Skin-prick test and RAST responses to cereals in children with atopic dermatitis. Characterization of IgE-binding components in wheat and oats by an immunoblotting method.
Hypersensitivity to cereals may occur via inhalation or ingestion. Although cereals are essential in the daily nutrition, only little information is available of the allergens causing symptoms in patients with atopic dermatitis (AD). The purpose of the present study was to analyse the IgE immune-response to various cereals and specific cereal fractions of wheat and oats in children with severe AD and correlate the results with challenge studies. Skin-prick tests (SPT) with a NaCl suspension of wheat, oats, rice, corn, millet and buckwheat and the ethanol soluble gliadin fraction of wheat were performed to 34 wheat/oats challenge positive or negative children with AD. Simultaneously serum total IgE and specific IgE antibody radioallergosorbent test (RAST), levels to wheat, oats and gluten were determined. In addition serum samples of these 34 AD patients and five age matched controls were analysed with IgE immunoblotting using neutral and acidic protein extracts of wheat and oats. From the 34 AD children 33 were SPT positive with wheat and 18 with oats. Positive RAST to wheat and oats could be detected in 32 and 30 samples respectively. From the oral wheat challenge positive children 12/14 appeared positive with gliadin SPT and revealed positive RAST to gluten, but each of the wheat challenge negative were negative in SPT with gliadin. In immunoblotting using neutral and acidic fractions of cereals the IgE binding with sera of challenge positive children showed the most intensive staining, but no correlation was found between different staining patterns and the clinical wheat sensitivity. The 26, 38 and 69 kDa bands in wheat and the 46 and 66 kDa in oats could be classified as major IgE binding proteins of these cereals (> 50% of the sera were positive). SPT with rice, corn, millet or buckwheat was positive in 16/34 patients. Intensive IgE staining to neutral/acidic soluble proteins in wheat and oats was seen, with major IgE binding to 26, 38 and 69 kDa proteins in wheat and 46 and 66 kDa in oats, but no specific IgE staining patterns correlating with clinical cereal sensitivity were found. The strong association between the positive oral wheat challenge and the positive SPT with the ethanol soluble gliadin suggests that also gliadin is an important allergen in wheat-allergic children with AD. The allergens in rice, corn, millet and buckwheat should be better studied before they can be recommended as alternatives for cereal allergic children.


Mad cows, mad corn and mad communities: the role of socio-cultural factors in the perceived risk of genetically-modified food.
The rapid globalization of the world economy has increased the need for a knowledge base of reliable socio-cultural differences in perceptions, values and ways of thinking about new food technologies. Awareness of socio-cultural differences is important because collaborative efforts to deal with food hazards presuppose some understanding of where, how and why the viewpoints of various stakeholders may differ. In the present paper factors that influence public perceptions of genetically-modified (GM) food are discussed, with a special focus on the unique circumstances of populations in the USA, Europe and developing countries. It is argued that effective communication and decision making about the risk of GM food depends critically on understanding how socio-cultural groups differ in their values and in the way they deal with the risks and benefits of new technologies. The implications of psychological aspects of perceived risk (including the roles of qualitative dimensions of risk, world views and trust) for public acceptance of new food technologies are highlighted.


Integrin alpha9beta1: Unique signaling pathways reveal diverse biological roles.
Integrins are transmembrane heterodimeric receptors responsible for transducing and modulating signals between the extracellular matrix and cytoskeleton, ultimately influencing cell functions such as adhesion and migration. Integrin alpha9beta1 is classified within a two member sub-family of integrins highlighted in part by its specialized role in cell migration. The importance of this role is demonstrated by its regulation of numerous biological functions including lymphatic valve morphogenesis, lymphangiogenesis, angiogenesis and hematopoietic homeostasis. Compared to other integrins the signaling mechanisms that transduce alpha9beta1-induced cell migration are not well described. We have recently shown that Src tyrosine kinase plays a key proximal role to control alpha9beta1 signaling. Specifically it activates inducible nitric oxide synthase (iNOS) and in turn nitric oxide (NO) production as a means to transduce cell migration. Furthermore, we have also described a role for FAK, Erk and Rac1 in alpha9beta1 signal transduction. Here we provide an over view of known integrin alpha9beta1 signaling pathways and highlight its roles in diverse biological conditions.


Increased risk of cancer in patients with retinal vein occlusion: a 12-year nationwide cohort study.
To investigate the association between incident retinal vein occlusion (RVO) and the subsequent development of cancer. In this nationwide population-based retrospective study using 2002-2013 National Health Insurance Service database which covers the entire South Korean population, 186 701 incident RVO patients and their 1:1 propensity-score matched controls were included. We defined the fixed cohort from January 1st, 2004 to December 31st, 2013; the cohort included patients who suffered incident RVO after entering the cohort and their matched controls, and excluded patients having any cancer history before entering the cohort. The association of RVO and cancer was assessed by time-varying covariate Cox regression models; Model 1 included RVO as a time-varying covariate, Model 2 included Model 1 plus demographic information and Model 3 included Model 2 and comorbidities. RVO was associated with an increased risk of subsequent cancer (HR=1.29; 95% CI, 1.26-1.31 in Model 1), which was consistent in Models 2 and 3. The incidence rate of overall cancer during the study period was 25.55 (95% CI, 25.19-25.91) per 1000 person-years in the RVO group and 18.62 (95% CI, 18.46-18.79) per 1000 person-years in the control group. In the subgroup analysis, haematological malignancies showed the highest association with RVO (HR=1.65; 95% CI, 1.49-1.83). Patients with RVO have an increased risk of subsequent cancer development even after adjusting for demographic factors and comorbidities. Further study is warranted to elucidate these associations to provide proper recommendations for RVO patients regarding the cancer screening.


Quantification of pH gradients and implications in insulator-based dielectrophoresis of biomolecules.
Direct current (DC) insulator-based dielectrophoretic (iDEP) microdevices have the potential to replace traditional alternating current dielectrophoretic devices for many cellular and biomolecular separation applications. The use of large DC fields suggest that electrode reactions and ion transport mechanisms can become important and impact ion distributions in the nanoliters of fluid in iDEP microchannels. This work tracked natural pH gradient formation in a 100 μm wide, 1 cm-long microchannel under applicable iDEP protein manipulation conditions. Using fluorescence microscopy with the pH-sensitive dye FITC Isomer I and the pH-insensitive dye TRITC as a reference, pH was observed to drop drastically in the microchannels within 1 min in a 3000 V/cm electric field; pH drops were observed in the range of 6-10 min within a 100 V/cm electric field and varied based on the buffer conductivity. To address concerns of dye transport impacting intensity data, electrokinetic mobilities of FITC were carefully examined and found to be (i) toward the anode and (ii) 1 to 2 orders of magnitude smaller than H⁺ transport which is responsible for pH drops from the anode toward the cathode. COMSOL simulations of ion transport showed qualitative agreement with experimental results. The results indicate that pH changes are severe enough and rapid enough to influence the net charge of a protein or cause aggregation during iDEP experiments. The results also elucidate reasonable time periods over which the phosphate buffering capacity can counter increases in H⁺ and OH⁻ for unperturbed iDEP manipulations.


What is Standard Dose of Rivaroxaban in Elderly Asian Patients with Atrial Fibrillation: 20ms versus. 15mg?
Although there is no age criterion for rivaroxaban dose reduction, elderly patients with atrial fibrillation (AF) are often prescribed an off-label reduced dose. We aimed to evaluate whether age is a necessary criterion for rivaroxaban dose reduction in Korean patients with AF. Among 2208 patients who prescribed warfarin or rivaroxaban, 552 patients over 75 years without renal dysfunction (creatinine clearance >50 mL/min) were compared based on propensity score matching. The rivaroxaban group was further divided into a 20 mg (R20; on-label) and a 15 mg (R15; off-label). Primary net clinical benefit (NCB) was defined as the composite of stroke, systemic embolism, major bleeding, and all-cause mortality. Secondary NCB was defined as the composite of stroke, systemic embolism, and major bleeding. Patients were followed for 1 year, or until the first outcome occurrence. Both rivaroxaban groups had comparable efficacy compared with warfarin. However, both R20 (0.9% vs 7.4%, p = .014) and R15 (2.3% vs 7.4%, p = .018) had a significant reduction in major bleeding. There were no differences in efficacy or safety outcomes between R20 and R15. R20 had significantly reduced primary (hazard ratio [HR] 0.33, 95% confidence interval [CI]: 0.12-0.93) and secondary (HR 0.31, 95% CI: 0.10-0.93) NCBs compared with warfarin. However, primary and secondary NCBs were not reduced in R15. In real-world practice with elderly patients with AF, off-label rivaroxaban dose reduction to 15 mg conferred no benefits. Therefore, guideline-adherent rivaroxaban 20 mg is favorable in elderly Korean patients with AF.


Positron emission tomography-computed tomography standardized uptake values in clinical practice and assessing response to therapy.
The use of standardized uptake values (SUVs) is now common place in clinical 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG) position emission tomography-computed tomography oncology imaging and has a specific role in assessing patient response to cancer therapy. Ideally, the use of SUVs removes variability introduced by differences in patient size and the amount of injected FDG. However, in practice there are several sources of bias and variance that are introduced in the measurement of FDG uptake in tumors and also in the conversion of the image count data to SUVs. In this article the overall imaging process is reviewed and estimates of the magnitude of errors, where known, are given. Recommendations are provided for best practices in improving SUV accuracy.


The Evolution of an Invasive Plant, Sorghum halepense L. ('Johnsongrass').
From noble beginnings as a prospective forage, polyploid Sorghum halepense ('Johnsongrass') is both an invasive species and one of the world's worst agricultural weeds. Formed by S. bicolor x S. propinquum hybridization, we show S. halepense to have S. bicolor-enriched allele composition and striking mutations in 5,957 genes that differentiate it from representatives of its progenitor species and an outgroup. The spread of S. halepense may have been facilitated by introgression from closely-related cultivated sorghum near genetic loci affecting rhizome development, seed size, and levels of lutein, a photochemical protectant and abscisic acid precursor. Rhizomes, subterranean stems that store carbohydrates and spawn clonal propagules, have growth correlated with reproductive rather than other vegetative tissues, and increase survival of both temperate cold seasons and tropical dry seasons. Rhizomes of S. halepense are more extensive than those of its rhizomatous progenitor S. propinquum, with gene expression including many alleles from its non-rhizomatous S. bicolor progenitor. The first surviving polyploid in its lineage in ∼96 million years, its post-Columbian spread across six continents carried rich genetic diversity that in the United States has facilitated transition from agricultural to non-agricultural niches. Projected to spread another 200-600 km northward in the coming century, despite its drawbacks S. halepense may offer novel alleles and traits of value to improvement of sorghum.


East Asian summer monsoon precipitation variability since the last deglaciation.
The lack of a precisely-dated, unequivocal climate proxy from northern China, where precipitation variability is traditionally considered as an East Asian summer monsoon (EASM) indicator, impedes our understanding of the behaviour and dynamics of the EASM. Here we present a well-dated, pollen-based, ~20-yr-resolution quantitative precipitation reconstruction (derived using a transfer function) from an alpine lake in North China, which provides for the first time a direct record of EASM evolution since 14.7 ka (ka = thousands of years before present, where the "present" is defined as the year AD 1950). Our record reveals a gradually intensifying monsoon from 14.7-7.0 ka, a maximum monsoon (30% higher precipitation than present) from ~7.8-5.3 ka, and a rapid decline since ~3.3 ka. These insolation-driven EASM trends were punctuated by two millennial-scale weakening events which occurred synchronously to the cold Younger Dryas and at ~9.5-8.5 ka, and by two centennial-scale intervals of enhanced (weakened) monsoon during the Medieval Warm Period (Little Ice Age). Our precipitation reconstruction, consistent with temperature changes but quite different from the prevailing view of EASM evolution, points to strong internal feedback processes driving the EASM, and may aid our understanding of future monsoon behaviour under ongoing anthropogenic climate change.


Multisystem crisis in a patient with presumptive renal cell carcinoma.
We describe the case of a patient who presented with a kidney lesion, lymphadenopathy, and bone metastasis. He developed a tetrad of high fever, encephalopathy, labile blood pressure, and multiple organ system failure. Initially, he was diagnosed with metastatic renal cell carcinoma (RCC). His fevers and encephalopathy were compatible with a putative paraneoplastic syndrome. Eventually, he was found to have malignant pheochromocytoma. To our knowledge, this is the first reported case of a malignant pheochromocytoma with multisystem crisis. Because of its atypical presentation and unusual findings, a high index of suspicion is necessary for the timely diagnosis of this clinical entity. Prompt diagnosis and appropriate treatments could improve the performance status and quality of life of such patients.


Effects of ion substitution on bile acid-dependent and -independent bile formation by rat liver.
To characterize the transport mechanisms responsible for formation of canalicular bile, we have examined the effects of ion substitution on bile acid-dependent and bile acid-independent bile formation by the isolated perfused rat liver. Complete replacement of perfusate sodium with choline and lithium abolished taurocholate-induced choleresis and reduced biliary taurocholate output by greater than 70%. Partial replacement of perfusate sodium (25 of 128 mM) by choline reduced bile acid-independent bile formation by 30% and replacement of the remaining sodium (103 mM) by choline reduced bile acid-independent bile formation by an additional 64%. In contrast, replacement of the remaining sodium (103 mM) by lithium reduced bile acid-independent bile formation by only an additional 20%, while complete replacement of sodium (128 mM) by lithium reduced bile formation by only 17%, and lithium replaced sodium as the predominant biliary cation. Replacement of perfusate bicarbonate by Tricine, a zwitterionic amino acid buffer, decreased bile acid-independent bile formation by greater than or equal to 50% and decreased biliary bicarbonate output by approximately 60%, regardless of the accompanying cation. In separate experiments, replacement of sodium by lithium essentially abolished Na,K-ATPase activity measured either as ouabain-suppressible ATP hydrolysis in rat liver or kidney homogenates, or as ouabain-suppressible 86Rb uptake by cultured rat hepatocytes. These studies indicate that bile acid(taurocholate)-dependent bile formation by rat liver exhibits a specific requirement for sodium, a finding probably attributable to the role(s) of sodium in hepatic sodium-coupled taurocholate uptake and/or in maintenance of Na,K-ATPase activity. The surprising finding that bile acid-independent bile formation was substantially unaltered by complete replacement of sodium with the permeant cation lithium does not appear to be explained by Na,K-ATPase-mediated lithium transport. Although alternative interpretations exist, this observation is consistent with the hypothesis that much of basal bile acid-independent bile formation is attributable to an ion pump other than Na,K-ATPase, which directly or indirectly mediates bicarbonate transport.


Characterization of an active ingredient made of nanoscale iron(oxyhydr)oxide for the treatment of hyperphosphatemia.
Kidney disease is one of the main non-communicable diseases. Every year millions of people worldwide die from kidney dysfunction. One cause is disturbances in the mineral metabolism, such as abnormally high phosphate concentrations in the blood, medically referred to as hyperphosphatemia. A new active ingredient based on nanoscale iron(oxyhydr)oxide with particle sizes below 3 nm surrounded by an organic coating has been developed for a more effective treatment. The examination of the structural properties of these particles within this study promises to gain further insights into this improved effectiveness. More than half of the active ingredient consists of organic substances, the rest is mostly iron(oxyhydr)oxide. Analyzes by transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) show that the organic molecules act as stabilizers and lead to ultrasmall iron(oxyhydr)oxide cores with a size of 1.0-2.8 nm. The nanoparticles coated with the organic molecules have an average size of 11.7 nm. At 4.2 K, the nanoparticles display a magnetic hyperfine field of 45.5 T in the Mössbauer spectrum, which is unusually low for iron(oxyhydr)oxide. The material is also not ferrimagnetic. Combining these results and taking into account the composition of the nanoparticles, we identify low crystalline ferrihydrite as the most likely phase in the iron(oxyhydr)oxide nuclei. At the same time, we want to emphasize that a final identification of the crystal structure in iron(oxyhydr)oxides can be impeded by ultrasmall particle sizes. In summary, by a combinatorial characterization, we are able to observe extraordinary properties of the ultrasmall nanomaterial, which is the basis for the investigation of the high phosphate-binding efficacy of this active ingredient.


Long noncoding RNA in cardiac aging and disease.
Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in Western society and present an important age-related risk. With the constant rise in life expectancy, prevalence of CVD in the population will likely increase further. New therapies, especially in the elderly, are needed to combat CVD. This review is focused on the role of long noncoding RNA (lncRNA) in CVD. RNA sequencing experiments in the past decade showed that most RNA does not code for protein, but many RNAs function as ncRNA. Here, we summarize the recent findings of lncRNA regulation in the diseased heart. The potential use of these RNAs as biomarkers of cardiac disease prediction is also discussed.


[Parental beliefs on medication and satisfaction with child healthcare].
The aim of this study is to explore a possible significant relationship between parental beliefs about medication and satisfaction with the medical care their children receive in two different healthcare settings. The study included a total of 1,517 parents whose children were being treated either in pediatric primary care or pediatric emergency centers in eastern Andalusia. Of these, 489 were men and 1,028 women. The research instruments used were the Beliefs about Medicines Questionnaire (BMQ) and the Scale of Satisfaction with Health Care Services. Our results indicate that high levels of negative beliefs about medication were significantly associated with lower levels of parent satisfaction with healthcare received. Satisfaction with pediatric healthcare depends on aspects relating to the healthcare system, but certainly personal psychological and social variables like beliefs and parent's previous expectations may play an important role too.


Viral hepatitis and injection drug use in Appalachian Kentucky: a survey of rural health department clients.
We identified correlates of exposure to hepatitis B and C viruses among health department clients in Appalachian Kentucky, a rural region noted for high poverty and low education. Additionally, we investigated risk factors for transmission, and the frequency of use of preventive measures. Patients screened for hepatitis B or C at four county health departments in Appalachian Kentucky were administered a routine prescreening questionnaire and an additional survey designed to obtain detailed personal and behavioral risk factor data. These data were linked to produce a more comprehensive dataset for analysis, including test results, which were attached to the prescreening questionnaire. In total, 92 health department clients participated in the study survey. Of these, test results were available for 80 of the clients. Very few subjects who enrolled in this study tested positive for hepatitis B. Twelve out of 80 participants (15%) tested positive for previous exposure to hepatitis C. No participants reported having human immunodeficiency virus. Transmission of hepatitis C in these rural Appalachian communities is predominantly due to injection drug use. Patients with hepatitis C exposure are similar in their demographic and risk profiles as those seen in urban areas and, despite small numbers, can have a serious impact on small, rural public health systems.


A longitudinal study of feline immunodeficiency virus-specific cytotoxic T lymphocytes in experimentally infected cats, using antigen-specific induction.
The evolution of the virus-specific cytotoxic T-lymphocyte response in two cats experimentally infected with feline immunodeficiency virus (FIV) was monitored. Effector cells were derived from peripheral blood lymphocytes during the acute and chronic phases of infection (0 to 21 and 62 to 127 weeks, respectively) and from the spleen and lymph nodes at 127 weeks after infection. Lymphocytes were restimulated in vitro with paraformaldehyde-fixed, autologous lymphoblasts which had been infected with recombinant vaccinia viruses expressing FIV GAG or ENV proteins. Unstimulated lymphocytes were also used as effectors in some assays. 51Cr-labelled autologous skin fibroblasts infected with recombinant vaccinia viruses were used as targets. FIV GAG-specific cytotoxic precursors were detected in restimulated circulating lymphocytes during acute infection in both cats. The onset of this activity was as early as 2 weeks postinfection (p.i.) in one cat. From 62 weeks p.i. neither FIV GAG- nor ENV-specific precursors could be detected in the peripheral blood. However, at 127 weeks p.i., GAG- and ENV-specific cytotoxic precursors were detected in lymphocytes isolated from lymph nodes. The FIV-specific cytotoxic cells were predominantly major histocompatibility complex class I restricted. No cytotoxic activity was detected from unstimulated lymphocytes. These studies demonstrate the use of an assay system for dissecting the FIV-specific cytotoxic cell response and show that precursor cells appear in the circulation very early after infection and prior to a detectable antibody response. Our results also suggest that the persistent high-level circulating antiviral cytotoxic T-lymphocyte responses seen in human immunodeficiency virus-infected humans may not be a feature of FIV infections in cats.


Pesticides Decrease Bacterial Diversity and Abundance of Irrigated Rice Fields.
Bacteria play an important role in soil ecosystems and their activities are crucial in nutrient composition and recycling. Pesticides are extensively used in agriculture to control pests and improve yield. However, increased use of pesticides on agricultural lands results in soil contamination, which could have adverse effect on its bacterial communities. Here, we investigated the effect of pesticides commonly used on irrigated rice fields on bacterial abundance and diversity. Irrigated soil samples collected from unexposed, pesticide-exposed, and residual exposure areas were cultured under aerobic and anaerobic conditions. DNA was extracted and analysed by 16S rRNA sequencing. The results showed overall decrease in bacterial abundance and diversity in areas exposed to pesticides. Operational taxonomic units of the genera Enterobacter, Aeromonas, Comamonas, Stenotrophomonas, Bordetella, and Staphylococcus decreased in areas exposed to pesticides. Conversely, Domibacillus, Acinetobacter, Pseudomonas, and Bacillus increased in abundance in pesticide-exposed areas. Simpson and Shannon diversity indices and canonical correspondence analysis demonstrated a decrease in bacterial diversity and composition in areas exposed to pesticides. These results suggest bacteria genera unaffected by pesticides that could be further evaluated to identify species for bioremediation. Moreover, there is a need for alternative ways of improving agricultural productivity and to educate farmers to adopt innovative integrated pest management strategies to reduce deleterious impacts of pesticides on soil ecosystems.


Randomness increases self-reported anxiety and neurophysiological correlates of performance monitoring.
Several prominent theories spanning clinical, social and developmental psychology suggest that people are motivated to see the world as a sensible orderly place. These theories presuppose that randomness is aversive because it is associated with unpredictability. If this is the case, thinking that the world is random should lead to increased anxiety and heightened monitoring of one's actions and their consequences. Here, we conduct experimental tests of both of these ideas. Participants read one of three passages: (i) comprehensible order, (ii) incomprehensible order and (iii) randomness. In Study 1, we examined the effects of these passages on self-reported anxiety. In Study 2, we examined the effects of the same manipulation on the error-related negativity (ERN), an event-related brain potential associated with performance monitoring. We found that messages about randomness increased self-reported anxiety and ERN amplitude relative to comprehensible order, whereas incomprehensible order had intermediate effects. These results lend support to the theoretically important idea that randomness is unsettling because it implies that the world is unpredictable.


Well water contamination in a rural community in southwestern Pennsylvania near unconventional shale gas extraction.
Reports of ground water contamination in a southwestern Pennsylvania community coincided with unconventional shale gas extraction activities that started late 2009. Residents participated in a survey and well water samples were collected and analyzed. Available pre-drill and post-drill water test results and legacy operations (e.g., gas and oil wells, coal mining) were reviewed. Fifty-six of the 143 respondents indicated changes in water quality or quantity while 63 respondents reported no issues. Color change (brown, black, or orange) was the most common (27 households). Well type, when known, was rotary or cable tool, and depths ranged from 19 to 274 m. Chloride, sulfate, nitrate, sodium, calcium, magnesium, iron, manganese and strontium were commonly found, with 25 households exceeding the secondary maximum contaminate level (SMCL) for manganese. Methane was detected in 14 of the 18 houses tested. The 26 wells tested for total coliforms (2 positives) and E. coli (1 positive) indicated that septic contamination was not a factor. Repeated sampling of two wells in close proximity (204 m) but drawing from different depths (32 m and 54 m), revealed temporal variability. Since 2009, 65 horizontal wells were drilled within a 4 km (2.5 mile) radius of the community, each well was stimulated on average with 3.5 million gal of fluids and 3.2 million lbs of proppant. PA DEP cited violations included an improperly plugged well and at least one failed well casing. This study underscores the need for thorough analyses of data, documentation of legacy activity, pre-drill testing, and long term monitoring.


Nociceptin and its natural and specifically-modified fragments: Structural studies.
The vibrational structures of Nociceptin (FQ), its short bioactive fragments, and specifically-modified [Tyr¹]FQ (1-6), [His¹]FQ (1-6), and [His(1,4)]FQ (1-6) fragments were characterized. We showed that in the solid state, all of the aforementioned peptides except FQ adopt mainly turn and disordered secondary structures with a small contribution from an antiparallel β-sheet conformation. FQ (1-11), FQ (7-17) [His¹]FQ (1-6), and [His(1,4)]FQ (1-6) have an α-helical backbone arrangement that could also slightly influence their secondary structure. The adsorption behavior of these peptides on a colloidal silver surface in an aqueous solution (pH = ∼8.3) was investigated by means of surface-enhanced Raman scattering (SERS). All of the peptides, excluding FQ (7-17), chemisorbed on the colloidal silver surfaces through a Phe⁴ residue, which for FQ, FQ (1-11), FQ (1-6), [Tyr¹]FQ (1-6), and [His¹]FQ (1-6) lies almost flat on this surface, while for FQ (1-13) and FQ (1-13)NH₂ adopts a slightly tilted orientation with respect to the surface. The Tyr¹ residue in [Tyr¹]FQ (1-6) does not interact with the colloidal silver surface, suggesting that the Tyr¹ and Phe⁴ side chains are located on the opposite sides of the peptide backbone, which can be also true for His¹ and Phe⁴ in [His¹]FQ (1-6). The lone pair of electrons on the oxygen atom of the ionized carbonyl group of FQ (1-13) and FQ (7-17) appears to be coordinated to the colloidal silver nanoparticles, whereas in the case of the remaining peptides, it only assists in the adsorption process, similar to the --NH⁴ group. We also showed that upon adsorption, the secondary structure of these peptides is altered.


Bacterial type VII secretion: An important player in host-microbe and microbe-microbe interactions.
Type VII secretion systems (T7SSs) are poorly understood protein export apparatuses found in mycobacteria and many species of Gram-positive bacteria. To date, this pathway has predominantly been studied in Mycobacterium tuberculosis, where it has been shown to play an essential role in virulence; however, much less studied is an evolutionarily divergent subfamily of T7SSs referred to as the T7SSb. The T7SSb is found in the major Gram-positive phylum Firmicutes where it was recently shown to target both eukaryotic and prokaryotic cells, suggesting a dual role for this pathway in host-microbe and microbe-microbe interactions. In this review, we compare the current understanding of the molecular architectures and substrate repertoires of the well-studied mycobacterial T7SSa systems to that of recently characterized T7SSb pathways and highlight how these differences may explain the observed biological functions of this understudied protein export machine.


The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology.
Throughout history malaria has proved to be a significant threat to human health. Between 300 and 500 million clinical cases occur each year worldwide, approximately 2 million of which are fatal, primarily in children. The vast majority of malaria-related deaths are due to infection with Plasmodium falciparum; P. vivax causes severe febrile illness but is rarely fatal. Following repeated exposure to infection, people living in malaria endemic areas gradually acquire mechanisms to limit the inflammatory response to the parasite that causes the acute febrile symptoms (clinical immunity) as well as mechanisms to kill parasites or inhibit parasite replication (antiparasite immunity). Children, who have yet to develop protective immune mechanisms are thus at greater risk of clinical malaria, severe disease and death than adults. However, two epidemiological observations indicate that this is, perhaps, an oversimplified model. Firstly, cerebral malaria - a common manifestation of severe malaria - typically occurs in children who have already acquired a significant degree of antimalarial immunity, as evidenced by lower mean parasite densities and resistance to severe anaemia. One potential explanation is that cerebral malaria is, in part, an immune-mediated disease in which immunological priming occurs during first infection, eventually leading to immunopathology on re-infection. Secondly, among travelers from nonendemic areas, severe malaria is more common - and death rates are higher - in adults than in children. If severe malaria is an immune-mediated disease, what might be priming the immune system of adults from nonendemic areas to cause immunopathology during their first malaria infection, and how do adults from endemic areas avoid severe immunopathology? In this review we consider the role of innate and adaptive immune responses in terms of (i) protection from clinical malaria (ii) their potential role in immunopathology and (iii) the subsequent development of clinical immunity. We conclude by proposing a model of antimalarial immunity which integrates both the immunological and epidemiological data collected to date.


An in vivo study of electrical charge distribution on the bacterial cell wall by atomic force microscopy in vibrating force mode.
We report an in vivo electromechanical atomic force microscopy (AFM) study of charge distribution on the cell wall of Gram+ Rhodococcus wratislaviensis bacteria, naturally adherent to a glass substrate, under physiological conditions. The method presented in this paper relies on a detailed study of AFM approach/retract curves giving the variation of the interaction force versus distance between the tip and the sample. In addition to classical height and mechanical (as stiffness) data, mapping of local electrical properties, such as bacterial surface charge, was proved to be feasible at a spatial resolution better than a few tens of nanometers. This innovative method relies on the measurement of the cantilever's surface stress through its deflection far from (>10 nm) the repulsive contact zone: the variations of surface stress come from the modification of electrical surface charge of the cantilever (as in classical electrocapillary measurements) likely stemming from its charging during contact of both the tip and the sample electrical double layers. This method offers an important improvement in local electrical and electrochemical measurements at the solid/liquid interface, particularly in high-molarity electrolytes when compared to techniques focused on the direct use of electrostatic force. It thus opens a new way to directly investigate in situ biological electrical surface processes involved in numerous practical applications and fundamental problems such as bacterial adhesion, biofilm formation, microbial fuel cells, etc.


Designing and implementing a skills program using a clinically integrated, multi-professional approach: using evaluation to drive curriculum change.
The essential procedural skills that newly graduated doctors require are rarely defined, do not take into account pre-vocational employer expectations, and differ between Universities. This paper describes how one Faculty used local evaluation data to drive curriculum change and implement a clinically integrated, multi-professional skills program. A curriculum restructure included a review of all undergraduate procedural skills training by academic staff and clinical departments, resulting in a curriculum skills map. Undergraduate training was then linked with postgraduate expectations using the Delphi process to identify the skills requiring structured standardised training. The skills program was designed and implemented without a dedicated simulation center. This paper shows the benefits of an alternate model in which clinical integration of training and multi-professional collaboration encouraged broad ownership of a program and, in turn, impacted the clinical experience obtained.


Detection of Epstein-Barr Virus in inflammatory pseudotumor.
Inflammatory pseudotumors appear to represent a heterogeneous group of diseases that share common histopathologic features. A subset of these tumors, particularly those in the spleen and liver, harbor the Epstein-Barr virus (EBV) in spindled cells. Methods for detecting EBV in these tumors and the reliability of the different detection methods are discussed. Some EBV-positive inflammatory pseudotumors contain an increase in EBV-positive follicular dendritic cells and demonstrate monoclonal EBV genomes. At least one such case has recurred locally as an unusual EBV-positive follicular dendritic cell tumor. These rare reports support the concept of a distinct EBV-positive, follicular dendritic cell type of inflammatory pseudotumor that may be at increased risk for local recurrence. Many more cases of this rare type of inflammatory pseudotumor must be studied and reported before the clinical validity of such a distinction can be proven. Although EBV detection in spindled cells is unusual, it has been demonstrated in rare smooth muscle tumors arising in immunosuppressed children and young adults.


Coexistent multiple myeloma and primary hyperparathyroidism.
A patient with multiple myeloma and hypercalcemia responded to cytotoxic chemotherapy. However, hypercalcemia persisted. Because of the absence of lytic bone lesions, the presence of a low serum phosphate level, and a family history of possible primary hyperparathyroidism, the patient was evaluated for this disorder. Serum parathyroid hormone and urinary cyclic adenosine monophosphate levels were elevated. Exploration of the neck disclosed two enlarged parathyroid glands (1,850 mg and 210 mg), which were excised. After surgery, the patient's serum calcium levels remained normal for one year. Progressive myeloma bone disease developed that eventually resulted in recurrent hypercalcemia and death. Autopsy revealed only evidence of myeloma.


[The role of the top-down inhibitory control in providing flexibility of cortical processes of recognition of emotional face expression].
On the ground of own and those found in literature it is argued that the neural mechanism of implicit estimation of time intervals between significant visual events should be considered in the framework of top-down cognitive control. Based on that view, putative mechanism of active inhibition are considered. Based on the set model on recognition of emotionally negative face expression it is shown that implicit estimation of time intervals between significant visual events plays an important role in providing flexibility of cognitive processes.


Expression and prognostic roles of TRPV5 and TRPV6 in non-small cell lung cancer after curative resection.
We investigated the expression of epithelial Ca2+ channel transient receptor potential vanilloid (TRPV) 5 and 6 in non-small-cell lung cancer (NSCLC) and assessed their prognostic role in patients after surgical resection. From January 2008 to January 2009, 145 patients who had undergone surgical resection of NSCLCs were enrolled in the study. Patient clinical characteristics were retrospectively reviewed. Fresh tumor samples as well as peritumor tissues were analyzed for TRPV5/6 expression using immune-histochemistry (IHC) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Patients were grouped based on their TRPV5 and TRPV6 levels in the tumor tissues, followed up after surgery, and statistically analyzed to examine the prognostic roles of TRPV5 and TRPV6 on patients' survival after surgical resection of NSCLCs. Using IHC, among the 145 patients who had undergone surgical resection of NSCLCs, strong protein expression (grade ≥ 2) of TRPV5 and TRPV6 was observed in a lower percentage of primary tumor tissues than in non-tumor tissues of same patients. Similar findings were obtained with the RT-PCR test for mRNA levels. Decreased overall mRNA levels of TRPV5 and TRPV6 were associated with a worse overall survival rate (p=0.004 and p=0.003 respectively) and shorter recurrence-free survival (p?0.001 and p?0.001 respectively). The combining effect of TRPV5 and TRPV6 on survival was further investigated using multivariate analysis. The results showed that a combination of low expression of TRPV5 and TRPV6 could be an independent predictor of poor recurrence-free survival (p=0.002). Decreased expression of TRPV5/6 in tumor tissues was observed in NSCLC patients and was associated with shorter median survival time after surgical resection. Combined expression of TRPV5 and TRPV6 in tumor tissues demonstrated promising prognostic value in NSCLC patients.


[Dynamic basic reproduction number based evaluation for current prevention and control of COVID-19 outbreak in China].
Objective: To evaluate the current status of the prevention and control of coronavirus disease (COVID-19) outbreak in China, establish a predictive model to evaluate the effects of the current prevention and control strategies, and provide scientific information for decision-making departments. Methods: Based on the epidemic data of COVID-19 openly accessed from national health authorities, we estimated the dynamic basic reproduction number R(0)(t) to evaluate the effects of the current COVID-19 prevention and control strategies in all the provinces (municipalities and autonomous regions) as well as in Wuhan and the changes in infectivity of COVID-19 over time. Results: For the stability of the results, 24 provinces (municipality) with more than 100 confirmed COVID-19 cases were included in the analysis. At the beginning of the outbreak, the R(0)(t) showed unstable trend with big variances. As the strengthening of the prevention and control strategies, R(0)(t) began to show a downward trend in late January, and became stable in February. By the time of data analysis, 18 provinces (municipality) (75%) had the R(0)(t)s less than 1. The results could be used for the decision making to free population floating conditionally. Conclusions: Dynamic R(0)(t) is useful in the evaluation of the change in infectivity of COVID-19, the prevention and control strategies for the COVID-19 outbreak have shown preliminary effects, if continues, it is expected to control the COVID-19 outbreak in China in near future.


Alpha-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells.
Staphylococcus aureus is a pathogen that causes serious infectious diseases eventually leading to septic and toxic shock. Classically S. aureus has been considered an extracellular pathogen, but cumulative evidence indicates that it invades cells and replicates intracellularly leading to staphylococcal persistence and chronic disease. It has been previously shown that this pathogen localizes to LC3-labeled compartments and subverts the autophagy pathway. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. In the present report we present evidence that the pore-forming toxin alpha-hemolysin (Hla) is a S. aureus secreted factor which participates in the activation of the autophagic pathway. In addition, our results indicate that although the toxin elicits an autophagic response this pathway is dysfunctional as indicated by the accumulation of the LC3-II form in cell lysates obtained from intoxicated cells. In addition, not only the purified Hla toxin but also the toxin-secreting pathogen prevented the maturation of autophagosomes. Interestingly, in cells infected with the wild-type strain of S. aureus the bacteria-containing compartments which recruited LC3 onto the limiting membrane did not accumulate the acidotropic probe LysoTracker. In contrast, those phagosomes containing the Hla(-) mutant (unable to produce the toxin) localized in an acidic compartment unlabeled by LC3. These results suggest that the LC3 protein is recruited only to those damaged vacuoles (i.e., perforated by the toxin), perhaps as an attempt to protect the cells. Furthermore, we have demonstrated that the toxin-dependent activation of autophagy (although it is regulated by calcium and requires Atg5) is independent of both PI3Kinase activity and Beclin 1 suggesting the involvement of a non-canonical autophagy pathway.


On the role of cyclic nucleotides in the transmitter choice made by cultured sympathetic neurons.
Previous investigations have established that electrical activity or chronic depolarization influences the development of neonatal rat sympathetic neurons in dissociated cell culture. Depolarization reduces their ability to respond to a cholinergic inducing factor produced by non-neuronal cells, allowing normal adrenergic differentiation to proceed (Walicke, P., R. Campenot, and P. Patterson (1977) Proc. Natl. Acad. Sci. U. S. A. 74: 5767-5771). The present study examines whether the developmental effects of depolarization are mediated through cyclic nucleotides. Addition of dibutyryl cAMP, dibutyryl cGMP, adenosine, prostaglandin E1, and cholera toxin all raise neuronal cyclic nucleotide levels and qualitatively mimic the developmental effects of depolarization. However, the quantitative decrease in acetylcholine production caused by these cyclic nucleotide agents is much smaller than that caused by depolarization. Short (48-hr) exposures to the cyclic nucleotide derivatives do not alter transmitter synthesis, indicating that long term developmental changes are involved. Chronic depolarization with elevated K+ increases neuronal cAMP 2-fold but has little effect on cGMP. The increase in cAMP is maintained during several weeks of depolarization and is present as early as the 3rd day in vitro, preceding the significant alterations in adrenergic and cholinergic differentiation. Exposure to 2 mM theophylline also increases neuronal cAMP, but in contrast to the other agents, it enhances cholinergic differentiation. In combination with elevated K+, theophylline further increases neuronal cAMP but still favors cholinergic differentiation. Thus, although cAMP satisfies some criteria for being the second messenger in the developmental effects of depolarization, several findings are consistent with the nucleotide playing a central role: (i) Depolarization has much larger effects on transmitter choice than the cyclic nucleotide agents and (ii) theophylline can uncouple cyclic nucleotide levels from the developmental events.


Nuclear acceptor sites for sex steroid hormone receptors in chromatin.
The steroid receptor interactions in vitro with specific acceptor sites composed of acceptor protein-DNA complexes fulfill many of the criteria of a physiologically significant binding system. Chromatin acceptor sites for many steroid receptors (especially for the progesterone and estrogen receptor) are specific since they are saturable and competitive with unlabelled receptors, have high affinity for the receptor, distinguish between functional and nonfunctional receptors and demonstrate target tissue specificity. Pure DNA as acceptor sites does not display many of these properties. Therefore, it is clear that certain chromatin proteins provide the necessary specificity for the acceptor sites for the steroid receptors. For the progesterone receptor in the chick oviduct, these nuclear sites appear to contain specific chromosomal proteins as well as specific DNA sequences. The substitution of other chromosomal proteins or the genomic DNAs from evolutionarily distant organisms results in a loss of the specific nuclear binding. The nuclear acceptor sites appear to be resistant to the DNase activity which is not characteristic of transcriptionally active domains of the genome. Further studies using the ovalbumin gene sequences from genomic clones also indicate that none of the sequences within this domain and the 3-k flanking regions appear to contain the specific acceptor sequences. These observations have led to development of a model suggesting that the steroid receptors bind to acceptor sites distant from the structural genes the steroids ultimately regulate. Neighboring these acceptor sites are regulatory genes which code for regulatory substances which in turn (as secondary messengers) regulate at great distances the expression of the structural gene. This model might better fit the sex steroids which require 1-2 h to measurably alter gene transcription, as opposed to the glucocorticoids which more rapidly alter gene expression.


Imaging with Raman spectroscopy.
Raman spectroscopy, based on the inelastic scattering of a photon, has been widely used as an analytical tool in many research fields. Recently, Raman spectroscopy has also been explored for biomedical applications (e.g. cancer diagnosis) because it can provide detailed information on the chemical composition of cells and tissues. For imaging applications, several variations of Raman spectroscopy have been developed to enhance its sensitivity. This review article will provide a brief summary of Raman spectroscopy-based imaging, which includes the use of coherent anti-Stokes Raman spectroscopy (CARS, primarily used for imaging the C-H bond in lipids), surface-enhanced Raman spectroscopy (SERS, for which a variety of nanoparticles can be used as contrast agents), and single-walled carbon nanotubes (SWNTs, with its intrinsic Raman signal). The superb multiplexing capability of SERS-based Raman imaging can be extremely powerful in future research where different agents can be attached to different Raman tags to enable the interrogation of multiple biological events simultaneously in living subjects. The primary limitations of Raman imaging in humans are those also faced by other optical techniques, in particular limited tissue penetration. Over the last several years, Raman spectroscopy imaging has advanced significantly and many critical proof-of-principle experiments have been successfully carried out. It is expected that imaging with Raman Spectroscopy will continue to be a dynamic research field over the next decade.


Biomechanics of soft tissues.
Recent developments in Computer-Integrated and Robot-Aided Surgery (in particular, the emergence of automatic surgical tools and robots (as well as advances in Virtual Reality techniques, call for closer examination of the mechanical properties of very soft tissues (such as brain, liver, kidney, etc.). Moreover, internal organs are very susceptible to trauma. In order to protect them properly against car crash and other impact consequences we need to be able to predict the organ deformation. Such prediction can be achieved by proper mathematical modelling followed by a computer simulation. The ultimate goal of our research into the biomechanics of these tissues is development of corresponding, realistic mathematical models. This paper contains experimental results of in vitro, uniaxial, unconfined compression of swine brain tissue obtained by the author in Mechanical Engineering Laboratory, Japan, and discusses liver and kidney in vivo compression experiments conducted in Highway Safety Research Institute and the Medical Centre of The University of Michigan. The stress-strain curves for investigated tissues are concave upward for all compression rates containing no linear portion from which a meaningful elastic modulus might be determined. The tissue response stiffened as the loading speed increased, indicating a strong stress (strain rate dependence. As the step in the direction towards realistic computer simulation of injuries and surgical procedures, this paper presents two mathematical representations of brain, liver and kidney tissue stiffness. Biphasic and single-phase models are discussed. The biphasic model is shown to be inappropriate due to its inability to account for strong stress-strain relationship. Agreement between the proposed single-phase models and experiment is good for compression levels reaching 30% and for loading velocities varying over five orders of magnitude. Presented mathematical models can find applications in computer and robot assisted surgery, e.g. the realistic simulation of surgical procedures (including virtual reality), control systems of surgical robots, and non-rigid registration, as well as ergonomic design for injury prevention.


In vitro cytotoxicity of resin-containing restorative materials after aging in artificial saliva.
Studies have reported that dental resin-based materials release substances which have biological liabilities. However, some current methods for detecting these substances may not be adequate to detect biologically relevant concentrations. In the current study, we hypothesized that resin-based materials exhibit cytotoxic effects and alter cellular function in vitro when high-pressure liquid chromatography (HPLC-UV detection) cannot detect any release of substances. We further hypothesized that this release continues even after aging the samples in artificial saliva. Five types of composite or compomer materials (Z-100, Tetric Ceram, Dyract AP, Solitaire, and Clearfil AP-X) and one organically modified ceramic material (Definite) were tested after aging in artificial saliva for 0, 7, or 14 days. Cytotoxicity was assessed using direct contact with fibroblasts and measurement of succinic dehydrogenase activity after 48 h of exposure post aging. Release of substances from the materials was assessed using HPLC with UV detection. Altered cellular function was estimated by measuring proliferation of MCF-7 cells with sulforhodamine staining. HPLC showed that whereas initial release of substances was higher without aging, this release dropped significantly after 7 or 14 days of aging, and was equivalent to the Teflon controls after 14 days for four of the materials (Tetric Ceram, Definite, Solitaire, and Clearfil AP-X). Without aging in saliva, all materials had cytotoxicities > 50% of the Teflon negative controls. After 14 days of aging, all materials except the Definite continued to show severe cytotoxicity. Only the Definite could be tested for its ability to alter cellular function because of the continuing toxicity of the other materials. This modified ceramic material caused a significant proliferative effect on the MCF-7 cells indicating that sufficient substances were released to alter cellular function. We concluded that all of these commercially available resin-based dental materials continue to release sufficient components to cause lethal effects or alter cellular function in vitro even after 2 weeks of aging in artificial saliva.


Preparation of a recombinant chimaera of insulin-like growth factor II and interleukin 3 with high proliferative potency for haemopoietic cells.
We have found that a slightly modified insulin-like growth factor II (IGF II) consisting of a chimaera of bombyxin and human IGF II (BOMIGF) is properly secreted in insect cells by using the baculovirus expression system. Human interleukin 3 (IL-3) was attached to the C-terminal amino acid residue of BOMIGF with peptide linkers containing five or twelve residues. Only the chimaera with the 12-residue linker had biological activities of both IGF II and IL-3. The chimaera had a significantly higher mitogenic activity than IL-3 in cell cultures of the human haemopoietic cell line TF-1 and its effect could be observed even at femtomolar concentrations. It was also able to stimulate thymidine incorporation in IGF II-dependent bovine fetal erythroid cells. The chimaera significantly increased the number of macroscopic haemopoietic colonies in cultures of human peripheral blood in comparison with IL-3 or mixtures of IL-3 and BOMIGF in vitro. Subcutaneous injection of a BOMIGF-mouse IL-3 chimaera in normal C57BL/6 mice resulted in a significant increase of the number of spleen stem cells producing macroscopic haemopoietic colonies. This new system for the biosynthesis of IGF-cytokine fusion proteins in insect cells might prove advantageous for the low-cost and high-yield production of molecules with complementary or synergistic biological activities.


Influence of pre-treatment step on PAHs analyses in contaminated soils.
There is no specific standardization for the pre-treatment of a soil sample for PAHs analyses. The ISO/FDIS 14507 method for soil quality gives a guidance for sample pre-treatment before measurement of organic contaminants in soil. It refers to cryogenic crushing which is not so easy to carry out. So, analysts lead to develop in house methods which can be very different from a laboratory to another and can involve deviations in the pollution quantification. This study has explored different ways of drying, grinding and sieving in order to determine the influence of the soil sample handling on the measured pollutant concentration. It appears that the influence of pre-treatment depends on the soil nature and on the PAHs distribution. As a conclusion, it is advised "light" drying ways like air drying or drying at 40 degrees C in a drying oven instead of more "drastic" ways (freeze-drying, cryogenic crushing) which can induce some losses. Crushing and sieving are also recommended for more reproducible measures.


Suprachoroideal haemorrhage in postoperative period of antiglaucoma surgery, case report.
Suprachoroidal haemorrhage (SCH) is a serious complication of intraocular procedures. Physiologically there is only a minimal amount of fluid in the suprachoroid space, pathologically the fluid volume increases, which causes ablation of the choroid. SCH could be divided into different cathegories, according to the character of the fluid into serous and haemorrhagic; by the time of occurrence in relation to the surgery into peroperative and postoperative. Diagnosis is based on biomicroscopic and ultrasound examinations. The ocular risk factors for SCH are glaucoma, myopia and aphakia; systemic risk factors include vascular fragility, arterial hypertension and blood coagulation disorders. In the pathogenesis hypotonia of the eye, that causes rupture of the ciliary vessels, plays a very important role. SCH can be treated both conservatively and surgically. As to pharmacotherapy we use gabapentin to suppress neuropathic pain and prednisone, topical mydriatics and anti-inflammatory agents. The type of surgical treatment differs according to time of occurrence, if SCH occurs during the operation, the intervention consists mainly in the wound closure and the repositioning of the weakening tissues; in postoperative forms, we choose drainage procedures, possibly vitreoretinal procedures. Our patient, an 80-year-old myop and chronic glaucomatic treated intensively both topically and systematically underwent trabeculectomy on his left eye due to unsatisfactory intraocular pressure (IOP) and significant glaucoma progression. The surgical intervention went without any complications. In the early post-operative period, there was persisting elevation of IOP, therefore sclera lap was discontinued and 5-fluorouracil was applied under the filter blister. Subsequent hypotonia caused a hemorrhagic SCH with intraocular hypertension, which was resolved by draining the blood with sclerotomias and thus releasing intraocular hypertension. The visual acuity of the left eye gradually improved to almost original values. Intraocular pressure, however, is not well compensated despite many following antiglaucoma surgeries. Therefore, even with the patients maximum therapy, glaucoma continues to progress. In our case, we confirm that it is possible to solve even the relatively most complicated cases of SCH. We stress the necessity to consider the presence of risk factors of the occurrence of SCH before indicating intraocular procedures and also recommend thinking carefully about other less invasive surgical techniques. In glaucoma, it is appropriate taking in account the prediction of life compared to the expected rate of progression of vision loss.


Rat multipotent mesenchymal stromal cells lack long-distance tropism to 3 different rat glioma models.
Viral gene therapy of malignant brain tumors has been restricted by the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas, and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy. To investigate MSC migration in detail after intratumoral and extratumoral implantation through syngeneic and orthotopic glioma models. Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance from rat gliomas. We found no evidence of long-distance MSC migration through the intact striatum toward syngeneic D74(RG2), N32, and N29 gliomas in the ipsilateral hemisphere or across the corpus callosum to gliomas located in the contralateral hemisphere. After intratumoral injection, MSCs migrated extensively, specifically within N32 gliomas. The MSCs did not proliferate within tumors, suggesting a low risk of malignant transformation of in vivo grafted cell vectors. Using a model for surgical glioma resection, we found that intratumorally grafted MSCs migrate efficiently within glioma remnants after partial surgical resection. The findings point to limitations for the use of MSCs as vectors in glioma gene therapy, although intratumoral MSC implantation provides a dense and tumor-specific vector distribution.


Chemical Characterization of Narcissus poeticus from Sirente -Velino (Apennines - Italy): Galantamine Accumulation and Distribution of Allergenic Compounds in the Flower.
Species of Narcissus (family Amaryllidaceae) are a potential source for large-scale extraction of alkaloids and fragrances. The bulbs typically accumulate a large number of alkaloids, including galantamine, a benzazepine alkaloid proven to be a cholinesterase inhibitor and which is used in the treatment of Alzheimer's disease. The presence of galantamine in N. poeticus L. collected in Abruzzo (Italy) was assessed and several levels of alkaloid were found in all parts of the plant (flower, stem, bulb and root) and not only in the bulb. The amount of galantamine obtained was tested by using two different extraction solvents. Extraction of N. poeticus absolute from the flowers was also performed, as this product is an important floral note in perfumery, and the distribution of allergenic compounds in the coronas and in the tepals was assessed. Moreover, the in vitro propagation of N.:Poeticus was tested as it may be a valuable resource from which to produce biomolecules, as an alternative to chemical synthetic processes.


Local interventions for the management of alveolar osteitis (dry socket).
Alveolar osteitis (dry socket) is a complication of dental extractions and occurs more commonly in extractions involving mandibular molar teeth. It is associated with severe pain developing 2 to 3 days postoperatively, a socket that may be partially or totally devoid of blood clot and in some patients there may be a complaint of halitosis. It can result in an increase in postoperative visits. To assess the effects of local interventions for the prevention and treatment of alveolar osteitis (dry socket) following tooth extraction. The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 29 October 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10), MEDLINE via OVID (1946 to 29 October 2012) and EMBASE via OVID (1980 to 29 October 2012). There were no restrictions regarding language or date of publication. We also searched the reference lists of articles and contacted experts and organisations to identify any further studies. We included randomised controlled trials of adults over 18 years of age who were having permanent teeth extracted or who had developed dry socket post-extraction. We included studies with any type of local intervention used for the prevention or treatment of dry socket, compared to a different local intervention, placebo or no treatment. We excluded studies reporting on systemic use of antibiotics or the use of surgical techniques for the management of dry socket because these interventions are evaluated in separate Cochrane reviews. Two review authors independently undertook risk of bias assessment and data extraction in duplicate for included studies using pre-designed proformas. Any reports of adverse events were recorded and summarised into a table when these were available. We contacted trial authors for further details where these were unclear. We followed The Cochrane Collaboration statistical guidelines and reported dichotomous outcomes as risk ratios (RR) and calculated 95% confidence intervals (CI) using random-effects models. For some of the split-mouth studies with sparse data it was not possible to calculate RR so we calculated the exact odds ratio instead. We used the GRADE tool to assess the quality of the body of evidence. Twenty-one trials with 2570 participants met the inclusion criteria; 18 trials with 2376 participants for the prevention of dry socket and three studies with 194 participants for the treatment of dry socket. The risk of bias assessment identified six studies at high risk of bias, 14 studies at unclear risk of bias and one studies at low risk of bias. When compared to placebo, rinsing with chlorhexidine mouthrinses (0.12% and 0.2% concentrations) both before and after extraction(s) prevented approximately 42% of dry socket(s) with a RR of 0.58 (95% CI 0.43 to 0.78; P < 0.001) (four trials, 750 participants, moderate quality of evidence). The prevalence of dry socket varied from 1% to 5% in routine dental extractions to upwards of 30% in surgically extracted third molars. The number of patients needed to be treated with (0.12% and 0.2%) chlorhexidine rinse to prevent one patient having dry socket (NNT) was 232 (95% CI 176 to 417), 47 (95% CI 35 to 84) and 8 (95% CI 6 to 14) for control prevalences of dry socket of 1%, 5% and 30% respectively.Compared to placebo, placing chlorhexidine gel (0.2%) after extractions prevented approximately 58% of dry socket(s) with a RR of 0.42 (95% CI 0.21 to 0.87; P = 0.02) (two trials, in 133 participants, moderate quality of evidence). The number of patients needed to be treated with chlorhexidine gel to prevent one patient having dry socket (NNT) was 173 (95% CI 127 to 770), 35 (95% CI 25 to 154) and 6 (95% CI 5 to 26) for control prevalences of dry socket of 1%, 5% and 30% respectively.A further 10 intrasocket interventions to prevent dry socket were each evaluated in single studies, and therefore there is insufficient evidence to determine their effects. Five interventions for the treatment of dry socket were evaluated in a total of three studies providing insufficient evidence to determine their effects. Most tooth extractions are undertaken by dentists for a variety of reasons, however, all but three studies included in the present review included participants undergoing extraction of third molars, most of which were undertaken by oral surgeons. There is some evidence that rinsing with chlorhexidine (0.12% and 0.2%) or placing chlorhexidine gel (0.2%) in the sockets of extracted teeth, provides a benefit in preventing dry socket. There was insufficient evidence to determine the effects of the other 10 preventative interventions each evaluated in single studies. There was insufficient evidence to determine the effects of any of the interventions to treat dry socket. The present review found some evidence for the association of minor adverse reactions with use of 0.12%, 0.2% and 2% chlorhexidine mouthrinses, though most studies were not designed to detect the presence of hypersensitivity reactions to mouthwash as part of the study protocol. No adverse events were reported in relation to the use of 0.2% chlorhexidine gel placed directly into a socket (though previous allergy to chlorhexidine was an exclusion criterion in these trials). In view of recent reports in the UK of two cases of serious adverse events associated with irrigation of dry socket with chlorhexidine mouthrinse, it is recommended that all members of the dental team prescribing chlorhexidine products are aware of the potential for both minor and serious adverse side effects.


The cross-table lateral radiograph results in a significantly increased effective radiation dose compared with the Dunn and single frog lateral radiographs.
A lateral radiograph of the proximal femur is critical in the evaluation of patients with suspected femoroacetabular impingement. Positioning patients for a cross-table lateral (XTL) image is difficult, which may result in repeat exposures and increased cumulative radiation. Alternatively, the 45-degree Dunn (Dunn) and single frog lateral (SFL) views have been shown to accurately reveal proximal femoral abnormalities in femoroacetabular impingement. The purpose of this study was to compare the effective radiation doses (ERD) for 3 lateral hip projections that provide similar diagnostic information. Patients presenting to the adolescent hip clinic with indicated examinations were evaluated with a standard anteroposterior (AP) pelvic radiograph and one of 3 lateral hip radiographs: XTL (n=16), Dunn (n=17), or SFL (n=27). Technical exposure parameters and published reference data for an AP pelvic radiograph were used to extrapolate the ERD. A simple Pearson r correlation test determined the relationships between body mass index, age, and ERD. The rate of repeat exposures per study was calculated. Body mass index positively correlated (r=0.34) and age and negatively correlated (r=-0.27) with ERD. ERD was increased for the XTL (0.83±0.98 mSv) over the Dunn (0.37±0.15 mSv) and SFL (0.22±0.11 mSv; P<0.05). Repeat exposures were performed in 10.4%, 4%, and 6% of XTL, Dunn, and SFL studies, respectively. The ERD for a single projection is highest for the XTL, and the examination is more likely to be repeated. The XTL radiograph should be avoided whenever possible and substituted with alternative images providing similar diagnostic information, such as the Dunn or SFL, to minimize lifetime cumulative radiation exposure to the patient. Level II.


Cervical spine injuries resulting from diving accidents in swimming pools: outcome of 34 patients.
Cervical spine injuries after diving into private swimming pools can lead to dramatic consequences. We reviewed 34 patients hospitalized in our center between 1996 and 2006. Data was collected from their initial admission and from follow-up appointments. The injuries were sustained by young men in 97% (mean age 27) and the majority happened during the summer (88%). Fractures were at C5-C7 in 70%. American Spinal Injury Association class (ASIA) on admission was A for 8 patients, B for 4, C for 4, D for 1, and E for 17. There were 23 surgical spine stabilizations. Final ASIA class was A for 6 patients, B for 1, C for 3, D for 5, and E for 18. The mean duration of hospitalization was 21.3 days in our neurosurgical center (mean overall cost: 36,000 Euros/patient) plus 10.6 months in rehabilitation center for the 15 patients admitted who had an ASIA class A to C. Mean overall direct cost for a patient with class A is almost 300,000 Euros, compared to around 10,000 Euros for patients with class D and E. In addition, a profound impact on personal and professional life was seen in many cases including 11 divorces and 7 job losses. Dangerous diving into swimming pools can result in spinal injuries with drastic consequences, including permanent physical disability and a profound impact on socio-professional status. Moreover, there are significant financial costs to society. Better prevention strategies should be implemented to reduce the impact of this public health problem.


Rapid delivery of internalized signaling receptors to the somatodendritic surface by sequence-specific local insertion.
The recycling pathway is a major route for delivering signaling receptors to the somatodendritic plasma membrane. We investigated the cell biological basis for the remarkable selectivity and speed of this process. We focused on the mu-opioid neuropeptide receptor and the beta(2)-adrenergic catecholamine receptor, two seven-transmembrane signaling receptors that traverse the recycling pathway efficiently after ligand-induced endocytosis and localize at steady state throughout the postsynaptic surface. Rapid recycling of each receptor in dissociated neuronal cultures was mediated by a receptor-specific cytoplasmic sorting sequence. Total internal reflection fluorescence microscopy imaging revealed that both sequences drive recycling via discrete vesicular fusion events in the cell body and dendritic shaft. Both sequences promoted recycling via "transient"-type events characterized by nearly immediate lateral spread of receptors after vesicular insertion resembling receptor insertion events observed previously in non-neural cells. The sequences differed in their abilities to produce distinct "persistent"-type events at which inserted receptors lingered for a variable time period before lateral spread. Both types of insertion event generated a uniform distribution of receptors in the somatodendritic plasma membrane when imaged over a 1 min interval, but persistent events uniquely generated a punctate surface distribution over a 10 s interval. These results establish sequence-directed recycling of signaling receptors in CNS neurons and show that this mechanism has the ability to generate receptor-specific patterns of local surface distribution on a timescale overlapping that of rapid physiological signaling.


Myocardial damage detected by late gadolinium enhancement cardiovascular magnetic resonance is associated with subsequent hospitalization for heart failure.
Hospitalization for heart failure (HHF) is among the most important problems confronting medicine. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) robustly identifies intrinsic myocardial damage. LGE may indicate inherent vulnerability to HHF, regardless of etiology, across the spectrum of heart failure stage or left ventricular ejection fraction (LVEF). We enrolled 1068 consecutive patients referred for CMR where 448 (42%) exhibited LGE. After a median of 1.4 years (Q1 to Q3: 0.9 to 2.0 years), 57 HHF events occurred, 15 deaths followed HHF, and 43 deaths occurred without antecedent HHF (58 total deaths). Using multivariable Cox regression adjusting for LVEF, heart failure stage, and other covariates, LGE was associated with first HHF after CMR (HR: 2.70, 95% CI: 1.32 to 5.50), death (HR: 2.13, 95% CI: 1.08 to 4.21), or either death or HHF (HR: 2.52, 95% CI: 1.49 to 4.25). Quantifying LGE extent yielded similar results; more LGE equated higher risks. LGE improved model discrimination (IDI: 0.016, 95% CI: 0.005 to 0.028, P=0.002) and reclassification of individuals at risk (continuous NRI: 0.40, 95% CI: 0.05 to 0.70, P=0.024). Adjustment for competing risks of death that shares common risk factors with HHF strengthened the LGE and HHF association (HR: 4.85, 95% CI: 1.40 to 16.9). The presence and extent of LGE is associated with vulnerability for HHF, including higher risks of HHF across the spectrum of heart failure stage and LVEF. Even when LVEF is severely decreased, those without LGE appear to fare reasonably well. LGE may enhance risk stratification for HHF and may enhance both clinical and research efforts to reduce HHF through targeted treatment.


[Chilaiditi syndrome associated the volvulus of the transverse colon].
The hepatodiaphragmatic interposition of the colon (Chilaiditi's Syndrome) and associated volvulus of the transverse colon is a rare cause of mechanical intestinal obstruction. The preoperative diagnosis is extremely difficult. We report a 26-year-old- male case, symptomatic since childhood, whose diagnosis by barium enema was confirmed surgically in Hospital Universitário de Taubaté. He underwent a transversectomy, and presented an intestinal obstruction in the post-operative period. Two reoperations were required. He has remained well, with outpatient supervision.


The effect of cation-anion difference on calcium requirement, feed intake, body weight gain, and blood gasses and mineral concentrations of dairy calves.
Our objective was to examine the effects of two diets with different cation-anion differences on Ca requirements in the growing calf. Holstein calves (n = 48, 24 males) were blocked at 56 to 70 d after birth (80+/-10 kg of body weight) according to sex and birth date and assigned randomly in a 2 x 3 factorial arrangement of dietary treatments containing cation-anion differences as meq (Na + K) - (Cl + S)/kg of diet dry matter and Ca content of 1) 0 and 0.35%, 2) 0 and 0.50%, 3) 0 and 0.65%, 4) 200 and 0.35%, 5) 200 and 0.50%, and 6) 200 and 0.65%. Feed intake and average daily gain did not differ among treatment groups. Plasma pH and Ca were unaffected by dietary Ca content or dietary cation-anion difference. Plasma Cl and P decreased linearly with increasing Ca content in the diet. Plasma HCO3 increased linearly with increased dietary Ca content. Plasma HCO3 and partial pressure of CO2 were higher in calves fed the 200 compared with calves fed the 0 cation-anion difference diets. Plasma Cl was, however, lower in calves fed the 200 compared with calves fed the 0 meq diets. An interaction of Ca content and dietary cation-anion difference was detected for plasma P content. Urinary pH increased linearly with increasing dietary Ca content. Calves fed the 200 meq dietary cation-anion difference had higher urinary pH values than those fed the 0 meq diet. Urinary P excretion was not altered by dietary cation-anion difference or Ca content of the diet. Calves fed the 0 meq diet had higher urinary cocnentrations of Ca and Cl when compared with those fed the 200 meq diet. Bone ash, P, Ca, Mg, and K content of the 10th rib were not affected by dietary treatments. Breaking strength of the seventh and ninth ribs increased quadratically with increasing dietary Ca content. Dietary cation-anion difference had no effect on the breaking strength of the seventh and ninth ribs. Varying the dietary cation-anion difference from 0 to 200 meq/kg of dietary dry matter had no effect on Ca requirement of the growing calf.


Second stage labor: what is normal?
Traditional management of second stage labor has come under scrutiny because of improved understanding of what normally occurs when second stage labor is allowed to proceed of its own accord without direction from birth attendants. When women bear down spontaneously as they feel the urge to push, either holding their breath briefly or with short exhalation of air, normal maternal and fetal physiological status is maintained and second stage labor does not appear to be lengthened. Using a variety of maternal positions during second stage labor can optimize physiologic functioning and increase maternal comfort.


Bactericidal effect of low-temperature atmospheric plasma against the Shigella flexneri.
Shigella flexneri (S. flexneri) is a common intestinal pathogenic bacteria that mainly causes bacillary dysentery, especially in low socioeconomic countries. This study aimed to apply cold atmospheric plasma (CAP) on S. flexneri directly to achieve rapid, efficient and environmentally friendly sterilization. The operating parameters of the equipment were determined by plasma diagnostics. The plate count and transmission electron microscope were employed to calculate bacterial mortality rates and observe the morphological damage of bacterial cells. Measurement of intracellular reactive oxygen species (ROS) and superoxide anions were detected by 2,7-dichlorodihydrofluorescein (DCFH) and Dihydroethidium fluorescence probes, respectively. The fluorescence intensity (a. u.) reflects the relative contents. Additionally, the experiment about the single effect of temperature, ultraviolet (UV), and ROS on bacteria was conducted. The peak discharge voltage and current during plasma operation were 3.92kV and 66mA. After discharge, the bacterial mortality rate of 10, 20, 30 and 40 s of plasma treatment was 60.71%, 74.02%, 88.11% and 98.76%, respectively. It was shown that the intracellular ROS content was proportional to the plasma treatment time and ROS was the major contributor to bacterial death. In summary, our results illustrated that the plasma treatment could inactivate S. flexneri efficiently, and the ROS produced by plasma is the leading cause of bacterial mortality. This highly efficient sterilization method renders plasma a highly promising solution for hospitals, clinics, and daily life.


Phosphoenolpyruvate phosphotransferase system components positively regulate Klebsiella biofilm formation.
Klebsiella pneumoniae is one of the leading causes of device-related infections (DRIs), which are associated with attachment of bacteria to these devices to form a biofilm. The latter is composed of not only bacteria but also extracellular polymeric substances (EPSes) consisting of extracellular DNAs, polysaccharides, and other macromolecules. The phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS) regulates diverse processes of bacterial physiology. In the genome of K. pneumoniae MGH 78578, we found an uncharacterized enzyme II complex homolog of PTS: KPN00353 (EIIA homolog), KPN00352 (EIIB homolog), and KPN00351 (EIIC homolog). The aim of this study was to characterize the potential physiological role of KPN00353, KPN00352, and KPN00351 in biofilm formation by K. pneumoniae. We constructed the PTS mutants and recombinant strains carrying the gene(s) of PTS. The recombinant K. pneumoniae strain overexpressing KPN00353-KPN00352-KPN00351 produced more extracellular matrix than did the vector control according to transmission and scanning electron microscopy. Judging by quantification of biofilm formation, of extracellular DNA (eDNA), and of capsular polysaccharide, the recombinant strain overexpressing KPN00353-KPN00352-KPN00351 produced more biofilm and capsular polysaccharide after overnight culture and more eDNA in the log phase as compared to the vector control. The genes, KPN00353-KPN00352-KPN00351, encode a putative enzyme II complex in PTS and positively regulate biofilm formation by enhancing production of eDNA and capsular polysaccharide in K. pneumoniae. Five proteins related to chaperones, to the citric acid cycle, and to quorum sensing are upregulated by the KPN00353-KPN00352-KPN00351 system.


Genome Editing of Wnt-1, a Gene Associated with Segmentation, via CRISPR/Cas9 in the Pine Caterpillar Moth, Dendrolimus punctatus.
The pine caterpillar moth, Dendrolimus punctatus, is a devastating forest pest. Genetic manipulation of this insect pest is limited due to the lack of genomic and functional genomic toolsets. Recently, CRISPR/Cas9 technology has been demonstrated to be a promising approach to modify the genome. To investigate gene functions during the embryogenesis, we introduced CRISPR/Cas9 system in D. punctatus to precisely and effectively manipulate gene expressions inmutant embryos. Compared to controls, knocking out of DpWnt-1, a gene well known for its role in the early body planning, led to high embryonic mortality. Among these mutants, 32.9% of the embryos and larvae showed an abnormal development. DpWnt-1 mutants predominantly exhibited abnormal posterior segments. In addition, multiple phenotypes were observed, including the loss of limbs and the head deformation, suggesting that DpWnt-1 signaling pathway is necessary for anterior segmentation and appendage development. Overall, our results demonstrate that CRISPR/Cas9 system is feasible and efficient in inducing mutations at a specific locus in D. punctatus. This study not only lays the foundation for characterizing gene functions in a non-model species, but also facilitates the future development of pest control alternatives for a major defoliator.


[Natural orifice translumenal endoscopic surgery].
Over the past few decades gastrointestinal endoscopy has developed from a purely diagnostic technique to one having numerous therapeutic gastrointestinal applications. Simultaneously, minimal invasive surgery is increasingly replacing traditional open abdominal procedures. These trends have led to a new and innovative way of accessing the peritoneal cavity through the orifices of the body (mouth, anus and vagina) by means ofendoscopic surgery: natural orifice translumenal endoscopic surgery (NOTES). Thanks to excellentcollaboration between surgeons and gastroenterologists and experimental animal research, NOTES has developed extremely rapidly over the past few years. Although many limitations need to be surmounted before NOTES can reach the human clinical trial stage, the prospect of safe, minimal invasive and scar-less surgery appears very promising. The near future will tell whether current barriers will be broken down and NOTES will acquire a fixed place in the diagnostic and therapeutic work-up of certain gastrointestinal afflictions.


A Retrospective Analysis of Chemical Constituents in Regulated and Unregulated E-Cigarette Liquids.
E-cigarette or vaping use-associated lung injury (EVALI) was identified with the incidents of a multi-state outbreak of acute lung injuries associated with the use of electronic cigarettes (e-cigs) and attributed to vitamin E acetate in off-market cannabis-based e-liquids. Aside from EVALI, hypersecretion of mucus, irritated nasal passages, and watery, red eyes have been defined as complaints associated with vaping standard nicotine-based e-liquids. The chemical composition of e-liquids varies between manufacturers and robust oversight of ingredients is lacking. Manufacturers use chemicals deemed "generally recognized as safe" (GRAS) by the FDA, a designation for chemicals used in foodstuffs to be ingested. Most "GRAS" chemicals are associated with at least one Global Harmonization System (GHS) warning class, ranging from irritant to toxic. Untargeted chemical analysis is critical to evaluate e-liquid products to determine chemical composition; equally important is the quantitation of components to help elucidate the potential harms from exceeding recommended exposure limits. Untargeted screening of e-liquids was accomplished using gas chromatography-mass spectrometry (GC-MS) and Direct Analysis in Real Time-AccuTOF™ mass spectrometry (DART-ToF-MS) and has identified 350 chemical constituents from 241 products analyzed. Nicotine, caffeine, menthol, and vitamin E were confirmed and quantitated by GC-MS, ethanol was confirmed and quantitated by headspace-gas chromatography-dual flame ionization detection (HS-GC-FID), and olivetol and cannabinoids were confirmed and quantitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Maximum identified concentrations of nicotine, caffeine, menthol, vitamin E, ethanol, olivetol, Δ9-tetrahydrocannabinol, and cannabidiol were 56.4, 26.9, 4.28, 307.9, 217.2, 399.6, 497.7, and 332.6 mg/ml, respectively. Evaluation of untargeted analysis and quantitation of unlabeled chemical components of e-liquids is essential to improving etiology of acute lung injury and less severe impacts of vaping, both short-term and long-term. The historical documentation of unlabeled ingredients can provide some insight for a retrospective analysis of health consequences and inform policy discussions.


Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough: A Systematic Review and Dose-Response Meta-Analysis.
Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. To evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023. Two reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo. Two reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID). Cough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events. Nine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, -6.2 mm [95% CI, -4.1 to -8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]). Compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.


Jatrophihabitans soli sp. nov., isolated from soil.
One bacterial strain, designated KIS75-12T, isolated from a soil sample collected from Wonsando island located in Boryeong city, Republic of Korea, was characterized as aerobic, Gram-stain-positive, non-flagellated and a short rod. It grew between temperatures of 15-37 °C, pH 4-9 and 0-3.0 % (w/v) NaCl. The 16S rRNA gene analysis showed the strain was moderately related to Jatrophihabitans endophyticus S9-650T (97.7 %) and revealed low sequence similarity (≤94.7 %) with all the other species with validly published names. Its major fatty acid was iso-C16 : 0. The predominant menaquinone of strain KIS75-12T was MK-9(H4). The polar lipids consisted of diphosphatidylglycerol and several small amounts of phosphatidylinositol, aminolipids and glycolipid. The peptidoglycan contained meso-A2pm as diagnostic diamino acid and the peptidoglycan type is A4γ. The genomic DNA G+C content of the type strain was 72.1 mol%. The combined phenotypic, chemotaxonomic and phylogenetic data showed that strain KIS75-12T could be clearly distinguished from the only member of the genus Jatrophihabitans,J. endophyticus. Therefore, the results of this study indicate the existence of a representative of a novel species of the genus Jatrophihabitans, for which we propose the name Jatrophihabitans soli sp. nov., with strain KIS75-12T ( = KACC 17298T = DSM 45908T = NBRC 109658T) as the type strain. An emended description of the genus Jatrophihabitans is also given.


The appropriate use of carotid endarterectomy.
For the first 30 years after carotid endarterectomy was first developed, anecdotal evidence was used to identify patients with internal carotid artery disease for whom this procedure would be appropriate. More recently, the appropriateness of carotid endarterectomy for symptomatic patients and asymptomatic subjects has emerged from 7 randomized trials. Risk of stroke and benefit from the procedure are greatest for symptomatic patients with at least 70% stenosis of the internal carotid artery. Within this group, carotid endarterectomy is most beneficial for the following patients: otherwise healthy elderly patients, those with hemispheric transient ischemic attack, those with tandem extracranial and intracranial lesions and those without evidence of collateral vessels. Risk of perioperative stroke and death is higher in the following groups, although they still benefit: patients with widespread leukoaraiosis, those with occlusion of the contralateral internal carotid artery and those with intraluminal thrombus. Patients with 50% to 69% stenosis experience lesser benefit, and some other groups may even be harmed by carotid endarterectomy, including women and patients with transient monocular blindness only. The procedure is indicated for patients presenting with lacunar stroke and for those with a nearly occluded internal carotid artery, but the benefit is muted. Patients with less than 50% stenosis do not benefit. In the largest randomized trial of asymptomatic subjects, the perioperative risk of stroke and death was very low (1.5%), but the results indicated that a prohibitively high number of subjects (83) must be treated to prevent one stroke in 2 years. The subsequent literature reported higher perioperative risks (2.8% to 5.6%). In asymptomatic individuals nearly half of the strokes that occur may be due to heart and small-vessel disease. These limitations counter any potential benefit. Another trial is in progress and may identify subgroups of asymptomatic subjects who would benefit. Meanwhile, most individuals without symptoms fare better with medical care.


Molecular evidence for Pleistocene glacial cycles driving diversification of a North American desert spider, Agelenopsis aperta.
The influence of historical climatic vs. geological changes on species diversification patterns was investigated in a widely distributed North American desert spider, Agelenopsis aperta (Araneae: Agelenidae), with particular reference to Pleistocene glacial cycles and earlier patterns of mountain building. Levels of sequence divergence obtained from the mitochondrial gene, cytochrome oxidase I, dated to the Pleistocene, eliminating Rocky Mountain orogeny as a cause of diversification, as orogeny ended 4 million years ago. The results of phylogenetic and network analyses showed the presence of three geographically defined clades, which were consistent with the presence of at least three glacial refugia: (i) east of the Rocky Mountains; (ii) between the Rocky Mountains and Sierra Nevadas; and (iii) west of the Sierra Nevadas. In addition, populations within the Rocky Mountains exhibited significantly lower genetic diversity than populations east of the Rocky Mountains and the haplotypes found within the Rockies were a subset of eastern haplotypes. These patterns suggest that a post-Pleistocene range expansion occurred out of an eastern glacial refugium into the Rocky Mountains. Examination of phylogeographical studies of other North American desert taxa indicated that mountain building explained diversification patterns more effectively for some taxa but Pleistocene climate change was more important for others, including A. aperta.


Gender Difference in Cancer Patients' Adherence to Analgesics and Related Outcomes of Pain Management.
Males and females have significant differences in certain medical outcomes. However, little research has explored the gender differences in cancer patient perceptions of analgesics, the relationship between gender and analgesic adherence, or the effectiveness of pain management. The objectives of this study were to compare gender differences associated with hesitancy to use analgesics, analgesic adherence, or pain management effectiveness and to examine whether gender can precisely predict analgesic adherence. The study was conducted in the outpatient oncology department of a medical center in Taiwan. A descriptive and cross-sectional design was used. The study samples were collected from 362 cancer patients. The participants completed the short version of the Barriers Questionnaire-Taiwan, the Morisky Analgesics Adherence Measure-Taiwan version, the Brief Pain Inventory-Chinese version, the Pain Management Index, and a demographic and disease questionnaire. The pain intensity and hesitancy to use analgesics scores were significantly higher among females than among males. The Pain Management Index results indicated that a larger percentage of males had adequate pain management. In addition, being male was a significant predictor of higher analgesic adherence (odds ratio, 1.93; P < .05). Gender could precisely predict cancer patients' medication adherence. Women experienced significantly greater pain than did men but also had more hesitancy to use analgesics, lower adherence, and inadequate pain management. Healthcare professionals should consider women as a high-risk group for inadequate pain control. It is crucial for health providers to consider the gender discrepancy when attempting to improve cancer pain management.