Depopulated vena caval homograft: a new venous conduit.
Completion of the Fontan procedure is frequently performed by using an extracardiac conduit between the inferior vena cava and the pulmonary artery. Most centers use a polytetrafluoroethylene graft for the extracardiac conduit, and because re-endothelialization is unlikely, anticoagulation is used for a variable period. This study explores the use of an alternate large-caliber venous conduit. The superior vena cava was replaced in 8 minipigs with either a polytetrafluoroethylene interposition graft (2 pigs) or a depopulated (acellular), cryopreserved superior vena caval homograft (6 pigs). After 6 months, the animals were killed, and the grafts were examined for patency and histology, including immunostaining. No anticoagulation was used. Polytetrafluoroethylene grafts have a cross-sectional luminal narrowing, ranging from 16% to 40%. Histology showed only partial intimal ingrowth, with excessive subendothelial fibrosis and early calcification. In contrast, the depopulated venous homografts showed minimal luminal narrowing, ranging from 2% to 9%. These grafts were completely repopulated by the recipient with an endothelial lining, which stained positively for factor VIII, and a subendothelial region appropriately recellularized by myofibroblasts, which stained positively for smooth muscle actin and procollagen. There was no evidence of an immune response to the venous homografts, as judged by staining for T-cell surface antigen, CD4, and CD8. Thrombus was not seen in any of the grafts. Depopulated, cryopreserved vena caval homografts might be superior conduits for cavopulmonary connection during completion of the Fontan operation by using the extracardiac conduit technique.


Imaging characteristics of neovascular pigment epithelial detachments and their response to anti-vascular endothelial growth factor therapy.
To evaluate the imaging characteristics of macular neovascular pigment epithelial detachments (PEDs) and their response to anti-vascular endothelial growth factor (VEGF) therapy. Patients with exudative age-related macular degeneration (AMD), idiopathic polypoidal choroidal vasculopathy, presumed ocular histoplasmosis syndrome (POHS) and central serous retinopathy (CSR) with choroidal neovascularisation (CNV) were included in the study. A retrospective chart review of 72 eyes of 64 patients was performed. Three types of PEDs were identified based on reflectivity of the material under the retinal pigment epithelium on optical coherence tomography: hollow (26 eyes with primarily hyporeflectivity under the PED), solid (30 eyes with primarily hyperreflective signal under the PED) and mixed (8 eyes with mixed reflectivity). The average number of anti-VEGF injections was 7 per eye and the average duration of follow-up was 16 months. Among eyes with exudative AMD, 7/21 hollow PEDs flattened, 1/19 solid PEDs flattened and 2/6 mixed PEDs flattened after anti-VEGF therapy. POHS and CSR with CNV were associated with subfoveal solid PEDs and were unchanged after therapy. Overall, 46% (12/26) with hollow PEDs, 25% (2/8) with mixed PEDs and 3% (1/30) with solid PEDs had flattening after anti-VEGF therapy. The likelihood of PED flattening was inversely related to the reflectivity of the PED. The more reflective the PED, the less likely resolution with anti-VEGF therapy occurred.


Positron emission tomography-computed tomography in the management of lung cancer: An update.
This communication presents an update on the current role of positron emission tomography-computed tomography (PET-CT) in the various clinical decision-making steps in lung carcinoma. The modality has been reported to be useful in characterizing solitary pulmonary nodules, improving lung cancer staging, especially for the detection of nodal and metastatic site involvement, guiding therapy, monitoring treatment response, and predicting outcome in non-small cell lung carcinoma (NSCLC). Its role has been more extensively evaluated in NSCLC than small cell lung carcinoma (SCLC). Limitations in FDG PET-CT are encountered in cases of tumor histotypes characterized by low glucose uptake (mucinous forms, bronchioalveolar carcinoma, neuroendocrine tumors), in the assessment of brain metastases (high physiologic 18F-FDG uptake in the brain) and in cases presenting with associated inflammation. The future potentials of newer PET tracers beyond FDG are enumerated. An evolving area is PET-guided assessment of targeted therapy (e.g., EGFR and EGFR tyrosine kinase overexpression) in tumors which have significant potential for drug development.


Performance of novel media in stratified filters to remove organic carbon from lake water.
Disinfection by-products (DBPs) are an ever-increasing occurrence in water networks, particularly those which abstract water from peatland areas. Although much research has been carried out to discover novel methods to remove specific DBPs, the removal of natural organic matter (NOM) from source water may provide a more sustainable solution in many areas. This study focuses on the removal of NOM by novel filters, which could be retrospectively fitted to any conventional water treatment facility. The filters comprised stratified layers of a variety of media, including sand, Bayer residue, granular activated carbon (GAC), and pyritic fill. The filters were operated under two loading regimes, continuous and intermittent, at loading rates similar to recognised design standards. The most successful filter design comprised stratified layers of sand, GAC, and pyritic fill. Over the duration of a 240 day study, these filters obtained average dissolved organic carbon removal rates of 40%, and achieved average specific ultra-violet absorbance reductions from 2.9 to 2.4 L mg-1 m-1. The study demonstrates that these novel filters may be used to reduce NOM levels, thus reducing the potential for DBP formation. Such designs can incorporate the use of waste media, making the overall design more sustainable and robust.


Clinical outcome of mitral regurgitation due to flail leaflet.
Mitral regurgitation due to flail leaflet is difficult to manage, because it is frequently asymptomatic yet carries a high risk of left ventricular dysfunction and because the natural history of the condition is poorly defined. We obtained clinical follow-up data through 1994-1995 in 229 patients with isolated mitral regurgitation due to flail leaflet; this condition was first diagnosed by echocardiography between 1980 and 1989. The 86 patients who were treated medically had a mortality rate significantly higher than expected (6.3 percent yearly, P=0.016 for the comparison with the expected rate in the U.S. population according to the 1990 census). Independent determinants of mortality were an older age, the presence of symptoms, and a lower ejection fraction. Patients who were even transiently in New York Heart Association functional class III or IV had a high mortality rate (34 percent yearly), but the rate was also notable (4.1 percent yearly) among those in class I or II. At 10 years, the mean (+/- SE) rates of heart failure, atrial fibrillation, and death or surgery were 63 +/- 8, 30 +/- 12, and 90 +/- 3 percent, respectively. In a multivariate analysis, surgical correction of mitral regurgitation (performed in 143 patients) was associated with a reduced mortality rate (hazard ratio, 0.29; 95 percent confidence interval, 0.15 to 0.56; P<0.001). When treated medically, mitral regurgitation due to flail leaflet is associated with excess mortality and high morbidity. Surgery is almost unavoidable within 10 years after the diagnosis and appears to be associated with an improved prognosis; this finding suggests that surgery should be considered early in the course of the disease.


Evidence for a nigro-pulvinar-lateralis posterior complex projection in the cat using horseradish peroxidase neuronal retrograde technique.
The possible existence of a direct projection from the substantia nigra to the pulvinar-lateral posterior complex (Pul-LP) was investigated in the cat by using the horseradish peroxidase technique. In particular horseradish peroxidase was injected in the Pul-LP of 8 animals, either unilaterally or bilaterally. Tissue sections obtained from the cat's brain 24-48 hrs. after injection were prepared according to Mesulam's method as slightly modified by the authors. Retrogradelly labelled neurons were observed in substantia nigra pars lateralis and reliculata ipsilaterally to the injected pulvinar-lateral posterior complex. A small number of labelled cells were also found in the contralateral substantia nigra. These findings demonstrate the existence of a close connection between two system which are involved in turning behavior: the nigrostriatal and the pulvinar-lateral posterior complex-superior colliculus.


Genetic polymorphisms in Parkinson disease subjects with and without hallucinations: an analysis of the cholecystokinin system.
Hallucinations in patients with Parkinson disease (PD), occurring in about one third of those receiving long-term dopaminergic therapy, contribute to morbidity and mortality. In matched Chinese PD subjects with and without hallucinations, the presence of the -45 C/T locus in the cholecystokinin (CCK) gene, particularly when combined with the CCK receptor, CCKAR (cholecystokinin A receptor), C polymorphism, was associated with increased hallucination risk. Because CCK gene polymorphisms vary across ethnic groups, the presence of similar associations in white PD subjects merits investigation. To determine whether polymorphisms of CCK and CCK receptor genes are associated with hallucinations in white PD subjects. Case-control study of PD subjects with and without chronic hallucinations matched for age and dopaminergic medication. Genomic DNA was analyzed for CCK, CCKAR, and CCKBR (cholecystokinin B receptor) polymorphisms by polymerase chain reaction. Genotype distributions and allele frequencies were compared between groups and in matched pairs. Comparing matched pairs, we found more frequent representation of the CCK T allele in hallucinating PD subjects, although this finding was not statistically significant (P =.06). Of 5 cases with both CCK T and CCKAR C alleles, 4 were hallucinators. Cases and controls did not differ in CCKAR or CCKBR polymorphisms. Our study supports a previous association of hallucinations in PD subjects with the CCK T allele and the combined CCK T and CCKAR C allele, suggesting that the CCK system may influence the development of hallucinations in PD subjects. The lower representation of the T allele in our white sample limited our statistical power. Further assessment of the T allele as a risk factor for hallucinations would include longitudinal study of nonhallucinators to detect the evolution of hallucinations relative to T allele frequency.


Seborrheic keratoses from the genital region may contain human papillomavirus DNA.
Sections from paraffin-embedded tissues of lesions interpreted as seborrheic keratoses localized to the pubic, genital, and crural regions were assayed for the presence of human papillomavirus types 6, 11, 16, 18, and 33 using DNA amplification followed by specific hybridization. Lesions with the histologic characteristics of condyloma were excluded from the study. Human papillomavirus DNA sequences were found in 24 (42%) of 57 seborrheic keratosis-like lesions from the genital region. No human papillomavirus DNA was detected in 27 control specimens that represented a variety of other processes occurring in this area. We conclude that human papillomavirus infection cannot be excluded in genital seborrheic keratoses.


Loss of imprinting of IGF2 correlates with hypomethylation of the H19 differentially methylated region in the tumor tissue of colorectal cancer patients.
Expression of the imprinted genes insulin-like growth factor 2 (IGF2) and H19 depends on the methylation pattern of their differentially methylated region (DMR) located on chromosome 11p15. In the present study, we examined the imprinting status of the IGF2 gene in 120 human colorectal cancer (CRC) patients and 150 normal controls. In addition, we analyzed the DNA methylation of the sixth CTCF-binding site in the DMR of IGF2/H19 in 81 CRC patients using bisulfate sequencing. Of a total of 81 informative (heterozygous) samples, 51 samples showed bialleic IGF2 expression in tumor samples; however, only 15 of 69 informative samples showed loss of imprinting (LOI) of IGF2 in normal controls. Statistically significant differences in the methylation status between the retention of imprinting (ROI) and LOI groups (66.1±14.9 vs. 16.7±9.2, p=0.008) were observed. The results of the present study suggest that LOI of IGF2 is important in the carcinogenesis of CRC. Hypomethylation of the sixth CTCF-binding site in the DMR of IGF2/H19 is linked to LOI and the common IGF2-H19 enhancer competition model for IGF2 imprinting does not apply to human CRC.


The X-C···π (X = F, Cl, Br, CN) carbon bond.
High-level ab initio calculations have been used to study the interactions between the CH3 group of CH3X (X = F, Cl, Br, CN) molecules and π-electrons. These interactions are important because of the abundance of both the CH3 groups and π-electrons in biological systems. Complexes between C2H4/C2H2 and CH3X molecules have been used as model systems. Various theoretical methods such as atoms in molecules theory, reduced density gradient analysis, and natural bond orbital analysis have been used to discern these interactions. These analyses show that the interaction of the π-electrons with the CH3X molecules leads to the formation of X-C···π carbon bonds. Similar complexes with other tetrel molecules, SiH3X and GeH3X, have also been considered.


Tardive dyskinesia: reversible and irreversible.
The long-term prognosis of tardive dyskinesia (TD) has been insufficiently studied. Symptoms are reversible in many patients, but an irreversible course is widely believed to be the expected outcome. This pessimistic view has led to the assumption that neuroleptics should not be used in patients with TD because these drugs will produce an inevitable aggravation of TD. To clarify this issue, 27 patients were serially evaluated over 5 years for changes in neuroleptic treatment, TD, and mental status. Ten patients were able to discontinue medications; 15 required continued low-dose neuroleptic therapy [average 223 mg/day chlorpromazine (CPZ) equivalents], and two needed high doses (1000-2000 mg/day CPZ equivalents) to control psychosis. The majority of patients improved by more than 50% in both treated and untreated groups. In 8 of 27 patients (29.6%) TD resolved; in 1 patient TD increased by 25%. Younger patients improved the most. Prognosis was most favorable if neuroleptics were discontinued, but improvement was still possible with low to moderate doses (less than 600 mg/day CPZ equivalents). The large majority of patients with schizophrenia or schizoaffective illness relapsed, and required continued drug treatment. TD must be evaluated over several years to monitor the resolving/persisting course. Control of psychosis and improvement of TD during low-dose neuroleptic treatment suggest the antipsychotic and neurological effects of neuroleptics may involve different thresholds or mechanisms of action.


Lead exposure, IQ, and behavior in urban 5- to 7-year-olds: does lead affect behavior only by lowering IQ?
Lead exposure in childhood lowers IQ scores, but its effect on children's behavior is less clear. Because IQ, per se, affects behavior, measuring the direct effect of lead requires measuring and then adjusting for IQ. In addition, either peak blood lead concentration, usually at 2 years old, or the lower blood lead level measured at school age may be the most relevant. Few studies have all of this information. The purpose of this work was to differentiate the direct effect of lead on behavior and the indirect effect through IQ and to examine the strength of the association for peak and concurrent blood lead concentration. Data come from a clinical trial of the chelating drug succimer to prevent cognitive impairment in 780 urban 12- to 33-month-olds with blood lead concentrations of 20 to 44 microg/dL. The children were followed from ages 2 to 7 years. The trial data were analyzed as a prospective observational study. Blood lead concentration at 2 years old was not associated with Conners' Parent Rating Scale-Revised scores at 5 years of age or Behavioral Assessment Systems for Children scores at 7 years of age. Blood lead level at 7 years of age had direct effects on the Behavioral Assessment Systems for Children behavioral symptoms index, externalizing, and school problems at age 7. Concurrent blood lead concentration was associated with externalizing and school problems scales at 7 years of age, and the effect was not entirely mediated through the effect of lead on IQ.


[The professor-student relationship in coping with dying].
The new guidelines for undergraduate courses in the field of health care imply a need to prepare professionals to deal with life and death. To study death and dying in the context of nurse education means to contribute to the humanization of education and to preparing humanistic and critical professionals. We performed individual interviews with professors so that each could reveal their thoughts about experiencing death and dying in the educational relationship between nurse/professor and the nursing student in the hospital environment. Content analysis was performed using ideas close to those of Heidegger, revealing that education towards the concept and experience of death appears to be possible only if there is reflection regarding human existence, thoughts, and accepting finitude. By understanding one's own attitudes towards death and existence, it is possible to perceive possibilities in education for care in the death process.


Host blood RNA signatures predict the outcome of tuberculosis treatment.
Biomarkers for tuberculosis treatment outcome will assist in guiding individualized treatment and evaluation of new therapies. To identify candidate biomarkers, RNA sequencing of whole blood from a well-characterized TB treatment cohort was performed. Application of a validated transcriptional correlate of risk for TB revealed symmetry in host gene expression during progression from latent TB infection to active TB disease and resolution of disease during treatment, including return to control levels after drug therapy. The symmetry was also seen in a TB disease signature, constructed from the TB treatment cohort, that also functioned as a strong correlate of risk. Both signatures identified patients at risk of treatment failure 1-4 weeks after start of therapy. Further mining of the transcriptomes revealed an association between treatment failure and suppressed expression of mitochondrial genes before treatment initiation, leading to development of a novel baseline (pre-treatment) signature of treatment failure. These novel host responses to TB treatment were integrated into a five-gene real-time PCR-based signature that captures the clinically relevant responses to TB treatment and provides a convenient platform for stratifying patients according to their risk of treatment failure. Furthermore, this 5-gene signature is shown to correlate with the pulmonary inflammatory state (as measured by PET-CT) and can complement sputum-based Gene Xpert for patient stratification, providing a rapid and accurate alternative to current methods.


[A clinical study of oral adenoid cystic carcinoma].
Author experienced a case of tubular type, and a case of solid & basaloid type in adenoid cystic carcinoma and presented these cases through the review of literature. The paralysis was found. Both cases showed perineural, muscular tissue and bony invasion. Respectively hemimaxillectomy, and subtotal maxillectomy were operated. The origin of adenoid cystic carcinoma was considered as myoepithelial cell combined with intercalated duct reserve cell.


CFTR: cystic fibrosis and beyond.
Cystic fibrosis (CF) remains the most common fatal hereditary lung disease. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene 25 years ago set the stage for: 1) unravelling the molecular and cellular basis of CF lung disease; 2) the generation of animal models to study in vivo pathogenesis; and 3) the development of mutation-specific therapies that are now becoming available for a subgroup of patients with CF. This article highlights major advances in our understanding of how CFTR dysfunction causes chronic mucus obstruction, neutrophilic inflammation and bacterial infection in CF airways. Furthermore, we focus on recent breakthroughs and remaining challenges of novel therapies targeting the basic CF defect, and discuss the next steps to be taken to make disease-modifying therapies available to a larger group of patients with CF, including those carrying the most common mutation ΔF508-CFTR. Finally, we will summarise emerging evidence indicating that acquired CFTR dysfunction may be implicated in the pathogenesis of chronic obstructive pulmonary disease, suggesting that lessons learned from CF may be applicable to common airway diseases associated with mucus plugging.


A case of lower limb ulcer caused by hydroxyurea in treating primary thrombocytosis.
Hydroxyuria is a common medication for treating blood system diseases, but ulcers in the lower limbs caused by this medication are often rare and not often suspected. We reported an elderly patient with lower limb ulcers caused by hydroxyurea treatment for primary thrombocytosis. When hydroxide is used, close observation of skin lesions and prompt handling of any skin disruption should prevent ulcers.


Hospital human resource planning in Slovakia.
The study is an attempt to provide empirical evidence, in the context of acute hospital care, of the current human resource practices in the health sector of the Slovak Republic. Using a sample of 72 acute care hospitals the research explored the perceived functions, typical customers and priorities of hospital human resource departments, ownership of a workforce plan, and the relationships between ownership of a workforce plan and type of hospital, as well as the degree to which different human resource activities are given priority. Cross-tabulation procedure revealed statistically significant relationships between ownership of a workforce plan and the degree of priority given to having a quick, efficient and cost-effective recruitment and selection system and, not surprisingly, the degree of priority given to ensuring that the human resource department has a workforce plan. The study evidence also indicates that, although the human resource staff in hospitals seem to be aware of their role in assisting hospital management in decision making, the human resource function in the Slovak hospitals still rather resembles that of a personnel administration than that of an important strategic human resource activity.


Ex vivo priming of endothelial progenitor cells with SDF-1 before transplantation could increase their proangiogenic potential.
As SDF-1 and its cognate receptor CXCR4 play a key role in the survival and mobilization of immature cells, we examined whether preconditioning of endothelial progenitor cells (EPCs) with SDF-1 could further promote their capacity to enhance angiogenesis. EPC exposure to 100 ng/mL SDF-1 for 30 min induced a proangiogenic phenotype, with cell migration and differentiation into vascular cords in Matrigel and increased their therapeutic potential in a nude mouse model of hindlimb ischemia. This pretreatment enhanced EPC adhesion to activated endothelium in physiological conditions of blood flow by stimulating integrin-mediated EPCs binding to endothelial cells. Pretreated EPCs showed significantly upregulated surface alpha4 and alphaM integrin subunit expression involved in the homing of immature cells to a neovasculature and enhanced FGF-2 and promatrix metalloproteinase (MMP)-2 secretion. All these effects were significantly attenuated by EPC incubation with AMD-3100, a CXCR4 antagonist, by prior HSPGs disruption and by HUVEC incubation with anti-intercellular adhesion molecule1 (ICAM-1) and anti-vascular cell adhesion molecule (VCAM) blocking antibodies. Pretreated EPCs adhered very rapidly (within minutes) and were resistant to shear stresses of up to 2500 s(-1). SDF-1 pretreatment during EPC expansion stimulates EPC adhesion to endothelial cells and thus augments the efficiency of cell therapy for ischemic vascular diseases.


Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane.
To evaluate the surgical results in a series of patients with diabetic macular edema associated with traction from a thickened and taut posterior hyaloid membrane and to identify features associated with better visual outcome. We reviewed the clinical records of ten consecutive patients who underwent pars plana vitrectomy in one eye for diabetic macular edema that was preoperatively attributed to thickening and traction of the posterior hyaloid membrane. Best-corrected, preoperative visual acuity was 20/200 in seven eyes, 20/300 in one eye, and 20/400 in two eyes. Intraoperatively, seven patients were found to have an attached posterior hyaloid membrane which was thickened and taut. Among these seven patients, postoperative best-corrected visual acuity improved by six lines in two eyes, by five lines in one eye, by two lines in one eye, and remained within one line of preoperative visual acuity in three eyes. The other three patients had an epiretinal membrane simulating an attached and thickened posterior hyaloid membrane. Vitrectomy effectively improved visual acuity in some eyes with diabetic macular edema associated with traction from a thickened and taut posterior hyaloid membrane. Despite careful preoperative examination with a fundus contact lens, however, in some patients it may be difficult to assess how the posterior hyaloid membrane contributes to the macular edema. In selected patients, early surgical intervention may be associated with better visual outcome.


The historical evolution of some intrinsic dimensions of quarantine.
The word "Quarantine" makes its first recorded appearance in the English language in the seventeenth century. It was originally a thirty-to-forty day period in which subjects suspected of carrying a contagious disease were subjected to detention and segregation with selective restraint regulations regarding circulation. Five dimensions are implicit in this original use of the term: "time", "disease", "context", "restraint" and "segregation". These dimensions have undergone modification through time, and more recently the term has come to indicate a more variable time period, adopted with reference to the compulsory physical separation not only of groups of human beings potentially exposed to contagious disease, but also of animals, goods and various means of transportation. Currently, "new" pathologies such as SARS and avian influenza must also be considered, and the context dimension has become much more various than in the past, while the restraint dimension is now connected with personal liberty and autonomy and not only with medical-health risks. Finally, the original palliative, rather than curative, segregation dimension has left space to specialised therapeutic quarantine units, in this way completing the medical and figurative evolution of the concept of quarantine through time.


Effect of prenatal calcium supplementation on bone during pregnancy and 1 y postpartum.
Low calcium intake during pregnancy may cause maternal skeletal calcium mobilization to meet fetal needs. The Recommended Dietary Allowance (RDA) for calcium in nonpregnant, pregnant, or lactating women aged 19-50 y is 1000 mg/d; most women in the United States report consuming 60-80% of the calcium RDA. An insufficient calcium intake could increase maternal bone loss during pregnancy and reduce bone recovery postpartum. The aim of this study was to determine the effect of maternal calcium supplementation on peripheral cortical and trabecular bone loss during pregnancy and bone gain postpartum. A total of 64 women were enrolled in the study at 16 wk of gestation and randomly assigned to receive 1000 mg Ca/d or placebo for the remainder of the pregnancy. Measurements were performed at 16, 26, and 36 wk of pregnancy and at 4 and 12 mo postpartum for serum 25-hydroxyvitamin D and markers of bone turnover. Trabecular and cortical bone mineral density (BMD) and content were assessed at the tibia and radius by peripheral quantitative computed tomography. Mean ± SD daily calcium intake at baseline was 733 ± 350 mg; only 25% of the women met the RDA. Thirty women (47% of those enrolled) remained in the study at 12 mo postpartum. After controlling for baseline bone value, serum 25-hydroxyvitamin D concentrations, length of breastfeeding, and body mass index, the calcium group had significantly greater increases in radial total BMD (P = 0.02) and tibial cortical BMD (P = 0.03) at 12 mo postpartum than the placebo group. Trabecular and total BMD at the tibia trended toward higher values (P < 0.06) in the calcium group than in the placebo group in the same models. These data show that supplemental calcium provided during pregnancy may improve bone recovery postpartum in women consuming a typical US diet. A larger study is warranted to solidify the conclusions. This trial was registered at clinicaltrials.gov as NCT01145573.


Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis.
To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS). This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS-quintile. Time to new/enlarging T2-hyperintense and gadolinium-enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile. A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS-quintile-adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29-0.70, p < 0.001; rate difference = 0.27, 95% CI = 0.14-0.40, p = 0.004). One would need to treat with newer rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [HR] = 0.51, 95% CI = 0.36-0.72, p < 0.001) and gadolinium-enhancing lesions (HR = 0.38, 95% CI = 0.23-0.63, p < 0.001) than those on injectables. Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long-term safety data for newer DMTs are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42-55.


Evidence-based practice in rural and remote clinical practice: where is the evidence?
To critically review the evidence regarding barriers to implementing research findings in rural and remote settings, and the ways those barriers have been addressed. A systematic review that included searching several electronic databases, Internet sites and reference lists of relevant articles, assessment of methodological quality of the studies, and data extraction and analysis where possible. Eligibility for the review was not limited by study design. Studies that reported on: (1) barriers to the implementation of evidence by health professionals in rural and remote areas, or (2) interventions for implementing evidence-based practice or an element of evidence-based practice in rural and remote areas. There were no experimental data available on the implementation of research findings in rural and remote clinical settings. The small amounts of empirical research undertaken (surveys) showed that some of the problems experienced by general practitioners were exacerbated by rural and remote location, particularly with relation to isolation, lack of time and locum cover, and poor information technology infrastructure. There is a paucity of empirical literature on implementing evidence-based practice in rural and remote settings. This is in contrast to the large amount of literature available on implementing evidence in other clinical settings. A clear finding from the literature was that getting evidence into practice needs to be context-specific and yet very little research has been conducted into the rural and remote context. Research is needed into how evidence can be implemented in contextually specific ways in rural and remote areas.


Usefulness of hydatid cyst fluid of Echinococcus granulosus developed in mice with secondary infection for serodiagnosis of cystic Echinococcosis in humans.
The aim of this work was to assess the usefulness of hydatid cyst fluid (HCF) of Echinococcus granulosus, obtained from mice experimentally infected with hydatid cyst tissue homogenates, for the serodiagnosis of cystic echinococcosis (CE) in humans. The sensitivity and specificity of HCF obtained from mice for the detection of immunoglobulin G (IgG) antibodies in the sera of CE patients were compared with those of HCF from sheep and/or from a human CE patient by using immunoblotting (IB) and an enzyme-linked immunosorbent assay (ELISA). HCFs obtained from three different host species all were highly useful for immunoblotting, and sera from 19 (95%) of 20 CE patients equally recognized the antigen B subunit (approximately 8 kDa). HCF from mice showed a cross-reaction with 9 of 20 alveolar echinococcosis (AE) sera (45%), whereas HCFs from two other host species cross-reacted with 14 of the AE sera (70%). Although 2 (10%) of 20 sera from neurocysticercosis (NCC) patients were false positive with HCF from both sheep and humans, none of these sera showed a positive reaction with HCF from mouse origin. ELISAs with HCFs from both mouse and sheep origins detected all 20 CE and AE sera; however, these ELISAs showed 45% (9 of 20) and 60% (12 of 20) false-positive reactions with 20 NCC sera, respectively. The presence of nonspecific human IgG in HCF obtained from a CE patient prevented us from applying it to the ELISA. HCF of E. granulosus, obtained from laboratory mice with a secondary infection with hydatid cyst tissue homogenates, appears to be highly useful for the serodiagnosis of CE in humans and may be useful in domestic animals.


Wheelchair propulsion demands during outdoor community ambulation.
Quantify manual wheelchair propulsion effort during outdoor community ambulation. Case series. Thirteen individuals (12 with SCI, 1 with spina bifida) who were experienced manual wheelchair users and had no current upper extremity injury or pain complaints. Measurements were obtained from instrumented wheelchair rims during steady-state propulsion as subjects traversed outdoor concrete sidewalk terrain that included smooth level, aggregate level, and a ramp with a smooth surface. Propulsion effort was assessed using the average propulsion moment, average instantaneous power, and work for both upper extremities. Propulsion effort, captured by the propulsion moment, work and power, varied across ground conditions (p<0.001). Propulsion effort was greater as the rolling resistance increased (i.e., smooth versus aggregate surfaces) and as the inclination angle progressed from level to inclined surfaces. There were no side-to-side differences across ground conditions for the propulsion moment or work. Power generation was significantly greater on the dominant compared to the non-dominant extremity during the more challenging aggregate surface and ramp conditions. Propulsion effort varies with demands imposed by different ground conditions. Quantification of wheelchair propulsion demands provides rehabilitations specialists with objective information to guide treatment of patients adapting to manual wheelchair use.


Back pain claim rates in Japan and the United States: framing the puzzle.
This is a cross-national comparison of workers' compensation claims for back pain in Japan and the United States (US). The main objective is to juxtapose rates of back pain claims in Japan and Washington state. Because the Washington state rate closely matches rates for other US states as well as the rate for the US as a whole, it is used to represent the US rate. A puzzle is to be framed: Why are back pain claim rates in Japan and the United States so disparate? Occupational back pain is common among workers in both Japan and the United States. Wage compensation for time off work is also substantial in both countries and potentially induces time off work at least as much in Japan as in the United States. Accordingly, back pain claim rates in Japan seemingly would be on the same order of magnitude as rates in the United States. Washington state rates are based on data from its state fund. Both Japan and Washington state rates are composed of the number of workers eligible to file worker compensation claims in a given year (denominator) and the number of back pain claims accepted during that year (numerator). Because rates may fluctuate from year-to-year, 5 years of data on rates are presented, 1995-1999. Central to the comparison are Japanese and Washington state rates of workers' compensation claims for back pain with more than 3 days compensated time loss from work. The back pain claim rate in 1999 was 60 times higher in Washington state than in Japan. The disparity in rates for the other years in the study (1995-1998) was similar. Back pain is common among workers both in Japan and the United States, but there is no simple or necessary relationship between that symptom and how it manifests itself in one country or another. Rather, the symptom is protean in its social manifestations. As for what shapes those manifestations-or, more specifically, what causes the startling disparity in back pain claim rates between Japan and the United States-that is a puzzle. Various solutions to the puzzle are discussed, but it remains essentially unsolved.


Clinical correlates of tobacco smoking in OCD: A UK, case-controlled, exploratory analysis.
Background Obsessive-compulsive disorder (OCD) is a biologically heterogeneous neuropsychiatric disorder. It is associated with impulsive as well as compulsive neurocognitive mechanisms. Cigarette smoking is common among most psychiatric patients; however, OCD patients are thought to show reduced rates. OCD smokers may thus represent a relatively uncommon OCD subtype, characterised by increased impulsivity. In this study, we aim to establish the prevalence of smoking in a large, well-defined OCD cohort. We investigate whether smokers with OCD differ from non-smokers with OCD on clinical measures of behavioural impulsivity and domains of personality and temperament, including reward-dependence and novelty-seeking. Method 183 of 200 outpatients with DSM-IV OCD were interviewed to determine smoking status. A sub-sample of 10 smokers was compared with 10 non-smokers, pair wise matched for age and gender. Patients were assessed for DSM co-morbidity, symptom profile, OCD severity, behavioural impulsivity and personality dimensions. Results Only 10 individuals (5.46%; five males) were smokers. Compared to OCD non-smokers, OCD smokers scored significantly higher on the Barratt Impulsiveness Scale (p < 0.001). They also scored significantly higher on TCI measures of novelty seeking (p < 0.001) and reward dependence (p < 0.001) and significantly lower on measures of harm avoidance (p < 0.001). Conclusions Tobacco smoking is rare in OCD. Significantly higher levels of behavioural impulsivity and temperamental factors associated with reward driven impulsivity are seen in OCD smokers compared to non-smokers. Tobacco smoking may indicate a possible source of neurocognitive heterogeneity in OCD.


Coagulation disorders and thromboembolic disease in COVID-19: review of current evidence in search of a better approach.
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been an unprecedented global health problem, causing more than 20 million infections and more than 900,000 deaths (September 2020). The SARS-CoV-2 infection, known as COVID-19, has various clinical presentations, from asymptomatic or mild catarrhal processes to severe pneumonia that rapidly progresses to acute respiratory distress syndrome (ARDS) and multiple organ failure. In the last few months, much scientific literature has been devoted to descriptions of different aspects of the coagulation disorders and arterial and venous thrombotic complications associated with COVID-19, particularly venous thromboembolism (VTE). These studies have revealed that SARS-CoV-2 could lead to a prothrombotic state reflecting the high cumulative incidence of associated thrombotic events, particularly in patients admitted to intensive care units (ICUs). As regards the coagulopathy observed in association with SARS-CoV-2 infection, the mechanisms that activate coagulation have been hypothesized as being linked to immune responses, through the release of pro-inflammatory mediators that interact with platelets, stimulate the expression of tissue factor, induce an upregulation of plasminogen activator inhibitor-1, suppress the fibrinolytic system and lead to endothelial dysfunction, triggering thrombogenesis. D-dimer elevation has been recognized as a useful biomarker of poor prognosis, although the best cut-off point for predicting VTE in COVID-19 patients has still not been clarified. This review will try to update all the available scientific information on this important topic with enormous clinical and therapeutic implications.


High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation.
POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome.


Convex probe endobronchial ultrasound: historical, contemporary, and cutting-edge applications.
The use of convex-probe endobronchial ultrasound (CP-EBUS) has revolutionized bronchoscopy. It has provided the option of a relatively safe, minimally invasive approach for the assessment of various intrathoracic diseases. In current practice, its most dramatic impact has been on the diagnosing and staging of lung cancer. It has served as an invaluable tool that has replaced mediastinoscopy in a variety of clinical scenarios. Many pulmonologists and thoracic surgeons consider CP-EBUS the most significant milestone in bronchoscopy after the development of the flexible bronchoscope itself. In this review, we summarize the historical aspects, current indications, technical approach, and future direction of CP-EBUS.


Potato Virus Y HCPro Suppression of Antiviral Silencing in Nicotiana benthamiana Plants Correlates with Its Ability To Bind In Vivo to 21- and 22-Nucleotide Small RNAs of Viral Sequence.
We have investigated short and small RNAs (sRNAs) that were bound to a biologically active hexahistidine-tagged Potato virus Y (PVY) HCPro suppressor of silencing, expressed from a heterologous virus vector in Nicotiana benthamiana plants, and purified under nondenaturing conditions. We found that RNAs in purified preparations were differentially enriched in 21-nucleotide (nt) and, to a much lesser extent, 22-nt sRNAs of viral sequences (viral sRNAs [vsRNAs]) compared to those found in a control plant protein background bound to nickel resin in the absence of HCPro or in a purified HCPro alanine substitution mutant (HCPro mutB) control that lacked suppressor-of-silencing activity. In both controls, sRNAs were composed almost entirely of molecules of plant sequence, indicating that the resin-bound protein background had no affinity for vsRNAs and also that HCPro mutB failed to bind to vsRNAs. Therefore, PVY HCPro suppressor activity correlated with its ability to bind to 21- and 22-nt vsRNAs. HCPro constituted at least 54% of the total protein content in purified preparations, and we were able to calculate its contribution to the 21- and the 22-nt pools of sRNAs present in the purified samples and its binding strength relative to the background. We also found that in the 21-nt vsRNAs of the HCPro preparation, 5'-terminal adenines were overrepresented relative to the controls, but this was not observed in vsRNAs of other sizes or of plant sequences.IMPORTANCE It was previously shown that HCPro can bind to long RNAs and small RNAs (sRNAs) in vitro and, in the case of Turnip mosaic virus HCPro, also in vivo in arabidopsis AGO2-deficient plants. Our data show that PVY HCPro binds in vivo to sRNAs during infection in wild-type Nicotiana benthamiana plants when expressed from a heterologous virus vector. Using a suppression-of-silencing-deficient HCPro mutant that can accumulate in this host when expressed from a virus vector, we also show that sRNA binding correlates with silencing suppression activity. We demonstrate that HCPro binds at least to sRNAs with viral sequences of 21 nucleotides (nt) and, to a much lesser extent, of 22 nt, which were are also differentially enriched in 5'-end adenines relative to the purified controls. Together, our results support the physical binding of HCPro to vsRNAs of 21 and 22 nt as a means to interfere with antiviral silencing.


Regional air quality in Leipzig, Germany: detailed source apportionment of size-resolved aerosol particles and comparison with the year 2000.
A detailed source apportionment of size-resolved aerosol particles in the area of Leipzig, Germany, was performed. Sampling took place at four sites (traffic, traffic/residential, urban background, regional background) in parallel during summer 2013 and the winters 2013/14/15. Twenty-one samples were taken per season with a 5-stage Berner impactor and analysed for particulate mass, inorganic ions, organic and elemental carbon, water-soluble organic carbon, trace metals, and a wide range of organic species. The compositional data were used to estimate source contributions to particulate matter (PM) in quasi-ultrafine (up to 140 nm), accumulation mode, and coarse size ranges using Positive Matrix Factorisation (PMF) receptor modelling. Traffic (exhaust and general traffic emissions), coal combustion, biomass combustion, photochemistry, general secondary formation, cooking, fungal spores, urban dust, fresh sea/road salt, and aged sea salt were all found to contribute to different extents to observed PM concentrations. PMF derived estimates agreed reasonably with estimates from established macrotracer approaches. Quasi-ultrafine PM originated mainly from traffic (20-50%) and photochemistry (30-50%) in summer, while it was dominated by solid fuel (mainly biomass) combustion in winter (50-70%). Tentatively identified cooking aerosol contributed up to 36% on average at the residential site. For accumulation mode particles, two secondary sources typically contributed 40-90% to particle mass. In winter, biomass and coal combustion contributions were up to ca. 25% and 45%, respectively. Main sources of coarse particles were diverse and included nearly all PMF-resolved ones depending on season and air mass origin. For PM10, traffic (typically 20-40% at kerbside sites), secondary formation (30-60%), biomass combustion (10-15% in winter), and coal combustion (30-40% in winter with eastern air mass inflow) were the main quantified sources. At the residential site, contributions from biomass combustion derived up to 60% from local emissions. Coal combustion as a significant source was only present during eastern air mass inflow and showed very similar concentrations at all sites, indicating the importance of trans-boundary air pollution transport in the study area. Overall, nearly half of the PM10 mass was attributed to urban sources by a simple subtractive approach with highest reduction potentials of up to 80% for local (urban) mitigation measures in ultrafine and coarse particles. Local increments of elemental carbon have decreased by about 50% as compared to the year 2000, corroborating results from a former study on the positive effects of a low emission zone, implemented in Leipzig in 2011.


Recent advances in immune modulation.
Successful gene therapy protocols rely on the hypo-responsiveness of the immune system to transgene products generated from gene transfer vectors. In order to prevent cytotoxic lymphocyte or antibody formation induced by transgene expression, various strategies derived from recent advances in immune tolerance induction protocols have been tested in gene therapy model systems. Current immunosuppressive drugs were used to nonspecifically target T-cell activation, clonal expansion, and differentiation into effector cells. Central tolerance can be induced from intrathymic deletion of T cells with thymically expressed antigens or generation of hematopoietic mixed chimerism. Peripheral tolerance to transgenes may be achieved by several different pathways including deletion of activated/effector T cells by depleting antibodies, generation of T cell apoptosis or anergy by costimulation blockade, and active suppression by T regulatory cells. This review outlines the development of these strategies using various immune modulation regimens and protocols to induce long-term immune tolerance specific to the transgene product.


Designing Patchy Interactions to Self-Assemble Arbitrary Structures.
One of the fundamental goals of nanotechnology is to exploit selective and directional interactions between molecules to design particles that self-assemble into desired structures, from capsids, to nanoclusters, to fully formed crystals with target properties (e.g., optical, mechanical, etc.). Here, we provide a general framework which transforms the inverse problem of self-assembly of colloidal crystals into a Boolean satisfiability problem for which solutions can be found numerically. Given a reference structure and the desired number of components, our approach produces designs for which the target structure is an energy minimum, and also allows us to exclude solutions that correspond to competing structures. We demonstrate the effectiveness of our approach by designing model particles that spontaneously nucleate milestone structures such as the cubic diamond, the pyrochlore, and the clathrate lattices.


[Microscopic innervation of the skin and annexes of the labium oris].
It is studied the skin and annexes innervation of cat and Wistar rat lips with argentic impregnation and acetylcholinesterase technique. It is made evident the existence of a subepithelial plexus from where some nervous fibers leave ending in the epithelial deep stratums and nervous fibers that finish in dermis thickness forming complex ramifications and different type I and II of SETO morphotypes of nervous receptors. They aren't found typical Merckel, Meissner o Paccini mechano-receivers. The nervous terminations in the transition skin-mucous zone are like the ones found in the rest of skin epidermis. Some intraepithelial fibers have been described at level of sudoriferous and sebaceus glands and sensitive corpuscles in connexion with pilous follicles.


Relative bioavailability of coumarin from cinnamon and cinnamon-containing foods compared to isolated coumarin: a four-way crossover study in human volunteers.
Cassia cinnamon contains high levels (up to 1 %) of coumarin. Heavy consumption of this spice may result in a dose exceeding the tolerable daily intake (TDI). In this context, the question was raised whether coumarin in the plant matrix of cinnamon has the same bioavailability as isolated coumarin. A four-way crossover study was performed, in which the same dose of 12 mg coumarin was administered in different formulations to 24 healthy volunteers. The relative extent of absorption measured as urinary excretion of the main metabolite 7-hydroxycoumarin (7OHC) was found to be 62.8% for isolated coumarin in a capsule (reference), 56.0% for cinnamon in capsules, 66.1% for cinnamon tea, and 54.7% for cinnamon in rice pudding (means, n=23, observation period 8 hours). Additionally, 7OHC plasma levels were measured for 105 minutes after administration and revealed a fast absorption of coumarin from cinnamon tea leading to the highest peak concentrations. The relative extent of absorption of coumarin from powder of cassia cinnamon is only slightly lower than that of isolated coumarin. Therefore, the TDI of coumarin can be used for risk assessment of coumarin exposure from cinnamon-containing meals.


Effects of fusion between tactile and proprioceptive inputs on tactile perception.
Tactile perception is typically considered the result of cortical interpretation of afferent signals from a network of mechanical sensors underneath the skin. Yet, tactile illusion studies suggest that tactile perception can be elicited without afferent signals from mechanoceptors. Therefore, the extent that tactile perception arises from isomorphic mapping of tactile afferents onto the somatosensory cortex remains controversial. We tested whether isomorphic mapping of tactile afferent fibers onto the cortex leads directly to tactile perception by examining whether it is independent from proprioceptive input by evaluating the impact of different hand postures on the perception of a tactile illusion across fingertips. Using the Cutaneous Rabbit Effect, a well studied illusion evoking the perception that a stimulus occurs at a location where none has been delivered, we found that hand posture has a significant effect on the perception of the illusion across the fingertips. This finding emphasizes that tactile perception arises from integration of perceived mechanical and proprioceptive input and not purely from tactile interaction with the external environment.


The role of collaborative interactivity in the observational practice of clinical skills.
Video-based observational practice can extend simulation-based learning outside the training space. This study explores the value of collaborative feedback provided during observational practice to the acquisition of clinical skills. Nursing students viewed a video demonstrating the proper ventrogluteal injection technique before performing a videotaped pre-test trial on a simulator. They were then assigned randomly to one of three observational practice groups: a group that observed the expert demonstration (EO group); a group that viewed the expert demonstration, self-assessed their individual pre-test and contrasted their self-assessments with expert feedback (ESO group), and a group that observed the expert demonstration, self-assessed and contrasted their assessments with those of an expert, and formed a community that engaged in peer-to-peer feedback (ESPO group). The observation of all videos, the provision of assessments and all networking occurred via an Internet-mediated network. After 2 weeks, participants returned for post-tests and transfer tests. The pre-test-post-test analyses revealed significant interactions (global rating scale: F((2,22)) =4.00 [p =0.033]; checklist: F((2,22)) =4.31 [p =0.026]), which indicated that post-test performance in the ESPO group was significantly better than pre-test performance. The transfer analyses revealed main effects for both the global rating scale (F((2,23)) =6.73; p =0.005) and validated checklist (F((2,23)) =7.04; p =0.004) measures. Participants in the ESPO group performed better on the transfer test than those in the EO group. The results suggest that video-based observational practice can be effective in extending simulation-based learning, but its effectiveness is mediated by the amount of time the learner spends engaged in the practice and the type of learning activities the learner performs in the observational practice environment. We speculate that increasing collaborative interactivity supports observational learning by increasing the extent to which the educational environment can accommodate learners' specific needs.


Stable megadalton TOC-TIC supercomplexes as major mediators of protein import into chloroplasts.
Preproteins are believed to be imported into chloroplasts through membrane contact sites where the translocon complexes of the outer (TOC) and inner (TIC) envelope membranes are assembled together. However, a single TOC-TIC supercomplex containing preproteins undergoing active import has not yet been directly observed. We optimized the blue native polyacrylamide gel electrophoresis (PAGE) (BN-PAGE) system to detect and resolve megadalton (MD)-sized complexes. Using this optimized system, the outer-membrane channel Toc75 from pea chloroplasts was found in at least two complexes: the 880-kD TOC complex and a previously undetected 1-MD complex. Two-dimensional BN-PAGE immunoblots further showed that Toc75, Toc159, Toc34, Tic20, Tic56 and Tic110 were all located in the 880-kD to 1.3-MD region. During active preprotein import, preproteins were transported mostly through the 1-MD complex and a smaller amount of preproteins was also detected in a complex of 1.25 MD. Antibody-shift assays showed that the 1-MD complex is a TOC-TIC supercomplex containing at least Toc75, Toc159, Toc34 and Tic110. Results from crosslinking and import with Arabidopsis chloroplasts suggest that the 1.25-MD complex is also a supercomplex. Our data provide direct evidence supporting that chloroplast preproteins are imported through TOC-TIC supercomplexes, and also provide the first size estimation of these supercomplexes. Furthermore, unlike in mitochondria where translocon supercomplexes are only transiently assembled during preprotein import, in chloroplasts at least some of the supercomplexes are preassembled stable structures.


Anaerobic infections and Clostridium difficile colitis emerging during antibacterial therapy.
Almost all cases of Clostridium difficile-related pseudomembranous colitis are related to antimicrobial therapy. Virtually all antibacterial agents have been implicated, notable exceptions being vancomycin and parenterally administered aminoglycosides. The most prominent causes of colitis are ampicillin, clindamycin and various cephalosporins. In general, this complication is related to suppression of indigenous flora and overgrowth of C. difficile. In the case of ampicillin, however, C. difficile is always susceptible. Beta-lactamase production by elements of the bowel flora leads to destruction of ampicillin and subsequently to increased counts of C. difficile and colitis. Much less well-appreciated, and much less studied, is overgrowth and subsequent infection by other types of anaerobic bacteria. Superinfection by anaerobes may follow the use of "intestinal antiseptics" such as oral neomycin; indeed, that is the rationale for the current practice in the U.S. of combining erythromycin or tetracycline with the oral aminoglycoside. Superinfection with anaerobes may also follow systemic administration of various antimicrobial compounds. Such superinfections may involve any site in the body, although sepsis and intraabdominal infection have been noted most commonly; all major types of anaerobes have been involved. A wide variety of antimicrobial compounds has been implicated in predisposing to anaerobic infection.


Relationships of Schistosoma haematobium, hookworm and malarial infections and metrifonate treatment to growth of Kenyan school children.
Relationships of S. haematobium, hookworm and malarial infections to growth 6 months after metrifonate treatment were studied in Kenyan primary school children in an area where poor growth, S. haematobium and hookworm were common and malaria was endemic. All children with light-moderate S. haematobium infections (1-500 eggs/10 ml adj) in 4 schools were examined (Exam 1), allocated at random to either placebo (MIP, n = 198) or metrifonate treatment (MIT, n = 201) groups, treated, and examined again 6 months later (Exam 2). An additional 19 heavily infected children (HIT group greater than 500 eggs/10 ml adj) were treated immediately after Exam 1 and also followed. The MIT and HIT groups exhibited more rapid growth between Exam 1 and 2 than did the placebo group. The MIT group gained significantly (P less than 0.001) more than the MIP group in weight (0.8 kg), percent weight for age (2.3 percentage points), weight for height squared (0.04 units), arm circumference (0.4 cm), percent arm circumference for age (1.7 percentage points) and in triceps and subscapular skinfold thicknesses. In addition, the placebo group showed statistically significant decreases between exams in percentage weight for age, percent arm circumference for age, both skinfold thicknesses for age and no significant increase in percent height for age while the MIT group exhibited highly significant increases in all anthropometric parameters.(ABSTRACT TRUNCATED AT 250 WORDS)


Urinary Amine and Organic Acid Metabolites Evaluated as Markers for Childhood Aggression: The ACTION Biomarker Study.
Biomarkers are of interest as potential diagnostic and predictive instruments in personalized medicine. We present the first urinary metabolomics biomarker study of childhood aggression. We aim to examine the association of urinary metabolites and neurotransmitter ratios involved in key metabolic and neurotransmitter pathways in a large cohort of twins (N = 1,347) and clinic-referred children (N = 183) with an average age of 9.7 years. This study is part of ACTION (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies), in which we developed a standardized protocol for large-scale collection of urine samples in children. Our analytical design consisted of three phases: a discovery phase in twins scoring low or high on aggression (N = 783); a replication phase in twin pairs discordant for aggression (N = 378); and a validation phase in clinical cases and matched twin controls (N = 367). In the discovery phase, 6 biomarkers were significantly associated with childhood aggression, of which the association of O-phosphoserine (β = 0.36; SE = 0.09; p = 0.004), and gamma-L-glutamyl-L-alanine (β = 0.32; SE = 0.09; p = 0.01) remained significant after multiple testing. Although non-significant, the directions of effect were congruent between the discovery and replication analyses for six biomarkers and two neurotransmitter ratios and the concentrations of 6 amines differed between low and high aggressive twins. In the validation analyses, the top biomarkers and neurotransmitter ratios, with congruent directions of effect, showed no significant associations with childhood aggression. We find suggestive evidence for associations of childhood aggression with metabolic dysregulation of neurotransmission, oxidative stress, and energy metabolism. Although replication is required, our findings provide starting points to investigate causal and pleiotropic effects of these dysregulations on childhood aggression.


Post Hepatectomy Liver Failure Risk Calculator for Preoperative and Early Postoperative Period Following Major Hepatectomy.
Post hepatectomy liver failure (PHLF) is associated with significant perioperative morbidity and mortality. A tool to identify patients at risk for PHLF may allow for earlier intervention to mitigate its severity and help clinicians when counseling patients. Our objective was to develop a PHLF risk calculator. Patients who underwent hepatectomy for any indication from 2014 to 2017 were identified from ACS NSQIP. A multivariable logistic regression model was developed that included preoperative and intraoperative variables. Model fit was assessed for discrimination using the C-statistic, and calibration using Hosmer and Lemeshow (HL) Chi square. Validation of the calculator was performed utilizing tenfold cross validation. Among 15,636 hepatectomy patients analyzed, the overall incidence of clinically significant PHLF was 2.8%. Preoperative patient factors associated with increased PHLF were male gender, preoperative ascites within 30 days of surgery, higher ASA class, preoperative total bilirubin greater than 1.2 mg/dl, and AST greater than 40 units/l. Disease related factors associated with PHLF included histology, and use of neoadjuvant therapy. Intraoperative factors associated with PHLF were extent of resection, open surgical approach, abnormal liver texture, and biliary reconstruction. The calculator's C-statistic was 0.83 and the HL Chi square was 10.9 (p = 0.21) demonstrating excellent discrimination and calibration. On tenfold cross validation, the mean test group C-statistic was 0.82 and the HL p value was 0.26. We present a multi-institutional preoperative and early postoperative PHLF risk calculator, which demonstrated excellent discrimination and calibration. This tool can be used to help identify high-risk patients to facilitate earlier interventions.


Percutaneous Computed Tomography-Guided Coaxial Core Biopsy for the Diagnosis of Pancreatic Tumors.
Endoscopic, ultrasound-guided tissue acquisition (EUS-TA) with rapid on-site evaluation is recommended as a first choice in the diagnosis of pancreatic lesions. Since EUS facilities and rapid on-site evaluation are not widely available, even in medical centers, an alternative for precise diagnoses of pancreatic tumor is warranted. The percutaneous computed tomography-guided, core needle biopsy (CT-CNB) is a commonly applicable method for biopsies. Our institute has developed a fat-transversing approach for pancreatic biopsies which is able to approach most tumors in the pancreas without penetrating organs or vessels. Herein, we report a 15-year experiment of pancreatic tumor coaxial CT-CNB in 420 patients. The success rate of tissue yielding by the technique was 99.3%. The overall sensitivity, specificity, and accuracy were 93.2%, 100%, and 93.4%, respectively. The diagnostic accuracy could be increased to 96.4% in 2016-2018 (after the learning curve period). The overall complication rate was 8.6%. Neither life-threatening major complications, nor seeding through the biopsy tract, were observed. Our study supported the hypothesis that CT-CNB could be a complementary option for diagnostic tissue acquisition in patients with unresectable or metastatic pancreatic tumors when EUS-TA is either unsuitable or unavailable.


Rapid correction by 1-alpha-hydroxycholecalciferol of hemichorea in surgical hypoparathyroidism.
A 45-year-old woman with long standing surgical hypoparathyroidism presented with right hemichorea of three months' duration. She had profound hypocalcaemia and hyperphosphataemia and extensive cerebral, cerebellar and basal ganglia calcification. Correction of the chemical abnormalities with 1α-hydroxycholecalciferol, calcium supplements and aluminium hydroxide resulted within 10 weeks in complete disappearance of the abnormal movements.


Systematic differences in membrane acyl composition associated with varying body mass in mammals occur in all phospholipid classes: an analysis of kidney and brain.
The acyl composition of membrane phospholipids in kidney and brain of mammals of different body mass was examined. It was hypothesized that reduction in unsaturation index (number of double bonds per 100 acyl chains) of membrane phospholipids with increasing body mass in mammals would be made-up of similar changes in acyl composition across all phospholipid classes and that phospholipid class distribution would be regulated and similar in the same tissues of the different-sized mammals. The results of this study supported both hypotheses. Differences in membrane phospholipid acyl composition (i.e. decreased omega-3 fats, increased monounsaturated fats and decreased unsaturation index with increasing body size) were not restricted to any specific phospholipid molecule or to any specific phospholipid class but were observed in all phospholipid classes. With increase in body mass of mammals both monounsaturates and use of less unsaturated polyunsaturates increases at the expense of the long-chain highly unsaturated omega-3 and omega-6 polyunsaturates, producing decreases in membrane unsaturation. The distribution of membrane phospholipid classes was essentially the same in the different-sized mammals with phosphatidylcholine (PC) and phosphatidylethanolamine (PE) together constituting approximately 91% and approximately 88% of all phospholipids in kidney and brain, respectively. The lack of sphingomyelin in the mouse tissues and higher levels in larger mammals suggests an increased presence of membrane lipid rafts in larger mammals. The results of this study support the proposal that the physical properties of membranes are likely to be involved in changing metabolic rate.


Efficacy of two dosage schedules of cephalexin in dermatologic infections.
Is the administration of oral antibiotics four times a day as necessary as some pharmacokinetic studies indicate? The efficacy of cephalexin administered twice a day was compared to the same drug administered four times a day for the treatment of skin and skin structure infections due to staphylococcus and/or streptococcus. The 154 outpatients in this four-clinic study ranged in age from 1 month to more than 70 years. A random number table was used to assign patients to either the twice a day or the four times a day regimen. The total daily dosage was the same in each regimen. Administration twice a day proved equally effective to the four times a day regimen. Both regimens were more than 97 percent effective and side effects were minimal.


Hormonal and growth factor responses to heavy resistance exercise protocols.
To examine endogenous anabolic hormone and growth factor responses to various heavy resistance exercise protocols (HREPs), nine male subjects performed each of six randomly assigned HREPs, which consisted of identically ordered exercises carefully designed to control for load [5 vs. 10 repetitions maximum (RM)], rest period length (1 vs. 3 min), and total work effects. Serum human growth hormone (hGH), testosterone (T), somatomedin-C (SM-C), glucose, and whole blood lactate (HLa) concentrations were determined preexercise, midexercise (i.e., after 4 of 8 exercises), and at 0, 5, 15, 30, 60, 90, and 120 min postexercise. All HREPs produced significant (P less than 0.05) temporal increases in serum T concentrations, although the magnitude and time point of occurrence above resting values varied across HREPs. No differences were observed for T when integrated areas under the curve (AUCs) were compared. Although not all HREPs produced increases in serum hGH, the highest responses were observed consequent to the H10/1 exercise protocol (high total work, 1 min rest, 10-RM load) for both temporal and time integrated (AUC) responses. The pattern of SM-C increases varied among HREPs and did not consistently follow hGH changes. Whereas temporal changes were observed, no integrated time (AUC) differences between exercise protocols occurred. These data indicate that the release patterns (temporal or time integrated) observed are complex functions of the type of HREPs utilized and the physiological mechanisms involved with determining peripheral circulatory concentrations (e.g., clearance rates, transport, receptor binding). All HREPs may not affect muscle and connective tissue growth in the same manner because of possible differences in hormonal and growth factor release.


Carbon Adsorbents With Dual Porosity for Efficient Removal of Uremic Toxins and Cytokines from Human Plasma.
The number of patients with chronic kidney disease increases while the number of available donor organs stays at approximately the same level. Unavoidable accumulation of the uremic toxins and cytokines for these patients comes as the result of malfunctioning kidneys and their high levels in the blood result in high morbidity and mortality. Unfortunately, the existing methods, like hemodialysis and hemofiltration, provide only partial removal of uremic toxins and/or cytokines from patients' blood. Consequently, there is an increasing need for the development of the extracorporeal treatments which will enable removal of broad spectrum of uremic toxins that are usually removed by healthy kidneys. Therefore, in this work we developed and tested ordered mesoporous carbons as new sorbents with dual porosity (micro/meso) that provide selective and efficient removal of a broad range of uremic toxins from human plasma. The new sorbents, CMK-3 are developed by nanocasting methods and have two distinct pore domains, i.e. micropores and mesopores, therefore show high adsorption capacity towards small water soluble toxins (creatinine), protein-bound molecules (indoxyl sulfate and hippuric acid), middle molecules (β-2-microglobulin) and cytokines of different size (IL-6 and IL-8). Our results show that small amounts of CMK-3 could provide selective and complete blood purification.


Spherical Cap Studs: A novel speed bump alternative to reduce discomfort with effective speed reduction.
The aim of this study is to assess the potential of Spherical Cap Studs (SCS) as a substitute for conventional speed bumps, with a focus on limiting two wheeler speed while minimizing discomfort to riders by comparing the speed reduction capabilities and discomfort levels associated with SCS and speed bumps. The study uses experimental approach to compare the speed limiting ability and discomfort caused to rider by the proposed SCS and a standard speed bump. Speed profiles were developed for two wheelers passing over both SCS and speed bump. The parameter employed to compare speed profiles is the Mean Absolute Percentage Difference (MAPD), offering valuable insights into how effectively the two traffic calming measures reduce two wheeler speeds. To compare discomfort, the study calculates the 'Vibration Dose Value' (VDV) experienced by riders when traversing both speed bump and SCS. Additionally, 'Static Compressive Stress' (Se) applied to the spinal cord is also calculated in both scenarios. The analysis of speed profiles reveals an MAPD value of 13.70% indicating that SCS exhibits speed reduction capabilities comparable to traditional speed bump. In terms of discomfort, the VDV for two wheelers passing over a speed bump is measured at 5.92 m/s1.75, whereas the VDV for SCS is found to be 5.16 m/s1.75. Similarly, the Static Compressive Stress (Se) experienced at a speed bump is 0.60 MPa, in contrast to the 0.33 MPa recorded for SCS. This data underscores a noteworthy 12.8% reduction in VDV and a substantial 45.57% reduction in Se. The study's findings support the potential adoption of SCS as an effective alternative to conventional speed bumps for controlling two wheeler speeds. SCS demonstrate a speed reduction capability similar to that of traditional speed bumps while significantly alleviating discomfort for riders. SCS is expected to be a promising solution for traffic calming purposes in various settings, such as markets, residential areas, institutional campuses, and parking lots.


Comparison of Acute Withdrawal and Slow Taper of Antiseizure Medications during Video Electroencephalographic Monitoring: Efficacy for Shortening of Hospital Stay.
Antiepileptic medications (ASMs) are withdrawn at the epilepsy monitoring unit to facilitate seizure recordings. The effect of rapid tapering of ASMs on the length of hospital stay has not been well documented. We compared the mean length of hospital stay between patients who underwent acute ASM withdrawal and slow dose tapering during long-term video electroencephalography (EEG) monitoring. We retrospectively investigated 57 consecutive patients admitted to the epilepsy monitoring unit regarding the mean length of hospital stay in the acute ASM withdrawal group (n = 30) and slow-taper group (n = 27). In the acute-withdrawal group, all ASMs were discontinued once the patients were admitted. In the slow-taper group, the doses of ASMs were gradually reduced by 15-30% daily. We also evaluated the safety of the acute-withdrawal and slow-taper protocols. The mean lengths of hospital stay were 3.8 ± 1.92 and 5.2 ± 0.69 days in the acute-withdrawal and slow-taper groups, respectively (p < 0.005). No severe adverse events, including status epilepticus, were observed. Acute ASM withdrawal has the advantage of significantly reducing the length of hospital stay over slow tapering, without any severe adverse effects.


New directions in the management of chronic pain: self-regulation theory as a model for integrative clinical psychology practice.
The next generation of empirically derived clinical health psychology involves use of self-regulation theory for understanding and treating chronic pain. Temporomandibular disorders serve as a model to illustrate how increasing self-regulatory strength facilitates small, behavioral changes that positively influence the underlying physiological factors known to be important in the etiology and maintenance of chronic pain conditions. For individuals with chronic temporomandibular disorders, physical self-regulation is an integrative clinical health psychology intervention that decreases both physical and psychological symptoms via improvements in self-regulatory strength and autonomic nervous system regulation. Suggestions for the application of self-regulation to other chronic pain disorders and future research directions are provided.


Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity.
NF-kappa B plays a critical role in the transcriptional regulation of proinflammatory gene expression in various cells. Cytokine-mediated activation of NF-kappa B requires activation of various kinases, which ultimately leads to the phosphorylation and degradation of I kappa B, the NF-kappa B cytoplasmic inhibitor. The food derivative curcumin has been shown to inhibit NF-kappa B activity in some cell types. In this report we investigate the mechanism of action of curcumin on cytokine-induced proinflammatory gene expression using intestinal epithelial cells (IEC). Curcumin inhibited IL-1 beta-mediated ICAM-1 and IL-8 gene expression in IEC-6, HT-29, and Caco-2 cells. Cytokine-induced NF-kappa B DNA binding activity, RelA nuclear translocation, I kappa B alpha degradation, I kappa B serine 32 phosphorylation, and I kappa B kinase (IKK) activity were blocked by curcumin treatment. Wound-induced p38 phosphorylation was not inhibited by curcumin treatment. In addition, mitogen-activated protein kinase/ERK kinase kinase-1-induced IL-8 gene expression and 12-O-tetraphorbol 12-myristate 13-acetate-responsive element-driven luciferase expression were inhibited by curcumin. However, I kappa B alpha degradation induced by ectopically expressed NF-kappa B-inducing kinase or IKK was not inhibited by curcumin treatment. Therefore, curcumin blocks a signal upstream of NF-kappa B-inducing kinase and IKK. We conclude that curcumin potently inhibits cytokine-mediated NF-kappa B activation by blocking a signal leading to IKK activity.


Delirium: Clinical Presentation and Outcomes in Older COVID-19 Patients.
The aim of the study is to describe the clinical characteristics and outcomes of a series of older patients consecutively admitted into a non-ICU ward due to SARS-CoV-2 infection (14, males 11), developing delirium. Hypokinetic delirium with lethargy and confusion was observed in 43% of cases (6/14 patients). A total of eight patients exhibited hyperkinetic delirium and 50% of these patients (4/8) died. The overall mortality rate was 71% (10/14 patients). Among the four survivors we observed two different clinical patterns: two patients exhibited dementia and no ARDS (acute respiratory distress syndrome), while the remaining two patients exhibited ARDS and no dementia. The observed different clinical patterns of delirium (hypokinetic delirium; hyperkinetic delirium with or without dementia; hyperkinetic delirium with or without ARDS) identified patients with different prognosis: we believe these observations may have an impact on the management of older subjects with delirium due to COVID-19.


Effects of Zr Addition on the Microstructural Evolution, Mechanical Properties, and Corrosion Behavior of Novel Biomedical Ti-Zr-Mo-Mn Alloys.
β-Type Ti alloys have been widely investigated as implant materials owing to their excellent mechanical properties, corrosion resistance, and biocompatibility. In the present work, the effects of Zr on the microstructure, mechanical properties, and corrosion behaviors of Ti-Zr-Mo-Mn alloys were systematically studied. With the increase of Zr content, the phase composition gradually changed from intragranular-α + β of (TZ)5:1MM alloy to grain-boundary-α + β of (TZ)2:1MM alloy and finally transferred to a single β phase structure of (TZ)1:1MM alloy. The (TZ)1:1MM alloy exhibited a good mechanical combination with a yield strength of 750.8 MPa, an elastic modulus of 61.3 GPa, and a tensile ductility of 14.6%. Moreover, the addition of Zr can effectively stabilize the passivation film and reduce the sensitivity of microgalvanic corrosion in simulated body fluid, leading to enhanced corrosion resistance in the TZMM alloys. X-ray photoelectron spectroscopy analysis together with the ion-sputtering technique revealed that the passivation films formed on TZMM alloys possessed a bilayered structure (outer Ti+Zr mixed-oxide layer and inner Zr-oxide-rich layer), in which the inner Zr oxide layer plays an important role in the corrosion resistance of the TZMM alloys. In vitro biocompatibility evaluations demonstrated that the TZMM alloys can support cell adhesion and proliferation with high biocompatibility comparable to that of CP-Ti, while in vivo biocompatibility evaluations validated the bone osteointegration ability of TZMM alloys after long-term implantation. The above results indicate that novel TZMM alloys are promising candidates for implant material.


Disease-specific target selection: a critical first step down the right road.
Relevance of a drug target for a disease is often inferred with strong belief but fragile evidence. Here, a program for early identification of human disease-specific drug targets using high-throughput genetic associations is described. Large numbers of well-characterized patients (>1000) and matched controls are screened for genetic associations using several thousand (>7000) single nucleotide polymorphisms from more than 1500 genes. The genes were selected because they are members of target classes for which there are precedents for high-throughput chemical screening technology. This review summarizes the methods and intensive data analyses leading to target gene identification for type 2 diabetes mellitus, including the statistical permutation methodology used to correct for many variables.


Intraductal papillary mucinous tumor of the pancreas: a pictorial essay.
Intraductal papillary mucinous tumor (IPMT) of the pancreas was identified and classified only recently. IPMT has a primarily intraductal, papillomatous growth pattern, which is associated with excessive mucin secretion and results in progressive ductal dilatation or cyst formation. The tumor occurs in four forms: segmental or diffuse involvement of the main pancreatic duct and macrocystic or microcystic involvement of a branch duct. In the past, many IPMTs may have been misdiagnosed as chronic pancreatitis because of their generally benign behavior. The correct diagnosis, once achieved only with endoscopic retrograde cholangiopancreatography (ERCP), can now be made with noninvasive imaging modalities, particularly computed tomography (CT) and magnetic resonance (MR) imaging. ERCP remains the imaging modality of choice for diagnosis of IPMT. With ERCP, the communication between the cystically dilated ductal segment or branch duct and the main pancreatic duct is easily demonstrated. However, reflux of contrast material due to an excess of mucin or an enlarged papillary orifice hinders filling of the ductal tree. Filling defects due to mucin globs or mural nodules are also important clues to the diagnosis. Bulging of the papilla into the duodenal lumen is virtually pathognomonic of IPMT and is well demonstrated with CT or MR imaging.


Open access clinic providing HIV-I antibody results on day of testing: the first twelve months.
To determine the sociodemographic profile, risk category, and prevalence of HIV-I infection among people attending a clinic providing counselling, medical advice, and results of HIV-I antibody testing on the day of consultation; to determine the stage of infection and peripheral blood CD4 cell count among attenders with detectable HIV-I antibodies. Analysis of prospectively collected data for the 12 months from March 1989. Same day testing clinic run by the HIV/AIDS team at an urban teaching hospital. 561 consecutive people choosing to attend and proceeding to HIV-I testing. The demand for the service caused it to run to capacity within six months. The median age of those attending was 28 years and 65% (364 patients) were male. The overall prevalence of HIV-I infection was 3.9% (22 patients). The greatest prevalence was in men reporting their primary risk as homosexual contact (11.9%, 13/109). The median CD4 cell count in the 22 patients who had detectable HIV-I antibodies was 0.31 x 10(9) cells/l (normal range 0.5 x 10(9)/l to 1.2 x 10(9)/l). Twenty of these patients were asymptomatic (Centers for Disease Control stages II or III), 14 had CD4 cell counts below 0.5 x 10(9)/l. There is a recognisable demand for a service providing rapid results of HIV-I antibody testing in this setting. The overall seroprevalence of 3.9% is comparable with the 5.8% reported from freestanding clinics in the United States. Most patients with HIV-I antibodies detected in this way are asymptomatic but could benefit from early medical intervention because of low CD4 cell counts.


Monodisperse microporous carbon nanospheres: An efficient and stable solid phase microextraction coating material.
The monodisperse microporous carbon nanospheres (MMCNSs) were applied in solid phase microextraction for the first time. The MMCNSs-fiber was prepared by sol-gel technique and good repeatability and reproducibility were obtained, due to the excellent monodispersity of the MMCNSs. The sol-gel-MMCNSs fiber exhibited superior extraction ability for polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs), compared with the commercial polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber and the fiber prepared with its precursor, the monodisperse microporous polystyrene nanospheres (MMPNSs). Moreover, the fiber has good thermostability and strong acid/base durability. The sol-gel-MMCNSs fiber was then employed to detect PAHs and OCPs in aqueous samples by combining with gas chromatography-mass spectrometer (GC-MS). Under the optimized conditions, the detection limits of the proposed method ranged from 0.10 to 5.5 ng L(-1). Furthermore, the method was successfully utilized for the analysis of PAHs and OCPs in real samples, with satisfactory recoveries in the range of 81.0-120% for the Pearl River water samples and 72.8-118% for the coking wastewater samples.


Threshold-like associations as a function of disturbance.
According to the intelligence-creativity threshold hypothesis, there should be a positive association between intelligence and creative potential up to a certain point, the threshold, after which a further increase in intelligence should have no association with creativity. In the present simulation study, the measured intelligence and creativity of virtual subjects were affected by their true abilities as well as a disturbance factor that varied in magnitude between subjects. The results indicate that the hypothesized threshold-like association could be due to some disturbing factor, for example, low motivation, illness, or linguistic confusion, that varies between individuals and that affects both measured intelligence and measured creativity, especially if the actual association between intelligence and creativity is weak. This, together with previous negative findings, calls the validity of the intelligence-creativity threshold hypothesis into question.


Effects of beta-mannanase in corn-soy diets on commercial leghorns in second-cycle hens.
beta-Mannanase (Hemicell) is a unique enzyme-based feed ingredient that can hydrolyze beta-mannan, an antinutritional fiber in feed. Because soybean meal contains beta-mannan and its derivatives, addition of beta-mannanase may improve soybean-meal utilization. The purpose of this study was to evaluate the effect of beta-mannanase on performance of commercial Leghorns fed corn-soybean meal based diets. In this experiment, 3 diets were formulated. The metabolizable energy content for diet 1 (high-energy diet) was 2,951 kcal/kg, which was 120 kcal/kg higher than diet 2 (low-energy diet supplemented with beta-mannanase) and diet 3 (low-energy diet without beta-mannanase). Hy-Line W-36 hens (n = 720, 98 wk old) were randomly divided into 3 dietary treatments (16 replicates of 15 hens per treatment). The trial lasted for 12 wk. Overall average feed conversion of hens fed the low-energy diet supplemented with beta-mannanase was similar to that of hens fed the high-energy diet, and both were significantly lower than that of hens fed the low-energy diet without beta-mannanase. There were no significant differences in overall average egg production and egg mass among 3 dietary treatments for the 12-wk period. However, the addition of beta-mannanase significantly increased average egg production and egg mass of hens fed the low-energy diet from wk 5 to 8. There were no significant differences in feed intake, egg specific gravity, egg weight, mortality, body weight, and body weight variability among the 3 dietary treatments. beta-Mannanase supplementation improved energy utilization of corn-soybean layer diets and has potential to reduce the cost of practical laying hen diets containing beta-mannan.


Co-delivery of Lapatinib and 5-Fluorouracil Transfersomes using Transpapillary Iontophoresis for Breast Cancer Therapy.
Combination chemotherapy, involving the intervention of two or more anti-neoplastic agents has been the cornerstone in breast cancer treatment, owing to the applications it holds in contrast to the mono-therapy approach. This research predominantly focussed on proving the synergy between Lapatinib (LPT) and 5-Fluorouracil (5-FU) and further enhancing its localized permeation via transfersome-loaded delivery and iontophoresis to treat breast tumors. The IC50 values for LPT and 5-FU were found to be 19.38 µg/ml and 5.7 µg/ml respectively and their synergistic effect was proven by the Chou-Talalay assay using CompuSyn software. Furthermore, LPT and 5-FU were encapsulated within transfersomes and administered via the transpapillary route. The drug-loaded carriers were characterized for their particle size, polydispersity index, zeta potential, and entrapment efficiency. The ex vivo rat skin permeation studies indicated that when compared to LPT dispersion and 5-FU solution, drug-loaded transfersomes exhibited better permeability and their transpapillary permeation was enhanced on using iontophoresis. Moreover, both LPT and 5-FU transfersomes were found to be stable for 3 months when stored at a temperature of 5 ± 3 °C. The results indicated that this treatment strategy could be an effective approach in contrast to some of the conventional treatments employed to date.


Concurrent periostalgia and chronic proximal deep posterior compartment syndrome in a collegiate track and field athlete: a case report.
Exercise-induced leg pain may be triggered by abnormally high compartment pressure. In addition to the more widely publicized anterior compartment syndrome, the deep posterior compartment syndrome can just as frequently occur, resulting in severe pain and disability due to muscle and nerve ischemia. Obtaining a thorough history and compartmental pressure measurements are the usual components in the accurate diagnosis of compartment syndromes. While few other disorders mimic compartment syndromes, differential diagnoses must be considered. Surgical management of deep compartment syndrome, consisting of fasciotomy or fasciectomy, or both, is successful for most patients. Tibial stress fracture or microfracture, tibial periostitis, tibial periostalgia, distal deep posterior chronic compartment syndrome, proximal deep chronic compartment syndrome, superficial lateral compartment syndrome, deep venous thrombosis, popliteal artery entrapment, or chronic compartment syndrome. Chronic deep compartment syndrome is one of the most common causes of exercise-induced leg pain in aerobic athletes. Therefore, the athletic trainer must be able to recognize the condition. Signs, symptoms, diagnosis, and surgical management of chronic deep compartment syndrome, chronic periostalgia, and superficial lateral compartment syndrame in a 21-year-old Division IA track and field athlete are presented. With the correct diagnosis, persistent and methodical reevaluation, and appropriate management, the athlete can expect a successful treatment outcome.


The effect of solution and gel forms of sodium hypochlorite on postoperative pain: a randomized clinical trial.
The aim of this study is to evaluate the effect of using gel and solution forms of NaOCI during the chemomechanical preparation of the root canals on postoperative pain at different time intervals. 114 patients with mandibular molar teeth and symptomatic irreversible pulpitis were included in the study. All patients were divided into two groups based on the irrigant used during root canal preparation (n=57): Group 1, 5.25% NaOCI, Group 2, 5.25% NaOCI gel. All groups were filled with gutta-percha and AH Plus root canal sealer using single-cone technique. VAS scale (1-10) was used for postoperative pain assessment. After endodontic treatment, all patients were asked to record their postoperative pain levels at the 6th, 24th, 48th, 72nd hours, and 1 week later. The data were analyzed using Chi-Squared, Independent Samples T, Cochran Q and Friedman tests. Statistically significant difference was not found between the distributions of pain levels at different times according to the groups (p>0.050). A statistically significant difference was observed between the distributions of pain levels measured at different times in the solution group (p<0.001). A statistically significant difference was found between the distributions of pain levels measured at different times in the gel group (p<0.001). In both groups, highest postoperative pain levels occurred in the first 6 hours. Pain levels of the gel group as 38,5% mild, 17.3% moderate, 5.8% severe and pain levels of the solution group were obtained as 46.2% mild, 26.9% moderate, 9.6% severe at the 6th hour. The use of the gel form of NaOCI during the chemomechanical preparation of the root canals showed similar postoperative pain when compared to the solution form.


Reduction of acetylene and hydrazine with a molybdenum-glutathione complex.
Crystalline preparations of a molybdenum-glutathione complex catalyze the reduction of acetylene to ethylene in the presence of borohydride. The reaction proceeds at rates up to 6 mol of C(2)H(2) produced per min per mol of bound Mo, which is 4% of the activity of a quantity of nitrogenase with an equivalent amount of Mo. The activity of the complex is enhanced 100-fold by ATP, but the addition of ADP has no effect. Stimulation in activity by GTP is about the same as that by ATP, and the effects of CTP or UTP are considerably less. Inhibition of acetylene-reduction activity by the addition of 32 mM orthophosphate was 14%, by 32 mM pyrophosphate 62%, by 0.2 atm of O(2) 65%, and by 0.5 atm of CO 12%; 0.5 atm of H(2) had no effect. The molybdenum-glutathione complex also catalyzes the reduction of hydrazine to ammonia in a reaction that is dependent upon borohydride. The reaction is enhanced about 7-fold by ATP and proceeds at a rate of 2 mol of NH(3) produced per min per mol of bound Mo.