[Clinico-pathological study of chronic thyroiditis (author's transl)].
Although chronic thyroiditis has been recently noticed as an autoimmune disease, the histological classification based on clinico-pathological correlation is still vague at present. The specimens subjected to this study were taken by exploratory excision from 63 patients who were clinically diagnosed as chronic thyroiditis. Histological observation was done regarding the progress of pathologic changes in the thyroid gland. Lymphoid type (14 cases): lymph-follicle formation with scattered infiltration of lymphocytes was the predominant feature in this group. No definite alteration of the thyroi- epithelium was observed. Some of the so-called focal thyroiditis may be included in the early stage of this group. Some of them may develop into tremendous proliferation of lymphoid tissue in its late stage. Oxyphilic cell type (34 cases): oxyphilic alteration of the epithelium was predominant, but lymphocytic infiltrations observed in varying degrees was not an essential feature of this group. Fibrosis may possibly become more prominent with destruction of thyroid follicles in the late stage. Hyperplastic type (9 cases): most follicles were lined by cuboidal or tall epithelium with papillary infolding and contained thin colloid and some cell aggregates. This type of thyroiditis also may result in a proliferation of interlobular fibrous tissue in its more advanced stage. Fibrous type (6 cases): this type of thyroiditis is believed to be a late stage of the other three types. The original type of thyroiditis, however, was not clear because of advanced fibrosis. Evidences of the progress of the histological changes were observed in 12 out of 40 patients in whom the specimens were taken from both lobes and in two others whose specimens were taken twice at different stages. Clinical correlation of this classification was studied. The lymphoid type was found in 14 out of 53 female patients, but in none of 10 males. In age distribution the hyperplastic type was observed to be more common than the other types among younger people. The clinical signs of hypothyroidism were recognized most frequently in the oxyphilic cell type but not in the hyperplastic type. Thyroid function test, however, demonstrated no definite differences among the four types. Relationships were discussed in this paper between this author's classification and that of Woolner--also relationships to Hashimoto's thyroiditis and Riedel's struma.


BRCA1 and BRCA2 have a limited role in familial prostate cancer.
Epidemiological studies have suggested that the breast cancer susceptibility genes, BRCA1 and BRCA2, may be involved in the development of prostate cancer. Several studies have screened prostate cancer populations for the presence of BRCA1 and BRCA2 mutations, with few mutations identified. In this study, 22 high-risk prostate cancer families (at least three cases of prostate cancer) were screened by conformation-sensitive gel electrophoresis (CSGE) for mutations in BRCA1 and BRCA2. To maximize the chance of finding mutations in these two genes, families were also selected for the presence of at least two cases of breast and/or ovarian cancer. We identified one previously reported BRCA2 missense mutation and two previously unreported BRCA2 intron polymorphisms. No BRCA1 or BRCA2 truncating mutations were detected. Thus, BRCA1 and BRCA2 appear to have a limited role in familial prostate cancer, and families with both prostate and breast cancer may result from mutations in other predisposition genes.


Circulating MicroRNA as Biomarkers: An Update in Prostate Cancer.
Prostate cancer (PCa) is the most common non-skin cancer among men. Currently available diagnostic tests for PCa are inadequate in terms of low specificity and poor sensitivity. microRNAs offer a hope to overcome these drawbacks by virtue of their cancer specific expression and high stability. They can readily be detected and quantified in frozen and as well as formalin-fixed paraffin-embedded tissues. Observation of circulating miRNA in serum/plasma samples and other body fluids holds a promise to quickly move from research and provide a biomolecule of clinical relevance and an improvement over presently available biomarkers. This review highlights the potential role of circulating miRNAs as molecular markers for cancer and as targets for therapeutic manipulation. Further, this review summarizes the current understanding of various circulating miRNA with respect to prostate cancer. To conclude, circulating miRNAs are an active area of current investigation and holds promise to serve a wide range of clinical applications and unwrap a new era in cancer diagnosis and therapeutics.


Pharmacology of the bipyridines: amrinone and milrinone.
The cardiovascular bipyridines amrinone and milrinone are positive inotropic agents with vasodilator properties. When their effects on the heart and circulation were studied in both isolated cardiac tissues and anesthetized animals, milrinone was found to be 30 times more potent than amrinone. The inotropic response of isolated atria and papillary muscles to the bipyridines was characterized by increases in isometric tension and in the rates of tension development and relaxation. In the anesthetized dog, amrinone (1.0 mg/kg iv) and milrinone (0.03 mg/kg iv) caused significant increases in left ventricular dP/dtmax, cardiac output, and heart rate, significant decreases in pulmonary arterial pressure, and no change in systemic blood pressure. Studies to elucidate the mechanism(s) of action of the bipyridines indicated that Ca++ and cyclic AMP (cAMP) play important roles. The inotropic response to milrinone was modified by changes in the rate of stimulation and the concentration of extracellular Ca++ and by depolarization with high K+ or pretreatment with a calcium-channel blocker. Reduction of the extracellular Na+ concentration of 75% of normal potentiated the inotropic response of papillary muscles to low concentrations of milrinone, suggesting possible activation of the Na+-Ca++ exchange mechanism. These results suggest that milrinone may stimulate the influx of Ca++ into the cardiac cell. The bipyridines are phosphodiesterase inhibitors that increase cardiac cAMP levels. However, a time-course analysis of the changes in cAMP levels during the inotropic response to the bipyridines indicated that the increase in isometric tension development preceded the increase in cAMP. Our data suggest that more than one mechanism may be involved in the initiation and maintenance of the inotropic response to the bipyridines.


Altered electrical properties in Drosophila neurons developing without synaptic transmission.
We examine the role of synaptic activity in the development of identified Drosophila embryonic motorneurons. Synaptic activity was blocked by both pan-neuronal expression of tetanus toxin light chain (TeTxLC) and by reduction of acetylcholine (ACh) using a temperature-sensitive allele of choline acetyltransferase (Cha(ts2)). In the absence of synaptic activity, aCC and RP2 motorneurons develop with an apparently normal morphology and retain their capacity to form synapses. However, blockade of synaptic transmission results in significant changes in the electrical phenotype of these neurons. Specifically, increases are seen in both voltage-gated inward Na(+) and voltage-gated outward K(+) currents. Voltage-gated Ca(2+) currents do not change. The changes in conductances appear to promote neuron excitability. In the absence of synaptic activity, the number of action potentials fired by a depolarizing ramp (-60 to +60 mV) is increased and, in addition, the amplitude of the initial action potential fired is also significantly larger. Silencing synaptic input to just aCC, without affecting inputs to other neurons, demonstrates that the capability to respond to changing levels of synaptic excitation is intrinsic to these neurons. The alteration to electrical properties are not permanent, being reversed by restoration of normal synaptic function. Whereas our data suggest that synaptic activity makes little or no contribution to the initial formation of embryonic neural circuits, the electrical development of neurons that constitute these circuits seems to depend on a process that requires synaptic activity.


Relative resistance of Menz and Washera sheep breeds to artificial infection with Haemonchus contortus in the highlands of Ethiopia.
The aim of this study was to evaluate the relative resistance of Menz and Washera sheep breeds to artificial infection with Haemonchus contortus. The challenge trial was conducted at the Debre Berhan Agricultural Research Center in Ethiopia. A total of 39 (Menz = 21, Washera = 18) lambs of about 6 months old were used for the trial. All lambs were initially treated against internal parasite using albendazole and Fasinex to free them from internal parasites and kept indoors. H. contortus third-stage larvae (L3) were prepared according to standard procedure from adult female parasite collected from abattoirs and recovered using the Baerman technique. Approximately 5000 infective larvae were inoculated to the experimental lambs at about 5 weeks after deworming. Fecal egg count (FEC), packed cell volume (PCV), FAffa MAlan CHArt (FAMACHA) score, lamb body weight, and survival of lambs were recorded at 28, 35, and 42 days after challenge. Breed effect was not significant (P > 0.05), whereas time of measurement and the interaction of breed and time had significant (P < 0.05) effects on FEC and PCV. At 28 days after challenge, Menz sheep had lower FEC than Washera sheep, whereas at days 35 and 42, the Washera sheep had lower FEC than Menz lambs. The PCV decreased significantly throughout the post-challenge period. Despite their parasite burden, Menz sheep were able to maintain live weight during the 42 days of challenge. Chi-square tests for breed differences in lamb survival were not significant at any time (28, 35, and 42 days after challenge). Lower FEC at 28 days and delayed rise in FEC after infection in Menz lamb would allow in delaying anthelmintic treatment. In addition to maintain body weights during the infection period, sheep of both breeds exhibited substantial variability in PCV and FEC, suggesting opportunity to consider parasite resistance in selection program.


Arithmetical calculation and related neuropsychological skills in subjects with isolated oral clefts.
The current study examined whether the arithmetical calculation skills of children, adolescents, and young adults with isolated cleft of the lip and/or palate (iCL/P) differ significantly from unaffected control participants. Comparisons of potential neuropsychological predictors of arithmetical calculation were also conducted to determine whether these variables differ significantly for participants with iCL/P. Participants (N = 176; 93 iCL/P and 83 Control) ranged in age from 7 to 26 years old. A standardized battery of achievement and neuropsychological skills was administered. Between group differences on math achievement was assessed through a univariate analysis of covariance. Relationships between neuropsychological measures and math achievement were analyzed separately for participants with iCL/P and controls through hierarchical linear regressions. Arithmetical calculation was significantly lower for the iCL/P group. Rapid naming, sustained attention, and visual-spatial organization were significant predictors for the iCL/P group; rapid naming was the lone variable that was significantly more predictive of arithmetical calculation for the iCL/P group than for control participants. These results suggest that inefficient verbal label retrieval related to short-term memory (STM) deficits underlie the calculation difficulties of individuals with iCL/P. These findings have implications for approaches to remediation, as well as future research. (PsycINFO Database Record


Intraparotid lymph node tuberculosis.
Parotid gland Mycobacterial infection is a rare disease that causes parotid swelling without disease-specific manifestations. We present a case of intraparotid lymph node tuberculosis that mimicked a tumour. Computed tomography of the head and neck indicated a left parotid enlargement involving two intraparotid lymph nodes. The cervical lymph nodes of the ipsilateral posterior triangle and the submandibular and jugulodigastric areas were also enlarged. Contrast enhancement indicated homogenous tissue with no necrotic areas. A biopsy revealed a caseating granuloma most likely due to tuberculosis. A purified protein derivative test gave strong positive results (35 mm). After one month of antituberculous treatment, the cervical lymphadenopathy and left parotid lumpiness disappeared. Tuberculous parotitis and neoplasms have similar clinical manifestations. In patients with a mass in the parotid gland, a high clinical suspicion of underlying tuberculosis is crucial for establishing an accurate diagnosis and the proper management.


Reverse vesicles of ferrum laurate metallosurfactant in non-aqueous solution dried to produce solid shells.
Ferrum laurate [Fe(OOCC(11) H(23))(3)] metallosurfactant can successfully self-assemble into reversed vesicles in organic media such as pure CHCl(3) and a mixed solvent of CHCl(3) and CH(3)OH. Deformed solid vesicles, including collapsed erythrocyte-like and broken hollow shells, were obtained directly by slectively drying the organic solvents. The morphology of the reversed vesicles of metallosurfactant in the organic media to hardly solid shells is maintained and it is ascribed to the evaporation rate of the solvents and the interactions between ferrum laurate and solvents.


Expansion of inpatient clinical pharmacy services through reallocation of pharmacists.
The redesign of an inpatient pharmacy practice model through reallocation of pharmacy resources in order to expand clinical services is described. A pharmacy practice model change was implemented at a nonprofit academic medical center to meet the increasing demand for direct patient care services. In order to accomplish this change, the following steps were completed: reevaluation of daily tasks and responsibilities, reallocation of remaining tasks to the most appropriate pharmacy staff member, determination of the ideal number of positions needed to complete each task, and reorganization of the model into a collection of teams. Data were collected in both the preimplementation and postimplementation periods to assess the impact of the model change on operational workflow and clinical service expansion. The mean ± S.D. times to order verification were 17 ± 52 minutes during the preimplementation period and 21 ± 70 minutes in the postimplementation period (p < 0.001). During the 3 months before and after implementation of the model change, the mean number of medication reconciliations performed increased from 114 to 144. After implementation of the model change, total interventions increased 194%. Notably, there was a 736% increase in the number of interventions focused on facilitating safe discharge. A pharmacy practice model change was successfully implemented by reallocating existing pharmacist and technician roles and increasing incorporation of pharmacy residents and students. This change led to an expansion of direct patient care coordination services without negatively affecting the operational responsibilities of the pharmacy or the need to hire additional staff.


Ischemia reperfusion injury in tumors: the role of oxygen radicals and nitric oxide.
Oxidative stress is a key process involved in the action of several therapeutic modalities used in cancer treatment. Ischemia reperfusion insult provides a model system for investigating the processes involved in determining the sensitivity of tumor tissue to oxidative stress. We have investigated the response of the murine CaNT tumor to ischemia reperfusion injury and the role that oxygen radicals and nitric oxide may play in this phenomenon. Our results show that little or no cell kill is detected in tumors exposed to up to 3 h of ischemia if the tumors are excised immediately before reperfusion. However, if reperfusion is permitted, then extensive cell kill is evident 24 h later. i.v. administration of superoxide dismutase or catalase, at the time when vascular reperfusion occurred, resulted in a significant protection against tumor cell kill, suggesting that the damage was mediated by oxygen radicals. Conversely, administration of an inhibitor of nitric oxide synthase, N omega-nitro-L-arginine, resulted in potentiation of tumor cell damage. Administration of a nitric oxide (NO) donor, diethylamine NO, at the time when vascular reperfusion occurred resulted in significant protection against tumor damage. These results suggest that nitric oxide is a potent mediator in determining tumor damage after ischemia reperfusion injury. The role of intrinsic NO production by murine tumors was investigated by measuring the accumulation of nitrate in the medium of tumor explants cultured in vitro in two tumors with differing sensitivity to ischemia reperfusion damage. The clamp-insensitive tumor SaS showed a greater nitrate accumulation than the clamp-sensitive tumor CaNT, which may confer a greater capacity for preventing tumor and endothelial cell damage after oxidative stress.


Efficacy of National Nosocomial Infection Surveillance score, acute-phase proteins, and interleukin-6 for predicting postoperative infections following major gastrointestinal surgery.
Postoperative infections should be detected earlier. We investigated the efficacy of the National Nosocomial Infection Surveillance (NNIS) score, interleukin-6 (IL-6) and various acute-phase proteins for predicting postoperative infections. Case series study at the Júlio Müller University Hospital. Thirty-two patients who underwent major gastrointestinal procedures between June 2004 and February 2005 were studied. The NNIS score and the evolution of serum IL-6 and various acute-phase proteins (C-reactive protein [CRP], albumin, prealbumin and transferrin) were correlated with postoperative infections and length of hospital stay (LOS). NNIS > 1 (p = 0.01) and low preoperative albumin (p = 0.02) significantly correlated with infection. IL-6 and CRP increased significantly more in patients with infections. Multivariate analysis showed greater risk of infection when NNIS > 1 (odds ratio, OR = 10.66; 95% confidence interval, CI: 1.1-102.0; p = 0.04); preoperative albumin < 3 g/dl (OR = 8.77; 95% CI: 1.13-67.86; p = 0.03); CRP > 30 mg/l on the second postoperative day (OR = 8.27; 95% CI: 1.05-64.79; p = 0.03) and > 12 mg/l on the fifth postoperative day (OR = 25.92; 95% CI: 2.17-332.71; p < 0.01); and IL-6 > 25 pg/ml on the fifth postoperative day (OR = 15.46; 95% CI: 1.19-230.30; p = 0.03). Longer LOS was associated with cancer, transferrin, IL-6 and albumin (p < 0.05). NNIS, albumin, CRP and IL-6 may be useful as predictive markers for postoperative infections. For predicting LOS, malignant condition, transferrin, albumin and IL-6 are useful.


Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk.
Growth hormone may be associated with the development of colorectal cancer directly and/or indirectly via increased serum level of insulin-like growth factor (IGF-I). Regular physical activity can decrease insulin resistance and modulates IGF-I production. A common polymorphism in the GH1 gene, rs2665802, was previously shown to be associated with lower IGF-I levels and decreased colorectal cancer (CRC) risk. We investigated the association of this polymorphism and physical activity with colorectal cancer risk in a case-control study. The analysis includes 3,041 (1,402 cases and 1,639 controls) participants in the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study in Northern Israel. Analysis was carried out separately in two sets. The first set included 1,248 subjects (625 cases, 623 controls), and the second validation set consisted of 1,793 subjects (777 cases, 1,016 controls). No association was found between the studied polymorphism and CRC risk. However, evaluation of gene environment interactions revealed an interaction between leisure time physical activity and the GH1 polymorphism, which was consistent in both sets (P(interaction) = 0.005). The genotype AA was associated with decreased risk of CRC among individuals who did not engage in any such activity (odds ratio, 0.76; 95% confidence interval, 0.52-0.98), whereas the same genotype was marginally associated with increased risk among individuals who reported physical activity (odds ratio, 1.38; 95% confidence interval, 0.98-1.94). We found that the A allele of the rs2665802 polymorphism is associated with reduced risk of CRC only among physically inactive individuals, indicating an interaction between physical activity and the growth hormone/IGF-I system. A replication of the observed findings and further investigation of the underlying mechanism is warranted.


Genetic dissection of thyroid hormone receptor beta: identification of mutations that separate hormone binding and transcriptional activation.
The thyroid hormone receptors (TR) are members of the nuclear receptor family of ligand-mediated transcription factors. The large region of TR that lies C-terminal to its DNA-binding domain subserves functions of ligand binding, dimerization, and transactivation. Little is known regarding the structural or functional determinants of these processes. We have utilized genetic screening in the yeast Saccharomyces cerevisiae to identify residues involved in these functions. Random mutations of the rat TR beta 1 isoform between amino acid residues 179 and 456 were screened, and mutants with reduced hormone-dependent activation of reporter gene activity were isolated. In this paper we describe the characterization of a class of mutants that exhibit a dissociation between hormone binding and transcriptional activation. These mutants retained hormone binding (> 15% of the wild-type level) yet failed to transactivate a reporter gene. A number of these mutations occurred within the D region, which links the DNA-binding and ligand-binding domains of the receptor. One subset of these mutations abrogated DNA binding, supporting a role of the D region in this process. The remainder retain DNA binding and thus highlight residues critical for receptor activation. In addition, an unexpected group of "superactivator" mutations that led to enhanced hormone-dependent activation in S. cerevisiae were found. These mutations localized to the carboxy-terminal portion of the receptor in a region which contains elements conserved across the superfamily of nuclear receptors. The hormone-dependent phenotype of these superactivator mutations suggests an important role of this segment in ligand-mediated transcriptional activation.


Heelys and street gliders injuries: a new type of pediatric injury.
Our goals were to highlight an increasing trend in orthopedic injuries in children as a result of "heeling" or "street gliding," to describe injuries sustained by children using Heelys (HSL, Carrollton, TX) and Street Gliders (Glowgadgets Ltd, Bristol, United Kingdom), and to increase public awareness and prevent such injuries. We prospectively recorded the data of all roller shoes injuries referred to our department during the summer school holiday. Using a data-collection sheet, we recorded demographic data, type of injury, mechanism and place of injury, heeling or street-gliding experience, use of safety equipment, methods of treatment, and intention to continue heeling or street gliding after recovery from injury. Over a 10-week period, 67 children suffered orthopedic injuries while using Heelys or Street Gliders. There were 56 girls and 11 boys with a mean age of 9.6 years. Upper limbs were the most common location of injury. Distal radius fractures were the most prevalent, followed by supracondylar fractures, elbow dislocations, and hand fractures. The majority of children suffered the injury while heeling or street gliding outdoors. Interestingly, 20% of the injuries happened while trying Heelys or Street Gliders for the first time, and 36% of the injuries occurred while learning (using 1-5 times) how to use them. None of the children used any sort of protective gear at the time of the injury. The majority of the injured children expressed their intention to continue heeling or street gliding after complete recovery from their injury. Our study shows that the majority of children with injuries from heeling or street gliding are girls. We recommend close supervision of children using Heelys or Street Gliders during the steep learning curve and usage of protective gear at all times. These new types of injuries have a serious impact on child health and constitute a burden for the pediatric orthopedic service.


[Infertility in women with galactorrhea].
Clinico-hormonal examinations of patients with sterility, galactorrhea, and regular menstrual cycle revealed endocrine abnormalities in only ten of 53 patients (18%). These abnormalities presented as latent hyperprolactinemia and hypothyrosis. Sterility causes in the rest 43 patients (82%) were benign uterine and ovarian tumors, external genital endometriosis, residual symptoms after genital inflammations. These data point to a necessity of examining this patients population with the use of hormonal and endoscopic methods of examination.


Prevalence estimates of substandard drugs in Mongolia using a random sample survey.
To determine the prevalence of substandard drugs in urban (Ulaanbaatar) and rural (selected provinces) areas of Mongolia, samples of 9 common, therapeutically important drugs were collected from randomly selected drug outlets in Ulaanbaatar and 4 rural provinces by "mystery shoppers". Samples were analyzed by visual inspection, registration status, and biochemical analysis. Samples failing to meet all Pharmacopeia quality tests were considered substandard. In the rural provinces, 69 out of 388 samples were substandard, giving an estimated prevalence of substandard drugs of 17.8% (95% CI: 14.1-22.0). There were 85 unregistered samples, giving a prevalence estimate of unregistered drugs of 21.9%. (95% CI: 17.9-26.3). In the urban Ulaanbaatar districts, 112 out of 848 samples were substandard, giving an estimated prevalence of substandard drugs of 13.2% (95% CI: 11.0-15.7). There were 150 unregistered samples, giving a prevalence estimate of unregistered drugs of 17.7% (95% CI: 15.2-20.4). In the rural provinces, 35 out of 85 (41.2%) unregistered samples were substandard; whereas 34 out of 303 (11.2%) registered samples were substandard. (p < 0.0001) In the urban districts, 18 out of 150 (12.0%) unregistered samples were substandard, whereas 94 out of 698 registered were substandard. (13.5%) (p = 0.6). The prevalence of substandard and unregistered drugs is higher in rural provinces. There is a significant association between substandard and unregistered drugs in the provinces but not in the urban districts. The underlying causes for substandard drugs need to be further investigated in order to help formulate strategies to improve pharmacovigilance and the drug supply quality in Mongolia.


Non-nucleoside reverse transcriptase inhibitors (NNRTIs): past, present, and future.
Non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) have become an inherent ingredient of the drug combination schemes that are currently used in the treatment of human immunodeficiency virus type 1 (HIV-1) infections. Starting from the 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 4,5,6,7-tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO) derivatives, numerous classes of compounds have been described as NNRTIs. Only three compounds have so far been approved for clinical use: nevirapine, delavirdine, and efavirenz. NNRTIs are notorious for rapidly leading to virus-drug resistance development, primarily based on the emergence of the K103N and Y181C mutations in the HIV-1 RT. Newer NNRTIs, such as capravirine, dapivirine (TMC 125), and DPC 083, are resilient to these 'NNRTI' mutations, and, therefore, offer considerable promise as future anti-HIV-1 drugs. NNRTIs are targeted at a specific 'pocket' binding site within the HIV-1 RT, that is distinct from, but both spatially and functionally related to, the catalytic site, where the nucleoside RT inhibitors (NRTIs) and nucleotide RT inhibitors (NtRTIs) interact. NNRTIs have acquired a definitive position, as part of a combination regimen with NRTIs and NtRTIs, in the first-line treatment of HIV-1 infections.


[Structure of receptive fields of visually sensitive neurons of the cat hippocampus].
Structure of receptive fields of visually sensitive neurons in areas CA1 and CA3 of the dorsal hippocampus was investigated in alert cats with the brain-stem pretrigeminal section. The receptive field (RF) structure of 76 hippocampal neurons was analyzed by methods of scanning the RF by moving stimuli and mapping all their surface by a stationary flashing spot. According to presented data the neurons were classified into three groups: neurons with homogeneous structure of the RF (54%), with nonhomogeneous (28%) and neurons more sensitive to stimulus motion (18%) than to a stationary flashing light. Experiments have shown that responses of hippocampal neurons are highly specific ones. Thus, 9% of neurons with the nonhomogeneous RF structure have shown specific responses to variation of the contrast and contours of moving stimuli. The presented results show that hippocampal visually driven neurons have well developed mechanism for processing visual sensory information and apparently this quality ensures participation of the limbic system in visually controlled behavior of the animal.


A randomized, phase II trial of cetuximab with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer.
The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase/mammalian target of rapamycin signaling pathway is frequently altered in head and neck squamous cell cancer (HNSCC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. A phase I trial demonstrated tolerability of this combination. This randomized phase II study evaluated PX-866 combined with cetuximab in patients with advanced, refractory HNSCC. Patients with recurrent or metastatic HNSCC who had received at least one and no more than two prior systemic treatment regimens were randomized (1 : 1) to cetuximab with or without PX-866 (8 mg p.o. daily; arms A and B, respectively). The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival (OS), toxicity, and correlation of key biomarkers with efficacy outcomes. Eighty-three patients were enrolled. There was a similar response rate between arms (10% versus 7%). Of patients for whom tissue was assessable, 57% were human papillomavirus (HPV) positive. Median PFS was 80 days in both arms and there was no difference in OS between the two arms (211 versus 256 days). Overall toxicity was higher in arm A compared with arm B, especially in terms of nausea (53% versus 23%), vomiting (45% versus 15%), fatigue (43% versus 23%), diarrhea (40% versus 21%), and hypokalemia (25% versus 10%). Grade 3 or higher adverse events were infrequent, but more common in the combination arm although without a specific pattern. PIK3CA mutations were observed in 17% of the cases assessed, and PTEN loss was infrequently observed. The addition of PX-866 to cetuximab did not improve PFS, RR, or OS in patients with advanced, refractory HNSCC enrolled without molecular preselection. In this contemporary cohort, HPV-positive patients comprised the majority, and neither HPV-positive nor HPV-negative patients derived clinical benefit for the addition of cetuximab plus PX-866.


High-Resolution Single-Cell Sequencing of Malaria Parasites.
Single-cell genomics is a powerful tool for determining the genetic architecture of complex communities of unicellular organisms. In areas of high transmission, malaria patients are often challenged by the activities of multiple Plasmodium falciparum lineages, which can potentiate pathology, spread drug resistance loci, and also complicate most genetic analysis. Single-cell sequencing of P. falciparum would be key to understanding infection complexity, though efforts are hampered by the extreme nucleotide composition of its genome (∼80% AT-rich). To counter the low coverage achieved in previous studies, we targeted DNA-rich late-stage parasites by Fluorescence-Activated Cell Sorting and whole genome sequencing. Our method routinely generates accurate, near-complete capture of the 23 Mb P. falciparum genome (mean breadth of coverage 90.7%) at high efficiency. Data from 48 single-cell genomes derived from a polyclonal infection sampled in Chikhwawa, Malawi allowed for unambiguous determination of haplotype diversity and recent meiotic events, information that will aid public health efforts.


Structure of active chromatin: higher-order folding of transcriptionally active chromatin in control and hypothyroid rat liver.
Investigation have been carried out into the salt-induced higher-order folding in the transcriptionally active chromatin region of rat liver nuclei by nuclease digestion, sedimentation and CD. The sensitivity of active chromatin in nuclei to micrococcal nuclease was suppressed by raising the ionic strength from 25 to 90 mM, indicating the occurrence of salt-induced condensation. The rate of sedimentation of fractionated inactive chromatin fragments of both moderate (approximately 3.5 kbp) and large (approximately 8.8 kbp) size increased maximally to the same extent, while that of active chromatin fragments was dependent on their size. The rate of sedimentation of moderately sized active chromatin fragments (approximately 5.5 kbp) showed a maximal 15% increase at 90 mM ionic strength. In contrast, a large increase (at least 60%) in the sedimentation rate of large active chromatin fragments (approximately 21 kbp) was observed at 65 mM ionic strength. A reasonable degree of higher-order folding was observed in large active chromatin fragment even at 25 mM ionic strength. On considering the percentage increase in sedimentation rate as a measure of the higher-order folding of chromatin, a different type of higher-order folding was observed in active chromatin fragments. Although the percentage increase in sedimentation decreased from 40 to 24% with an increase in the size of active chromatin from approximately 3 to approximately 9 kbp, a further increase in size up to 16 kbp brought the percentage increase back to 40%. CD studies agreed with the conclusions drawn from sedimentation studies. Active chromatin from hypothyroid rats showed similar folding behaviour, but the order of folding was slightly lower than for control active chromatin, at all sizes.


Iatrogenic Cushing syndrome and secondary adrenal insufficiency related to concomitant triamcinolone and ritonavir administration: a case report and review.
Triamcinolone is a long-acting glucocorticoid medication that can be responsible for transient suppression of the hypothalamic–pituitary–adrenal (HPA) axis. This physiologic alteration may persist for weeks after repeated or even single localized injection of this agent. However, when this glucocorticoid agent is given to patients receiving the HIV protease inhibitor (PI) ritonavir (RTV),inhibition of their shared cytochrome P450 3A4 degradation pathway leads to an increased bioavailability of triamcinolone, with subsequent heightening and prolongation of the glucocorticoid serum levels. In those instances, iatrogenic Cushing syndrome may ensue. The authors encountered such an event in an HIV-infected patient on chronic treatment with an antiretroviral regimen containing RTV. The patient's clinical presentation and laboratory investigations confirmed a diagnosis of Cushing syndrome and secondary adrenal insufficiency. This was believed to have occurred in close association following cervical vertebral column facet joint injections with triamcinolone acetonide for cephalagia deemed related to cervical spine disease. The discontinuation of the RTV-boosted PI therapy alone, promoting the clearance of the elevated triamcinolone serum levels and restoration of HPAhomeostasis, proved successful in this patient. For this case, the authors review the published English medical literature relating to this uncommon phenomenon.


Genetic divergence and fine scale population structure of the common bottlenose dolphin (Tursiops truncatus, Montagu) found in the Gulf of Guayaquil, Ecuador.
The common bottlenose dolphin, Tursiops truncatus, is widely distributed along the western coast of South America. In Ecuador, a resident population of bottlenose dolphins inhabits the inner estuarine area of the Gulf of Guayaquil located in the southwestern part of the country and is under threat from different human activities in the area. Only one genetic study on South American common bottlenose dolphins has been carried out to date, and understanding genetic variation of wildlife populations, especially species that are identified as threatened, is crucial for defining conservation units and developing appropriate conservation strategies. In order to evaluate the evolutionary link of this population, we assessed the phylogenetic relationships, phylogeographic patterns, and population structure using mitochondrial DNA (mtDNA). The sampling comprised: (i) 31 skin samples collected from free-ranging dolphins at three locations in the Gulf of Guayaquil inner estuary, (ii) 38 samples from stranded dolphins available at the collection of the "Museo de Ballenas de Salinas," (iii) 549 mtDNA control region (mtDNA CR) sequences from GenBank, and (iv) 66 concatenated sequences from 7-mtDNA regions (12S rRNA, 16S rRNA, NADH dehydrogenase subunit I-II, cytochrome oxidase I and II, cytochrome b, and CR) obtained from mitogenomes available in GenBank. Our analyses indicated population structure between both inner and outer estuary dolphin populations as well as with distinct populations of T. truncatus using mtDNA CR. Moreover, the inner estuary bottlenose dolphin (estuarine bottlenose dolphin) population exhibited lower levels of genetic diversity than the outer estuary dolphin population according to the mtDNA CR. Finally, the estuarine bottlenose dolphin population was genetically distinct from other T. truncatus populations based on mtDNA CR and 7-mtDNA regions. From these results, we suggest that the estuarine bottlenose dolphin population should be considered a distinct lineage. This dolphin population faces a variety of anthropogenic threats in this area; thus, we highlight its fragility and urge authorities to issue prompt management and conservation measures.


Comorbidities and complications of polycystic ovary syndrome: An overview of systematic reviews.
Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting reproductive-aged women with adverse reproductive, metabolic and psychological outcomes. It has a complex pathophysiology and therefore requires a multidiscipline clinical approach. However, there remains limited research synthesizing the broad clinical implications of PCOS which would assist clinicians in the management of PCOS. To summarize and appraise methodological quality of systematic reviews and meta-analyses evaluating complications and comorbidities associated with PCOS. A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed until 15 September 2017. Article selection, data extraction and quality appraisal of included reviews using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool were performed in duplicate. A narrative synthesis of the findings was conducted. Twenty-three reviews were included. All reviews were of low (n = 2) to moderate quality (n = 21). PCOS was associated with adverse pregnancy outcomes (n = 2), impaired glucose tolerance (n = 6), insulin resistance (n = 6), increased risk of type 2 diabetes (n = 1), cardiovascular disease (n = 10), metabolic syndrome (n = 2), psychological stress (n = 7), endometrial cancer (n = 1) and vitamin D deficiency (n = 1). Obesity exacerbates many of these outcomes. There is a large body of reliable evidence for adverse metabolic outcomes and smaller, but consistent evidence for psychological issues in PCOS. We identified a shortage of systematic reviews regarding pregnancy outcomes of PCOS and significant gaps in knowledge of the association between PCOS and subclinical hyperthyroidism, vitamin D levels and cancers which future studies could aim to address.


[Stomach resection from mini-approach in complicated ulcers of duodenal posterior wall].
6 cases of Bilrot-I stomach resection from mini-approach for ulcers of duodenal posterior wall complicated by pyloric stenosis and penetration into pancreatic head are described. Precise technique was used. Orientation of the incision to pancreatic head and suprapyloric gastrotomy create good conditions for orientation, precise dissection of the affected part of the duodenum and creation of one-layer gastroduodenoanastomosis. Tunnelization of retrobulbar fat tissue and alternating traction up by dissected stomach made surgery easier. The operated patients were followed up from 1 months to 2 years: function of anastomosis was satisfactory.


Children's ideas for the design of AAC assistive technologies for young children with complex communication needs.
This study examined children's preferences and priorities for the design of assistive technologies to enhance communication for children with complex communication needs. Six children without disabilities were provided with drawing and craft materials and were asked to develop low-tech prototypes of inventions to support the communication of a young child who had significant speech and motor impairments. The design process and the inventions were analyzed using qualitative methods. Results showed that the children's inventions differed significantly from the designs of current AAC technologies. Their inventions were not simply speech prostheses; rather, they integrated multiple functions (e.g., communication, social interaction, companionship, play, artistic expression, telecommunications) and provided dynamic contexts to support social interactions with others, especially peers. The children characterized the systems as companions and utilized innovative names, bright colors, lights, transformable shapes, popular themes, humor, and amazing accomplishments to capture interest, enhance appeal, build self-esteem, and establish a positive social image. The systems were easily personalized to reflect the user's age, personality, attitude, interests, and preferences. Re-designing AAC technologies to incorporate these types of functions and features may increase their appeal and make them easier for young children to learn and use. Results are discussed with reference to implications for future research and development.


Growth Hormone Therapy in Decompensated Cirrhosis: An Open-Label, Randomized Control Trial.
Effect of long-term growth-hormone (GH) therapy in decompensated cirrhosis (DC) is unknown. We studied the safety and efficacy of GH therapy on malnutrition, nitrogen metabolism, and hormonal changes in patients with DC. Patients with DC were randomized to standard medical therapy plus GH (group A; n = 38) or standard medical therapy alone (group B; n = 38). Body mass index, midarm muscle circumference (MAMC), hand grip strength (HGS), liver frailty index (LFI), skeletal muscle index (SMI), nitrogen balance, Child-Turcotte-Pugh, model for end-stage liver disease, quality of life (QOL), serum albumin, GH, insulin like growth factor-1, and acid labile subunit (ALS) were assessed at baseline and at 12 months. The mean difference between baseline and 12-months in SMI (-6.122 [-9.460 to -2.785] cm 2 /m 2 ), body mass index (-2.078 [-3.584 to -0.5718] kg/m 2 ), MAMC (-1.960 [-2.928 to -0.9908] cm), HGS (-5.595 [-7.159 to -4.031] kg), albumin (-0.3967 [-0.6876 to -0.1057] g/dL), LFI (0.3328 [0.07786-0.5878]), Child-Turcotte-Pugh (0.9624 [0.1435-1.781]), model for end-stage liver disease (1.401 [0.04698-2.75]), insulin-like growth factor-1 (-6.295 [-11.09 to -1.495] ng/dL), and ALS (-8.728 [-14.12 to -3.341] pg/mL) were statistically significantly better ( P < 0.05) in group A. There was no improvement in nutritional parameters, clinical scores, QOL scores, or nitrogen balance in group B. The mean difference between group A and B in SMI, HGS, MAMC, LFI, ALS, physical component summary, and mental component summary at 12 months was also statistically significant. Survival at 12 months was similar in both groups ( P = 0.35). No serious adverse events were observed. Long-term use of GH is safe in DC and leads to improvement in malnutrition and possibly QOL. However, there is no improvement in 12-month survival (NCT03420144).


Thioredoxin Profiling of Multiple Thioredoxin-Like Proteins in Staphylococcus aureus.
Hydrogen sulfide (H2S) is thought to signal through protein S-sulfuration (persulfidation; S-sulfhydration) in both mammalian systems and bacteria. We previously profiled proteome S-sulfuration in Staphylococcus aureus (S. aureus) and identified two thioredoxin-like proteins, designated TrxP and TrxQ, that were capable of reducing protein persulfides as a potential regulatory mechanism. In this study, we further characterize TrxP, TrxQ and the canonical thioredoxin, TrxA, by identifying candidate protein substrates in S. aureus cells using a mechanism-based profiling assay where we trap mixed disulfides that exist between the attacking cysteine of a FLAG-tagged Trx and a persulfidated cysteine on the candidate substrate protein in cells. Largely non-overlapping sets of four, 32 and three candidate cellular substrates were detected for TrxA, TrxP, and TrxQ, respectively, many of which were previously identified as global proteome S-sulfuration targets including for example, pyruvate kinase, PykA. Both TrxA (k cat = 0.13 s-1) and TrxP (k cat = 0.088 s-1) are capable of reducing protein persulfides on PykA, a model substrate detected as a candidate substrate of TrxP; in contrast, TrxQ shows lower activity (k cat = 0.015 s-1). This work reveals that protein S-sulfuration, central to H2S and reactive sulfur species (RSS) signaling, may impact cellular activities and appears to be regulated in S. aureus largely by TrxP under conditions of sulfide stress.


A new anticancer compound, oblongifolin C, inhibits tumor growth and promotes apoptosis in HeLa cells through Bax activation.
Oblongifolin C (OC) was identified as a potent apoptosis inducer from an herbal plant, Garcinia yunnanensis, during our previous bioassay-guided drug screening. In this study, we investigated the signaling pathways through which OC activated apoptosis in HeLa cells. We also compared the IC(50) values of OC with that of etoposide, paclitaxel and vinblastine in multiple cancer cell lines including HER2 and P-glycoprotein overexpressing cells. In addition, the in vivo antitumor effect of OC was studied in nude mice model. Our results showed that OC induced a caspase-dependent apoptosis by triggering a series of events in HeLa cells including Bax translocation, cytochrome c release, caspase-3 activation, chromosome fragmentation followed by caspase-8 activation, Bid cleavage and eventually cell death. Addition of a pan-caspase inhibitor or overexpression of an anti-apoptotic protein, Bcl-xL, prevented OC-induced cell death. Moreover, OC exhibited a wide anticancer spectrum in multiple cancer cell lines with comparable IC(50) values, regardless of the expression levels of HER2 and P-glycoprotein. In contrast, the IC(50) values of three clinical anticancer drugs, etoposide, paclitaxel and vinblastine were significantly elevated in HER2 and/or P-glycoprotein overexpressing cells. Furthermore, OC showed a similar antitumor effect but lower general toxicity than etoposide against xenografted human tumors in nude mice model. All these data suggested that OC is a promising apoptosis inducer with the potential to be developed into a clinical anticancer drug.


Density functional theory-based simulations of sum frequency generation spectra involving methyl stretching vibrations: effect of the molecular model on the deduced molecular orientation and comparison with an analytical approach.
The knowledge of the first hyperpolarizability tensor elements of molecular groups is crucial for a quantitative interpretation of the sum frequency generation (SFG) activity of thin organic films at interfaces. Here, the SFG response of the terminal methyl group of a dodecanethiol (DDT) monolayer has been interpreted on the basis of calculations performed at the density functional theory (DFT) level of approximation. In particular, DFT calculations have been carried out on three classes of models for the aliphatic chains. The first class of models consists of aliphatic chains, containing from 3 to 12 carbon atoms, in which only one methyl group can freely vibrate, while the rest of the chain is frozen by a strong overweight of its C and H atoms. This enables us to localize the probed vibrational modes on the methyl group. In the second class, only one methyl group is frozen, while the entire remaining chain is allowed to vibrate. This enables us to analyse the influence of the aliphatic chain on the methyl stretching vibrations. Finally, the dodecanethiol (DDT) molecule is considered, for which the effects of two dielectrics, i.e. n-hexane and n-dodecane, are investigated. Moreover, DDT calculations are also carried out by using different exchange-correlation (XC) functionals in order to assess the DFT approximations. Using the DFT IR vectors and Raman tensors, the SFG spectrum of DDT has been simulated and the orientation of the methyl group has then been deduced and compared with that obtained using an analytical approach based on a bond additivity model. This analysis shows that when using DFT molecular properties, the predicted orientation of the terminal methyl group tends to converge as a function of the alkyl chain length and that the effects of the chain as well as of the dielectric environment are small. Instead, a more significant difference is observed when comparing the DFT-based results with those obtained from the analytical approach, thus indicating the importance of a quantum chemical description of the hyperpolarizability tensor elements of the methyl group.


The role of p21cip1 in adaptation of CHO cells to suspension and protein-free culture.
The up-regulation of cyclin-dependent kinase inhibitor p21 has been shown to enhance productivity of monoclonal antibodies and has been linked to various regulatory processes. To identify the potential role of p21 in adaptation to suspension and protein-free cultures, we studied the survival and growth of anchorage- and serum-dependent CHO cell lines that differed only in the period of p21-induced arrest. p21 overexpression led to rapid adaptation of cells to suspension and protein-free cultures. The period taken to achieve adaptation was correlated with the time the cells were arrested after transfer from the monolayer and serum-fed culture. Interestingly, cell aggregation associated with protein-free suspension culture was reduced in p21 culture in response to the loss of cellular adherence. The processes of adaptation to suspension and arrest did not decrease monoclonal antibody productivity. In contrast, following adaptation to protein-free growth media, an overall increase in specific productivity was observed. The ability of cells to survive in protein-free suspension cultures was due to the requirement of G1 cells to growth factors and to their relatively high resistance to the hydrodynamic forces. This improved process has the advantage of reducing the duration of critical path activity for developing CHO commercial cell lines from 72 to 36 days.


[Neoton (exogenic phosphocreatinine) in combined therapy of chronic cardiac failure].
To evaluate clinicohemodynamic effect of neoton (exogenic phosphocreatine) given in an intravenous course, the drug was added to standard scheme in 53 patients with chronic cardiac failure (6.0 g/day i.v. drip for 5 days or 3.0 g/day for 10 days). 20 control patients received standard therapy alone. A course neoton produced an increase in the ejection fraction, a reduction in end-diastolic and end-systolic left ventricular volumes. It is recommended to include neoton in the scheme of chronic cardiac failure treatment in the dose 3.0 g/day for 10 days.


[Clinico-anatomical analysis of the causes of death in ruptures of intracranial arterial aneurysms].
Causes of lethal outcome in patients after subarachnoid hemorrhage due to cerebral aneurysm rupture were analysed. The major death cause in the operated patients was cerebral edema and dislocation, while in non-operated ones it was the penetration of blood into the ventricles of the brain. Cerebral edema and dislocation syndrome were mainly caused after surgery by ischemic changes in cerebral tissue. A relationship between the aneurysm localization and the extent of subarachnoid hemorrhage was revealed as well as between the hematoma localization and incidence of hemorrhage into the ventricles of the brain.


[The morphological evaluation of a heart ventricle made from the latissimus dorsi muscle in an experiment].
In experiment of 16 animals the morpho-functional transformations taking place in skeletal-muscular transplant while various methods of artificial heart ventricle creation and his training application were studied. It was established that, as a rule, in autotransplant the reversible structural changes are taking place, what stipulates the necessity of keeping of the "latent" period 14-21 days long between the operation conducted and the beginning of training stimulation of heart ventricles, manufactured of a skeletal muscle.


Uterine artery embolisation for management of refractory postpartal haemmorhage.
Management of Postpartal Haemorrhage (PPH) refractory to medical management continues to be a formidable condition, further compounded by unstable haemodynamic condition and associated coagulopathy, usually associated with this condition. Though surgical exploration is the usual therapeutic option for such patients, selective pelvic arterial embolisation is gaining the popularity in view of its safety and efficacy profile. Uterine preservation further adds to its advantages.We present our experience of managing 5 such patients with Uterine Artery Embolisation (UAE). The current status of UAE as therapeutic modality for management of refractory PPH is discussed.


MinGenome: An In Silico Top-Down Approach for the Synthesis of Minimized Genomes.
Genome minimized strains offer advantages as production chassis by reducing transcriptional cost, eliminating competing functions and limiting unwanted regulatory interactions. Existing approaches for identifying stretches of DNA to remove are largely ad hoc based on information on presumably dispensable regions through experimentally determined nonessential genes and comparative genomics. Here we introduce a versatile genome reduction algorithm MinGenome that implements a mixed-integer linear programming (MILP) algorithm to identify in size descending order all dispensable contiguous sequences without affecting the organism's growth or other desirable traits. Known essential genes or genes that cause significant fitness or performance loss can be flagged and their deletion can be prohibited. MinGenome also preserves needed transcription factors and promoter regions ensuring that retained genes will be properly transcribed while also avoiding the simultaneous deletion of synthetic lethal pairs. The potential benefit of removing even larger contiguous stretches of DNA if only one or two essential genes (to be reinserted elsewhere) are within the deleted sequence is explored. We applied the algorithm to design a minimized E. coli strain and found that we were able to recapitulate the long deletions identified in previous experimental studies and discover alternative combinations of deletions that have not yet been explored in vivo.


Biodegradation of a poly(alpha-amino acid) hydrogel. I. In vivo.
A new hydrogel material has been prepared by crosslinking a hydrophilic, nonionic poly(amino acid), poly(2-hydroxyethyl-L-glutamine). The material properties of the hydrogel can be controlled by variation in the crosslink density, and the swelling ratio was found to be a sensitive and convenient method for measuring the extent of in vivo biodegradation of implanted specimens. Degradation of the material was observed only during the first 2 weeks of subcutaneous implantation in rats, and is attributed to hydrolysis by proteolytic enzymes released during the acute and chronic stages of the normal inflammatory response.


Synchronous in-line regeneration of wavelength-division multiplexed solitons signals in optical fibers.
A new synchronization technique for simultaneous in-line modulation and regeneration of wavelength-division multiplexed (WDM) soliton signals in optical fibers is proposed. A specific wavelength-mapping rule makes synchronization compatible with frequency-guiding Fabry-Perot filters. As an example, a 4 x 10 Gbitys WDM regenerated soliton system is demonstrated numerically. We also show that the technique is fully compatible with dispersion management, which alleviates detrimental WDM collisions. Thus the possibility of combining wavelength-division multiplexing and regeneration opens up new perspectives for ultrahigh-bit-rate transoceanic soliton systems.


[Right neglect with hemiasomatognosia, mental confusion, apraxia and agraphia without aphasia].
A 74 year-old woman was admitted with a right hemiplegia resulting from a left infarct that had totally destroyed the territory supplied by the middle and anterior cerebral arteries. The patient presented with anosognosia and hemiasomatognosia and negligence of the right half-field. She was aprosodic, not aphasic, and there was a severe apraxia and total agraphia. These neuropsychological disorders are discussed in relation to the contradictory data relative to the manual lateralization of the patient. Findings in this case of a "crossed apraxia" show that management of language and of the propositional gestures are not necessarily ensured by the same hemisphere. It also appears that manual preference may be a poor clue for interpretation in terms of functional lateralization.


Effects of borehole wells on water utilization in Schistosoma haematobium endemic communities in Coast Province, Kenya.
To determine the impact of the introduction of borehole wells on water use patterns and the consequent risk of transmission of Schistosoma haematobium in 3 endemic villages in Kenya, we performed a survey (a 1:6 sample of affected households) to identify sources of water and types of water utilization before and after well introduction. Water usage was also determined in 2 unaffected neighboring villages not given borehole wells, but having continuous access to piped water from communal taps. Prior to borehole well construction, significantly more high-risk water use occurred in the borehole villages vs. comparison villages in terms of water gathered for cooking, drinking, dish washing, and bathing; residents of both types of villages preferred high-risk sources (marshes and ponds) for clothes washing. Following well introduction, there were significant declines in the use of high-risk water for drinking, cooking, and dish washing, but not for bathing or clothes washing. A higher proportion of individuals from the 3 borehole villages reported some type of continued contact with high-risk water sources. Despite well introduction and a 3 year chemotherapy program among school-aged children, a 21-28% incidence of infection persisted among children in the villages, suggesting minimal impact on transmission. Regular monitoring for S. haematobium infected snail sites showed no decline in the number or proportion of infected snails. Borehole well introduction can significantly alter some forms of water usage, but social and water quality factors may limit the ability of communal wells to reduce S. haematobium transmission.


The natural history of hepatitis C virus (HCV) infection.
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, as well as the most common indication for liver transplantation in many countries. Although the incidence of hepatitis C infection has dramatically decreased during the past decade, the worldwide reservoir of chronically infected persons is estimated at 170 million, or 3% of the global population. There is much controversy surrounding the natural history of hepatitis C infection. The rate of chronic HCV infection is affected by a person's age, gender, race, and viral immune response. Approximately 75%-85% of HCV-infected persons will progress to chronic HCV infection, and are at risk for the development of extrahepatic manifestations, compensated and decompensated cirrhosis, and hepatocellular carcinoma (HCC). The rate of progression to cirrhosis is highly variable, and is influenced by several factors, including the amount of alcohol consumption, age of initial HCV infection, degree of inflammation and fibrosis on liver biopsy, HIV and HBV coinfection, and comordid conditions. An estimated 10%-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. Persons with cirrhosis are at increased risk of developing HCC. An understanding of the natural history of hepatitis C is essential to effectively manage, treat, and counsel individuals with HCV infection.


Low-probability states, data statistics, and entropy estimation.
A fundamental problem in the analysis of complex systems is getting a reliable estimate of the entropy of their probability distributions over the state space. This is difficult because unsampled states can contribute substantially to the entropy, while they do not contribute to the maximum likelihood estimator of entropy, which replaces probabilities by the observed frequencies. Bayesian estimators overcome this obstacle by introducing a model of the low-probability tail of the probability distribution. Which statistical features of the observed data determine the model of the tail, and hence the output of such estimators, remains unclear. Here we show that well-known entropy estimators for probability distributions on discrete state spaces model the structure of the low-probability tail based largely on a few statistics of the data: the sample size, the maximum likelihood estimate, the number of coincidences among the samples, and the dispersion of the coincidences. We derive approximate analytical entropy estimators for undersampled distributions based on these statistics, and we use the results to propose an intuitive understanding of how the Bayesian entropy estimators work.


Opiate agonist-induced re-distribution of Wntless, a mu-opioid receptor interacting protein, in rat striatal neurons.
Wntless (WLS), a mu-opioid receptor (MOR) interacting protein, mediates Wnt protein secretion that is critical for neuronal development. We investigated whether MOR agonists induce re-distribution of WLS within rat striatal neurons. Adult male rats received either saline, morphine or [d-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) directly into the lateral ventricles. Following thirty minutes, brains were extracted and tissue sections were processed for immunogold silver detection of WLS. In saline-treated rats, WLS was distributed along the plasma membrane and within the cytoplasmic compartment of striatal dendrites as previously described. The ratio of cytoplasmic to total dendritic WLS labeling was 0.70±0.03 in saline-treated striatal tissue. Morphine treatment decreased this ratio to 0.48±0.03 indicating a shift of WLS from the intracellular compartment to the plasma membrane. However, following DAMGO treatment, the ratio was 0.85±0.05 indicating a greater distribution of WLS intracellularly. The difference in the re-distribution of the WLS following different agonist exposure may be related to DAMGO's well known ability to induce internalization of MOR in contrast to morphine, which is less effective in producing receptor internalization. Furthermore, these data are consistent with our hypothesis that MOR agonists promote dimerization of WLS and MOR, thereby preventing WLS from mediating Wnt secretion. In summary, our findings indicate differential agonist-induced trafficking of WLS in striatal neurons following distinct agonist exposure. Adaptations in WLS trafficking may represent a novel pharmacological target in the treatment of opiate addiction and/or pain.


Reliability and failure modes of implant-supported Y-TZP and MCR three-unit bridges.
Chipping within veneering porcelain has resulted in high clinical failure rates for implant-supported zirconia (yttria-tetragonal zirconia polycrystals [Y-TZP]) bridges. This study evaluated the reliability and failure modes of mouth-motion step-stress fatigued implant-supported Y-TZP versus palladium-silver alloy (PdAg) three-unit bridges. Implant-abutment replicas were embedded in polymethylmethacrylate resin. Y-TZP and PdAg frameworks, of similar design (n = 21 each), were fabricated, veneered, cemented (n = 3 each), and Hertzian contact-tested to obtain ultimate failure load. In each framework group, 18 specimens were distributed across three step-stress profiles and mouth-motion cyclically loaded according to the profile on the lingual slope of the buccal cusp of the pontic. PdAg failures included competing flexural cracking at abutment and/or connector area and chipping, whereas Y-TZP presented predominantly cohesive failure within veneering porcelain. Including all failure modes, the reliability (two-sided at 90% confidence intervals) for a "mission" of 50,000 and 100,000 cycles at 300 N load was determined (Alta Pro, Reliasoft, Tucson, AZ, USA). No difference in reliability was observed between groups for a mission of 50,000. Reliability remained unchanged for a mission of 100,000 for PdAg, but significantly decreased for Y-TZP. Higher reliability was found for PdAg for a mission of 100,000 cycles at 300 N. Failure modes differed between materials.


Trend in dental research output in Iran over a period of 20 years (1990-2009).
The number of scientific papers is a conventional metric for the measurement of a country's research performance in a particular area. To evaluate the trend in Iranian publications of dental research results in peer-reviewed international scientific journals over the period 1999-2009, using national and international databases, and to compare the results with other countries. The search process was performed by two independent persons in PubMed and Iranian Medline (IranMedex). Data extraction included the year of publication, total number of dental papers in each year, total number of Iranian dental papers in each year and number of papers with a high level of evidence; these were compared with those in other Asian countries. The total number of dental articles indexed in PubMed during the studied period was 207,689, with 671 being written by researchers who stated their affiliation as Iran. Although the proportion of Iranian dental articles to all published dental articles was 0.01% in 1990, this increased to 1.4% in 2009. Of all clinical trials indexed in PubMed from 1990 to 2009, only 0.62% had an author from Iran. The collaboration rate of authors ranged between 1 and 10. Turkey and Iran had a larger number of dental research publications compared with other Asian countries assessed in this study. During the last two decades, there has been a considerable increase in the number of dental papers by Iranian researchers indexed in the PubMed database.


Age-related epigenetic drift deregulates SIRT6 expression and affects its downstream genes in human peripheral blood mononuclear cells.
Sirtuin 6 (SIRT6) exerts a protective effect on health and extends the lives of model organisms. We, therefore, aimed to clarify whether age-related epigenetic drift is responsible for differences in SIRT6 expression in peripheral blood mononuclear cells (PBMCs) of healthy young (n = 55, mean age 27.5 ± 4.4 years), middle-aged (n = 51, 65.4 ± 3.3 years), and long-lived (n = 51, 93.9 ± 3.6 years) humans. In silico analysis was performed using the STRING network. No age-related differences were observed in the percentage of SIRT6 CpG island methylation. However, the age affected the expression of miR-34a-5p, miR-125a-5p, miR-186-5p, miR-342-5p and miR-766-3p (all p < 0.0001), miR-181-2-3p and Let-7c (both p = 0.0003), and miR-103a-3p (p = 0.0069). A negative association was observed between SIRT6 mRNA and miR-186-5p (rs = -0.25, p = 0.026), and a positive association was observed with miR-34a-5p (rs = 0.31, p = 0.0055) and miR-181a-2-3p (rs = 0.39, p = 0.0002). SIRT6 mRNA also negatively correlated with the expression of TP53 (rs = -0.41, p = 0.0126) and MYC (rs = -0.35, p = 0.0448). Notably, the expression of several miRNAs and genes was similar in young and long-lived groups but different from the middle-aged group. We conclude that age-related epigenetic changes can affect the expression of SIRT6 in PBMCs and, in this way, possibly influence immunosenescence. Moreover, molecular events could differentiate 'normal' ageing from that of long-lived individuals.


Transforming growth factor-beta and cellular immune responses in synovial fluids.
Mononuclear cells in synovial fluids (SF) from patients with rheumatoid arthritis and other arthropathies are characterized by functional and phenotypic changes, including impaired mitogen responsiveness and inverted ratios of CD4+/CD8+ T lymphocytes. This is related to previously described activities in synovial fluids that inhibit proliferation of lymphocytes induced by mitogens and cytokines. The present study examines the relationship of these activities and transforming growth factor beta (TGF-beta), which is now known as the most potent endogenous inhibitor of lymphocyte function. It is shown that most of the activity in SF that inhibits IL-1-induced thymocyte or T cell proliferation is neutralized by a specific antibody to TGF-beta. Analysis of the SF in the CCL64 assay, a standard test for TGF-beta, showed a close correlation between the levels of immunosuppressive activity and TGF-beta. SF contain spontaneously active inhibitors of T cell function and this is caused by the presence of active TGF-beta. Higher titers are found after transient acidification, which is known to activate the latent form of TGF-beta. Characterization of the TGF-beta isoforms showed that most of the material in SF is TGF-beta 2. Analysis of TGF-beta effects on T cell subsets demonstrated that it completely inhibits proliferation of CD4+ cells whereas at the same concentrations of purified or rTGF-beta CD8+ cells are only inhibited by maximally 31.1%. SF also preferentially inhibit CD4+ Th cell proliferation and this effect is neutralized by antibody to TGF-beta. Collectively these results indicate that the presence of TGF-beta accounts for most of the immunosuppressive activities in SF and that this factor may be responsible for functional and phenotypic changes of SF lymphocytes.


THE EXPERIMENTAL INFECTION OF THE HUMAN BODY LOUSE, PEDICULUS HUMANUS CORPORIS, WITH MURINE AND EPIDEMIC LOUSE-BORNE TYPHUS STRAINS.
Experiments are described which demonstrate that human body lice (Pediculus humanus corporis), were infected experimentally with murine and epidemic louse-borne strains of typhus fever by feeding on suitably prepared rabbits. Details of the two methods of infection, the "bleb technique" and the "I.V. technique," are presented. It is concluded that the experimental infection of human lice with typhus can be accomplished very easily and rapidly with these methods. The possible applications of the method are discussed.


IL-8 is one of the major chemokines produced by monkey airway epithelium after ozone-induced injury.
A rhesus monkey interleukin (IL)-8 cDNA clone with >94% homology to the human IL-8 gene was isolated by differential hybridization from a cDNA library of distal airways after ozone inhalation. In situ hybridization and immunohistochemistry showed increased IL-8 mRNA and protein levels in epithelial cells at 1 h but not at 24 h after inhalation of ozone. The appearance of IL-8 in airway epithelial cells correlated well with neutrophil influx into airway epithelia and lumens. Air-liquid interface cultures of tracheobronchial epithelial cells were exposed to ozone in vitro. We observed a transient increase in IL-8 secretion in culture medium immediately after ozone exposure and a dose-dependent increase in IL-8 secretion and mRNA production. In vitro neutrophil chemotaxis showed a parallel dose and time profile to epithelial cell secretion of IL-8. Treatment with anti-IL-8 neutralizing antibody blocked >80% of the neutrophil chemotaxis in vitro. These results suggest that IL-8 is a key chemokine in acute ozone-induced airway inflammation in primates.


Prevalence of Yersinia species in goat flocks.
To investigate the epidemiology of Yersinia species in healthy goats in New Zealand, in particular to determine the prevalence of farms with infected goats, the prevalence of infected goats on those farms, the serotypes involved, and potential risk factors for carriage. A cross-sectional study of the prevalence of Yersinia infection in infected flocks in a study population of thirty commercial goat farms in the Manawatu region of New Zealand. Infection was detected on 60% of farms in an initial study. In a prevalence study on 18 infected farms, the study population comprised 6770 animals (mean of 376, median of 175 and range of 36 to 1295 goats/farm). Of 902 goats (296 < 1 year, 178 1 to 2 years, and 428 > 2 years) sampled from the study population, 135 (73 < 1 year, 21 1 to 2 years, and 41 > 2 years) were excreting Yersinia spp, giving an overall prevalence of 14.97% (95% confidence interval [CI]; 12.8 to 17.4) with individual farm prevalences ranging from 0.0 (+ 7.9) to 58.14% (95% Cl, 43.3 to 71.6). Goats < 1 year were more likely to be infected than 1-2 year and > 2 year old animals (relative risk [RR] = 2.1; 95% Cl, 1.3 to 3.3) and 2.6 (95% Cl, 1.8 to 3.6) respectively), but there was no significant difference between risks for 1 to 2 year and > 2 year goats (RR = 1.2; 95% CI, 0.7 to 2.0). Yersinia enterocolitica was the most common species isolated in the youngest age group, with prevalence declining with increasing age, while other species were more common in the older age groups. Yersinia infections were common in goats in the study region, with younger animals apparently more susceptible to infection and in particular to infection with Y enterocolitica. The prevalence on infected farms appeared to decrease as flock size increased and to increase as stocking rates and the number of paddocks grazed increased.


The rice blast fungus MoRgs1 functioning in cAMP signaling and pathogenicity is regulated by casein kinase MoCk2 phosphorylation and modulated by membrane protein MoEmc2.
GTP-binding protein (G-protein) and regulator of G-protein signaling (RGS) mediated signal transduction are critical in the growth and virulence of the rice blast pathogen Magnaporthe oryzae. We have previously reported that there are eight RGS and RGS-like proteins named MoRgs1 to MoRgs8 playing distinct and shared regulatory functions in M. oryzae and that MoRgs1 has a more prominent role compared to others in the fungus. To further explore the unique regulatory mechanism of MoRgs1, we screened a M. oryzae cDNA library for genes encoding MoRgs1-interacting proteins and identified MoCkb2, one of the two regulatory subunits of the casein kinase (CK) 2 MoCk2. We found that MoCkb2 and the sole catalytic subunit MoCka1 are required for the phosphorylation of MoRgs1 at the plasma membrane (PM) and late endosome (LE). We further found that an endoplasmic reticulum (ER) membrane protein complex (EMC) subunit, MoEmc2, modulates the phosphorylation of MoRgs1 by MoCk2. Interestingly, this phosphorylation is also essential for the GTPase-activating protein (GAP) function of MoRgs1. The balance among MoRgs1, MoCk2, and MoEmc2 ensures normal operation of the G-protein MoMagA-cAMP signaling required for appressorium formation and pathogenicity of the fungus. This has been the first report that an EMC subunit is directly linked to G-protein signaling through modulation of an RGS-casein kinase interaction.


Frequency Combs in a Lumped-Element Josephson-Junction Circuit.
We investigate the dynamics of a microwave-driven Josephson junction capacitively coupled to a lumped-element LC oscillator. In the regime of driving where the Josephson junction can be approximated as a Kerr oscillator, this minimal nonlinear system has been previously shown to exhibit a bistability in phase and amplitude. In the present study, we characterize the full phase diagram and show that besides a parameter regime exhibiting bistability, there is also a regime of self-oscillations characterized by a frequency comb in its spectrum. We discuss the mechanism of comb generation which appears to be different from those studied in microcavity frequency combs and mode-locked lasers. We then address the fate of the comblike spectrum in the regime of strong quantum fluctuations, reached when nonlinearity becomes the dominant scale with respect to dissipation. We find that the nonlinearity responsible for the emergence of the frequency combs also leads to its dephasing, leading to broadening and ultimate disappearance of sharp spectral peaks. Our study explores the fundamental question of the impact of quantum fluctuations for quantum systems which do not possess a stable fixed point in the classical limit.


Environmental and health data needed to develop national surveillance systems in industrially contaminated sites.
this paper is based upon work from COST Action ICSHNet. Public health surveillance (PHS) of industrially contaminated sites (ICSs) is likely to play a role in supporting the monitoring of harmful aspects of ICSs and related interventions. Environmental public health tracking (EPHT) has been proposed and developed as an approach to PHS when environmental factors affecting health are involved. to identify existing arrangements for continuous collection and analysis of environmental and health data to guide the development of an optimal EPHT approach which would support the characterization of the impact on health of ICS. a literature search was conducted in PubMed following a structured approach to identify methodological aspects relevant to surveillance of ICSs. In addition, eight further studies on this topic, mainly from three European Countries (Spain, Italy, and France), were included by the research team. the identified 17 examples of surveillance studies include a heterogeneous variety of industrial activities, covering from cross-national to local scenarios. Continuous monitoring systems for gathering environmental data related to ICSs were used only in two cases; a qualitative approach and/or punctual sampling for soil, air, and water of local foodstuff took place in the rest. Exposure assessment was conducted according to four main methods: qualitative definition for the presence/absence of a source, distance to a source, dispersion modelling, and biomonitoring. Health data relied on routinely vital statistics, hospital admission records, specific morbidity registers, and cancer and congenital abnormalities registries. our revision identified an overall lack of national surveillance programmes of ICSs, rather than gaps in individual dimensions of surveillance. The epidemiological approaches reviewed provided methods, some of which could be adopted for an EPHT in ICSs. However, a large proportion of examples suffers from poor exposure characterization, relying on a qualitative definition approach, which cannot account for the multiple pathways that take place in ICSs. Use of more individual data from health registries combined with improved environmental data collection and exposure assessment would improve future surveillance.


Lysosome-associated membrane glycoprotein (LAMP)--preliminary study on a hidden antigen target for vaccination against schistosomiasis.
Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. From these, we selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relatively high expression in the gastrodermis, their potentially important biological function, divergence from homologous molecules of the host and possible apical membrane expression in the gastrodermis. Bacterially expressed recombinant peptides corresponding to regions excluding trans-membrane domains of the selected vaccine targets were used in blinded vaccine trials in CBA mice using alum-CpG as adjuvant. Vaccine trials using the recombinant insoluble Sm-LAMP protein showed 16-25% significant reduction in total worm burden. Faecal egg count reduction was 52% and 60% in two trials, respectively, with similar results for the solubly expressed protein. Liver egg burden was reduced significantly (20% and 38%) with an insoluble recombinant Sm-LAMP in two trials, but not with the soluble recombinant form. Parasite fecundity was not affected by either Sm-LAMP protein preparations in the trials. It is concluded that Sm-LAMP may provide limited protection towards S. mansoni infections but could be used in combination with other vaccine candidates, to provide more comprehensive protection.


Skin sympathetic fiber α-synuclein deposits: a potential biomarker for pure autonomic failure.
This study aimed to test whether peripheral α-synuclein staining might be useful for pure autonomic failure (PAF) diagnosis, helping to differentiate degenerative from acquired peripheral autonomic neuropathy. We studied 21 patients with chronic peripheral autonomic neuropathy showing sympathetic and parasympathetic involvement as confirmed by cardiovascular reflexes and microneurography from the peroneal nerve. Twelve patients showed a specific cause of neuropathy (acquired autonomic neuropathy) whereas 9 had no specific acquired causes fulfilling the diagnostic criteria for PAF. Fifteen matched healthy subjects served as controls. Subjects underwent skin biopsy from thigh and leg to study skin innervation and phosphorylated α-synuclein deposits in the peripheral axons. Somatic and autonomic skin innervations were significantly decreased in patients with peripheral autonomic neuropathy compared to controls. No differences were found between acquired autonomic neuropathy and PAF. The deposits of α-synuclein were not found in controls but served to distinguish acquired from degenerative autonomic peripheral neuropathy: all patients with PAF showed α-synuclein deposits, which were absent in patients with acquired autonomic neuropathy. Colocalization study disclosed α-synuclein neuritic inclusions in the postganglionic sympathetic adrenergic and cholinergic nerve fibers. Our study demonstrated that a search for neuritic inclusions of phosphorylated α-synuclein in the skin sympathetic nerve fibers could provide a sensitive in vivo biomarker for degenerative peripheral autonomic neuropathy and may shed more light on the pathogenesis of PAF.


Dental caries and associated factors at age 12 in the Brazilian.
This study aims to analyze the index of decayed, missing and filled teeth (DMFT) at age 12 in the Midwest Region and to identify associated factors, according to the National Oral Health Survey "SB Brasil 2010". This is a cross-sectional population-based study from the SB Brasil 2010 database, conducted in the capitals of Mato Grosso, Mato Grosso do Sul, Goiás, Federal District and a sample of municipalities in the region. Data were analyzed by the chi-square test and prevalence ratios with their respective confidence intervals, at a significance level of 5%. The Poisson regression was used in the multiple analysis to study the association between the outcome variable and the explanatory variables. The independent variables that were associated with the DMFT were: the state of residence in Mato Grosso, Goiás and Mato Grosso do Sul; the per capita income ≤ R$500.00; difficulties eating and sleeping, and reason for the visit was Pain/Extraction/Treatment/Other. Mean DMFT was 2.14 and the prevalence of dental caries affected 41% of adolescents.


HOMOSTROPHIC REFLEX AND STEREOTROPISM IN DIPLOPODS.
1. With suitable arthropods, such as the diplopods, it can be shown that body orientation following passive unilateral tension involves the homostrophic reflex. The phenomenon is exhibited when the animal is quiescent and during forward locomotion, but nothing of the sort appears in backward locomotion. 2. Receptors for the homostrophic reflex are in the body wall and are distributed throughout the length of the animal. 3. The effector nerves take their origin from the ganglia of the head alone. 4. The diplopods are stereotropic, the head turning toward the side in contact with a solid surface only as long as some part of the body maintains contact. Under suitable conditions stereotropism may mask the homostrophic reflex. 5. When a diplopod is in contact with two lateral surfaces of equal extent the path upon emergence is a straight one, conforming to the law of the parallelogram of forces.


DAPSA, carotid plaque and cardiovascular events in psoriatic arthritis: a longitudinal study.
To examine whether Disease Activity in Psoriatic Arthritis (DAPSA) reflecting the inflammatory component of psoriatic arthritis (PsA) can predict cardiovascular (CV) events independent of traditional CV risk factors and subclinical carotid atherosclerosis. A cohort analysis was performed in patients with PsA who had been followed since 2006. The outcome of interest was first CV event. Four different CV disease (CVD) risk scores and DAPSA were computed at baseline. The presence of carotid plaque (CP) and carotid intima-media thickness (CIMT) was also determined in a subgroup of patients using high-resolution ultrasound. The association between DAPSA, CVD risk scores, CP, CIMT and the occurrence of CV events was assessed using Cox proportional hazard models. 189 patients with PsA (mean age: 48.9 years; male: 104 (55.0%)) were recruited. After a median follow-up of 9.9 years, 27 (14.3%) patients developed a CV event. Higher DAPSA was significantly associated with an increased risk of developing CV events (HR: 1.04, 95% CI (1.01 to 1.08), p=0.009). The association remained significant after adjusting for all CV risk scores in the multivariable models. In the subgroup analysis, 154 patients underwent carotid ultrasound assessment and 23 (14.9%) of them experienced a CV event. CP was associated with increased risk of developing CV events after adjusting for three CV risk scores and DAPSA, with HR ranging from 2.35 to 3.42. Higher DAPSA and the presence of CP could independently predict CVD events in addition to traditional CV risk scores in patients with PsA.


Mini-Mental State Examination among lower educational levels and illiterates: Transcultural evaluation.
Cognitive performance among illiterates and low educational levels is poorer than that observed in individuals with greater schooling. This difference can be a confounding factor in reaching an accurate diagnosis of cognitive impairment. In addition, there is great heterogeneity in performance among illiterates, probably due to different environmental demands and sociocultural backgrounds. Many reports have described the influence of education on neuropsychological measures and screening tests such as the Mini-Mental State Examination (MMSE). To analyze performance in two samples with the same educational level, but different social and cultural backgrounds. Subjects from two different locations in Brazil (rural sample from Northern region and urban sample residing in the largest city of the Southeastern region) were matched for age and education, and submitted to the MMSE. Significant differences between the groups were found in total scores on the MMSE and in temporal orientation and serial-sevens sub-items for which the urban sample performed best but analysis of illiterates alone yielded the same results, except for the copying pentagons task which was performed better by the rural sample. Cultural and social backgrounds, as well as demands from the environment, influence results of screening tests. Factors other than education must be taken into account when analyzing tests.


Unrelated queens coexist in colonies of the termite Macrotermes michaelseni.
Relatedness increases the likelihood of cooperation within colonies of social insects. Polygyny, the coexistence of numerous reproductive females (queens) in a colony, is common in mature colonies of the termite Macrotermes michaelseni. In this species, polygyny results from pleometrosis and from several female alates that jointly found a new colony. To explain this phenomenon, it was suggested that only related females cooperate and survive during maturation of colonies. Using multilocus fingerprints as well as microsatellites, we showed that nestmate queens in mature colonies are unrelated. Furthermore, we found that all nestmate queens contributed to the production of steriles. Even in mature colonies, several matrilines of steriles coexist within a colony. Although genetic diversity within colonies may increase the likelihood of conflicts, high genetic diversity may be important for foraging, colony growth, and resistance to disease and parasites.


Distinguishing between hidden testes and anorchia: the role of endocrine evaluation in infancy and childhood.
Non-palpable testes remain a diagnostic challenge, often involving exploratory laparoscopy. We evaluated the diagnostic value of a wide range of reproductive hormones in order to distinguish between bilateral cryptorchidism and bilateral anorchia. In this retrospective study, we identified and included 36 boys with non-palpable testes (20 with cryptorchidism, 3 with congenital hypogonadotropic hypogonadism (CHH), and 13 with anorchia) at first examination during childhood. Information on karyotype, phenotype, surgical results from laparoscopy, and biochemistry was retrieved from patient files. We compared serum concentrations of AMH, inhibin B, FSH, LH, testosterone, estradiol, and hCG stimulation testing in cryptorchid and anorchid boys to serum concentrations in a large, age-matched control group. Receiver-operating characteristic curves were used to determine the cut-off values of each reproductive hormone as a predictor of the presence of functional testicular tissue. Concentrations of AMH in 0-1 year olds: ≥155 pmol/L and >1-15 year olds: ≥19 pmol/L, inhibin B (≥22 pg/mL and ≥4 pg/mL), FSH (≤28.9 IU/L and ≤20.3 IU/L) and hCG-induced testosterone (>1-15 year olds: ≥2 nmol/L) were significantly sensitive and specific markers in predicting the presence of functional testicular tissue in boys with non-palpable testes. In infancy, anorchid infants had significantly elevated gonadotropin levels, while CHH had low levels. Our findings suggest that laparoscopy may not be necessary in all boys with non-palpable testes if reproductive hormones unequivocally confirm the presence of functional testicular tissue. However, proving the absence may still be a diagnostic challenge.


Real-life data on heart failure before and after implantation of resynchronization and/or defibrillation devices - the Síncrone study.
The aim of this study was to document clinical practice in Portugal regarding the use of electronic cardiac devices in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The Síncrone study was an observational prospective multicenter registry conducted in 16 centers in Portugal between 2006 and 2014. It included adult patients with a diagnosis of HF, LVEF <35% and indication for implantable cardioverter-defibrillator (ICD) and/or cardiac resynchronization therapy (CRT) devices, according to the recommendations of the European Society of Cardiology at the beginning of the study. Patients were followed for one year according to the practice of each center. A total of 486 patients were included in the registry, half of whom received an ICD and the other half a CRT pacemaker (CRT-P) or CRT defibrillator (CRT-D). Mean age was 65±12 years and the most frequent causes of HF were ischemic (47%) and idiopathic dilated cardiomyopathy (28%). Overall mortality at one year was 3.6% and the hospitalization rate was 11%, significantly higher in patients with CRT-P/CRT-D than with ICD (17% vs. 5.6%, p<0.001). Patients who received CRT-P/CRT-D experienced significant reductions in QRS duration (160±21 vs. 141±24 ms, p<0.001) as well as improvement in New York Heart Association functional class. The Síncrone study shows that the use of implantable devices in HF with reduced LVEF in Portugal is in accordance with international recommendations and that patients presented functional improvement and reduced one-year mortality.


Synergistic or antagonistic modulation of oviposition response of two swallowtail butterflies, Papilio maackii and P. protenor, to Phellodendron amurense by its constitutive prenylated flavonoid, phellamurin.
Papilio maackii females prefer a rutaceous plant, Phellodendron amurense, for oviposition, whereas another semi-sympatric Rutaceae feeder, Papilio protenor, never exploits this plant as a host in nature. However, the larvae of both species perform well on this plant in the laboratory. Phellamurin, a flavonoid present in the organic fraction from P. amurense inhibits egg laying by P. protenor. We examined whether phellamurin is involved in the differential acceptance of P. amurense by the two butterflies. The ovipositing females of P. maackii readily accepted P. amurense and a methanolic extract of the foliage, while P. protenor rejected them entirely. However, the aqueous fraction derived from the extract elicited significant oviposition responses of similar levels from the two species. Phellamurin did not induce oviposition behavior in P. protenor females. In contrast, P. maackii was stimulated to oviposit by phellamurin at concentrations exceeding 0.2%. The response was dose-dependent and reached ca. 70% at 2% phellamurin, which is approximately equivalent to its natural abundance in young leaves of P. amurense. Since the aqueous fraction was very stimulatory to both species, the combined effect of phellamurin and the aqueous fraction on oviposition was tested. The addition of phellamurin to the aqueous fraction enhanced the ovipositional activity of P. maackii, but dramatically suppressed the oviposition response of P. protenor even at 0.1% concentration. These results, taken together with those obtained from electrophysiological recordings with foretarsal chemosensilla, indicate that phellamurin acts as an oviposition stimulant for P. maackii, and as a potent deterrent for P. protenor. The results suggest that host range expansion or host shifts may be made by ovipositing females that overcome phytochemical barriers.


The penetration of methanol into bovine cardiac and hepatic tissues is faster than ethanol and formalin.
Methanol, ethanol and formalin are commonly used as fixatives to preserve biological tissues from decay in the preparation of histological sections. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether methanol penetrates tissues at similar rates to other fixatives. This study aimed to compare the penetration rates of methanol, ethanol and formalin into bovine heart and liver tissues. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of tissue before and after immersion in different fixatives for 1, 2, 6 or 10 h. Data were analysed using two-way ANOVA, followed by Bonferroni's post-hoc test. The penetration distance of methanol was significantly greater in both heart and liver tissues compared with that of ethanol (N=4, P<0.001). Methanol or ethanol immersion led to similar shrinkage of both tissues (P>0.05). The penetration rate of formalin was similar to that of ethanol in both tissues however it was significantly slower than methanol (N=4, P<0.005 in the heart; P<0.001 in the liver). The mean penetration coefficients of methanol, formalin and ethanol in the heart tissue were 2.609, 1.994 and 1.801, respectively, and 3.012, 2.153 and 2.113, respectively, in the liver tissue. The penetration coefficient of methanol was significantly greater than that of ethanol or formalin in both tissues (P<0.001 for each comparison). In conclusion, methanol penetrates tissue significantly faster than ethanol and formalin.