Clamping down on drugs: the Escherichia coli multidrug efflux protein MdtM.
Multidrug resistance is principally a consequence of the active transport of drugs out of the cell by proteins that are integral membrane transporters. In the following review, we present a synthesis of current understanding of the Escherichia coli multidrug resistance transporter, MdtM, a 410 amino acid residue protein that belongs to the large and ubiquitous major facilitator superfamily (MFS).


The Relevance of Social Theory in the Practice of Environmental Management.
In this paper I argue that the dominance of certain paradigms and theories on policies can have an influence on the value added by impact assessments. A link exists between paradigms and theories and policies and consequently the practices humans develop to tackle real world problems. I also argue that different types of thinking (contained in paradigms and theories) need to be integrated, at least at the scientific level, to enhance our understanding of social phenomena. This in turn can have a positive influence on policy processes that follow impact assessment recommendations. I am not arguing for the adoption of theoretical positions by practitioners, Instead, I contend that if impact assessments are informed by a variety of paradigms and theories, the policy practitioner might have a better understanding of the issue and the moral choices he or she needs to make. I will highlight the connection between theory and policies with practical examples from the social impact assessment of the De Hoop Dam, which was constructed on the Steelpoort River. I also argue for an integration of different theories to give a deeper understanding of real world problems.


Animal models of HBV infection.
The mechanisms determining hepatitis B virus (HBV) persistence and pathogenesis are not fully elucidated, but appear to be multi-factorial. Current medication to repress viral replication is available; however, the unique replication strategies employed by HBV enable the virus to persist within the infected hepatocytes. Consequently, cure is rarely achieved. Progresses in HBV research and preclinical testing of antiviral agents have been limited by the narrow species- and tissue-tropism of the virus, the paucity of infection models available and the restrictions imposed by the use of chimpanzees, the only animals fully susceptible to HBV infection. Mice are not HBV permissive but major efforts have focused on the development of mouse models of HBV replication and infection, such as the generation of humanized mice. By presenting the different animal models available, this review will highlight the most important and clinically relevant findings that have been retrieved from the respective systems.


Priority screening of contaminants of emerging concern in drinking water sources of eastern China: Assessing risks based on exposure-activity ratios (EARs).
Increasing and widely detected contaminants of emerging concern (CECs) pose a threat to drinking water safety. Compared with traditional methods, the exposure-activity ratio (EAR) method based on the ToxCast database may have unique advantages in risk assessment of drinking water sources because it provides massive multi-target high-throughput screening toxicity effect data assessment for chemicals with missing traditional toxicity data. In this study, 112 CECs at 52 sampling sites in drinking water sources in Zhejiang Province of eastern China were investigated. Based on EARs and occurrence, priority chemicals were identified as difenoconazole (priority level 1), dimethomorph (priority level 2), acetochlor, caffeine, carbamazepine, carbendazim, paclobutrazol and pyrimethanil (priority level 3). Different from single observable biological effect in traditional methods, a variety of observable biological effects caused by high-risk targets were explored through adverse outcomes pathways (AOPs), revealing ecological risks as well as human health risks, for example, hepatocellular adenomas and carcinomas. Furthermore, the difference between the maximum EAR for a given chemical in a sample (EARmax) and the toxicity quotient (TQ) in priority screening of CECs was compared. The results show that screening priority CECs based on the EAR method is acceptable and more sensitive, suggesting the difference between in vitro and in vivo toxic effects and the necessity of incorporating the harm degree of biological effects into the EAR method to screen priority chemicals in the future.


Factors Affecting Delayed Presentation and Diagnosis of Breast Cancer in Asian Developing Countries Women: A Systematic Review.
Advance in screening strategies and management had steadily decreased the mortality rates of breast cancer. In developing countries, conducting screening and early diagnosis of breast cancers may face several problems. This systematic review aims to determine factors affecting the delayed diagnosis of breast cancer in developing countries in Asia. Literature research was conducted through Pubmed, ScienceDirect, Scopus, EbscoHost, Cochrane Library, and Google Scholar. The main keywords were "breast cancer", "delayed diagnosis" and "developing countries". Both quantitative and qualitative studies were included. A total of 26 studies were included. The definition of delayed presentation or diagnosis varied from 1 month to 6 months. Among all the factors from patients and providers, breast symptoms and examinations consistently showed a significant contribution in reducing delayed diagnosis. Strengthened by qualitative studies, patients' knowledge and perception also had a major role in delayed diagnosis. Among Asian developing countries, breast symptoms and examination, as well as individual knowledge and perception, are the main factors related to delayed diagnosis of breast cancer.


Public Health Approaches to Promoting University Students' Mental Health: A Global Perspective.
Provide a critical overview of recent global advances in student mental health from a public health perspective, highlighting key challenges and gaps in the literature. Mental disorders and suicidality are common among university students globally. However, there is a significant treatment gap even though evidence-based treatments are available. To overcome barriers to treatment, public health interventions should be conceptualized within a developmental paradigm that takes cognizance of the developmental tasks of young adulthood. Traditional one-on-one treatment approaches will not be a cost-effective or sustainable way to close the treatment gap among students. A range of evidence-based interventions is available to promote students' mental health; however, novel approaches are needed to scale up services and adapt intervention delivery to suit student specific contexts. Digital interventions and peer-to-peer interventions could be a cost-effective way to scale-up and expand the range of services.


Temperature thresholds for bacterial symbiosis with a sponge.
The impact of elevated seawater temperature on bacterial communities within the marine sponge Rhopaloeides odorabile was assessed. Sponges were exposed to temperatures ranging between 27 and 33 degrees C. No differences in bacterial community composition or sponge health were detected in treatments between 27 and 31 degrees C. In contrast, sponges exposed to 33 degrees C exhibited a complete loss of the primary cultivated symbiont within 24 h and cellular necrosis after 3 days. Furthermore, denaturing gradient gel electrophoresis (DGGE) and clone sequence analysis detected a dramatic shift in bacterial community composition between 31 and 33 degrees C. Within the first 24 h most of the DGGE bands detected in samples from 27 to 31 degrees C were absent from the 33 degrees C sponges whereas eight bands were detected exclusively in the 33 degrees C sponges. The 16S rRNA sequencing revealed that most of the microbes from sponges exposed to 27-31 degrees C had highest homology to known sponge-associated bacteria. In contrast, many of the microbes from sponges exposed to 33 degrees C were similar to sequences previously retrieved from diseased and bleached corals. The 16S rRNA clone library analysis also detected a significant shift in bacterial community structure. The 27 degrees C library was composed of Proteobacteria, Actinobacteria, Nitrospira, Acidobacteria and Chloroflexi whereas the 33 degrees C library contained sequences from the Proteobacteria, Bacteroidetes and Firmicutes. The clear shifts in community composition at elevated temperatures can be attributed to the loss of symbionts and to the establishment of alien microbial populations including potential pathogens. Breakdown of symbioses and stress in the sponge occurred at temperatures identical to those reported for coral bleaching, indicating that sponges may be similarly threatened by climate change.


Dynamics of Intestinal Carriage of Extended-Spectrum Beta-lactamase-Producing Enterobacteriaceae in the Dutch General Population, 2014-2016.
In the Netherlands, the prevalence of intestinal extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in community-dwelling subjects is ~5%. Little is known about the dynamics of ESBL-E carriage. In a nationwide, population-based study (2014-2016) with 4177 community-dwelling subjects, fecal samples from 656 subjects were collected after 1 (time point [T] = 1) and 6 (T = 2) months. The growth of ESBL-E was quantified and a whole-genome sequence analysis was performed. Subjects were categorized as either an incidental, short-term, or long-term carrier or as a noncarrier. Risk factors were determined by random forest models and logistic regression. The transmissibility and duration of ESBL-E carriage was quantified using a transmission model, which also incorporated previous study data. Out of 656 participants, 96 were ESBL-E carriers at T = 0. Of these, 66 (10.1%) subjects were incidental carriers, 22 (3.3%) were short-term carriers, and 38 (5.8%) were long-term carriers; the remaining 530 (80.8%) were noncarriers. The risk factors for long-term carriage were travelling to Asia, swimming in a sea/ocean, and not changing the kitchen towel daily. The log-transformed colony forming units ratio at T = 0 was predictive for ESBL-E carriage at T = 1 (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.6) and T = 2 (OR, 1.2; 95% CI, 1.1-1.4). Model simulations revealed a median decolonization rate of 2.83/year, an average duration of carriage of 0.35 years, and an acquisition rate of 0.34/year. The trend of the acquisition rate during the study period was close to 0. The risk factors for long-term ESBL-E carriage were travel- and hygiene-related. The dynamics of ESBL-E carriage in the general Dutch population are characterized by balancing decolonization and acquisition rates.


Air core notch-coil magnet with variable geometry for fast-field-cycling NMR.
In this manuscript we present details on the optimization, construction and performance of a wide-bore (71 mm) α-helical-cut notch-coil magnet with variable geometry for fast-field-cycling NMR. In addition to the usual requirements for this kind of magnets (high field-to-power ratio, good magnetic field homogeneity, low inductance and resistance values) a tunable homogeneity and a more uniform heat dissipation along the magnet body are considered. The presented magnet consists of only one machined metallic cylinder combined with two external movable pieces. The optimal configuration is calculated through an evaluation of the magnetic flux density within the entire volume of interest. The magnet has a field-to-current constant of 0.728 mT/A, allowing to switch from zero to 0.125 T in less than 3 ms without energy storage assistance. For a cylindrical sample volume of 35 cm(3) the effective magnet homogeneity is lower than 130 ppm.


Tannic acid-accelerated fenton chemical reaction amplification for fluorescent biosensing: The proof-of-concept towards ultrasensitive detection of DNA methylation.
As a promising biomarker, the level of methylated DNA usually changes in the early stage of the cancer. Ultrasensitive detection of the changes of methylated DNA offers possibility for early diagnosis of cancer. In this work, a tannic acid-accelerated Fenton chemical reaction amplification was firstly proposed for the construction of ultrasensitive fluorescent assay. Tannic acid was used as reductant to accelerate Fenton reaction procedure through the conversion of Fe3+/Fe2+, generating hydroxyl radicals (·OH) continuously. The produced ·OH oxidized massive non-fluorescent terephthalic acid (TA) to fluorescent-emitting hydroxy terephthalic acid (TAOH). In this way, the fluorescent signal could be greatly enhanced and the sensitivity was improved almost 116 times. The proposed signal amplification strategy was further applied to detect of DNA methylation with the assistance of liposome encapsulated with tannic-Fe3+ complexes. The methylated DNA was firstly captured through the hybridization with its complementary DNA that were pre-modified in the 96-well plate via the combination between streptavidin (SA) and biotin. Then, 5 mC antibody on the surface of liposomes specially recognized and combined with methylation sites, which brought large amount of tannic-Fe3+ complexes to participate Fenton reaction. The fluorescence of generated TAOH was depended on the concentration of methylated DNA. The assay showed good analytical performance for methylated DNA with a limit of detection (LOD) of 1.4 fM. It's believed that tannic acid-accelerated Fenton chemical reaction amplification strategy provides a promising platform for ultrasensitive fluorescent detection of low abundant biomarkers.


[Housing Situation Among People with Substance Use Disorder in a Psychiatric Centre in Berlin, Germany - A Cross-Sectional Patient Survey].
To investigate the housing situation, service use and substance use among patients with substance use disorders seeking psychiatric treatment. Structured interview among 540 psychiatric inpatients including day clinics in a psychiatric centre in Berlin, Germany. Patients under instable housing conditions were significantly more often diagnosed with a comorbid psychotic disorder and were significantly younger when first psychiatric or substance use treatment occurred, on average before onset of homelessness. Homelessness among people with substance use disorder seeking psychiatric treatment is associated with disadvantageous treatment factors such as early age of psychiatric treatment and comorbid psychotic disorders. Therefore, addressing social difficulties especially after inpatient treatment and close cooperation between different care providers should be of high importance among these groups.


Regio- and enantioselective cyclobutene allylations.
Catalytic asymmetric allylation of lactone 1 with allyl boronates leads to functionalized cyclobutenes in high regio- and stereoselectivity.


Estimating the Prevalence of AATD Patients in the UK to Identify Underdiagnosis and Determine the Eligibility for Potential Augmentation Therapy.
Alpha 1 antitrypsin deficiency (AATD) is a genetic risk factor for chronic obstructive pulmonary disease (COPD). Whilst testing for the condition is relatively simple, there is a disconnect in published literature between genetic epidemiology and numbers of patients known to specialists. This makes planning services for patients difficult. We aimed to estimate the number of patients likely to have lung disease eligible for specific AATD therapy within the UK. The THIN database was used to determine the prevalence of AATD and symptomatic COPD. This, and published rates of AATD were used to extrapolate THIN data to the population size of the UK to give an indicative population size for symptomatic AATD patients who have lung disease. The Birmingham AATD registry was used to describe age at diagnosis, rate of lung disease and symptomatic lung disease for patients with PiZZ (or equivalent) AATD, together with the time from symptom onset to diagnosis, in order to aid interpretation of the THIN data and improve modeling. THIN data showed COPD prevalence of 3%, and AATD prevalence of 0.005-0.2%, depending on how stringently AATD diagnostic codes were applied. The majority of Birmingham AATD patients were diagnosed between the ages 46-55, whilst patients recorded in THIN tended to be older. The rate of COPD was similar in the THIN and Birmingham patients diagnosed with AATD. Modelling to the size of the UK demonstrated a likely symptomatic AATD population of between 3016 and 9866 people. AATD is likely to be under-diagnosed in the UK. Based on projected patient numbers an expansion to specialist services is desirable, in particular if specific therapy for AATD such as augmentation were to be introduced to the healthcare system.


Comparing the performance of IBIS and BulletTRAX-3D technology using bullets fired through 10 consecutively rifled barrels.
This study evaluates the abilities of the Integrated Ballistics Identification System (IBIS) and BulletTRAX-3D electronic imaging systems to identify bullets fired by the same weapon in a large database of images. Ten consecutively rifled handgun barrels were test fired to obtain reference sample and known match sample pairs for upload onto both bullet acquisition systems. Both copper-jacketed and lead bullets were uploaded, to account for variations in the manner in which markings are reproduced on the different metal compositions. Ranked correlation lists were examined and evaluated. For copper-jacketed bullet correlations, both IBIS and BulletTRAX-3D identified all reference samples to their known matches within the top 10 positions. For lead bullets, BulletTRAX-3D identified all reference samples to their known match in the top 10 positions while IBIS identified only 30%. For inter composition comparisons, BulletTRAX-3D was more successful than IBIS, identifying 100% of reference samples to their known match in the top 20 for copper-jacketed to lead comparisons and 90% for lead to copper-jacketed comparisons. These results suggest that BulletTRAX-3D is more effective than IBIS in the analysis of a wider range of bullet types and it was also found to produce images of superior quality.


Extended and saturation prostatic biopsy in the diagnosis and characterisation of prostate cancer: a critical analysis of the literature.
To review and critically analyse all the recent literature on the detection and characterisation of prostate cancer by means of extended and saturation protocols. A systematic review of the literature was performed by searching MedLine from January 1995 to April 2007. Electronic searches were limited to the English language, and the key words "prostate cancer," "diagnosis," "transrectal ultrasound (TRUS)," "prostate biopsy," and "prognosis" were used. The prostate biopsy technique has changed significantly since the original Hodge sextant biopsy protocol. Several types of local anaesthesia are now available, but periprostatic nerve block (PPNB) has proved to be the most effective method to reduce pain during TRUS biopsy. It remains controversial whether PPNB should be associated with other medications. The optimal extended protocol (sextant template with at least four additional cores) should include six standard sextant biopsies, with additional biopsies (up to 12 cores) taken more laterally (anterior horn) to the base and medially to the apex. Repeat biopsies should be based on saturation biopsies (number of cores >/= 20) and should include the transition zone, especially in a patient with an initial negative biopsy. As a means of increasing accuracy of prostatic biopsy and reducing unnecessary prostate biopsy, colour and power Doppler imaging, with or without contrast enhancement, and elastography now can be successfully adopted, but their routine use is still controversial. Extended and saturation biopsy schemes should be performed at first and repeat biopsy, respectively. The widespread use of local anaesthesia makes the procedures more comfortable.


Previous convictions or accidents and the risk of subsequent accidents of older drivers.
The over-involvement of elderly drivers in collisions has a potentially adverse effect on highway safety. The question for most experts in traffic research is whether we can predict the individual risk of accidents and which variables are the best predictors, especially for this population. For a better understanding of the elderly drivers' problems, this study aimed to describe the most common types of accidents in the elderly population of drivers living in Quebec (> or = 65 years of age). The second objective of the study was to analyse the relationship between previous accidents or convictions and the risk of subsequent accidents. The results show that: (1) elderly drivers are characterised by error accidents involving more than one car, especially at intersections, (2) prior accidents are a better predictor for accident risk than prior convictions and (3) these trends steadily increase with each age group (drivers 65 years old to 80 years or more). The results are discussed in relation to the literature on risk behaviour of the elderly drivers.


Heavy metals affect regulatory volume decrease (RVD) in nematocytes isolated from the jellyfish Pelagia noctiluca.
The environmental contamination caused by heavy metals raises the question of their effect on biological systems. Among bio-indicators useful to monitor the toxicological effects of these chemicals, Cnidarians offer a unique model. Cnidarians possess highly specialized stinging cells, termed nematocytes, which respond to hyposmotic solution with well established homeostatic parameters as an acute osmotic phase (OP), leading to cell swelling, and then a slower regulatory volume decrease (RVD) phase, causing cell shrinkage. Here we report the effect of 65% artificial sea water (ASW) containing heavy metals, such as Cd, La, Co, Cu and Zn (concentrations comprised between 100 and 0.1 μM) on both OP and RVD in nematocytes isolated from the jellyfish Pelagia noctiluca by 605 mM NaSCN plus 0.01 mM Ca(2+). The exposure of the cells to Co and La inhibited RVD but not OP. However, Cu, Cd and Zn prevented the OP in a dose-dependent manner and, hence, also the detection of RVD. These results suggest that, in isolated nematocytes, heavy metal pollutants impair RVD either directly or indirectly through interference with the OP, thus negating RVD. Although further studies need to clarify the exact mechanisms whereby heavy metals exert their toxicity, it is evident that nematocytes of Cnidarians could serve as a model for ecotoxicological investigations.


Traumatic globe dislocation into the paranasal sinuses: Literature review and treatment guidelines.
Traumatic globe dislocation into the paranasal sinuses is rare. Only 24 cases have been reported in the English-language literature indexed in PUBMED. This form of injury frequently occurs as a result of high-energy blunt trauma mainly associated to traffic accidents. Traumatic globe dislocation into the paranasal sinuses can be explained by the mechanism of blowout fracture when strong blunt trauma forces are applied to the globe fracturing the thin orbital walls and displacing the eyeball. Medical and surgical management of severe globe displacement is still controversial. However, the majority of researchers agreed that the globe should be replaced into the orbital cavity as soon as possible. The present study aims to describe a case of traumatic globe dislocation into the maxillary sinus suggesting treatment guidelines based on English-language literature from 1971 to 2015.


Prevention of Hip Fractures: Trade-off between Minor Benefits to Individuals and Large Benefits to the Community.
Goeffrey Rose postulated that a population-based measure bringing a small benefit to each individual can yield large benefits to the community. We aimed to test this axiom by quantifying the relationship between change in bone mineral density (BMD) and hip fracture incidence between two prospective cohorts separated by ~10 years. In this prospective population-based Dubbo Osteoporosis Epidemiology Study (DOES), the participants aged 60+ were recruited in two waves: the initial cohort (1311 women, 842 men) in 1989 to 1992 and the second cohort (974 women, 544 men) in 1999 to 2001. The incident hip fracture was radiologically ascertained. Femoral neck BMD was measured biannually. Multivariable-adjusted Cox's proportional hazards models were adjusted for the predefined covariates such as age, BMI, lifestyle factors, falls, and prior fracture. Compared with the initial cohort, the second cohort had a higher femoral neck BMD by ~0.04 g/cm2 in women and 0.03 g/cm2 in men. However, the prevalence of osteoporosis in the second cohort was halved (prevalence ratio 0.51, 95% CI 0.36 to 0.73 in women; 0.45, 0.24 to 0.84 in men), and its hip fracture incidence was significantly reduced (hazard ratio 0.54, 95% CI, 0.38 to 0.78 in women; 0.39, 0.19 to 0.80 in men). Sensitivity analyses indicated that the "effect" was unlikely due to unmeasured confounders. These findings suggest that a population-wide strategy aimed at enhancing BMD across the entire population could lead to a substantial decrease in the incidence of hip fractures. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Troglomorphism in the middle Triassic crinoids from Poland.
In this paper, we document the Middle Triassic marine fauna recovered from the fissure/cave system of Stare Gliny (southern Poland) developed in the Devonian host dolomite. The fossils are mostly represented by in situ preserved and small-sized holdfasts of crinoids (Crinoidea) that are attached to the cave walls. Other fossils found in the cave infills include articulated brittle stars and brachiopods. Our findings constitute the oldest Mesozoic evidence for troglophile crinoids. We suggest that troglomorphism in these echinoderms was likely related to protection against predation, which underscores the magnitude of anti-predatory adaptations to increased predation pressure that occurred during the Early Mesozoic Marine Revolution.


Concerted modification of nucleotides at functional centers of the ribosome revealed by single-molecule RNA modification profiling.
Nucleotides in RNA and DNA are chemically modified by numerous enzymes that alter their function. Eukaryotic ribosomal RNA (rRNA) is modified at more than 100 locations, particularly at highly conserved and functionally important nucleotides. During ribosome biogenesis, modifications are added at various stages of assembly. The existence of differently modified classes of ribosomes in normal cells is unknown because no method exists to simultaneously evaluate the modification status at all sites within a single rRNA molecule. Using a combination of yeast genetics and nanopore direct RNA sequencing, we developed a reliable method to track the modification status of single rRNA molecules at 37 sites in 18 S rRNA and 73 sites in 25 S rRNA. We use our method to characterize patterns of modification heterogeneity and identify concerted modification of nucleotides found near functional centers of the ribosome. Distinct, undermodified subpopulations of rRNAs accumulate upon loss of Dbp3 or Prp43 RNA helicases, suggesting overlapping roles in ribosome biogenesis. Modification profiles are surprisingly resistant to change in response to many genetic and acute environmental conditions that affect translation, ribosome biogenesis, and pre-mRNA splicing. The ability to capture single-molecule RNA modification profiles provides new insights into the roles of nucleotide modifications in RNA function.


MICROSCOPIC COLITIS: CONSIDERATIONS FOR GASTROENTEROLOGISTS, ENDOSCOPISTS, AND PATHOLOGISTS.
•Diagnosis of microscopic colitis necessitates effective communication among gastroenterologists, endoscopists, and pathologists. •The gastroenterologist should refer every patient with chronic watery diarrhea to perform a colonoscopy in spite of the benign course of the disease and the absence of alarm symptoms. •The endoscopist should take 2 or 3 biopsy samples of the colonic mucosa from the right and left colon, put in separate recipients, despite that the mucosa looked macroscopically normal. •The pathologist should be encouraged to use objective histological criteria to make the diagnosis. Microscopic colitis is a chronic inflammatory bowel disease characterized by non-bloody diarrhea that can range from mild to severe. It is difficult to attribute up to 10-20% of chronic diarrhea to microscopic colitis. The three determinants factors of the diagnosis are characteristic clinical symptoms, normal endoscopic picture of the colon, and pathognomonic histological picture. This manuscript aimed to update considerations and recommendations for professionals involved (gastroenterologist, endoscopists and pathologist) in the diagnosis of MC. In addition, a short recommendation about treatment.


Curtailment of Civil Liberties and Subjective Life Satisfaction.
This analysis focuses on the lockdown measures in the context of the Covid-19 crisis in Spring 2020 in Germany. In a randomized survey experiment, respondents were asked to evaluate their current life satisfaction after being provided with varying degrees of information about the lethality of Covid-19. We use reactance as a measure of the intensity of a preference for freedom to explain the variation in the observed subjective life satisfaction loss. Our results suggest that it is not high reactance alone that is associated with large losses of life satisfaction due to the curtailment of liberties. The satisfaction loss occurs in particular in combination with receiving information about the (previously overestimated) lethality of Covid-19. The online version contains supplementary material available at 10.1007/s10902-021-00491-1.


Matrix protein gene nucleotide and predicted amino acid sequence demonstrate that the first US avian pneumovirus isolate is distinct from European strains.
Avian pneumovirus (APV) is the etiological agent of turkey rhinotracheitis (TRT). Outbreaks of TRT first occurred in the US during May, 1996 and continued through June, 1997. This is the first report of these virus types in the US that was previously considered exotic to the US and Canada. The US isolate, APV/CO, was replicated in chick embryo fibroblasts (CEF) and poly-A RNA from APV/CO infected CEF cells was purified for cDNA synthesis. Degenerate oligonucleotide primers were used to amplify nucleotide sequences coding for the matrix (M) protein gene. Although the type A and B European APV M genes share 75% identity in their coding sequences, they have only 60% identity with the US APV/CO M protein gene. Predicted M proteins of European APV type A and B isolates share 89% identity in their amino acid sequence. However, the predicted M protein of APV/CO has only 78% identity with APV type A and 77% identity with APV type B protein sequences. Phylogenetically the US APV/CO isolate separates as a unique virus relative to European APV type A and B strains that cluster together. Sequence information for the APV/CO M protein gene and predicted amino acids of the M protein confirm the unique nature of this isolate compared to its European counterparts. This correlates with the inability to serologically detect the US APV/CO isolate using diagnostics based on European viruses.


Neuropeptide Y-induced operant responding for sucrose is not mediated by dopamine.
Neuropeptide Y (NPY) induces feeding in previously satiated animals after injection into the hypothalamus, especially the perifornical region (PFH). NPY also appears to have rewarding properties as evidenced by its ability to produce a conditioned place preference following injection into the nucleus accumbens (N.Acc), an effect ostensibly mediated by mesolimbic dopamine (DA). Since the progressive-ratio (PR) operant schedule has also been used to assess an organism's motivation to respond for rewarding stimuli, we tested the possibility that NPY increases PR responding for sucrose pellets. Adult male rats were injected with NPY (0-235 pmol) bilaterally through cannulae aimed to terminate in the PFH. This produced a dose-dependent increase in the total number of responses made and the number of reinforcers earned. The DA receptor blocker, alpha-flupenthixol (FLU)(0-0.2 mg/kg intraperitoneally), attenuated both NPY(156 pmol)-induced and drug-free PR responding while having no effect on NPY(156 pmol)-induced free-feeding. FLU injected directly into the N.Acc (0-5 microg) also failed to reduce sucrose free-feeding. These results suggest that distinct reward mechanisms are activated during PFH NPY-induced feeding vs. PR responding, since FLU disrupted the latter but not the former.


The measurement of body-image dissatisfaction-satisfaction: is rating importance important?
Some researchers have argued that evaluative body image may be better assessed by measures that weight dissatisfaction-satisfaction ratings by their subjective importance to individuals. The Body Areas Satisfaction Scale (BASS) is a frequently used, standardized assessment of evaluative body image, albeit one that does not use differential item weights. This investigation, with 410 female and male college students, examined whether an importance-weighted revision of the BASS would have incremental validity relative to the original version in the prediction of multiple criterion variables. Results confirmed the reliability and validity of unweighted and weighted versions. However, the validity of weighted versions did not surpass that of the original BASS. The extremity of individuals' satisfaction and dissatisfaction ratings appears inherently to reflect the importance placed on physical attributes for self-evaluation. Moderated regression analyses offered only weak support for the interaction of average satisfaction and average importance ratings beyond their main effects. The simpler, unweighted BASS is an acceptable assessment of evaluative body image.


Review: Remotely controlled magneto-regulation of therapeutics from magnetoelastic gel matrices.
Surface active magnetic nanoparticles especially superparamagnetic iron oxides are already occupying a major domain in medical therapeutics. Arresting of these magnetic nanoparticles into polymer hydrogel is a spatial assembly of nanoparticles that serves the precise delivery of drug molecules. Magnetic hydrogels are very less cultured area still in the biomedical field. This review embraces how the external magnetic field (either static or oscillating) affects the payload release from the hydrogel matrix and their magneto-regulative deformation. Besides these, we also discussed how the ferrosponge and biphasic ferrogel based scaffold type systems impact over the release kinetics and tunability of drug release behaviours.


Deep Learning Approach for the Development of a Novel Predictive Model for Prostate Cancer.
We developed a deep learning approach for accurate prediction of PCA patients one year earlier with minimal features from electronic health records. The area under the receiver operating curve for prediction of PCA was 0.94. Moreover, the sensitivity and specificity of CNN were 0.87 and 0.88, respectively.


Severe malformations in calves associated with bovine viral diarrhoea (BVD) virus infection in a dairy cattle herd.
During late may 2004, Some dairy cows at Al-Kharj area of central Saudi Arabia, gave birth to severely malformed calves which died, few hours to few days following birth. Samples were collected from the affected calves and their dams of virological and serological investigations. Bovine viral diarrhoea virus was detected by capture enzyme linked immuno-sorbent assay (ELISA) in the brains of affected calves. Serum antibodies were detected in the dams. The present study indicated that in spite of vaccination against BVD in the country, still severe affections of the disease are encountered. Further insight epidemiological studies to elucidate the BVD situation in Saudi Arabia is urgently needed.


Arsenic upregulates the expression of angiotensin II Type I receptor in mouse aortic endothelial cells.
Although chronic arsenic exposure is a well-known risk for cardiovascular disease and has a strong correlation with hypertension, the molecular pathogenesis underlying arsenic exposure-induced hypertension remains poorly understood. To delineate the pathogenesis, we examined changes in the mRNA levels of 2 angiotensin II Type I receptor (AT1R) subtypes, AT1AR and AT1BR, in a mouse aortic endothelial cell line, END-D. Quantitative real-time PCR analysis revealed significant increases in the mRNA levels of 2 AT1R subtypes, AT1AR and AT1BR following sodium arsenite (SA) treatment. Flow cytometry analysis revealed that SA increases the generation of reactive oxygen species (ROS) in a dose-dependent manner. In addition, western blot analysis revealed that SA enhances the phosphorylations of c-Jun N-terminal kinases (JNK) and activated protein 1 (AP-1). These phosphorylations were inhibited by N-acetylcysteine (NAC), an anti-oxidant. Finally, SA-induced AT1R expression was found to be prevented both by NAC and specific JNK inhibitor, SP6001325, strongly indicating that AT1R upregulation is a result of the ROS-mediated activation of the JNK signaling pathway. Taken together, our results indicate that arsenic indeed upregulates the AT1R expression, thus highlighting a role of arsenic-induced aberrant AT1R signaling in the pathogenesis of hypertension.


Bilateral simultaneous extensor mechanism disruption following simultaneous bilateral total knee replacement.
Extensor disruptions of the knee following the total knee replacements are uncommon. We describe a case of postoperative bilateral simultaneous extensor mechanism disruption following simultaneous bilateral total knee replacement. On both sides, the patient sustained open wounds. The extensor mechanism was successfully repaired on both sides, but the outcome is less than satisfactory.


Spectrophotometric method for fast quantification of ascorbic acid and dehydroascorbic acid in simple matrix for kinetics measurements.
A simple, rapid and reliable method was developed for quantifying ascorbic (AA) and dehydroascorbic (DHAA) acids and validated in 20mM malate buffer (pH 3.8). It consists in a spectrophotometric measurement of AA, either directly on the solution added with metaphosphoric acid or after reduction of DHAA into AA by dithiothreitol. This method was developed with real time measurement of reactions kinetics in bulk reactors in mind, and was checked in terms of linearity, limits of detection and quantification, fidelity and accuracy. The linearity was found satisfactory on the range of 0-6.95mM with limits of detection and quantification of 0.236mM and 0.467mM, respectively. The method was found acceptable in terms of fidelity and accuracy with a coefficient of variation for repeatability and reproducibility below 6% for AA and below 15% for DHAA, and with a recovery range of 97-102% for AA and 88-112% for DHAA.


Stenting and the rate of pancreatic fistula following pancreaticoduodenectomy.
To evaluate the efficacy of transanastomotic pancreatic duct internal stenting in the reduction of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. Retrospective study. Mayo Clinic. Between January 1, 1999, and September 30, 2010, 553 patients underwent pancreaticoduodenectomy by a single surgeon. Rates of POPF, morbidity, and mortality between stent and no-stent groups. The clinically relevant POPF (International Study Group on Pancreatic Fistula definition grade B or C) rates in the stent and no-stent groups were similar (9.6% [43 of 449 patients] and 12.5% [13 of 104 patients], respectively; P = .38). Postoperative outcomes and morbidity were also similar between the 2 groups. Mortality was 0.7% (3 of 449 patients) for the stent group and 1.0% (1 of 104 patients) for the no-stent group. Four patients (0.9%) required endoscopic retrieval of the anastomotic stent. In subset analysis, the clinically relevant POPF rates in patients with a small pancreatic duct (≤3 mm; n = 167) were similar in the stent and no-stent groups (17.7% [23 of 130 patients] and 24.3% [9 of 37 patients], respectively; P = .38). In patients with a soft pancreatic gland (n = 64), rates of clinically relevant pancreatic fistulae were also similar in the stent and no-stent groups (31.7% [13 of 41 patients] and 17.4% [4 of 23 patients], respectively; P = .20). Internal transanastomotic pancreatic duct stenting does not decrease the frequency or severity of POPF. The effect of stenting on long-term anastomotic patency warrants further investigation.


Low-Volume On-Chip Single-Cell Whole Genome Amplification for Multiple Subsequent Analyses.
Multiple analyses such as DNA profiling, sequencing, or comparative genome hybridization (CGH) done on the single-cell level long for pre-amplification due to the diploid human genome. Isothermal whole genome amplification allows amplification of long DNA templates from single cells. When analysis needs to be performed under rare cell conditions additional care needs to be taken due to the fact that, even after pre-enrichment, few candidate target cells are still dispersed among an overwhelming number of non-target background cells. Here, we describe a protocol where we define a population of candidate target cells based on specific staining. Candidate cells are then isolated by laser microdissection and pressure catapulting (LMPC) and transferred onto a microliter reaction slide. This slide allows monitoring the single-cell isolation process and isothermal whole genome amplification in less than 2 μL. The amplification products obtained from single cells can be forwarded to multiple analyses.


[The immune-enzyme testing of titers of serum anti-botulin antibodies type A during immunization of patients with botulin trianiatoxin].
The article discusses the effectiveness of the technique of immune-enzyme detection of anti-botulin antibodies type A in human blood serum. The presence of antibodies is registered in blood serum after second and subsequent immunization with botulin trianatoxin (titer from 1:400 to 1:3200). The establishment of relationship between the registered titers of anti-botulin antibodies and the activity of serum during protection of white mice from toxin revealed the correlation coefficient between these values as 0.58.


The Importance of Ticks in Q Fever Transmission: What Has (and Has Not) Been Demonstrated?
Q fever is a widespread zoonotic disease caused by Coxiella burnetii, a ubiquitous intracellular bacterium infecting humans and a variety of animals. Transmission is primarily but not exclusively airborne, and ticks are usually thought to act as vectors. We argue that, although ticks may readily transmit C. burnetii in experimental systems, they only occasionally transmit the pathogen in the field. Furthermore, we underscore that many Coxiella-like bacteria are widespread in ticks and may have been misidentified as C. burnetii. Our recommendation is to improve the methods currently used to detect and characterize C. burnetii, and we propose that further knowledge of Coxiella-like bacteria will yield new insights into Q fever evolutionary ecology and C. burnetii virulence factors.


Acute myocardial dysfunction and recovery: a common occurrence after coronary bypass surgery.
To evaluate whether acute myocardial dysfunction was common in the early postoperative period, serial hemodynamic measurements and radionuclide evaluation of ventricular function were performed before and after operation in 24 patients undergoing elective coronary bypass surgery. All patients had uncomplicated surgery, and no patient sustained an intraoperative infarction. In 96% of patients, significant depression in right and left ventricular ejection fraction was seen postoperatively, reaching a nadir at 262 +/- 116 min after coronary bypass. Left ventricular ejection fraction was 58 +/- 12% preoperatively and 37 +/- 10% at trough. Right ventricular function displayed a similar pattern. These findings were also associated with depressed cardiac and left ventricular stroke work index despite maintenance of adequate ventricular filling pressures and mean arterial pressure. The depression in ventricular function was partially reversible within 8 to 10 h after surgery. Left ventricular ejection fraction had increased to 55 +/- 13% at 426 +/- 77 min after coronary bypass and showed complete recovery within 48 h. Left ventricular end-systolic and end-diastolic volume index increased significantly postoperatively, but recovery in left ventricular ejection fraction was mostly due to decreases in end-systolic volume index (50 +/- 22 ml at trough and 32 +/- 16 ml at recovery). Depressed myocardial function was independent of bypass time, number of grafts placed, preoperative medications or core temperatures postoperatively. Postoperative therapy with pressors or inotropic agents delayed but did not prevent the occurrence of postoperative ventricular dysfunction. Despite improvements in operative techniques and methods of myocardial protection, postoperative left ventricular dysfunction continues to be common in patients undergoing cardiopulmonary bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)


Sphingosine kinase 1 is upregulated with lysophosphatidic acid receptor 2 in human colorectal cancer.
To examine the expression of SphK1, an oncogenic kinase that produces sphingosine 1-phosphate (S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid (LPA) receptor overexpressed in various cancers, in human colorectal cancer. Real-time reverse-transcription polymerase chain reaction was used to measure the mRNA expression of SphK1, LPAR2, and the three major S1P receptors in 27 colorectal cancer samples and corresponding normal tissue samples. We also examined the correlation between the expression of SphK1 and LPAR2. Colorectal cancer tissue in 22 of 27 patients had higher levels of SphK1 mRNA than in normal tissue. In two-thirds of the samples, SphK1 mRNA expression was more than two-fold higher than in normal tissue. Consistent with previous reports, LPAR2 mRNA expression in 20 of 27 colorectal cancer tissue samples was higher compared to normal tissue samples. Expression profiles of all three major S1P receptors, S1PR1, S1PR2, and S1PR3, varied without any trend, with no significant difference in expression between cancer and normal tissues. A highly significant positive correlation was found between SphK1 and LPAR2 expression [Pearson's correlation coefficient (r) = 0.784 and P < 0.01]. The mRNA levels of SphK1 and LPAR2 did not correlate with TNM stage. Our findings suggest that S1P and LPA may play important roles in the development of colorectal cancer via the upregulation of SphK1 and LPAR2, both of which could serve as new therapeutic targets in the treatment of colorectal cancer.


"TUR syndrome" after transurethral resection of the prostate using suprapubic drainage.
In a retrospective study of 522 consecutive patients who were subjected to transurethral resection of the prostate with suprapubic trocar technique, six patients were suspected of having transurethral prostatic resection syndrome. The majority of the transurethral resections were performed by surgical or urological trainees. Only two patients fulfilled the criterion for TUR syndrome caused by absorption of irrigating fluid and defined as an electrolyte dilution corresponding to a plasma sodium level below 120 mmol/l. In the present paper the symptomatology and treatment of TUR syndrome are outlined with reference to the literature. The trocar technique clearly has minimized the risk of TUR syndrome, which emphasizes the value of the method.


[Selective spinal arteriography. Its bearing on diagnosis and therapy of spinal processes, particularly arteriovenous malformations (author's transl)].
Selective spinal arteriogrpahy is a neuroradiologic technique not yet generally known. For the experienced examiner it is not more dangerous than cerebral catheter-angiography. It is most important for the diagnosis of spinal arteriovenous malformations. Here it is an essential examination even when myelography has already shown clear findings. In certain cases in can be used for therapy (artificial embolisation). In other spinal processes further experience will be needed.


Jeremy Safran: a hero's journey.
In this essay I explore Jeremy Safran's intellectual career as a hero's journey or monomyth within the specific context of psychotherapy research. I argue that he fits such model in the sense that his work - though deeply informed by theories - was singularly focused and driven by his own sense of his role and mission within the profession. Rather than attempting to review in detail the entire scope or specific parts of his research contributions, I look at his scholarship as a kind of quest, a pursuit that was trans-theoretical but unified by foundational questions about the unique nature of the relationship between therapist and patient.


Alcohol use in shiftworkers.
It has been suggested that shiftworkers may consume alcohol to help them sleep, resulting in greater consumption. A large study in Australian workers suggested that those on non-standard schedules (outside 8am-6pm, Monday-Friday) do not drink more, but are at increased odds of binge drinking (heavy periods of drinking followed by abstinence) than workers on standard schedules. However, differences in types of non-standard schedules were not examined in the study. The current study examined the alcohol intake of Australian shiftworkers on fixed and rotating shifts. Shiftworkers (n=118, age=43.4±9.9y, 68% male) on 12h-rotating (n=29), 8h-rotating (n=29), morning (n=33) and night (n=27) schedules from printing, postal, nursing and oil industries participated. They completed a Cancer Council Dietary Questionnaire, recording frequency and amount of alcohol consumed on average per day over the preceding year. They also completed a shortened Standard Shiftwork Index, including questions on shift schedule, sleep duration, tiredness, gender and age. Average alcohol consumption was 9.6±13.1 standard drinks/week. One in six reported using alcohol as a sleep aid between shifts at least sometimes and nearly one third reported consuming 12 or more drinks in 24h. Alcohol consumption was higher for males and decreased with age. Controlling for gender and age, there were no significant differences between shift types in standard drinks/week (p=0.50). However, those on 12-h rotating shifts consumed more drinks per 24h (p=0.04) and had less sleep (p<0.001). Results support the suggestion that shiftworkers are likely to binge drink, particularly younger, male workers and those on long, rotating shifts. Alcohol use in shiftworkers may put increased pressure on already vulnerable physiological systems.


eNOS gene variants and the risk of premature myocardial infarction.
Endothelial nitric oxide synthase (eNOS) as well as nitric oxide play an important role in the regulation of cardiovascular function. There are limited and controversial data regarding the impact of polymorphisms of eNOS gene that is implicated in the vasoconstrictive properties of the endothelium in the pathogenesis of premature myocardial infarction (MI). We examined whether two common polymorphisms of eNOS gene (G894T and T786C) are associated with the development of premature MI. We recruited 107 patients with premature MI and compared them to 103 age- and sex- matched controls. All patients underwent coronary angiogram and were classified into the subgroup of patients with 'normal' or 'near normal' coronary arteries and the subgroup of patients with significant coronary artery disease (≥ 50% stenosis in lumen diameter of coronary arteries). The genetic polymorphisms of eNOS gene were assayed with polymerase chain reaction and reverse hybridization. Nineteen patients (17.8%) had 'normal' or 'near normal' coronary arteries. A significantly higher frequency of homozygosity for the 786C (32%) and the 894T (21%) alleles of the eNOS gene in patients who develop early MI in the setting of angiographically 'normal' or 'near normal' coronary arteries were found. Our data suggest that the T786C and the G894T genetic polymorphisms are associated with the development of MI in very young individuals, whose coronary arteries are characterized by very small atheromatic burden.


A case of myelodysplastic syndrome developed blastic crisis of chronic myelogenous leukemia with acquisition of major BCR/ABL.
We describe a rare case of myelodysplastic syndrome that developed chronic myelogeneous leukemia with acquisition of Philadelphia chromosome. The major BCR/ABL transcript was confirmed by molecular analysis. Shortly thereafter, the patient showed transformation to blastic crisis. Hematological remission was achieved after 3 months of treatment with imatinib mesylate. The patient relapsed with additional chromosomal abnormalities and the disease became refractory to the treatment. Acquisition of the Philadelphia chromosome is an infrequent event in myelodysplastic syndrome, and the addition of this change to the initial genetic abnormality that caused MDS may have been associated with the accelerated clinical course of this patient.


Determination of capsaicinoids in peppers by microwave-assisted extraction-high-performance liquid chromatography with fluorescence detection.
A new method has been developed for the extraction of capsaicinoids (nordihydrocapsaicin, capsaicin, dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin) in peppers employing microwave-assisted extraction. The parameters studied are: extraction solvent (methanol, ethanol, acetone, ethyl acetate and water), temperature (50-200 degrees C), sample quantity (0.1-1 g), volume of solvent (15-50 mL) and the extraction time (5-20 min). The results found for the optimum conditions are: 125 degrees C as extraction temperature, 25 mL of solvent, 0.5 g of freshly triturated peppers and extraction for 5 min, employing 100% ethanol as solvent. The capsaicinoids obtained were stable under the optimised extraction conditions. The resulting method presents a high degree of reproducibility (R.S.D.<6%).


Pitted keratolysis.
Pitted keratolysis (PK) is a common superficial bacterial skin infection confined to the stratum corneum. It is clinically characterized by multifocal, discrete, pits or crater-like punched-out lesions, commonly over the pressure-bearing aspects of the foot. It is asymptomatic and associated with malodour. The surface is often moist and macerated. The diagnosis of PK is often clinical and diagnostic procedures are usually unnecessary. Lifestyle modifications form the cornerstone of the management of PK. It responds well to topical antimicrobials.


A Comparison of Activity Monitor Data from Devices Worn on the Wrist and the Waist in People with Parkinson's Disease.
It is unclear if it is appropriate for people with Parkinson's disease (PD) to wear activity monitors on the wrist because of the potential influence of impairments on the data. The objective of this study was to determine (1) whether activity monitor data collected from devices worn at the wrist and waist are comparable and (2) the contribution of PD impairments to any differences in step and activity counts at the wrist and waist. A total of 46 community-dwelling people with PD wore an accelerometer at the wrist and waist simultaneously for 1 week. Motor impairments (rigidity, bradykinesia, tremor, dyskinesia) were assessed using the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (motor examination) and part IV (motor complications). Higher values were recorded by the wrist monitor for steps/day (wrist, 9236 [standard deviation (SD) 3812]; waist, 5324 [SD 2800]; difference 3912; P < 0.001) and activity counts/day (wrist, 872,590 [SD 349,148]; waist, 186,491 [SD 101,989]; difference 686,099; P < 0.001). However, the wrist and waist values were strongly correlated (steps, r = 0.89; counts, r = 0.74; P ≤ 0.001). Increased tremor and dyskinesia explained 19% of the variation in the difference in average steps/day, and these variables plus reduced bradykinesia explained 24% of the variation in the difference in average activity counts/day. Wrist monitors are likely to overestimate activity, particularly in people with tremor and dyskinesia. Nonetheless, activity monitors can be worn on the wrist if the aim is to monitor change rather than accurately record activity.


[Experimental study of radiofrequency thermocoagulation and applied anatomy of posterior rami of lumbar nerves].
To determine points of radiofrequency thermocoagulation of the posterior rami of the lumbar nerves and to choose an effective temperature at which the conduction of painful impulse can be blocked. The posterior rami of the lumbar nerves were dissected in 15 corpses of adults. The ultrastructure of nerve fibres, changes of sensary conduction velocity (SCV) and the waveform of the unmedullated fibres which conduct painful impulse (c wave) were observed after the sciatic nerves of rabbits were coagulated at various temperatures (60 degrees C, 70 degrees C, 80 degrees C, 90 degrees C). "Transverse Process Root Area" and "Transverse Process Point" can be regarded as primary marks of thermocoagulation of the posterior rami of the lumbar nerves. Stimulation of square-wave can make the location more accurate. While the temperature of thermocoagulation reached 80 degrees C, none of painful afferent nerve fibres survived. With accurate location and good control of temperature, radiofrequency thermocoagulation will be an effective therapy for the patients suffering from pain resulted from pathological changes of the posterior rami of the lumbar nerves.


Juvenile and adult xanthogranuloma: A 30-year single-center experience and review of the disorder and its relationship to other histiocytoses.
Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis whose cell of origin, etiology and pathogenesis are not fully understood. We aimed to provide an update on histopathologic and immunophenotypic profile of this well-characterized entity whose relationship to the other histiocytoses has received renewed attention in light of recent molecular genetic studies. A retrospective review of all the cases with the pathologic diagnosis of "xanthogranuloma" was performed on our archives from 1989 to 2019. A total of 525 patients with 547 lesions diagnosed as JXG were identified with the median age of 4.5 years, a male predominance (M:F ratio 1.3:1) and a predilection for the head and neck region (40.8%). Cutaneous lesions comprised 76.8% cases and another 15.7% presented within soft tissues. The most common non-soft tissue, extracutaneous lesions included the brain (2.6%), and lungs (1.8%). Three basic histopathologic patterns were identified: early classic (EJXG) (14.2%), classic (CJXG) (45.3%), and transitional JXG (TJXG) (40.5%). Multinucleated giant cells, either Touton or non-Touton, were most frequently present in CJXG followed by TJXG. Mitosis was rare (<1/10 high-power field) among different patterns. There was an association among the patterns and lymphocytic infiltrates (P = 0.036), and presence of Touton or non-Touton giant cells (P < 0.001 for both) but not for mitotic count (P = 0.105) or eosinophilic infiltrates (P = 0.465). Additionally, there was a correlation between age groups and presence of non-Touton giant cells (P = 0.012) but not for Touton cells (P = 0.127). We have demonstrated that immunophenotypic expression of the lesion was not associated with age at diagnosis nor morphologic pattern: factor XIIIa 192/204 (94.1%), CD11c 75/77 (97.4%), CD4 82/84 (97.6%), CD68 200/201 (99.5%), CD163 15/15 (100%), CD1a 1/110 (0.9%), S-100 48/152 (31.6%), CD31 15/21 (71.4%), and vimentin 104/105 (99.0%). We have documented in a substantial series of cases of JXG that there is a correlation between one of the three basic histopathologic patterns with age at diagnosis, but with a consistent immunophenotype among the three patterns. Considering sensitivity and specificity rates, we suggest that a combination of CD11c, CD4, CD1a and either CD163 (preferred) or CD68 stains provides more specific diagnostic yield in the differentiation of JXG from other histiocytic disorders. JXG is also discussed in terms of its relationship and distinction from other similar histiocytic disorders in the context of MAPK/ERK pathway mutations.


Morphological and molecular-genetic characterization of Chloromyxum trilineatum n. sp. (Myxosporea: Bivalvulida) in the gall bladder of pale chub (Zacco platypus) in Japan.
The genus Chloromyxum (Myxozoa: Myxosporea: Bivalvulida) is defined as having ridged or smooth bivalvular myxospores containing four polar capsules, with/without caudal filaments. Currently containing more than 140 nominal species, this genus is reasonably speciose with myxospores of unique but heterogeneous morphology. Recent phylogenetic studies have demonstrated its polyphyletic nature. During our myxosporean survey of freshwater fish, a new coelozoic myxosporean species, Chloromyxum trilineatum n. sp., was detected in the gall bladder of the pale chub, Zacco platypus (Cypriniformes: Cyprinidae), which originated from central Japan. Spores were subspherical, measuring 8.5-9.1 (8.8) μm in length, 7.6-8.2 (8.0) μm in width, and 6.8-7.8 (7.4) μm in thickness (n = 20). The valvular surface was smooth and three or four distinct ridges ran parallel to the suture line. Four almost equal polar capsules, 2.9-3.8 (3.3) μm in length and 1.6-2.4 (2.0) μm in width, assembled at the apical part of the spores. The partial nucleotide sequence of the 18S ribosomal RNA gene, 2014 bp in length, was closest to that of morphologically distinct Chloromyxum ellipticum, infecting the gall bladder of grass carp (Ctenopharyngodon idella) in China with 96.99% (1673/1725) identity and three insertion/deletion (indel) sites, followed by Chloromyxum legeri, infecting the gall bladder of common carp (Cyprinus carpio) in the Czech Republic with 89.97% (1803/2004) identity and 14 indel sites. Other myxosporean species, including Chloromyxum spp. from the gall bladder or urinary system of freshwater and marine fish, were phylogenetically distant from the present species.


Do Renshaw cells tell spinal neurones how to interpret muscle spindle signals?
In vertebrates many alpha motoneurone pools are subjected both to recurrent inhibition via Renshaw cells and to proprioceptive feedback via muscle fibres and proprioceptors, particularly spindles. In these cases, the two feedback loops have a common input (alpha motoneurone output) and a common target (alpha motoneurones). This implies that the target alpha motoneurones receive a compound information dispatched by the source alpha motoneurones, but processed in different ways via the two feedback paths. Since the Renshaw cells monitor the input to skeletal muscle, and the spindles (and Golgi tendon organs) monitor certain aspects of muscle output, both feedback paths in conjunction contain information about the mechanical state of skeletal muscle. Based on these interrelationships the following hypothesis is discussed. At a micro-level, muscle spindles might provide information about motor unit contractions to the homonymous alpha motoneurones. This information is filtered and enhanced by recurrent inhibition via Renshaw cells. This is effected by correlation of the signals which are propagated through the two feedback loops after having been initiated by firing of the same alpha motoneurone(s). The effects of the correlation can be strengthened by (a) topographical order in the feedback connections, (b) heterosynaptic modulation, and (c) tendencies towards synchronous discharge between motoneurones. The information about the unfused contractions of a muscle unit (or a small group of them), thus retrieved from the barrage of signals delivered by proprioceptive afferents, could then play a role in shaping the precise discharge pattern of the innervating motoneurone. This in turn may be of importance for mechanisms of optimal force production during muscle fatigue.


Evaluation of the BD Phoenix automated identification and susceptibility testing system in clinical microbiology laboratory practice.
The Phoenix Automated Microbiology System (BD Biosciences, USA) is a new, fully automated system for the rapid identification and antimicrobial susceptibility testing of gram-positive and gram-negative bacteria. The objective of this study was to evaluate the quality of performance of the Phoenix system in the identification and antimicrobial susceptibility testing of 260 gram-negative ( n=174) and gram-positive ( n=86) isolates collected from Polish hospitals in recent years. Two Phoenix panel types for identification/antimicrobial susceptibility testing, NMIC/ID-5 for gram-negative rods and PMIC/ID-4 for gram-positive cocci, were used in the analysis according to the manufacturer's recommendations. The results produced by the system were compared with data obtained by reference or conventional microbiological methods. A high rate of agreement between the Phoenix and the conventional methods was observed for identification, ranging from 100% for gram-positive cocci to 96.0% for gram-negative nonfermenters and 92.5% for members of the family Enterobacteriaceae. Similarly, a high level of agreement characterized the antimicrobial susceptibility data obtained with the Phoenix and by the agar dilution method (2,361 test results). For staphylococci, enterococci and Enterobacteriaceae, the methods were 100% concordant in determining the category of susceptibility of isolates to the majority of the antimicrobial agents tested. A category agreement value of below 90% was found for the susceptibility of enterococci and gram-negative nonfermenters to ciprofloxacin (84.6% and 88.5%, respectively) and for susceptibility of Stenotrophomonas maltophilia to trimethoprim-sulfamethoxazole (80.0%).


Phycoremediation integrated approach for the removal of pharmaceuticals and personal care products from wastewater - A review.
Pharmaceuticals and personal care products (PPCPs) are of emerging concerns because of their large usage, persistent nature which promised their continuous disposal into the environment, as these pollutants are stable enough to pass through wastewater treatment plants causing hazardous effects on all the organisms through bioaccumulation, biomagnification, and bioconcentration. The available technologies are not capable of eliminating all the PPCPs along with their degraded products but phycoremediation has the advantage over these technologies by biodegrading the pollutants without developing resistant genes. Even though phycoremediation has many advantages, industries have found difficulty in adapting this technology as a single-stage treatment process. To overcome these drawbacks recent research studies have focused on developing technology that integrated phycoremediation with the commonly employed treatment processes that are in operation for treating the PPCPs effectively. This review paper focuses on such research approaches that focused on integrating phycoremediation with other technologies such as activated sludge process (ASP), advanced oxidation process (AOP), Up-flow anaerobic sludge blanket reactor (UASBR), UV irradiation, and constructed wetland (CW) with the advantages and limitations of each integration processes. Furthermore, augmenting phycoremediation by co-metabolic mechanism with the addition of sodium chloride, sodium acetate, and glucose for the removal of PPCPs has been highlighted in this review paper.


Identification of genes associated with complex traits by testing the genetic dissimilarity between individuals.
Using the exome sequencing data from 697 unrelated individuals and their simulated disease phenotypes from Genetic Analysis Workshop 17, we develop and apply a gene-based method to identify the relationship between a gene with multiple rare genetic variants and a phenotype. The method is based on the Mantel test, which assesses the correlation between two distance matrices using a permutation procedure. Using up to 100,000 permutations to estimate the statistical significance in 200 replicate data sets, we found that the method had 5.1% type I error at an α level of 0.05 and had various power to detect genes with simulated genetic associations. FLT1 and KDR had the most significant correlations with Q1 and were replicated 170 and 24 times, respectively, in 200 simulated data sets using a Bonferroni corrected p-value of 0.05 as a threshold. These results suggest that the distance correlation method can be used to identify genotype-phenotype association when multiple rare genetic variants in a gene are involved.


LTBP-1 blockade in dioxin receptor-null mouse embryo fibroblasts decreases TGF-beta activity: Role of extracellular proteases plasmin and elastase.
In mouse embryonic fibroblasts (MEF) lacking dioxin receptor (AhR), high levels of latent transforming growth factor-beta (TGF-beta)-binding protein-1 (LTBP-1) correlated with increased TGF-beta1 activity, an observation suggesting that LTBP-1 could contribute to maintain TGF-beta1 levels. Here, using small interfering RNAs (siRNA), we have first analyzed if LTBP-1 expression affected TGF-beta1 activity in MEF cells. We have then determined how LTBP-1 levels could alter the activity of extracellular proteases known to activate TGF-beta1, and finally, whether protease inhibition could reduce TGF-beta1 activation. LTBP-1 inhibition by siRNA in AhR-/- MEF decreased the amount of active TGF-beta1 and reduced plasminogen activators (PA)/plasmin and elastase activities and thrombospondin-1 (TSP-1) expression, without significantly affecting their mRNA levels. On the contrary, LTBP-1 siRNA restored matrix metalloproteinase-2 (MMP-2) activity in AhR-/- MEF. Interestingly, whereas a TGF-beta1 neutralizing antibody mimicked many of the LTBP-1 siRNA effects on extracellular proteases, addition of recombinant TGF-beta1 protein increased proteases activity over basal levels in AhR-/- MEF. These proteases contributed to TGF-beta activation since their specific inhibitors reduced active TGF-beta levels in these cells. These results suggest that LTBP-1 contributes to TGF-beta1 activation in MEF, possibly by influencing the activities of PA/plasmin, elastase, TSP-1, and MMP-2. TGF-beta1, on the other hand, could be also involved in maintaining the activity of these extracellular proteases. Thus, LTBP-1 appears to play a role in TGF-beta1 activation through a process involving extracellular protease activities, which, in turn, could be affected by TGF-beta1 levels.


Toxicity of two toxins from the Florida red tide marine dinoflagellate, Ptychodiscus brevis.
The purification and crystallization of T17, a toxin from Ptychodiscus brevis, is reported. The toxicity of this compound and a second toxin known as T34 are compared by i.v., i.p. and oral administration in mice. Both toxins produce symptoms characteristic of muscarnic stimulants; hypersalivation, rhinorrhea and excessive urination and defecation being the most commonly observed. T17, which is orally toxic, is believed to be the agent responsible for Neurotoxic Shellfish Poisoning.


A piece in the puzzle: an ion channel candidate gene for schizophrenia.
Mutations in ion channels have been found to cause a variety of mendelian genetic diseases, and polyglutamine repeat expansion is a newly recognized pathogenic mechanism that causes several rare, genetic, late-onset neurological syndromes. Polymorphic polyglutamine tracts are present in a recently described human, calcium-activated potassium channel, KCNN3 (also known as hKCa3), and alleles of this gene that contain longer repeats have been associated with schizophrenia. The physiological function of the channel is consistent with an etiological role in this disease; drugs designed to target this channel might therefore provide novel psychotherapeutics.


Nurse-led intervention improves adherence to HIV medication.
A nurse-led self-management programme for people with HIV can significantly improve adherence to medication for the condition.


Sulfur ligation in copper enzymes and models.
Biological copper-sulfur entities display versatile and unusual coordination chemistry. The role of the sulfur ligation is briefly reviewed through examples from selected copper enzymes and relevant biomimetic models. Copper thiolate complexes are of particular interest because of their key roles in a number of ubiquitous metalloenzymes such as Type I (blue copper proteins) or in the binuclear Cu(A) electrons transfer site found in both cytochrome c oxidase (CcO) and nitrous oxide reductase (N2OR). The possible roles of the S(Met) ligand in monoxygenases are described in relation to recently proposed pathways. Some prospective regarding the biological relevance of disulfide copper ligation and possible radical copper bonds in catalytic cycle are also discussed.


Multi-omics-based characterization of the influences of Mycobacterium tuberculosis virulence factors EsxB and PPE68 on host cells.
Mycobacterium tuberculosis, the ancient master of causing tuberculosis, is one of the most successful pathogens capable of persistently colonizing host lungs. The EsxB (CFP-10) of ESX-1 system and PPE68 of the PPE family contribute to the virulence of M. tuberculosis. However, the virulence potential and pathogenetic characteristics of these two proteins during M. tuberculosis infection remain unclear. In this study, two prokaryotic expression plasmids for EsxB or PPE68 of M. tuberculosis were constructed and the recombinant proteins His-EsxB or His-PPE68 were purified. The proteome and transcriptome of MH-S cells treated with His-EsxB or His-PPE68 were explored, followed by validating the expression of the identified differentially expressed genes (DEGs) using quantitative PCR. A total of 159/439 specific proteins or 633/1117 DEGs were obtained between control and His-EsxB or His-PPE68 treated groups in the MH-S proteomes and transcriptomes. Additionally, 37/60 signal pathways were predicted in the His-EsxB or His-PPE68 treated groups and "Cytokine-cytokine receptor interaction" was the most represented pathway. Furthermore, the expression of the DEGs (IL-1β, IL-6, and TNF-α) was significantly upregulated, suggesting that these DEGs contributed to the host response during EsxB or PPE68 treatment. These findings provide detailed information on developing an effective intervention strategy to control M. tuberculosis infection.


Analysis of outgrowth of Bacillus subtilis spores lacking penicillin-binding protein 2a.
The loss of Bacillus subtilis penicillin-binding protein (PBP) 2a, encoded by pbpA, was previously shown to slow spore outgrowth and result in an increased diameter of the outgrowing spore. Further analyses to define the defect in pbpA spore outgrowth have shown that (i) outgrowing pbpA spores exhibited only a slight defect in the rate of peptidoglycan (PG) synthesis compared to wild-type spores, but PG turnover was significantly slowed during outgrowth of pbpA spores; (ii) there was no difference in the location of PG synthesis in outgrowing wild-type and pbpA spores once cell elongation had been initiated; (iii) outgrowth and elongation of pbpA spores were dramatically affected by the levels of monovalent or divalent cations in the medium; (iv) there was a partial redundancy of function between PBP2a and PBP1 or -4 during spore outgrowth; and (v) there was no difference in the structure of PG from outgrowing wild-type spores or spores lacking PBP2a or PBP2a and -4; but also (vi) PG from outgrowing spores lacking PBP1 and -2a had transiently decreased cross-linking compared to PG from outgrowing wild-type spores, possibly due to the loss of transpeptidase activity.


Fate of ingested hepatitis B antigen in blood-sucking insects.
The fate of ingested hepatitis B antigen (HBsAg) in two mosquito species and two Hemiptera species was compared with the rate of blood meal digestion by these insects. In both mosquito species HBsAg was detected by radioimmunoassay for only a few hours after ingestion, disappearing well before the time of blood meal digestion. Production of a protease by the mosquito midgut may have been responsible for destruction of the antigen. In contrast, in the bedbug HBsAg remained detectable throughout a 5-week testing period. Moreover, titers rose during the last week, when blood meal digestion was complete, suggesting possible replication of the antigen. At no time was antigen detected in eggs or feces of any species tested, but juvenile bedbugs fed HBsAg when in the fourth or fifth instar stage still contained antigen after molting. These studies suggest that bedbugs may potentially be a more dangerous source of hepatitis B transmission than mosquitoes.


Organ and subcellular distribution of cadmium in rats exposed to cadmium, mercury, and selenium.
Four groups of rats were given: cadmium chloride (Cd), cadmium chloride and mercuric chloride (Cd + Hg), cadmium chloride and sodium selenite (Cd + Se), or cadmium chloride, mercuric chloride, and sodium selenite (Cd + Hg + Se). All animals received subcutaneous doses of 115mCdCl2 (0.3 mg Cd/kg) every other day for 2 weeks. Mercuric chloride was administered intravenously at doses of 0.5 mg Hg/kg every other day, and Na2 75SeO3 intragastrically at doses of 0.1 mg Se/kg every day for a fortnight. The whole-body and organ retention of cadmium changed slightly with the type of exposure. A significant interaction effect of the examined elements was noted in the nuclear and soluble fractions of the liver and kidneys. Mercury decreased the cadmium concentration in both the nuclear and soluble fractions of the kidneys and diminished the effect of selenium on the cadmium level in the soluble fraction of the kidneys. In the liver the presence of mercury contrary to selenium, lowered the cadmium level in the nuclear fraction. The pattern of cadmium binding to proteins of the soluble fraction of the kidneys and liver remained the same in all groups of animals.


[Toxological problems inherent in varnish and paint products used in aeronautics].
Paint products and the need for their employment on aircraft and spacecraft are described and reference is made to the types of poisoning that may arise from their application. The main solvents and diluents are listed, together with their toxicological features. Lastly, mention is made of technical products required by the aeronautical regulations, the dangers associated with them, and the preventive measures required.


Influence of cholesterol depletion in plasma membrane of rat brain synaptosomes on calcium-dependent and calcium-independent exocytosis.
It is well established that calcium-dependent neurotransmitter release and exocytosis can be regulated by altering the cholesterol content of the plasma membrane. We have compared the influence of cholesterol depletion of synaptosomal plasma membrane by 15 mM methyl-beta-cyclodextrin (MCD) treatment on calcium-dependent release of D-[(3)H]aspartate induced by the calcium ionophore A23187 and on calcium-independent release induced by hypertonic shrinking or polyvalent cations. We found that decrease of cholesterol concentration by 9.3% inhibited calcium-dependent release of d-[(3)H]aspartate induced by calcium ionophore A23187 by four times while release induced by 300 microM Gd(3+), 150 mM and 500 mM sucrose remained unchanged. Further we have investigated the influence of MCD on exocytosis monitored by the fluorescent dye, acridine orange. Cholesterol depletion inhibited calcium-dependent exocytosis induced by calcium ionophore A23187 but had virtually no influence on calcium-independent exocytosis induced by hypertonic shrinking or Gd(3+). In summary, we found that the cholesterol content in synaptosomal plasma membrane is important for calcium-dependent exocytosis.


Heat stability, its measurement, and its lack of utility in the assessment of the potential allergenicity of novel proteins.
Thermal stability has been reported as a shared characteristic among some of the major food allergens and appears to have originated from the observation that some cooked foods retain their ability to cause allergic reactions by Immunoglobulin E (IgE) binding and the subsequent cascade of events that mediate allergic reactions. Based on this observation, the thermal stability of novel food proteins, like those in transgenic crops, is considered correlative with allergenic risk and has prompted requests from some regulatory agencies for additional testing to address safety concerns. Because human testing and serum IgE screening are not feasible nor are they necessarily useful for evaluating the thermal stability of a novel food protein, a protein function assay is often used to assess the thermal stability in the context of an allergenicity risk assessment. Some regulatory authorities also require immunodetection using polyclonal IgG antibodies and gel based methods. Here we review why heat stability as measured by these functional and immunodetection assays does not correlate with allergenicity and provides no useful safety information in assessing the allergenic potential of novel food proteins.


Plasma metals and cancer incidence in patients with type 2 diabetes.
There is limited evidence on the relationships between plasma levels of multiple metals and risk of incident cancer in patients with type 2 diabetes mellitus (T2DM). We examined the associations between plasma levels of 12 metals (iron, copper, zinc, selenium, chromium, manganese, molybdenum, cobalt, nickel, arsenic, cadmium, and lead) and cancer risk in 4573 T2DM patients using Cox proportional hazards models. With a median follow-up of 10.2 years, 541 incident cancers were identified. The multiple-metals model revealed that each 1-SD increase in ln-transformed plasma copper (HR: 1.14; 95%CI: 1.02, 1.27) and lead (HR:1.20; 95%CI:1.03, 1.39) were significantly associated with increased cancer incidence while each 1-SD increase in ln-transformed plasma zinc (HR: 0.82; 95%CI: 0.71, 0.96) and chromium (HR: 0.88; 95%CI: 0.82, 0.94) were significantly associated with decreased cancer incidence. When all participants were further stratified into four subgroups by the quartile levels (Q1-4) of plasma metals, manganese showed significant positive associations with cancer incidence in the upper two quartiles (P trend = 0.003) while nickel showed significant negative associations with cancer incidence in Q2 and 4 groups (P trend = 0.033) compared with participants in Q1 group. Collectively, monitoring of metal levels in diabetic patients needs to be strengthened, which is of great significance for the prevention of incident cancer.


[New aspects of congenital melanocytic nevi].
In recent years, prospective studies with increasing patient numbers have been published on the subject of congenital melanocytic nevi (CMN) and neurocutaneous melanocytosis (NCM). Moreover, medical experts and patient support groups have intensified their collaboration. This article summarizes current aspects of pathogenesis, clinical features, and therapy of CMN and NCM.


Selective intra-arterial cytotostatic injections in malignant head and neck tumors.
Regional intra-arterial drug administration has been advocated in order to reduce the risks of systemic complications in conjunction with systemic tumor chemotherapy. We have been using superselective angiographic techniques to administer the antitumor drug mitomycin C directly into the feeding arteries of the tumor in 15 patients with advanced malignant head and neck tumors. No complications were observed. In five patients the tumor decreased significantly in size, in four patients, tumor cell necrosis was found. A marked decrease in pain was reported by nine of the 15 patients.


Characterization of multiple nestin isoforms in the goldfish brain.
Nestin is an intermediate filament protein involved in neurogenesis in fish, mice, and humans. In this study we used rapid amplification of cDNA ends PCR to isolate goldfish nestin (nes). PCR analysis and sequencing revealed three different nes transcripts of 4003, 2446, and 2126 nucleotides, which are predicted to generate proteins of 860, 274, and 344 amino acids in length. Sequence analysis suggests that these nes transcripts are likely a result of alternative splicing. We next applied a multiple-antigenic peptide strategy to generate a goldfish-specific nestin antibody. Western blotting with this antibody together with mass spectrometry verified the presence of major nestin protein isoforms with differing molecular weights (~70, 40 and 30kDa). We further examined expression patterns of these nestin protein isoforms in different parts of the goldfish brain and pituitary and found the telencephalon to express all three isoforms at a distinct level and abundance. We report that multiple nestin isoforms are present indicating another level of complexity for the regulation of intermediate filaments in comparison to mammals. Studying the differential roles and regulation of these nestins could lead to a better understanding of cellular remodeling during neurogenesis and the unparalleled regenerative abilities after damage in the teleost CNS.


Silencing of Jagged1 inhibits cell growth and invasion in colorectal cancer.
Dysregulated Notch signaling has a critical role in the tumorigenesis. Jagged1, a Notch ligand, is overexpressed in various human cancers. Recent studies revealed the involvement of Jagged1 in colorectal cancer (CRC) development. These basic studies provide a promising potential for inhibition of the Notch pathway for the treatment of CRC. Herein, we aimed to investigate the consequences of targeting Jagged1 using shRNA on CRC both in vitro and in vivo to test their potential to inhibit this key element for CRC treatment. We found that downregulation of Jagged1 with lentiviral Jagged1-shRNA resulted in decreased colon cancer cell viability in vitro, most likely mediated through reduced cell proliferation. Importantly, Jagged1 knockdown induced G0/G1 phase cell cycle arrest, with reduced Cyclin D1, Cyclin E and c-Myc expression. Silencing of Jagged1 reduced the migration and invasive capacity of the colon cancer cells in vitro. Furthermore, colon cancer cells with knockdown of Jagged1 had much slower growth rate than control cells in a xenograft mouse model in vivo, with a marked downregulation of cell proliferation markers (PCNA, Ki-67, and c-Myc) and metastasis markers (MMP-2 and MMP-9). These findings rationalize a mechanistic approach to CRC treatment based on Jagged1-targeted therapeutic development.


The characteristics of post-neurosurgical bacterial meningitis in elective neurosurgery in 2012: A single institute study.
Most post-neurosurgical meningitis research has been focused on large cohorts with numerous cases followed over several years. However, the characteristics of post-neurosurgical meningitis in an entire single year are still unclear, and knowledge of these characteristics might influence the selection of appropriate antibiotics and therapeutic strategies for the successful management of this disease. Our aim is to obtain a better understanding of post-neurosurgical meningitis over a single entire year. Patients with positive meningitis cultures after neurosurgical operations in our hospital during the entire year of 2012 were included in the analysis. We report demographic characteristics, morbidity during different seasons, clinical and bacteriological profiles, sensitivity to antibiotics and causes of the post-neurosurgical meningitis infections in our cohort. Of the 6407 patients who underwent neurosurgical procedures during the study period, 146 developed post-neurosurgical meningitis and the overall incidence of meningitis was 2.28%. The incidence of meningitis was significantly higher in patients who underwent surgery in the autumn and winter than spring or summer (p=0.000). The most common organisms causing meningitis were Gram-positive bacteria, followed by the Klebsiella and Baumannii species. Compound sulfamethoxazole (52.6%) and vancomycin (10.5%) were the most active antibiotics against Gram-positive bacteria strains, whereas meropenem (43.8%) and polymyxin (18.8%) were active against Gram-negative bacillus strains. Post-neurosurgical meningitis usually occurs in the autumn and winter of the year in our hospital. Gram-positive organisms, which are sensitive to compound sulfamethoxazole and vancomycin, are the most common causative pathogens of post-neurosurgical meningitis in the northern mainland of China.


Cytochrome P450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications.
In recent years the use of the opioid oxycodone has increased markedly and replacing morphine as the first-line choice of opioid in several countries. There are formulations for oral immediate, oral extended release and intravenous use. The bioavailability is higher than for morphine and less variable. Oxycodone is primarily metabolized in the liver by the cytochrome P450 (CYP) enzymes with CYP3A as the major metabolic pathway and CYP2D6 as the minor metabolic pathway to noroxycodone, oxymorphone and noroxymorphone. Oxycodone exerts its analgesic effect via the µ-opioid receptor. The metabolism of CYP2D6 substrates varies to a large degree between individuals as a result of allele functionality. Poor metabolizers (PM) have two non-functional alleles, extensive metabolizers (EM) are homozygous with two functional alleles or heterozygous with one functional allele and ultrarapid metabolizers (UM) have more than two functional alleles. There are pronounced interethnic differences in the allele distribution. On the basis of studies performed thus far, oxycodone concentrations in comparison with EM are similar in PM and reduced in UM. The pharmacokinetics in UM are insufficiently investigated. Simultaneous inhibition of both CYP3A and CYP2D6 results in increased oxycodone concentrations and such a combination should be avoided. A similar effect is to be expected with use of a CYP3A inhibitor in CYP2D6 PM. Concomitant use of enzyme inducers such as rifampicin, St John's wort and carbamazepine should be avoided because of the risk of subtherapeutic concentrations of oxycodone. When the dosage of morphine may result in unpredictable bioavailability, like in patients with severe hepatic cirrhosis, oxycodone might be beneficial because it has higher and less variability in bioavailability between patients than morphine.


Relative RF coil performance in carotid imaging.
Computer simulations and measurements on human volunteers were used to test the extent to which the quality of carotid imaging might be improved by coil arrays that are not limited by a constraint on the number of RF coil receiver ports. Analytic near-field equations for the magnetic and electric fields of a rectangular loop resonator were used to estimate the relative signal-to-noise ratio (rSNR) along the length of a simulated carotid artery as a function of loop size, loop position and vessel depth. The sizes, positions and number of elements in a linear coil array that resulted in the maximum composite SNR along the length of a simulated carotid artery were then estimated. The linear array results were used to predict the total number of elements needed for optimal imaging of the carotid arteries. Also, three normal volunteers were imaged with a variety of RF coils, and the rSNR measurements along the lengths of the carotid artery were evaluated for each coil combination. The analytic simulation and the human volunteer measurements both show that improved SNR (e.g., >300% at the bifurcation) can be obtained with coils tailored to each specific region of the carotid artery in comparison to that obtained with four-element arrays designed and used to image the entire carotid artery. The resulting number of coil ports, 16 to 24, required for full coverage of the carotid arteries is consistent with the number of channels just becoming available on recently developed clinical scanners.


[The influence of ionizing radiation on the development of posterior capsule opacification in vitro].
Histologically, the posterior capsule opacification (PCO) corresponds to regenerative tissue of transformed lens epithelial cells (LECs) with extracellular matrix production. In this study, the influence of ionizing radiation on proliferating LECs and the development of PCO was investigated in vitro. Each four and 14 pork lenses, respectively, were irradiated with 6 MeV electrons with single doses of 8, 10, 12, and 20 Gy. 1-2 h after irradiation the lens was removed by capsulorrhexis and hydrodissection. After fixation of the capsular bag in a special device the proliferation of residual LECs was examined daily. The experiment was considered to be finished when the capsular bag was completely opacified by confluent cell proliferates. Single dose irradiation with electrons in a dose range from 8 to 12 Gy significantly protracted the development of PCO with complete inhibition of PCO after application of 20 Gy. To inhibit PCO in vitro, a single dose of 20 Gy is necessary. The actual in vitro model allows an optimal investigation of PCO formation under different external influences and is therefore very suitable for radiobiological questions.


Characterization of biodegradable poly(D,L-lactide-co-glycolide) polymers and microspheres.
Characterization of biodegradable polymers used for controlled drug delivery is essential to ensure reproducibility of in vitro and in vivo performance. Selected characterization techniques established for poly(D,L-lactide-co-glycolide) (PLGA) copolymers included DSC to analyse thermal behavior, 13C-NMR to determine exact comonomer ratios and comonomer sequencing, cloud point titration to establish solubility, SEC to monitor molecular weight averages and polydispersity, SEM to observe surface morphology, BET gas adsorption to analyse surface area, tapped bulk density measurements to suggest internal pore structure and porosity and finally in vitro degradation to analyse degradation times and profiles. Comonomer ratios of 50:50 PLGAs were found to be closer to stated values for Boehringer Ingelheim polymers than for polymers from two other suppliers. Implementing such a characterization program for biodegradable polymers ensures the production of reproducible and reliable controlled drug delivery systems.


A time-stratified case-crossover study of fine particulate matter air pollution and mortality in Guangzhou, China.
Few studies in China investigate health impact of fine particulate matter (PM(2.5)) due to lack of monitoring data and the findings are controversial. The aim of this study is to examine the short-association between PM(2.5) and daily mortality in Guangzhou, the economic center of south China. In Guangzhou, we measured daily PM(2.5) concentrations between 2007 and 2008 and conducted a time-stratified case-crossover analysis to explore the association between PM(2.5) and daily mortality, and examine potential effect modifiers including age, sex, and education. The averaged PM(2.5) concentration in 2007-2008 was 70.1 μg/m(3) in Guangzhou, which was approximately seven times higher than the WHO Air Quality Guidelines for PM(2.5) (annual average: 10 μg/m(3)). Regression analysis showed that ambient PM(2.5) was associated with mortality from all causes and cardiorespiratory diseases. An increase of 10 μg/m(3) in 2-day moving average (lag01) concentration of PM(2.5) corresponds to 0.90% [95% confidence interval (CI): 0.55, 1.26%] increase of total mortality, 1.22% (95% CI: 0.63, 1.68%) increase of cardiovascular mortality, and 0.97% (95% CI: 0.16, 1.79%) increase of respiratory mortality. The associations were stronger in the elderly (aged 65 years or more), in females, and in those with low education level, but the differences were statistically insignificant. After adjustment for nitrogen dioxide (NO(2)), however, the effects of PM(2.5) decreased and became statistically insignificant. Our findings provided new information for the adverse health effects of PM(2.5) in China, and may have some implications for environmental policy making and standard setting in Guangzhou.


Power calculations for detecting differences in efficacy of fecal microbiota donors.
Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of other indications, notably inflammatory bowel disease. The immense variability in human stool, combined with anecdotal reports from FMT studies, have suggested the existence of "donor effects", in which stool from some FMT donors is more efficacious than stool from other donors. In this study, simulated clinical trials were used to estimate the number of patients that would be required to detect donor effects under a variety of study designs. In most cases, reliable detection of donor effects required more than 100 patients treated with FMT. These results suggest that previous reports of donor effects need to be verified with results from large clinical trials and that patient biomarkers may be the most promising route to robustly identifying donor effects.


Apoptotic DC-SIGN+ cells in normal human decidua.
Normal pregnancy and spontaneous abortion in humans and mice are associated with immune responses. The decidua harbors dendritic cells identifiable in humans by their expression of DC-SIGN. Because dendritic cells are essential for immune response regulation, decidual DC-SIGN+ cells may play a role in normal or pathological pregnancy outcomes. Previous reports suggested that DC interact with NK cells in decidua, although the functional significance of this phenomenon remains unknown. We studied the presence of conjugates of DC-SIGN+ cells with CD56+ NK cells in normal human decidua. Conjugates of DC-SIGN+ cells with CD56+ NK cells were studied in leukocyte suspensions of normal human decidua (6-11 weeks) by flow cytometry and confocal microscopy. The presence of apoptotic cells was determined by the TUNEL assay, incubation with annexin V and confocal microscopy in decidual leukocyte suspensions and by the TUNEL assay in decidual sections. We observed conjugates of decidual DC-SIGN+ cells with CD56+ NK cells (40.2±26.1% of all the DC-SIGN+ cells by flow cytometry and 52.3±10.2% by confocal microscopy). We also found that a proportion of DC-SIGN+ cells were in apoptosis, since they were TUNEL+ (40.2±7.2% of all DC-SIGN+ cells in decidual sections) and annexin V+ (34.4±15.2% in leukocyte suspensions). And sorted DC-SIGN+ cells had multilobulated nuclei. The conjugates of decidual DC-SIGN+ cells with CD56+ NK cells strongly suggest that these latter cells induce apoptosis in DC-SIGN+ cells during normal pregnancy. We discuss this possibility in the context of maternal-fetal tolerance.