Characterization of the lectin from females of Phlebotomus duboscqi sand flies.
Lectin from females of the important sand fly vector, Phlebotomus duboscqi (Diptera: Psychodidae), was isolated by immunoaffinity chromatography using a minicolumn with immobilized anti-lectin immunoglobulins. Carbohydrate-binding specificity of active fractions corresponded to that of midgut and salivary gland lysates. Haemagglutination was inhibited by d-glucosamine, d-galactosamine and d-mannosamine. The homogeneity and molecular mass of the purified lectin was examined by SDS/PAGE in both reducing and nonreducing conditions. The active fractions showed one band strongly stained by Coomassie blue or silver nitrate; the molecular mass of the lectin was 42 kDa under nonreducing and 44 kDa under reducing conditions. SDS/PAGE of active fractions from the gel filtration revealed four to six protein bands, but the 42/44-kDa protein present in all active fractions was the only component reacting with specific antibodies in Western blots. Localization of the lectin in the gut of females was studied using indirect immunofluorescence on sections. The positive reaction of specific antibodies was localized in the lumen and along the microvillar surfaces of epithelial cells. The lectin was partially sequenced and characterized by MS. Peptide maps were obtained by MALDI-TOF MS, and several sequence tags were identified from tandem mass spectra on an ion trap. These sequences displayed high similarity to salivary protein precursors previously identified in a cDNA library of the sand flies Phlebotomus papatasi and Lutzomyia longipalpis. Two main hypotheses on the role of female lectin in Leishmania development are discussed.


Investigating the cow skin and teat canal microbiomes of the bovine udder using different sampling and sequencing approaches.
There is a need for standardized, efficient, and practical sampling methods to support large population-based studies of the internal and external epithelial microbiomes of the bovine udder. The primary objective of this study was to evaluate different sampling devices for the isolation of microbial DNA originating from the internal and external teat epithelium. Secondary objectives were to survey and compare the microbial diversity of external and teat canal epithelial microbiomes using amplicon and shotgun metagenomic sequencing approaches. To address these objectives, we enrolled a convenience sample of 24 Holstein dairy cows and collected samples from the external epithelium at the base of udder, the external teat barrel epithelium, the external teat apex epithelium, and the teat canal epithelium. Extracted DNA was quantified and subjected to PCR amplification of the V4 hypervariable region of the 16S rRNA gene and sequenced on the Illumina MiSeq platform (Illumina Inc., San Diego, CA). A subset of samples was subjected to a shallow shotgun metagenomic assay on the Illumina HiSeq platform. For samples collected from the external teat epithelium, we found that gauze squares consistently yielded more DNA than swabs, and Simpson's reciprocal index of diversity was higher for gauze than for swabs. The teat canal epithelial samples exhibited significantly lower diversity than the external sampling locations, but there were no significant differences in diversity between teat apex, teat barrel, and base of the udder samples. There were, however, differences in the microbial distribution and abundances of specific bacteria across external epithelial surfaces. The proportion of shotgun sequence reads classified as Bos taurus was highly variable between sampling locations, ranging from 0.33% in teat apex samples to 99.91% in teat canal samples. These results indicate that gauze squares should be considered for studying the microbiome of the external epithelium of the bovine udder, particularly if DNA yield must be maximized. Further, the relative proportion of host to non-host DNA present in samples collected from the internal and external teat epithelium should be considered when designing studies that utilize shotgun metagenomic sequencing.


Trabecular bone loss at a distant skeletal site following noninvasive knee injury in mice.
Traumatic injuries can have systemic consequences, as the early inflammatory response after trauma can lead to tissue destruction at sites not affected by the initial injury. This systemic catabolism may occur in the skeleton following traumatic injuries such as anterior cruciate ligament (ACL) rupture. However, bone loss following injury at distant,unrelated skeletal sites has not yet been established. In the current study, we utilized a mouse knee injury model to determine whether acute knee injury causes a mechanically significant trabecular bone loss at a distant, unrelated skeletal site (L5 vertebral body).Knee injury was noninvasively induced using either high-speed (HS; 500 mm/s) or lowspeed(LS; 1 mm/s) tibial compression overload. HS injury creates an ACL rupture by midsubstance tear, while LS injury creates an ACL rupture with an associated avulsion bone fracture. At 10 days post-injury, vertebral trabecular bone structure was quantified using high-resolution microcomputed tomography (lCT), and differences in mechanical properties were determined using finite element modeling (FEM) and compressive mechanical testing. We hypothesized that knee injury would initiate a loss of trabecular bone structure and strength at the L5 vertebral body. Consistent with our hypothesis, we found significant decreases in trabecular bone volume fraction (BV/TV) and trabecular number at the L5 vertebral body in LS injured mice compared to sham (8.8% and 5.0%, respectively), while HS injured mice exhibited a similar, but lower magnitude response (5.1% and 2.5%, respectively). Contrary to our hypothesis, this decrease intrabecular bone structure did not translate to a significant deficit in compressive stiffness or ultimate load of the full trabecular body assessed by mechanical testing or FEM. However,we were able to detect significant decreases in compressive stiffness in both HS and LS injured specimens when FE models were loaded directly through the trabecular bone region (9.9% and 8.1%, and 3, respectively). This finding may be particularly important for osteoporotic fracture risk, as damage within vertebral bodies has been shown to initiate within the trabecular bone compartment. Altogether, these data point to a systemic trabecular bone loss as a consequence of fracture or traumatic musculoskeletal injury, which may be an underlying mechanism contributing to increased risk of refracture following an initial injury. This finding may have consequences for treatment of acute musculoskeletal injuries and the prevention of future bone fragility.


High-titer autoantibodies against glutamic acid decarboxylase plus autoantibodies against insulin and IA-2 predicts insulin requirement in adult diabetic patients.
Antibodies against glutamic acid decarboxylase (GADA) is known to be a good predictive marker for insulin-dependency among adult diabetic patients. However, since not all of the GADA-positive patients will develop insulin requirement, we investigated whether other markers, that is, antibodies against IA-2 (IA-2A), insulin autoantibodies (IAA) and HLA class II type, would affect its predictive value for insulin requirement. Adult diabetic patients in the non-insulin-requiring stage were screened for GADA and registered in the study if positive. At the end of the follow-up period, 15 of the 43 GADA-positive patients required insulin. Among GADA-positive patients, the GADA titers of the insulin-requiring patients were significantly higher (199 U vs. 5.8 U, P<0.001) and high-titer GADA was more frequently detected among insulin-requiring patients (80%vs. 11%, P<0.0001). IAA was more frequently detected in insulin-requiring patients (40%vs. 0%, P<0.001), and IA-2A was detected only among insulin-requiring patients. Combinations of these three antibodies (GADA with either IAA or IA-2A) had 100% positive predictive value. In conclusion, the GADA test is a good screening test for predicting insulin requirement in adult diabetic patients and both the IAA and IA-2A tests are useful second line tests.


An Application of Hydraulic Tomography to a Large-Scale Fractured Granite Site, Mizunami, Japan.
While hydraulic tomography (HT) is a mature aquifer characterization technology, its applications to characterize hydrogeology of kilometer-scale fault and fracture zones are rare. This paper sequentially analyzes datasets from two new pumping tests as well as those from two previous pumping tests analyzed by Illman et al. (2009) at a fractured granite site in Mizunami, Japan. Results of this analysis show that datasets from two previous pumping tests at one side of a fault zone as used in the previous study led to inaccurate mapping of fracture and fault zones. Inclusion of the datasets from the two new pumping tests (one of which was conducted on the other side of the fault) yields locations of the fault zone consistent with those based on geological mapping. The new datasets also produce a detailed image of the irregular fault zone, which is not available from geological investigation alone and the previous study. As a result, we conclude that if prior knowledge about geological structures at a field site is considered during the design of HT surveys, valuable non-redundant datasets about the fracture and fault zones can be collected. Only with these non-redundant data sets, can HT then be a viable and robust tool for delineating fracture and fault distributions over kilometer scales, even when only a limited number of boreholes are available. In essence, this paper proves that HT is a new tool for geologists, geophysicists, and engineers for mapping large-scale fracture and fault zone distributions.


Interdye Hole Transport Accelerates Recombination in Dye Sensitized Mesoporous Films.
Charge recombination between oxidized dyes attached to mesoporous TiO2 and electrons in the TiO2 was studied in inert electrolytes using transient absorption spectroscopy. Simultaneously, hole transport within the dye monolayers was monitored by transient absorption anisotropy. The rate of recombination decreased when hole transport was inhibited selectively, either by decreasing the dye surface coverage or by changing the electrolyte environment. From Monte Carlo simulations of electron and hole diffusion in a particle, modeled as a cubic structure, we identify the conditions under which hole lifetime depends on the hole diffusion coefficient for the case of normal (disorder free) diffusion. From simulations of transient absorption and transient absorption anisotropy, we find that the rate and the dispersive character of hole transport in the dye monolayer observed spectroscopically can be explained by incomplete coverage and disorder in the monolayer. We show that dispersive transport in the dye monolayer combined with inhomogeneity in the TiO2 surface reactivity can contribute to the observed stretched electron-hole recombination dynamics and electron density dependence of hole lifetimes. Our experimental and computational analysis of lateral processes at interfaces can be applied to investigate and optimize charge transport and recombination in solar energy conversion devices using electrodes functionalized with molecular light absorbers and catalysts.


Clinical profile, predisposing factors, and associated co-morbidities of children with cerebral palsy in South India.
Cerebral palsy (CP) is the most common physical disorder of children. Causes like jaundice and birth injury though are decreasing; complications resulting from the survival of low birth weight babies are replacing some of the older etiologies. Hence, this study was planned. The objective was to study the clinical patterns, predisposing factors, and co-morbidities in children with CP. The present study is a hospital based prospective study conducted from January 2012 to January 2013 in children presenting to neurodevelopmental clinic at a tertiary care teaching hospital in India. Hundred cases with clinical features suggestive of CP were included in the study. Cases were evaluated by history, clinical examination, and necessary investigations. Results of the study showed 81% of spastic, 12% of hypotonic, 5% of dystonic, and 2% of mixed CP cases. The mean age of presentation was 2 year, 2 month, and male to female ratio of 1:2. Pregnancy-induced hypertension (PIH) was the most common antenatal complication observed in 6%. Four percent had neonatal sepsis and 19% were born premature. Associated co-morbidities were mental retardation (55%), seizure disorder (46%), visual problems (26%), hearing problems (19%), and failure to thrive (47%). Sex distribution observed in our study was male to female ratio of 1.2, which was comparable with a multicenter study in Europe. PIH was observed in 6% of cases, which was comparable with prior studies. Birth asphyxia was observed in 43% of cases. Eighty-one percent of the cases constituted a spastic variety of CP which was comparable to other studies. Perinatal asphyxia was the important etiological factor. We found preventable intranatal causes (60%) and antenatal causes (20%) forming a significant proportion. Co-morbidities were significantly observed in our study.


Charged amino acids required for signal transduction by the m3 muscarinic acetylcholine receptor.
The five muscarinic acetylcholine receptor (mAChR) subtypes, termed m1-m5, transduce agonist signals across the plasma membrane by activating guanine nucleotide binding (G) proteins. The large cytoplasmic domain joining the fifth and sixth transmembrane segments of mAChRs plays a critical role in controlling the specificity of G protein coupling. In this study, we determined which sequences within this domain are required for activation of signaling by the m3 mAChR. By measuring the ability of normal and mutant m3 mAChRs to couple to the G protein pathway leading to activation of phospholipase C and Ca(2+)-dependent chloride currents in RNA-injected Xenopus oocytes, we found that two clusters of charged residues near the fifth and sixth transmembrane segments were required for normal signaling; furthermore, the position of these sequences was critical for their function. Finally, analysis of deletion mutant m3 mAChRs confirmed the importance of these sequences; receptors containing as few as 22 out of 239 amino acids of the cytoplasmic domain were fully active in signaling if they included the critical charged residues. Sequence comparisons suggest that similar charged sequences may be required for signal transduction by many G protein-coupled receptors.


Carbon monoxide in acute lung injury.
Despite modern clinical practice in critical care medicine, acute lung injury still causes unacceptably high rates of morbidity and mortality. Therefore, the challenge today is to identify new and effective strategies in order to improve the outcome of these patients. Carbon monoxide, endogenously produced by the heme oxygenase enzyme system, has emerged as promising gaseous therapeutic that exerts protective effects against inflammation, oxidative and mechanical stress, and apoptosis, thus potentially limiting acute lung injury. In this review we discuss the effects of inhaled carbon monoxide on acute lung injury that results from ischemia-reperfusion, transplantation, sepsis, hyperoxia, or mechanical ventilation, the latter referred to as ventilator-induced lung injury. Multiple investigations using in vivo and in vitro models have demonstrated anti-inflammatory, anti-apoptotic, and anti-proliferative properties of carbon monoxide in the lung when applied at low dose prior to or during stressful stimuli. The molecular mechanisms that are modulated by carbon monoxide exposure are still not fully understood. Carbon monoxide mediated lung protection involves several signaling pathways including mitogen activated protein kinases, nuclear factor-κB, activator protein-1, Akt, peroxisome proliferating- activated receptor-γ, early growth response-1, caveolin-1, hypoxia-inducible factor-1α, caspases, Bcl-2-family members, heat shock proteins, or molecules of the fibrinolytic axis. At present, clinical trials on the efficacy and safety of CO investigate whether the promising laboratory findings might be translatable to humans.


TRIM65 in White Matter Lesions, Innate Immunity, and Tumor.
Most of the tripartite motif (TRIM) family proteins have E3 ubiquitin ligase activities and also have a variety of functions in cellular processes such as intracellular signal transduction, apoptosis, innate immunity, and carcinogenesis. TRIM65 is a member of the TRIM family. More pieces of evidence have shown a unique role and importance of TRIM65 protein in the occurrence and development of some diseases. In this review, the importance of TRIM65 in white matter lesions, innate immunity, and the effect of tumors were mainly reviewed.


Advanced embryo development during extended in vitro culture: observations of formation and hatching patterns in non-transferred human blastocysts.
Human embryos not chosen for fresh transfer or cryopreservation were maintained in extended in vitro culture for up to 9 days after fertilization to observe blastocyst formation and hatching features. These non-transferred embryos were derived from 64 consecutive IVF cycles, and were not cryopreserved either because of compromised morphology or because the patients did not consent to cryopreservation for personal reasons. Embryos were cultured individually to monitor daily growth until developmental arrest, and differential blastocyst formation and hatching were analysed among groups of patients and embryos. In the population studied, hatching occurred most commonly on day 7 after fertilization (range 5-9 days). A total of 301 blastocysts was observed, of which 116 (38.5%) eventually hatched in vitro irrespective of day of formation. A trend towards earlier blastocyst formation and a greater likelihood of hatching was noted in this population. Both blastocyst formation and hatching appeared negatively correlated with increasing maternal age and higher basal serum FSH concentrations on day 3 of development, although these trends did not reach statistical significance. Comparison of intracytoplasmic sperm injection (ICSI) (n = 25) and conventional insemination (n = 39) cycles showed a similar rate of blastocyst formation in both groups (54 and 52%, respectively; P > 0.05), but hatching patterns varied significantly between these groups (4.1 versus 61.6%, respectively; P < 0.0001). The discovery of marked impairment of hatching among non-transferred ICSI embryos supports the case for reconsideration of the appropriateness of assisted blastocyst hatching in selected cases.


Spatially resolved distribution models of POP concentrations in soil: a stochastic approach using regression trees.
Background concentrations of selected persistent organic pollutants (polychlorinated biphenyls, hexachlorobenzene, p,p'-DDT including metabolites) and polyaromatic hydrocarbons in soils of the Czech Republic were predicted in this study, and the main factors affecting their geographical distribution were identified. A database containing POP concentrations in 534 soil samples and the set of specific environmental predictors were used for development of a model based on regression trees. Selected predictors addressed specific conditions affecting a behavior of the individual groups of pollutants: a presence of primary and secondary sources, density of human settlement, geographical characteristics and climatic conditions, land use, land cover, and soil properties. The model explained a high portion of variability in relationship between the soil concentrations of selected organic pollutants and available predictors. A tree for hexachlorobenzene was the most successful with 76.2% of explained variability, followed by trees for polyaromatic hydrocarbons (71%), polychlorinated biphenyls (68.6%), and p,p'-DDT and metabolites (65.4%). The validation results confirmed that the model is stable, general and useful for prediction. The stochastic model applied in this study seems to be a promising tool capable of predicting the environmental distribution of organic pollutants.


[Serum and aqueous humor antibodies to beta-2 glycoprotein I in patients with glaucoma and cataract].
Evaluation of the serum and aqueous humor antibodies to beta-2 glycoprotein I in patients with glaucoma. 48 persons (38 women and 17 men), aged 30-86 (mean age 70), suffering from glaucoma was examined. There were 19 with POAG, 18 with PACG and 11 with PEXG. All patients have undergone trabeculectomy. The group of 20 operated patients, because of age-related cataracta (7 men and 13 women), aged 47-82 (mean age 65), constituted a control group. All patients agreed with samples collection. In plasma and anterior chamber fluid, the level of antibodies to b-2 glycoprotein I classes IgA and IgG were measured using ELISA method (commercial kits produced by Euroimmun), according to producer's instruction. Statistical analysis was performed using U Mann-Whitney test when both groups were compared and Spearman test to comparisons concerning single group. Significant changes between glaucoma and cataract patients were observed in anti-b-2 glycoprotein I antibodies class IgA in aqueous humour (p=0.04) and in serum (p=0.03). Knowledge of the immunological pathogenesis in the glaucomatous nerve damage can be curtailed or even prevented with the use of proper agents. Indeed, there are many intriguing new therapeutic possibilities on the horizon. To determine the clinical potential of serum antibodies in glaucoma patients, a randomized clinical trial would be necessary. It is the preliminary communication.


Hemicrania Continua With Scintillating Scotoma: A Rare Presentation.
Headache can be a primary or secondary disorder. The characteristics of headache and its associated features, especially the presence of red flag signs, are important in distinguishing secondary from primary causes. Hemicrania continua is a type of primary headache disorder characterized by a continuous unilateral headache with episodes of exacerbations and association with cranial autonomic symptoms, which include several ocular symptoms. The absolute response to indomethacin remains the hallmark of this disease. We would like to report a rare case of hemicrania continua with scintillating scotoma during exacerbations apart from the typical autonomic features of conjunctival injection, ptosis, eyelid edema, and lacrimation.


Expanded Pharmacy Practice Implementation: Lessons from Remote Practice.
The aim of this study is to explore pharmacist perspectives of the implementation of a community pharmacy-based ear health service in rural communities. A community pharmacy-based health service model was designed and developed to provide an accessible ear care service (LISTEN UP-Locally Integrated Screening and Testing Ear aNd aUral Program) and pharmacist's perspectives of the implementation of LISTEN UP were explored. Thematic analysis was conducted and data coded according to the Consolidated Framework for Implementation Research. A total of 20 interviews were conducted with 10 pharmacists, averaging 30 min. Visualistion of the ear canal was reported as the greatest advantage of the service, whilst the time required for documentation reported as a complexity. The number of pharmacists working at one time and the availability of a private consultation room were identified as the two limiting factors for execution. On reflection, the need for government funding for service viability and sustainability was highlighted. Expanded pharmacy practice is emerging for the Australian pharmacy profession. Rural community pharmacists are recognised as integral members of healthcare teams, providing accessible medication supply and health advice to seven million people in Australia who call rural and remote regions home. However, there are no structured models supporting them to provide expanded services to improve health outcomes in their communities. This study provides lessons learnt to guide future design and development of expanded models of pharmacy practice.


Does radiographic beam angle affect the radiocapitellar ratio measurement of subluxation in the elbow?
Radial head alignment is the key to determine elbow reduction after treatment of subluxations or Monteggia fractures. The radiocapitellar ratio (RCR) quantifies the degree of subluxation, by evaluating radial head alignment with the capitellum of the humerus; this ratio is reproducible when measured on true lateral radiographs of nonsubluxated elbows. However, the impact of beam angulation on RCR measurement is unknown. Our hypotheses were that the RCR of the nonsubluxated elbow would remain in the normal range as the beam angle changed and that the RCR variability would increase for the subluxated elbow with small deviations in the beam angle. Radiographs were taken of six healthy cadaveric extremities using beam angles ranging from -20° to 20° along the inferosuperior axis and from -20° to 20° along the dorsoventral axis. The same views then were taken of the six arms with anterior radiocapitellum subluxation followed by posterior radiocapitellum subluxation. RCRs were measured by one observer. As a reference value, the RCR was measured in the 0° to 0° position and the difference between each RCR in a nonreference position was subtracted from each RCR reference to obtain the delta-RCR. An ANOVA was performed to assess the main and interactive effects on the RCR measured in each C-arm position compared with the RCR measured on a true lateral radiograph. The RCR remained in the normal range even as the beam angle of the C-arm varied between -20° and 20°. The position of the beam did not affect the RCR in anteriorly subluxated elbows (p = 0.777), whereas RCR variation increased especially in the presence of posterior radial head subluxation when the C-arm position was 10° or more out of plane (p = 0.006). The inferosuperior malposition of the C-arm had a greater impact on quantification of radial head alignment measurement. Despite that, the RCR measurement is reliable in reduced and subluxated elbows on lateral radiographs with a C-arm position deviation of as much as 20°. Identification of a subluxated elbow could be made on any lateral radiograph with a beam angulation deviation of as much as 20°. This suggests that the RCR is a useful diagnostic tool for clinical and research purposes, although for subluxated elbows, it is important to pay careful attention to the inferosuperior position of the C-arm.


Anlotinib Enhances the Antitumor Activity of High-Dose Irradiation Combined with Anti-PD-L1 by Potentiating the Tumor Immune Microenvironment in Murine Lung Cancer.
Radioimmunotherapy has become one of the most promising strategies for cancer treatment. Preclinical and clinical studies have demonstrated that antiangiogenic therapy can improve the efficacy of immunotherapy and sensitize radiotherapy through a variety of mechanisms. However, it is undefined whether angiogenesis inhibitors can enhance the effect of radioimmunotherapy. In this study, we aim to explore the role of anlotinib (AL3818) on the combination of radiotherapy and immune checkpoint inhibitors in Lewis lung carcinoma mouse. C57BL/6 mouse subcutaneous tumor model was used to evaluate the ability of different treatment regimens in tumor growth control. Immune response and immunophenotyping including the quantification and activation were determined by flow cytometry, multiplex immunofluorescence, and multiplex immunoassay. Triple therapy (radiotherapy combined with anti-PD-L1 and anlotinib) increased tumor-infiltrating lymphocytes and reversed the immunosuppressive effect of radiation on the tumor microenvironment in mouse model. Compared with radioimmunotherapy, the addition of anlotinib also boosted the infiltration of CD8+ T cells and M1 cells and caused a decrease in the number of MDSCs and M2 cells in mice. The levels of IFN-gamma and IL-18 were the highest in the triple therapy group, while the levels of IL-23, IL-13, IL-1 beta, IL-2, IL-6, IL-10, and Arg-1 were significantly reduced. NF-κB, MAPK, and AKT pathways were downregulated in triple therapy compared with radioimmunotherapy. Thus, the tumor immune microenvironment was significantly improved. As a consequence, triple therapy displayed greater benefit in antitumor efficacy. Our findings indicate that anlotinib might be a potential synergistic treatment for radioimmunotherapy to achieve better antitumor efficacy in NSCLC patients by potentiating the tumor immune microenvironment.


[A case of huge liver metastasis from colon cancer successfully treated by hepatic intraarterial infusion of low-dose 5-FU].
A 71-year-old man with unresectable liver metastasis from colon cancer was treated by hepatic intraarterial infusion of low dose 5-FU (250 mg/body/day). The tumor measured 18 cm by ultrasonography and has reduced gradually to five cm during three years. Both serum CEA and CA 19-9 levels were as high as 49.9 ng/ml and 5,500 U/ml respectively, before treatment, but normalized. This case suggested that this hepatic intraarterial infusion of low-dose 5-FU might be effective to treat unresectable liver metastasis, especially with portal tumor thrombosis.


Identity of the RNase MRP- and RNase P-associated Th/To autoantigen.
To characterize the molecular identity of the Th/To autoantigen, which is targeted by autoantibodies in scleroderma and which is associated with the human RNase MRP and RNase P ribonucleoprotein complexes. Proteins immunoprecipitated by anti-Th/To+ patient antisera from biotinylated total HeLa cell extracts were analyzed by immunoblotting. The association of autoantigenic proteins with the RNase MRP complex was analyzed by reconstitution experiments and ultraviolet crosslinking. The reactivity of patient sera with all known RNase MRP/RNase P proteins was analyzed by immunoprecipitation of the individual recombinant proteins. The previously defined Th40 autoantigen appeared to be identical to the Rpp38 protein. Paradoxically, Rpp38 did not bind to the P3 domain of the RNase MRP RNA, as suggested by previously published data for Th40, and only half of the anti-Th/To+ sera contained anti-Rpp38 reactivity. Two other RNase MRP/RNase P subunits, Rpp20 and Rpp25, were found to interact with the P3 domain. The previously reported 40-kd species associated with this domain appeared to consist of Rpp20 and/or Rpp25 associated with a nuclease-resistant RNA fragment. Finally, we demonstrated that almost all tested anti-Th/To+ patient sera contained autoantibodies to Rpp25 and hPop1, indicating that these proteins harbor the most frequently targeted Th/To determinants. Our data unequivocally define the identity of the Th/To autoantigen and demonstrate that Th/To autoepitopes are found on several protein subunits of RNase MRP/RNase P.


Maintaining and Supporting Seniors' Wellbeing through Foreign Language Learning: Psycholinguistics of Second Language Acquisition in Older Age.
This study concerns aspects of positive psychology connected to foreign language learning (FLL) in an older healthy generation. The positive psychology perspective stresses the positive aspects of improved wellbeing in participants who engage in various activities, particularly mental and brain-training practices. Therefore, the aim of this study was to explore older people's subjective feelings connected to their FLL as one of the crucial ways to improve their quality of life (QoL). The objective of the research was to determine the subjective satisfaction level of the participants of a second language (L2) acquisition course. The research sample (experimental group) consisted of 105 respondents who were Czech citizens and 55+ years old. Two control groups were set up. The first (young control) consisted of 102 young adults (university students), also Czech citizens, aged between 19 and 23 years. The second control group (elderly control) consisted of 102 subjects older than 55 years, similar in age to the experimental group. A standardized online questionnaire survey was the principal research method, identical both for the experimental and control groups. The findings clearly showed that language training significantly improved the subjective positive feelings and wellbeing of the older participants, regardless of their objective progress in FLL itself. These results stood in opposition to the young control group and were different from the elderly control group. The results revealed that FLL is an effective tool for enhancing the overall wellbeing of older people, which was shown in their expression of their feelings of happiness, satisfaction, and positive motivation to learn an L2. In addition, FLL objectively affected their mental health in a positive way and expanded their social networks. Moreover, FLL was a meaningful activity for them, despite the weak objective learning outcomes due to the decline of cognitive functions, helping them find their general purpose of life, as well as life motivation as expressed in the survey. These findings are crucial, as it has already been proven that wellbeing is directly connected with good health and longevity. Therefore, national governments and all stakeholders dealing with the present issue of the aging population should pay undivided attention to the enhancement of older people's wellbeing by all possible intervention approaches, including FLL. There is limited research into the issue and the findings of this investigation could be an impetus for further research into the topic from the perspectives of cognitive science, psychology, and psycholinguistics.


Mineral and bone disorders and survival in hemodialysis patients with and without polycystic kidney disease.
Maintenance hemodialysis (MHD) patients with polycystic kidney disease (PKD) have better survival than non-PKD patients. Mineral and bone disorders (MBD) are associated with accelerated atherosclerosis and cardiovascular death in MHD patients. It is unknown whether the different MBD mortality association between MHD populations with and without PKD can explain the survival differential. Survival models were examined to assess the association between different laboratory markers of MBD [such as serum phosphorous, parathyroid hormone (PTH), calcium and alkaline phosphatase] and mortality in a 6-year cohort of 60,089 non-PKD and 1501 PKD MHD patients. PKD and non-PKD patients were 57±13 and 62±15 years old and included 46 and 45% women and 14 and 32% Blacks, respectively. Whereas PKD individuals with PTH 150 to <300 pg/mL (reference) had the lowest risk for mortality, the death risk was higher in patients with PTH<150 [hazard ratio (HR): 2.16 (95% confidence interval 1.53-3.06)], 300 to <600 [HR: 1.30 (0.97-1.74)] and ≥600 pg/mL [HR: 1.46 (1.02-2.08)], respectively. Similar patterns were found in non-PKD patients. Fully adjusted death HRs of time-averaged serum phosphorous increments<3.5, 5.5 to <7.5 and ≥7.5 mg/dL (reference: 3.5 to <5.5 mg/dL) for PKD patients were 2.82 (1.50-5.29), 1.40 (1.12-1.75) and 2.25 (1.57-3.22). The associations of alkaline phosphatase and calcium with mortality were similar in PKD and non-PKD patients. Bone-mineral disorder markers exhibit similar mortality trends between PKD and non-PKD MHD patients, although some differences are observed in particular in low PTH and phosphorus ranges.


Lions Quest Skills for Adolescence Program as a School Intervention to Prevent Substance Use-a Pilot Study Across Three South East European Countries.
Development of personal and social skills in a classroom prevents later drug use and alcohol abuse, and influence-related risk factors. However, clinical trials on the potential impact of such programs from low- or middle-income countries remain limited. Lions Quest Skills for Adolescence (LQSFA), a school-based prevention intervention supporting life skills, was implemented in three South East European countries. This was a collaboration between the United Nations Office on Drugs and Crime, the Lions Clubs International Foundation, and the Ministries of Education of Serbia, the Former Yugoslav Republic of Macedonia and Montenegro. The pilot was a multisite non-randomized trial. A total of 2964 elementary school students received the intervention through 232 instructors trained by the same internationally certified trainer. These were compared to 2232 students following the regular curriculum, which does not include LQFSA, in the same elementary schools. The assessment was done at the beginning and at the end of the same academic year (period of 10 months). Despite limited fluctuations, the overall results indicated an encouraging outcome on the current use of substances (alcohol, cigarettes, and marijuana) as well as intention to using these substances in the next 3 months among current users. This study attempts to address this aforementioned gap in literature and contributes to the body of research demonstrating the value, feasibility, and transferability of life skills programs in achieving prevention outcomes in South East Europe. Moreover, it paves the way to a future randomized clinical trial to further corroborate the results, overcoming limitation in current study design.


Molecular analysis of X-ray-induced mutants at the HPRT locus in V79 Chinese hamster cells.
Spontaneous and X-ray-induced mutants at the hypoxanthine phosphoribosyl transferase (HPRT) locus have been isolated from V79 Chinese hamster cells and characterized at the biochemical and cytogenetic levels. Fourteen spontaneous and 24 X-ray-induced clones were azaguanine and thioguanine resistant, did not grow in HAT medium (AZRTGRHATS) and failed to incorporate significant levels of [14C]hypoxyanthine. Cytogenetic analysis of two spontaneous and eight X-ray-induced mutants revealed no major X chromosome rearrangements. In two induced mutants, one of which was hypotetraploid (mode 35-39) with 2 X chromosomes, the short arm of the chromosome (Xp) was slightly shorter than normal. A third mutant was hyperdiploid (mode 22-23) compared with the parental clone (mode 21). When compared with wild-type clones, no other cytogenetic changes were evident in the remaining mutants. Analysis at the DNA level using a Chinese hamster HPRT cDNA probe showed major deletion of HPRT sequences in two and partial deletion in another two induced mutants. In two of the mutants with deletions of HPRT sequences there was a visible shortening of the Xp arm. In the other six mutants two spontaneous and four induced) no karyotypic changes or alterations in restriction fragment patterns were detected suggesting that they carry small deletions or point mutations at the HPRT locus.


The complete mitochondrial genome of the green crab spider Oxytate striatipes (Araneae: Thomisidae).
The complete mitochondrial genome (KM507783) of the green crab spider Oxytate striatipes was determined. The mitochondrial genome of O. striatipes was 14,407 bp long with a total base composition of 35.80% A, 42.40% T, 8.60% C, and 13.20% G. Total length of 13 protein-coding genes was 10,801 bp and 9 of them were encoded on heavy strand. COX1 started with TTA, uncommon start codon in invertebrate mitogenomes. The total length of 22 tRNA genes was 1202 bp, varying from 46 bp (tRNA(Thr)) to 67 bp (tRNA(Trp) and tRNA(Gln)). The standard cloverleaf secondary structure was found in 8 tRNA genes and TV-replacement loop was not found in the other 14 tRNA genes.


[Humanized antibodies as therapeutics].
Since 1997, nine humanized antibodies received the approval of the FDA to be used as drugs for the treatment of various diseases including transplant rejections, metastatic breast and colon cancers, leukaemia, non-Hodgkin lymphomas, allergic conditions or multiple sclerosis. This review describes techniques used to engineer these antibodies and presents the recent evolutions of these techniques : SDRs grafting or << abbreviated >> CDRs grafting. Based on the illustrative examples of several antibodies, Mylotarg, Herceptin or Xolair, the therapeutic effectiveness of humanized antibodies are underlined and, with the example of Tysabri, the sometimes dramatic adverse effects associated with their clinical use is stressed. In a second part, this review presents some future and realistic avenues to improve the effectiveness of the humanized antibodies, to decrease their immunogenicity and to reduce their cost.


Development of a Click Beetle Luciferase Reporter System for Enhanced Bioluminescence Imaging of Listeria monocytogenes: Analysis in Cell Culture and Murine Infection Models.
Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that is widely used as a model organism for the analysis of infection biology. In this context, there is a current need to develop improved reporters for enhanced bioluminescence imaging (BLI) of the pathogen in infection models. We have developed a click beetle red luciferase (CBR-luc) based vector (pPL2CBRopt) expressing codon optimized CBR-luc under the control of a highly expressed Listerial promoter (PHELP) for L. monocytogenes and have compared this to a lux-based system expressing bacterial luciferase for BLI of the pathogen using in vitro growth experiments and in vivo models. The CBR-luc plasmid stably integrates into the L. monocytogenes chromosome and can be used to label field isolates and laboratory strains of the pathogen. Growth experiments revealed that CBR-luc labeled L. monocytogenes emits a bright signal in exponential phase that is maintained during stationary phase. In contrast, lux-labeled bacteria produced a light signal that peaked during exponential phase and was significantly reduced during stationary phase. Light from CBR-luc labeled bacteria was more efficient than the signal from lux-labeled bacteria in penetrating an artificial tissue depth assay system. A cell invasion assay using C2Bbe1 cells and a systemic murine infection model revealed that CBR-luc is suited to BLI approaches and demonstrated enhanced sensitivity relative to lux in the context of Listeria infection models. Overall, we demonstrate that this novel CBR reporter system provides efficient, red-shifted light production relative to lux and may have significant applications in the analysis of L. monocytogenes pathogenesis.


A constant current triboelectric nanogenerator arising from electrostatic breakdown.
In situ conversion of mechanical energy into electricity is a feasible solution to satisfy the increasing power demand of the Internet of Things (IoTs). A triboelectric nanogenerator (TENG) is considered as a potential solution via building self-powered systems. Based on the triboelectrification effect and electrostatic induction, a conventional TENG with pulsed AC output characteristics always needs rectification and energy storage units to obtain a constant DC output to drive electronic devices. Here, we report a next-generation TENG, which realizes constant current (crest factor, ~1) output by coupling the triboelectrification effect and electrostatic breakdown. Meanwhile, a triboelectric charge density of 430 mC m-2 is attained, which is much higher than that of a conventional TENG limited by electrostatic breakdown. The novel DC-TENG is demonstrated to power electronics directly. Our findings not only promote the miniaturization of self-powered systems used in IoTs but also provide a paradigm-shifting technique to harvest mechanical energy.


A method for evaluating root-knot nematode infection in rice using a transparent paper pouch.
The root-knot nematode (RKN) Meloidogyne incognita is one of the most economically damaging plant-parasitic nematodes. Molecular studies of the plant-RKN interaction have been vigorously carried out in dicotyledonous model plants, while the host range of M. incognita is wide including monocotyledonous plants. As M. incognita causes quality and yield losses in rice (Oryza sativa L.) cultivated in both upland and irrigated systems, we developed a method to examine the plant-RKN interaction in this model monocotyledonous crop plant. Here, we show that a transparent paper pouch could be used to evaluate nematode infection rates in rice with similar results to that of the traditional soil method. The system using a transparent paper pouch can be used to observe the spatial and temporal distribution of developing galls and can save the space of growth chamber.


The Governance of UK Dairy Antibiotic Use: Industry-Led Policy in Action.
This article analyses the progress made in the UK with regard to tackling antibiotic "misuse and overuse" in food-producing animals. Moving beyond statistical realities, the paper examines how the UK's industry-led policy approach is shaping practice. Using a multi-sited ethnography situated in Actor Network Theory and Callon's sociology of markets, the UK dairy supply chain policies and practices were studied. Findings reveal that dairy industry policies only partially address the complex network of people, animals, and the environment in which dairy antibiotics circulate. Antibiotic "misuse and overuse" in agriculture is far from a behavioural matter, with solely farmers and veterinarians to blame. Instead, antibiotic use in food animals is embedded in complex economic networks that constrain radical changes in dairy husbandry management and antibiotic use on farms. More attention toward the needs of the dairy supply chain actors and wider environmental considerations is essential to reduce the dairy sector's dependency on antibiotics and support transition toward responsible farming in the UK.


EUS-guided FNA of solid pancreatic masses: high yield of 2 passes with combined histologic-cytologic analysis.
EUS-guided FNA (EUS-FNA) is an established tissue-acquisition technique, with most studies concentrating on cytologic analyses of specimens, with only few data existing on histologic assessment. To assess the sensitivity of a combined analysis of histologic followed by cytologic tissue diagnosis. A retrospective 3-center study. In consecutive patients undergoing FNA of solid pancreatic masses, core specimens were harvested for histology; residual tissue was examined cytologically. Only unequivocally positive results were regarded as malignant. Criterion standards were positive results from EUS-FNA or other histologic findings, or, if negative, clinical follow-up data (minimum 12 months). Among 192 patients (110 men; mean age 63 years) with mostly pancreatic-head masses (72.4%), overall, adequate tissue was obtained in 98.9% of all cases, with a mean of 1.88 needle passes and an overall sensitivity of 82.9% (95% CI, 76.0%-88.5%). Histology and subsequent cytology provided adequate tissue and sensitivities of 86.5% and 60%, and 92.7% and 68.1%, respectively. Excluding cases with inadequate specimens, sensitivities rose by 4% to 10%. Histology showed a trend for superiority over cytology only in characterizing nonadenocarcinoma tumor types. No differences in sensitivity were found between the centers involved. Retrospective design, different processing of cytologic specimens. At EUS-FNA in pancreatic masses, combined histologic-cytologic analysis achieved a sensitivity of more than 80%, despite a low number of needle passes and may thus save time. Histology alone did not reach higher sensitivity than cytology. In particular situations, eg, rare tumors, histology may still be required.


Techniques employed for detection of hot particles in the marine environment.
During the decommissioning of the Maine Yankee nuclear plant, several methods were developed and employed to survey for hot particles in the marine environment surrounding the site. The methods used and the sensitivities achieved in the search for environmentally dispersed particles during the various decommissioning activities performed are described in detail. Surveys were performed on dry soil, exposed marine sediment and submerged marine sediment. Survey techniques ranged from the use of the basic NaI detector coupled to a count rate meter to an intrinsic germanium detector deployed in a submarine housing coupled to a multi-channel analyser. The initial surveys consisted of collecting samples of marine sediment, spreading them out over a 1 m2 surface in a thin layer, and scanning the deposited sediment by hand using a 5 cm by 5 cm NaI detector coupled to a standard count rate meter. This technique was later replaced by walkover scans with the 5 cm by 5 cm NaI detector moved in a serpentine pattern over the sediment surface. By coupling the detector to a 'smart meter', an alarm set point could be used to alert the surveyor to the presence of a particle within the instrument's field of view. A similar technique, with the detector mounted in a watertight housing secured to the end of a pole, was also employed to scan underwater locations. The most sensitive method developed for performing underwater surveys was the use of the intrinsic germanium detector placed in a submarine housing. Detailed descriptions of the methods employed and the results obtained are presented. This work demonstrates that there are several approaches to surveying for discrete particles in the marine environment and the relative merits of each are considered.


Dural tear and myelomalacia caused by an airgun pellet in a cat.
An 8-year-old cat was presented with severe neurological deficits secondary to a traumatic cervical spinal cord injury caused by an airgun pellet. This report describes, for the first time, the myelographic findings of a dural rupture in a cat and also describes a bilateral Horner's syndrome in a cat.


Angiotensin II increases the intracellular calcium activity in podocytes of the intact glomerulus.
Angiotensin II increases the intracellular calcium activity in podocytes of the intact glomerulus. Knowledge about biological functions of podocytes in the glomerulus is limited because of its unique anatomical location. Here we introduce a new method for measuring the intracellular calcium activity ([Ca2+]i) in the podocyte in the intact glomerulus. With the help of fluorescence high-resolution digital imaging and a recently developed ultraviolet laser-scanning microscope, [Ca2+]i was measured in fura-2-loaded glomeruli and single podocytes of intact microdissected rat glomeruli. Angiotensin II (Ang II) increased [Ca2+]i reversibly in a biphasic and concentration-dependent manner. In contrast to Ang II, bradykinin, thrombin, arginine vasopressin, and serotonin did not change [Ca2+]i in the glomerulus. At reduced extracellular Ca2+ activity, Ang II released [Ca2+]i from intracellular stores, but the second phase, corresponding to a Ca2+ influx from the extracellular space, was absent. The L-type Ca2+ channel blocker nicardipine did not influence the Ang II-mediated [Ca2+]i increase, and an increase of the extracellular K+ concentration did not change [Ca2+]i in the glomerulus. The angrotensin II type I (AT1) receptor antagonist losartan inhibited the Ang II-mediated [Ca2+]i increase. Confocal [Ca2+]i measurements using fura-2 or fluo-3 or fluo-4 on the single cell level show that some of the Ang II-mediated [Ca2+]i response originated from podocytes. Costaining with calcein allowed the identification of podocytes because of the characteristic morphology and location in relationship to the capillary network. These data suggest that podocytes in the intact glomerulus respond to Ang II with an increase of [Ca2+]i via an AT1 receptor.


Synthesis and properties of plasma-polymerized polypyrrole/Au composite nanofibers.
Nanostructured composites have a wide variety of potential applications in microelectronics, chemical sensors, and electrochemical energy production. Here, we report the chemical, structural, and electrochemical characteristics of a nanostructured composite material formed from plasma-polymerized polypyrrole-coated Au fibers. The properties of the plasma-polymerized polypyrrole (PPPy) films were characterized by FTIR, X-ray photoelectron spectroscopy (XPS), and UV-Vis spectroscopy, as well as cyclic voltammetry (CV), and scanning electron microscopy (SEM). These spectroscopy analyses suggest that thermal treatment of the materials results in elimination of loosely-bound, low mass oligomers in the films. Mass spectral analysis of the plasma phase suggests that plasma polymerization of the pyrrole takes place on the substrate surface as a result of diffusion of radicals produced in the plasma. In addition, thermal treatment enhances the electrochemical properties of the PPPy films because of changes in the surface morphology and bulk structure of the films. However, as-deposited PPPy films coated on Au nanotubes demonstrate better electrochemical properties than as-deposited PPPy films coated on flat ITO electrodes as a result of the increase in surface area and decrease in film thickness.


Multiple Peripheral Osteomas Related to Frontal Exposure by Bicoronal Incision.
Osteoma of the skull is a benign slow-growing osteogenic lesion typically composed of well-differentiated mature bone tissue. It is characterized by the proliferation of compact or cancellous bone and is found almost exclusively in the head and neck region. Central, peripheral, and extraskeletal are the major variants of craniofacial osteomas. Trauma, inflammation, developmental disorders, and genetic defects are considered their etiologic factors. Paranasal sinuses, especially frontal and ethmoidal sinuses, are the favorite locations of peripheral craniofacial osteomas.Peripheral osteomas are usually benign, innocuous lesions, but their size, prominence, and visibility on the face necessitate a surgical intervention.The authors describe a rare patient in whom multiple osteomsas were located in the frontal area likely related to an exposure of the site by bicoronal incision made 10 years earlier.


Reduced bone density of the hip in elderly patients with Parkinson's disease.
Parkinson's disease (PD) is a major cause of falls and reduced mobility in elderly people. Fractures often occur as a result of these falls but there have been no studies of bone mineral density (BMD) in PD. We have prospectively studied 29 elderly women (mean age 77 years) and 26 elderly men (mean age 74 years) with PD over 2 years and compared them with similar numbers of age- and sex-matched controls. Bone mineral density was measured by dual X-ray absorptiometry. Women were more likely to sustain fractures (38% compared with 8% of men). Mean BMD of the lumbar spine was similar in the 55 combined PD patients compared with combined controls. However, the total hip BMD was 10% lower (p = 0.014) and the neck of femur BMD 12% lower (p < 0.004) in the 51 PD patients compared with controls. The relatively lower hip BMD in elderly PD men and women combined with their abnormal gait and tendency to fall backwards or to the side may explain their excess risk of hip fractures, particularly in women. The neuromuscular deficit in PD may differentially reduce hip BMD relative to other sites and may thus be amenable to measures designed to improve mechanical loading in the lower limbs in the early stages of PD.


Changes of optical properties of dental nano-filled resin composites after curing and thermocycling.
The objective was to evaluate the color changes after curing, polishing, and thermocycling of a nano-filled resin composite. A nano-filled composite was grouped into two shades of enamel (EN) and translucent (TL). One hybrid composite was used as a control (CL). Color of specimens of 10 mm in diameter and 2 mm in thickness was measured on a reflection spectrophotometer with SCE geometry under the D65 illumination over white and black backgrounds. Color before curing and after curing, polishing and thermocycling was measured. Color change (DeltaE(*) (ab)), translucency parameter (TP), and contrast ratio (CR) were compared. Average DeltaE(*) (ab) after curing was 4.6 in the EN group and 10.4 in the TL group compare to 2.9 in CL. Polishing caused average DeltaE(*) (ab) of 3.3-3.6, which was not different by the shade group (p > 0.05). After 2000 cycles of thermocycling, average DeltaE(*) (ab) was 1.4-1.8, which was not different by the shade group (p > 0.05). TP values increased after curing in the EN group, but decreased in the TL group (p < 0.05). TP values after thermocycling decreased in the EN group but did not change in TL (p = 0.05). TP values of TL shades were higher than those of EN regardless of specimen conditions (p < 0.05). Changes in CR values showed similar trends to those of TP values in translucency. Changes of color and translucency after curing, polishing, and thermocycling varied by the shade group.


Evidence that ribosomal protein S10 participates in control of transcription termination.
We report the isolation of an Escherichia coli K-12 strain with a mutation, nusE71, that results in a change in ribosomal protein S10. Phage lambda fails to grow in hosts carrying the nusE71 mutation because the lambda N gene product is not active. The N product regulates phage gene expression by altering transcription complexes so that they can overcome termination barriers. This suggests that a ribosomal protein is involved in antitermination of transcription.


Outside the "Cultural Binary": Understanding Why Latin American Collectivist Societies Foster Independent Selves.
Cultural psychologists often treat binary contrasts of West versus East, individualism versus collectivism, and independent versus interdependent self-construal as interchangeable, thus assuming that collectivist societies promote interdependent rather than independent models of selfhood. At odds with this assumption, existing data indicate that Latin American societies emphasize collectivist values at least as strongly as Confucian East Asian societies, but they emphasize most forms of independent self-construal at least as strongly as Western societies. We argue that these seemingly "anomalous" findings can be explained by societal differences in modes of subsistence (herding vs. rice farming), colonial histories (frontier settlement), cultural heterogeneity, religious heritage, and societal organization (relational mobility, loose norms, honor logic) and that they cohere with other indices of contemporary psychological culture. We conclude that the common view linking collectivist values with interdependent self-construal needs revision. Global cultures are diverse, and researchers should pay more attention to societies beyond "the West" and East Asia. Our contribution concurrently illustrates the value of learning from unexpected results and the crucial importance of exploratory research in psychological science.


Toward the Total Synthesis of Amphidinolide N: Synthesis of the C8-C29 Fragment.
A synthesis of the C8-C29 fragment of amphidinolide N, a potent cytotoxic macrolide isolated from the marine dinoflagellate Amphidinium sp., has been achieved. The key features of the synthesis involve a convergent union of the C9-C15 and C16-C29 fragments by Steglich esterification and the construction of a pyran unit through a Tebbe methylenation/ring-closing metathesis sequence.


Speculations on the rodent carcinogenicity of 30 chemicals currently under evaluation in rat and mouse bioassays organised by the U.S. National Toxicology Program.
As a contribution to the second round of rodent carcinogenesis prediction organised by the U.S. National Institute of Environmental Health Sciences (NIEHS), speculative predictions for 30 chemicals currently under evaluation in U.S. National Toxicology Program (NTP) rodent bioassays are presented. Core chemical data received from NIEHS were supplemented by relevant information from commercially available scientific databases to provide input for reasoned assessment. For each chemical, carcinogenesis by a genotoxic or nongenotoxic mechanism or noncarcinogenesis is predicted; species-and target organ-specific predictions are also presented, together with arbitrary indices of confidence in each such prediction. In all or nearly all cases, an element of informed speculation was a necessary part of the prediction process, but the rationale for each decision is briefly described. It is predicted that ten chemicals will prove noncarcinogenic, five will be carcinogenic to mice only, and 15 will induce tumours in both species.


Longitudinal studies of cardiac troponin I concentrations in serum from male cynomolgus monkeys: resting values and effects of oral and intravenous dosing on biologic variability.
There is a paucity of information regarding cardiac troponin (cTn) concentrations in peripheral blood of nonhuman primates (NHP). Even less is known regarding cTn concentrations in monkeys that are restrained for oral or intravenous (iv) dosing. The objectives of these studies were to (1) determine cardiac troponin I (cTnI) concentration in resting Cynomolgus monkeys and investigate biologic variability in cTnI concentration over time, (2) determine cTnI changes in restrained monkeys given sham oral dosing, and (3) determine cTnI changes in restrained NHP given a sham intravenous dosing. The Research Use Only Erenna cTnI ultrasensitive immunoassay based on single molecule counting technology was used to determine serum cTnI concentration in longitudinal studies of male Cynomolgus monkeys at rest, and after sham oral and intravenous dosing. Animals were catheterized prestudy, and blood samples were collected by an automated sampling device to limit disturbance of the animals during studies. In resting monkeys cTnI concentrations were relatively low and constant and ranged from 0.2 to 9.6 pg/mL (mean = 2.5 pg/mL), with minimal variability during a 24-hour period. Animals given sham oral dosing also had low cTnI concentration with little variability similar to the resting values. Several animals restrained for intravenous dosing had a small transient increase in cTnI concentration (~5-25 pg/mL) that resolved quickly within one to 3 hours postinjection. Results of this longitudinal study provide information that may be important in differentiating effects of animal handling from those associated with compound-related effects in preclinical toxicology studies of drugs in development.


[Spectroscopic studies on the binding of sibutramine hydrochloride and bovine serum albumin].
To study the binding of sibutramine hydrochloride (SH) and bovine serum albumin (BSA) in physiological condition by spectroscopic method. The quenching mechanism of the fluorescence of bovine serum albumin by sibutramine hydrochloride was studied with the fluorescence and the absorption spectroscopy. The binding constants K and the number of binding sites were determined at different temperatures according to Scatchard equation and the main binding force was discussed by thermodynamic equations. The effect of the drug on bovine serum albumin conformation was also studied by using synchronous fluorescence spectroscopy. The quenching mechanism of sibutramine hydrochloride to bovine serum albumin was static quenching. The binding constants K at 8 degrees C, 25 degrees C, 37 degrees C were 1.21 x 10(5), 8.31 x 10(4), 6.97 x 10(4) L x mol(-1) with one binding site, respectively. The thermodynamic parameters of the reaction were deltaH = -9.70 kJ x mol(-1), deltaS = 56.41 J x mol(-1) x K(-1). The binding force is electrostatic interaction. Sibutramine hydrochloride can be deposited and transported by serum protein in vivo. Sibutramine hydrochloride has nearly no effect on the serum protein conformation.


Cdc6 is required for meiotic spindle assembly in Xenopus oocytes.
During the maturation of Xenopus oocytes, Cdc6 expression is necessary to establish replication competence to support early embryonic DNA replication. However, Cdc6 is expressed before the completion of MI, at a time when its function as a replication factor is not required, suggesting additional roles for Cdc6 in meiosis. Confocal immunofluorescence microscopy revealed that Cdc6 protein was distributed around the spindle precursor at the time of germinal vesicle breakdown (GVBD), and localized to the margin of the nascent spindle early in prometaphase. Cdc6 subsequently localized to spindle poles in late prometaphase, where it remained until metaphase arrest. Microinjection of antisense oligonucleotides specific for Cdc6 mRNA disrupted spindle assembly, resulting in defects including delayed spindle assembly, misoriented and unattached anaphase spindles, monasters, multiple spindles, microtubule aggregates associated with condensed chromosomes, or the absence of recognizable spindle-like structures, depending on the level of residual Cdc6 expression. Furthermore, Cdc6 co-localized with γ-tubulin in centrosomes during interphase in all somatic cells analyzed, and associated with spindle poles in mitotic COS cells. Our data suggest a role for Cdc6 in spindle formation in addition to its role as a DNA replication factor.


Treatment with erythropoietin and loss of dialyser clearance.
Hyperkalaemia as well as increased predialysis values for creatinine and phosphate have been reported in many clinical recombinant human erythropoietin (rHu-EPO) trials in haemodialysis patients. These problems were overcome in most cases by increasing the dose of dialysis. With the exception of urea clearance, solute clearances should decrease with increased haematocrit values. Urea in red blood cells is in diffusion equilibrium with plasma water and it can be assumed that urea clearance is only minimally affected by an increasing haematocrit. Equilibration between red cells and plasma for larger solutes (creatinine) is slow compared to dialyser transit time, so that intracellular creatinine is effectively prevented from participating in the dialytic exchange. Therefore, as the haematocrit increases, the amount of creatinine removed should decrease. These considerations are particularly important for red cell potassium and phosphate, which virtually do not equilibrate with plasma water. In fact, loss of clearance has been reported to range from 5% to 10% for urea and 15% to 20% for creatinine, potassium and phosphate after correction of anaemia. This is particularly relevant in the setting of rapid, high efficiency dialysis with treatment times of 2 h, where more frequent episodes of hyperkalaemia and increased requirements of phosphate binders have been reported. For those who prescribe dialysis by using urea modelling (Kt/V), the dialyser clearance K may have to be corrected for effective blood water clearance and the dose prescribed should be increased, because urea modelling will overestimate the clearance of other uraemic solutes.


Frequency of celiac disease in individuals with Down syndrome in the United States.
Ninety-three individuals with Down syndrome (DS) were screened to investigate the prevalence of celiac disease (CD) in the United States. Five of the 93 individuals were antiendomysial antibody (EMA) positive. Of the 5 who tested positive for EMA, 4 were biopsied, 1 refused biopsy. Three of the 4 individuals biopsied manifested changes of CD on small bowel biopsy. This gives a frequency of 3.2% of confirmed CD in our DS individuals and suggests the need for periodic screening for celiac disease in this population.


[Study on the sexual development of adolescent male].
The investigation of the testicular volume, the penis length and the T, FSH, LH, PRL levels in serum were taken in 289 adolescent males to provide the valuable data for andrology. The adolescent males were grouped according to their age. The testicular volume was measured with testicular model and the T, FSH, LH, PRL levels in serum were determined by immunoenzymetric assay. The male sexual development was rapid from age 11 to 16 and close to that of adult at age 18. Serum PRL of adolescent males was higher than that of adult males. The age 11 to 16 is a period of rapid growth in sexual maturation. PRL may play an important role in sexual maturation.


[The effect of family and social relations on the consumption of psychotropic drugs by the aged].
Psychotropic drugs are the second most commonly used medication by Quebec's elderly. The objective of this study is to test a theoretical model of psychotropic drug use in the elderly. The principal hypothesis is that the quality of relationships the elderly person has with others, particularly with his or her children, has a direct influence on his or her psychological well-being, which, in turn, directly affects the consumption of psychotropic agents. A survey was conducted on a sample of 500 elderly people, aged 65-84 years, living at home. 31.8% of the respondents used psychotropic drugs during the three-month period preceding the interview. Path analysis led to the elaboration of a modified model for the consumption of psychotropic drugs by the elderly which indicates that the best predictors of consumption are both the psychological well-being and the state of health of the individual. More elevated is the psychological well-being, less is the consumption of psychotropic drugs, whereas poor health condition increases it. The quality of an individual's social relationships has a direct influence on his or her psychological well-being, whereas family relationships are of lesser importance. Our model accounts for 13% of the predictors of psychotropic consumption by the elderly.


[Study and clinical application of the theory "moxibustion can be used for heat syndrome"].
In order to study on the clinically difficult problem, "is moxibustion suitable for heat syndrome?" cite and analyze relative papers in classical treaties about acupuncture and moxibustion, in combination with the many years' practical experiences of the author and experimental studies of modern medicine. And Textually research the treatment principle of "positive and negative go against" and the treatment method of "using heat to induce heat", which is a theoretical basis of "moxibustion being suitable for heat syndrome". Experimental studies have proved that moxibustion has bacteriostatic effect, and functions abatement of fever and improving microcirculation. It is indicated that moxibustion is suitable to treatment of all heat syndromes including excess-heat and deficiency-heat syndromes.


The clinical epidemiology of human T-lymphotropic virus type II (HTLV-II).
Human T-lymphotropic virus type II (HTLV-II) is endemic among Amerindian tribes and is also prevalent at high levels among certain U.S. and European intravenous drug users (IVDU), and at lower levels among blood donors. Most epidemiologic evidence supports transmission via parenteral, breast-feeding, and sexual routes, although more quantitative studies of the latter two routes are needed. There is growing evidence that HTLV-II causes a neurologic syndrome similar to HTLV-I-associated myelopathy, but there is some controversy as to whether the clinical features of this illness differ between HTLV-II and HTLV-I cases. Preliminary evidence also suggests that HTLV-II may predispose to skin and soft tissue bacterial infections among IVDU. Questions amenable to future research are discussed.


Assessment of Fall Risk in Elderly Rural Population.
Background: Fall risk assessment is an essential component of a comprehensive fall reduction and prevention program. Fall risk assessment is done to identify patients' risk for falls and ultimately prevent falls from occurring. The aim of the study was to identify the risk factors for fall in the elderly population. Methods:This study included 250 elderly patients > 60 years (105 males, 145 females) attending Medicine OPD in a tertiary care hospital. Detailed history including the previous h/o falls, medication history elicited and divided study subjects into two groups: fallers and non-fallers. Cardiovascular, neurological, and musculoskeletal system examinations were done. Handgrip, 30 seconds chair standing test (CST), "timed up and go" test (TUG), and performance-oriented mobility assessment (POMA) were performed. Results:The prevalence of falls in our study was 27.6%. The mean age of fallers was 72.22±6.219 years (P 0.002). Females had significant falls compared to males (p < 0.001). In binary logistic regression, age >80 [OR-3.8, CI (1.8-8.1); p 0.016], female gender [OR-19.2, CI (3.03-122.2); p 0.002], visual impairment [OR-8.9, CI (1.4-55.4); p 0.019], postural hypotension [OR-59.8, CI (3.3-1.07); p 0.006] and presence of more than three risk factors [OR-9.6, CI (4.6-2.01); p 0.000] were significantly associated with fall in our study. Conclusion:Falls among older people were common, especially among individuals aged over 80. Females were more prone to fall. The number of risk factors, visual impairment, and postural hypotension increased the fall risk. Simple clinical assessment can identify high-risk patients.


Incidence of salmonellae in meat and meat products.
Standard enrichment, plating, and biochemical techniques were used to assess the incidence of Salmonella species on beef and pork carcasses and processed meat products. The incidence of Salmonella in pork carcasses was 56% and in beef carcasses, 74%. These figures are about the same as previously reported for pork but much higher than previously reported for beef carcasses; however, they represent only three to five abattoirs in Georgia and do not necessarily represent contamination levels throughout the country. Examination of carcasses by area did not indicate greater incidence of Salmonella in any one area. Two areas suggested for representative sampling are the cervical and anal areas of the carcass. Of the sausage samples examined, 38% of the fresh pork sausage, 9% of the smoked pork sausage, and 1 sample (souse) of 16 samples of miscellaneous sausage products were contaminated. Examination of subsamples indicated that Salmonella, when present in sausage products, could be found in any section of the entire sample.


Design of Cavity-Backed Bow-Tie Antenna with Matching Layer for Human Body Application.
This paper presents the broadband antenna for the microwave radiometric sensing of internal body temperature. For broadband operation, the bow-tie antenna was designed and backed with a cylindrical cavity, which decreased environmental electromagnetic interference and also improved the directivity of the antenna. The broadband impedance-transforming balun in microstrip form was also designed to feed the bow-tie antenna, and was located inside the cavity. An impedance-matching dielectric layer (IMDL) was introduced on top of the bow-tie antenna, for impedance match with the human body with high permittivity. The fabricated antenna was measured in free space with the IMDL removed, showing an input reflection coefficient lower than -10 dB from 2.64 to > 3.60 GHz with antenna gain over 6.0 dBi and radiation efficiency over 74.7% from 2.7 to 3.5 GHz. The IMDL was re-installed on the cavity-backed bow-tie antenna to measure the antenna performance for the human head with relative permittivity of about 40. The measured reflection coefficient was as low as -28.9 dB at 2.95 GHz and lower than -10 dB from 2.65 to > 3.5 GHz. It was also shown that the designed antenna recovered a good impedance match by adjusting the permittivity and thickness of the IMDL for the different parts of the human body with different permittivities.


Properties of a Solubilized Microsomal Auxin-binding Protein from Coleoptiles and Primary Leaves of Zea mays.
An auxin-binding protein can be solubilized from microsomal membranes of Zea mays using either Triton X-100 extraction of the membranes or buffer extraction of the acetone-precipitated membranes. This paper describes the properties of the binding protein solubilized by these two methods. The binding is assayed by gel filtration chromatography in the presence of naphthalene [2-(14)C]acetic acid. Binding is rapid and reversible with an optimum at pH 5. Both preparations show similar molecular weights by gel filtration (80,000 daltons) at pH 7.6 and 0.1 molar NaCl, and both aggregate at low ionic strength. They appear to be the same active molecular species. The binding activity is destroyed by trypsin, pronase or para-chloromercuribenzoic acid, but not significantly reduced by phospholipase C, DNase, RNase, or dithioerythritol. Since saturating amounts of naphthalene acetic acid protect the molecule from inhibition by para-chloromercuribenzoic acid, it is concluded that the binding protein has a sulfhydryl group at the binding site, or protects such a group in its binding conformation. The dissociation constant of the protein for naphthalene acetic acid is 4.6 x 10(-8) molar with 30 picomoles of sites per gram of tissue fresh weight. Binding constants were estimated for 13 other natural and synthetic auxins by competition with naphthalene[2-(14)C]acetic acid. Their dissociation constants are in general agreement with published values for their binding to intact membranes and their biological activity, although several exceptions were noted. A supernatant factor from the same tissue changes the apparent affinity of the protein for naphthalene acetic acid. This factor may be the same one as has been previously reported to alter the affinity of intact microsomes for auxin.


Jones v. Berkshire Area Health Authority, 2 July 1986.
The High Court of the UK awarded 40,000 pounds in damages to the plaintiff, who, after being sterilized, had given birth to a child. The award included damages for anguish and distress and the cost of raising the child.


[The effects of premedication on induction doses of propofol and hemodynamic responses during induction].
We chose five sedatives for premedication and investigated the effect of these drugs on the induction doses of propofol. One hundred patients were allocated into one of five groups of 20. These groups consisted of control group (C) given only atropine 0.5 mg i.m.; CL group (plus clonidine 0.15 mg orally); H group (plus hydroxyzine 25 mg i.m.); M group (plus midazolam 3 mg i.m.) and D group (plus diazepam 10 mg orally). The induction dose was measured using loss of count technique. Arterial pressure and heart rate were measured, before and after propofol induction as well as after intubation. We also calculated rate pressure products (RPP) at each point. The induction doses were significantly lower in M-group than those in C-group. On the other hand, in hemodynamic responses, RPP was unchanged in any groups after propofol induction and after the intubation. Both propofol and midazolam have been known to have a depressive effect on the central nervous system via GABA-A receptor-mediated inhibition, although the exact receptor for propofol is unknown. We thought, therefore, that when the interaction occurred, both midazolam and propofol had the same effect on the GABA-A receptor and increased chloride ion flux through the channels. Hydroxyzine and clonidine, however, do not share a common receptor or exert effect on the GABA-A receptor. We consider that this was one of the reasons why induction doses of both H and CL group could not decrease significantly. We concluded that midazolam 3 mg decreased propofol induction dose significantly. Both midazolam 3 mg and clonidine 0.15 mg decreased RPP before induction and hemodynamic responses to induction and intubation were stable.


Distribution and second messenger coupling of four somatostatin receptor subtypes expressed in brain.
The mRNA distribution in the brain and the coupling to cellular effector systems of four somatostatin receptors (SSTR1-4) was studied. All four SRIF receptor subtypes were expressed in cortex and hippocampus. In addition, SSTR1 mRNA was relatively abundant in the spinal cord whereas SSTR2 mRNA was also present in the striatum. The SSTR3 gene was predominantly expressed in the olfactory bulb and in the cerebellum. Conflicting results about the effector coupling of SSTR1-3 have been published previously. We have stably expressed human SSTR1-4 in HEK 293 human embryonal kidney cells. Agonist binding to the receptor subtypes, including the recently cloned SSTR4, inhibited the formation of forskolin-induced cAMP. Is is concluded that, in an appropriate cellular environment, all four receptor subtypes can functionally couple to the inhibition of adenylyl cyclase.


Nailfold capillaroscopy microscopy - an interdisciplinary appraisal.
Nailfold capillaroscopy is a method of great diagnostic value in the differential diagnosis of primary versus secondary Raynaud´s phenomenon, of systemic sclerosis versus other so called connective tissue diseases and of additional diagnostic value in other entities. Rheumatologists, dermatologists, and angiologists in Germany have convened in an interdisciplinary working group in which they synergistically combined their expertise to develop a common nomenclature and standards for the technical performance of nailfold capillary microscopy. The article gives an overview of historical and technical aspects of capillaroscopy, morphologic findings, and disease-specific patterns. It also provides a critical appraisal of its significance in the diagnosis and sequelae of these interdisciplinarily-managed diseases including its performance in children and gives an excursion in the potential perspectives of capillaroscopy in less common indications.


Prediction Model for Gastric Cancer Incidence in Korean Population.
Predicting high risk groups for gastric cancer and motivating these groups to receive regular checkups is required for the early detection of gastric cancer. The aim of this study is was to develop a prediction model for gastric cancer incidence based on a large population-based cohort in Korea. Based on the National Health Insurance Corporation data, we analyzed 10 major risk factors for gastric cancer. The Cox proportional hazards model was used to develop gender specific prediction models for gastric cancer development, and the performance of the developed model in terms of discrimination and calibration was also validated using an independent cohort. Discrimination ability was evaluated using Harrell's C-statistics, and the calibration was evaluated using a calibration plot and slope. During a median of 11.4 years of follow-up, 19,465 (1.4%) and 5,579 (0.7%) newly developed gastric cancer cases were observed among 1,372,424 men and 804,077 women, respectively. The prediction models included age, BMI, family history, meal regularity, salt preference, alcohol consumption, smoking and physical activity for men, and age, BMI, family history, salt preference, alcohol consumption, and smoking for women. This prediction model showed good accuracy and predictability in both the developing and validation cohorts (C-statistics: 0.764 for men, 0.706 for women). In this study, a prediction model for gastric cancer incidence was developed that displayed a good performance.


Do hypertension and diabetes mellitus influence the site of atherosclerotic plaques?
The concomitant occurrence of atherosclerotic plaques in carotid, coronary and peripheral vessels has been described in a number of studies. A few studies were, on the contrary, done for determining the role of hypertension and/or type 2 diabetes mellitus for the occurrence of the atherosclerotic plaques in different anatomical sites. Moreover these studies deal with atherosclerotic lesions that are generally considered, without differentiating their morphology as a function of the underlying disease, territory, and risk factors. Primary aim of this study is, thus, to verify whether the two most common causes for atherosclerotic disease, i.e., hypertension and type 2 diabetes mellitus, may influence the site of appearance of the atherosclerotic plaque. A second aim is to verify if the anatomical site of the plaque influences plaque morphology and vulnerability. A retrospective study of 244 patients affected with type 2 diabetes mellitus or hypertension was performed; 114 subjects were affected by moderate-severe and drugs-treated hypertension (Group A); 55 were affected by type 2 diabetes mellitus in treatment with oral antidiabetic drugs (Group B); 75 were diagnosed as affected by the association hypertension and diabetes (Group C). The inclusion criteria were: exhaustive images of the cardiovascular system (coronary angiography, colour Doppler ultrasound of lower limb arteries and carotid arteries, transthoracic Doppler echocardiography ) and a serum lipid profile (total serum cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides). Three different anatomical sites: carotid axis, ilio-femoral arteries and coronary district, were considered. In each site a plaque lesion-classification was performed to describe the morphology of the plaque. In patients with hypertension, carotid district seems to be the preferential site of onset of atherosclerotic plaques even if a statistical significant association between the two conditions was not found. Statistical evaluation didn't show significant association between different risk factors and coronary district too. On the opposite, a significant association (p < 0.001) between diabetes and the presence of atherosclerotic plaques into lower limb district was found. A very significant association (p < 0.001) between type 2-diabetes and the presence of non-ulcerative plaques was found too. Our study underlines the relationship between vessel plaques localization and concomitant risk factors for atherosclerosis and suggests a possible difference in plaque morphology and biological behaviour related to different anatomical site.


Biosafety testing of genetically modified ryegrass (Lolium perenne) using a model for the optimum selection of test invertebrates.
Selection of test species for use in biosafety evaluation of genetically modified plants is challenging but important, as regulators in many jurisdictions require tests to determine the potential for adverse environmental impacts before the release of plants into the environment. This contribution provides an example of an evidence-based process whereby species from the receiving environment can be ranked in order of susceptibility to potential impact, and guide test species selection. The case study used for this example was ryegrass, a forage plant, which had been modified to produce elevated levels of the lipid triacylglyceride. The previously described priority ranking of nontarget invertebrates model (PRONTI), designed to rank invertebrates for biosafety testing, has been adapted for use with these plants, which could, potentially, be beneficial to invertebrate populations, and applied to data on 246 known pasture invertebrate species. The output from the model for the top 20 ranked pasture invertebrate species is discussed, the attributes of these are considered along with the level of uncertainty in the information used. Consideration is given to how the model output can be interpreted and used in a biosafety risk assessment. While some subjectivity is involved in establishing the scores, all invertebrate species are subjected to the same analysis, and treated equally. In this way, regulators have a method of a risk assessment that is evidence-based, and transparent in its assumptions thereby avoiding potential for bias.


Radiotherapy mucositis in head and neck cancer: prevention by low-energy surface laser.
Modern radiotherapy (RT) planning techniques and the use of oral supportive care have reduced the occurrence of acute radiation-induced toxicities. Oral mucositis remains a major concern in patients with head and neck cancer as it can compromise treatment compliance and outcome. To report the rate of mucositis with the preventive use of surface low-level laser therapy in patients with head and neck cancer. Forty patients treated with definitive (n=27) or adjuvant (n=13) RT using volumetric arc therapy between August 2014 and October 2015 for squamous cell carcinoma of the head and neck were included. All patients were treated using photobiomodulation using surface low-level laser therapy (Heltschl kind FL 3500, 350 mW), 3 times a week during the whole treatment course. The grade of mucositis was obtained from week 1 to week 7 and at 1 month. The median RT dose was 70 Gy (64-70). Concomitant chemotherapy was administered in 29 patients. According to the Common Terminology Criteria for Adverse Events (CTCAE) v. 3, grade 0, 1, 2 and 3 mucositis was observed in 9 (22.5%), 9 (22.5%), 16 (40%) and 6 (15%) patients at week 7, and 32 (80%), 2 (5%), 3 (7.5%) and 3 (7.5%) patients at 1 month following treatment. No grade 4 occurred. Median average and maximum dose to the oral mucosa was 42 Gy (12.9-66.3) and 66.6 Gy (39-76), respectively. Despite a substantial dose to the oral mucosa, the rate of acute radiation-induced mucositis of grade ≥3 remains low in patients receiving extraoral low-energy laser during RT.


[Water supply for Peking ducks--possible alternatives for bathing].
In order to investigate possible advantages of open water drinkers such as troughs and bells in the intensive husbandry of ducks, we evaluated in this study the effect of open water systems on the behavior and health of peking ducks. In this investigation six fattening trials each with 1152 Cherry Valley Peking ducks were analyzed. The average fattening period was 47 to 49 days. The ducks were kept on straw in six standardized compartments each 32 qm with 192 ducks. 25% of the compartment with perforated grid, with one of the tested water systems. In contrast to pens with nipple-drinkers only, the ducks in pens with open water troughs/showers had the opportunity to exhibit their natural drinking behavior and water associated activities in accordance with the animal welfare requirements. In the free-choice pens the open water systems were significantly preferred, and over a 24-hour period the ducks in watering areas with open water troughs showed higher activity. Limiting the access to the open water systems to eight, four or two hours per day led to an increased use per time unit. Ducks with access to nipple drinkers only showed a significantly higher percentage of plugged up nostrils than animals from pens with open water drinkers. Open water drinkers had also a positive impact on the plumage condition.


Skipping has lower knee joint contact forces and higher metabolic cost compared to running.
The health benefits of running based exercise programs are plentiful however the high rate of injury in these programs often reduces or eliminates exercise participation. Skipping has shorter steps, reduced vertical ground reaction forces (GRFs), and lower knee extensor torques, compared to running forming the basis of the present hypothesis that skipping would have lower tibio-femoral and patello-femoral joint contact forces. The purpose of this study was to compare knee contact forces between skipping and running at the same speed. We also compared metabolic cost of these two gaits to examine the idea that the larger vertical displacement in skipping is a primary factor in its previously reported high metabolic cost. The study evaluated joint contact forces through musculoskeletal modeling with GRF and 3D kinematic data and metabolic cost using oxygen consumption data from 20 young, healthy, trained participants as they skipped and ran on an instrumented treadmill at 2.68 m/s. Skipping, compared to running, had substantially lower tibio-femoral and patello-femoral joint contact forces and linear impulses on both per-step and per-kilometer (i.e. lower cumulative loads) bases and also 30% higher metabolic cost. The lower joint loads in skipping were directly associated with its shorter steps and the higher metabolic cost was directly associated to its larger vertical displacement through the stride. As joint loads may predispose individuals to running related injuries, skipping presents an attractive alternative exercise modality with additional increased aerobic benefits.


Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer.
To compare markers of ovarian reserve between women exposed to cytotoxic chemotherapy for early stage breast cancer and matched controls. Cross-sectional evaluation of markers of ovarian reserve. Dana-Farber/Brigham and Women's Cancer Center, Massachusetts General Hospital, and Faulkner Hospital in Boston, MA. Breast cancer survivors with continued menses after chemotherapy were compared with age-matched, gravidity-matched controls. Antral follicle count (AFC), anti-Müllerian hormone (AMH), FSH, inhibin B (InB), and E(2) on day 2, 3, or 4 of the menstrual cycle. A Bonferroni correction was performed to correct for multiple comparisons. Twenty survivors and 20 controls were evaluated; 50% of survivors were currently on tamoxifen. Median AFC was 6 for survivors and 9.5 for controls. There were significant differences between the two groups in AFC, AMH, and nonsignificant differences in FSH and InB, all indicating better ovarian reserve in controls. The AFC and AMH levels were highly correlated (r = 0.72). Survivors on tamoxifen had lower AFC, AMH, InB, and higher E(2) than nontamoxifen-treated survivors. Premenopausal breast cancer survivors have diminished ovarian reserve compared with controls.


A Silicon-Based Adaptable Edge Coherent Radar Platform for Seamless Health Sensing and Cognitive Interactions With Human Subjects.
Empowered by the rapid advancements of semiconductor techniques, emerging areas such as industry 4.0, precise healthcare, pervasive communications, intelligent robots, and smart buildings are to be realized, which put substantial demands on low-power and high-performance cognitive edge sensors. Capabilities of precise sensing and seamless interactions with human subjects are pivotal to boosting versatile Internet of Everything (IoE) applications. However, it is challenging to attain various kinds of intuitive sensing based on one edge sensor. A novel silicon-based phased-array coherent radar sensing platform is proposed to attain versatile application-driven capabilities by focusing the wideband radar beams accurately at the target's direction to attain precise sensing. The coherent radar platform can support a maximum 60° field-of-view sensing range with smaller than 2° optimum steering step resolution and -70-dBm sensitivity. The silicon-based mixed-signal coherent radar chip platform is fabricated by a 65-nm CMOS process and owns the convenience for massive deployments at the edge. A series of experiments were conducted to validate the integrated radar platform's adaptable capabilities and salient performances on human subject detection, vital signs monitoring, and motion recognition. Notably, the adaptable multifunction integrated radar platform opens up the enticing possibility for next-generation monolithic edge devices supporting seamless health sensing and cognitive interactive functions with human subjects.


Regulation of cytochrome P-450 (CYP) 1B1 in mouse Hepa-1 variant cell lines: A possible role for aryl hydrocarbon receptor nuclear translocator (ARNT) as a suppressor of CYP1B1 gene expression.
Cytochrome P-450 (CYP) 1B1 expression in mouse hepatoma (Hepa-1) wild-type (WT) cells was compared with responses in Hepa-1 variants LA1 and LA2, which, respectively, exhibit low aryl hydrocarbon receptor (AhR) level and defective AhR nuclear translocator (ARNT) protein. 10T1/2 mouse embryo fibroblasts express predominantly CYP1B1 and at a 100 times higher level than in Hepa-1 cells, whereas they express about 300-fold lower CYP1A1 than Hepa-1 cells. The expression of CYP1B1 in WT and LA1 variant, although at a much lower level, follows that of CYP1A1, reflecting their common regulation through the AhR. The LA2 (ARNT-defective) cells showed a major difference between CYP1B1 and CYP1A1 expression. Although CYP1A1 mRNA levels in LA2 were extremely low and unresponsive to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), basal CYP1B1 mRNA and protein were expressed at levels similar to those seen in TCDD-induced WT. The elevated basal CYP1B1 mRNA in LA2 cells decreased by 50% after transient transfection of ARNT cDNA, in parallel with substantial restoration of CYP1A1 induction. This implicates ARNT as a suppressor of CYP1B1 basal expression in Hepa cells. In transient CYP1B1-luciferase constructs in LA2 cells, ARNT shows stimulatory effects in the enhancer region but an inhibitory effect on the proximal promoter. Two CYP1B1 enhancer elements [xenobiotic-responsive element (XRE) 1/2 and XRE4] formed TCDD-unresponsive complexes of similar mobility to TCDD-stimulated AhR-ARNT complex with XRE5. However, because these two complexes were formed to the same extent in LA2 as in WT cells, they cannot be due to ARNT or contribute to ARNT-regulated suppression.


Risk factors for falls in multiple sclerosis: an observational study.
People with multiple sclerosis (MS) experience frequent falls, which are associated with impairments and limitations to activities and participations. The objective of this paper is to evaluate falls risk factors using robust clinical measures. A total of 150 individuals (confirmed MS diagnosis, Expanded Disability Status Scale (EDSS) 3.5-6.5) were recruited, with 148 participants included in the final analysis. Demographic data were collected and performance assessed in eight predictor measures (Physiological Profile Assessment (PPA), Brief Ataxia Rating scale, Ashworth scale (Ashworth), Modified Falls Efficacy scale, Symbol Digit Modalities Test, dual-task interference, lying/standing blood pressure, static/dynamic visual acuity). Participants prospectively recorded falls over three months using a daily diary. People were classified as "fallers" based on reports of ≥ two falls. A total of 104 participants recorded 672 falls; 78 (52.7%) reported ≥ two falls. Continence issues, previous falls history and use of prescribed medications were each associated with increased risk of being a "faller". Ashworth and PPA risk score contributed significantly to a logistic regression model predicting faller/non-faller classification. The reduced model (Ashworth, PPA, EDSS) showed fair-to-good predictive ability (ROC c-statistic 0.73, sensitivity 70%, specificity 69%). This study confirms the high prevalence of falls in ambulant people with MS. Important potentially modifiable risk factors are identified, suggesting aspects to target in falls interventions.