Chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.


Choroid plexus papilloma in a girl with hypomelanosis of Ito.
The authors report a case of choroid plexus papilloma in a girl with hypomelanosis of Ito, and they review the literature in brief. Hypomelanosis of Ito is a rare neurocutaneous syndrome characterized by cutaneous hypopigmented whorls, streaks, and patches along lines of Blaschko. Most patients exhibit CNS manifestations, including psychomotor retardation, seizures, hypotonia, and ataxia. A 6-year-old girl with hypomelanosis of Ito was referred to the authors' hospital with bilateral tumors in the lateral ventricles. The right lateral ventricle tumor was surgically removed. Immunohistochemical investigations revealed the tumor to be a choroid plexus papilloma (WHO Grade I). A chromosomal investigation revealed that the tumor tissue demonstrated a large loss of heterozygosity at chromosome 10. The case reported here serves as a reminder that de novo brain tumors may arise in patients with chromosomal mosaicism.


HIV testing and clinical status upon admission to a specialized health care unit in Pará, Brazil.
OBJECTIVE To analyze the clinical and laboratory characteristics of HIV-infected individuals upon admission to a reference health care center. METHODS This cross-sectional study was conducted between 1999 and 2010 on 527 individuals with confirmed serological diagnosis of HIV infection who were enrolled in an outpatient health care service in Santarém, PA, Northern Brazil. Data were collected from medical records and included the reason for HIV testing, clinical status, and count of peripheral CD4+ T lymphocytes upon enrollment. The data were divided into three groups, according to the patient's year of admission - P1 (1999-2002), P2 (2003-2006), and P3 (2007-2010) - for comparative analysis of the variables of interest. RESULTS In the study group, 62.0% of the patients were assigned to the P3 group. The reason for undergoing HIV testing differed between genders. In the male population, most tests were conducted because of the presence of symptoms suggesting infection. Among women, tests were the result of knowledge of the partner's seropositive status in groups P1 and P2. Higher proportion of women undergoing testing because of symptoms of HIV/AIDS infection abolished the difference between genders in the most recent period. A higher percentage of patients enrolling at a more advanced stage of the disease was observed in P3. CONCLUSIONS Despite the increased awareness of the number of HIV/AIDS cases, these patients have identified their serological status late and were admitted to health care units with active disease. The HIV/AIDS epidemic in Pará presents specificities in its progression that indicate the complex characteristics of the epidemic in the Northern region of Brazil and across the country.


A Dysregulated DNA Methylation Landscape Linked to Gene Expression in MLL-Rearranged AML.
Translocations of the KMT2A (MLL) gene define a biologically distinct and clinically aggressive subtype of acute myeloid leukaemia (AML), marked by a characteristic gene expression profile and few cooperating mutations. Although dysregulation of the epigenetic landscape in this leukaemia is particularly interesting given the low mutation frequency, its comprehensive analysis using whole genome bisulphite sequencing (WGBS) has not been previously performed. Here we investigated epigenetic dysregulation in nine MLL-rearranged (MLL-r) AML samples by comparing them to six normal myeloid controls, using a computational method that encapsulates mean DNA methylation measurements along with analyses of methylation stochasticity. We discovered a dramatically altered epigenetic profile in MLL-r AML, associated with genome-wide hypomethylation and a markedly increased DNA methylation entropy reflecting an increasingly disordered epigenome. Methylation discordance mapped to key genes and regulatory elements that included bivalent promoters and active enhancers. Genes associated with significant changes in methylation stochasticity recapitulated known MLL-r AML expression signatures, suggesting a role for the altered epigenetic landscape in the transcriptional programme initiated by MLL translocations. Accordingly, we established statistically significant associations between discordances in methylation stochasticity and gene expression in MLL-r AML, thus providing a link between the altered epigenetic landscape and the phenotype.


The biology of macrophages in osteopetrosis. Structure and function.
Osteoclasts from ia rats are present in excessive numbers, contain an excessive amount of the lysosomal enzyme acid phosphatase, and show reduced-bone-resorptive function due to lack of ruffled borders. Given the current theory of a mononuclear phagocytic cell origin for osteoclasts, it was anticipated that the presence or absence of similarities between macrophages of both phenotypes might address the relatedness of these two cells. Thus, peritoneal macrophages from littermate normal and incisors-absent (ia) osteopetrotic rats were examined for differences in structure, acid phosphatase content, and phagocytic activity. The results of this investigation did not reveal any significant differences in these parameters in mutants compared with normal littermates. From these data it is suggested that macrophages are distinct, differentiated cells with functions separate from those of osteoclasts but that they may be related through a common stem cell early in development. Use of more immature cells or monocyte subpopulations may represent better choices for future studies of defects within the mononuclear phagocyte system in the ia mutation.


Staging Treatment Intensity and Defining Resistant Depression: Historical Overview and Future Directions.
To review existing staging models and definitions of treatment-resistant depression (TRD) and offer future directions within the context of up-to-date evidence. A PubMed search was conducted on February 25, 2018, for articles in English on TRD staging or definition using the following keywords: depressive disorder, treatment-resistant OR treatment resistant depression cross-referenced with staging OR degree OR level OR definition. Relevant cross-references from identified articles were also included. A total of 18 articles were identified that included a proposed TRD staging model, a proposed TRD definition, empirical work to support a model or definition, or any combination thereof. Included articles were summarized in chronological order in terms of the date the TRD staging model (and accompanying TRD definition if applicable) was first proposed. Findings from validation studies pertaining to staging or definition were then synthesized. Five staging models were identified. Strengths identified across staging models include rigorous assessment of adequacy of treatment, differentiation of resistance versus symptom return, assignment of equal weights to different pharmacotherapies, and accounting for augmentation. Future considerations should include differential weighting to specific augmentation agents based on available evidence, added weight to electroconvulsive therapy and ketamine treatments, and the addition of evidence-based psychotherapies. Dichotomous versus continuous approaches to TRD diagnosis were considered, with the latter (beginning with 1 failed trial) best explaining available data from large trials. The most up-to-date evidence in the literature should guide future research in the definition and staging of TRD.


Hypnosis, hypnotizability and treatment.
There is broad agreement that a phenomenon we call "hypnosis" exists. However, there is no generally accepted definition of hypnosis. A brief historical overview of the use of hypnosis in healing practices demonstrates how it evolved willy-nilly, and like Topsy, "just growed" into its current status in medicine, psychiatry, psychology and dentistry. The mechanisms underlying hypnosis and how hypnosis differs from other cognitive states are almost totally unknown. With the exceptions of suggestions for pain control, current concepts of high, medium, low or non-hypnotizability do not reliably predict clinical outcomes for most medical, psychiatric or dental disorders. We do know that it is relatively easy to reliably evaluate hypnotizability, but other than choosing volunteers or subjects who will or will not exhibit traditional hypnotic phenomena, we rarely know what to do with that evaluation with actual clinical patients. Four case studies, representative of many others, chosen retrospectively from a practice that spans 45 years, illustrate how traditional or modern hypnotizability assessment is irrelevant in the clinical setting. Although the four patients differed obviously and vastly in hypnotizability, they all benefited from the use of hypnosis.


Suggested Biomarkers for Major Depressive Disorder.
Currently, the diagnosis of major depressive disorder (MDD) mainly relies on clinical examination and subjective evaluation of depressive symptoms. There is no non-invasive, quantitative test available today for the diagnosis of MDD. In MDD, exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment, and predicting the treatment response. In this article, it is aimed to review the findings of suggested biomarkers such as growth factors, cytokines and other inflammatory markers, oxidative stress markers, endocrine markers, energy balance hormones, genetic and epigenetic features, and neuroimaging in MDD and to evaluate how these findings contribute to the pathophysiology of MDD, the prediction of treatment response, severity of the disorder, and identification of subtypes. Among these, the findings related to the brain-derived neurotrophic factor, the hypothalamo-pituitary-adrenal axis, cytokines, and neuroimaging may be strong candidates for being biomarkers MDD, and may provide critical information in understanding biological etiology of depression. Although the findings are not sufficient yet, we think that the results of epigenetic studies will also provide very important contributions to the biomarker research in MDD. The availability of biomarkers in MDD will be an advancement that will facilitate the diagnosis of the disorder, treatment choices in the early stages, and prediction of the course of the disorder.


An introduction of co-management approach into Babon River management in Semarang, Central Java, Indonesia.
The Babon River lies over three regions, i.e. Semarang District where the upstream is located while downstream it passes through Semarang Municipality and Demak District. This river has been used for many purposes by the neighbouring communities (e.g. water source, canal disposal, mining, etc). Thereafter many transboundary environmental problems have arisen here. The environmental management strategy (using a top-down approach) such as Program Kali Bersih (Clean River Program) on Babon River, which had been implemented by the Bapedalda of Semarang Municipality, is not successfully achieving the targets. In the past, most policies were formulated based on top-down orientation. Hence, the communities' participation was not paid enough attention. Co-management is a participative-management approach to empower the stakeholders (related parties) to achieve a certain goal. This study seeks answers to the research questions: (1) whether the co-management approach has good prospects for managing the Babon River; and (2) what kinds of strategy should be formulated to empower the stakeholders to manage the Babon River in the study area. The study employed a multistage sampling method to select the location of the study areas and key-persons sample. Rowosari, Penggaron Kidul and Karangtoro were selected to represent the upstream, middle stream and downstream areas, respectively. The descriptive statistics method had been used to describe the significance of river resource attributes' characters. Institutional analysis approach, introduced by Pomeroy and Williams, was adopted with necessary modification in this study. The results showed that the level of participation of the community in the three segments of the Babon River is different. The prospects for the co-management approach to manage the river resource in the study area are fairly good and in the upstream area are better than in the other two segments. The level of participation is far from complete; nevertheless the response from society towards development is quite good. There are five significant attributes in Babon River, which affect the community participation in river management, namely: (1) intensity of resource commercialisation; formal education of the community; and dependency of the community toward the resources, resource products distribution and resource damage. These variables could influence the pattern of participation of the community in the study area. The other stakeholders such as industrial or plant owners, academics, and the related institutions have not been explored in detail in this study. The co-management model that has been developed in this study has the prospect of encouraging the community and other stakeholders' empowerment in economic activities, natural resource conservation, and environmental law enforcement, as part of achieving the ultimate goal of sustainable environmental management.


Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients.
To determine the value of pretransplant studies in predicting day 100 nonrelapse toxic mortality following high-dose therapy. A retrospective review of 383 consecutive hematopoietic stem-cell transplants was performed with attention to toxic mortality and pretransplant factors. Univariate log-rank analysis was used to yield the most significant cut-off values for individual factors. Multivariate analysis using Cox proportional hazards regression determined factors independently predictive of early toxic death. Nonrelapse toxic mortality before day 100 occurred in 23 of 383 (6.0%) transplant recipients. Factors associated with an increased risk of toxic death by univariate analysis included forced expiratory volume in 1 second (FEV1) less than 78% of predicted (P = .0002), allogeneic versus autologous transplant (P = .0003), diffusion capacity of carbon monoxide less than 52% of predicted (P = .002), serum creatinine concentration greater than 1.1 mg/dL (P = .003), Eastern Cooperative Oncology Group performance status greater than 0 (P = .006), preparative regimen containing total-body irradiation versus chemotherapy alone (P = .006), marrow versus blood stem cell (P = .01), serum ALT greater than 50 IU/L (P = .02), diagnosis of hematologic disorder versus solid tumor (P = .06), serum bilirubin level greater than 1.1 mg/dL (P = .08), left ventricular ejection fraction (P = .09), and growth factor use (P = .09). In the multivariate model, transplant type (relative risk, 4.2), FEV1 (relative risk, 4.5), performance status (relative risk, 3.7), serum creatinine (relative risk, 3.8), and serum bilirubin (relative risk, 3.7) were found to be independent predictors of early toxic mortality. The pretransplant evaluation is a useful tool to identify patients at risk for early toxic mortality following high-dose therapy.


Two separate decay timescales of a detonation wave modeled by the Burgers equation and their relation to its chaotic dynamics.
This study uses a simplified detonation model to investigate the behavior of detonations with galloping-like pulsations. The reactive Burgers equation is used for the hydrodynamic equation, coupled to a pulsed source whereby all the shocked reactants are simultaneously consumed at fixed time intervals. The model mimics the short periodic amplifications of the shock front followed by relatively lengthy decays seen in galloping detonations. Numerical simulations reveal a sawtooth evolution of the front velocity with a period-averaged detonation speed equal to the Chapman-Jouguet velocity. The detonation velocity exhibits two distinct groups of decay timescales, punctuated by reaction pulses. At each pulse, a rarefaction wave is created at the reaction front's last position. A characteristic investigation reveals that characteristics originating from the head of this rarefaction take 1.57 periods to reach and attenuate the detonation front, while characteristics at the tail take an additional period. The leading characteristics are amplified twice, by passing through the reaction fronts of subsequent pulses, before arriving at the shock front, while the trailing characteristics are amplified three times. This leads to the two distinct groups of timescales seen in the detonation front speed.


Occupational injuries and perception of hazards among road-side welding workers.
A cross-sectional survey was conducted to understand the extent of occupational injuries and the perception of hazards among the road-side welders in the city of Karachi. Burns and foreign body in eyes were reported to be the most common injuries. Few workers perceived their occupation as hazardous. Consequently, few of them reported using protective measures. A 3-step strategy was recommended to improve occupational safety for this and other related groups of workers.


Parallel improvement of sodium and chloride transport defects by miglustat (n-butyldeoxynojyrimicin) in cystic fibrosis epithelial cells.
Cystic fibrosis, an autosomal recessive disease frequently diagnosed in the Caucasian population, is characterized by deficient Cl- transport due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A second major hall-mark of the disease is Na+ hyperabsorption by the airways, mediated by the epithelial Na+ channel (ENaC). In this study, we report that in human airway epithelial CF15 cells treated with the CFTR corrector miglustat (n-butyldeoxynojyrimicin), whole-cell patch-clamp experiments showed reduced amiloride-sensitive ENaC current in parallel with a rescue of defective CFTR Cl- channel activity activated by forskolin and genistein. Similar results were obtained with cells maintained in culture at 27 degrees C for 24 h before electrophysiology experiments. With monolayers of polarized CF15 cells, short-circuit current (Isc) measurements also show normalization of Na+ and Cl- currents. In excised nasal epithelium of cftr(F508del/F508del) mice, like with CF15 cells, we found normalization of amiloride-sensitive Isc. Moreover, oral administration of miglustat (6 days) decreased the amiloride-sensitive Isc in cftr(F508del/F508del) mice but had no effect on cftr-/- mice. Our results thus show that rescuing the trafficking-deficient F508del-CFTR by miglustat down-regulates Na+ absorption. A miglustat-based treatment of CF patients may thus have a beneficial effect both on Cl- and Na+ transports.


Microcosting quantity data collection methods.
Microcosting studies collect detailed data on resources used and the value of those resources. Such studies are useful for estimating the cost of new technologies or new community-based interventions, for producing estimates in studies that include nonmarket goods, and for studying within-procedure cost variation. The objectives of this article were to (1) describe basic microcosting methods focusing on quantity data collection; and (2) suggest a research agenda to improve methods in and the interpretation of microcosting. Examples in the published literature were used to illustrate steps in the methods of gathering data (primarily quantity data) for a microcosting study. Quantity data collection methods that were illustrated in the literature include the use of (1) administrative databases at single facilities, (2) insurer administrative data, (3) forms applied across multiple settings, (4) an expert panel, (5) surveys or interviews of one or more types of providers; (6) review of patient charts, (7) direct observation, (8) personal digital assistants, (9) program operation logs, and (10) diary data. Future microcosting studies are likely to improve if research is done to compare the validity and cost of different data collection methods; if a critical review is conducted of studies done to date; and if the combination of the results of the first 2 steps described are used to develop guidelines that address common limitations, critical judgment points, and decisions that can reduce limitations and improve the quality of studies.


[Current periodical publications on cardiology].
A revision is made of the periodic publications specializing in cardiology that at present are being edited in the world. Ninety-nine titles of actual importance with a perioricity over two numbers per year formed the material of study. The oldest publication began to be printed in the year of 1908, changed name in 1937, and today is titled Archives des Maladies du Coeur et de Vaisseax. In Spanish, the first journal specializing in cardiology started in Mexico 50 years ago; in 1944 it changed name, and at present in continues to be published with the title of Archivos del Instituto de Cardiología de México. In the first decade of this century, only one publication on cardiology with the above mentioned characteristics appeared. In the first seven months of 1979, five appeared. Considerations are made concerning the alarming growth of the contemporary medical biobliography, and of cardiology in particular.


Evaluation of poly-aromatic hydrocarbons (PAHs) in the aquatic species of Suez Gulf water along El-Sokhna area to the Suez refineries.
The Egyptian Red Sea environment especially along El-Sokhna area to the Suez refineries (Suez) is severely contaminated with organic compounds, as well as overfishing. This may be well contributory to recent serious declines in fish stocks. Fish embryos are also particularly vulnerable to oil exposure, even at extremely low concentrations of less than one part per billion. Consequently, even traces of oil pollution at levels often considered safe for wildlife can cause severe damage to fish. Sixteen polycyclic aromatic hydrocarbons (PAHs) were investigated in ten fish species of aquatic species by high performance liquid chromatography (HPLC). The compositions of PAHs determined in all samples were measured in order to use them as chemical markers for identifying different sources of PAH pollutants in the studied region. The total content of these16 PAHs ranged from 399.616 up to 67,631.779 ng/g wet weight. The data show that these values are considered to be alarmingly high enough to cause lethal toxicity effect by accumulation. All studied aquatic species samples are characterized by relatively high concentrations of the six-membered ring PAHs. The origin of PAHs in the collected samples is either petrogenic, biogenic, or mixed petrogenic and biogenic.


Regulation of tomato leaf curl viral gene expression in host tissues.
The regulation of expression of the two virion-sense (V1 and V2) and four complementary-sense (C1, C2, C3, and C4) open reading frames (ORFs) of Tomato leaf curl virus (TLCV) was studied in both stably and transiently transformed Nicotiana tabacum tissues with fusions with the beta-glucuronidase (GUS) reporter gene. GUS-expressing transgenic lines were obtained with each of the four complementary-sense gene-GUS fusion constructs and with truncated versions of the virion-sense gene-GUS fusion constructs (V1GUSdeltaC and V2GUSdeltaC) lacking complementary-sense sequences encoding the C1, C2, and C3 ORFs. However, little or no GUS expression was observed in kanamycin-resistant plants transformed with full-length, virion-sense gene constructs (V1GUS and V2GUS) constituting the complete viral genome. In contrast, V1GUS and V2GUS were found to direct high-level GUS expression in transient assays with tobacco protoplasts, suggesting that integration of viral constructs containing functional, complementary-sense genes may lead to repression or deletion of the introduced constructs in transgenic tissues. V2GUS expression in the transient protoplast assay was found to be severely curtailed by specific mutation of the C2 ORF, supporting a role for the C2 protein in transactivation of TLCV virion-sense gene expression. TLCV ORF-GUS constructs displayed distinctive tissue expression patterns in transgenic tobacco plants that could be divided into constitutive (C1, C4, and V2GUSdeltaC), predominantly vascular (C2, C3), or reduced expression in cells associated with the vascular bundles (V1GUSdeltaC). The significance of these results is discussed in terms of current models of gene function and regulation in geminiviruses.


Age-related changes in cellular localization and enzymatic activities of cathepsins B, L and D in the rat trigeminal ganglion neuron.
Altered localization and cellular level of three distinct lysosomal proteinases, cathepsins B (CB), L (CL), and D (CD), with aging were investigated in the rat trigeminal ganglion (TG) by immunohistochemical and quantitative analyses. At the light microscopic level, the intracytoplasmic distribution of these three enzymes was found to change with aging: These lysosomal proteinases in the TG of young rats (2-3 months of age) were widely and evenly distributed throughout the cytoplasm as coarse intracytoplasmic granules, whereas they were localized at focal cytoplasmic sites of the TG neurons of aged rats (28-31 months of age) as coarse aggregates. A similar distribution was observed with a major lysosomal membrane sialoglycoprotein having an apparent molecular mass of 107 kDa (LGP107). The cellular distribution of the three cathepsins as well as LGP107 in the TG neurons of aged rats corresponded well with that of autofluorescent lipofuscin. At the electron microscopic level, the age-related redistribution of these cathepsins in the TG neurons was found to be due to their great accumulation in autolysosomes localized at the focal perinuclear sites. The cellular levels of CB and CL determined by activity measurement in the TG of the young rats were 1.8 and 1.7 times as much as those of the aged rats respectively. In contrast, no significant difference was observed between the CD activities in the two age groups. These results strongly suggest that age related changes in localization and cellular level of CB, CL, and CD in TG neurons are closely linked with the increased formation of autolysosomes and lipofuscins, which is the most ubiquitous age-related cytological alteration.


Metal Concentrations in Wild-Harvested Phaeophyta Seaweed from the Atlantic Ocean (Canary Islands, Spain).
Seaweeds are being consumed more often worldwide and are a source of essential minerals, fiber, vitamins, amino acids, and various bioactive compounds that have many beneficial effects on human health. However, marine pollution and the high capacity of seaweed to absorb metals may mean this food can also be dangerous to human health. The concentrations of some trace elements (B, Ba, Fe, Ni, Li, and V) and toxic metals (Al, Cd, and Pb) were determined in various species of wild seaweeds in the Phaeophyta group of brown algae from the Atlantic Ocean. Inductively coupled plasma atomic emission spectrometry revealed high concentrations of Al (256 mg/kg dry weight), Pb (3.92 mg/kg dry weight), and Cd (0.20 mg/kg dry weight) in Padina pavonica. Pb contributed the most to the tolerable daily intake (TDI) of toxic metals in these samples; 57.2 and 45.3% of the TDI for Pb was found in 5 g of dehydrated P. pavonica and Halopteris scoparia, respectively. This percent contribution is half of the recommended TDI for this metal, which is 34.24 μg/day; therefore, high consumption of these species is discouraged. The maximum TDIs established by various institutions for the other metals were not exceeded from the daily consumption of 5 g of the other dehydrated seaweeds evaluated in this study.


Retention of low-fitness genotypes over six decades of admixture between native and introduced tiger salamanders.
Introductions of non-native tiger salamanders into the range of California tiger salamanders have provided a rare opportunity to study the early stages of secondary contact and hybridization. We produced first- and second-generation hybrid salamanders in the lab and measured viability among these early-generation hybrid crosses to determine the strength of the initial barrier to gene exchange. We also created contemporary-generation hybrids in the lab and evaluated the extent to which selection has affected fitness over approximately 20 generations of admixture. Additionally, we examined the inheritance of quantitative phenotypic variation to better understand how evolution has progressed since secondary contact. We found significant variation in the fitness of hybrids, with non-native backcrosses experiencing the highest survival and F2 hybrids the lowest. Contemporary-generation hybrids had similar survival to that of F2 families, contrary to our expectation that 20 generations of selection in the wild would eliminate unfit genotypes and increase survival. Hybrid survival clearly exhibited effects of epistasis, whereas size and growth showed mostly additive genetic variance, and time to metamorphosis showed substantial dominance. Based on first- and second- generation cross types, our results suggest that the initial barrier to gene flow between these two species was relatively weak, and subsequent evolution has been generally slow. The persistence of low-viability recombinant hybrid genotypes in some contemporary populations illustrates that while hybridization can provide a potent source of genetic variation upon which natural selection can act, the sorting of fit from unfit gene combinations might be inefficient in highly admixed populations. Spatio-temporal fluctuation in selection or complex genetics has perhaps stalled adaptive evolution in this system despite selection for admixed genotypes within generations.


Postnatal development of cerebrovascular structure and the neurogliovascular unit.
The unceasing metabolic demands of brain function are supported by an intricate three-dimensional network of arterioles, capillaries, and venules, designed to effectively distribute blood to all neurons and to provide shelter from harmful molecules in the blood. The development and maturation of this microvasculature involves a complex interplay between endothelial cells with nearly all other brain cell types (pericytes, astrocytes, microglia, and neurons), orchestrated throughout embryogenesis and the first few weeks after birth in mice. Both the expansion and regression of vascular networks occur during the postnatal period of cerebrovascular remodeling. Pial vascular networks on the brain surface are dense at birth and are then selectively pruned during the postnatal period, with the most dramatic changes occurring in the pial venular network. This is contrasted to an expansion of subsurface capillary networks through the induction of angiogenesis. Concurrent with changes in vascular structure, the integration and cross talk of neurovascular cells lead to establishment of blood-brain barrier integrity and neurovascular coupling to ensure precise control of macromolecular passage and metabolic supply. While we still possess a limited understanding of the rules that control cerebrovascular development, we can begin to assemble a view of how this complex process evolves, as well as identify gaps in knowledge for the next steps of research. This article is categorized under: Nervous System Development > Vertebrates: Regional Development Vertebrate Organogenesis > Musculoskeletal and Vascular Nervous System Development > Vertebrates: General Principles.


Melanin-independent accumulation of turgor pressure in appressoria of Phakopsora pachyrhizi.
Appressoria of some plant-pathogenic fungi accumulate turgor pressure that produces a mechanical force enabling the direct penetration of hyphae through the epidermis. Melanin functions as an impermeable barrier to osmolytes, which allows appressoria to accumulate high turgor pressure. Deficiency of melanin in appressoria reduces turgor pressure and compromises the infection process. In Phakopsora pachyrhizi, the soybean rust pathogen, the appressoria are hyaline. Our objective was to ensure the absence of a melanin layer specifically between the appressorial cell wall and plasma membrane, as well as to determine the turgor pressure of P. pachyrhizi appressoria. We demonstrated that two melanin biosynthesis inhibitors neither reduced turgor pressure nor compromised the infection process. Transmission electron microscopy also showed the absence of a melanin layer between the appressorial cell wall and plasma membrane. In addition, the turgor pressure of P. pachyrhizi appressoria was 5 to 6 MPa, based on extracellular osmolytes used to simulate different osmotic pressures. This is the first report showing that turgor pressure accumulation of P. pachyrhizi appressoria was independent of melanin.


Transient insomnia versus chronic insomnia: a comparison study of sleep-related psychological/behavioral characteristics.
Vulnerability to transient insomnia is regarded as a predisposing factor for chronic insomnia. However, most individuals with transient insomnia do not develop chronic insomnia. The current study investigated the differential contributing factors for these two conditions to further the understanding of this phenomenon. Chronic insomnia patients and normal sleepers with high and low vulnerability to transient insomnia completed measures of pre-sleep arousal, dysfunctional sleep beliefs, and sleep-related safety behaviors. Both cognitive and somatic pre-sleep arousals were identified as significant predictors for transient insomnia. Dysfunctional beliefs regarding worry about insomnia and cognitive arousal were predictors for chronic insomnia. Sleep-related safety behavior, although correlated with insomnia severity, was not a significant predictor for both conditions. Dysfunctional beliefs associated with worry and losing control over sleep are the most critical factors in differentiating chronic insomnia from transient insomnia. These factors should be addressed to help prevent individuals with high sleep vulnerability from developing chronic sleep disturbance.


Epithelioid hemangioendothelioma of the lumbar vertebral column: case report and review of literature.
Epithelioid hemangioendothelioma is a recently described, rare vasoformative vascular tumor of variable biological behavior. Its principal sites of occurrence are soft tissues, liver, lung, and bone. There have been no formal case reports of this tumor occurring in the vertebral column, and there are no reports in the literature of surgical treatment for vertebral epithelioid hemangioendothelioma. We present a case of primary vertebral epithelioid hemangioendothelioma occurring in the L2 vertebral body. Surgical treatment, pathological findings, imaging characteristics, and a review of the literature are presented.


The incidence of parasomnias in child bruxers versus nonbruxers.
Bruxism in children has been reported to occur in association with certain parasomnias (i.e., sleep talking, bed wetting). Various dental, medical, neurological, and psychological risk factors also have been correlated with bruxism. A case-control study was therefore conducted to test the null hypothesis that there is no difference between bruxers and nonbruxers in the occurrence rate of other parasomnias and these reported risk factors. A 54-item survey questionnaire was developed and mailed to 342 pediatric patients, half of whom were avowed to be bruxers by their parents. These patients were selected randomly from a private pediatric practice in Northern California. One-hundred fifty-two subjects (77 bruxers and 75 controls) returned the questionnaire, and stepwise logistic regression analysis revealed that five of the 54 factors (nocturnal muscle cramps, bed wetting, colic, drooling while sleeping, and sleep talking) showed significant differences between bruxers and controls (odds ratios ranged from 3.11 to 1.95). These findings strongly suggest the possibility of a common sleep disturbance underlying these nonsleep-stage specific parasomnias.


Swelling of the Müller fibers in the chicken retina.
A high potassium concentration (33 meq) in the solution superfusing the isolated chicken retina causes an increase in the tissue transparency. An L-glutamate (1 mM) or L-proline (10 mM) solution has the same effect. Swelling of the Müller fibers, which have a radial position in the retina, could explain the transparency increase. This possibility was investigated in electron micrographs of retinas subjected to these treatments and fixed by freeze-substitution to preserve the water distribution in the tissue. The Müller fibers in the controls had a mean diameter of 0.22 micrometer. The fibers in retinas bathed for 2 min in the high [K+] solution were more than three times as thick (0.74 micrometer); the fibers in glutamate-treated retinas were more than twice as thick (0.49 micrometer). The fibers in the proline-treated retinas had a diameter of 0.39 micrometer. The glutamate- and proline-induced swelling may be due to a K+ release from neuronal elements, acting on the Müller fibers. The fiber swelling was postulated to be the expression of different Donnan equilibriums of fibers bathed in solutions of different K+ concentrations. The observed swelling caused by the high [K+] solution was compared with the theoretical swelling of the fiber as an ideal Donnan system, postulating permeabilities for different ions of the fiber membrane. This suggested that the high [K+] solution causes an increase in Na+ permeability in addition to the permeability of the membrane for K+, Cl-, and HCO3-. Chemical fixation with glutaraldehyde and formaldehyde in an Na-phosphate buffer yielded micrographs in which the Müller fibers of retinas treated with a high [K+] or a glutamate solution had diameters similar to those of the control preparations.


The demography of slow aging in male and female Drosophila mutant for the insulin-receptor substrate homologue chico.
Hypomorphic mutants affecting the Drosophila insulin/IGF signal pathway are reported to increase longevity in females but not in males. To understand this sex-difference, we conducted a large-scale demographic study with three new isogenic strains of alleles at chico, the insulin-receptor substrate homologue. We verify that female dwarf homozygotes (ch1/ch1) and normal-sized heterozygotes (ch1/+) are long-lived, as originally reported. We find for the first time that male heterozygotes are long-lived relative to wildtype, by about 50%. The life span of male ch1/ch1 is similar to that of wildtype but these dwarf males age at a slow demographic rate. The levels of demographic frailty and of age-independent mortality are elevated in ch1/ch1 males, counteracting the effect of slow aging upon life expectancy. Mortality deceleration occurs amongst the oldest-old wildtype adults, as seen in many organisms. Remarkably, in similarly sized cohorts of male and female ch1/ch1 and of male ch1/+ mortality deceleration is absent. Mortality deceleration is a phenotype of chico.


Effect of cervical artificial disc replacement on adjacent inferior intervertebral space stress.
The aim of this study was to investigate the effects of C5/6 cervical artificial disc replacement (CADR), discectomy and intervertebral fusion on adjacent inferior (C6/7) intervertebral space stress, and provide a basis for application of CADR. Eleven fresh-frozen multisegmental (C3-T1) cervical spine specimens from healthy adults were studied. For analysis of stress on the adjacent inferior (C5/6) segment, they were divided into intact group, discectomy group, CADR group and interbody fusion group. The axial load (25-150 N) was exerted on each group. The changes of the adjacent inferior (C6/7) intervertebral space stress were observed. The adjacent inferior intervertebral space stress in the CADR group was near to that of the intact group, without significant difference (p > 0.05). The stress in the discectomy group was significantly higher than in the intact group, and lower than in the interbody fusion group (p < 0.05 and p < 0.01, respectively). The stress in the interbody fusion group was significantly higher than in the intact and CADR groups, respectively (p < 0.01).


The Expression Levels and Cellular Localization of Pigment Epithelium Derived Factor (PEDF) in Mouse Testis: Its Possible Involvement in the Differentiation of Spermatogonial Cells.
Pigment epithelium derived factor (PEDF) is a multifunctional secretory soluble glycoprotein that belongs to the serine protease inhibitor (serpin) family. It was reported to have neurotrophic, anti-angiogenic and anti-tumorigenic activity. Recently, PEDF was found in testicular peritubular cells and it was assumed to be involved in the avascular nature of seminiferous tubules. The aim of this study was to determine the cellular origin, expression levels and target cells of PEDF in testicular tissue of immature and adult mice under physiological conditions, and to explore its possible role in the process of spermatogenesis in vitro. Using immunofluorescence staining, we showed that PEDF was localized in spermatogenic cells at different stages of development as well as in the somatic cells of the testis. Its protein levels in testicular homogenates and Sertoli cells supernatant showed a significant decrease with age. PEDF receptor (PEDF-R) was localized within the seminiferous tubule cells and in the interstitial cells compartment. Its RNA expression levels showed an increase with age until 8 weeks followed by a decrease. RNA levels of PEDF-R showed the opposite trend of the protein. Addition of PEDF to cultures of isolated cells from the seminiferous tubules did not changed their proliferation rate, however, a significant increase was observed in number of meiotic/post meiotic cells at 1000 ng/mL of PEDF; indicating an in vitro differentiation effect. This study may suggest a role for PEDF in the process of spermatogenesis.


Effectiveness of oseltamivir treatment among children with influenza A or B virus infections during four successive winters in Niigata City, Japan.
Oseltamivir has been used for treatment of influenza A and B infections, but recent reports documented that it was less active against the latter. We compared the effectiveness of oseltamivir in children between laboratory confirmed influenza A and B over 4 influenza seasons from 2001 to 2005 in a pediatric clinic in Japan. Among 1,848 patients screened, 299 influenza A and 209 influenza B patients were administered oseltamivir (treated groups), and 28 influenza A and 66 influenza B patients were assigned as non-treated groups. The duration of fever, defined as period when patients had the maximum temperature higher than 37.5 degrees C in three-time measurements in a day after the clinic visit, was evaluated among the four groups. In uni-variate analysis, the duration of fever was shorter for treated group than non-treated for influenza A (1.8 +/- 0.9 days vs 2.6 +/- 1.3 days, p < 0.01), but it was not significant for influenza B (2.4 +/- 1.3 days vs 2.8 +/- 1.2 days, p = 0.9). The fever duration was longer in treated influenza B than A patients (p < 0.01). Multi-variate analysis indicated younger age (< 6 years old) and higher body temperature at the clinic visit prolonged the duration of fever. Adjusted average duration of fever indicated that oseltamivir was effective for both types, but more effective on influenza A, and the benefit increased for younger children. Our data provide evidence that oseltamivir is beneficial for influenza infections, but the effectiveness is differed by type and age.


Necrotizing enterocolitis and hemolysis associated with Clostridium perfringens.
Two newborns had necrotizing enterocolitis (NEC) and severe hemolytic anemia. Clostridium perfringens was identified in the peritoneal fluid of both infants, supporting the previous association of C perfringens with hemolysis reported in adult patients. Infants with NEC and hemolytic anemia should be aggressively treated with surgical debridement and high-dose parenteral penicillin G potassium. Similarly, Gram's stain of peritoneal fluid and resected bowel at laparotomy for NEC may be useful for early identification of the primary organism.


Psychoactive drug use among medical doctors is higher than in the general population.
We surveyed a representative sample of practising physicians and a representative sample of subjects from the Swiss general population (SOMIPOPS Survey) concerning their annual use of sleeping pills and tranquillizers. 77% of the physicians (n = 466) and 72% of the general population (n = 4255) responded. After adjustment for age and sex 37.1% of the doctors (general population 21.1% P less than 0.001) claimed to have taken these drugs for therapeutic purposes. The proportion of psychiatrists who reported taking sleeping pills and tranquillizers daily (10.6%) were significantly greater than for the population of doctors as a whole and for the general population (P less than 0.05). Regular users (i.e. subjects taking one mood altering drug at least once a week) accounted for 11.1% of the medical population compared with 6.8% of the general population (P less than 0.01). This over-consumption was wholly due to the greater number of regular users of psychoactive drugs amongst doctors less than 50 years of age relative to the general population or to subjects in higher management (from P less than 0.05 to P less than 0.001). Without this specific over-use, members of the medical profession would not have been found to use more psychoactive drugs than the general population and the executives. This result suggests that it would be worth investigating the mechanisms of response and adjustment (coping) to the specific stress that appears to be inherent in the exercise of medical practice.


DNA as an important target in radiation-induced apoptosis of MYC and MYC plus RAS transfected rat embryo fibroblasts.
This study uses a radiation chemistry approach to determine if DNA is an important target for radiation-induced apoptosis of myc (MR4) and myc plus ras (3.7) transfected rat embryo fibroblast cell lines. The radiation protection efficiency of four thiols was compared with net molecular charge ranging from -1 to +2: mercaptopropionic acid (Z= -1), mercaptoethanol (Z=0), cysteamine (Z= +1), N(2-mercaptoethyl)-1,3-diaminopropane (Z= +2). Protection factors were determined for these thiols against radiation-induced apoptosis (Apoalert assay), mitotic cell death (clonogenic assay) and double-strand break (dsb) induction (pulse field gel electrophoresis) in MR4 and 3.7 cells. Theoretical protection factors for these thiols against dsb induction were also calculated from second-order chemical repair constants for single-strand breaks (ssb) and the concentration of added thiols in MR4 and 3.7 cell lines. The charge-dependent increases observed for measured protection factors against radiation-induced apoptosis did not differ significantly between the two cell lines, nor did they differ significantly from the corresponding increases observed for radiation-induced mitotic cell killing and for induction of dsb. The calculated protection factor for dsb also showed a thiol charge-dependent increase similar to the measured protection factors for all of the other parameters studied. These results are consistent with the hypothesis that DNA is an important target for radiation-induced apoptosis.


Declining malaria parasite prevalence and trends of asymptomatic parasitaemia in a seasonal transmission setting in North-Western Burkina Faso between 2000 and 2009-2012.
Malaria transmission was reported to have declined in some East African countries. However, a comparable trend has not been confirmed for West Africa. This study aims to assess the dynamics of parasite prevalence and malaria species distribution over time in an area of highly seasonal transmission in Burkina Faso. The aim was also to compare frequency of asymptomatic parasitaemia between wet and dry season by parasite density status and age group. During the years 2009-2012, six cross-sectional studies were performed in the rural village Bourasso in the Nouna Health District in north-west Burkina Faso. In subsequent rainy and dry seasons blood samples were collected to assess the parasite prevalence, species, density and clinical parameters. In total, 1,767 children and adults were examined and compared to a baseline collected in 2000. The microscopical parasite prevalence (mainly P. falciparum) measured over the rainy seasons decreased significantly from 78.9% (2000) to 58.4%, 55.9% and 49.3%, respectively (2009-2011; p <0.001). The frequency of Plasmodium malariae infections (mono- and co-infections) decreased parallel to the overall parasite prevalence from 13.4% in 2000 to 2.1%, 4.1% and 4.7% in 2009-2011 (p <0.001). Comparing parasite-positive subjects from the rainy season versus dry season, the risk of fever was significantly reduced in the dry season adjusting for parasite density (grouped) and age group. The results of this study suggest a decline of malaria transmission over the rainy seasons between 2000 and 2009-2011 in the region of Nouna, Burkina Faso. The decreased transmission intensity was associated with lower prevalence of P. malariae infections (both mono-infections and co-infections). Asymptomatic parasitaemia was more frequent in the dry season even adjusting for parasite density and age group in a multivariate regression. Possible reasons for this observation include the existence of less pathogenic Plasmodium falciparum genotypes prevailing in the dry season, or the effect of a reduced incidence density during the dry season.


The metabolic syndrome in Hong Kong Chinese. The interrelationships among its components analyzed by structural equation modeling.
To examine the pattern of the metabolic syndrome in Chinese and the causal relationships among its components, including aging, obesity, hyperglycemia, hypertension, hypertriglyceridemia, and hyperinsulinemia in these subjects. Based on a 75-g oral glucose tolerance test, the World Health Organization criteria were used for the diagnosis of glucose intolerance in a population-based study involving 1.513 Chinese subjects in two work sites. Demographic data including age, family history of diabetes, BMI, waist-to-hip ratio (WHR), and sitting blood pressure (BP) were documented. Fasting plasma glucose, triglyceride (TG) and insulin concentrations, and spot urinary albumin concentration (Ualb) were also measured. Structural equation modeling incorporating factor analysis and path analysis was performed to examine the causal relationships among these variables and their interactions. Subjects who were treated with antidiabetic and/or antihypertensive drugs or who had a plasma creatinine level > or = 150 mumol/l were excluded (n = 52). The prevalence of diabetes and impaired glucose tolerance (IGT) were 3.9% (n = 34) and 7.2% (n = 63) in men (n = 881) and 3.1% (n = 18) and 6.7% (n = 39) in women (n = 580), respectively. In both groups, glucose intolerance was associated with increasing age, higher BMI, WHR, BP, Ualb, serum TG, and insulin levels as well as higher prevalence rates of positive family history of diabetes. Structural equation modeling showed that age was a significant determinant for both BMI and WHR. Age and obesity accounted for most of the variance of BP, Ualb, plasma glucose, insulin and TG levels either directly or indirectly. Plasma glucose was determined by a positive family history of diabetes, age, and BMI while TG was dependent on BMI and WHR. Serum insulin was mainly determined by a positive family history of diabetes, obesity, plasma glucose, and TG levels. Apart from age and obesity, BP was also determined by serum insulin, both of which had causal effects on Ualb. This model emphasizes the centrality of aging and obesity as well as a positive family history of diabetes as major determinants of the components of the metabolic syndrome. These components in turn had causal effects upon one another. Apart from a familial tendency, a central neurohormonal mechanism may account for these abnormalities mediated primarily through obesity and in close association with aging.


[Changes of crop yield and soil fertility under long-term fertilization and nutrients-recycling and reutilization on a black soil: IV. Soil organic carbon and its fractions].
A long-term experiment was conducted on a black soil of Northeast China to study the effects of applying chemical fertilizers and recycled organic manure (ROM) on the changes of soil organic carbon and its fractions. The results showed that from 1985 to 2004, soil total organic carbon (TOC) decreased by 7.83% in control,4.56% in N application, 1.61% in N + P application, and 5.56% in ROM application, but increased by 0.33% in N + P + K application. Comparing with single application of ROM, its application with chemical fertilizers, i. e., N + ROM, N + P + ROM, and N + P + K + ROM, increased the TOC concentration by 0.35%, 1.05% and 0.64%, respectively. The readily oxidized carbon (ROC) in fertilization treatments was increased by 8.64% to approximately 28.4%, and the increment was higher in treatments of chemical fertilizers plus ROM than in treatments of chemical fertilizers. The ROC was significantly correlated with soil TOC (Y = 14.192X + 23.9, R2 = 0.802) and stalk yields (Y = 19032X - 7950.6, R2 = 0.759). Light fraction organic carbon (LF-C) had the same trends with ROC. After 20 years fertilization, the organic carbon in soil humic acid and fulvic acid was decreased by 1.64% to approximately 26.23% and 2.33% to approximately 28.68%, respectively, but in treatments of chemical fertilizers plus ROM, the decreasing trend was slowed down.


A Generalized Spatial Measure for Resilience of Microbial Systems.
The emergent property of resilience is the ability of a system to return to an original state after a disturbance. Resilience may be used as an early warning system for significant or irreversible community transition; that is, a community with diminishing or low resilience may be close to catastrophic shift in function or an irreversible collapse. Typically, resilience is quantified using recovery time, which may be difficult or impossible to directly measure in microbial systems. A recent study in the literature showed that under certain conditions, a set of spatial-based metrics termed recovery length, can be correlated to recovery time, and thus may be a reasonable alternative measure of resilience. However, this spatial metric of resilience is limited to use for step-change perturbations. Building upon the concept of recovery length, we propose a more general form of the spatial metric of resilience that can be applied to any shape of perturbation profiles (for example, either sharp or smooth gradients). We termed this new spatial measure "perturbation-adjusted spatial metric of resilience" (PASMORE). We demonstrate the applicability of the proposed metric using a mathematical model of a microbial mat.


Effect of Nanohole Spacing on the Self-Imaging Phenomenon Created by the Three-Dimensional Propagation of Light through Periodic Nanohole Arrays.
We present a detailed study of the inter-nanohole distance that governs the self-imaging phenomenon created by the three-dimensional propagation of light through periodic nanohole arrays on plasmonic substrates. We used scanning near-field optical microscopy (SNOM) to map the light intensity distributions at various heights above 10×10 nanohole arrays of varying pitch sizes on silver films. Our results suggest the inter-hole spacing has to be greater than the wavelength of the incident light to create the self-imaging phenomenon. We also present Finite-Difference Time-Domain (FDTD) calculations which show qualitative corroboration of our experimental results. Both our experimental and FDTD results show that the self-imaging phenomenon is more pronounced for structures with larger pitch sizes. We believe this self-imaging phenomenon is related to the Talbot imaging effect that has also been modified by a plasmonic component and can potentially be used to provide the basis for a new class of optical microscopes.


Modeling the developmental neurotoxicity of nicotine in vitro: cell acquisition, growth and viability in PC12 cells.
Although nicotine is a developmental neurotoxicant, it also can exert neuroprotective effects. In the current study, we used PC12 cells to determine the developmental phases in which these disparate actions are expressed and to compare the concentrations required for each. In undifferentiated cells, 1 or 10 microM nicotine had little or no effect on cell number (assessed by measuring DNA) but exerted positive trophic actions, characterized by transient enhancement of cell growth (increased total protein/DNA ratio) and persistent enhancement of cell viability (decreased proportions of cells stained with trypan blue). When differentiation was initiated with nerve growth factor, nicotine elicited a different spectrum of actions, with decreases in cell number, impaired neuritic outgrowth (reduced ratio of membrane/total protein) and weakened viability. In either undifferentiated or differentiating cells, nicotine increased lipid peroxidation (determined as thiobarbituric acid reactive species), providing evidence for oxidative damage. Our results indicate that nicotine exerts positive trophic effects primarily on undifferentiated cells, whereas with differentiation the effects undergo a transition to neurotoxicity. These findings support the view that the neurodevelopmental actions of nicotine depend not only upon the magnitude and duration of the exposure, but most importantly on the developmental stage (e.g., differentiation state) in which exposure occurs.


Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.
Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.


Candida albicans Agglutinin-Like Sequence (Als) Family Vignettes: A Review of Als Protein Structure and Function.
Approximately two decades have passed since the description of the first gene in the Candida albicans ALS (agglutinin-like sequence) family. Since that time, much has been learned about the composition of the family and the function of its encoded cell-surface glycoproteins. Solution of the structure of the Als adhesive domain provides the opportunity to evaluate the molecular basis for protein function. This review article is formatted as a series of fundamental questions and explores the diversity of the Als proteins, as well as their role in ligand binding, aggregative effects, and attachment to abiotic surfaces. Interaction of Als proteins with each other, their functional equivalence, and the effects of protein abundance on phenotypic conclusions are also examined. Structural features of Als proteins that may facilitate invasive function are considered. Conclusions that are firmly supported by the literature are presented while highlighting areas that require additional investigation to reveal basic features of the Als proteins, their relatedness to each other, and their roles in C. albicans biology.


Particulate metal exposures induce plasma metabolome changes in a commuter panel study.
Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.


Craniomaxillofacial injury in sport: a review of prevention research.
Current decision making in prevention of sport related craniomaxillofacial injury is based on available data derived from surveillance and attitude based studies. The literature on this type of injury prevention lacks the high quality scientific design and evidence on which mandatory interventions can be based. Currently available prevention methodology can provide a better understanding of injury mechanisms and produce valid interventions.


Nucleotide sequence characterization of a Drosophila retrotransposon, 412.
The nucleotide sequence of the internal region of a Drosophila retrotransposon. 412, was determined. The genome of 412 was found to consist of two long open-reading frames (ORFs 1 and 2), an unusually long putative leader region and long terminal repeats (LTRs). As with 17.6, 297 and gypsy, ORFs 1 and 2 slightly overlap each other and are out of phase by +2. ORF2 includes the nucleotide sequences coding for the putative protease, reverse transcriptase and integrase, and is similar in entire organization to the pol gene of Moloney murine leukaemia virus. In spite of the difference in insertion specificity, integrase, an enzyme presumably responsible for insertion, was found to be similar in amino acid sequence to the counterparts of 17.6, 297 and gypsy. There is no ORF in 412 which corresponds to retroviral env or ORF3s of 17.6 and 297. Analysis of 412 transcripts suggested that 412 LTR is composed of U3, R and U5. The gene for a potential primer tRNA for putative reverse transcription of 412 was also surveyed and the 3'-terminal 15 nucleotides of a putative arginine tRNA were found to be exactly complementary to the putative primer-binding site of 412.


Paris polyphylla saponins II inhibits invasive, migration and epithelial-mesenchymal transition of melanoma cells through activation of autophagy.
Malignant melanoma is a kind of malignant tumor derived from normal epidermal melanocytes or original nevus cells. It has a high degree of malignancy, rapid progress, dangerous condition, and poor prognosis. In recent years, the innovation of traditional Chinese medicine has broadened the scope and effect of tumor treatment. It is a hotspot and breakthrough to find new anti-tumor invasion and migration drugs from natural plants or traditional Chinese medicine. This study explored the role of PPII in promoting autophagy to inhibit EMT of melanoma cells, the role of the PI3K/Akt signaling pathway in the invasion and migration of melanoma cells induced by PPII. We found that PPII effectively inhibited the proliferation, invasion and migration of melanoma B16 and B16F10 in vitro, and induced autophagy. We also established the xenograft tumor and metastatic tumor model of C57BL/6 mice with B16F10 cells. Results showed that PPII effectively inhibited the growth of transplanted tumors, induced autophagy and inhibited the expression level of EMT related protein; Metastasis experiment showed that PPII inhibited the invasion and migration of B16F10, the effect of inhibiting lung metastasis is the most significant. Further mechanism studies showed that the inhibition of PPII on melanoma invasion and migration is related to its induction of autophagy and then inhibition of EMT.


Novel Use of Stimulating Fence-Post Technique for Functional Mapping of Subcortical White Matter During Tumor Resection: A Technical Case Series.
Maximal safe resection remains a key principle in infiltrating glioma management. Stimulation mapping is a key adjunct for minimizing functional morbidity while "fence-post" procedures use catheters or dye to mark the tumor border at the start of the procedure prior to brain shift. To report a novel technique using stereotactically placed electrodes to guide tumor resection near critical descending subcortical fibers. Navigated electrodes were placed prior to tumor resection along the deep margin bordering presumed eloquent tracts. Stimulation was administered through these depth electrodes for subcortical motor and language mapping. Twelve patients were included in this preliminary technical report. Seven patients (7/12, 58%) were in asleep cases, while the other 5 cases (5/12, 42%) were performed awake. Mapping of motor fibers was performed in 8 cases, and language mapping was done in 1 case. In 3 cases, both motor and language mapping were performed using the same depth electrode spanning corticospinal tract and the arcuate fasciculus. Stereotactic depth electrode placement coupled with stimulation mapping of white matter tracts can be used concomitantly to demarcate the border between deep tumor margins and eloquent brain, thus helping to maximize extent of resection while minimizing functional morbidity.


Subclinical Agoraphobia Symptoms and Regional Brain Volumes in Non-clinical Subjects: Between Compensation and Resilience?
Background: Symptoms of anxiety are present not only in panic disorder or other anxiety disorders, but are highly prevalent in the general population. Despite increasing biological research on anxiety disorders, there is little research on understanding subclinical or sub-threshold symptoms relating to anxiety in non-clinical community samples, which could give clues to factors relating to resilience or compensatory changes. Aims:This study focused on brain structural correlates of subclinical anxiety/agoraphobia symptoms from a multi-center imaging study. Methods: We obtained high-resolution structural T1 MRI scans of 409 healthy young participants and used the CAT12 toolbox for voxel-based morphometry (VBM) analysis. Subjects provided self-ratings of anxiety using the SCL-90-R, from which we used the phobia subscale, covering anxiety symptoms related to those of panic and agoraphobia spectrum. Results: We found significant (p < 0.05, FDR-corrected) correlations (mostly positive) of cortical volume with symptom severity, including the right lingual gyrus and calcarine sulcus, as well as left calcarine sulcus, superior, middle, and inferior temporal gyri. Uncorrected exploratory analysis also revealed positive correlations with GMV in orbitofrontal cortex, precuneus, and insula. Conclusions: Our findings show brain structural associations of subclinical symptoms of anxiety, which overlap with those seen in panic disorder or agoraphobia. This is consistent with a dimensional model of anxiety, which is reflected not only functionally but also on the structural level.


Probing amyloid fibril formation of the NFGAIL peptide by computer simulations.
Amyloid fibril formation, as observed in Alzheimer's disease and type II diabetes, is currently described by a nucleation-condensation mechanism, but the details of the process preceding the formation of the nucleus are still lacking. In this study, using an activation-relaxation technique coupled to a generic energy model, we explore the aggregation pathways of 12 chains of the hexapeptide NFGAIL. The simulations show, starting from a preformed parallel dimer and ten disordered chains, that the peptides form essentially amorphous oligomers or more rarely ordered beta-sheet structures where the peptides adopt a parallel orientation within the sheets. Comparison between the simulations indicates that a dimer is not a sufficient seed for avoiding amorphous aggregates and that there is a critical threshold in the number of connections between the chains above which exploration of amorphous aggregates is preferred.


[The cholinergic system of the striatum: its participation in the motor and sensory components of motor behavior].
This review deals with the recent data on participation of the dorsal striatum cholinergic system in orientation behavior and in regulation of attention to significant stimuli, which was realized via the range of subcortical structures, among them the intralaminar thalamic nuclei (CM-Pf) and pedunculopontine nuclei (PPN) play an especially important role. On the basis of our own experimental data it was suggested that by using an adequate pharmacological effects upon striatal cholinergic system, it was possible to change the sensory and motor components of movement behavior. Whereas the unilateral microinjections of cholinergic receptor agonists lead to behavioral changes only on the day of injection, the bilateral injections change the formed type of the movement behavior for a long time. An important role of the dorsal striatal cholinergic system in switching and modulation of the indirect efferent pathway was substantiated. By this mechanism, inhibition of nonspecific sensory afferentation at different subcortical levels and an increase of significant sensory signals can take place. A manifestation of this mechanism can be the sharp improvements of differentiation of sensory stimuli after activation of the striatal cholinergic system. On the other hand, the cholinergic striatal limitation of movement activity (a decrease of locomotion, an increase of tonic component of movement and streamlining of posture) may be the important factors for making a decision in a difficult situation.


Antineutrophil cytoplasmic antibodies reacting with the pro form of proteinase 3 and disease activity in patients with Wegener's granulomatosis and microscopic polyangiitis.
Antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) are diagnostic markers for the small vessel vasculitides Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Correlation of disease activity with PR3 ANCA levels, as determined by standard methods, is not apparent in every patient. PR3 ANCA react with yet to be identified conformational epitopes. We have identified PR3 ANCA subsets that react differentially with mature recombinant PR3 (rPR3; lacking the N-terminal activation dipeptide) and the pro form of this enzyme (pro-rPR3). The present study was performed to determine the association of these PR3 ANCA subsets with disease activity. Sera from 61 PR3 ANCA-positive patients with WG or MPA were assayed by capture enzyme-linked immunosorbent assay using pro-rPR3 and rPR3 as target antigens, and were correlated with disease activity as determined by the Birmingham Vasculitis Activity Score (BVAS). Median levels of PR3 ANCA reacting with pro-rPR3 were higher during active (n = 32) than during inactive (n = 29) disease (P = 0.016). Reactivity with mature rPR3 was not significantly different (P = 0.71). Serial followup in individual patients also indicated better correlation of PR3 ANCA reactivity with pro-rPR3 than with mature rPR3. PR3 ANCA subsets reactive with epitopes accessible on pro-PR3 correlate better with disease activity than do subsets reactive with epitopes accessible only on mature PR3. This observation may explain why ANCA levels determined with current standard methods are suboptimal for monitoring disease activity. It raises new questions about the primary target of the PR3 ANCA immune response in patients with small vessel vasculitis.


Effects of low-frequency magnetic fields on bacterial growth rate.
A large number of cultures of the bacterium E. coli have been grown in weak alternating magnetic fields of square waveform, at frequencies of 50 Hz and 16.66 Hz. Control cultures were simultaneously grown under ambient conditions identical except for the almost complete absence of any magnetic field. The mean generation time (MGT) for a culture subjected to alternating magnetic fields is significantly reduced by comparison with that for the control cultures. Application of the F-ratio test indicates a probability of less than one in two million that the effects observed are due to chance. A marked threshold effect is observed, along with strong indications of periodicity in the graph of MGT against magnetic field strength. Within the limits of experimental error, these effects correspond to integral changes in the number of magnetic flux quanta linking an individual bacterial cell during the process of division.


Hair lead levels to evaluate the subclinical impact of lead on growth in Sardinian children (Italy).
The aim of this study was to determine if there are significant relationships between lead concentrations in children's hair and height, sitting height, and estimated leg length. We analyzed three samples collected at different times: 1998, 2002, 2007. The total sample consisted of 825 children between 11 and 14 years of age living in different municipalities of Sardinia (Italy). Inductively coupled plasma atomic emission spectrometry (1998), inductively coupled plasma atomic absorption spectrometry (2002), and inductively coupled mass spectrometry (2007) were used to measure the lead concentration in hair (PbH). Some AAS measurements were also performed on the 1998 and 2007 samples to check the reliability of the data. The mean PbH is much higher in 1998 (5.84 μg/g) than in 2002 (1.49 μg/g) and 2007 (0.78 μg/g). Multivariate regression analysis of the three samples, controlling for age and sex, indicates a subclinical impact of lead on growth that differs according to the mean lead concentration in the hair. In fact, for 1998, the relationships between all three anthropometric variables and logPbH are significantly negative. For 2002, there are significant negative associations between height and estimated leg length and logPbH but not between sitting height and logPbH. For 2007, there are not significant associations between logPbH and anthropometric variables. Our results support the use of hair lead levels as a biomarker to assess the impact of subclinical lead on the physical growth of children, especially when the study area presents medium and/or high levels of lead pollution.


NMR studies of ligand carboxylate group interactions with arginine residues in complexes of Lactobacillus casei dihydrofolate reductase with substrates and substrate analogues.
In a series of complexes of Lactobacillus casei dihydrofolate reductase (DHFR) formed with substrates and substrate analogues, the (1)H/(15)N NMR chemical shifts for the guanidino group of the conserved Arg 57 residue were found to be sensitive to the mode of binding of their H(eta) protons to the charged oxygen atoms in ligand carboxylate groups. In all cases, Arg 57 showed four nonequivalent H(eta) signals indicating hindered rotation about the N(epsilon)-C(zeta) and C(zeta)-N(eta) bonds. The H(eta)(12) and H(eta)(22) protons have large downfield shifts as expected for a symmetrical end-on interaction with the ligand carboxylate group. The chemical shifts are essentially the same in the complexes with folate and p-aminobenzoyl-L-glutamate (PABG) and similar to those found previously for the methotrexate complex reflecting the strong and similar hydrogen bonds formed with the carboxylate oxygens. Interestingly, the rates of rotation about the N(epsilon)-C(zeta) bond for the complexes containing the weakly binding PABG fragment are almost identical to those measured in the complex with methotrexate, which binds 10(7) times more tightly. In the methotrexate complex, this rotation depends on correlated rotations about the N(epsilon)-C(zeta) bond of Arg 57 and the C(alpha)-C' bond of the ligand glutamate alpha-carboxylate group. Thus, even in a fragment such as PABG, which has a much faster off-rate, the carboxylate group binds to the enzyme in a similar way to that in a parent molecule such as folate and methotrexate with the rotation about the N(epsilon)-C(zeta) bond of Arg 57 being essentially the same in all the different complexes.


Nitric oxide modulators: an emerging class of medicinal agents.
Nitric oxide, a unique messenger in biological system, is ubiquitously present virtually in all tissues revealing its versatile nature of being involved in diverse physiological functions such as vascular tone, inhibition of platelet aggregation, cell adhesion, neurotransmission and enzyme and immune regulation. The tremendous advancements made in the past few decades in this area suggests that the nitric oxide modulation either by its exogenous release through nitric oxide donors or inhibition of its synthesis by nitric oxide synthase inhibitors in physiological milieu may provide newer clinical strategies for the treatment of some diseases. In this review, an attempt is made to document and understand the biological chemistry of different classes of nitric oxide modulators that would prove to be a fruitful area in the years to come.


DNA → RNA: What Do Students Think the Arrow Means?
The central dogma of molecular biology, a model that has remained intact for decades, describes the transfer of genetic information from DNA to protein though an RNA intermediate. While recent work has illustrated many exceptions to the central dogma, it is still a common model used to describe and study the relationship between genes and protein products. We investigated understanding of central dogma concepts and found that students are not primed to think about information when presented with the canonical figure of the central dogma. We also uncovered conceptual errors in student interpretation of the meaning of the transcription arrow in the central dogma representation; 36% of students (n = 128; all undergraduate levels) described transcription as a chemical conversion of DNA into RNA or suggested that RNA existed before the process of transcription began. Interviews confirm that students with weak conceptual understanding of information flow find inappropriate meaning in the canonical representation of central dogma. Therefore, we suggest that use of this representation during instruction can be counterproductive unless educators are explicit about the underlying meaning.


Aquatic eddy correlation: quantifying the artificial flux caused by stirring-sensitive O2 sensors.
In the last decade, the aquatic eddy correlation (EC) technique has proven to be a powerful approach for non-invasive measurements of oxygen fluxes across the sediment water interface. Fundamental to the EC approach is the correlation of turbulent velocity and oxygen concentration fluctuations measured with high frequencies in the same sampling volume. Oxygen concentrations are commonly measured with fast responding electrochemical microsensors. However, due to their own oxygen consumption, electrochemical microsensors are sensitive to changes of the diffusive boundary layer surrounding the probe and thus to changes in the ambient flow velocity. The so-called stirring sensitivity of microsensors constitutes an inherent correlation of flow velocity and oxygen sensing and thus an artificial flux which can confound the benthic flux determination. To assess the artificial flux we measured the correlation between the turbulent flow velocity and the signal of oxygen microsensors in a sealed annular flume without any oxygen sinks and sources. Experiments revealed significant correlations, even for sensors designed to have low stirring sensitivities of ~0.7%. The artificial fluxes depended on ambient flow conditions and, counter intuitively, increased at higher velocities because of the nonlinear contribution of turbulent velocity fluctuations. The measured artificial fluxes ranged from 2-70 mmol m(-2) d(-1) for weak and very strong turbulent flow, respectively. Further, the stirring sensitivity depended on the sensor orientation towards the flow. For a sensor orientation typically used in field studies, the artificial flux could be predicted using a simplified mathematical model. Optical microsensors (optodes) that should not exhibit a stirring sensitivity were tested in parallel and did not show any significant correlation between O2 signals and turbulent flow. In conclusion, EC data obtained with electrochemical sensors can be affected by artificial flux and we recommend using optical microsensors in future EC-studies.


Successful contracting of prevention services: fighting malnutrition in Senegal and Madagascar.
There are very few documented large-scale successes in nutrition in Africa, and virtually no consideration of contracting for preventive services. This paper describes two successful large-scale community nutrition projects in Africa as examples of what can be done in prevention using the contracting approach in rural as well as urban areas. The two case-studies are the Secaline project in Madagascar, and the Community Nutrition Project in Senegal. The article explains what is meant by 'success' in the context of these two projects, how these results were achieved, and how certain bottlenecks were avoided. Both projects are very similar in the type of service they provide, and in combining private administration with public finance. The article illustrates that contracting out is a feasible option to be seriously considered for organizing certain prevention programmes on a large scale. There are strong indications from these projects of success in terms of reducing malnutrition, replicability and scale, and community involvement. When choosing that option, a government can tap available private local human resources through contracting out, rather than delivering those services by the public sector. However, as was done in both projects studied, consideration needs to be given to using a contract management unit for execution and monitoring, which costs 13-17% of the total project's budget. Rigorous assessments of the cost-effectiveness of contracted services are not available, but improved health outcomes, targeting of the poor, and basic cost data suggest that the programmes may well be relatively cost-effective. Although the contracting approach is not presented as the panacea to solve the malnutrition problem faced by Africa, it can certainly provide an alternative in many countries to increase coverage and quality of services.


[The prevalence of multiple sclerosis in the Alcoi Health district].
The epidemiological studies done in Spain in recent years show higher figures for the prevalence of multiple sclerosis than before. Spain is therefore now in the area with a high risk of contracting the disease. We have made a new study to confirm the current prevalence of the disorder in the Alcoi Health District. Between 1 March 1986 and the prevalence day, 31 December 1997 we recorded the patients with definite or probable multiple sclerosis, as defined on Poser's criteria, after intensive fieldwork and reevaluation of all possible patients by a neurologist from the Neurology Unit. On the prevalence day there were 130,786 inhabitants in the district. On the prevalence day we found 54 patients with definite multiple sclerosis and no patient with probable multiple sclerosis. The rate of prevalence was 41.28 cases per 100,000 inhabitants (95% CI: 31-53.6). During the study we counted an incidence of 45 cases with an average rate of 2.82 cases per 100,000 inhabitants per year. We also describe the clinical characteristics of the patients. The rate of prevalence found is much higher than that described for the district in studies using similar methodology. This increase, together with the discrepancy between the incidence found and the prevalence, makes us consider that possibly the prevalence has increased in recent years.


Canadian clinical trial of antilymphocyte globulin in human cadaver renal transplantation.
A multicentre, randomized clinical trial of antilymphocyte globulin (ALG) was conducted among patients who had undergone cadaver kidney transplantation; follow-up was continued for a minimum of 1 year. Of the 179 patients 92 were given conventional treatment only, while 87 were given in addition ALG (from a standardized, highly immunosuppressive, common pool of equine ALG), 20 mg/kg-d intravenously for 10 days after transplantation. The ALG-treated group had better accumulated graft survival, fewer nephrectomies, better graft function, less than half the number of acute rejection episodes and less prednisone use. There was a beneficial drug (ALG)-related effect in both the graft and the host during the first 3 months after transplantation.


Quantitative proteomics reveals that peroxidases play key roles in post-flooding recovery in soybean roots.
Soybean is an important legume crop that exhibits markedly reduced growth and yields under flooding conditions. To unravel the mechanisms involved in recovery after flooding in soybean root, gel-free proteomic analysis was performed. Morphological analysis revealed that growth suppression was more severe with increased flooding duration. Out of a total of 1645 and 1707 identified proteins, 73 and 21 proteins were changed significantly during the recovery stage following 2 and 4 days flooding, respectively. Based on the proteomic, clustering, and in silico protein-protein interaction analyses, six key enzymes were analyzed at the mRNA level. Lipoxygenase 1, which was increased at the protein level during the recovery period, was steadily down-regulated at the mRNA level. The peroxidase superfamily protein continuously increased in abundance during the course of recovery and was up-regulated at the mRNA level. HAD acid phosphatase was decreased at the protein level and down-regulated at the transcript level, while isoflavone reductase and an unknown protein were increased at both the protein and mRNA levels. Consistent with these findings, the enzymatic activity of peroxidase was decreased under flooding stress but increased significantly during the recovery sage. These results suggest that peroxidases might play key roles in post-flooding recovery in soybean roots through the scavenging of toxic radicals.


Association of All-Cause and Cause-Specific Mortality Risks With Pyoderma Gangrenosum.
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. Few studies have evaluated the mortality outcomes of patients with PG. To investigate all-cause and cause-specific mortality in patients with PG. This retrospective population-based cohort study used data from the National Health Insurance Service database of Korea and the National Death Registry of Korea from patients with incident PG (≥3 documented visits with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code of L88) during January 2003 to December 2019. For comparison, a 1:20 cohort of age-, sex-, insurance type-, and income level-matched controls without any documented visit with an ICD-10 code of L88 during the entire observation was included. Pyoderma gangrenosum. The participants were observed from the index date to their death, emigration, or the end of the observation period to investigate all-cause and cause-specific mortality during the 17-year study period. In total, 3386 patients with PG (1450 women [42.8%]; mean [SD] age, 57.8 [16.4] years) and 67 720 controls (29 000 women [42.8%]; mean [SD] age, 57.8 [16.3] years) were analyzed. All-cause mortality risk was greater in patients with PG than in controls (adjusted hazard ratio [aHR], 2.122; 95% CI, 1.971-2.285) after adjustment for smoking, drinking, body mass index, and comorbidities. Patients experienced greater mortality of infectious disease (aHR, 3.855; 95% CI, 2.640-5.628), neoplasm (aHR, 1.618; 95% CI, 1.363-1.920), hematologic disease (aHR, 12.298; 95% CI, 3.904-38.734), endocrine disease (aHR, 6.322; 95% CI, 5.026-7.953), neurologic disease (aHR, 2.039; 95% CI, 1.337-3.109), cardiovascular disease (aHR, 1.979; 95% CI, 1.645-2.382), respiratory disease (aHR, 1.757; 95% CI, 1.365-2.263), gastrointestinal disease (aHR, 2.278; 95% CI, 1.522-3.408), connective tissue disease (aHR, 8.685; 95% CI, 4.963-15.199), and kidney/urogenital disease (aHR, 3.617; 95% CI, 2.488-5.259) than controls. Compared with idiopathic PG (aHR, 2.062; 95% CI, 1.897-2.241), PG that was associated with solid organ cancer (aHR, 2.313; 95% CI, 1.956-2.737) and hematologic cancer (aHR, 8.330; 95% CI, 5.473-12.679) showed greater mortality, whereas PG that was associated with inflammatory bowel diseases showed a slightly better prognosis (aHR, 1.742; 95% CI, 0.964-3.148). The results of this cohort study suggest that patients with PG had a higher all-cause and cause-specific mortality risk than the general population.


Seroepizootiologic study of bovine respiratory syncytial virus in a beef herd.
A seroepizootiologic study of bovine respiratory syncytial virus in a beef herd was conducted from February 1983 through March 1984. During the study period, 3 separate respiratory tract disease epizootics were recognized in calves after they had been split into 3 groups. Bovine respiratory syncytial virus infection was diagnosed in each epizootic on the basis of serologic evidence, postmortem findings, and immunofluorescent examination of lung tissue. Additionally, there was serologic evidence for involvement of bovine adenovirus type 3 in the epizootics in 2 of the groups of calves, but not in the 3rd. In 2 groups of calves, respiratory tract disease occurred in 2 stages, with the 1st stage being mild followed by apparent recovery. The 2nd stage, which was associated with a change to colder weather, was clinically more severe, with death loss occurring.


Conversion of Uric Acid into Ammonium in Oil-Degrading Marine Microbial Communities: a Possible Role of Halomonads.
Uric acid is a promising hydrophobic nitrogen source for biostimulation of microbial activities in oil-impacted marine environments. This study investigated metabolic processes and microbial community changes in a series of microcosms using sediment from the Mediterranean and the Red Sea amended with ammonium and uric acid. Respiration, emulsification, ammonium and protein concentration measurements suggested a rapid production of ammonium from uric acid accompanied by the development of microbial communities containing hydrocarbonoclastic bacteria after 3 weeks of incubation. About 80 % of uric acid was converted to ammonium within the first few days of the experiment. Microbial population dynamics were investigated by Ribosomal Intergenic Spacer Analysis and Illumina sequencing as well as by culture-based techniques. Resulting data indicated that strains related to Halomonas spp. converted uric acid into ammonium, which stimulated growth of microbial consortia dominated by Alcanivorax spp. and Pseudomonas spp. Several strains of Halomonas spp. were isolated on uric acid as the sole carbon source showed location specificity. These results point towards a possible role of halomonads in the conversion of uric acid to ammonium utilized by hydrocarbonoclastic bacteria.


[Mumps vaccine virus transmission].
In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.


Laser drilling of nano-pores in sandwiched thin glass membranes.
We report on a novel method of using an excimer laser to drill ultra-small pores in borosilicate glass membranes. By introducing a thin layer of liquid between sandwiches of two glass slides, we can shrink the pore size and smoothen the surface on the exit side. We are able to push the minimal exit pore diameter down to 90 nm, well below the laser wavelength of 193 nm. This is achieved with substrates over 150 microm thick. Compared to other methods, this technique is fast, inexpensive, and produces high quality smooth pores.


UnderstAID, an ICT Platform to Help Informal Caregivers of People with Dementia: A Pilot Randomized Controlled Study.
Information and communications technology (ICT) could support ambient assisted living (AAL) based interventions to provide support to informal caregivers of people with dementia, especially when they need to cope with their feelings of overburden or isolation. An e-learning platform (understAID application) was tested by informal caregivers from Denmark, Poland, and Spain to explore the technical and the pedagogical specifications, as well as evaluating the impact of its use on the psychological status of the participants. 61 informal caregivers completed the study taking part in the experimental (n = 30) or control (n = 31) groups. 33.3% of the caregivers were satisfied with the application and around 50% of the participants assessed it as technically and pedagogically acceptable. After using understAID the caregivers in the experimental group significantly decreased their depressive symptomatology according to the Center for Epidemiologic Studies Depression scale, but a possible benefit on their feelings of competence and satisfaction with the caring experience was also observed. The low scores obtained for satisfaction were highlighting issues that need to be modified to meet the informal caregivers' needs in national, social, and cultural context. Some possible biases are also considered and discussed to be taken into account in future improvements of understAID application.


MegaNatural®-BP grape seed extract and maintenance of normal blood pressure: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006.
Following an application from Praline i Čokolada j.d.o.o. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Croatia, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to MegaNatural®-BP grape seed extract and maintenance of normal blood pressure. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. MegaNatural®-BP, a grape seed extract standardised for total phenolics, gallic acid and the catechin and epicatechin content, is sufficiently characterised. The proposed claimed effect, maintenance of normal blood pressure (BP), is a beneficial physiological effect. Among the two human intervention studies provided from which conclusions could be drawn, one showed an effect of MegaNatural®-BP (300 mg/day) on BP in adults with normal and high normal BP when consumed daily for 6 weeks, whereas the second study did not show an effect of MegaNatural®-BP at the same daily dose consumed for 8 weeks in adults with normal and high normal blood pressure or stage 1 hypertension. The evidence provided did not establish a plausible mechanism by which the food could exert the claimed effect in vivo in humans. The evidence provided is insufficient to establish a cause and effect relationship between the consumption of MegaNatural®-BP and maintenance of normal blood pressure.