The Impact of Visual Impairment on Quality of Life.
Our goal was to identify and describe factors relating to quality of life (QOL) in subjects with low vision and blindness in Iran's Sistan and Baluchestan Province. This cross-sectional study was carried out in randomly selected subjects with vision disability who were covered by the Zahedan Welfare Organization in Zahedan, Iran. The following factors related to visual impairment were evaluated: visual field (VF), visual acuity (VA), and stereopsis. Data were collected using a demographic questionnaire and the Influence of Vision Impairment (IVI) questionnaire. One-hundred and twenty-one patients were enrolled for participation in the study. T-test analyses indicated that the mean QOL score for women was significantly lower than that for men (P < 0.001). Mann-Whitney U tests indicated that mean social (P = 0.003) and leisure (P = 0.009) QOL scores were significantly lower in participants without stereopsis. In addition, participants with tunnel vision scored lower on the mobility and self-care categories (P < 0.001) than others. The results of this study indicate that providing education, providing employment, improving, and expanding social programs for the blind and individuals with low vision people, especially women, are necessary.


Prediction models for evaluating the heavy metal uptake by spinach (Spinacia oleracea L.) from soil amended with sewage sludge.
The risk evaluation of polluted soil requires the application of precise models to predict the heavy metal uptake by plants so possible human risks can be identified. Therefore, the present work was conducted to develop regression models for predicting the concentrations of heavy metals in spinach plants from their concentration in the soil by using the organic matter content and soil pH as co-factors. The soil improved with sewage sludge was slightly alkaline and had a relatively high organic matter content. Similar to the soil analysis, Fe had the highest median concentration, while Cd had the lowest concentration in the roots and leaves. Heavy metals accumulated in the roots and leaves in the order Fe > Mn > Zn > Cu > Cr > Ni > Co > Pb > Cd. The bio-concentration factor of the investigated heavy metals, from soil to roots, did not exceed one. The spinach was recognized by a translocation factor <1.0 for all of the heavy metals except Zn. Plant heavy metal concentrations were positively correlated with the soil organic matter content and negatively correlated with soil pH. The leaf Cr, Fe and Zn and the root Cr, Fe, Pb and Zn concentrations were positively correlated with the respective soil heavy metals. In addition, a linear correlation was found between the bio-concentration factor of heavy metals and soil pH and organic matter content. Regression models with high model efficiency and coefficients of determination and low mean normalized average errors, which indicate the efficiency of the models, were produced for predicting the plant heavy metal contents by using the soil pH and organic matter content as co-factors.


Hypoxia induces autophagy in cardiomyocytes via a hypoxia-inducible factor 1-dependent mechanism.
Hypoxia frequently accompanies such vascular disorders as atherosclerosis, thrombosis and ischemia/reperfusion injury. Myocardial ischemia/reperfusion, in particular, is a major contributor to cardiomyocyte impairment. Autophagy is a dynamic, self-catabolic process that has been implicated in a wide range of physiological processes and the pathogenesis of diverse diseases. The aim of the present study was to investigate the promotion of autophagy by hypoxia in a rat H9c2 heart cell line and determine the regulatory role of hypoxia-inducible factor 1 (HIF-1) in the hypoxia-induced autophagy in H9c2 cells, using quantitative green fluorescent protein-microtubule-associated protein 1 light chain 3 analysis and electron microscopy of autophagic vesicles. In addition, western blot and quantitative polymerase chain reaction analysis of autophagy-associated markers was conducted. In addition, the role of HIF-1-mediated autophagy in the hypoxia-induced impairment of H9c2 cells was examined, as a measure of cellular viability, using an MTT assay. The results demonstrated that autophagy was induced in H9c2 cells under hypoxia, and the autophagy induction triggered by hypoxia could be enhanced by HIF-1α overexpression and inhibited by HIF-1α knockdown. Furthermore, the HIF-1-mediated autophagy ameliorated the reduction in the H9c2 cell viability induced by hypoxia. These findings provide a novel insight into the hypoxic-ischemic injury to cardiomyocytes and give evidence for the occurrence of HIF-1-mediated autophagy in myocardial ischemia.


The effects of dimensionality on electrochemical sensors based on carbon nanotubes and metallic nanowires.
Electrochemistry based unidimensional nanoelectrodes, such as carbon nanotubes and metallic nanowires, is now a reality that is leaving the academy and reaching a broad range of high-tech companies around the world. The intrinsic properties of electron-electron interactions, sizes and geometries significantly differentiate those nanostructures from conventional macroelectrodes or electrodes with sizes in a millimetric range. The inherent properties as well as the configuration of carbon nanotubes and metallic nanowires as electrochemical sensors are the main focus of this review. Applications and some future trends on developing of a clear pathway for assembly and integration of these into functional materials, are summarized as well.


Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells.
Plasma cells (PCs) derived from germinal centers (GCs) secrete the high-affinity antibodies required for long-term serological immunity. Nevertheless, the process whereby GC B cells differentiate into PCs is uncharacterized, and the mechanism underlying the selective PC differentiation of only high-affinity GC B cells remains unknown. In this study, we show that differentiation into PCs is induced among a discrete subset of high-affinity B cells residing within the light zone of the GC. Initiation of differentiation required signals delivered upon engagement with intact antigen. Signals delivered by T follicular helper cells were not required to initiate differentiation but were essential to complete the differentiation process and drive migration of maturing PCs through the dark zone and out of the GC. This bipartite or two-signal mechanism has likely evolved to both sustain protective immunity and avoid autoantibody production.


Nickel-Catalyzed Coupling of N-Sulfonyl-1,2,3-triazole with H-Phosphine Oxides: Stereoselective and Site-Selective Synthesis of α-Aminovinylphosphoryl Derivatives.
A nickel-catalyzed coupling of N-sulfonyl-1,2,3-triazole with various H-phosphine oxides for the construction of C(sp2)-P bonds is established. This unexpected reaction proceeds through a formal nickel-bound ketenimine pathway, representing a previously unknown 1,2-reactivity type of an azavinyl carbene. The method provides an efficient approach to the stereoselective and site-selective synthesis of α-aminovinylphosphoryl derivatives with moderate to good yield. A plausible mechanism is proposed based on experimental and theoretical studies.


The interrelationships between serotonin production and locomotion in different light regimes in southwestern Michigan opilionids, Leiobunum longipes.
The comparison was made of the effect of LL and DD with LD 14:10 photoperiods on the 24-h secretion cycle of serotonin secretion and the activity patterns of Leiobunum longipes from Southwestern Michigan. LL and DD altered the normal activity patterns but did not change the pattern of serotonin secretion. The activity pattern in normal photoperiod (LD 14:10) produced a 12-h cosinor pattern, resulting in a 24-h biphasic activity peak model. The activity peaked in both scotophase and photophase . The altered patterns in LL and DD were different. In LL a rhythmic component could not be statistically determined. A high, irregular level of activity was seen, higher than the mean level in LD. In DD a combined 24 and 48 h cosinor pattern best fit the observed data. The major peaks occurred in nature during every other photophase and alternate scotophase time in the constant photoperiod conditions. Serotonin secretion patterns in LD, LL, and DD statistically fitted a 24-h cosinor model. Peak secretion times occurred in mid photophase for LD and LL. A later photophase peak was seen in DD. LL animals showed a mean level of serotonin and secretion pattern which was not statistically different from LD. The hypothesis that LD photoperiods direct a peak of serotonin secretion which initiated the activity pattern could not be accepted.


Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.
Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy. Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed. During the study period, 1038 patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects. Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.


S-1-containing chemotherapy for patients with non-small-cell lung cancer: A population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group.
To evaluate the efficacy and safety of S-1 monotherapy, S-1-containing combined chemotherapy and S-1 containing chemoradiotherapy for non-small cell lung cancer (NSCLC), a population-based observational study was performed. The efficacy and safety of the chemotherapies were evaluated at 13 institutes in a prefecture of Japan between April 2011 and March 2015. Datasets were obtained from 282 patients with NSCLC. For either wild-type or mutated epidermal growth factor receptor (EGFR), these three therapy groups generated almost identical response results and toxicity profiles as those in previously reported clinical trials, although the present study appeared to have slightly lower survival rates compared with those in the previous clinical trials. This may be due to the inclusion of patients in poor condition, and S-1 therapy being administered in the second, or later, line of therapy. In conclusion, the present study has confirmed that S-1-containing chemotherapy is effective against wild- and mutated-type EGFR NSCLC, and it is also tolerable in clinical practice.


[Primary appendagitis epiploica: diagnosis and follow-up with CT (case report)].
Primary appendagitis epiploica is a rare benign self-limiting inflammatory condition of the colonic epiploic appendices. It causes acute localized abdominal pain thought to be the result of torsion or spontaneous vascular thrombosis of epiploic appendices. This is a non-surgical situation that clinically mimics other conditions requiring surgery such as acute diverticulitis or appendicitis. In this report, CT findings of this rare disease are presented at the stage of initial diagnosis and follow-up.


Effects of root exudates of woody species on the soil anti-erodibility in the rhizosphere in a karst region, China.
Rhizospheres, the most active interfaces between plants and soils, play a central role in the long-term maintenance of the biosphere. The anti-erodibility of soils (AES) regulated by the root exudates is crucial to the soil stability in the rhizospheres. However, scientists still debate (1) the key organic matter of the root exudates affecting the AES and (2) the interspecific variation of these root exudates. We used an incubation of soils to test the effects of the root exudates from eight woody plant species on the change in soil aggregation and identified the organic matter in these root exudates with gas chromatography-mass spectrometry (GC-MS) and biochemical methods. Furthermore, the relationships between the organic matter in the exudates and the AES in the rhizospheres of 34 additional tree species were analyzed. The water-stable aggregates of the soils incubated with the root exudates increased by 15%-50% on average compared with control samples. The interspecific differences were significant. The root exudates included hundreds of specific organic matter types; hydrocarbon, total sugar, total amino acids, and phenolic compounds were crucial to the AES. These organic matter types could explain approximately 20-75% of the variation in the total effect of the root exudates on the AES, which was quantified based on the aggregate status, degree of aggregation, dispersion ratio, and dispersion coefficient. The effects of the root exudates on the AES and the interspecific variation are as important as that of root density, litters, and vegetation covers. Many studies explored the effects of root density, litters, vegetation covers, and vegetation types on the AES, but little attention has been paid to the effects of the root exudates on the AES. Different plants secrete different relative contents of organic matter resulting in the variation of the effect of the root exudates on the AES. Our study quantified the causal relationships between the root exudates and the AES using modeling experiments in laboratory and field observations and indicated the interspecific variation of the AES and organic matter of the root exudates. More organic compounds of the exudates related to the AES were recognized in this study. These results enhance the understanding of the soil stability at a slope and can be applied to ecosystem restoration.


Genetic variability of hepatitis A virus isolates in Rio de Janeiro: implications for the vaccination of school children.
The epidemiology of hepatitis A virus (HAV) infection is shifting from high to intermediate endemicity in Brazil, resulting in increased numbers of susceptible individuals and a greater potential for the emergence of outbreaks. Universal vaccination against HAV has been recommended for children, but updated sero-epidemiological data are necessary to analyze the level of natural immunity and to identify candidates for preventive measures. In addition, more molecular studies are necessary to characterize the genotypes involved in HAV infections and outbreaks. Sera from 299 school children (5-15 years old) and 25 school staff members, collected during an outbreak of HAV at a rural public school in June 2000, were tested for IgM and total anti-HAV antibodies (ELISA). Viral RNA was amplified by RT-PCR from anti-HAV IgM-positive sera and from 19 fecal samples. Direct nucleotide sequencing of the VP1/2A region was carried out on 18 PCR-positive samples. Acute HAV infection was detected by anti-HAV IgM in 93/299 children and in 3/25 adult staff members. The prevalence of total anti-HAV antibodies in IgM-negative children under 5 years of age was only 10.5%. HAV-RNA was detected in 46% IgM-positive serum samples and in 16% stool samples. Sequence analysis showed that half the isolates belonged to subgenotype IA and the other half to IB. On the basis of these data, mass vaccination against HAV is recommended without prevaccination screening, especially for children before they enter school, since nearly 90% of the children under 5 years were susceptible. Molecular characterization indicated the endemic circulation of specific HAV strains belonging to subgenotypes IA and IB.


Prescription opioid initiation, correlates, and consequences among a sample of OEF/OIF military personnel.
Prescription opioid (PO) misuse represents a major health risk for many service members and veterans. This paper examines the pathways to misuse among a sample of U.S. veterans who recently returned from Iraq and Afghanistan to low-income, predominately minority sections of New York City. Recreational PO misuse was not common on deployment. Most PO misusers initiated use subsequent to PO use for pain management, an iatrogenic pathway. However, most PO users did not misuse them. Veterans that misused POs were more likely to have other reintegration problems including drug and alcohol use disorders, traumatic brain injury (TBI), unemployment, and homelessness.


Understanding droplet jetting on varying substrate for biological applications.
In the inkjet printing process, the droplet experience two phases, namely the jetting and the impacting phases. In this review article, we aim to understand the physics of a jetted ink, which begins during the droplet formation process. Following which, we highlight the different impacts during which the droplet lands on varying substrates such as solid, liquid, and less commonly known viscoelastic material. Next, the article states important process-specific considerations in determining the success of inkjet bioprinted constructs. Techniques to reduce cell deformation throughout the inkjet printing process are highlighted. Modifying postimpact events, such as spreading, evaporation, and absorption, improves cell viability of printed droplet. Last, applications that leverage on the advantage of pixelation in inkjet printing technology have been shown for drug screening and cell-material interaction studies. It is noteworthy that inkjet bioprinting technology has been integrated with other processing technologies to improve the structural integrity and biofunctionality of bioprinted construct.


Knowledge, Attitude and Practice (KAP) Assessment on LifeStyle, Public Health Measures Practiced by Society and Their Impact to Contain COVID-19 Transmission Among Afar Community in Selected Parts of Afar Region, Ethiopia.
Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus, RNA family. It has continued to spread across the world after its first outbreak in China in 2019. On 11 March 2020 the WHO declared COVID-19 a pandemic given its global public health and economic impacts. To assess knowledge, attitude and practice (KAP) on lifestyle, public health measures practiced by society and their impact to contain COVID-19 transmission in the Afar community, Afar Region, Ethiopia. Community-based cross-sectional study design was conducted from May to July, 2020, on purposively selected districts and the Peasant Association (PA). Simple random sampling was applied to select households and study participants. Structured and semi-structured questionnaire was used to collect information from study participants. The collected data were entered into Microsoft Excel and transferred to SPSS version 20 for analysis. Both descriptive and analytical analysis was provided and a p-value of less than 0.05 was considered as statistically significant. Of the total (266) study participants, most of them had no formal education (61.7%) and were aged from 35-40 (34.2%). More than half, 67.7% and 56.8%, of participants did not know chewing chat and smoking cigarettes as a risk factor for COVID-19, respectively. Almost half, 49.6%, of participants live in a house which is non-partitioned and without ventilation. The participants were took part in public gatherings such as funerals (27.1%), weddings (13.9%), meetings (13.5%) and went to a market (9%) during the pandemic. Nearly half (47.7%) of the study participants did not wear facemasks. Of the total, 27.4% and 71.4% participants lost their daily income more than and less than half, respectively. This study revealed knowledge, attitude and practice of the community in the area to contain COVID-19 spread were minimal. Therefore, more improvement of public health measures will be required.


The concept of double bundle ACL simulation with a single bundle patellar tendon graft. A cadaveric feasibility study.
There is significant interest in the restoration of the double-bundle anatomy of the native ACL when performing ACL reconstruction. Possible techniques include those utilizing two separate grafts with independent tunnels and those that attempt to mimic this anatomy with a single graft and fewer tunnels. Many of the latter techniques require specific instrumentation and are technically challenging. We demonstrate that the double-bundle anatomy of the native ACL can theoretically be mimicked by a single-bundle reconstruction. We performed single bundle ACL reconstruction with a bone-patellar tendon-bone (BTB) graft in two cadaveric knees. Both grafts were placed to mimic the native ACL footprints - one reconstruction was performed with rectangular bone blocks and oval tunnels and one was performed utilizing a standard BTB graft and round tunnels. Qualitative assessment of graft behavior was made as the knees were taken through a range of motion. The ACL graft was able to qualitatively mimic the behavior of the native ACL in both knees provided the bone blocks were correctly orientated. ACL reconstruction with a single BTB graft can qualitatively mimic the behavior of the two bundles of the native ACL. The key to ensuring this behavior was noted to be appropriate orientation of the graft in the tunnels. Quantitative biomechanical investigations are necessary to evaluate the impact of graft orientation on function.


[Uterine fibroids embolization: results about 454 cases].
To determine the effectiveness of uterine arterial embolization (UAE) as primary treatment in the management of symptomatic leiomyomas. UAE was performed on 454 patients (age range: 21-68) with menorrhagia, bulk-related symptoms or both, due to leiomyomas. The effectiveness of this therapy in the control of symptoms and reduction of uterine and leiomyoma volume was measured by clinical and imaging controls at 3, 6 and 9 months after the procedure. Four hundred and thirty-three patients were evaluated, and 42 failures were observed (9.6%). Six months after the procedure, 391 patients were symptom-free. Follow-up ultrasonic examination showed an average reduction of 55% in dominant myoma volume at 6 months, 70% at 1 year. Twenty-seven women became pregnant (30 pregnancies). Complications related to procedure, and requiring surgery, occurred in three cases. Principal complications are amenorrhoea and fibroid sloughs. Severe complications are rarely found. UAE is an efficient therapy in the management of symptomatic myomas and proves to be a valid alternative to surgical procedure. The future of this mini-invasive and conservative technique appears to be a very promising one.


Orthokeratology. Part II: Evaluating the Tabb method.
This summary of the experimental design and methodology of a study evaluating ocular response to orthokeratology presents a method of orthokeratology that involves modifying the optic zone diameter, intermediate, and peripheral curve zones of a PMMA contact lens. An evaluation of the Tabb method of orthokeratology to determine the ocular tissue changes most responsible for observed refractive and acuity changes found that noncorneal parameters measured did not change, whereas two corneal parameters measured did change as orthokeratology occurred. The corneal parameters that appeared most involved in refractive and acuity changes were corneal thickness and shape factor. The Tabb method of orthokeratology did not cause an increase in corneal with-the-rule astigmatism.


Glucocorticoid receptor binding to calf thymus DNA. 2. Role of a DNA-binding activity factor in receptor heterogeneity and a multistep mechanism of receptor activation.
In the preceding paper [Cavanaugh, A. H., & Simons, S. S., Jr. (1990) Biochemistry (preceding paper in this issue)], we characterized an apparently identical factor in the cytosol and the nuclear extract of HTC cells that is required for the DNA binding of approximately 43% of the activated receptor-glucocorticoid complexes. In the present study, both those activated complexes that are influenced by this factor and the role of this factor in the process of activation are examined. We find that sodium arsenite inhibits only the DNA binding of those complexes that require factor. Conversely, methyl methane-thiolsulfonate inhibits the DNA binding of only those complexes that are independent of factor. These results provide direct chemical evidence for two populations of activated complexes. Double-reciprocal plots revealed that the increase in DNA binding with endogenous factor occurred by recruiting new complexes for DNA binding as opposed to increasing the binding affinity of existing complexes. These results further suggest that factor associates only with the receptor-steroid complex and does not additionally interact with DNA. A saturable association of factor with complexes was indicated since the amount of available factor in cytosolic solutions decreased after activation of the complexes. Sodium molybdate is known to inhibit the activation of HTC cell receptor-steroid complexes. When factor was added to complexes that had been subjected to activating conditions in the presence of the inhibitor sodium molybdate, no increased DNA binding was observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Peritumoral Cbl is a strong independent prognostic marker after curative resection of hepatocellular carcinoma.
Growing evidences support the concept that peritumoral microenvironment gene expression is an important element for physicians to make an accurate prognosis. Nonetheless, the correlation between peritumoral ubiquitin ligases and the hepatocellular carcinoma (HCC) survival remains unclear till this present. The expression of intratumoral and peritumoral Casitas B-lineage Lymphoma (Cbl) and epidermal growth factor receptor (EGFR) in hepatocellular carcinomas (HCCs) followed by curative resection was assessed by tissue microarray-based immune-histochemistry in two independent cohorts (n = 352). Their respective prognostic values and other clinicopathologic factors were then evaluated. The peritumoral Cbl density, much higher than that in intratumoral tissue, was an independent prognostic factor for overall survival (P < 0.001) and time to recurrence (P < 0.001) of HCCs after curative resection. The hazard ratio were 1.587 and 1.689, respectively. However, there was no correlation between intratumoral Cbl and prognosis. The peritumoral Cbl was also associated with prognosis even in HCC subgroups with small tumor size, negative AFP, without microvascular invasion and negative HBeAg. After a thorough analysis pertaining to the key role of Cbl on ubiquitination and degradation of activated receptor tyrosine kinases, we eventually discovered the negative correlation between peritumoral Cbl and EGFR (P = 0.015). Furthermore, the combination of peritumoral Cbl and EGFR serves as a much stronger indicator to make an accurate prognosis, especially during early recurrence (P < 0.001). These findings suggest that low expression of peritumoral Cbl and EGFR were positively associated with tumor size, microvascular invasion and patients survival after hepatectomy, highlighting the key role of peritumoral liver milieu in HCC progression.


Multiple pals gene modules control a balance between immunity and development in Caenorhabditis elegans.
The immune system continually battles against pathogen-induced pressures, which often leads to the evolutionary expansion of immune gene families in a species-specific manner. For example, the pals gene family expanded to 39 members in the Caenorhabditis elegans genome, in comparison to a single mammalian pals ortholog. Our previous studies have revealed that two members of this family, pals-22 and pals-25, act as antagonistic paralogs to control the Intracellular Pathogen Response (IPR). The IPR is a protective transcriptional response, which is activated upon infection by two molecularly distinct natural intracellular pathogens of C. elegans-the Orsay virus and the fungus Nematocida parisii from the microsporidia phylum. In this study, we identify a previously uncharacterized member of the pals family, pals-17, as a newly described negative regulator of the IPR. pals-17 mutants show constitutive upregulation of IPR gene expression, increased immunity against intracellular pathogens, as well as impaired development and reproduction. We also find that two other previously uncharacterized pals genes, pals-20 and pals-16, are positive regulators of the IPR, acting downstream of pals-17. These positive regulators reverse the effects caused by the loss of pals-17 on IPR gene expression, immunity, and development. We show that the negative IPR regulator protein PALS-17 and the positive IPR regulator protein PALS-20 colocalize inside and at the apical side of intestinal epithelial cells, which are the sites of infection for IPR-inducing pathogens. In summary, our study demonstrates that several pals genes from the expanded pals gene family act as ON/OFF switch modules to regulate a balance between organismal development and immunity against natural intracellular pathogens in C. elegans.


The occurrence and sources of natural antibody in human bile and serum against the O antigens of two Escherichia coli serotypes.
Paired serum and bile samples from normal subjects as well as patients with biliary disease were tested for natural antibody to two individual Escherichia coli O antigens by ELISA. Serum antibody was most commonly of IgM and IgG class. Antibody was less frequently detected in bile and was more commonly IgM than IgA, with IgG activity detected infrequently. Little relation was apparent between antibody in paired samples; activity could be present in both serum and bile or in either fluid alone. Titres in paired samples also did not correspond when 'normalized' with respect to the concentrations of relevant isotypes; bile was frequently enriched for natural antibody as a proportion of total immunoglobulin compared with serum. Secretory component-bound antibody was detectable in some biles that contained IgA and/or IgM activity and in the serum of 33% of subjects with biliary disorders but not in normal sera. A series of paired samples taken from three individuals was also examined for antibody against each subject's own intestinal commensal E. coli. Serum IgM and IgG activity was present in all samples, but antibody in bile was less frequent and was of IgM or IgA class. These results suggest that natural antibody in human bile occurs independently of antibody in serum and that it is substantially derived from local sources.


Endophthalmitis caused by gram-positive bacteria resistant to vancomycin: Clinical settings, causative organisms, antimicrobial susceptibilities, and treatment outcomes.
To report the clinical settings, causative organisms, antimicrobial susceptibilities, and treatment outcomes of patients with endophthalmitis caused by gram-positive bacteria resistant to vancomycin. Retrospective case series of all patients with culture-proven endophthalmitis caused by gram-positive bacteria resistant to vancomycin between January 2010 and December 2016 in LV Prasad Eye Institute, Visakhapatnam, India. The current study included 14 patients. The clinical settings were post-cataract surgery in 8/14 (57.1%) and open globe injury in 6/14 (42.8%). Primary intervention for all patients included tap and intravitreal antibiotic injection. During subsequent follow-up, pars plana vitrectomy was performed in 6 patients and one patient underwent penetrating keratoplasty. Mean number of intravitreal antibiotic injections performed were 3.4 per patient. The most common organisms isolated were coagulase-negative Staphylococci in 6/14 (42.8%), Staphylococcus aureus in 5/14 (35.7%), Streptococcus sp in 2/14 (14.2%) and Bacillus sp in 1/14 (7.14%). In addition to vancomycin, resistance to multiple drugs (three or more groups of antibiotics) was found in all 14 cases. Antimicrobial susceptibility results showed susceptibility to amikacin in 7/14 (50.0%), gatifloxacin in 6/14 (42.8%), moxifloxacin in 3/13 (23.0%), cefazoline in 5/14 (35.7%), cefuroxime in 3/14 (21.4%), ciprofloxacin in 2/14 (14.2%) and linezolid in 5/5 (100%). The mean duration of follow-up was 30.7 weeks (6 weeks-90 weeks). At last follow-up, visual acuity (VA) of 20/200 or better was recorded in 7/14 (50%) and VA < 5/200 occurred in 7/14 (50%). Antimicrobial susceptibility testing may help in selection of suitable antimicrobial agents for repeat intravitreal injection. Inspite of retreatment with intravitreal antibiotics, these patients generally had poor VA outcomes.


Prognostic Value of Intrinsic Subtypes in Hormone Receptor-Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib.
The value of the intrinsic subtypes of breast cancer (luminal A, luminal B, human epidermal growth factor receptor 2 [currently known as ERBB2, but referred to as HER2 in this study]-enriched, and basal-like) in the metastatic setting is currently unknown. To evaluate the association of the intrinsic subtypes of breast cancer with outcome and/or benefit in hormone receptor (HR)-positive metastatic breast cancer. Unplanned retrospective analysis of 821 tumor samples (85.7% primary and 14.3% metastatic) from the EGF30008 phase 3 clinical trial (NCT00073528), in which postmenopausal women with HR-positive invasive breast cancer and no prior therapy for advanced or metastatic disease were randomized to letrozole with or without lapatinib, an epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor. Tumor samples were classified into each subtype using the research-based PAM50 classifier. Prior neoadjuvant/adjuvant antiestrogen therapy was allowed. Patients with extensive symptomatic visceral disease were excluded. Treatment effects were evaluated using interaction tests. Primary and secondary end points were progression-free survival and overall survival. The median (range) age was 62 (31-94) years. Intrinsic subtype was the strongest prognostic factor independently associated with progression-free survival and overall survival in all patients, and in patients with HER2-negative (n = 644) or HER2-positive (n = 157) diseases. Median progression-free survival differed across the intrinsic subtypes of clinically HER2-negative disease: luminal A (16.9 [95% CI, 14.1-19.9] months), luminal B (11.0 [95% CI, 9.6-13.6] months), HER2-enriched (4.7 [95% CI, 2.7-10.8] months), and basal-like (4.1 [95% CI, 2.5-13.8] months). Median OS also differed across the intrinsic subtypes: luminal A (45 [95% CI, 41-not applicable {NA}] months), luminal B (37 [95% CI, 31-42] months), HER2-enriched (16 [95% CI, 10-NA] months), and basal-like (23 [95% CI, 12-NA] months). Patients with HER2-negative/HER2-enriched disease benefited from lapatinib therapy (median PFS, 6.49 vs 2.60 months; progression-free survival hazard ratio, 0.238 [95% CI, 0.066-0.863]; interaction P = .02). This is the first study to reveal an association between intrinsic subtype and outcome in first-line HR-positive metastatic breast cancer. Patients with HR-positive/HER2-negative disease with a HER2-enriched profile may benefit from lapatinib in combination with endocrine therapy. The clinical value of intrinsic subtyping in hormone receptor-positive metastatic breast cancer warrants further investigation, but patients with luminal A/HER2-negative metastatic breast cancer might be good candidates for letrozole monotherapy in the first-line setting regardless of visceral disease and number of metastases.


Harvesting of organs: the nursing issues.
The RCN Congress of 1991 discussed the ethics of harvesting' organs from patients who are brainstem dead but whose organs are being kept viable (through technological means) to enable them to be removed for transplantation. This review of the legal, ethical and nursing implications of organ harvesting is intended to act as a framework for local discussion and policy formulation.


A blessing in disguise: resolution of tardive dyskinesia with development of cervical myelitis.
Tardive dyskinesia (TD), which is frequently seen in patients treated with dopamine receptor blocking agents, is difficult to manage. We report on a young Chinese man with bipolar disorder who developed TD after haloperidol treatment, involving the trunk, limbs, and orofacial area. TD persisted despite switching to atypical antipsychotic agents and treatment with valproate, benzodiazepines, and tetrabenazine. Resolution only occurred years later when he developed quadriplegia arising from infective myelitis of the cervical cord (C4-5). He had concomitant vertebral osteomyelitis, which was successfully treated with intravenous antibiotics. With intensive rehabilitation, he recovered the use of his limbs, but had no recurrence of TD. We attribute the resolution of orofacial dyskinesias with a cervical lesion to the interconnections between the orofacial area and cervical spine via the trigeminal nucleus (which has fibers descending as far caudally as C6), as well as to resetting of cortical maps.


Standardization of the Feulgen reaction: the influence of chromatin condensation on the kinetics of acid hydrolysis.
The purpose of the present study was to investigate the influence of chromatin compactness on the kinetics of acid hydrolysis in the Feulgen reaction in cytology. Tissue imprints of rabbit liver, of human bronchial carcinoma and of human blood smears, fixed with alcohol, formaldehyde or with Böhm's solution with and without prior air drying, were stained with a standardized pararosanilin-Feulgen reagent. The time for hydrolysis varied between 7.5 and 120 min. The integrated optical density (IOD) of the cell nuclei was measured with an image analyzer (IBAS 2000). Cells with condensed chromatin (lymphocytes, small cell carcinoma, formaldehyde fixed cells) showed a slow increase of staining intensity and late plateau phase as compared with cells with decondensed chromatin. DNA in condensed nuclei was less susceptible to acid hydrolysis. The degree of chromatin compactness which determines the sensitivity of DNA to hydrolysis is influenced by the type of fixation, cell type and by the functional status of the cell. The conclusion is that Feulgen staining intensities of cells with different degrees of chromatin compactness cannot be compared unless measured in the respective plateau phases of the relevant hydrolysis curves which must be determined individually for each cell type.


Neural correlates to automatic behavior estimations from RGB-D video in epilepsy unit.
To augment neural monitoring, a minimally intrusive multi-modal capture system was designed and implemented in the epilepsy clinic. This system provides RGB-D audio-video synchronized with patient electrocorticography (ECoG), which records neural activity across cortex. We propose an automated approach to studying the human brain in a naturalistic setting. We demonstrate coarse functional mapping of ECoG electrodes correlated to contralateral arm movements. Motor electrode mapping was generated by analyzing continuous movement data recorded over several hours from epilepsy patients in hospital rooms. From these recordings we estimate the kinematics of patient hand movement behaviors using computer vision algorithms. We compare movement behaviors to neural data collected from ECoG, specifically high-γ (70-110 Hz) spectral features. We present a functional map of electrode responses to natural arm movements, generated using a statistical test. We demonstrate that our approach has the potential to aid in the development of automated functional brain mapping using continuous video and neural recordings of patients in clinical settings.


Gabapentin and methylphenidate treatment of a preadolescent with attention deficit hyperactivity disorder and bipolar disorder.
Gabapentin is an anticonvulsant drug released in the United States in 1993 for use as adjunctive therapy in refractory partial epilepsy. The mechanism of action of gabapentin is unknown, but the drug has very favorable pharmacokinetics and a good safety profile, which allows its use in high-risk patients. Several reports have described the successful use of gabapentin for bipolar disorders in adults, but there are no controlled studies in the use of gabapentin in children and adolescents. We describe a 12-year-old boy with a history of attention deficient hyperactivity disorder (ADHD), reading disorder, mixed receptive and expressive language disorder, encopresis, and bipolar disorder II who was treated with gabapentin 200 mg/day added to methylphenidate 30 mg/day. Within 3 weeks the improvement and stabilization of mood symptoms was remarkable, as noted by mother, teacher, and clinician, and remained so for 6 months of follow-up. Comorbid bipolar disorder and ADHD is a hotly debated topic in the child and adolescent psychiatric literature, with rates of comorbid ADHD and bipolar disorder ranging from 22% to 90%. Controlled studies are needed to evaluate the possible antimanic mood stabilizing and/or antidepressant properties or gabapentin in youths.


Interaction Analysis of Adenovirus L5 Protein With Pancreatic Cancer Cell Surface Receptor to Analyze Its Affinity for Oncolytic Virus Therapy.
This study seeks to investigate the interaction profile of the L5 protein of oncolytic adenovirus with the overexpressed surface receptors of pancreatic cancer. This is an important area of research because pancreatic cancer is one of the most fatal malignancies with a very low patient survival rate. Multiple therapies to date to improve the survival rate are reported; however, they show a comparatively low success rate. Among them, oncolytic virus therapy is a type of immunotherapy that is currently under deliberation by researchers for multiple cancer types in various clinical trials. Talimogene laherparepvec (T-VEC) is the first oncolytic virus approved by the US Food and Drug Administration (FDA) for melanoma. The oncolytic virus not only kills cancer cells but also activates the anticancer immune response. Therefore, it is preferred over others to deal with aggressive pancreatic cancer. The efficacy of therapy primarily depends on how effectively the oncolytic virus enters and infects the cancer cell. Cell surface receptors and their interactions with virus coat proteins are a crucial step for oncolytic virus entry and a pivotal determinant. The L5 proteins of the virus coat are the first to interact with host cell surface receptors. Therefore, the objective of this study is to analyze the interaction profile of the L5 protein of oncolytic adenovirus with overexpressed surface receptors of pancreatic cancer. The L5 proteins of three adenovirus serotypes HAdV2, HAdV5, and HAdV3 were utilized in this study. Overexpressed pancreatic cancer receptors include SLC2A1, MET, IL1RAP, NPR3, GABRP, SLC6A6, and TMPRSS4. The protein structures of viral and cancer cell protein were docked using the High Ambiguity Driven protein-protein DOCKing (HADDOCK) server. The binding affinity and interaction profile of viral proteins against all the receptors were analyzed. Results suggest that the HAdV3 L5 protein shows better interaction as compared to HAdV2 and HAdV5 by elucidating high binding affinity with 4 receptors (NPR3, GABRP, SLC6A6, and TMPRSS4). The current study proposed that HAdV5 or HAdV2 virus pseudotyped with the L5 protein of HAdV3 can be able to effectively infect pancreatic cancer cells. Moreover, the current study surmises that the affinity maturation of HAdV3 L5 can enhance virus attachment with all the receptors of cancer cells.


HIV-1 trans activator of transcription protein elicits mitochondrial hyperpolarization and respiratory deficit, with dysregulation of complex IV and nicotinamide adenine dinucleotide homeostasis in cortical neurons.
HIV-1 causes a common, progressive neurological disorder known as HIV-associated dementia (HAD). The prevalence of this disorder has increased despite the use of highly active antiretroviral therapy, and its underlying pathogenesis remains poorly understood. However, evidence suggests that some aspects of HAD may be reversible. To model the reversible aspects of HAD, we have used the HIV-1 neurotoxin trans activator of transcription protein (Tat) to investigate nonlethal changes in cultured neurons. Exposure of rodent cortical neurons to sublethal concentrations of Tat elicits mitochondrial hyperpolarization. In this study, we used the cationic lipophilic dye rhodamine 123 to confirm this observation, and then performed follow-up studies to examine the mechanism involved. In intact neurons, we found Tat elicited a rapid drop in internal mitochondrial pH, and addition of Tat to purified mitochondrial extracts inhibited complex IV of the electron transport chain. To correlate enzyme activity in mitochondrial extracts with results in intact cells, we measured neuronal respiration following Tat exposure. Cortical neurons demonstrated decreased respiration upon Tat treatment, consistent with inhibition of complex IV. We examined mitochondrial Ca(2+) homeostasis using a mitochondrial targeted enhanced yellow fluorescent protein-calmodulin construct. We detected a decrease in mitochondrial calcium concentration following exposure to Tat. Finally, we measured the energy intermediate NAD(P)H after Tat treatment, and found a 20% decrease in the autofluorescence. Based on these findings, we suggest that decreased NADPH and calcium concentration contribute to subsequent respiratory decline after exposure to Tat, with detrimental effects on neuronal signaling.


Sport and exercise headache: Part 1. Prevalence among university students.
Sport- and exercise-related headaches have been recognized over the last 20 years, but their prevalence is unknown. A nine-page questionnaire was used to study the prevalence of sports headaches among two contrasting populations of Otago University students: medical students (n = 178) and physical education students (n = 190). Both populations had a similar response rate of approximately 80%. It was found that 35% of respondents had experienced sport- and exercise-related headaches among the two populations, with similar rates for men and women seen in both. Comparison of the two populations showed no significant difference in the rate of sports headache among women, whereas the men physical education students has a significantly higher rate of sports headache than the men medical students. A high frequency of trauma-related headaches in contact sports accounted for this higher rate among the men physical education students. This study demonstrated that sport-and exercise-related headaches are a common problem among university students.


Patterns of drainage and recurrence following sentinel lymph node biopsy for cutaneous melanoma of the head and neck.
To analyze lymphatic drainage patterns and recurrence patterns in patients undergoing sentinel lymph node biopsy (SLNB) for cutaneous head and neck melanoma. Retrospective review of a consecutive series with a mean follow-up of 35 months. Tertiary cancer care center. Fifty-one patients with clinically node-negative cutaneous melanoma of the head and neck region staged by means of SLNB. Sentinel lymph nodes (SLNs) were identified using preoperative lymphatic mapping along with intraoperative gamma probe evaluation and isosulfan blue dye injection. Patients with a positive SLNB finding by hematoxylin-eosin or immunohistochemical evaluation underwent completion lymphadenectomy of the affected lymphatic basin and were considered for further adjuvant treatment. Patients with a negative SLNB finding were observed clinically. Location characteristics of SLNs, incidence of positive SLNs, same-basin recurrence, and disease-free survival. The mean number of SLNs per patients was 2.75. The extent of SLNB included removal of 1 node (n = 11), multiple nodes from 1 basin (n = 18), 1 node in multiple basins (n = 7), and multiple nodes in multiple basins (n = 15). Drainage to unexpected basins was found in 13 of 51 patients. Parotid region drainage was identified in 18 patients. There were no same-basin recurrences in patients with a negative SLNB finding. Thirty-six-month disease-free survival was 88.9% for patients with a negative SLN and 72.9% for patients with a positive SLN (P=.17). The number and location of SLNs is variable and difficult to predict for head and neck cutaneous melanoma. Preoperative lymphoscintigraphy is an important planning instrument to guide complete removal of all SLNs. Based on 3-year follow-up, this procedure can be expected to provide low same-basin recurrence rates for patients with a negative SLN.


5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer.
5-FU is used as the main backbone of chemotherapy regimens for patients with colorectal and other gastrointestinal cancers. Despite development of new strategies that allowed enhancing clinical effectiveness and tolerability of 5-FU, 10-30% of patients treated with 5-FU-based regimens experience severe treatment-related toxicity. In our study, we evaluated the 5-FU exposure-toxicity relationship and investigated the efficacy of PK-guided dosing in increasing tolerability of 5-FU-based chemotherapy. 50.7% of patients required dose adjustments after cycle 1. Percentage of patients within 5-FU AUC range was 49.3%, 66.9%, 61.0% at cycle 1, 2 and 3 respectively (p = 0.002 cycle 1 vs cycle 2). At all 3 cycles, lower incidences of grade I/II toxicities were observed for patients below or within range compared with those above range (19.4% vs 41.3%, p < 0.001 respectively). Our analysis confirms that the use of BSA-guided dosing results in highly variable 5-FU exposure and strongly suggests that PK-guided dosing can improve tolerability of 5-FU based chemotherapy in patients with gastrointestinal cancers, thus supporting 5-FU therapeutic drug monitoring. 155 patients with gastrointestinal cancers, who were to receive 5-FU-based regimens were included in our study. At cycle 1, the 5-FU dose was calculated using patient's Body Surface Area (BSA) method. A blood sample was drawn on Day 2 to measure 5-FU concentration. At cycle 2, the 5-FU dose was adjusted using a PK-guided dosing strategy targeting a plasma AUC range of 18-28 mg·h/L, based on cycle 1 concentration. Assessments of toxicity was performed at the beginning of every cycle.


Awareness of testicular cancer in New Zealand men.
Testicular cancer is the most common malignancy in young men and is frequently associated with delays in presentation. It has been postulated that ignorance and poor awareness of this type of cancer may contribute to such delays, which may result in high stage disease and subsequent treatment-related morbidity. This study was undertaken to assess the level of awareness of testicular cancer in a sample of 500 men from Wellington, New Zealand, and to specifically examine awareness related to the age, race, and socio-economic level of the respondents. Sixty-one per cent of men returned a satisfactorily completed questionnaire. Most (70%) were unaware that cancer of the testis could develop. Of those who correctly identified testis cancer as occurring, half recognized the most commonly affected age group, 40% understood testis cancer could be treated, and 14% believed testis cancer could be cured with treatment. The lowest awareness score (mean +/- s.d.) were found in the 18-30 age group. The score in this group (2.82 +/- 1.47) was significantly lower than that seen in the 31-40 (mean 3.66 +/- 1.81, P = 0.009) or 41-50 (mean 3.57 +/- 2.16, P = 0.036) age groups. Differences were also seen between ethnic groups, with Maori having significantly lower scores than non-Maori (Maori, mean 2.69 +/- 1.52; non-Maori, 3.45 +/- 1.83; P = 0.044). Higher scores were associated with higher socio-economic grouping. The overall poor awareness of men in this study supports the need for a public education programme aimed at encouraging men to seek early advice following the recognition of testicular masses.


[Non-myeloablative allogenic peripheral blood stem cell transplantation for treatment of advanced renal cell carcinoma].
Non-myeloablative allogenic peripheral blood stem cell transplantation (mini-transplant) is becoming a preferred treatment for those recipients in whom the potential toxicity risk of standard ablative allogeneic therapy may be acceptable. Graft-versus-tumor effect may be generated against epithelial malignancies that are similar to the graft-versus-leukemia activity documented in human hematological malignancies. Renal cell carcinoma has been shown to be responsive to immunotherapy with recombinant human cytokines and may be an ideal model for exploring this novel therapy. Clinical investigations have demonstrated regression of advanced renal cell carcinoma occurs in some patients following non-myeloablative allogenic peripheral blood stem cell transplantation. However, graft-versus-host disease remains a significant toxicity of nonablative transplantation, and directions for further study include the identification of the definitive tumor antigens involved in the graft-versus-tumor effect and means of selecting those patients who will benefit the most from this promising approach with due regard to improve its safety.


Clinical manifestations of adult hereditary spherocytosis with novel SPTB gene mutations and hyperjaundice: A case report.
The aim of the present study was to enhance understanding of the diagnosis and treatment of atypical hereditary spherocytosis (HS), and to broaden the diagnostic thoughts of physicians for patients with jaundice. A 28-year-old male presented with jaundice, bile duct stone, and splenomegaly, but without anemia. Other causes of jaundice were excluded, and gene sequencing revealed a novel heterozygous variant of c.1801C>T (p.Q601X) in exon 14 of the SPTB (NM_01355436) gene on chromosome 14 (chr14: 65260580) in the patient's blood; the biological parents and child of the patient did not have similar variants. A splenectomy was performed on the patient and his bilirubin levels returned to normal after surgery. Thus, a novel gene variant causing HS was identified. This variant may result in the truncation of β-hemoglobin in the erythrocyte membrane, leading to loss of normal function, jaundice, and hemolytic anemia. The clinical manifestations of the patient were hyperjaundice and an absence of typical hemolysis during the course of the disease, which caused challenges for diagnosis by the clinicians. Following a definitive diagnosis, genetic testing and response to treatment identified a gene variant site for a novel hemolytic anemia.


Depth-dependent PSF calibration and aberration correction for 3D single-molecule localization.
Three-dimensional single molecule localization microscopy relies on the fitting of the individual molecules with a point spread function (PSF) model. The reconstructed images often show local squeezing or expansion in z. A common cause is depth-induced aberrations in conjunction with an imperfect PSF model calibrated from beads on a coverslip, resulting in a mismatch between measured PSF and real PSF. Here, we developed a strategy for accurate z-localization in which we use the imperfect PSF model for fitting, determine the fitting errors and correct for them in a post-processing step. We present an open-source software tool and a simple experimental calibration procedure that allow retrieving accurate z-positions in any PSF engineering approach or fitting modality, even at large imaging depths.


Overlap among neurocutaneous syndromes. Observations on encephalocraniocutaneous lipomatosis.
The authors report a case of encephalocraniocutaneous lipomatosis (ECCL) in a female infant. Clinical manifestations in this case showed significative overlap with another neurocutaneous syndrome, namely oculocerebrocutaneous (OCC) Delleman's syndrome. This may support the theory of somatic mosaicism. The patient underwent a cerebrospinal fluid (CSF) shunt procedure due to marked tetraventricular hydrocephalus that was not present at birth. The need for close and multidisciplinary follow-up of these patients is stressed.


Comparative Study of TCM Syndrome Scale for Liver Disease and Chronic Liver Disease Questionnaire Based on Assessment of Posthepatitic Cirrhosis.
Objective. To compare and analyze the relevance and applied value of chronic liver disease questionnaire (CLDQ) and Traditional Chinese Medicine liver disease questionnaire (TCMLDQ) in patients with posthepatitic cirrhosis. Methods. The data of 146 patients' scales of CLDQ and TCMLDQ which based on the characteristics of chinese medical symptoms were collected. We made comparative analysis of the relationship between these two scales by the linear regression model and canonical correlation method and evaluated the advantages and disadvantages of two scales about its items setting and dimension definition. Result. There is a negative correlation in total scores between the two scales and the linear regression equation: CLDQ = 239.38 - 1.232TCMLDQ. The further canonical correlation analysis was used to analyze the two extracted canonical correlative variables with significances (P < 0.05), and the results showed that the overall negative correlation between the two scales mainly came from contributions of both the four dimensions of TCMLDQ (CS, GSYX, GYPX, and OS) and the five dimensions of CLDQ (AS, FA, SS, AC, and EF). Conclusion. These two scales have good consistency in the evaluation of severity and life quality of liver cirrhosis patients, so we suggested that TCMLDQ can be used to evaluate the severity and life quality of patients with posthepatitic cirrhosis.


Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation and cytokine production.
Dendritic-cell (DC)-associated C-type lectin receptors (CLRs) take up antigens to present to T cells and regulate DC functions. DCAL-2 is a CLR with a cytosolic immunoreceptor tyrosine-based inhibitory motif (ITIM), which is restricted to immature DCs (iDCs), monocytes, and CD1a+ DCs. Cross-linking DCAL-2 on iDCs induced protein tyrosine phosphorylation and MAPK activation as well as receptor internalization. To test if DCAL-2 is involved in DC maturation and cytokine expression, we stimulated iDCs with anti-DCAL-2 mAb with or without LPS, zymosan, or CD40L. While anti-DCAL-2 did not induce iDCs to mature, it did up-regulate CCR7 expression and IL-6 and IL-10 production. DCAL-2 signals augmented DC maturation induced by LPS or zymosan, increasing both CCR7 and DC-LAMP expression. Of interest, DCAL-2 ligation had the opposite effects on TLR versus CD40L signaling: anti-DCAL-2 suppressed TLR-induced IL-12 expression, but significantly enhanced CD40L-induced IL-12 production. DCAL-2 ligation also suppressed the ability of TLR-matured DCs to induce IFN-gamma-secreting Th1 cells but augmented the capacity of CD40L-matured DCs to polarize naive T cells into Th1 cells. Thus, DCAL-2 may program DCs differently depending on whether DCs are signaled via TLRs or by T cells. DCAL-2 may be a potential immunotherapeutic target for modulating autoimmune diseases or for developing vaccines.


A simple rule to describe interactions between visual categories.
Humans can rapidly categorise visual objects when presented in isolation. However, in everyday life we encounter multiple objects at the same time. Far less is known about how simultaneously active object representations interact. We examined such interactions by asking participants to categorise a target object at the basic (Experiment 1) or the superordinate (Experiment 2) level while the representation of another object was still active. We found that the "prime" object strongly modulated the response to the target implying that the prime's category was rapidly and automatically accessed, influencing subsequent categorical processing. Using drift diffusion modelling, we show that a prime, whose category is different from that of the target, interferes with target processing primarily during the evidence accumulation stage. This suggests that the state of category-processing neurons is altered by an active representation and this modifies the processing of other categories. Interestingly, the strength of interference increases with the similarity between the distractor and the target category. Considering these results and previous studies, we propose a general principle that category interactions are determined by the distance from a distractor's representation to the target's task-relevant categorical boundary. We argue that this principle arises from the specific architectural organisation of categories in the brain.


Effects of endogenous melatonin on glutamate and GABA rhythms in the striatum of unilateral 6-hydroxydopamine-lesioned rats.
We have previously reported a time-dependent increase in melatonin (MLT) and decrease in dopamine (DA) in striatal dialysate 3 weeks after unilateral 6-hydroxydopamine (6-OHDA) lesioning in the rat substantia nigra pars compacta (SNc) and medial forebrain bundle (MFB). This study aimed to investigate dynamic and circadian variations in DA, MLT, glutamate (Glu) and γ-aminobutyric acid (GABA) in striatal dialysates in the same 6-OHDA animal model. These neurotransmitters were determined using high-performance liquid chromatography (HPLC). Three weeks following 6-OHDA lesioning, there was a significant increase in extracellular Glu (156%) and decrease in GABA (15%) and DA (85%) in the lesioned striatum. These changes continued over time. Concomitantly, MLT was increased by 107% in the lesioned striatal dialysates after 4 weeks, and continued to increase gradually over time. Six weeks post-treatment, levels of MLT secretion at 12 time points were higher, and the peak time of MLT secretion was earlier, in 6-OHDA-lesioned rats compared with vehicle-treated rats. In addition, significant variations in extracellular levels of Glu and GABA between day and night were observed in vehicle-treated rat striatum. However, no circadian variations were observed in the striatum of unilateral 6-OHDA-lesioned rats. Six weeks post-treatment, MLT levels correlated well with Glu and GABA levels at corresponding time-points in the striatum ipsilateral to the injected side in both groups, and increased MLT levels also correlated well with changes in Glu and GABA in the striatum in 6-OHDA-lesioned rats. These data suggest that 6-OHDA lesioning affects the endogenous productions of DA, MLT, Glu and GABA, and changes the MLT secretion pattern. Augmented striatal MLT levels and advanced MLT secretion pattern caused by unilateral intracerebral injection of 6-OHDA may influence the variations in Glu and GABA between day and night.


CERA: Clerkships Need National Curricula on Care Delivery, Awareness of Their NCC Gaps.
The Society of Teachers of Family Medicine's (STFM) National Clerkship Curriculum (NCC) was created to standardize and improve teaching of a minimum core curriculum in family medicine clerkships, promoting the Triple Aim of better care and population health at lower cost. It includes competencies all clerkships should teach and tools to support clerkship directors (CDs). This 2014 CERA survey of clerkship directors is one of several needs assessments that guide STFM's NCC Editorial Board in targeting improvements and peer-review processes. CERA's 2014 survey of CDs was sent to all 137 CDs at US and Canadian allopathic medical schools. Primary aims included: (1) Identify curricular topics of greatest need, (2) Inventory the percent of family medicine clerkships teaching each NCC topic, and (3) Determine if longitudinal or blended clerkship have unique needs. This survey also assessed use of NCC to advocate for teaching resources and collaborate with colleagues at other institutions. Ninety-one percent of CDs completed the survey. Sixty-four percent reported their clerkship covers all of the NCC minimum core, but on detailed analysis, only 1% teach all topics. CDs need curricula on care delivery topics (cost-effective approach to acute care, role of family medicine in the health care system, quality/safety, and comorbid substance abuse). Single-question assessments overestimate the percentage of clerkships teaching all of the NCC minimum core. Clerkships need national curricula on care delivery topics and tools to help them find their curricular gaps.


The diagnosis and clinical manifestations of activated protein C resistance: a case report and review of the literature.
Activated protein C resistance (APCR) is a recently discovered, medically important cause of venous thrombosis. More than 95% of cases are due to factor V Leiden (FVL), a mutated form of factor V that is resistant to degradation by activated protein C. The prevalence of this disorder, which is inherited in an autosomal dominant fashion, is approximately 5% among asymptomatic people of European heritage. In addition, 20 to 60% of patient cohorts with previous thrombosis demonstrate APCR, making it the most common known genetic cause of abnormal thrombophilia. Current laboratory techniques available for diagnosis include functional assays, such as the APC ratio, as well as DNA-based tests that detect the specific genetic anomaly responsible for FVL. A case report is presented, along with a review of the literature highlighting epidemiology, pathogenesis, clinical features and methods for laboratory diagnosis.


Memory deficits associated with khat (Catha edulis) use in rodents.
Khat products and chewing practices are common in East Africa, Middle East for centuries with concomitant socio-economic and public health repercussions. We assessed memory deficits associated with khat use in rodents. Young male CBA mice, 5-7 weeks old (n = 20), weighing 25-35 g were used. Mice were treated with either 40, 120 or 360 mg/kg body weight (bw) methanolic khat extract, or 0.5 ml saline for 10 days. Spatial acquisition, reversal and reference memory were assessed using modified Morris Water maze (MMWM). Mice treated with 40 mg/kg khat extract had longer (t4 = 4.12 p = 0.015) and t4 = 2.28 p = 0.065) escape latency on first and second day during reversal relative to the baseline. Under 120 mg/kg khat dose, the escape latency was shorter (t4 = -2.49 p = 0.05) vs (t3 = -2.5 p = 0.05) on third and fourth day. Further, treatment with 360 mg/kg khat extract resulted in significantly longer time (49.13, 33.5, 40.2 and 35.75) vs. (23.5 s), compared to baseline. Mice treated with khat or control preferred the target quadrant post acquisition while differential pattern was seen during reversal phase. Mice treated with 40 or 120 mg/kg khat showed significant preference for target quadrant. Substantial time (19.9) was spent in the old target compared to the new (16.9 s) by animals treated with highest dose however, the difference was not significant. There is a biological plausibility that chronic khat use may induce memory deficits and impair cognitive flexibility. The differential patterns of memory deficits may reflect the differences in dose effect as well as time dependent impairment.


Seismic evidence for olivine phase changes at the 410- and 660-kilometer discontinuities.
The view that the seismic discontinuities bounding the mantle transition zone at 410- and 660-kilometer depths are caused by isochemical phase transformations of the olivine structure is debated. Combining converted-wave measurements in East Asia and Australia with seismic velocities from regional tomography studies, we observe a correlation of the thickness of, and wavespeed variations within, the transition zone that is consistent with olivine structural transformations. Moreover, the seismologically inferred Clapeyron slopes are in agreement with the mineralogical Clapeyron slopes of the (Mg,Fe)2SiO4 spinel and postspinel transformations.


Local and hematological alterations induced by Philodryas olfersii snake venom in mice.
Envenomation by the South American opisthoglyphous snake Philodryas olfersii causes local pain, edema, erythema and ecchymosis; systemic envenomation is rare. In this work, we examined the inflammatory activity of P. olfersii venom (10, 30 and 60 μg) in mouse gastrocnemius muscle 6 h after venom injection. Intramuscular injection of venom did not affect hematological parameters such as red cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The venom caused thrombocytopenia (at all three doses), leukopenia and lymphopenia (both at the two highest doses), as well as neutrophilia (30 μg), monocytosis (30 μg) and basophilia (10 μg). Of the cytokines that were screened [IL-1β, IL-6, IL-10, IL-13, IL-17, TNF-α, IFN-γ, MIP-2 and KC] and IGF-1, only IGF-1 showed a significant increase in its circulating concentration, seen with 60 μg of venom; there were no significant changes in the cytokines compared to control mice. Histological analysis revealed the presence of edema, an inflammatory infiltrate and progressive myonecrosis. Edema and myonecrosis were greatest with 60 μg of venom, while the inflammatory infiltrate was greatest with 10 μg of venom. All venom doses caused the migration of polymorphonuclear and mononuclear leukocytes into muscle, but with no significant dose-dependence in the response. These findings show that, at the doses tested, P. olfersii venom does not cause hematological alterations and has limited effect on circulating cytokine concentrations. These data also confirm that the principal effects of the venom in mice are local edema, inflammatory cell infiltration and myonecrosis.


A Simple Nanocellulose Coating for Self-Cleaning upon Water Action: Molecular Design of Stable Surface Hydrophilicity.
Coating solid surfaces with cellulose nanofibril (CNF) monolayers via physical deposition was found to keep the surfaces free of a variety of oils, ranging from viscous engine oil to polar n-butanol, upon water action. The self-cleaning function was well correlated with the unique molecular structure of the CNF, in which abundant surface carboxyl and hydroxy groups are uniformly, densely, and symmetrically arranged to form a polar corona on a crystalline nanocellulose strand. This isotropic core-corona configuration offers new and easily adoptable guidance to design self-cleaning surfaces at the molecular level. Thanks to its excellent self-cleaning behavior, the CNF coating converted conventional meshes into highly effective membranes for oil-water separation with no prior surface treatment required.


Bilious vomiting in the newborn: How often is it pathologic?
Intestinal obstruction is one of the most common reasons for admission to a neonatal surgical unit and frequently is manifest by bilious vomiting. Not all cases of neonatal bilious vomiting are caused by intestinal obstruction. This study aimed to investigate the outcome of neonates with bilious vomiting. A prospective audit was undertaken of all neonates with a history of bilious vomiting referred to a regional pediatric surgical unit during a 2-year period (1998 to 2000). Infants with bilious nasogastric aspirates but no vomiting were not included. Demographic details, symptomatology, investigations, and final diagnoses were recorded. Subsequent clinical progress was ascertained by out-patient review or telephone interview. Sixty-three consecutive neonates (35 boys, 28 girls) were identified with a median gestational age of 40 (range 31 to 42) weeks and median birth weight of 3.5 kg (range 1.67 to 4.64). Median age at presentation was 26 hours (range, 9 hr to 28 days). A surgical cause of bilious vomiting was identified in 24 (38%): Hirschsprung's disease (n = 9), small bowel atresia (n = 5), intestinal malrotation (n = 4), meconium ileus (n = 3), meconium plug (n = 1), colonic atresia (n = 1), and milk inspissation (n = 1). Nineteen of these had both abdominal signs and an abnormal plain abdominal radiograph, and 4 had an abnormal abdominal radiograph only. In one infant with intestinal malrotation, clinical examination and plain radiography were unremarkable. After definitive surgery, all 24 infants were well at a median age of 14 (7 to 28) months. No surgical cause for bilious vomiting was found in 39 (62%) neonates whose symptoms resolved with conservative management. These data emphasize the maxim that bilious vomiting in the newborn should be attributed to intestinal obstruction until proved otherwise. However, in this prospective audit, bilious vomiting was not caused by intestinal obstruction in 62% of cases, and most of these infants suffered no further sequelae.


Association between human opioid receptor genes polymorphisms and pressure pain sensitivity in females*.
This study examined the association between pressure pain sensitivity and various single nucleotide polymorphisms (SNPs) of human micro-, kappa-, and delta-opioid receptor (i.e. OPRM1, OPRK1, and OPRD1) genes in 72 healthy adult Taiwanese women of Han Chinese race. Pressure pain threshold and tolerance were measured by an algometer and polymorphisms of the opioid receptor genes determined from blood samples. Our data revealed that pressure pain threshold, but not tolerance, in subjects with the minor allele (termed 'GA') genotype of the IVS2+31G>A polymorphism of the OPRM1 gene was significantly higher than those with major allele (termed 'GG') genotype. Neither pressure pain threshold nor tolerance between major and minor alleles of other SNPs of the OPRM1, OPRK1, and OPRD1 genes were significantly different. These data suggest an association between the IVS2+31G>A SNP of the OPRM1 gene and pressure pain sensitivity in healthy adult females.


Engineered Escherichia coli as a Controlled-Release Biocarrier for Electrochemical Immunoassay.
Micro/nanocarriers hold great potential in bioanalysis for molecular recognition and signal amplification but are frequently hampered by harsh synthesis conditions and time-consuming labeling processes. Herein, we demonstrate that Escherichia coli (Ec) can be engineered as an efficient biocarrier for electrochemical immunoassay, which can load ultrahigh amounts of redox indicators and simultaneously be decorated with detection antibodies via a facile polydopamine (PDA)-mediated coating approach. Compared with conventional carrier materials, the entire preparation of the Ec biocarrier is simple, highly sustainable, and reproducible. Moreover, immune recognition and electrochemical transduction are performed independently, which eliminates the accumulation of biological interference on the electrode and simplifies electrode fabrication. Using human epidermal growth factor receptor 2 (HER2) as the model target, the proposed immunosensor exhibits excellent analytical performance with a low detection limit of 35 pg/mL. The successful design and deployment of Ec biocarrier may provide new guidance for developing biohybrids in biosensing applications.


[Pathogenesis and prevention of venous and arterial thromboembolic events in patients after deep vein thrombosis of lower extremities].
To define the role of thrombophilic and other procoagulant conditions in pathogenesis of deep vein thrombosis and the effectiveness of pathogenetic secondary prevention of venous and arterial thromboembolic events. The study included 107 patients for the period 2007-2016 who were divided into 3 groups. The main group (n=40) - lifelong individual antithrombotic therapy with warfarin predominantly; the second (control) group (n=39) - warfarin administration for 3-6 months; the third (additional) group (n=28) - specific life-long therapy depending on procoagulant status which was assessed according to original scale. The main anticoagulants were rivoroxaban or dabigatran etexilate. Recurrent venous thromboembolic complications (RVTE) were observed in one (2.5%) patient of the first group and in 8 (20.5%) cases of the second group. In the third group RVTE were absent (significant differences, p<0.03 and 0.001, respectively). Arterial thromboembolic diseases were noted in 1 (2.5%) patient of the first group, in 4 (10.25%) cases of the second group and in none of the third group (significantly only for group II vs. group III, p<0.01). Individual antithrombotic therapy reduces the incidence of recurrent venous and arterial thromboembolic events in patients with idiopathic deep vein thrombosis.


Bronchoscopy as an indicator of tracheobronchial fungal infection in non-neutropenic intensive-care unit patients.
We aimed to establish that a bronchoscopic view can be as reliable as microbiology, and support an empirical tracheobronchial fungal infection (TBFI) treatment decision. We retrospectively studied 95 respiratory failure patients with suspected TBFI admitted to the intensive-care unit (ICU) in 2008 with sticky secretions, hyperaemic mucosa, and whitish plaques on bronchoscopic view. Patients not suspected of having TBFI were chosen as a control group (n = 151). Broncheoalveolar lavage (BAL) fluid was cultured, and biopsy samples were taken from the lesions. Biopsy samples positive for fungi were defined as 'proven', only BAL-positive (+ fungi) cases were 'probable TBFI', and BAL-negative (- fungi) cases were 'possible TBFI'. BAL (+ fungi) and BAL (- fungi) in the control group were defined as 'colonization' and 'no TBFI', respectively. The sensitivity, specificity and positive and negative predictive values of BAL (+ fungi) were 85.1% (63/74), 81.4% (140/172), 66.3% (63/95), and 92.7% (140/151), respectively. Biopsies were performed in 78 of 95 patients, and 28 were proven TBFI with fungal elements, and 100% were BAL (+ fungi). Probable TBFI was seen in 30 of 95 patients with BAL (+ fungi), and possible TBFI (BAL(- fungi)) in 25 of 95. Among the 95 patients, microbiology revealed fungi (90.5% Candida species; 9.5% Aspergillus) in 63 (66.3%). In the controls, the colonization and no TBFI rates were 11 of 151 and 140 of 151, respectively. Observing sticky secretions, hyperaemic mucosa and whitish plaques by bronchoscopy is faster than and may be as reliable as microbiology for diagnosing TBFI. These findings are relevant for empirical antifungal therapy in suspected TBFI patients in the ICU.


Inhibition of fish gill lipoxygenase and blood thinning effects of green tea extract.
The objective of the present study was to determine whether green tea extracts are inhibitory to lipid oxidations catalyzed by lipoxygenase (LOX) and hemoglobin (Hb) using fish as an animal model. Green tea was extracted with water. LOX was extracted from the gills of grey mullet and tilapia, respectively. The LOX activity was determined using chemiluminescence and high-pressure liquid chromatography. The green tea extract showed inhibitory effects on both LOX-catalyzed and Hb-catalyzed oxidation of arachidonic acid and linoleic acid. Blood thinning effects were observed ex vivo by mixing the green tea extract with fish red blood cells and showed that the flow behavior of fish blood becomes closer to the Newtonian type with a thinner consistency. Similar effects were found on tilapia and grey mullet.


Transfusion-associated graft-versus-host disease.
We reported two patients showed similar clinical course after blood transfusion. Case 1 was 74-year-old female, received transfusion of 200 ml of whole blood from her son, because of hemorrhagic shock for fematemesis from gastric ulcer. After transfusion, she died of liver dysfunction and severe aplastic anemia. Case 2 was a 73-year-old male, received transfusion of three unites of concentrated red blood cells for anemia following the orthopaedic treatment. High fever and erythema was appeared suddenly after transfusion. He died of liver dysfunction and the autopsy was performed. In case 1 the diagnosis was transfusion-associated graft-versus-host disease (GVHD) and in case 2 drug-induced-aplastic anemia (DIAA) was suspected. Differentiating the diagnosis between GVHD and DIAA is clinically difficult.


Personal Guides: Heterogeneous Robots Sharing Personal Tours in Multi-Floor Environments.
GidaBot is an application designed to setup and run a heterogeneous team of robots to act as tour guides in multi-floor buildings. Although the tours can go through several floors, the robots can only service a single floor, and thus, a guiding task may require collaboration among several robots. The designed system makes use of a robust inter-robot communication strategy to share goals and paths during the guiding tasks. Such tours work as personal services carried out by one or more robots. In this paper, a face re-identification/verification module based on state-of-the-art techniques is developed, evaluated offline, and integrated into GidaBot's real daily activities, to avoid new visitors interfering with those attended. It is a complex problem because, as users are casual visitors, no long-term information is stored, and consequently, faces are unknown in the training step. Initially, re-identification and verification are evaluated offline considering different face detectors and computing distances in a face embedding representation. To fulfil the goal online, several face detectors are fused in parallel to avoid face alignment bias produced by face detectors under certain circumstances, and the decision is made based on a minimum distance criterion. This fused approach outperforms any individual method and highly improves the real system's reliability, as the tests carried out using real robots at the Faculty of Informatics in San Sebastian show.


Luminescent Thermochromism and White-Light Emission of a 3D [Ag4Br6] Cluster-Based Coordination Framework with Both Adamantane-like Node and Linker.
Herein, we report a dia-type metal-organic hybrid network based on the [Ag4Br6] clusters and hexamethylenetetramine molecules wherein both the inorganic nodes and organic linkers feature adamantane-like geometry with a Td symmetry. The silver bromine complex presents a dual emission and exhibits an interesting luminescent thermochromism behavior. Remarkably, white-light emission can be readily realized through variation of the temperature. In addition, the title compound is expected to be competent as a luminescent thermometer for temperature identification.


[Alcohol and risk of coronary heart disease].
More than 60 prospective cohort studies have shown a consistent association between regular and moderate alcohol consumption and decrease in risk of coronary heart disease, ischemic stroke and heart failure by 20 to 40% as compared to heavy alcohol intake or drinking no alcohol. Lower protective effects were found in young, in women and in men living outside the Mediterranean area. Moreover, some biological characteristics of alcohol, particularly red wine, could interfere with the athero-thrombotic process and contribute to increase the plausibility for the protective effects of alcohol on cardiovascular diseases. However, the results of meta-analyses also demonstrate harmful effects in relation with dose and pattern of alcohol consumption. In regard to the available scientific data, alcohol consumption cannot be include in the recommendations for the prevention of cardiovascular diseases. On the other hand alcohol should not be prohibited when consumption remains mild to moderate.


Immune response in hosts with cadaveric dural grafts. Report of two cases.
The use of cadaveric human dura has been critical in the repair of dural defects since the dawn of neurosurgery. Reports in the literature of immune response to this type of graft have been extremely rare. Two patients are presented who received cadaveric dural implants with resulting meningeal signs and cerebrospinal fluid eosinophilia several weeks after surgery. Peripheral eosinophilia was present in one patient. The signs and symptoms resolved temporarily during corticosteroid therapy and permanently upon removal of the offending grafts. These cases illustrate that an immune-type reaction can occur with significant morbidity in patients receiving cadaveric dural grafts. A proposed mechanism for this response is discussed.


Actin-Based Transport Adapts Polarity Domain Size to Local Cellular Curvature.
Intracellular structures and organelles such as the nucleus, the centrosome, or the mitotic spindle typically scale their size to cell size [1]. Similarly, cortical polarity domains built around the active form of conserved Rho-GTPases, such as Cdc42p, exhibit widths that may range over two orders of magnitudes in cells with different sizes and shapes [2-6]. The establishment of such domains typically involves positive feedback loops based on reaction-diffusion and/or actin-mediated vesicle transport [3, 7, 8]. How these elements may adapt polarity domain size to cellular geometry is not known. Here, by tracking the width of successive oscillating Cdc42-GTP domains in fission yeast spores [9], we find that domain width scales with local cell-surface radii of curvature over an 8-fold range, independently of absolute cell volume, surface, or Cdc42-GTP concentration. This local scaling requires formin-nucleated cortical actin cables and the fusion of secretory vesicles transported along these cables with the membrane. These data suggest that reaction-diffusion may set a minimal domain size and that secretory vesicle transport along actin cables may dilute and extend polarity domains to adapt their size to local cell-surface curvature. This work reveals that actin networks may act as micrometric curvature sensors and uncovers a generic morphogenetic principle for how polarity domains define their size according to cell morphologies.


Common factors: post hoc explanation or empirically based therapy approach?
Laska, Gurman, and Wampold (2014, pp. 467-481) seek to expand the lens of evidence-based practice by incorporating the common factors perspective. We comment on Laska et al.'s arguments along with the methods used to reach their conclusions. Although we share their view that the common factors explanation for therapeutic equivalence across various orientations observed in the treatment outcome literature is both parsimonious and supported by the scientific evidence, we take issue with their suggestion that there exists a common factors "approach" to treatment in general or evidence-based practice more specifically. We provide clarification and friendly amendments to their language and perspective on the psychotherapy process and outcome research literature and its application in evidence-based practice.


A mass spectrometry plate reader: monitoring enzyme activity and inhibition with a Desorption/Ionization on Silicon (DIOS) platform.
A surface-based laser desorption/ionization mass spectrometry assay that makes use of Desorption/Ionization on Silicon Mass Spectrometry (DIOS-MS) has been developed to monitor enzyme activity and enzyme inhibition. DIOS-MS has been used to characterize inhibitors from a library and then to monitor their activity against selected enzyme targets, including proteases, glycotransferase, and acetylcholinesterase. An automated DIOS-MS system was also used as a high-throughput screen for the activity of novel enzymes and enzyme inhibitors. On two different commercially available instruments, a sampling rate of up to 38 inhibitors per minute was accomplished, with thousands of inhibitors being monitored. The ease of applying mass spectrometry toward developing enzyme assays and the speed of surface-based assays such as DIOS for monitoring inhibitor effectiveness and enzyme activity makes it attractive for a broad range of screening applications.


Evaluation of epidemiologic and animal data associating pesticides with Parkinson's disease.
Exposure to pesticides may be a risk factor for developing Parkinson's disease (PD). To evaluate the evidence regarding this association in the scientific literature, we examined both analytic epidemiologic studies of PD cases in which exposure to pesticides was queried directly and whole-animal studies for PD-like effects after systemic pesticide exposure. Epidemiologic studies were considered according to study quality parameters, and results were found to be mixed and without consistent exposure-response or pesticide-specific patterns. These epidemiologic studies were limited by a lack of detailed and validated pesticide exposure assessment. In animal studies, no pesticide has yet demonstrated the selective set of clinical and pathologic signs that characterize human PD, particularly at levels relevant to human populations. We conclude that the animal and epidemiologic data reviewed do not provide sufficient evidence to support a causal association between pesticide exposure and PD.


Immunofluorescent localization of myosin at the anterior pole of the coccidian, Toxoplasma gondii.
Indirect immunofluorescence using anti-myosin rabbit sera showed myosin localized in a characteristic pattern at the anterior pole of Toxoplasma gondii. This polar fluorescent staining was abolished by pre-absorption of the anti-sera with myosin extracted from avian muscle. Both intracellular and extracellular T. gondii showed similar patterns when formaldehyde-fixed, but neither showed polar fluorescence when acetone was used as the sole fixative. Immunofluorescent staining of live T. gondii revealed no polar fluorescence, suggesting that myosin is not present on the outer parasite membrane. Anti-myosin serum did not prevent host cell invasion and plaque formation in the presence of human complement. Inhibition of contractile proteins with cytochalasin D inhibited T. gondii motility and infectivity in a plaque formation assay. The pattern of polar fluorescence described here resembles the IgM-associated polar staining frequently detected in human sera, but we believe it is a different phenomenon because human sera that showed such staining retained their activity after pre-absorption with avian myosin. The unusual localization of myosin at the anterior pole of T. gondii tachyzoites may play a role in the function of anterior organelles, which are thought to facilitate the invasion of host cells.


Striking decrease in blood loss with a urologist-assisted standardized multidisciplinary approach in the management of abnormally invasive placenta.
The aim of this study was to investigate the outcome of a standardized multidisciplinary approach using a modified surgical technique in the management of abnormally invasive placenta (AIP), with special reference to blood loss and the need for transfusion. Data were collected retrospectively in women managed with a recently adopted multidisciplinary strategy using a modified surgical approach, involving a urologist (study group: 10 patients). Women managed before the introduction of this standardized management served as a control group (nine patients). Comparisons were made between the study group and the control group. The main outcome measures were blood loss and the need for transfusion in the two groups. Standardized multidisciplinary management, involving a modified surgical technique performed by a urologist, decreased blood loss in the study group compared with the control group [median 1400 ml (range 400-3000 ml) vs median 8000 ml (2300-40000 ml); p < .001]. It also decreased postoperative complications and the need for transfusion of blood products. Standardized multidisciplinary management of patients with AIP, using a modified surgical technique, reduces the risks of massive obstetric hemorrhage, the need for massive transfusion and the risk of postoperative complications. Involving an experienced urologist appears to be of paramount importance in the management of AIP.


Estimation of the Electrode-Fiber Bioelectrical Coupling From Extracellularly Recorded Single Fiber Action Potentials.
Selective peripheral neural interfaces are currently capable of detecting minute electrical signals from nearby nerve fibers as single fiber action potential (SFAP) waveforms. Each detected single unit has a distinct shape originating from the unique bioelectrical coupling that exists between the neuroprosthetic electrode, the nerve fiber and the extracellular milieu. The bioelectrical coupling manifests itself as a series of low-pass Bessel filters acting on the action currents along the nerve fiber. Here, we present a method to estimate the electrode-fiber bioelectrical coupling through a quantitative analysis of the spectral distribution of the single units extracellularly recorded with the thin-film longitudinal intrafascicular electrode (tfLIFE) in an in vivo mammalian peripheral nerve animal model. The bioelectrical coupling estimate is an estimate of the electrode sensitivity function traversed by the nerve fiber, suggesting that it is as a means to directly measure the spatial relationship between the nerve fiber and electrode. It not only reflects a shape change to the SFAP, but has implications for in situ nerve fiber location tracking, in situ diagnostics of nerves and neuroproshetic electrodes, and assessment of the biocompatibility of neural interfaces and the health of the reporting nerve fibers.


Association between harmful oral habits and the structures and functions of the stomatognathic system: perception of parents/guardians.
To verify the occurrence and associate the presence and duration of harmful oral habits with the structures and functions of the stomatognathic system. This is a cross-sectional, exploratory study. Participants' participation was formalized by the signing of an Informed Consent Form. The non-probabilistic sample comprised 289 children aged one to 12 years assisted at a Family Health Strategy unit. The data were obtained through a questionnaire to identify harmful oral habits applied to the children's parents and/or guardians. The results were considered at 5% level of significance. The statistical analyses were performed using the SPSS 19.0 software and the chi-squared association test was employed to investigate the categorical variables. The breastfeeding rate found was 85%; however, only 32.4% of the children were exclusively breastfed until six months of age. The most prevalent habits and those currently maintained were use of conventional bottle (28.62%) and conventional pacifier (23.18%). Significant correlation (p=0.001) was found between keeping the mouth open and oral and oronasal breathing. The presence of habits such as using orthodontic bottle (p=0.016) and orthodontic pacifier (p=0.001) was associated with the breathing mode reported. Habit duration was associated with the perception of changes in speech (p=0.046) and with malocclusion (p=0.014). The presence and duration of harmful oral habits were associated with the perception of changes in the structures and functions of the stomatognathic system regarding occlusion, breathing, and speech, accounting for a significant portion of the demand for rehabilitation.


First clinical evaluation of the C-MAC D-Blade videolaryngoscope during routine and difficult intubation.
In the present preliminary study we evaluated the C-MAC® D-Blade (Karl Storz, Tuttlingen, Germany), a new videolaryngoscopic C-MAC blade for difficult intubation, during both routine and difficult intubations. First, both the conventional direct laryngoscopy and the D-Blade were used in 15 consecutive patients with normal airways during routine induction of anesthesia. Second, the D-Blade was used as a rescue device in 20 of 300 (6.7%) consecutive patients, when conventional direct laryngoscopy failed. In the 15 patients during routine induction of anesthesia, with direct laryngoscopy, a Cormack-Lehane (C/L) grade 1 and grade 2a view was seen in 7 and 8 patients, respectively. It was possible to insert the D-Blade and to get a video view of the glottis on the first attempt in all patients; with the D-Blade, all 15 patients had a C/L 1 view. The time to successful intubation with the D-Blade was 15 (8-26) seconds (median (range)). In the 20 patients, in whom unexpected difficulty with direct laryngoscopy was observed, C/L grades 3 and 4 were present in 15 and 5 patients, respectively. With the use of the D-Blade, indirect C/L video view improved to C/L class 1 in 15 patients, and to 2a in 5 patients, respectively. The time from touching the laryngoscope to optimal laryngoscopic view was 11 (5-45) seconds and for successful intubation 17 (3-80) seconds. In all 35 patients, with the D-Blade no direct view of the glottis was possible and subsequently a semiflexible tube guide was required.