Health-related quality of life after burns: a prospective multicenter cohort study with 18 months follow-up.
Health-related quality of life (HRQOL) is an important parameter after medical treatments. Knowledge of (predictors of) diminished quality of life can help improve medical outcome. The aim of this study was to quantify health loss in patients with burns and to assess the contribution of injury extent, age, gender, and psychologic factors to HRQOL and speed of recovery. A multicenter prospective cohort design was used to address these aims. Data were obtained from 260 adults with burns. Patients completed the EQ-5D at 3 weeks, 3, 6, 9, and 18 months after burn and psychologic questionnaires during hospitalization. Patients' scores were compared with an age- and gender-weighted normpopulation. Patients suffered from substantial health losses at short term, but after 18 months the majority reached a HRQOL comparable with the norm population with the exception of patients requiring two or more surgeries. The best predictor of long-term HRQOL and the speed of recovery was the number of surgeries, followed by psychologic problems. Both predicted baseline and trajectories of improvement. Symptoms of traumatic stress were most debilitating over time. Both injury severity and psychologic problems play a pivotal role in reduced HRQOL and the speed of recovery. The number of surgeries seems to give a practically useful indication of the expected recovery speed that could aid in decision making and provides adequate information for patients in the aftermath of their initial surgical treatment. Screening for traumatic stress is recommended.


Nucleotide sequence of dihydrofolate reductase type VI.
The complete sequence of the type VI dihydrofolate reductase (DHFR) gene from plasmid pUK672 was determined. The structural gene coded for a polypeptide of 157 amino acids which had a deduced mol. wt of 17,424. Comparison with amino-acid sequences of the type I, type V and Escherichia coli K12 chromosomal DHFRs showed that there was 63%, 61% and 31% homology respectively. Putative RNA polymerase and ribosomal binding sites were identified proximal to the initiation codon and a feature consistent with transcription termination was present distal to the coding region. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed that the enzyme had a subunit mol. wt of 17,500.


Does dietary intake by Tehranian adults align with the 2005 dietary guidelines for Americans? Observations from the Tehran lipid and glucose study.
The aim of this study was to compare dietary intakes by Tehranian adults with recent dietary guidelines for the Americans. The study made a cross-sectional assessment of the dietary patterns of Tehranian adults using a validated food-frequency questionnaire. It included 2,510 subjects (1,121 men and 1,389 women) aged 19-70 years. They were the participants of the third follow-up survey of the Tehran Lipid and Glucose Study (2005-2008). The dietary patterns were assessed using the latest World Health Organization (WHO)'s nutritional goals and Dietary Guidelines for the Americans Adherence Index (DGAI) 2005. The mean [standard deviation (SD)] DGAI score for this population was 8.31 (1.9). Participants in the highest quartile category of DGAI were more likely to be female, older, non-smoking, and physically active than those in the lowest quartile category (p < 0.001). Percentage of participants meeting the DGA recommendations was low, especially for starchyvegetables (2.3%), orange vegetables (16.2%), lean meat (9.2%), grains (12.0%), and legumes (6.4%). Over-consumption of grains was observed in almost half of the participants while approximately 20% of the subjects over-consumed milk and meat groups. Intakes of most nutrients examined were significantly associated with the DGAI 2005 score (p < 0.001), except for vitamin E, vitamin B12, and vitamin D. The least adherence with the WHO goals was observed with n-3 PUFAs, sodium, fruit, and vegetable intakes. The results revealed that the dietary patterns of most Tehranian adults did not comply with the 2005 DGA and nutritional goals of WHO/Food and Agriculture Organization.


Print versus electronic journals: a preliminary investigation into the effect of journal format on research processes.
To begin investigating the impact of electronic journals on research processes such as information seeking, the authors conducted a pilot journal-use study to test the hypothesis that patrons use print and electronic journals differently. We placed fifteen high-use print titles also available in electronic format behind the circulation desk; patrons were asked to complete a survey upon requesting a journal. We also conducted a parallel survey of patrons using library computers. Both surveys asked patrons to identify themselves by user category and queried them about their journal use. During the month-long study, patrons completed sixty-nine surveys of electronic and ninety surveys of print journal use. Results analysis indicated that fellows, students, and residents preferred electronic journals, and faculty preferred print journals. Patrons used print journals for reading articles and scanning contents; they employed electronic journals for printing articles and checking references. Users considered electronic journals easier to access and search than print journals; however, they reported that print journals had higher quality text and figures. This study is an introductory step in examining how electronic journals affect research processes. Our data revealed that there were distinct preferences in format among categories. In addition to collection management implications for libraries, these data also have implications for publishers and educators; current electronic formats do not facilitate all types of uses and thus may be changing learning patterns as well.


Design and production in Aspergillus niger of a chimeric protein associating a fungal feruloyl esterase and a clostridial dockerin domain.
A chimeric enzyme associating feruloyl esterase A (FAEA) from Aspergillus niger and dockerin from Clostridium thermocellum was produced in A. niger. A completely truncated form was produced when the dockerin domain was located downstream of the FAEA (FAEA-Doc), whereas no chimeric protein was produced when the bacterial dockerin domain was located upstream of the FAEA (Doc-FAEA). Northern blot analysis showed similar transcript levels for the two constructs, indicating a posttranscriptional bottleneck for Doc-FAEA production. The sequence encoding the first 514 amino acids from A. niger glucoamylase and a dibasic proteolytic processing site (kex-2) were fused upstream of the Doc-FAEA sequence. By using this fusion strategy, the esterase activity found in the extracellular medium was 20-fold-higher than that of the wild-type reference strain, and the production yield was estimated to be about 100 mg of chimeric protein/liter. Intracellular and extracellular production was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, dockerin-cohesin interaction assays, and Western blotting. Labeled cohesins detected an intact extracellular Doc-FAEA of about 43 kDa and a cleaved-off dockerin domain of about 8 kDa. In addition, an intracellular 120-kDa protein was recognized by using labeled cohesins and antibodies raised against FAEA. This protein corresponded to the unprocessed Doc-FAEA form fused to glucoamylase. In conclusion, these results indicated that translational fusion to glucoamylase improved the secretion efficiency of a chimeric Doc-FAEA protein and allowed production of the first functional fungal enzyme joined to a bacterial dockerin.


Functional correlations of spatial quantitative EEG and intelligences in a nonalphabetical language group.
This study investigated any functional correlations between intelligences and spatially recorded quantitative electroencephalograms (QEEGs) in a nonalphabetical language group. Participants, between 6 and 8 years old, were sampled in a teaching hospital located at the central Taiwan region. The Chinese Wechsler Intelligence Scale for Children-III (WISC-III) intelligence test and quantitative electroencephalograph recording procedures were both administrated to collect data. Intelligences were divided into two categories, verbal and performance intelligences, for statistical investigations. Statistical analyses of the noncontaminated QEEG dataset investigated the differentiability of each frequency on a single cortical region and coherence between cortical regions. Low QEEG frequencies were found to have a significant correlation with intelligences on some cortical regions. Coherence between symmetric cortical regions was found to be an important factor in predicting intelligences. Results showed the feasibility of functional brain mapping in the particular language population.


Diversity in prokaryotic glycosylation: an archaeal-derived N-linked glycan contains legionaminic acid.
VP4, the major structural protein of the haloarchaeal pleomorphic virus, HRPV-1, is glycosylated. To define the glycan structure attached to this protein, oligosaccharides released by β-elimination were analysed by mass spectrometry and nuclear magnetic resonance spectroscopy. Such analyses showed that the major VP4-derived glycan is a pentasaccharide comprising glucose, glucuronic acid, mannose, sulphated glucuronic acid and a terminal 5-N-formyl-legionaminic acid residue. This is the first observation of legionaminic acid, a sialic acid-like sugar, in an archaeal-derived glycan structure. The importance of this residue for viral infection was demonstrated upon incubation with N-acetylneuraminic acid, a similar monosaccharide. Such treatment reduced progeny virus production by half 4 h post infection. LC-ESI/MS analysis confirmed the presence of pentasaccharide precursors on two different VP4-derived peptides bearing the N-glycosylation signal, NTT. The same sites modified by the native host, Halorubrum sp. strain PV6, were also recognized by the Haloferax volcanii N-glycosylation apparatus, as determined by LC-ESI/MS of heterologously expressed VP4. Here, however, the N-linked pentasaccharide was the same as shown to decorate the S-layer glycoprotein in this species. Hence, N-glycosylation of the haloarchaeal viral protein, VP4, is host-specific. These results thus present additional examples of archaeal N-glycosylation diversity and show the ability of Archaea to modify heterologously expressed proteins.


Expression of mTOR and downstream signalling components in the JEG-3 and BeWo human placental choriocarcinoma cell lines.
Emerging data suggest that nutritional status and body weight are related to reproductive function, and nutrient imbalances during pregnancy lead to changes in the expression of fetal genes. Recent studies show that the mTOR acts as a placental growth signalling sensor and its expression is down-regulated in intrauterine growth restriction. To date, very little is known about the expression of this signalling pathway in choriocarcinoma, one of the most lethal germ cell cancers. In this study, cultures of fusigenic (BeWo) and non-fusigenic (JEG-3) human choriocarcinoma cell lines were used to investigate the expression of mTOR and its downstream signalling components. The effects of an inducer of syncytialisation (forskolin) on mTOR, eIF4E binding proteins (4EBPs) and ribosomal protein S6 kinases (S6Ks) in BeWo cells were also assessed. RT-PCR studies revealed that mTOR, 4EBP and S6Ks are expressed at mRNA level in both JEG-3 and BeWo cells. Semi-quantitative RT-PCR analysis revealed that in early stages of syncytialisation (50 microM forskolin for 48 h), the expression of mTOR and 4EBP was down-regulated when compared to unstimulated cells. In fully syncytialised cells (50 microM forskolin for 72 h) the expression of both genes was similar to basal levels. Interestingly, the phosphorylation (Ser371, Thr389) status of p70S6K remained unaltered upon forskolin treatment. These data validate BeWo cells as an experimental model to study the effects of forskolin-induced syncytialisation on mTOR signalling.


The effect of mTOR inhibition alone or combined with MEK inhibitors on brain metastasis: an in vivo analysis in triple-negative breast cancer models.
mTOR inhibitor rapamycin and its analogs are lipophilic, demonstrate blood-brain barrier penetration, and have shown promising antitumor effects in several types of refractory tumors. We thus try to explore the therapeutic effects of mTOR inhibitors on brain metastasis models. We examined the effects of different dose of mTOR inhibitors (rapamycin, Temsirolimus-CCI-779) on cell invasion in two brain metastatic breast cancer cell lines (MDA-MB231-BR and CN34-BrM2). Antibody microarray and immunoblotting were applied to detect signaling pathways underlying the dose differential drug effects. The in vivo effects of single drug (CCI-779), and drug combination of CCI-779 with SL327 (a brain penetrant MEK inhibitor) to eliminate the unfavorable activation of MAPK pathway were evaluated in MDA-MB231-BR brain metastases xenograft mice. The two mTOR inhibitors, rapamycin and CCI-779, inhibited the invasion of brain metastatic cells only at a moderate concentration level, which was lost at higher concentrations secondary to activation of the MAPK signaling pathway. Pharmacological inhibition of ERK1/2 by PD98059 and SL327 restored the anti-invasion effects of mTOR inhibition in vitro. In vivo, a significant decrease was noted in the average number of micro and large metastatic lesions as well as the whole brain GFP expression in the CCI-779 1 mg/kg/day treated group compared with that in the vehicle group (P < 0.05). However, 10 mg/kg CCI-779 treatment did not show significant anti-metastasis effect on the animal model. High-dose CCI-779 eliciting the ERK MAPK activation in the brain metastatic lesion was corroborated. Combined with the brain penetrant MEK inhibitor SL327, high-dose CCI-779 significantly reduces the brain metastasis, and the combination treatment prohibited perivascular invasion of tumor cells and inhibits tumor angiogenesis in vivo. This study provides evidence on the potential value of CCI-779 as well as CCI-779 + SL327 in prohibiting breast cancer brain metastasis.


A cost-effectiveness analysis of using TheraBite in a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy.
Previous studies have shown that a "Preventive Exercise Program" (PREP) is cost-effective compared to the standard exercise program provided in "Usual Care" (UC) in patients with advanced head and neck cancer. The current paper specifically estimates the cost-effectiveness of the TheraBite jaw rehabilitation device (TB) which is used as part of the PREP, compared to Speech Language Pathology (SLP) sessions as part of UC, and herewith intents to inform reimbursement discussions regarding the TheraBite device. Costs and outcomes [quality-adjusted life-years (QALYs)] of the TB compared to SLP were estimated using a Markov model of advanced head and neck cancer patients. Secondary outcome variables were trismus, feeding substitutes, facial pain, and pneumonia. The incremental cost-effectiveness ratio (ICER) was estimated from a health care perspective of the Netherlands, with a time horizon of 2 years. The total health care costs per patient were estimated to amount to €5,129 for the TB strategy and €6,915 for the SLP strategy. Based on the current data, the TB strategy yielded more quality-adjusted life-years (1.28) compared to the SLP strategy (1.24). Thus, the TB strategy seems more effective (+0.04) and less costly (-€1,786) than the SLP only strategy. At the prevailing threshold of €20,000/QALY the probability for the TB strategy being cost-effective compared to SLP was 70 %. To conclude, analysis of presently available data indicates that TB is expected to be cost-effective compared to SLP in a preventive exercise program for concomitant chemo-radiotherapy for advanced head and neck cancer patients.


Opportunity for Collaboration Between Radiation Injury Treatment Network Centers and Medical Toxicology Specialists.
The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers. We determined the locations of existing RITN centers and assessed their proximity to various medical toxicology resources, including medical toxicology fellowship programs, inpatient toxicology services, outpatient toxicology clinics, and poison control centers. Data were derived from publicly available Internet sources in March 2015. The majority of RITN centers do not have a medical toxicology fellowship, an inpatient toxicology service, or an outpatient toxicology clinic within the same institution. Fifty-seven percent of RITN centers have at least one of these resources located in the same city, however, and 73% of centers have at least one of these resources or a poison control center within the same city. Ninety-five percent of RITN centers have at least one medical toxicology resource within the state. Most RITN centers are located in the same city as at least one medical toxicology resource. Establishing relationships between RITN centers and medical toxicologists needs to be explored further.


The extent of shifts in vegetation phenology between rural and urban areas within a human-dominated region.
Urbanization is one of the major environmental challenges facing the world today. One of its particularly pressing effects is alterations to local and regional climate through, for example, the Urban Heat Island. Such changes in conditions are likely to have an impact on the phenology of urban vegetation, which will have knock-on implications for the role that urban green infrastructure can play in delivering multiple ecosystem services. Here, in a human-dominated region, we undertake an explicit comparison of vegetation phenology between urban and rural zones. Using satellite-derived MODIS-EVI data from the first decade of the 20th century, we extract metrics of vegetation phenology (date of start of growing season, date of end of growing season, and length of season) for Britain's 15 largest cities and their rural surrounds. On average, urban areas experienced a growing season 8.8 days longer than surrounding rural zones. As would be expected, there was a significant decline in growing season length with latitude (by 3.4 and 2.4 days/degree latitude in rural and urban areas respectively). Although there is considerable variability in how phenology in urban and rural areas differs across our study cities, we found no evidence that built urban form influences the start, end, or length of the growing season. However, the difference in the length of the growing season between rural and urban areas was significantly negatively associated with the mean disposable household income for a city. Vegetation in urban areas deliver many ecosystem services such as temperature mitigation, pollution removal, carbon uptake and storage, the provision of amenity value for humans and habitat for biodiversity. Given the rapid pace of urbanization and ongoing climate change, understanding how vegetation phenology will alter in the future is important if we wish to be able to manage urban greenspaces effectively.


Performance of serial CT ASPECTS for predicting stroke outcomes in patients with thrombolyzed acute ischemic stroke.
The objective of this study was to compare the sensitivity and specificity of serial ASPECTS for predicting IHM and unfavorable outcome defined by a modified Rankin Scale score ≥3 at the time of discharge from the hospital in thrombolyzed AACIS patients. This retrospective study examined thrombolyzed AACIS patients admitted at Saraburi Hospital, a regional health-care facility in Thailand. The study was conducted between January 2015 and July 2022. The comparative predictive performance of the baseline ASPECTS, 24-h ASPECTS, and change in ASPECTS for IHM and unfavorable outcome was examined using the receiver operating characteristic (ROC) curves. The optimal cutoff values were identified based on Youden's index and the nonparametric method to compare the area under the ROC curve (AuROC) among the three scales. The potential confounders adjusted by multivariable logistic regression were reported odds ratio (OR) and 95% confidence interval (CI). Three hundred and forty-five patients with thrombolyzed AACIS were analyzed; the median age was 61.8 ± 15.2 years. 53.0% were male, and the median National Institutes of Health Stroke Scale score was 11 points (interquartile range: 8-17). The AuROC for predicting IHM was 0.823 for the baseline ASPECTS, 0.955 for 24-h ASPECTS, and 0.920 for the change in ASPECTS. For predicting unfavorable outcome, the AuROC was 0.744 for the baseline ASPECTS, 0.853 for 24-h ASPECTS, and 0.800 for the change in ASPECTS. After adjusting for other factors, the OR for predicting IHM was 14.38 (95% CI: 1.69-122.57) for 24-h ASPECTS and 16.7 (95% CI: 4.36-64.01) for the change in ASPECTS. Regarding unfavorable outcome, the adjusted OR was 5.58 (95% CI: 1.83-17.01) for 24-h ASPECTS and 4.85 (95% CI: 2.45-9.60) for the change in ASPECTS. The 24-h ASPECTS and change in ASPECTS could be more precise predictors for predicting IHM and unfavorable outcome in patients with thrombolyzed AACIS.


Selective patching in carotid endarterectomy: is patching always necessary?
The value of carotid patching in carotid endarterectomy in achieving low perioperative morbidity and long-term freedom from restenosis is controversial. We hypothesized that if large internal carotid arteries were closed primarily and smaller arteries selectively patched, there would be no difference in early or long-term results between the two groups. A retrospective analysis of 133 carotid endarterectomies performed by one surgeon in a community teaching hospital was performed to evaluate a selective approach to patching vs primary closure. Primary closure was performed if the arteriotomy could be closed without tension over a Javid shunt. Seventy-seven arteries underwent primary closure and 56 underwent patching (Vein-14, PTFE-17, Dacron-25). Postoperative (>6 month) duplex scans were available on 46/77 (60%) patients undergoing primary closure, and 33/56 (59%) of patients with patch repair. There were 2 perioperative neurologic deficits, both in the patch group. Restenosis of equal or greater than 50% at 11 months occurred in 5/46 (10.8%) of patients with primary closure and 2/34 patients (5.9%) with patch closure (p=ns). No patient in either group had a late neurologic event or required a redo operation. Selective primary closure is not associated with increased risk of perioperative neurologic events or statistically significant evidence of late postoperative stenosis if primary closure is performed in large internal carotid arteries.


Complement Factor I Gene Polymorphism in a Turkish Age-Related Macular Degeneration Population.
Evaluation of Complement Factor I (CFI) rs10033900 and rs2285714 polymorphism frequencies in patients with age-related macular degeneration (AMD) and healthy controls in a Turkish population. A total of 111 eyes of 111 AMD patients and 96 eyes of 96 healthy controls, only one eye of individuals, were included in the study; however, 2 patients' and 4 controls' samples were excluded as analyses could not be performed for rs10033900 polymorphism. The AMD patients and control group (>50 years) lacked corneal, lenticular, vitreal opacity. However, these patients did not have any retinal diseases apart from AMD. Venous blood samples of patients were collected. Central macular thickness, subfoveal choroidal thickness (SCT), presence of reticular drusen, epiretinal membrane, and pigment epithelial detachment were investigated using Spectral-Domain Optical Coherence Tomography, and the largest diameter of atrophic areas measured. Drusen properties were documented from fundus photographs. The lesion width was calculated by using fundus fluorescein angiography. There was no difference between patient and control groups and polymorphism distributions. The frequency of the CT allele was higher in patients with dry-type AMD with retinal pigment epithelial abnormality (p = 0.041). SCT was significantly thinner in TT allele carriers with rs2285714 polymorphism (p = 0.030). No significant relationship was found between the other parameters and polymorphism distributions. Con-clusion: CFI rs10033900 and rs2285714 polymorphisms in a Turkish population were not associated with AMD.


Plants as bio-indicators of subsurface conditions: impact of groundwater level on BTEX concentrations in trees.
Numerous studies have demonstrated trees' ability to extract and translocate moderately hydrophobic contaminants, and sampling trees for compounds such as BTEX can help delineate plumes in the field. However, when BTEX is detected in the groundwater, detection in nearby trees is not as reliable an indicator of subsurface contamination as other compounds such as chlorinated solvents. Aerobic rhizospheric and bulk soil degradation is a potential explanation for the observed variability of BTEX in trees as compared to groundwater concentrations. The goal of this study was to determine the effect of groundwater level on BTEX concentrations in tree tissue. The central hypothesis was increased vadose zone thickness promotes biodegradation of BTEX leading to lower BTEX concentrations in overlying trees. Storage methods for tree core samples were also investigated as a possible reason for tree cores revealing lower than expected BTEX levels in some sampling efforts. The water level hypothesis was supported in a greenhouse study, where water table level was found to significantly affect tree BTEX concentrations, indicating that the influx of oxygen coupled with the presence of the tree facilitates aerobic biodegradation of BTEX in the vadose zone.


Amoeboid swimming in a channel.
Several micro-organisms, such as bacteria, algae, or spermatozoa, use flagellar or ciliary activity to swim in a fluid, while many other micro-organisms instead use ample shape deformation, described as amoeboid, to propel themselves either by crawling on a substrate or swimming. Many eukaryotic cells were believed to require an underlying substratum to migrate (crawl) by using membrane deformation (like blebbing or generation of lamellipodia) but there is now increasing evidence that a large variety of cells (including those of the immune system) can migrate without the assistance of focal adhesion, allowing them to swim as efficiently as they can crawl. This paper details the analysis of amoeboid swimming in a confined fluid by modeling the swimmer as an inextensible membrane deploying local active forces (with zero total force and torque). The swimmer displays a rich behavior: it may settle into a straight trajectory in the channel or navigate from one wall to the other depending on its confinement. The nature of the swimmer is also found to be affected by confinement: the swimmer can behave, on average over one swimming cycle, as a pusher at low confinement, and becomes a puller at higher confinement, or vice versa. The swimmer's nature is thus not an intrinsic property. The scaling of the swimmer velocity V with the force amplitude A is analyzed in detail showing that at small enough A, V∼A(2)/η(2) (where η is the viscosity of the ambient fluid), whereas at large enough A, V is independent of the force and is determined solely by the stroke cycle frequency and the swimmer size. This finding starkly contrasts with models where motion is based on ciliary and flagellar activity, where V∼A/η. To conclude, two definitions of efficiency as put forward in the literature are analyzed with distinct outcomes. We find that one type of efficiency has an optimum as a function of confinement while the other does not. Future perspectives are outlined.


Effectiveness of zinc supplementation plus oral rehydration salts compared with oral rehydration salts alone as a treatment for acute diarrhea in a primary care setting: a cluster randomized trial.
The purpose of this work was to evaluate whether education about zinc supplements and provision of zinc supplements to caregivers is effective in the treatment of acute diarrhea and whether this strategy adversely affects the use of oral rehydration salts. Six clusters of 30,000 people each in Haryana, India, were randomly assigned to intervention and control sites. Government and private providers and village health workers were trained to prescribe zinc and oral rehydration salts for use in diarrheal episodes in 1-month-old to 5-year-old children in intervention communities; in the control sites, oral rehydration salts alone was promoted. In 2 cross-sectional surveys commencing 3 months (survey 2) and 6 months (survey 3) after the start of the intervention, care-seeking behavior, drug therapy, and oral rehydration salts use during diarrhea, diarrheal and respiratory morbidity, and hospitalization rates were measured. In the 2 surveys, zinc was used in 36.5% (n = 1571) and 59.8% (n = 1649) and oral rehydration salts in 34.8% (n = 1571) and 59.2% (n = 1649) of diarrheal episodes occurring in the 4 weeks preceding interviews in the intervention areas. In control areas, oral rehydration salts were used in 7.8% (n = 2209) and 9.8% (n = 2609) of episodes. In the intervention communities, care seeking for diarrhea reduced by 34% (survey 3), as did the prescription of drugs of unknown identity (survey 3) and antibiotics (survey 3) for diarrhea. The 24-hour prevalences of diarrhea and acute lower respiratory infections were lower in the intervention communities (survey 3). All-cause, diarrhea, and pneumonia hospitalizations in the preceding 3 months were reduced in the intervention compared with control areas (survey 3). Diarrhea is more effectively treated when caregivers receive education on zinc supplementation and have ready access to supplies of oral rehydration salts and zinc, and this approach does not adversely affect the use of oral rehydration salts; in fact, it greatly increases use of the same.


Identification and functional analysis of the genes encoding dibenzothiophene-desulfurizing enzymes from thermophilic bacteria.
Thermophilic bacteria Bacillus subtilis WU-S2B and Mycobacterium phlei WU-F1 desulfurize dibenzothiophene (DBT) and alkylated DBTs through specific cleavage of the carbon-sulfur bonds over a temperature range up to 52 degrees C. In order to identify and functionally analyze the DBT-desulfurization genes, the gene cluster containing bdsA, bdsB, and bdsC was cloned from B. subtilis WU-S2B. The nucleotide and amino acid sequences of bdsABC show homologies to those of the other known DBT-desulfurization genes and enzymes; e.g. a nucleotide sequence homology of 61.0% to dszABC of the mesophilic bacterium Rhodococcus sp. IGTS8 and 57.8% to tdsABC of the thermophilic bacterium Paenibacillus sp. A11-2. Deletion and subcloning analysis of bdsABC revealed that the gene products of bdsC, bdsA and bdsB oxidized DBT to DBT sulfone (DBTO(2)), converted DBTO(2) to 2'-hydroxybiphenyl-2-sulfinate (HBPSi), and desulfurized HBPSi to 2-hydroxybiphenyl (2-HBP), respectively. Resting cells of a recombinant Escherichia coli JM109 harboring bdsABC converted DBT to 2-HBP over a temperature range of 30-52 degrees C, indicating that the gene products of bdsABC were functional in the recombinant. The activities of DBT degradation at 50 degrees C and DBT desulfurization (2-HBP production) at 40 degrees C in resting cells of the recombinant were approximately five times and twice, respectively, as high as those in B. subtilis WU-S2B. The recombinant E. coli cells also degraded alkylated DBTs, such as 2,8-dimethylDBT and 4,6-dimethylDBT. The nucleotide sequences of B. subtilis WU-S2B bdsABC and the corresponding genes from M. phlei WU-F1 were found to be completely identical to each other although the strains are genetically different.


DASH: a novel analysis method for molecular dynamics simulation data. Analysis of ligands of PPAR-gamma.
A novel molecular dynamics (MD) analysis algorithm, DASH, is introduced in this paper. DASH has been developed to utilize the sequential nature of MD simulation data. By adjusting a set of parameters, the sensitivity of DASH can be controlled, allowing molecular motions of varying magnitudes to be detected or ignored as desired, with no knowledge of the number of conformations required being prerequisite. MD simulations of three synthetic ligands of the orphan nuclear receptor PPARgamma were generated in vacuo using Tripos's SYBYL and used as the training set for DASH. Two X-ray crystal structures of PPARgamma complexed with Rosiglitazone were compared to gain knowledge of the pharmacophoric conformation; this showed that the conformation of the ligand is significantly different between the two structures, indicating that there is no distinct conformation in which rosiglitazone binds to PPARgamma but multiple binding modes. An investigation into simulation length was carried out. A simulation of 5 ns was found to give highly variable results, whereas a simulation of 25 ns gave a representative window of motion for molecules of this size. DASH was compared with Ward's hierarchical cluster analysis method. The results show that DASH analysis is as good as Ward analysis in some areas (e.g. conformation identification) and is superior in others (e.g. speed and input size).


Amino acid residues of serum and CSF protein in multiple sclerosis. Clinical application of statistical discriminant analysis.
Statistical discriminant analysis of the amino acid compostion of serum and cerebrospinal fluid (CSF) proteins provides an objective method for distinguishing between normal controls and patients with multiple sclerosis (MS). This method also results in a high degree of specificity in separating MS patients from those with other diseases of the nervous system. The CSF protein serine residue is highly correlated with the CSF IgG and holds promise for a more sensitive diagnostic test for MS than the currently used CSF IgG. Finally, the serum/CSF protein serine ratio seems to correlate best with clinically determined degree of activity for the disease, the most active cases having the lowest ratio. These results suggest that investigation of the amino acid composition of serum and CSF protein in multiple sclerosis and, possibly, in other diseases might lead to the development of clinically useful tests of diagnosis and degree of activity of MS.


Application of surgical navigation in styloidectomy for treating Eagle's syndrome.
The present study aimed to evaluate the feasibility, accuracy, and clinical effect of intraoperative navigation for resection of elongated styloid process (ESP) in Eagle's syndrome. Twelve patients with Eagle's syndrome with clinically and radiologically established diagnoses of ESP were included in this study. Preoperatively, all patients accepted three-dimensional computed tomography scan, and their skulls' digital imaging and communications in medicine data were inputed into the navigation system workstation to make a virtual surgical plan in advance. During surgery, the intraoperative navigation was performed to excise the ESP accurately for both intraoral (without tonsillectomy) and extraoral approaches following the virtual plan. Postoperatively, the amount of bleeding, duration of operation and hospitalization, and the length of resected styloid process (SP) were measured and compared with those cases that had traditional styloidectomy without the help of surgical navigation (SN). A simple visual analog scale questionnaire was also used to assess patients' satisfaction and the surgery effect after 3 months. In total, 17 SPs from 12 patients were precisely resected by intraoral parapharyngeal approach and small cervical approach with the aid of SN. No severe complications occurred in any patients. The length of resected SPs was 21.93±14.26 mm. The average amount of bleeding and duration of operation were 22.50±8.54 mL and 40.35±11.81 minutes, respectively, which were all less than with traditional styloidectomy. The visual analog scale analysis showed that the discomfort in all patients was relieved, while ten patients' symptoms were improved greatly, and two patients had some improvement. The higher accuracy of surgery, lesser amount of bleeding, decreased duration of surgery and hospitalization, absence of complications, and improved subjective symptoms indicated that SN is an effective and minimally invasive surgical procedure suitable for resection of ESP for treating Eagle's syndrome.


[Vagotomy in surgery of perforated gastric and duodenal ulcers].
Vagotomy is recommended by the author for the treatment of peptic ulcers. Vagotomy in combination with operations on the stomach and without them was used in 92 of 148 patients operated upon for the ulcer perforation. Lethality following suturing of the perforation hole was 7.7%, following vagotomy and the elimination of the perforation hole it was 1,1%. On the basis of the data obtained the author recommends vagotomy for the treatment of gastroduodenal ulcers complicated by perforation.


Transplanted neocortical neurons migrate selectively into regions of neuronal degeneration produced by chromophore-targeted laser photolysis.
Selective degeneration of neocortical callosal pyramidal neurons by noninvasive laser illumination was used for directed studies of neocortical transplantation, to test the hypothesis that transplanted embryonic neurons may seek to restore normal cytoarchitecture within an appropriately permissive local environment. At long wavelengths that penetrate through tissue without major absorption, photolysis can cause extremely selective degeneration to desired subpopulations of targeted neurons in vivo (Macklis and Madison, 1991; Madison and Macklis, 1993). Cell death is geographically defined and slowly progressive, allowing control over the anatomical substrate for transplantation. Targeting occurs by retrograde incorporation of cytolytic chromophores that are activated by specific-wavelength light. Intermixed neurons, glia, axons, blood vessels, and connective tissue remain intact. Degeneration was effected within neocortical lamina II/III of neonatal mouse pups following targeting in utero or early postnatally with photoactive nanospheres. Total neuron density was reduced typically by 25-30% within defined areas, with approximately 60% loss of large projection neurons and no change in the number of small, presumptive interneurons. Embryonic day 17 neocortical cell suspensions, which included recently postmitotic neurons destined to form lamina II/III, were transplanted lateral to these regions of ongoing neuron degeneration in juvenile mice. Cellular injections spanned laminae II-V, to provide donor neurons with both lateral and laminar choice for possible migration and integration. Donor cells were labeled in vitro with unique fluorescent and electron-dense nanospheres that allowed distinct identification of donor cells at both light and electron microscopic levels. Control experiments included neocortical transplants into intact age-matched hosts, into hosts with kainic acid lesions to neocortex, or distant to the region of photolytic neuronal degeneration; embryonic cerebellar transplants to the regions of selective photolytic degeneration; and grafts of hypoosmotically lysed neocortical cells to lesioned regions. After survival times of 1 hr to 12 weeks, labeled neurons were identified morphologically and positions were digitized for qualitative and quantitative analysis of position and specificity of migration and cellular integration; electron microscopy was used to confirm further the donor identities of migrated neurons. Neurons placed near host zones of photolytic neuron degeneration migrated up to 780 microns specifically within these zones; approximately 44% of donor neurons migrated significantly beyond the injection site to enter these regions. Migration and integration did not occur in normal, unaffected deeper layers IV-VI of these experimental mice, or in the normal lamina II/III bordering the transplantation site on the side opposite the neuron-deficient region. Control grafts of all five types revealed only minimal local spread without laminar preference.(ABSTRACT TRUNCATED AT 400 WORDS)


Abnormalities and virus-like particles in spermatozoa from bulls latently infected with bluetongue virus.
Abnormalities were commonly observed in spermatozoa, and bluetongue virus (BTV) was isolated from semen of 2 known BTV carrier bulls and 2 of 4 BTV seropositive field bulls. The spermatozoal abnormalities ranged from a small cavity between the acrosome and nucleus with some involvement of the nucleus, to an enlargement of the cavity accompanied by vesiculation that could affect the entire acrosome. Virus-like particles were occasionally observed in the affected spermatozoa, but were present in all samples. A positive relationship was found between infectivity of semen samples from BTV latently infected bulls and the observation of abnormalities and virus-like particles in the heads of affected spermatozoa.


Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed.
Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of basic fibroblast growth factor (bFGF) induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed.


Microparticle-enhanced polygalacturonase production by wild type Aspergillus sojae.
Polygalacturonases (PGs), an important industrial enzyme group classified under depolymerases, catalyze the hydrolytic cleavage of the polygalacturonic acid chain through the introduction of water across the oxygen bridge. In order to produce and increase the concentration of this enzyme group in fermentation processes, a new approach called microparticle cultivation, a promising and remarkable method, has been used. The aim of this study was to increase the PG activity of Aspergillus sojae using aluminum oxide (Al2O3) as microparticles in shake flask fermentation medium. Results indicated that the highest PG activity of 34.55 ± 0.5 U/ml was achieved with the addition of 20 g/L of Al2O3 while the lowest activity of 15.20 ± 0.2 U/mL was obtained in the presence of 0.1 g/L of Al2O3. In fermentation without microparticles as control, the activity was 15.64 ± 3.3 U/mL. Results showed that the maximum PG activity was 2.2-fold higher than control. Additionally, smaller pellets formed with the addition of Al2O3 where the lowest pellet diameter was 955.1 µm when 10 g/L of the microparticle was used. Also, it was noticed that biomass concentration gradually increased with increasing microparticle concentration in the fermentation media. Consequently, the PG activity was significantly increased in microparticle-enhanced shake flask fermentation. In fact, these promising preliminary data can be of significance to improve the enzyme activity in large-scale bioreactors.


[Aponeurotic suspension of a vesico-urethral anastomosis after radical prostatectomy].
In order to try to enhance postoperative continence rates after radical retropubic prostatectomy, a fascial sling suspension was performed at the time of the operation in 75 patients (group 2). Postoperative continence was compared to that of the 63 previous patients (group 1). Complete continence rate were 43 of 75 (57%) in group 2 and 17 of 63 (27%) in group 1 (p = 0.0003) at 1 month, 57 of 75 (76%) in group 2 and 36 of 63 (57%) in group 1 (p = 0.0149) at 3 months, 65 of 75 (87%) in group 2 and 46 of 63 (73%) in group 1 at 6 months, 69 of 75 (92%) in group 2 and 50 of 63 (79%) in group 1 at 9 months, and 72 of 75 (96%) in group 2 and 51 of 63 (81%) in group 1 at 12 months. Fascial sling suspension resulted in an earlier return and more complete recovery of urinary continence in men undergoing radical prostatectomy.


Aspirin in coronary heart disease. The Coronary Drug Project Research Group.
The Coronary Drug Project Aspirin Study (CDPA), started in late 1972 and terminated in early 1974, involved men selected from three groups originally receiving dextrothyroxine or estrogen therapy in the Coronary Drug Project. All patients had a history of myocardial infarction, most of them several years earlier. Length of follow-up ranged from 10-28 months (average 22 months). A total of 1529 patients were recruited and were randomly assigned on a double-blind basis to aspirin therapy -- one 324-mg tablet three times daily or a corresponding placebo treatment. Data indicate a high level of adherence to the study protocol. No major differences were recorded in use of nonstudy medications in the two treatment groups. Overall mortality was 5.8% in the aspirin group and 8.3% in the placebo group (an observed difference of 30%). This difference, suggestive of a beneficial effect for aspirin in the treatment of post-myocardial infarction men, was not large enough to be conclusive.


Detection and occurrence of the 60- and 52-kD Ro (SS-A) antigens and of autoantibodies against these proteins.
The simultaneous detection of anti-La, anti-60-kD Ro and anti-52-kD Ro antibodies by immunoblotting is greatly improved by changing the crosslinking level in the gel to an acrylamide/bisacrylamide ratio of 19:1. Using this method for the analysis of a number of systemic lupus erythematosus (SLE) and Sjögren's syndrome patient sera it was observed that antibody to the 52-kD Ro protein without anti-60-kD Ro antibody was restricted to Sjögren's syndrome patients (9/26), whereas antibody to the 60-kD Ro protein without contaminating anti-52-kD Ro antibody was only found in SLE patients (8/38). Moreover, in Sjögren's syndrome patient sera anti-Ro antibody was found only in combination with anti-La antibody (20/26), whereas in SLE patient sera anti-Ro antibody could be found without detectable anti-La specificity (4/38). Double immunofluorescence microscopy revealed that the 52-kD Ro and the 60-kD Ro proteins co-localize in the cytoplasm as well as in the nucleus, whereas immunoprecipitation of [32P]-labelled HeLa cell extract with monospecific anti-52-kD Ro and anti-60-kD Ro sera showed that both proteins are associated with the Ro RNAs. These data suggest the presence of both the 52-kD and the 60-kD Ro proteins in the same ribonucleoprotein complexes. To study the evolutionary conservation of the 52-kD Ro, the 60-kD Ro and the La proteins, extracts of cell lines derived from various mammalian species were analysed on Western blots using monospecific human antibodies. In contrast to the 60-kD Ro and the La antigens which are well conserved in evolution, the 52-kD Ro antigen could be detected in primate cells only by this immunological approach.


Trustworthy Intrusion Detection in E-Healthcare Systems.
In Internet of Things (IoT)-based network systems (IoT-net), intrusion detection systems (IDS) play a significant role to maintain patient health records (PHR) in e-healthcare. IoT-net is a massive technology with security threats on the network layer, as it is considered the most common source for communication and data storage platforms. The security of data servers in all sectors (mainly healthcare) has become one of the most crucial challenges for researchers. This paper proposes an approach for effective intrusion detection in the e-healthcare environment to maintain PHR in a safe IoT-net using an adaptive neuro-fuzzy inference system (ANFIS). In the proposed security model, the experiments present a security tool that helps to detect malicious network traffic. The practical implementation of the ANFIS model on the MATLAB framework with testing and training results compares the accuracy rate from the previous research in security.


Metabolic Derangement in Acute and Chronic Liver Disorders.
This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed.


First-principles prediction of the thermal conductivity of two configurations of difluorinated graphene monolayer.
Lattice thermal conductivity (κL) plays a crucial role in the thermal management of electronic devices. In this study, we systematically investigate the thermal transport properties of monolayer fluorinated graphene using a combination of machine learning-based interatomic potentials and the phonon Boltzmann transport equation. At a temperature of 300 K, we find that the κL values for chair-configured fluorinated graphene monolayers are 184.24 W m-1 K-1 in the zigzag direction and 205.57 W m-1 K-1 in the armchair direction. For the boat configuration, the κL values are 120.45 W m-1 K-1 and 64.26 W m-1 K-1 in the respective directions. The disparities in κL between these two configurations predominantly stem from differences in phonon relaxation times, which can be elucidated by examining the Grüneisen parameters representing the degree of anharmonicity. A more in-depth analysis of bond strengths, as assessed by the crystal orbital Hamiltonian population, reveals that the stronger in-plane CC bonds in chair-configured fluorinated graphene monolayers are the primary contributors to the observed variations in anharmonicity.


Radioprotective effects of an acidic polysaccharide of Panax ginseng on bone marrow cells.
An acidic polysaccharide of Panax ginseng (APG), so called ginsan is known to have important immunomodulatory activities. It was recently reported that APG has radioprotective effects in mice but the detailed mechanism was not fully elucidated. This study examined the effects of APG on bone marrow cells (BMs). The phenotypical and functional changes in APG-treated BMs after gamma radiation were studied. The benefit of APG on BMs damaged by gamma radiation was determined by measuring the cell viability. Using 2 different assays, a pretreatment with APG significantly increased the viability of BMs against gamma radiation. APG-treated BMs had a significantly higher amount of IL-12, which is a major cytokine for immune responses, compared with the medium-treated BMs. The expression of MHC class II molecules of APG-treated BMs was also increased, and APG-treated BMs showed significantly higher levels of allogeneic CD4(+) T lymphocyte proliferation. Furthermore, APG-treated mice had a larger number of BMs after gamma radiation than the control mice, and the BMs of APG-treated mice were successfully cultured into dendritic cells, which are the representative antigenpresenting cells. Overall, this study shows that APG alters the phenotype of BMs, increases the viability and alloreactivity of BMs after gamma radiation both in vitro and in vivo. Therefore, APG may be a good candidate radioprotective agent for BMs.


The nephrotoxicity of Aristolochia manshuriensis in rats is attributable to its aristolochic acids.
Although Aristolochia manshuriensis (AM), which was incriminated in the Japanese variety of Chinese herbs nephropathy, has been recently shown to be nephrotoxic in rats, less is known about whether this toxicity is attributable to its aristolochic acids (AA). We compared the renal effect of AM with that of Akebia quinata (AQ), which has similar components to AM but is free of AA; we also compared this effect of AM with that of pure AA, and studied its possible mechanism. In study 1, rats were divided into four groups. Each group was orally given either 0.4 g of AM, 4 g of AM, or 4 g of AQ per day, or vehicle, for 5 days. In study 2, rats were given 4 g of AM (which contained 4 mg of AA), or 4 mg of pure AA per day, or vehicle, for 5 days. Renal function, and renal histology were evaluated on day 5 in study 1 and on days 1, 3, 5, and 14 in study 2. In study 2, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and proliferating cell nuclear antigen (PCNA) staining were also performed. In study 3, rats were treated in the same way as in study 2, but were all killed on day 5. Concentrations of AA (I + II) were measured in serum and urine in study 2, and in the kidney, lung, heart, liver, and spleen in study 3. In study 1, only the rats that received 4 g/day of AM developed tubular necrosis, azotemia, proteinuria, and glucosuria. In study 2, both AM- and AA-treated rats showed progressive tubular damage, decreased renal function, and increased urinary protein excretion. The degree of these alterations was comparable in the AM and AA groups. Moreover, the concentrations of AA (I + II), in serum, urine, and kidney were also comparable in the AM- and AA-treated rats. High levels of AA were detected in the lung and kidney. Apoptotic tubular cells increased on day 5 and had decreased by day 14 after the withdrawal of AM or AA. Meanwhile, proliferating tubular cells progressively increased from day 3 to day 14. Our study indicates that the renal toxicity of AM can be attributed to its AA component. Tubular cell apoptosis might be one of the mechanisms involved in this renal injury.


Cardiovascular complications of obstructive sleep apnea.
Obstructive sleep apnea (OSA) is a common disorder with an increasing public health burden. It is characterized by repeated upper airway narrowing and closure, leading to apneas, hypopneas and increased respiratory effort-related arousals. Continuous positive airway pressure is an effective modality of treatment for OSA. Apart from being responsible for daytime sleepiness and cognitive impairment, OSA has been implicated in various systemic diseases, particularly of the cardiovascular system. This article reviews some of the extensive literature implicating OSA in the development of cardiovascular diseases and describes the intermediary pathophysiologic mechanisms involved. Repetitive nocturnal oxygen desaturation and reoxygenation and increased intrathoracic pressure changes related to OSA result in the intermediary pathophysiologic mechanisms that affect the neural, humoral, thrombotic, inflammatory and metabolic pathways responsible for the development of cardiovascular disorders. This review also examines evidence that suggests that OSA may be a specific cause of certain cardiovascular disorders.


Cardioprotective and Antifibrotic Effects of Low-Dose Renin-Angiotensin-Aldosterone System Inhibitors in Type 1 Diabetic Rat Model.
Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin-angiotensin-aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima-media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.


Automatic construction of restriction site maps.
A computer program is described which constructs maps of restriction endonuclease cleavage sites in DNA molecules, given only the fragment lengths. The program utilizes fragment length data from single and double restriction enzyme digests to generate maps for linear or circular molecules. The search for a map can be limited to the unknown (insert) region of a recombinant phage or plasmid. Typical restriction maps with four or five enzymes which cut at three to five unknown sites can be calculated in a few minutes.


Long-term surveillance of high-risk children.
We followed a group of high-risk children, both those who passed early developmental screenings and those who did not. Three hundred sixty-two children who had previously passed screenings were evaluated at 5 years of age. Significant differences were found between this group and a comparison group in mean scores on verbal, perceptuomotor, and preacademic tests. Children who had previously failed screenings at or before 30 months of age were followed up through telephone interviews with referral agencies and records review. Ninety percent proved to have significant problems, and 67% were in special education programs at 5 years of age. This study demonstrates the need for long-term follow-up of high-risk children at least to the age of school entry.


Prognostic factors for clinical failure of exacerbations in elderly outpatients with moderate-to-severe COPD.
Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood. We aimed to identify pretherapy factors predictive of clinical failure in elderly (≥60 years old) outpatients with acute Anthonisen type 1 exacerbations. NCT00656747. Based on the moxifloxacin in AECOPDs (acute exacerbations of chronic obstructive pulmonary disease) trial (MAESTRAL) database, this study evaluated pretherapy demographic, clinical, sputum bacteriological factors using multivariate logistic regression analysis, with internal validation by bootstrap replicates, to investigate their possible association with clinical failure at end of therapy (EOT) and 8 weeks posttherapy. The analyses found that the independent factors predicting clinical failure at EOT were more frequent exacerbations, increased respiratory rate and lower body temperature at exacerbation, treatment with long-acting anticholinergic drugs, and in vitro bacterial resistance to study drug. The independent factors predicting poor outcome at 8 weeks posttherapy included wheezing at preexacerbation, mild or moderate (vs extreme) sleep disturbances, lower body temperature at exacerbation, forced expiratory volume in 1 second <30%, lower body mass index, concomitant systemic corticosteroids for the current exacerbation, maintenance long-acting β2-agonist and long-acting anticholinergic treatments, and positive sputum culture at EOT. Several bacteriological, historical, treatment-related factors were identified as predictors of early (EOT) and later (8 weeks posttherapy) clinical failure in this older outpatient population with moderate-to-severe chronic obstructive pulmonary disease. These patients should be closely monitored and sputum cultures considered before and after treatment.


Efficient cellulase production by Trichoderma reesei in continuous cultivation on lactose medium with a computer-controlled feeding strategy.
A low-foaming hydrophobin II deletant of the Trichoderma reesei strain Rut-C30 was used for production of cellulases by continuous cultivation on lactose medium in a laboratory fermenter. The control paradigm of the addition of new medium to the continuous process was based on the growth dynamics of the fungus. A decrease in the rate of base addition to the cultivation for pH-minimum control was used as an indicator of imminent exhaustion of carbon source for growth and enzyme induction. When the amount of base added per 5 min computation cycle decreased below a given value, new medium was added to the fermenter. When base addition for pH control thereafter increased above the criterion value, due to increased growth, the medium feed was discontinued or decreased. The medium feeding protocol employed was successful in locking the fungus in the stage of imminent, but not actual, exhaustion of carbon source. According to the results of a batch cultivation of the same strain on the same medium, this is the phase of maximal enzyme productivity. The medium addition protocol used in this work resulted in a very stable continuous process, in which cellulase productivity was maintained for several hundred hours at the maximum level observed in a batch cultivation for only about 10 h. Despite a major technical disturbance after about 420 h, the process was restored to stability. When the cultivation was terminated after 650 h, the level of enzyme production was still maximal, with no signs of instability of the process.


Observation of Three-Body Correlations for Photons Coupled to a Rydberg Superatom.
We report on the experimental observation of nontrivial three-photon correlations imprinted onto initially uncorrelated photons through an interaction with a single Rydberg superatom. Exploiting the Rydberg blockade mechanism, we turn a cold atomic cloud into a single effective emitter with collectively enhanced coupling to a focused photonic mode which gives rise to clear signatures in the connected part of the three-body correlation function of the outgoing photons. We show that our results are in good agreement with a quantitative model for a single, strongly coupled Rydberg superatom. Furthermore, we present an idealized but exactly solvable model of a single two-level system coupled to a photonic mode, which allows for an interpretation of our experimental observations in terms of bound states and scattering states.


No Effect of Levothyroxine and Levothyroxine-Induced Subclinical Thyrotoxicosis on the Pharmacokinetics of Sorafenib in Healthy Male Subjects.
Patients receiving the multikinase inhibitor sorafenib for locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine often receive concomitant levothyroxine for thyrotropin (TSH) suppression. In the Phase 3 DTC trial (DECISION), sorafenib exposure was approximately twofold higher than that observed in other cancers. This study assessed sorafenib pharmacokinetics without and with concomitant levothyroxine to examine whether a levothyroxine interaction or levothyroxine-induced subclinical thyrotoxicosis results in increased sorafenib exposure in patients with DTC. This was an open-label, two-period sequential treatment study in healthy male subjects. In period 1, day 1, subjects received a single oral dose of sorafenib 400 mg, followed by a minimal 10-day washout. In period 2, day 1, levothyroxine 300 μg was administered orally once daily (q.d.) for 14 days. After 10 days, a single oral concomitant dose of sorafenib 400 mg was given. Blood samples for sorafenib pharmacokinetic analyses were obtained pre-dose and at time points up to 96 hours after sorafenib dosing. Samples for thyroid tests were collected before and after levothyroxine dosing. Twenty-five subjects completed the study and were evaluable for pharmacokinetic analysis. Levothyroxine 300 μg q.d. was well tolerated and induced subclinical thyrotoxicosis, producing full suppression of TSH (M ± SD = 0.032 ± 0.027 mIU/L) and increased free thyroxine (from 0.94 ± 0.09 to 1.77 ± 0.33 ng/dL) and free triiodothyronine (from 2.87 ± 0.28 to 4.24 ± 0.66 pg/mL) levels by day 11 of period 2. The geometric mean (%CV) sorafenib maximum concentration (Cmax) without and with levothyroxine was 2.09 (68.1) and 1.78 (63.9) mg/L, respectively, with a corresponding geometric mean area under the curve of 68.1 (68.2) and 64.3 (66.3) mg·h/L. Median (range) time to Cmax was 4.00 (2.98-16.0) and 4.02 (1.98-36.0) hours, respectively. Mean (%CV) half-life was 24.0 (25.3) and 25.7 (21.0) hours. All study drug-related adverse events were mild and included headache and fatigue for sorafenib, and headache, increased alanine aminotransferase and glutamate dehydrogenase, fatigue, and nervousness for levothyroxine. Levothyroxine 300 μg q.d. for 14 days was well tolerated, induced subclinical thyrotoxicosis, and did not affect sorafenib pharmacokinetics. The findings suggest that concomitant use of levothyroxine with sorafenib is not likely responsible for the previously reported increase in sorafenib exposure in patients with DTC. However, the possible effects of long-term levothyroxine dosing were not assessed.


Roles of bacteriophage GVE2 endolysin in host lysis at high temperatures.
The holin-endolysin system is used by double-stranded DNA phages to lyse their bacterial hosts at the terminal stage of the phage reproduction cycle. Endolysins are proteins with one of several muralytic activities able to digest the bacterial cell wall for phage progeny release. However, the functions of thermophilic bacteriophage endolysin in host lysis have not been extensively investigated. In this study, the roles of the endolysin of a thermophilic bacteriophage, GVE2, from a deep-sea hydrothermal vent, which could infect Geobacillus sp. E263 at high temperatures, were characterized. The results showed that GVE2 could lead to lysis of host cells. The confocal microscopy data showed that GFP-endolysin aggregated in GVE2-infected Geobacillus sp. E263 cells, showing the involvement of endolysin in the lysis process at high temperatures. The results revealed that the GVE2 endolysin and holin interacted directly. It was found that the endolysin could interact with the host protein ABC transporter, suggesting that host proteins might participate in the regulation of the lysis process. Therefore, our study presents a novel insight into the mechanism of the lysis process of a thermophilic bacterium by its phage at high temperatures, which should be helpful in revealing the roles of thermophilic bacteriophages in the biosphere of deep-sea hydrothermal vents.


Relationship of insulin binding and insulin-stimulated tyrosine kinase activity is altered in type II diabetes.
The insulin receptor contains an alpha subunit with insulin binding properties and a beta subunit with insulin-stimulated tyrosine kinase function. Preparations containing insulin and insulinlike growth factor I (IGF-I) receptors were obtained from solubilized human red cell membranes by affinity chromatography. After separate assays for insulin binding and insulin-stimulated tyrosine kinase activities, a high degree of correlation was found between these activities in preparations from normals and diabetics. Identical studies using IGF-I as the ligand showed a lesser degree of correlation. We compared 24 normal subjects and 14 untreated type II diabetics and found significant diminution in the slope of the line coupling insulin binding and insulin-stimulated kinase activities in the diabetics. This difference was not observed in a similar study of IGF-I-related activities. Compared to normal controls, untreated type II diabetics have reduced tyrosine kinase activity stimulated per unit insulin binding.


Advances in measurement science.
Year after year, physicists measure various quantities with increasing accuracy and see various objects in increasing detail. These advances are vital, because science's understanding of the physical world is necessarily limited by the accuracy with which science can measure that world. The Instrument and Measurement Science Topical Group of the American Physical Society sponsored several symposia at the recent APS March meeting in New Orleans that discussed recent advances in measurement and observation.


Twenty years of systemic therapy for breast cancer.
The past 2 decades of systemic therapy for breast cancer have been a period of monumental change, in terms of both theory and technology. Adjuvant therapy developed from two strands of research--one in systemic chemotherapy and one in hormonal therapy--both of which were aided by the application of higher statistical methodology to clinical trials. The agent with the single greatest public health impact in oncology has been tamoxifen, but problems with tamoxifen therapy led to the development of the aromatase inhibitors, and further research led to the use of hormonal therapy in a chemopreventive capacity. The evolution of systemic chemotherapy for breast cancer has been an interplay between theory-driven approaches and new agents. By the late 1980s, accumulating data revealed that overexpression of HER2 (erbB2) played an important role in a substantial portion of breast cancers, which prompted the development of trastuzumab (Herceptin), an agent targeting HER2-positive disease. Determining HER2 status proved essential to assessing patient eligibility for trastuzumab therapy. Decoding of the human genome and application of bioinformatics further revolutionized the possibilities in breast cancer treatment.


Treatment of osseous metastases in patients with renal cell carcinoma.
The records of 99 patients treated at one institution for osseous metastases secondary to renal cell carcinoma were reviewed. Patients were followed up for at least 24 months or until death. Survival was analyzed with respect to age, gender, disease-free interval, location of osseous metastases, number of osseous metastatic sites, resection of osseous metastases, and primary tumor resection. The mean age of the 72 men and 27 women was 60 years (range, 34-82 years) and the mean followup was 20 months (range, 2-81 months). Twenty-six patients (26%) had a solitary osseous metastasis, 47 patients (48%) had multiple osseous metastases, and 26 patients (26%) had additional visceral involvement such as the lung and brain at the time of diagnosis. In 49 patients (49%), the renal cell carcinoma was diagnosed concurrently with detection of the osseous metastasis. The presence of one osseous renal carcinoma metastasis, wide resection of the lesion, and a history of nephrectomy were identified as independent predictors of survival in patients with renal cell carcinoma. The eight patients who had wide resection of a solitary osseous metastasis in combination with a nephrectomy had a disease-specific survival rate of 100% (mean followup, 69 months; range, 24-76 months). Patients who present with these characteristics are candidates for aggressive surgical treatment with curative intent.


Cryptosporidium parvum and Isospora belli infections among patients with and without diarrhoea.
To assess the importance of Cryptosporidium parvum and Isospora belli infections as a cause of diarrhoea among patients admitted to the Medical Wards in Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. Prospective case control study. One hundred and twenty one patients with diarrhoea and 122 patients without diarrhoea. Demonstration of C. parvum and I. belli oocysts by examination of at least one stool sample per patient using phenol auramine-O-fluorescence staining and an immuno-fluorescent assay with monoclonal antibodies against Cryptosporidium, seropositivity for HIV and AIDS. In 22% of the patients with diarrhoea an infection with C. parvum or I. belli was found. Thirteen (11%) of them had a C. parvum and 14 (12%) an I. belli infection; a mixed infection was found in one patient. In the control group, three (3%) C. parvum and three (3%) I. belli infections were seen. The prevalence of both infections was very significantly higher in the cohort of diarrhoea patients than in the controls, 13/108 versus 3/119 (p=0.0099) for C. parvum, and 14/107 versus 3/119 (p=0.0056) for I. belli. Infections were only seen in HIV positive patients. Two hundred and four (84%) patients were HIV positive and 145 (60%) of them had AIDS. C. parvum and I. belli infections are a significant cause of diarrhoea among medical in-patients at QECH. Examinations of stool specimen for parasites among hospitalised patients with diarrhoea provide data for a more appropriate management.


Community health and pediatric nurses' knowledge, attitudes, and behaviors regarding child sexual abuse.
Community health and other child care nurses can play a major role in the prevention, early detection, referral, treatment, and rehabilitation of victims of child sexual abuse (CSA) and their families. It is not known, however, whether these health care professionals are well prepared or feel sufficiently confident to address these challenges. The present study provides some information on this matter by examining their knowledge, attitudes, practices, and degree of confidence concerning CSA. The total population of community health and pediatric nurses of a Canadian province were surveyed using a mail out questionnaire. The results revealed that these nurses need and want to improve their knowledge and skills regarding the identification, referral, and treatment of victims of CSA. Small but significant differences were noted between the nurses and other professional and non-professional workers who had been surveyed in a previous study regarding their applied knowledge of CSA, attitudes toward victim credibility and culpability, and punishment for offenders.


Investigating the impact of a 20 miles per hour speed limit intervention on road traffic collisions, casualties, speed and volume in Belfast, UK: 3 year follow-up outcomes of a natural experiment.
Evidence regarding the effectiveness of 20 miles per hour (mph) speed limit interventions is limited, and rarely have long-term outcomes been assessed. We investigate the effect of a 20 mph speed limit intervention on road traffic collisions, casualties, speed and volume at 1 and 3 years post-implementation. An observational, repeated cross-sectional design was implemented, using routinely collected data for road traffic collisions, casualties, speed and volume. We evaluated difference-in-differences in collisions and casualties (intervention vs control) across three different time series and traffic speed and volume pre-implementation, at 1 and 3 years post-implementation. Small reductions in road traffic collisions were observed at year 1 (3%; p=0.82) and year 3 post-implementation (15%; p=0.31) at the intervention site. Difference-in-differences analyses showed no statistically significant differences between the intervention and control sites over time for road traffic collisions. There were 16% (p=0.18) and 22% (p=0.06) reductions in casualty rates at years 1 and 3 post-implementation, respectively, at the intervention site. Results showed little change in mean traffic speed at year 1 (0.2 mph, 95% CI -0.3 to 2.4, p=0.14) and year 3 post-implementation (0.8, 95% CI -1.5 to 2.5, p=0.17). For traffic volume, a decrease in 57 vehicles per week was observed at year 1 (95% CI -162 to -14, p<0.00) and 71 vehicles at year 3 (95% CI -213 to 1, p=0.05) post-implementation. A 20 mph speed limit intervention implemented at city centre scale had little impact on long-term outcomes including road traffic collisions, casualties and speed, except for a reduction in traffic volume. Policymakers considering implementing 20 mph speed limit interventions should consider the fidelity, context and scale of implementation.


A histologically visible representation of the fingers and palm in primate area 3b and its immutability following long-term deafferentations.
An isomorph of the glabrous hand is visible in primary somato-sensory cortex (area 3b) of owl monkeys in brain sections cut parallel to the surface and stained for myelin. A mediolateral row of five ovals, separated by myelin-light septa, represents digits and corresponds precisely with cortical sites activated by light touch on individual digits in microelectrode recordings. A number of caudal ovals relate to pads of the palm. A more distinct septum separates the hand from the more lateral face representation. Within the face representation, two large myelin-dense ovals can be identified that are activated by the upper or lower face in a caudo-rostral sequence. Accidental finger loss or dorsal column section, deafferentations that result in reorganization of the physiological map in area 3b, do not alter the morphological map. The proportions for each digit and palm in the morphological map do not vary across normal and deafferented animals. Similar isomorphs were also seen in area 3b of squirrel and macaque monkeys. We conclude that the anatomical isomorph for the body surface representation in area 3b is a reliable reflection of normal cortical organization and may be a common feature of the primate area 3b. The isomorph can provide a reference in studies of somatotopic reorganization.


Magnesium sulfate protects blood-brain barrier integrity and reduces brain edema after acute ischemic stroke in rats.
Brain edema is a fatal complication of acute ischemic stroke and associated with worse outcomes in patients. This study was designed to evaluate the effects of magnesium sulfate on vasogenic brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia-reperfusion (IR) in a rat model of ischemic stroke. A total of 72 male Sprague-Dawley rats were categorized into the following three primary groups: sham, control ischemic, magnesium-sulfate-treated (300 mg/kg loading dose, followed by an additional 100 mg/kg) ischemic (n = 24 in each group). Transient focal cerebral ischemia was induced by 60-min-long occlusion of the left middle cerebral artery, followed by 24-h-long reperfusion. Sensorimotor deficits, infarct volume, and brain edema were evaluated at the end of the reperfusion period. The BBB permeability was assessed by Evans Blue extravasation technique. Lipid peroxidation levels were assessed by measuring the malondialdehyde content in the brain tissue homogenate, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were detected according to the technical manual of the assay kits. Induction of cerebral ischemia in the control group produced considerable BBB damage in conjunction with severe brain edema formation. Treatment with magnesium sulfate significantly attenuated brain edema and protected BBB integrity in the ischemic lesioned hemisphere. In addition, magnesium sulfate reduced lipid peroxidation and increased antioxidant protection of brain tissue by upregulating the activities of antioxidant enzymes. Treatment with magnesium sulfate protected BBB integrity against IR-induced damage and reduced vasogenic edema formation partly via antioxidant mechanisms in a rat model of acute ischemic stroke.


Wild Rodents and Their Ectoparasites in an Enzootic Plague Focus, Western Iran.
Introduction: Entomological surveys of ectoparasites and their hosts are an essential tool for assessing the risks of rodent-borne diseases transmitted to humans by arthropod vectors. Objectives: This study was carried out to update the epidemiological data of plague with respect to species compositions of the rodents and their ectoparasites at enzootic foci located in Kurdistan Province, Iran. Methods: The rodents' habitats were selected based on past records of plague and subclimates in each study district with especial attention to the vegetation type. The trapped rodents were anesthetized using a chloroform chamber, and the animals were then examined for ectoparasites by brushing their hair over a pan containing water. The ectoparasites were collected with a fine brush and preserved in 70% ethanol in screw cap tubes. Results: A total of 208 rodents were trapped from three districts. Taxonomic ranking of the rodents indicated that the specimens belonged to 2 suborders of Myomorpha and Sciuromorpha, 4 families (Muridae, Muscardinidae, Cricetidae, and Sciuridae), 7 genera, including Meriones, Apodemus, Mus, Sciurus, Microtus, and Dryomys, and 15 species. Out of 208 rodents, only 56 (26.9%) were infested with 22 species of ectoparasites. Totally, 312 ectoparasites were isolated from 56 rodents, including 12 flea species (54.5%), 6 mite species (27.3%), 3 tick species (13.6%), and one louse species (4.6%). Five species of fleas were recorded for the first time in Kurdistan Province, including Ctenophthalmus iranus persicus, Paraceras melis melis, Nosopsyllus iranus iranus, Paraceras sp., and Ctenophyllus spp. Conclusion: The finding revealed new records for rodents and ectoparasites in Kurdistan Province, as well as changes in dominant rodent species and their ectoparasites compared to previous studies. This phenomenon can influence the changes in the incidence of plague and its epidemiology.


Acute effect of sidestream cigarette smoke extract on vascular endothelial function.
Acute exposure to passive smoking adversely affects vascular function by promoting oxidative stress and endothelial dysfunction. However, it is not known whether tobacco sidestream (SS) smoke has a greater deleterious effect on the endothelium than non-tobacco SS smoke and whether these effects are related to nicotinic endothelial stimulation. To test these hypotheses, endothelial-dependent relaxation and superoxide anion production were assessed in isolated rat aortas incubated with tobacco SS smoke, non-tobacco SS smoke, or pure nicotine. Tobacco SS smoke decreased the maximal relaxation to acetylcholine (Ach) from 79 +/- 6% to 57 +/- 7.3% (% inhibition of phenylephrine-induced plateau, P < 0.001) and increased superoxide anion production from 31 +/- 9.7 to 116 +/- 24 count/10 sec/mg (P < 0.01, lucigenin-enhanced chemiluminescence technique). The non-tobacco SS smoke extract had no significant effect on the response to Ach but increased superoxide anion production in the aortic wall to 133 +/- 2 count/10 sec/mg (P < 0.001). Furthermore, concentration-response curves to Ach and superoxide production remained unaltered with nicotine (0.001, 0.01, or 0.1 mM). In conclusion, despite similar increases in vascular wall superoxide production with tobacco and non-tobacco SS smoke, only the tobacco SS smoke extracts affected endothelium-dependent vasorelaxation. Nicotine alone does not reproduce the effects seen with tobacco SS smoke, suggesting that the acute endothelial toxicity of passive smoking cannot simply be ascribed to a nicotine-dependent mechanism.


[Optical studies and aids in the treatment of posttraumatic urethral strictures].
The paper presents the results of treatment of 172 patients of whom 50 had anterior urethral strictures and 122 posterior ones. In 167 of 172 patients urethral resection was performed irrespective of the site of constriction. The urethral patency was restored in 162 (97%) patients, whereas the operation was ineffective in 5 (3%). A relapse of stricture occurred in 16 (10%) of 162 patients in different periods following the operation, good results were obtained with repeated operations in 10 (6.2%). Sexual potency was observed in 30 (18.5%) patients. In patients with short strictures, optical urethrotomy by excising the scar tissue by a loop with a Storz resectoscope. The operation was ended with bladder drainage with a Foley No. 14 or No. 16 catheter for 1 to 2 weeks. All the operated patients showed good results within 4 to 12 months. No decreased sexual potency was seen in anybody. In addition, hydrocortisone solution was instilled around the scars in the area of anastomosis by using a urethroscope in 6 patients after urethral resection, but in one patient granulations were excised, which promoted improvement of therapy outcomes. In the authors' opinion, it is expedient to use irrigation urethroscopy as the choice of method for treating posttraumatic urethral strictures. Urethral resection is considered to be the basic therapy method. Optical urethrotomy is more preferable in strictures less than 1 cm in length. Following the resection urethroscopy is regarded to be indicated, which makes it possible to correct the outcomes of the basic operation.


Association of a KCNA5 gene polymorphism with systemic sclerosis-associated pulmonary arterial hypertension in the European Caucasian population.
Pulmonary arterial hypertension (PAH) has emerged as a leading cause of death in systemic sclerosis (SSc). The genetic basis of PAH has been unraveled in recent years, with a major role played by transforming growth factor β receptors; however, some other candidate genes have also been advocated, including potassium voltage-gated channel, shaker-related subfamily, member 5 (KCNA5). We undertook this study to determine whether KCNA5 polymorphisms confer susceptibility to SSc and its vascular phenotype, including PAH. Four KCNA5 single-nucleotide polymorphisms (SNPs), rs10744676, rs1860420, rs3741930, and rs2284136, were genotyped in a discovery set of 638 SSc patients and 469 controls. In addition, rs10744676 was genotyped in an independent replication sample (938 SSc patients and 564 controls) and in a cohort of 168 patients with different PAH subtypes. The KCNA5 rs10744676 variant was found to be associated with SSc in the discovery sample, with an odds ratio (OR) of 0.62 (95% confidence interval [95% CI] 0.48-0.79, adjusted P = 0.0003) in comparison with controls (C allele frequency 11.4% versus 17.2%). When subphenotypes were investigated, an association was found solely for PAH associated with SSc (OR 0.31 [95% CI 0.13-0.71], adjusted P = 0.04). The other KCNA5 SNPs tested were not associated with any SSc subset. The above association with PAH associated with SSc was replicated in the second set. In the combined population, rs10744676 was strongly associated with PAH associated with SSc in comparison with controls (OR 0.36 [95% CI 0.21-0.63], P = 0.0002). In the independent cohort of patients with PAH, after investigating PAH subtypes, only rs10744676 showed an association with PAH associated with SSc. Our results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc.


Pulmonoprotective Action of Zataria multiflora Ethanolic Extract on Cyclophosphamide-Induced Oxidative Lung Toxicity in Mice.
To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice. Mice were intraperitoneally pre-treated with various doses of Zataria multiflora extract (50, 100, 200, and 400 mg/kg) once daily for 7 consecutive days. Animals were then injected with a single 200 mg/kg intraperitoneal dose of CP 1 h after the last administration of O. vulgare. Twenty-four hours later, mice were euthanized, the lungs were immediately removed, and biochemical and histological studies were conducted. A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with Zataria multiflora significantly inhibited the elevation of lipid peroxidation level and the depletion in glutathione content, and superoxide dismutase and catalase activities induced by CP in lung. In addition, Zataria multiflora effectively alleviated CP-induced histopathological abnormality and pulmonary damages in mice lung tissues. The results reveal that Zataria multiflora protects lung tissues from CP-induced toxicity and suggest a role for oxidative stress in the pathogenesis of lung toxicity produced by CP in mice. Because Zataria multiflora has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a good supplement for reducing organ toxicity in patients undergoing chemotherapy, besides their consolidated ethnopharmacological uses.


Use of helical computed tomography for the assessment of acetabular osteolysis after total hip arthroplasty.
Acetabular osteolysis is a major problem affecting long-term survival of total hip prostheses. Since lytic lesions may be asymptomatic until extensive bone loss has occurred, early detection of lytic lesions is important. The purposes of this study were to determine the efficacy and potential role of high-resolution helical (or spiral) computed tomography with metal-artifact minimization in the early detection of osteolysis of the pelvis and to use the method to determine if there was a relationship between the extent of osteolysis and the amount of polyethylene wear. Forty patients (fifty hips) who had undergone primary cementless total hip arthroplasty between 1988 and 1994 were evaluated as part of an ongoing prospective study. These patients had a history of high-level activity that was believed to place them at increased risk for accelerated polyethylene wear. The most recent follow-up radiographs were compared with the three-month postoperative radiographs. Helical computed tomography scans with metal-artifact minimization were made, and evidence of osteolytic lesions on these scans was compared with that on the radiographs. Two-dimensional wear analysis was performed with use of digitized radiographs, and the results were compared with loss of bone volume as calculated from the computed tomography scans. Acetabular lysis was identified on the radiographs of sixteen hips and on the computed tomography scans of twenty-six hips. Radiographs underestimated the extent of the lysis in thirteen of the sixteen hips. There was no correlation (r = 0.036) between linear wear and the measured volume of bone loss, with the numbers available. On the basis of the amount of lysis seen on the computed tomography scans, one patient underwent a revision procedure. Helical computed tomography with metal-artifact minimization is more sensitive for identifying and quantifying osteolysis after total hip arthroplasty than is plain radiography. Since computed tomography scans show both the extent and the location of lytic lesions, they are useful to guide treatment decisions as well as to assist in planning for surgical intervention, when needed, in patients with suspected osteolysis.


Mentorship in Radiology.
Mentoring is an extremely important component of academic medicine, including radiology, yet it is not specifically emphasized in radiology training, and many academic radiology departments in the United States, Canada, and elsewhere do not have formal mentoring programs for medical students, residents, fellows, or junior faculty. The purpose of this article is to overview the current status of mentorship in radiology, to discuss the importance of mentorship at multiple levels and its potential benefits in particular, as well as how to conduct a successful mentor-mentee relationship. The literature on mentorship in radiology and in academic medicine in general is reviewed.


The identification of a novel splicing mutation in the DMD gene of a Chinese family.
The proband is a five-year-old boy diagnosed with Duchenne muscular dystrophy (DMD) by clinical manifestations and laboratory examination, but clinical phenotype of his parents is normal. In the study, his mother had a second pregnancy, and they went to obstetrics for genetic counseling to make informed reproductive choices.


Nitrous oxide from soil denitrification: factors controlling its biological production.
Increasing concentrations of nitrate, nitrite, and molecular oxygen enhanced production of nitrous oxide relative to molecular nitrogen during denitrification in soils. Soil acidity interacted with nitrate to increase the ratio of nitrous oxide to molecular nitrogen. In response to anoxic conditions, nitrous oxide production initially increased but nitrous oxide was then consumed, a pattern which resulted from the sequential synthesis of nitrogenous oxide reductases.


Single Anesthesia Strategy for Definitive Management of Bilateral Ground Glass Opacities Using Robotic Bronchoscopic Localization and Resection.
This case series describes 2 patients who underwent a single anesthesia strategy for definitive management of bilateral ground-glass opacities harboring adenocarcinoma-spectrum lesions using robotic navigational localization paired with robotic thoracoscopic resection.


Bioterrorism. DOD retreats on plan for anthrax vaccine.
Anthrax bacterium, once the deadly scourge of goat-hair workers, has become the bane of the U.S. defense establishment. Without infecting a single soldier, it has created a logistical headache for the Pentagon, as military contractors have fallen far short of supplying a vaccine that will protect all troops and be acceptable to health authorities. Last week military officials were forced to beat a hasty retreat in their current efforts, raising the hackles of legislators who already had serious doubts about the program.


Epidemiology of ankle and foot overuse injuries in sports: A systematic review.
Studies regarding ankle and foot overuse injuries are quite diverse in research methodology, data reporting, and outcomes. The aims of this systematic review were to analyze the methodology of published studies regarding ankle and foot overuse injuries in different sports disciplines and to summarize epidemiological data of ankle and foot overuse injuries. Four electronic databases, PubMed (MEDLINE), EMBASE, CINAHL, and SPORTDiscus(®) were systematically searched up to June 2011. A total of 89 articles on 23 sports disciplines were included in this review. Soccer, running, and gymnastics were the most frequently studied sports. Achilles tendinopathy, plantar fasciitis, and stress fracture were the most frequently studied injuries. Study design and reporting methods were heterogeneous. Most studies suffered from a weak methodology and poor reporting. The most common weaknesses were lack of a clear case definition, describing assessment procedures and reporting sample characteristics. Due to methodological heterogeneity of studies, inter-sports and intra-sports comparisons and meta-analysis were not possible. Methodology of most studies on incidence and prevalence of ankle and foot overuse injuries is insufficient. Based on the results, we recommend authors to clearly define cases, describe assessment procedures and report sample characteristics adequately.