Differentiation of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons in Mouse Hippocampal Slice Cultures.
Potential clinical applications of neurons derived from human induced pluripotent stem cells (hiPSC-neurons) for drug screening and transplantation therapies have received considerable attention. However, it remains unclear whether and how transplanted hiPSC-neurons are incorporated into pre-existing neural circuits. Here we developed a co-culture system of hiPSC-neurons and mouse hippocampal slices to examine the differentiation of hiPSC-neurons in pre-existing neural circuits. hiPSC-neurons transplanted in mouse hippocampal slices expressed the hippocampal neuron-specific markers HuB and Prox1 after 7 days of culture, while those markers were scarcely expressed in hiPSC-neurons cultured on glass dishes. Furthermore, hiPSC-neurons transplanted in the dentate gyrus (DG) of slice cultures grew to exhibit dentate granule cell-like morphologies, including besom-shaped dendrites. Similarly, hiPSC-neurons transplanted in the CA1 region of slice cultures grew to exhibit CA1 pyramidal cell-like morphologies, including primary apical and multiple basal dendrites with synaptic spines. Additionally, these cells projected axons toward the entorhinal cortex (EC) as observed in vivo. These data suggest that hiPSC-neurons were anatomically integrated into pre-existing neural circuits in a region-specific manner. Thus, the co-culture system will be useful for the study of efficient strategies to differentiate transplanted hiPSC-neurons.


Surgery for rheumatic tricuspid valve disease in children.
Rheumatic valvular disease in children is common in underprivileged countries and often damages the tricuspid valve (in addition to the mitral and aortic valves). Fifteen children aged 12 to 16 years underwent tricuspid valve surgery. Fourteen were graded as Class IV disability; five were operated during rheumatic activity. The tricuspid valve was replaced in ten patients, four had annuloplastic procedures and one underwent tricuspid commissurotomy. There was one operative death and four late deaths. Eight of the ten long-term survivors are in Class I and the remainder in Class II functional ability. It may be concluded that in children who can be protected from additional bouts of carditis and thromboembolism, the surgical treatment of advanced multivalvular disease including the tricuspid valve is most rewarding, and dramatic clinical improvement with return to normal or near-normal hemodynamics may be expected.


Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis I.
Treatments now available for mucopolysaccharidosis I require early detection for optimum therapy. Therefore, we have developed an assay appropriate for newborn screening of the activity of the relevant enzyme, alpha-L-iduronidase. We synthesized a new alpha-L-iduronidase substrate that can be used to assay the enzyme by use of tandem mass spectrometry together with an internal standard or by fluorometry. The assay uses a dried blood spot on a newborn screening card as the enzyme source. The assay protocol uses a simple liquid-liquid extraction step before mass spectrometry. We optimized enzyme reaction conditions and procedures for the assay, including the concentration of substrate, the reaction pH, the incubation time, and mass spectrometer operation. We also assessed inter- and intraassay imprecision. When the assay was tested on dried blood spots, the alpha-L-iduronidase activity measured for 5 patients with mucopolysaccharidosis I was well below the interval found for 10 randomly chosen newborns. Inter- and intraassay imprecision were <10%. The synthesis of the alpha-L-iduronidase substrate is practical for use on a scale needed to support newborn screening demands. This newly developed tandem mass spectrometry assay has the potential to be adopted for newborn screening of mucopolysaccharidosis I. This assay has advantages over a previously reported assay also developed in this laboratory and has the potential to be performed in a multiplex fashion to measure several lysosomal enzymes relevant to treatable lysosomal storage diseases.


Psychiatric pharmacogenomic testing in clinical practice.
The clinical adoption of psychiatric pharmacogenomic testing has taken place rapidly over the past 7 years. Initially, drug-metabolizing enzyme genes, such as the cytochrome P450 2D6 gene (CYP2D6), were identified. Genotyping the highly variable cytochrome P450 2D6 gene now provides clinicians with the opportunity to identify both poor metabolizers and ultrarapid metabolizers of 2D6 substrate medications. Subsequently, genes influencing the pharmacodynamic response of medications have been made available for clinical practice. Among the earliest "target genes" was the serotonin transporter gene (SLC6A4) which has variants that have been shown to influence the clinical response of patients of European ancestry when they are treated with selective serotonin reuptake inhibitors. Genotyping of some of the serotonin receptor genes is also available to guide clinical practice. The quantification of the clinical utility of pharmacogenomic testing is evolving, and ethical considerations for testing have been established. Given the increasingly clear cost-effectiveness of genotyping, it has recently been predicted that pharmacogenomic testing will routinely be ordered to guide the selection and dosing of psychotropic medications.


Opioid analgesic involvement in drug abuse deaths in American metropolitan areas.
I measured the role of opioid analgesics in drug abuse-related deaths in a consistent panel of 28 metropolitan areas from the Drug Abuse Warning Network. The number of reports of opioid analgesics increased 96.6% from 1997 to 2002; methadone, oxycodone, and unspecified opioid analgesics accounted for 74.3% of the increase. Oxycodone reports increased 727.8% (from 72 to 596 reports). By 2002, opioid analgesics were noted more frequently than were heroin or cocaine. Dramatic increases in the availability of such opioids have made their abuse a major, growing problem.


Potential mechanisms of resistance to venetoclax and strategies to circumvent it.
Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges. In order to gain a more comprehensive insight into the nature of venetoclax resistance mechanisms, we evaluated the changes in the BCL-2 family members at the genetic and expression levels in seven different venetoclax-resistant derived leukemia and lymphoma cell lines. Gene and protein expression analyses identified a number of different alterations in the expression of pro- and anti-apoptotic BCL-2 family members. In the resistant derived cells, an increase in either or both the anti-apoptotic proteins BCL-XL or MCL-1, which are not targeted by venetoclax was observed, and either concomitant or exclusive with a decrease in one or more pro-apoptotic proteins. In addition, mutational analysis also revealed a mutation in the BH3 binding groove (F104L) that could potentially interfere with venetoclax-binding. Not all changes may be causally related to venetoclax resistance and may only be an epiphenomenon. For resistant cell lines showing elevations in BCL-XL or MCL-1, strong synergistic cell killing was observed when venetoclax was combined with either BCL-XL- or MCL-1-selective inhibitors, respectively. This highlights the importance of BCL-XL- and MCL-1 as causally contributing to venetoclax resistance. Overall our study identified numerous changes in multiple resistant lines; the changes were neither mutually exclusive nor universal across the cell lines tested, thus exemplifying the complexity and heterogeneity of potential resistance mechanisms. Identifying and evaluating their contribution has important implications for both patient selection and the rational development of strategies to overcome resistance.


Simultaneous detection and typing strategy for human papillomaviruses based on PCR and restriction endonuclease mapping.
The aim of this study was to devise a simple and reliable method for simultaneous detection and typing of genital human papillomaviruses (HPVs). The method comprises three steps (i) amplification of sample DNA with the L1 consensus primers, (ii) digestion of PCR products with restriction endonuclease RsaI and (iii) hybridization of digested PCR products with a unique oligonucleotide probe that detects different fragments of the six most common genital HPV genotypes, namely, HPV types 6, 11, 16, 18, 31 and 33. Seventeen clinical specimens were analyzed by this method and compared to Southern blot using full genomic HPV DNA probes and to PCR using type-specific probes. All three tests agreed with at least one HPV type; however, the new method identified more additional HPV types in cases of mixed infections.


Ocular hypotensive activity of pirbuterol eye drops in rabbits.
The IOP-lowering effect of pirbuterol, a beta-2 adrenergic agonist, was studied in rabbits. In normotensive rabbits, pirbuterol 0.5% eye drops reduced IOP by 20-25%. In ocular hypertensive rabbits (by glucose 5% venous infusion), pirbuterol reduced IOP by 20% (0.1% concentration) to 40% (0.5% and 1% concentration). A slight decrease in the effect was noticed after seven days of treatment.


[Hyperbaric oxygen in the treatment of perineal Crohn's disease era of infliximab: a renewal interest?].
Despite the growing number of therapeutic methods and the recent introduction of new drugs more active in the therapeutic arsenal, lesions of the ano-perineal Crohn's disease remains difficult to support. Hyperbaric oxygen (HBO) was made before the era of infliximab, an interesting therapeutic approach in which the current position remains unclear. To assess HBO efficacy in the treatment of anal fistulas refractory Crohn's disease. Literature review. Hyperbaric oxygen therapy was used in the 90's when the biotherapy was not part of the armamentarium for Crohn's disease. Research conducted has identified only nine publications evaluating the efficacy of hyperbaric oxygen therapy in the treatment of anal fistulas refractory Crohn's disease. Among the nine publications, we have retained only four: two clinical trials and two clinical cases. The total number of patients was 22: 12 women and 10 men. The average age of patients was 37 years. The average number of session was 42 sessions. Remission was observed in 15 patients (68.18%) whereas with Infliximab rate is 66%. Adverse events were observed in 2 patients (16.6%). Indeed, instead of considering them as two different alternatives, it should be combined to obtain a synergy to increase response rates, shorten the healing and especially to decrease the recurrence rate. Only a prospective randomized controlled trial (with two arms: biotherapy versus biotherapy associated with hyperbaric oxygen therapy) could accommodate this technique in the armamentarium of perineal lesions of Crohn's disease.


Tick paralysis: atypical presentation, unusual location.
We present 2 unrelated cases of tick paralysis presenting within a 2-month period in the greater Philadelphia region, a geographic area in which this disease is highly unusual. Our first patient demonstrated early onset of prominent bulbar palsies, an atypical presentation. Our second patient, residing in a nearby but distinct community, presented with ascending paralysis 2 months after the first. The atypical presentation of our first patient and the further occurrence within a few months of a second patient, both from the Northeastern United States where this diagnosis is rarely made, suggest the need to maintain a high index of suspicion for this disease in patients presenting with acute onset of cranial nerve dysfunction or muscle weakness. Through simple diagnostic and therapeutic measures (ie, careful physical examination to locate and remove the offending tick), misdiagnosis and unnecessary morbidity can be avoided.


Generation of a library of particles having controlled sizes and shapes via the mechanical elongation of master templates.
Herein we describe a versatile and readily scalable approach for the fabrication of particles with a variety of shapes and sizes from a single master template by augmenting the particle replication in nonwetting templates (PRINT) method with mechanical elongation. Repetition of the elongation steps in one direction leads to the fabrication of linear particles with high aspect ratio (AR), over 40 times greater than in the original master, while a range of particle shapes can be obtained by repeating the elongation procedure while changing the stretching direction, generating diamond, rectangular, curved parallelogram particles from a single cubic master.


The Challenges of Crizotinib Treatment in a Child With Anaplastic Large Cell Lymphoma.
Survival in cases involving childhood malignancy is reaching nearly 80% in high-income countries, yet cancer remains one of the leading disease-related causes of death in children. In adult oncology the role of targeted therapies is established, but information regarding the use of these therapies in children is limited, largely because targeted therapies were developed in the context of adult pathologies. The few pediatric reports regarding crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, seem promising. This case of an 8-year-old male with an ALK-positive anaplastic large cell lymphoma highlights the challenges of treating children with crizotinib. Our experience with crizotinib was more challenging than described in the limited pediatric reports. Not only was the tumor response poorer than described in the reports, but a substantial amount of side-effects and practical difficulties, such as the method of administration and dosing, made management challenging. Many challenges for the use of targeted therapy in pediatric care currently persist. The limited research in pediatric populations leaves uncertainty regarding efficacy and short- and long-term side effects as well as practical difficulties. Despite a clear underlying biological rationale for certain targeted therapies, their contribution toward improving the outcome of childhood cancer remains largely unclear.


Untangling the tau gene association with neurodegenerative disorders.
Pathological tau protein inclusions have long been recognized to define the diverse range of neurodegenerative disorders called the tauopathies, which include Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration. Mutations in the tau gene, MAPT, cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), and common variation in MAPT is strongly associated with the risk of PSP, corticobasal degeneration and, to a lesser extent, AD and Parkinson's disease (PD), implicating the involvement of tau in common neurodegenerative pathway(s). This review will discuss recent work towards the unravelling of the functional basis of this MAPT gene association. The region of chromosome 17q21 containing MAPT locus is characterized by the complex genomic architecture, including a large inversion that leads to a bipartite haplotype architecture, an inversion-mediated deletion and multiplications resulting from non-allelic homologous recombination between the MAPT family of low-copy repeats.


Mandatory Reporting and Adolescent Sexual Assault.
Adolescents experience alarmingly high rates of sexual violence, higher than any other age-group. This is concerning as sexual violence can have detrimental effects on teens' personal and relational well-being, causing long-term consequences for the survivor. Still, adolescents are hesitant to report the assault or seek out services and resources. When an adolescent survivor does seek out services, they may interact with a provider who is a mandatory reporter. This scoping review sought to synthesize the current U.S.-based research on the role, challenges, and impact of mandatory reporting (MR) in the context of adolescent sexual assault. Database searches using key words related to MR, sexual assault, and adolescence identified 29 peer-reviewed articles. However, none of these articles reported on empirical investigations of the phenomenon of interest and instead consisted of case studies, commentaries, and position papers. The scoping review was expanded to provide a lay of the land of what we know about the intersection of adolescent sexual assault and MR. Results of the review indicate that though implemented broadly, MR policies vary between individuals, organizations, and states and have historically been challenging to implement due to this variation, conflicts with other laws, tension between these policies and providers' values, and other factors. Based on the available literature, the impact of MR in the context of adolescent sexual assault is unknown. There is a critical need for research and evaluation on the implementation and impact of MR policies, especially in the context of adolescents and sexual violence.


Are nudging and pricing strategies on food purchasing behaviors equally effective for all? Secondary analyses from the Supreme Nudge virtual supermarket study.
Nudging and pricing strategies are effective in promoting healthier purchases. However, whether the effects are equal across individuals with different personal characteristics is unknown. This exploratory study aimed to examine differential effects of nudging and pricing strategies on food purchases across individuals' levels of impulsivity, price sensitivity, decision-making styles, and food choice motives. Data from a virtual supermarket experiment where participants were exposed to five study conditions (control, nudging, pricing, salient pricing, and salient pricing with nudging) was used. Participants completed questionnaires assessing their impulsivity, price sensitivity, decision-making styles, and food choice motives. The outcome was the percentage of healthy food purchases. Effect modification was analyzed by adding interaction terms to the statistical models and post-hoc probing was conducted for statistically significant interaction terms. We used data from 400 Dutch adult participants (61.3% female, median age 30.0 years (IQR 24.0)). The effects of the nudging and pricing conditions on healthy food purchases were not modified by impulsivity, price sensitivity, decision-making styles, and the food choice motives 'health' and 'price'. Only the interactions of the food choice motive 'natural content of foods' x pricing (B = -1.02, 90%CI = -2.04; -0.01), the food choice motive 'weight control' x nudging (B = -2.15, 90%CI = -3.34; -0.95), and 'weight control' x pricing (B = -1.87, 90%CI = -3.11; -0.62) were statistically significant. Post-hoc probing indicated that nudging and/or pricing strategies were more effective in individuals who gave lower priority to these food choice motives. The effects of nudging and pricing strategies on increasing healthy food purchasing behaviors, at least in a virtual environment, do not seem to be influenced by personal characteristics and may therefore be implemented as general health promoting strategies.


MIRUReader: MIRU-VNTR typing directly from long sequencing reads.
Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing is widely used to genotype Mycobacterium tuberculosis complex in epidemiological studies for tracking tuberculosis transmission. Recent long-read sequencing technologies from Pacific Biosciences and Oxford Nanopore Technologies can produce reads that are long enough to cover the entire repeat regions in each MIRU-VNTR locus which was previously not possible using the short reads from Illumina high-throughput sequencing technologies. We thus developed MIRUReader for MIRU-VNTR typing directly from long sequence reads. Source code and documentation for MIRUReader program is freely available at https://github.com/phglab/MIRUReader. Supplementary data are available at Bioinformatics online.


Dynamics of the Composition of Plasmodium Species Contained within Asymptomatic Malaria Infections in the Central Region of Ghana.
Monitoring changes in the composition of the Plasmodium species circulating within the population over a period can inform appropriate treatment recommendations. This study monitored variations in the prevalence of four common human Plasmodium species carried by children with asymptomatic malaria infections over a two-year period. Two cross-sectional studies were conducted in November 2017 and December 2019. A total of 210 children aged between 4 and 13 years were recruited in 2017, and 164 similarly aged children were recruited in 2019. Approximately 150 μl of finger-pricked blood was used to prepare thick and thin blood smears as well as spot Whatman® #3 filter paper. Genomic DNA was extracted from the dried blood spots and used in PCR to amplify the 18S rRNA gene from four different human Plasmodium parasites. Parasite prevalence by microscopy and the prevalence of P. falciparum detected by PCR was relatively similar at the two time points (Pearson chi-square = 0.405, p=0.525, and Pearson chi-square = 0.452, p=0.501, respectively). However, the prevalence of PCR detectable P. malariae increased by 8.5-fold, whilst P. ovale increased from 0 to 9% in the children sampled in 2019 relative to the children sampled in 2017. The only parasite species identified by microscopy in this study was P. falciparum, and no P. vivax was identified by either microscopy or PCR in the study population during the study period. There is the need to implement molecular diagnostic tools for malaria parasite surveillance in Ghana. This will enable the identification and treatment of all circulating malaria parasites including P. malariae and P. ovale, whose population is expanding in parts of Ghana including Simiw.


Working length variation during multiple-visit endodontic treatment: An observational study.
This study investigated variation in working length during multiple-visit endodontic treatment. Patients (N = 106) with pulpitis or pulp necrosis, with or without apical periodontitis, were included. During the first appointment, glide path was performed with ProGlider and shaping with ProTaper Next. Working length was detected four times. Working length was then re-recorded prior to filling during the second appointment and a 0.5 mm threshold was selected as the minimum clinically meaningful variation. A logistic regression model was used to evaluate the impact of tooth anatomy, preoperative pulp status, apical periodontitis and lesions of endodontic origin on working length variation. Working length varied between first and second appointments in 34% of patients. The presence of apical periodontitis was the only variable significantly associated with variation in working length (p = 0.011). These data suggest that working length should be re-checked prior to root canal filling to prevent procedural errors.


Cytochemical and immunocytochemical characterization of nuclear bodies during hibernation.
Brown adipose tissue and liver of hibernating, arousing and euthermic individuals of the dormouse Muscardinus avellanarius were studies using ultrastructural cytochemistry and immunocytochemistry with the aim to investigate possible fine structural modifications of the cell nucleus during the seasonal cycle. The general morphology of brown adipocyte and hepatocyte nuclei was similar in the three experimental groups. However, three nuclear structural constituents were identified only in hibernating individuals: coiled bodies (CBs) and amorphous bodies (ABs) were observed in hepatocytes and, together with bundles of nucleoplasmic fibrils (NF), were present in brown adipocytes of hibernating dormice. In arousing animals only some structural constituents suggestive of poorly structured CBs were found. The latter showed the same immunocytochemical features as CBs of hibernating individuals, suggesting that they are disappearing CBs. A possible involvement of CBs in storing and/or processing RNA which must be rapidly and abundantly released upon arousal is discussed. ABs similarly to CBs contain RNA and nucleoplasmic ribonucleoproteins (RNPs) and could also be involved in mRNA pathways. NF do not contain nucleic acids or RNPs and seem to be composed of protein-aceous material; their functional role in the nuclear metabolism of hibernating brown adipocytes remains unclear.


High serum leptin levels are associated with central arterial stiffness in geriatric patients on hemodialysis.
Central arterial stiffness predicts cardiovascular (CV) mortality in hemodialysis (HD) patients. The aging process transforms lipid distribution and thus alters adipokine secretion. The harmful effects of leptin on CV events may change in the elderly. The purpose of this study was to investigate the relationship between leptin and central arterial stiffness markers through carotid-femoral pulse wave velocity (cfPWV) in geriatric HD patients. Patients over 65 years old on chronic HD were recruited. Blood samples were collected, and the cfPWV was measured with the SphygmoCor system. The patients with cfPWV values >10 m/s were defined as the high arterial stiffness group. In total, 30 (51.7%) of the 58 geriatric patients on chronic HD in this study were in the high arterial stiffness group. The high arterial stiffness group had higher rates of diabetes mellitus (P = 0.019), hypertension (P = 0.019), and higher systolic blood pressure (P = 0.018), pulse pressure (P = 0.019), body mass index (P = 0.018), serum leptin levels (P = 0.008), and hemoglobin levels (P = 0.040) than those in the low arterial stiffness group. Multivariable forward stepwise linear regression analysis showed logarithmically transformed leptin (log-leptin, β =0.408, adjusted R 2 change = 0.164; P = 0.001) and diabetes (β =0.312, adjusted R 2 change = 0.085; P = 0.009) were associated with cfPWV values in geriatric HD patients. Moreover, an increased serum leptin level (odds ratio: 1.053; 95% confidence interval: 1.007-1.100; P = 0.023) was an independent factor for central arterial stiffness among geriatric HD patients after multivariate logistic regression analysis. In this study, a higher serum leptin level was correlated with central arterial stiffness in geriatric HD patients.


The impact of foreign R&D on the innovation performance of China's high-tech industry and its spatial spillover effect.
The inflow of foreign R&D has brought vigor and vitality to the development of the high-tech industry (HTI). Using the panel data of HTI in 23 provinces (autonomous provinces and municipalities) in China from 2007 to 2016, this paper firstly calculates the Moran index of HTI's innovation performance (IP), and finds a spatial agglomeration effect. After rigorous testing, we determine the most suitable spatial metering model. Finally, the spatial effect is further decomposed into three kinds of effects: direct effect, indirect effect, and total effect. This paper studies the impact of foreign research and development (R&D) on IP of HTI and its spatial spillover effects. According to the research, foreign R&D has a significant role in promoting IP of HTI in China, and has specific spatial spillover effects. Significantly, foreign R&D has substantial positive spillover effects of space. When IP of HTI is measured by product innovation, there is no obvious space overflow. However, panel regression showed a significant positive effect. In terms of the influence on product IP of HTI, foreign R&D plays an almost equal role as local R&D. In terms of the impact on technological IP of HTI, foreign R&D input plays a positive role. It has a spatial spillover effect, the degree of impact is lower than that of domestic R&D input. Local governments should formulate relevant policies to encourage the fluidity of technical knowledge and overcome the sticky problem of foreign R&D technical knowledge, which is an essential aspect of absorbing foreign R&D technical knowledge in the future.


Environmental impacts of dredging and other sediment disturbances on corals: a review.
A review of published literature on the sensitivity of corals to turbidity and sedimentation is presented, with an emphasis on the effects of dredging. The risks and severity of impact from dredging (and other sediment disturbances) on corals are primarily related to the intensity, duration and frequency of exposure to increased turbidity and sedimentation. The sensitivity of a coral reef to dredging impacts and its ability to recover depend on the antecedent ecological conditions of the reef, its resilience and the ambient conditions normally experienced. Effects of sediment stress have so far been investigated in 89 coral species (~10% of all known reef-building corals). Results of these investigations have provided a generic understanding of tolerance levels, response mechanisms, adaptations and threshold levels of corals to the effects of natural and anthropogenic sediment disturbances. Coral polyps undergo stress from high suspended-sediment concentrations and the subsequent effects on light attenuation which affect their algal symbionts. Minimum light requirements of corals range from <1% to as much as 60% of surface irradiance. Reported tolerance limits of coral reef systems for chronic suspended-sediment concentrations range from <10 mg L(-1) in pristine offshore reef areas to >100 mg L(-1) in marginal nearshore reefs. Some individual coral species can tolerate short-term exposure (days) to suspended-sediment concentrations as high as 1000 mg L(-1) while others show mortality after exposure (weeks) to concentrations as low as 30 mg L(-1). The duration that corals can survive high turbidities ranges from several days (sensitive species) to at least 5-6 weeks (tolerant species). Increased sedimentation can cause smothering and burial of coral polyps, shading, tissue necrosis and population explosions of bacteria in coral mucus. Fine sediments tend to have greater effects on corals than coarse sediments. Turbidity and sedimentation also reduce the recruitment, survival and settlement of coral larvae. Maximum sedimentation rates that can be tolerated by different corals range from <10 mg cm(-2) d(-1) to >400 mg cm(-2) d(-1). The durations that corals can survive high sedimentation rates range from <24 h for sensitive species to a few weeks (>4 weeks of high sedimentation or >14 days complete burial) for very tolerant species. Hypotheses to explain substantial differences in sensitivity between different coral species include the growth form of coral colonies and the size of the coral polyp or calyx. The validity of these hypotheses was tested on the basis of 77 published studies on the effects of turbidity and sedimentation on 89 coral species. The results of this analysis reveal a significant relationship of coral sensitivity to turbidity and sedimentation with growth form, but not with calyx size. Some of the variation in sensitivities reported in the literature may have been caused by differences in the type and particle size of sediments applied in experiments. The ability of many corals (in varying degrees) to actively reject sediment through polyp inflation, mucus production, ciliary and tentacular action (at considerable energetic cost), as well as intraspecific morphological variation and the mobility of free-living mushroom corals, further contribute to the observed differences. Given the wide range of sensitivity levels among coral species and in baseline water quality conditions among reefs, meaningful criteria to limit the extent and turbidity of dredging plumes and their effects on corals will always require site-specific evaluations, taking into account the species assemblage present at the site and the natural variability of local background turbidity and sedimentation.


Histochemical localization of putative stem cells in irreversible pulpitis.
Our study aimed to observe the distribution of putative stem cells in irreversible pulpitis and to investigate the expression of specific molecules. Extracted third molar teeth were collected and divided into two groups: the normal pulp group and inflamed pulp group. Real-time PCR was applied to detect the expression of several embryonic and dentinogenic genes. The expression of mesenchymal cell markers (STRO-1, CD90, and CD146) and stromal cell-derived factor 1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) proteins was examined by immunohistochemical analysis. The expression levels of most embryonic and dentinogenic genes were not statistically different between the two groups. Immunohistochemical analysis revealed that in inflamed pulp, cells with positive expression for STRO-1, CD90, and CD146 mainly resided in two specific niches, both adjacent to inflammatory sites: one in the pulp core and another in the odontoblast layer. SDF-1α- and CXCR4-positive cells were significantly correlated with STRO-1-positive cells. Double immunofluorescence analysis indicated that STRO-1-positive cells overlapped with SDF-1α- and CXCR4-positive cells near the inflammatory site. This study gave a direct observation of putative stem cells distributed in irreversible pulpitis and implied a role of SDF-1α/CXCR4 signaling in stem cell-based therapies for reparative dentinogenesis.


Serological reactivity to Ehrlichia canis, Anaplasma phagocytophilum, Neorickettsia risticii, Borrelia burgdorferi and Rickettsia conorii in dogs from northwestern Spain.
The aim of the present work was to investigate the seroprevalence against Ehrlichia canis (Ec), Anaplasma phagocytophilum (Ap), Neorickettsia risticii (Nr), Rickettsia conorii (Rc), and Borrelia burgdorferi (Bb) in two different clusters of canine samples from Northwestern Spain. Cluster 1 included 479 dogs presented at veterinary clinics located in Ourense and Pontevedra. Cluster II included 170 dogs from the public kennel of Ourense. All 649 canine serum samples were analyzed by immunofluorescent antibody test. Prevalences against the above-mentioned agents in cluster I were: Rc (24.6%), Bb (6.26%), Ec (3.13%), Ap (5.01%), and Nr (1.04%), whereas for cluster II were: Rc (50%), Bb (8.8%), Ec (54.7%), Ap (45.3%), and Nr (4.7%). Rc was significantly associated with age and history of exposure to ticks, and Bb showed a statistical relationship with age and clinical status. Ec and Ap were related to the occupation of the dogs, with stray dogs being the most frequently seropositive. Furthermore, seroreactivity against Ec and Ap was significantly higher in Ourense than in Pontevedra. The univariate analysis demonstrated a significant concomitant seroreactivity between Ec and Ap and between Rc and Ec and Ap antigens. The seroreactivity to Nr must be interpreted very cautiously as this infectious agent has been seldom reported outside North America.


Avian Cephalic Vascular Anatomy, Sites of Thermal Exchange, and the Rete Ophthalmicum.
The general anatomy of avian cephalic blood vessels is well known and there are published details of their role in physiological thermoregulation. Unfortunately, the finer details of vascular pathways to and from sites of thermal exchange are not well known. Additionally, the role of the rete ophthalmicum (RO), a vascular heat exchanger in the temporal region, has been investigated in terms of brain temperature regulation, yet only the arteries have received substantial attention. Without anatomical details of both the arterial and venous pathways, the role of blood vessels in physiological thermoregulation is incomplete. Cephalic vascular anatomy of multiple avian taxa was investigated using a differential-contrast, dual-vascular injection technique and high-resolution X-ray microcomputed tomography. Sites of thermal exchange (oral, nasal, and orbital regions) and the RO were given special attention due to their known roles in cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and their ability to deliver cooled blood to the RO and dural venous sinus. Sites of thermal exchange were supplied by arteries directly and through collateral pathways. Veins were found to offer multiple pathways that could influence the temperature of neurosensory tissues, as well as pathways that would bypass neurosensory tissues. These results question the paradigm that arterial blood from the RO is the primary method of brain cooling in birds. A shift in the primary role of the RO from brain cooling to regulating and maintaining the temperature of the avian eye should be further investigated. Anat Rec, 299:1461-1486, 2016. © 2016 Wiley Periodicals, Inc.


Socioeconomic Status and Hypertension Control in Sub-Saharan Africa: The Multination EIGHT Study (Evaluation of Hypertension in Sub-Saharan Africa).
Systemic hypertension is a rapidly growing epidemic in Africa. The role of socioeconomic status on blood pressure control has not been well studied in this part of the world. We, therefore, aimed to quantify the association of socioeconomic status both at the individual and at the country level with blood pressure control in Sub-Saharan Africa. We conducted a cross-sectional survey in urban clinics of 12 countries, both low income and middle income, in Sub-Saharan Africa. Standardized blood pressure measures were made among the hypertensive patients attending the clinics. Blood pressure control was defined as blood pressure <140/90 mm Hg, and hypertension grades were defined according to the European Society of Cardiology guidelines. A total of 2198 hypertensive patients (58.4±11.8 years; 39.9% men) were included. Uncontrolled hypertension was present in 1692 patients (77.4%), including 1044 (47.7%) with ≥grade 2 hypertension. The proportion of uncontrolled hypertension progressively increased with decreasing level of patient individual wealth, respectively, 72.8%, 79.3%, and 81.8% (P for trend, <0.01). Stratified analysis shows that these differences of uncontrolled hypertension according to individual wealth index were observed in low-income countries (P for trend, 0.03) and not in middle-income countries (P for trend, 0.26). In low-income countries, the odds of uncontrolled hypertension increased 1.37-fold (odds ratio, 1.37 [0.99-1.90]) and 1.88-fold (odds ratio, 1.88 [1.10-3.21]) in patients with middle and low individual wealth as compared with high individual wealth. Similarly, the grade of hypertension increased progressively with decreasing level of individual patient wealth (P for trend, <0.01). Strategies for hypertension control in Sub-Saharan Africa should especially focus on people in the lowest individual wealth groups who also reside in low-income countries.


Serological Evidence of Pandemic H1N1 Influenza Virus Infections in Greek Swine.
The introduction of the 2009 pandemic H1N1 (pH1N1) influenza virus in pigs changed the epidemiology of influenza A viruses (IAVs) in swine in Europe and the rest of the world. Previously, three IAV subtypes were found in the European pig population: an avian-like H1N1 and two reassortant H1N2 and H3N2 viruses with human-origin haemagglutinin (HA) and neuraminidase proteins and internal genes of avian decent. These viruses pose antigenically distinct HAs, which allow the retrospective diagnosis of infection in serological investigations. However, cross-reactions between the HA of pH1N1 and the HAs of the other circulating H1 IAVs complicate serological diagnosis. The prevalence of IAVs in Greek swine has been poorly investigated. In this study, we examined and compared haemagglutination inhibition (HI) antibody titres against previously established IAVs and pH1N1 in 908 swine sera from 88 herds, collected before and after the 2009 pandemic. While we confirmed the historic presence of the three IAVs established in European swine, we also found that 4% of the pig sera examined after 2009 had HI antibodies only against the pH1N1 virus. Our results indicate that pH1N1 is circulating in Greek pigs and stress out the importance of a vigorous virological surveillance programme.


Multilocus Sequence Typing and Antifungal Susceptibility of Vaginal and Non-vaginal Candida glabrata Isolates From China.
Candida glabrata is a common cause of Candida infections. In our present study, we investigated the antifungal susceptibility and molecular epidemiology of vaginal and non-vaginal C. glabrata isolates. Seventy-six vaginal C. glabrata strains isolated from patients with vulvovaginal candidiasis and 57 non-vaginal C. glabrata isolates were collected at two hospitals in Shanghai, China. Antifungal susceptibility was examined using a broth microdilution method. Multilocus sequence typing was used for genotyping. Overall, 28 (21.1%), 28 (21.1%), and 29 (21.8%) C. glabrata isolates were resistant to fluconazole, itraconazole, and voriconazole, respectively. Briefly, 18 (23.7%), 18 (23.7%), and 19 (25%) vaginal strains were resistant to fluconazole, itraconazole, and voriconazole. While the resistance to these antifungals were all 17.5% (10/57) in non-vaginal strains. All isolates retained susceptibility to amphotericin B, and only four non-vaginal isolates were caspofungin resistant. Genotyping identified 17 ST patterns. In non-vaginal samples, the same genotypes appear as in the vaginal samples, except for one genotype (ST-182), while in the vaginal samples more genotypes appear (ST8, ST19, ST45, ST55, ST66, ST80, ST138, and ST17). The most common genotype was ST7 (81 strains), followed by ST10 (14 strains) and ST15 (11 strains). The majority of resistant phenotype strains (25/30, 83.3%) correlated to the predominant genotype (ST7), and the rest belonged to ST3 (2/30, 6.7%), ST10 (1/30, 3.3%), ST19 (1/30, 3.3%), and ST45 (1/30, 3.3%). Our survey revealed cross-resistance in vaginal and non-vaginal C. glabrata isolates. Moreover, there is no genotype associated with the resistance phenotype.


PicoGmeter, a custom-made fluorometer for the quantification of dsDNA by PicoGreen fluorescence.
The accurate determination of DNA concentration is essential for many processes in molecular biology and physiology and includes both gel- and cuvette-based methods. The recently introduced fluorescent dye, PicoGreen, has several advantages over other methods because it is sensitive and specific for double-stranded DNA (dsDNA). The dye is excited at 480 nm and emits at 520 nm when bound to dsDNA. This report describes the construction and use of PicoGmeter, a simple, inexpensive, fixed-wavelength fluorometer suitable for measuring PicoGreen fluorescence. PicoGmeter employs a blue light emitting diode (LED) for excitation and a photodiode to measure fluorescence. When compared to a commercially available instrument, PTI DeltaScan, the PicoGmeter performed admirably. Calibration curves for both instruments were superimposeable. Moreover, there was no significant difference between concentrations of DNA estimated by both instruments. A Bland and Altman analysis revealed that the PicoGmeter was equivalent to the PTI DeltaScan for estimating dsDNA concentration by the PicoGreen method. This simple, inexpensive, battery-operated fluorometer will allow investigators to employ the PicoGreen method without incurring the cost of purchasing a spectrofluorometer.


Efficient and reliable numerical integration of exchange-correlation energies and potentials.
An adaptive numerical integrator for the exchange-correlation energy and potential is presented. It uses the diagonal elements of the exchange-correlation potential matrix as a grid generating function. The only input parameter is the requested grid tolerance. In combination with a defined cell function the adaptive grid generation scales almost linear with the number of basis functions in a system. With the adaptive numerical integrator the self-consistent field energy error, which is due to the numerical integration of the exchange-correlation energy, converges with increasing adaptive grid size to a reference value. The performance of the adaptive numerical integration is analyzed using molecules with first, second, and third row elements. Especially for transition metal systems the adaptive numerical integrator shows considerably improved performance and reliability.


Regulation of Three Nitrogenase Gene Clusters in the Cyanobacterium Anabaena variabilis ATCC 29413.
The filamentous cyanobacterium Anabaena variabilis ATCC 29413 fixes nitrogen under aerobic conditions in specialized cells called heterocysts that form in response to an environmental deficiency in combined nitrogen. Nitrogen fixation is mediated by the enzyme nitrogenase, which is very sensitive to oxygen. Heterocysts are microxic cells that allow nitrogenase to function in a filament comprised primarily of vegetative cells that produce oxygen by photosynthesis. A. variabilis is unique among well-characterized cyanobacteria in that it has three nitrogenase gene clusters that encode different nitrogenases, which function under different environmental conditions. The nif1 genes encode a Mo-nitrogenase that functions only in heterocysts, even in filaments grown anaerobically. The nif2 genes encode a different Mo-nitrogenase that functions in vegetative cells, but only in filaments grown under anoxic conditions. An alternative V-nitrogenase is encoded by vnf genes that are expressed only in heterocysts in an environment that is deficient in Mo. Thus, these three nitrogenases are expressed differentially in response to environmental conditions. The entire nif1 gene cluster, comprising at least 15 genes, is primarily under the control of the promoter for the first gene, nifB1. Transcriptional control of many of the downstream nif1 genes occurs by a combination of weak promoters within the coding regions of some downstream genes and by RNA processing, which is associated with increased transcript stability. The vnf genes show a similar pattern of transcriptional and post-transcriptional control of expression suggesting that the complex pattern of regulation of the nif1 cluster is conserved in other cyanobacterial nitrogenase gene clusters.


Factors influencing outcomes of surgical therapy of peri-implantitis: A secondary analysis of 1-year results from a randomized clinical study.
To identify predictors of treatment outcomes following surgical therapy of peri-implantitis. We performed a secondary analysis of data from a randomized controlled trial (RCT) comparing access flap with or without bone replacement graft. Outcomes at 12 months were probing pocket depth (PPD), bleeding on probing (BOP), soft-tissue recession (REC) and marginal bone level (MBL) change. Multilevel regression analyses were used to identify predictors. We also built an explanatory model for residual signs of inflammation. Baseline PPD was the most relevant predictor, showing positive associations with final PPD, REC and MBL gain, and negative association with probability of pocket closure. Smokers presented higher residual PPD. Absence of keratinized mucosa at baseline increased the probability of BOP but was otherwise not indicative of outcomes. Plaque at 6 weeks was detrimental in terms of residual PPD and BOP. Treatment allocation had an effect on REC. Final BOP was explained by residual PPD ≥6 mm and plaque at more than two sites. Baseline PPD was the most relevant predictor of the outcomes of surgical therapy of peri-implantitis. Pocket closure should be a primary goal of treatment. Bone replacement grafts may be indicated in aesthetically demanding cases to reduce soft-tissue recession. The importance of smoking cessation and patient-performed plaque control is also underlined.


Welcome Back to Your Future: The Assessment of Dementia by the Latent Variable "δ".
The latent variable "δ" (for "dementia") has been proposed as a phenotype for all cause dementia. δ is extracted from cognitive batteries by a specific confirmatory factor analysis in a structural equation modeling framework. δ appears to be uniquely responsible for cognition's association with functional status. Because it is extracted from Spearman's general intelligence factor "g", this has broad implications for dementia's assessment and pathophysiology. This issue of the Journal of Alzheimer's Disease brings together several demonstrations of δ's psychometric properties by investigative groups from three continents. In their aggregate, they suggest that δ homologs may have far ranging applications in dementia's clinical assessment and biomarker selection.


Extracellular matrix degradation by cultured mesangial cells: mediators and modulators.
Decreased degradation of the glomerular extracellular matrix (ECM) is thought to contribute to the accumulation of glomerular ECM that occurs in diabetic nephropathy and other chronic renal diseases. Several lines of evidence indicate a key role for the plasminogen activator/plasminogen/plasmin system in glomerular ECM degradation. However, which of the two plasminogen activators (PAs) present in renal tissue, tissue plasminogen activator (tPA) or urokinase-type plasminogen activator (uPA), is responsible for plasmin generation and those factors that modulate the activity of this system remain unclear. This study utilized mesangial cells isolated from mice with gene deletions for tPA, uPA, and plasminogen activator inhibitor 1 (PAI-1) to further delineate the role of the PA/plasminogen/plasmin system in ECM accumulation. ECM degradation by uPA-null mesangial cells was not significantly different from controls (92% +/- 1%, n = 12). In contrast, ECM degradation by tPA-null mesangial cells was markedly reduced (-78 +/- 1%, n = 12, P < 0.05) compared with controls, whereas tPA/uPA double-null mesangial cells degraded virtually no ECM. Previous studies from this laboratory have established that transforming growth factor-beta1 (TGFbeta1) inhibits ECM degradation by cultured mesangial cells by increasing the production of PAI-1, the major physiological PA inhibitor. In keeping with this observation, TGFbeta1 (1 ng/ml) had no effect on ECM degradation by PAI-1-null MC. High glucose levels (30 mM) in the presence or absence of insulin (0.1 mM) caused a moderate increase in ECM degradation by normal human mesangial cells. In contrast, glycated albumin, whose concentration is known to increase in diabetes, produced a dose-dependent (0.2-0.5 mg/ml) inhibition of ECM degradation by normal human mesangial cells. Taken together, these results document the importance of tPA versus uPA in renal plasmin production and indicate that in contrast to elevated glucose, glycated albumin may contribute to ECM accumulation in diabetic nephropathy.


C57BL/6N Mice Are More Resistant to Ehrlich Ascites Tumors Than C57BL/6J Mice: The Role of Macrophage Nitric Oxide.
BACKGROUND Effectiveness of the immune defense formed by the genotype often determines the predisposition to cancer. Nitric oxide (NO) produced by macrophages is an important element in this defense. MATERIAL AND METHODS We hypothesized that genetic characteristics of NO generation systems can predetermine the vulnerability to tumor development. The study was conducted on mice of 2 genetic substrains - C57BL/6J and C57BL/6N - with Ehrlich ascites carcinoma (EAC). NO production in the tumor was changed using ITU, an iNOS inhibitor; c-PTIO, a NO scavenger; and SNP, a NO donor. Macrophage NO production was estimated by nitrite concentration in the culture medium. iNOS content was measured by Western blot analysis. Macrophage phenotype was determined by changes in NO production, iNOS level, and CD markers of the phenotype. RESULTS The lifespan of C57BL/6N mice (n=10) with EAC was 25% longer (p<0.01) than in C57BL/6J mice (n=10). Decreased NO production 23% reduced the survival duration of C57BL/6N mice (p<0.05), which were more resistant to tumors. Elevated NO production 26% increased the survival duration of C57BL/6J mice (p<0.05), which were more susceptible to EAC. Both the NO production and the iNOS level were 1.5 times higher in C57BL/6N than in C57BL/6J mice (p<0.01). CD markers confirmed that C57BL/6N macrophages had the M1 and C57BL/6J macrophages had the M2 phenotype. CONCLUSIONS The vulnerability to the tumor development can be predetermined by genetic characteristics of the NO generation system in macrophages. The important role of NO in anti-EAC immunity should be taken into account in elaboration of new antitumor therapies.


Design, measurement and processing of region-specific DNA methylation assays: the mass spectrometry-based method EpiTYPER.
EpiTYPER® is a mass spectrometry-based bisulfite sequencing method that enables region-specific DNA methylation analysis in a quantitative and high-throughput fashion. The technology targets genomic regions of 100-600 base pairs and results in the quantitative measurement of DNA methylation levels largely at single-nucleotide resolution. It is particularly suitable for larger scale efforts to study candidate regions or to validate regions from genome-wide DNA methylation studies. Here, we describe in detail how to design and perform EpiTYPER measurements and preprocess the data, providing details for high quality measurements not provided in the standard EpiTYPER protocol.


Exact result in strong wave turbulence of thin elastic plates.
An exact result concerning the energy transfers between nonlinear waves of a thin elastic plate is derived. Following Kolmogorov's original ideas in hydrodynamical turbulence, but applied to the Föppl-von Kármán equation for thin plates, the corresponding Kármán-Howarth-Monin relation and an equivalent of the 4/5-Kolmogorov's law is derived. A third-order structure function involving increments of the amplitude, velocity, and the Airy stress function of a plate, is proven to be equal to -ɛℓ, where ℓ is a length scale in the inertial range at which the increments are evaluated and ɛ the energy dissipation rate. Numerical data confirm this law. In addition, a useful definition of the energy fluxes in Fourier space is introduced and proven numerically to be flat in the inertial range. The exact results derived in this Rapid Communication are valid for both weak and strong wave turbulence. They could be used as a theoretical benchmark of new wave-turbulence theories and to develop further analogies with hydrodynamical turbulence.


PI 3 kinase-dependent Akt kinase and PKCepsilon independently regulate interferon-gamma-induced STAT1alpha serine phosphorylation to induce monocyte chemotactic protein-1 expression.
Monocyte chemotactic protein-1 (MCP-1) recruits activated phagocytes to the site of tissue injury. Interferon-gamma (IFN-gamma) present in the microenvironment of glomerulus acts on mesangial cells to induce local production of MCP-1. The mechanism by which IFN-gamma stimulates expression of MCP-1 is not clear. We therefore examined the role of PI 3 kinase signaling in regulating the IFN-gamma-induced MCP-1 expression in mesangial cells. Blocking PI 3 kinase activity with Ly294002 attenuated IFN-gamma-induced MCP-1 protein and mRNA expression. IFN-gamma increased Akt kinase activity in a PI 3 kinase-dependent manner. Expression of dominant negative Akt kinase inhibited serine phosphorylation of STAT1alpha, without any effect on its tyrosine phosphorylation, and decreased IFN-gamma-induced expression of MCP-1. These data for the first time indicate a role for PI 3 kinase-dependent Akt kinase in MCP-1 expression. We have recently shown that along with Akt, PKCepsilon is a downstream target of PI 3 kinase in IFN-gamma signaling. Similar to dominant negative Akt kinase, dominant negative PKCepsilon also inhibited serine phosphorylation of STAT1alpha without any effect on tyrosine phosphorylation. Dominant negative PKCepsilon also abrogated MAPK activity, resulting in decrease in IFN-gamma-induced MCP-1 expression. Furthermore, Akt and PKCepsilon are present together in a signaling complex. IFN-gamma had no effect on this complex formation, but did increase PKCepsilon-associated Akt kinase activity. PKCepsilon did not regulate IFN-gamma-induced Akt kinase. Finally, expression of dominant negative Akt kinase blocked IFN-gamma-stimulated MAPK activation. These data provide the first evidence that PI 3 kinase-dependent Akt and PKCepsilon activation independently regulate MAPK activity and serine phosphorylation of STAT1alpha to increase expression of MCP-1.


Spatial correlations in the near field of random media.
The conventional coherence theory suggests that the fields radiated by statistically homogeneous sources correlate over spatial regions of the order of the wavelength irrespective of the distance from the surface of the source. Contrary to these predictions, we show that the spatial correlations of optical fields in close proximity of highly scattering, randomly inhomogeneous media depend on this distance and, moreover, their extent can be significantly smaller than the wavelength. The contribution of evanescent fields is experimentally demonstrated and the coherence length in the near field is shown to relate to the coherence properties at the surface which are, in turn, determined by the structural characteristics of the random media.


An examination of the effect of castor oil packs on constipation in the elderly.
This research, conducted at two rest homes in Manisa, Turkey, was undertaken to examine the effect of castor oil pack (COP) administrations on constipation in the elderly. Study participants were monitored for 7 days before, 3 days during, and 4 days after COP administration utilizing the Recall Bias and Visual Scale Analog (RB-VSAQ) as well as the Standard Diary developed by Pamuk et al. Wilcoxon Signed Ranks, Repeated Measures, Bonferroni, and Mann-Whitney U tests were used for data analysis. Eighty percent of study subjects had been constipated for 10 years or longer. COP administration did not have an effect on the number of bowel movements or amount of feces, but decreased the feces consistency score, straining during defecation and feeling of complete evacuation after a bowel movement, thus decreasing symptoms of constipation. We conclude that COP may be used for controlling symptoms of constipation.


Distribution and variable expression of secretory pathway protein reticulocalbin in normal human organs and non-neoplastic pathological conditions.
Reticulocalbin (RCN) is one member of the Ca(2+)-binding proteins in the secretory pathway and is localized in the endoplasmic reticulum. RCN may play a role in the normal behavior and life of cells, although its detailed role remains unknown. Overexpression of RCN may also play a role in tumorigenesis, tumor invasion, and drug resistance. The new antibody for human RCN is used in the distribution of RCN in normal human organs of fetuses and adults with or without inflammation. Immunohistochemical examination demonstrated a broad distribution of RCN in various organs of fetuses and adults, predominantly in the endocrine and exocrine organs. However, RCN expression was heterogeneous in each constituent cell of some organs. Among non-epithelial organs, vascular endothelial cells, testicular germ cells, neurons, and follicular dendritic cells showed strong staining. Plasma cells were the only RCN-positive cells among hematopoietic and lymphoid cells. In inflammatory conditions, RCN expression was enhanced in both epithelial and non-epithelial cells. Heterogeneous expression of RCN indicates that the amount of RCN needed for cell behavior and life may be variable, depending on each cell type and, therefore, RCN may be helpful in establishing the cell origin of neoplasms in some organs. However, further study is needed to establish the significance of RCN in tumorigenesis and in some peculiar features of neoplasms.


Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients.
Intravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients. However, it may also enhance the generation of hydroxyl radicals. Recently, plasma proteins have been demonstrated to be extremely susceptible to oxidative stress. Therefore, we investigated the effect of IVIR on the oxidative status of albumin, a major plasma protein, in HD patients. Eleven hemodialysis (HD) patients were treated with 40 mg of saccharated ferric oxide intravenously after every dialysis session for four weeks, and 11 age-/gender-matched HD patients were treated with vehicle. We performed high performance liquid chromatography (HPLC) analysis of serum albumin and determined the levels of reduced and oxidized albumin. Carbonyl formation of plasma proteins were also measured using an anti-2,4 dinitrophenylhydrazine antibody in patients with or without IVIR. IVIR resulted in an increase in both disulfide form (f(HNA-1)) and oxidized form (f(HNA-2)) of albumin in HD patients (36.0 +/- 6.03 vs. 41.7 +/- 6.27; 5.46 +/- 1.50 vs. 8.7 +/- 2.22, respectively, P < 0.05). The findings here also show that IVIR substantially increased plasma protein carbonyl content by oxidizing albumin. In addition, we found a strong correlation between plasma carbonyl content and the levels of oxidized albumin (f(HNA-1) and f(HNA-2)) in HD patients (R= 0.674 and R= 0.724, respectively, P < 0.01). The results of this study indicate that the HPLC analysis of serum albumin represents a potentially useful method for the quantitative and qualitative evaluation of oxidative stress in HD patients, and strongly suggest the possibility that oxidative stress, generated by IVIR, enhances the oxidation of albumin in those patients.


Self-gated cine phase-contrast balanced SSFP flow quantification at 0.55 T.
To implement cine phase-contrast balanced SSFP (PC-bSSFP) for low-field 0.55T cardiac MRI by exploiting the intrinsic flow sensitivity of the bSSFP slice-select gradient and the in-plane phase-cancelation properties of radial trajectories, enabling self-gated and referenceless PC-bSSFP flow quantification at 0.55 T. A free-running, tiny golden-angle radial PC-bSSFP approach was implemented on 0.55T and 1.5T systems. Cardiac and respiratory self-gating was incorporated to enable electrocardiogram-free scanning during breath-hold and free-breathing. By exploiting the intrinsic in-plane phase-cancelation properties of radial acquisitions and background phase fitting, referenceless single-point PC-bSSFP was realized. In vivo data were acquired in the ascending aorta of healthy subjects at 0.55 T and 1.5 T during breath-hold and free-breathing. Flow data, SNR, and velocity-to-noise ratio were compared relative to data obtained with phase-contrast spoiled gradient-echo variants. Velocities acquired with PC-bSSFP compared well with data from phase-contrast spoiled gradient-echo (RMSEv = 5.8 cm/s). PC-bSSFP at 0.55 T resulted in high-quality cine magnitude images and phase maps with sufficient SNR and velocity-to-noise ratio. Breath-hold and free-breathing PC-bSSFP performed very similarly, with comparable flow quantification (RMSEv = 5.7 cm/s). Referenceless single-point PC-bSSFP results agreed well with two-point PC-bSSFP (-1.8 ± 5.2 cm/s) while reducing scan times 2-fold. PC-bSSFP is feasible on low-field 0.55T systems, producing high-quality cine images while permitting simultaneous aortic flow measurements during breath-hold and free-breathing and without the need for electrocardiogram gating.


Treatment of postoperative main portal vein and superior mesenteric vein thrombosis with balloon angioplasty and/or stent placement.
Thrombolysis and mechanical thrombectomy have been used to treat postoperative main portal vein and superior mesenteric vein thrombosis. To evaluate the safety and efficacy of balloon angioplasty and/or stent placement without thrombolysis or thrombectomy for treating such thromboses. Fourteen patients with postoperative main portal vein or superior mesenteric vein thrombosis underwent percutaneous transhepatic balloon angioplasty and/or stent placement without thrombolysis or thrombectomy. The rates of technical and clinical success, major complications, and recurrence were evaluated retrospectively. Initial technical success was achieved in 13 of the 14 patients (93%). After the procedures, these 13 patients showed brisk portal inflow, without a significant amount of residual thrombus in the stented lumen or embolism. One patient was considered to be a technical failure despite showing a brisk portal inflow because 50% stenosis and partial residual thrombus remained in the stented lumen. Initial clinical success was achieved in 13 patients. One patient with technical success died of acute respiratory distress syndrome 8 days after the procedure, whereas one patient with technical failure achieved clinical success. One patient experienced acute rethrombosis 8 days after the procedure. During the median follow-up period of 16.3 months, rethrombosis occurred in six patients (43%), including one patient with acute rethrombosis. Balloon angioplasty and/or stent placement without thrombolysis or thrombectomy may be a safe and effective treatment modality for postoperative main portal vein and superior mesenteric vein thrombosis.


Alternations in interleukin-1β and nuclear factor kappa beta activity (NF-kB) in rat liver due to the co-exposure of Cadmium and Arsenic: Protective role of curcumin.
Cadmium chloride (Cd) and sodium arsenite (As) are two prominent examples of non-biodegradable substances that accumulate in ecosystems, pose a serious risk to human health and are not biodegradable. Although the toxicity caused by individual use of Cd and As is known, the toxicity of combined use (Cd+As) to mammals is poorly understood. The present study aims to investigate the hepatoprotective effect of curcumin (CUR), a naturally occurring bioactive component isolated from the root stem of Curcuma longa Linn., in preventing liver damage caused by a Cd+As mixture. A group of 30 Sprague-Dawley rats were subjected to intraperitoneal administration of Cd+As (0.44 mg/kg+5.55 mg/kg i.p.) and CUR (100 or 200 mg/kg) for a period of 14 days. The experimental results showed that the animals treated with Cd+As exhibited changes in liver biochemical parameters, inflammation and oxidative stress at the end of the experiment. Administration of CUR significantly reduced inflammation, oxidative stress and lipid peroxidation in the Cd+As plus CUR groups compared to the Cd+As group. Furthermore, histological examination of the liver tissue showed that administration of CUR had led to a significant reduction in the liver damage observed in the Cd+As group. The present study provides scientific evidence for the protective effects of CUR against lipid peroxidation, inflammation, oxidative stress and liver damage induced by Cd+As in the liver of rats. The results of our in vivo experiments were confirmed by those of our molecular modelling studies, which showed that CUR can enhance the diminished antioxidant capacity caused by Cd+As.


Biotransformation of androst-4-ene-3,17-dione and nandrolone decanoate by genera of Aspergillus and Fusarium.
The ability of five fungal species belonging to two genera of Aspergillus and Fusarium has been examined in the microbial transformation of androst-4-ene-3, 17-dione (AD). Furthermore, the biotransformation of nandrolone decanoate (2) by F. fujikuroi has been studied. AD (1) was converted by cultures of Aspergillus sp. PTCC 5266 to form 11α-hydroxy-AD (3) as the only product, with a yield of 86% in 3 days. Moreover, two hydroxylated metabolites 11α-hydroxy-AD (3, 65%) and 7β-hydroxy-AD (4; 18%) were isolated in biotransformation of AD by A. nidulans. On the other hand, it was metabolized by F. oxysporum to produce 14α-hydroxy-AD (5; 38%) and testosterone (6; 12%). Microbial transformation of AD by F. solani led to the production of 11α-hydroxy-AD (3; 54%) and testosterone (6; 14%). AD was reduced at the 17-position by F. fujikuroi to produce testosterone in the yield of 42%. Finally, nandrolone decanoate was transformed by F. fujikuroi via hydrolysis and oxidation at the 17-position to produce two metabolites namely 17β-hydroxyestr-4-en-3-one (7, 25.4%) and estr-4-en-3,17-dione (8, 33%), respectively. The all metabolites were purified and subsequently identified based on their spectra data analysis and comparing them to the literature data.


Toxic epidermal necrolysis--an unusual cause of colonic perforation. Report of a case.
Toxic epidermal necrolysis (TEN) is a rare and severe reaction to certain drugs that results in full-thickness epidermal necrosis of the skin. Other mucosal surfaces such as the oropharynx, esophagus, conjunctiva, and genitalia may also be affected. Specific involvement of the colon is distinctly unusual. A case of TEN that resulted in complete small bowel necrosis and colonic perforation is reported. Early and aggressive surgical resection dealt successfully with this complication and, along with supportive care, allowed resolution of the systemic condition to occur. Five additional cases of colonic necrosis complicating TEN are reviewed.


The 50 Most Cited Articles in the Indications, Risk Factors, Techniques, and Outcomes of ACL Revision Surgery.
The rate of anterior cruciate ligament (ACL) retear remains high and revision ACL reconstruction has worse outcomes compared with primaries. To make advances in this area, a strong understanding of influential research is necessary. One method for systematically evaluating the literature is by citation analysis. This article aims to establish and evaluate "classic" articles. With consideration of these articles, this article also aims to evaluate gaps in the field and determine where future research should be directed. The general approach for data collection and analysis consisted of planning objectives, employing a defined strategy, reviewing search results using a multistep and multiauthor approach with specific screening criteria, and analyzing data. The collective number of citations for all publications within the list was 5,203 with an average of 104 citations per publication. "Biomechanical Measures during Landing and Postural Stability Predict Second Anterior Cruciate Ligament Injury after Anterior Cruciate Ligament Reconstruction and Return to Sport" by Paterno et al contained both the highest number of total citations and the highest number of citations per year, with 403 total citations and 43.9 citations per year. The most recurring level of evidence were level II (n = 18) and level III (n = 17). "Clinical Outcomes" was the most common article type (n = 20) followed by "Risk Factors" (n = 10). The American Journal of Sports Medicine had the highest recorded Cite Factor with over 50% of the articles (n = 27) published. The most productive authors included R.W. Wright (n = 6), S.D. Barber-Westin (n = 5), F.R. Noyes (n = 5), and K.P. Spindler (n = 5). Historically, influential studies have been published in the realms of clinical outcome and risk factor identification. It has been established that revision ACL reconstruction has worse outcomes and more high-level studies are needed. Additionally, prospective studies that apply the knowledge for current known risk factor mitigation are needed to determine if graft tear rates can be lowered.


The current epidemic of childhood obesity and its implications for future coronary heart disease.
This article acquaints readers with the data sources documenting the dramatic increases of overweight and obesity in the United States in the past 40 years, explains the reference standards for ascertaining measures of overweight in adults and children, and cites evidence that establishes obesity as a risk factor for premature death. Also reviewed are reports documenting recent increases in the frequency of type 2 diabetes mellitus and glucose intolerance and selected reports emanating from four longitudinal studies performed in large populations of adults, children, and adolescents linking excessive adiposity to coronary heart disease risk factors. A brief discussion of the challenges that pediatricians and other primary care health providers face in helping to diminish the prevalence of obesity and its attendant health problems is presented.


Assessment of fetal growth by customized growth charts.
Customized fetal growth charts take account of the individual variation in the fetal growth potential based on non-pathological maternal and fetal characteristics. Application of these customized weight charts might improve the distinction between pathological growth-restricted fetuses and fetuses that are small but have reached their growth potential. Current models for customized growth standards have been based on birth weight and fetal growth data. Variables used for customization are gestational age, maternal age, parity, ethnicity, height, weight and fetal sex. Thus far, it remains controversial whether these maternal and fetal characteristics used for customization are strong enough predictors for fetal growth on an individual level and are truly physiological characteristics. The currently available customized growth charts might be of benefit for use in epidemiological studies and clinical practice. Further studies are needed to validate these customized growth models and to examine whether and to what extend they improve identification of children that are at risk for morbidity in the perinatal period and later in life.


Comparison of the analgesic effects of robenacoxib, buprenorphine and their combination in cats after ovariohysterectomy.
The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n=10; GB), robenacoxib (2mg/kg, n=10; GR) or their combination at the same dosages (n=10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ≥ 3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone.


Automatic feedback control of relative blood volume changes during hemodialysis improves blood pressure stability during and after dialysis.
Automatic feedback systems have been designed to control relative blood volume changes during hemodialysis (HD) as hypovolemia plays a major role in the development of dialysis hypotension. Of these systems, one is based on the concept of blood volume tracking (BVT). BVT has been shown to improve intra-HD hemodynamic stability. We first questioned whether BVT also improves post-HD blood pressure stability in hypotension-prone patients and second, whether BVT is effective in reducing the post-HD weight as many hypotension-prone patients are overhydrated because of an inability to reach dry weight. After a 3-week period on standard HD, 12 hypotension-prone patients were treated with two consecutive BVT treatment protocols. During the first BVT period of 3 weeks, the post-HD target weight was kept identical compared with the standard HD period (BVT-constant weight; BVT-cw). During the second BVT period of 6 weeks, we gradually tried to lower the post-HD target weight (BVT-reduced weight; BVT-rw). In the last week of each period, we studied intra-HD and 24 hr post-HD blood pressure behavior by ambulatory blood pressure measurement (ABPM). Pre- and post-HD weight did not differ between standard HD and either BVT-cw or BVT-rw. Heart size on a standing pre-dialysis chest X-ray did not change significantly throughout the study. There were less episodes of dialysis hypotension during BVT compared with standard HD (both BVT periods: p<0.01). ABPM data were complete in 10 patients. During the first 16 hr post-HD, systolic blood pressure was significantly higher with BVT in comparison with standard HD (both BVT periods: p<0.05). The use of BVT in hypotension-prone patients is associated with higher systolic blood pressures for as long as 16 hr post-HD. BVT was not effective in reducing the post-HD target weight in this patient group.


Outreach and diagnosis: Saudi Arabia's experience.
The World Federation of Hemophilia (WFH) is an international nonprofit organization dedicated to improving and sustaining the lives of individuals with haemophilia. According to the World Federation of Hemophilia (WFH) annual global survey, haemophilia A has a prevalence of 105 per million males and 28 per million males of haemophilia B in a global population of 6 billion. The annual global survey reported 295 000 individuals with haemophilia, von Willebrand disease and other bleeding disorders in 113 countries. WFH estimated approximately 70% of patients with haemophilia under diagnosed globally. The variability of occurrence of these disorders in different ethnicities, lack of awareness and diagnostic facilities/expertise led to the prevalence of other bleeding disorders being much more underestimated. The main reason for the gap between detected (reported) and estimated numbers of patients with bleeding disorders includes the lack of laboratory facilities and trained personnel required to establish an accurate diagnosis for bleeding disorders.


Metabolic syndrome resolution in children and adolescents after 10 weeks of weight loss.
Without aggressive intervention, childhood obesity and the metabolic syndrome may result in lifelong physical consequences. Interventions that emphasize healthy eating and regular exercise are crucial to stop this epidemic and its ramifications. This paper discusses the incidence of the metabolic syndrome and cardiovascular risk factors before and after a weight loss program. A retrospective review was conducted in 135 children and adolescents (aged 6 to 19) who completed a 10-week medically supervised weight loss program. Outcome measures included mean change in each component of the metabolic syndrome, total cholesterol, low-density lipoprotein cholesterol, and hemoglobin A(1c). After 10 weeks of weight loss, a mean (SD) weight loss of 9.24 (19.5) kg was attained. Resolution of the metabolic syndrome was seen in 75.5% of children and adolescents. Weight loss can reverse metabolic syndrome and decrease cardiovascular risk in as little as 10 weeks.


OxyR-Dependent Transcription Response of Sinorhizobium meliloti to Oxidative Stress.
Reactive oxygen species such as peroxides play an important role in plant development, cell wall maturation, and defense responses. During nodulation with the host plant Medicago sativa, Sinorhizobium meliloti cells are exposed to H2O2 in infection threads and developing nodules (R. Santos, D. Hérouart, S. Sigaud, D. Touati, and A. Puppo, Mol Plant Microbe Interact 14:86-89, 2001, https://doi.org/10.1094/MPMI.2001.14.1.86). S. meliloti cells likely also experience oxidative stress, from both internal and external sources, during life in the soil. Here, we present microarray transcription data for S. meliloti wild-type cells compared to a mutant deficient in the key oxidative regulatory protein OxyR, each in response to H2O2 treatment. Several alternative sigma factor genes are upregulated in the response to H2O2; the stress sigma gene rpoE2 shows OxyR-dependent induction by H2O2, while rpoH1 expression is induced by H2O2 irrespective of the oxyR genotype. The activity of the RpoE2 sigma factor in turn causes increased expression of two more sigma factor genes, rpoE5 and rpoH2 Strains with deletions of rpoH1 showed improved survival in H2O2 as well as increased levels of oxyR and total catalase expression. These results imply that ΔrpoH1 strains are primed to deal with oxidative stress. This work presents a global view of S. meliloti gene expression changes, and of regulation of those changes, in response to H2O2IMPORTANCE Like all aerobic organisms, the symbiotic nitrogen-fixing bacterium Sinorhizobium meliloti experiences oxidative stress throughout its complex life cycle. This report describes the global transcriptional changes that S. meliloti makes in response to H2O2 and the roles of the OxyR transcriptional regulator and the RpoH1 sigma factor in regulating those changes. By understanding the complex regulatory response of S. meliloti to oxidative stress, we may further understand the role that reactive oxygen species play as both stressors and potential signals during symbiosis.


Risperidone-induced priapism.
Priapism is well documented as a potential side effect of psychotropic medications. To date, there have been no reports of risperidone-induced priapism in the urologic literature. We report a case of risperidone-induced priapism requiring surgical treatment.


Corneal Eccentricity in a Rural Japanese Population: The Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS).
To determine normal corneal eccentricity in a rural Japanese population and to examine factors associated with eccentricity value. This used data from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) project between 2009 and 2012. Residents of Minamiaizu and Tadami in Fukushima, Japan, who were aged 40 years or over, were invited for a comprehensive eye examination. For 1371 patients with no history of internal eye surgery, corneal eccentricity was measured using a Pentacam. Of 1371 people recruited to the study, 1215 (1215 eyes) met the inclusion criteria. The overall mean eccentricity was 0.46 (SD = 0.18; range, -0.85 to 0.88). Corneal eccentricity was significantly associated with age, spherical equivalent, pupil diameter, anterior chamber angle, anterior chamber volume, and central corneal thickness, but not with gender or body mass index. In this study, the normal cornea in this Japanese population was prolate. Corneal eccentricity was likely to decrease with increasing age. Also, spherical equivalent and other anterior segment parameters had an influence on corneal eccentricity. Corneal eccentricity measurements might be helpful in the diagnosis of corneal diseases and in calculations for intraocular lens implantation and corneal refractive surgery.


Evaluation of the effects of elastic compression in patients with postphlebitic limbs by laser-Doppler flowmetry.
Laser-Doppler flowmetry has been used to study the skin microcirculation in 20 normal limbs and 80 limbs of patients with venous hypertension and leg ulceration due to deep venous reflux. It was found that limbs with venous hypertension had a high skin resting blood flow (BRF) and an impaired veno-arteriolar reflex (VR). There was a marked improvement in both BRF and VR after elastic compression for three weeks and an association between this improvement and the rate of healing of the leg ulcers. The results indicate that elastic compression may affect the microcirculation even though it does not alter the venous pressure measurements when the elastic stockings are removed.


Targeted-mitochondria antioxidants therapeutic implications in inflammatory bowel disease.
The role of the mitochondria, particularly its implications in cellular redox and oxidative balance is important for cell survival, and is involved in a variety of human diseases including inflammatory bowel disease (IBD). In this review we address mitochondria physiology and reactive oxygen species as cognate to IBD. Several studies have reported altered mitochondria function in intestinal epithelium in IBD. However, mitochondrion significance in this disease has not been much investigated. Finally, we suggest potential for antioxidants targeted to mitochondria in IBD therapy as a treatment strategy.


Budesonide as induction therapy for incomplete microscopic colitis: A randomised, placebo-controlled multicentre trial.
Incomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first-line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo-controlled trial to evaluate budesonide as induction therapy for MCi. Patients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as a mean of <3 stools/day and a mean of <1 watery stool/day in the 7 days before week 8. Due to insufficient patient recruitment, the trial was discontinued prematurely. The intention-to-treat analysis included 44 patients (21 budesonide and 23 placebo). The primary endpoint of clinical remission at week 8 was obtained by 71.4% on budesonide and 43.5% on placebo (p = 0.0582). All clinical secondary endpoints were in favour of budesonide. Budesonide decreased the number of soft or watery stools (16.3 vs. 7.7, p = 0.0186) and improved health-related quality of life for all four dimensions of the short health scale. Adverse events with a suspected relation to study drug were reported in one patient in the budesonide group and two patients in the placebo group. Neither serious nor severe adverse events occurred during the double-blind phase. Budesonide decreased the frequency of soft or watery stools and improved the patients' quality of life significantly in MCi, but the primary endpoint was not met due to the low sample size (type 2 error). Budesonide was safe and well tolerated during the 8-weeks treatment course.


Microstructure Evolution and Flow Stress Model of a 20Mn5 Hollow Steel Ingot during Hot Compression.
20Mn5 steel is widely used in the manufacture of heavy hydro-generator shaft due to its good performance of strength, toughness and wear resistance. However, the hot deformation and recrystallization behaviors of 20Mn5 steel compressed under high temperature were not studied. In this study, the hot compression experiments under temperatures of 850-1200 °C and strain rates of 0.01/s-1/s are conducted using Gleeble thermal and mechanical simulation machine. And the flow stress curves and microstructure after hot compression are obtained. Effects of temperature and strain rate on microstructure are analyzed. Based on the classical stress-dislocation relation and the kinetics of dynamic recrystallization, a two-stage constitutive model is developed to predict the flow stress of 20Mn5 steel. Comparisons between experimental flow stress and predicted flow stress show that the predicted flow stress values are in good agreement with the experimental flow stress values, which indicates that the proposed constitutive model is reliable and can be used for numerical simulation of hot forging of 20Mn5 hollow steel ingot.


Experimental investigation of threaded cup performance during insertion in total hip replacement.
Cementless threaded cups are often used in Europe on the acetabular side of a total hip arthroplasty (THA), with some products achieving excellent clinical results. Titanium and titanium alloys are nowadays accepted as the materials of choice for these implants. In contrast, however, there is no consensus about the ideal thread design. This in vitro and human cadaver study aimed to compare the insertion torques of commercially available threaded cups during insertion. The aims were (1) to see whether the clinical experience of surgeons using these cups specifically related to insertion torque could be reproduced in the experiment and (2) to assess whether or not the cup size and thread design has a statistically significant influence on the insertion torque. Using a biaxial testing machine the cups were screwed into pre-machined polyurethane blocks and the insertion torque was recorded by an appropriate sensor. Clear differences were seen between the four different designs. A variance analysis using statistical software showed that both the cup size (p=0.003) and the thread design (p=0.0009) significantly affect the insertion torque. The human cadaver study allowing a right-left comparison of two different cups within the same specimen confirmed the insertion torque data of the experimental study. In addition, the trends observed during the course of the insertion agreed with the clinical experience of the orthopaedic surgeons consulted as part of this study. (Hip International 2004; 14: 11-7).


Patient knowledge and misconceptions of osteoarthritis assessed by a validated self-completed knowledge questionnaire (PKQ-OA).
To design and validate an osteoarthritis (OA) patient knowledge questionnaire (PKQ-OA) and to use it to assess the patients' level of knowledge of their disease, treatments and appropriate management techniques. The PKQ-OA comprises 16 multiple choice questions with 30 correct answers. It was developed in two phases and tested for face validity, readability (Flesch Reading Index) and understanding, reliability (Kuder-Richardson Formula 20) and reproducibility (test/retest). The questionnaire was then used to assess knowledge of disease and management of OA in a cohort of 83 patients with established disease. The PKQ was found to be fairly easy to read, reliable (r = 0.75) and reproducible (r = 0.81; P < 0.01). The overall median score for the PKQ-OA was 19 ranging from 8 to 26. There was a highly significant association between the scores obtained and the number of years patients had spent in formal education, higher scores equating with greater length of education (P < 0.005). The majority of patients was knowledgeable about the symptoms of OA and exercise, but confused joint protection and energy conservation. The most worrying finding was the lack of knowledge regarding analgesics and some aspects of non-steroidal anti-inflammatory drug (NSAID) therapy. Less than a third of patients knew that analgesics could be taken prophylactically and 70% did not know that they should be taken when pain starts to build. Among the patients 34% did not know that NSAIDs should be taken with or following food. The PKQ-OA is a readable, reliable and reproducible questionnaire. It is quick to complete and score and could be used in out patient clinics or GP surgeries to assess knowledge of patients with OA.


Effects of fluid composition on mist composition.
In a reported study, mists of selected synthetic metalworking fluids were generated in laboratory experiments by two processes, nebulization (atomization) and air sparging (bubbling). Short-chain fatty acid species were determined by in situ trimethylsilyl derivatization. Comparison of relative amounts of the short-chain acids collected from mists generated by nebulization with those generated by sparging showed that the sparged mists had significantly higher amounts of neodecanoic, nonanoic, and dodecanedioic acids. Comparison of the amounts of acids collected by the resin cartridges to amounts found on the filters showed that significant losses of octanoic and isononanoic acids occurred over 8 hours of collection and that only dodecanedioic acid was not lost from the filter over a 22-hour sampling period. In another reported metalworking mist study, contaminants of metalworking fluids, e.g., tramp oils, were shown in laboratory experiments to increase the misting potential of water-based metalworking fluids. Significantly, tramp oil contamination caused less misting in synthetic fluids than soluble and semi-synthetic fluids.


Effect of Allium sativum (garlic) diallyl disulfide (DADS) on human non-small cell lung carcinoma H1299 cells.
This study was undertaken to elucidate the effect of diallyl disulfide from Allium sativum, an oil-soluble organosulfur compound found in garlic, in suppressing human non-small cell lung carcinoma H1299 cells. A potent increase in apoptotic cells has accompanied 1) a decrease in cell viability, 2) an increase of the fraction of G2/M-phase cells by up to 48.80 %, and 3) a transient increase of the phospho-p42/44 (phosphorylated p42/44 MAPK) in a time- and concentration-dependent manner. These results indicated that diallyl disulfide could induce apoptosis in human non-small cell lung carcinoma H1299 cells via, at least partly, G2/M-phase block of the cell cycle, related to a rise in MAPK phosphorylation.


NGSCheckMate: software for validating sample identity in next-generation sequencing studies within and across data types.
In many next-generation sequencing (NGS) studies, multiple samples or data types are profiled for each individual. An important quality control (QC) step in these studies is to ensure that datasets from the same subject are properly paired. Given the heterogeneity of data types, file types and sequencing depths in a multi-dimensional study, a robust program that provides a standardized metric for genotype comparisons would be useful. Here, we describe NGSCheckMate, a user-friendly software package for verifying sample identities from FASTQ, BAM or VCF files. This tool uses a model-based method to compare allele read fractions at known single-nucleotide polymorphisms, considering depth-dependent behavior of similarity metrics for identical and unrelated samples. Our evaluation shows that NGSCheckMate is effective for a variety of data types, including exome sequencing, whole-genome sequencing, RNA-seq, ChIP-seq, targeted sequencing and single-cell whole-genome sequencing, with a minimal requirement for sequencing depth (>0.5X). An alignment-free module can be run directly on FASTQ files for a quick initial check. We recommend using this software as a QC step in NGS studies. https://github.com/parklab/NGSCheckMate.


Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.
Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.


Selective aggregation of polyanion-coated gold nanorods induced by divalent metal ions in an aqueous solution.
A simple, accurate method for detecting metal ions in an aqueous solution using functionalized gold nanorods (AuNRs) is described. The method involves the complexing of divalent metal ions with poly(acrylic acid) (PAA) and, the localized surface plasmon resonance (LSPR) phenomena of AuNRs. Changes in the longitudinal surface plasmon bands (LSPBs) were monitored using aggregates of PAA-coated AuNRs with various divalent metal ions via UV-vis spectroscope. Functionalized AuNRs underwent robust aggregate formation by chelation with divalent metal ions (e.g., Cu2+, Zn2+, Cd2+, and Fe2+). Copper ions formed largest aggregates within 2 h, because complexation between Cu2+ and dicarboxylate has the highest deltaH and -deltaG values. This process represents an easy and useful method for detecting certain divalent metal ions, and the aggregates are also, in some cases, clearly visible to the naked eye.


The perceived impacts of monitoring activities on intergovernmental relationships: some lessons from the Ecological Monitoring Network and Water in Focus.
An increasing stream of monitoring activities is entering the public sector. This article analyzes the perceived impacts of monitoring activities on intergovernmental relationships. Our theoretical framework is based on three approaches to monitoring and intergovernmental relationships, namely, a rational, a political, and a cultural perspective. Our empirical insights are based on two Dutch case studies, namely, the Ecological Monitoring Network and the Water in Focus reports. The conclusion is that monitoring activities have an impact on intergovernmental relationships in terms of standardizing working processes and methods, formalizing information relationships, ritualizing activities, and developing shared concepts ("common grammar"). An important challenge is to deal with the politicization of intergovernmental relationships, because monitoring reports can also stimulate political discussions about funding, the design of the instrument, administrative burdens, and supervisory relationships.


Ethical issues in stem cell research.
Like most cutting edge medical technology, human stem cell research raises a number of difficult and important ethical issues and concerns, requiring potential benefits to be balanced against the need to protect the rights and welfare of citizens. Much of the debate involves research using embryonic stem (ES) cells, which in turns revolves around the moral status of the human embryo, and the level of respect and protection that should be accorded. This is an especially sensitive issue in pluralistic societies where different, if not conflicting, cultural and religious perspectives exist. Another contentious issue as far as the derivation of ES cells is concerned is the intent involved in producing the embryos, specifically whether it is ethically permissible to allowing embryos to be made solely for the purpose of research. These and several other relevant ethical issues will be discussed, including a comparison of guidelines and positions adopted in different countries.