Association between the cerebral inflammatory and matrix metalloproteinase responses after severe traumatic brain injury in humans.
An increasing number of preclinical investigations have suggested that the degree of expression of the matrix metalloproteinase (MMP) family of endopeptidases may explain some of the variability in neurological damage after traumatic brain injury (TBI). As cytokines are a prominent stimulus for MMP expression in animals, we conducted a prospective multimodal monitoring study and determined their association with temporal MMP expression after severe TBI in eight critically ill adults. High cutoff, cerebral microdialysis (n=8); external ventricular drainage (n=3); and arterial and jugular venous bulb catheters were used to measure the concentration of nine cytokines and eight MMPs in microdialysate, cerebrospinal fluid (CSF), and plasma over 6 days. Severe TBI was associated with a robust central inflammatory response, which was largely similar between microdialysate and CSF. At all time points after injury, this response was predominated by the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8. Use of univariate generalized estimating equations suggested that the concentration of several MMPs varied with cytokine levels in microdialysate. The largest of these changes included increases in microdialysate concentrations of MMP-8 and MMP-9 with increases in the levels of IL-1α and -2 and IL-1α and -2 and TNF-α, respectively. In contrast, the microdialysate level of MMP-7 decreased with increases in microdialysate concentrations of IL-1β, -2, and -6. These findings support the observations of animal studies that cross-talk exists between the neuroinflammatory and MMP responses after acute brain injury. Further study is needed to determine whether this link between cerebral inflammation and MMP expression may have clinical relevance to the care of patients with TBI.


Evidence for increased cardiovascular disease risk in patients with chronic kidney disease.
Chronic kidney disease is becoming recognized as an important risk factor for cardiovascular disease. Recent publications on cardiovascular disease risk in chronic kidney disease, cardiovascular disease risk factors in chronic kidney disease and clinical trials for cardiovascular disease risk reduction in chronic kidney disease are summarized. An American Heart Association statement published in 2003 recommended that patients with chronic kidney disease be considered as members of the 'highest risk group' for subsequent cardiovascular disease events. In the past year, several large prospective studies have reported that cardiovascular disease risk is independently associated with chronic kidney disease markers, e.g. elevated serum creatinine, low estimated glomerular filtration rate and microalbuminuria. The populations studied have included community samples of middle-aged and older adults, subjects with myocardial infarction, those undergoing coronary angiography, and transplant patients. There is a very strong crude association between a low glomerular filtration rate and cardiovascular disease and mortality. Much of the association is explained by traditional cardiovascular disease risk factors, but an independent risk remains. Studies have documented a disturbing underutilization of preventive treatments for cardiovascular disease among patients with chronic kidney disease. Studies of non-traditional cardiovascular disease risk factors are reviewed. The utility of targeting these for cardiovascular disease risk reduction needs to be proved. A summary of large ongoing clinical trials intended to reduce cardiovascular disease risk in chronic kidney disease is presented. Increasing data support the importance of chronic kidney disease as a predictor of cardiovascular disease risk. However, treatments designed to lower cardiovascular disease risk are used less often in patients with chronic kidney disease than in patients without chronic kidney disease. There is a need for increased application and testing of cardiovascular disease prevention treatments in chronic kidney disease.


Use of antibiotics in children: a Danish nationwide drug utilization study.
We aimed to describe the use of systemic antibiotics among children in Denmark. National data on drug use in Denmark were extracted from the Danish National Prescription Database. We used prescription data for all children in Denmark aged 0 to 11 years from January 1, 2000 to December 31, 2012. We obtained data on 5,884,301 prescriptions for systemic antibiotics issued to 1,206,107 children. The most used single substances were phenoxymethylpenicillin (45%), amoxicillin (34%) and erythromycin (6%). The highest incidence rate of antibiotic treatment episodes was observed among children younger than 2 at 827 per 1000 children in 2012. Incidence rates were relatively stable throughout the study period. One-year prevalences in 2012 were 485, 363 and 190 per 1000 children among children aged 0-1, 2-4 and 5-11, respectively. A gradual shift from narrow-spectrum penicillin V to the broader-spectrum amoxicillin was found among children younger than 5. The use of macrolides decreased slightly, especially among those aged 0-1. Minor regional differences were noted, with somewhat higher use in the Capital Region. Skewness in use was most notable among those aged 0-1. There was little evidence of heavy users. Prescribing rate of antibiotics to children in Denmark remained stable at a high level from 2000 to 2012. An increase in the use of broad-spectrum beta-lactam penicillin was noted, but otherwise the prescribing pattern adhered well to National guidelines with respect to choice of antibiotics.


Infant sudden death: Mutations responsible for impaired Nav1.5 channel trafficking and function.
Two genetic variants in SCN5A, encoding the Nav1.5 Na+ channel α-subunit, were found in a 5-month-old girl who died suddenly in her sleep. The first variant is a missense mutation, resulting in an amino acid change (Q1832E), which has been described (but not characterized) in a patient with Brugada syndrome. The second is a nonsense mutation that produces a premature stop codon and a C-terminal truncation (R1944Δ). To investigate their functional relevance with patch clamp experiments in transfected HEK-293 cells. The Q1832E mutation drastically reduced Nav1.5 current density. The R1944Δ C-terminal truncation had negligible effects on Nav1.5 current density. Neither of the mutations affected the voltage dependence of steady activation and inactivation or influenced the late Na+ current or the recovery from inactivation. Biochemical and immunofluorescent approaches demonstrated that the Q1832E mutation caused severe trafficking defects. Polymerase chain reaction cloning and sequencing the victim's genomic DNA allowed us to determine that the two variants were in trans. We investigated the functional consequences by coexpressing Nav1.5(Q1832E) and Nav1.5(R1944Δ), which led to a significantly reduced current amplitude relative to wild-type. These sudden infant death syndrome (SIDS)-related variants caused a severely dysfunctional Nav1.5 channel, which was mainly due to trafficking defects caused by the Q1832E mutation. The decreased current density is likely to be a major contributing factor to arrhythmogenesis in Brugada syndrome and the sudden death of this SIDS victim.


Cell membrane permeable esters of D-myo-inositol 1,4,5-trisphosphate.
d-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3, or IP3) is a ubiquitous second messenger that regulates cytosolic Ca2+ activities ([Ca2+]i). To study this signaling branch in intact cells, we have synthesized a caged and cell permeable derivative of IP3, ci-IP3/PM, from myo-inositol in 9 steps. Ci-IP3/PM is a homologue of cm-IP3/PM, a caged and cell permeable IP3 ester developed earlier. In ci-IP3/PM, 2- and 3-hydroxyl groups of myo-inositiol are protected by an isopropylidene group; whereas in cm-IP3/PM, a methoxymethylene is used. Ci-IP3/PM can be loaded into cells non-invasively to high concentrations without activating IP3 receptors (IP3Rs). UV uncaging of loaded ci-IP3 released i-IP3, a potent agonist of IP3Rs, and evoked Ca2+ release from internal stores. Interestingly, elevations of [Ca2+]i by i-IP3 lasted longer than [Ca2+]i transients by m-IP3, the uncaging product of cm-IP3. To understand this difference, we measured the metabolic stability of i-IP3 and m-IP3. Like natural IP3 which is known to be rapidly metabolized in cells, m-IP3 could only be detected within several seconds after uncaging cm-IP3. In contrast, i-IP3 was metabolized at a much slower rate. By exploiting different metabolic rates of m-IP3 and i-IP3, we developed two procedures for activating IP3Rs in cells without UV uncaging. The first method involves photolyzing ci-IP3/PM in vitro to generate i-IP3/PM. Successive additions of low micromolar i-IP3/PM to NIH 3T3 cells caused graded Ca2+ releases, confirming that "quantal Ca2+ release" occurs in fully intact cells with normal ATP supplies and undisrupted endoplasmic reticulum. The second technique utilizes two photon uncaging. After locally illuminating cells loaded with cm-IP3 with femtosecond-pulsed near-infrared light (730 nm), we observed a burst of Ca2+ activity in the uncaging area. This local Ca2+ rise rapidly propagated across cells and could be repeated many times in different sub-cellular locations to produce artificial Ca2+ oscillations of defined amplitudes and frequencies. The complementary advantages of these IP3 prodrugs should provide new approaches for studying IP3-Ca2+ signaling in intact cell populations with high spatiotemporal resolutions.


Color difference formulas tested by use with chromatic discrimination data and new formulas.
A set of five color difference formulas, cdf-G*, one for each of five regions of the CIE1931 chromatic diagram, is proposed and compared with the CIELUV, CIELAB, and LABNHU formulas. The cdf-G* formulas fit more closely several sets of color difference data. They are useful for color difference applications.


Lung parenchima changes in neurofibromatosis type 1.
Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is one of the most common single-gene disorders (mutation on chromosome 17q) and usually associated with cutaneous, musculoskeletal and neurological disorders in humans. NF1 is generally complicated with one or more neurobehavioral disorders or tumors located in the peripheral nervous system such as neurofibromas, peripheral nerve sheath tumor, pheochromocytoma, etc. In the available medical literature, the thoracic manifestations of NF1 have been rarely described in these patients. There are few reports about intrathoracic neurogenic tumors, kyphoscoliosis, pneu- monitis and pulmonary fibrosis in patients with NF1. A 65-year-old female was admitted to the Intensive Care Unit at the Lung Clinic of Belgrade University Clinical Center of Serbia. The patient's general condition was poor with shortness of breath and present cyanosis. At the same time, the skin changes similar to NF1 were noticed, which were additionally documented by her medical history and diagnosed as NF1. After the application of noninvasive mechanical ventilation and other emergency respiratory medicine measures, the patient soon felt better. The parenchymal changes were viewed by subsequent X-rays and CT scanning of the thorax. This is a case report presenting the NF1 associated with the abnormality of lung parenchyma established during diagnostic procedures at the Intensive Care Unit, Clinic of Pulmonology.


Residual cell division measurements are unreliable as indicators of the timing of events in the Saccharomyces cerevisiae cell cycle.
We report here an analysis of the execution point of the temperature-sensitive Saccharomyces cerevisiae cell cycle mutant, cdc27-47. When a logarithmically growing culture was shifted from standard growth conditions (strain 27.8B growing in YEPD at 25 degrees C) to the restrictive temperature cell division ceased abruptly and reproducibly within one population doubling time, the extent of cell division indicating an execution point early in the cell cycle. Approximately 50% of stationary-phase cells were able to divide when refed with fresh medium at 37 degrees C, showing that the execution point could be passed before 'start'. This makes the sharp cut-off in cell division difficult to explain. This difficulty was compounded by observations of the cell cycle stage at which individual cells acquired the capacity to divide at 37 degrees C. Half the cells that were budded at the time of a temperature shift-up formed three division-blocked cells, and in 11 of these 13 cases, two were descended from the original mother cell and one from the original bud. Thus, mother and daughter cells pass the execution point independently; daughters usually during G1, and mothers usually in the budded phase of the previous cycle. The sharp cut-off in cell division is therefore spurious, and a mechanism is proposed to account for it, which has implications for the interpretation of the execution points of other cdc mutants. In addition, the expression of the cdc27-47 execution point was modified by both genetic and environmental factors, being affected by carbon source, by the petite condition, and by genetic background. This illustrates the difficulties of interpreting execution point data and the dangers of extrapolation of cell cycle parameters between strains and growth conditions.


Development of FuGO: an ontology for functional genomics investigations.
The development of the Functional Genomics Investigation Ontology (FuGO) is a collaborative, international effort that will provide a resource for annotating functional genomics investigations, including the study design, protocols and instrumentation used, the data generated and the types of analysis performed on the data. FuGO will contain both terms that are universal to all functional genomics investigations and those that are domain specific. In this way, the ontology will serve as the "semantic glue" to provide a common understanding of data from across these disparate data sources. In addition, FuGO will reference out to existing mature ontologies to avoid the need to duplicate these resources, and will do so in such a way as to enable their ease of use in annotation. This project is in the early stages of development; the paper will describe efforts to initiate the project, the scope and organization of the project, the work accomplished to date, and the challenges encountered, as well as future plans.


Potent preventive action of curcumin on radiation-induced initiation of mammary tumorigenesis in rats.
This investigation evaluated the preventive effect of curcumin on radiation-induced tumor initiation in rat mammary glands. Fifty-four female rats were mated and then divided into two groups at day 11 of pregnancy. As the control group, 27 rats were fed a basal diet during the experimental period. As the experimental group, 27 rats were fed a diet containing 1% curcumin between day 11 of pregnancy and parturition (day 23 of pregnancy). All rats of both groups received whole body irradiation with 1.5 Gy gamma-rays from a (60)Co source at day 20 of pregnancy and were then implanted with a diethylstilbestrol pellet 1 month after weaning. A high incidence (70.3%) of mammary tumorigenesis was observed in the control group. The tumor incidence (18.5%) was significantly reduced in the rats fed curcumin during the initiation stage. The appearance of the first palpable tumor was delayed by 6 months in the curcumin-fed group and the average latent period until the appearance of mammary tumors was 2.5 months longer in the curcumin-fed group than in the control group. By histological examination, the proportion of adenocarcinoma (16.7%) in total tumors in the curcumin-fed rats was found to be decreased to half that (32.1%) in the control group. Compared with the control rats, the body weight of rats in the experimental group was decreased slightly by administration of the curcumin diet from day 11 of pregnancy, in spite of a similar intake of diet, but had recovered to the level of the control by the end of the experiment. At the time of irradiation, curcumin did not have any effect on organ weight or on the development and differentiation of mammary glands of pregnant rats. In addition, the serum concentrations of fatty acids, thiobarbituric acid-reactive substances and ovarian and pituitary hormones, except LH, remained at the control level. Also, no change in litter size and body weight of pups born from curcumin-fed rats indicated no toxicity of curcumin. These results suggest that curcumin does not have any side-effects and is an effective agent for chemoprevention acting at the radiation-induced initiation stage of mammary tumorigenesis.


A Transformative Approach to Academic Medicine: The Partnership Between the University of Arizona and Banner Health.
The University of Arizona Health Network (UAHN) was a modestly successful health care delivery organization with a vibrant academic portfolio and stable finances. By 2013, however, market forces, health care financing changes, and the burden of technology and informatics upgrades led to a compromised financial position at UAHN, a situation experienced by many academic medical centers. Concurrently, Banner Health had been interested in forming an academic partnership to enhance innovation, including the incorporation of new approaches into health care delivery, and to recruit high-quality providers to the organization. In 2015, the University of Arizona (UA) and Banner Health entered into a unique partnership known as Banner - University Medicine. The objective was to create a statewide system that provides reliable, compassionate, high-quality health care across all of its providers and facilities and to make a 30-year commitment to UA's College of Medicine in Tucson and the College of Medicine in Phoenix to support the State of Arizona's position as a first-tier research and training destination with world-class physicians. The goal of the Banner - University Medicine partnership is to create a nationally leading organization that transforms health care by delivering better care, enhanced service, and lower costs through new approaches focused on wellness. Key elements of this partnership are highlighted in this Commentary, including the unique governance structure of the Academic Management Council, the creation of the Academic Enhancement Fund to support the UA Colleges of Medicine in Tucson and Phoenix, and novel approaches to medical education, research, innovation, and care.


Renal toxicity in patients with multiple myeloma receiving zoledronic acid vs. ibandronate: a retrospective medical records review.
This retrospective study investigated the rates of renal impairment in patients with multiple myeloma treated with zoledronic acid and ibandronate. We retrospectively reviewed medical records in a German oncology clinic, from May 2001 to December 2005. Creatinine measurements were analyzed from baseline (before zoledronic acid or ibandronate treatment) to last evaluation for each patient. A total of 84 patients were included. Zoledronic acid increased the risk of renal impairment by approximately 3-fold compared with ibandronate (renal impairment rates: zoledronic acid 37.7% vs. ibandronate 10.5%, relative risk [RR]=3.6, P=0.0029 serum creatinine [SCr]; 62.3% vs. 23.7%, RR=2.6, P=0.0001 glomerular filtration rate [GFR]). Ibandronate-treated patients switched from zoledronic acid had a significantly higher risk of renal impairment than patients receiving ibandronate monotherapy (zoledronic acid over ibandronate 39.1% vs. ibandronate monotherapy 6.7%, RR= 5.9, P=0.028 [SCr]; 65.2% vs 26.7%, RR=2.4, P=0.022 [GFR]). Multivariate analysis found significantly higher hazard ratios for zoledronic acid over ibandronate (SCr: Cox = 4.38, P=0.01; Andersen-Gill=8.22, P < 0.01; GFR: Cox = 4.31, P < 0.01; Andersen-Gill = 3.71, P < 0.01). Overall, this retrospective study suggests that multiple myeloma patients are more likely to experience renal impairment with zoledronic acid than with ibandronate. The risk of renal impairment increased if patients had received prior therapy with zoledronic acid.


Visualization of the endogenous NF-kappa B p50 subunit in the nucleus of follicular dendritic cells in germinal centers.
NF-kappa B, a 50 kDa/65 kDa (p50/p65) heterodimer, is a ubiquitous transcription factor involved in the positive regulation of various immune genes. The aim of this study was to determine whether NF-kappa B is related to a particular cell type and/or differentiation step during immunopoiesis. Using in situ hybridization on sections from non HIV hyperplastic lymph nodes, we found that the gene of the 105 kDa precursor of p50 was overexpressed in the light zone of germinal centers, with a network aspect, which suggested the involvement of follicular dendritic cells (FDC). By immunohistochemistry, p50 protein was detected in the cytoplasm and nucleus of FDC, confirming the involvement of FDC. Furthermore, p50 protein was detected in the cytoplasm of all lymphocytes. Thus, we focused our study on isolated FDC clusters from normal tonsils. As showed on tissue sections, we detected the p50 in both cytoplasm and nucleus of FDC. Nuclei of lymphocytes from FDC clusters were negative. We next studied p65 and c-Rel protein expression in FDC clusters. p65 was detected in the cytoplasm of FDC, whereas nuclei were negative. Furthermore, p65 was detected in the nuclei of some lymphocytes. c-Rel protein was detected only in the cytoplasm of lymphocytes and not in the nucleus and cytoplasm of FDC. Our results indicated that, in the context of T cell-dependent B cell immunopoiesis occurring in FDC clusters, p50 is mainly related to FDC with a massive overexpression in the nuclei, whereas p65 is expressed in a scattered manner in the nuclei of lymphocytes and c-Rel protein exclusively in the cytoplasm of lymphocytes from FDC clusters. These results suggested that the two subunits of NF-kappa B and the c-Rel protein have different roles in different cell types during B cell immunopoiesis.


Radiation therapy for subclinical carcinoma in cervical lymph nodes.
Radiotherapy alone was used to treat 187 patients with a head and neck cancer and clinically uninvolved lymph nodes. Delayed lymph node metastases developed in 35 (19%) patients, and concomitant tumor at the primary site was present in 90% of them. In two (1%) of the 187 patients, delayed metastases developed in the irradiated nodes with the primary tumor controlled; both of these patients received a radiation dose of less than 5,000 rad. Metastases in supraclavicular and posterior cervical regions occurred in 4% of the patients; and these sites were not included in the original radiation fields. The following conclusions were reached: (1) a radiation dose of 5,000 rad or more can eradicate 99% of the subclinical carcinomas in lymph nodes; (2) whole-neck irradiation is not indicated in patients with N0 stage tumor; and (3) surgical resection of primary tumors alone, without added neck dissection, may be adequate if postoperative radiation therapy is planned.


Gating the electron transfer at a monocopper centre through the supramolecular coordination of water molecules within a protein chamber mimic.
Functionality of enzymes is strongly related to water dynamic processes. The control of the redox potential for metallo-enzymes is intimately linked to the mediation of water molecules in the first and second coordination spheres. Here, we report a unique example of supramolecular control of the redox properties of a biomimetic monocopper complex by water molecules. It is shown that the copper complex based on a calix[6]arene covalently capped with a tetradentate [tris(2-methylpyridyl)amine] (tmpa) core, embedding the metal ion in a hydrophobic cavity, can exist in three different states. The first system displays a totally irreversible redox behaviour. It corresponds to the reduction of the 5-coordinate mono-aqua-CuII complex, which is the thermodynamic species in the +II state. The second system is detected at a high redox potential. It is ascribed to an "empty cavity" or "water-free" state, where the CuI ion sits in a 4-coordinate trigonal environment provided by the tmpa cap. This complex is the thermodynamic species in the +I state under "dry conditions". Surprisingly, a third redox system appears as the water concentration is increased. Under water-saturation conditions, it displays a pseudo-reversible behaviour at a low scan rate at the mid-point from the water-free and aqua species. This third system is not observed with the Cu-tmpa complex deprived of a cavity. In the calix[6]cavity environment, it is ascribed to a species where a pair of water molecules is hosted by the calixarene cavity. A molecular mechanism for the CuII/CuI redox process with an interplay of (H2O) x (x = 0, 1, 2) hosting is proposed on the basis of computational studies. Such an unusual behaviour is ascribed to the unexpected stabilization of the CuI state by inclusion of the pair of water molecules. This phenomenon strongly evidences the drastic influence of the interaction between water molecules and a hydrophobic cavity on controlling the thermodynamics and kinetics of the CuII/CuI electron transfer process.


Autoimmune Pituitary Disease: New Concepts With Clinical Implications.
Some endocrine disorders, including hypophysitis and isolated adrenocorticotropic hormone (ACTH) deficiency, are caused by an autoimmune response to endocrine organs. Although the pathogenesis of some autoimmune endocrine diseases has been elucidated, it remains obscure for most. Anti-PIT-1 hypophysitis (anti-PIT-1 antibody syndrome) is a newly described pituitary autoimmune disease characterized by acquired and specific growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies. This disorder is associated with a thymoma or neoplasm that ectopically expresses pituitary-specific transcription factor 1 (PIT-1) protein. Circulating anti-PIT-1 antibody is a disease marker, and PIT-1-reactive cytotoxic T cells (CTLs) play a pivotal role in disease development. In addition, isolated ACTH deficiency appears to be caused by autoimmunity to corticotrophs; however, the pathogenesis remains unclear. A recently described case of isolated ACTH deficiency with large cell neuroendocrine carcinoma (LCNEC) showed ectopically expressed proopiomelanocortin (POMC), and circulating anti-POMC antibody and POMC-reactive CTLs were also detected. As CTL infiltrations around corticotrophs were also observed, isolated ACTH deficiency may be associated at least in part with a paraneoplastic syndrome. Although several underlying mechanisms for pituitary autoimmunity have been proposed, these observations highlight the importance of paraneoplastic syndrome as a cause of pituitary autoimmune disease. In this review, we focus on the pathophysiology and connection of anti-PIT-1 hypophysitis and isolated ACTH deficiency and discuss the state-of-art knowledge for understanding pituitary autoimmunity.


Altered Resting-State Network in Adolescents with Problematic Internet Use.
Problematic internet use (PIU) is increasingly recognized as a mental health concern, particularly among adolescents. The resting-state functional connectivity (rsFC) of the triple-network model has been described inconsistently in PIU. Using resting-state fMRI (rsFMRI) and hypothesizing a lower rsFC between default mode (DMN) and central executive networks (CEN) but a higher rsFC within the salience network (SN), this study scrutinized the neural substrates of PIU adolescents. A total of 30 adolescents with PIU and 30 control subjects underwent rsFMRI. The severity of PIU was evaluated by the Internet Addiction Test. Additionally, personality traits as well as emotional and behavioral problems were evaluated by the Temperament and Character Inventory (TCI) and the Strength and Difficulties Questionnaire (SDQ), respectively. Focusing on the DMN, SN, and CEN, we compared rsFC values between PIU and the control. Subsequently, within the combined group of subjects, TCI and SDQ correlation and mediation effects were investigated. Higher rsFC values of the left lateral prefrontal cortex (LPFC(L)) with the left anterior insula (aIns(L)) were observed for PIU than for the control, while rsFCs of the LPFC(L) with the medial PFC (MPFC), LPFC(L), as well as with the right lateral parietal cortex (LP(R)) were lower for PIU. Among these significant group differences, the rsFC between the LPFC(L) and MPFC was mediated by emotional symptoms (standardized β = -0.12, 95% CI -0.29, -0.0052). The dysfunctional attention switching and incentive salience regulated by the SN were implicated as being a neural correlate of PIU, and this relationship would in part be explained by the emotional dysregulation associated with PIU in adolescents.


Optimum laser parameters for port-wine stain treatment.
The choice of suitable laser parameters is important for effective treatment of port-wine stains. The considerations in the choice of laser parameters are discussed with the aim of coagulating and sealing the abnormal blood vessels and completely denaturing the associated perivascular tissues, while confining the thermal damage to the vicinity of the abnormal vessels. A mathematical model was used to simulate the volume absorbed photon intensity in skin for argon, dye, Nd:YAG, and CO 2 lasers. The model computes the number of photons absorbed within each region, and an optimum wavelength is chosen by selecting that which has the highest absorption ratio in the blood vessel compared with absorption in the epidermis and dermis. The model further computes the input energy and the corresponding pulse duration required to seal the blood vessels and hence remove the port-wine stain.


Gene expression profiling reveals molecular marker candidates of laryngeal squamous cell carcinoma.
Laryngeal squamous cell carcinoma is very common in head and neck cancer, with high mortality rates and poor prognosis. In this study, we compared expression profiles of clinical samples from 13 larynx tumors and 10 non-neoplastic larynx tissues using a custom-built cDNA microarray containing 331 probes for 284 genes previously identified by informatics analysis of EST databases as markers of head and neck tumors. Thirty-five genes showed statistically significant differences (SNR > or = | 1.0 |, p< or =0.001) in the expression between tumor and non-tumor larynx tissue samples. Functional annotation indicated that these genes are involved in cellular processes relevant to the cancer phenotype, such as apoptosis, cell cycle, DNA repair, proteolysis, protease inhibition, signal transduction and transcriptional regulation. Six of the identified transcripts map to intronic regions of protein-coding genes and may comprise non-annotated exons or as yet uncharacterized long ncRNAs with a regulatory role in the gene expression program of larynx tissue. The differential expression of 10 of these genes (ADCY6, AES, AL2SCR3, CRR9, CSTB, DUSP1, MAP3K5, PLAT, UBL1 and ZNF706) was independently confirmed by quantitative real-time RT-PCR. Among these, the CSTB gene product has cysteine protease inhibitor activity that has been associated with an antimetastatic function. Interestingly, CSTB showed a low expression in the tumor samples analyzed (p<0.0001). The set of genes identified here contribute to a better understanding of the molecular basis of larynx cancer, and provide candidate markers for improving diagnosis, prognosis and treatment of this carcinoma.


[Can therapeutic education enrich psychiatric care?].
There are different ways of approaching therapeutic education in psychiatry. While the behavioural approach is based on acquisition and success, psychoanalysis focuses more on the patient's self-knowledge. The systemic approach is interested in social interaction and collective potential.


The need for enhanced psychological support in esophageal cancer-an exploratory study of the perception of HCPs, patients, and carers.
Esophageal cancer patients and carers report significant levels of psychological distress. Despite this, only a small number of patients and carers engage with existing psychological services. This study aims to explore the perception of esophageal cancer patients, carers, and healthcare professionals (HCPs) of psychological distress and current provision of support, the need for and format of tailored support and barriers to patient/carer engagement. Semistructured interviews were undertaken with n = 14 esophageal cancer patients, carers, and HCPs. Directed content analysis was utilized to code the transcripts according to the preconceived categories as defined by study aim. Participants reported key periods for heightened distress around diagnosis and postsurgery on discharge from hospital. Provision of existing support was not felt to be adequate. A number of patient/carer barriers to engaging with support were identified in addition to HCP barriers. Participants perceived enhanced psychological support as a priority supportive care need with a number of recommendations for tailoring existing support services more adequately to the clinical population. With reports of heightened psychological morbidity yet with few esophageal cancer patients engaging with psychological services, there is an impetus to develop detailed care pathways to facilitate meeting this prioritized support need.


Peanut agglutinin (PNA) binding sites: a useful marker for hormonal dependence in experimental breast cancer.
Histochemical studies were performed with the labeled lectin from Arachis hypogaea (peanut agglutinin, PNA) to detect the occurrence, distribution, and amount of this lectin receptor in N-nitrosomethylurea-induced rat mammary carcinomas. Since in normal rat mammary tissue, the formation and secretion of PNA binding sites are controlled by the combined action of estrogen and prolactin, the amount of secretion-associated PNA binding sites was correlated with tumor response to either ovariectomy or antiestrogenic treatment with tamoxifen. Free as well as sialic acid-substituted PNA binding sites which were represented by the disaccharide beta-D-Gal(1-3)NAcGal occurred in the apical cytoplasm of tumor cells and within the secretions of acinar and tubular structures. In contrast the whole tumor cell membrane contained predominantly sialic acid-substituted PNA binding sites. All of the tumors investigated contained some secretion-associated PNA binding sites. The values showed a continuum from very low to very high amounts. The number of PNA binding sites associated with secretory activity was lower in hormone-independent than in hormone-dependent tumors. Furthermore, there was an inverse relationship between mitotic and secretory activities with positive PNA staining. In conclusion, these studies revealed that the secretory PNA index, mitotic index, and especially the ratio of secretory PNA index to mitotic index represent useful parameters to select tumors for endocrine therapy in this experimental model.


Influenza-associated aspergillosis in critically-ill patients-a retrospective bicentric cohort study.
Influenza was recently reported as a risk factor for invasive aspergillosis (IA). We aimed to describe prognostic factors for influenza-associated IA (IAA) and poor outcome and mortality in critically ill patients in Switzerland. All adults with confirmed influenza admitted to the ICU at two Swiss tertiary care centres during the 2017/2018 influenza season were retrospectively evaluated. IAA was defined by clinical, mycological and radiological criteria: a positive galactomannan in bronchoalveolar lavage or histopathological or cultural evidence in respiratory specimens of Aspergillus spp., any radiological infiltrate and a compatible clinical presentation. Poor outcome was defined as a composite of in-hospital mortality, ICU length of stay (LOS), invasive ventilation for > 7 days or extracorporeal membrane oxygenation. Of 81 patients with influenza in the ICU, 9 (11%) were diagnosed with IAA. All patients with IAA had poor outcome compared to 26 (36%) patients without IAA (p < 0.001). Median ICU-LOS and mortality were 17 vs. 3 days (p < 0.01) and 3/9 (33%) vs. 13/72 (18%; p = 0.37) in patients with vs. without IAA, respectively. Patients with IAA had significantly longer durations of antibiotic therapy, vasoactive support and mechanical ventilation. Aspergillus was the most common respiratory co-pathogen (9/40, 22%) followed by classical bacterial co-pathogens. IAA was not associated with classical risk factors. Aspergillus is a common superinfection in critically ill influenza patients associated with poor outcome and longer duration of organ supportive therapies. Given the absence of classical risk factors for aspergillosis, greater awareness is necessary, particularly in those requiring organ supportive therapies.


Lessons learned from urgent computing in Europe: Tackling the COVID-19 pandemic.
PRACE (Partnership for Advanced Computing in Europe), an international not-for-profit association that brings together the five largest European supercomputing centers and involves 26 European countries, has allocated more than half a billion core hours to computer simulations to fight the COVID-19 pandemic. Alongside experiments, these simulations are a pillar of research to assess the risks of different scenarios and investigate mitigation strategies. While the world deals with the subsequent waves of the pandemic, we present a reflection on the use of urgent supercomputing for global societal challenges and crisis management.


The interferon stimulated gene 12 inactivates vasculoprotective functions of NR4A nuclear receptors.
Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection. The underlying mechanisms that regulate the activity of NR4A1 during vascular injury are not clear. We therefore searched for modulators of NR4A1 function that are present during vascular inflammation. We report that the protein encoded by interferon stimulated gene 12 (ISG12), is a novel interaction partner of NR4A1 that inhibits the transcriptional activities of NR4A1 by mediating its Crm1-dependent nuclear export. Using 2 models of vascular injury, we show that ISG12-deficient mice are protected from neointima formation. This effect is dependent on the presence of NR4A1, as mice deficient for both ISG12 and NR4A1 exhibit neointima formation similar to wild-type mice. These findings identify a previously unrecognized feedback loop activated by interferons that inhibits the vasculoprotective functions of NR4A nuclear receptors, providing a potential new therapeutic target for interferon-driven pathologies.


The role of immunoglobulin A in prolonged and relapsing hepatitis A virus infections.
Hepatitis A virus (HAV) infections result in different courses of the disease, varying between normal, prolonged and relapsing. However, the reason for these heterogeneous clinical appearances is not understood. As HAV-anti-HAV IgA immunocomplexes (HAV-IgA) infect hepatocytes, IgA was postulated as a carrier supporting hepatotropic transport of HAV, and it was speculated that this carrier mechanism contributes to the various clinical outcomes. In this study, the IgA-carrier mechanism was investigated in a mouse model. We show that HAV-IgA immunocomplexes efficiently reached the liver not only in HAV-seronegative mice, but also, and this is in contrast to free-HAV particles, in immunized HAV-seropositive animals. This IgA-mediated transport of HAV to the liver in the presence of immunity depended on the stage of development of the immune response. We conclude that over a period of several weeks after infection, anti-HAV IgA is able to promote an enterohepatic cycling of HAV, resulting in continuous endogenous reinfections of the liver. Our experiments indicate that highly avid IgG antibodies, which are present at later times of the infection, can terminate the reinfections. However, the endogenous reinfections in the presence of a developing neutralizing immunity might contribute to prolonged as well as to relapsing courses of HAV infections. Furthermore, the results show that serum IgA may act as an infection protracting factor.


RHPN1‑AS1 promotes ovarian carcinogenesis by sponging miR‑6884‑5p thus releasing TOP2A mRNA.
Ovarian cancer, a severe lethal gynecological malignancy, is characterized by both high morbidity and mortality. Long noncoding RNAs (lncRNAs) have recently caused extensive concern due to their regulatory function in various human tumors. There are a mounting number of lncRNAs that are in extreme need of research, serving as biomarkers for diagnosis and therapy for ovarian cancer. In the present study, RT‑qPCR was employed to detect how Rhophilin Rho GTPase binding protein 1 antisense RNA1 (RHPN1‑AS1), miR‑6884‑5p and DNA topoisomerase IIα (TOP2A) are expressed in ovarian cancer tissues or cell lines. BrdU, MTT, colony formation and cell adhesion assays, caspase‑3 activity, flow cytometry and wound healing assay were employed to assess cell proliferation, viability, colony number, adhesion, apoptosis and migration in ovarian cancer, respectively. RHPN1‑AS1 was determined to be enriched in ovarian cancer tissues and cell lines. Silencing of RHPN1‑AS1 was reported to increase cell apoptosis and impair cell proliferation, viability, colony number, adhesion and migration in vitro. Furthermore, RHPN1‑AS1 was able to sponge miR‑6884‑5p which directly targets TOP2A in ovarian cancer. Notably, silencing of RHPN1‑AS1 functionally reversed the oncogenic effect induced by the miR‑6884‑5p inhibitor, while the miR‑6884‑5p inhibitor markedly restored the inhibition of ovarian carcinogenesis modulated by silencing TOP2A in ovarian cancer. RHPN1‑AS1 was found to promote ovarian carcinogenesis via sponging miR‑6884‑5p thus releasing TOP2A, and RHPN1‑AS1 may act as a promising biomarker for the prognosis and therapy of ovarian cancer.


Structural Basis of the Subcellular Topology Landscape of Escherichia coli.
Cellular proteomes are distributed in multiple compartments: on DNA, ribosomes, on and inside membranes, or they become secreted. Structural properties that allow polypeptides to occupy subcellular niches, particularly to after crossing membranes, remain unclear. We compared intrinsic and extrinsic features in cytoplasmic and secreted polypeptides of the Escherichia coli K-12 proteome. Structural features between the cytoplasmome and secretome are sharply distinct, such that a signal peptide-agnostic machine learning tool distinguishes cytoplasmic from secreted proteins with 95.5% success. Cytoplasmic polypeptides are enriched in aliphatic, aromatic, charged and hydrophobic residues, unique folds and higher early folding propensities. Secretory polypeptides are enriched in polar/small amino acids, β folds, have higher backbone dynamics, higher disorder and contact order and are more often intrinsically disordered. These non-random distributions and experimental evidence imply that evolutionary pressure selected enhanced secretome flexibility, slow folding and looser structures, placing the secretome in a distinct protein class. These adaptations protect the secretome from premature folding during its cytoplasmic transit, optimize its lipid bilayer crossing and allowed it to acquire cell envelope specific chemistries. The latter may favor promiscuous multi-ligand binding, sensing of stress and cell envelope structure changes. In conclusion, enhanced flexibility, slow folding, looser structures and unique folds differentiate the secretome from the cytoplasmome. These findings have wide implications on the structural diversity and evolution of modern proteomes and the protein folding problem.


Hepatotoxicity due to pemoline. Report of two cases.
Pemoline, a central nervous system stimulant, has been used extensively in Great Britain and Europe for a variety of conditions including memory failure and depression. In the 10 years that the drug has been used no report of hepatotoxicity has appeared. A prospective study of efficacy and safety of pemoline was started in the United States approximately 3 years ago. This report describes two patients who developed reversible liver abnormalities while receiving pemoline during the study and following rechallenge with the drug.


Distribution of SARS-CoV-2 Lineages in the Czech Republic, Analysis of Data from the First Year of the Pandemic.
In the Czech Republic, the current pandemic led to over 1.67 million SARS-CoV-2- positive cases since the recording of the first case on 1 March 2020. SARS-CoV-2 genome analysis is an important tool for effective real-time quantitative PCR (RT-qPCR) diagnostics, epidemiology monitoring, as well as vaccination strategy. To date, there is no comprehensive report on the distribution of SARS-CoV-2 genome variants in either the Czech Republic, including Central and Eastern Europe in general, during the first year of pandemic. In this study, we have analysed a representative cohort of SARS-CoV-2 genomes from 229 nasopharyngeal swabs of COVID-19 positive patients collected between March 2020 and February 2021 using validated reference-based sequencing workflow. We document the changing frequency of dominant variants of SARS-CoV-2 (from B.1 -> B.1.1.266 -> B.1.258 -> B.1.1.7) throughout the first year of the pandemic and list specific variants that could impact the diagnostic efficiency RT-qPCR assays. Moreover, our reference-based workflow provided evidence of superinfection in several samples, which may have contributed to one of the highest per capita numbers of COVID-19 cases and deaths during the first year of the pandemic in the Czech Republic.


A VPE-like protease NtTPE8 exclusively expresses in the integumentary tapetum and is involved in seed development.
Programmed cell death (PCD) is an essential process for development, and shows conserved cytological features in both plants and animals. Caspases are well-known critical components of the PCD machinery in animals. However, currently few typical counterparts have been identified in plants and only several caspase-like proteases are known to be involved in plant PCD, indicating the existence of great challenge for confirming new caspase-like proteases and elucidating the mechanisms regulating plant PCD. Here, we report a novel cysteine protease, NtTPE8, which was extracted from tobacco seeds and confirmed as a new caspase-like protease. Recombinant NtTPE8 exhibited legumain and caspase-like proteolytic activities, both of which could be inhibited by the pan-caspase inhibitor (Z-VAD-FMK). Notably, NtTPE8 possessed several caspase activities and the capacity to cleave the cathepsin H substrate FVR, indicating a unique character of NtTPE8. NtTPE8 was exclusively expressed in the integumentary tapetum and thus, is the first specific molecular marker reported to date for this cell type. Down-regulation of NtTPE8 caused seed abortion, via disturbing early embryogenesis, indicating its critical role in embryogenesis and seed development. In conclusion, we identified a novel caspase-like cysteine protease, NtTPE8, exclusively expressed in the integumentary tapetum that is involved in seed development.


Selenated NHC-Pd(II) Pincer Complex Catalyzed, Temperature-Dependent Selective Hydroamination and Oxidative Amination of Olefins: Formation of Enamine Esters and β-Amino Esters under Solvent-Free and Aerobic Conditions.
NHC-Pd(II) pincer catalyzed oxidative amination and hydroamination of olefins is developed under solvent-free aerobic conditions. Reaction offered a temperature-controlled synthesis of (Z)-enamine and β-amino esters to provide easy access and remarkable functional group tolerance for a variety of enamines. The developed approach renders an opportunity of scalability and flexibility, and besides this, the produced enamines can be transformed into many N-containing heterocycles, underscoring its potential usage in synthetic and pharmaceutical chemistry. Moreover, it is the first report for coupling of aniline with styrene.


Characterization of Bacillus halodurans alpha-galactosidase Mel4A encoded by the mel4A gene (BH2228).
A family-4 alpha-galactosidase Mel4A of Bacillus halodurans was expressed in Escherichia coli and characterized. Recombinant enzyme rMel4A depended on NAD+, some divalent cations such as Mn2+, and reducing reagents such as dithiothreitol. rMel4A was active on small saccharides such as raffinose but not on highly polymerized galactomannan. Immunological analysis indicated that raffinose induced the production of Mel4A in B. halodurans.


A study of irradiated bone. III. Scintigraphic and radiographic detection of radiation-induced osteosarcomas.
Within 1 yr after localized irradiation of a hind limb with single (1756 rads) or fractionated (4650 rads in 3 wk) x-ray doses, radiation-induced osteosarcomas were observed in four of nine single-dose rabbits and two of 11 fractionated-dose rabbits. Tumors were observed in the proximal tibia in five cases and the distal femur in one case. In terms of production of osteoid or osseous tissue, three tumors were well differentiated, one slightly differentiated, and two (spindle-cell tumors) undifferentiated. This report summarizes the Tc-99m pyrophosphate (TcPPi) imaging and autoradiographic, radiographic, and histologic studies of these osteosarcomas. The four differentiated osteosarcomas were detected 1--2.5 mo earlier by TcPPi imaging than by radiography, whereas the two undifferentiated tumors were suspected 2 wk or 3.5 mo earlier radiographically. Autoradiograms showed TcPPi localization in bone produced by differentiated osteosarcomas, and in regions of reactive bone resorption and formation peripheral to tumors. The results support a recommendation for combined radiographic and scintigraphic techniques for the early detection of osteosarcomas.


How is myogenesis initiated in chordates?
Expression of transcriptor factors MyoD, Myf5, myogenin and MRF4 forms the basis of myogenesis. In Acrania, Pisces and Amphibia, as in Aves, myogenesis is initiated by MyoD. In Mammalia expression of Myf5 initiates myogenesis. Signal proteins Wnt and Shh induce the expression of genes encoding for MyoD or Myf5. In fishes and amphibians expression of MyoD starts in non-segmented mesoderm and then in myotomal cells. In birds and mammals expression of MyoD or Myf5 is initiated in the cells of the dermatomyotome. Embryonic myotomes are post-mitotic. Proliferating cells Pax3 and Pax7-positive and mesenchymal cells take part in the growth of myotomal muscles. Cells migrating to the limb bud contain regulatory proteins Six4/Six1, Pax3, Lbx1 and c-met. Rectus abdominis develops from cells that contain Pax3 and Lbx1.


Pod-1, a mesoderm-specific basic-helix-loop-helix protein expressed in mesenchymal and glomerular epithelial cells in the developing kidney.
Basic-helix-loop-helix (bHLH) proteins are transcriptional regulatory proteins that govern cell fate determination and differentiation in a variety of tissues. We have identified a novel bHLH protein, named Pod-1, that belongs to a recently-described subfamily of bHLH proteins that have essential roles in the embryonic development of mesodermal tissues. In the adult human and mouse, Pod-1 was most highly expressed in the kidney, lung and heart. In developing mouse embryos, Pod-1 was selectively expressed in mesenchymal cells at sites of epithelial-mesenchymal interaction in the kidney, lung, intestine and pancreas. Pod-1 was also expressed in visceral glomerular epithelial cells (podocytes) in the kidney, and its expression coincided with the onset of podocyte differentiation. The expression of Pod-1 in embryonic kidney explants was inhibited using antisense oligonucleotides. Inhibition of Pod-1 expression resulted in decreased mesenchymal cell condensation around the ureteric bud and a 40% decrease in ureteric branching. Pod-1 is the first tissue-restricted basic-helix-loop-helix protein that has been identified in the developing kidney where it may play a role in the regulation of morphogenetic events.


Draft Genome Sequences for Canadian Isolates of Pectobacterium carotovorum subsp. brasiliense with Weak Virulence on Potato.
Pectobacterium carotovurum subsp. brasiliense causes soft rot and blackleg diseases on potato. Here, we report the draft genome sequences of three weakly virulent P. carotovurum subsp. brasiliense strains isolated in Canada. Analysis of these genome sequences will help to pinpoint differences in virulence among P. carotovurum subsp. brasiliense strains from tropical/subtropical and temperate regions, such as Canada and United States. A small number of key factors for adaptation to this bacterium's specific environmental niche were also evaluated.


Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study.
Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms.


ZNF322, a novel human C2H2 Kruppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways.
Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporal-spatial manner. The C(2)H(2) zinc finger-containing transcription factors have been implicated as critical regulators of multiple cardiac-expressed genes and are important for human heart development and diseases. Here we have identified and characterized a novel zinc-finger gene named ZNF322 using degenerated primers from a human embryo heart cDNA library. The gene contains four exons and spans 23.2kb in chromosome 6p22.1 region, and transcribes a 2.7kb mRNA that encodes a protein with 402 amino acid residues. The predicted protein contains 9 tandem C(2)H(2)-type zinc-finger motifs. Northern blot analysis shows that ZNF322 is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 80 days to 24 weeks. When overexpressed in COS-7 cells, ZNF322-EGFP fusion protein is detected in the nucleus and cytoplasm. Reporter gene assays show that ZNF322 is a transcriptional activator. Furthermore, overexpression of ZNF322 in COS-7 cells activates the transcriptional activity of SRE and AP-1. Together, these results suggest that ZNF322 is a member of the zinc-finger transcription factor family and may act as a positive regulator in gene transcription mediated by the MAPK signaling pathways.


In Situ Synthesis of Mesoporous TiO2 Nanofibers Surface-Decorated with AuAg Alloy Nanoparticles Anchored by Heterojunction Exhibiting Enhanced Solar Active Photocatalysis.
We designed an electrospinning synthesis protocol to obtain in situ, the mesoporous TiO2 nanofibers, which are surface-decorated with plasmonic AuAg nanoparticles (AuAg-mTNF-H). Such alloy nanoparticles are found to be partially exposed on the surface of the nanofibers. Characterization by HRTEM and EDS confirmed the formation of 1:1 AuAg alloy nanoparticles on the surface of TiO2 nanofibers with heterojunction at the interfaces. On the basis of electron microscopic characterization, we proposed that, during the formation of the nanofibers, the incorporated metal ions with surface capping of negative charges migrated toward the outer surface of the nascent fibers under the influence of high positive voltage required for electrospinning. As a result, after the subsequent thermal treatment, the crystallization of TiO2 nanofibers and the formation of alloy nanoparticles took place, leading to the formation of a deep heterojunction through partial embedment of the nanoparticles. The formation of AuAg alloy also restricted the oxidation of Ag, thus making the nanoparticles highly stable in ambient condition. Accordingly, such unique AuAg-mTNF-H photocatalyst shows strong light absorption property covering the entire range of visible wavelengths with stability. The solar light harvesting property of AuAg-mTNF-H was verified by monitoring solar light induced H2 evolution via water splitting and photodecomposition of MB. In both the cases AuAg-mTNF-H showed excellent H2 evolution and photodecomposition of dye.


Omega-3 supplementation and cardiovascular disease: formulation-based systematic review and meta-analysis with trial sequential analysis.
Omega-3 supplements are popular for cardiovascular disease (CVD) prevention. We aimed to assess the association between dose-specific omega-3 supplementation and CVD outcomes. We included double-blind randomised clinical trials with duration ≥1 year assessing omega-3 supplementation and estimated the relative risk (RR) for all-cause mortality, cardiac death, sudden death, myocardial infarction and stroke. Primary analysis was a stratified random-effects meta-analysis by omega-3 dose in 4 a priori defined categories (<1, 1, 2, ≥3 of 1 g capsules/day). Complementary approaches were trial sequential analysis and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid, sample size, statin use, study duration. Seventeen studies (n=83 617) were included. Omega-3 supplementation as ≤1 capsule/day was not associated with any outcome under study; futility boundaries were crossed for all-cause mortality and cardiac death. For two capsules/day, we observed a statistically significant reduction of cardiac death (n=3, RR 0.55, 95% CI 0.33 to 0.90, I2=0%); for ≥3 capsules/day we observed a statistically significant reduction of cardiac death (n=3, RR 0.82, 95% CI 0.68 to 0.99, I2=0%), sudden death (n=1, RR 0.70, 95% CI 0.51 to 0.97) and stroke (n=2, RR 0.74, 95% CI 0.57 to 0.95, I2=0%). Omega-3 supplementation at <2 1 g capsules/day showed no association with CVD outcomes; this seems unlikely to change from future research. Compared with the robust scientific evidence available for low doses, the evidence for higher doses (2-4 1 g capsules/day) is weak. The emerging postulated benefit from high-dose supplementation needs replication and further evaluation as to the precise formulation and indication.


Evaluation of hypothalamic-specific autoimmunity in patients with narcolepsy.
An autoimmune-mediated mechanism is considered the most probable etiology for narcolepsy. However, this hypothesis remains unproven. Since narcolepsy is characterized by dysfunction of the hypothalamic hypocretinergic (orexinergic) system, we evaluated the presence of hypothalamic-specific antibodies in sera and CSF of 25 hypocretin-deficient and 6 non-deficient narcoleptic patients by immunohistochemistry and analyzing a screening of a rat cDNA expression hypothalamic library. There was no hypothalamic-specific reactivity in serum or CSF by inmmunohistochemistry. The screening of the hypothalmic library detected some reactive clones but not a common reactivity. Our study did not find any evidence of hypothalamic-specific autoimmunity in narcolepsy.


The impact of 'open throat' technique on vibrato rate, extent and onset in classical singing.
Mitchell, Kenny et al. (2003) identified 'open throat' as integral to the production of an even and consistent sound in classical singing. In this study, we compared vibrato rate, extent and onset of six advanced singing students under three conditions: 'optimal' (O), representing maximal open throat; 'sub-optimal' (SO), using reduced open throat; and loud sub-optimal (LSO), using reduced open throat but controlling for the effect of loudness. Fifteen expert judges correctly identified the sound produced when singers used open throat with 85% accuracy. Having verified the technique perceptually, we used a series of univariate repeated measures ANOVAs with planned orthogonal contrasts to test the hypotheses that frequency modulations associated with vibrato rate, extent and onset would vary outside acceptable or desirable parameters for SO and LSO. Hypotheses were confirmed for vibrato extent and onset but not for rate. There were no significant differences between SO and LSO on any of the vibrato parameters. As vibrato is considered a key indicator of good singing, these findings suggest that open throat is important to the production of a good sound in classical singing.


The Effect of Perceived Threats and Response Efficacy on Adaptation to Smog: An Instrumental Variables Design.
Threats and response efficacyperceptions are core conceptsof the protection motivationtheory, and recent years have witnessed a considerable growth of research on the effect of thesefactors on adaptation to air pollution. However, few studies use appropriate designs to deal with endogeneity issues, a situation that raises serious questions on the validity of their findings. To overcome this problem, this study uses the instrumental variables method to test the effect of perceived threats and response efficacy on adaptation to smog episodes. The results of this study show that the conjunction of a moderate to high perception of threats with a high perception of response efficacy is positively associated with the adoption of the recommended behavior. The increase of perceived threats does not seem to have an effect on the behavior of individuals with low response efficacy perception. Moreover, change in perceived response efficacy does not lead to any change in the behavior of individuals with low threat perceptions. Concerning policy implications, this study suggests that smog warnings and health communication campaigns could be more effective if they provide accurate information simultaneously on air pollution level, its adverse effects, and advice on how to mitigate these effects.


Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment.
Dendritic cells (DCs), the mononuclear cells that initiate immune response, and osteoclasts, the multinucleated bone-resorbing cells, are derived from monocyte/macrophage precursor cells. Granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor (M-CSF) reciprocally regulate the differentiation of both lineages in mice. Using human monocyte-derived DCs generated in vitro, we show that immature DCs transdifferentiate into functional osteoclasts (OCs) in the presence of M-CSF and receptor activator of nuclear factor-kappaB ligand (RANKL). Transdifferentiation operates through fusion of intermediate adherent bipolar fusiform mononuclear cells expressing CD14, CD1a, and RANKL and able to induce RANKL(+) T-cell proliferation. Surprisingly, DC fusion in vitro is faster and more efficient than monocyte fusion to form multinucleated giant cells. The transdifferentiation process reported here supports the existence of a high cellular plasticity within differentiated myeloid phagocytes. Importantly, this process is greatly enhanced by rheumatoid arthritis synovial fluid and involves proinflammatory cytokines such as interleukin 1 or tumor necrosis factor alpha, as well as components of the extracellular matrix such as hyaluronic acid. Our data therefore suggest that DC-derived OCs may be directly involved in the osteolytic lesions observed in human inflammatory bone diseases such as rheumatoid arthritis or in particular forms of Langerhans cell histiocytosis, characterized by accumulation of immature skin DCs and chronic lytic bone lesions.


Vegetable but not fruit consumption reduces the risk of type 2 diabetes in Chinese women.
We examined associations between fruit and vegetable intake and the incidence of type 2 diabetes (T2D) in a population-based prospective study of 64,191 women with no history of T2D or other chronic diseases at study recruitment and with valid dietary information. Dietary intake was assessed by in-person interviews using a validated FFQ. During 297,755 person-years of follow-up, 1608 new cases of T2D were documented. We used a Cox regression model to evaluate the association of fruit and vegetable intake (g/d) with the risk of T2D. Quintiles of vegetable intake and T2D were inversely associated. The relative risk for T2D for the upper quintile relative to the lower quintile of vegetable intake was 0.72 (95%CI: 0.61-0.85; P < 0.01) in multivariate analysis. Individual vegetable groups were all inversely and significantly associated with the risk of T2D. Fruit intake was not associated with the incidence of diabetes in this population. Our data suggest that vegetable consumption may protect against the development of T2D.


Redistribution of material labelled with [3H]mannose in amoebae induced to undergo pinocytosis.
The synthesis, transport, and disposition of material labelled with [3H]mannose were studied by electron microscopic radioautography in normal amoebae and in cells that had internalized cell surface as a result of being induced to undergo pinocytosis. Control amoebae were injected with the precursor and placed in normal medium. The Golgi apparatus and rough endoplasmic reticulum were heavily labelled at the earliest intervals, while radioactivity of the cell surface peaked 12 h after injection of precursor. The experimental cells were injected, placed in bovine serum albumin solution from 15 to 60 min after injection, and then removed to normal medium until fixation. Incorporation of the precursor into the rough endoplasmic reticulum was near normal, but the proportions of grains associated with the Golgi apparatus and the cell surface were greatly reduced. The percentage of grains overlying vacuoles increased 12 h after injection, notably in the case of polymorphous vacuoles and dense vacuoles, both of which were identified as lysosomes with the acid phosphatase reaction. The results suggest that addition to the surface of components labelled with [3H]mannose was diminished following induction of pinocytosis. Incorporation of the precursor appeared to be shifted from cell surface material to lysosomal contents, possibly lysosomal enzymes. It is thought that this shift occurred in response to the need for the cell to digest unusually large amounts of endocytosed protein. Recycling of cell surface under these conditions is considered possible.


In Vivo Non-radioactive Assessment of mGlu5 Receptor-Activated Polyphosphoinositide Hydrolysis in Response to Systemic Administration of a Positive Allosteric Modulator.
mGlu5 receptor-mediated polyphosphoinositide (PI) hydrolysis is classically measured by determining the amount of radioactivity incorporated in inositolmonophosphate (InsP) after labeling of membrane phospholipids with radioactive inositol. Although this method is historically linked to the study of mGlu receptors, it is inappropriate for the assessment of mGlu5 receptor signaling in vivo. Using a new ELISA kit we showed that systemic treatment with the selective positive allosteric modulator (PAM) of mGlu5 receptors VU0360172 enhanced InsP formation in different brain regions of CD1 or C57Black mice. The action of VU0360172 was sensitive to the mGlu5 receptor, negative allosteric modulator (NAM), MTEP, and was abolished in mice lacking mGlu5 receptors. In addition, we could demonstrate that endogenous activation of mGlu5 receptors largely accounted for the basal PI hydrolysis particularly in the prefrontal cortex. This method offers opportunity for investigation of mGlu5 receptor signaling in physiology and pathology, and could be used for the functional screening of mGlu5 receptor PAMs in living animals.


Poxviral protein E3-altered cytokine production reveals that DExD/H-box helicase 9 controls Toll-like receptor-stimulated immune responses.
Host pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) detect viruses and other pathogens, inducing production of cytokines that cause inflammation and mobilize cells to control infection. Vaccinia virus (VACV) encodes proteins that antagonize these host innate immune responses, and elucidating the mechanisms of action of these viral proteins helped shed light on PRR signaling mechanisms. The VACV virulence factor E3 is one of the most intensely studied VACV proteins and has multiple effects on host cells, many of which cannot be explained by the currently known cellular targets of E3. Here, we report that E3 expression in human monocytes alters TLR2- and TLR8-dependent cytokine induction, and particularly inhibits interleukin (IL)-6. Using MS, we identified DExD/H-box helicase 9 (DHX9) as an E3 target. Although DHX9 has previously been implicated as a PRR for sensing nucleic acid in dendritic cells, we found no role for DHX9 as a nucleic acid-sensing PRR in monocytes. Rather, DHX9 suppression in these cells phenocopied the effects of E3 expression on TLR2- and TLR8-dependent cytokine induction, in that DHX9 was required for all TLR8-dependent cytokines measured, and for TLR2-dependent IL-6. Furthermore, DHX9 also had a cell- and stimulus-independent role in IL-6 promoter induction. DHX9 enhanced NF-κB-dependent IL-6 promoter activation, which was directly antagonized by E3. These results indicate new roles for DHX9 in regulating cytokines in innate immunity and reveal that VACV E3 disrupts innate immune responses by targeting of DHX9.


A macrocyclic chelator with unprecedented Th⁴⁺ affinity.
A novel macrocyclic octadentate ligand incorporating terephthalamide binding units has been synthesized and evaluated for the chelation of Th(4+). The thorium complex was structurally characterized by X-ray diffraction and in solution with kinetic studies and spectrophotometric titrations. Dye displacement kinetic studies show that the ligand is a much more rapid chelator of Th(4+) than prevailing ligands (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and diethylenetriaminepentaacetic acid). Furthermore, the resulting complex was found to have a remarkably high thermodynamic stability, with a formation constant of 10(54). These data support potential radiotherapeutic applications.


Body Size Plasticity of Weevil Larvae (Curculio davidi) (Coleoptera: Curculionidae) and Its Stoichiometric Relationship With Different Hosts.
Parasites obtain energy and nutrients from the host, and their body size is also usually limited by host size. However, the regulatory mechanisms that control the plasticity of parasite body sizes and the stoichiometric relationships with their hosts remain unclear. Here we investigated the concentrations of 14 elements (C, H, O, N, P, S, K, Na, Ca, Mg, Al, Fe, Mn, and Zn) in the acorns of three oak species (Quercus spp.), in their endoparasitic weevil (Curculio davidi Fairmaire) (Coleoptera: Curculionidae) larvae and in the larval feces, and the weight of weevil larvae within different hosts in a warm-temperate zone of China. Our results showed that the three acorn species exhibited significant differences in C, H, O, P, K, Mg, and Mn concentrations. However, in the weevil larvae, only P, Mn, and C:P ratio revealed significant differences. Weevil larvae preferentially absorbed and retained N, Zn, Na, and P, whereas Mn, K, Ca, and O were passively absorbed and transported. The weevil larvae weight was associated with acorn stoichiometry, and positively correlated with acorn size. Weevil larvae P decreased, but Mn and C:P increased with their weight, implying highly variable in somatic stoichiometry are coupled with the plasticity of body size. Interestingly, weevil larvae weight was negatively correlated with acorn infection rate, indicating small-size parasitic insects might have higher fitness level in parasite-host systems than larger-size ones. Our results suggest that variation in P, Mn, and C:P in parasites may play critical roles in shaping their body size and in improving their fitness.


Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9.
Intracellular zinc homeostasis is strictly regulated by zinc binding proteins and zinc transporters. In the present study, we quantified in a first global view the expression of all characterized human zinc exporters (hZnT-1-9) in different leukocyte subsets in response to zinc supplementation and depletion and analyzed their influence on alterations in the intracellular zinc concentration. We found that hZnT-1 is the most regulated zinc exporter. Furthermore, we discovered that hZnT-4 is localized in the plasma membrane similar to hZnT-1. hZnT-4 is most highly expressed in Molt-4, up-regulated after treatment with PHA and is responsible for the measured decrease of intracellular zinc content after high zinc exposure. In addition, we found that hZnT-5, hZnT-6, and hZnT-7 in Raji as well as hZnT-6 and hZnT-7 in THP-1 are up-regulated in response to cellular zinc depletion. Those zinc exporters are all localized in the Golgi network, and this type of regulation explains the observed zinc increase in both cell types after up-regulation of their expression during zinc deficiency and, subsequently, high zinc exposure. Furthermore, we detected, for the first time, the expression of hZnT-8 in peripheral blood lymphocytes, which varied strongly between individuals. While hZnT-2 was not detectable, hZnT-3 and hZnT-9 were expressed at low levels. Further on, the amount of expression was higher in primary cells than in cell lines. These data provide insight into the regulation of intracellular zinc homeostasis in cells of the immune system and may explain the variable effects of zinc deficiency on different leukocyte subsets.


Intrarenal localization of angiotensinogen mRNA by RNA-DNA dot-blot hybridization.
The renal renin-angiotensin system plays an important role in the control of renal hemodynamics and in the etiology of some types of hypertension. Angiotensinogen is the prohormone for angiotensins I and II. In the present communication, we report for the first time the presence of mRNA coding for angiotensinogen in the kidney. Indeed, the intrarenal location appears to be predominantly in the renal medulla. Additionally, an investigation of the effect of uninephrectomy on the intrarenal angiotensinogen mRNA suggests that regulation of mRNA levels in the kidney does occur.


Chagas disease stroke and associated risk factors: A case-control study.
The intricate relationship between Chagas disease and ischemic stroke remains unclear. Limited evidence exists concerning secondary prophylaxis, etiological diagnosis, and stroke-related determinants. This study aims to discern factors linked to stroke in Chagas disease by contrasting patients with and without a history of ischemic stroke. Retrospective data from all outpatient Chagas disease patients from two Brazilian hospitals - one Chagas center and one stroke clinic - were examined. Descriptive analyses were conducted to identify stroke-associated factors. Variables were compared between patients with and without ischemic stroke history. Among 678 subjects, 72 had experienced stroke. Univariate associations with stroke included male gender, heart failure, prior or ongoing alcoholism, electrocardiographic features (non-sinus rhythm, left bundle branch, right bundle branch block, left anterosuperior fascicular block, atrial fibrillation), as well as echocardiographic findings indicative of reduced left ventricular ejection fraction and segmental abnormalities. After logistic regression (multivariate analysis), congestive heart failure, right bundle branch block, left anterosuperior divisional block, and atrial fibrillation retained independent associations. In this study, cardiac involvement emerged as the predominant factor correlated with stroke in Chagas disease. While atherosclerosis-related risk factors were prevalent, their influence on ischemic stroke in Chagas disease appeared limited.


Postoperative care after tonsillectomy: what's the evidence?
The purpose of this review is to evaluate the current literature regarding postoperative management after tonsillectomy in children. Controversy remains regarding the ideal medication regimen to manage pain after tonsillectomy. Acetaminophen and ibuprofen are routinely used, although concerns of more severe postoperative hemorrhage with ibuprofen remain. Narcotics are prescribed commonly, but with extreme caution in children with severe obstructive sleep apnea. Although not always utilized by the authors, additional adjunctive medications such as perioperative dexamethasone, ketamine, and local infiltration of lidocaine into tonsillar pillars may decrease postoperative pain. Systematic reviews have shown that dexamethasone does not increase risk of posttonsillectomy bleeding. Adenotonsillectomy is one of the most common procedures performed on children and may have significant morbidity from postoperative pain and bleeding. Managing pain remains challenging and the optimal treatment regimen has not been definitively identified. Many medications and alternative therapies have been studied and suggest possible benefit.


Uptake and binding of uranyl ions by barley roots.
After undergoing the processing for electron microscopy, bound uranyl ions are revealed as characteristic electron-opaque crystals. Meristematic walls and associated vesicles become heavily labeled, while pinocytotic accumulation into vacuoles seems probable in cap cells and those just behind the meristem. The endodermal Casparian strip and suberinized lamella are effective barriers to the passage of uranyl ions.


[CAR-T Immunotherapy and Non-small Cell Lung Cancer: Bottleneck and Dawn].
With the deeper understanding of the pathophysiology and pathogenesis of non-small cell lung cancer (NSCLC) which threatens human health, NSCLC treatment has entered a new era. Transition from traditional treatment based on surgery, radiotherapy and chemotherapy to individualized and precise targeted therapy and safer and more effective immunotherapy. Immune checkpoint inhibitor therapy has been approved as a first-line or second-line treatment for advanced NSCLC, and has achieved extraordinary clinical results. Meanwhile, other types of immunotherapy are rarely explored in NSCLC. Chimeric antigen receptor modified T cells (CAR-T cells) perform well in treating several hematological malignancies. However, it is not ideal for treating patients with solid tumors including NSCLC. This review aims to systematically explain the latest progress of CAR-T in the treatment of NSCLC, mainly including: CAR molecular target selection, CAR-T function enhancement and related toxicity management, as well as the difficulties and prospects of CAR-T treatment of NSCLC. It aims to open up new perspectives and unique ideas for the immunotherapy of NSCLC, and contribute to the building of tumor immunotherapy. .


[Activity of the glutathione system of antioxidant defense in rats under the action of L-glutamic acid].
The data on the effects of glutamic acid (L-Glu), which is one of three amino acid - precursors ofglutathione on animals organism is quite controversial because research in this area remain relevant. The aim of our research was to find out what impact the additional introduction of L-Glu on the activity glutathione system of antioxidant defence and the content of lipid peroxidation products in various organs and tissues of rats. The effect of additional (285 and 715 mg/kg, respectively) introduction to the diet of L-Glu on the activity of antioxidant enzymes and intensity of peroxidation processes in various tissues of rats was studied. It is shown that in the liver, spleen and kidneys of rats which received additional 715 mg/kg of L-Glu content of reduced glutathione and glutathione peroxidase activity increased. A decrease of the content of lipid hydroperoxides and TBA-active products in tissues of animals which received additional 285 and 715 mg/kg of L-Glu into the diet was found. We have also found that the enrichment of rat's diet by L-Glu during 30 days resulted in a change of glutathione part of antioxidant system and intensity of lipid peroxidation. More intensive changes in these indices were observed in animals which received additional 715 mg/kg of L-Glu into the diet.


The importance and need of more meta-research studies in medical ethics journals.
Meta-research aims to research the process of research itself, and as such, it can be used to study threats to research integrity and potentially better understand them. This commentary assesses the prevalence of meta-research studies published in medical ethics journals to understand their representation. The retrieved articles were organized by meta-research area: methods, reporting, reproducibility, evaluation, and incentives. An analysis of articles published in the last two years in the 16 highest ranked medical ethics journals suggests that meta-research studies seemed to be not well represented in these journals. In this sample, less than 2% of the articles were classified as meta-research studies. Furthermore, some meta-research areas such as reproducibility and incentives are relatively unexplored currently in medical ethics journals. This commentary discusses the meaning of the specific meta-research areas and provides some examples of articles in medical research ethics that fit into each meta-research area. As a conclusion of this commentary, some action should be taken to encourage more meta-research publications in medical ethics journals for their potential to advance medical ethics science.


The impact of gender and age matching for long-term graft survival in living donor renal transplantation.
In renal transplantation, donor age and allograft size are known to have an important influence on the outcome of the graft reflecting functional renal mass. Women tend to have smaller kidneys with 17% fewer nephrons than male kidneys. The number of glomeruli per kidney as well as the mean glomerular volume closely correlate with kidney weight and negatively correlate with subject age. We evaluated the impact of gender and age matching in living-donor renal transplantation on long-term graft survival. Four groups were discerned among 614 renal transplants, according to donor and recipient gender: Group 1 was male donor to male recipient; Group 2 was male donor to female recipient; Group 3 was female donor to male recipient; and Group 4 was female donor to female recipient. We analyzed long-term graft survival and risk factors between the four groups as well as according to age matching. Statistical significance was determined by the Kaplan-Meier method and log rank test (P < .05). The graft survival rates at 1, 3, 5, and 10 years were 92.62%, 88.13%, 82.37%, and 76.07%, respectively. The risk factors affecting long-term graft survival were donor age, donor gender, acute rejection rate, and HLA-DR matching. Among the four groups, the graft survival rates of Group 3 (female donor to male recipient) were significantly different from the other groups (P = .0165). Also, the long-term graft survival rates according to age differences were significantly different between older donors than recipients and younger donors than recipients in each group (P = .0213). The importance of inadequate renal mass is magnified in high-risk recipients. Age matching could perhaps improve the results of transplantation, particularly when kidneys from older donors are used. Consideration of age and gender as criteria for the choice of donors and recipients may be considered in organ allocation.


Effects of increasing dietary inclusion of camelina cake on growth performance of growing-finishing pigs.
The objective of this experiment was to determine the dietary inclusion rate of camelina cake (CC) that would support the growth performance of growing-finishing pigs similar to that of a corn-soybean meal-based diet. Pigs (n = 192; BW = 35.2 kg; Duroc x (Yorkshire x Landrace)), balanced for sex and initial weight, were assigned to pens (8 pigs/pen) and pens were assigned randomly to one of four dietary treatments (6 pens/treatment). Treatments consisted of a non GMO corn-soybean meal control diet (CON), or CON containing 5% (5CC), 10% (10CC), or 15% (15CC) camelina cake. Feed disappearance on a pen basis and individual body weights of pigs were recorded every other week to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) on a pen basis. Prior to harvest, real-time ultrasonic measurements of back fat depth and loin eye area were collected on all live pigs. Pigs were harvested as a single group at about 23 weeks of age at a commercial abattoir. Data were analyzed using Proc Glimmix with dietary treatment as a fixed effect and pen serving as the experimental unit. Growth performance data collected over time were analyzed using repeated measures within the Proc Glimmix procedure. Overall, pigs fed CON exhibited similar ADG to those consuming 5CC and higher ADG than pigs consuming 10CC and 15CC diets (1.10 kg vs. 1.05 kg for 10CC and 1.02 kg for 15CC; P < 0.05 for both mean comparisons). Pigs fed CON consumed more feed than pigs fed any of the CC diets (ADFI = 2.66 kg for CON vs. 2.46 kg for 5CC, 2.46 kg for 10CC and 2.47 kg for 15CC; P < 0.05 for all). These differences resulted in heavier (P < 0.05) CON-fed pigs at marketing than 10CC or 15CC-fed pigs. There were no differences in any carcass traits analyzed. From these data, we conclude that feeding up to 5% CC in corn-soybean meal-based diets did not negatively influence growth performance, or carcass traits of growing-finishing pigs.


Ecological metrics and methods for GPS movement data.
The growing field of movement ecology uses high resolution movement data to analyze animal behavior across multiple scales: from individual foraging decisions to population-level space-use patterns. These analyses contribute to various subfields of ecology-inter alia behavioral, disease, landscape, resource, and wildlife-and facilitate facilitate novel exploration in fields ranging from conservation planning to public health. Despite the growing availability and general accessibility of animal movement data, much potential remains for the analytical methods of movement ecology to be incorporated in all types of geographic analyses. This review provides for the Geographical Information Sciences (GIS) community an overview of the most common movement metrics and methods of analysis employed by animal ecologists. Through illustrative applications, we emphasize the potential for movement analyses to promote transdisciplinary GIS/wildlife-ecology research.


Correlation between Kinesia system assessments and clinical tremor scores in patients with essential tremor.
The primary aim of this study was to determine whether scores on The Essential Tremor Rating Assessment Scale (TETRAS) correlate with quantitative assessments using the Kinesia™ (CleveMed) system in patients with essential tremor (ET). Patients sequentially evaluated and diagnosed with ET at the Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine were enrolled in the study. The Kinesia portable device was attached to the wrist and subjects were instructed to hold their arms in an outstretched position and then touch their nose while data were wirelessly transmitted to a computer. Subjects were rated on the arm where the system was placed using specific TETRAS items. A linear regression model was constructed for each task using the logarithmic values of both clinical scores and objective motion data parameters to compute a Kinesia score. Twenty subjects underwent complete clinical TETRAS and Kinesia quantitative assessments. TETRAS clinical scores significantly correlated with predicted Kinesia quantitative variables for postural (r = 0.738; P < 0.001) and kinetic (r = 0.57; P = 0.009) tremor. We conclude that the Kinesia system may, therefore, have a utility in quantitative assessments of ET when combined with standard clinical assessment.


Influence of sediment chemistry and sediment toxicity on macroinvertebrate communities across 99 wadable streams of the Midwestern USA.
Simultaneous assessment of sediment chemistry, sediment toxicity, and macroinvertebrate communities can provide multiple lines of evidence when investigating relations between sediment contaminants and ecological degradation. These three measures were evaluated at 99 wadable stream sites across 11 states in the Midwestern United States during the summer of 2013 to assess sediment pollution across a large agricultural landscape. This evaluation considers an extensive suite of sediment chemistry totaling 274 analytes (polycyclic aromatic hydrocarbons, organochlorine compounds, polychlorinated biphenyls, polybrominated diphenyl ethers, trace elements, and current-use pesticides) and a mixture assessment based on the ratios of detected compounds to available effects-based benchmarks. The sediments were tested for toxicity with the amphipod Hyalella azteca (28-d exposure), the midge Chironomus dilutus (10-d), and, at a few sites, with the freshwater mussel Lampsilis siliquoidea (28-d). Sediment concentrations, normalized to organic carbon content, infrequently exceeded benchmarks for aquatic health, which was generally consistent with low rates of observed toxicity. However, the benchmark-based mixture score and the pyrethroid insecticide bifenthrin were significantly related to observed sediment toxicity. The sediment mixture score and bifenthrin were also significant predictors of the upper limits of several univariate measures of the macroinvertebrate community (EPT percent, MMI (Macroinvertebrate Multimetric Index) Score, Ephemeroptera and Trichoptera richness) using quantile regression. Multivariate pattern matching (Mantel-like tests) of macroinvertebrate species per site to identified contaminant metrics and sediment toxicity also indicate that the sediment mixture score and bifenthrin have weak, albeit significant, influence on the observed invertebrate community composition. Together, these three lines of evidence (toxicity tests, univariate metrics, and multivariate community analysis) suggest that elevated contaminant concentrations in sediments, in particular bifenthrin, is limiting macroinvertebrate communities in several of these Midwest streams.


Immunocytochemical localization of the intrinsic factor-cobalamin receptor in dog-ileum: distribution of intracellular receptor during cell maturation.
Absorption of cobalamin is facilitated by the binding of the intrinsic factor-cobalamin complex (IF-cbl) to specific receptors in the ileum. The physical and biochemical characteristics of this ligand-receptor binding reaction have been extensively studied, but little is known about the cellular mechanisms or receptor synthesis, intracellular transport, and expression on the microvillus surface membrane. We attempted to delineate these mechanisms by using ultrastructural immunocytochemistry to localize the IF-cbl receptor in the crypt, mid-villus, and villus tip regions of mucosal biopsies obtained from the ileum of anesthetized dogs. Prior to initiating the ileal localization studies, the antisera to purified canine IF-cbl receptor that was employed in our studies was shown to have specificity for site (e.g., ileal enterocytes vs. other cells within the gastrointestinal tract) and immunohistochemical specificity. Receptor synthesis in endoplasmic reticulum begins in crypt enterocytes, but continues in cells throughout the villus. In the mid-villus region synthesized receptor translocates vectorially to the microvillus surface associated with membranous vesicles and then inserts into the microvillus pit. Receptor remains fixed to the microvillus pit and does not distribute uniformly over the brush border membrane. All villus tip enterocytes contained IF-cbl receptor in microvillus pits, vesicles, and endoplasmic reticulum, but in addition extensive perinuclear membrane staining was evident as well as re-internalized receptor associated with multivesicular bodies. Basolateral membranes contained no receptor at any level of the villus. These observations suggest that the IF-cbl receptor (a) translocates to the apical cell surface at the mid-villus region by transport in vesicles, (b) directly inserts into and then remains fixed in microvillus pits, (c) is elaborated on the luminal surface most extensively in villus tip cells, and (d) although reinternalized, does not move IF and/or cbl to the basolateral cell surface.


A Mechanism for Production of Hydroxyl Radicals by the Brown-Rot Fungus Coniophora Puteana: Fe(III) Reduction by Cellobiose Dehydrogenase and Fe(II) Oxidation at a Distance from the Hyphae.
In timber infested by brown-rot fungi, a rapid loss of strength is attributed to production of hydroxyl radicals (HO.). The hydroxyl radicals are produced by the Fenton reaction [Fe(II)/H2O2], but the pathways leading to Fe(II) and H2O2 have remained unclear. Cellobiose dehydrogenase, purified from cultures of Coniophora puteana, has been shown to couple oxidation of cellodextrins to conversion of Fe(III) to Fe(II). Two characteristics of brown rot are release of oxalic acid and lowering of the local pH, often to about pH 2. Modelling of Fe(II) speciation in the presence of oxalate has revealed that Fe(II)-oxalate complexes are important at pH 4-5, but at pH 2 almost all Fe(II) is in an uncomplexed state which reacts very slowly with dioxygen. Diffusion of Fe(II) away from the hyphae will promote conversion to Fe(II)-oxalate and autoxidation with H2O2 as product. Thus the critical Fe(II)/H2O2 combination will be generated at a distance, enabling hydroxyl radicals to be formed without damage to the hyphae.


Novel sternoclavicular hook plate for the treatment of posterior sternoclavicular dislocation: a retrospective study.
Controversies regarding the optimal internal fixation method for posterior sternoclavicular dislocation (SCD) exist. Therefore, this study aimed to investigate the clinical efficacy of a new type of sternoclavicular hook plate for treating posterior SCD. Eleven patients (eight men and three women) with posterior SCD who underwent treatment with the new sternoclavicular hook plate from June 2011 to January 2022 were retrospectively analyzed. The patients' ages ranged from 33 to 71 years (54.91 ± 13.58 years). Operation time, blood loss, length of hospital stay, and postoperative complications were recorded. Postoperative joint reduction and healing were evaluated using radiography and computed tomography. The Constant-Murley and Rockwood sternoclavicular joint scores were used to evaluate the functional recovery of the affected limb 12 months after surgery. All 11 patients were followed up for 12-24 months (18.00 ± 3.74 months). All incisions healed by first intention. The healing time ranged from 9 to 13 days (10.82 ± 1.54 days), and the joint healing time was 3-4 months (3.55 ± 0.52 months). The operation time was 45-75 min (59.55 ± 11.06 min), intraoperative blood loss was 22-58 mL (39.91 ± 11.07 mL), and the length of hospitalization was 6-14 days (9.91 ± 3.27 days). There were no complications such as infections, internal fixation failure, or nerve injury. The Constant-Murley score was 93.64 ± 9.01 at 12 months postoperatively. The Rockwood score was 13.36 ± 1.86, of which nine cases were excellent, one case was good, and one case was fair. The novel sternoclavicular hook plate is effective for the treatment of posterior SCD. This novel device can facilitate early joint functional exercises and good functional recovery.


[Post-traumatic diaphragmatic rupture. Report of 20 cases].
From 1977 to 1987, 20 patients (18 men and 2 women) with left post-traumatic diaphragmatic rupture, were managed by the General Surgery Service of the Hospital de Especialidades, Centro Médico de Occidente, IMSS; 13 as urgencies (65%) and 7 as elective procedures (35%). Hernia was due to closed trauma in 80% of the cases. Predominant symptoms were chest pain (85%) and dyspnea (50%). The Stomach was the herniated viscus in 16 instances. CXR showed suggestive data in 95% of the cases. Primary closure was achieved in 95% of the cases, in 8 patients thoraco-abdominal aproach was necessary. There were 50% morbidity (35% athelectasis, 30% wound sepsis) and 10% mortality rates.


Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF.
Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat breast cancer metastasis, a leading cause of cancer-related death in women. However, the precise mechanisms behind MAM-mediated metastatic tumor outgrowth have not been fully elucidated. Using mouse models of metastatic breast cancer, we showed that MAMs uniquely expressed hepatocyte growth factor (HGF) in metastatic tumors. We also demonstrated that a selected population of cancer cells with high metastatic potential (cancer cells that can establish metastatic tumors in mice with higher number and incidence than parental cells) had higher expression of HGF receptor, MNNG HOS transforming gene (MET), and were more responsive to HGF released from macrophages compared with the parental cells. Blockade of MET signaling in cancer cells suppressed metastatic tumor expansion, in part, through activation of natural killer cells. Results from this study suggest an approach to prevent life-threatening metastatic tumor formation using blockade of MAM-induced MET signal activation in metastatic cancer cells.