Bacterio-plankton transformation of diazepam and 2-amino-5-chlorobenzophenone in river waters.
Benzodiazepines are a large class of commonly-prescribed drugs used to treat a variety of clinical disorders. They have been shown to produce ecological effects at environmental concentrations, making understanding their fate in aquatic environments very important. In this study, uptake and biotransformations by riverine bacterio-plankton of the benzodiazepine, diazepam, and 2-amino-5-chlorobenzophenone, ACB (a photo-degradation product of diazepam and several other benzodiazepines), were investigated using batch microcosm incubations. These were conducted using water and bacterio-plankton populations from contrasting river catchments (Tamar and Mersey, UK), both in the presence and absence of a peptide, added as an alternative organic substrate. Incubations lasted 21 days, reflecting the expected water residence time in the catchments. In River Tamar water, 36% of diazepam (p < 0.001) was removed when the peptide was absent. In contrast, there was no removal of diazepam when the peptide was added, although the peptide itself was consumed. For ACB, 61% was removed in the absence of the peptide, and 84% in its presence (p < 0.001 in both cases). In River Mersey water, diazepam removal did not occur in the presence or absence of the peptide, with the latter again consumed, while ACB removal decreased from 44 to 22% with the peptide present. This suggests that bacterio-plankton from the Mersey water degraded the peptide in preference to both diazepam and ACB. Biotransformation products were not detected in any of the samples analysed but a significant increase in ammonium concentration (p < 0.038) was measured in incubations with ACB, confirming mineralization of the amine substituent. Sequential inoculation and incubation of Mersey and Tamar microcosms, for 5 periods of 21 days each, did not produce any evidence of increased ability of the microbial community to remove ACB, suggesting that an indigenous consortium was probably responsible for its metabolism. As ACB degradation was consistent, we propose that the aquatic photo-degradation of diazepam to ACB, followed by mineralization of ACB, is a primary removal pathway for these emerging contaminants. As ACB is photo-produced by several benzodiazepines, this pathway should be relevant for the removal of other benzodiazepines that enter the freshwater environment.


Direct Uranium Isotopic Analysis of Swipe Surfaces by Microextraction-ICP-MS.
The ability to directly measure uranium isotope ratios on environmental swipes has been achieved through a solution-based microextraction process and represents a significant advancement toward the development of a rapid method to analyze international nuclear safeguard samples. Here, a microextraction probe is lowered and sealed onto the swipe surface, and analytes within the sampling site (∼8 mm2) are dissolved and extracted into a flowing solvent of 2% nitric acid (HNO3). The mobilized species are subsequently directed into an inductively coupled plasma-mass spectrometer (ICP-MS) for accurate and precise isotope ratio determination. This work highlights the novelty of the sampling mechanism, particularly with the direct coupling of the microextraction probe to the ICP-MS and measurement of uranium isotope ratios. The preliminary method detection limit for the microextraction-ICP-MS method, utilizing a quadrupole-based MS, was determined to be ∼50 pg of 238U. Additionally, precise and accurate isotope ratio measurements were achieved on uranium reference materials for both the major (235U/238U) and minor (234U/238U and 236U/238U) ratios. While the present work is focused on directly measuring uranium isotopic systems on swipe surfaces for nuclear safeguards and verification applications, the benefits would extend across many applications in which direct solid sampling is sought for elemental and isotopic analysis.


Gene expression of catabolic inflammatory cytokines peak before anabolic inflammatory cytokines after ACL injury in a preclinical model.
The response of the joint to anterior cruciate ligament (ACL) injury has not been fully characterized. In particular, the characterization of both catabolic factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), and markers of ongoing tissue damage (CRP), and anabolic factors, including vascular endothelial growth factor (VEGF), transforming growth factor β-induced (TGFβI), and the presence of CD163+ macrophages, have not been well defined. In this study, we hypothesized ACL injury would catalyze both catabolic and anabolic processes and that these would have different temporal profiles of expression. Adolescent Yucatan minipigs were subjected to ACL transection. Within the joint, gene expression levels of IL-6, IL-8, VEGF, and TGFβI were quantified in the synovium, ligament, and provisional scaffold located between the torn ligament ends at days 1, 5, 9, and 14 post-injury. Macrophage infiltration was also assessed in the joint tissues over the two week period. Serum C-reactive protein (CRP) levels were measured at multiple time points between 1 hour to 14 days after injury. Increases in IL-6 and IL-8 gene expression peaked at day 1 after injury in the synovium and ligament. CRP levels were significantly increased at day 3 before returning to pre-injury levels. VEGF and TGFβI gene expression did not significantly increase until day 9 in the synovium and were unchanged in the other tissues. CD163+ macrophages increased in the ligament and synovium until day 9. Taken together, these results suggest that the response within the joint is primarily catabolic in the first three days after injury, switching to a more anabolic phase by nine days after injury. The effect of medications which alter these processes may thus depend on the timing of administration after injury.


Some clinical approaches to the homeless mentally ill.
Clinicians who work with homeless people are likely to encounter a very broad spectrum of mental disorders and residential patterns. As with any other patient population, the particulars of clinical interventions must be guided by the specific constellations of biological, psychological, and social needs. However, for individuals who not only suffer from serious psychiatric disorders, but are also homeless, effective approaches may require significant modifications of traditional techniques and changes in the prioritization, timing, and framing of specific interventions. In this article we will focus on people who are severely and persistently mentally ill and who have been sleeping for months or years in shelters or in public spaces such as parks, streets, and bus terminals.


Endoscopic ultrasound-guided drainage of pancreatic fluid collections.
Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recognized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, percutaneous and non-EUS-guided endoscopic drainage. EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to percutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct access to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the subsequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. With the introduction of the EUS-scope equipped with a large operative channel which permits drainage of the PFCs in "one step", EUS-GD has been increasingly carried out in many tertiary care centers and has expanded the safety and efficacy of this modality, allowing access to and drainage of overly challenging fluid collections. However, the nature of the PFCs determines the outcome of this procedure. The technique and review of current literature regarding EUS-GD of PFCs will be discussed.


Research protocol: The initiation, design and establishment of the Global Angelman Syndrome Registry.
Angelman syndrome (AS) is a rare neurodevelopmental disorder affecting between 1 in 15 000 and 1 in 24 000 individuals. The condition results in severe developmental and expressive language delays, motor impairments and a unique behavioural phenotype consisting of excessive laughter, smiling and sociability. While many studies have contributed knowledge about the causes and natural history of the syndrome, large scale longitudinal studies are required to advance research and therapeutics for this rare syndrome. This article describes the protocol for the Global Angelman Syndrome Registry, and some initial findings. Due to the rarity of AS and the variability in symptom presentation, the registry team will strive for complete case ascertainment. Parents and caregivers will submit data to the registry via a secure internet connection. The registry consists of 10 modules that cover patient demographics; developmental, diagnostic, medical and surgical history, behaviour and development, epilepsy, medications and interventions and sleep. Since its launch at https://angelmanregistry.info in September 2016, almost 470 individuals with AS have been signed up to the registry worldwide: 59% are from North and South America, 23% are from Europe, 17% are from the Asia Pacific region and 1% are from the Middle East or Africa. The majority of registrants are children, with only 16% aged over 20 years. Most participants indicated a chromosome deletion (76%), with fewer participants indicating a mutation, uniparental disomy or imprinting defect (20%). Findings indicate a need to consider recruitment strategies that target caregivers of older children and adults, and parents and caregivers from non-English speaking backgrounds.


Retinal and optic nerve diseases.
A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device.


A sex-specific switch between visual and olfactory inputs underlies adaptive sex differences in behavior.
Although males and females largely share the same genome and nervous system, they differ profoundly in reproductive investments and require distinct behavioral, morphological, and physiological adaptations. How can the nervous system, while bound by both developmental and biophysical constraints, produce these sex differences in behavior? Here, we uncover a novel dimorphism in Drosophila melanogaster that allows deployment of completely different behavioral repertoires in males and females with minimum changes to circuit architecture. Sexual differentiation of only a small number of higher order neurons in the brain leads to a change in connectivity related to the primary reproductive needs of both sexes-courtship pursuit in males and communal oviposition in females. This study explains how an apparently similar brain generates distinct behavioral repertoires in the two sexes and presents a fundamental principle of neural circuit organization that may be extended to other species.


Fate of sympathetic trunk ganglia after cutting in German meat plants.
To minimize risks from pathogenic prion proteins, particular tissues from bovines and other ruminants have been declared specified risk materials (SRMs), which are required to be removed from the food chain. However, in particular for the sympathetic trunk (ST) as a part of the autonomous nervous system (ANS), which represents a potential transfer route for abnormal prion proteins (PrP(Sc)), this is not the case. Consequently, its destination during cutting procedures deserves attention. In this survey, the handling of the ST in beef cutting plants was recorded during ongoing work. To ease these observations, the ST was separated into five parts, and eight destinations for cuts were identified. By means of an observation sheet, the destination of the respective tissue was recorded. About one-third of the ST went into human consumption, another one-third was disposed of as SRMs, and the last one-third was used for nonfood purposes or disposed of. The rear thoracic and sacral ganglia primarily remained naturally connected to the bones going as SRMs. The stellate, front thoracic, and lumbar ganglia went in a different percent into the food chain. Frequently, workers in the same plant decided differently, even from case to case, on the destination of the tissue, which indicates a lack of standardization.


Suramin affects DNA synthesis in HeLa cells by inhibition of DNA polymerases.
Suramin, a polysulfonated naphthylurea widely used in the treatment of trypanosomiasis and onchocerciasis, is currently being investigated as an antitumor agent for the treatment of advanced cancer. Suramin exerts a wide variety of biological effects. We have shown that suramin inhibits cell proliferation and DNA synthesis in cultured HeLa cells. The replication in vitro of SV40 DNA is completely abolished by 40 microM suramin. The inhibition of DNA replication is due to inhibition of DNA polymerases alpha and delta, the replicative enzymes in eukaryotic cells. DNA polymerase alpha is sensitive to lower concentrations of suramin [concentration to achieve 50% inhibition (IC50) of 8 microM] than is DNA polymerase delta (IC50 36 microM), whereas DNA polymerase beta is relatively insensitive to the drug (IC50 of 90 microM). Suramin inhibits other replicative DNA polymerases such as Escherichia coli polymerase I (Klenow fragment) and Thermus aquaticus polymerase. Suramin is noncompetitive with both substrate deoxyribonucleotides and template-primers with respect to DNA polymerase inhibition. Much lower concentrations (8-30 microM) of the drug are required for 50% inhibition of DNA polymerases than for 50% inhibition of other enzymes such as protein kinase C and reverse transcriptase. These results show an important biological effect of this drug and indicate the need for more studies before its clinical use as an antitumor agent.


Psychosocial factors that shape patient and carer experiences of dementia diagnosis and treatment: a systematic review of qualitative studies.
Early diagnosis and intervention for people with dementia is increasingly considered a priority, but practitioners are concerned with the effects of earlier diagnosis and interventions on patients and caregivers. This systematic review evaluates the qualitative evidence about how people accommodate and adapt to the diagnosis of dementia and its immediate consequences, to guide practice. We systematically reviewed qualitative studies exploring experiences of community-dwelling individuals with dementia, and their carers, around diagnosis and the transition to becoming a person with dementia. We searched PubMed, PsychINFO, Embase, CINAHL, and the British Nursing Index (all searched in May 2010 with no date restrictions; PubMed search updated in February 2012), checked reference lists, and undertook citation searches in PubMed and Google Scholar (ongoing to September 2011). We used thematic synthesis to identify key themes, commonalities, barriers to earlier diagnosis, and support identified as helpful. We identified 126 papers reporting 102 studies including a total of 3,095 participants. Three overarching themes emerged from our analysis: (1) pathways through diagnosis, including its impact on identity, roles, and relationships; (2) resolving conflicts to accommodate a diagnosis, including the acceptability of support, focusing on the present or the future, and the use or avoidance of knowledge; and (3) strategies and support to minimise the impact of dementia. Consistent barriers to diagnosis include stigma, normalisation of symptoms, and lack of knowledge. Studies report a lack of specialist support particularly post-diagnosis. There is an extensive body of qualitative literature on the experiences of community-dwelling individuals with dementia on receiving and adapting to a diagnosis of dementia. We present a thematic analysis that could be useful to professionals working with people with dementia. We suggest that research emphasis should shift towards the development and evaluation of interventions, particularly those providing support after diagnosis.


Risk factors for childhood malnutrition in Roma settlements in Serbia.
Children living in Roma settlements in Central and Eastern Europe face extreme levels of social exclusion and poverty, but their health status has not been well studied. The objective of this study was to elucidate risk factors for malnutrition in children in Roma settlements in Serbia. Anthropometric and sociodemographic measures were obtained for 1192 Roma children under five living in Roma settlements from the 2005 Serbia Multiple Indicator Cluster Survey. Multiple logistic regression was used to relate family and child characteristics to the odds of stunting, wasting, and underweight. The prevalence of stunting, wasting, and underweight was 20.1%, 4.3%, and 8.0%, respectively. Nearly all of the children studied fell into the lowest quintile of wealth for the overall population of Serbia. Children in the lowest quintile of wealth were four times more likely to be stunted compared to those in the highest quintile, followed by those in the second lowest quintile (AOR = 2.1) and lastly by those in the middle quintile (AOR = 1.6). Children who were ever left in the care of an older child were almost twice as likely to stunted as those were not. Children living in urban settlements showed a clear disadvantage with close to three times the likelihood of being wasted compared to those living in rural areas. There was a suggestion that maternal, but not paternal, education was associated with stunting, and maternal literacy was significantly associated with wasting. Whether children were ever breastfed, immunized or had diarrhoeal episodes in the past two weeks did not show strong correlations to children malnutrition status in this Roma population. There exists a gradient relationship between household wealth and stunting even within impoverished settlements, indicating that among poor and marginalized populations socioeconomic inequities in child health should be addressed. Other areas on which to focus future research and public health intervention include maternal literacy, child endangerment practices, and urban settlements.


Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia.
On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the feasibility of treating adult patients aged 18-50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. coli L-asparaginase during consolidation. Between 2002 and 2008, 92 eligible patients aged 18-50 years were enrolled at 13 participating centers. Seventy-eight patients (85%) achieved a complete remission (CR) after 1 month of intensive induction therapy. With a median follow-up of 4.5 years, the 4-year disease-free survival (DFS) for the patients achieving a CR was 69% (95% confidence interval (CI) 56-78%) and the 4-year overall survival (OS) for all eligible patients was 67% (95% CI 56-76%). The 4-year DFS for the 64 patients who achieved a CR and were Philadelphia chromosome negative (Ph-) was 71% (95% CI 58-81%), and for all 74 Ph- patients the 4-year OS was 70% (95% CI 58-79%). We conclude that a pediatric-like treatment strategy for young adults with de novo ALL is feasible, associated with tolerable toxicity, and results in improved outcomes compared with historical regimens in young adult patients with ALL.


Fluoride intake and urinary fluoride excretion in 4- and 8-year-old children living in urban and rural areas of Southwest Nigeria.
To estimate and compare total daily fluoride intake (TDFI), daily urinary fluoride excretion (DUFE), daily fluoride retention (DFR), fractional urinary fluoride excretion (FUFE) and fractional fluoride retention (FFR) in 4- and 8 year-old Nigerians and explore associations between these outcomes to improve understanding of fluoride metabolism. Using a cross-sectional observational study, 72 four-year-olds and 72 eight-year-olds were recruited from nursery and primary schools (respectively) in lower and higher water F areas of urban and rural localities in Oyo State, southwest Nigeria. TDFI from diet and toothpaste ingestion was assessed using a validated Food Frequency Questionnaire and visual scale of toothpaste used during toothbrushing. DUFE was measured by collecting a 24-hour urine sample, FUFE estimated as the ratio between DUFE and TDFI, DFR estimated as TDFI-TDFE (where TDFE = DUFE + estimated faecal F excretion (ie TDFI × 10%), and FFR was estimated as [(TDFI-DFR)/TDFI] × 100. Data were analysed using ANOVA with post hoc tests and Student's t tests and strengths of associations between key variables measured. Mean (SD) TDFI, DUFE, DFR, FUFE and FFR were 0.137 (0.169) mg/kg bw/d, 0.032 (0.027) mg/kg bw/d, 0.091 (0.147) mg/kg bw/d, 44% (44%) and 46% (44%), respectively, for 4-year-olds. Corresponding values for 8-year-olds (n = 63) were 0.106 (0.130) mg/kg bw/d, 0.022 (0.017) mg/kg bw/d, 0.073 (0.107) mg/kg bw/d, 36% (30%) and 54% (30%), respectively. Dietary contribution to TDFI was 79% and 75% (respectively), for 4- and 8-year-olds. Mean (SD) TDFI from toothpaste ingestion was 0.021 (0.013) mg/kg bw/d in 4-year-olds, 0.014 (0.010) mg/kg bw/d in 8-year-olds (P = .002) but with no differences between areas. Differences in dietary F intake determined the main differences in F exposure between areas. The positive correlation between TDFI and DUFE was weak for 4-year-olds (r = +.29) and strong for 8-year-olds (r = +.64). A strong positive correlation was observed between TDFI and DFR for both age groups: (r) = +.98 for 4-year-olds and (r) = +.99 for 8-year-olds. Fluoride intake in these 4- and 8-year-old Nigerians was much higher than the "optimal range" of 0.05-0.07 mg/kg bw/d in rural, higher F water areas, with diet as the main contributor. F retention was similar in both age groups, with almost half of TDFI retained in the body. In terms of risk vs benefit for fluorosis and dental caries, this finding should be considered when mitigating against excessive fluoride exposure and planning F-based prevention.


Investigating electrochemical removal of bacterial biofilms from stainless steel substrates.
Electrochemical removal of biofilms deserves attention because of its ease of use and environmentally friendly nature. We investigated the influence of electrode potential and treatment time on the removal of a 10-day old Pseudomonas aeruginosa biofilm formed on stainless steel 316 L substrates. At electrode potentials more positive than -1.5 V vs. Ag/AgCl, lower removal rates were observed and only partial removal of the biofilm was achieved during a 1-min time interval. Electrostatic repulsion between the film and electrode surface is believed to drive biofilm detachment under these conditions. However, when the biofilm-coated substrates were treated at potentials negative of -1.5 V vs. Ag/AgCl, complete removal of a biofilm was achieved within seconds. Under these conditions, vigorous evolution of hydrogen gas is believed to be responsible for the film removal, mechanically detaching the bacteria and extracellular polymeric matrix from the substrate. Stainless steel substrates were also subjected to repeated cycles of biofilm formation and electrochemical removal. High removal efficiencies were maintained throughout this process suggesting the potential of the proposed technology for application on conductive surfaces in various industrial settings.


Improved serial analysis of V1 ribosomal sequence tags (SARST-V1) provides a rapid, comprehensive, sequence-based characterization of bacterial diversity and community composition.
Serial analysis of ribosomal sequence tags (SARST) is a recently developed technology that can generate large 16S rRNA gene (rrs) sequence data sets from microbiomes, but there are numerous enzymatic and purification steps required to construct the ribosomal sequence tag (RST) clone libraries. We report here an improved SARST method, which still targets the V1 hypervariable region of rrs genes, but reduces the number of enzymes, oligonucleotides, reagents, and technical steps needed to produce the RST clone libraries. The new method, hereafter referred to as SARST-V1, was used to examine the eubacterial diversity present in community DNA recovered from the microbiome resident in the ovine rumen. The 190 sequenced clones contained 1055 RSTs and no less than 236 unique phylotypes (based on > or = 95% sequence identity) that were assigned to eight different eubacterial phyla. Rarefaction and monomolecular curve analyses predicted that the complete RST clone library contains 99% of the 353 unique phylotypes predicted to exist in this microbiome. When compared with ribosomal intergenic spacer analysis (RISA) of the same community DNA sample, as well as a compilation of nine previously published conventional rrs clone libraries prepared from the same type of samples, the RST clone library provided a more comprehensive characterization of the eubacterial diversity present in rumen microbiomes. As such, SARST-V1 should be a useful tool applicable to comprehensive examination of diversity and composition in microbiomes and offers an affordable, sequence-based method for diversity analysis.


Proteomic changes associated with metabolic syndrome in a fructose-fed rat model.
Metabolic syndrome (MetS), characterized by a constellation of disorders such as hyperglycemia, insulin resistance, and hypertension, is becoming a major global public health problem. Fructose consumption has increased dramatically over the past several decades and with it the incidence of MetS. However, its molecular mechanisms remain to be explored. In this study, we used male Sprague-Dawley (SD) rats to study the pathological mechanism of fructose induced MetS. The SD rats were fed a 60% high-fructose diet for 16 weeks to induce MetS. The induction of MetS was confirmed by blood biochemistry examination. Proteomics were used to investigate the differential hepatic protein expression patterns between the normal group and the MetS group. Proteomic results revealed that fructose-induced MetS induced changes in glucose and fatty acid metabolic pathways. In addition, oxidative stress and endoplasmic reticulum stress-related proteins were modulated by high-fructose feeding. In summary, our results identify many new targets for future investigation. Further characterization of these proteins and their involvement in the link between insulin resistance and metabolic dyslipidemia may bring new insights into MetS.


Genetic alterations of RD(INK4/ARF) enhancer in human cancer cells.
Recent identification of an enhancer element, RD(INK4/ARF) (RD), in the prominent INK4/ARF locus provides a novel mechanism to simultaneously regulate the transcription of p15(INK4B) (p15), p14(ARF) , and p16(INK4A) (p16) tumor suppressor genes. While genetic inactivation of p15, p14(ARF) , and p16 in human tumors has been extensively studied, little is known about genetic alterations of RD and its impact on p15, p14(ARF) , and p16 in human cancer. The purpose of this study was to investigate the potential existence of genetic alterations of RD in human cancer cells. DNAs extracted from 17 different cancer cell lines and 31 primary pheochromocytoma tumors were analyzed for deletion and mutation of RD using real-time PCR and direct DNA sequencing. We found that RD was deleted in human cancer cell lines and pheochromocytoma tumors at frequencies of 41.2% (7/17) and 13.0% (4/31), respectively. While some of these RD deletion events occurred along with deletions of the entire INK4/ARF locus, other RD deletion events were independent of genetic alterations in p15, p14(ARF) , and p16. Furthermore, the status of RD was poorly associated with the expression of p15, p14(ARF) , and p16 in tested cancer cell lines and tumors. This study demonstrates for the first time that deletion of the RD enhancer is a prevalent event in human cancer cells. Its implication in carcinogenesis remains to be further explored.


Risk factors for breast cancer development by tumor characteristics among women with benign breast disease.
Among women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown. Using a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models. Breast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14-14.01) with only one ER-negative case, P-heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21-3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size. Most tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status.


Respiratory and cardiovascular effects of doxapram and theophylline for the treatment of asphyxia in neonatal calves.
Respiratory stimulants are widely used in asphyxic neonatal calves despite a lack of data about their effectiveness and indications of possible side effects. The effect of doxapram and theophylline on respiratory, cardiovascular, and acid-base variables was investigated in 10 healthy neonatal calves (Bos Taurus). A venous, a peripheral arterial, and a pulmonary arterial catheter were placed, and central venous, pulmonary, and systemic blood pressures and cardiac output were measured using thermodilution technique. Doxapram, but not theophylline, led to an immediate increase in respiratory rate (P <or= 0.01). The arterial pCO(2) decreased to 27.1+/-4.7 mm Hg within 30 sec after doxapram administration and to 46.3+/-5.8 mm Hg within 120 min after theophylline administration (P<0.0001). The systolic pulmonary pressure increased from 70+/-8mm Hg (mean+/-SD) to 93+/-19 mm Hg within 30 sec after doxapram, but decreased after theophylline. The pulmonary vascular resistance also increased after doxapram and decreased after theophylline (P<0.01). Doxapram had a more pronounced and faster effect on respiratory rate and elimination of CO(2) than theophylline. Doxapram, but not theophylline, is indicated for treatment of postnatal asphyxia in calves, but there are potential cardiovascular side effects.


Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.
Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis.


Reduction of myocardial ischaemia-reperfusion injury by inactivating oxidized phospholipids.
Myocardial ischaemia followed by reperfusion (IR) causes an oxidative burst resulting in cellular dysfunction. Little is known about the impact of oxidative stress on cardiomyocyte lipids and their role in cardiac cell death. Our goal was to identify oxidized phosphatidylcholine-containing phospholipids (OxPL) generated during IR, and to determine their impact on cell viability and myocardial infarct size. OxPL were quantitated in isolated rat cardiomyocytes using mass spectrophotometry following 24 h of IR. Cardiomyocyte cell death was quantitated following exogenously added OxPL and in the absence or presence of E06, a 'natural' murine monoclonal antibody that binds to the PC headgroup of OxPL. The impact of OxPL on mitochondria in cardiomyocytes was also determined using cell fractionation and Bnip expression. Transgenic Ldlr-/- mice, overexpressing a single-chain variable fragment of E06 (Ldlr-/--E06-scFv-Tg) were used to assess the effect of inactivating endogenously generated OxPL in vivo on myocardial infarct size. Following IR in vitro, isolated rat cardiomyocytes showed a significant increase in the specific OxPLs PONPC, POVPC, PAzPC, and PGPC (P < 0.05 to P < 0.001 for all). Exogenously added OxPLs resulted in significant death of rat cardiomyocytes, an effect inhibited by E06 (percent cell death with added POVPC was 22.6 ± 4.14% and with PONPC was 25.3 ± 3.4% compared to 8.0 ± 1.6% and 6.4 ± 1.0%, respectively, with the addition of E06, P < 0.05 for both). IR increased mitochondrial content of OxPL in rat cardiomyocytes and also increased expression of Bcl-2 death protein 3 (Bnip3), which was inhibited in presence of E06. Notably cardiomyocytes with Bnip3 knock-down were protected against cytotoxic effects of OxPL. In mice exposed to myocardial IR in vivo, compared to Ldlr-/- mice, Ldlr-/--E06-scFv-Tg mice had significantly smaller myocardial infarct size normalized to area at risk (72.4 ± 21.9% vs. 47.7 ± 17.6%, P = 0.023). OxPL are generated within cardiomyocytes during IR and have detrimental effects on cardiomyocyte viability. Inactivation of OxPL in vivo results in a reduction of infarct size.


Cloning DPB3, the gene encoding the third subunit of DNA polymerase II of Saccharomyces cerevisiae.
DNA polymerase II purified from Saccharomyces cerevisiae contains polypeptides with apparent molecular masses of greater than 200, 80, 34, 30 and 29 kDa, the two largest of which (subunits A and B) are encoded by the essential genes POL2 and DPB2. By probing a lambda gt11 expression library of yeast DNA with antiserum against DNA polymerase II, we isolated a single gene, DPB3, that encodes both the 34- and 30-kDa polypeptides (subunit C and C'). The nucleotide sequence of DPB3 contained an open reading frame encoding a 23-kDa protein, significantly smaller than the observed molecular masses, 34- or 30-kDa, which might represent post-translationally modified forms of the DPB3 product. The predicted amino acid sequence contained a possible NTP-binding motif and a glutamate-rich region. NTP-binding motif and a glutamate-rich region. A dpb3 deletion mutant (dpb3 delta) was viable and yielded a DNA polymerase II lacking the 34- and 30-kDa polypeptides. dpb3 delta strains exhibited an increased spontaneous mutation rate, suggesting that the DPB3 product is required to maintain fidelity of chromosomal replication. Since a fifth, 29-kDa polypeptide was present in DNA polymerase II preparations from wild-type cell extracts throughout purification, the subunit composition appears to be A, B, C (or C and C') and D. The 5' nontranscribed region of DPB3 contained the MulI-related sequence ACGCGA, while the 0.9-kb DPB3 transcript accumulated periodically during the cell cycle and peaked at the G1/S boundary. The level of DPB3 transcript thus appears to be under the same cell cycle control as those of POL2, DPB2 and other DNA replication genes. DPB3 was mapped to chromosome II, 30 cM distal to his7.


The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice.
RBTN2 is activated by the chromosomal translocation t(11;14) (P13;p11) in some T cell leukaemias. Histologically similar T cell tumours develop with long latency in transgenic mice when either CD2 or thy1.1 promoters control rbtn2 expression. During the asymptomatic period, perturbation of T cell differentiation occurs in the thymus. The major anomalies present during this phase are an increase in the percentage of large thymocytes lacking CD4 and CD8 markers and also of small thymocytes express both the T cell marker CD3 and the B cell-specific form of CD45. These abnormal T cell populations can be clonal and thus a primary result of aberrant expression of the LIM-protein Rbtn2 is alteration of T cell differentiation preceding overt malignancy. These data provide a biological explanation for the role of Rbtn2 in tumorigenesis and presumably RBTN2 expression in T cells after the translocation t(11;14) in children has the same effect.


Hydranencephaly treatments: retrospective case series and review of the literature.
The objective of this study was to review treatment options for infants with hydranencephaly and to consider the pros and cons of each treatment modality. This paper is a review of hydranencephaly as well as a retrospective analysis evaluating the outcomes of 52 infants with hydranencephaly who were treated at the Kijabe Hospital, Kijabe, Kenya, in one of four ways: ventriculoperitoneal shunt (VPS) insertion, endoscopic choroid plexus coagulation (CPC), open choroid plexectomy (CPlx), and palliative care. The primary outcome measure was control of head size, with the aim of improving patient care. One-year mortality was a secondary outcome. Of the 52 patients analyzed, 11 underwent VPS insertion, 17 CPC, 14 CPlx, and 10 were treated palliatively. Head size was controlled at the 3-month evaluation interval in 5 of 7 infants treated with VPS, 10 of 16 of those treated with CPC, 6 of 9 of those treated with CPlx, and 1 of 4 treated palliatively. The number of infants in each category with complete follow-up data that were needed to analyze change in head size was lower than the total number of patients included in each category. Mortality at 1 year of age was 9 of 11 in the VPS group, 14 of 17 in the CPC group, 6 of 14 in the CPlx group, and 7 of 10 in the palliative group. Head size decreased by 1 cm or more in similar proportions (62%-71%) of infants with hydranencephaly who were treated by VPS insertion, CPC, and CPlx, and progressed in those who received palliative care. Mortality at 1 year of age was similar in infants treated by a VPS, CPC, and palliative care (70%-82%), but lower (43%) in those treated with CPlx.


Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere.
Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei. Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes. Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases. However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere. It is thought that amines may enhance nucleation, but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid-amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid-dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.


Identification of MIB producers and odor risk assessment using routine data: A case study of an estuary drinking water reservoir.
Identification of MIB(2-methylisoborneol)-producing cyanobacteria in source water has been a big challenge for reservoir authorities because it normally requires isolation of cyanobacteria strains. Here, a protocol based on Pearson's product moment correlation analysis combined with standardized data treatment and expert judgement was developed to sort out the MIB producer(s), mainly based on routine monitoring data from an estuary drinking water reservoir in the Yangtze River, China, and a risk model using quantile regressions was established to evaluate the risk of MIB occurrences. This reservoir has suffered from MIB problems in summer since 2011. Among 323 phytoplankton species, Planktothrix was judged to be the MIB producer in this reservoir because it exhibited the highest correlation coefficient (R = 0.60) as well as the lowest false positive-ratio (FP% = 0) and false-negative rate (FN% = 14). The low false-positive rate is particularly important, since MIB should not detected without detection of the producer. A high light extinction coefficient (k=5.57±2.48 m-1) attributed to high turbidity loading in the river water lowered the subsurface water light intensity, which could protect the low irradiance Planktothrix from excessive solar radiation, and allow them to grow throughout the summer. The risk model shows that the probability of suffering unacceptable MIB concentrations (>15 ng L-1) in water is as high as 90% if the cell density of Planktothrix is >609.0 cell mL-1, while the risk will be significantly reduced to 50% and 10% at cell densities of 37.5 cell mL-1 and 9.6 cell mL-1, respectively. The approach developed in this study, including the protocol for identification of potential producers and the risk model, could provide a reference case for the management of source water suffering from MIB problems using routine monitoring data.


"Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases", summary of the ERS Research Seminar in Budapest, Hungary, September, 1999.
In recent years, there has been increasing interest in noninvasive monitoring of airway inflammation and oxidative stress. Several volatile and nonvolatile substances can be measured in exhaled breath and have been suggested as potential biomarkers of these events. Exhaled gases, including carbon monoxide (CO), alkanes (ethane, pentane), and substances measured in breath condensate, such as hydrogen peroxide (H2O2) and isoprostanes were all suggested as potential markers of oxidative stress in the lung. A European Respiratory Society (ERS) International Research Seminar entitled "Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases" was organized by the Airway Regulation and Provocation Group of the Clinical Allergy and Immunology Assembly in Budapest, Hungary in September, 1999 to integrate the latest knowledge on these issues and accelerate further improvement in this area. During this 2-day event several issues were raised about: the use and standardization of measurements in exhaled breath; problems of measuring expired H2O2 and other mediators in breath condensate; role and regulation of haemoxygenase (HO)-1 in the lung; and conditions and factors influencing exhaled CO. This report is a summary of the main presentations at the seminar, together with the current areas of research in this rapidly expanding field.


Point Prevalence Study of Mobilization Practices for Acute Respiratory Failure Patients in the United States.
Early mobility in mechanically ventilated patients is safe, feasible, and may improve functional outcomes. We sought to determine the prevalence and character of mobility for ICU patients with acute respiratory failure in U.S. ICUs. Two-day cross-sectional point prevalence study. Forty-two ICUs across 17 Acute Respiratory Distress Syndrome Network hospitals. Adult patients (≥ 18 yr old) with acute respiratory failure requiring mechanical ventilation. We defined therapist-provided mobility as the proportion of patient-days with any physical or occupational therapy-provided mobility event. Hierarchical regression models were used to identify predictors of out-of-bed mobility. Hospitals contributed 770 patient-days of data. Patients received mechanical ventilation on 73% of the patient-days mostly (n = 432; 56%) ventilated via an endotracheal tube. The prevalence of physical therapy/occupational therapy-provided mobility was 32% (247/770), with a significantly higher proportion of nonmechanically ventilated patients receiving physical therapy/occupational therapy (48% vs 26%; p ≤ 0.001). Patients on mechanical ventilation achieved out-of-bed mobility on 16% (n = 90) of the total patient-days. Physical therapy/occupational therapy involvement in mobility events was strongly associated with progression to out-of-bed mobility (odds ratio, 29.1; CI, 15.1-56.3; p ≤ 0.001). Presence of an endotracheal tube and delirium were negatively associated with out-of-bed mobility. In a cohort of hospitals caring for acute respiratory failure patients, physical therapy/occupational therapy-provided mobility was infrequent. Physical therapy/occupational therapy involvement in mobility was strongly predictive of achieving greater mobility levels in patients with respiratory failure. Mechanical ventilation via an endotracheal tube and delirium are important predictors of mobility progression.


Referential communication tasks: performance by normal and pragmatically impaired children.
Two groups of children, a pragmatically impaired (PI) group and a group of language-normal (LN) age-matched peers, were compared by use of a referential communication task. Experimenter and child both played the roles of listener and instructor during the task and, in addition, the experimenter sometimes failed to give adequate information when in the role of instructor. Lexical content and structural complexity were controlled, and it was hypothesised that difficulties for the PI group would arise when in the role of instructor, as a result of failing to specify necessary information in order for the experimenter to respond appropriately. In fact, the main difference between the two groups arose when the experimenter failed to give adequate information to the child; the LN children were quick to realise this and to request clarification, whereas the PI children requested clarification to a lesser extent and appeared less aware of the need to do so. Possible explanations for this pattern of results are explored.


Lycopene/tomato consumption and the risk of prostate cancer: a systematic review and meta-analysis of prospective studies.
Lycopene/tomato has been discussed as a potential effecter in the prevention and therapy of prostate cancer; however, no systematic review has been reported to illustrate its effect recently. In the present study, a meta-analysis was carried out to determine whether intake of lycopene and tomato/tomato products could reduce the risk of prostate cancer. Eleven cohort studies and six nested case-control studies were identified through searching of international journal databases and reference lists of relevant publications. Two reviewers independently assessed the study quality and extracted data from each identified study; only studies with sufficient quality were included in the review. The main outcome of interest was incidence of prostate cancer. Compared with consumers of lower raw tomato intake, the odds ratio (OR) of incidence of prostate cancer among consumers of higher raw tomato intake was 0.81 [95% confidential interval (CI) 0.59-1.10]; for consumers of higher level of cooked tomato intake versus lower cooked tomato intake, this OR was 0.85 (95% CI 0.69-1.06); the OR of higher lycopene intake versus lower lycopene intake for prostate cancer was 0.93 (95% CI 0.86-1.01) and the OR for higher level of serum lycopene versus lower serum lycopene level was 0.97 (95% CI 0.88-1.08). It's suggested that tomato may play a modest role in the prevention of prostate cancer. Further research would be needed to determine the type and quantity of tomato products regarding their potential in preventing prostate cancer.


Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon.
Secretagogues acting at a variety of receptor types activate electrogenic K(+) secretion in guinea pig distal colon, often accompanied by Cl(-) secretion. Distinct blockers of K(Ca)1.1 (BK, Kcnma1), iberiotoxin (IbTx), and paxilline inhibited the negative short-circuit current (I(sc)) associated with K(+) secretion. Mucosal addition of IbTx inhibited epinephrine-activated I(sc) ((epi)I(sc)) and transepithelial conductance ((epi)G(t)) consistent with K(+) secretion occurring via apical membrane K(Ca)1.1. The concentration dependence of IbTx inhibition of (epi)I(sc) yielded an IC(50) of 193 nM, with a maximal inhibition of 51%. Similarly, IbTx inhibited (epi)G(t) with an IC(50) of 220 nM and maximal inhibition of 48%. Mucosally added paxilline (10 μM) inhibited (epi)I(sc) and (epi)G(t) by ∼50%. IbTx and paxilline also inhibited I(sc) activated by mucosal ATP, supporting apical K(Ca)1.1 as a requirement for this K(+) secretagogue. Responses to IbTx and paxilline indicated that a component of K(+) secretion occurred during activation of Cl(-) secretion by prostaglandin-E(2) and cholinergic stimulation. Analysis of K(Ca)1.1α mRNA expression in distal colonic epithelial cells indicated the presence of the ZERO splice variant and three splice variants for the COOH terminus. The presence of the regulatory β-subunits K(Ca)β1 and K(Ca)β4 also was demonstrated. Immunolocalization supported the presence of K(Ca)1.1α in apical and basolateral membranes of surface and crypt cells. Together these results support a cellular mechanism for electrogenic K(+) secretion involving apical membrane K(Ca)1.1 during activation by several secretagogue types, but the observed K(+) secretion likely required the activity of additional K(+) channel types in the apical membrane.


Evaluation of cefazolin as a surrogate marker for cefpodoxime susceptibility for urinary tract isolates.
Of the cephalosporins, cefpodoxime has the most published clinical data for the treatment of urinary tract infections. In 2014, the Clinical and Laboratory Standards Institute (CLSI) guidelines recommended that cefazolin should be used as the surrogate marker for cefpodoxime among urinary tract isolates, replacing cephalothin. This study attempted to determine how well cefazolin serves as the surrogate marker. Additionally, it investigated how cefuroxime compared with cefazolin as a surrogate marker. The MicroScan Walkaway Plus system was used to determine susceptibility for cefazolin and cefuroxime on consecutive urine cultures with a colony count of ≥ 50 000 organisms. Only Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis isolates were included, following CLSI guidelines. Simultaneously, an Etest for cefpodoxime was conducted. The cefpodoxime interpretation was compared with that of the other two agents, and the categorical agreement was calculated, defined as the percentage of identical susceptibility interpretations. Cefazolin (92 %) had a significantly higher categorical agreement than cefuroxime (85 %) among 284 isolates (P = 0.011). The major error rate was 4.4 % for cefazolin and 1.1 % for cefuroxime. The very major error rate was 64 % for cefazolin and 18 % for cefuroxime among the 11 cefpodoxime-resistant isolates. Cefazolin was a better predictor of cefpodoxime susceptibility than the previously recommended agent, cephalothin. However, cefuroxime had better major and very major error rates than cefazolin.


Modeling of Longitudinal Changes in Left Ventricular Dimensions among Female Adolescent Runners.
Left ventricular (LV) enlargement has been linked to sudden cardiac death among young athletes. This study aimed to model the effect of long-term incessant endurance training on LV dimensions in female adolescent runners. Japanese female adolescent competitive distance runners (n = 36, age: 15 years, height: 158.1 ± 4.6 cm, weight: 44.7 ± 6.1 kg, percent body fat: 17.0 ± 5.2%) underwent echocardiography and underwater weighing every 6 months for 3 years. Since the measurement occasions varied across subjects, multilevel analysis was used for curvilinear modeling of changes in running performance (velocities in 1500 m and 3000 m track race), maximal oxygen uptake (VO2max), body composition, and LV dimensions. Initially, LV end-diastolic dimension (LVEDd) and LV mass were 47.0 ± 3.0 mm and 122.6 ± 15.7 g, respectively. Running performance and VO2max improved along with the training duration. The trends of changes in fat-free mass (FFM) and LVEDd were similarly best described by quadratic polynomials. LVEDd did not change over time in the model including FFM as a covariate. Increases in LV wall thicknesses were minimal and independent of FFM. LV mass increased according to a quadratic polynomial trend even after adjusting for FFM. FFM was an important factor determining changes in LVEDd and LV mass. Although running performance and VO2max were improved by continued endurance training, further LV cavity enlargement hardly occurred beyond FFM gain in these adolescent female runners, who already demonstrated a large LVEDd.


Comparison of Hospital-Based and Home-Based Obstructive Sleep Apnoea Severity Measurements with a Single-Lead Electrocardiogram Patch.
Obstructive sleep apnoea (OSA) is a global health concern, and polysomnography (PSG) is the gold standard for assessing OSA severity. However, the sleep parameters of home-based and in-laboratory PSG vary because of environmental factors, and the magnitude of these discrepancies remains unclear. We enrolled 125 Taiwanese patients who underwent PSG while wearing a single-lead electrocardiogram patch (RootiRx). After the PSG, all participants were instructed to continue wearing the RootiRx over three subsequent nights. Scores on OSA indices-namely, the apnoea-hypopnea index, chest effort index (CEI), cyclic variation of heart rate index (CVHRI), and combined CVHRI and CEI (Rx index), were determined. The patients were divided into three groups based on PSG-determined OSA severity. The variables (various severity groups and environmental measurements) were subjected to mean comparisons, and their correlations were examined by Pearson's correlation coefficient. The hospital-based CVHRI, CEI, and Rx index differed significantly among the severity groups. All three groups exhibited a significantly lower percentage of supine sleep time in the home-based assessment, compared with the hospital-based assessment. The percentage of supine sleep time (∆Supine%) exhibited a significant but weak to moderate positive correlation with each of the OSA indices. A significant but weak-to-moderate correlation between the ∆Supine% and ∆Rx index was still observed among the patients with high sleep efficiency (≥80%), who could reduce the effect of short sleep duration, leading to underestimation of the patients' OSA severity. The high supine percentage of sleep may cause OSA indices' overestimation in the hospital-based examination. Sleep recording at home with patch-type wearable devices may aid in accurate OSA diagnosis.


Airway symptoms among house painters in relation to exposure to volatile organic compounds (VOCS)--a longitudinal study.
The increased use of water-based paint (WBP) for indoor application during the last decade has drastically changed the exposure conditions for Swedish house painters. WBP has a lower emission of volatile organic compounds (VOCs) than solvent-based paint (SBP), but contains more reactive compounds, such as biocides, glycol ethers, and other high molecular solvents. The aim of this study was to compare the incidence of airway symptoms and self-reported asthma in house painters with a different degree of use of WBP and SBP. The incidence of seven general airway symptoms, and three work-related symptoms, was analysed by means of a self-administered questionnaire, in a cohort of 207 house painters followed from 1989 to 1992. Different airway symptoms were compared with clinical information obtained by a methacholine challenge test and dynamic spirometry in a selected subgroup of 44 painters. Information on the degree of use of SBP and WBP was used to estimate the total exposure to volatile organic compounds (TVOC) for each individual. In total, 175 men in the cohort worked as painters during the study period. No increase of asthma or respiratory symptoms was observed among those 50 painters with a pure exposure to WBP (estimated TVOC 1-3 mg m-3). Most painters (N = 125) had a mixed exposure to SBP and WBP, the main source of the TVOC being the limited use of SBP. WBP was perceived as less irritative than SBP, but complaints on airway irritation from WBP increased during the study period. The most pronounced increase of airway irritation in relation to both SBP and WBP, was observed among those 35 painters with the highest solvent exposure (estimated TVOC 100-380 mg m-3). An increase of respiratory symptom index and shortness of breath, in relation to estimated TVOC exposure was also observed. Selection effects were detected. Painters leaving their job during the study period had more non-specific hyper-reactivity symptoms, and more airway irritation from WBP, as compared to painters remaining at their occupation. Our study indicates that VOC emissions from SBPs may contribute to the development of respiratory symptoms and airway irritation. We found no increase of respiratory symptoms among painters exposed only to WBPs. There were, however, indications that VOC exposure from WBPs may cause airway irritation in some subjects. Because of selection effects, cross-sectional studies on respiratory symptoms in relation to occupational exposure to paint emissions may be inconclusive.


Gene array technology to determine host responses to Salmonella.
Gene expression array technology is a powerful new tool that has already been used to expand our understanding of host-pathogen interactions. There has been a rapid increase in published reports describing use of this approach to profile host responses to pathogenic bacteria and viruses. The large number of array studies currently in progress coupled with increasing accessibility of this new technology promises a plethora of gene expression data on host response to infection in the near future. Recent insights into macrophage and epithelial cell responses to Salmonella infection garnered from array studies are outlined and used as a basis to discuss various future research directions using gene arrays that will advance the field of cellular microbiology. There is an exciting potential for the gene expression data generated in such studies to provide insights into host physiology, the pathophysiology of disease and novel therapeutics.


Centrally mediated release by cocaine of endogenous epinephrine and norepinephrine from the sympathoadrenal medullary system of unanesthetized rats.
A radioenzymatic-paper chromatographic method for a simultaneous assay of catecholamines was used to study the effect of cocaine on the release of endogenous catecholamines from the sympathoadrenal medullary system into the blood of unanesthetized rats. Twenty-four hours after arterial cannulation, the "basal" levels of norepinephrine (NE) and epinephrine (EPI) in blood obtained through the catheter from conscious, undisturbed rats were 0.48 +/- 0.06 and 0.36 +/- 0.06 ng/ml, respectively. Administration, via the arterial catheter, of cocaine (0.4-10 mg/kg) produced dose-related increases in NE (0.59 +/- 0.03 to 1.58 +/- 0.34 ng/ml) and EPI (1.15 +/- 0.16 to 6.67 +/- 0.46 ng/ml). Inhibition of catechol O-methyltransferase by tropolone (40 mg/kg) enhanced by 5- to 10-fold the maximal response to cocaine without altering significantly the basal plasma levels of EPI or NE. Bilateral splanchnic denervation reduced the cocaine-tropolone-induced release of EPI and NE by 75 and 50%, respectively. Desipramine (10 mg/kg) failed to alter significantly plasma levels of NE or EPI, even after tropolone. Thus, the increment in plasma levels of NE and EPI in conscious rats given cocaine is mainly the result of a centrally mediated adrenal medullary discharge of catecholamines, rather than inhibition of catecholamine uptake.


Advances in stem cell therapy for spinal cord injury.
Spinal cord injury (SCI) is a devastating condition producing great personal and societal costs and for which there is no effective treatment. Stem cell transplantation is a promising therapeutic strategy, though much preclinical and clinical research work remains. Here, we briefly describe SCI epidemiology, pathophysiology, and experimental and clinical stem cell strategies. Research in stem cell biology and cell reprogramming is rapidly advancing, with the hope of moving stem cell therapy closer to helping people with SCI. We examine issues important for clinical translation and provide a commentary on recent developments, including termination of the first human embryonic stem cell transplantation trial in human SCI.


Rhomboid proteases and their biological functions.
The rhomboids are a well-conserved family of intramembrane serine proteases, which are unrelated to the classical soluble serine proteases. Their active site is buried within the plane of the membrane, and they cleave substrates in or near transmembrane domains. Although recently discovered, it is becoming clear that rhomboids control many important cellular functions. This review briefly describes recent biochemical and structural work that begins to explain how proteolysis occurs in a hydrophobic environment, but then focuses more extensively on the emerging biological functions of rhomboids. Although the function of most rhomboids is not yet known, they have already been implicated in growth factor signaling, mitochondrial function, host cell invasion by apicomplexan parasites, and protein translocation across membranes in bacteria. By exploiting cellular membrane trafficking machinery, rhomboids have evolved novel strategies to regulate proteolysis.


The reliability of the carbon dioxide-rebreathing, indirect Fick method of cardiac output determination in patients with pulmonary disease.
1. The CO2-rebreathing indirect Fick method of cardiac-output measurement was compared with the standard invasive direct Fick method for oxygen during rest and treadmill exercise in 15 patients with pulmonary disease characterized by the common feature of expiratory-airflow limitation. 2. The correlation coefficient for all 37 determinations was 0.94 (P less than 0.01); in patients who had a Pa-ETCO2 (arterial end-tidal PCO2 gradient) of greater than 5 mmHg, the coefficient was 0.69 (P less than 0.05), and in the remainder, with a normal Pa-ETCO2, 0.98 (P less than 0.01). 3. The difference in correlation between these two latter groups is statistically significant. 4. It is concluded that the indirect method is valid in most patients with pulmonary disease, but that the correlation with the direct Fick method is significantly worse when the Pa-ETCO2 exceeds 5 mmHg.


SPINS: standardized protein NMR storage. A data dictionary and object-oriented relational database for archiving protein NMR spectra.
Modern protein NMR spectroscopy laboratories have a rapidly growing need for an easily queried local archival system of raw experimental NMR datasets. SPINS (Standardized ProteIn Nmr Storage) is an object-oriented relational database that provides facilities for high-volume NMR data archival, organization of analyses, and dissemination of results to the public domain by automatic preparation of the header files required for submission of data to the BioMagResBank (BMRB). The current version of SPINS coordinates the process from data collection to BMRB deposition of raw NMR data by standardizing and integrating the storage and retrieval of these data in a local laboratory file system. Additional facilities include a data mining query tool, graphical database administration tools, and a NMRStar v2. 1.1 file generator. SPINS also includes a user-friendly internet-based graphical user interface, which is optionally integrated with Varian VNMR NMR data collection software. This paper provides an overview of the data model underlying the SPINS database system, a description of its implementation in Oracle, and an outline of future plans for the SPINS project.


Estimating the critical immunity threshold for preventing hepatitis A outbreaks in men who have sex with men.
Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R 0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R 0 of 1·71-3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R 0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.


Exposure to volatile organic compounds and loss of pulmonary function in the elderly.
Volatile organic compounds (VOCs) are reported to cause adverse effects on pulmonary function in occupationally exposed workers. However, evidence is lacking on the effect in the general population. We hypothesised that VOCs impair pulmonary function through enhancing oxidative stress, especially in the elderly population. A longitudinal panel study of 154 elderly people was performed in South Korea. Repeated spirometric tests were performed up to eight times on different days for each subject. We also measured urinary concentrations of metabolites of the VOC and markers of oxidative stress (malondialdehyde and 8-oxo-2'-deoxyguanosine) on the same day of spirometric tests. A mixed linear regression model was used to evaluate the association among the VOC metabolites, oxidative stress markers and spirometric tests. We found that the urinary levels of hippuric acid and methylhippuric acid, which are metabolites of toluene and xylene, respectively, were significantly associated with reduction of forced expiratory volume in 1 s (FEV₁), FEV₁/forced vital capacity (FVC), and forced expiratory flow at 25-75% of FVC. We also found significant associations between the metabolites of VOCs and the markers of oxidative stress. In addition, the oxidative stress markers were associated with pulmonary function parameters. This study suggests that exposure to toluene and xylene exert a harmful effect on pulmonary function by exacerbating oxidative stress in elderly people.


Indications for surgery in patients with localized pulmonary infection.
Nowadays, antibiotic and antifungal therapy is effective in treating some of the infections that can involve the lung parenchyma in a localized manner, such as bacterial abscess and infection with nonresistant tuberculosis strains. However, other localized pulmonary infections, for example aspergilloma and mucormycosis, are highly resistant to nonsurgical therapy, and in these diseases there are no generally successful options that do not include surgical resection. This article reviews the indications for surgical intervention in the treatment of common infections involving the lung, and also focuses on the general approaches to their management.


Social and emotional training in Swedish schools for the promotion of mental health: an effectiveness study of 5 years of intervention.
The school is an obvious arena for interventions designed to promote mental health among children. A set of educational techniques named social and emotional learning, which focuses on students' self-control, social competence, empathy, motivation and self-awareness, has shown promising results in the United States. This is a study of the application of a similar method in Sweden (referred to as social and emotional training) for school years 2000/2001 through to 2004/2005. It is an effectiveness rather than an efficacy study, largely administered by school personnel, which relates duration of the training (1-5 years) to a set of outcomes previously found to be associated with mental health. Positive and significant effects were found on five of seven variables: internalizing problems, externalizing problems, mastery (reflecting self-efficacy or hopelessness), self-image and self-esteem and contentment in school. Effect sizes were medium. Somewhat surprisingly, no relationship was found between the intervention and the promotion of social skills. Nor was there any detectable long-term impact on bullying. Controlling for student gender did not moderate any of the effects.


Sex and Racial/Ethnic Differences in Positive Outcomes in Delinquent Youth After Detention: A 12-Year Longitudinal Study.
Longitudinal studies of delinquent youth have focused on criminal recidivism, not on psychosocial outcomes in adulthood. This omission is critical because after detention most youth return to the community, where they become the responsibility of pediatric health care professionals. To investigate 8 positive outcomes among delinquent youth 5 and 12 years after detention, focusing on sex and racial/ethnic differences. In the Northwestern Juvenile Project, a longitudinal US study of long-term outcomes of delinquent youth after detention, participants were interviewed in detention between November 20, 1995, and June 14, 1998, and reinterviewed up to 9 times during the 12-year study period, through May 12, 2011. Data analysis was conducted between November 18, 2013, and July 25, 2016. Juvenile detention. Achievement of positive outcomes in 8 domains: educational attainment, residential independence, gainful activity, desistance from criminal activity, mental health, abstaining from substance abuse, interpersonal functioning, and parenting responsibility. Outcomes were assessed with widely used measures supplemented by correctional records. The study included 1829 youth at baseline (1172 males and 657 females; mean [SD] age, 14.9 [1.4] years). At the end of the study, 1520 (83.1%) of the original sample remained (944 males and 576 females; mean [SD] age, 27.6 [1.4] years). Twelve years after detention, females were more likely than males to have positive outcomes for gainful activity (odds ratio [OR], 2.53; 95% CI, 1.86-3.44), desistance from criminal activity (OR, 5.89; 95% CI, 4.38-7.92), residential independence (OR, 3.41; 95% CI, 2.57-4.52), parenting responsibility (OR, 18.65; 95% CI, 12.29-28.30), and mental health (OR, 1.48; 95% CI, 1.13-1.92). Twelve years after detention, only 21.9% of males and 54.7% of females had achieved more than half of the outcomes. As youth aged, the number of positive outcomes increased only modestly (mean increase for males, 0.37; 95% CI, 0.13-0.62; for females, 0.29; 95% CI, 0.13-0.45). Among males, non-Hispanic white individuals were significantly more likely to achieve most positive outcomes compared with minorities, but less likely to abstain from substance abuse. For example, 12 years after detention, non-Hispanic white males had nearly 3 times the odds of educational attainment compared with African American (OR, 2.82; 95% CI, 1.77-4.50) and Hispanic males (OR, 2.91; 95% CI, 1.75-4.82), and 2 to 5 times the odds of gainful activity compared with African American (OR, 5.17; 95% CI, 3.16-8.45) and Hispanic males (OR, 2.58; 95% CI, 1.56-4.26). Latent class analysis shows that African American males fared the worst, with lives characterized by incarceration, criminal activity, and few positive outcomes. Our findings highlight racial/ethnic disparities among youth in achieving positive outcomes after detention. To improve outcomes, pediatric health care professionals should recognize the importance of psychosocial health, partner with on-site psychosocial services in their practices, and facilitate access to services in the community.


Molecular characterization of Staphylococcus aureus isolates causing skin and soft tissue infections (SSTIs).
Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is an important cause of pyogenic skin and soft tissue infections (SSTIs). The aim of present study is to investigate the molecular characteristic of Staphylococcus aureus isolates isolated from the pus samples from the patients with purulent skin and soft tissue infections in Wenzhou, China. Between December 2002 and June 2008, a total of 111 nonduplicate S. aureus isolates were collected from the pus samples of the patients with SSTIs in a teaching hospital in Wenzhou, China. All the tested isolates were confirmed as S. aureus using a Staph SPA agglutination kit, Gram's stain and a Vitek-60 microbiology analyzer. The homology among the tested isolates was determined by pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) was used to determine the sequence types (STs) of the selected isolates. The genotypes of SCCmec were determined by a multiplex PCR in the MRSA isolates. Panton-Valentine leukocidin (PVL) genes and mecA were also determined by another multiplex PCR. Among the 111 S. aureus isolates, 48 and 63 isolates were community-acquired and hospital-acquired respectively. Sixty isolates were confirmed as MRSA harboring mecA detected by PCR. A total of 32 PFGE clonal types were obtained by PFGE, with 10 predominant patterns (types A to J). Twenty-five different STs including ST398 and three novel STs were found among 51 selected isolates. The main STs were ST239, ST1018, ST59, ST7 and ST88. Of 60 MRSA isolates, SCCmec II, III, IV and SCCmec V were found in three, 50, three and two isolates, respectively. The positive rates of PVL genes in overall isolates, HA-isolates, CA-isolates, MRSA isolates and MSSA isolates were 23.4% (26/111), 20.6% (13/63), 27.1% (13/48), 21.7% (13/60) and 25.5% (13/51), respectively. Eight (33.3%, 8/24) of 24 CA-MRSA isolates and 5 (13.9%, 5/36) of 36 HA-MRSA isolates were positive for PVL genes. ST239-MRSA-SCCmecIII and ST1018-MRSA-SCCmecIII clones were found to be main clones and spread between community and hospital. S. aureus isolates causing SSTIs showed considerable molecular heterogeneity and harbored high prevalence of PVL genes. Clonal spread was responsible for the dissemination of the isolates of S. aureus associated with SSTIs.


Association between Asian dust exposure and respiratory function in children with bronchial asthma in Nagasaki Prefecture, Japan.
Studies on the adverse effects of Asian dust (AD) on respiratory function in children are scarce. The objective of this study was to examine the association between AD and respiratory function by measuring peak expiratory flow rates (PEFRs) in asthmatic children. The study was carried out from March to May from 2014 through 2016. One hundred ten children with bronchial asthma were recruited from four hospitals in the Goto Islands and south Nagasaki area in Nagasaki prefecture. The parents were asked to record their children's PEFRs every morning/evening and clinical symptoms in an asthma diary. AD was assessed from light detection and ranging data, and a linear mixed-effects model was used to estimate the effects of AD on daily PEFR. Time-stratified case-crossover analyses were performed to examine the association between AD and asthma attacks defined by reduction levels in PEFR. AD was detected on 11 days in the Goto Islands, and on 23 days in the south Nagasaki area. After adjusting for age, sex, temperature, and daily oxidants, we found a consistent association between AD and a 1.1% to 1.7% decrease in PEFR in the mornings and a 0.7% to 1.3% decrease in the evenings at a lag of 0 to 5 days. AD was not associated with the number of asthma attacks, respiratory symptoms, or other symptoms at any lag days examined. Exposure to AD was associated with reduced PEFR, although the effects were not large enough to induce clinically apparent symptoms, in clinically well-controlled asthmatic children.


Suppression of T-cell expansion by melanoma is exerted on resting cells.
Immunotherapeutic cancer protocols often rely on the ability to promote proliferative expansion of tumor-specific T-cell, but the influence of cancer on in vivo T-cell expansion remains largely undefined. The ability of control and B16F10 melanoma-bearing C57BL/6 mice to expand lymphocytic choriomeningitis virus antigen-specific T-cell populations in response to acute viral infection was compared by using flow cytometric assays of splenocytes. The ability to expand virus-specific CD8+ and CD4+ T-cells was globally and markedly suppressed in tumor-bearing mice. Expanded cytotoxic T lymphocytes (CTLs) retained in vivo and in vitro functionality, suggesting that melanoma growth did not induce T-cell anergy. The magnitude of suppressed proliferative expansion was proportional to the extent of tumor burden. Melanoma-induced suppression of CTL expansion was correlated with upregulated apoptotic activity and hampered the induction of memory precursor effector cells. Adoptive transfer of resting LCMV antigen-specific T-cells before or after tumor establishment demonstrated that a critical period of in vivo exposure of resting T-cells to growing melanoma was responsible for the induction of suppressed expansion. This suppression was durable; surgical resection of melanoma after in vivo exposure to resting T-cells but before antigenic stimulation did not restore full expansion. These data suggest that growing melanoma tumors exert a global, antigen-independent influence on resting T-cells that fundamentally reprograms their ability to undergo proliferative expansion in response to subsequent antigenic stimulation. This finding may have direct implications for T-cell-based immunotherapeutic strategies.


Ancestral polymorphism of Mhc class II genes in mice: implications for balancing selection and the mammalian molecular clock.
To investigate the evolutionary dynamics at Mhc class II DR genes of mice (genus Mus), we sequenced the peptide binding regions (PBRs) of 41 DRB (= E beta) genes and eight DRA (= E alpha) genes from 15 strains representing eight species. As expected trees of these PBR sequences imply extensive maintenance of ancestral DRB alleles across species. We use a coalescent simulation model to show that the number of interspecific coalescent events (c) observed on these trees was higher than the number expected for neutral genealogies and similar sample sizes and is more consistent with balancing selection that with neutrality. Patterns of ancestral polymorphism in mouse DRB alleles were also used to examine the tempo of synonymous substitution in the PBR of mouse class II genes. Both absolute and relative rate tests on DRA and DRB genes imply increased substitution rates at two- and fourfold degenerate sites of mice and rats relative to primates, and decreased rates for the DRB genes of primates relative to ungulate and carnivore relatives. Thus rates of synonymous substitution at Mhc DR genes in mammals appear to be subject to generation time effects in ways similar to those found at other mammalian genes.


Controlling the Raman response of inhomogeneously distributed multiple vibrational modes with optimally shaped light fields.
We demonstrate that Raman-effect-assisted transformations of ultrashort pulses in materials with inhomogeneously distributed multiple vibrational modes can be tailored by optimally ordered pulse sequences and appropriate optical sampling. This suggests attractive strategies for a synthesis of few-cycle pulses, enhanced spectral transformation of light fields, and pulse shaping in silica fibers and other materials with multiple Raman modes.


Antioxidant and Hepatoprotective Activities of Ethanolic Extracts of Leaves of Premna esculenta Roxb. against Carbon Tetrachloride-Induced Liver Damage in Rats.
Premna esculenta Roxb. (family Verbenaceae) is a shrub used by the ethnic people of Chittagong Hill Tracts of Bangladesh for the treatment of hepatocellular jaundice. The present study was done to evaluate the hepatoprotective and the in vivo antioxidant activity of ethanolic extracts of leaves of the plant in carbon tetrachloride-induced liver damage in rats. Hepatotoxicity was induced in rats by i.p. injection of CCl4 diluted with olive oil (1:1 v/v; 1 mL/kg body weight) on alternate days for 7 days. After 7 days of pretreatment of test extracts, the biochemical markers such as Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Alkaline Phosphatase (ALP), total protein, and albumin were estimated followed by the measurement of liver cytosolic antioxidant enzymes such as superoxide dismutase, catalase, and peroxidase. The data were analyzed using one-way analysis of variance (ANOVA) followed by Dunnett's t-test. The extract both at the doses of 200 and 400 mg/kg p.o. significantly (P < 0.001) reduced the elevated levels of SGPT, SGOT, ALP and increased the reduced levels of total protein and albumin compared to the CCl4-treated animals. The extracts also showed a significant (P < 0.001) increase in the reduced levels of superoxide dismutase (SOD), catalase, and peroxidase. The effects of the extracts on these parameters were comparable with those of the standard, silymarin. The findings of the study indicate that the leaf extract of P. esculenta showed a potential hepatoprotective activity and the protective action might have manifested by restoring the hepatic SOD, catalase, and peroxidase levels. The results justify the traditional use of this plant in liver disorders.


Is there a potential international market for Danish welfare pork? - A consumer survey from Denmark, Sweden, and Germany.
This cross-country study investigates the potential to improve pig welfare by exploiting consumer demand, domestically and in export markets, for welfare pork produced in indoor production systems. The analysis is based on questionnaire data collected in 2019 focusing on demand for Danish welfare pork both in Denmark and in two nearby export markets, Sweden and Germany. To reduce hypothetical bias, a willingness-to-pay indicator is combined with an indicator of positive interest in buying a fictive Danish welfare labelled pork. We find that the market potential is relatively weak. Our findings indicate that there is some, albeit limited, potential in Denmark and Germany while demand is practically non-existing in Sweden, probably because the pig welfare guaranteed by Swedish legislation is similar to what is provided by the fictive welfare label employed in the study. Hence, consumer demand alone cannot secure enhanced pig welfare. Moreover, we found national differences in the characteristics of consumers who are interested in Danish welfare pork.


Long-lasting transition toward sustainable elimination of desert malaria under irrigation development.
In arid areas, people living in the proximity of irrigation infrastructure are potentially exposed to a higher risk of malaria due to changes in ecohydrological conditions that lead to increased vector abundance. However, irrigation provides a pathway to economic prosperity that over longer time scales is expected to counteract these negative effects. A better understanding of this transition between increased malaria risk and regional elimination, in particular whether it is slow or abrupt, is relevant to sustainable development and disease management. By relying on space as a surrogate for stages of time, we investigate this transition in a semidesert region of India where a megairrigation project is underway and expected to cover more than 1,900 million hectares and benefit around 1 million farmers. Based on spatio-temporal epidemiological cases of Plasmodium vivax malaria and land-use irrigation from remote sensing sources, we show that this transition is characterized by an enhanced risk in areas adjacent to the trunk of the irrigation network, despite a forceful and costly insecticide-based control. Moreover, this transition between climate-driven epidemics and sustained low risk has already lasted a decade. Given the magnitude of these projects, these results suggest that increased health costs have to be planned for over a long time horizon. They further highlight the need to integrate assessments of both health and environmental impacts to guide adaptive mitigation strategies. Our results should help to define and track these transitions in other arid parts of the world subjected to similar tradeoffs.


P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis.
Snake venoms are composed of pharmacologically active proteins that are evolutionarily diverse, stable and specific to targets. Hence, venoms have been explored as a source of bioactive molecules in treating numerous diseases. Recent evidences suggest that snake venom proteins may affect the formation of new blood vessels. Excessive angiogenesis has been implicated in several pathologies including tumours, diabetic retinopathy, arthritis, inter alia. In the present study, we have examined the effects of P-I metalloproteinases isolated from Bothrops moojeni (BmMP-1) and Bothrops atrox (BaMP-1) and L-amino acid oxidases (LAAO) isolated from B. moojeni (BmLAAO) and B. atrox (BaLAAO) on biochemical and functional aspects of angiogenesis. P-I metalloproteinases and LAAO were purified from venom by molecular size exclusion and ion-exchange chromatography and subsequently confirmed using mass spectrometry. The P-I metalloproteinases were characterized by azocaseinolytic, fibrinogenolytic and gelatinase activity and LAAO activity was assessed by enzyme activity on L-amino acids. Influence of these proteins on apoptosis and cell cycle in endothelial cells was analysed by flow cytometry. The angiogenic activity was determined by in vitro 3D spheroid assay, Matrigel tube forming assay, and in vivo agarose plug transformation in mice. P-I metalloproteinases exhibited azocaseinolytic activity, cleaved α and partially β chain of fibrinogen, and displayed catalytic activity on gelatin. LAAO showed differential activity on L-amino acids. Flow cytometry analysis indicated that both P-I metalloproteinases and LAAO arrested the cells in G0/G1 phase and further induced both necrosis and apoptosis in endothelial cells. In vitro, P-I metalloproteinases and LAAO exhibited significant anti-angiogenic properties in 3D spheroid and Matrigel models by reducing sprout outgrowth and tube formation. Using agarose plug transplants in mice harbouring P-I metalloproteinases and LAAO we demonstrated a marked disruption of vasculature at the periphery. Our research suggests that P-I metalloproteinases and LAAO exhibit anti-angiogenic properties in vitro and in vivo.


Precision surface measurement.
Surface size, geometry and texture are some of the most influential subjects in the fields of precision and ultra-precision engineering, defining the functional interface through which emerging products operate. Next-generation products demand super-smooth surfaces, freeform geometries or even deterministically introduced microstructures to provide functional performance. Technological progress using these surfaces types is possible only if the associated manufacturing processes are rigorously controlled and the surfaces are measurable. Metrology for advanced surfaces is not established. The current state of the art is challenged in respect to (i) surface characteristics, extremity of size, ultra precision, quality, geometric complexity, or combinations of these aspects, and (ii) measurement technology for the manufacturing environment, in particular, online, non-contact, high speed, ease of use, small footprint and robustness. This study addresses the challenges in this subject area and discusses some fundaments and principles derived from interdisciplinary research. The combination of these aspects is enabling the creation of manufacturing-environment-based measurement technology. This is expected to facilitate advanced surface manufacture over a wide range of sectors, including large science programmes and high-technology engineering.


COVID-19 Conspiracy Theories Discussion on Twitter.
The coronavirus disease 2019 (COVID-19) pandemic was an unexpected event and resulted in catastrophic consequences with long-lasting behavioral effects. People began to seek explanations for different aspects of COVID-19 and resorted to conspiracy narratives. The objective of this article is to analyze the changes on the discussion of different COVID-19 conspiracy theories throughout the pandemic on Twitter. We have collected a data set of 1.269 million tweets associated with the discussion on conspiracy theories between January 2020 and November 2021. The data set includes tweets related to eight conspiracy theories: the 5G, Big Pharma, Bill Gates, biological weapon, exaggeration, FilmYourHospital, genetically modified organism (GMO), and the vaccines conspiracy. The analysis highlights several behaviors in the discussion of conspiracy theories and allows categorizing them into four groups. The first group are conspiracy theories that peaked at the beginning of the pandemic and sharply declined afterwards, including the 5G and FilmYourHospital conspiracies. The second group associated with the Big Pharma and vaccination-related conspiracy whose role increased as the pandemic progressed. The third are conspiracies that remained persistent throughout the pandemic such as exaggeration and Bill Gates conspiracies. The fourth are those that had multiple peaks at different times of the pandemic including the GMO and biological weapon conspiracies. In addition, the number of COVID-19 new cases was found to be a significant predictor for the next week tweet frequency for most of the conspiracies.


Stable carbon isotope evidence for nitrogenous fertilizer impact on carbonate weathering in a small agricultural watershed.
The isotopic signature of Dissolved Inorganic Carbon (DIC), δ(13)C(DIC), has been investigated in the surface waters of a small agricultural catchment on calcareous substratum, Montoussé, located at Auradé (south-west France). The Montoussé catchment is subjected to intense farming (wheat/sunflower rotation) and a moderated application of nitrogenous fertilizers. During the nitrification of the NH(4)(+), supplied by fertilization, nitrate and H(+) ions are produced in the soil. This anthropogenic acidity is combined with the natural acidity due to carbonic acid in weathering processes. From an isotopic point of view, with 'natural weathering', using carbonic acid, δ(13)C(DIC) is intermediate between the δ(13)C of soil CO(2) produced by organic matter oxidation and that of the carbonate rocks, while it has the same value as the carbonates when carbonic acid is substituted by another acid like nitric acid derived from nitrogen fertilizer. The δ(13)C(DIC) values range from -17.1‰ to -10.7‰ in Montoussé stream waters. We also measured the δ(13)C of calcareous molassic deposits (average -7.9‰) and of soil organic carbon (between -24.1‰ and -26‰) to identify the different sources of DIC and to estimate their contribution. The δ(13) C(DIC) value indicates that weathering largely follows the carbonic acid pathway at the springs (sources of the stream). At the outlet of the basin, H(+) ions, produced during the nitrification of N-fertilizer, also contribute to weathering, especially during flood events. This result is illustrated by the relationship between δ(13)C(DIC) and the molar ratio NO(3)(-)/(Ca(2+) + Mg(2+)). Consequently, when the contribution of nitrate increases, the δ(13)C(DIC) increases towards the calcareous end-member. This new isotopic result provides evidence for the direct influence of nitrogen fertilizer inputs on weathering, CO(2) consumption and base cation leaching and confirms previous results obtained using the chemistry of the major ions present in the field, and in soil column experiments.