Lack of an endogenous anti-inflammatory protein in mice enhances colonization of B16F10 melanoma cells in the lungs.
Emerging evidence indicates a link between inflammation and cancer metastasis, but the molecular mechanism(s) remains unclear. Uteroglobin (UG), a potent anti-inflammatory protein, is constitutively expressed in the lungs of virtually all mammals. UG-knock-out (UG-KO) mice, which are susceptible to pulmonary inflammation, and B16F10 melanoma cells, which preferentially metastasize to the lungs, provide the components of a model system to determine how inflammation and metastasis are linked. We report here that B16F10 cells, injected into the tail vein of UG-KO mice, form markedly elevated numbers of tumor colonies in the lungs compared with their wild type littermates. Remarkably, UG-KO mouse lungs overexpress two calcium-binding proteins, S100A8 and S100A9, whereas B16F10 cells express the receptor for advanced glycation end products (RAGE), which is a known receptor for these proteins. Moreover, S100A8 and S100A9 are potent chemoattractants for RAGE-expressing B16F10 cells, and pretreatment of these cells with a blocking antibody to RAGE suppressed migration and invasion. Interestingly, in UG-KO mice S100A8/S100A9 concentrations in blood are lowest in tail vein and highest in the lungs, which most likely guide B16F10 cells to migrate to the lungs. Further, B16F10 cells treated with S100A8 or S100A9 overexpress matrix metalloproteinases, which are known to promote tumor invasion. Most notably, the metastasized B16F10 cells in UG-KO mouse lungs express MMP-2, MMP-9, and MMP-14 as well as furin, a pro-protein convertase that activates MMPs. Taken together, our results suggest that a lack of an anti-inflammatory protein leads to increased pulmonary colonization of melanoma cells and identify RAGE as a potential anti-metastatic drug target.


AtMYB32 is required for normal pollen development in Arabidopsis thaliana.
AtMYB32 gene is a member of the R2R3 MYB gene family coding for transcription factors in Arabidopsis thaliana. Its expression pattern was analysed using Northern blotting, in situ hybridization and promoter-GUS fusions. AtMYB32 is expressed in many tissues, but most strongly in the anther tapetum, stigma papillae and lateral root primordia. AtMYB32-GUS was induced in leaves and stems following wounding, and in root primordia by auxin. T-DNA insertion populations were screened and two insertion mutants were identified, both of which were partially male sterile, more than 50% of the pollen grains being distorted in shape and lacking cytoplasm. AtMYB4 is closely related to AtMYB32 and represses the CINNAMATE 4-HYDROXYLASE gene. Distorted pollen grains were produced in both AtMYB4 insertion mutant and overexpression lines. In an AtMYB32 insertion mutant, the transcript levels of the DIHYDROFLAVONOL 4-REDUCTASE and ANTHOCYANIDIN SYNTHASE genes decreased while the level of the CAFFEIC ACID 0-METHYLTRANSFERASE transcript increased. Change in the levels of AtMYB32 and AtMYB4 expression may influence pollen development by changing the flux along the phenylpropanoid pathways, affecting the composition of the pollen wall.


The concept of social care and the analysis of contemporary welfare states.
Care is now a widely-used concept in welfare state research, firmly established in the literature by feminist analysis. We believe that the concept as it has been used and developed to date has limitations that have hampered its development as a general category of welfare state analysis. In essence we argue that the political economy aspects of the concept have remained underdeveloped. The main purpose of this article is to elaborate a care-centered concept--which we name social care--that countenances and develops care as an activity and set of relations lying at the intersection of state, market and family (and voluntary sector) relations. We are especially concerned to examine what the concept of social care can tell us about welfare state variation and welfare state change and development. The article works systematically through these themes, beginning with a brief historical sketch of the concept of care and then moving on to elaborate the analytic potential of the concept of social care. In the latter regard we make the case that it can lead to a more encompassing analysis, helping to overcome especially the fragmentation in existing scholarship between the cash and service dimensions of the welfare state and the relative neglect of the latter. The concept of social care serves to shift the centre of analysis from specific policy domains so that instead of focusing on cash benefits or services in isolation it becomes possible to consider them as part of a broader set of inter-relating elements. In this and other regards, the concept has the potential to say something new about welfare states.


Nutritional care of elderly patients in acute care settings: A qualitative study.
Poor nutritional status is common in older adult patients. The present study aimed to explore barriers and facilitators to nutritional care of elderly patients in acute care settings. Data were collected through individual face-to-face interviews with 12 registered nurses, and analyzed using interpretive description methodology. Two core themes emerged from the analysis of data: (i) neglected care, with three subthemes of "support but also independence," "unsupportive environment" and "responsibility of the family;" and (ii) a humanitarian ethic, with two subthemes of "respect and dignity" and "humanitarian care." As an integral part of holistic care, elderly patient nutrition should be emphasised in health professional education, and promoted through managerial support, multidisciplinary collaborations, and implementation of appropriate monitoring and evaluation systems.


Changing pattern of esophageal cancer incidence in New Mexico.
Multiple reports indicate that esophageal adenocarcinoma incidence has increased during the past 20 yr, especially in non-Hispanic white men. We retrospectively reviewed adenocarcinoma and squamous cell carcinoma cases in our heterogeneous state population to determine the effect of ethnicity on histology. We searched the New Mexico Tumor Registry for all cases of esophageal cancer from 1973 to 1997. Inclusion criteria included histological diagnosis of adenocarcinoma or squamous cell carcinoma, self-reported ethnicity, and gender. Age-adjusted incidence rates for both adenocarcinoma or squamous cell carcinoma were compared among ethnic groups in 5-yr intervals. Six hundred fifteen patients met inclusion criteria. Esophageal adenocarcinoma age-adjusted incidence rates/100,000 increased significantly during the 25-yr period: 1973-1977, 0.25 cases; 1978-1982, 0.33 cases; 1983-1987, 0.45 cases; 1988-1992, 0.85 cases; and 1993-1997, 1.19 cases; p < 0.001. In comparison, squamous cell carcinoma age-adjusted incidence rates did not increase significantly during the study period. In non-Hispanic whites, the histological age-adjusted incidence rate changed during the 1993-1997 period compared to other periods: 1993-1997, squamous cell carcinoma 1.01 and adenocarcinoma 1.42, p < 0.001. In Hispanics, the age-adjusted incidence rate of adenocarcinoma increased significantly in the fifth period compared to other periods, p < 0.001. In all minority groups, squamous cell carcinoma remained the predominant type. Esophageal adenocarcinoma age-adjusted incidence increased in New Mexico from 1973 to 1997. This increase was found in non-Hispanic whites and Hispanics and became predominant in non-Hispanic whites. Squamous cell carcinoma remains the primary type in minorities. This study suggests that ethnicity may influence esophageal cancer histology or ethnic background may place an individual at increased risk for certain types of esophageal cancer.


Dust in pig buildings.
It is well documented in the international scientific literature that airborne dust in pig houses can cause serious health problems for humans as well as for animals. Extensive research has been carried out in different countries during the last few decades to improve the scientific understanding of air quality issues related to intensive animal production. Research and review papers were presented at the international symposium on Dust Control in Animal Production Facilities, held in Denmark in 1999. Different techniques have been used in order to reduce dust burdens in pig confinement buildings, but up to date only the procedure of spraying oil or a mixture of oil and water has contributed to reducing the indoor dust concentrations significantly. This article summarizes the current level of understanding of dust issues in intensive animal production buildings, mainly on the basis of papers presented at the above-mentioned symposium.


Regulatory interactions between the Pho and sigma(B)-dependent general stress regulons of Bacillus subtilis.
When Bacillus subtilis is subjected to phosphate starvation, the Pho and sigma(B)-dependent general stress regulons are activated to elicit, respectively, specific and non-specific responses to this nutrient-limitation stress. A set of isogenic mutants, with a beta-galactosidase reporter gene transcriptionally fused to the inactivated target gene, was used to identify genes of unknown function that are induced or repressed under phosphate limitation. Nine phosphate-starvation-induced (psi) genes were identified: yhaX, yhbH, ykoL and yttP were regulated by the PhoP-PhoR two-component system responsible for controlling the expression of genes in the Pho regulon, while ywmG (renamed csbD), yheK, ykzA, ysnF and yvgO were dependent on the alternative sigma factor sigma(B), which controls the expression of the general stress genes. Genes yhaX and yhbH are unique members of the Pho regulon, since they are phosphate-starvation induced via PhoP-PhoR from a sporulation-specific sigma(E) promoter or a promoter that requires the product of a sigma(E)-dependent gene. Null mutations in key regulatory genes phoR and sigB showed that the Pho and sigma(B)-dependent general stress regulons of Bacillus subtilis interact to modulate the levels at which each are activated.


Long-term stable, sub-femtosecond timing distribution via a 1.2-km polarization-maintaining fiber link: approaching 10(-21) link stability.
Long-term stable, sub-femtosecond timing distribution over a 1.2-km polarization-maintaining (PM) fiber-optic link using balanced optical cross-correlators for link stabilization is demonstrated. Novel dispersion-compensating PM fiber was developed to construct a dispersion-slope-compensated PM link, which eliminated slow timing drifts and jumps previously induced by polarization mode dispersion in standard single-mode fiber. Numerical simulations of nonlinear pulse propagation in the fiber link confirmed potential sub-100-as timing stability for pulse energies below 70 pJ. Link operation for 16 days showed ~0.6 fs RMS timing drift and during a 3-day interval only ~0.13 fs drift, which corresponds to a stability level of 10(-21).


Fibroblast growth factors (FGFs) prime the limb specific Shh enhancer for chromatin changes that balance histone acetylation mediated by E26 transformation-specific (ETS) factors.
Sonic hedgehog (Shh) expression in the limb bud organizing centre called the zone of polarizing activity is regulated by the ZRS enhancer. Here, we examine in mouse and in a mouse limb-derived cell line the dynamic events that activate and restrict the spatial activity of the ZRS. Fibroblast growth factor (FGF) signalling in the distal limb primes the ZRS at early embryonic stages maintaining a poised, but inactive state broadly across the distal limb mesenchyme. The E26 transformation-specific transcription factor, ETV4, which is induced by FGF signalling and acts as a repressor of ZRS activity, interacts with the histone deacetylase HDAC2 and ensures that the poised ZRS remains transcriptionally inactive. Conversely, GABPα, an activator of the ZRS, recruits p300, which is associated with histone acetylation (H3K27ac) indicative of an active enhancer. Hence, the primed but inactive state of the ZRS is induced by FGF signalling and in combination with balanced histone modification events establishes the restricted, active enhancer responsible for patterning the limb bud during development.


Antipyrine kinetics in Nigerian women in chronic renal failure.
Antipyrine was given orally to five patients with Chronic renal failure and nine normal subjects. Plasma antipyrine levels were measured by high pressure liquid chromatography method, the plasma half-life of the drug was determined and used as an index of drug oxidation. The mean (+/- s.d.) plasma antipyrine half-life in patients with chronic renal failure (7.8 +/- 2.6 h) was significantly shorter than in normal subjects (13.1 +/- 2.3 h) (P less than 0.001). There was no significant difference in the volume of distribution but there was a significant difference in the clearance in ml.kg-1h-1 (P less than 0.001). The results suggest that oxidation of antipyrine by hepatic microsomal enzymes is increased in patients with chronic renal failure. The role of this in the apparent resistance among our patients to antihypertensive agents needs further study.


A study of paclitaxel, carboplatin, and bortezomib in the treatment of metastatic malignant melanoma: a phase 2 consortium study.
Chemotherapy has not been reported to have a significant impact on survival for patients with metastatic melanoma. Bortezomib was shown to have additive/synergistic effects with several chemotherapeutic agents, including paclitaxel and platinum. A phase 1 trial of this 3-drug combination reported that 6 of 28 patients treated with bortezomib followed by paclitaxel and carboplatin achieved a partial response (including 2 of 5 patients with metastatic melanoma). A 2-stage phase 2 clinical trial was conducted to assess the antitumor activity of this 3-agent combination in patients with metastatic melanoma who had received at most 1 prior chemotherapy for metastatic disease. Treatment included bortezomib at a dose of 1.3 mg/m2 intravenously on Days 1, 4, and 8; paclitaxel at a dose of 175 mg/m2; and carboplatin at an area under the concentration (AUC) of 6 on Day 2 of a 21-day cycle. The primary endpoint of this trial was tumor response rate (TRR). Seventeen eligible patients were enrolled. A median of 4 cycles were administered (range, 1-7 cycles). Three patients discontinued treatment due to persistent grade 4 (based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) neutropenia with grade 3 leukopenia (2 patients) or grade 4 pulmonary embolism (1 patient). Grade>or=3 toxicities included neutropenia (71%), leukopenia (41%), thrombocytopenia (29%), and arthralgia (12%). Two partial responses were observed (TRR, 11.8%). Four patients had stable disease at >12 weeks. The median progression-free survival was 3.2 months, and the median overall survival was 7.0 months. Due to insufficient clinical efficacy, this trial did not proceed to second-stage accrual. The combination of paclitaxel, carboplatin, and bortezomib demonstrated limited clinical benefit and was associated with significant toxicity.


Mutagenesis data in the automated prediction of transmembrane helix dimers.
We present a molecular modeling protocol that selects modeled protein structures based on experimental mutagenesis results. The computed effect of a point mutation should be consistent with its experimental effect for correct models; mutations that do not affect protein stability and function should not affect the computed energy of a correct model while destabilizing mutations should have unfavorable computed energies. On the other hand, an incorrect model will likely display computed energies that are inconsistent with experimental results. We added terms to our energy function which penalize models that are inconsistent with experimental results. This creates a selective advantage for models that are consistent with experimental results in the Monte Carlo simulated annealing protocol we use to search conformational space. We calibrated our protocol to predict the structure of transmembrane helix dimers using glycophorin A as a model system. Inclusion of mutational data in this protocol compensates for the limitations of our force field and the limitations of our conformational search. We demonstrate an application of this structure prediction protocol by modeling the transmembrane region of the BNIP3 apoptosis factor.


Modulation of Formation, Physicochemical Properties, and Digestion of Ovotransferrin Nanofibrils with Covalent or Non-Covalent Bound Gallic Acid.
The impact of covalent or non-covalent bound gallic acid (GA) on the formation, physicochemical properties, and digestion of ovotransferrin (OTF) nanofibrils was comprehensively studied. Thioflavin T fluorescence results revealed that bound GA could inhibit OTF nanofibrillation and that the fibril-inhibitory activity of bound GA was dose dependent. Covalent bound GA exerted stronger inhibition on OTF nanofibrillation than an equal amount of non-covalent bound GA. Atomic force microscopy revealed that covalent bound GA shortened OTF nanofibrils significantly, while non-covalent bound GA did not change the contour length of OTF fibrils remarkably. Bound GA altered diameter of OTF nanofibrils. Both covalent and non-covalent bound GA could alter the zeta potential, surface hydrophobicity, and rheological properties of OTF nanofibrils. Bound GA endowed OTF nanofibrils with a strong antioxidant activity. In vitro gastrointestinal digestion results showed that covalent bound GA elevated the fibril digestion rate better than non-covalent bound GA. Polyphenol binding provided a new approach to modulating the physicochemical properties of protein nanofibrils.


Self-Assembled Nanomaterials for Enhanced Phototherapy of Cancer.
Following the wisdom of nature to assemble functional candidates into exquisite nanoarchitectures is emerging as a promising field of research and has been widely applied in biomedical sciences. Owing to their excellent properties of structural controllability, functional diversity, dynamic adjustability, and prominent biocompatibility, the self-assembled nanoarchitectures come to play a pivotal role in fighting against cancer. This review outlines the most up-to-date developments in constructing phototherapeutic nanomaterials for photodynamic and photothermal therapy (PDT and PTT) of tumors, with emphasis on design ideas, building blocks, and advantageous characteristics of self-assembly. The prominent activities of cancer therapy obtained by these photoinduced nanotheranostics are also explored in-depth, together with the connections between the specific nanostructures and unique features, providing a comprehensive understanding of the self-assembled nanomaterials in improving the outcomes of PDT and PTT. This review aims to highlight the significance of self-assembled nanomaterials in enhancing phototherapeutic efficacy and to promote its development in various research interests ranging from material science and nanoscience to biomedicine and clinical medicine.


Parasite zoonoses and wildlife: One Health, spillover and human activity.
This review examines parasite zoonoses and wildlife in the context of the One Health triad that encompasses humans, domestic animals, wildlife and the changing ecosystems in which they live. Human (anthropogenic) activities influence the flow of all parasite infections within the One Health triad and the nature and impact of resulting spillover events are examined. Examples of spillover from wildlife to humans and/or domestic animals, and vice versa, are discussed, as well as emerging issues, particularly the need for parasite surveillance of wildlife populations. Emphasis is given to Trypanosoma cruzi and related species in Australian wildlife, Trichinella, Echinococcus, Giardia, Baylisascaris, Toxoplasma and Leishmania.


Cochlear implants in single-sided deafness - clinical results of a Swiss multicentre study.
The aim of this multicentre, prospective, open, nonrandomised clinical trial was to demonstrate the clinical efficiency and outcomes of cochlear implants (CIs) in adult patients with post-lingual single-sided deafness (SSD). A group of five left and five right SSD participants were investigated with various clinical tests and questionnaires before and 12 months after CI activation. Changes in hearing thresholds, speech understanding in noise, sound localisation, tinnitus (Tinnitus Handicap Inventory; THI), subjective hearing ability (Speech, Spatial and Qualities of Hearing Scale; SSQ), and quality of life (WHOQOL-BREF) were assessed. In addition, the pre- and postoperative results of the SSD patients were compared with an age- and gender-matched normal hearing control group. Surgery was uncomplicated in all patients. Two years after implantation, 9 of the 10 patients used their CI regularly for an average of more than 11 hours a day. A significant improvement in speech understanding in noise measured in the sound field using the Oldenburg sentence test could be demonstrated in the two situations in which patients with SSD experience the greatest difficulty: speech from the front and noise at the healthy ear, and speech to the implanted ear and noise from the front. The sound localisation test showed significant improvement of the mean localisation error and the root mean square error after CI activation. Furthermore, a significant reduction of the THI was measured, and the SSQ showed a significant improvement in the subscale speech comprehension and in the subscale spatial hearing. Also, quality of life measured with the WHOQOL-BREF showed a general improvement, which was significant in the global subscale. For this questionnaire, there was no significant difference between the normal-hearing control group and the patients after 12 months of CI use. This study confirmed the clinical benefit of cochlear implantation in patients with SSD. The significant improvement of speech understanding in noise, sound localisation, tinnitus perception, subjective hearing ability, and in particular the improved quality of life support the recommendation that patients with recently acquired SSD should be offered a CI. (Clinical trial registration number on clinicaltrial.gov: NCT01749592).


Duration of isoflurane-based surgical anesthesia determines severity of brain injury and neurological deficits after a transient focal ischemia in young adult rats.
Tremendous efforts and funds invested in discovery of novel drug treatments for ischemic stroke have so far failed to deliver clinically efficacious therapies. The reasons for these failures are not fully understood. An indiscriminate use of isoflurane-based surgical anesthesia with or without nitrous oxide may act as an unconstrained, untraceable source of data variability, potentially causing false-positive or false-negative results. To test this hypothesis, a common transient suture middle cerebral artery occlusion (tMCAO) model of ischemic stroke in young adult male rats was used to determine the impact of a typical range of anesthesia durations required for this model on data variability (i.e., infarct volume and neurological deficits). The animals were maintained on spontaneous ventilation. The study results indicated that: (1) Variable duration of isoflurane anesthesia prior, during and after tMCAO is a significant source of data variability as evidenced by measurements of infarct volume and neurological deficits; and (2) Severity of brain injury and neurological deficits after tMCAO is inversely related to the duration of isoflurane anesthesia: e.g., in our study, a 90min isoflurane anesthesia nearly completely protected brain tissues from tMCAO-induced injury and thus, would be expected to obscure the effects of stroke treatments in pre-clinical trials. To elevate transparency, rigor and reproducibility of stroke research and minimize undesirable effects of isoflurane on the outcome of novel drug testing, we propose to monitor, minimize and standardize isoflurane anesthesia in experimental surgeries and make anesthesia duration a required reportable parameter in pre-clinical studies. Specifically, we propose to adopt 20-30min as an optimal anesthesia duration that both minimizes neuroprotective effects of isoflurane and permits a successful completion of surgical procedures in a suture tMCAO model of ischemic stroke in rodents. As the mechanisms and neuroprotective, metabolic and immune effects of general anesthesia are not fully understood, the results of this study cannot be blindly generalized to other anesthetics, animal species and experimental models.


Hippocampal GABA enables inhibitory control over unwanted thoughts.
Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled.


Comparison of Autologous vs Homologous Costal Cartilage Grafts in Dorsal Augmentation Rhinoplasty: A Systematic Review and Meta-analysis.
Augmentation rhinoplasty requires adding cartilage to provide enhanced support to the structure of the nose. Autologous costal cartilage and irradiated homologous costal cartilage (IHCC) are well-accepted rhinoplasty options. Tutoplast is another alternative cartilage source. No studies, to our knowledge, have definitively demonstrated a higher rate of complications with IHCC grafts compared with autologous costal cartilage grafts. To compare rates of outcomes in the published literature for patients undergoing septorhinoplasty with autologous costal cartilage vs IHCC grafts vs Tutoplast grafts. For this systematic review and meta-analysis, the MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for articles published from database inception to February 2019 using the following keywords: septorhinoplasty, rhinoplasty, autologous costal cartilage graft, cadaveric cartilage graft, and rib graft. Abstracts and full texts were reviewed in duplicate, and disagreements were resolved by consensus. Only patients who underwent an en bloc dorsal onlay graft were included for comparison to ensure a homogenous study sample. A total of 1308 results were found. After duplicate records were removed, 576 unique citations remained. Studies were published worldwide between January 1, 1990, and December 31, 2017. Independent extraction by 2 authors was performed. Data were pooled using a random-effects model. All reported outcomes after septorhinoplasty and rates of graft warping, resorption, infection, contour irregularity, and revision surgery among patients receiving autologous grafts vs IHCC vs Tutoplast cartilage grafts. Of 576 unique citations, 54 studies were included in our systematic review; 28 studies were included after applying inclusion and exclusion criteria. Our search captured 1041 patients of whom 741 received autologous grafts and 293 received IHCC grafts (regardless of type). When autologous cartilage (n = 748) vs IHCC (n = 153) vs Tutoplast cartilage (n = 140) grafts were compared, no difference in warping (5%; 95% CI, 3%-9%), resorption (2%; 95% CI, 0%-2%), contour irregularity (1%; 95% CI, 0%-3%), infection (2%; 95% CI, 0%-4%), or revision surgery (5%; 95% CI, 2%-9%) was found. No difference was found in outcomes between autologous and homologous costal cartilage grafts, including rates of warping, resorption, infection, contour irregularity, or revisions, in patients undergoing dorsal augmentation rhinoplasty. En bloc dorsal onlay grafts are commonly used in augmentation rhinoplasty to provide contour and structure to the nasal dorsum.


The PSP-associated MAPT H1 subhaplotype in Guadeloupean atypical parkinsonism.
The aim of this study was to determine whether the H1 subhaplotype in MAPT associated with progressive supranuclear palsy (PSP) in Caucasians confers risk for PSP-like atypical parkinsonism in Guadeloupe, a tauopathy. Guadeloupean controls and patients with atypical and idiopathic parkinsonism and ethnically and age-matched controls were genotyped for H1 and H2 alleles, then for the H1 subhaplotype associated with PSP in Caucasians, using previously described haplotype-tagging single nucleotide polymorphisms (Ht-SNPs) in linkage disequilibrium at the MAPT locus. Most Guadeloupean controls and patients were homozygous for the H1 allele; only 5% were heterozygous for the H2 allele, consistent with the European contribution to the racial admixture in Guadeloupe, but equivalent to the frequency found in Caucasian PSP patients. The frequencies of the Ht-SNPs used to determine the PSP-associated H1 subhaplotype in both Guadeloupean controls and parkinsonians were similar, indicating that the H1 subhaplotype associated with PSP in Caucasians was not a risk factor for PSP-like atypical parkinsonism in Guadeloupe. Interestingly, they were also similar to the frequencies in Caucasian PSP patients. The major H1 subhaplotype in Guadeloupe, determined by analysis of linkage desequibrium, differed from the major Caucasian subhaplotype, but corresponded to minor alleles previously described.


SARS-CoV-2 genome and antibodies in breastmilk: a systematic review and meta-analysis.
To systematically review and meta-analyse the rate of SARS-CoV-2 genome identification and the presence of SARS-CoV-2 antibodies in breastmilk of mothers with COVID-19. A systematic review of studies published between January 2019 and October 2020 without study design or language restrictions. Data sourced from Ovid Embase Classic+Embase, PubMed, Web of Science, Scopus, relevant bibliographies and the John Hopkins University COVID-19 database. Mothers with confirmed COVID-19 and breastmilk tested for SARS-CoV-2 by RT-PCR or for anti-SARS-CoV-2 antibodies. Presence of SARS-CoV-2 genome and antibodies in breastmilk. We included 50 articles. Twelve out of 183 women from 48 studies were positive for SARS-CoV-2 genome in their breastmilk (pooled proportion 5% (95% CI 2% to 15%; I2=48%)). Six infants (50%) of these 12 mothers tested positive for SARS-CoV-2, with one requiring respiratory support. Sixty-one out of 89 women from 10 studies had anti-SARS-CoV-2 antibody in their breastmilk (pooled proportion 83% (95% CI 32% to 98%; I2=88%)). The predominant antibody detected was IgA. SARS-CoV-2 genome presence in breastmilk is uncommon and is associated with mild symptoms in infants. Anti-SARS-CoV-2 antibodies may be a more common finding. Considering the low proportion of SARS-CoV-2 genome detected in breastmilk and its lower virulence, mothers with COVID-19 should be supported to breastfeed.


Correlating excessive daytime sleepiness with body mass index, waist circumference, and lipid profile in shift workers.
To determine the correlation between excessive daytime sleepiness and body mass index, waist circumference, and lipid profile of shift workers at Dr. Moewardi General Hospital, Surakarta. This cross-sectional study was carried out at the Dr. Moewardi Hospital, Surakarta, Indonesia between October 2018 and July 2019. The participants were recruited using purposive sampling. Multiple linear regression with backward elimination was performed to identify the odds ratios between Epworth Sleepiness Scale scores, anthropometric measurements, and lipid profiles. A p-value of <0.05 indicated statistically significant correlations. Of the 150 included participants, 127 (84.67%) were women. Statistical analyses revealed odds ratios of 2.38 (95% confidence interval [CI] 1.14-4.89, p=0.000) for daytime sleepiness severity and total cholesterol levels, and 2.45 (95% CI 1.36-4.98, p=0.020) for daytime sleepiness severity and high-density lipoprotein levels. Increased total cholesterol and decreased high-density lipoprotein levels increase the risk of excessive daytime sleepiness in shift workers.


Temperate performance and metabolic adaptations following endurance training performed under environmental heat stress.
Endurance athletes are frequently exposed to environmental heat stress during training. We investigated whether exposure to 33°C during training would improve endurance performance in temperate conditions and stimulate mitochondrial adaptations. Seventeen endurance-trained males were randomly assigned to perform a 3-week training intervention in 18°C (TEMP) or 33°C (HEAT). An incremental test and 30-min time-trial preceded by 2-h low-intensity cycling were performed in 18°C pre- and post-intervention, along with a resting vastus lateralis microbiopsy. Training was matched for relative cardiovascular demand using heart rates measured at the first and second ventilatory thresholds, along with a weekly "best-effort" interval session. Perceived training load was similar between-groups, despite lower power outputs during training in HEAT versus TEMP (p < .05). Time-trial performance improved to a greater extent in HEAT than TEMP (30 ± 13 vs. 16 ± 5 W, N = 7 vs. N = 6, p = .04), and citrate synthase activity increased in HEAT (fold-change, 1.25 ± 0.25, p = .03, N = 9) but not TEMP (1.10 ± 0.22, p = .22, N = 7). Training-induced changes in time-trial performance and citrate synthase activity were related (r = .51, p = .04). A group × time interaction for peak fat oxidation was observed (Δ 0.05 ± 0.14 vs. -0.09 ± 0.12 g·min-1 in TEMP and HEAT, N = 9 vs. N = 8, p = .05). Our data suggest exposure to moderate environmental heat stress during endurance training may be useful for inducing adaptations relevant to performance in temperate conditions.


European Respiratory Society clinical practice guideline: palliative care for people with COPD or interstitial lung disease.
There is increased awareness of palliative care needs in people with COPD or interstitial lung disease (ILD). This European Respiratory Society (ERS) task force aimed to provide recommendations for initiation and integration of palliative care into the respiratory care of adult people with COPD or ILD. The ERS task force consisted of 20 members, including representatives of people with COPD or ILD and informal caregivers. Eight questions were formulated, four in the Population, Intervention, Comparison, Outcome format. These were addressed with full systematic reviews and application of Grading of Recommendations Assessment, Development and Evaluation for assessing the evidence. Four additional questions were addressed narratively. An "evidence-to-decision" framework was used to formulate recommendations. The following definition of palliative care for people with COPD or ILD was agreed. A holistic and multidisciplinary person-centred approach aiming to control symptoms and improve quality of life of people with serious health-related suffering because of COPD or ILD, and to support their informal caregivers. Recommendations were made regarding people with COPD or ILD and their informal caregivers: to consider palliative care when physical, psychological, social or existential needs are identified through holistic needs assessment; to offer palliative care interventions, including support for informal caregivers, in accordance with such needs; to offer advance care planning in accordance with preferences; and to integrate palliative care into routine COPD and ILD care. Recommendations should be reconsidered as new evidence becomes available.


Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire.
We tested the hypothesis that coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD) as assessed by a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) is in agreement with CFR measurements assessed by intracoronary Doppler flow wire. Contrast-enhanced transthoracic second harmonic echo Doppler is a novel noninvasive method to detect blood flow velocity and reserve in the LAD. However, it has not yet been validated versus a gold-standard method. Twenty-five patients undergoing CFR assessment in the LAD by Doppler flow wire were also evaluated by contrast-enhanced transthoracic Doppler to record blood flow in the distal LAD at rest and during hyperemia obtained by adenosine i.v. infusion. In five patients CFR was evaluated twice (before and after angioplasty). As a result of the combined use of i.v. contrast and second harmonic Doppler technology, feasibility in assessing coronary flow reserve equaled 100%. The agreement between the two methods was high. In fact, in all but five patients the maximum difference between the two CFR measurements was 0.38. Overall, the prediction (95%) interval of individual differences was -0.69 to +0.72. Reproducibility of CFR measurements was also high. The limits of the agreement (95%) between the two measurements were -0.32 to +0.32. Coronary flow reserve in the LAD as assessed by contrast-enhanced transthoracic echo Doppler along with harmonic mode concurs very closely with Doppler flow wire CFR measurements. This new noninvasive method allows feasible, reliable and reproducible assessment of CFR in the LAD.


Making prediabetes visible in primary health care: a qualitative study of health care professionals' perspectives.
People with prediabetes are at high risk of developing type 2 diabetes and its complications, such as cardiovascular diseases and premature mortality. Primary prevention and health maintenance are therefore imperative. Evidence has shown that prediabetes can be prevented or delayed with behavioural change, mainly in eating habits and physical activity. Interventions that use a person-centered approach can lead to improvements in self-management, quality of life, and health outcomes. Nevertheless, there is a need for further research that engages healthcare professionals and people with prediabetes in constructing and implementing preventive programs. The purpose of this study is to explore and describe how healthcare professionals perceive prediabetes, the current challenges in its detection and treatment, and what is needed to improve quality of care. This qualitative study was conducted in Region Stockholm. A total of 26 primary health care professionals participated in individual interviews: 15 diabetes nurses and/or district nurses, five general practitioners, five dietitians, and one physiotherapist. Interview transcripts were analyzed with qualitative content analysis. The analysis revealed two main themes that emphasize the need to make prediabetes more visible in primary health care. Despite the healthcare professionals' engagement and their motivation to improve prediabetes care, ad hoc practices and the absence of clear screening guidelines and referral pathways made it harder to focus on primary prevention. Supporting professionals in implementing structured care for people with prediabetes might encourage more efficient interprofessional collaboration and contribute to better strategies for promoting behavioural change. Establishing prediabetes care guidelines, supporting health care professionals´ knowledge and skills in prediabetes care, and implementing interprofessional referral pathways are some steps to enhance prediabetes detection and care precedence in primary health care. These steps could lead to more preventive care and ensure patient safety and health care equity.


Lipidomics in biomedical research-practical considerations.
Lipids have many central physiological roles including as structural components of cell membranes, energy storage sources and intermediates in signaling pathways. Lipid-related disturbances are known to underlie many diseases and their co-morbidities. The emergence of lipidomics has empowered researchers to study lipid metabolism at the cellular as well as physiological levels at a greater depth than was previously possible. The key challenges ahead in the field of lipidomics in medical research lie in the development of experimental protocols and in silico techniques needed to study lipidomes at the systems level. Clinical questions where lipidomics may have an impact in healthcare settings also need to be identified, both from the health outcomes and health economics perspectives. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.


Sources of radiographic distortion in conventional and computed tomography of the temporal bone.
To identify those bony regions of the glenoid fossa where, due to the inclination, there is an increased risk of radiographic distortion in conventional and computed tomography (CT). The inclination of the roof and posterior wall of the glenoid fossa was determined relative to established imaging planes. Measurements were performed on 50 corrected coronal MR and 50 axial CT images and 200 sagittal cryosections of 50 temporomandibular joints (TMJs). The location of regions with unfavourable bone wall inclination was identified using the condyle as a reference. The inclination of parts of the fossa roof exceeded the limit for reliable depiction in corrected sagittal and coronal planes in 40% and 8% of the joints respectively. The inclination of parts of the posterior wall of the fossa exceeded the limit for reliable depiction in corrected sagittal and in true sagittal planes in 100% and 84% of the joints respectively. In 84% of the joints the inclination exceeded the limit for reliable depiction in the axial plane. For both bone walls the regions with unfavourable inclination were in the medial part of the joint. The angulation of parts of the roof and posterior wall of the glenoid fossa in relation to established imaging planes makes them highly susceptible to distortion. The oblique coronal projection is well suited for depiction of the roof of the fossa and preferable to a sagittal projection. An oblique axial projection is required for the posterior wall.


Food after deprivation rewards the earlier eating.
Food intake can be increased by learning to anticipate the omission of subsequent meals. We present here a new theory that such anticipatory eating depends on an associative process of instrumental reinforcement by the nutritional repletion that occurs when access to food is restored. Our evidence over the last decade from a smooth-brained omnivore has been that food after deprivation rewards intake even when those reinforced ingestive responses occur long before the physiological signals from renewed assimilation. Effects of food consumed after self-deprivation might therefore reward extra eating in human beings, through brain mechanisms that could operate outside awareness. That would have implications for efforts to reduce body weight. This food reward mechanism could be contributing to the failure of the dietary component of interventions on obesity within controlled trials of the management or prevention of disorders such as hypertension, atherosclerosis and type 2 diabetes.


Evaluation of full cortical allografts in 25 dogs.
Twenty-five dogs received 26 cortical allografts from Apr 9, 1976 through Jan 31, 1982. Cortical allografts were used to reconstruct fractures of the femur, humerus, tibia, radius, and ulna. These grafts were used to replace comminuted fragments; to lengthen bones; to correct malunions, delayed unions, and nonunions; and in one case, to replace bone lost to sequestrum formation in an infected fracture site. All fractures were stabilized by use of standard ASIF techniques and dynamic compression plates. Frozen bone allografts were used in all cases. These were harvested aseptically and stored in a household freezer for 3 days to one year before use. Clinically normal function was achieved in 96% of the dogs.


Update on risk stratification and treatment of newly diagnosed multiple myeloma.
Multiple myeloma is the second most common hematologic malignancy. Chromosomal aberrations are important prognostic determinants that influence the clinical decision-making in newly-diagnosed multiple myeloma (NDMM). Patients are considered high-risk if any of the following features are detected: hypodiploidy, deletion 13 by cytogenetics, t(4;14), t(14;16), t(14;20) and/or 17 p deletion. In the absence of these features patients are considered standard risk. Outside of trials, risk-adapted therapy in the transplant-eligible high-risk patients advocates use of bortezomib-based induction therapy followed by autologous stem cell transplantation (ASCT) and bortezomib-based maintenance therapy. High-risk, transplant-ineligible patients should also utilize bortezomib as initial therapy since it is known to overcome the poor prognosis associated with some high-risk features. The goal of therapy in high-risk patients is to attain and maintain a state of complete remission as much as possible. In contrast, the standard-risk, transplant-eligible patients may be treated with either lenalidomide-dexamethasone or bortezomib-based therapy followed by ASCT. In such patients, ASCT can also be deferred until first relapse if the patients are tolerating initial therapy well. Lenalidomide maintenance therapy in the post-transplant setting in standard-risk patients is controversial and not recommended routinely. For transplant-ineligible standard-risk patients, multiple options exist, although in the absence direct comparisons, we prefer lenalidomide plus low-dose dexamethasone over melphalan-based combinations. This review outlines evidence-based management approaches in NDMM, with a focus on risk-adapted therapy.


Contemporary issues in the diagnosis of prostate cancer for the radiologist.
Prostate cancer diagnostic techniques have improved considerably in recent years, but they must yet be optimised to ensure cancer detection at a potentially curable stage. Arrangements for prostate biopsy vary throughout Europe, and prostate biopsy may be undertaken by urologists or radiologists. This review discusses current issues relevant for radiologists involved in the detection of early prostate cancer. Prostate biopsy should be based on a systematic approach involving 8-12 cores obtained with peri-prostatic infiltration of local anaesthetic. Quality issues being considered by the United Kingdom Prostate Cancer Risk Management Programme are discussed.


Role of Surgical Approach to Synchronous Colorectal Liver Metastases: A Retrospective Analysis.
This study is a retrospective analysis of exploring the efficiency of surgical management on patients with synchronous colorectal liver metastasis (SCLM). Nine hundred fifty-three consecutive patients with SCLM from Weifang People's Hospital of Shandong Province between January 2006 and December 2015 were reviewed. The values of different factors were analyzed, such as different surgical indications of liver metastases, simultaneous or staged resection of primary colorectal cancer and liver metastases, and primary tumor resection (PTR) of asymptomatic patients with unresectable liver metastases. Median survival time (47.3 months) and 5-year survival rate (31%) for patients with resected liver metastases were significantly superior to that of with nonoperative treatment (17.2 months, 4%, P<0.001); enlarging the standard of liver metastases resection can improve the resection rates (31.0% vs 13.6%, P<0.001); for patients with resectable liver metastases, the in-hospital cost for simultaneous resection group was lower than that in the staged resection group (36,698 vs 45,134 RMB, P<0.001); for patients of the asymptomatic primary tumor with unresectable liver metastases, PTR was associated with improved median survival (18.0 vs 15.0 months, P=0.006). For patients with SCLM, liver resection is considered the best treatment; expanding indications of liver resection can improve the resection rates. Simultaneous resection of the primary tumor and liver metastases were indicated in patients with resectable SCLM; PTR was recommended for asymptomatic patients with unresectable hepatic metastases.


The Pain Self-Efficacy Questionnaire: Cross-Cultural Adaptation into Italian and Assessment of Its Measurement Properties.
The Pain Self-Efficacy Questionnaire (PSEQ) is a patient self-reported measurement instrument that evaluates pain self-efficacy beliefs in patients with chronic pain. The measurement properties of the PSEQ have been tested in its original and translated versions, showing satisfactory results for validity and reliability. The aims of this study were 2 fold as follows: (1) to translate the PSEQ into Italian through a process of cross-cultural adaptation, (2) to test the measurement properties of the Italian PSEQ (PSEQ-I). The cross-cultural adaptation was completed in 5 months without omitting any item of the original PSEQ. Measurement properties were tested in 165 patients with chronic low back pain (CLBP) (65% women, mean age 49.9 years). Factor analysis confirmed the one-factor structure of the questionnaire. Internal consistency (Cronbach's α = 0.94) and test-retest reliability (ICCagreement = 0.82) of the PSEQ-I showed good results. The smallest detectable change was equal to 15.69 scale points. The PSEQ-I displayed a high construct validity by meeting more than 75% of a priori hypotheses on correlations with measurement instruments assessing pain intensity, disability, anxiety, depression, pain catastrophizing, fear of movement, and coping strategies. Additionally, the PSEQ-I differentiated patients taking pain medication or not. The results of this study suggest that the PSEQ-I can be used as a valid and reliable tool in Italian patients with CLBP.


Time, Irreversibility and Entropy Production in Nonequilibrium Systems.
The aim of this review is to shed light on time and irreversibility, in order to link macroscopic to microscopic approaches to these complicated problems. After a brief summary of the standard notions of thermodynamics, we introduce some considerations about certain fundamental aspects of temporal evolution of out-of-equilibrium systems. Our focus is on the notion of entropy generation as the marked characteristic of irreversible behaviour. The concept of time and the basic aspects of the thermalization of thermal radiation, due to the interaction of thermal radiation with matter, are explored concisely from complementary perspectives. The implications and relevance of time for the phenomenon of thermal radiation and irreversible thermophysics are carefully discussed. The concept of time is treated from a different viewpoint, in order to make it as clear as possible in relation to its different fundamental problems.


Quantification of Vibrio parahaemolyticus, Vibrio vulnificus and Vibrio cholerae in French Mediterranean coastal lagoons.
Vibrio parahaemolyticus, Vibrio vulnificus and Vibrio cholerae are human pathogens. Little is known about these Vibrio spp. in the coastal lagoons of France. The purpose of this study was to investigate their incidence in water, shellfish and sediment of three French Mediterranean coastal lagoons using the most probable number-polymerase chain reaction (MPN-PCR). In summer, the total number of V. parahaemolyticus in water, sediment, mussels and clams collected from the three lagoons varied from 1 to >1.1 × 10³ MPN/l, 0.09 to 1.1 × 10³ MPN/ml, 9 to 210 MPN/g and 1.5 to 2.1 MPN/g, respectively. In winter, all samples except mussels contained V. parahaemolyticus, but at very low concentrations. Pathogenic (tdh- or trh2-positive) V. parahaemolyticus were present in water, sediment and shellfish samples collected from these lagoons. The number of V. vulnificus in water, sediment and shellfish samples ranged from 1 to 1.1 × 10³ MPN/l, 0.07 to 110 MPN/ml and 0.04 to 15 MPN/g, respectively, during summer. V. vulnificus was not detected during winter. V. cholerae was rarely detected in water and sediment during summer. In summary, results of this study highlight the finding that the three human pathogenic Vibrio spp. are present in the lagoons and constitute a potential public health hazard.


Maternal mortality and manpower. Comparisons in relation to anaesthetists, obstetricians, and paediatricians in England and Wales and in Japan.
In 1982 maternal mortality in England and Wales was given seven per 100 000 compared to 18 per 100 000 total births in Japan. This represented 160 more deaths in Japan. Perinatal mortality rates were similar in England and Wales and Japan, being 11.3 and 10.1 per 1000 respectively. The prevalence of obstetricians and paediatricians per 100 000 total births are approximately similar in England and Wales and in Japan, whereas the rates for anaesthetists are five times less in Japan. In England and Wales, 13% of maternal deaths were related to anaesthetic misadventures, but the Japanese incidence is not known. However, more than 50% of anaesthetics for Caesarean sections in district hospitals in Japan are administered by obstetricians. A pilot study in Japan would be necessary to determine the precise role of anaesthetic provision on maternal mortality. Maternal mortality may prove a useful indicator of anaesthetic service deficiency.


Diet, inflammation, and chronic kidney disease: getting to the heart of the matter.
Cardiovascular disease (CVD) remains a leading cause of death in patients with chronic kidney disease (CKD). CVD is now thought to result from the interplay of several factors including inflammation, oxidative stress and endothelial dysfunction. Advanced glycation end products (AGE) are known to be elevated in patients with CKD and these compounds possess these pro-oxidant, pro-inflammatory and anti-endothelial properties. There has been a great deal of literature linking diet and inflammation, and recent work has shown the diet to be a significant contributor to the body's AGE pool. We herein hypothesize that a diet high in AGE plays an important role in the initiation of chronic subclinical inflammation that seems to underlie the high prevalence of CVD in CKD patients. Herein we will briefly examine the evidence linking different components of diet with inflammation in CKD patients. We will then focus on the role of dietary AGEs in inflammation and potentially CVD in CKD, and in conclusion, we will propose dietary modifications as part of a multifactorial approach to ameliorate unhealthy lifestyles among CKD patients. The most important message is that simple changes in culinary technique rather than in the food nutrient composition may be the most important part of preventing CVD in this population.


Examining gender differences in adolescent exposure to food and beverage marketing through go-along interviews.
This study explores how adolescents engage with unhealthy food and beverage marketing in online settings, from a gender perspective. Employing an online ethnography approach and using go-along interviews, we explored the experiences of adolescent boys and girls aged 13-17 as they navigated their online experiences with digital food and beverage marketing. Notable themes emerged, including the identification of predatory actions by food companies, the role of protective factors such as family, and the influence of social media influencers in shaping adolescent dietary preferences. Importantly, this research unearthed gender disparities in the participants' responses. Girls, in particular, exhibited a heightened awareness of the protective role played by their families, emphasized the influence of color in marketing strategies, recognized the significance of gender in marketing, and reported exposure to alcohol advertisements-findings that boys less frequently echoed. The study underscores the importance of adolescence as a critical phase in development, during which food companies target these impressionable individuals, driven by their independence and potential for brand loyalty. Moreover, it highlights the potential avenue of gender-specific marketing, offering valuable insights into the gendered dimensions of adolescents' food marketing experiences. By examining the interplay between digital food marketing and gender, this research addresses a critical gap in the literature, shedding light on how gender influences adolescents' perceptions, responses, and behaviors in the context of food marketing strategies. These findings have the potential to inform adolescents of the marketing techniques that target them and guide policymakers in developing and implementing evidence-based regulations aimed at safeguarding adolescents from exposure to unhealthy food marketing.


Nonsyndromic paucity of interlobular bile ducts: report of 10 patients.
Only a few reports of nonsyndromic paucity of interlobular bile ducts (NS-PILBD) have been published. The authors' aim was to outline the clinical and laboratory profile of patients with NS-PILBD diagnosed at a tertiary referral center. The authors reviewed all the reports of pediatric liver biopsies performed between 1991 and 2000 at their institution. Upon diagnosis of NS-PILBD, patients' records were examined for clinical, laboratory, and histologic data, and liver biopsy specimens were re-evaluated. Three hundred biopsies were performed in children during the study period, of which 64 were in infants younger than 1 year. NS-PILBD was diagnosed in 10 of 64 (16%) biopsy specimens. Mean age at presentation was 10 days (range, 1 day-6 weeks), and mean follow-up was 4.5 years (range, 1-9 years). An underlying condition was identified in 70% of children with NS-PILBD: namely congenital cytomegalovirus (n = 2), progressive familial intrahepatic cholestasis (PFIC, n = 2), mitochondrial DNA depletion (n = 1), Niemann-Pick type C (n = 1), and arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC syndrome; n = 1). All children presented with jaundice. Four children had initially acholic stools. At their last follow-up visit, failure to thrive was present in five children, and cholestasis in six children. Mortality was noted only in children with metabolic diseases (n = 2). In the study, NS-PILBD was common in young children undergoing liver biopsy. Although NS-PILBD is nonspecific, a wide survey for inborn errors of metabolism should be included in the diagnostic work-up of NS-PILBD. In the authors' center, the association of certain metabolic diseases with NS-PILBD carries a grave prognosis.


Inclusive jet production in pp(macro) collisions.
We report a new measurement of the pseudorapidity (eta) and transverse-energy ( E(T)) dependence of the inclusive jet production cross section in pp(macro) collisions at square root of s = 1.8 TeV using 95 pb(-1) of data collected with the D0 detector at the Fermilab Tevatron. The differential cross section d(2)sigma/(dE(T)d eta) is presented up to eta = 3, significantly extending previous measurements. The results are in good overall agreement with next-to-leading order predictions from QCD and indicate a preference for certain parton distribution functions.


A novel botulinum neurotoxin topical gel: Treatment of allergic rhinitis in rats and comparative safety profile.
Rhinitis affects a significant proportion of adults and children with typically seasonal or chronic symptoms. Botulinum neurotoxin type A (BoNTA) is a well-known cholinergic antagonist widely used in a number of approved neurological and esthetic indications. This study was designed to assess the therapeutic effect of RT001, a novel topical gel formulation of BoNTA, in the treatment of allergic rhinitis using a rat model and to compare its safety profile with that of an aqueous formulation of BoNTA complex. A rat model of allergic rhinitis was used involving induction of classic rhinitis signs (sneezing and nasal itch) in addition to nasal inflammatory pathology to assess the degree of therapeutic effect of RT001. Comparative safety of RT001 and BoNTA complex was assessed in guinea pigs based on lethality and body weight gain. Clinical signs of rhinitis were significantly (p < 0.01) relieved after a single intranasal administration of RT001 and resolved to normal baseline levels within 5 days after treatment. Mucosal inflammation characterized by edema, congestion, and vascular dilatation along with increased expression of vasoactive intestinal peptide was noted in control animals after allergy induction, whereas RT001 treatment resolved inflammation to essentially normal baseline levels. Safety studies in guinea pigs via intranasal dosing revealed ∼31-fold greater safety factor for RT001 when compared with BoNTA complex. These results suggest that topical intranasal application of RT001 is effective in relief of clinical signs and inflammatory pathology associated with allergic rhinitis in a rodent model and may provide a safe treatment for rhinitis.


Phase I study of hepatic arterial degradable starch microspheres and mitomycin.
Intraarterial administration of 40-microns degradable starch microspheres (DSM) in a drug solution can temporarily retard flow of the drug-blood column through the arteriolar-capillary bed and lead to increased local drug deposition. Premonitory to Phase II-III efficacy studies applying this concept to regional therapy, it was necessary to determine the DSM dose to use. Patients with hepatic cancers were treated with varying doses of DSM with mitomycin C coadministered into the hepatic artery to define a dose of DSM which produces acceptable toxicity with maximal hepatic drug deposition as determined by a reduction in systemic mitomycin C exposure. Comparison of six patients receiving 6 ml of DSM (6 X 10(6) particles/ml) with ten patients receiving 15 ml showed a lower incidence and decreased severity of acute toxicity in terms of nausea/vomiting (16% versus 50%) and right upper quadrant hepatic pain (none versus 40%) with 6 ml of DSM. Reduction in systemic mitomycin C exposure evaluated by decrements in the area under the concentration curve in peripheral blood with time due to DSM was similar in both groups. Another seven patients were treated with escalating doses of DSM concurrently with 5 mg of mitomycin C. Although all seven patients tolerated 6 ml of DSM, higher doses (9 ml, 12 ml, 15 ml) led to incremental patient drop-out due to severe, acute right upper quadrant pain with only two patients able to receive 15 ml of DSM. In these patients, 6 ml of DSM appeared nearly equivalent to higher doses in terms of systemic exposure to mitomycin C. Eleven additional patients were evaluated for tolerance to repeated 6-ml dosing of DSM. Four patients had epigastric pain correlating with flow to the stomach demonstrated by nuclide angiography. The seven patients with no pain and no flow to stomach were treated with good tolerance for three-plus courses. Thus, 6 ml of DSM appear to be appropriate for Phase II-III studies.


The anti-tumor histone deacetylase inhibitor SAHA and the natural flavonoid curcumin exhibit synergistic neuroprotection against amyloid-beta toxicity.
With the trend of an increasing aged population worldwide, Alzheimer's disease (AD), an age-related neurodegenerative disorder, as one of the major causes of dementia in elderly people is of growing concern. Despite the many hard efforts attempted during the past several decades in trying to elucidate the pathological mechanisms underlying AD and putting forward potential therapeutic strategies, there is still a lack of effective treatments for AD. The efficacy of many potential therapeutic drugs for AD is of main concern in clinical practice. For example, large bodies of evidence show that the anti-tumor histone deacetylase (HDAC) inhibitor, suberoylanilidehydroxamic acid (SAHA), may be of benefit for the treatment of AD; however, its extensive inhibition of HDACs makes it a poor therapeutic. Moreover, the natural flavonoid, curcumin, may also have a potential therapeutic benefit against AD; however, it is plagued by low bioavailability. Therefore, the integrative effects of SAHA and curcumin were investigated as a protection against amyloid-beta neurotoxicity in vitro. We hypothesized that at low doses their synergistic effect would improve therapeutic selectivity, based on experiments that showed that at low concentrations SAHA and curcumin could provide comprehensive protection against Aβ25-35-induced neuronal damage in PC12 cells, strongly implying potent synergism. Furthermore, network analysis suggested that the possible mechanism underlying their synergistic action might be derived from restoration of the damaged functional link between Akt and the CBP/p300 pathway, which plays a crucial role in the pathological development of AD. Thus, our findings provided a feasible avenue for the application of a synergistic drug combination, SAHA and curcumin, in the treatment of AD.


Collagenases and cracks in the plaque.
The core of an atheromatous plaque contains lipids, macrophages, and cellular debris, typically covered by a fibrous cap that separates the thrombogenic core from the blood. Rupture of the fibrous cap causes most fatal myocardial infarctions. Interstitial collagen confers tensile strength on the cap, as it does in skin and tendons. In 1994, Peter Libby and colleagues demonstrated overexpression of collagenolytic enzymes in atheromatous plaques and implicated MMPs in the destabilization of these lesions.


Treatment of rats with the JAK-2 inhibitor fedratinib does not lead to experimental Wernicke's encephalopathy.
Recent clinical trials suggest that patients with myelofibrosis can develop Wernicke's encephalopathy (WE) when treated with fedratinib, a specific Janus kinase-2 (JAK-2) inhibitor. To investigate this issue, we have examined (1) if fedratinib can produce or alter the course of this disorder, (2) its effects on thiamine-dependent enzyme activity and thiamine status, and (3) its influence on the uptake of thiamine. Animals administered fedratinib for 28days at a comparable dose used to treat human cases of myelofibrosis showed no evidence of clinical signs of thiamine deficiency (TD). Rats treated with a combination of fedratinib and TD exhibited no neurological differences in their progress to the symptomatic stage when compared to thiamine-deficient animals only. Treatment with the JAK-2 inhibitor did not compromise erythrocyte transketolase activity, and thiamine status was not affected in a major way unlike animals with TD. In addition, treatment of cultured astrocytes with fedratinib did not diminish the uptake of thiamine into these cells. Our findings suggest that treatment with fedratinib does not lead to or alter the progress of TD, and do not support the notion that administration of this JAK-2 inhibitor directly results in the development of WE due to inhibition of thiamine transport. Known adverse effects of fedratinib involving compromised gastrointestinal function may be an important indirect contributing factor to previously reported cases of WE in patients with myelofibrosis.


Antiproliferative and cytotoxic effects of some sigma2 agonists and sigma1 antagonists in tumour cell lines.
To establish the activity of sigma ligands at sigma1 and sigma2 receptor, we chose two tumour cell lines, the human SK-N-SH neuroblastoma and the rat C6 glioma lines, which express sigma2 receptors at a high density and sigma1 receptors in their high-affinity or low-affinity state. We tested the sigma2 receptor agonist PB28 and the sigma2 antagonist AC927, and (+)-pentazocine and NE100 as agonist and antagonist, respectively, at sigma1 receptors, with regard to antiproliferative and cytotoxic effects. In addition, 1,3-di(2-tolyl)guanidine (DTG) and haloperidol were tested as reference compounds displaying nearly equipotent sigma affinity (sigma2>sigma1 and sigma1>sigma2, respectively). In both SK-N-SH and C6 cells, PB28 and NE100 displayed the most potent results both in antiproliferative and cytotoxic assay while AC927 and (+)-pentazocine were inactive in both assays. The cytotoxic and antiproliferative effects of DTG and haloperidol reflected their sigma1 antagonist activity and sigma2 agonist activity. Moreover, our results in the tumour cell lines correlated well with those for sigma2 activity found previously in a functional assay in the guinea-pig bladder. These findings establish a new model for evaluating both sigma2 and sigma1 receptor activity of sigma ligands, which could be useful for developing new ligands having mixed sigma2 agonist/sigma1 antagonist activity as potential antineoplastic agents.


Seasonal variation of leaf wax n-alkane production and δ(2)H values from the evergreen oak tree, Quercus agrifolia.
In order to understand the timing of leaf wax synthesis in higher plants, we analysed the variability in leaf wax n-alkane concentration, composition (expressed as average chain length (ACL)), and δ(2)Hwax values as well as plant source water δ(2)H values (xylem and leaf water) in the evergreen tree Quercus agrifolia over a period of 9 months, beginning with leaf flush. We identified three distinct periods of leaf development with the first month following leaf flush being characterized by de novo synthesis and possibly removal of n-alkanes. During the following 3 months, n-alkane concentrations increased sevenfold and δ(2)Hwax and ACL values increased, suggesting this period was the major leaf wax n-alkane formation period. During the remaining 4 months of the experiment, stable values suggest cessation of leaf wax n-alkane formation. We find that n-alkane synthesis in Q. agrifolia takes place over 4 months, substantially longer than that observed for deciduous trees.


Inhibition of anaerobic wastewater treatment after long-term exposure to low levels of CuO nanoparticles.
CuO nanoparticles (NPs) are released into wastewater due to the widespread use and generation as by-product in various applications (e.g. semiconductor manufacturing). However, information on the behavior and impact of CuO NPs on wastewater treatment processes is very limited. The objective of this study was to evaluate the fate and long-term effect of CuO NPs (average size = 37 nm) on high-rate anaerobic bioreactors. A laboratory-scale upflow anaerobic sludge blanket reactor was operated with a synthetic wastewater containing low concentrations of CuO NPs (1.4 mg Cu L(-1)) and a mixture of volatile fatty acids for 107 days. CuO NPs were largely removed during anaerobic treatment and on the average only 20-32% of the NPs fed to the reactor escaped with the effluent. Scanning electron microscopy and chemical analysis confirmed that CuO NPs were partitioned into the anaerobic sludge. While short-term exposure to CuO NPs (1.4 mg Cu L(-1)) only caused minor inhibition to methanogenesis, extended exposure caused severe toxicity and reduced the acetoclastic methanogenic activity by more than 85%. Moreover, the reactor performance was completely disrupted and the methane production decreased by more than 50%. The study is the first to demonstrate a significant long-term effect of low levels of CuO NPs on methanogenesis.


An experimental model of acute humoral rejection of renal allografts associated with concomitant cellular rejection.
Acute humoral rejection (AHR), which occurs in up to 8% of kidney transplant recipients, is a significant cause of renal allograft dysfunction and loss. More efficacious treatment modalities are needed to eliminate or curtail alloantibody production and its deleterious effects on the kidney. The availability of animal models mimicking human AHR is essential to understand its pathophysiology and develop new treatment strategies. Using a mouse kidney transplant model, we demonstrate that presensitization of recipients with donor skin grafts results in rejection of subsequent renal allografts. All presensitized mice developed renal failure 8.6 +/- 4.3 days after engraftment, with serum creatinine values near 100 micromol/dl. Graft histology revealed mild, diffuse, interstitial, mononuclear cell infiltrates; prominent peritubular capillary inflammatory cell margination; patchy interstitial hemorrhage; interstitial edema; and focal glomerular fibrin deposition. Complement (C3d) deposition was diffuse and prominent in peritubular capillaries. Serum analysis demonstrated high levels of circulating alloantibodies with broad cross-reactivity to many MHC haplotypes. The clinical setting and histological findings of our model strongly resemble AHR, which is frequently associated with cellular rejection, a situation commonly encountered in human renal allograft recipients. This animal model provides a valuable tool to study the pathogenesis of AHR, its relationship to cellular alloimmunity, its contribution to graft injury, and the effects of various potential therapeutic interventions.


Evaluation of Genotoxic Pressure along the Sava River.
In this study we have performed a comprehensive genotoxicological survey along the 900 rkm of the Sava River. In total, 12 sites were chosen in compliance with the goals of GLOBAQUA project dealing with the effects of multiple stressors on biodiversity and functioning of aquatic ecosystems. The genotoxic potential was assessed using a complex battery of bioassays performed in prokaryotes and aquatic eukaryotes (freshwater fish). Battery comprised evaluation of mutagenicity by SOS/umuC test in Salmonella typhimurium TA1535/pSK1002. The level of DNA damage as a biomarker of exposure (comet assay) and biomarker of effect (micronucleus assay) and the level of oxidative stress as well (Fpg-modified comet assay) was studied in blood cells of bleak and spirlin (Alburnus alburnus/Alburnoides bipunctatus respectively). Result indicated differential sensitivity of applied bioassays in detection of genotoxic pressure. The standard and Fpg-modified comet assay showed higher potential in differentiation of the sites based on genotoxic potential in comparison with micronucleus assay and SOS/umuC test. Our data represent snapshot of the current status of the river which indicates the presence of genotoxic potential along the river which can be traced to the deterioration of quality of the Sava River by communal and industrial wastewaters. The major highlight of the study is that we have provided complex set of data obtained from a single source (homogeneity of analyses for all samples).


The US tobacco control community's view of the future of tobacco harm reduction.
Tobacco harm reduction (THR) has garnered recent attention due to the introduction of novel nicotine delivery products ostensibly intended to reduce risk for inveterate cigarette smokers. This study evaluates the grassroots tobacco control community's knowledge, opinions, and beliefs about THR. A web/mail survey conducted in October and November 2002, with a telephone survey of a sample of non-respondents. The 2833 US based registrants for the 2001 National Conference on Tobacco or Health. Respondents' awareness of THR, perception of its importance, support for regulation, and perception of which THR products should be recommended to inveterate cigarette smokers. 70% of respondents were aware of THR but respondents had low recognition of specific products at the forefront of the debate, such as Swedish snuff. Half believe THR will reduce smoking cessation and cause nicotine experimentation by children; 63% anticipate unintended adverse side effects. More expect THR to have a negative than a positive impact on health. Large majorities support government regulation of THR and conventional tobacco products, but fewer than 30% expect legislation regulating either. Most would recommend nicotine patches (76%) and gum (70%) to inveterate smokers, but no other product was supported by a majority. Scientists are more supportive of THR than activists, while respondents focusing on national/international issues are more supportive than those concentrating on local/state issues. Many members of the US tobacco control community are unaware of the THR "movement", while others possess only rudimentary familiarity with it. If and as THR achieves an increasingly prominent role on the tobacco-or-health scene, this community will have to become educated about THR, and be prepared to advocate for regulatory policies that will maximise the potential for positive outcomes. The potential for negative outcomes remains significant.


Immediate effect of ankle balance taping on dynamic and static balance of soccer players with acute ankle sprain.
[Purpose] This study aimed to evaluate the immediate effect of ankle balance taping on balance ability of soccer players with acute ankle sprain. [Subjects and Methods] This study was conducted with 16 subjects who were diagnosed with ankle sprain. A cross-over randomized design was used. Each subject performed three interventions in a random order. Subjects were randomly assigned to an ankle balance taping, placebo taping, and no taping. For dynamic and static balance, ability was measured using BIORescue (RM Ingenierie, Rodes, France). Limit of stability, sway length and sway speed for one minute were measured. [Results] The Limit of Stability, Sway length and Sway speed differed significantly among the three different taping methods. [Conclusion] In this study, we found that ankle balance taping was effective in terms of improving balance ability of soccer players with an ankle sprain.


Longitudinal Changes in Combat-Related Posttraumatic Stress Disorder Among Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans With Hazardous Alcohol Use: The Role of Avoidance Coping.
Military personnel who have experienced combat trauma are at risk for developing posttraumatic stress disorder (PTSD). A greater recognition of the complex array of vulnerability factors that contribute to PTSD severity has led researchers to examine other non-combat-related factors. This longitudinal study examined a number of pre-, peri-, and postdeployment factors hypothesized to contribute to PTSD symptomatology among returning Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans presenting with at least subthreshold PTSD symptoms and hazardous alcohol use in a primary care setting. Purported risk factors included childhood family environment, severity of combat exposure, postdeployment social support, alcohol dependence severity, and an avoidant coping style. At baseline, postdeployment social support and avoidant coping contributed to PTSD severity. Only avoidant coping was associated with changes in PTSD symptom at 1-year follow-up. Reducing avoidant coping may deter the maintenance of PTSD among veterans with PTSD symptoms and hazardous alcohol use.


Should asymptomatic atrophic retinal holes be treated prophylactically in pseudophakic eyes after Nd:YAG laser posterior capsulotomy?
Retinal detachment (RD) following cataract extraction is a serious and potentially sight-threatening event that will often necessitate further surgical intervention. Of the several risk factors reported in the literature, Neodymium:YAG laser posterior capsulotomy has been reported to increase the risk of RD following cataract surgery up to 4.9-fold. The purpose of this study is to investigate the difference of characteristics in pseudophakic RD with or without Nd:YAG laser posterior capsulotomy and the possible role of atrophic retinal holes in pseudophakic RD after posterior capsulotomy. Retrospective review of 78 cases of pseudophakic RD after uncomplicated extracapsular lens extraction and intraocular lens implantation was done. Twenty-one of them received Nd:YAG laser posterior capsulotomy before RD. We measured the numbers, types, and locations of retinal breaks and several other risk factors associated with RD. Analysis was performed with the system of Statistical Products and Services Solutions (SPSS). The ratio of retinal holes only in retinal breaks that caused retinal detachment was significantly higher in the capsulotomy group than the non-capsulotomy group (12/21 vs 14/57, p = 0.05). Only three patients in the capsulotomy group claimed significant symptoms before the detachment. There was no significant difference in mean number of retinal breaks and break location. Other risk factors predisposing to RD did not differ significantly between the two groups (13/21 vs 23/57, p = 0.12), nor did the interval from cataract surgery to RD (31.20 vs 29.44 months, p = 0.48). This primitive study suggests that asymptomatic atrophic retinal holes, usually not regarded as an absolute risk factor for RD, might lead to RD preferentially after Nd:YAG laser posterior capsulotomy. Early identification and treatment of such breaks might decrease the incidence of pseudophakic RD. We suggest that it is necessary to perform detailed preoperative and postoperative fundus examination and treat prophylactically any identified breaks, including asymptomatic atrophic retinal holes, in pseudophakic eyes after Nd:YAG laser posterior capsulotomy.


The activity of daily living (ADL) subgroups and health impairment among Chinese elderly: a latent profile analysis.
Disability in aged people became one of the major challenges in China due to the acceleration of population aging. Nevertheless, there were limited methods to appropriately discriminate the degree of combined basic activity of daily living (BADL) and instrumental activity of daily living (IADL). The present study explored an empirical typology of the activity of daily living (ADL) and its association with health status among the elderly in China. Data throughout the Chinese Longitudinal Healthy Longevity Survey (CLHLS) was retrieved and Latent profile analysis (LPA) was conducted to identify the subgroups of ADL for included elderly subjects. Multinomial regression was performed to detect the effect of identified characteristics with ADL subgroups, and the restricted cubic spine was drawn to show the changes in the relationship between age-specific ADL disability and BMI. The overall participants (n=8108) were divided into three ADL classes by LPA - 'no BADL limitation-no IADL limitation' (Class one, n=6062, 75%), 'no BADL limitation- IADL impairment' (Class two, n=1526, 19%), and 'BADL impairment- IADL impairment' (Class three, n=520, 6%). Compared with the participants in Class one, the oldest-old, living without spouse, lacking of exercise, short in social activities, having experience of falls, having comorbidity of diabetes, heart disease, stroke, decreased cognitive function, depression symptom were highly associated with Class two and Class three. Additionally, malnutrition and asthma were associated with combined BADL/IADL impairment (Class three), while illiteracy was only associated with IADL impairment (Class two). Furthermore, a statistically significant U-shape association was detected between age and BADL/IADL disability (Class three vs. Class two) as well as BMI and BADL/IADL disability (Class three vs. Class one). The elderly aged 80-90 with IADL impairment were less likely to evolve into combined BADL/IADL impairment, and the elderly who were underweight or obese may have higher risk of combined BADL/IADL impairment. A novel functional assessment was explored based on LPA, by which elderly people could be classified into three distinct classes of combined BADL/IADL. The predictors identified with particular IADL/BADL classes could draw early attention to the onset of functional disability and enlighten targeted interventions to address consequent problems of aged people.


Lessons learned from implementation of voice recognition for documentation in the military electronic health record system.
This study evaluated the implementation of voice recognition (VR) for documenting outpatient encounters in the electronic health record (EHR) system at a military hospital and its 12 outlying clinics. Seventy-five clinicians volunteered to use VR, and 64 (85 percent) responded to an online questionnaire post implementation to identify variables related to VR continuance or discontinuance. The variables investigated were user characteristics, training experience, logistics, and VR utility. Forty-four respondents (69 percent) continued to use VR and overall felt that the software was accurate, was faster than typing, improved note quality, and permitted closing a patient encounter the same day. The discontinuation rate of 31 percent was related to location at an outlying clinic and perceptions of inadequacy of training, decreased productivity due to VR inaccuracies, and no improvement in note quality. Lessons learned can impact future deployment of VR in other military and civilian healthcare facilities.


Weather as a trigger of stroke. Daily meteorological factors and incidence of stroke subtypes.
The conclusions of previous studies show little agreement concerning the relationship between weather and the incidence of stroke. We analyse the relationship between daily meteorological conditions and daily as well as seasonal stroke incidence. 1,286 consecutive strokes assessed during 3 years (2001-2003) from the reference area of Hospital del Mar were classified as intracerebral haemorrhage (ICH) (n = 243) or ischaemic stroke (IS) (n = 1,043). IS was divided in non-lacunar stroke (NLS) (n = 732) and lacunar stroke (LS) (n = 311). Daily meteorological data were obtained from 'Observatori Fabra' of Barcelona: atmospheric pressure (AP), relative humidity, maximum, minimum, and mean temperatures, and the variation of all these measures compared with the previous day. Total stroke (TS) incidence showed little association with AP (coefficient of confidence, CC: -0.072; p = 0.022), but was higher with the AP variations (CC: 0.127; p < 0.001). NLS were related to AP falls (OR: 2.41; p < 0.001) whilst ICHs were associated with AP rises (OR: 2.07; p = 0.01). NLS and temperature showed an inverse correlation; however, it lost its significance after adjusting for AP variations. The daily incidences of NLS and ICH were higher in autumn and in winter, but depended strongly on the daily variations of AP. No other associations were found. The incidences of NLS and ICH are related to AP changes compared with the previous day. AP changes largely explain the seasonal and daily variations in the incidence of stroke. These data may help to explain the controversy in previous studies and to promote studies focused on the trigger mechanisms of stroke.


Treatment algorithm use to optimize management of symptomatic patients with a history of mania.
While monotherapy has significant limitations in bipolar disorder, few published data addressing alternatives exist. Treatment algorithms have been proposed, but none have undergone empirical evaluation. This study provides a systematic prospective, open evaluation of the effectiveness and tolerability of a treatment algorithm for patients with histories of mania. Twenty-eight symptomatic outpatients from a public mental health facility who were diagnosed as having either bipolar I or schizoaffective illness, bipolar type, entered the study. Minimum blood levels of lithium and divalproex sodium were defined. Medications were pushed to predetermined levels (as tolerated) before proceeding to the next algorithm step. Clinical symptoms were assessed monthly using the Brief Psychiatric Rating Scale (BPRS, 27 item) and Clinical Global Impressions scale. Pretreatment and posttreatment clinical symptoms were compared. Over 50% of patients attained 30% improvement from baseline BPRS after 4 months. Thirty-six percent of patients (N = 10) became mood stable, 46% (N = 13) remained mood unstable, and 18% (N = 5) dropped out before completing the algorithm. Although patients who finished the algorithm were taking more medication, either dosage and/or drugs, somatic complaints did not increase. The potential benefit of a defined treatment algorithm was demonstrated for these complex and persistently ill patients. Despite long treatment histories, patients improved with more frequent visits and addition of medication(s). A randomized controlled trial comparing a similar treatment algorithm with treatment-as-usual is warranted.


Prevalence of Disabilities and Health Care Access by Disability Status and Type Among Adults - United States, 2016.
Persons with disabilities face greater barriers to health care than do those without disabilities (1). To identify characteristics of noninstitutionalized adults with six specific disability types (hearing, vision, cognition, mobility, self-care, and independent living),* and to assess disability-specific disparities in health care access, CDC analyzed 2016 Behavioral Risk Factor Surveillance System (BRFSS) data. The prevalences of disability overall and by disability type, and access to health care by disability type, were estimated. Analyses were stratified by three age groups: 18-44 years (young adults), 45-64 years (middle-aged adults), and ≥65 years (older adults). Among young adults, cognitive disability (10.6%) was the most prevalent type. Mobility disability was most prevalent among middle-aged (18.1%) and older adults (26.9%). Generally, disability prevalences were higher among women, American Indians/Alaska Natives (AI/AN), adults with income below the federal poverty level (FPL), and persons in the South U.S. Census region. Disability-specific disparities in health care access were prevalent, particularly among young and middle-aged adults. These data might inform public health programs of the sociodemographic characteristics and disparities in health care access associated with age and specific disability types and guide efforts to improve access to care for persons with disabilities.


Potentiating the efficacy of molecular targeted therapy for hepatocellular carcinoma by inhibiting the insulin-like growth factor pathway.
Insulin-like growth factor (IGF) signaling pathway is an important regulatory mechanism of tumorigenesis and drug resistance in many cancers. The present study explored the potential synergistic effects between IGF receptor (IGFR) inhibition and other molecular targeted agents (MTA) in HCC cells. HCC cell lines (Hep3B, PLC5, and SK-Hep1) and HUVECs were tested. The MTA tested included sorafenib, sunitinib, and the IGFR kinase inhibitor NVP-AEW541. The potential synergistic antitumor effects were tested by median dose effect analysis and apoptosis assay in vitro and by xenograft models in vivo. The activity and functional significance of pertinent signaling pathways and expression of apoptosis-related proteins were measured by RNA interference and Western blotting. We found that IGF can activate IGFR and downstream AKT signaling activities in all the HCC cells tested, but the growth-stimulating effect of IGF was most prominent in Hep3B cells. NVP-AEW541 can abrogate IGF-induced activation of IGFR and AKT signaling in HCC cells. IGF can increase the resistance of HCC cells to sunitinib. The apoptosis-inducing effects of sunitinib, but not sorafenib, were enhanced when IGFR signaling activity was inhibited by NVP-AEW541 or IGFR knockdown. Chk2 kinase activation was found contributory to the synergistic anti-tumor effects between sunitinib and IGFR inhibition. Our data indicate that the apoptosis-potentiating effects of IGFR inhibition for HCC may be drug-specific. Combination therapy of IGFR inhibitors with other MTA may improve the therapeutic efficacy in HCC.


[The biochemical characteristics of the products of the vital activity of Yersinia pseudotuberculosis in relation to the cultivation temperature].
For the first time the metabolic processes, taking place during "cold" cultivation of Y. pseudotuberculosis and involving organic and amino acids, were shown to be more economical, thus permitting the bacteria to maintain its viability for a rather long time at low temperature without the need to consume these substances from outside. At higher temperature the bacteria switches its metabolic paths to the consumption of nutrient substances in greater amounts from outside, increasing its constructive metabolism.


Deep phylogenetic analysis of haplogroup G1 provides estimates of SNP and STR mutation rates on the human Y-chromosome and reveals migrations of Iranic speakers.
Y-chromosomal haplogroup G1 is a minor component of the overall gene pool of South-West and Central Asia but reaches up to 80% frequency in some populations scattered within this area. We have genotyped the G1-defining marker M285 in 27 Eurasian populations (n= 5,346), analyzed 367 M285-positive samples using 17 Y-STRs, and sequenced ~11 Mb of the Y-chromosome in 20 of these samples to an average coverage of 67X. This allowed detailed phylogenetic reconstruction. We identified five branches, all with high geographical specificity: G1-L1323 in Kazakhs, the closely related G1-GG1 in Mongols, G1-GG265 in Armenians and its distant brother clade G1-GG162 in Bashkirs, and G1-GG362 in West Indians. The haplotype diversity, which decreased from West Iran to Central Asia, allows us to hypothesize that this rare haplogroup could have been carried by the expansion of Iranic speakers northwards to the Eurasian steppe and via founder effects became a predominant genetic component of some populations, including the Argyn tribe of the Kazakhs. The remarkable agreement between genetic and genealogical trees of Argyns allowed us to calibrate the molecular clock using a historical date (1405 AD) of the most recent common genealogical ancestor. The mutation rate for Y-chromosomal sequence data obtained was 0.78×10-9 per bp per year, falling within the range of published rates. The mutation rate for Y-chromosomal STRs was 0.0022 per locus per generation, very close to the so-called genealogical rate. The "clan-based" approach to estimating the mutation rate provides a third, middle way between direct farther-to-son comparisons and using archeologically known migrations, whose dates are subject to revision and of uncertain relationship to genetic events.


Feasibility of collecting oral fluid samples in the home setting to determine seroprevalence of infections in a large-scale cohort of preschool-aged children.
Oral fluid is a non-invasive biological sample, which can be returned by post, making it suitable for large-scale epidemiological studies in children. We report our experience of oral fluid collection from 14 373 preschool-aged children in the UK Millennium Cohort Study. Samples were collected by mothers in the home setting following the guidance of trained interviewers, and posted to the laboratory. Samples were received from 11 698 children (81.4%). Children whose mothers were of Black Caribbean ethnicity and who lived in non-English-speaking households were less likely to provide a sample, and those with a maternal history of asthma more likely to provide a sample [adjusted risk ratio (95% CI) 0.85 (0.73-0.98), 0.87 (0.77-0.98) and 1.03 (1.00-1.05) respectively]. Collection of oral fluid samples is feasible and acceptable in large-scale child cohort studies. Formal interpreter support may be required to increase participation rates in surveys that collect biological samples from ethnic minorities.


An Assessment of Anxiety about the Viral Epidemic and Work-Related Stress in Family Physicians in Turkey: How Does COVID-19 Vaccination Period Affect Anxiety and Stress?
Our study aimed to evaluate the extent of family physicians' anxiety about the viral epidemic and work-related stress associated with the viral epidemic as well as examining the effects of COVID-19 vaccination period on such situations. Data collection forms including the SAVE-9 scale, prepared for this cross-sectional study, were converted into online questionnaires and sent to family physicians in order to evaluate and examine the extent of anxiety and stress of family physicians working as family physicians in different provinces of Turkey via e-mails and communication groups between December, 2020 and March, 2021. The responses of 500 family physicians who were accessible in this way and volunteered to participate in the study were recorded to be analysed. Of all the 500 physicians, the SAVE-9 scale was re-administered to the subgroup of 50 family physicians in the post-vaccination period. The responses were compared with those received in the pre-vaccination period. Of all the 500 family physicians in this study, 40.6% of them were found to be in a state of anxiety about the viral epidemic. In particular, the scores of anxiety about the viral epidemic and of work-related stress were found much higher in female physicians and in those reporting that they had inadequate income. While there was a significant decline in the scores of anxiety about the viral epidemic in the subgroup in the post-vaccination period of health care workers, no statistically significant change was found in work-related stress scores. Family physicians have been suffering anxiety due to the pandemic. The vaccination period has a positive impact on anxiety levels.


Widespread prevalence of wolbachia in laboratory stocks and the implications for Drosophila research.
Wolbachia is an intracellular microbe harbored by a wide variety of arthropods (including Drosophila) and filarial nematodes. Employing several different strategies including male killing, induced parthenogenesis, cytoplasmic incompatibility, and feminization, and acting by as-yet-unknown mechanisms, Wolbachia alters host reproduction to increase its representation within a population. Wolbachia is closely associated with gametic incompatibility but also interacts with Drosophila in other, little understood ways. We report here significant and widespread infection of Wolbachia within laboratory stocks and its real and potential impact on Drosophila research. We describe the results of a survey indicating that approximately 30% of stocks currently housed at the Bloomington Drosophila Stock Center are infected with Wolbachia. Cells of both reproductive tissues and numerous somatic organs harbor Wolbachia and display considerable variation in infection levels within and between both tissue types. These results are discussed from the perspective of Wolbachia's potential confounding effects on both host fitness and phenotypic analyses. In addition to this cautionary message, the infection status of stock centers may provide further opportunities to study the genetic basis of host/symbiosis.