Quantifying undesired parallel components in Thévenin-equivalent acoustic source parameters.
The calibration of an ear probe to determine its Thévenin-equivalent acoustic source parameters facilitates the measurement of ear-canal impedance and reflectance. Existing calibration error metrics, used to evaluate the quality of a calibration, are unable to reveal undesired parallel components in the source parameters. Such parallel components can result from, e.g., a leak in the ear tip or improperly accounting for evanescent modes, and introduce errors into subsequent measurements of impedance and reflectance. This paper proposes a set of additional error metrics that are capable of detecting such parallel components by examining the causality of the source admittance in the frequency domain and estimating the source pressure in the time domain. The proposed and existing error metrics are applied to four different calibrations using two existing calibration methods, representing typical use cases and introducing deliberate parallel components. The results demonstrate the capability of the proposed error metrics in identifying various undesired components in the source parameters that might otherwise go undetected.


Effects of repeated anaesthesia on gill and general health of Atlantic salmon, Salmo salar.
Fish are the second most widely utilized vertebrate group used for scientific procedures in the United Kingdom, but the development and application of 3Rs (the principles of replacement, reduction, and refinement) in aquaculture disease research lags behind methodologies in place for mammalian studies. With a need for individual monitoring and non-lethal sampling, the effect of repeat anaesthesia on experimental fish needs to be better understood. This study analyses the effect of repeat anaesthesia with MS-222, metomidate and AQUI-S upon the gill and general health of post-smolt Atlantic salmon Salmo salar. A single, lethal dose of anaesthetic was compared with seven anaesthetizing time points over 28 days, terminating in a lethal dose. No anaesthetic showed significant differences in accumulation in the muscle tissue, or changes in plasma glucose after repeated or single dosing. Fish repeatedly anaesthetized with MS-222 or AQUI-S exhibited upregulation of osmoregulatory genes in the gill and AQUI-S-treated individuals showed, histologically, epithelial lifting from the lamellae capillary irrespective of whether they had a single or repeated dose history. No significant changes were seen in inflammatory or stress genes in the head kidney of fish repeatedly anaesthetized with AQUI-S or metomidate, however MS-222 treatment resulted in upregulation of tnfα3. Repeated anaesthesia with MS-222 and metomidate gave a significant decrease and increase in peripheral blood neutrophils, respectively. This study concludes that no increase in cumulative stress or inflammation is induced by the repeated anaesthetization of S. salar with any of the tested anaesthetics, however gill osmotic regulation and blood parameters may be affected.


pH changes caused by bacterial growth in contaminated platelet concentrates.
While platelet concentrates are stored at room temperature, lactic and other acids are produced and the pH decreases as the buffering capacity of the plasma is exhausted. Platelet viability will be compromised if the pH decreases to pH 6.0 and below. Similarly, a pH decrease can be produced also by bacterial contamination if the organisms produce acid as an end product. Thus the determination of pH could serve as a sensitive indicator of bacterial contamination. This hypothesis was tested by us by inoculating known organisms into platelet concentrations. It was found that the pH may decrease, may remain unchanged, or, in a few cases, even increase. Visual signs of contamination could be observed but not consistently enough to be entirely dependable. Therefore, this method does not appear to detect bacterial contamination reliably in platelet concentrates.


A 31-Year-Old Man with COVID-19-Associated Empyema and Lupus Anticoagulant.
BACKGROUND COVID-19 was declared a pandemic in March 2020 in the United States. It has been associated with high mortality and morbidity all over the world. COVID-19 can cause a significant inflammatory response leading to coagulopathy and this hypercoagulable state has been associated with worse clinical outcomes in these patients. The published data regarding the presence of lupus anticoagulant in critically ill COVID-19-positive patients is limited and indicates varying conclusions so far. CASE REPORT Here, we present a case of a 31-year-old man who was admitted to the hospital with COVID-19 pneumonia, complicated with superadded bacterial empyema and required video-assisted thoracoscopic surgery with decortication. This patient also had prolonged prothrombin time on preoperative labs, which was not corrected with mixing study. Further workup detected positive lupus anticoagulant and anti-cardiolipin IgM along with alteration in other coagulation factor levels. The patient was treated with fresh frozen plasma and vitamin K before surgical intervention. He had an uneventful surgical course. He received prophylactic-dose low molecular weight heparin for venous thromboembolism prophylaxis and did not experience any thrombotic events while hospitalized. CONCLUSIONS COVID-19 infection creates a prothrombotic state in affected patients. The formation of micro-thrombotic emboli results in significantly increased mortality and morbidity. Routine anticoagulation with low molecular weight heparin can prevent thrombotic events and thus can improve patient outcomes. In patients with elevated prothrombin time, lupus anticoagulant/anti-cardiolipin antibody-positivity should be suspected, and anticoagulation prophylaxis should be continued perioperatively for better outcomes.


[General trends in the pathomorphosis of surgical diseases of the thyroid after the Chernobyl catastrophe].
An analysis is presented of changes in the patterns of surgical pathologies of the thyroid gland that had occurred during the 15-yr follow-up of the Kiev Region representatives operated on in a specialized clinic facility. Increase in the incidence rates of autoimmune Hashimoto's thyroiditis, benign and malignant tumours of the thyroid gland--such were main trends in pathomorphosis of thyroidal pathologies having been noted during the post-ChPP accident years. Increase in the number of cases of carcinoma with concurrent hyperplastic and autoimmune thyroid diseases attests to the need for a comprehensive evaluation of patients presenting with different forms of goiter as well as for their surgical treatment in a timely fashion.


Neurotrophic factor for serotonergic neurons prevents degeneration of grafted raphe neurons in the cerebellum.
Earlier studies in this laboratory have shown that partial serotonergic (5-HT) deafferentation from the hippocampus induced a homotypic sprouting. The 5-HT-denervated hippocampus was further found to be a favorable environment for the growth of grafted 5-HT, but not for norepinephrinergic neurons. In the current study, we have extracted a trophic factor in the denervated hippocampus with hypotonic solution in high-speed supernatant fraction. The trophic extract was assayed in a unique experimental paradigm--test the growth of grafted 5-HT neurons in the cerebellum, which receives the least 5-HT innervation, and where grafted 5-HT neurons have seldom survived. The diluted trophic extract (1:200) produced a dramatic increase in (a) the survival rate, (b) the 5-HT fiber-density, and (c) the 5-HT and 5-hydroxyindoleacetic acid levels of grafted 5-HT neurons in the cerebellum. In addition, Nissl-counterstaining showed that the size of the grafted raphe also apparently increased. The concentrated trophic extract (1:1) did not increase the survival rate of the grafted raphe neurons. These results indicate that (a) the supernatant in the 5-HT-denervated hippocampus contains a potent neurotrophic factor to 5-HT neurons (b) which can either directly or indirectly also support non-5-HT raphe neurons, and (c) possibly an inhibitory factor is present which is detrimental to 5-HT neurons in high concentration.


Increased light-use efficiency sustains net primary productivity of shaded coffee plants in agroforestry system.
In agroforestry systems, shade trees strongly affect the physiology of the undergrown crop. However, a major paradigm is that the reduction in absorbed photosynthetically active radiation is, to a certain extent, compensated by an increase in light-use efficiency, thereby reducing the difference in net primary productivity between shaded and non-shaded plants. Due to the large spatial heterogeneity in agroforestry systems and the lack of appropriate tools, the combined effects of such variables have seldom been analysed, even though they may help understand physiological processes underlying yield dynamics. In this study, we monitored net primary productivity, during two years, on scales ranging from individual coffee plants to the entire plot. Absorbed radiation was mapped with a 3D model (MAESPA). Light-use efficiency and net assimilation rate were derived for each coffee plant individually. We found that although irradiance was reduced by 60% below crowns of shade trees, coffee light-use efficiency increased by 50%, leaving net primary productivity fairly stable across all shade levels. Variability of aboveground net primary productivity of coffee plants was caused primarily by the age of the plants and by intraspecific competition among them (drivers usually overlooked in the agroforestry literature) rather than by the presence of shade trees.


Autochthonous dengue fever, Tokyo, Japan, 2014.
After 70 years with no confirmed autochthonous cases of dengue fever in Japan, 19 cases were reported during August-September 2014. Dengue virus serotype 1 was detected in 18 patients. Phylogenetic analysis of the envelope protein genome sequence from 3 patients revealed 100% identity with the strain from the first patient (2014) in Japan.


Subureteric polydimethylsiloxane injection in the treatment of vesico-ureteric reflux.
Endoscopic treatment of vesico-ureteric reflux is a viable alternative to open surgery. We evaluated the effectiveness of polydimethylsiloxane in the endoscopic treatment of vesico-ureteric reflux. In the period between September 1994 and March 1996, 30 ureteral units of 20 children with vesico-ureteric reflux were treated by means of subureteric polydimethylsiloxane injection. Median age was 8 years in the group including 8 female and 12 male patients. Of the 30 ureteral units, 26 had no reflux at the end of the first injection. Two of the remaining four units were not refluxing after the second injection procedure. Contralateral reflux was observed postoperatively in two of the eleven patients who were treated for unilateral disease. It seems that endoscopic polydimethylsiloxane injection is an effective procedure in the treatment of vesico-ureteric reflux.


Screening for IL28B gene variants identifies predictors of hepatitis C therapy success.
Recent research has shown that genetic variation in the IL28B gene predicts both chronicity of HCV infection and sustained virological response (SVR) to antiviral standard therapy. Because HCV affects 170 million people worldwide and is a leading cause of cirrhosis and hepatocellular carcinoma, screening for prognostic factors in routine clinical practice requires rapid and reliable assays. The frequencies of gene polymorphisms IL28B rs8099917, rs12979860 and rs12980275 were investigated in two cohorts of 89 and 187 unrelated HCV-infected Caucasian patients and 195 non-infected participants. This was carried out by means of newly developed sensitive Pyrosequencing™ screening assays. The minor alleles were more frequent in patients (n=276) than in controls (n=195), with odds ratios (recessive hereditary model) of 2.2-11.6, indicating a moderate to large genotype effect size. The positive predictive values of the minor alleles for chronicity of HCV infection were 68.3%, 64.8% and 65.8% for rs8099917, rs12979860 and rs12980275, respectively. The minor alleles were also more frequent in patients who had a non-SVR (n=49) than in SVR patients (n=40), with odds ratios of 1.1-3.5 showing a small to moderate genotype effect size. The positive predictive values for non-SVR were 56.9%, 79.2% and 74% for rs8099917, rs12979860 and rs12980275, respectively. With the screening for IL28B polymorphisms rs12980275, rs8099917 and rs12979860, which are associated with HCV chronicity and with reduced SVR rates, an important prognostic factor of the therapy of chronic hepatitis C can be easily diagnosed.


Neurocysticercosis and nursing implications.
Neurocysticercosis causes significant neurologic morbidity and mortality in many countries and is increasing in frequency in the United States. The disease should be considered in any patient who has lived in or traveled to an area where it is endemic and who presents clinically with signs of increased intracranial pressure, stroke, seizures, or other neurologic deficits. Neurocysticercosis can be a life-threatening disease depending on the size, location, and active or inactive status of the cysts. Neurocysticercosis is treatable both medically and surgically according to symptoms. The sooner the correct diagnosis is made, the greater the chances for recovery and prevention of further neurologic deterioration. The nurse who is knowledgeable about the cause and treatment for neurocysticercosis can assist in controlling the incidence of this disease, decreasing complications, and averting needless mortality.


A novel dinuclear species in the aqueous distribution of aluminum in the presence of citrate.
The chemistry of aluminum was explored in the presence of the physiological ligand citric acid and in low-pH aqueous media. As a result, the first dinuclear aluminum-citrate complex (NH4)4[Al2-(C6H4O7)(C6H5O7)2].4H2O was isolated at low pH (approximately 3.5), and was characterized by FT-IR spectroscopy and X-ray crystallography. The structural analysis reveals the presence of a dinuclear assembly of two aluminum ions octahedrally coordinated to three citrate ligands of differing protonation state. The NMR solution behavior of this complex emphasizes its time-dependent transformation into a number of variable nature species, ultimately leading to the thermodynamically stable trinuclear species. It also establishes the participation of the dinuclear complex as a viable component of the aqueous Al(III)-citrate speciation. The chemical and structural features of this novel low molecular mass species provide considerable insight into citrate's ability, as a natural ligand, to influence the chemistry of aluminum in a pH-dependent fashion, and potentially affect aluminum's (bio)distribution, absorption, accumulation, and biotoxicity at sensitive biological sites.


Glycosaminoglycans and infection.
Glycosaminoglycans (GAGs) are complex linear polysaccharides expressed in intracellular compartments, at the cell surface, and in the extracellular environment where they interact with various molecules to regulate many cellular processes implicated in health and disease. Subversion of GAGs is a pathogenic strategy shared by a wide variety of microbial pathogens, including viruses, bacteria, parasites, and fungi. Pathogens use GAGs at virtually every major portals of entry to promote their attachment and invasion of host cells, movement from one cell to another, and to protect themselves from immune attack. Pathogens co-opt fundamental activities of GAGs to accomplish these tasks. This ingenious strategy to subvert essential activities of GAGs likely prevented host organisms from deleting or inactivating these mechanisms during their evolution. The goal of this review is to provide a mechanistic overview of our current understanding of how microbes subvert GAGs at major steps of pathogenesis, using select GAG-pathogen interactions as representative examples.


Of mice and men: Pinpointing species differences in adipose tissue biology.
The prevalence of obesity and metabolic diseases continues to rise, which has led to an increased interest in studying adipose tissue to elucidate underlying disease mechanisms. The use of genetic mouse models has been critical for understanding the role of specific genes for adipose tissue function and the tissue's impact on other organs. However, mouse adipose tissue displays key differences to human fat, which has led, in some cases, to the emergence of some confounding concepts in the adipose field. Such differences include the depot-specific characteristics of visceral and subcutaneous fat, and divergences in thermogenic fat phenotype between the species. Adipose tissue characteristics may therefore not always be directly compared between species, which is important to consider when setting up new studies or interpreting results. This mini review outlines our current knowledge about the cell biological differences between human and mouse adipocytes and fat depots, highlighting some examples where inadequate knowledge of species-specific differences can lead to confounding results, and presenting plausible anatomic explanations that may underlie the differences. The article thus provides critical insights and guidance for researchers working primarily with only human or mouse fat tissue, and may contribute to new ideas or concepts in the important and evolving field of adipose biology.


Gefitinib inhibits M2-like polarization of tumor-associated macrophages in Lewis lung cancer by targeting the STAT6 signaling pathway.
M2-like polarized tumor-associated macrophages (TAMs) play a pivotal role in promoting cancer cell growth, invasion, metastasis and angiogenesis. The identification of M2-like TAMs during tumor progression is an attractive approach for cancer therapy. In this study, we investigated the relevance of macrophage polarization and the antitumor effect of gefitinib in Lewis Lung cancer (LLC) in vitro and in vivo. Gefitinib at a concentration below 2.5 μmol/L did not cause significant growth inhibition on LLC and RAW 264.7 cell lines and bone marrow-derived macrophage (BMDMs). However, a small concentration of gefitinib (0.62 μmol/L) significantly inhibited IL-13-induced M2-like polarization of macrophages, evidenced by the decreased expression of the M2 surface markers CD206 and CD163, down-regulation of specific M2-marker genes (Mrc1, Ym1, Fizz1, Arg1, IL-10 and CCL2) as well as inhibition of M2-like macrophage-mediated invasion and migration of LLC cells. In RAW 264.7 cells, gefitinib inhibits IL-13-induced phosphorylation of STAT6, which was a crucial signaling pathway in macrophage M2-like polarization. In LLC mice metastasis model, oral administration of gefitinib (75 mg·kg-1·d-1, for 21 d) significantly reduced the number of lung metastasis nodules, down-regulated the expression of M2 marker genes and the percentages CD206+ and CD68+ macrophages in tumor tissues. These results demonstrated that gefitinib effectively inhibits M2-like polarization both in vitro and in vivo, revealing a novel potential mechanism for the chemopreventative effect of gefitinib.


Thoracic endovascular aortic repair for type B aortic dissection.
Thoracic endovascular aortic repair (TEVAR) has emerged as an acceptable off-label treatment modality for aortic dissection. We report our experience in endovascular treatment of this disease with an emphasis on defining the patterns of morbidity. We retrospectively reviewed all (n = 90) patients with thoracic aortic disease who received a TEVAR between February 2005 and December 2007. Aortic dissection was the indication in 23 (26%) patients (48% acute, 52% chronic; Stanford A 17%, Stanford B 83%). For the purposes of this report, we concentrated on the type B dissection (17 patients). Eighty-two percent of the patients were symptomatic on presentation, and 56% of cases were performed either urgently or emergently. Technical success was achieved in 100% of cases, with an average operative time of 178 + or - 119 min. Forty-seven percent required a left subclavian bypass. Thirty-day mortality was 5.5% and morbidity was 12%. Postoperative complications included respiratory failure in 28% of cases, gastrointestinal symptoms in 11%, and cerebrovascular symptoms in 5.5%. No renal failure occurred. While cerebrospinal fluid drain was used in 35% of cases, transient spinal cord ischemia was observed in 5.5%. Average length of stay was 13 + or - 12 days; 63% of patients were discharged home, 12% required rehabilitation, and 25% were discharged to a skilled nursing facility. There was no association between outcome and mode of presentation or anatomic extent. Aortic dissection remains a challenging clinical entity, and the advent of TEVAR has improved outcomes but still carries considerable morbidity, with distinct patterns between mode of presentation and anatomic extent.


A molecular map of long non-coding RNA expression, isoform switching and alternative splicing in osteoarthritis.
Osteoarthritis is a prevalent joint disease and a major cause of disability worldwide with no curative therapy. Development of disease-modifying therapies requires a better understanding of the molecular mechanisms underpinning disease. A hallmark of osteoarthritis is cartilage degradation. To define molecular events characterizing osteoarthritis at the whole transcriptome level, we performed deep RNA sequencing in paired samples of low- and high-osteoarthritis grade knee cartilage derived from 124 patients undergoing total joint replacement. We detected differential expression between low- and high-osteoarthritis grade articular cartilage for 365 genes and identified a 38-gene signature in osteoarthritis cartilage by replicating our findings in an independent dataset. We also found differential expression for 25 novel long non-coding RNA genes (lncRNAs) and identified potential lncRNA interactions with RNA-binding proteins in osteoarthritis. We assessed alterations in the relative usage of individual gene transcripts and identified differential transcript usage for 82 genes, including ABI3BP, coding for an extracellular matrix protein, AKT1S1, a negative regulator of the mTOR pathway and TPRM4, coding for a transient receptor potential channel. We further assessed genome-wide differential splicing, for the first time in osteoarthritis, and detected differential splicing for 209 genes, which were enriched for extracellular matrix, proteoglycans and integrin surface interactions terms. In the largest study of its kind in osteoarthritis, we find that isoform and splicing changes, in addition to extensive differences in both coding and non-coding sequence expression, are associated with disease and demonstrate a novel layer of genomic complexity to osteoarthritis pathogenesis.


On the Auditory-Proprioception Substitution Hypothesis: Movement Sonification in Two Deafferented Subjects Learning to Write New Characters.
The aim of this study was to evaluate the compensatory effects of real-time auditory feedback on two proprioceptively deafferented subjects. The real-time auditory feedback was based on a movement sonification approach, consisting of translating some movement variables into synthetic sounds to make them audible. The two deafferented subjects and 16 age-matched control participants were asked to learn four new characters. The characters were learned under two different conditions, one without sonification and one with sonification, respecting a within-subject protocol. The results revealed that characters learned with sonification were reproduced more quickly and more fluently than characters learned without and that the effects of sonification were larger in deafferented than in control subjects. Secondly, whereas control subjects were able to learn the characters without sounds the deafferented subjects were able to learn them only when they were trained with sonification. Thirdly, although the improvement was still present in controls, the performance of deafferented subjects came back to the pre-test level 2 h after the training with sounds. Finally, the two deafferented subjects performed differently from each other, highlighting the importance of studying at least two subjects to better understand the loss of proprioception and its impact on motor control and learning. To conclude, movement sonification may compensate for a lack of proprioception, supporting the auditory-proprioception substitution hypothesis. However, sonification would act as a "sensory prosthesis" helping deafferented subjects to better feel their movements, without permanently modifying their motor performance once the prosthesis is removed. Potential clinical applications for motor rehabilitation are numerous: people with a limb prosthesis, with a stroke, or with some peripheral nerve injury may potentially be interested.


Cholic acid micelles--controlling the size of the aqueous cavity by PEGylation.
Data show that cholic acid (CA) micelles are less densely packed and much smaller than micelles formed by typical surfactants, suggesting that CA derivatives can be used to synthesize drug nanocarriers. Presumably, the formation of internal cavities is favored by the facial characteristics of the CA molecule, i.e. the convex molecular structure that is hydrophobic on one side and hydrophilic on the other. Here, we present a thermodynamical approach to quantify the effect of facial characteristics on forces governing the self-assembling process of CA molecules. We show that facial characteristics favor the entrapment of water molecules at interfaces upon CA aggregation, which weakens the attraction between CA hydrophobic moieties. Our computer simulations suggest that these effects contribute significantly to the tendency of CA molecules to form small "hollow-core" micelles. The attachment of polyethylene glycol (PEG) molecular chains to CA increases the repulsive forces in the system, reducing even further the micelle size. We use the present molecular model and experimental critical micelle concentration (cmc) data for CA-PEG systems to predict the change of the micelle size and cavity volume with the increase of the PEG chain length (x). Our computations indicate that the CA-PEG micelles are good candidates for drug delivery. The structural stability of CA-PEG micelles was further assessed by molecular dynamics simulations. We also tested the drug loading efficiency of this system and found an average of 0.5 mg paclitaxel load per 20 mg of CA-PEG polymer. The present study helps to identify critical parameters that control structural properties of the CA based nanocarriers and suggests practical means to optimize the ratio between micelle size and volume of the internal cavity.


Risk factors for household food insecurity in the Eastern Caribbean Health Outcomes Research Network cohort study.
Globally, 1.3 billion people were considered food insecure as of 2022. In the Caribbean region, the prevalence of moderate or severe food insecurity was 71.3% as of 2020, the highest of all subregions in Latin America. Experienced based measurement scales, like the Latin American and Caribbean Food Security Scale, are efficient measurement tools of food insecurity used globally. The Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study is a population-based longitudinal cohort study in the two Caribbean U.S. territories of Puerto Rico and the U.S. Virgin Islands, as well as in Barbados and Trinidad & Tobago. The purpose of this research was to examine the demographic, psychosocial, behavioral, and environmental risk factors associated with household food insecurity (HFI) among adults ≥40 years of age in the ECHORN cohort. A cross-sectional analysis of baseline ECHORN cohort study data was conducted. The primary outcome was household food insecurity (none, mild, moderate/severe). A total of 16 known and potential risk factors were examined for their association with HFI. The ANOVA and chi-square statistics were used in bivariate analysis. Ordinal logistic regression was used for the multivariable and sex stratified analyses. More than one-quarter of the sample (27.3%) experienced HFI. In bivariate analyses, all risk factors examined except for sex, were significantly associated with HFI status. In the multivariable analysis, all variables except sex, education, marital status, smoking status, and residing in Puerto Rico were significant predictors of HFI in the adjusted model. In sex stratified analysis, depression, food availability, self-rated physical health, and island site were significantly associated with increased odds of worsening HFI for women, but not for men. Source of potable water was an important risk factor for both men and women. The prevalence of HFI in the ECHORN cohort study is comparable to other studies conducted in the region. While women did not have an increased risk of HFI compared to men, a different set of risk factors affected their vulnerability to HFI. More research is needed to understand how water and food security are interrelated in the ECHORN cohort.


Extracellular and mixotrophic symbiosis in the whale-fall mussel Adipicola pacifica: a trend in evolution from extra- to intracellular symbiosis.
Deep-sea mussels harboring chemoautotrophic symbionts from hydrothermal vents and seeps are assumed to have evolved from shallow-water asymbiotic relatives by way of biogenic reducing environments such as sunken wood and whale falls. Such symbiotic associations have been well characterized in mussels collected from vents, seeps and sunken wood but in only a few from whale falls. Here we report symbioses in the gill tissues of two mussels, Adipicola crypta and Adipicola pacifica, collected from whale-falls on the continental shelf in the northwestern Pacific. The molecular, morphological and stable isotopic characteristics of bacterial symbionts were analyzed. A single phylotype of thioautotrophic bacteria was found in A. crypta gill tissue and two distinct phylotypes of bacteria (referred to as Symbiont A and Symbiont C) in A. pacifica. Symbiont A and the A. crypta symbiont were affiliated with thioautotrophic symbionts of bathymodiolin mussels from deep-sea reducing environments, while Symbiont C was closely related to free-living heterotrophic bacteria. The symbionts in A. crypta were intracellular within epithelial cells of the apical region of the gills and were extracellular in A. pacifica. No spatial partitioning was observed between the two phylotypes in A. pacifica in fluorescence in situ hybridization experiments. Stable isotopic analyses of carbon and sulfur indicated the chemoautotrophic nature of A. crypta and mixotrophic nature of A. pacifica. Molecular phylogenetic analyses of the host mussels showed that A. crypta constituted a monophyletic clade with other intracellular symbiotic (endosymbiotic) mussels and that A. pacifica was the sister group of all endosymbiotic mussels. These results strongly suggest that the symbiosis in A. pacifica is at an earlier stage in evolution than other endosymbiotic mussels. Whale falls and other modern biogenic reducing environments may act as refugia for primal chemoautotrophic symbioses between eukaryotes and prokaryotes since the extinction of ancient large marine vertebrates.


[Determination of thiourea dioxide in lotus seed paste fillings by solid phase extraction-liquid chromatography-tandem mass spectrometry].
A method of solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) was developed to determine thiourea dioxide which was illegally added into lotus seed paste fillings. An amount of 0.05% (v/v) acetic acid was used to extract thiourea dioxide from fillings, and the BOND ELUT PLEXA column (60 mg/3 mL) was used as the SPE column to clean-up the extraction. Then, an Agilent HILIC column (100 mm x 2.1 mm, 3.5 microm) was applied to separate target compounds by using the mobile phases of 0.01 mol/L ammonium acetate (pH 3.5) and acetonitrile. Qualitative and quantitative analyses were operated by the multiple reaction monitoring (MRM) mode. The calibration curve showed a good linearity for the target compound in the detection range of 10 - 1 000 microg/L. The limit of detection (LOD) and limit of quantitation (LOQ) of this method were 8.0 microg/kg and 30.0 microg/kg, respectively. The recoveries were in the ranges of 75.3% - 80.7% with the RSDs of no more than 4.83%. This proposed method was rapid, highly specific and suitable for the confirmation and quantitative determination of thiourea dioxide in lotus seed paste fillings.


A subset of morphologically distinct mammary myoepithelial cells lacks corresponding immunophenotypic markers.
Immunostaining for smooth muscle actin (SMA) is commonly used to elucidate mammary myoepithelial (ME) cells, whose presence or absence is a reliable criterion for differentiating in situ and invasive carcinomas. However, some morphologically distinct ME cells fail to stain for SMA. This study intended to assess whether these SMA-negative cells also lack the expression of other ME cell markers. Hematoxylin/eosin and SMA immunostained sections from 175 breast cancer patients were examined. Three cases were found to harbor ducts that showed morphologically distinct ME cell layers, but showed no SMA immunostaining in at least one-third of the layer or the entire layer. Eight additional consecutive sections from each case were stained for SMA, using a black chromogen, and each was then re-stained for one of eight additional markers supposed to exclusively or preferentially stain ME cells, using a red chromogen. SMA-negative ME cells were re-examined for the expression of other markers. SMA-negative ME cells in two cases also failed to display immunoreactivity for other markers, including calponin, CD10, smooth muscle myosin heavy chain, protease inhibitor 5 (maspin), Wilms' tumor-1, and cytokeratins 5, 14, and 17 (CK5, CK14, and CK17). However, in one case SMA-negative ME cells displayed immunoreactivities for maspin, CK5, CK14, and CK17. The distribution of these ME cells is independent of ductal size, length, and architecture. A subset of morphologically identifiable ME cells lack the expression of nine corresponding immunophenotypic markers, suggesting that ME cells might also be subject to different normal and pathological alterations.


Comparative effectiveness of high-dose versus standard-dose influenza vaccination on numbers of US nursing home residents admitted to hospital: a cluster-randomised trial.
Immune responses to influenza vaccines decline with age, reducing clinical effectiveness. We compared the effect of the more immunogenic high-dose trivalent influenza vaccine with a standard-dose vaccine to identify the effect on reducing hospital admissions of nursing home residents in the USA. We did a single-blind, pragmatic, comparative effectiveness, cluster-randomised trial with a 2 × 2 factorial design. Medicare-certified nursing homes in the USA located within 50 miles of a Centers for Disease Control and Prevention influenza reporting city were recruited, so long as the facilities were not located in a hospital, had more than 50 long-stay residents, had less than 20% of the population aged under 65 years, and were not already planning to administer the high-dose influenza vaccine to residents. Enrolled nursing homes were randomised to a facility-wide standard of care for the residents of either high dose or standard dose as the vaccine for the 2013-14 influenza season and half of each group were randomly allocated to free vaccines for staff. Individual residents were included in the analysis group if they were aged 65 years or older and were long-stay residents (ie, had been in the facility 90 days or more before commencing the influenza vaccination programme). The analysts and investigators with access to the raw data were masked to study group by coding the groups until after the analyses were complete. The primary outcome was hospital admissions related to pulmonary and influenza-like illness between Nov 1, 2013, and May 31, 2014, identified from Medicare hospital claims available for residents who were without private health insurance (ie, those who were considered Medicare fee-for-service). We obtained data from the Centers for Medicare & Medicaid Services (CMS) and enrolled facilities. The analyses used marginal Poisson and Cox proportional hazards regression, accounting for clustering of residents within homes, on an intention-to-treat basis, adjusting for facility clustering and prespecified covariates. Safety data were voluntarily reported according to the standard of care. This trial is registered with ClinicalTrials.gov, number NCT01815268. 823 facilities were recruited to the study between March and August, 2013, to participate in the trial, of which 409 facilities were randomised for residents to receive high-dose vaccine, and 414 facilities for residents to receive standard-dose vaccine. The facilities housed 92 269, of whom 75 917 were aged 65 years or older and 53 008 were also long-stay residents, and 38 256 were matched to Medicare hospital claims as of Nov 1, 2013. Staff vaccination rates did not differ between groups, so analyses focused on the high-dose versus standard-dose vaccine comparison. On the basis of Medicare fee-for-service claims, the incidence of respiratory-related hospital admissions was significantly lower in facilities where residents received high-dose influenza vaccines than in those that received standard-dose influenza vaccines (0·185 per 1000 resident-days or 3·4% over 6 months vs 0·211 per 1000 resident-days or 3·9% over 6 months; unadjusted relative risk of 0·888, 95% CI 0·785-1·005, 0=0·061, and adjusted relative risk 0·873, 0·776-0·982, p=0·023). When compared with standard-dose vaccine, high-dose influenza vaccine can reduce risk of respiratory-related hospital admissions from nursing home residents aged 65 years and older. Sanofi Pasteur, Swiftwater, PA, USA.


Cytotoxic antibodies to cloned rat islet cells in serum of patients with diabetes mellitus.
We have found complement-dependent cytotoxic antibodies in the serum of 8 of 24 patients with insulin-dependent diabetes mellitus using a 51Cr cytotoxicity assay with monolayers of cloned rat islet cells (clones RINm 5F and RINm 14B). In contrast, complement-dependent cytotoxicity with 51Cr release greater than 24% was found with sera from 34 controls or from 5 patients with polyglandular failure without diabetes, and was present in only 1 serum our of 12 from patients with insulin-independent diabetes mellitus. The prevalence of antibodies appears to decrease with duration of insulin-dependent diabetes, and in one patient studied, cytotoxic antibodies were present at the time of diagnosis of diabetes. Cytotoxicity is independent of insulin synthesis, as evidenced by the linear correlation of cytotoxicity of sera for the insulin-producing clone RINm 5F and the somatostatin-producing clone RINm 14B. The present study identifies nonspecies-specific cytotoxic antibodies in the serum of patients with diabetes mellitus, and the assay used should facilitate studies of humoral immunity in the pathogenesis of diabetes mellitus.


Efficacy and safety of superficial chemical peeling in treatment of active acne vulgaris.
Acne vulgaris is an extremely common condition affecting the pilosebaceous unit of the skin and characterized by presence of comedones, papules, pustules, nodules, cysts, which might result in permanent scars. Acne vulgaris commonly involve adolescents and young age groups. Active acne vulgaris is usually associated with several complications like hyper or hypopigmentation, scar formation and skin disfigurement. Previous studies have targeted the efficiency and safety of local and systemic agents in the treatment of active acne vulgaris. Superficial chemical peeling is a skin-wounding procedure which might cause some potentially undesirable adverse events. This study was conducted to review the efficacy and safety of superficial chemical peeling in the treatment of active acne vulgaris. It is a structured review of an earlier seven articles meeting the inclusion and exclusion criteria. The clinical assessments were based on pretreatment and post-treatment comparisons and the role of superficial chemical peeling in reduction of papules, pustules and comedones in active acne vulgaris. This study showed that almost all patients tolerated well the chemical peeling procedures despite a mild discomfort, burning, irritation and erythema have been reported; also the incidence of major adverse events was very low and easily manageable. In conclusion, chemical peeling with glycolic acid is a well-tolerated and safe treatment modality in active acne vulgaris while salicylic acid peels is a more convenient for treatment of darker skin patients and it showed significant and earlier improvement than glycolic acid.


Vitamin B12 deficiency from the perspective of a practicing hematologist.
B12 deficiency is the leading cause of megaloblastic anemia, and although more common in the elderly, can occur at any age. Clinical disease caused by B12 deficiency usually connotes severe deficiency, resulting from a failure of the gastric or ileal phase of physiological B12 absorption, best exemplified by the autoimmune disease pernicious anemia. There are many other causes of B12 deficiency, which range from severe to mild. Mild deficiency usually results from failure to render food B12 bioavailable or from dietary inadequacy. Although rarely resulting in megaloblastic anemia, mild deficiency may be associated with neurocognitive and other consequences. B12 deficiency is best diagnosed using a combination of tests because none alone is completely reliable. The features of B12 deficiency are variable and may be atypical. Timely diagnosis is important, and treatment is gratifying. Failure to diagnose B12 deficiency can have dire consequences, usually neurological. This review is written from the perspective of a practicing hematologist.


Adrenocortical carcinoma presenting as a rupture and extensive retroperitoneal haemorrhage.
Adrenocortical carcinoma (ACC) is an extremely rare tumour. We are reporting a 45-year-male patient who had a history of sudden severe worsening epigastric pain and fullness in abdomen, with giddiness. The radiological investigations showed a large right suprarenal mass with extensive destruction and retroperitoneal haemorrhage, with extra capsular, periportal and liver metastases. Exploratory laparotomy was done for excisions of mass and surrounding tissue. On histopathological examination, diagnosis was given as Adreno Cortical Carcinoma with capsular, vascular, and soft tissue nodular involvement.


Tobacco use, exposure to secondhand smoke, and cessation counseling training of dental students around the world.
The Global Health Professions Student Survey (GHPSS) has been conducted among third-year dental students in schools in forty-four countries, the Gaza Strip/West Bank, and three cities (Baghdad, Rio de Janeiro, and Havana) (all called "sites" in this article). In more than half the sites, over 20 percent of the students currently smoked cigarettes, with males having higher rates than females in thirty sites. Over 60 percent of students reported having been exposed to secondhand smoke in public places in thirty-seven of forty-eight sites. The majority of students recognized that they are role models in society and believed they should receive training on counseling patients to quit using tobacco, but few reported receiving formal training. Tobacco control efforts must discourage tobacco use among dentists, promote smoke-free workplaces, and implement programs that train dentists in effective cessation-counseling techniques.


Near Infrared Photoimmunotherapy with Combined Exposure of External and Interstitial Light Sources.
Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer treatment that induces highly selective necrotic/immunogenic cell death after systemic administration of a photoabsorber antibody conjugate and subsequent NIR light exposure. However, the depth of NIR light penetration in tissue (approximately 2 cm) with external light sources limits the therapeutic effects of NIR-PIT. Interstitial light exposure using cylindrical diffusing optical fibers can overcome this limitation. The purpose in this study was to compare three NIR light delivery methods for treating tumors with NIR-PIT using a NIR laser system at an identical light energy; external exposure alone, interstitial exposure alone, and the combination. Panitumumab conjugated with the photoabsorber IRDye-700DX (pan-IR700) was intravenously administered to mice with A431-luc xenografts which are epithelial growth factor receptor (EGFR) positive. One and 2 days later, NIR light was administered to the tumors using one of three methods. Interstitial exposure alone and in combination with external sources showed the greatest decrease in bioluminescence signal intensity. Additionally, the combination of external and interstitial NIR light exposure showed significantly greater tumor size reduction and prolonged survival after NIR-PIT compared to external exposure alone. This result suggested that the combination of external and interstitial NIR light exposure was more effective than externally applied light alone. Although external exposure is the least invasive means of delivering light, the combination of external and interstitial exposures produces superior therapeutic efficacy in tumors greater than 2 cm in depth from the tissue surface.


Structure and substrate-induced conformational changes of the secondary citrate/sodium symporter CitS revealed by electron crystallography.
The secondary Na+/citrate symporter CitS of Klebsiella pneumoniae is the best-characterized member of the 2-hydroxycarboxylate transporter family. The recent projection structure gave insight into its overall structural organization. Here, we present the three-dimensional map of dimeric CitS obtained with electron crystallography. Each monomer has 13 a-helical transmembrane segments; six are organized in a distal helix cluster and seven in the central dimer interface domain. Based on structural analyses and comparison to VcINDY, we propose a molecular model for CitS, assign the helices, and demonstrate the internal structural symmetry. We also present projections of CitS in several conformational states induced by the presence and absence of sodium and citrate as substrates. Citrate binding induces a defined movement of a helices within the distal helical cluster. Based on this, we propose a substrate translocation site and conformational changes that are in agreement with the transport model of ''alternating access''.


Semen Astragali Complanati: an ethnopharmacological, phytochemical and pharmacological review.
Semen Astragali Complanati (SAC), the dried ripe seed of Flatstem Milkvetch (Astragalus complanatus Bunge) (Leguminosae), is commonly used in traditional Chinese medicine (TCM) for treating muscle, liver, kidney, blood, skin and reproductive system diseases. Relevant information about SAC was gathered via "Google Scholar", "ISI Web of Knowledge", "PubMed", "ScienceDirect", "Medline Plus", "ACS", "CNKI" and "Wiley Online Library" and from books in local libraries. The major contents of SAC include fatty acids, amino acids, polysaccharides, flavonoids, triterpene glycosides and trace elements. Previous scientific studies have reported that SAC exhibits a number of therapeutic effects on chronic diseases such as cardiovascular diseases, diabetes mellitus and cancers. It has been found that flavonoids are the main bioactive component in SAC. However most of the previous studies have shown the effects brought by the total flavonoid fraction extracted from SAC only; further studies are warranted for the biological effects produced by individual components. There are only a few studies on the toxicity of SAC and the overall results show that its toxicity is quite low or even non-existent. SAC is a valuable TCM herb with multiple pharmacological effects for treating some chronic diseases. More studies on SAC will help us to have a better understanding of its pharmacological mechanisms so as to provide more scientific evidence to explain its traditional uses, identify its therapeutic potential on other diseases and understand its possible harmful effects. Based on previous studies, it is easy to identify that antioxidant effect of SAC might play an important role on its pharmacological effects. Studying the effects of SAC on handling intracellular reactive oxygen species may be a potential direction to help understanding the molecular mechanisms of SAC on preventing and/or treating chronic diseases.


The complexities of fibromyalgia and its comorbidities.
Fibromyalgia syndrome (FMS) is defined as chronic, widespread musculoskeletal pain and tenderness with concomitant mood and cognitive dysfunction. Several comorbidities have been reported to be associated with FMS. We reviewed the literature concerning the most noteworthy chronic conditions associated with FMS. There is mounting evidence displaying the concurrence of fibromyalgia and coexisting medical and psychiatric conditions. Such comorbidities may blur the classical clinical presentations and erroneously lead to misinterpretation of disease activity. The recognition of this fact should be underlined, as misrecognition may lead to excessive therapy and avoidable side-effects of medications on the one hand and to a better handling of FMS on the other hand, leading to improved clinical outcomes. A greater proportion of psychiatric and rheumatologic disorders are associated with FMS patients than the population. Consequently, physicians treating patients with either condition should keep in mind that these patients may have such comorbidities and should be treated accordingly.


Guidelines for adapting cognitive stimulation therapy to other cultures.
Cognitive stimulation therapy (CST) has been shown to be an useful and cost effective intervention that increases cognition and quality of life of people with mild to moderate dementia. It is increasing in popularity in the UK and worldwide, and a number of research teams have examined its effectiveness in other contexts and cultures. However, it is necessary to develop clear evidence-based guidelines for cultural modification of the intervention. This article describes a community-based developmental approach to adapt CST to different cultures, following the five phases of the formative method for adapting psychotherapy (FMAP), an approach that involves collaborating with service users as a first step to generate and support ideas for therapy adaptation. Examples based on clinical and practical experience are presented, along with suggestions for applying these changes in different cultural contexts.


A seven-year experience with patients with juvenile nasopharyngeal angiofibroma.
Juvenile nasopharyngeal angiofibroma (JNA) is a rare tumor in adolescent males. It originates in the nasopharynx. To present the experience of JNA management at an Otorhinolaryngology Service between 2001 and 2008. Demographical data, clinical presentation, investigations as well as the treatment of sixteen JNA patients were reviewed and collected from medical records from the ORL Service. Cross-sectional, retrospective and descriptive study. All JNA patients were male. The average age at diagnosis was 16.8 years (range 9-23 years). More than 56% of the patients were classified as Fisch II. Preoperative embolization was carried out in ten (62.5%) patients. All 16 patients were submitted to primary surgical resection. Two patients (66.7%) who didn't receive preoperative embolization required intraoperative blood transfusion. The overall recurrence rate was 43.75% and the cure rate was 93.75%. Preoperative embolization minimizes intraoperative blood loss. The recurrence rate was related to advanced tumoral stage at diagnostic and the lack of preoperative embolization. Surgery combined with preoperative embolization is the major treatment for JNA. All the patients should undergo preoperative imaging studies, especially CT, to assist in surgical planning and follow-up.


HLA-DR antigen-negative acute myeloid leukemia.
Human leukocyte antigen (HLA) Class II antigens are variably expressed on acute myeloid leukemia (AML) blasts. The biological and clinical significance of HLA Class II antigen expression by AML cells is not known. Therefore, we sought to characterize cases of AML without detectable HLA-DR expression. Samples from 248 consecutive adult AML patients were immunophenotyped by multiparameter flow cytometry at diagnosis. HLA-DR antigens were not detected on AML cells from 43 patients, including 20 with acute promyelocytic leukemia (APL), and 23 with other subtypes of AML. All APL cases had t(15;17), but there were no characteristic chromosome abnormalities in non-APL cases. No direct expression of other antigens was identified in HLA-DR-negative APL and non-APL cases. Interestingly, cells from three HLA-DR-negative non-APL patients had similar morphology to that of the hypogranular variant of APL. This morphology, however, was not present in any HLA-DR-positive AML cases. Treatment response was similar in the 23 HLA-DR-negative non-APL and the 205 HLA-DR-positive patients. Finally, relapse was infrequently associated with changes in HLA-DR antigen expression, as the HLA-DR antigen was lost at relapse in only 4% of HLA-DR-positive cases, and was gained at relapse in only 17% of HLA-DR-negative cases. We conclude that HLA-DR-negative AML includes approximately equal numbers of APL and non-APL cases, and that the morphology of HLA-DR-negative non-APL cases can mimic the hypogranular variant of APL. The diagnosis of APL cannot be based on morphology and lack of HLA-DR antigen expression; rather, it requires cytogenetic or molecular confirmation.


Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells.
Adenosine monophosphate (AMP)-activated kinase (AMPK) is a molecular energy sensor regulated by the tumor suppressor LKB1. Starvation and growth factors activate AMPK through the DNA damage sensor ataxia-telangiectasia mutated (ATM). We explored the regulation of AMPK by ionizing radiation (IR) and its role as a target for radiosensitization of human cancer cells. Lung, prostate, and breast cancer cells were treated with IR (2-8 Gy) after incubation with either ATM or AMPK inhibitors or the AMPK activator metformin. Then, cells were subjected to either lysis and immunoblotting, immunofluorescence microscopy, clonogenic survival assays, or cell cycle analysis. IR induced a robust phosphorylation and activation of AMPK in all tumor cells, independent of LKB1. IR activated AMPK first in the nucleus, and this extended later into cytoplasm. The ATM inhibitor KU-55933 blocked IR activation of AMPK. AMPK inhibition with Compound C or anti-AMPK alpha subunit small interfering RNA (siRNA) blocked IR induction of the cell cycle regulators p53 and p21(waf/cip) as well as the IR-induced G2/M arrest. Compound C caused resistance to IR, increasing the surviving fraction after 2 Gy, but the anti-diabetic drug metformin enhanced IR activation of AMPK and lowered the surviving fraction after 2 Gy further. We provide evidence that IR activates AMPK in human cancer cells in an LKB1-independent manner, leading to induction of p21(waf/cip) and regulation of the cell cycle and survival. AMPK appears to (1) participate in an ATM-AMPK-p21(waf/cip) pathway, (2) be involved in regulation of the IR-induced G2/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.


[Histopathology of nephroblastomas (author's transl)].
Nephrectomy specimens from 42 patients with nephroblastoma were investigated. With the exception of one specimen (the patient had been treated preoperatively), all of the tumors were suitable for grading procedures. When the tumors were classified by the grading procedure of Lawler et al. (1975), the moderately tubulus-rich type++ was the most common (22 out of 41 patients). When the classification of Beckwith and Palmer (1978) was applied, the mixed type of nephroblastoma dominated correspondingly (19 out of 41 patients). Patients with an increased risk can be identified particularly well with the classification of Beckwith and Palmer. The following histologic features are indications of an unfavourable prognosis: focal or diffuse "anaplasia" of the tumor tissue, or a sarcomatous component in a stroma-rich nephroblastoma. The children with sarcomatous nephroblastoma (5 patients) were remarkably young (the oldest was 16 months of age), whereas the children with anaplastic nephroblastoma (3 patients) were much older (62, 67, and 72 months). In five children equivalents of the nephroblastomatosis complex (nodular renal blastema in all 5 patients, sclerosing metanephric hamartoma in 2 patients, and Wilms' tumorlet in one patient) were found in the non-infiltrated tissue of the same kidney.


Evolution of Sex-Biased Gene Expression and Dosage Compensation in the Eye and Brain of Heliconius Butterflies.
Differences in behavior and life history traits between females and males are the basis of divergent selective pressures between sexes. It has been suggested that a way for the two sexes to deal with different life history requirements is through sex-biased gene expression. In this study, we performed a comparative sex-biased gene expression analysis of the combined eye and brain transcriptome from five Heliconius species, H. charithonia, H. sara, H. erato, H. melpomene and H. doris, representing five of the main clades from the Heliconius phylogeny. We found that the degree of sexual dimorphism in gene expression is not conserved across Heliconius. Most of the sex-biased genes identified in each species are not sex-biased in any other, suggesting that sexual selection might have driven sexually dimorphic gene expression. Only three genes shared sex-biased expression across multiple species: ultraviolet opsin UVRh1 and orthologs of Drosophila Krüppel-homolog 1 and CG9492. We also observed that in some species female-biased genes have higher evolutionary rates, but in others, male-biased genes show the fastest rates when compared with unbiased genes, suggesting that selective forces driving sex-biased gene evolution in Heliconius act in a sex- and species-specific manner. Furthermore, we found dosage compensation in all the Heliconius tested, providing additional evidence for the conservation of dosage compensation across Lepidoptera. Finally, sex-biased genes are significantly enriched on the Z, a pattern that could be a result of sexually antagonistic selection.


A review of the effectiveness of respirators in reducing exposure to polycyclic aromatic hydrocarbons for coke oven workers.
In 2011 recommendations for the prescription of lung cancer in coke oven workers were made in the UK. In the 1970s, a powered helmet respirator, the Airstream helmet, was introduced to the UK coking industry with the aim of reducing exposure to polycyclic aromatic hydrocarbons (PAH) aerosols and consequent lung cancer risks for workers on the coke oven tops. This review set out to identify the level of protection afforded by the Airstream helmet, when the helmets could be considered to have provided effective protection and whether the levels of protection have been maintained to the current time. Five approaches were taken to identify review material, including searching the peer-reviewed and grey literature; searching material held in the National Archive; using a Freedom of Information to the Health and Safety Executive; interviews with employees involved in the introduction of the Airstream helmet; and acquisition of company reports. The two principal companies involved in coke production in the UK took different approaches to the introduction of the Airstream helmets. Because of this, it can only be considered that effective wearing occurred in the industry as a whole from 1982 onwards. Exposure measurements made by British Steel in the late 1970s suggested that the mean protection factor of the Airstream helmet was ~10 (5th percentile~2.5), regardless of whether exposure was assessed as the inhalable aerosol or other measures more specific to aerosol of PAH. More recent data collected using biological monitoring has identified that average urinary levels of 1-hydroxypyrene (1-HP) generally correspond with the inhalation occupational exposure limit for benzene soluble material. Although on occasions, relatively high air concentrations in-mask and urinary 1-HP concentrations have been identified, underlining the necessity to maintain close supervision of workers wearing respirators. Overall, we concluded that the wearing of helmet respirators has effectively controlled long-term average exposure to PAH for most workers on coke ovens since 1982.


[Clinico-electrophysiological changes in the neuromuscular system of patients with vibration disease].
Neuromuscular alterations associated with vibratory disease related to the pathology of spinal motoneurons, axon (degeneration, demyelinization), synapse, muscle. The site, nature and the intensity of the process depended on the duration of work with vibroinstruments, industrial characteristics. During specialized employment, the patients manifested aggravation of the clinical and neurophysiological parameters of the denervation process. Compensatory innervation of the muscles (branching of axon terminals, establishment of new neuromuscular contacts, ets.) was most effective in polishers and riveters. Foundry cleaners demonstrated a tendency toward progress of neuromuscular pathology. To explain motor disorders in patients with vibratory disease, the mechanisms of microtraumatization of nerve endings followed by involvement of the neurotrophic and neuroreflectory systems are suggested.


Entrapment of amino acids in gas phase surfactant assemblies: The case of tryptophan confined in positively charged (1R,2S)-dodecyl (2-hydroxy-1-methyl-2-phenylethyl) dimethylammonium bromide aggregates.
The ability of positively charged aggregates of the surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB) to incorporate D-tryptophan or L-tryptophan in the gas phase has been investigated by electrospray ion mobility mass spectrometry (ESI-IM-MS). Strongly impacted by the pH of the electrosprayed solutions, both protonated (T+ ) and deprotonated (T- ) tryptophan are effectively included into the aggregates, whereas, tryptophan in zwitterionic (T0 ) form is practically absent in singly charged DMEB aggregates but can be found in multiply charged ones. The ability to incorporate tryptophan increases with the aggregation number and charge state of aggregates. More than 1 tryptophan species can be entrapped (aggregates including up to 5 tryptophan are observed). Collision induced dissociation experiments performed on the positively singly charged DMEB hexamer containing 1 T- show that at low collision energies the loss of a DMEB molecule is preferred with respect to the loss of the DMEB cation plus T- species which, in turn, is preferred with respect to the loss of mere tryptophan, suggesting that the deprotonated amino acid is preferentially located in proximity of a DMEB head group and with the ionic moiety pointing towards the core of the aggregate. The analysis of the collision cross sections (CCS) of bare and tryptophan containing aggregates allowed evaluating the contributions of tryptophan and bromide ions to the total aggregate CCS. No significant discrimination between D-tryptophan and L-tryptophan by the chiral DMEB aggregates has been evidenced by mass spectra data, CID experiments, and CCS values.


DNA-electrochemical biosensors: AFM surface characterisation and application to detection of in situ oxidative damage to DNA.
In recent years increased attention has been focused on the ways in which drugs interact with DNA, with the goal of understanding the toxic as well as chemotherapeutic effects of many molecules. The development of fast and accurate methods of DNA damage detection is important, especially caused by anticancer drugs or hazard compounds. The DNA-electrochemical biosensor is a very good model for evaluation of nucleic acid damage, and electrochemical detection a particularly sensitive and selective method for the investigation of specific interactions. The electrochemical sensor for detecting DNA damage consists of a glassy carbon electrode with DNA immobilized on its surface. The starting materials or the redox reaction products can be pre-concentrated on the dsDNA-biosensor surface, enabling electrochemical probing of the presence of short-lived radical intermediates and of their damage to dsDNA. AFM images were used to characterize different procedures for immobilization of nanoscale DNA surface films on carbon electrodes before and after interaction with hazard compounds. The electrochemical transduction is dynamic in that the electrode is itself a tuneable charged reagent as well as a detector of all surface phenomena, which greatly enlarges the electrochemical biosensing capabilities.


[European Union health strategy: public health for European people].
The member States have exclusive authority over health, but the European Union has the responsibility, pursuant to the provisions of Article 152 of the Treaty, of rounding out the policies of the member Status in order to enhance public health, prevent diseases and avoid sources of hazards to human health, which includes the fight against the most serious, widespread diseases (by supporting the research of their aetiology, their transmission and prevention), as well as health information and education and the surveillance of serious transborder threats to health, alerting in the event of such threats and combating the same. In order to fulfil these obligations, the European Commission presented the White Paper "Together for Health: A Strategic Approach for the EU 2008-2013" on October 23, 2007. But the community-based health strategy has been being taking shape for some time now by means of different documents which have progressively been prefiguring it, thus being the result of long years of continuous work which has been being done since the early nineties. Throughout this time, the Directorate General of Public Health has been taking part in the process of preparing these documents and thus in what is now being presented as the EU health strategy. The main idea around which this work revolves is that there is a patent continuity and clear public health content in both the White Paper and in the documents which preceded it in time.


N-acetylcysteine adsorption by activated charcoal.
N-acetylcysteine was adsorbed by activated charcoal, lending in vitro support to previous clinical of activated charcoal for NAC in biologic fluid was significantly greater than in nonbiologic fluid and has important clinical implications. Although some have advocated lavage to remove activated charcoal prior to the administration of NAC, the avid adsorption of NAC suggested that activated charcoal may not be justifiable for acetaminophen overdosage when NAC therapy is indicated. Studies in humans are required to substantiate the clinical significance of this in vitro adsorption.


Management of primary nocturnal enuresis.
Most parents believe that their child should not be wetting the bed by age 5. Statistics show that 10% to 20% of 5 year olds continue with a least one episode of nocturnal enuresis per month. There is evidence that successful treatment leads to improved self-concept in children (Moffatt, Kato, & Pless, 1987). Treatment consists of various behavior modifications or pharmacologic regimes. Nurses and nurse practitioners in family practice, pediatric practice, school health, and urologic practice are in ideal roles to seek out and manage children with primary nocturnal enuresis.


CT demonstration of fat tissue in malignant renal neoplasms: atypical Wilms' tumors.
It has been implied that the recognition of fat in a renal tumor suggests that the lesion is benign. Several authors have suggested tht angiomyolipoma is the only common renal tumor containing mature adipose tissue. Other neoplasms may contain mature fat that can be identified with current diagnostic imaging techniques. Under discussion is our experience with Wilms' tumor containing a predominance of adipose tissue.


Effect of culture phasing and a polysaccharide on production of xylanase by mixed culture of Trichoderma reesei D1-6 and Aspergillus wentii Pt 2804.
A significant increase in extracellular xylanase activity was observed in the mixed culture fermentation of Trichoderma reesei D1-6 and Aspergillus wentii Pt 2804 when A. wentii inoculation was phased by 15 h. A. wentii produced a polysaccharide, chiefly consisting of glucose monomeric units, which was required for expression of maximum xylanase activity. Expression of high activity of xylanase in the A. wentii phased mixed culture compared to that in either T. reesei or A. wentii single cultures appeared to be controlled by the combined action of a polysaccharide produced by A. wentii and the relative growth of the two fungi in the mixed culture.


[Prescription, dispensing, and regulation of psychoactive anorexigenic drugs in Belo Horizonte, Minas Gerais, Brazil].
This retrospective study in Belo Horizonte, Minas Gerais, Brazil, aimed to provide indicators on the sale and consumption of anorexigenic substances. During the first stage, 2,906 of 168,237 prescriptions received by pharmacies in 2003 were analyzed, showing low quality of prescriptions. Projected consumption in defined daily doses was 19.75 DDD/1,000 inhabitants/day in 2003. Fenproporex (59.8%) was the most widely consumed drug. One pharmacy was responsible for 39.8% of the pharmaceutical sales. During the second stage, 14,554 sales records from this "blockbuster" pharmacy were analyzed, from April to August 2005; 9.2% of sales were for anorexigenic products, 91.8% of which prescribed in association with another substance. The data suggest irrational use of anorexigenic drugs by these consumers and highlight the need for proper regulation of these products. It is important to understand both the role of pharmacies in this regulation and that of physicians in the rational use of these substances.


Substrate upregulation of the human small intestinal peptide transporter, hPepT1.
1. Molecular mechanisms underlying physiological adaptation to increased levels of dietary peptides have been elucidated by studying the response to the substrate glycyl-L-glutamine (Gly-Gln) of the proton-coupled peptide transporter, hPepT1, in the Caco-2 human intestinal cell line. Vmax for apical uptake of [14C]glycyl-[14C]sarcosine was increased 1.64 (+/- 0.34)-fold after incubation of Caco-2 cells for 3 days in a peptide-rich medium (4 mM Gly-Gln replacing 4 mM Gln). 2. A full-length Caco-2 hPepT1 cDNA clone was identical to human small intestinal hPepT1 with the exception of a single amino acid substitution Ile-662 to Val. Transcript sizes, on Northern blots of Caco-2 poly(A)+ RNA probed with a 630 bp 5' hPepT1 cDNA probe, correspond to the reported band pattern seen with human small intestinal RNA. The dipeptide-induced increase in substrate transport was accompanied by a parallel increase of 1.92 (+/- 0.30)-fold (n = 9) in hPepT1 mRNA. This was in part due to an increase in hPepT1 mRNA half-life from 8.9 +/- 1.1 to 12.5 +/- 1.6 h (n = 3), but the increase in half-life does not account fully for the observed increase in mRNA levels, suggesting that there was also a dipeptide-mediated increase in hPepT1 transcription. 3. Anti-hPepT1-specific antipeptide antibodies localized hPepT1 exclusively to the apical membrane of human small intestinal enterocytes and Caco-2 cells. Gly-Gln supplementation of media resulted in a 1.72 (+/- 0.26)-fold (n = 5) increase in staining intensity of Caco-2 cells. 4. We conclude that Caco-2 cells provide an appropriate model for the study of adaptation of intestinal hPepT1, at the molecular level, to increased levels of dietary peptide. The magnitude of functional increase in apical peptide transport activity in response to Gly-Gln can be fully accounted for by the increased levels of hPepT1 protein and mRNA, the latter mediated by both enhanced hPepT1 mRNA stability and increased transcription. The signalling pathway between increased dietary peptide and hPepT1 upregulation, therefore, involves direct action on the enterocyte, independent of hormonal and/or neural control.


Novel Two-Stage Fine Milling Enables High-Throughput Determination of Glyphosate Residues in Raw Agricultural Commodities.
Dramatic process-efficiency gains for residue analysis of glyphosate in raw agricultural commodities (RACs) were achieved by development and validation of a two-stage fine-milling process. This secondary milling produced a uniform and consistent product that could be reproducibly measured with 75 mg analytical test portions. The milligram scale sample size enabled the direct weighing of sample into a liquid-handler-compatible 96-well format. A high-throughput workflow based on this innovative comminution approach for the quantitation of glyphosate, a nonselective herbicide, and its main degradation product, aminomethylphosphonic acid, was validated in various RACs and used to demonstrate the applicability of the two-step milling process. The precision and reproducibility of 75 mg analytical portions taken through this assay was used to demonstrate the feasibility of using a two-stage fine-milling technique for pesticide residue applications. An RSD of less than 10% was achieved in endogenous glyphosate residues in multiple RACs. Comparable recoveries and superior precision were achieved with this new method as compared with a validated 10 g scale method.


Mode of action of the Arabidopsis thaliana phytoalexin camalexin and its role in Arabidopsis-pathogen interactions.
The virulent Arabidopsis thaliana pathogen Pseudomonas syringae pv. maculicola strain ES4326 (Psm ES4326) and other gram-negative bacteria are sensitive to camalexin (3-thiazol-2'-yl-indole), the Arabidopsis phytoalexin. Furthermore, Psm ES4326 is unable to degrade camalexin or to become tolerant to it. Apparently, Psm ES4326 is a successful pathogen even though it elicits synthesis of a host phytoalexin to which it is sensitive. Assays of membrane integrity revealed that, like other phytoalexins, camalexin disrupts bacterial membranes, suggesting that camalexin toxicity is a consequence of membrane disruption. A screen for camalexin-resistant mutants of Psm ES4326 yielded only partially resistant mutants, which displayed partial resistance in both killing and membrane integrity assays. These mutants were also resistant to low concentrations of tetracycline and nalidixic acid, suggesting that they were affected in components of the outer membrane. The mutants were not distinguishable from Psm ES4326 in virulence assays. Camalexin was toxic to Arabidopsis cells growing in tissue culture. However, comparison of the extent of cell death associated with disease symptoms in infected leaves of wild-type Arabidopsis and a camalexin-deficient mutant suggested that camalexin does not contribute significantly to cell death in infected tissue.


Rising under-5 mortality in Africa: who bears the brunt?
To identify the socioeconomic and geographical groups in which the recent under-5 mortality increase observed in several African countries was most pronounced, and to explore the contribution of a number of proximate determinants of under-5 mortality. Time trends in under-5 mortality were assessed with Cox Proportional Hazards regression analysis, using Demographic and Health Surveys data for Burkina Faso, Cameroon, Côte d'lvoire, Kenya and Zimbabwe for the late 1980s - 1990s. We tested for differences in time trends between socioeconomic and rural/urban subgroups, and described the inequalities in time trends in living conditions, malnutrition and health care use. Under-5 mortality increased substantially (ranging from 25% to 71% in 10 years) within the five countries. In Kenya, the increase was the largest among children born to less educated mothers (test for difference between educational groups: P = 0.074) and in rural areas (P = 0.090). In Cameroon, the increase was the largest among the higher educated (P = 0.013), and in Zimbabwe among the higher educated (P = 0.098) and in urban areas (P = 0.093). For Burkina Faso and Côte d'Ivoire, we did not observe statistically significant differences between educational and rural/urban subgroups. The decline in skilled delivery attendance in Zimbabwe and Kenya was similar among the less and higher educated. The decline in immunization coverage during the mid-1990s in Zimbabwe was the largest in the group with the highest mortality increase, but in Kenya it was as large among the less and higher educated. Whereas in Kenya the increase in malnutrition was the largest in the group with the highest mortality increase, this was not the case in Zimbabwe. The recent increase in under-5 mortality in some African countries was highly concentrated in specific population subgroups. Exactly which groups were most affected was highly variable. It cannot be assumed that lower socioeconomic groups are always most vulnerable. Strategies to halt the under-5 mortality increase should be based on disaggregate information for individual countries.


TNF-α antagonists differentially induce TGF-β1-dependent resuscitation of dormant-like Mycobacterium tuberculosis.
TNF-α- as well as non-TNF-α-targeting biologics are prescribed to treat a variety of immune-mediated inflammatory disorders. The well-documented risk of tuberculosis progression associated with anti-TNF-α treatment highlighted the central role of TNF-α for the maintenance of protective immunity, although the rate of tuberculosis detected among patients varies with the nature of the drug. Using a human, in-vitro granuloma model, we reproduce the increased reactivation rate of tuberculosis following exposure to Adalimumab compared to Etanercept, two TNF-α-neutralizing biologics. We show that Adalimumab, because of its bivalence, specifically induces TGF-β1-dependent Mycobacterium tuberculosis (Mtb) resuscitation which can be prevented by concomitant TGF-β1 neutralization. Moreover, our data suggest an additional role of lymphotoxin-α-neutralized by Etanercept but not Adalimumab-in the control of latent tuberculosis infection. Furthermore, we show that, while Secukinumab, an anti-IL-17A antibody, does not revert Mtb dormancy, the anti-IL-12-p40 antibody Ustekinumab and the recombinant IL-1RA Anakinra promote Mtb resuscitation, in line with the importance of these pathways in tuberculosis immunity.


[Use of health services in Brazil: association with overweight and body fat indicators].
The aim of the study was to analyze the association between use of health services and obesity in Brazilian adults. We carried out a population-based cross-sectional study in 100 districts of five Brazilian regions. The outcomes were: home care, use of medical services in the primary health care, use of medical services outside of the primary health care, use of emergency services and hospitalization. Excess weight was assessed by measurement of BMI and waist circumference (WC). Among the 8,603 subjects studied, the medical care in the primary health care was 14% and 18% higher among obese and high risk of WC, respectively, after controlled for socio-demographic variables and physical inactivity, but lost significance when adjusted for hypertension and diabetes. For the emergency services, both exposures resulted in increase of nearly 20% in the use of this service, after adjustments. The excess weight increased the use of medical services in the primary health care and emergency services.


Urban Park Development and Pediatric Obesity Rates: A Quasi-Experiment Using Electronic Health Record Data.
Childhood obesity affects ~20% of children in the United States. Environmental influences, such as parks, are linked with increased physical activity (PA). To examine whether changes in Body Mass Index (BMI) z-score were associated with construction of a new park. A quasi-experimental design was used to determine whether living in proximity of a park was associated with a reduction in BMI z-score. Children were selected from health clinics within an 11 mile radius of the park. A repeated-measure ANOVA was employed for analysis of the relationship between exposure (new park) and BMI z-score. Participants were 1443 (median age 10.3 range (2-17.9 years), BMI: z-score 0.84 ± 1.09) African American (77.4%) adolescents. Change in BMI z-score was not statistically different for children living at different distances from the park after controlling for age, gender, race, ethnicity, or payer type (p = 0.4482). We did observe a small 0.03 increase in BMI z-score from pre- to post-park (p = 0.0007). There was a significant positive association between child's baseline age and BMI z-score (p < 0.001). This study found proximity to a park was not associated with reductions in BMI z-score. Additional efforts to understand the complex relationship between park proximity, access, and PA are warranted.


Concordance of non-invasive mechanical and serum tests for liver fibrosis evaluation in chronic hepatitis C.
To determine the sensitivity and specificity of liver stiffness measurement (LSM) and serum markers (SM) for liver fibrosis evaluation in chronic hepatitis C. Between 2012 and 2014, 81 consecutive hepatitis C virus (HCV) patients had METAVIR score from liver biopsy compared with concurrent results from LSM [transient elastography (TE) [FibroScan®/ARFI technology (Virtual Touch®)] and SM [FIB-4/aspartate aminotransferase-to-platelet ratio index (APRI)]. The diagnostic performance of these tests was assessed using receiver operating characteristic curves. The optimal cut-off levels of each test were chosen to define fibrosis stages F ≥ 2, F ≥ 3 and F = 4. The Kappa index set the concordance analysis. Fifty point six percent were female and the median age was 51 years (30-78). Fifty-six patients (70%) were treatment-naïve. The optimal cut-off values for predicting F ≥ 2 stage fibrosis assessed by TE were 6.6 kPa, for acoustic radiation force impulse (ARFI) 1.22 m/s, for APRI 0.75 and for FIB-4 1.47. For F ≥ 3 TE was 8.9 kPa, ARFI was 1.48 m/s, APRI was 0.75, and FIB-4 was 2. For F = 4, TE was 12.2 kPa, ARFI was 1.77 m/s, APRI was 1.46, and FIB-4 was 3.91. The APRI could not distinguish between F2 and F3, P = 0.92. The negative predictive value for F = 4 for TE and ARFI was 100%. Kappa index values for F ≥ 3 METAVIR score for TE, ARFI and FIB-4 were 0.687, 0.606 and 0.654, respectively. This demonstrates strong concordance between all three screening methods, and moderate to strong concordance between them and APRI (Kappa index = 0.507). Given the costs and accessibility of LSM methods, and the similarity with the outcomes of SM, we suggest that FIB-4 as well as TE and ARFI may be useful indicators of the degree of liver fibrosis. This is of particular importance to developing countries.


Forest productivity mitigates human disturbance effects on late-seral prey exposed to apparent competitors and predators.
Primary production can determine the outcome of management actions on ecosystem properties, thereby defining sustainable management. Yet human agencies commonly overlook spatio-temporal variations in productivity by recommending fixed resource extraction thresholds. We studied the influence of forest productivity on habitat disturbance levels that boreal caribou - a threatened, late-seral ungulate under top-down control - should be able to withstand. Based on 10 years of boreal caribou monitoring, we found that adult survival and recruitment to populations decreased with landscape disturbance, but increased with forest productivity. This benefit of productivity reflected the net outcome of an increase in resources for apparent competitors and predators of caribou, and a more rapid return to the safety of mature conifer forests. We estimated 3-fold differences in forest harvesting levels that caribou populations could withstand due to variations in forest productivity. The adjustment of ecosystem provisioning services to local forest productivity should provide strong conservation and socio-economic advantages.


Role of ephrinB2 expression in endothelial cells during arteriogenesis: impact on smooth muscle cell migration and monocyte recruitment.
Expression of the arterial marker molecule ephrinB2 in endothelial cells is a prerequisite for adequate remodeling processes of the developing or angiogenic vasculature. Although its role in these processes has been extensively studied, the impact of ephrinB2 on the remodeling of adult arteries is largely unknown. To this end, we analyzed its expression during a biomechanically induced arteriolar remodeling process known as arteriogenesis and noted a significant increase in ephrinB2 expression under these conditions. By examining those biomechanical forces presumed to drive arteriogenesis, we identified cyclic stretch as a critical inducer of ephrinB2 expression in endothelial cells. Subsequent functional analyses in vitro revealed that endothelial cells expressing ephrinB2 limit the migration of smooth muscle cells, thereby enhancing segregation of both cell types. Moreover, MCP-1 induced transmigration of monocytes through a monolayer of endothelial cells overexpressing a truncated variant of ephrinB2 was clearly impeded. Taken together, these data suggest that expression of ephrinB2 in adult endothelial cells is up-regulated during arterial remodeling and controlled by cyclic stretch, a well-known inducer of such processes. This stretch-induced ephrinB2 expression may be pivotal for arteriogenesis as it limits smooth muscle cell migration within defined borders and controls monocyte extravasation.


International practice variation in postoperative imaging of chronic subdural hematoma patients.
The value of CT scanning after burr hole surgery in chronic subdural hematoma (CSDH) patients is unclear, and practice differs between countries. At the Brigham and Women's Hospital (BWH) in Boston, Massachusetts, neurosurgeons frequently order routine postoperative CT scans, while the University Medical Center Utrecht (UMCU) in the Netherlands does not have this policy. The aim of this study was to compare the use of postoperative CT scans in CSDH patients between these hospitals and to evaluate whether there are differences in clinical outcomes. The authors collected data from both centers for 391 age- and sex-matched CSDH patients treated with burr hole surgery between January 1, 2002, and July 1, 2016, and compared the number of postoperative scans up to 6 weeks after surgery, the need for re-intervention, and postoperative neurological condition. BWH patients were postoperatively scanned a median of 4 times (interquartile range [IQR] 2-5), whereas UMCU patients underwent a median of 0 scans (IQR 0-1, p < 0.001). There was no significant difference in the number of re-operations (20 in the BWH vs 27 in the UMCU, p = 0.34). All re-interventions were preceded by clinical decline and no recurrences were detected on scans performed on asymptomatic patients. Patients' neurological condition was not worse in the UMCU than in the BWH (p = 0.43). While BWH patients underwent more scans than UMCU patients, there were no differences in clinical outcomes. The results of this study suggest that there is little benefit to routine scanning in asymptomatic patients who have undergone surgical treatment of uncomplicated CSDH and highlight opportunities to make practice more efficient.


Effect of tardive dyskinesia on quality of life in patients with bipolar disorder, major depressive disorder, and schizophrenia.
Tardive dyskinesia (TD) is a common but serious hyperkinetic movement disorder and side effect of antipsychotic medications used to treat bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ). The purpose of this study was to evaluate health-related quality of life (HRQoL) in a population with diagnoses for BD, MDD, or SZ by comparing patients with TD (n = 197) with those without TD (n = 219). HRQoL in each group was also compared with HRQoL of the general population. This study employed a cross-sectional web-based survey. HRQoL was assessed by four instruments: the SF-12 Health Survey, Version 2 (SF-12v2), the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF), the Social Withdrawal subscale of the Internalized Stigma of Mental Illness Scale (SW-ISMI); and two questions on movement disorders. Patients with TD had significantly worse HRQoL and social withdrawal than those without. The differences were more pronounced for physical HRQoL domains than for mental health domains. Patients with more-severe TD, assessed through either self-rating or clinician rating, experienced significantly worse HRQoL than did those with less-severe TD. The impact of TD was substantially greater in patients with SZ than in those with BD or MDD. Compared with the general population, patients with BD, MDD, or SZ experienced significantly worse HRQoL regardless of TD status, although this deficit in HRQoL was greater among those with TD. The presence of TD is associated with worse HRQoL and social withdrawal. The most severe impact of TD is on physical aspects of patients' HRQoL.


Strategies for the Management of Spike Protein-Related Pathology.
In the wake of the COVID-19 crisis, a need has arisen to prevent and treat two related conditions, COVID-19 vaccine injury and long COVID-19, both of which can trace at least part of their aetiology to the spike protein, which can cause harm through several mechanisms. One significant mechanism of harm is vascular, and it is mediated by the spike protein, a common element of the COVID-19 illness, and it is related to receiving a COVID-19 vaccine. Given the significant number of people experiencing these two related conditions, it is imperative to develop treatment protocols, as well as to consider the diversity of people experiencing long COVID-19 and vaccine injury. This review summarizes the known treatment options for long COVID-19 and vaccine injury, their mechanisms, and their evidentiary basis.


A cross-sectional study of sexual dysfunction in chinese mainland female patients with rheumatoid arthritis.
This study aims to investigate the effects of rheumatoid arthritis (RA) on Chinese mainland female patients' sexual function compared with healthy subjects and to determine the risk factors of sexual dysfunction. A total of 151 female RA patients (mean age: 46.3±8.6 years) and 146 healthy female controls (mean age 45.7±7.6 years) were included in this cross-sectional study whose data were collected consecutively by questionnaires between November 2017 and June 2019. Data were collected by using demographics, disease-related information, Female Sexual Function Index, Dyadic Adjustment Scale, Medical Coping Modes Questionnaire, other psychological parameters and the Short Form-36. Our results showed that the prevalence of female sexual dysfunction was 67.5% in RA patients, which was significantly higher than the controls (54.1%) (p<0.05). Body mass index, resignation coping style, physical component summary, marital dysfunction and postmenopausal status were significant correlation factors by backward stepwise binary logistic regression. Rheumatoid arthritis negatively affected sexual function of patients who had considerably impaired sexual function compared to controls.


Benefits and risks with glyburide and glipizide in elderly NIDDM patients.
To compare the efficacy, benefits, and risks of glyburide and glipizide in elderly patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty-one elderly outpatients (mean age 70 yr) were treated for 8 wk, after being dose-titrated to achieve a fasting plasma glucose (FPG) concentration of less than 7.8 mM with glyburide or glipizide in a randomized crossover trial. FPG and postprandial plasma glucose, serum C-peptide, and HbA1c levels were measured. In 13 patients, self-monitoring of blood glucose (SMBG) with a memory meter was performed seven times per week. Glipizide (11.9 mg) and glyburide (8.4 mg) produced similar fasting and postprandial plasma glucose and HbA1c concentrations. No significant differences in basal or stimulated C-peptide levels were detected. Despite a few patient reports of hypoglycemia, a high incidence of SMBG readings less than 4.5 mM was attributed to the use of both drugs. Both treatments proved effective for glycemic control; however, both second-generation sulfonylureas are associated with a significant risk of hypoglycemia in elderly NIDDM patients. The proper use of sulfonylureas in this population should include close surveillance of ambulatory glucose monitoring and intensive and repeated patient education about the risks of hypoglycemia.


A novel 27 kDa lipoprotein antigen from Mycobacterium bovis.
A novel Mycobacterium bovis antigen was identified from an expression library using sera from naturally infected cattle. The Escherichia coli recombinant clone expressed a 27 kDa protein, named P27. A rabbit serum against the recombinant antigen recognized a protein of 27 kDa in cellular extracts from M. bovis and M. tuberculosis. No protein was recognized in the culture supernatant. Sequence analysis indicated that P27 has a molecular mass of 24 kDa, showing a characteristic signal sequence for lipoprotein modification (a signal peptidase type II site). The gene is identical to a gene identified in the M. tuberculosis genome sequencing project. Cellular fractionation experiments suggested that P27 is an integral membrane protein. The antigen was recognized by individual sera and peripheral blood mononuclear cells (PBMC) from diseased cattle. PCR experiments with specific primers directed to the P27 structural gene indicated that it is only present in the M. tuberculosis species complex. In conclusion, a novel immunogenic lipoprotein in M. bovis/M. tuberculosis has been identified. The results presented here and elsewhere suggest that mycobacterial lipoproteins should be considered in the design of new recombinant vaccines and diagnostic methods.


Criminal Justice and Community Psychology: Our Values and Our Work-The Introduction to the Special Issue.
This special issue of The American Journal of Community Psychology originated from the Society for Community Research and Action Criminal Justice interest group, with a goal of exploring the work of community psychologists intersecting with criminal justice research, practice, and policy and shaped by our shared values-equity, collaboration, creative maladjustment, social justice, and social science in the service of social justice. In this introduction, we discuss the socio-historical context of the special issue, followed by an outline of the special issue organization, and brief summary of the included papers. Across 13 papers and an invited commentary, we see the ways in which community psychologists are: (1) delivering and evaluating services, programming, or other supports to address the needs of system-involved people; and (2) working to improve the systems, structures, and interactions with units of criminal justice systems. Across these two sections, authors highlight the guiding role of our values to influence change within and outside of criminal-legal systems.


Decreased maturation of dendritic cells in the central airways of COPD patients is associated with VEGF, TGF-β and vascularity.
Dendritic cells (DCs) have a pivotal role in the onset and regulation of innate and adaptive immune responses. Moreover, DCs can interact with angiogenic modulators, resulting in modification of their biology and participation in angiogenesis. This study was designed to evaluate the relationship between the density of DCs, vascularity and expression of angiogenic factors [vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β and basic fibroblast growth factor (bFGF)] in the central airways of chronic obstructive pulmonary disease (COPD) patients. The study included 20 patients with moderate/severe COPD and 8 healthy control subjects. Bronchial biopsies were evaluated by immunohistochemistry. Specimens were examined for CD83 and CD207 to mark mature and immature DCs, respectively, for collagen IV to evaluate vascularity, and for VEGF, TGF-β and bFGF. Compared to controls, COPD patients had a significant reduction of CD83+ cells and an increased CD207/CD83 ratio (p < 0.05). Vascularity, VEGF, TGF-β and bFGF were also significantly increased in COPD patients as compared to controls (p < 0.01). In COPD patients, CD83+ cells were inversely related to VEGF and TGF-β expression (p < 0.05). Moreover, the CD207/CD83 ratio was positively related to VEGF, TGF-β and vascularity (p < 0.05). Finally, CD207+ cells were inversely related to FEV1 (p < 0.05). Our results show a reduced maturation of DCs in COPD that was related to airway vascularity and angiogenic factors (VEGF and TGF-β). Additionally, immature DCs were significantly related to disease severity. We propose that the interplay between airway vascular changes, on one hand, and DCs maturation on the other, may play a key role in the pathogenetic mechanisms of COPD.