Jump height as performance indicator for the selection of youth football players to national teams.
Different jump tests such as the Countermovement Jump (CMJ), Abalakov Jump (AJ) and Standing Long Jump (SLJ) are often used in practice to evaluate muscular power and functional performance in football. These tests are also used in different selection processes and talent identification, but the significance of the tests for the selection of youth players to national teams are relatively unknown. The aim of this study was to compare jump ability between youth football players selected or not selected for the national team. In this cross-sectional study, 22 players (aged 17±2 years), 11 national players (NP) and 11 non-national players (NNP) were evaluated in three different jump tests; CMJ, AJ and SLJ. Mean scores for the tests were analyzed and compared. Significant differences were found between the groups regarding jump height in favor of the NP group in both the CMJ (NP 39.9±5.0 cm vs. NNP 34.2±4.9 cm, P=0.013) and the AJ (NP 47.1±5.4 vs. NNP 40.9±4.7, P=0.010). No group difference was found regarding jump length in SLJ (NP 246.2±17.9 vs. NNP 232.9±16.5, P=0.084). The results suggest that tests, measuring jump height, could be used as a performance indicator and part of the selection process of youth football players to national teams, whereas the use of jump length could be questioned.


NPFF increases fusogenic proteins syncytin 1 and syncytin 2 via GCM1 in first trimester primary human cytotrophoblast cells.
Neuropeptide FF (NPFF) is well-known for its roles in the central nervous system. Despite studies demonstrating that NPFF receptor 2 (NPFFR2) mRNA is highest in placenta, nothing is known about NPFF-NPFFR2 functions in placental development. Here, we investigated the effects of NPFF-NPFFR2 on expression of syncytial [human chorionic gonadotropin (hCG) β] and fusogenic [syncytin 1, syncytin 2, and glial cells missing 1 (GCM1)] genes in first trimester primary human cytotrophoblast cells. By analyzing two publicly available microarray data sets, we found that NPFF is consistently expressed throughout gestation whereas NPFFR2 increases in first trimester and is elevated in placenta samples from women with preeclampsia. Immunohistochemistry showed that NPFFR2, syncytin 1/2, and GCM1 each displayed unique patterns of expression among different trophoblast populations in first trimester placenta. Treatment of primary human cytotrophoblast cells with NPFF increased the mRNA and protein levels of hCG β, syncytin 1, syncytin 2, and GCM1; and knockdown of NPFFR2 abolished these effects. Interestingly, GCM1 mediated NPFF-induced upregulation of syncytin 1 and syncytin 2, but not hCG β, in primary human cytotrophoblasts. Our results demonstrate that NPFF acts via NPFFR2 to enhance production of hCG β and promote GCM1-dependent expression of syncytin 1 and 2 in human cytotrophoblasts.


Survival signaling by Notch1: mammalian target of rapamycin (mTOR)-dependent inhibition of p53.
Notch signaling is believed to promote cell survival in general. However, the mechanism is not clearly understood. Here, we show that cells expressing intracellular domain of human Notch1 (NIC-1) are chemoresistant in a wild-type p53-dependent manner. NIC-1 inhibited p53 by inhibiting its activating phosphorylations at Ser(15), Ser(20), and Ser(392) as well as nuclear localization. In addition, we found that inhibition of p53 by NIC-1 mainly occurs through mammalian target of rapamycin (mTOR) using phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway as the mTOR inhibitor, rapamycin treatment abrogated NIC-1 inhibition of p53 and reversed the chemoresistance. Consistent with this, rapamycin failed to reverse NIC-1-induced chemoresistance in cells expressing rapamycin-resistant mTOR. Further, ectopic expression of eukaryotic initiation factor 4E (eIF4E), a translational regulator that acts downstream of mTOR, inhibited p53-induced apoptosis and conferred protection against p53-mediated cytotoxicity to similar extent as that of NIC-1 overexpression but was not reversed by rapamycin, which indicates that eIF4E is the major target of mTOR in Notch1-mediated survival signaling. Finally, we show that MCF7 (breast cancer) and MOLT4 (T-cell acute lymphoblastic leukemia) cells having aberrant Notch1 signaling are chemoresistant, which can be reversed by both PI3K and mTOR inhibitors. These results establish that Notch1 signaling confers chemoresistance by inhibiting p53 pathway through mTOR-dependent PI3K-Akt/PKB pathway and imply that p53 status perhaps is an important determinant in combination therapeutic strategies, which use mTOR inhibitors and chemotherapy.


Cardiorespiratory effects of pneumatic trousers in critically ill patients.
Although pneumatic antishock trousers (PT) are widely used in prehospital and emergency care, little is known about their cardiorespiratory effects in critically ill patients. To examine this issue, we measured hemodynamic and oxygen metabolism variables in ten critically ill patients. All patients were studied with PTs uninflated, after five minutes of PT inflation to 40 mm Hg, and five minutes after PT deflation. Significant increase in mean arterial pressure, systemic vascular resistance, and pulmonary artery pressures were present after PT inflation. No significant changes in cardiac index, stroke index, arterial or mixed venous blood gas values, or oxygen delivery were found. There was a downward trend in VO2 that was on the border of statistical significance. Regression analysis of cardiorespiratory variables on blood volume demonstrated no physiologic effects of external counterpressure in hypovolemic, hypervolemic, or normovolemic patients. We concluded that PT inflation increases BP through its effects on peripheral resistance. No significant autotransfusion effect was present, and there was a suggestive impairment in oxygen metabolism.


Infections in total hips secondary to a primary source elsewhere.
This is a report of 3 cases in which a primary infection in a site other than a total hip led to infection in the hip itself. One hip infection appeared to arise in a tooth abscess, a second in the urinary tract, and one from the respiratory tract. All infections resulted in the necessity of removing the components of the total hip. It is suggested that patients who have had previous total hip replacement should be warned to consult their physician when the possibility of an infection is present, and that antibiotic coverage be given during this period of time. Cultures of infected sites should be made in patients who have had total hip replacements, in order that organisms and their sensitivity may be identified in the event that antibiotic therapy is needed, subsequently.


Single-Level Total Disc Replacement: Index-Level and Adjacent-Level Revision Surgery Incidence, Characteristics, and Outcomes.
The literature reports that index level (IL) revision spine surgery (RSS) and adjacent level (AL) RSS are diminished in lumbar TDR compared with fusion procedures. There is a paucity of PROMs reported after RSS. To present the incidence of RSS at the IL and AL following single-level lumbar total disc replacement (TDR) and to document patient-related outcome measures (PROMs) associated with RSS. PROMs and timelines were analyzed for 32 RSS patients from a prospective cohort study of 401 patients treated with TDR for single-level degenerative disc disease. The data collected prospectively are analyzed from baseline (prior to index surgery) to latest follow-up following RSS. PROMs, including visual analog scales for back and leg, Oswestry Disability Index, and Roland-Morris Disability Questionnaire, were collected preoperatively; postoperatively at 3, 6, and 12 months; and annually thereafter until RSS. The time to RSS was recorded, and PROMs for RSS (IL, AL, or both) were documented, analyzed, and compared. The median time to RSS in the IL cohort was 35 months (interquartile range [IQR] = 9-51 months). The median time to RSS cohort was 70 months (IQR = 41.3-105.3 months). Timepoints facilitate PROM discussion for RSS. Patients in both groups achieved thresholds for the minimum clinically important difference for pain and disability scores. The small sample size in each group contributed to the variability demonstrated by the 95% CIs, thereby cautioning definitive conclusions. This study reveals that statistically significant and modest clinical improvements in PROMs can be achieved in RSS for lumbar TDR at IL and AL. The surgical approach and technique are reflective of the pathology and suggest that anterior RSS for AL degeneration and posterior RSS for IL pathology yield similar results. Statistical and clinical improvements can be achieved in IL-RSS and AL-RSS following single level TDR. It is essential for clinicians to understand and verify the underlying IL and/or AL pathology to select an appropriate management strategy and to facilitate balanced informed discussions with patients.


Comprehensive Characterization of the Transmitted/Founder env Genes From a Single MSM Cohort in China.
The men having sex with men (MSM) population has become one of the major risk groups for HIV-1 infection in China. However, the epidemiological patterns, function of the env genes, and autologous and heterologous neutralization activity in the same MSM population have not been systematically characterized. The env gene sequences were obtained by the single genome amplification. The time to the most recent common ancestor was estimated for each genotype using the Bayesian Markov Chain Monte Carlo approach. Coreceptor usage was determined in NP-2 cells. Neutralization was analyzed using Env pseudoviruses in TZM-bl cells. We have obtained 547 full-length env gene sequences by single genome amplification from 30 acute/early HIV-1--infected individuals in the Beijing MSM cohort. Three genotypes (subtype B, CRF01_AE, and CRF07_BC) were identified and 20% of the individuals were infected with multiple transmitted/founder (T/F) viruses. The tight clusters of the MSM sequences regardless of geographic origins indicated nearly exclusive transmission within the MSM population and limited number of introductions. The time to the most recent common ancestor for each genotype was 10-15 years after each was first introduced in China. Disparate preferences for coreceptor usages among 3 genotypes might lead to the changes in percentage of different genotypes in the MSM population over time. The genotype-matched and genotype-mismatched neutralization activity varied among the 3 genotypes. The identification of unique characteristics for transmission, coreceptor usage, neutralization profile, and epidemic patterns of HIV-1 is critical for the better understanding of transmission mechanisms, development of preventive strategies, and evaluation of vaccine efficacy in the MSM population in China.


Uptake, impact, and effectiveness of rotavirus vaccination in the United States: review of the first 3 years of postlicensure data.
Rotavirus vaccine was recommended for routine use in US infants in 2006. Before the introduction of vaccine, rotavirus was the most common cause of severe gastroenteritis in children <5 years of age in the United States. We reviewed published data to summarize the US experience during the first 3 years of its rotavirus vaccination program. Rotavirus seasons have been delayed and diminished in magnitude during the postvaccine era compared with the prevaccine era. Hospitalizations, emergency department visits, and outpatient visits due to gastroenteritis have declined dramatically in children < 5 years of age including in children age-ineligible to have received vaccine, suggesting indirect benefits of vaccination. Rotavirus vaccine has been widely accepted by pediatricians. Vaccine coverage is steadily increasing but remains lower than coverage levels of other routine infant immunizations. The implementation of routine childhood immunization against rotavirus has rapidly and dramatically reduced the large health burden of rotavirus gastroenteritis in US children. Continued monitoring of rotavirus diarrhea is needed to determine if immunity wanes as vaccinated children get older and to better quantify the indirect benefits of vaccination. Ongoing surveillance will also enable monitoring of the long-term impact of vaccination on rotavirus epidemiology.


Localised palatal tooth surface loss and its treatment with porcelain laminates.
Localised tooth surface loss and subsequent caries in a young patient due to an unusual dietary habit is reported. The treatment and management of such conditions is discussed. Tooth surface loss is a condition seen with increasing frequency, often associated with the retention of the natural dentition into older age. In these older patients, abrasion and attrition tend to predominate as the causative factors but, in younger patients, acid erosion is frequently implicated. The acid involved may be dietary, in the form of carbonated beverages, fruit juices, vinegar or excessive intake of citrus fruits. If not derived from the diet, gastric acid may be the source if the patient has gastric reflux, perhaps associated with an ulcer or, in cases of anorexia nervosa or bulimia, where the patient deliberately induces vomiting and bathes the teeth in acid. There is a preponderance of female patients in the latter categories, although not exclusively so. Sometimes patients develop habits where an acidic substance is held in contact with certain teeth and the erosive process is more localised. This is illustrated in the case quoted by Reuter where grapefruit was held against the palatal surfaces of the upper anterior teeth resulting in enamel loss affecting that area. In all these cases of erosion the affected tooth surface was reported as being hard and shiny, lacking any of the features normally associated with dental caries.(ABSTRACT TRUNCATED AT 250 WORDS)


Glioblastoma multiforme in a patient with chronic granulomatous disease treated with subtotal resection, radiation, and thalidomide: case report of a long-term survivor.
We report on a child with chronic granulomatous disease who at the age of 13 years was diagnosed with glioblastoma multiforme of the left thalamus. Therapy included subtotal resection, radiation to the tumor bed (60 Gy), and concomitant chemotherapy with daily thalidomide (250 mg/m2), both during radiation and for 5 years thereafter. Currently, she is 9 years from diagnosis and has no evidence of disease. Therapy with thalidomide did not increase her infection complications and provided excellent quality of life. This is the first report of glioblastoma multiforme in a patient with chronic granulomatous disease treated with surgery, radiation, and thalidomide who is a long-term survivor.


MicroRNAs: Novel Crossroads between Myeloma Cells and the Bone Marrow Microenvironment.
Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulate in the bone marrow, where a complex microenvironment made by different cell types supports proliferation, survival, and drug resistance of tumor cells. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at posttranscriptional level. Emerging evidence indicates that miRNAs are aberrantly expressed or functionally deregulated in MM cells as the result of multiple genetic or epigenetic mechanisms and that also the tumor microenvironment regulates MM cell functions by miRNAs. Consistently, modulation of miRNA levels in MM cells has been demonstrated to impair their functional interaction with the bone marrow microenvironment and to produce significant antitumor activity even able to overcome the protective bone marrow milieu. This review will describe the most recent findings on miRNA function in the context of MM bone marrow microenvironment, focusing on the therapeutic potential of miRNA-based approaches.


Emotional change in its "natural habitat": Measuring everyday emotion regulation with passive and active ambulatory assessment methods.
Ambulatory assessment methods have made it possible to study psychological phenomena in real-time, with translational potential for psychotherapy process research. This article uses case example data to demonstrate applications of ambulatory assessment to measuring emotion regulation, a process with relevance across diagnoses and treatment modalities that may be particularly important to measure in situ. Two methods are reviewed: Ecological Momentary Assessment (EMA), which enables self-reported momentary assessments as people go about their days, and the Electronically Activated Recorder (EAR), an unobtrusive naturalistic observation methodology that collects short audio recordings from participants' moment-to-moment environments, capturing an acoustic diary of their social interactions, daily behaviors, and natural daily language use. Using case example data from research applying EMA and EAR methods in the context of adolescent self-injurious thoughts and behaviors, we illustrate how EMA can be used to measure emotion regulation over time and across contexts, and how EAR can assess the behaviors and social-environmental factors that interact with emotion regulation in clinically important ways. We suggest applications of this measurement approach for investigations of clients' emotional change over the course of psychotherapy, as well as potential clinical applications of these methods.


Metformin and Autoimmunity: A "New Deal" of an Old Drug.
Metformin (dimethyl biguanide) is a synthetic derivative of guanidine, isolated from the extracts of Galega officinalis, a plant with a prominent antidiabetic effect. Since its discovery more than 50 years ago, metformin represents a worldwide milestone in treatment of patients with type 2 diabetes (T2D). Recent evidence in humans indicates novel pleiotropic actions of metformin which span from its consolidated role in T2D management up to various regulatory properties, including cardio- and nephro-protection, as well as antiproliferative, antifibrotic, and antioxidant effects. These findings, together with ground-breaking studies demonstrating its ability to prolong healthspan and lifespan in mice, provided the basis for defining metformin as a potential antiaging molecule. Moreover, emerging in vivo and in vitro evidence support the novel hypothesis that metformin can exhibit immune-modulatory features. Studies suggest that metformin interferes with key immunopathological mechanisms involved in systemic autoimmune diseases, such as the T helper 17/regulatory T cell balance, germinal centers formation, autoantibodies production, macrophage polarization, cytokine synthesis, neutrophil extracellular traps release, and bone or extracellular matrix remodeling. These effects may represent a powerful contributor to antiaging and anticancer properties exerted by metformin and, from another standpoint, may open the way to assess whether metformin can be a candidate molecule for clinical trials involving patients with immune-mediated diseases. In this article, we will review the available preclinical and clinical evidence regarding the effect of metformin on individual cells of the immune system, with emphasis on immunological mechanisms related to the development and maintenance of autoimmunity and its potential relevance in treatment of autoimmune diseases.


Translation and cultural adaptation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module for quality of life assessment in patients with lung cancer in Brazil.
To translate the European Organisation for Research and Treatment of Cancer (EORTC) 29-item Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC29, developed for the assessment of quality of life in patients with lung cancer) to Portuguese, conducting a pilot study of the Portuguese-language version and adapting it for use in Brazil. For the translation, cultural adaptation, and pilot testing of the QLQ-LC29, we followed the guidelines established by the EORTC. The translation (English → Portuguese) and back-translation (Portuguese → English) were both carried out by translators, working independently, who were native speakers of one language and fluent in the other. After review, a draft version was created for pilot testing in lung cancer patients in Brazil. A total of 15 patients diagnosed with lung cancer completed the Portuguese-language version of the questionnaire. At the end of the process, we conducted a structured interview to identify any patient difficulty in understanding any of the questions. The final versions were sent to the EORTC and were approved. The Portuguese-language version of the EORTC QLQ-LC29 appears to be a useful, important, reliable questionnaire that is a valid tool for assessing quality of life in patients with lung cancer in Brazil.


Progestin implants can rescue demi-embryo pregnancies in goats: a case study.
Survival after transfer of demi-embryos (i.e., half-embryos produced by embryo splitting) to recipients usually is lower than survival after transfer of intact embryos. Reduced survival after demi-embryo transfer could be due to loss of viability after splitting, failure of a viable demi-embryo to prevent corpus luteum (CL) regression in the recipient female, or a combination of factors. From a retrospective analysis of pregnancy and embryo survival rates after demi-embryo transfer in sheep and goats, we report the rescue of caprine demi-embryo pregnancies in which CL regression occurred at the end of diestrus despite the presence of a viable conceptus in the uterus with progestin implants. Day 5 or 6 morulae and blastocysts were flushed from superovulated ewes and does and split into demi-embryos of approximately equal halves. Demi-embryos were either transferred fresh to synchronized recipients of the homologous species or frozen in liquid nitrogen. Approximately half of the recipient does and ewes were treated with norgestomet implants on Day 10 of the embryo transfer cycle and again 2 wk later. Serum collected on Day 25 from recipients with implants was assayed for progesterone to determine if a CL of pregnancy had been maintained. Pregnancy was diagnosed by ultrasonography on Day 35 of gestation. Corpus luteum regression occurred despite the presence of a viable conceptus in the uterus in 6 of 55 progestin-treated caprine demi-embryo recipients and in 0 of 66 ovine demi-embryo recipients. Five of the caprine pregnancies were maintained to term with norgestomet implants and produced 5 live kids. The sixth fetus, which was carried by a progestin implant-treated 8-mo-old doeling, died at approximately 50 d of gestation. These results suggest that, at least in goats, some demi-embryos may provide inadequate signaling for maternal recognition of pregnancy, and such pregnancies can be rescued with progestin treatment to the doe.


Elucidation of the Mechanisms through Which the Reactive Metabolite Diclofenac Acyl Glucuronide Can Mediate Toxicity.
We have previously reported that mice lacking the efflux transporter Mrp3 had significant intestinal injury after toxic diclofenac (DCF) challenge, and proposed that diclofenac acyl glucuronide (DCF-AG), as a substrate of Mrp3, played a part in mediating injury. Since both humans and mice express the uptake transporter OATP2B1 in the intestines, OATP2B1 was characterized for DCF-AG uptake. In vitro assays using human embryonic kidney (HEK)-OATP2B1 cells demonstrated that DCF-AG was a substrate with a maximal velocity (Vmax) and Km of 17.6 ± 1.5 pmol/min per milligram and 14.3 ± 0.1 μM, respectively. Another key finding from our in vitro assays was that DCF-AG was more cytotoxic compared with DCF, and toxicity occurred within 1-3 hours of exposure. We also report that 1 mM DCF-AG caused a 6-fold increase in reactive oxygen species (ROS) by 3 hours. Investigation of oxidative stress through inhibition of superoxide dismutase (SOD) revealed that DCF-AG had 100% inhibition of SOD at the highest tested dose of 1 mM. The SOD and ROS results strongly suggest DCF-AG induced oxidative stress in vitro. Lastly, DCF-AG was screened for pharmacologic activity against COX-1 and COX-2 and was found to have IC50 values of 0.620 ± 0.105 and 2.91 ± 0.36 μM, respectively, which represents a novel finding. Since cyclooxygenase (COX) inhibition can lead to intestinal ulceration, it is plausible that DCF-AG can also contribute to enteropathy via COX inhibition. Taken in context, the work presented herein demonstrated the multifactorial pathways by which DCF-AG can act as a direct contributor to toxicity following DCF administration.


Impact, healthcare utilization and costs of travel-associated mosquito-borne diseases in international travellers: a prospective study.
International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus. Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers' first contact with the health system in their country of residence. The patients were presented with a structured 52-question self-administered questionnaire after full recovery to collect information on patients' healthcare utilization and out-of-pocket costs both in the destination and home country, and about income and other financial losses due to the illness. A total of 134 patients participated in the study (malaria, 66; dengue, 51; chikungunya, 8; Zika virus, 9; all fully recovered; median age 40; range 18-72 years). Prior to travelling, 42% of patients reported procuring medical evacuation insurance. Across the four illnesses, only 7% of patients were hospitalized abroad compared with 61% at home. Similarly, 15% sought ambulatory services whilst abroad compared with 61% at home. The average direct out-of-pocket hospitalization cost in the destination country (USD $2236; range: $108-$5160) was higher than the direct out-of-pocket ambulatory cost in the destination country (USD $327; range: $0-$1560), the direct out-of-pocket hospitalization cost at home (USD $35; range: $0-$120) and the direct out-of-pocket ambulatory costs at home (US$45; range: $0-$192). Respondents with dengue or malaria lost a median of USD $570 (Interquartile range [IQR] 240-1140) and USD $240 (IQR 0-600), respectively, due to their illness, whilst those with chikungunya and Zika virus lost a median of USD $2400 (IQR 1200-3600) and USD $1500 (IQR 510-2625), respectively. Travellers often incur significant costs due to travel-acquired diseases. Further research into the economic impact of these diseases on travellers should be conducted.


Membrane localization and topology of a viral assembly protein.
The gene I protein (pI) of the filamentous bacteriophage f1 is required for the assembly of this virus. Antibodies specific to either the amino or carboxyl terminus of this protein were used to determine the location and topology of the gene I protein in f1-infected bacteria. pI is anchored in the inner membrane of Escherichia coli cells via a 20-amino-acid hydrophobic stretch, with its carboxyl-terminal 75 residues located in the periplasm and its amino-terminal 253 amino acids residing in the cytoplasm. By using the carboxyl-terminal pI antibody, a smaller protein, pI*, is also detected in f1-infected cells at a ratio of one to two molecules per molecule of pI. Analysis of proteins produced from a gene I amber mutant plasmid or bacteriophage suggests that pI* is most likely the result of an in-frame internal translational initiation event at methionine 241 of the 348-amino-acid pI. pI* is shown to be an integral inner membrane protein inserted in the same orientation as pI. The relation of the cellular locations of pI and pI* to some of the proposed functions of pI is discussed.


Macrolides: a treatment alternative for bronchiolitis obliterans organizing pneumonia?
Some macrolides have been found to exert anti-inflammatory effects. Lung diseases such as asthma, panbronchiolitis, cystic fibrosis, and bronchiectasis are thought to respond to the immunomodulatory properties of macrolides. We report three cases of idiopathic bronchiolitis obliterans organizing pneumonia, now called cryptogenic organizing pneumonia, and three cases of radiation-related bronchiolitis obliterans organizing pneumonia that responded to macrolide therapy. An explanation of why macrolides may have anti-inflammatory effects in patients with these syndromes is discussed. These cases help to reinforce accumulating data that macrolides are beneficial as anti-inflammatory agents and organizing pneumonia may be another pulmonary disease that can benefit from such therapy.


Distinctive structural hallmarks and biological activities of the multiple cathelicidin antimicrobial peptides in a primitive teleost fish.
Cathelicidin antimicrobial peptides (CAMPs) represent a crucial component of the innate immune system in vertebrates. Although widely studied in mammals, little is known about the structure and function of fish CAMPs. Further to the previous findings, two more cathelicidin genes and multiple transcripts from rainbow trout were identified in the present study. Interestingly, we found that trout have evolved energy-saving forms of cathelicidins with the total deletion of the characteristic cathelin-like domain. Sequence analysis revealed that salmonid CAMPs have formed a special class of antimicrobial peptides in vertebrates with three distinctive hallmarks: the N terminus is intensified by positive charges, the central region consists of repetitive motifs based on RPGGGS, and the C terminus is lowly charged. Immunofluorescence localization of trout CAMPs demonstrated that these peptides expressed mainly at the mucosal layer of gut. Meanwhile, signals around sinusoids were also detected in head kidney. Moreover, the biological activities of trout CAMPs were proved to be mediated by the N terminus. Additionally, the repetitive motifs characteristically existing in Salmonidae increased the structural flexibilities of peptides and further increased the antibacterial and IL-8-stimulating activities. Unlike most α helical and cytotoxic mammalian CAMPs, trout CAMPs, mainly consisting of β-sheet and random coil, exhibited no cytotoxic activities. The distinctive structural features of trout CAMPs provide new insights into the understanding of the evolution of CAMPs in vertebrates. Moreover, the high bacterial membrane selectivity of trout CAMPs will help to design excellent peptide antibiotics.


Outcome measurement in pulmonary rehabilitation.
The measurement of outcomes of therapy is becoming ever more important as part of the overall management of an individual patient. This is particularly true when considering pulmonary rehabilitation for a patient with chronic lung disease. Health, clinical, and behavioral domains should be assessed when evaluating the effectiveness of pulmonary rehabilitation. This assessment of outcomes can be easily made using currently available tools.


The efficacy and safety of vardenafil in East Asian men with erectile dysfunction.
Previous clinical studies assessing the efficacy and safety of vardenafil, an oral phosphodiesterase type 5 inhibitor, in men with erectile dysfunction (ED) have consisted mostly of Caucasian patients. The aim of this article is to describe the efficacy and safety of vardenafil in men of East Asian ethnicity with ED. Data were pooled from two 12-week, double-blind studies that included 306 East Asian men randomized to placebo or 10 mg of vardenafil. Efficacy variables included the International Index of Erectile Function-erectile function (IIEF-EF) domain score, questionnaires of Sexual Encounter Profile (SEP2 and SEP3), and a Global Assessment Question (GAQ). Safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse events. A total of 306 East Asian men with ED were treated with placebo (N = 151) or vardenafil (N = 155). Mean baseline IIEF-EF domain scores (placebo, 13.4; vardenafil, 14.2) were consistent with moderate ED. At end point, the patients treated with vardenafil had a significantly greater increase in IIEF-EF domain score compared with placebo (24.2 vs. 15.9; P < 0.0001). The average per patient penetration (SEP2) success rate was significantly higher in the vardenafil group compared with placebo (88% vs. 58%; P < 0.0001). Moreover, the average per patient intercourse completion (SEP3) success rate was significantly higher in the vardenafil group compared with placebo (69% vs. 23%; P < 0.0001). Positive GAQ responses were reported by 85% of patients receiving vardenafil, compared with 33% of those receiving placebo. The most frequent adverse events were vasodilatation (primarily facial flushing), rhinitis, and headache, all of which were of mild intensity. Vardenafil is an effective, well-tolerated oral drug for the treatment of East Asian men with moderate ED of broad-spectrum etiology.


ZnO-coated CuO nanowire arrays: fabrications, optoelectronic properties, and photovoltaic applications.
We report a growth of p-CuO nanowire arrays with a simple thermal oxidation and a fabrication of nanowire-based heterojunctions by coating the p-CuO nanowire arrays in an n-ZnO layer through a thermal decomposition method. Their optoelectronic properties and photovoltaic performance were investigated. Compared with the conductance in the dark, a 154% increase in photoconductance was obtained under a white light illumination of 100 mW/cm2. The heterojunctions exhibit an obvious photocurrent increment of 0.264 mA under the illumination of 141 mW/cm2. After annealing the heterojunctions at 100°C for 25 min, a larger open-circuit voltage of 0.37 V was obtained, the short-circuit current density increase to 0.63 mA/cm2 from original 0.49 mA/cm2. The overall power conversion efficiency is 0.1%.


Differences between non-profit and for-profit hospices: patient selection and quality.
This research compares the behavior of non-profit organizations and private for-profit firms in the hospice industry, where there are financial incentives created by the Medicare benefit. Medicare reimburses hospices on a fixed per diem basis, regardless of patient diagnosis. Because under this system patients with lower expected costs are more profitable, hospices can selectively enroll patients with longer lengths of stay. While it is illegal for hospices to reject potential patients explicitly, they can influence their patient mix through referral networks. A fixed per diem rate also creates an incentive shirk on quality and to substitute lower skilled for higher skilled labor, which has implications for quality of care. By using within-market variation in hospice characteristics, the empirical evidence suggests that for-profit hospices differentially take advantage of these incentives. The results show that for-profit hospices engage in patient selection through significantly different referral networks than non-profits. They receive more patients from long-term care facilities and fewer patients through more traditional paths, such as physician referrals. This mechanism of patient selection is supported by the result that for-profits have fewer cancer patients and more patients with longer lengths of stay. While non-profit and for-profit hospices report similar numbers of staff visits per patient, for-profit firms make significantly less use of skilled nursing providers. We also find some weak evidence of lower levels of quality in for-profit hospices.


Peritoneal expression of Matrilysin helps identify early post-operative recurrence of colorectal cancer.
Recurrence of colorectal cancer (CRC) following a potentially curative resection is a challenging clinical problem. Matrix metalloproteinase-7 (MMP-7) is over-expressed by CRC cells and supposed to play a major role in CRC cell diffusion and metastasis. MMP-7 RNA expression was assessed by real-time PCR using specific primers in peritoneal washing fluid obtained during surgical procedure. After surgery, patients underwent a regular follow up for assessing recurrence. transcripts for MMP-7 were detected in 31/57 samples (54%). Patients were followed-up (range 20-48 months) for recurrence prevention. Recurrence was diagnosed in 6 out of 55 patients (11%) and two patients eventually died because of this. Notably, all the six patients who had relapsed were positive for MMP-7. Sensitivity and specificity of the test were 100% and 49% respectively. Data from patients have also been corroborated by computational approaches. Public available coloncarcinoma datasets have been employed to confirm MMP7 clinical impact on the disease. Interestingly, MMP-7 expression appeared correlated to Tgfb-1, and correlation of the two factors represented a poor prognostic factor. This study proposes positivity of MMP-7 in peritoneal cavity as a novel biomarker for predicting disease recurrence in patients with CRC.


A self-directed summative examination in problem-based learning in dentistry: a new approach.
This paper describes and evaluates a new method of assessment in PBL, which was developed with two cohorts of dental students. The method involves students in PBL groups designing PBL problems and assessment tasks that are in line with the objectives of the course and the principles of PBL. Construction of tasks and feedback were provided. The student groups based the summative assessment on a selection of the PBL assessments provided. The evaluation indicates that senior students are capable of designing challenging PBL assessment tasks that are in line with course objectives and PBL principles. This experience raised the pass rates of the students compared those of with earlier cohorts of students. The students rated the method favourably; they considered it enabled them to demonstrate their competences and that it was more closely in line with PBL principles than other methods of assessment that they had experienced. The method is a promising innovation, which could be used in a variety of PBL courses.


Emphysema and airway obstruction in non-smoking South African gold miners with long exposure to silica dust.
Occupational exposure to silica dust is associated with significant impairment of lung function. The present study investigates which pathological changes in the lung are associated with impairment of lung function in silica dust exposed workers who were life-long non-smokers. 242 South African white gold miners who were lifelong non-smokers and who had a necropsy at death were studied. The pathological features identified at necropsy were the degree and type of emphysema, the presence of airway disease, and the degree of silicosis in the lung parenchyma and pleura. These features were related to lung function tests done a few years before death, to type of impairment (obstructive or restrictive), and to cumulative silica dust exposure. The degree of emphysema found at necropsy was not associated with a statistically significant impairment of lung function or with dust exposure. The degree of silicosis in the lung parenchyma and the large airways disease (based on mucus gland hyperplasia) were associated with a statistically significant impairment of lung function. The large airway disease was, however, not positively associated with dust exposure or silicosis. In miners with a moderate or a higher degree of limitation of airflow the main findings were silicosis, heart disease, and obesity. The presence of small airways disease could not be established from the necropsy material. The results indicate that the level of exposure to silica dust to which these miners were exposed, without a confounding effect of tobacco smoking, is not associated with a degree of emphysema that would cause a statistically significant impairment of lung function. Silicosis of the lung parenchyma was associated with loss of lung function. Other factors that may play a part in impairment of lung function in these miners are obesity and heart disease.


Effect of different iodine intake on schoolchildren's thyroid diseases and intelligence in rural areas.
Reports are increasingly appearing on the side effects caused by excessive iodine intake. Our objective was to find out whether iodine excess would impair the thyroid function and intelligence of schoolchildren in rural areas of China. A comparative epidemiological study was made on thyroid function and intelligence of the schoolchildren in the areas of low, moderate or excessive intake of iodine. In the area of low intake of iodine (Panshan, Liaoning province, median urinary iodine (MUI) was 99 microg/L), of moderate intake of iodine (Zhangwu, Liaoning Province, MUI was 338 microg/L) and of excessive intake of iodine (Huanghua, Hebei Province, MUI was 631 microg/L). The numbers of schoolchildren from each area selected to take part in a Chinese version of Raven's Test were 190, 236 and 313, respectively, and then 116, 110 and 112 of them were tested for thyroid function, thyroid autoantibody (TAA) and urinary iodine (UI). There were no significant differences in the incidences of overt hyperthyroidism, subclinical hyperthyroidism and overt hypothyroidism in Panshan, Zhangwu and Huanghua. But significant differences were found in the incidences of subclinical hypothyroidism (P = 0.001) in these three areas. The incidences of subclinical hypothyroidism in Huanghua and Zhangwu were 4.76 and 3.37 times higher than that in Panshan. TAA were negative in all the schoolchildren with subclinical hypothyroidism except for one. No significant difference was found among the rates of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in these three areas. Mean serum thyroglobulin (TG) value of Huanghua was markedly higher than those of the other two (P = 0.02). Mean serum TG value of Zhangwu was higher than that of Panshan but the difference was not significant. Mean IQ value of the schoolchildren in Huanghua was markedly higher than that for Zhangwu (P = 0.001). Mean IQ value of the schoolchildren in Panshan was lower than that of Huanghua and higher than that of Zhangwu but, again, the differences were not significant. The increase of iodine intake may increase the risk for schoolchildren of subclinical hypothyroidism. In the area of iodine excess, most of the subclinical hypothyroidism cases are not of autoimmune origin. No obvious effect of excess iodine was found on mental development of schoolchildren.


Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus.
Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH. The goal of the present study was to analyze and quantify the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant's demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH.


A Perspective for Understanding Trauma and the Criminal Juvenile Justice System: Using a Trauma-Informed Lens for Meaningful and Sustained Change.
Trauma exposure and posttraumatic stress disorder are common and are associated with a wide range of negative psychiatric and physical outcomes. Furthermore, a large percentage of justice-involved youth have high rates of trauma exposure and trauma-related symptoms. Addressing these issues would improve outcomes at the level of the justice system overall and in the lives of justice-involved youth. Nonetheless, awareness, education, and implementation of trauma-informed approaches in the criminal juvenile justice system are lacking. This article explores current literature that operationalizes trauma-informed practices and approaches in the criminal and juvenile justice systems. Unfortunately, there is no shared understanding or definition of trauma and no predictability in trauma-informed practices and approaches in the criminal juvenile justice system. Despite the presence of written policies, the application and execution of such policies are limited and inconsistent throughout the system. These limitations contribute to ongoing, systemic institutional racism, lack of mental health or substance abuse treatment, limited diversion options, and unnecessary jail and prison sentences, which together amplify financial and humanitarian costs. We argue that in order for the criminal juvenile justice system to become trauma-informed, it should (1) meet basic needs of clients, (2) check and change narratives, and check underlying assumptions, (3) focus on skill building/habilitation, (4) move away from punishment and toward rehabilitation and humanitarian approaches, and (5) heal and support members that work in and for the system. We conclude that there is a need to improve processes for education, training, and coaching in, and consistent application of, trauma-informed practices and approaches within the criminal and juvenile justice systems.


"Sobriety equals getting rid of hepatitis C": A qualitative study exploring the interplay of substance use disorder and hepatitis C among hospitalized adults.
People who use drugs (PWUD) commonly experience complex illness, psychosocial stressors, housing insecurity, and stigma, which may play key roles in their struggles with addiction. In a study of hospitalized PWUD with hepatitis C virus infection (HCV), participants described treating HCV as "part of recovery." These findings led us to explore how hospitalization and acute illness altered patients' perceptions of substance use disorder (SUD) and HCV. Researchers audio recorded in-depth semi-structured individual interviews of 27 hospitalized adults with SUD and HCV seen by an addiction consult service (ACS) at an urban academic medical center between June and November 2019. Research staff transcribed interviews and dual coded them deductively and inductively at the semantic level. Researchers used a matrix visualization to discern relationships among codes and conducted a thematic analysis. Many participants believed addictions treatment should precede an HCV cure for varying reasons. Some wanted to avoid reinfection; others believed "getting clean" afforded the mental clarity to address health issues, including HCV. Patients newly engaged in SUD treatment described HCV treatment as a "step towards recovery" and could serve as motivation to continue SUD treatment. Participants believed HCV cure could facilitate sobriety by "mentally putting drugs in the past" and was a future-oriented action toward "better health." Many participants described the compounded stigma of having HCV infection and SUD by multiple groups, including friends/family who do not use drugs, other drug users, and health care workers. Hospitalized adults with SUD and HCV believed addictions engagement should precede HCV treatment and HCV cure could play an important role in their "recovery" journey. Discussing HCV treatment during hospitalization may be an opportunity to support engagement in SUD treatment and targets an untreated patient population critical for achieving HCV elimination.


Pinewood Nematode, Bursaphelenchus xylophilus, Associated with Red Pine, Pinus resinosa, in Western Maryland.
Red pines Pinus resinosa in Garrett and Allegany counties, Maryland, were examined during 1982-84 to determine distribution of the pinewood nematode, Bursaphelenchus xylophilus, within and among trees. Approximately 25-year-old (younger) and 47-year-old (older) trees were subdivided into the following categories: 1) trees with mostly green needles; 2) trees with mostly reddish-brown needles; 3) trees lacking needles but with bark intact; 4) trees lacking both needles and bark; and 5) trees with chlorotic, bleached-green needles. Bursaphelenchus xylophilus was found infecting 68% of younger red pines and 77% of older red pines. Nematodes were not evenly distributed in trees within any given tree decadence category or in trees of the same age. Nematodes were recovered from 20% of wood samples from trunks and primary and secondary branches in younger pines and from 15 % of older red pines. On the basis of tree decadence category, the highest incidence of infection in younger trees (31%) was in bleached-green needled trees (category 5), whereas in older trees the highest infection (25%) occurred in green needled trees (category 1). At both sites trunks were infected more often than branches.


Basic building blocks for the switch-preserving transformation of shuffle interconnections.
The transformations of a two-dimensional shuffle on a 4 × 4 array into a one-dimensional shuffle on a vector of length 16 (and vice versa) are recognized as basic building blocks for the switch-preserving transformation of shuffle patterns of any size. [The switch-preserving transformation means the transformation of one-dimensional shuffles into two-dimensional and d-dimensional shuffles (d ≥ 3) and vice versa without the subdivision of switches.] The switch-preserving transformation of shuffle patterns on large arrays is defined recursively by means of the presented basic building blocks. Thi concept of the transformation is restricted to the two-dimensional symmetric generalized perfect shuffle on arrays with equal sides (squares) being an even multiple of four. (Generalized means arbitrary decomposition of each coordinate, and thus an arbitrary shuffle may be defined; perfect is the counterpart to imperfect and refers to the regularity or absence of failures; symmetric means the same decomposition of the data length for both coordinates.) The relationship of the results to multistage interconnection networks is clarified.


Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib.
The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC). Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to the next-generation ALK-TKI alectinib and potential strategies to overcome this resistance. We established a cell line model of alectinib resistance, and analyzed a resistant tumor specimen from a patient who had relapsed on alectinib. We developed Ba/F3 models harboring alectinib-resistant ALK mutations and evaluated the potency of other next-generation ALK-TKIs in these models. We tested the antitumor activity of the next-generation ALK-TKI ceritinib in the patient with acquired resistance to alectinib. To elucidate structure-activity relationships of ALK mutations, we performed computational thermodynamic simulation with MP-CAFEE. We identified a novel V1180L gatekeeper mutation from the cell line model and a second novel I1171T mutation from the patient who developed resistance to alectinib. Both ALK mutations conferred resistance to alectinib as well as to crizotinib, but were sensitive to ceritinib and other next-generation ALK-TKIs. Treatment of the patient with ceritinib led to a marked response. Thermodynamics simulation suggests that both mutations lead to distinct structural alterations that decrease the binding affinity with alectinib. We have identified two novel ALK mutations arising after alectinib exposure that are sensitive to other next-generation ALK-TKIs. The ability of ceritinib to overcome alectinib-resistance mutations suggests a potential role for sequential therapy with multiple next-generation ALK-TKIs.


Electron microscopy and microchemical analysis of cystic fibrosis diploid fibroblasts in vitro.
Fibroblasts derived from cystic fibrosis homozygotes and heterozygotes were compared to normal fibroblasts topologically, ultrastructurally, and microchemically. Topological examinations, by means of scanning electron microscopy (SEM) revealed no significant differences between the 3 genotypes surveyed. The cells were generally flattened and/or fusiform structures that were more or less devoid of surface details. However, the dividing cells, in all of the populations surveyed, were found to have a more or less spherical configuration involving a highly complicated surface. The surface manifestations included blebs, ridges, and microvilli. Representative samples of the cells in all stages of growth, lag phase, exponential phase, and plateau phase, were surveyed in this study. Ultrastructurally, the fibroblasts of the 3 genotypes were found to have similar cytological detail. Highly infolded nuclei, distinct organelle components, and surface details, also seen in the SEM study, were observed. Numerous bundles of microfilaments were noted within the cytoplasm. Metachromatic granules were observed in cells from all 3 genotypes. Microchemical analysis, by means of energy dispersive X-ray analysis, demonstrated slight but recognizable differences in the elemental composition of the 3 genotypes. Of notable interest were the peak intensities of calcium and sulfur. The CF homozygous cells presented higher values for both of the elements when compared to the values observed in the CF heterozygous and normal cell populations. Although consistent differences could be observed in the CF genotypes when compared to the non-CF cells, no attempt was made to quantitate the concentrations of each of the elements within the cells.


Association between vitamin D receptor BsmI gene polymorphism and periodontitis: a meta-analysis in a single ethnic group.
Although many researchers have studied on the association between vitamin D receptor (VDR) BsmI polymorphism and periodontitis, this association remains elusive. To further assess the effects of VDR BsmI polymorphism on the risk of periodontitis, a meta-analysis was performed in a single ethnic group. We searched PubMed and Chinese databases for relevant studies till April 2017. The strength of the associations were assessed used pooled odds ratios (ORs) and 95% confidence intervals (CIs). Six studies including 757 periodontitis cases and 670 controls were identified at last. In the total analyses, VDR BsmI polymorphism was not associated with the risk of periodontitis in all models. The subgroup analyses suggested a significantly reduced risk of periodontitis in South China. In conclusion, our meta-analysis showed that VDR BsmI polymorphism was associated with the decreased risk of periodontitis in Chinese individuals from South China, and further studies in other ethic groups are required for definite conclusions.


Response of gut microbiota to fasting and hibernation in Syrian hamsters.
Although hibernating mammals wake occasionally to eat during torpor, this period represents a state of fasting. Fasting is known to alter the gut microbiota in nonhibernating mammals; therefore, hibernation may also affect the gut microbiota. However, there are few reports of gut microbiota in hibernating mammals. The present study aimed to compare the gut microbiota in hibernating torpid Syrian hamsters with that in active counterparts by using culture-independent analyses. Hamsters were allocated to either torpid, fed active, or fasted active groups. Hibernation was successfully induced by maintaining darkness at 4 degrees C. Flow cytometry analysis of cecal bacteria showed that 96-h fasting reduced the total gut bacteria. This period of fasting also reduced the concentrations of short chain fatty acids in the cecal contents. In contrast, total bacterial numbers and concentrations of short chain fatty acids were unaffected by hibernation. Denaturing gradient gel electrophoresis of PCR-amplified 16S rRNA gene fragments indicated that fasting and hibernation modulated the cecal microbiota. Analysis of 16S rRNA clone library and species-specific real-time quantitative PCR showed that the class Clostridia predominated in both active and torpid hamsters and that populations of Akkermansia muciniphila, a mucin degrader, were increased by fasting but not by hibernation. From these results, we conclude that the gut microbiota responds differently to fasting and hibernation in Syrian hamsters.


Genetics of Alzheimer disease in the pre- and post-GWAS era.
Since the 1990s, the genetics of Alzheimer disease (AD) has been an active area of research. The identification of deterministic mutations in the APP, PSEN1, and PSEN2 genes responsible for early-onset autosomal dominant familial forms of AD led to a better understanding of the pathophysiology of this disease. In the past decade, the plethora of candidate genes and regions emerging from genetic linkage and smaller-scale association studies yielded intriguing 'hits' that have often proven difficult to replicate consistently. In the last two years, 11 published genome-wide association studies (GWASs) in AD confirmed the universally accepted role of APOE as a genetic risk factor for late-onset AD as well as generating additional candidate genes that require confirmation. It is unclear whether GWASs, though a promising novel approach in the genetics of complex diseases, can help explain most of the underlying genetic risk for AD. This review provides a brief summary of the genetic studies in AD preceding the GWAS era, with the main focus on the findings from recent GWASs. Potential approaches that could provide further insight into the genetics of AD in the post-GWAS era are also discussed.


Morphological and Histochemical Changes Occurring during the Life-span of Root-tip Galls on Lolium perenne Induced by Longidorus elongatus.
The RNA and protein content of perennial ryegrass root-tip galls induced by Longidorus elongatus were measured from transverse sections and the morphology described. Galls progressed through five distinct stages and were viable for only 10-12 days at 18 C, after which they collapsed and became necrotic. In the initial stage hypertrophy occurred and cells contained enlarged nuclei and nucleoli, a greater proportion of cytoplasm, and increased concentrations of protein. This was followed by hyperplasia; cells divided to give two or four daughter cells, accompanied by a proportionate reduction in volumes of cytoplasm, nuclei, and nucleoli and reduced concentrations of RNA and protein. The third stage was secondary hypertrophy with enlarged, amoeboid nuclei and nucleoli and a significant increase in concentration of RNA and protein. In the final two stages, as feeding by L. elongatus progressively removed cell contents, most cells were devoid of inclusions and galls collapsed and were invaded by soil bacteria. This ordered development and exploitation of galls suggests that L. elongatus may have two phases in its feeding.


[Neuropathic pain syndromes: from their diagnosis to the return to work. Proposal of a model for rapid evaluation and therapy based on their pathogenic mechanisms].
The therapeutic approach to neuropathic pain differs significantly among physicians. This is in large part because of the relative paucity of randomized clinical trials and the scarcity of comparative studies with different drugs. Clinical studies on the efficacy of a drug or a technique are generally referred to the pathologic diagnosis and not to the pain mechanism. We have learned from animal models the different pain mechanisms which may be involved in the peripheral nerves and the spinal cord. Unfortunately, one mechanism could be responsible for many different symptoms, while the same symptom can be caused by different mechanisms. The authors propose a simple model to evaluate the patients in order to define the mechanisms involved an to select the treatment strategy. The diagnostic model allows classification of the patient into four groups according to pain mechanism (spinal neurons sensitization due to deafferentation, ectopic discharges in peripheral nociceptive C fibers, spinal neurons sensitization due to ectopic discharges in peripheral nociceptive C fibers, spinal neurons sensitization due to nociceptors sensitization). The authors propose also a second step in which a fifth mechanism, adrenosensitivity, is evaluated. Treatment options may target any of the mechanisms discussed. Drugs and analgesic techniques can be classified according to their action on pain mechanisms. The authors identify in the literature some drugs and techniques which can be tested in each defined groups. A complementary and multidisciplinary rehabilitative approach of chronic pain patients is recommended.


Major effects on teratogen-induced facial clefting in mice determined by a single genetic region.
A major correlation has been found between the incidence of glucocorticoid-induced cleft palate and the chromosome 8 segment identified by N-acetyl transferase in mice. The resistant strain became fully susceptible while the susceptible strain became resistant when this chromosomal region, representing less than 0.7% of the genome, was transferred from one strain to the other by the construction of congenic strains. 6-Aminonicotinamide-induced cleft palate and phenytoin-induced cleft lip with or without cleft palate are also influenced by this genetic region but not as strongly. In both cases the susceptible strain became quite resistant to the teratogen-induced clefting when the N-acetyl transferase region of chromosome 8 was transferred. However, this chromosomal region does not make the resistant strain susceptible to these two teratogens.


Wood chemistry analysis and expression profiling of a poplar clone expressing a tyrosine-rich peptide.
Our study has identified pathways and gene candidates that may be associated with the greater flexibility and digestibility of the poplar cell walls. With the goal of facilitating lignin removal during the utilization of woody biomass as a biofuel feedstock, we previously transformed a hybrid poplar clone with a partial cDNA sequence encoding a tyrosine- and hydroxyproline-rich glycoprotein from parsley. A number of the transgenic lines released more polysaccharides following protease digestion and were more flexible than wild-type plants, but otherwise normal in phenotype. Here, we report that overexpression of the tyrosine-rich peptide encoding sequence in these transgenic poplar plants did not significantly alter total lignin quantity or quality (S/G lignin ratio), five- and six-carbon sugar contents, growth rate, or susceptibility to a major poplar fungal pathogen, Septoria musiva. Whole-genome microarray analysis revealed a total of 411 differentially expressed transcripts in transgenic lines, all with decreased transcript abundance relative to wild-type plants. Their corresponding genes were overrepresented in functional categories such as secondary metabolism, amino acid metabolism, and energy metabolism. Transcript abundance was decreased primarily for five types of genes encoding proteins involved in cell-wall organization and in lignin biosynthesis. The expression of a subset of 19 of the differentially regulated genes by qRT-PCR validated the microarray results. Our study has identified pathways and gene candidates that may be the underlying cause for the enhanced flexibility and digestibility of the stems of poplar plants expressing the TYR transgene.


The real-world patient experience of fingolimod and dimethyl fumarate for multiple sclerosis.
Oral disease-modifying therapies offer equivalent or superior efficacy and greater convenience versus injectable options. To compare patient-reported experiences of fingolimod and dimethyl fumarate. Adult relapsing-remitting multiple sclerosis patients treated with fingolimod or dimethyl fumarate were recruited from an online patient community and completed an online survey about treatment side effects, discontinuation, and satisfaction. 281 patients in four groups completed the survey: currently receiving fingolimod (CF, N = 61), currently receiving dimethyl fumarate (CDMF, N = 129), discontinued fingolimod (DF, N = 32) and discontinued dimethyl fumarate (DDMF, N = 59). Reasons for treatment switch were to take oral treatment (CF: 63.3 %, CDMF: 61.8 %), side effects of prior medication (CF: 67.3 %, CDMF: 44.1 %) and lack of effectiveness of prior medication (CF: 38.8 %, CDMF: 31.4 %). Main reasons for discontinuation were side effects (DF: 46.9 %, DDMF: 67.8 %) and lack of effectiveness (DF: 25.0 %, DDMF: 15.3 %). CDMF patients had an increased risk of abdominal pain, flushing, diarrhea, and nausea. Treatment satisfaction was highest among CF patients followed by CDMF, DF, and then DDMF patients. Discontinuation was driven by experience of side effects. Patients currently taking dimethyl fumarate were more likely to experience a side effect versus patients currently taking fingolimod. Examination of the relationship between tolerability and adherence/persistence is needed.


Oscillations make a self-scaled model for honeybees' visual odometer reliable regardless of flight trajectory.
Honeybees foraging and recruiting nest-mates by performing the waggle dance need to be able to gauge the flight distance to the food source regardless of the wind and terrain conditions. Previous authors have hypothesized that the foragers' visual odometer mathematically integrates the angular velocity of the ground image sweeping backward across their ventral viewfield, known as translational optic flow. The question arises as to how mathematical integration of optic flow (usually expressed in radians/s) can reliably encode distances, regardless of the height and speed of flight. The vertical self-oscillatory movements observed in honeybees trigger expansions and contractions of the optic flow vector field, yielding an additional visual cue called optic flow divergence. We have developed a self-scaled model for the visual odometer in which the translational optic flow is scaled by the visually estimated current clearance from the ground. In simulation, this model, which we have called SOFIa, was found to be reliable in a large range of flight trajectories, terrains and wind conditions. It reduced the statistical dispersion of the estimated flight distances approximately 10-fold in comparison with the mathematically integrated raw optic flow model. The SOFIa model can be directly implemented in robotic applications based on minimalistic visual equipment.


Research on bell-shaped vibratory angular rate gyro's character of resonator.
Bell-shaped vibratory angular rate gyro (abbreviated as BVG) is a new type Coriolis vibratory gyro that was inspired by Chinese traditional clocks. The resonator fuses based on a variable thickness axisymmetric multicurved surface shell. Its characteristics can directly influence the performance of BVG. The BVG structure not only has capabilities of bearing high overload, high impact and, compared with the tuning fork, vibrating beam, shell and a comb structure, but also a higher frequency to overcome the influence of the disturbance of the exterior environment than the same sized hemispherical resonator gyroscope (HRG) and the traditional cylinder vibratory gyroscope. It can be widely applied in high dynamic low precision angular rate measurement occasions. The main work is as follows: the issue mainly analyzes the structure and basic principle, and investigates the bell-shaped resonator's mathematical model. The reasonable structural parameters are obtained from finite element analysis and an intelligent platform. Using the current solid vibration gyro theory analyzes the structural characteristics and principles of BVG. The bell-shaped resonator is simplified as a paraboloid of the revolution mechanical model, which has a fixed closed end and a free opened end. It obtains the natural frequency and vibration modes based on the theory of elasticity. The structural parameters are obtained from the orthogonal method by the research on the structural parameters of the resonator analysis. It obtains the modal analysis, stress analysis and impact analysis with the chosen parameters. Finally, using the turntable experiment verifies the gyro effect of the BVG.


Cross-Cultural and Construct Validity of the Animated Activity Questionnaire.
The Animated Activity Questionnaire (AAQ) assesses activity limitations in patients with hip/knee osteoarthritis and consists of video animations; the patients choose the animation that best matches their own performance. The AAQ has shown good validity and reliability. This study aims to evaluate cross-cultural and construct validity of the AAQ. Cross-cultural validity was assessed using ordinal logistic regression analysis to evaluate differential item functioning (DIF) across 7 languages. Construct validity was assessed by testing correlations between the AAQ and a patient-reported outcome measure (PROM) and performance-based tests. Data from 1,239 patients were available. Compared to the Dutch language (n = 279), none of the 17 items showed DIF in English (n = 202) or French (n = 193), 1 item showed uniform DIF in Spanish (n = 99) and Norwegian (n = 62), and 2 items showed uniform DIF in Danish (n = 201). In all these languages, the occurrence of DIF did not influence the total score, which remained comparable with the original Dutch version. For Italian (n = 203) versus Dutch, however, 6 items showed uniform DIF, and 1 item showed nonuniform DIF, indicating some problems with the cross-cultural validity between these countries. With regard to construct validity, the correlations with PROM (0.74) and performance-based tests (0.36-0.68) were partly as expected (>0.60). The AAQ, an innovative tool to measure activity limitations that can be placed on the continuum between PROMs and performance-based tests, showed a good overall cross-cultural validity, and seems to have great potential for international use in research and daily clinical practice in many European countries.


The death knoll for the MMSE: has it outlived its purpose?
The Mini-Mental State Examination (MMSE) is arguably the best-known cognitive screen in the world. Originally designed to assess cognitive impairment in elderly populations, it has become one of the first steps toward a dementia diagnosis. Routinely used in the clinic and in research internationally, the MMSE, despite its flaws, has managed to retain its popularity for more than 30 years. This review explores when and how the test is used, lists its advantages and disadvantages, and ultimately questions its value. The specific issue that is addressed here is whether the test has outlived its original purpose. The conclusion is that although the MMSE may be a useful tool in many circumstances where a cognitive screen is required, practitioners should be wary of using MMSE total scores as a shortcut toward a dementia diagnosis.


Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy.
Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts. In the 1990s and early 2000s, Caucasian patients with type 1 diabetes with persistent macroalbuminuria in chronic kidney disease stages 1-3 were identified in the Joslin Clinic (U.S., 432), Finnish Diabetic Nephropathy Study (FinnDiane) (Finland, 486), Steno Diabetes Center Copenhagen (Denmark, 368), and INSERM (France, 232) and were followed for 3-18 years with annual creatinine measurements to ascertain ESRD and deaths unrelated to ESRD. During 15,685 patient-years, 505 ESRD cases (rate 32/1,000 patient-years) and 228 deaths unrelated to ESRD (rate 14/1,000 patient-years) occurred. Risk of ESRD was associated with male sex; younger age; lower estimated glomerular filtration rate (eGFR); higher albumin/creatinine ratio, HbA1c, and systolic blood pressure; and smoking. Risk of death unrelated to ESRD was associated with older age, smoking, and higher baseline eGFR. In adjusted analysis, ESRD risk was highest in Joslin versus reference FinnDiane (hazard ratio [HR] 1.44, P = 0.003) and lowest in Steno (HR 0.54, P < 0.001). Differences in eGFR slopes paralleled risk of ESRD. Mortality unrelated to ESRD was lowest in Joslin (HR 0.68, P = 0.003 vs. the other cohorts). Competing risk did not explain international differences in the outcomes. Despite almost universal renoprotective treatment, progression to ESRD and mortality in patients with type 1 diabetes with advanced nephropathy are still very high and differ among countries. Finding causes of these differences may help reduce risk of these outcomes.


Targeted contrast agents--an adjunct to whole-body imaging: current concepts.
This article reviews the potential use of a combination of whole-body imaging and targeted contrast agents in improving diagnostics, with a particular focus on oncology imaging. It looks at the rationale for nanoparticles and their development as targeted contrast agents. It subsequently describes many of the advances made thus far in developing tissue-specific contrast agents capable of targeting tumors that combined with whole-body imaging may enable superior cancer detection and characterization.


Breastfeeding the infant with a cleft defect.
Infants with cleft defects should be assisted to feed at the breast whenever a mother chooses this as the method of feeding. This is an ideal choice for such infants because it encourages normal, physiologic muscular involvement of the mouth and face, it benefits speech development, and it provides protection against upper respiratory infections, particularly otitis media. Successful breastfeeding helps normalize the infant to the family. Unfortunately, the attitude that infants with cleft defects cannot be breastfed often has been the first and most consistent response that the parents and families receive from their health care providers. Health care professionals must provide interventions to facilitate breastfeeding and thus normalize and empower these infants. The first days of life are extremely important for imprinting and learning what position works best.


Hemodynamic mechanisms in anaphylaxis.
Intravenous administration of ascaris suum antigen (1 mg) as well as histamine (5 mg) was associated with rapid and marked reductions in cardiac output (QT) and systemic arterial pressure (Pa) in anesthetized mechanically ventilated dogs. When venous return was maintained constant by an external pump reservoir system, both antigen and histamine caused rapid reductions in the reservoir blood volume consistent with peripheral pooling. In addition, interruption of the splanchnic arterial inflow by occlusion of the descending thoracic aorta restored the cardiac output to control during histamine shock, whereas QT during antigen shock was unaffected by aortic occlusion, even though the circulatory failure was of similar magnitude. Therefore, we conclude that differences in responses of antigen and histamine shock to aortic occlusion indicate that mechanisms leading to peripheral pooling of blood are different with the two agents. In addition, stability of left atrial pressure following the administration of either agent, when the venous return is maintained constant, suggests that intrinsic myocardial dysfunction is not a major initiating mechanism in the two shock states studied.


Psychological Resilience and Cognitive Function Among Older Military Veterans.
The purpose of this study was to explore the association between psychological resilience and cognitive function in military veterans. We obtained public-use data from the Health and Retirement Study (HRS) for this cross-sectional study of military veterans aged 52 to 101 years (n = 150). We estimated a multivariable linear regression model in which cognitive function served as the dependent variable and psychological resilience served as the independent variable. After controlling for demographics, health conditions, and health behaviors, veterans who had higher psychological resilience scores had better cognitive function (b = 0.22, p = 0.03). Our findings suggest that psychological resilience may be associated with cognitive function among veterans. These findings highlight the importance of assessing psychological resilience in gerontological social work practice.


Submicromolar La3+ concentrations block the calcium release-activated channel, and impair CD69 and CD25 expression in CD3- or thapsigargin-activated Jurkat cells.
The calcium release-activated channel (CRAC) opened in Jurkat cells activated either with CD3 monoclonal antibody or the endoplasmic reticulum Ca2(+)-ATPase blocker, thapsigargin, is blocked by La3+ with an IC50 of 20 nM. Similarly, the entry of Mn2+, used as a surrogate for Ca2+, is also blocked by submicromolar La3+ concentrations. La3+ seems to play its role simply by plugging the CRAC because this ion does not penetrate the cells, as demonstrated by chelation experiments with EGTA. Blocking the Ca2+ influx in activated Jurkat cells results in a lack of expression of CD25, a chain of the interleukin-2 receptor and of CD69, a marker of T-cell activation. By contrast, the very early steps of the T-cell signalling pathway such as the release of Ca2+ from intracellular stores and the subsequent inhibition of phosphatidylserine synthesis are not affected by La3+.


β-Cyclodextrin functionalized magnetic mesoporous silica colloid for cholesterol separation.
Although cholesterol plays significant biochemical function in the human body, excess of it leads to various disorders, and thus, its control/separation is important in medical science and food industries. However, efficient and selective separation of cholesterol is challenging because cholesterol often exists in microheterogeneous or insoluble forms in remote organ and exists with other chemicals/biochemicals. Here, we have described a colloidal magnetic mesoporous silica (MMS)-based approach for efficient separation of cholesterol in different forms. MMS is functionalized with β-cyclodextrin for selective binding with cholesterol via host-guest interaction. The colloidal form of MMS offers effective interaction with cholesterol of any form, and magnetic property of MMS offers easier separation of bound cholesterol. Functionalized MMS is efficient in separating cholesterol crystals, water-insoluble cholesterol, and the microheterogeneous form of cholesterol from milk or a cellular environment. Developed material can be used to remove cholesterol from a complex bioenvironment and extended for large-scale cholesterol separation from food.


Stool culture: are you getting value for money?
To assess the best medium for primary isolation of enteric pathogens; to determine the need for a second primary culture medium; and to gather information on stool culture media used in 20 other randomly selected laboratories. Specimens were cultured on desoxycholate citrate agar (DCA), Hektoen enteric agar (Hektoen), and xylose lysine deoxycholate agar (XLD). Non-lactose fermenters were screened with Rapidec Z (bio-Mérieux) and identified with API 10S (bio-Mérieux) where appropriate. Shigellas were identified with API 20E (bio-Mérieux) and serology, and salmonellas biochemically and by serology. A telephone survey was carried out to enquire into different culture practices and whether they had been evaluated for cost effectiveness. The isolation rate of enteric pathogens on primary stool culture media was 97% on DCA, 88% on XLD, and 76% on Hektoen. Seventeen of 18 shigellas grew on DCA, 13 of 18 on XLD, and 14 of 18 on Hektoen. DCA missed one Salmonella, XLD three, and Hektoen 13. XLD and Hektoen both missed Yersinia enterocolitica. The telephone survey revealed a diverse range of both primary and subculture plates. There was little evidence of evaluation of stool media, but firm personal convictions concerning the advantages and disadvantages of each type of medium at each stage of culture. DCA performed best and was the most cost effective of the three media. Neither XLD nor Hektoen were satisfactory as primary culture media because they grew fewer pathogens than DCA.


Binding partners of the kinase domains in Drosophila obscurin and their effect on the structure of the flight muscle.
Drosophila obscurin (Unc-89) is a titin-like protein in the M-line of the muscle sarcomere. Obscurin has two kinase domains near the C-terminus, both of which are predicted to be inactive. We have identified proteins binding to the kinase domains. Kinase domain 1 bound Bällchen (Ball, an active kinase), and both kinase domains 1 and 2 bound MASK (a 400-kDa protein with ankyrin repeats). Ball was present in the Z-disc and M-line of the indirect flight muscle (IFM) and was diffusely distributed in the sarcomere. MASK was present in both the M-line and the Z-disc. Reducing expression of Ball or MASK by siRNA resulted in abnormalities in the IFM, including missing M-lines and multiple Z-discs. Obscurin was still present, suggesting that the kinase domains act as a scaffold binding Ball and MASK. Unlike obscurin in vertebrate skeletal muscle, Drosophila obscurin is necessary for the correct assembly of the IFM sarcomere. We show that Ball and MASK act downstream of obscurin, and both are needed for development of a well defined M-line and Z-disc. The proteins have not previously been identified in Drosophila muscle.


Deciphering endocytosis in Caenorhabditis elegans.
We discuss in this review recent studies using the worm Caenorhabditis elegans to decipher endocytic trafficking in a multicellular organism. Recent advances, including in vivo assay systems, new genetic screens, comparative functional analysis of conserved proteins, and RNA-mediated interference (RNAi) in C. elegans, are being used to study the functions of known membrane trafficking factors and to identify new ones. The ability to monitor endocytosis in vivo in worms allows one to test current endocytosis models and to demonstrate the physiological significance of factors identified by genetic and biochemical methods. The available human genome sequence facilitates comparative studies where human homologs of new factors identified in C. elegans can be quickly assayed for similar function using traditional cell biological methods in mammalian cell systems. New studies in C. elegans have used a combination of these techniques to reveal novel metazoan-specific trafficking factors required for endocytosis. Many more metazoan-specific trafficking factors and insights into the mechanisms of endocytosis are likely to be uncovered by analysis in C. elegans.


Hypertrophic osteoarthropathy effectively treated with zoledronic acid.
Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by digital clubbing, arthralgias, and tissue swelling and is frequently described in association with bronchogenic carcinoma. The associated pain can be disabling, and symptoms are often resistant to conventional analgesic medications. We present a patient with HOA of the lower extremities and wrists that developed after bronchogenic carcinoma. The pain and swelling completely resolved after a single administration of 4 mg of zoledronic acid. The proposed pathogenesis of HOA and the mechanisms by which bisphosphonates might alleviate symptoms are reviewed.


Inhibition of penile tunica albuginea myofibroblasts activity by adipose-derived stem cells.
The activation of tunica albuginea myofibroblasts (MFs) serves an essential role in Peyronie's disease (PD). Increasing evidence has reported that adipose tissue-derived stem cells (ADSCs) have been demonstrated to attenuate the symptoms of PD in animal models. However, the mechanisms of the antifibrotic effects of ADSCs in PD remain to be fully elucidated. In the present study, the inhibitory effects and possible mechanism of ADSCs on the activation of MFs derived from rat penile tunica albuginea were investigated. ADSCs were obtained from the paratesticular fat of Sprague Dawley rats. MFs were transformed from rat penile tunica albuginea fibroblasts through stimulation with 5 ng/ml tumor growth factor-β1. Transwell cell cultures were adopted for co-culture of ADSCs and MFs. Western blot analysis was used to assess changes in the expression levels of α smooth muscle actin (αSMA), collagen I, phosphorylated (p)-SMAD family member 2 (Smad2), Smad2, ras homolog family member A (RhoA), Rho associated coiled-coil containing protein kinase (ROCK)1 and ROCK2, caspase3, caspase9, and matrix metalloproteinases (MMPs). Collagen gel assays were used to assess cell contractility. Additionally, the concentration of hydroxyproline in the culture medium was detected using commercially available kits. It was demonstrated that ADSCs reduced the expression of αSMA and collagen I of MFs. Furthermore, p-Smad2, RhoA, ROCK1 and ROCK2 expression was significantly reduced in the MFs+ADSCs group compared with that in the MFs-only culture, while the expression of MMPs (MMP2, MMP3, MMP9 and MMP13) and caspases (caspase3 and caspase9) was upregulated. In addition, ADSCs were able to downregulate the concentration of hydroxyproline in the culture medium of MFs and reverse the contraction of MFs. Collectively, these results suggested that ADSCs inhibited the activation of MFs, decreased collagen production, and suppressed the contraction of myofibroblasts, via Smad and RhoA/ROCK signaling pathways. Furthermore, ADSCs reduced the deposition of collagen and promoted the apoptosis of MFs via MMPs, and caspases. Accordingly, the application of ADSCs may provide a novel therapeutic strategy for PD.


Effects of low sodium dialysate in chronic hemodialysis patients: an echocardiographic study.
Chronic kidney disease (CKD) and hemodialysis (HD) patients who cannot restrict sodium consumption in their diets sometimes develop significant saline excess and hypertension between dialyses. This study assessed the effect of relatively low sodium dialysate dialysis on changes of echocardiography in hemodialysis patients. Eighteen patients with end stage renal failure on chronic HD were studied (8 females, 10 males) with a mean age 48.3 +/- 14.6 (24-70) years. The mean time on HD was 30.8 +/- 14.0 (12-60) months. Patients with hematocrit levels under 24% were excluded from the study. In all patients, echocardiography was performed thrice weekly before and after eight-week HD treatment with low sodium dialysate hemodialysis by the same operator (135 mEq/L for patients with sodium levels less than 137, 137 for patients with sodium levels over 137). Left atrium (LA) and left ventricle (LV) volumes and ejection fractions were measured, specifically: LV systolic diameter (LVSD), LV diastolic diameter (LVDD), interventricular septum (IVS), tricuspid regurgitation (TR), mitral regurgitation (MR), pulmonary artery pressure (PAP), and inferior vein cava diameter (IVCD). In terms of echocardiographic parameters, LVSD, TR, PAP, and IVCD were statistically decreased after low-sodium dialysate treatments (p = 0.002, 0.04, 0.013, and 0.00, respectively). Predialysis systolic and diastolic blood pressure (BP), post-dialysis systolic blood pressure, and interdialytic weight gain was statistically decreased when compared to basal levels (p = 0.00, p = 0.011, p = 0.022, p = 0.001, respectively). A reduction of the dialysate sodium concentration based on the predialysis sodium levels of the patients could reduce the systolic BP and decrease the volume load on the heart as assessed by echocardiography. Within this short period, postdialysis diastolic BP could not be lowered. The effect of this approach should be studied in broad and lengthy series.


Inducibility of class II major histocompatibility complex antigens by interferon gamma is associated with reduced tumorigenicity in C3H mouse fibroblasts transformed by v-Ki-ras.
Paired lines of C3H mouse fibroblasts transformed with murine sarcoma virus (Kirsten strain) were prepared that express high or low levels of class II major histocompatibility complex antigen after treatment with interferon gamma (IFN-gamma). Here, we described a comparison of the tumorigenicity of these lines in euthymic syngeneic and thymus-deficient nu/nu mice and in mice depleted of IFN-gamma. The class II-inducible cells are clearly less tumorigenic than the noninducible cells in syngeneic mice, but of similar tumorigenicity in nu/nu mice and in mice treated with antibodies to deplete IFN-gamma. We propose that in this system, IFN-gamma induction of class II antigens on the tumor cell surface operates to limit tumor growth; ras expression, which inhibits induction of class II antigens, prevents this and so allows tumor growth.


Hemorrhagic fever with renal syndrome in Yugoslavia: antigenic characterization of hantaviruses isolated from Apodemus flavicollis and Clethrionomys glareolus.
Hantavirus antigens were detected in lung tissues of 8/113 Apodemus flavicollis and 2/17 Clethrionomys glareolus captured in 1984 in Fojnica, a region of Yugoslavia endemic for hemorrhagic fever with renal syndrome; hantavirus antigens were not detected in lung tissues from 126 other mammals collected in Fojnica. Three hantaviruses, 2 from A. flavicollis and 1 from C. glareolus, were isolated directly in Vero E6 cells and were partially characterized. The isolates from A. flavicollis, designated Fojnica virus, were antigenically similar but not identical to Hantaan virus strain 76-118, whereas the isolate from C. glareolus was antigenically indistinguishable from Puumala virus, strain Hällnäs B1. These data are consistent with previous studies that indicate the existence of at least 2 hantavirus serotypes in Yugoslavia.


Dehydroindigo, the forgotten indigo and its contribution to the color of Maya Blue.
A comprehensive investigation of the electronic spectral and photophysical properties of the oxidized form of indigo, dehydroindigo (DHI), has been carried out in solution at 293 K. It is shown that dehydroindigo readily converts into its neutral keto form, the blue indigo, in a process which depends on the solvent and water content of the medium. DHI was investigated in toluene, in benzene, and in methanol and it was found that both the oxidized and the keto indigo forms are present in solution. In marked contrast to what has been found for keto-indigo, where the internal conversion channel dominates >99% of the excited state deactivation, or with the fully reduced leuco-indigo, where fluorescence, internal conversion, and singlet-to-triplet intersystem crossing coexist, in the case of DHI in toluene and benzene, the dominant excited state deactivation channel involves the triplet state. Triplet state yields (phi(T)) of 70-80%, with negligible fluorescence (< or = 0.01%) are observed in these solvents. In methanol the phi(T) value decreases to approximately 15%, with an increase of the fluorescence quantum yield to 2%, which makes these processes competitive with the S(1) --> S(0) internal conversion deactivation process. The data are experimentally compatible with the existence of a lowest lying singlet excited state of n,pi* origin in toluene and of pi,pi* origin in methanol. A time-resolved investigation in the picosecond time domain suggests that the emission of DHI involves three interconnected species (involving rotational isomerism), with relative contributions depending on the emission wavelength. DFT calculations (B3LYP 6-31G** level) were performed in order to characterize the electronic ground (S(0)) and excited singlet (S(1)) and triplet (T(1)) states of DHI. The HOMO-LUMO transition was found to accompany an n --> pi* transition of the oxygen nonbonding orbitals to the central CC and adjacent C-N bonds. Calculations also revealed that in S(0) the two indole-like moieties deviate from planarity from ca. 20 degrees, whereas in S(1) and T(1) the predicted structure is basically planar; a gradual decrease of the carbon-carbon central bond distance is seen in the order S(0), S(1), T(1). An additional study on the blue pigment Maya Blue was made, and the comparison between the solid-state spectra of indigo, DHI, and Maya Blue suggests that, in line with recent investigations, DHI is present together with indigo in Maya Blue. These results are relevant to the discussion of the involvement of dehydroindigo in the palette of colors of the ancient Maya Blue pigment.


Proteins IEF (isoelectric focusing) 31 and IEF 46 are keratin-type components of the intermediate-sized filaments: keratins of various human cultured epithelial cells.
Mouse polyclonal antibodies have been raised against two human proteins (IEF [isoelectric focusing] 31, Mr = 50,000; IEF 46, Mr = 43,500) that have previously been shown to be present in HeLa cytoskeletons enriched in intermediate-sized filaments. Immunoprecipitation studies show that both proteins share common antigenic determinants with each other and with the putative human keratins IEF 36 and 44, also present in HeLa cytoskeletons. Indirect immunofluorescence studies showed that both antibodies revealed similar filamentous networks in various cultured epithelial cells of human origin. These included AMA (transformed amnion), HeLa (cervical carcinoma), normal amnion cells, Fl-amnion (transformed amnion), WISH-amnion (transformed amnion), Chang liver (liver), and Detroid-98 (sternal marrow). Human cells that did not react with both antibodies included skin fibroblasts, lung fibroblasts (WI-38), SV40-transformed lung fibroblasts, Molt 4 (leukemia), lymphocytes, and monocytes. These results were in complete agreement with the presence or absence of both proteins in two-dimensional gels of the different cell types. Exposure of AMA cells to demecolcine (24 h; 10 micrograms/ml) caused the total collapse of vimentin filaments but, as seen by indirect immunofluorescence, caused only a partial redistribution of the IEF 31 and 46 filaments. These results are taken to suggest that both proteins are components of the intermediate-sized filaments of the "keratin" type. The antibodies could be clearly differentiated by staining human bladder carcinoma EJ 19 cells, as only the IEF 46 antibody stained a filamentous network in these cells The occurrence of keratins IEF 31, 36, 44, and 46 in different cultured human epithelial cells has been studied using two-dimensional gel electrophoresis.


Maternal exposure to the antiepileptic drug vigabatrin affects postnatal development in the rat.
The objective was to investigate, in the rat, the effects of maternal exposure to vigabatrin (VGB) on the postnatal motor-cognitive behaviour of the offspring. We used an experimental evaluator-blind, placebo-controlled study in the rat. Ten pregnant rats were divided into five groups and treated with different doses of VGB (250, 500, 750, 1000 mg/kg/day) or placebo from gestation day (GD) 6 to GD10. After delivery, 56 pups (40 pups prenatally exposed to VGB and 16 pups exposed to placebo) were evaluated for motor-cognitive behaviour throughout postpartum day 40. At the end of testing sessions the animals were sacrificed and brain tissues processed for biochemical analysis of GABA levels. Body weight of pups and young rats whose mothers were treated with a dose of 750 mg/kg/day were significantly lower both at birth and during the whole postnatal life with respect to the control groups. Young rats of this group exhibited impaired performance in both the open-field and water maze tasks. Brain GABA contents were dramatically increased in this group of rats. No other significant nutritional, biochemical or behavioural changes were observed after treatments with doses of VGB lower than 750 mg/kg/day. The exposure to a dose of 1000 mg/kg caused abortion. Maternal exposure to VGB at relatively high doses (750 mg/kg/day) is likely to cause some important changes of the nutritional status during the pre- and postnatal life. Thus, the biochemical and cognitive abnormalities observed in this study could be related to some disturbances of brain development induced by malnutrition and/or to a disturbance of neuronal programming of the gabaergic system.


Brunsting-Perry type localized bullous pemphigoid, possibly induced by furosemide administration and sun exposure.
A 56-year-old male visited our hospital complaining of irregular-shaped atrophic erythematous plaques with blood crust, erosion, pigmentation, and depigmentation, localized on his forehead, bilateral cheeks, and ear lobes, for over one year. He has been receiving peritoneal dialysis and furosemide administration due to chronic renal failure for four years. Direct immunofluorescence examination exhibited linear depositions of IgG and C3 in the basement membrane zone. Antibodies against the recombinant NC16a-domain of BP180 were negative by enzyme-linked immunosorbent assays (ELISA), though BP230 ELISA was positive. Immunoblotting using extracts of normal human epidermis demonstrated that the patient's serum reacted with BP180 and BP230. IgG class autoantibodies to recombinant proteins of the C-terminal domain of BP180 were also detected by immunoblotting. This case was diagnosed as localized bullous pemphigoid (LBP). Oral administration of prednisolone 10 mg daily was started and furosemide administration was ceased. The eruptions disappeared thereafter with superficial scars. This is the second reported case of Brunsting-Perry type LBP associated with IgG class autoantibodies to the C-terminal domain of BP180. Furthermore, photosensitivity caused by furosemide administration may contribute to the induction and exacerbation of the lesions.