Long-Term Results of the Risk-Stratified Treatment of TCF3-PBX1-Positive Pediatric Acute Lymphoblastic Leukemia in China.
Acute lymphoblastic leukemia (ALL) with t(1;19)/TCF3-PBX1 is a common genotype, and its prognosis has significantly improved owing to risk stratification and intensive treatment. This study aimed to determine the outcomes and prognostic factors of patients with TCF3-PBX1 treated with the modified Berlin-Frankfurt-Münster protocol. Between 2005 and 2017, a total of 1051 pediatric patients with ALL were enrolled. TCF3-PBX1 was detected by reverse-transcriptase PCR and/or cytogenetic analysis. Clinical characteristics and treatment outcomes were analyzed and compared in patients with TCF3-PBX1 and with other B-precursor ALL (B-ALL). TCF3-PBX1 was detected in 64 patients with ALL (6.1%), and all were of B-cell lineage. These patients were more likely to express the pre-B-ALL immunophenotype (P < .001), be in the National Cancer Institute high-risk group (P = .030), and exhibit more rapid disease clearance during induction therapy (P < .001) compared to patients with other B-ALL. However, the outcomes of this genotype were not better than those of other patients with intermediate risk. At a median (range) follow-up of 60.6 (0.8-184.5) months, the estimated 5-year overall survival was 85.2 ± 4.6% versus 88.2 ± 1.8% (P = .500) and 5-year event-free survival was 76.8 ± 5.5% versus 83.0 ± 2.0% (P = .210) for patients with TCF3-PBX1 and those with other B-ALL. After adjusting for other risk factors, reemergent minimal residual disease (MRD) was the most significant poor prognostic indicator for patients with TCF3-PBX1. The overall outcome of patients with TCF3-PBX1 was intermediate at our institution. Sequential MRD measurement is important for this genotype. Thus, more efforts should be made to eradicate reemergent MRD to improve prognosis.


Influence of internal muscle properties on muscle shape change and gearing in the human gastrocnemii.
Skeletal muscles bulge when they contract. These three-dimensional shape changes, coupled with fiber rotation, influence a muscle's mechanical performance by uncoupling fiber velocity from muscle belly velocity (i.e., gearing). Muscle shape change and gearing are likely mediated by the interaction between internal muscle properties and contractile forces. Muscles with greater stiffness and intermuscular fat, due to aging or disuse, may limit a muscle's ability to bulge in width, subsequently causing higher gearing. The aim of this study was to determine the influence of internal muscle properties on shape change, fiber rotation, and gearing in the medial (MG) and lateral gastrocnemii (LG) during isometric plantar flexion contractions. Multimodal imaging techniques were used to measure muscle shear modulus, intramuscular fat, and fat-corrected physiological cross-sectional area (PCSA) at rest, as well as synchronous muscle architecture changes during submaximal and maximal contractions in the MG and LG of 20 young (24 ± 3 yr) and 13 older (70 ± 4 yr) participants. Fat-corrected PCSA was positively associated with fiber rotation, gearing, and changes in thickness during submaximal contractions, but it was negatively associated with changes in thickness at maximal contractions. Muscle stiffness and intramuscular fat were related to muscle bulging and reduced fiber rotation, respectively, but only at high forces. Furthermore, the MG and LG had varied internal muscle properties, which may relate to the differing shape changes, fiber rotations, and gearing behaviors observed at each contraction level. These results indicate that internal muscle properties may play an important role in mediating in vivo muscle shape change and gearing, especially during high-force contractions.NEW & NOTEWORTHY Here, we measured internal muscle properties in vivo to determine their influence on the varying shape change and gearing behaviors in the synergistic gastrocnemii muscles. These relationships have previously only been hypothesized or examined within isolated muscles during supramaximal contractions. Our results contribute to a more comprehensive understanding of the factors that influence a muscle's mechanical response to force with implications for preventing or treating muscle deficits associated with aging, disease, and disuse.


Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases during normal human pulmonary development.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in lung development because they play an important role in the turnover of the extracellular matrix. Although limited data on MMP and TIMP expression are available from animal studies during prenatal pulmonary development, little is known about their expression during human fetal lung development. The aim of this study was to investigate the expression of MMP-1, -2, -9, TIMP-1, -2 and -3 in human fetal lungs from 9 to 42 weeks of gestation. Forty-five normal human fetal lung samples were analysed by immunohistochemistry. MMP-1, -9, TIMP-1, -2 and -3, but not MMP-2, were expressed in the epithelium at all gestational ages. The endothelium of all vessels and the arterial smooth muscle cells expressed MMP-1, -2, -9, TIMP-2 and -3, but not TIMP-1, at all developmental stages. The extensive distribution of MMPs and TIMPs throughout all stages of human lung development suggests that they play a significant role in the remodelling that occurs in the interstitium and epithelial basement membrane during lung development and in pulmonary vascular development. These data will serve as a base line for comparison with neonatal lung pathology, including pulmonary hypertension.


Copper deficiency and effects of copper supplementation in a herd of red deer (Cervus elaphus).
Copper (Cu) deficiency was diagnosed in a Norwegian red deer (Cervus elaphus) herd subsequent to deaths due to emaciation in late autumn 1999. The animals had free access to salt licks containing 3000 mg Cu/kg. An evaluation of the herd revealed poor calf growth rate, low weights of adult hinds, dull and light-coloured hair coats and cases of diarrhoea. The herd was subsequently monitored throughout a three-year period of Cu-supplementation. The monitoring regimen included clinical observation, copper serum examination, weighing, faecal parasitological examination, and reproduction control by ultrasound. During the period January 2000 to May 2001, the animals were treated with Cu oxid capsules (1 g CuO/10 kg liveweight) at 2-4 months intervals, with the exception of March to September 2000. The animals were fed continuously with Cu-enriched concentrates containing 300 mg Cu/kg, at a rate of 1/2 kg per head and day, from May 2001 to January 2003. Following both copper supplementation regimens adequate serum Cu concentrations were measured, and markedly improved body weights, coat quality and reproductive results were observed, except for the period from March to September 2000 when no treatment was given. The results showed that in a deer herd, with a diet low in Cu, supplementation with CuO capsules had to be given at intervals of a few months to maintain adequate serum Cu levels. Free access to Cu-containing salt licks did not meet the animals' Cu demand. Good and stable results were achieved by the daily feeding of Cu-enriched concentrates.


Soluble factors released by activated cytotoxic T lymphocytes interfere with death receptor pathways in neuroblastoma.
Neuroblastoma (NB) is often described as an unfavorable target for both HLA-restricted and death receptor-mediated elimination by cytotoxic T lymphocytes (CTLs) due to low or absent HLA class I and caspase-8 expression. We investigated the effects of soluble factors released by CTLs activated by TCR triggering (named as activated supernatant; AS) on the levels and composition of cell surface molecules involved in HLA-restricted and HLA-independent NB cell recognition (surface immune phenotype). Using a panel of long-term propagated NB cell lines and freshly isolated primary human NB cells, we analyzed surface expression of the (1) cognate receptors for TNFalpha, Fas and TRAIL; (2) HLA class I and II heterodimers; (3) adhesion molecules; (4) the intracellular expression and activation of caspase-8, as well as (5) the susceptibility of NB cells to death receptor-mediated killing prior to and after exposure to AS. The exposure of NB cells to soluble factors released by activated CTLs skewed the surface immune phenotype of both long term cultured and primary NB cells, induced the expression and activation of caspase-8 and increased the susceptibility of tumor cells to lysis by TRAIL and Fas-agonistic antibody. Blocking experiments identified IFNgamma and TNFalpha as main factors responsible for modulating the surface antigens of NB cells by AS. Our data suggest that recruitment of CTLs activated on third party targets into the vicinity of the NB tumor mass, may override the "silent" immune phenotype of NB cells via the action of soluble factors.


scROSHI: robust supervised hierarchical identification of single cells.
Identifying cell types based on expression profiles is a pillar of single cell analysis. Existing machine-learning methods identify predictive features from annotated training data, which are often not available in early-stage studies. This can lead to overfitting and inferior performance when applied to new data. To address these challenges we present scROSHI, which utilizes previously obtained cell type-specific gene lists and does not require training or the existence of annotated data. By respecting the hierarchical nature of cell type relationships and assigning cells consecutively to more specialized identities, excellent prediction performance is achieved. In a benchmark based on publicly available PBMC data sets, scROSHI outperforms competing methods when training data are limited or the diversity between experiments is large.


The longitudinal study of rat hippocampus influenced by stress: early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats.
Epidemiologic studies indicate that early adverse experience is related to learning disabilities in adults, but the neurobiological mechanisms have not yet been identified. We used longitudinal animal experiments to test the hypothesis that early life stress enhances hippocampal vulnerability and working memory deficit in adult rats. The expression of Synaptophysin (SYN) and apoptosis (Apo) in hippocampal CA3 and dentate gyrus (DG) regions were examined to evaluate the effects of environmental factors on the hippocampus. The working memory errors via radial 8-arm maze were studied to evaluate the long-term effect of early stress on rats' spatial learning ability. Our results indicated that chronic restraint stress in early life and forced cold water swimming stress in adulthood reduced SYN expression and increased Apo levels in rat hippocampus, but the hippocampal damage tended to recover when rats returned to a non-stress environment. In addition, when the rats were exposed to forced cold water swimming stress during adulthood, SYN expression (CA3 and DG regions) and Apo levels (CA3 region) in rat hippocampus showed statistical difference between early restraint stress group and non-early restraint stress group (rats exposed to stress in adulthood only). One month after the two groups of rats returned to non-stress environment, this difference of SYN expression (CA3 and DG regions) and working memory deficit between the two groups was still statistically significant. Our study findings suggested that early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats, and reduces structural plasticity of hippocampus.


Statistical Analysis Options for Antibody Array Data.
In this chapter, we introduce the application of R, a statistical programming language in the analysis of antibody array data. We start from a brief introduction of R itself and then cover data filtration and transformation, data visualization, differential expression analysis with/without variance correction, co-expression network, functional enrichment analysis, and statistical modeling.


Adherence to the World Cancer Research Fund/American Institute for Cancer Research and Korean Cancer Prevention Guidelines and cancer risk: a prospective cohort study from the Health Examinees-Gem study.
The purpose of this study was to explore the association between adherence to 2 cancer prevention recommendations and cancer risk. In total, 104,386 individuals aged 40-69 years old who were recruited between 2004 and 2013 in the Health Examinees-Gem study were included. Adherence scores were constructed based on 8 items from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations, including body weight, physical activity, diet, alcohol consumption and breastfeeding, and on 6 items from the Korean cancer prevention guidelines (smoking status, eating vegetables and fruits, salty foods, alcohol intake, physical activity, and body weight). A Cox proportional hazards model was used to estimate the associations between adherence scores and the risk of total and 5 major cancers. The multivariable hazard ratio (HR) for total cancer with the high adherence score versus the lowest score (4.25-7.00 vs. 0.00-3.25) for the WCRF/AICR guidelines was 0.91 (95% confidence interval [CI], 0.82 to 1.00) in men. A reduced breast cancer risk was observed among women with the highest score. Men within the highest category of the Korean cancer prevention guideline score (3.25-6.00) had an HR of 0.80 (95% CI, 0.73 to 0.88) for developing total cancer compared to men within the lowest score (0.00-2.50). The higher adherence group among men showed lower risks of developing stomach, colorectal, and lung cancers. Adhering to guidelines for cancer prevention can help to reduce the risk of developing cancer in Korean men. The association might differ by cancer type and gender.


Modulation of DNA breakage induced via the Fenton reaction.
The conversion of the covalently closed circular double-stranded supercoiled DNA (pBR322) to a relaxed circle was used to investigate DNA nicking induced by Fe2+ and H2O2. In our experimental conditions of ionic strength (150 mM NaCl), pH = 7 and temperature (37 degrees C), the dose-response curve for the ferrous iron mediated H2O2 dependent DNA nicking is peculiar. For a fixed concentration of ferrous iron (2 microM), the concentration of H2O2 producing a maximum extent of DNA nicking was about 10-30 microM. The DNA single-strand breakage decreased with an increase of H2O2 concentration. We have investigated the effects of several factors such as the nature of the buffer, ionic strength, temperature and pH. Buffer components leading to the autoxidation of ferrous iron to ferric iron (phosphate) or to the scavenging of reactive oxygen species (Tris) greatly alter the dose-response curve. The H2O2 concentrations required for producing the maximum extent of DNA single-strand breaks at 4 degrees C and 56 degrees C were respectively 30 microM and 3 microM. At pH = 10, the pattern of the dose-response curve was totally different. The data showed that the peculiar dose-response curve for the ferrous iron mediated H2O2 dependent DNA nicking greatly depended on the experimental conditions.


Comparison of trichiasis recurrence after primary bilamellar tarsal rotation or anterior lamellar repositioning surgery performed for trachoma.
To compare the trichiasis recurrence rate following bilamellar tarsal rotation or anterior lamellar repositioning, performed as primary surgery for trachomatous trichiasis. Retrospective consecutive case series. All cases of trachomatous trichiasis undergoing primary surgical correction at Alice Springs Hospital, Alice Springs, Northern Territory, Australia, between 1 June 2001 and 11 June 2011 were included. Retrospective chart review. Key baseline, operative and outcome details were collected from the notes. Recurrent trichiasis was defined as one or more lashes touching the cornea, resulting in recurrent symptoms of trichiasis and warranting further surgery in the opinion of the treating ophthalmologist. Sixty-seven BTR and eighteen ALR procedures were performed, with BTR being performed from 2001 to 2008, and ALR from 2008 to 2011. The mean follow-up times were significantly different for the BTR group (1654 days) and for the ALR group (673 days)(P < 0.001). Kaplan-Meier survival analysis did not reveal any significant differences in recurrence rate between the two procedures overall (P = 0.935). Analysis of the 2008 calendar year (the only year where both procedures were performed and therefore had equal follow-up times) suggested that ALR might have a lower recurrence rate (1/10 ALR recurrences vs. 4/6 BTR recurrences, P = 0.181). The results do not demonstrate a difference in the recurrence rate between the two techniques. Inconsistent follow times however leave uncertainty in this result, and a larger prospective randomised study is warranted to address this question.


The organization of repeated nucleotide sequences in the replicons of mammalian DNA.
Chinese hamster ovary cells were irradiated with 100-5,000 rads of X-rays and inhibition of the initiation of replicons after irradiation was demonstrated by analyzing nascent DNA sedimented in alkaline sucrose gradients. The renaturation kinetics of DNA synthesized during 60 min of incubation after irradiation was compared with that of DNA synthesized during the 60 min after sham irradiation and with that of parental DNA. Nascent DNA from cells whose replicon initiation was inhibited renatured faster than nascent DNA from control cells in the COt range of repeated nucleotide sequences, suggesting that regions of the replicon not close to origins are enriched in repeated sequences and that regions close to origins are enriched in unique sequences. A class of repeated nucleotide sequences may be involved in the regulation of replicon initiation.


The filament-forming protein Pil1 assembles linear eisosomes in fission yeast.
The cortical cytoskeleton mediates a range of cellular activities such as endocytosis, cell motility, and the maintenance of cell rigidity. Traditional polymers, including actin, microtubules, and septins, contribute to the cortical cytoskeleton, but additional filament systems may also exist. In yeast cells, cortical structures called eisosomes generate specialized domains termed MCCs to cluster specific proteins at sites of membrane invaginations. Here we show that the core eisosome protein Pil1 forms linear cortical filaments in fission yeast cells and that purified Pil1 assembles into filaments in vitro. In cells, Pil1 cortical filaments are excluded from regions of cell growth and are independent of the actin and microtubule cytoskeletons. Pil1 filaments assemble slowly at the cell cortex and appear stable by time-lapse microscopy and fluorescence recovery after photobleaching. This stability does not require the cell wall, but Pil1 and the transmembrane protein Fhn1 colocalize and are interdependent for localization to cortical filaments. Increased Pil1 expression leads to cytoplasmic Pil1 rods that are stable and span the length of cylindrical fission yeast cells. We propose that Pil1 is a novel component of the yeast cytoskeleton, with implications for the role of filament assembly in the spatial organization of cells.


Social class, socially-induced loss, recruitment and breeding of red grouse.
Individually marked red grouse (Lagopus lagopus scoticus) could be distinguished as territorial or non-territorial from November till the next spring. Territorial birds survived well and many reared young, but numerous nonterritorial birds died or disappeared, and none paired up or reared young. Differences in spring sex ratio between years had already been set in the previous autumn's territorial stock. Many old birds which had been territorial in earlier seasons lost territories after an annual re-distribution of territory each October-November. Thereafter very few of them were seen alive on the area over the winter, and many were found dead, whereas nearly all old birds that kept their territories were still there in spring. The number of birds in spring and the fate of individuals over winter were predicted reasonably accurately from observations of behaviour in the previous November-December. Thus, differences of social class in autumn were critical to a bird's survival to breed in the next summer and to its chances of contesting for territory and breeding in subsequent years.


SUMOylation of the hepatoma-derived growth factor negatively influences its binding to chromatin.
Hepatoma-derived growth factor is a nuclear targeted mitogen containing a PWWP domain that mediates binding to DNA. To date, almost nothing is known about the molecular mechanisms of the functions of hepatoma-derived growth factor, its routes of secretion and internalization or post-translational modifications. In the present study, we show for the first time that hepatoma-derived growth factor is modified by the covalent attachment of small ubiquitin-related modifier 1 (SUMO-1), a post-translational modification with regulatory functions for an increasing number of proteins. Using a basal SUMOylation system in Escherichia coli followed by a MALDI-TOF-MS based peptide analysis, we identified the lysine residue SUMOylated located in the N-terminal part of the protein adjacent to the PWWP domain. Surprisingly, this lysine residue is not part of the consensus motif described for SUMOylation. With a series of hepatoma-derived growth factor mutants, we then confirmed that this unusual location is also used in mammalian cells and that SUMOylation of hepatoma-derived growth factor takes place in the nucleus. Finally, we demonstrate that SUMOylated hepatoma-derived growth factor is not binding to chromatin, in contrast to its unSUMOylated form. These observations potentially provide new perspectives for a better understanding of the functions of hepatoma-derived growth factor.


Detection of brain tumor invasion and micrometastasis in vivo by expression of enhanced green fluorescent protein.
To determine whether fluorescence from human brain tumor cells transfected with the enhanced green fluorescent protein (EGFP) gene in vitro and xenotransplanted into the brain of nude mice would permit the detection of brain tumor invasion and metastasis in vivo. Daoy medulloblastoma cells were transfected with a long terminal repeat-based retroviral vector containing the EGFP gene. Stable EGFP-expressing clones were isolated and stereotactically injected into the frontal cortex of nude mice. Four weeks later, whole brain sections were examined using fluorescence microscopy, immunohistochemistry, and routine hematoxylin and eosin staining for the visualization and detection of tumor cell invasion and metastasis. We demonstrate that EGFP-transduced Daoy cells maintain stable high-level EGFP expression in the central nervous system during their growth in vivo. EGFP fluorescence clearly demarcated the primary tumor margins and readily allowed for the visualization of distant micrometastases and local invasion on the single-cell level. Small metastatic and locally invasive foci, including those immediately adjacent to the tumor's leading invasive edge, were virtually undetectable by routine hematoxylin and eosin staining and immunohistochemistry. EGFP expression also persisted in vitro after cell reculture from brain tissue extracts. We show, for the first time, that EGFP-transduced human brain tumor cells can be visualized by fluorescence microscopy after intracerebral implantation. This method is superior to routine hematoxylin and eosin staining and immunohistochemistry for the detection and study of physiologically relevant patterns of brain tumor invasion and metastasis in vivo.


Microcantilever biosensors.
Biosensors are sensors in which biomolecular interactions are used as sensing reactions. Biomolecular interactions, when combined with a microcantilever platform, can produce an extremely powerful biosensing design. The resonance frequency of a microcantilever shifts sensitively due to mass loading from molecular interaction as in the case of any acoustic sensors. In addition, the microcantilevers also undergo bending if the molecular adsorption is confined to a single surface of a microcantilever. This cantilever bending is due to a differential surface stress caused by the forces involved in the adsorption process and is amplified by making the cantilever surfaces chemically different. Lack of specificity, the main disadvantage of the cantilevers, can be overcome by using the extremely selective biochemical reactions such as receptor-ligand, antibody-antigen, or enzyme-substrate reactions. Here we review the microcantilever technology and discuss a number of highly sensitive biochemical sensor applications based on microcantilevers.


Increased risk of hyperlipidemia in patients with major depressive disorder: a population-based study.
We conducted this study to examine the prevalence and incidence of hyperlipidemia among Taiwanese patients with major depressive disorder (MDD). We used a random sample of 766,427 subjects who were ≥ 18 years old in 2005. Subjects with at least one primary diagnosis of MDD were identified. Individuals with a primary or secondary diagnosis of hyperlipidemia or medication treatment for hyperlipidemia were also identified. We compared the prevalence of hyperlipidemia in MDD patients with the general population in 2005. We followed this cohort from 2006 to 2010 to detect incident cases of hyperlipidemia in MDD patients compared with the general population. The prevalence of hyperlipidemia in patients with MDD was higher than in the general population (14.4% vs. 7.9%, odds ratio 1.67; 95% confidence interval, 1.53-1.82) in 2005. The average annual incidence of hyperlipidemia in patients with MDD was also higher than in the general population (3.62% vs. 2.55%, risk ratio 1.35; 95% confidence interval, 1.24-1.47) from 2006 to 2010. Higher incidence of hyperlipidemia was associated with MDD group, increased age, diabetes, hypertension, and higher socioeconomic status. Patients with MDD had a higher prevalence and incidence of hyperlipidemia compared with the general population. Younger MDD patients and MDD patients with first-generation antipsychotic exposure or antidepressant exposure had an increased risk of hyperlipidemia compared with individuals in the general population.


Lung disease in Niemann-Pick disease.
Lung involvement in children with Niemann-Pick disease has rarely been studied systematically. To assess the involvement of the lung and the value of bronchoalveolar lavage in children with Niemann-Pick diseases. Retrospective analysis of patient records. Thirteen patients, with type A (n = 1), type B (n = 10), and type C (n = 2) Niemann-Pick disease, aged 2 months to 9 years at diagnosis, were included in the study. Lung involvement was assessed by clinical evaluation, chest radiograph, lung computed tomography (CT) scan, pulmonary function tests, and bronchoalveolar lavage fluid analysis. Respiratory symptoms were present at diagnosis in 10 patients and developed during follow up in the three other patients. All patients showed signs of interstitial lung disease on chest X-ray and lung CT scan. Bronchoalveolar lavage fluid analysis (n = 7) revealed a marked accumulation of foamy macrophages (Niemann-Pick cells) in all patients. At follow up, one patient died of respiratory failure, five patients required long term oxygen therapy and seven other patients presented a chronic obstructive pulmonary disease (n = 6) or chronic cough (n = 1). Lung disease was observed in all the patients included in the present study. Bronchoalveolar lavage may be useful in Niemann-Pick diseases by showing the presence of characteristic Niemann-Pick cells.


Comprehensive search for intra- and inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: genes and pseudogenes.
The human genome carries a high load of proviral-like sequences, called Human Endogenous Retroviruses (HERVs), which are the genomic traces of ancient infections by active retroviruses. These elements are in most cases defective, but open reading frames can still be found for the retroviral envelope gene, with sixteen such genes identified so far. Several of them are conserved during primate evolution, having possibly been co-opted by their host for a physiological role. To characterize further their status, we presently sequenced 12 of these genes from a panel of 91 Caucasian individuals. Genomic analyses reveal strong sequence conservation (only two non synonymous Single Nucleotide Polymorphisms [SNPs]) for the two HERV-W and HERV-FRD envelope genes, i.e. for the two genes specifically expressed in the placenta and possibly involved in syncytiotrophoblast formation. We further show--using an ex vivo fusion assay for each allelic form--that none of these SNPs impairs the fusogenic function. The other envelope proteins disclose variable polymorphisms, with the occurrence of a stop codon and/or frameshift for most--but not all--of them. Moreover, the sequence conservation analysis of the orthologous genes that can be found in primates shows that three env genes have been maintained in a fully coding state throughout evolution including envW and envFRD. Altogether, the present study strongly suggests that some but not all envelope encoding sequences are bona fide genes. It also provides new tools to elucidate the possible role of endogenous envelope proteins as susceptibility factors in a number of pathologies where HERVs have been suspected to be involved.


Coupling and decoupling of marine stramenopiles and cyanobacteria in eutrophic coastal waters of Korea.
The spatiotemporal distribution of MASTs (MArine STramenopiles), mostly affiliated with heterotrophic protists, and their interactions with Synechococcales were investigated in an anthropogenically polluted bay of the East Sea using 18S rRNA and 16S rRNA gene sequences. The bay was characterized by strong stratification between the surface and bottom layers and cold and nutrient-rich water intrusion in summer, whereas the bay water was well mixed in winter. MAST-3, MAST-6, MAST-7, and MAST-9 were the major MAST clades, whereas the dominance of MAST-9 declined from >80 % in summer to <10 % in winter and the diversity of MAST communities increased in winter. Co-occurrence network analysis via the sparse partial least squares revealed that MAST-3 had a Synechococcales-specific interaction during the study periods but prey-specific interactions with other MAST clades were not detected. Temperature and salinity markedly influenced the relative abundance of major MAST clades. The relative abundance of MAST-3 increased at temperatures above 20 °C and salinities above 33 ‰, however, the abundance of MAST-9 decreased under the same conditions. Analysis of the metabolic functions of cyanobacteria using the FAPROTAX (Functional Annotation of Prokaryotic Taxa) indicated that the response of photosynthetic cyanobacteria to NH4+ and PO43- was significant in summer but these functions were not tightly coupled with the abundance of Synechococcales. Similarly, strong associations of MAST-3 with high temperature/salinity and Synechococcales were indicative of coupled cascading during bottom-up processes. However, other major MAST clades were likely decoupled with Synechococcales and environmental conditions in which cyanobacteria can thrive. Therefore, our results demonstrated that MAST communities can couple or decouple with environmental variables and potential prey depending on MAST clades. Collectively, our findings provide novel insights into the role of MAST communities in microbial food webs in eutrophic coastal waters.


Factors predicting screen time related to physical and behavioural complaints in primary school children.
Physical and behavioural problems from extended usage of electronic devices are issues among primary school children. This study is aimed to investigate the prevalence of physical and behavioural complaints arising from the electronic device usage and to identify the potential factors that predicted the complaints. This was a primary school-based cross-sectional study using multistage cluster sampling, conducted at Bau district in Sarawak, Malaysia in 40 primary schools. A questionnaire was used to collect information of usage pattern in insufficient lighting, timing and position. The physical and behavioural complaints were traced. Data analysis was performed using SPSS version 22. A p-value < 0.05 with 95% CI was considered as statistically significant. About 52.8% of the 569 students used digital devices in a bright room, 69.8% in the day time and 54.4% in sitting position. The physical complaints were headache (32.9%), neck, shoulder and back pain (32.9%) followed by by eye strain (31.8%). Regarding behavioural problems, 25.7% of the students had loss of interest in study and outdoor activities (20.7%), skipped meals (19.0%) and arguments/disagreements with parents (17.9%). After logistic regression analysis, the lying position (OR=1.71, 95% CI: 1.096, 2.688) and darkroom lighting (OR=2.323 95% CI: 1.138, 4.744) appeared to be potential predictors of the complaint. One-quarter of the students studied experienced physical complaints, and one-fifth had behavioural problems associated with the use of electronic devices. Lying position and darkroom lighting are the potential predictors of complaints. Therefore, we suggest that the children should use electronic devices in the sitting position with adequate room lighting.


In-vivo dose determination in a human after radon exposure: proof of principle.
Radon-222 is pervasive in our environment and the second leading cause of lung cancer induction after smoking while it is simultaneously used to mediate anti-inflammatory effects. During exposure, radon gas distributes inhomogeneously in the body, making a spatially resolved dose quantification necessary to link physical exposure conditions with accompanying risks and beneficial effects. Current dose predictions rely on biokinetic models based on scarce input data from animal experiments and indirect exhalation measurements of a limited number of humans, which shows the need for further experimental verification. We present direct measurements of radon decay in the abdomen and thorax after inhalation as proof of principle in one patient. At both sites, most of the incorporated radon is removed within ~ 3 h, whereas a smaller fraction is retained longer and accounts for most of the deposited energy. The obtained absorbed dose values were [Formula: see text] µGy (abdomen, radon gas) and [Formula: see text] µGy (thorax, radon and progeny) for a one-hour reference exposure at a radon activity concentration of 55 kBq m-3. The accumulation of long-retained radon in the abdomen leads to higher dose values at that site than in the thorax. Contrasting prior work, our measurements are performed directly at specific body sites, i.e. thorax and abdomen, which allows for direct spatial distinction of radon kinetics in the body. They show more incorporated and retained radon than current approaches predict, suggesting higher doses. Although obtained only from one person, our data may thus represent a challenge for the barely experimentally benchmarked biokinetic dose assessment model.


Estrogen causes cell death of estrogen receptor stably transfected cells via apoptosis.
We examined the effect of estrogen on the growth of estrogen receptor (ER) stably transfected cells (Rat1 + ER). 17-Beta-estradiol (E2, 10 nM) inhibited approximately 35-50% of Rat1 + ER growth after 3 d of treatment. The half-maximal growth inhibition occurred at 0.5-0.75 nM of E2 concentration and was saturated above 10 nM. This E2-induced antiproliferative effect was mediated through the ER since E2 did not cause any change in ER-negative parental Rat1 cells. Cells started to detach from plates and the adherent cells exhibited nuclear condensation. Apoptotic cell populations showed a 25% increase at 2 d of E2 treatment over controls that were quantified by fluorescence-activated cell sorter analysis. This indicates that E2 induced apoptosis in Rat1 + ER cells.


[Detection to changes in hyoid and tongue positions, and pharyngeal airway following mandibular setback surgery by cone beam CT].
To observe changes in tongue and hyoid position, and pharyngeal airway in patients with skeletal class III malocclusion after the combined orthodontic and orthognathic treatment. Twenty patients were involved in this study. Cone beam CT (CBCT) was performed on patients one week before and six months after treatment. Raw data were reconstructed into three-dimensional model. To set up a three-dimensional reference frame, which was based by point "S", the sagittal and transversal measurements, cross sectional areas, partial and total volumes were computed. The three-dimensional position changes of chin, hyoid bone and tongue were measured in order to analyze the amount of mandibular setback relationship with the changes of pharyngeal airway, hyoid bone and tongue positions. After treatment, the pharyngeal airway was constricted significantly. The hyoid significantly moved inferoposteriorly by 5.72 mm (backward) and 2.76 mm (downward) and the tongue moved posteriorly by 4.04 mm after surgery (P < 0.05). Among the 19 correlated indexes between the amount of mandibular setback and other measurements, 14 of which were significantly correlated (P < 0.05). The strongest correlation was found between the amount of mandibular setback and total volumes of pharyngeal airway (r = 0.834, P < 0.01). Following combination therapy, the pharyngeal airway space decreased, the hyoid moved inferoposteriorly and tongue moved posteriorly. There were great correlations between the amount of mandibular setback and the changes.


Genetic time traveling: sequencing old herbarium specimens, including the oldest herbarium specimen sequenced from kingdom Fungi, reveals the population structure of an agriculturally significant rust.
Sequencing herbarium specimens can be instrumental in answering ecological, evolutionary, and taxonomic inquiries. We developed a protocol for sequencing herbarium specimens of rust fungi (Pucciniales) and proceeded to sequence specimens ranging from 4 to 211 yr old from five different genera. We then obtained sequences from an economically important biological control agent, Puccinia suaveolens, to highlight the potential of sequencing herbarium specimens in an ecological sense and to evaluate the following hypotheses: (1) The population structure of a plant pathogen changes over time, and (2) introduced pathogens are more diverse in their native range. Our efforts resulted in sequences from 87 herbarium specimens that revealed a high level of diversity with a population structure that exhibited spatial-temporal patterns. The specimens sequenced from Europe showed more diversity than the ones from North America, uncovering an invasion pattern likely related to its European native host in North America. Additionally, to the best of our knowledge, the specimen from France collected in c. 1811 is the oldest herbarium specimen sequenced from kingdom Fungi. In conclusion, sequencing old herbarium specimens is an important tool that can be extrapolated to better understand plant-microbe evolution and to evaluate old type specimens to solidify the taxonomy of plant pathogenic fungi.


Characterization of naturally occurring airborne diacetyl concentrations associated with the preparation and consumption of unflavored coffee.
Diacetyl, a suspected cause of respiratory disorders in some food and flavorings manufacturing workers, is also a natural component of roasted coffee. We characterized diacetyl exposures that would plausibly occur in a small coffee shop during the preparation and consumption of unflavored coffee. Personal (long- and short-term) and area (long-term) samples were collected while a barista ground whole coffee beans, and brewed and poured coffee into cups. Simultaneously, long-term personal samples were collected as two participants, the customers, drank one cup of coffee each per h. Air sampling and analyses were conducted in accordance with OSHA Method 1012. Diacetyl was detected in all long-term samples. The long-term concentrations for the barista and area samples were similar, and ranged from 0.013⿿0.016 ppm; long-term concentrations for the customers were slightly lower and ranged from 0.010⿿0.014 ppm. Short-term concentrations ranged from below the limit of detection (<0.0047 ppm)⿿0.016 ppm. Mean estimated 8 h time-weighted average (8 h TWA) exposures for the barista ranged from 0.007⿿0.013 ppm; these values exceed recommended 8 h TWA occupational exposure limits (OELs) for diacetyl and are comparable to long-term personal measurements collected in various food and beverage production facilities. The concentrations measured based on area sampling were comparable to those measured in the breathing zone of the barista, thus exceedances of the recommended OELs may also occur for coffee shop workers who do not personally prepare coffee (e.g., cashier, sanitation/maintenance). These findings suggest that the practicality and scientific basis of the recommended OELs for diacetyl merit further consideration.


Clinical and immunological aspects of hepatitis B virus infection in children receiving multidrug cancer chemotherapy.
For two reasons hepatitis B virus infection is an important problem in patients with cancer. First, multidrug cancer chemotherapy may reactivate or worsen a previously benign chronic HBV infection. Second, patients undergoing cancer chemotherapy are at an increased risk of acquiring and spreading HBV which may result in an endemic infection. HBV reactivation may precipitate into a severe acute disease including fulminant hepatitis. In contrast, the acquisition of HBV during cancer chemotherapy commonly takes a mild clinical course but frequently leads to persistently high viremia. This state of immunotolerance to viral antigens allows viral replication without any sign of liver cell destruction. Withdrawal of chemotherapy does not cause significant changes if infection occurred during cytotoxic chemotherapy. Infection with HBV during cancer chemotherapy, therefore, may be considered as a model of an induced antigen-specific immunotolerance. In agreement with this hypothesis, vaccination against HBV during cancer chemotherapy does not prevent spread of HBV in oncology wards as it does not produce significant anti-HBs titers. Furthermore, vaccination even suppresses the immune response to later booster doses after chemotherapy has been withdrawn.


Alzheimer's disease: A hypothesis on pathogenesis.
Alzheimer's disease (AD) is the major cause of dementia. It is a systemic disorder whose major manifestations are in the brain. AD cases can be categorized into two groups on the basis of the age of onset-before or after about age 60. The majority of cases, 90-95 percent, are in the late onset category. Early onset cases are largely, if not all, familial (FAD). These are caused by mutations in the genes for the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). In contrast late onset cases are mainly sporadic. The disorder is characterized by intraneuronal fibrillary tangles, plaques, and cell loss. The brain lesions in both early and late-onset AD are the same, and in the same distribution pattern, as those seen in individuals with Down's syndrome (DS) and in smaller numbers in normal older individuals. Extensive studies of AD have yet to result in a generally accepted hypothesis on the pathogenesis of the disorder. Major emphasis has been placed on the role of amyloid, the neurotoxin formed by the action of free radicals on preamyloid. The observation that AD lesions are frequently present in normal older individuals prompted the hypothesis that AD is the result of faster than normal aging of the neurons associated with it. This hypothesis provides plausible explanations for FAD and AD. FAD is associated with mutations in APP, PS1, and PS2. These substances, along with their normal counterparts, undergo proteolytic processing in the endoplasmic reticulum (ER). The mutated compounds, aside from increasing the ratio of βA42 to βA40, may down-regulate the calcium buffering activity of the ER in a manner akin to one or more of the many compounds known to do so. Decreases in the ER calcium pool would cause compensatory increases in other calcium pools, particularly in mitochondria. Increases in mitochondrial calcium levels are associated with enhanced formation of superoxide radical formation, and hence of the rate of aging. SAD may be caused by nuclear and/or mitochondrial DNA mutations beginning early in life that enhance mitochondrial superoxide radical formation in the neurons associated with the disorder. The above explanations for FAD and AD are suggestive of measures to prevent and for treatment.


Radiotherapy and pregnancy.
We present the updated recommendations of the French society for radiation oncology on radiotherapy and pregnancy. The occurrence of cancer during pregnancy is a rare event (approximately 1 in 1000 pregnancies). The risks for the embryo or the foetus depend on the gestational age at the time of irradiation. The main risks are malformations with microcephaly and mental retardation. There is also a risk of radiation-induced cancer in the unborn child. In the case of only supradiaphragmatic irradiation, radiotherapy can be performed most often in pregnant women without risk to the foetus. On the other hand, in the case of an indication for subdiaphragmatic irradiation, therapeutic termination of the pregnancy should be proposed. In all cases, when radiotherapy is chosen, a phantom estimation of the dose delivered to the foetus, confirmed by in vivo measurement, is recommended. Conformational radiotherapy is the preferred technique because of the lower dose delivered to the foetus (except in tumour locations where other techniques such as IMRT are recommended).


Exploded view of higher order G-quadruplex structures through click-chemistry assisted single-molecule mechanical unfolding.
Due to the long-range nature of high-order interactions between distal components in a biomolecule, transition dynamics of tertiary structures is often too complex to profile using conventional methods. Inspired by the exploded view in mechanical drawing, here, we used laser tweezers to mechanically dissect high-order DNA structures into two constituting G-quadruplexes in the promoter of the human telomerase reverse transcriptase (hTERT) gene. Assisted with click-chemistry coupling, we sandwiched one G-quadruplex with two dsDNA handles while leaving the other unit free. Mechanical unfolding through these handles revealed transition dynamics of the targeted quadruplex in a native environment, which is named as native mechanical segmentation (NMS). Comparison between unfolding of an NMS construct and that of truncated G-quadruplex constructs revealed a quadruplex-quadruplex interaction with 2 kcal/mol stabilization energy. After mechanically targeting the two G-quadruplexes together, the same interaction was observed during the first unfolding step. The unfolding then proceeded through disrupting the weaker G-quadruplex at the 5'-end, followed by the stronger G-quadruplex at the 3'-end via various intermediates. Such a pecking order in unfolding well reflects the hierarchical nature of nucleic acid structures. With surgery-like precisions, we anticipate this NMS approach offers unprecedented perspective to decipher dynamic transitions in complex biomacromolecules.


Malaria in South Asia: prevalence and control.
The "Malaria Evolution in South Asia" (MESA) program project is an International Center of Excellence for Malaria Research (ICEMR) sponsored by the US National Institutes of Health. This US-India collaborative program will study the origin of genetic diversity of malaria parasites and their selection on the Indian subcontinent. This knowledge should contribute to a better understanding of unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and Plasmodium vivax infections. In this first of two reviews, we highlight malaria prevalence in India. In particular, we draw attention to variations in distribution of different human-parasites and different vectors, variation in drug resistance traits, and multiple forms of clinical presentations. Uneven malaria severity in India is often attributed to large discrepancies in health care accessibility as well as human migrations within the country and across neighboring borders. Poor access to health care goes hand in hand with poor reporting from some of the same areas, combining to possibly distort disease prevalence and death from malaria in some parts of India. Corrections are underway in the form of increased resources for disease control, greater engagement of village-level health workers for early diagnosis and treatment, and possibly new public-private partnerships activities accompanying traditional national malaria control programs in the most severely affected areas. A second accompanying review raises the possibility that, beyond uneven health care, evolutionary pressures may alter malaria parasites in ways that contribute to severe disease in India, particularly in the NE corridor of India bordering Myanmar Narayanasamy et al., 2012.


[Modified sternal turnover with pedicle of abdominal rectus muscle for pectus excavatum].
To assess surgical correction for children with pectus excavatum. Modified sternal turnover operation with rectus abdominalis pedicle was performed on 20 children with pectus excavatum since 1987. The patients were successfully corrected and no recurrence was seen during 6 to 36 months after operation. Human bone density examination showed same results in some patients before and six months after operation. Modified sternal turnover operation has the following advantages: easy to operate; less bleeding; better blood supply to the turned sternum; rapid postoperative recovery; satisfied correction of deformity and no recurrence. It should be widely used clinically.


B cells masquerade as dendritic cells.
In a recent paper, Schriek et al. show that, in a complement-dependent reaction, marginal zone B cells (MZBs) steal MHC class II (MHCII) from dendritic cells (DCs). Activation of T cells by stolen MHCII complexes potentially allows MZBs to augment or regulate T cell activation in ways that are distinct from DCs.


The monitoring of optimal experience. A tool for psychiatric rehabilitation.
This article illustrates the use of quantitative time-sampling data in developing a psychology of "optimal experience" to help in the psychiatric development of adequate rehabilitation approaches. The Experience-Sampling Method was used on a sample of 47 Italian adolescent students to measure fluctuations in their experience. We found that the ratio of subjectively experienced challenges and skills was a fundamental parameter that predicted optimal experience as well as boredom and anxiety. In contrast, "low" experience in daily life was viewed as a risk factor that could be minimized to increase the quality of life. Monitoring fluctuations in optimal and low experience may therefore be an important tool in developing personalized psychiatric rehabilitation plans.


Altered serotonergic neurotransmission but normal hypothalamic-pituitary-adrenocortical axis activity in mice chronically treated with the corticotropin-releasing hormone receptor type 1 antagonist NBI 30775.
Antagonists of the corticotropin-releasing hormone receptor type 1 (CRH-R1) are regarded as promising tools for the treatment of stress-related psychiatric disorders. Owing to the intricate relationship between CRH and serotonin (5-HT), we studied the effects of chronic oral treatment of C57Bl6/N mice with the CRH-R1 antagonist NBI 30775 (formerly known as R121919) on hippocampal serotonergic neurotransmission during basal (on 15th day of treatment) and stress (forced swimming; on 16th day of treatment) conditions by in vivo microdialysis. Given the important role of CRH in the regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity and behavior, the effects of NBI 30775 on dialysate-free corticosterone levels, and on home cage and forced swimming-related behavior were also assessed. Chronic administration of NBI 30775 (18.4+/-0.9 mg/kg/day) did not result in alterations in food consumption and body weight. NBI 30775 caused complex changes in hippocampal serotonergic neurotransmission. Whereas no effects on the diurnal rhythms of 5-HT and its metabolite 5-hydroxyindoleacetic acid were found, the responses of the neurotransmitter and its metabolite to 10 min of forced swim stress were reduced and prolonged, respectively. NBI 30775 did not change free corticosterone levels over the diurnal rhythm. Moreover, NBI 30775-treated mice showed a similar forced swim stress-induced increase in corticosterone as observed in the control group. No effects of NBI 30775 on home cage, and swim stress-related active behaviors (climbing, swimming) and immobility were found. Thus, whereas chronic antagonism of CRH-R1 did not compromise HPA axis performance and behavior, distinct changes in serotonergic neurotransmission developed. Owing to the important role of 5-HT in the pathophysiology of mood and anxiety disorders, the latter observation may contribute to the therapeutical efficacy of CRH-R1 antagonists in these illnesses.


Viscocanalostomy versus trabeculotomy ab externo in primary congenital glaucoma: 1-year follow-up of a prospective controlled pilot study.
To study the effectiveness of viscocanalostomy in patients with primary congenital glaucoma of the isolated trabecular dysgenesis category and compare it with trabeculotomy ab externo. Eight patients with bilateral primary congenital glaucoma were enrolled in the study. After establishing the diagnosis, the more severely affected eye was randomly selected to undergo either trabeculotomy ab externo or viscocanalostomy, whereas the second eye underwent the other surgery 2 weeks after the first. The patients were examined on day 1, week 1, week 4 and thereafter every 4 weeks. Intraocular pressure (IOP) and corneal diameter measurements were obtained at week 1, month 6 and at the last reported follow-up. The paired-sample's Student's t test was applied for statistical analysis. The mean (standard deviation (SD)) follow-up period was 12.5 (1.86) months. Preoperative IOP of eyes undergoing trabeculotomy (34.0 (2.6) mm Hg) and that of eyes undergoing viscocanalostomy (32.3 (4.1) mm Hg) showed no significant difference (p>0.1). A drop in IOP was noted in both groups at week 1, month 6 and at the last follow-up visit (p<0.001). Similarly, a decrease in the postoperative vertical and horizontal corneal diameters was noted in the two study groups. Viscocanalostomy proved to be as effective as trabeculotomy ab externo in lowering IOP. Moreover, it is likely to be a good surgical alternative with a higher long-term success rate in eyes with more aggressive disease.


Clinical guideline SEOM: hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. Surveillance with abdominal ultrasound every 6 months should be offered to patients with a high risk of developing HCC: Child-Pugh A-B cirrhotic patients, all cirrhotic patients on the waiting list for liver transplantation, high-risk HBV chronic hepatitis patients (higher viral load, viral genotype or Asian or African ancestry) and patients with chronic hepatitis C and bridging fibrosis. Accurate diagnosis, staging and functional hepatic reserve are crucial for the optimal therapeutic approach. Characteristic findings on dynamic CT/MR of arterial hyperenhancement with "washout" in the portal venous or delayed phase are highly specific and sensitive for a diagnosis of HCC in patients with previous cirrhosis, but a confirmed histopathologic diagnosis should be done in patients without previous evidence of chronic hepatic disease. BCLC classification is the most common staging system used in Western countries. Surgical procedures, local therapies and systemic treatments should be discussed and planned for each patient by a multidisciplinary team according to the stage, performance status, liver function and comorbidities. Surgical interventions remain as the only curative procedures but both local and systemic approaches may increase survival and should be offered to patients without contraindications.


Negative aging stereotypes and the agentic-communal dichotomy.
Prior research has documented negative aging stereotypes. Our hypothesis is that these only apply when a certain dimension of traits is employed and when older persons occupy certain roles. 42 college students were asked to rate the extent to which each of several "agentic" traits, e.g., active, aggressive, independent, and "communal" traits, e.g., understanding, warm, helpful, characterized a roommate and college professor, both of whom were stated to be either 23 or 65 years of age. For the roommate (but not the professor), the young person was seen as more agentic than the older person. No differences were found on the dimension of communality. It was concluded that young college students may attribute negative behaviors to older persons but this is more likely when the negative behaviors are agentic in nature and the older person occupies certain roles such as "retired person."


Immunohistochemical studies on the localization of cancer associated antigens DU-PAN-2 and CA19-9 in carcinomas of the digestive tract.
The immunohistochemical localization of DU-PAN-2 antigen and CA19-9 antigen in carcinomas of the digestive tract was studied using an immunoperoxidase technique. Staining for DU-PAN-2 antigen and CA19-9 antigen was observed in 104 (79%) and 96 (73%) of 131 carcinomas of the digestive tract, respectively. Diffuse staining (more than 20% of carcinoma cell stained) for DU-PAN-2 was detected in 14 of 21 (67%) pancreatic carcinomas and 11 of 19 (58%) carcinomas of the biliary tract (including cholangiocarcinoma). Diffuse staining for CA19-9 was detected in 15 (71%) of pancreatic carcinomas and nine (47%) of the carcinomas of the biliary tract. In colon carcinomas, no diffuse staining for DU-PAN-2 was observed, whereas diffuse staining for CA19-9 was found in 41%. There was a positive correlation between the differentiation degree (or grade) of the adenocarcinomas of the colon and the expression of CA19-9, but not that of DU-PAN-2. These immunohistochemical studies showed that DU-PAN-2 antigen is expressed diffusely in most cases of adenocarcinoma of the pancreas and biliary tract and is more specific for adenocarcinomas of the pancreas and biliary tract than CA19-9.


Polycystic nephropathy in slender lorises (Loris lydekkerianus).
In a colony of slender lorises, 20 deaths that occurred over a period of 11 years were investigated postmortem. Juvenile/adult polycystic nephropathy was observed in one newborn and 13 adult slender lorises. Although polycystic kidney disease (PKD) in humans and other animals is known to be inherited, it is not clear whether kidney alterations in slender lorises are genetically transmitted, stress related, or induced by microbiological influences.


Walnut paste: oxidative stability and effect of grape skin extract addition.
Walnut paste, obtained by roasting and grinding of kernels, was characterized and supplemented with encapsulated grape skin extract aiming to evaluate its potential effect on oxidative stability and/or antioxidant capacity. Based on the oxidation induction period in screening trials 5000 ppm (w/w) extract addition was selected as effective in inhibiting oxidation processes. Walnut paste with and without 5000 ppm grape skin extract were maintained for 15 days at 60 °C, simulating 2 year storage at 20 °C, based on an estimated activation energy of 80,327 kJ/mol for walnut lipid oxidation. Monitoring of data from peroxides, conjugated dienes and trienes, total phenolics, ABTS, ORAC, FRAP, and tocopherols values showed the deterioration of walnut paste started at the end of the observed period, even remaining below the threshold of unacceptability. Moreover, 5000 ppm extract addition did not prove to enhance oxidative stability nor antioxidant properties of the walnut paste. In the future, specific parameters of oxidation kinetics and antioxidant activity in the advanced phase of storage could be investigated.


Detecting the manipulation of digital clinical records in dental practice.
Radiography provides many advantages in the diagnosis and management of dental conditions. However, dental X-ray images may be subject to manipulation with malicious intent using easily accessible computer software. In this study, we sought to evaluate a dentist's ability to identify a manipulated dental X-ray images, when compared with the original, using a variant of the methodology described by Visser and Kruger. Sixty-six dentists were invited to participate and evaluate 20 intraoral dental X-ray images, 10 originals and 10 modified, manipulated using Adobe Photoshop to simulate fillings, root canal treatments, etc. Participating dentists were correct in identifying the manipulated image in 56% of cases, 6% higher than by chance and 10% more than in the study by Visser and Kruger. Malicious changes to dental X-ray images may go unnoticed even by experienced dentists. Professionals must be aware of the legal consequences of such changes. A system of detection/validation should be created for radiographic images.


The utility of international shoulder joint replacement registries and databases: a comparative analytic review of two hundred and sixty one thousand, four hundred and eighty four cases.
National registries are valuable tools for understanding the results of shoulder arthroplasty across populations. These databases provide an unselected view of shoulder joint replacement within geographical areas that cannot be obtained from case series or prospective studies. They can be particularly helpful in determining which diagnoses, patients, procedures, and prostheses have higher than expected rates of revision. In an attempt to determine the generalizability of registry data, we asked, 'how similar are the patients and procedures among the different national registries?' We analyzed national shoulder arthroplasty registries and databases accessed via Internet portals and through a PubMed literature search. Seven national/regional registries and five publications regarding national shoulder arthroplasty data were identified; these sources contained a combined total of 261,484 shoulder arthroplasty cases. The percentages of hemiarthroplasty, anatomic (aTSA) and reverse total shoulders (rTSA), the diagnoses leading to arthroplasty, the mean patient age, and the distribution of patient gender varied significantly among these different databases. This study indicates that the indications for and application of shoulder arthroplasty have important geographical variations and that these variations must be considered when comparing outcomes of shoulder arthroplasty from different locations. Without controlling for age, gender, diagnosis and procedure type, the results from one national registry may not be applicable to patients from a different location. In that national data provide the opportunity to reduce costs by identifying implants and procedures with higher failure rates, the funding of registries needs to be free of conflicts of interest.


Successful long-term disease-free survival following multimodal treatments in a patient with a repeatedly recurrent refractory adrenal cortical carcinoma.
A 47-year-old male patient underwent surgery for a 10-cm adrenal cortical carcinoma. A large invasive adrenal mass was surgically removed en bloc with the right kidney and the lower lobe of the liver. Two months postoperatively, a 7-cm recurrent mass developed in the right psoas muscle. After a partial response was achieved by irradiation (40 Gy) and high-dose chemotherapy (carboplatin and etoposide) with peripheral blood stem cell transplantation, the patient underwent surgery with a wide excision of the psoas muscle. Twelve months after the initial surgery, an 8-cm rib metastasis developed and the patient again underwent surgery after a combination of irradiation (50 Gy) and chemotherapy (cisplatin and etoposide). The patient has been doing well without any evidence of recurrence for 5 years. Refractory or metastatic adrenal cortical carcinomas have been thought to be lethal, therefore, the present case provides support for multimodal treatments of refractory adrenocortical cancers.


Systematic review of pleural-amniotic shunt insertion vs. conservative management in isolated bilateral fetal hydrothorax without hydrops.
In the management of bilateral fetal hydrothorax where the fetus is non-hydropic and apparently otherwise normal, we wished to determine if pleural-amniotic shunt insertion was better than conservative management in terms of mortality. A systematic review was conducted between 1992 and 2017. Data extracted was inspected for heterogeneity. Where there was comparative data available, the odds ratio (OR) and confidence interval (CI) were calculated. Seven studies were included in this systematic review. There was a paucity of comparative data where only 2 studies (28 cases) allowed for direct comparison. Within the limitations of the study, there was no difference between shunt insertion vs. conservative management in terms of stillbirth or miscarriage (OR = 1.00, 95% CI 0.12-8.34, heterogeneity I2 = 0%, p = 1.00). There is insufficient data available to determine whether the outcome is improved by pleural-amniotic shunt insertion compared with conservative management in cases of bilateral fetal hydrothorax where the fetus is non-hydropic and otherwise normal.


[Injury of the profunda femoris artery with bleeding requiring transfusion due to secondary dislocation of the lesser trochanter after osteosynthesis of an intertrochanteric femoral fracture].
A 95-year-old patient suffered bleeding that required a transfusion after closed reduction and internal fixation (CRIF) of an intertrochanteric femoral fracture with a proximal femoral nail. After mobilization of the patient the secondarily dislocated fragment of the lesser trochanter perforated a side branch of the profunda femoris artery. The bleeding could be stopped by embolization and a few days later the patient could be discharged with stable hemoglobin levels. A continuing decrease of hemoglobin levels despite repeated transfusion of red blood cells is indicative of active bleeding. Accurate identification of the source of the bleeding after osteosynthesis of proximal femoral fractures is decisive for the correct treatment.


Standardising the elusive diagnosis of NEC in the premature infant - A practical score.
The perceived risk of necrotising enterocolitis (NEC) can result in overtreatment of the otherwise adapting preterm neonate. We aim to develop an assessment tool to aid the decision making in the management of preterm neonates at risk of NEC. An evidence-based assessment tool was designed bringing together clinical, laboratory and radiological signs commonly associated with NEC. A numerical score was awarded for each sign, with those more specific to NEC being graded higher. A multi-centre validation was conducted of the proposed assessment tool over three tertiary neonatal units. A total of 125 patients were included, 53 (42.4 %) with a final diagnosis of NEC and 72 (57.6 %) with an alternative diagnosis. The NEC group had a significantly higher total score compared to the non-NEC group; 15(2-28) vs. 4(1-9) (p ≤ 0.0001). In ROC analysis, using a cut-off of eight, the assessment tool gave a sensitivity of 92.3 % and a specificity of 90.4 % for identifying NEC compared to an alternative diagnosis. This comprehensive scoring system encourages a full assessment of the infant before deciding on withholding feeds, starting antibiotics, and transferring to a surgical centre. It is a safe objective measure to support a diagnosis of NEC in the presence of certain clinical signs.


Survival Prognostic Value of Morphological and Metabolic variables in Patients with Stage I and II Non-Small Cell Lung Cancer.
The prognosis of patients with non-small cell lung cancer (NSCLC) is important, as patients with resectable disease and poor prognostic variables might benefit from neoadjuvant therapy. The goal of this study is to evaluate SUVmax, SUVmax ratio, CT volume (CTvol), metabolic tumour volume (MTV) and total lesion glycolisis (TLG) as survival prognostic markers. In addition, we defined two variables; MTV x SUVmax (MTVmax) and CTvol x SUVmax (CTvolmax) and assessed whether they can be used as prognostic markers. Patients with stage I-II NSCLC who underwent 18 F FDG PET/CT and surgery were evaluated. Cox proportional-hazard model was used to determine the association between variables and survival. Similar analysis was performed in cases with no lymph node (LN) involvement. One hundred and eighty-one patients were included (at the end of the study, 140 patients were alive). SUVmax with a cut-off value of 8.2 was significant survival prognostic factor regardless of LN involvement (P = 0.012). In cases with no LN involvement, SUVmax and CTvol (≥7.1 ml) were significant survival prognostic factors with P = 0.004 and 0.03, respectively. SUVmax may be a useful prognostic variable in stage I-II NSCLC while morphologic tumour volume might be useful in cases with no lymph node involvement. • Identifying variables that predict the prognosis of patients with NSCLC is important. • SUVmax in primary lung tumour is a useful independent prognostic variable. • (CTvol) is an independent prognostic variable if no lymph nodes are involved.


Drug-Induced Liver Injury Resources and Reporting for the Clinician.
Although many risk factors for developing drug-induced liver injury (DILI) have been identified and more than 1000 medications and herbal and dietary supplements are known to cause liver dysfunction, idiosyncratic drug reactions remain unpredictable and erratic. Varying effects of individual drugs on the event cascade and patient genetic polymorphisms lead to different clinical presentations. Mechanisms and causality scales have been developed to guide the clinician in diagnosis, and several databases and registries are available for reference and reporting. We identify and summarize the resources available to clinicians to help diagnose, manage, and report DILI and to identify hepatotoxic drugs.


Three-year survival and recurrence after first-ever stroke: the Joinville stroke registry.
Data estimating the recurrence and risk of death are lacking in low and middle income countries, where two thirds of the stroke burden occurs. Previously we had shown that the incidence and mortality have been decreasing over the last 18 years in Joinville, Southern Brazil. In this study, we aim to determine the recurrence rates, survival rates and the cause of death in 3 years after their first-ever incident in a urban population-based setting. From the Joinville Stroke Registry, we identified all the cases of first-ever stroke that occurred from October 2009 to September 2010. Multiple overlapping sources of information were used to ensure the completeness of case identification. Patients were followed up prospectively at regular intervals from 30-days to 3 years after the index event. Kaplan-Meir and Cox proportional hazards were used to assess the cumulative risk of death and recurrence. We registered 407 first-ever stroke patients. After 3 years, 136 (33%) had died. In the first year of stroke the risk of death was 28% (95% CI, 25 to 32). Beyond the first year, approximately 3 to 5% of survivors died each year. The cumulative risk of death in ischemic stroke (IS) subtypes was 3.6 higher for cardioembolic (CE) IS (hazard ratio 3.6, 95% CI, 2.1 to 6.4; p = 0.001) and 3.3 times higher for undetermined IS (HR 3.3, 95% CI 1.9 to 5.8; p = 0.001) compared to small artery occlusion IS. Over 3 years, the overall stroke recurrence risk was 9% (35/407). We found no difference in stroke recurrence risk between IS subtypes. Cardiovascular disease was the main cause of death all follow up time. Compared to other cohort studies conducted between 10 and 20 years ago in high-income countries, our recurrence rates and 3-year risk of death were similar. Among IS subtypes, we confirmed that CE has highest risk of death. The most common cause of death after a first-ever stroke is cardiovascular disease. This has implications for the uptake of current secondary preventive strategies and the development of new strategies.


Artificial intelligence and high-resolution anoscopy: automatic identification of anal squamous cell carcinoma precursors using a convolutional neural network.
High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell cancer (ASCC) precursors. Although it is superior to other diagnostic methods, particularly cytology, the visual identification of areas suspected of having high-grade squamous intraepithelial lesions remains difficult. Convolutional neural networks (CNNs) have shown great potential for assessing endoscopic images. The aim of the present study was to develop a CNN-based system for automatic detection and differentiation of HSIL versus LSIL in HRA images. A CNN was developed based on 78 HRA exams from a total of 71 patients who underwent HRA at a single high-volume center (GH Paris Saint-Joseph, Paris, France) between January 2021 and January 2022. A total of 5026 images were included, 1517 images containing HSIL and 3509 LSIL. A training dataset comprising 90% of the total pool of images was defined for the development of the network. The performance of the CNN was evaluated using an independent testing dataset comprising the remaining 10%. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve (AUC) were calculated. The algorithm was optimized for the automatic detection of HSIL and its differentiation from LSIL. Our model had an overall accuracy of 90.3%. The CNN had sensitivity, specificity, positive and negative predictive values of 91.4%, 89.7%, 80.9%, and 95.6%, respectively. The area under the curve was 0.97. The CNN architecture for application to HRA accurately detected precursors of squamous anal cancer. Further development and implementation of these tools in clinical practice may significantly modify the management of these patients.


Regional cerebral blood flow in patients with subarachnoid haemorrhage.
With a multidetector scintillation camera regional cerebral blood flow, rCBF, was evaluated in 13 patients with subarachnoid haemorrhage. Mean CBF was subnormal, and there seems to be a relationship between CBF and severity of the neurological deficit. The regional pattern showed ischaemic as well as hyperaemic areas. Vasospasms mostly produced ischaemic areas, roughly corresponding to the region supplied by the involved artery. The hyperaemic areas were striking. This hyperaemia can perhaps be regarded as a reaction to initial ischaemia.


Wearable breath monitoring via a hot-film/calorimetric airflow sensing system.
Monitoring the breath information from two nostrils can detect breath-related health problems. In this work, we introduce a wearable hot-film/calorimetric breath sensing system composed of a hot-film senor in the center and two calorimetric sensors on two sides. This design has the advantages of low power consumption of 60 mW and good sensitivity to simultaneously measure the mix breath velocity and individual breath airflow signals from the two nostrils. In prototype demonstrations, abnormal breath conditions (apnea, hypopnea, polypnea) and the asymmetric breath conditions between the right and left nostril have been recorded and analyzed for potential usages in the diagnosis of specific breath-related diseases.


Dissection of the Superficial Temporal Artery: Significance and Performance with Bipolar Forceps.
Adequate bypass harvesting of the superficial temporal artery (STA) is a standard procedure for every neurosurgeon, so mastery of techniques for its management and care is mandatory. Here, we report the effectiveness of using the bipolar forceps as a novel procedure. This procedure improves safety, efficiency, and bleeding compared to the usual dissection. In cases requiring an STA donor, this technique may be as useful as the traditional method and could become part of the neurosurgeon's armamentarium.


Quantitative variation of a 60S ribosomal protein during growth of the fungus Podospora anserina.
During the growth phase, in the fungus Podospora anserina, a variation is observed in the composition of the ribosomal proteins. A protein of the 60S subunit which is absent in the ribosomes from 2 days old cultures becomes gradully more abundant as the culture time is prolonged.


The relay of high-frequency sensory signals in the Whisker-to-barreloid pathway.
The present study investigated the operational features of whisker-evoked EPSPs in barreloid cells and the ability of the whisker-to-barreloid pathway to relay high rates of whisker deflection in lightly anesthetized rats. Results show that lemniscal EPSPs are single-fiber events with fast rise times (<500 microsec) that strongly depress at short inter-EPSP intervals. They occur at short latencies (3.84 +/- 0.96 msec) with little jitters (<300 microsec) after electrical stimulation of the whisker follicle. Waveform analysis indicates that one to three lemniscal axons converge on individual barreloid cells to produce EPSPs of similar rise times but different amplitudes. When challenged by high rates of whisker deflection, cells in the whisker-to-barreloid pathway demonstrate a remarkable frequency-following ability. Primary vibrissa afferents could follow in a phase-locked manner trains of sinusoidal deflections at up to 1 kHz. Although trigeminothalamic cells could still faithfully follow deflection rates of 200-300 Hz, the actual frequency-following ability of individual cells depends on the amplitude, velocity, and direction of displacements. The discharges of trigeminothalamic cells induce corresponding phase-locked EPSPs in barreloid cells, which trigger burst discharges at stimulus onset. During the following cycles of the stimulus train, few action potentials ensue because of the strong synaptic depression at lemniscal synapses. It is concluded that the whisker-to-barreloid pathway can relay vibratory inputs with a high degree of temporal precision, but that the relay of this information to the cerebral cortex requires the action of modulators, and possibly phase-locked discharges among an ensemble of relay cells.


Construction of Epstein-Bar virus cocktail peptide fused with Fcγ of IgG: as a potential delivery system for vaccine development.
Epstein-Barr virus (EBV) associated with several diseases such as contagious mononucleosis chronic active EBV infection, and diverse sorts of malignant tumors. Therefore, using applicable vaccines could be advantageous for public health. Yet, the vaccine has been unavailable to protect from EBV so far. In the current study, to develop a multi-peptide vaccine for EBV and assess its expression in Pichia pastoris yeast system, three immunodominant sequences in glycoprotein (gp) 85, gp350 and latent membrane protein 1 (LMP1) were chosen. To construct fusion peptide, -GGGGS- liker was applied. After cloning the fusion peptide in the pPICZαA expression vector, this recombinant vector processed and transfected into Pichia pastoris host cells. The expression of high level of EBV fusion peptide was confirmed by dot blot and SDS-PAGE procedures. The Pichia pastoris is capable of supporting EBV fusion peptide expression. The application of this fusion peptide as a peptide vaccine to fight EBV is suggested.


Water stress preconditioning to improve drought resistance in young apricot plants.
The effect of water stress preconditioning was studied in 1-year-old apricot plants (Prunus armeniaca L., cv. Búlida). Plants were submitted to different treatments, T-0 (control treatment) and T-1, drip irrigated daily; T-2 and T-3, irrigated daily at 50% and 25% of T-0, respectively; T-4 and T-5, irrigated to field capacity every 3 and 6 days, respectively. After 30 days, irrigation was withheld for 10 days, maintaining the T-0 treatment irrigated daily. After this period, the plants were re-irrigated to run-off and treated as control treatment. The stomatal closure and epinasty observed in response to water stress represented adaptive mechanisms to drought, allowing the plants to regulate water loss more effectively and prevent leaf heating. A substantial reduction in the irrigation water supplied combined with a high frequency of application (T-3 treatment) promoted plant hardening; the plants enduring drought better, due to their greater osmotic adjustment (0.77 MPa), which prevented severe plant dehydration and leaf abscission. Such a preconditioning treatment may be valuable for young apricot plants in the nursery stage in order to improve their subsequent resistance to drought. A 50% reduction in daily irrigation (T-2 treatment) did not significantly affect either gas exchange rates or leaf turgor, which suggests that water should be applied frequently if deficit irrigation is to be implemented.


Genetic control of immunity to Eimeria tenella. Interaction of MHC genes and non-MHC linked genes influences levels of disease susceptibility in chickens.
The relative importance of MHC genes and background genes in the genetic control of disease susceptibility and the development of protective immunity to E. tenella infection was investigated in eight different strains of 15I5-B congenic and four inbred chicken strains. RPRL 15I5-B congenic chickens that share a common genetic background but express different B haplotypes demonstrated wide variations in disease susceptibility and the development of acquired resistance to E. tenella infection. Infection of chickens sharing a common B haplotype but expressing different genetic backgrounds showed quite contrasting levels of susceptibility to secondary E. tenella infection. In all chicken strains examined, infected chickens developed high levels of serum and biliary anti-coccidial antibodies regardless of their B haplotypes. Furthermore, no correlation between antibody levels and the phenotypically expressed levels of disease resistance was demonstrated. These findings lend support to the view that interaction of MHC genes and non-MHC genes influences the outcome of host response to E. tenella infection.


Dietary diversity, environment and health-related factors of under-five children: evidence from cassava commercialization households in rural South-West Nigeria.
Diverse and quality diets are crucial to sustainable growth and development of under-five children, especially those of rural farming households. This study investigated the dietary diversity, environment, and health-related factors of young children. The study employed the use of cross-sectional survey data from 140 under-five children of cassava farming households in Ogun and Oyo states, South-West Nigeria. The study estimated factors influencing dietary diversity of under-five children and assessed children dietary diversity, and the availability of some environment and health-related factors of the farming households. The findings indicated that 98.7% and 97.5% of children consumed grains, with roots and tubers while 36.7% and 36.3% consumed legumes in Ogun and Oyo states respectively. The results also found that 48.6% of children sampled met the minimum cut-off point of 4 food groups with dietary diversity mean score of 3.28. The logit regression analysis indicated that child's age, mothers' age, distance to farm, and food expenditure were among the significant determinants of children dietary diversity. Therefore, this study seeks the collaborative efforts of stakeholders in providing nutrition-sensitive intervention programs for household members, especially mothers and young children in order to promote consumption of diversified diets and enhance healthy living of rural farming households.


Formation of alanine and glutamine in chick (Gallus domesticus) skeletal muscle.
1. Incubation of extensor digitorum communis muscles from fed chicks in the presence of plasma concentrations of branched-chain amino acids (BCAA) increased the formation of glutamate, glutamine and alanine. This effect was inhibited by 1.5 mM L-cycloserine. 2. 2-Oxoisocaproate (0.1 and 0.5 mM) increased the formation of leucine but decreased that of glutamate, glutamine and alanine. 3. NH4Cl (0.3 mM) increased the formation of glutamine, and decreased the release and intracellular concentrations of glutamate and alanine. 4. Our results demonstrate that alanine and glutamine are synthesized de novo in chick skeletal muscle and demonstrate the similarity in alanine and glutamine synthesis in skeletal muscle between the domestic fowl and mammals.


Randomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma.
We conducted a randomized, non-comparative, multi center, phase II clinical trial in order to investigate the efficacy of axitinib, an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the vascular endothelial growth factor receptors, in patients with recurrent glioblastoma following prior treatment with radiation and temozolomide. Forty-four patients were randomly assigned to receive treatment with axitinib (5 mg BID starting dose; N = 22) or "physicians best alternative choice of therapy" that consisted of bevacizumab (N = 20) or lomustine (N = 2). Six-month progression-free survival served as the primary endpoint. The estimated 6-month progression-free survival rate was 34 % (95 % CI 14-54) for patients treated with axitinib and 28 % (95 % CI 8-48) with best alternative treatment; median overall survival was 29 and 17 weeks, respectively. Objective responses according to RANO criteria were documented in 28 % of patients treated with axitinib and 23 % of patients treated with best alternative therapy. A decrease in maximal uptake of 18F-fluoro-ethyL-tyrosine (18F-FET) by the glioblastoma on PET imaging was documented in 85 % of patients at the time of response on axitinib. Corticosteroid treatment could be stopped in four and tapered in seven out of the 15 patients who were treated with steroids at baseline in the axitinib cohort. Most frequent axitinib related grade ≥3 adverse events consisted of fatigue (9 %), diarrhea (9 %), and oral hyperesthesia (4.5 %). We conclude that axitinib has single-agent clinical activity and a manageable toxicity profile in patients with recurrent glioblastoma.


A Rare Case of Falsely Elevated High-Sensitivity Cardiac Troponin T due to Antibody Interference and a Literature Review.
This study aimed to demonstrate potential measures to discern interference and establish an algorithm for identifying interference in an hs-cTnT assay with a clinical discrepancy. Laboratory error and disease factors were first excluded. Then, a serial dilution test, polyethylene glycol (PEG) precipitation, and heterophile antibody blocking reagents (HBRs) were performed to confirm the interference substance. In addition, high-speed centrifugation and western blot were tried. The sample diluted linearly (R2 = 0.9966). However, there was a dramatic reduction in the concentration of hs-cTnT concentration to a normal level after both PEG precipitation and HBR1 treatment. The results were inconclusive in high-speed centrifugation and western blot assay. This study elucidated a heterophile antibody interference in measurement of hs-cTnT alone on a Roche analyzer.


Identification of metabolites of fluorine-18-labeled M2 muscarinic receptor agonist, 3-(3-[(3-fluoropropyl)thio]-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine, produced by human and rat hepatocytes.
An accurate, rapid method for the determination of unmetabolized 3-(3-[(3-[18F]fluoropropyl)thio]-1,2,5-thiadiazol-4-yl)-1.2,5,6-tetrahydro-1-methylpyridine (FP-TZTP), a selective M2 muscarinic agonist, is necessary in order to obtain quantitative information from positron emission tomography (PET) imaging. Using LC-MS-MS to analyze products from cultured human and rat hepatocytes, we identified metabolites resulting from oxidation of the nitrogen in the tetrahydropyridine ring, sulfur-oxidation, demethylation of the tertiary amine, and oxidation of the tetrahydropyridine ring. From the knowledge of the structure of the metabolites, we have developed a two-step extraction sequence that allows rapid determination of the parent fraction in plasma without time-consuming chromatographic analysis.


The Diabetes Health Plan and Healthcare Utilization Among Beneficiaries with Low Incomes.
The socioeconomic status (SES) gradient in hospital and emergency room utilization among adults with type 2 diabetes (T2DM) is partially driven by cost-related non-adherence. To test the impact of the Diabetes Health Plan (DHP), a diabetes-specific health plan incorporating value-based insurance design principles on healthcare utilization among low-income adults with T2DM. To examine the impact of the DHP on healthcare utilization, we employed a difference-in-differences (DID) study design with a propensity-matched comparison group. We modeled count and dichotomous outcomes using Poisson and logit models, respectively. Cohort of adults (18-64) with T2DM, with an annual household income <$ 30,000, and who were continuously enrolled in an employer-sponsored UnitedHealthcare plan for at least 2 years between 2009 and 2014. The DHP reduces or eliminates out-of-pocket costs for disease management visits, diabetes-related medicines, and diabetes self-monitoring supplies. The DHP also provides access to diabetes-specific telephone case management as well as other online resources. Number of disease management visits (N = 1732), any emergency room utilization (N = 1758), and any hospitalization (N = 1733), within the year. DID models predicting disease management visits suggested that DHP-exposed beneficiaries had 1.7 fewer in-person disease management visits per year (- 1.70 [95% CI: - 2.19, - 1.20], p < 0.001), on average, than comparison beneficiaries. Models for emergency room (0.00 [95% CI: - 0.06, 0.06], p = 0.966) and hospital utilization (- 0.03 [95% CI: - 0.08, - 0.01], p = 0.164) did not demonstrate statistically significant changes associated with DHP exposure. While no relationship between DHP exposure and high-cost utilization was observed in the short term, fewer in-person disease management visits were observed. Future studies are needed to determine the clinical implications of these findings.


Unicompartmental Knee Arthroplasty in a Patient with Nail-Patella Syndrome: A Case Report.
A 46-year-old woman with a medical history of nail-patella syndrome (NPS) presented with chronic right knee pain. Radiographic and physical examination revealed isolated medial tibiofemoral osteoarthritis and a hypoplastic laterally subluxed patella. The patient was successfully treated with a medial unicompartmental knee arthroplasty (UKA). In patients with NPS and osteoarthritis limited to one tibiofemoral compartment, a UKA may be successfully performed.


Haploid accumulation and translational control of phosphoglycerate kinase-2 messenger RNA during mouse spermatogenesis.
The intracellular location of the mRNA for the testis-specific isozyme of phosphoglycerate kinase-2 (PGK-2) has been determined for two spermatogenic cell types. The mRNA activity for PGK-2 from the polysomal and nonpolysomal fractions of pachytene primary spermatocytes or round spermatids has been assayed by cell-free translation with the polypeptide products monitored by immunoprecipitation, followed by one-dimensional or two-dimensional electrophoresis and fluorography. The results reveal that the majority of PGK-2 mRNA activity of round spermatids was present in the polysomal fraction while the relatively less abundant PGK-2 mRNA of pachytene primary spermatocytes was present in the nonpolysomal fraction. No PGK-2 mRNA activity was observed in the cytoplasmic RNA from primitive type A spermatogonia or prepubertal Sertoli cells. These data indicate that mature PGK-2 mRNA first appears in the cytoplasm of spermatogenic cells during the prophase of meiosis and increases in amount after meiosis. Although mature PGK-2 mRNA is present in meiotic cells it is not actively translated until after meiosis has been completed. Thus, mRNA accumulation and translational mechanisms are involved in the control of phosphoglycerate kinase-2 synthesis during spermatogenesis.


Disposition of perfluorinated acid isomers in Sprague-Dawley rats; part 1: single dose.
Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 microg/kg body weight perfluorooctane sulfonate (C(8)F(17)SO(3)(-), PFOS), perfluorooctanoic acid (C(7)F(15)CO(2)H, PFOA), and perfluorononanoic acid (C(8)F(17)CO(2)H, PFNA) and 30 microg/kg body weight perfluorohexane sulfonate (C(6)F(13)SO(3)(-), PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m-PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure-property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples.


A multicenter study of nutraceutical drinks for cholesterol (evaluating effectiveness and tolerability).
We hypothesized that a nutraceutical formulation containing small amounts of bioactive constituents that exert cholesterol-lowering effects by different mechanisms may exhibit synergistic efficacy with a clean tolerability profile. The purpose of this study was to evaluate nutraceutical fruit-flavored drinks with and without red yeast rice (RYR) for effects on low-density lipoprotein (LDL) and total cholesterol. In double-blinded fashion, 79 subjects were randomized to one of three fruit-flavored drinks, ie, a placebo, and two active drinks containing niacin, phytosterol esters, L-carnitine, vitamin C, and Co-Q-10, one with and without RYR, twice daily. Primary end points were LDL and total cholesterol percent reductions from baseline. Secondary end points were high-density lipoprotein and C-reactive protein percent change from baseline. Physician contact and laboratory work were obtained at baseline, 4 weeks, and 8 weeks of subject participation. A total of 59 subjects completed the study. The placebo group and the group receiving the nutraceuticals without RYR showed no change in primary or secondary end points. The nutraceutical drink with RYR reduced total cholesterol at week 4 by 13% (-35 mg/dL) and week 8 by 14% (-46 mg/dL). LDL cholesterol decreased 17.1% at 4 weeks (-28 mg/dL) and 17.8% at week 8 (-30 mg/dL). In the effective drink arm containing nutraceuticals and RYR there were no biochemical or subjective intolerance, with the exception of one subject who experienced headache. A nutraceutical drink with RYR can be a safe and effective natural alternative to pharmacologic therapies for people intolerant to or refusing statins but still in need of achieving and maintaining a healthy and low cholesterol level.


Child health advocacy in Saudi Arabia: Traditional medicine as a model.
The purpose of this work is to describe the opportunities and challenges faced by health advocates in Kingdon of Saudi Arabia (KSA) regarding traditional medicine practices, which commonly result in health issues affecting children in the community. A literature review was conducted of all articles identified in PubMed with the following keywords: alternative medicine, traditional medicine, KSA, and advocacy. No articles from other countries with similar cultural backgrounds were excluded, and recommendation from authors were listed at the end of the article. Traditional medicine, traditional herbal medications, and spiritual treatments, which are common practices in the community, present major opportunities for advocacy in KSA. Because these practices are conducted without appropriate supervision, many adverse events result, thus affecting children and families. Many challenges are described herein, such as use of these practices in treating benign self-limited conditions; the surrounding culture and beliefs; and the dilemma of achieving child protection. At the system level, national policies and legislation, as well as research, are lacking. Moreover, health care facilities have longer waiting lists than traditional medicine facilities. Recommendations include improving knowledge, facilitating behavioral changes, data collection, bylaw enactment, and providing better access to health care facilities, all of which are supported by Saudi Vision 2030.