Lipid screening in HIV-infected veterans.
Lipid screening is recommended for patients taking protease inhibitors (PIs). We examined data from the Veterans Administration Immunology Case Registry to assess lipid screening among HIV-infected veterans who received PIs for at least 6 consecutive months during 1999 and 2001. We estimated crude and adjusted associations between lipid screening and patient characteristics (age, gender, HIV exposure, and race/ethnicity), comorbidities (AIDS, cardiovascular disease, diabetes, hypertension, smoking, and hyperlipidemia), and facility characteristics (urban location, case management, guidelines, and quality improvement programs). Among 4065 patients on PIs, clinicians screened 2395 (59%) for lipids within 6 months of initiating treatment. Adjusting for patient characteristics, comorbidities, facility traits, and clustering, lipid screening was more common among patients who were cared for in urban areas (relative risk [RR] = 1.3, confidence limits: 1.0-1.5), diabetic (RR = 1.2, confidence limits: 1.1-1.3), or previously hyperlipidemic (RR = 1.4, confidence limits: 1.3-1.5) and less common among patients with a history of intravenous drug use (IVDU) (RR = 0.90, confidence limits: 0.79-1.0) or unknown HIV risk (RR = 0.85, confidence limits: 0.75-0.95). Six in 10 patients taking PIs receive lipid screening within 6 months of PI use. Systemic interventions to improve overall HIV quality of care should also address lipid screening, particularly among patients with unknown or IVDU HIV risk and those cared for in nonurban areas.


Dermatofibrosarcoma protuberance: case reports.
Dermatofibrosarcoma protuberance (DFSP) is a relatively uncommon soft tissue neoplasm with intermediate to low grade malignancy, rarely metastasizing to regional lymph node or distant site but with proclivity for local recurrence due to inadequate resection. We evaluated the clinical histories and treatment outcomes of five consecutive patients who had histologic diagnosis of DFSP in the University of Calabar Teaching Hospital between 2000 and 2004. The five cases reported had histologic diagnosis, sought for after excision. The male:female ratio was 2:3 with an age range of 17-35 years (mean, 26.6 years). Two of the lesions involved the neck and the other three sites involved were the anterior chest wall, groin and proximal thigh. Three of the lesions were recurrent. DFSP is an uncommon tumour, painless, cutaneous and multilobulated lesions should arouse the suspicion of this tumour. Early presentation, pre-operative histologic diagnosis and postoperative evaluation of resection margins would enhance the goal of ensuring adequate excision for improved outcome.


Cross-modal plasticity of tactile perception in blindness.
This review focusses on cross-modal plasticity resulting from visual deprivation. This is viewed against the background of task-specific visual cortical recruitment that is routine during tactile tasks in the sighted and that may depend in part on visual imagery. Superior tactile perceptual performance in the blind may be practice-related, although there are unresolved questions regarding the effects of Braille-reading experience and the age of onset of blindness. While visual cortical areas are clearly more involved in tactile microspatial processing in the blind than in the sighted, it still remains unclear how to reconcile these tactile processes with the growing literature implicating visual cortical activity in a wide range of cognitive tasks in the blind, including those involving language, or with studies of short-term, reversible visual deprivation in the normally sighted that reveal plastic changes even over periods of hours or days.


Photochemistry and phototoxicity of aloe emodin.
Photochemical pathways leading to the phototoxicity of the aloe vera constituent aloe emodin were studied. The results indicate a photochemical mechanism involving singlet oxygen to be the most likely pathway responsible for the observed phototoxicity. Aloe emodin was found to efficiently generate singlet oxygen when irradiated with UV light (phidelta = 0.56 in acetonitrile). The survival of human skin fibroblast cells in the presence of aloe emodin was found to decrease upon irradiation with UV light. A further decrease in cell survival was observed in D2O compared with H2O, suggesting the involvement of singlet oxygen as the primary pathway. Laser flash photolysis experiments were also carried out on aloe emodin alone and in the presence of various biological substrates. Aloe emodin proved to be relatively photostable (phi = 1 x 10(-4)) and a poor photo-oxidant (E*red = +1.02 V). Only absorption bands caused by the triplet state of aloe emodin (lambdamax = 480 nm) and the aloe emodin conjugate base (lambdamax = 520 nm) were observed in the transient spectra.


Impact of Predilatation Prior to Transcatheter Aortic Valve Implantation With the Self-Expanding Acurate neo Device (from the Multicenter NEOPRO Registry).
Safety and feasibility of transfemoral Acurate neo implantation without systematic predilatation are not fully investigated. Our aim was to evaluate the use and impact of pre-implantation balloon aortic valvuloplasty (pre-BAV) before transcatheter aortic valve implantation (TAVI) with Acurate neo. The NEOPRO Registry retrospectively included 1,263 patients who underwent transfemoral TAVI with Acurate neo at 18 centers between January 2012 and March 2018. Information on pre-BAV was available for 1,262 patients (99.9%). Primary end points were pre-discharge moderate-to-severe paravalvular aortic regurgitation (PAR II+), 30-day new permanent pacemaker implantation, and 30-day all-cause mortality or stroke. A total of 1,262 patients who underwent TAVI with (n = 1,051) or without predilatation (n = 211) were included. A reduction in the pre-BAV rate was observed during the study period (from 95.7% in the first date quintile to 78.4% in the last date quintile). Patients who underwent pre-BAV had higher degrees of aortic valve (AV) and left ventricular outflow tract (LVOT) calcification. Primary endpoints were similar between pre-BAV and no pre-BAV groups (PAR II+ 5.5% vs 3.4%, p = 0.214; 30-day permanent pacemaker implantation 9.0% vs 8.0%, p = 0.660; 30-day death or stroke 4.9% vs 4.4%, p = 0.743). The need for postdilatation and other procedural outcomes were comparable between groups. Predilatation did not have a significant impact on primary endpoints across AV and LVOT calcification subgroups (subgroup analyses) and was not independently associated with primary endpoints (multivariate analyses). In conclusion, transfemoral Acurate neo implantation without predilatation appears to be feasible and safe, especially in patients with milder degrees of AV and LVOT calcification.


Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS) treated with anthracycline-containing chemotherapy.
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with poor treatment outcomes. The aim of this study was to evaluate whether lymphopenia at diagnosis would have an adverse effect on survival in patients with PTCL-NOS treated with anthracycline-containing chemotherapy. A total of 118 patients with PTCL-NOS treated with anthracycline-containing chemotherapy from 4 Korean institutions were included. Thirty-six patients (30.5%) had a low absolute lymphocyte count (ALC, < 1.0 × 109/L) at diagnosis. Patients with lymphopenia had shorter overall survival (OS) and progression-free survival (PFS) rates compared with patients with high ALCs (P = 0.003, P = 0.012, respectively). In multivariate analysis, high-intermediate/high-risk International Prognostic Index (IPI) scores and lymphopenia were both associated with shorter OS and PFS. Treatment-related mortality was 25.0% in the low ALC group and 4.8% in the high ALC group (P = 0.003). In patients considered high-intermediate/high-risk based on IPI scores, lymphopenia was also associated with shorter OS and PFS (P = 0.002, P = 0.001, respectively). This study suggests that lymphopenia could be an independent prognostic marker to predict unfavorable OS and PFS in patients with PTCL-NOS treated with anthracycline-containing chemotherapy and can be used to further stratify high-risk patients using IPI scores.


Differential proteomic analysis of late-stage and recurrent breast cancer from formalin-fixed paraffin-embedded tissues.
The heterogeneity of breast cancer requires the discovery of more incisive molecular tools that better define disease progression and prognosis. Proteomic analysis of homogeneous tumor cell populations derived by laser microdissection from formalin-fixed, paraffin-embedded (FFPE) tissues has proven to be a robust strategy for conducting retrospective cancer biomarker investigations. We describe an MS-based analysis of laser microdissected cancerous epithelial cells derived from twenty-five breast cancer patients at defined clinical disease stages with the goal of identifying protein abundance characteristics indicative of disease progression and recurrence. Comparative analysis of stage 0 and stage III patients revealed 113 proteins that significantly differentiated these groups and included known factors associated with disease pathogenesis, such as CDH1 and CTNNB1, as well as those previously implicated in breast cancer, such as TSP-1. Similar analyses of patients presenting with stage II disease that did or did not exhibit recurrence two years postdiagnosis revealed 42 proteins that significantly differentiated these subgroups and included IRS-1 and PARK7. These data provide evidence supporting the utility of FFPE tissues for functional proteomic analyses and protein biomarker discovery and yielded protein candidates indicative of disease stage and recurrence in breast cancer that warrant further investigation for diagnostic utility and biological relevance.


The C-681G polymorphism of the PPAR-γ gene is associated with susceptibility to non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is defined as excessive accumulation of fatty acid in the liver, a common disease in the world. The research of single nucleotide polymorphisms (SNPs) provides a new approach for managing NAFLD. SNPs may increase or decrease the functions of the target genes and their encoding proteins. Peroxisome proliferator-activated receptor (PPAR) plays a key role in modulating metabolism of hepatic triglycerides and consequently magnitude of NAFLD. In this study, we investigated the effect of three SNPs in the PPAR-γ gene i.e. rs10865710 (C-681G), rs7649970 (C-689T) and rs1801282 (C34G, also termed Pro12Ala) on susceptibility to NAFLD. The participants were selected from our epidemiological survey. Totally 169 participants were enrolled in NAFLD group, and 699 healthy subjects were included as controls. PCR-RFLP was applied to detect the SNPs. The G allele frequency of rs10865710 in NAFLD group (41.1%) was significantly higher than that (34.8%) in controls (p = 0.03). Differences in other two loci (rs7649970 and rs1801282) were not statistically significant between the two groups (p > 0.05). This result was confirmed by haplotype analysis. The GCC haplotype (a set of 3 adjacent SNPs in linkage disequilibrium, corresponding to the three alleles of above polymorphisms in order) was a risk factor for the susceptibility to NAFLD (p = 0.03). This study has revealed that the G allele of rs10865710 in the PPAR-γ gene is associated with the increased susceptibility to NAFLD. Our findings may provide novel diagnostic biomarkers and therapeutic targets for NAFLD.


[Determinants of cellular atypia detection in the cervical screening program in Rio de Janeiro, Brazil].
To identify the main determinants of cellular atypia detection in the cervical screening program in the state of Rio de Janeiro, Brazil, using data from the Cervical Cancer Information System SISCOLO. A random sample of 65 535 Pap smears performed in 2007 was obtained from SISCOLO. This sample was used to produce a logistic regression model to identify variables that impact the process of detecting cellular atypia. A ROC curve was used to define the most suitable cutoff point to classify the presence or absence of atypia. A sensitivity analysis was performed to assess the impact on the model of factors related to the organization of the service model. The variables of impact were "reference laboratory," which reflects laboratory production scale; "presence of cellular elements representative of the transformation zone," which reflects the quality of the sampling; "immature squamous metaplasia," "presence of other benign cellular changes," and "absence of typical vaginal microorganisms." Each increase of 1 year in age was associated with a 1.7% reduction in the chance of detecting atypia. The ROC curve defined a cutoff of 4.5%, which allowed the maximization of the model's sensitivity (73.0%) and specificity (66.8%). Sensitivity analysis indicated an increase of 46.4% in the frequency of atypia following a simulated increase in the number of samples analyzed in the excellence (42.9%) and in the presence of cellular elements representative of the transformation zone (43.0%). The model revealed that the detection of atypical cells is strongly influenced by organizational factors such as adequate sample collection and laboratory size. Because these factors can be changed by adequate management practices, the proposed model may be an important tool to improve cervical screening programs.


Predictors of loss to follow-up among patients on ART at a rural hospital in KwaZulu-Natal, South Africa.
Improved HIV outcomes as a result of expanded antiretroviral therapy (ART) access is threatened by increasing rates of loss to follow up (LTFU) among those on ART, largely reported in urban populations. Some reports suggest that LTFU rates are overestimated due to patient movement to other facilities and inadequate medical records. To define the proportion disengaging from HIV care as well as the characteristics of those LTFU in order to design and implement appropriate interventions to increase retention. We performed a retrospective review of patients who discontinued ART at a central hospital ART clinic in rural South Africa and compared with patients receiving care at the 15 primary health clinics (PHCs) to determine the true proportion of those who were LTFU. We also compared those who discontinued ART with those who did not at the central hospital ART clinic to determine predictors of loss to follow up. Among 3242 patients on ART, 820 were originally marked as LTFU. Among all patients, 272 (8.4%) were found at a clinic on treatment, 56 (1.7%) were found at a clinic from which they had since discontinued treatment, and 10 (0.3%) returned to care between June and July 2016, leaving 475 (14.7%) unaccounted for and thus categorized as 'true' LTFU. Factors found to be associated with discontinuation include being male, age 18-35, having a CD4 count under 200 cells/μL, and being on ART for under six months. Young men with low CD4 counts early after ART initiation are at highest risk of ART disengagement in this rural South African HIV clinic. Novel interventions targeting this group are needed to improve retention in care.


Induction of apoptosis by sphingosine, sphinganine, and C(2)-ceramide in human colon cancer cells, but not by C(2)-dihydroceramide.
Complex dietary sphingolipids such as sphingomyelin and glycosphingolipids have been reported to inhibit the development of colon cancer. This protective role may be the result of the conversion of complex sphingolipids to bioactive metabolites including sphingoid bases (sphingosine and sphinganine) and ceramide, which inhibit proliferation and stimulate apoptosis. In the current study, we evaluated the significance of the 4,5-trans double bond by comparing the effects of sphingosine and the cell permeable short-chain ceramide analog C(2)-ceramide to those of sphinganine and C(2)-dihydroceramide, which lack this structural feature. The effects of the sphingoid bases, C(2)-ceramide, and C(2)-dihydroceramide on apoptosis were determined by detecting 200-bp DNA ladders or hypo-diploid areas (sub-G(0)/G(1)), indicative of apoptosis, in HCT-116 human colon cancer cells. In addition, the effects of the sphingoid bases at an apoptotic concentration for 12 hours on cell cycle distribution were determined by flow cytometry. The results indicated that the sphingoid bases and C(2)-ceramide induced apoptosis, whereas C(2)-dihydroceramide had no effects. Sphingoid bases arrested the cell cycle at the G(2)/M phase. The present study provides evidence that the 4,5-trans double bond is necessary for the apoptotic effect of C(2)-ceramide, but not for that of sphingoid bases.


[The morphological criteria of thromboangiitis and arteriosclerosis obliterans of the vessels of the lower extremities].
The differences in pathology of the leg and foot arteries are described in patients with thromboangiitis obliterans (60 cases) and atherosclerosis (30 cases). Based on the operative and biopsy material it has been shown that thromboangiitis obliterans is associated with immune inflammation of the arteries, manifesting itself by productive or, more rarely, by necrotic arteritis. In the latter condition, the wall of the impaired vessels contains immune complexes. In patients with atherosclerosis, the muscular type arteries of the legs and feet show dystrophic and fibroblastic lesions seen primarily in the intima and manifesting themselves by the enlargement of its connective tissue. No immune complexes were discovered in the wall of such arteries.


Average annual cost of Parkinson's disease in a Brazilian multiethnic population.
With the current demographic transition, it is estimated that by 2050 Brazil will have a population of 90 million people aged 60 years or more, and in parallel Parkinson's disease (PD) will bring a considerable economic burden to our society. Brazil is considered multiracial due to its colonization, generating important social and regional inequalities. Knowing the costs of the PD may aid to improve local public policies. However, in Brazil, no estimates of these values have been made so far. To evaluate direct, indirect, and out-of-pocket costs in Brazilian people with PD (PwP). Categorical and numerical data were collected through a customized and standardized cost-related-questionnaire from 1055 PwP nationwide, from 10 tertiary movement disorders centers across all Brazilian regions. The estimated average annual cost of PwP was US$ 4020.48. Direct and indirect costs accounted for 63% and 36% of the total, respectively, and out-of-pocket costs were 49%. There were no evidence of differences in the total cost of PD across the regions of the country; however, differences were reported between the stages of the Hoehn and Yahr scale (H&Y). This data suggests a considerable burden of PD for Brazilian society in general, not only for the public health system, but mainly for those with PD.


Vitamin D deficiency accelerates ageing and age-related diseases: a novel hypothesis.
Ageing can occur at different rates, but what controls this variable rate is unknown. Here I have developed a hypothesis that vitamin D may act to control the rate of ageing. The basis of this hypothesis emerged from studyng the various cellular processes that control ageing. These processes such as autophagy, mitochondrial dysfunction, inflammation, oxidative stress, epigenetic changes, DNA disorders and alterations in Ca2+ and reactive oxygen species (ROS) signalling are all known to be regulated by vitamin D. The activity of these processes will be enhanced in individuals that are deficient in vitamin D. Not only will this increase the rate of ageing, but it will also increase the probability of developing age-related diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and cardiovascular disease. In individual with normal vitamin D levels, these ageing-related processes will occur at lower rates resulting in a reduced rate of ageing and enhanced protection against these age-related diseases.


Down-regulation in vivo of PGE receptors and adenylate cyclase stimulation.
Down-regulation in vivo of liver plasma membrane receptors for prostaglandin E (PGE) was investigated in Sprague-Dawley rats using the 16,16-dimethyl analogue of PGE2, This analogue was used for subcutaneous injections because it escapes the rapid pulmonic degradation characteristic of PGE and was recognized well by liver plasma membrane receptors. Following treatment with the analogue, the concentration of PGE receptors was significantly decreased (-37%, P less than 0.001), but the binding affinity was not altered. There was no evidence for carry-through of the analogue into the isolated plasma membrane preparation. It was also demonstrated that GTP decreased the binding affinity between PGE and its receptor. Down-regulation of receptor concentration was associated with a significant decrease (P less than 0.001) in PGE1-stimulated plasma membrane adenylate cyclase activity. These data provide the novel demonstration that rat liver plasma membrane receptor for PGE can be down-regulated in vivo and that this causes a corresponding decrease in PGE-induced plasma membrane adenylate cyclase activity.


[Surfactant system of lung in rats with different resistance to stress under alloxan diabetes].
It is shown that the surface active properties of lung under experimental diabetes mellitus was decreased on the background of increased LPL content in alveolar space. Surfactant changes correlated with the level of glucose, glycosylated hemoglobin and 11-oxycorticosteroids in blood. The obtained results indicate that the degree of impairment in the pulmonary surfactant system in alloxan diabetes depends on the resistance or susceptibility of animals to stress.


Fibroblast-seeded collagen gels in response to dynamic equibiaxial mechanical stimuli: A biomechanical study.
The remodeling of fibroblast-seeded collagen gels in response to dynamic mechanical stimuli was investigated by using a newly developed biaxial culture system capable of cyclically stretching planar soft tissues. Fibroblast-seeded collagen gels were subjected to three distinct dynamic mechanical conditions for six days: Cyclic Equibiaxial Stretching at two constant strain magnitudes (CES-7% and CES-20%), and Cyclic Equibiaxial Stretching with incrementally Increasing stain magnitude (ICES, 7% → 15% → 20% each for two days). The frequency of cyclic stretching was set at 1 Hz. At the end of culture, mechanical properties of the gels were examined by biaxial mechanical testing and checked again upon the removal of seeded cells. Collagen microstructure within the gels was illustrated by multiphoton microscopy. The mRNA levels of collagen type I and type III and fibronectin in the cells were examined by reverse transcription PCR. The protein expression of α-smooth muscle actin was detected by immunohistochemistry. We found that the gels cultured under cyclic stretching were stiffer than those cultured under static stretching. Particularly, the stiffness appeared to be significantly enhanced when the ICES was employed. The enhancement of mechanical properties by cyclic stretching appeared to persist upon cell removal, suggesting an irreversible remodeling of extracellular matrix. Second harmonic generation images showed that collagen fibers became thicker and more compact in the gels cultured under cyclic stretching, which may explain the mechanical findings. The mRNA expression of collagen type I in the cells of the ICES was significantly greater than that of the other groups except for the CES-20%. This study suggests that when cyclic stretching is to be used in engineering soft tissues, incrementally increasing strain magnitude may prove useful in the development of the tissue.


Twenty Year Trends and Sex Differences in Young Adults Hospitalized With Acute Myocardial Infarction.
Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI among young patients, or whether clinical management differs by sex. The Atherosclerosis Risk in Communities (ARIC) Surveillance study conducts hospital surveillance of AMI in 4 US communities (MD, MN, MS, and NC). AMI was classified by physician review, using a validated algorithm. Medications and procedures were abstracted from the medical record. Our study population was limited to young patients aged 35 to 54 years. From 1995 to 2014, 28 732 weighted hospitalizations for AMI were sampled among patients aged 35 to 74 years. Of these, 8737 (30%) were young. The annual incidence of AMI hospitalizations increased for young women but decreased for young men. The overall proportion of AMI admissions attributable to young patients steadily increased, from 27% in 1995 to 1999 to 32% in 2010 to 2014 ( P for trend=0.002), with the largest increase observed in young women. History of hypertension (59% to 73%, P for trend<0.0001) and diabetes mellitus (25% to 35%, P for trend<0.0001) also increased among young AMI patients. Compared to young men, young women presenting with AMI were more often black and had a greater comorbidity burden. In adjusted analyses, young women had a lower probability of receiving lipid-lowering therapies (relative risk [RR]=0.87; 95% confidence interval [CI], 0.80-0.94), nonaspirin antiplatelets (RR=0.83; 95% CI, 0.75-0.91), beta blockers (RR=0.96; 95% CI, 0.91-0.99), coronary angiography (RR=0.93; 95% CI, 0.86-0.99) and coronary revascularization (RR = 0.79; 95% CI, 0.71-0.87). However, 1-year all-cause mortality was comparable for women versus men (HR=1.10; 95% CI, 0.83-1.45). The proportion of AMI hospitalizations attributable to young patients increased from 1995 to 2014 and was especially pronounced among women. History of hypertension and diabetes among young patients admitted with AMI increased over time as well. Compared with young men, young women presenting with AMI had a lower likelihood of receiving guideline-based AMI therapies. A better understanding of factors underlying these changes is needed to improve care of young patients with AMI.


Eliminating the Trade-off Between Resolution and Sampling Rate in Magnetic Induction Based Cardiorespiratory Sensors.
This paper proposes a novel algorithm that allows a significant improvement of the resolution of frequency modulated magnetic induction sensors while providing high sampling rates. We have implemented this approach in a frequency modulated magnetic induction sensor and our first measurements demonstrate the improvement of the sensor's signal quality.


Selenium deficiency exacerbates LPS-induced necroptosis by regulating miR-16-5p targeting PI3K in chicken tracheal tissue.
Multiple tissue necrosis is one of the morphological features of selenium deficiency-mediated injury. MicroRNA (miRNA) participates in the occurrence and development of necroptosis by regulating target genes. Necroptosis is a programmed form of necrosis, and it is closely related to lipopolysaccharide (LPS)-induced injury. Our aim was to investigate whether Se deficiency can promote tracheal injury caused by LPS through miRNA-induced necroptosis. By establishing models of tracheal injury in Se-deficient chickens, we verified the targeting relationship between chicken-derived miR-16-5p and PI3K through bioinformatics, qRT-PCR and WB analyses, and we measured the changes in the expression of genes related to the PI3K/AKT pathway, RIP3/MLKL pathway and MAPK pathway and of heat shock proteins. Under the condition of Se deficiency, the following results were observed: PI3K/AKT expression decreased with the upregulation of miR-16-5p, the expression of necroptosis-related factors (TNF-α, RIP1, FADD, RIP3 and MLKL) increased, and the expression of Caspase 8 significantly decreased (p < 0.05). Light microscopy observations indicated that cell necrosis was the main pathological change due to Se deficiency injury in the tracheal epithelium. The MAPK pathway was activated, and HSP expression was upregulated, indicating that the MAPK pathway and HSPs are both involved in Se deficiency-mediated necroptosis. In addition, Se deficiency promoted the expression of necroptosis-related genes in LPS-treated chickens (p < 0.05), and the pathological changes of cell necrosis were more obvious. In conclusion, we demonstrated that Se deficiency regulates the miR-16-5p-PI3K/AKT pathway and exacerbates LPS-induced necroptosis in chicken tracheal epithelial cells by activating necroptosis-related genes.


Occlusal Migration of Teeth Adjacent to Implant Prostheses in Adults: A Long-Term Study.
To evaluate the effect of continuous tooth eruption on the outcomes of single-implant-supported restorations in the anterior maxilla of adults. Seventy-six patients (age: 21 to 78 years) treated with single-implant-supported restorations in the esthetic zone were included. Radiographs obtained at crown placement and follow-up examinations from 1 to 15 years postloading were analyzed with regard to vertical incisal plane changes of the implant-supported crown relative to adjacent teeth. Infraocclusion increased over time by 0.08 ± 0.02 mm/year. Infraocclusion was more pronounced (P = .04) for delayed (0.09 mm/year) versus immediate implant placement (0.06 mm/year) and for younger versus older adults (0.0013 mm/year per additional year of age; P = .014). No statistically significant association between infraocclusion and sex, ethnicity, implant site, timing of implant temporization, surgical protocol, and type of restoration was found. Infraocclusion of single-implant-supported maxillary anterior restorations may result in esthetic concerns over time. Greater infraocclusion occurs in delayed implant placement and in younger individuals.


Involvement of Src and Syk tyrosine kinases in HIV-1 transfer from dendritic cells to CD4+ T lymphocytes.
Dendritic cells (DCs) are considered as key mediators of the early events in HIV-1 infection at mucosal sites. Although several aspects of the complex interactions between DCs and HIV-1 have been elucidated, there are still basic questions that remain to be answered about DCs/HIV-1 interplay. In this study, we examined the contribution of nonreceptor TKs in the known ability of DCs to efficiently transfer HIV-1 to CD4(+) T cells in trans. Experiments performed with specific inhibitors of Src and Syk family members indicate that these tyrosine kinases (TKs) are participating to HIV-1 transfer from immature monocyte-derived DCs (IM-MDDCs) to autologous CD4(+) T cells. Experiments with IM-MDDCs transfected with small interfering RNAs targeting Lyn and Syk confirmed the importance of these nonreceptor TKs in HIV-1 transmission. The Src- and Syk-mediated effect on virus transfer was linked with infection of IM-MDDCs in cis-as monitored by quantifying integrated viral DNA and de novo virus production. The process of HIV-1 transmission from IM-MDDCs to CD4(+) T cells was unaffected following treatment with protein kinase C and protein kinase A inhibitors. These data suggest that Src and Syk TKs play a functional role in productive HIV-1 infection of IM-MDDCs. Additional work is needed to facilitate our comprehension of the various mechanisms underlying the exact contribution of Src and Syk TKs to this phenomenon.


Peer promotion programs and social networks in Ghana: methods for monitoring and evaluating AIDS prevention and reproductive health programs among adolescents and young adults.
This article summarizes the observations and lessons learned regarding the application of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) prevention and reproductive health evaluation methodologies in the context of adolescent and young adult populations and discusses the use of peer network evaluation to understand the dynamics of peer promotion. To examine the interpersonal communication process of peer education, this study tested a new approach using multiple semistructured interviews and network analysis to collect data on 106 peer educators and 526 of their contacts. These evaluation activities were conducted at three sites in Ghana during April 1998, in both periurban and rural locations in both in-school and out-of-school settings. By evaluating the social networks of peer educators it was possible to gain a better understanding of the process of peer education in terms of (a) defining the composition of peer contacts, (b) identifying the social norms that play a critical role in youth decision making, and (c) observing the range of messages and services transmitted during peer education. The objective of this paper is to disseminate the experience of the Center for Education and Development of Population Activities (CEDPA) and Focus on Young Adult's cooperative development of evaluation methodologies for peer promotion and to highlight utilization of these methodologies in a case study in Ghana. The results will be discussed in terms of their possible implications for program managers, researchers, and international agencies.


Heterogeneity of Radial Glia-Like Cells in the Adult Hippocampus.
Adult neurogenesis is tightly regulated by the neurogenic niche. Cellular contacts between niche cells and neural stem cells are hypothesized to regulate stem cell proliferation or lineage choice. However, the structure of adult neural stem cells and the contact they form with niche cells are poorly described. Here, we characterized the morphology of radial glia-like (RGL) cells, their molecular identity, proliferative activity, and fate determination in the adult mouse hippocampus. We found the coexistence of two morphotypes of cells with prototypical morphological characteristics of RGL stem cells: Type α cells, which represented 76% of all RGL cells, displayed a long primary process modestly branching into the molecular layer and type β cells, which represented 24% of all RGL cells, with a shorter radial process highly branching into the outer granule cell layer-inner molecular layer border. Stem cell markers were expressed in type α cells and coexpressed with astrocytic markers in type β cells. Consistently, in vivo lineage tracing indicated that type α cells can give rise to neurons, astrocytes, and type β cells, whereas type β cells do not proliferate. Our results reveal that the adult subgranular zone of the dentate gyrus harbors two functionally different RGL cells, which can be distinguished by simple morphological criteria, supporting a morphofunctional role of their thin cellular processes. Type β cells may represent an intermediate state in the transformation of type α, RGL stem cells, into astrocytes.


Responsiveness and sensitivity of the Early Childhood Oral Health Impact Scale to primary dental care for early childhood caries.
This study examined the responsiveness of the Early Childhood Oral Health Impact Scale (ECOHIS) to dental treatment of early childhood caries (ECC) in a primary dental care setting. Parents of children participating in a randomized controlled trial completed the ECOHIS at baseline and follow-up, and rated the global oral health transition of their child at follow-up ('worsened', 'no change', 'improved'). Change scores were calculated and longitudinal construct validity assessed by examining the association between change scores and global oral health transition groups. ECOHIS changes from baseline to follow-up within global transition groups were also evaluated. Effect sizes, minimally important difference, and Guyatt's responsiveness index were calculated to examine the scale's sensitivity and responsiveness. After 11.3 months, complete questionnaire data were available for 189 participants; 59% reported 'improved' oral health. The follow-up scores were significantly lower in the child psychology, parental distress and family impact section, P < 0.001, and in the child social interaction, family function and the total ECOHIS scores, P < 0.05, Wilcoxon signed-rank test. There was a significant difference in changed scores among the global transition groups, P < 0.05, Kruskal-Wallis test, and the difference was significant between 'worsened' and 'improved' groups for the family impact and the total ECOHIS scores, Dunn test, P < 0.05. Effect sizes were small, 0.17, 0.33, 0.30 for the child impact, family impact and total ECOHIS scores, respectively, for those reporting 'improved' oral health. The responsiveness of the ECOHIS to the treatment of ECC in primary dental care settings was modest, and its use to measure treatment effects in primary care settings requires further investigations.


Fixed partial dentures and crowns supported by very small diameter dental implants in compromised sites.
Very small diameter (1.8-3.3 mm) dental implants may be successfully used to support fixed partial dentures in edentulous sites of compromised bone width or length. Very small implants can be successfully used in highly selected sites where there is adequate bone density and bone volume for immediate implant stability. Adequate or augmentable attached gingiva may be a requirement. A small diameter implant presents less of an obstacle for angiogenesis and there is less percutaneous exposure and bone displacement as compared with standard sized implants. In posterior sites, rounded and narrow prosthetic teeth present small occlusal tables to minimize axial and off-axial directed forces. Multiple splinted implants may be necessary to minimize metal fatigue from cyclic loading. Anterior restorations supported by mini implants may need occlusal relief to minimize the effects of cyclic loading.


Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis.
Between 1 January 1984 and 31 December 1987, 206 enterococcal blood isolates at the University of Wisconsin Hospital and Clinics were analyzed for high-level aminoglycoside resistance (hereafter high-level aminoglycoside resistance is simply referred to as "resistance") and hemolysin production. Of 190 Enterococcus faecalis isolates, 68 (35.8%) were resistant to gentamicin. Of these 68 strains, 67 (98.5%) contained a gene coding for the bifunctional aminoglycoside-modifying 6'-aminoglycoside acetyltransferase-2"-aminoglycoside phosphotransferase [AAC(6')-APH(2")] enzyme. Of 190 isolates, 85 (44.7%) were hemolytic and contained a gene coding for component A of the enterococcal hemolysin. Sixty-two of 68 (91.2%) gentamicin-resistant isolates but only 23 of 122 (18.8%) gentamicin-susceptible isolates were hemolytic (P less than 0.001). Twelve of the hemolytic, gentamicin-resistant E. faecalis blood isolates, but only 2 of 9 nonhemolytic or gentamicin-susceptible isolates, had identical chromosomal DNA restriction endonuclease digestion patterns, suggesting a common derivation for these strains. A historical cohort study from 1 July 1985 to 31 March 1987 identified by regression analysis postsurgical intensive care unit status (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.1 to 22.8) and prior treatment with an expanded- or broad-spectrum cephalosporin (OR, 3.0; 95% CI, 0.9 to 10.1) as risk factors for gentamicin-resistant E. faecalis bacteremia. Patients with hemolytic, gentamicin-resistant E. faecalis bacteremia had a fivefold-increased risk for death within 3 weeks of their bacteremia compared with patients with nonhemolytic, gentamicin-susceptible strains (95% CI, 1.0 to 25.4).


The association between ethnicity, socioeconomic status and compliance to pediatric weight-management interventions - A systematic review.
High dropout rates and low compliance to pediatric weight-management programs have been reported. Socioeconomic status (SES) and ethnicity have been suggested as potentially important determinants of dropout and non-compliance. This review aims to assess the association between SES, ethnicity and study- and intervention dropout and non-compliance among participants in pediatric weight-management programs. PubMed, Embase, MEDLINE, Scopus, Cochrane, Web-of-Science and Google Scholar were searched for eligible studies up to March 2014. Included were randomised controlled trials (RCT), controlled clinical trials and cohort studies evaluating pediatric weight-management programs. Studies had to report dropout or non-compliance to the study or intervention with regard to ethnicity or SES. Associations between SES and ethnicity and dropout and non-compliance were analysed descriptively. Fourteen RCTs and 16 cohort studies were included, studying 7264 children and adolescents, aged 2-20 years. Twenty-four studies presented data on dropout or non-compliance regarding ethnicity and 26 studies presented data regarding SES. Black participants showed higher dropout rates in weight-management interventions (range 65-67%) than White participants (range 22-27%), and low family income was associated with lower compliance to weight-management interventions. Black ethnicity and low family income seemed to be associated with higher dropout and lower compliance to pediatric weight-management interventions. Future qualitative studies may be needed to assess underlying reasons for increased dropout and non-compliance in these sub-populations.


Neutrophil-derived leukotriene B4 is required for inflammatory arthritis.
Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.


Assessing patient safety in Canadian ambulatory surgery facilities: A national survey.
There has been increased interest regarding patient safety and standards of care in Canadian ambulatory surgery facilities where surgical procedures are performed. The Canadian Association for Accreditation of Ambulatory Surgical Facilities (CAAASF) is a national organization formed to establish and maintain standards to ensure that surgical procedures conducted outside of public hospitals are performed safely. To determine how many procedures are performed annually at CAAASF member sites, and to examine complication rates and several key patient safety practices. All 69 facilities accredited by the CAAASF were surveyed. The survey focused on procedural data, complication rates and patient safety interventions. In 2010, 40,240 estimated procedures were performed. A total of 263 (0.007%) complications were reported. Sixteen (0.0004%) patients required reoperations in hospital and 19 (0.0004%) patients required transfer to hospital on the day of surgery. There were only two mortalities within 30 days of surgery reported in the past five years. With regard to patient safety practices, 93% used antimicrobial prophylaxis, 100% used strategies to maintain normothermia and 82% used measures for venous thromboembolism prevention. The present study is the first to report on the Canadian experience in ambulatory surgery facilities and provides insight into current practices at these facilities. Appropriate accreditation of ambulatory surgery facilities, well-established patient safety-related standards of care, careful patient selection and procedures performed by qualified health care professionals with appropriate certification practicing within the scope of their practice form the basis for safe and effective ambulatory surgery.


EVIDENCE OF LEPTOSPIRA SEROVARS IN WILDLIFE AND LEPTOSPIRAL DNA IN WATER SOURCES IN A NATURAL AREA IN EAST-CENTRAL ILLINOIS, USA.
We identified seven Leptospira serovars in wildlife and the presence of leptospiral DNA in water sources at a natural area within a fragmented habitat in Illinois, US. These serovars have been implicated in domestic animal and human leptospirosis, a reemerging zoonotic disease, whose reservoirs include wildlife and domestic animals. We live trapped medium-sized mammals (n=351) near building (H-sites) or forest sites (F-sites). Using serology, we evaluated exposure to Leptospira (L. interrogans serovars Autumnalis, Bratislava, Canicola, Icterohaemorrhagiae, Pomona; L. kirschneri serovar Grippotyphosa; L. borgpetersenii serovar Hardjo). Using PCR, we tested for the presence of leptospires in eight water samples (ponds, creeks, and rainwater runoff) collected near trapping sites. We identified antibody titers in raccoons (Procyon lotor; 121/221) and Virginia opossums (Didelphis virginiana; 60/112), but not in feral cats (Felis catus; 0/18). We found significant differences in overall Leptospira seroprevalence between years (P=0.043) and animal's age in 2008 (P=0.005) and 2009 (P=0.003). Serovars Autumnalis, Bratislava, and Grippotyphosa showed significant differences among age groups with the highest seroprevalence in adults. Females had a higher seroprevalence for Icterohaemorragiae in 2008 (P=0.003) and Hardjo in 2009 (P=0.041). Risk of exposure to Leptospira was higher at F-sites compared to H-sites (odds ratio 2.3, 95% confidence interval 1.3-3.9, P=0.002). We captured more animals with titers >1:800 at H-sites, but there was no association between titer levels and capture site. Six of eight water sources were Leptospira-positive; however, there was no correlation between trapping locations of seropositive animals and positive water sources. Natural areas create opportunities for interspecies interactions, favoring leptospires transmission across species. Understanding that Leptospira serovars are present in natural areas is an integral part of the safe human and pet recreational use of these areas. Our study should raise awareness and build on public education designed to prevent disease transmission between species.


Coagulation and Fibrinolysis in Kidney Graft Rejection.
Coagulation system is currently considered an integrated part of innate immunity. Clotting activation in response to bacterial surface along with complement cascade priming represents the first line of defense against pathogens. In the last three decades, we learned that several coagulation factors, including factor II or thrombin and factor X, can interact with specific cell surface receptors activated by an unusual proteolytic mechanism and belonging to a novel class of G-protein-coupled receptors known as protease-activated receptors (PARs). PARs are expressed by a variety of cells, including monocytes, dendritic cells, and endothelial cells and may play a key role in the modulation of innate immunity and in the regulation of its interaction with the adaptive branch of the immune system. Also, the fibrinolytic system, in which activation is controlled by coagulation, can interact with innate immunity, and it is a key modulator of extracellular matrix deposition eventually leading to scarring and fibrosis. In the setting of kidney transplantation, coagulation and fibrinolytic systems have been shown to play key roles in the ischemia/reperfusion injury featuring delayed graft function and in the pathogenesis of tissue damage following acute and chronic rejection. In the present review, we aim to describe the mechanisms leading to coagulation and fibrinolysis activation in this setting and their interaction with the priming of the innate immune response and their role in kidney graft rejection.


"Sticky" brains and sticky encounters in a U.S. pediatric pain clinic.
In the U.S. multidisciplinary pediatric pain clinic where I conducted 18 months of fieldwork, a widely held explanatory model tied the neurobiology of intractable pain to certain features of pervasive developmental disorders (PDD) such as concrete thinking, an interest in details, and hyper-attentiveness. Clinicians used terms such as "sticky brains" and "sticky neurons" to describe the perseverative thoughts and quirky behavior that characterized a sizable subset of the program's chronic pain patients who were believed to show signs of PDD, and consequently, did not respond well to treatment. Drawing on observations of clinical consultations, team meetings, and interviews with clinicians and families, I examine the meta-discursive processes by which clinical difficulties were inscribed onto difficult patients. Specifically, I demonstrate how discourse on sticky brains worked to re-classify challenging patients as psychologically abnormal, rationalizing their failed response to standard treatment. I argue that 'stickiness' provides an appropriate metaphor not only for a particular neurobiological configuration, but also for challenging clinical encounters. By illuminating the interactional processes through which clinical difficulties are managed, interpreted, and explained, the paper advances anthropological theorizing on the performative work of diagnosis and institutionalized misrecognition.


Threshold electrical stimulation (TES) in ambulant children with CP: a randomized double-blind placebo-controlled clinical trial.
A randomized double-blind placebo-controlled clinical trial was carried out to determine whether a group of stable children with cerebral palsy (36 males, 21 females; mean age 10 years 11 months, range 5 to 18 years) would improve their motor skills after 12 months of threshold electrical stimulation (TES). Two thirds received active and one third received inactive stimulators. For the primary outcome we constructed a set of plausible motor function tests and studied the change in summary indices of the performance measurements. Tests were videotaped and assessed blindly to record qualitative changes that might not be reflected in performance measurements. We also judged range of motion, degree of spasticity, and muscle growth measured by CT. Fifty seven of 82 outpatients who were able to walk at least with a walker, completed all 12 months of treatment (hemiplegia n=25, diplegia n=32). There was no significant difference between active and placebo treatment in any of the tested groups, nor combined. Visual and subjective assessments favoured TES (ns), whereas objective indices showed the opposite trend. We conclude that TES in these patients did not have any significant clinical effect during the test period.


Occurrence and pathogenicity of Mycoplasma hominis in the upper urinary tract: a review.
In two studies Mycoplasma hominis was isolated from the upper urinary tracts of seven of 80 patients with symptoms of acute pyelonephritis and three of 18 patients with signs of acute exacerbation of chronic pyelonephritis. M. hominis was not recovered from the upper urinary tract of 22 patients with chronic pyelonephritis without acute exacerbation or from 60 patients with noninfectious urinary tract disease. In an additional study, specimens were cultured from patients with antibodies to M. hominis in urine. All of these patients had acute pyelonephritis; M. hominis was isolated from the upper urinary tract of seven patients. Thus, M. hominis was cultured from the upper urinary tract of a total of 17 patients. No other microorganisms were recovered from 12 of these patients. The titer of antibody to M. hominis significantly increased or decreased in the serum of 13 patients, and antibodies were demonstrated in the urine of nine. These results suggest that M. hominis may be a cause of acute pyelonephritis in humans; the organism is estimated to account for approximately 5% of such cases. The clinical signs of infection in the patients studied were subtle, and the symptoms did not involve the lower urinary tract. The diagnosis of acute pyelonephritis due to M. hominis can be established by culture of the organism from the upper urinary tract and its likely if antibodies are present in urine; in contrast, culture of M. hominis from catheter-collected urine or detection of a serum antibody response is not sufficient evidence for this diagnosis.


State-of-the-art uroradiologic imaging in the diagnosis of prostate cancer.
In the diagnostic process of prostate cancer, several radiologic imaging modalities significantly contribute to the detection and localization of the disease. These range from transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) to positron emission tomography (PET). Within this review, after evaluation of the literature, we will discuss the advantages and disadvantages of these imaging modalities in clarifying the patient's clinical status as to whether he has prostate cancer or not and if so, where it is located, so that therapy appropriate to the patient's disease may be administered. TRUS, specifically with the usage of intravenous contrast agents, provides an excellent way of directing biopsy towards suspicious areas within the prostate in the general (screening) population. MRI using functional imaging techniques allows for highly accurate detection and localization, particularly in patients with prior negative ultrasound guided biopsies. A promising new development is the performance of biopsy within the magnetic resonance scanner. Subsequently, a proposal for optimal use of radiologic imaging is presented and compared with the European and American urological guidelines on prostate cancer.


Open Mastoid Cavity Obliteration With a High-Porosity Hydroxyapatite Ceramic Leads to High Rate of Revision Surgery and Insufficient Cavity Obliteration.
To assess long-term results and present experience with a high-porosity hydroxyapatite ceramic for obliterating large open mastoid cavities. Cross-sectional cohort study. Tertiary academic referral center. All patients who underwent tympanomastoid surgery for chronic middle ear disease or revision surgery with reduction of an open mastoid cavity using a highly porous hydroxyapatite matrix material (HMM) between May 2005 and June 2013 were assessed for eligibility. Twenty three patients (56.9 ± 18.3 yr) were included. Primary middle ear surgery or revision surgery using a HMM. Pure-tone average, computed tomography (CT), and magnetic resonance imaging (MRI) to investigate osseoinduction, osseointegration and presence of cholesteatoma, current quality of life assessed by Zurich Chronic Middle Ear Inventory and change in quality of life post-intervention assessed by the Glasgow Benefit Inventory. Patients were reexamined after a mean follow-up period of 88.3 months (SD 21.4 mo) after obliteration of the open mastoid cavity with HMM. Compared with visit 1, patients showed a significantly reduced ABG at visit 2 (29.22 dB ± 2.71 dB versus 12.77 dB ± 3.46 dB).CT scan was carried out in 21 patients (91%) patients and 17 patients (74%) underwent MRI.Revision surgery was required in a total of 17 cases (74%). In four patients recurrent cholesteatoma was found at follow up. Poor cavity obliteration, a high rate of revision surgery and difficult differentiation between recurrent cholesteatoma and granulation tissue in CT scan was observed.


Characterization of TRP-1 mRNA levels in dominant and recessive mutations at the mouse brown (b) locus.
The mouse brown locus encodes a putative membrane-bound metalloenzyme, tyrosinase-related protein-1 (TRP-1). We have examined the effect on mRNA expression of the locus of a number of mutant alleles. The common null mutant allele, brown, produces wild-type levels of TRP-1 mRNA, which is nonfunctional. Another recessive allele, cordovan-Harwell, has an intermediate, dark-brown phenotype and produces only very low levels of presumably normal TRP-1 mRNA. Two dominant alleles appear to act by killing the melanocyte in which they are expressed. One of them, Light, has normal size and amounts of TRP-1 mRNA. The other, White-based brown, produces no detectable TRP-1 mRNA. It has a gross DNA rearrangement at the 5' end, and we speculate that this results in activation of transcription of sequences not usually seen in melanocytes, and that this is toxic to the cell. The relationship between phenotype and molecular structure at the locus is discussed, and we draw some general principles applicable to other developmental genes.


Abscisic acid enhances tolerance of wheat seedlings to drought and regulates transcript levels of genes encoding ascorbate-glutathione biosynthesis.
Glutathione (GSH) and ascorbate (ASA) are associated with the abscisic acid (ABA)-induced abiotic tolerance in higher plant, however, its molecular mechanism remains obscure. In this study, exogenous application (10 μM) of ABA significantly increased the tolerance of seedlings of common wheat (Triticum aestivum L.) suffering from 5 days of 15% polyethylene glycol (PEG)-stimulated drought stress, as demonstrated by increased shoot lengths and shoot and root dry weights, while showing decreased content of hydrogen peroxide (H2O2) and malondialdehyde (MDA). Under drought stress conditions, ABA markedly increased content of GSH and ASA in both leaves and roots of ABA-treated plants. Temporal and spatial expression patterns of eight genes encoding ASA and GSH synthesis-related enzymes were measured using quantitative real-time reverse transcription polymerase chain reaction (qPCR). The results showed that ABA temporally regulated the transcript levels of genes encoding ASA-GSH cycle enzymes. Moreover, these genes exhibited differential expression patterns between the root and leaf organs of ABA-treated wheat seedlings during drought stress. These results implied that exogenous ABA increased the levels of GSH and ASA in drought-stressed wheat seedlings in time- and organ-specific manners. Moreover, the transcriptional profiles of ASA-GSH synthesis-related enzyme genes in the leaf tissue were compared between ABA- and salicylic acid (SA)-treated wheat seedlings under PEG-stimulated drought stress, suggesting that they increased the content of ASA and GSH by differentially regulating expression levels of ASA-GSH synthesis enzyme genes. Our results increase our understanding of the molecular mechanism of ABA-induced drought tolerance in higher plants.


Is ultrasound-measured abdominal fat thickness a reliable method for predicting metabolic diseases in obese and overweight women?
Background: Central fat deposition seems to be a risk factor for developing metabolic and cardiovascular diseases in overweight and obese individuals. Ultrasound is an accurate and non-invasive tool for measuring abdominal fat thickness and can precisely separate subcutaneous from visceral fat. This study was conducted to apply ultrasonography as a simple and reliable method to measure subcutaneous and visceral abdominal fat thickness and evaluate the relationship between this measured abdominal fat thickness and metabolic risk factors. Methods: A total of 80 overweight and obese women were included in this study. Anthropometric indices and abdominal fat thickness were measured using ultrasound. The association between abdominal fat thickness and metabolic risk factors with anthropometric indices was assessed using correlation coefficient. Results: The mean (± SD) of subcutaneous and visceral fat thickness was 2.71±0.92 and 5.46±1.88, respectively. There was a relationship between waist circumference and visceral and subcutaneous fat thickness. Also, there was a relationship between ultrasound- measured visceral fat thickness and fasting blood glucose and triglyceride. Conclusion: Ultrasonography is a simple and reliable method to measure abdominal fat thickness as an important predictor of metabolic diseases.


Effects of dietary fibre on serum lipid levels and fecal bile acid excretion.
Epidemiologic studies have suggested that dietary fibre protects humans against coronary heart disease, but interpretation of the data is confounded by coexisting differences in both dietary and environmental variables. The hypocholesterolemic action of dietary fibre varies: in general mucilaginous fibres such as pectin and oat bran are more effective than particulate fibres such as wheat bran. Although the mechanism of action of mucilaginous fibres is not completely understood, there is evidence that they induce small increases in the fecal excretion of bile acids and neutral steroids that are not fully compensated for by de novo cholesterol synthesis.


Interaction of Oatp1b2 expression and nonalcoholic steatohepatitis on pravastatin plasma clearance.
The downregulation of hepatic uptake transporters, including those of the OATP family, are a well known consequence of nonalcoholic steatohepatitis (NASH). Prior studies have shown that the combination of NASH and Oatp1b2 knockout synergistically reduces the clearance of pravastatin (PRAV) in the methionine and choline deficient (MCD) mouse model of NASH, and the current study therefore aimed to determine the impact of NASH and genetic heterozygosity of Oatp1b2 on PRAV clearance, modeling the overlap between the 24% of the human population who are heterozygous for non-functioning OATP1B1, and the ~15% with NASH, potentially placing these people at higher risk of statin-induced myopathy. Therefore, male C57BL/6 wild-type (WT), Oatp1b2+/- (HET), and Oatp1b2-/- (KO) mice were fed either a control (methionine and choline sufficient) or methionine and choline-deficient (MCD) diet to induce NASH. After six weeks of feeding, pravastatin was administered via the carotid artery. Blood and bile samples were collected throughout 90 min after PRAV administration. The concentration of PRAV in plasma, bile, liver, kidney, and muscle was determined by liquid chromatography-tandem mass spectrometry. MCD diet did not alter the plasma AUC values of PRAV in either WT or HET mice. However, the MCD diet increased plasma AUC by 4.4-fold in KO mice. MCD diet and nonfunctional Oatp1b2 synergistically increased not only plasma AUC but also the extrahepatic tissue concentration of pravastatin, whereas the partially decreased function of Oatp1b2 and NASH together were insufficient in significantly altering PRAV pharmacokinetics. These data suggest that a single copy of fully functional OATP1B1 in NASH patients may be sufficient to avoid the increase of pravastatin toxicity.


Different cation requirements for aggregation of BHK cells and their transformed derivatives.
BHK21 cells singly dissociated by trypsin aggregate in medium with calcium ions, but not in medium with magnesium ions. Their malignant derivatives (pyBHK) induced by polyoma virus, after dissociation with trypsin, aggregate equally well in medium with either calcium or magnesium ions. When EDTA is used for dissociation of cells from culture on a substrate, neither BHK21 nor pyBHK cells require addition to the medium of divalent cations for rapid aggregation. Trypsin-dissociated BHK21 cells become aggregative in medium without divalent cations, when they are incubated for 60 min in dispersion with medium containing calcium ions before aggregation. In the case of pyBHK cells, incubation in dispersion in the medium with calcium or magnesium ions is effective in this respect. Calcium and magnesium ions are equally effective for adhesion of both BHK21 and pyBHK cells to non-cellular substrate or to a cell monolayer. We discuss the different cation requirements for aggregation of BHK21 and their transformed derivatives in relation to the recovery process of cell surfaces after exposure to trypsin.


Intraspecific Competition and Inbreeding Depression: Increased Competitive Effort by Inbred Males Is Costly to Outbred Opponents.
A recent theoretical model suggests that intraspecific competition is an important determinant of the severity of inbreeding depression. The reason for this is that intraspecific competition is density dependent, leading to a stronger negative effect on inbred individuals if they are weaker competitors than outbred ones. In support of this prediction, previous empirical work shows that inbred individuals are weaker competitors than outbred ones and that intraspecific competition often exacerbates inbreeding depression. Here, we report an experiment on the burying beetle Nicrophorus vespilloides, in which we recorded the outcome of competition over a small vertebrate carcass between an inbred or outbred male resident caring for a brood and a size-matched inbred or outbred male intruder. We found that inbred males were more successful as intruders in taking over a carcass from a male resident and were injured more frequently as either residents or intruders. Furthermore, inbred males gained less mass during the breeding attempt and had a shorter adult life span than outbred males. Finally, successful resident males reared a substantially smaller brood comprised of lighter larvae when the intruder was inbred than when it was outbred. Our results shows that inbred males increased their competitive effort, thus contradicting previous work suggesting that inbred males are weaker competitors. Furthermore, our results shows that inbred intruders impose a greater cost to resident males, suggesting that outbred individuals can suffer fitness costs as a result of competition with inbred ones.


Gamma-secretase-dependent proteolysis of CD44 promotes neoplastic transformation of rat fibroblastic cells.
The metalloprotease-dependent extracellular domain cleavage of the adhesion molecule CD44 is frequently observed in human tumors and is thought to promote metastasis. This cleavage is followed by gamma-secretase-dependent release of CD44 intracellular domain (CD44-ICD), which exhibits nuclear signaling activity. Using a reversible Ret-dependent oncogenic conversion model and a restricted proteomic approach, we identified a positive correlation between the neoplastic transformation of Rat-1 cells and the expression of standard CD44. In these transformed cells, CD44 was found to undergo a sequential metalloprotease and gamma-secretase cleavage, resulting in an increase in expression of CD44-ICD. We showed that this proteolytic fragment possesses a transforming activity. In support of this role, a significant and specific reduction in Ret-induced transformation of Rat-1 cells was observed following drug-mediated inhibition of gamma-secretase. Taken together, these findings suggest that the shedding of CD44 may not only modulate metastasis but also affects earlier events in tumorigenesis through the release of CD44-ICD.


The retina of the newborn human infant.
We have examined a pair of eyes from a normal, full-term infant who died at 8 days as a result of accidental injury. Eyes were obtained immediately after death, fixed, and sectioned for light microscopy. Results from both eyes were substantially the same. The macular region was still drastically immature at 1 week. Even though a foveal depression existed, all cell layers were still present across it. Furthermore, the inner nuclear layer was divided into two separate layers. The receptor layer was reduced to one or two cells thick; receptors had both inner and outer segments, but they were very short and stumpy. The region of immaturity covered about 5 degrees of the retina. These findings suggest that the central region of a human infant's retina is probably not fully functional at birth.


The apparent inducibility of tumour marker glycoproteins in a melanoma cell line selected for growth in low levels of glucose.
It has been reported previously that malignancy in hybrid cells is associated with changes in two glycoproteins of molecular mass 90,000 and 100,000. In the current paper the characteristics of a clonal derivation of a murine melanoma cell line (PG19G-), selected for growth in low levels of glucose, are described. The cells had considerably reduced amounts of the 90 K and 100 K glycoproteins as judged by lectin affinity-labelling. When the level of glucose in the medium is raised the two glycoproteins become detectable after a few hours. This inducibility is specific for D-glucose and D-mannose at concentrations in excess of 300 mg/l and is inhibited by cytochalasin B but not by cytochalasin A. The 90 K glycoprotein differs from the 100 K in that its level varies with the glucose concentration even in the parent cell line PG19 and in other tumour lines. This is not the case for the 100 K glycoprotein, the synthesis and/or glycosylation of these two glycoproteins are, therefore, governed by separate control mechanisms. The relationship of the glucose-sensitive proteins to the glucose transporter is discussed.


Large-area spectrally encoded confocal endomicroscopy of the human esophagus in vivo.
Diagnosis of esophageal diseases is often hampered by sampling errors that are inherent in endoscopic biopsy, the standard of care. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal endomicroscopy technology that has the potential to visualize cellular features from large regions of the esophagus, greatly decreasing the likelihood of sampling error. In this paper, we report results from a pilot clinical study imaging the human esophagus in vivo with a prototype SECM endoscopic probe. In this pilot clinical study, six patients undergoing esophagogastroduodenoscopy (EGD) for surveillance of Barrett's esophagus (BE) were imaged with the SECM endoscopic probe. The device had a diameter of 7 mm, a length of 2 m, and a rapid-exchange guide wire provision for esophageal placement. During EGD, the distal portion of the esophagus of each patient was sprayed with 2.5% acetic acid to enhance nuclear contrast. The SECM endoscopic probe was then introduced over the guide wire to the distal esophagus and large-area confocal images were obtained by helically scanning the optics within the SECM probe. Large area confocal images of the distal esophagus (image length = 4.3-10 cm; image width = 2.2 cm) were rapidly acquired at a rate of ∼9 mm2 /second, resulting in short procedural times (1.8-4 minutes). SECM enabled the visualization of clinically relevant architectural and cellular features of the proximal stomach and normal and diseased esophagus, including squamous cell nuclei, BE glands, and goblet cells. This study demonstrates that comprehensive spectrally encoded confocal endomicroscopy is feasible and can be used to visualize architectural and cellular microscopic features from large segments of the distal esophagus at the gastroesophageal junction. By providing microscopic images that are less subject to sampling error, this technology may find utility in guiding biopsy and planning and assessing endoscopic therapy. Lasers Surg. Med. 49:233-239, 2017. © 2016 Wiley Periodicals, Inc.


Multilocus sequence analysis supports the taxonomic position of Astragalus glycyphyllos symbionts based on DNA-DNA hybridization.
In this study, the phylogenetic relationship and taxonomic status of six strains, representing different phenons and genomic groups of Astragalus glycyphyllos symbionts, originating from Poland, were established by comparative analysis of five concatenated housekeeping gene sequences (atpD, dnaK, glnA, recA and rpoB), DNA-DNA hybridization and total DNA G+C content. Maximum-likelihood phylogenetic analysis of combined atpD, dnaK, glnA, recA and rpoB sequence data placed the studied bacteria into the clade comprising the genus Mesorhizobium. In the core gene phylograms, four A. glycyphyllos nodule isolates (AG1, AG7, AG15 and AG27) formed a cluster common with Mesorhizobium ciceri, whereas the two other A. glycyphyllos symbionts (AG17 and AG22) were grouped together with Mesorhizobium amorphae and M. septentrionale. The species position of the studied bacteria was clarified by DNA-DNA hybridization. The DNA-DNA relatedness between isolates AG1, AG7, AG15 and AG27 and reference strain M. ciceri USDA 3383T was 76.4-84.2%, and all these A. glycyphyllos nodulators were defined as members of the genomospecies M. ciceri. DNA-DNA relatedness for isolates AG17 and AG22 and the reference strain M. amorphae ICMP 15022T was 77.5 and 80.1%, respectively. We propose that the nodule isolates AG17 and AG22 belong to the genomic species M. amorphae. Additionally, it was found that the total DNA G+C content of the six test A. glycyphyllos symbionts was 59.4-62.1 mol%, within the range for species of the genus Mesorhizobium.


Infants' First Solid Foods: Impact on Gut Microbiota Development in Two Intercontinental Cohorts.
The introduction of solid foods is an important dietary event during infancy that causes profound shifts in the gut microbial composition towards a more adult-like state. Infant gut bacterial dynamics, especially in relation to nutritional intake remain understudied. Over 2 weeks surrounding the time of solid food introduction, the day-to-day dynamics in the gut microbiomes of 24 healthy, full-term infants from the Baby, Food & Mi and LucKi-Gut cohort studies were investigated in relation to their dietary intake. Microbial richness (observed species) and diversity (Shannon index) increased over time and were positively associated with dietary diversity. Microbial community structure (Bray-Curtis dissimilarity) was determined predominantly by individual and age (days). The extent of change in community structure in the introductory period was negatively associated with daily dietary diversity. High daily dietary diversity stabilized the gut microbiome. Bifidobacterial taxa were positively associated, while taxa of the genus Veillonella, that may be the same species, were negatively associated with dietary diversity in both cohorts. This study furthers our understanding of the impact of solid food introduction on gut microbiome development in early life. Dietary diversity seems to have the greatest impact on the gut microbiome as solids are introduced.


Structural imbalance and resource shortage in the Australian mental health sector.
Resource shortages and 'unmet need' are two economic problems reported in the Australian mental health sector. 'Unmet need' arises with a 'structural imbalance', the non-correspondence between the use of mental health services and the extent of need for those services. Another problem reported in literature is 'met non-need', people who use mental health services and do not have a diagnosis of mental illness. To develop an approach to measure the resource shortage and the structural imbalance by using (i) data on consumers of mental health services ('service utilisation'), (ii) data on those who do not consume such services ('service non-utilisation'). These data are cross-classified with data on (i) people who do have a diagnosis of mental illness (proxy of 'need'), and (ii) people who do not have a diagnosis of mental illness (proxy of 'non-need'). A conceptual framework (using 'polar' cases), which is often used in economics, is employed to define perfect 'structural balance' and perfect 'structural imbalance'. This framework allows the measurement of the degree of structural imbalance. Enumeration involves the cross-classified population sub-groups of 'need' and 'service utilisation' in tabular form, conceived of by reference to Yerushalmy's cross-classification approach for determining the sensitivity and specificity of diagnostic procedures in medicine. Venn diagrams are also applied for resource shortage evaluation. The study relies on the data of the Australian Bureau of Statistics 1997 epidemiological survey, the Australian national survey, Mental Health and Wellbeing: Profile of Adults. Clear evidence of resource insufficiency is found. The study shows also an extensive structural imbalance. A total of 1,477,500 subjects affected by mental disorders are found in the 'unmet need' category. This group (receiving no mental health services) represents 62 per cent of people with a diagnosis of mental disorder, and 11 per cent of the Australian population. On the other hand, a group of 591,600 people consume mental health services and do not meet the criteria of mental illness. This group is 4.4 per cent of the Australian population. In the absence of a measure of expenditure, this study adopted 'people' as a proxy for expenditure. The available data do not enable us to determine how much 'met non-need' is due to the 'Worried Well', or to those who use government-subsidised services for other reasons (sport, executive performance etc). Commitment to quantification within the mental health sector is a relatively recent habit by the Australian Government. Policy formation often simply follows scandals to cope with adverse publicity and evidence-based policy is needed. Preliminary evidence of this study indicates resource insufficiency in the Australian mental health sector. This is a policy issue to be distinguished from the 'unmet need' and 'met non-need' arising from structurally imbalanced resource allocation. Separate policy targets require separate policy instruments.


The Seed Semipermeable Layer and Its Relation to Seed Quality Assessment in Four Grass Species.
The existence of a semipermeable layer in grass seeds has been extensively reported, yet knowledge of its influence on tests for seed viability and vigor that depend upon measurement of electrical conductivity (EC) is limited. This study determined the presence and location of the semipermeable layer, and its relation to seed viability and vigor assessment, in seeds of four important grass species-Elymus nutans Griseb., Lolium perenne L., Leymus chinensis (Trin.) Tzvel., and Avena sativa L. Intact seeds of E. nutans, Lolium perenne, and Leymus chinensis exhibited little staining with triphenyl tetrazolium chloride (TTC), and there were no differences in EC between seeds with different germination percentage (GP) (P > 0.05). After piercing the seed coat, however, all three species displayed positive staining with TTC, along with a significant negative correlation between EC and GP (E. nutans: R2 = 0.7708; Lolium perenne: R2= 0.8414; Leymus chinensis: R2 = 0.859; P < 0.01). In contrast, both intact and pierced seeds of A. sativa possessed a permeable seed coat that showed positive staining with TTC and EC values that were significantly negatively correlated with GP [R2 = 0.9071 (intact) and 0.9597 (pierced); P < 0.01]. In commercial seed lots of A. sativa, a field emergence test indicated that EC showed a significant negative correlation with field emergence at two sowing dates (R2= 0.6069, P < 0.01 and 0.5316, P < 0.05). Analysis of seed coat permeability revealed the presence of a semipermeable layer located in the seed coat adjacent to the endosperm in E. nutans, Lolium perenne, and Leymus chinensis; however, no semipermeable layer was observed in A. sativa. This is the first report of the absence of a semipermeable layer in a grass species. The existence of a semipermeable layer is one of the most important factors affecting seed viability and vigor testing (based on EC measurement) in E. nutans, Lolium perenne, and Leymus chinensis. Increasing the permeability of the semipermeable layer, e.g., by piercing the seed coat, may permit the use of EC measurement to assess seed vigor in species that possess such a layer.


True coronary bifurcation lesions: meta-analysis and review of literature.
Percutaneous intervention of true coronary bifurcation lesions is challenging. Based on the results of randomized trials and registry data, the approach of stenting of main vessel only with balloon dilatation of the side branch has become the default approach for false bifurcation lesions except when a complication occurs or in cases of suboptimal result. However, the optimal stenting strategy for true coronary bifurcation lesions - to stent or not to stent the side branch - is still a matter of debate. The purpose of this study was, therefore, to compare the clinical and angiographic outcomes of the double stent technique (stenting of the main branch and side branch) over the single stent technique (stenting of main vessel only with balloon dilatation of the side branch) for treatment of true coronary bifurcation lesions, with drug-eluting stents (DES). Comparative studies published between January 2000 and February 2009 of the double stent technique vs. single stent technique with DES for true coronary bifurcations were identified using an electronic search and reviewed using a random effects model. The primary endpoints of our study were side-branch and main-branch restenoses, all-cause mortality, myocardial infarction (MI) and target lesion revascularization (TLR) at longest available follow-up. The secondary endpoints of our analysis were postprocedural minimal luminal diameter (MLD) of the side branch and main branch, follow-up MLD of side branch and main branch and stent thrombosis. Heterogeneity was assessed and sensitivity analysis was performed to test the robustness of the overall summary odds ratios (ORs). Five studies comprising 1145 patients (616 single stent and 529 double stent) were included in the analysis. Three studies were randomized comparisons between the two techniques for true coronary bifurcation lesions. Incomplete reporting of data in the primary studies was common. The lengths of clinical and angiographic follow-up ranged between 6 and 12 months and 6 and 7 months, respectively. Postprocedural MLD of the side branch was significantly smaller in the single stent group [standardized mean difference (SMD) -0.71, 95% CI -0.88 to -0.54, P < 0.000, I2 = 0%]. The odds of side-branch restenosis (OR 1.11, 95% CI 0.47-2.67, P = 0.81, I2 = 76%), main-branch restenois (OR 0.88, 95% CI 0.56-1.39, P = 0.58, I = 0%), all-cause mortality (OR 0.52, 95% CI 0.11-2.45, P = 0.41, I2 = 0%), MI (OR 0.92, 95% CI 0.34-2.54, P = 0.87, I = 49%) and TLR (OR 0.87, 95% CI 0.46-1.65, P = 0.68, I2 = 0%) were similar between the two groups. Postprocedural MLD of the main branch [standardized mean difference (SMD) -0.08, 95% CI -0.42 to -0.26, P < 0.65, I2 = 67%], follow-up MLD of side branch (SMD -0.19, 95% CI -0.40 to 0.01, P < 0.31, I2 = 15%) and main branch MLD (SMD 0.17, 95% CI -0.18 to 0.542, P < 0.35, I2 = 65%) were also similar between the two groups. In patients undergoing percutaneous coronary intervention (PCI) for true coronary bifurcations, there is no added advantage of stenting both branches as compared with a conventional one-stent strategy. The results, however, need to be interpreted considering the poor study methods and/or poor quality of reporting in publications. We propose to move forward and consider the conduct of more systematic, well-designed and scientific trials to investigate the treatment of true coronary bifurcation lesions.


How to encourage intrinsic motivation in the clinical teaching environment?: a systematic review from the self-determination theory.
Internalization of students' motivation towards an intrinsic form is associated with increased interest, commitment, learning, and satisfaction with education. Self-Determination theory postulates that intrinsic motivation and autonomous forms of self-regulation are the desired type of motivation; as they have been associated with deep learning, better performance and well-being. It claims three basic psychological needs have to be satisfied in order to achieve intrinsic motivation. These are the needs for autonomy, competence and relatedness. This study aims to provide a review on how these basic psychological needs are encouraged in undergraduate students so they can be transferred to the clinical teaching environment. Electronic searches were performed across four databases (Medline, Embase, PsycINFO, and ERIC), relevant journals, and retrieved bibliography of selected articles. In total, searches produced 4,869 references, from which 16 studies met the inclusion criteria. Main themes were coded in three categories: The support of autonomy, competence and relatedness. The research-based evidence appears to be of reasonable quality, and indicates that teachers should work to satisfy students' basic psychological needs to foster internalization of self-regulation. Our findings suggest that teachers should interact with students in a more 'human centred' teaching style, as these actions predict motivational internalization. Several themes emerged from different contexts and further investigation should expand them. This review identified actions that clinical teachers could implement in their daily work to support students' self-determination. Autonomy supportive teaching in health professions educations would benefit students and may actually result in more effective health care delivery.


Effect of Electrohydraulic Extracorporeal Shockwave Therapy on the Repair of Bone Defects Grafted With Particulate Allografts.
This study determined the effect of electrohydraulic extracorporeal shockwave therapy (ESWT) on the healing of mandible defects repaired using particulate allogenic bone grafts. This study included 20 male Wistar rats aged 12 weeks. In all the animals, a critical-sized defect of 4-mm diameter was created in the mandible and the defect area was filled with particulate allograft. Next, the rats were divided into 2 groups, allograft (G) (n = 10) and allograft + ESWT (GE) (n = 10). On days 3, 5, and 7 after the grafting, rats in the GE group received ESWT involving 200 pulses with an energy flux density of 0.19 mJ/mm. Five rats in each group were sacrificed at the end of week 4 and at the end of week 8. Defect areas were examined radiologically by performing high-resolution computed tomography and stereologically by using the Cavalieri method. Obtained data were compared by performing statistical analysis. Radiological evaluation showed that bone density was higher in rats in the G group than in those in the GE group at week 4. In contrast, bone density was higher in rats in the GE group than in those in the G group at week 8. Stereological examination showed that new bone, connective tissue, and capillary volumes were higher in rats in the GE group than in those in the G group at both weeks 4 and 8. The authors' results indicate that repeated doses of ESWT accelerate the healing of bone defects repaired using allogenic bone grafts.


Progressive multifocal leukoencephalopathy-associated mutations in the JC polyomavirus capsid disrupt lactoseries tetrasaccharide c binding.
The human JC polyomavirus (JCPyV) is the causative agent of the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). The Mad-1 prototype strain of JCPyV uses the glycan lactoseries tetrasaccharide c (LSTc) and serotonin receptor 5-HT2A to attach to and enter into host cells, respectively. Specific residues in the viral capsid protein VP1 are responsible for direct interactions with the α2,6-linked sialic acid of LSTc. Viral isolates from individuals with PML often contain mutations in the sialic acid-binding pocket of VP1 that are hypothesized to arise from positive selection. We reconstituted these mutations in the Mad-1 strain of JCPyV and found that they were not capable of growth. The mutations were then introduced into recombinant VP1 and reconstituted as pentamers in order to conduct binding studies and structural analyses. VP1 pentamers carrying PML-associated mutations were not capable of binding to permissive cells. High-resolution structure determination revealed that these pentamers are well folded but no longer bind to LSTc due to steric clashes in the sialic acid-binding site. Reconstitution of the mutations into JCPyV pseudoviruses allowed us to directly quantify the infectivity of the mutants in several cell lines. The JCPyV pseudoviruses with PML-associated mutations were not infectious, nor were they able to engage sialic acid as measured by hemagglutination of human red blood cells. These results demonstrate that viruses from PML patients with single point mutations in VP1 disrupt binding to sialic acid motifs and render these viruses noninfectious. IMPORTANCE Infection with human JC polyomavirus (JCPyV) is common and asymptomatic in healthy individuals, but during immunosuppression, JCPyV can spread from the kidney to the central nervous system (CNS) and cause a fatal, demyelinating disease, progressive multifocal leukoencephalopathy (PML). Individuals infected with HIV, those who have AIDS, or those receiving immunomodulatory therapies for autoimmune diseases are at serious risk for PML. Recent reports have demonstrated that viral isolates from PML patients often have distinct changes within the major capsid protein. Our structural-functional approach highlights that these mutations result in abolished engagement of the carbohydrate receptor motif LSTc that is necessary for infection. Viruses with PML-associated mutations are not infectious in glial cells, suggesting that they may play an alternative role in PML pathogenesis.


Number of pregnancies and ovariectomy modify mammary carcinoma development in transgenic HER-2/neu female mice.
We studied effect of pregnancy and ovariectomy on the development of mammary tumors in homozygous female HER-2/neutransgenic mice. The mean life span of uniparous mice was decreased by 16% in comparison to the control (P<0.05) and of mice which have two pregnancies decreased by 11% (P<0.05). Ovariectomy at the age of 2 months was followed by 32.7% increase in mean life span of mice. The incidence or multiplicity of mammary adenocarcinomas did not change in uniparous mice, whereas the size of the tumors and metastatic potential were decreased as compared to the virgins. When mice have two full-time pregnancies, there was an increase in multiplicity of mammary carcinomas and significant (2.1-fold) decrease in the survival time of tumor-bearing mice. Ovariectomy significantly decreased the total incidence of mammary carcinomas, the number of tumors per tumor-bearing animal, and inhibited metastasizing into lungs. Our results indicate that pregnancy accelerated the development of mammary adenocarcinomas in transgenic HER-2/neu mice whereas ovariectomy inhibits their development.


Chromosomal assignment of six muscle-specific genes in cattle.
Six genes expressed in skeletal or smooth muscle were assigned to bovine chromosomes using rodent, human or bovine cDNA probes. Myogenic determination factor (MYOD1) was 100% concordant with Bos taurus chromosome (BTA) 15, and myogenin (MYOG) was 95% concordant with BTA 16. Smooth muscle caldesmon (CALD1) and the skeletal muscle chloride channel gene (CLCN1) were 100% concordant with BTA 4. Myogenic factor 5 (MYF5) was 90% concordant with BTA 5; this assignment was confirmed by fluorescence in situ hybridization of a bovine genomic MYF5 probe to BTA 5 band 13 and the homologous band on river buffalo 4q. In some metaphases, specific hybridization signals were also observed on BTA 15 band 23, and the equivalent river buffalo homologue, with the MYF5 genomic probe. Because MYOD1 and MYF5 share both nucleotide and functional homology and because MYOD1 was mapped in somatic cell hybrids to BTA 15, we suggest that MYOD1 may be located at BTA 15 band 23. Herculin/myogenic factor 6 (MYF6) was assigned indirectly to BTA 5 by the hybridization of MYF5 and MYF6 probes to the same HindIII fragment in bovine genomic DNA. The assignment of MYF6 to BTA 5 is consistent with the tandem arrangement of MYF5 and MYF6 in human, mouse and chicken, where these tightly linked genes are separated by < 6.5 kb of DNA.


Admission hyperglycemia and TIMI frame count in primary percutaneous coronary intervention.
We evaluated the relationship between admission blood glucose levels and estimated coronary flow by the thrombolysis in myocardial infarction (TIMI) frame count (TFC) method in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). The TFC of 121 consecutive patients with STEMI were evaluated after pPCI. Patients with admission glucose levels > 198 mg/dL (11 mmol/L) were defined as hyperglycemic. Hyperglycemia was observed in 36 (29.8%) patients. The TFC was significantly higher in patients with hyperglycemia (70.75 [10-96] vs 56.87 [8-100], P = .04). No-reflow frequency was higher in the hyperglycemia group (44.4% vs 23.5%, P = .02). In multivariate linear regression analysis admission glucose was an independent predictor of high TFC (B = 0.21, P = .02). Our findings suggest that admission blood glucose is a predictor of TFC which reflects coronary blood flow.


ATMIN is a transcriptional regulator of both lung morphogenesis and ciliogenesis.
Initially identified in DNA damage repair, ATM-interactor (ATMIN) further functions as a transcriptional regulator of lung morphogenesis. Here we analyse three mouse mutants, Atmin(gpg6/gpg6), Atmin(H210Q/H210Q) and Dynll1(GT/GT), revealing how ATMIN and its transcriptional target dynein light chain LC8-type 1 (DYNLL1) are required for normal lung morphogenesis and ciliogenesis. Expression screening of ciliogenic genes confirmed Dynll1 to be controlled by ATMIN and further revealed moderately altered expression of known intraflagellar transport (IFT) protein-encoding loci in Atmin mutant embryos. Significantly, Dynll1(GT/GT) embryonic cilia exhibited shortening and bulging, highly similar to the characterised retrograde IFT phenotype of Dync2h1. Depletion of ATMIN or DYNLL1 in cultured cells recapitulated the in vivo ciliogenesis phenotypes and expression of DYNLL1 or the related DYNLL2 rescued the effects of loss of ATMIN, demonstrating that ATMIN primarily promotes ciliogenesis by regulating Dynll1 expression. Furthermore, DYNLL1 as well as DYNLL2 localised to cilia in puncta, consistent with IFT particles, and physically interacted with WDR34, a mammalian homologue of the Chlamydomonas cytoplasmic dynein 2 intermediate chain that also localised to the cilium. This study extends the established Atmin-Dynll1 relationship into a developmental and a ciliary context, uncovering a novel series of interactions between DYNLL1, WDR34 and ATMIN. This identifies potential novel components of cytoplasmic dynein 2 and furthermore provides fresh insights into the molecular pathogenesis of human skeletal ciliopathies.


Acquisition and transmission of Theileria parva by vector tick, Rhipicephalus appendiculatus.
In order to investigate the transmission dynamics of Theileria parva (T. parva) by the brown ear tick, Rhipicephalus appendiculatus (R. appendiculatus), under experimental conditions, detection of T. parva in ticks and cattle was performed by a quantitative real-time PCR assay. A calf inoculated with a T. parva mixture became PCR-positive for T. parva infection on day 8 post-inoculation, and subsequently, nymphal ticks were introduced and maintained to feed on the infected calf for 6 days. Engorged nymphs were collected daily and allowed to molt into adults, and overall, 70.8% (121/171) of the adult ticks acquired the T. parva infection. Furthermore, the T. parva infection rate in ticks under field conditions was monitored by real-time PCR in R. appendiculatus ticks collected from a traditionally managed pastoral land of Zambia, on which Sanga breed cattle are traditionally reared and the area has endemic East Coast fever (ECF). A total of 70 cattle were randomly selected in the same area and 67 (95.7%) were found to be serologically positive for R. appendiculatus tick antigen (RIM36). Twenty-nine (43.3%) of the 67 serologically positive cattle were real-time PCR-positive for T. parva, although no piroplasms could be detected in the blood smears. Unexpectedly, out of 614 R. appendiculatus nymphal and adult ticks collected by flagging vegetation, 4.1% were positive for T. parva DNA. However, since the rate of transmission of T. parva from infected cattle to ticks and vice versa and the serological evidence of exposure to R. appendiculatus ticks in naturally exposed cattle were relatively high, it would be wise in such a case to consider vector control as well as vaccination against ECF as control measures.


A semi-Markov model for multistate and interval-censored data with multiple terminal events. Application in renal transplantation.
The semi-Markov assumption emphasizes the importance of time spent in a state. In order to compute this type of multistate model, most transition times are always considered to be exactly identified or right censored. However, in the longitudinal analysis of chronic diseases, investigators are often confronted with interval-censored data (transition times are known to have occurred in some interval). Thus, the two key issues are the modeling of the duration dependence and the interval censoring. In this article, we define a semi-Markov model, allowing for interval censoring, for parametric hazard functions with a union or logical sum- or intersection-shape and for determination of initial states according to covariates. Our modeling approach is specific to each transition, so as to obtain a more coherent model. Parallel to competing risks models, the multistate model takes into account several final events. We consider an example of kidney transplant recipient follow-up to illustrate the utility of the method.


Intraosseous samples can be used for creatinine measurements--an experimental study in the anaesthetised pig.
Intraosseous (IO) access is a valuable tool in prehospital locations and in emergency departments when other forms of vascular access are unavailable. Creatinine is often used for dose adjustment of drugs that may be administered through intraosseous cannulae. We aimed to study the possibility of analysing creatinine in intraosseous samples and study the accuracy and precision of such measurements. Eight pigs with endotoxin induced septic shock were sampled hourly for six hours and analysed for plasma creatinine. Samples were collected from arterial, venous, and IO cannulae. There was an increase in creatinine values during the later part of the experiment. The coefficients of variation between the three sampling sites were less than 10% at all sampling times. Based on our findings intraosseous samples can be used for creatinine determination in emergency settings.