-15 g/day of salt) in most countries, with regional variations. Increasing levels of sodium intake have a positive association with higher blood pressure. Randomized controlled trials report a reduction in blood pressure with reducing sodium intake from moderate to low levels, which is the evidence that forms the basis for international guidelines recommending all people consume less than 2.0 g of sodium per day. However, no randomized trials have demonstrated that reducing sodium leads to a reduction in cardiovascular disease (CVD). In their absence, the next option is to examine the association between sodium consumption and CVD in prospective cohort studies. Several recent prospective cohort studies have indicated that while high intake of sodium (>6 g/d) is associated with higher risk of CVD compared to those with moderate intake (3 to 5 g/d), lower intake (<3 g/day) is also associated with a higher risk (despite lower blood pressure levels). However, most of these studies were conducted in populations at increased risk of cardiovascular disease. Current epidemiologic evidence supports that an optimal level of sodium intake is in the range of about 3-5 g/day, as this range is associated with lowest risk of CVD in prospective cohort studies. Randomized controlled trials, comparing the effect of low sodium intake to moderate intake on incidence of cardiovascular events and mortality, are required to truly define optimal intake range.


Microtubules as platforms for assaying actin polymerization in vivo.
The actin cytoskeleton is continuously remodeled through cycles of actin filament assembly and disassembly. Filaments are born through nucleation and shaped into supramolecular structures with various essential functions. These range from contractile and protrusive assemblies in muscle and non-muscle cells to actin filament comets propelling vesicles or pathogens through the cytosol. Although nucleation has been extensively studied using purified proteins in vitro, dissection of the process in cells is complicated by the abundance and molecular complexity of actin filament arrays. We here describe the ectopic nucleation of actin filaments on the surface of microtubules, free of endogenous actin and interfering membrane or lipid. All major mechanisms of actin filament nucleation were recapitulated, including filament assembly induced by Arp2/3 complex, formin and Spir. This novel approach allows systematic dissection of actin nucleation in the cytosol of live cells, its genetic re-engineering as well as screening for new modifiers of the process.


[Functional characteristic and molecular topology of voltage independent sodium channels].
The channel proteins so far known are transmembrane oligomers arranged in a manner that the polar residues are lining the central ion-conducting hydrophilic pore. In the last decade, electrophysiology and molecular biology studies revealed the principal similarity in the functional properties and membrane topology within a large family of sodium-conducting channels. Amiloride-sensitive channels are expressed in the apical membranes of renal epithelia. Moreover, in different mammalian cells non-voltage-gated sodium-selective channels have been recently found. According to molecular cloning of the respective DNAs and amino acid sequence analysis, epithelial channel subunits, degenerins and some other channel proteins display a significant homology in the regions forming two presumable transmembrane domains. This paper reviews some relevant data and current opinions of the superfamily of sodium-conducting cation channels.


Generation and analysis of 3D cell culture models for drug discovery.
Successful preclinical drug testing relies in part on data generated using in vitro cell culture models that recapitulate the structure and function of tumours and other tissues in vivo. The growing evidence that 3D cell models can more accurately predict the efficacy of drug responses compared to traditionally utilised 2D cell culture systems has led to continuous scientific and technological advances that enable better physiologically representative in vitro modelling of in vivo tissues. This review will provide an overview of the utility of current 3D cell models from a drug screening perspective and explore the future of 3D cell models for drug discovery applications.


The utility of Kohlberg's theory of moral development among adult probationers in a restitution field setting.
Probationers ordered to pay restitution were classified by Kohlberg's Stages of Moral Development in order to (a) identify background correlates of moral development; (b) explore the relation between moral development and restitution compliance; and (c) differentially identify facilitating circumstances of restitution. The research was conducted in Albuquerque, New Mexico, from 1978 to 1980. Sixty-three probationers were interviewed and classified by moral development, I-level, and by ratings on relevant personality dimensions. Six-month follow-up data were collected from probation records. The results revealed significant relationships (p less than .05) between moral development and ethnicity, education, occupation, income, prior fines, weapons possession, knowing the victim, I-level, responsibility, and empathy. In addition, high-maturity offenders were more likely to reimburse their victims than were low-maturity offenders. Finally, multivariate analysis revealed numerous circumstances of restitution that differentially impacted upon offenders' compliance with the terms of restitution.


Testosterone-induced abrogation of self-healing of Plasmodium chabaudi malaria in B10 mice: mediation by spleen cells.
This study investigates the suppressive effect of testosterone (Te) on the self-healing of Plasmodium chabaudi malaria in female mice of the strain C57BL/10, and, in particular, the possible role of spleen cells in mediating this Te effect. Our data show the following. (i) About 80% of B10 mice infected with 10(6) P. chabaudi-infected erythrocytes are capable of self-healing the infections. This capability is progressively impaired and finally abrogated after pretreating the B10 mice with Te for 3 weeks. (ii) The spleen is Te responsive. This becomes evident in a reduction of total spleen cells from 1.05 x 10(8) to 0.54 x 10(8) on average after Te treatment for 3 weeks. Moreover, Te treatment causes an increase in the relative proportion of CD8+ cells by about 4% and a decrease of Ig+ cells by about 4.5%, as revealed by flow cytometry. (iii) Spleen cells mediate the suppressive Te effect as revealed by adoptive transfer experiments. The percentage of self-healing mice dramatically decreases to about 8% when they receive, just prior to infection, nucleated spleen cells isolated from mice treated with Te for 3 weeks. This suppressive effect can be transferred by T cells in particular but also by non-T cells, though to a lesser extent. (iv) The adoptively transferred cells mediate their suppressive effect on self-healing only if the recipient mice receive Te during infection. Our data suggest that spleen cells become functionally changed by the Te treatment for 3 weeks. Particularly T cells, but also non-T cells, gain P. chabaudi-specific suppressive activities, and the cells require a Te-induced factor(s) to mediate these activities.


Colour vision of the foraging swallowtail butterfly papilio xuthus
This paper demonstrates that foraging summer-form females of the Japanese yellow swallowtail butterfly Papilio xuthus have colour vision. The butterflies were trained to feed on sucrose solution placed on a disk of a particular colour in a cage set in the laboratory. After a few such training runs, a butterfly was presented with the training colour randomly positioned within an array of disks of other colours, but with no sucrose solution. The results indicate that the butterflies learn rapidly to select the training colour reliably among different colours. The training colour was also correctly selected when it was covered with neutral density filters to reduce its brightness, or even when the colour was presented together with disks of a variety of shades of grey. These results demonstrate convincingly, for the first time, that a butterfly has true colour vision.


Clinicopathlogic and immunohistochemical characteristics of triple negative invasive lobular carcinoma.
Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts. Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC. Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs. TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.


Facial palsy in Heerfordt's syndrome: electrophysiological localization of the lesion.
Heerfordt's syndrome is characterized by fever, uveitis, swelling of the parotid gland, and facial nerve palsy and represents a variety of neurosarcoidosis. Since the first description of the syndrome, discussion about the lesion site has been controversial and has included the assumption of direct nerve compression by parotid gland swelling or a lesion within the facial canal in light of observations of accompanying taste disturbance. We report on a 26-year-old man with typical Heerfordt's syndrome who developed bilateral facial nerve palsy. Electrical and magnetic stimulation of the whole facial motor path provided strong evidence for a pathological process that: (i) began in the cerebellopontine angle; (ii) spread distally into the facial canal; and (iii) could be characterized by proximal demyelination. The patient recovered completely within 6 weeks under immunosuppressive therapy with steroids.


Effect of preoperative estrogen on complications after proximal hypospadias repair: A randomized controlled trial.
Proximal hypospadias repair has many postoperative complications such as urethrocutaneous fistulae, wound dehiscence, and urethral stricture. The beneficial effect of estrogen to promote wound healing has been known. We designed a study to determine whether preoperative stimulation of tissue with estrogen can reduce the postoperative complications associated with wound healing in patients undergoing hypospadias repair. Patients with proximal hypospadias requiring two-stage repairs (chordee correction followed by urethral tubularization) were randomized to estrogen and control groups before the second stage of surgery. In the former, topical estrogen cream (0.5 mg of estriol) was applied to the ventral penis for a month, whereas normal saline gel was applied to the latter; the urethroplasty was carried out thereafter. Patients were followed up for complications. There were 29 patients in the estrogen group and 31 in the placebo group after the exclusion criteria were met. There was no significant difference in the overall postoperative complications between the estrogen group (44.8%) and the placebo group (51.6%). The occurrence of urethrocutaneous fistula (37.9% vs. 51.6%) and dehiscence (41.4% vs. 45.2%) was not significantly different between the estrogen and placebo groups. Neourethral stricture occurred in four patients in the estrogen group, while none of the patients in the placebo group developed stricture. The preoperative application of topical estrogen cream to the ventral penis failed to demonstrate any significant effect on wound healing and complications.


Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells.
Clinically significant elevations in the expression of manganese superoxide dismutase (Sod2) are associated with an increased frequency of tumor invasion and metastasis in certain cancers. The aim of this study was to examine whether increases in Sod2 activity modulate the migratory potential of tumor cells, contributing to their enhanced metastatic behavior. Overexpression of Sod2 in HT-1080 fibrosarcoma cells significantly enhanced their migration 2-fold in a wound healing assay and their invasive potential 3-fold in a transwell invasion assay. Severity of invasion was directly correlated to Sod2 expression levels and this invasive phenotype was similarly observed in 253J bladder tumor cells, in which Sod expression resulted in a 3-fold increase in invasion compared with controls. Further, migration and invasion of the Sod2-expressing cells was inhibited following overexpression of catalase, indicating that the promigratory/invasive phenotype of Sod2-expressing cells is H(2)O(2) dependent. Sod2 overexpression was associated with a loss of vinculin-positive focal adhesions that were recovered in cells coexpressing catalase. Tail vein injections of Sod2-GFP-expressing HT-1080 cells in NCR nude mice led to the development of pulmonary metastatic nodules displaying high Sod2-GFP expression. Isolated tumors were shown to retain high Sod2 activity in culture and elevated levels of the matrix degrading protein matrix metalloproteinase-1, and a promigratory phenotype was observed in a population of cells growing out from the tumor nodule. These findings suggest that the association between increased Sod2 activity and poor prognosis in cancer can be attributed to alterations in their migratory and invasive capacity.


Iron sulfate and feed pelleting to detoxify free gossypol in cottonseed diets for dairy cattle.
Thirty-two lactating cows were fed ad libitum diets with 1) 18.7% soybean meal, 2) diet 1 plus 500 ppm supplemental Fe from FeSO4.H2O, 3) 15% whole cottonseed, or 4) diet 3 plus 500 ppm Fe from FeSO4.H2O. Dry matter intakes were similar except for cows fed diet 2, which was lower. Cows fed whole cottonseed diets ingested 23 g/d of free gossypol per cow. Free gossypol apparently excreted was lower than its intake. Iron excretion was similar to Fe intake. Blood metabolites and productive performance did not differ among the diet groups. No signs of gossypol toxicity were observed. Twelve neonatal Holstein male calves were fed a commercial milk replacer for 4 wk, then were allowed ad libitum access to diets with 1) 27% soybean meal, 2) 50% whole cottonseed, or 3) diet 2 plus 500 ppm Fe from FeSO4.H2O. Dry matter intakes were similar but slightly lower for calves fed diet 3. Daily individual intakes of free gossypol from diets 2 and 3 were 2 g, which was lower than the expected 4 g due to an apparent effect of pelleting. Blood metabolites did not differ among the groups, and calves averaged about .6 kg of daily gain on these diets. A follow-up study showed that pelleting reduced free gossypol by as much as 70% in whole cottonseed and by 48% in cottonseed meal. Pelleting represents a mechanism to decrease the toxicity of gossypol in cottonseed products.


Equine alternative pathway activation by unsensitized rabbit red blood cells.
The equine alternative complement pathway has been partially characterized and compared to the equine classical activation pathway. A dose-dependent lysis of RbRBC was observed with peak lytic values noted within 10 minutes at 37 degrees C when rabbit red blood cells (RbRBC) were used as an alternative pathway activator. Sheep red blood cells (SRBC) sensitized with rabbit hemolysin or partially purified equine IgM antibodies were equally sensitive to lysis. Dilution of the commercial hemolysin by 1/5 reduced lysis from 90% to 38% in the presence of constant cell numbers. Hemolysis of SRBC peaked at 10 minutes and the majority of lysis occurred within 10 minutes. Dilution of equine sera by as little as 1/5 decreased hemolytic activity for SRBC to 21.5% from greater than 90% with undiluted sera. The alternative pathway protein, equine factor B, was tested using RbRBC and monitored by its differential susceptibility to heat treatment at 50 degrees C. This treatment led to almost complete inactivation after a 15-minute incubation. An apparent heat-dependent decay of certain classical pathway components was also observed after 50 degrees C treatment. This sensitivity was indicated by a reduction in the lytic activity for sensitized SRBC. Treatment for 15 minutes at 56 degrees C with either RbRBC or SRBC was sufficient to abolish hemolytic activity in all equine sera tested. Chelation of cations with 0.04 M EDTA blocked expression of alternative and classical pathway activation; however, chelation of Ca++ ions with 10 mM EGTA containing 1 mM Mg++ ions permitted lysis of the RbRBC but not the SRBC. A dose-related Mg++-ion dependence for RbRBC hemolytic activity was observed as the concentration of Mg++ was increased to 1.0 mM. In addition, our results obtained with pre-colostral foal serum strongly suggest that natural antibody to RbRBC was of little importance in the lysis observed with these cells. These results also show that the equine alternative pathway activation may require Ca++ ions. If Ca++ ions are required, the equine alternative pathway is quite different from any other mammalian complement system so far described. Our results suggest that the alternative pathway of activation is of major importance in the equine complement system. Confirmation of this hypothesis requires both purification of the components involved as well as further characterization.


Attenuation by sphingosine-1-phosphate of rat microvessel acute permeability response to bradykinin is rapidly reversible.
To evaluate the hypothesis that sphingosine-1-phosphate (S1P) and cAMP attenuate increased permeability of individually perfused mesenteric microvessels through a common Rac1-dependent pathway, we measured the attenuation of the peak hydraulic conductivity (L(p)) in response to the inflammatory agent bradykinin (BK) by either S1P or cAMP. We varied the extent of exposure to each agent (test) and measured the ratio L(p)(test)/L(p)(BK alone) for each vessel (anesthetized rats). S1P (1 μM) added at the same time as BK (concurrent, no pretreatment) was as effective to attenuate the response to BK (L(p) ratio: 0.14 ± 0.05; n = 5) as concurrent plus pretreatment with S1P for 30 min (L(p) ratio: 0.26 ± 0.06; n = 11). The same pretreatment with S1P, but with no concurrent S1P, caused no inhibition of the BK response (L(p) ratio 1.07 ± 0.11; n = 8). The rapid on and off action of S1P demonstrated by these results was in contrast to cAMP-dependent changes induced by rolipram and forskolin (RF), which developed more slowly, lasted longer, and resulted in partial inhibition when given either as pretreatment or concurrent with BK. In cultured endothelium, there was no Rac activation or peripheral cortactin localization at 1 min with RF, but cortactin localization and Rac activation were maximal at 1 min with S1P. When S1P was removed, Rac activation returned to control within 2 min. Because of such differing time courses, S1P and cAMP are unlikely to act through fully common effector mechanisms.


Enabling occupation at the end of life: A literature review.
Occupation, or meaningful activity, can contribute to the well-being and quality of life of all individuals. It is thus a logical tautology that occupation should be enabled for those at the end of life. Our present review examines current provision of these processes by Occupational Therapist, who can be much-valued members of multidisciplinary palliative care teams. Following a literature search and critical selection, 10 global papers were identified examining occupation and occupational therapy at the end of life in the acute, hospice, and community environments. Universally, there appeared to be a dearth of therapists working in end-of-life care. Provision of palliative care in hospitals was found to be compensatory or rehabilitative. Hospice therapy emerged as pleasingly occupational, though the number of hospice places was disappointingly few. Community literature was sparse, so it proved challenging to draw definitive conclusions. Promising research refracted light on occupation at home; however, it also revealed stretched domiciliary services, where clients are not well informed about the potential scope of occupational therapy. A "good death" involving a quality end-of-life experience is the foundational goal overarching all therapy and medicine in the provision of palliative care. Arguably, an occupation-focused approach provided by therapists meets client needs to enable meaningful experiences in the limited time left to them. Current occupational therapy practice environments are not necessarily achieving these goals in commensurate fashion. There is a need to promote the role of occupational therapy and circumscribe what therapists can offer. Further research is necessitated across all environments and future funding for therapist positions in palliative teams. End-of-life care can be complex and challenging; however, therapists can facilitate fulfillment of client-centered occupational goals. In engaging with personally constructed nuances of meaning, quality of life can be improved in those deserving of a significant and emotionally rich daily existence during their final days.


The structures of the carbohydrate moieties of the alpha subunit of human chorionic gonadotrophin.
The alpha subunit of human chorionic gonadotrophin was reduced with dithiothreitol followed by carboxymethylation with iodoacetic acid. The modified glycoprotein was hydrolysed with trypsin to give various peptides, the identities of which were established, and glycopeptides. The glycopeptides were separated by gel filtration and ion-exchange chromatography; they were subjected to component analysis and were found to represent the two carbohydrate moieties in the parent glycoprotein. Sequential removal with glycoside hydrolases of monosaccharide units from the glycopeptides demonstrated (1) that galactose, mannose, glucosamine (2-amino-2-deoxyglucose) and neuraminic acid (5-amino-3,5-dideoxy-glycero-galacto-2-nonulosonic acid) residues possess the D configurations, (2) that the glucosamine units are N-acetylated and (3) the order of the monosaccharide units in the chain, the neuraminic acid units being furthest from the peptide backbone of the subunit and substituting the D-galactose units. Methylation analysis of the glycopeptides by adaptation of the Hakomori technique demonstrated that: (4) D-galactose, D-mannose and N-acetylglucosamine (2-acetamido-2-deoxy-D-glucose) units exist in the pyranose forms; (5) the D-galactopyranose units are linked in the 1 and 6 positions; (6) the D-mannopyranose units exist in several forms, one in a terminal non-reducing position, one as 1,2-linked residues and some as 1,6-linked branch points; (7) the N-acetylglucosamine units are 1,6-linked. On the basis of the results of methylation and enzymic analysis, structures are proposed for the carbohydrate moieties and the assignments are compared with other data previously obtained by periodate-oxidation studies [Kennedy et al. (1974) Carbohydr. Res. 36, 369-377].


Lactate Dehydrogenase Polyclonal Antibody Sandwich ELISA for Determination of Endpoint Heating Temperatures of Ground Beef.
An enzyme-linked immunosorbent assay (ELISA) for the protein marker lactate dehydrogenase (LDH) was developed to determine endpoint heating temperature (EPT) of ground beef. Ground beef was placed in 10 by 75 mm tubes and heated to temperatures between 62 and 74°C at 2°C intervals. Electrophoresis and immunoblotting of meat extracts indicated a decrease in the intensity of the LDH band as temperature was increased. Polyclonal antibodies (PAb) against bovine muscle LDH were produced and a sandwich ELISA devised using biotinylated PAb as the detecting antibody. The LDH content decreased (P < 0.05) in ground beef heated between 66 and 74°C and was less than 4 μg/g of meat at the recommended minimum endpoint of 69°C. The ELISA was used to estimate the EPT of commercially cooked beef patties.


Modulation of the motor system during visual and auditory language processing.
Studies of embodied cognition have demonstrated the engagement of the motor system when people process action-related words and concepts. However, research using transcranial magnetic stimulation (TMS) to examine linguistic modulation in primary motor cortex has produced inconsistent results. Some studies report that action words produce an increase in corticospinal excitability; others, a decrease. Given the differences in methodology and modality, we re-examined this issue, comparing conditions in which participants either read or listened to the same set of action words. In separate blocks of trials, participants were presented with lists of words in the visual and auditory modality, and a TMS pulse was applied over left motor cortex, either 150 or 300 ms after the word onset. Motor evoked potentials (MEPs) elicited were larger following the presentation of action words compared with control words. However, this effect was only observed when the words were presented visually; no changes in MEPs were found when the words were presented auditorily. A review of the TMS literature on action word processing reveals a similar modality effect on corticospinal excitability. We discuss different hypotheses that might account for this differential modulation of action semantics by vision and audition.


Symmetry Breaking Enhancing the Activity of Electrocatalytic CO2 Reduction on an Icosahedron-Kernel Cluster by Cu Atoms Regulation.
Recently, CO2 hydrogenation had a new breakthrough resulting from the design of catalysts to effectively activate linear CO2 with symmetry-breaking sites. However, understanding the relationship between symmetry-breaking sites and catalytic activity at the atomic level is still a great challenge. In this study, a set of gold-copper alloy Au13Cux (x = 0-4) nanoclusters were used as research objects to show the symmetry-controlled breaking structure on the surface of nanoclusters with the help of manipulability of the Cu atoms. Among them, Au13Cu3 nanocluster displays the highest degree of symmetry-breaking on its crystal structure compared with the other nanoclusters in the family. Where the three copper atoms occupying the surface of the icosahedral kernel unevenly with one copper atom is coordinately unsaturated (CuS2 motif relative to CuS3 motif). As expected, Au13Cu3 has an excellent hydrogenation activity of CO2, in which the current density is as high as 70 mA cm-2 (-0.97 V) and the maximum FECO reaches 99% at -0.58 V. Through the combination of crystal structures and theoretical calculations, the excellent catalytic activity of Au13Cu3 is revealed to be indeed closely related to its asymmetric structure.


Molecular methods of enhancing lumbar spine fusion.
An optimal method for spinal fusion would induce rapid growth of bone via an osteoconductive and osteoinductive implant. This study examines the spinal fusion enhancement potential of some osteoconductive and osteoinductive biomaterials. Four similar canines received unilateral posterolateral fusions on the left side at T13-L1 and L4-L5 and on the right side at L2-L3 and L6-L7. The experiments were grouped as follows: Group A, autogenous bone harvested from the iliac crest; Group B, autogenous bone and collagen; Group C, no implant; and Group D, autogenous bone, collagen, and recombinant human bone morphogenetic protein-2. Radiographic assessment, three-dimensional computed tomographic volumetric analysis, and biomechanical testing were performed at each level. For Groups A and B, the fusions demonstrated moderate bone formation at 6 and 12 weeks postoperatively. Group D fusions exhibited earlier and more dramatic increases in volume and radiodensity and eventually were comparable in size to the vertebral bodies. Average fusion volumes computed from three-dimensional computed tomographic analysis were: Group A = 1.243 cc, Group B = 0.900 cc, Group C = 0.000 cc, and Group D = 6.668 cc (P = 0.003 compared to Group A). Group D exhibited flexion and extension biomechanical properties much greater than controls. The addition of recombinant human bone morphogenetic protein-2 consistently yielded the strongest fused segments and, on average, enhanced extension stiffness by 626% and flexion stiffness by 1120% over controls. The most advantageous spinal fusion implant matrix consisted of recombinant human bone morphogenetic protein-2, autogenous bone, and collagen. Future investigators, however, need to examine the appropriate quantities of the individual components and clarify the efficacy of the matrix for the various types of spinal fusion approaches.


Compensatory hypertrophy of the liver after external beam radiotherapy for primary liver cancer.
We investigated whether external beam radiotherapy (EBRT) could induce compensatory liver hypertrophy in liver cancers and assessed related clinical factors. A total of 82 consecutive patients receiving EBRT for hepatocellular carcinoma (n = 77) or cholangiocarcinoma (n = 5) from April 2012 to June 2014 were recruited and divided into two subgroups according to tumor location in the right or left lobe. The left lateral and right lobes were considered as unirradiated volumes accordingly. Total liver volume (TLV), nontumor liver volume (NLV), left and right lobe whole volume (LLWV and RLWV, respectively), volume of liver irradiated < 30 Gy (V< 30 Gy), Child-Pugh (CPS) score, future liver remnant (FLR) ratio, and percentage of FLR hypertrophy from baseline (%FLR) were assessed. In the right lobe group, %FLR hypertrophy and LLWV increased significantly at all follow-ups (p < 0.001). %FLR hypertrophy steadily increased until the fourth follow-up. Multivariate analysis showed that the factor associated with maximum %FLR hypertrophy was tumor extent (upper or lower lobe vs. both lobes; p = 0.022). Post-RT treatments including transarterial chemoembolization or hepatic arterial infusion chemotherapy were associated with a CPS increase ≥ 2 (p = 0.002). Analysis of the RT only subgroup also showed a significant increase of %FLR until the fourth follow-up (p < 0.001). In the left lobe group, %FLR hypertrophy and RLWV showed no significant changes during follow-up. Significant compensatory hypertrophy of the liver was observed, with a steady increase of %FLR hypertrophy until the fourth follow-up (median: 396 days). Locally advanced tumors extending across the upper and lower right lobe were a significant factor for compensating hypertrophy after EBRT.


Purification and characterization of mouse serum interferon.
Mouse serum interferon (MSIF) induced by intravenous injection with Newcastle disease virus (NDV) was subjected to purification by using Sephadex G-100 gel filtration and DEAE cellulose column chromatography. Purified IF fractions were characterized by polyacrylamide gel disc electrophoresis (PGDE) and immunodiffusion technique. Either on Sephadex G-100 gel filtration eluting with 0.1M phosphate buffer (pH 7.4) containing 0.001 M EDTA, or DEAE cellulose column chromatography eluting with 0.05 M Tris-HCl buffer (pH 8.4) containing 0.001 M EDTA and gradual increasing molarity of NaCl, two peaks were found to be associated with IF activity. The first peak from Sephadex gel filtration (I100) showed an ambiguous band located between alpha2 and beta-globulin on PGDE, while the second peak on DEAE chromatography (IID) showed no particular band on PGDE. Both the second peak which appeared on Sephadex gel filtration (II100) and the first peak appeared on DEAE chromatography (ID) presented the clear band between alpha1 and alpha2-globulin. Among these four peak fractions, ID was least contaminated by other serum protein components. Immunodiffusion analysis of whole MSIF against anti-MSIF revealed that there was only one particular band which was probably identical to II100 and ID that appeared in Ouchterlony's plate. Whole MSIF was also analysed by using cellulose acetate membrane electrophoresis (CAME). The pattern of CAME showed that the percentages of area at alpha1 and beta-globulin on the recording trace for MSIF seemed to be larger than those of control normal mouse serum.


Courgette Production: Pollination Demand, Supply, and Value.
Courgette (Cucurbita pepo L.) production in the United Kingdom is estimated to be worth £6.7 million. However, little is known about this crop's requirement for insect-mediated pollination (pollinator dependence) and if pollinator populations in a landscape are able to fulfil its pollination needs (pollination deficit). Consequently, pollination experiments were conducted over 2 yr to explore pollinator dependence and pollination deficit in field-grown courgette in the United Kingdom. Results showed that pollination increased yield by 39% and there was no evidence of pollination limitation on crop yield. This was evidenced by a surprisingly low pollination deficit (of just 3%) and no statistical difference in yield (length grown, circumference, and weight) between open- and hand-pollinated crops. Nonetheless, the high economic value of courgettes means that reducing even the small pollination deficit could still increase profit by ∼£166/ha. Interestingly, 56% of fruit was able to reach marketable size and shape without any pollination. Understanding a crop's requirement for pollinators can aid growers in their decision-making about what varieties and sites should be used. In doing so, they may increase their agricultural resilience and further their economic advantage.


Effect of isoflavones on lipids and bone turnover markers in menopausal women.
The purpose of this analysis was to compare the effects of two dietary supplements derived from red clover to placebo on lipids and bone turnover markers in symptomatic menopausal women. The study was a 12-week randomized, double-blind, placebo-controlled trial. Two hundred and fifty-two menopausal women ages 45-60 years experiencing > or =35 hot flashes per week were randomly assigned to Promensil (82 mg total isoflavones), Rimostil (57.2 mg total isoflavones), or placebo. Primary outcome measures were mean absolute changes for HDL-cholesterol, serum osteocalcin, and urinary N-telopeptide. Secondary outcome measures were mean changes of total cholesterol, LDL-cholesterol, the ratio of HDL- to LDL-cholesterol, and triglycerides. Ninety-eight percent of participants completed the 12-week protocol. Women taking Rimostil or Promensil compared to those taking placebo had greater mean increases in HDL-cholesterol; however, this change was small in magnitude (<2 mg/dl) and did not reach significance. There was a significant decrease in triglyceride levels among women taking Rimostil (14.4 mg/dl, P = 0.02) or Promensil (10.9 mg/dl, P = 0.05) compared to those taking placebo. The decrease was primarily among women with elevated baseline triglyceride levels (P for interaction = 0.009). There were no differences in mean changes of total cholesterol, LDL-cholesterol, or the ratio of HDL- to LDL-cholesterol among treatment groups. There were no statistically significant differences among treatment groups for bone turnover markers. Compared with placebo, both of the supplements containing isoflavones decrease levels of triglycerides in symptomatic menopausal women; however, this effect is small in magnitude.


Overlapping intimate partner violence and sex trading among high-risk women: Implications for practice.
Despite research indicating higher than average rates of intimate partner violence (IPV) across groups of vulnerable women, less is known about the prevalence and types of IPV experienced by women who trade sex for money, drugs, shelter or food, a high risk group for poor health and psychosocial outcomes. Using a cross-sectional design and multivariate logistic regression analyses, this study examined the relationship between IPV and sex trading in a convenience sample of 346 HIV-negative, drug-involved women in relationships, recruited during 2005-2010 in New York City. About 41% and 36% of participants reported lifetime and recent IPV, respectively, by their main partner, with significant differences by recent engagement in sex trading (p < 0.01). Results of multivariate analyses indicated that sex trading was associated with recent severe physical or sexual IPV (OR = 3.07, p < 0.01) and that depression, having ever been married, child sexual abuse, and income were associated with IPV (p < 0.05). Women who reported childhood sexual abuse and recent sex trading had a 7.37 higher odds (p < 0.01) for reporting severe physical or sexual IPV compared to those who reported neither. Findings highlight the need to expand screening and interventions among women who trade sex.


N-terminus of the rat adenine glycosylase MYH affects excision rates and processing of MYH-generated abasic sites.
Repair of most modified and mispaired bases in the genome is initiated by DNA glycosylases, which bind to their respective targets and cleave the N-glycosyl bond to initiate base excision repair (BER). The mammalian homolog of the Escherichia coli MutY DNA glycosylase (MYH) cleaves adenine residues paired with either oxidized or non-modified guanines. MYH is crucial for the avoidance of mutations resulting from oxidative DNA damage. Multiple N-terminal splice variants of MYH exist in mammalian cells and it is likely that different variants result in the production of enzymes with altered properties. To investigate whether modifications in the N-terminus are consequential to MYH function, we overexpressed intact and N-terminal-deletion rat MYH proteins and examined their activities. We found that deletion of 75 amino acids, which perturbs the catalytic core that is conserved with E.coli MutY, abolished excision activity. In contrast, deletions limited to the extended mammalian N-terminal domain, differentially influenced steady-state excision rates. Notably, deletion of 50 amino acids resulted in an enzyme with a significantly lower K(m) favoring formation of excision products with 3'-OH termini. Our findings suggest that MYH isoforms divergent in the N-terminus influence excision rates and processing of abasic sites.


Molluscicide for the control of schistosomiasis in irrigation schemes: a study in Southern Rhodesia.
The development of large areas of irrigation farming in the south-eastern lowveld of Southern Rhodesia has produced the risk of severe transmission of schistosomiasis over an extent of some 30 000 ha. Control measures instituted by the Ministry of Health were primarily directed against the large and widely distributed snail populations by using molluscicides. The chemical was applied to the irrigation water by drip-feed methods once every 6-8 months. The drains, however, were treated routinely by pairs of rangers searching for snails and applying chemical where they were found. The efficacy of control operations has been assessed by longitudinal studies in children free from infection to determine the incidence of infection. The results indicate that transmission of both Schistosoma haematobium and S. mansoni has been reduced to a level below that measured in areas of the country where irrigation is not practised. The total annual cost for this work was US$ 54 800-55 500.


B cell subsets contribute to renal injury and renal protection after ischemia/reperfusion.
Ischemia/reperfusion (I/R) triggers a robust inflammatory response within the kidney. Numerous components of the immune system contribute to the resultant renal injury, including the complement system. We sought to identify whether natural Abs bind to the postischemic kidney and contribute to complement activation after I/R. We depleted peritoneal B cells in mice by hypotonic shock. Depletion of the peritoneal B cells prevented the deposition of IgM within the glomeruli after renal I/R and attenuated renal injury after I/R. We found that glomerular IgM activates the classical pathway of complement, but it does not cause substantial deposition of C3 within the kidney. Furthermore, mice deficient in classical pathway proteins were not protected from injury, indicating that glomerular IgM does not cause injury through activation of the classical pathway. We also subjected mice deficient in all mature B cells (μMT mice) to renal I/R and found that they sustained worse renal injury than wild-type controls. Serum IL-10 levels were lower in the μMT mice. Taken together, these results indicate that natural Ab produced by peritoneal B cells binds within the glomerulus after renal I/R and contributes to functional renal injury. However, nonperitoneal B cells attenuate renal injury after I/R, possibly through the production of IL-10.


Thalamic energy dysfunction is associated with thalamo-cortical tract damage in multiple sclerosis: A diffusion spectroscopy study.
Diffusion-weighted 1H magnetic resonance spectroscopy (DW-MRS) allows to quantify creatine-phosphocreatine brain diffusivity (ADC(tCr)), whose reduction in multiple sclerosis (MS) has been proposed as a proxy of energy dysfunction. To investigate whether thalamic ADC(tCr) changes are associated with thalamo-cortical tract damage in MS. Twenty patients with MS and 13 healthy controls (HC) were enrolled in a DW-MRS and DW imaging (DWI) study. From DW-MRS, ADC(tCr) and total N-acetyl-aspartate diffusivity (ADC(tNAA)) were extracted in the thalami. Three thalamo-cortical tracts and one non-thalamic control tract were reconstructed from DWI. Fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD), reflecting microstructural integrity, were extracted for each tract. Associations between thalamic ADC(tCr) and tract metrics were assessed using linear regression models adjusting for age, sex, thalamic volume, thalamic ADC(tNAA), and tract-specific lesion load. Lower thalamic ADC(tCr) was associated with higher MD and RD of thalamo-cortical projections in MS (MD: p = 0.029; RD: p = 0.017), but not in HC (MD: p = 0.625, interaction term between thalamic ADC(tCr) and group = 0.019; RD: p = 0.320, interaction term = 0.05). Thalamic ADC(tCr) was not associated with microstructural changes of the control tract. Reduced thalamic ADC(tCr) correlates with thalamo-cortical tract damage in MS, showing that pathologic changes in thalamic energy metabolism are associated with structural degeneration of connected fibers.


Reactive perforating collagenosis.
Seven patients with reacting perforating collagenosis (RPC) were diagnosed from 1974 to 1982. Experimental production of lesions in two patients confirmed the contributory role of superficial trauma. The pathogenesis of RPC involves transepithelial elimination of altered collagenous bundles. This process may be observed in a wide variety of disparate skin diseases.


Paradoxical muscle movement in human standing.
In human standing, gravity causes forward toppling about the ankle joint which is prevented by activity in the soleus and gastrocnemius muscles. It has long been assumed that when people sway forwards the calf muscles are stretched and conversely that they shorten with backward sway. Consequently, for many years, two explanations for standing stabilization have flourished. First, tonic muscle activity itself may generate adequate intrinsic ankle stiffness. Second, if intrinsic ankle stiffness is inadequate, the resistance to stretch of the calf muscles may be augmented by stretch reflexes or by central control. These explanations require that the passive tissue (Achilles' tendon, foot) transmitting the calf muscle tension is stiff. However, our recent measurements have indicated that this passive tissue is not stiff during standing. Accordingly, we predicted a counterintuitive mode of control where the muscles and body must, on average, move in opposite directions (paradoxical movements). Here we use dynamic ultrasound imaging in vivo with novel automated tracking of muscle length to test our hypothesis. We show that soleus and gastrocnemius do indeed move paradoxically, shortening when the body sways forward and lengthening when the body returns. This confirms that intrinsic ankle stiffness is too low to stabilize human standing. Moreover, it shows that the increase in active tension is associated with muscle shortening. This pattern cannot be produced by muscle stretch reflexes and can only arise from the anticipatory neural control of muscle length that is necessary for balance.


Iodination of vasopressin analogues with agonistic and antagonistic properties: effects on biological properties and affinity for vascular and renal vasopressin receptors.
Twelve L- and D-tyrosine-containing vasopressin analogues were prepared in their mono- and diiodinated forms. These include six arginine vasopressin (AVP) vascular (V1) type antagonists/antidiuretic (V2) agonists, four V1/V2 antagonists, and two V1/V2 agonists, one of which is AVP itself. Ten peptides were iodinated on the tyrosyl residue in position 2; two were iodinated on a tyrosyl amide residue replacing the glycyl amide residue at position 9. All peptides were tested both for their biological activities in vivo (rat vasopressor and antidiuretic tests) and for their ability to bind to vasopressin receptors of the V1 (vascular) and V2 (renal) types from rat liver and rat kidney membranes, respectively. It is shown that monoiodination of the tyrosyl residue in the vasopressin analogues that were tested either preserves or reduces to a highly variable extent the in vivo and in vitro biological activities of these analogues. In most cases diiodonitation resulted in a marked decrease in biological activity. The effects of iodination on the affinity of vasopressin analogues for hepatic V1 receptors and renal V2 receptors were more related to the affinity of the noniodinated peptide for these receptors than to the biological properties (antagonist versus agonist) of the tested analogues, the nature (L versus D) of the iodinated tyrosyl residue, or the position (2 versus 9) at which this residue was introduced. The loss of affinity due to iodination was usually more pronounced for peptides exhibiting high affinity for vasopressin receptors. However, we show that among the monoiodinated peptides some (especially monoiodinated [2-D-Tyrosine]-AVP) retained enough affinity for vasopressin binding sites to suggest that their radioiodinated conterparts would be promising labeled ligands for use in studies in vasopressin receptors.


Case-finding tools for the diagnosis of OAB in women: A narrative review.
Overactive bladder (OAB) remains underdiagnosed with many patients never seeking medical help. Methods to aid early identification and treatment of OAB will be hugely beneficial, and to this end several case-finding tools have been developed. The aim of this review is to critically analyse the literature regarding case-finding tools that have been validated specifically for the detection of OAB in women. A literature search of the PubMed database was performed until July 2019 using the search terms screening and OAB or lower urinary tract symptoms (LUTS). Names of individual case-finding tools included in the sixth International Consultation on Incontinence were also searched on the PubMed database. Original articles on the validation of patient-reported screening questionnaires for the detection of OAB in women were included. A total of 22 studies met the inclusion criteria and were included in this review. The validation studies of 11 case-finding tools were assessed. All demonstrated good sensitivity and specificity for OAB or incontinence symptoms, and five tools have been most extensively validated for this condition (bladder control self-assessment questionnaire [B-SAQ], OAB-V8, OAB-V3, OAB symptom score, and questionnaire for urinary incontinence diagnosis). B-SAQ and OAB-V8 demonstrated high sensitivity whilst actionable bladder symptom screening tool was the most specific. B-SAQ was the only tool in this review to encompass screening for "red-flag" symptoms (hematuria, pain), and it has also been validated in a primary care setting. Several case-finding tools have been demonstrated to have high accuracy for diagnosing OAB in women. B-SAQ encompasses other LUTS as well as "red-flag" symptoms; its use should be promoted in primary care.


Disparities in breast cancer screening: is it ethical?
Breast cancer incidence and mortality rise dramatically as women get older. Approximately 48% of newly diagnosed breast cancers occur in women 65 and over, while nearly 57% of the breast cancer deaths occur in these same women. A number of studies have found that elderly women are at increased risk for being diagnosed with advanced-stage breast cancer; nevertheless, it appears that elderly women do not have more poor prognostic factors that are associated with early relapse or short survival than younger women. Considering the fact that the population is aging and the increased incidence and mortality of breast cancer in the elderly, it is important to determine what can be done to reduce breast cancer mortality in the older segments of the population. Breast cancer screening with clinical breast exam and mammography, by leading to earlier diagnosis and therapy, improves the prognosis for survival. Nevertheless, data from the 1992 US National Health Interview Survey revealed that about 27% of women 65 and over had never even had a single mammogram. Of those who did have a mammogram, fewer than two-thirds had it within one year prior to the survey. The data for clinical breast exam were less discouraging, but nearly 20% of these women had never had an exam. From an ethical perspective, women in their mid-70s have an average of about 12 years of life remaining, and should be given every opportunity to live out these years in good health.


Dapagliflozin attenuates human vascular endothelial cell activation and induces vasorelaxation: A potential mechanism for inhibition of atherogenesis.
Sodium glucose transporter type 2 inhibitors may reduce cardiovascular events in type 2 diabetes. Our study aimed to determine the effect of the sodium glucose transporter type 2 inhibitor dapagliflozin on endothelial cell activation, vasoreactivity and atherogenesis using in vitro and in vivo models and identify associated molecular mechanisms. In vitro studies utilised human vascular endothelial cells stimulated with tumour necrosis factor α or hyperglycaemic conditions. In vivo studies were performed in C57Bl/6J mice to evaluate direct vasorelaxation responses evoked by acute dapagliflozin administration and acute vaso-protective effects of dapagliflozin on hyperglycaemia-induced endothelial dysfunction. Adult and aged Apolipoprotein E-deficient mice maintained on a high-fat diet were used to investigate endothelial-dependent vascular reactivity and atherogenesis. Dapagliflozin treatment (1.0 mg/kg/day) was administered for 4 weeks. In vitro studies demonstrated dapagliflozin-mediated attenuation of tumour necrosis factor α- and hyperglycaemia-induced increases in intercellular adhesion molecule-1, vascular cell adhesion molecule-1, plasminogen activator inhibitor type 1 and NFκB expression. Acute dapagliflozin administration dose-dependently induced endothelium-independent vasorelaxation. Chronic dapagliflozin treatment improved endothelial function and significantly reduced in vivo vascular adhesion molecule and phospho-IκB expression together with macrophage vessel wall infiltration. These observations identify a potential role for dapagliflozin in the attenuation of atherogenesis and identify anti-inflammatory molecular mechanisms associated with these effects.


A receptor-based model for dopamine-induced fMRI signal.
This report describes a multi-receptor physiological model of the fMRI temporal response and signal magnitude evoked by drugs that elevate synaptic dopamine in basal ganglia. The model is formulated as a summation of dopamine's effects at D1-like and D2-like receptor families, which produce functional excitation and inhibition, respectively, as measured by molecular indicators like adenylate cyclase or neuroimaging techniques like fMRI. Functional effects within the model are described in terms of relative changes in receptor occupancies scaled by receptor densities and neuro-vascular coupling constants. Using literature parameters, the model reconciles many discrepant observations and interpretations of pre-clinical data. Additionally, we present data showing that amphetamine stimulation produces fMRI inhibition at low doses and a biphasic response at higher doses in the basal ganglia of non-human primates (NHP), in agreement with model predictions based upon the respective levels of evoked dopamine. Because information about dopamine release is required to inform the fMRI model, we simultaneously acquired PET (11)C-raclopride data in several studies to evaluate the relationship between raclopride displacement and assumptions about dopamine release. At high levels of dopamine release, results suggest that refinements of the model will be required to consistently describe the PET and fMRI data. Overall, the remarkable success of the model in describing a wide range of preclinical fMRI data indicate that this approach will be useful for guiding the design and analysis of basic science and clinical investigations and for interpreting the functional consequences of dopaminergic stimulation in normal subjects and in populations with dopaminergic neuroadaptations.


Is There a Higher Incidence of Sporadic Renal Angiomyolipoma in Childhood Cancer Survivors?
Cancer treatment can cause various long-term side effects, including those that impact ultrasound findings. During follow-up of childhood cancer survivors (CCSs), we often detected sporadic renal angiomyolipomas without histological confirmation (SAMLs), which is why we initiated this study. We compared the occurrence of SAML in CCSs to the previously reported data from a non-cancer population and correlated SAML with cancer treatment-related factors. The cohort included 1098 CCSs (median age at cancer diagnosis (dg) 4.3 years) who had ultrasound follow-up (2014-2019). Of the CCSs, 525 (48%) were female, 132 (12%) had subsequent neoplasms (SNs), and 110 (10%) had genetic syndromes. CCSs were treated for lymphomas 269 (24%) and solid tumors 829 (76%). None of the CCSs had tuberous sclerosis complex (TSC). SAML developed in 48 (4.4%) CCSs; of these, 20 (42%) had SNs. The coincidence of SAMLs and SNs was found in CCSs with a follow-up period exceeding 20 years. The median age at SAML dg was 27.9 years (interquartile range (IQR) 22.3-34.1), and the median time to SAML dg was 22.6 years (IQR 17.4-27.6). Twenty-one (44%) CCSs developed multiple or bilateral SAMLs lesions; of these, six (12%) were in the radiotherapy field. SAML occurrence correlated with radiotherapy of the retroperitoneum (1.65-fold higher with 95% CI 0.90-3.02). The correlations with other cancer treatment factors and with female sex were less clear. This study revealed the occurrence of SAMLs in CCSs to be 10 times higher than that in non-cancer studies. The current characteristics of CCSs with SAMLs: younger age, and more bilateral or multiple lesions are more similar to TSC associated angiomyolipoma. Moreover, we observed a coincidence of SAMLs with SNs. Our results support the hypothesis that SAML development in CCSs is not simply a late effect of therapy, and indicates other factors are involved in SAML development.


RIBONUCLEIC ACID SYNTHESIS DURING MITOSIS AND MEIOSIS IN THE MOUSE TESTIS.
The pattern of ribonucleic acid synthesis during germ cell development, from the stem cell to the mature spermatid, was studied in the mouse testis, by using uridine-H(3) or cytidine-H(3) labeling and autoradiography. Incorporation of tritiated precursors into the RNA occurs in spermatogonia, resting primary spermatocytes (RPS), throughout the second half of pachytene stage up to early diplotene, and in the Sertoli cells. Cells in leptotene, zygotene, and in the first half of pachytene stage do not synthesize RNA. No RNA synthesis was detected in meiotic stages later than diplotene, with the exception of a very low rate of incorporation in a fraction of secondary spermatocytes and very early spermatids. At long intervals after administration of the tracer, as labeled cells develop to more mature stages, late stages of spermatogenesis also become labeled. The last structures to become labeled are the residual bodies of Regaud. Thus, the RNA synthesized during the active meiotic stages is partially retained within the cell during further development. The rate of RNA synthesis declines gradually with the maturation from type A to intermediate to type B spermatogonia and to resting primary spermatocytes. "Dormant" type A spermatogonia synthesize little or no RNA. The incorporation of RNA precursors occurs exclusively within the nucleus: at later postinjection intervals the cytoplasm also becomes labeled. In spermatogonia all mitotic stages, except metaphase and anaphase, were shown to incorporate uridine-H(3). RNA synthesis is then a continuous process throughout the cell division cycle in spermatogonia (generation time about 30 hours), and stops only for a very short interval (1 hour) during metaphase and anaphase.


Alyssin and Iberin in Cruciferous Vegetables Exert Anticancer Activity in HepG2 by Increasing Intracellular Reactive Oxygen Species and Tubulin Depolymerization.
To determine the chemopreventive potential of alyssin and iberin, the in vitro anticancer activities and molecular targets of isothiocyanates (ITCs) were measured and compared to sulforaphane in hepatocellular carcinoma cell HepG2. The SR-FTIR spectra observed a similar pattern vis-à-vis the biomolecular alteration amongst the ITCs-treated cells suggesting a similar mode of action. All of the ITCs in this study cause cancer cell death through both apoptosis and necrosis in concentration dependent manner (20-80 μM). We found no interactions of any of the ITCs studied with DNA. Notwithstanding, all of the ITCs studied increased intracellular reactive oxygen species (ROS) and suppressed tubulin polymerization, which led to cell-cycle arrest in the S and G2/M phase. Alyssin possessed the most potent anticancer ability; possibly due to its ability to increase intracellular ROS rather than tubulin depolymerization. Nevertheless, the structural influence of alkyl chain length on anticancer capabilities of ITCs remains inconclusive. The results of this study indicate an optional, potent ITC (viz., alyssin) because of its underlying mechanisms against hepatic cancer. As a consequence, further selection and development of effective chemotherapeutic ITCs is recommended.


Plasma cell leukemia with plasmablastic morphology in a dog.
A 5-y-old female Golden Retriever was presented with a 2-wk history of hyporexia, vomiting, diarrhea, lethargy, weight loss, polyuria, and polydipsia. Clinical examination and ultrasonography revealed multiple organ enlargement with gallbladder and kidney nodules suggestive of disseminated neoplasia. Hematologic and biochemical analyses revealed pancytopenia, hypercalcemia, and monoclonal IgA gammopathy suspicious for a plasma cell neoplasm. Bone marrow and blood smear examination revealed neoplastic atypical cells highly suggestive of lymphoid origin. Autopsy confirmed the presence of homogeneous white masses and multifocal pale infiltrates in the spleen, kidney, small intestine, gallbladder, and urinary tract. Histologic features were consistent with a multicentric atypical plasma cell tumor. Tumor cells were negative for CD204, IBA-1, E-cadherin, CD3, CD5, CD79a, CD20, and PAX5, and positive for MUM1, consistent with plasma cell origin. The presence of > 20% of circulating blastic plasma cells was consistent with primary plasma cell leukemia with plasmablastic morphology, a disease rarely described in veterinary medicine.


[Effect of aromatic compounds and Mn2+ on the ligninolytic enzyme complex from the fungus Pleurotus floridae (FRIES) Kummer--a white-rot wood fungus].
The influence of aromatic compounds and Mn ions on activities of ligninolityc enzymes from white-rot fungus Pleurotus floridae has been studied. The specific inducers: vanillic acid and vanillyl alcohol--for activity of manganese-dependent peroxidase; vanillyl alcohol--for activity of cellobiose: quinone oxidoreductase during submerged, fermentation of Pleurotus floridae in Kirk's medium have been revealed. The inducers of laccase activity among studied aromatic compounds have not been revealed. The influence of Mn2+ in concentration range 0.4-68.4 mM on activities of ligninolytic enzymes of submerged culture of fungus P. floridae has been studied. Concentration of Mn ions 32.4 mM was optimal for manganese-dependent peroxidase activity.


Lumbar Fusion including Sacroiliac Joint Fixation Increases the Stress and Angular Motion at the Hip Joint: A Finite Element Study.
Adult spinal fusion surgery improves lumbar alignment and patient satisfaction. Adult spinal deformity surgery improves saggital balance not only lumbar lesion, but also at hip joint coverage. It was expected that hip joint coverage rate was improved and joint stress decreased. However, it was reported that adjacent joint disease at hip joint was induced by adult spinal fusion surgery including sacroiliac joint fixation on an X-ray study. The mechanism is still unclear. We aimed to investigate the association between lumbosacral fusion including sacroiliac joint fixation and contact stress of the hip joint. A 40-year-old woman with intact lumbar vertebrae underwent computed tomography. A three-dimensional nonlinear finite element model was constructed from the L4 vertebra to the femoral bone with triangular shell elements (thickness, 2 mm; size, 3 mm) for the cortical bone's outer surface and 2-mm (lumbar spine) or 3-mm (femoral bone) tetrahedral solid elements for the remaining bone. We constructed the following four models: a non-fusion model (NF), a L4-5 fusion model (L5F), a L4-S1 fusion model (S1F), and a L4-S2 alar iliac screw fixation model (S2F). A compressive load of 400 N was applied vertically to the L4 vertebra and a 10-Nm bending moment was additionally applied to the L4 vertebra to stimulate flexion, extension, left lateral bending, and axial rotation. Each model's hip joint's von Mises stress and angular motion were analyzed. The hip joint's angular motion in NF, L5F, S1F, and S2F gradually increased; the S2F model presented the greatest angular motion. The average and maximum contact stress of the hip joint was the highest in the S2F model. Thus, lumbosacral fusion surgery with sacroiliac joint fixation placed added stress on the hip joint. We propose that this was a consequence of adjacent joint spinopelvic fixation. Lumbar-to-pelvic fixation increases the angular motion and stress at the hip joint.


"You must first save her life": community perceptions towards induced abortion and post-abortion care in North and South Kivu, Democratic Republic of the Congo.
Structural barriers such as a restrictive legal environment, limited medical resources, and high-costs inhibit access to safe abortion in the Democratic Republic of the Congo (DRC); these barriers are exacerbated by two decades of conflict. Socio-normative barriers further complicate access to safe abortion and post-abortion care (PAC) in DRC, where fear of abortion-related stigma may lead women to avoid PAC services. Programme partners support the Ministry of Health to provide good quality contraceptive and PAC services in North and South Kivu, DRC. This paper presents results from focus group discussions that explored community members' attitudes towards women who induce abortion and their care-seeking behaviour in programme areas. Results indicate that while abortion stigma was widespread, community members' attitudes towards women who induced abortions were not one-dimensional. Although they initially expressed negative opinions regarding women who induced abortion, beliefs became more nuanced as discussion shifted to the specific situations that could motivate a woman to do so. For example, many considered it understandable that a woman would induce abortion after rape: perhaps unsurprising, given the prevalence of conflict-related sexual violence in this area. While community members believed that fear of stigma or associated negative social consequences dissuaded women from seeking PAC, a majority believed that all women should have access to life-saving PAC. This commitment to ensuring that women who induced abortion have access to PAC, in addition to the professed acceptability of induced abortion in certain situations, indicates that there could be an opening to destigmatise abortion access in this context.


Lack of identifiable biologic behavior in a series of porcine mesh explants.
Biologic matrices used in abdominal wall reconstruction are purported to undergo remodeling into connective tissue resembling native collagen. Key steps in that process include inflammatory response at the mesh/tissue interface, cellular penetration, and neovascularization of the matrix, followed by fibroblast proliferation and collagen deposition. We aimed to examine the concept of biologic mesh remodeling/regeneration in a series of explanted porcine biologic meshes. A cohort of patients who underwent removal of porcine biologic mesh was identified in a prospective database. Mesh/tissue samples were analyzed using standard hematoxylin/eosin and Masson's trichrome staining. Main outcome measures included: inflammatory response at the mesh/tissue interface, foreign body reaction (FBR), cellular penetration, neovascularization, and new collagen deposition. All evaluations were performed by a blinded senior pathologist using established grading scales. A total of 14 cases with implant time ranging from 4 to 33 months were identified and analyzed. All meshes were placed as intraperitoneal underlay. There were 7 non-cross-linked and 7 cross-linked grafts. Cross-linked grafts were associated with mild FBR and moderate fibrous capsule formation. Similarly, non-cross-linked grafts had mild-to-moderate FBR and encapsulation. Furthermore, non-cross-linked grafts were associated with no neovascularization and minimal peripheral mesh neocellularization. Cross-linked grafts demonstrated neither neovascularization nor neocellularization. Although no grafts were associated with any quantifiable new collagen deposition within the porcine biologic matrix, minimal biodegradation/remodeling was observed at the periphery of the non-cross-linked grafts only. The biologic behavior of porcine meshes is predicated on their ability to undergo mesh remodeling with resorption and new collagen deposition. In the largest series of human biologic explants, we detected no evidence of xenograft remodeling, especially in the cross-linked group. Although underlay mesh placement and other patient factors may have contributed to our findings, the concept of porcine biologic mesh regeneration does not seem to be prevalent in the clinical setting.


Combined extracranial-intracranial bypass surgery with stent-assisted coil embolization for moyamoya disease with a ruptured wide-necked basilar trunk aneurysm: a case report.
A ruptured wide-necked basilar trunk aneurysm is uncommon in patients with moyamoya disease. The optimal treatment is unclear. We report a safe and beneficial treatment modality for moyamoya disease with aneurysms located in the posterior circulation. A 37-year-old man presenting with subarachnoid hemorrhage was admitted to our hospital. Emergent cerebral angiography demonstrated moyamoya disease associated with a wide-necked basilar trunk aneurysm. We performed bilateral extracranial-intracranial bypass surgeries prior to stent-assisted coil embolization of the aneurysm after the acute phase. No complication occurred and the patient was discharged with no neurological deficit. Follow-up digital subtraction angiography (DSA) performed 6 months after the surgery showed that all the anastomosises were patent and bilateral collateral vascular compensation was fully established with no recanalization of the basilar trunk aneurysm post embolization.We also found that high-flow bypass did not contribute to cerebral revascularization as imagined despite the good patency. Combined extracranial-intracranial bypass surgery with endovascular treatment proved to be an efficient therapeutic modality for moyamoya disease with aneurysms located in the posterior circulation. High-flow bypass surgery was not essential due to the inefficiency and the high risk of postoperative cerebral hyperperfusion syndrome.


Toxicity of the recombinant human hyaluronidase ALT-BC4 on embryonic development.
Cumulus-oocyte complexes (COCs), which contain immature oocytes, are matured in vitro for in vitro embryo production. Oocyte and cumulus cells are then separated using hyaluronidase. To date, there have only been a few reported cases of the toxic effects of hyaluronidase on porcine oocytes. The aim of this study was to compare the effects of bovine testis-derived hyaluronidase and recombinant human hyaluronidase on oocyte denudation and quality. Porcine COCs were matured for 44 h and denuded using different hyaluronidase concentrations and exposure times. Then, oocytes were activated by electrical parthenogenesis. In experiment 1, COCs were denuded using bovine-derived, ovine-derived (Hirax), and human recombinant (ALT-BC4) hyaluronidases for 10 and 20 min. In experiment 2, bovine-derived and human recombinant (ALT-BC4 and ICSI Cumulase®) hyaluronidases were used to denude the COCs for 2 and 20 min. In both experiments the oocytes were all completely denuded, and there was no degeneration. Rate of embryo development was significantly increased in group treated ALT-BC4 for 2 min and not significantly different in other treatment groups. In general it slightly decreased with longer exposure times. These results have confirmed that different sources of hyaluronidase do not have detrimental effects on the quality of porcine oocytes and suggest that the human recombinant hyaluronidase ALT-BC4 is suitable for oocyte denudation with an increased blastocyst rate.


Regulation of energy metabolism during social interactions in rainbow trout: a role for AMP-activated protein kinase.
Rainbow trout (Oncorhynchus mykiss) confined in pairs form social hierarchies in which subordinate fish typically experience fasting and high circulating cortisol levels, resulting in low growth rates. The present study investigated the role of AMP-activated protein kinase (AMPK) in mediating metabolic adjustments associated with social status in rainbow trout. After 3 days of social interaction, liver AMPK activity was significantly higher in subordinate than dominant or sham (fish handled in the same fashion as paired fish but held individually) trout. Elevated liver AMPK activity in subordinate fish likely reflected a significantly higher ratio of phosphorylated AMPK (phospho-AMPK) to total AMPK protein, which was accompanied by significantly higher AMPKα1 relative mRNA abundance. Liver ATP and creatine phosphate concentrations in subordinate fish also were elevated, perhaps as a result of AMPK activity. Sham fish that were fasted for 3 days exhibited effects parallel to those of subordinate fish, suggesting that low food intake was an important trigger of elevated AMPK activity in subordinate fish. Effects on white muscle appeared to be influenced by the physical activity associated with social interaction. Overall, muscle AMPK activity was significantly higher in dominant and subordinate than sham fish. The ratio of phospho-AMPK to total AMPK protein in muscle was highest in subordinate fish, while muscle AMPKα1 relative mRNA abundance was elevated by social dominance. Muscle ATP and creatine phosphate concentrations were high in dominant and subordinate fish at 6 h of interaction and decreased significantly thereafter. Collectively, the findings of the present study support a role for AMPK in mediating liver and white muscle metabolic adjustments associated with social hierarchy formation in rainbow trout.


ZM336372, a Raf-1 activator, causes suppression of proliferation in a human hepatocellular carcinoma cell line.
Hepatocellular carcinoma has been described to exhibit characteristics similar to that of neuroendocrine tumors (NETs). This includes similar anti-neoplastic responses to extracellular signal-regulated kinase (ERK) activation. NET cells and HepG2 cells have both shown growth inhibition with ERK activation. ZM336372, a Raf-1 activating agent, has been shown to cause growth inhibition and suppression of hormone secretion in a neuroendocrine cell line. Here we examine treatment of the HepG2 cell line with ZM336732 to determine if a similar anti-proliferative response will be obtained. HepG2 cells were treated with ZM336372 or solvent (dimethyl sulfoxide). The resulting effect on the proliferation was measured using the 3,4-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Western blot analysis was performed to examine the activation of the Raf-1/mitogen-activated protein kinase kinase/ERK pathway, chromogranin A production, and p21CIP1 level. Growth inhibition was observed with ZM336372 in a dose-dependent fashion. Minimal baseline phosphorylation of ERK 1/2 was observed; however, activation was observed after treatment with ZM336372. Chromogranin A secretion was suppressed due to treatment with ZM336372. A dose-dependent up-regulation of p21CIP1 was observed in response to ZM336372 treatment. ZM336372 causes growth inhibition, suppression of hormone secretion, and up-regulation of cell cycle inhibitors in a human hepatocellular carcinoma cell line, similar to that previously seen in NETs.


Humoral immune response to the hypervariable region of hepatitis C virus differs between genotypes 1b and 2a.
Antibody to the hypervariable region (HVR) of HCV is thought to have neutralizing activity. The HCV genotype is known to affect the clinical course of infection. The antibody response to HVR and its relationship to the virologic and clinical characteristics were investigated in 21 patients with chronic hepatitis C. HVRs amplified by polymerase chain reaction from serum HCV were expressed as glutathione S-transferase fusion proteins. From 8 to 34 clones per serum sample were obtained (375 clones total), and the anti-HVR antibody in serum was assessed by Western blot. Both the incidence of fusion proteins positive for anti-HVR antibody and the activity of antibody were significantly higher in 6 patients with genotype 2a than in 15 patients with genotype 1b. This result suggests that the quantity of humoral response to HVR affects the clinical outcome of infection with these two HCV genotypes.


Strengthening teachers' abilities to implement a vision health program in Taiwanese schools.
We designed a school-based, nationwide program called the 'New Era in Eye Health' to strengthen teacher training and to examine whether the existence of a government vision care policy influenced teachers' vision care knowledge and students' behavior. Baseline data and 3-month follow-up data were compared. A random sample of teachers (n = 660) from school vision health clusters in 22 cities/counties in Taiwan were invited to participate in our study and 436 agreed to participate (response rate = 66.1%). The mean age of participant teachers was 41.2 years, while the length of service mean was 14.6 years. For monitoring teacher outcomes, five cities/counties were selected as the intensely monitored group based on certain criteria. Sunlight diaries (n = 5434) were distributed and 3342 (61.5%) were returned. Teachers showed significant improvements in knowledge and behavior on the school vision health questionnaire. At the 3-month follow-up, the number of recesses as recorded by students' 'sunlight diary' increased. When teachers had better knowledge and behavior, recesses also increased. This study provided valuable insights to guide dissemination efforts for school vision health interventions and to help teachers implement research into their school vision health activities.


Function of PEA3 Ets transcription factors in mammary gland development and oncogenesis.
The Ets gene families of mice and man currently comprise 27 genes that encode sequence-specific transcription factors. Ets proteins share an approximately 85 amino acid structurally conserved ETS DNA binding domain. Genetic analyses in model organisms suggest roles for Ets proteins in embryonic development and various adult physiological processes. Chromosomal translocations involving several ETS genes are associated with Ewing's sarcomas and leukemias, whereas the overexpression of some ETS genes is linked with numerous malignancies, including breast cancer. Indeed PEA3, ETS-1, PDEF, and ELF-3 transcripts have all been reported to be elevated in human breast tumors. Some of the ETS genes that are overexpressed in human breast tumors are also overexpressed in mouse models of this disease. Notably, pea3, as well as its close paralogs er81 and erm, which comprise the pea3 subfamily of ets genes, are coordinately overexpressed in mouse mammary tumors. Genetic analyses in mice reveal required roles for one or more of the PEA3 subfamily Ets proteins in the initiation and progression of mouse mammary tumors. The pea3 subfamily genes are normally expressed in the primitive epithelium of mouse mammary buds during embryogenesis, and these three genes are expressed in epithelial progenitor cells during postnatal mammary gland development. Loss-of-function mutations in the mouse pea3 gene results in increased numbers of terminal end buds and an increased fraction of proliferating cells in these structures, suggesting a role for PEA3 in progenitor cell renewal or terminal differentiation. Taken together these observations suggest that the PEA3 subfamily proteins play key regulatory roles in both mammary gland development and oncogenesis.