[Early diagnosis of intra-uterine growth restriction by ultrasonographic estimation of fetal weight].
Aiming to reduce the perinatal and late morbidity and lethality through opportune prenatal intervention, this study proposed to sequentially evaluate the echographic fetal weight at the 25th and 27th weeks of gestation, establishing cut-off values for echographic fetal weight useful in the diagnosis of small-for-gestational-age at this gestation time, and developing a mathematical model able to recognize the probability of a newborn small-for- gestational-age. Eighty-five newborns were evaluated, 35 small and 50 adequate for gestational age. The mothers who underwent prenatal care at our Institution were healthy or presented chronic arterial hypertension as the only disease, no history of addictions, gemellarity or malformed fetuses. All mothers performed ultrasonographic exams at the 25th and 27th weeks for estimation of the fetal weight. The exams were able to detect the inadequate development of those fetuses small-for-gestational-age group. The cut-off values for echographic fetal weight were established as 775 grams and 1015 grams for the 25th and 27th weeks, respectively. A mathematical model was developed, capable of quantifying the probability of newborns exhibiting insufficient intra-uterine growth, being small-for-gestational-age.


Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography.
We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS). Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category. 49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS-comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged <30 years vs >80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001). New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance.


The role of AMPK in macrophage metabolism, function and polarisation.
AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays a key role in regulating cellular energy homeostasis and multiple aspects of cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming of macrophages, but also counter-regulates the inflammatory function of macrophages and promotes their polarisation toward the anti-inflammatory phenotype. AMPK is located at the intersection of macrophage metabolism and inflammation. The metabolic characteristics of macrophages are closely related to immune-related diseases, infectious diseases, cancer progression and immunotherapy. This review discusses the structure of AMPK and its role in the metabolism, function and polarisation of macrophages. In addition, it summarises the important role of the AMPK pathway and AMPK activators in the development of macrophage-related diseases.


Mutagenicity: QSAR - quasi-QSAR - nano-QSAR.
Mutagenic potential of biphenyl-4-amines and multi-walled carbon nanotubes (MWCNTs) have been modeled by optimal descriptors. The optimal descriptors are calculated with the Monte Carlo method by means of the CORAL software (http://www.insilico.eu/coral). The optimal descriptor is a translator of eclectic data into prediction of various endpoints in general and into the prediction of the mutagenic potential (TA100) in particular. So-called, quasi-SMILES are suggested as representation of various circumstances which can influence the endpoint. The correlation weights of various circumstances are the basis of the approach. The statistical characteristics of models for the mutagenic potential (decimal logarithm of TA100) for the external invisible validation sets are the following (i) in the case of biphenyl-4- amines: n=7-11; r(2)=0.649±0.046; s=0.211±0.029; and (ii) in the case of MWCNTs: n=6, r(2)=0.804±0.107; s=0.048±0.01.


Normal foot loading parameters and repeatability of the Footscan® platform system.
The Footscan® platform system is one of the most commonly used clinical tools for the measurement of the foot pressure. The present study was designed to assess the repeatability of the system and identify the range of loading parameters observed in the normal foot. Measurements were collected from 32 healthy participants, 15 females and 17 males, twice at an interval of 1 week. Peak pressure (PP), contact time (CT), contact area (CA), pressure-time integral (PTI), and maximum force (MaF) were recorded; these parameters were investigated in 10 areas of the foot: medial heel, lateral heel, midfoot, first to fifth metatarsals, hallux, and toes 2-5. The intra-session repeatability was evaluated by calculating the intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) across the three repeated trials within the same session. The inter-session repeatability was assessed using the average of the three trials in each session to determine the ICCs and CVs. The ICCs showed moderate to good repeatability for every variable of interest, and the CVs were all <28%. The highest zones of PP were found under the second and third metatarsals, followed by the medial heel. The CT was 68.5-82.8% of the total stance time under the metatarsal heads. CA was highest under the midfoot, PTI was highest under the second metatarsal, and MaF was highest under the medial heel. Footscan® platform system was found to be repeatable. Thus, it can be used as a valuable tool in the assessment of plantar pressure distribution, and the normal values of the foot loading parameters identified in this study can be employed to provide a reference range for the gait analysis performed by the Footscan® system.


Land-use effects on mosquito biodiversity and potential arbovirus emergence in the Southern Amazon, Brazil.
The Amazon rainforest is considered the largest reservoir of culicids and arboviruses in the world. It has been under intense human-driven alteration, especially in the so-called 'Arc of Deforestation', located in the eastern and southern regions. The emergence and transmission of infectious diseases are increasing, potentially due to land-use change. We used landscape-scale mosquito surveillance across a forest fragmentation gradient in the southern Amazon to evaluate the relationship between forest disturbance and the composition and structure of mosquito communities with a particular focus on the potential for arbovirus emergence in the region. Generalized linear models and logistic regression were used to associate the degree of landscape disturbance with arbovirus vectors' richness and abundance. A total of 1,960 culicids, belonging to 50 species, were collected from 2015 to 2016. Among these species, 20 have been associated with the transmission of arboviruses. Our results show an association of land use, more specifically small size of forest remnants with more irregular shape and higher edge density, with the increase of arbovirus vectors' richness and abundance. Six species of mosquito vectors exhibited a higher probability of occurrence in landscapes with medium or high degrees of disturbance. Our results indicate that land-use change influences mosquito communities with potential implications for the emergence of arboviruses.


Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel.
NaV1.7 is a voltage-gated sodium ion channel implicated by human genetic evidence as a therapeutic target for the treatment of pain. Screening fractionated venom from the tarantula Grammostola porteri led to the identification of a 34-residue peptide, termed GpTx-1, with potent activity on NaV1.7 (IC50 = 10 nM) and promising selectivity against key NaV subtypes (20× and 1000× over NaV1.4 and NaV1.5, respectively). NMR structural analysis of the chemically synthesized three disulfide peptide was consistent with an inhibitory cystine knot motif. Alanine scanning of GpTx-1 revealed that residues Trp(29), Lys(31), and Phe(34) near the C-terminus are critical for potent NaV1.7 antagonist activity. Substitution of Ala for Phe at position 5 conferred 300-fold selectivity against NaV1.4. A structure-guided campaign afforded additive improvements in potency and NaV subtype selectivity, culminating in the design of [Ala5,Phe6,Leu26,Arg28]GpTx-1 with a NaV1.7 IC50 value of 1.6 nM and >1000× selectivity against NaV1.4 and NaV1.5.


Injuries among children in home and out-of-home care.
As the number of children receiving care in out-of-home settings increases in the United States, the risk of injury in such settings has become the subject of intense research. This study examined the relative safety of out-of-home care compared with care in a child's own home. This community based prospective cohort study of 656 families in three adjacent counties in the Piedmont region of North Carolina characterizes the patterns and rates of injuries among children less than 5 years of age in three child care settings, home care (HC), center based care (CBC), and other out-of-home care (OOHC). Information about minor and severe injuries was obtained from parents using monthly telephone interviews over a one year period. Statistical modeling designed to handle unbalanced data with correlated observations was used as the primary tool for analysis. Rate of minor injuries was highest in CBC, followed by HC, and then OOHC. However, these differences for OOHC may have been due to reporting biases and errors in rate estimates. There were no significant differences in severe injury rates among the three settings. The risk of serious injury among children under 5 in CBC is not different from that of children in HC or OOHC despite the fact that the risk of minor injury is higher.


Acute exacerbations of progressive-fibrosing interstitial lung diseases.
Acute exacerbation of interstitial lung disease (ILD) is associated with a poor prognosis and high mortality. Numerous studies have documented acute exacerbation in idiopathic pulmonary fibrosis (IPF), but less is known about these events in other ILDs that may present a progressive-fibrosing phenotype. We propose defining acute exacerbation as an acute, clinically significant respiratory deterioration, typically less than 1 month in duration, together with computerised tomography imaging showing new bilateral glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILDs. Drawing on observations in IPF, it is suspected that epithelial injury or proliferation and autoimmunity are risk factors for acute exacerbation in ILDs that may present a progressive-fibrosing phenotype, but further studies are required. Current acute exacerbation management strategies are based on recommendations in IPF, but no randomised controlled trials of acute exacerbation management have been performed. Although there are no formal strategies to prevent the development of acute exacerbation, possible approaches include antifibrotic drugs (such as nintedanib and pirfenidone), and minimising exposure to infection, airborne irritants and pollutants. This review discusses the current knowledge of acute exacerbation of ILDs that may present a progressive-fibrosing phenotype and acknowledges limitations of the data available.


Cell growth inhibition by all-trans retinoic acid in SKBR-3 breast cancer cells: involvement of protein kinase Calpha and extracellular signal-regulated kinase mitogen-activated protein kinase.
All-trans retinoic acid (ATRA), a synthetic derivative of vitamin A, inhibits the growth of breast cancer cells. To elucidate the mechanism by which ATRA causes cell growth inhibition, we examined changes in cell cycle and intracellular signaling pathways, focusing on protein kinase C (PKC) and mitogen-activated protein kinase (MAPK). Using the estrogen receptor-negative, retinoid receptor-positive breast cancer cell line SKRB-3, we found that treatment with ATRA significantly decreased the expression of PKCalpha, as well as reducing ERK MAPK phosphorylation. ATRA treatment leads to dephosphorylation of Rb, and consequently to G(1) arrest. Marked changes in the expression of cyclins (particularly cyclins A and E) were observed in SKBR-3 cells treated with ATRA. Using a series of pharmacological and molecular approaches, we found evidence that ATRA-induced SKBR-3 cell growth inhibition involves the deregulation of the PKCalpha-MAPK pathway. These data suggest that retinoids interfered with signal transduction pathways that are crucial for cell cycle progression, and highlight the complexities of the biological effects of retinoid derivatives.


Intermolecular potential calculations for polynuclear aromatic hydrocarbon clusters.
Calculations of intermolecular potentials are presented for homo-molecular and hetero-molecular clusters of 24 peri-condensed PAH spanning monomer masses ranging from 78 to 1830 Da. Binding energies of homo-molecular dimers rise rapidly with molecular size and asymptotically approach the experimentally established exfoliation energy for graphite of 5.0 kJ mol(-1) (carbon atom)(-1). Binding energies of hetero-molecular dimers correlate well with the reduced mass of the pair. From calculations of homo-molecular stacks, binding energies were observed to increase with each added molecule and rise asymptotically, approaching a limit which scales linearly with monomer molecular mass. These results are reviewed in the context of molecular growth in flames and in the context of astrophysical observations.


Lactic acidosis update for critical care clinicians.
Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid overproduction or underutilization. The quantitative dimensions of these two mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic acid, also termed type A lactic acidosis, occurs when the body must regenerate ATP without oxygen (tissue hypoxia). Circulatory, pulmonary, or hemoglobin transfer disorders are commonly responsible. Overproduction of lactate also occurs with cyanide poisoning or certain malignancies. Underutilization involves removal of lactic acid by oxidation or conversion to glucose. Liver disease, inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine) deficiency, and uncoupling of oxidative phosphorylation are the most common causes. The kidneys also contribute to lactate removal. Concerns have been raised regarding the role of metformin in the production of lactic acidosis, on the basis of individual case reports. The risk appears to be considerably less than with phenformin and involves patients with underlying severe renal and cardiac dysfunction. Drugs used to treat lactic acidosis can aggravate the condition. NaHCO(3) increases lactate production. Treatment of type A lactic acidosis is particularly unsatisfactory. NaHCO(3) is of little value. Carbicarb is a mixture of Na(2)CO(3) and NaHCO(3) that buffers similarly to NaHCO(3) but without net generation of CO(2). The results from animal studies are promising; however, clinical trials are sparse. Dichloroacetate stimulates pyruvate dehydrogenase and improves laboratory values, but unfortunately not survival rates, among patients with lactic acidosis. Hemofiltration has been advocated for the treatment of lactic acidosis, on the basis of anecdotal experiences. However, kinetic studies of lactate removal do not suggest that removal can counteract lactate production in any meaningful way. The ideal treatment is to stop acid production by treating the underlying disorder.


Nurr1-Based Therapies for Parkinson's Disease.
Previous studies have documented that orphan nuclear receptor Nurr1 (also known as NR4A2) plays important roles in the midbrain dopamine (DA) neuron development, differentiation, and survival. Furthermore, it has been reported that the defects in Nurr1 are associated with Parkinson's disease (PD). Thus, Nurr1 might be a potential therapeutic target for PD. Emerging evidence from in vitro and in vivo studies has recently demonstrated that Nurr1-activating compounds and Nurr1 gene therapy are able not only to enhance DA neurotransmission but also to protect DA neurons from cell injury induced by environmental toxin or microglia-mediated neuroinflammation. Moreover, modulators that interact with Nurr1 or regulate its function, such as retinoid X receptor, cyclic AMP-responsive element-binding protein, glial cell line-derived neurotrophic factor, and Wnt/β-catenin pathway, have the potential to enhance the effects of Nurr1-based therapies in PD. This review highlights the recent progress in preclinical studies of Nurr1-based therapies and discusses the outlook of this emerging therapy as a promising new generation of PD medication.


Challenges of design, implementation, acceptability, and potential for, biomedical technologies in the Peruvian Amazon.
Biomedical technologies have the potential to be advantageous in remote communities. However, information about barriers faced by users of technology in general and in remote Indigenous communities is scarce. The purpose of this study was to characterize the leading challenges faced by researchers who have used biomedical technologies in the Peruvian Amazon. This exploratory, qualitative study with a phenomenological approach depicts the lived experience of participants who were researchers with experience working with biomedical technologies in the Peruvian Amazon in the past five years. Analysis was based on three core themes: design, implementation, and acceptability. Sub-themes included environment, community, and culture. Of the 24 potential participants identified and contacted, 14 agreed to participate, and 13 met inclusion criteria and completed semi-structured interviews. Results were sent to each participant with the opportunity to provide feedback and partake in a 30-minute validation meeting. Five participants consented to a follow-up meeting to validate the results and provide further understanding. Participants recognized significant challenges, including technologies designed out-of-context, difficulty transporting the technologies through the Amazon, the impact of the physical environment (e.g., humidity, flooding), and limited existing infrastructure, such as electricity and appropriately trained health personnel. Participants also identified cultural factors, including the need to address past experiences with technology and health interventions, understand and appropriately communicate community benefits, and understand the effect of demographics (e.g., age, education) on the acceptance and uptake of technology. Complementary challenges, such as corruption in authority and waste disposal, and recommendations for technological and health interventions such as co-design were also identified. This study proposes that technological and health interventions without efforts to respect local cultures and health priorities, or understand and anticipate contextual challenges, will not meet its goal of improving access to healthcare in remote Amazon communities. Furthermore, the implications of corruption on health services, and improper waste disposal on the environment may lead to more detrimental health inequities.


Major and minor axes of the normal mitral annulus.
A dilated or abnormally shaped mitral annulus is a common cause of mitral valve regurgitation, and may be cured by annuloplastic surgery. Multiplane transesophageal echocardiography (TEE) is the diagnostic technique of choice. Our aim was to evaluate and suggest two-dimensional TEE reference values from a standardized procedure of measuring the mitral annular major and minor axes, and their cyclic changes. The annulus was approximated elliptic in the horizontal plane. The intercommissural (IC, major axis) and anteroposterior (AP, minor axis) distances were measured at end-systole (ES), at maximal valve opening (MO), and at end-diastole (ED) from a mid-esophageal view, in 13 men and eight women with normal echocardiographic findings. Indexed values and reproducibility were calculated. The success rate was 100% at ES, 90% at MO, and 29% at ED. ES distances were largest (p <0.001) and most reproducible (5-5.9%). Body weight, but not height or age, had a significant impact. ES 95% prediction intervals for IC were 27 to 46 mm (16-23 mm/m2) and 22 to 36 mm (13-18 mm/m2) for AP (p <0.001). Corresponding body weight-corrected intervals were 0.39 to 0.59 (IC) and 0.32 to 0.48 (AP) mm/kg. No subject had IC:AP <1.1 together with an AP >0.45 mm/kg. Among measurements made at ES, MO and ED, those at ES provided the most reproducible results, and high-quality images were obtained in normal, non-obese subjects. The distances should be judged in relation to body weight or surface area and each other. The largest IC distance and the most elliptic shape were at ES, while the annulus was minimal at ED. The procedure and normal ranges presented may contribute to the evaluation of patients with mitral regurgitation.


Evaluation of the Venom Ex apparatus in the initial treatment of puff adder envenomation. A study in rabbits.
The Venom Ex apparatus has been evaluated for the treatment of puff adder bite. Rabbits were injected with double the lethal dose of puff adder venom, followed by treatment with the Venom Ex cutting and suction apparatus. Controls received no treatment. The percentage of venom extracted as determined by radial immunodiffusion was very low after intramuscular injection and significantly higher after subcutaneous injection. However, all treated and control animals injected subcutaneously, recovered while all animals injected intramuscularly died, irrespective of treatment. Blood venom levels were extremely low in all animals. Venom Ex treatment did not improve survival or affect local necrosis significantly.


Keratinocyte apoptosis in epidermal remodeling and clearance of psoriasis induced by UV radiation.
Psoriasis is a common chronic skin disorder, but the mechanisms involved in the resolution and clearance of plaques remain poorly defined. We investigated the mechanism of action of UVB, which is highly effective in clearing psoriasis and inducing remission, and tested the hypothesis that apoptosis is a key mechanism. To distinguish bystander effects, equal erythemal doses of two UVB wavelengths were compared following in vivo irradiation of psoriatic plaques; one is clinically effective (311 nm) and one has no therapeutic effect on psoriasis (290 nm). Only 311 nm UVB induced significant apoptosis in lesional epidermis, and most apoptotic cells were keratinocytes. To determine clinical relevance, we created a computational model of psoriatic epidermis. Modeling predicted apoptosis would occur in both stem and transit-amplifying cells to account for plaque clearance; this was confirmed and quantified experimentally. The median rate of keratinocyte apoptosis from onset to cell death was 20 minutes. These data were fed back into the model and demonstrated that the observed level of keratinocyte apoptosis was sufficient to explain UVB-induced plaque resolution. Our human studies combined with a systems biology approach demonstrate that keratinocyte apoptosis is a key mechanism in psoriatic plaques clearance, providing the basis for future molecular investigation and therapeutic development.


Towards developing a vaccine for rheumatic heart disease.
Rheumatic heart disease (RHD) is the most serious manifestations of rheumatic fever, which is caused by group A Streptococcus (GAS or Streptococcus pyogenes) infection. RHD is an auto immune sequelae of GAS pharyngitis, rather than the direct bacterial infection of the heart, which leads to chronic heart valve damage. Although antibiotics like penicillin are effective against GAS infection, improper medical care such as poor patient compliance, overcrowding, poverty, and repeated exposure to GAS, leads to acute rheumatic fever and RHD. Thus, efforts have been put forth towards developing a vaccine. However, a potential global vaccine is yet to be identified due to the widespread diversity of S. pyogenes strains and cross reactivity of streptococcal proteins with host tissues. In this review, we discuss the available vaccine targets of S. pyogenes and the significance of in silico approaches in designing a vaccine for RHD.


p38α MAPK-mediated induction and interaction of FOXO3a and p53 contribute to the inhibited-growth and induced-apoptosis of human lung adenocarcinoma cells by berberine.
Berberine (BBR), a component from traditional Chinese medicine, has been shown to possess anti-tumor activity against a wide spectrum of cancer cells including human lung cancer, but the detailed mechanism underlining this has not been well elucidated. In this study, the effect of berberine on cell growth and apoptosis were assessed by MTT, flow cytometry and Hoechst 33258 staining assays. The phosphorylation of p38 MAPK and ERK1/2, and expressions of p38 MAPK isoforms α and β, total ERK1/2, p53, FOXO3a and p21 protein were evaluated by Western Blot analysis. Silencing of p38 MAPK isoform α and β, p53, FOXO3a and p21 were performed by siRNA methods. Exogenous expression of FOXO3a was carried out by electroporated transfection assays. We showed that BBR significantly inhibited growth and induced cell cycle arrest of non small cell lung cancer (NSCLC) cells in the G0/G1 phase in a dose-dependent manner. Furthermore, we found that BBR increased phosphorylation of p38 MAPK and ERK1/2 in a time-dependent and induced protein expression of tumor suppressor p53 and transcription factor FOXO3a in a dose-dependent fashion. The specific inhibitor of p38 MAPK (SB203580), and silencing of p38α MAPK by small interfering RNAs (siRNAs), but not ERK1/2 inhibitor (PD98059) blocked the stimulatory effects of BBR on protein expression of p53 and FOXO3a. Interestingly, inhibition of p53 using one specific inhibitor (Pifithrin-α) and silencing of p53 using siRNAs overcome the inhibitory effect of BBR on cell growth. Silencing of FOXO3a appeared to attenuate the effect of BBR on p53 expression, cell proliferation and apoptosis. Furthermore, BBR induces the protein expression of cell cycle inhibitor p21 (CIP1/WAF1), which was not observed in cells silencing of p53 or FOXO3α gene. Intriguingly, exogenous expression of FOXO3a enhanced the expression of p21 (CIP1/WAF1) and strengthened BBR-induced apoptosis. Our results show that BBR inhibits proliferation and induces apoptosis of NSCLC cells through activation of p38α MAPK signaling pathway, followed by induction of the protein expression of p53 and FOXO3a. The latter contribute to the BBR-increased p21 (CIP1/WAF1) protein expression. The exogenous FOXO3a, interaction and mutually exclusive events of p53 and FOXO3a augment the overall response of BBR.


Bacterial Viability within Dental Calculus: An Untrodden, Inquisitive Clinico-Patho- Microbiological Research.
Chronic inflammatory periodontal diseases i.e. gingivitis and periodontitis are one of the most common afflictions faced by human beings. Dental plaque, which is a pool of pathogenic microorganisms, remains to be current mainstay in etiopathogenesis. Dental calculus, which is a mineralized product of this plaque remains ignored and is considered merely as an ash heap of minor significance. However, the intriguing array in disease etiopathogenesis bulldozed researchers to suspect the role of calculus in disease chrysalis but still the viability of bacteria inside calculus and thus its pathogenicity remains an intricacy; the answer to which lies in the Pandora's Box. The present study was undertaken to investigate the viability of bacteria within dental calculus along with their identification. Also, to classify dental calculus on the basis of mineralization and to observe the variation of viable microflora found in dental calculus with the extent of mineralization and disease severity. A total of 60 samples were obtained, by harvesting two samples of supragingival calculus from each patient having chronic inflammatory periodontal disease. These samples were divided into two groups (Group A and Group B). Samples of Group A were kept non-irradiated and samples of Group B were exposed to UV radiation. The samples were categorized into less, moderately and highly mineralized according to the force required for crushing them. All the crushed calculus samples were then divided into three parts. These were used for dark-field microscopy, gram staining and bacterial cultures. Bacterial identification of the cultures obtained was also carried out by performing various biochemical assays. The present study revealed the presence of motile spirochaetes within the samples under dark-field microscope. Gram staining revealed presence of numerous gram positive cocci and gram negative bacilli. Bacterial cultures showed growth of variety of aerobic and capnophilic microorganisms. The present study concludes the presence of viable aerobic and capnophilic bacteria inside dental calculus which may reside within the lacunae and channels in the calculus.


Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals.
The location of neurons generating the rhythm of breathing in mammals is unknown. By microsection of the neonatal rat brainstem in vitro, a limited region of the ventral medulla (the pre-Bötzinger Complex) that contains neurons essential for rhythmogenesis was identified. Rhythm generation was eliminated by removal of only this region. Medullary slices containing the pre-Bötzinger Complex generated respiratory-related oscillations similar to those generated by the whole brainstem in vitro, and neurons with voltage-dependent pacemaker-like properties were identified in this region. Thus, the respiratory rhythm in the mammalian neonatal nervous system may result from a population of conditional bursting pacemaker neurons in the pre-Bötzinger Complex.


Histone deacetylase 1/Sp1/microRNA-200b signaling accounts for maintenance of cancer stem-like cells in human lung adenocarcinoma.
The presence of cancer stem-like cells (CSCs) is one of the mechanisms responsible for chemoresistance that has been a major hindrance towards lung adenocarcinoma (LAD) treatment. Recently, we have identified microRNA (miR)-200b as a key regulator of chemoresistance in human docetaxel-resistant LAD cells. However, whether miR-200b has effects on regulating CSCs remains largely unclear and needs to be further elucidated. Here, we showed that miR-200b was significantly downregulated in CD133+/CD326+ cells that exhibited properties of CSCs derived from docetaxel-resistant LAD cells. Also, restoration of miR-200b could inhibit maintenance and reverse chemoresistance of CSCs. Furthermore, suppressor of zeste-12 (Suz-12) was identified as a direct and functional target of miR-200b, and silencing of Suz-12 phenocopied the effects of miR-200b on CSCs. Additionally, overexpression of histone deacetylase (HDAC) 1 was identified as a pivotal mechanism responsible for miR-200b repression in CSCs through a specificity protein (Sp) 1-dependent mechanism, and restoration of miR-200b by HDAC1 repression significantly suppressed CSCs formation and reversed chemoresistance of CSCs by regulating Suz-12-E-cadherin signaling. Also, downregulation of HDAC1 or upregulation of miR-200b reduced the in vivo tumorigenicity of CSCs. Finally, Suz-12 was inversely correlated with miR-200b, positively correlated with HDAC1 and up-regulated in docetaxel-resistant LAD tissues compared with docetaxel-sensitive tissues. Taken together, the HDAC1/miR-200b/Suz-12-E-cadherin signaling might account for maintenance of CSCs and formation of chemoresistant phenotype in docetaxel-resistant LAD cells.


Demonstration of digital phase-sensitive boosting to extend signal reach for long-haul WDM systems using optical phase-conjugated copy.
We demonstrate a hybrid optical/digital phase-sensitive boosting (PSB) technique for long-haul wavelength division multiplexing (WDM) transmission systems. The approach uses four-wave mixing (FWM) to generate a phase-conjugated idler alongside the original signal. At the receiver, the signal and idler are jointly detected, and the phases of the idler symbols are conjugated and summed with the signal symbols to suppress noise and nonlinear phase distortion. The proposed hybrid PSB scheme is independent of modulation format and does not require an optical phase-locked loop to achieve phase matching required by conventional phase-sensitive amplifiers. Our simulation and experimental results of 112-Gb/s dual-polarization quadrature phase-shift-keying (DP-QPSK) transmission confirmed the principle of the PSB scheme, attaining a Q-factor improvement of 2.4 dB over conventional single-channel transmission after 4,800 km of dispersion-managed fiber (DMF) link at the expense of 50% reduction in spectral efficiency and extending the system reach by 60% to 7,680 km.


Structural and functional characteristics of chimeric avidins physically adsorbed onto functionalized polythiophene thin films.
Stabilized bioreceptor layers are of great importance in the design of novel biosensors. In earlier work, chimeric avidins enabled immobilization of biotinylated antibodies onto gold surfaces with greater stability compared to more conventional avidins (wild-type avidin and streptavidin). In the present study, the applicability of chimeric avidins as a general binding scaffold for biotinylated antibodies on spin-coated functionalized polythiophene thin films has been studied by surface plasmon resonance and atomic force microscopy. Novel chimeric avidins showed remarkably increased binding characteristics compared with other avidins, such as wild-type avidin, streptavidin, and bacterial avidin when merely physically adsorbed onto the polythiophene surface. They gave the highest binding capacities, the highest affinity constant, and the highest stability for biotinylated probe immobilization. Introduction of carboxylic acid groups to polythiophene layer further enhanced the binding level of the avidins. Polythiophene layers functionalized with chimeric avidins thus offered a promising generic platform for biosensor applications.


Selective vulnerability of the inner ear to decompression sickness in divers with right-to-left shunt: the role of tissue gas supersaturation.
Inner ear decompression sickness has been strongly associated with the presence of right-to-left shunts. The implied involvement of intravascular bubbles shunted from venous to arterial circulations is inconsistent with the frequent absence of cerebral symptoms in these cases. If arterial bubbles reach the labyrinthine artery, they must also be distributing widely in the brain. This discrepancy could be explained by slower inert gas washout from the inner ear after diving and the consequent tendency for arterial bubbles entering this supersaturated territory to grow because of inward diffusion of gas. Published models for inner ear and brain inert gas kinetics were used to predict tissue gas tensions after an air dive to 4 atm absolute for 25 min. The models predict half-times for nitrogen washout of 8.8 min and 1.2 min for the inner ear and brain, respectively. The inner ear remains supersaturated with nitrogen for longer after diving than the brain, and in the simulated dive, for a period that corresponds with the latency of typical cases. It is therefore plausible that prolonged inner ear inert gas supersaturation contributes to the selective vulnerability of the inner ear to short latency decompression sickness in divers with right-to-left shunt.


Barium isotopes in allende meteorite: evidence against an extinct superheavy element.
Carbon and chromite fractions from the Allende meteorite that contain isotopically anomalous xenon-131 to xenon-136 (carbonaceous chondrite fission or CCF xenon) at up to 5 x 10(11) atoms per gram show no detectable isotopic anomalies in barium-130 to barium-138. This rules out the possibility that the CCF xenon was formed by in situ fission of an extinct superheavy element. Apparently the CCF xenon and its carbonaceous carrier are relics from stellar nucleosynthesis.


Management of pregnancy sensitized with anti-Inb with monocyte monolayer assay and maternal blood donation.
Maternal red blood cell (RBC) alloantibodies can cause hemolytic disease of the fetus and newborn (HDFN). Although much is described about common antibodies associated with HDFN, management of a pregnancy complicated by a maternal rare antibody presents several challenges related to assessment of fetal anemia risk, availability of blood for transfusion to the mother and/or the fetus or newborn if needed, and planning for delivery in the case of maternal hemorrhage. Here we report the laboratory medicine workup of a patient who presented for obstetrical care in the United States in the third trimester and had a rare antibody (anti-Inb). Prenatal antibody detection testing demonstrated maternal anti-Inb in a 28-year-old woman (gravida 4 para 1021). Ultrasound could not rule out fetal anemia. Monocyte monolayer assay was performed to assess for the clinical significance of the anti-Inb and revealed that the antibody may be capable of causing accelerated clearance of antigen-positive RBCs. A local and national query revealed that no appropriate units of RBCs were available for either the mother or neonate. Given this information, serial maternal autologous blood donations were performed, and a comprehensive care plan with a multidisciplinary approach for delivery, neonatal management, and preparation for hemorrhage was developed. Published data and our experience suggest that maternal blood donation appears to be a safe and effective way to manage mothers who cannot safely use the community blood supply. Involvement of obstetric, transfusion medicine, anesthesia, and neonatology providers was imperative for a favorable outcome. The antibody did not cause clinically significant anemia in this infant.


Refinement and Usability Analysis of an eHealth App for Ankylosing Spondylitis as a Complementary Treatment to Physical Therapy: Development and Usability Study.
Mobile eHealth apps have been used as a complementary treatment to increase the quality of life of patients and provide new opportunities for the management of rheumatic diseases. Telemedicine, particularly in the areas of prevention, diagnostics, and therapy, has become an essential cornerstone in the care of patients with rheumatic diseases. This study aims to improve the design and technology of YogiTherapy and evaluate its usability and quality. We newly implemented the mobile eHealth app YogiTherapy with a modern design, the option to change language, and easy navigation to improve the app's usability and quality for patients. After refinement, we evaluated the app by conducting a study with 16 patients with AS (4 female and 12 male; mean age 48.1, SD 16.8 y). We assessed the usability of YogiTherapy with a task performance test (TPT) with a think-aloud protocol and the quality with the German version of the Mobile App Rating Scale (MARS). In the TPT, the participants had to solve 6 tasks that should be performed on the app. The overall task completion rate in the TPT was high (84/96, 88% completed tasks). Filtering for videos and navigating to perform an assessment test caused the largest issues during the TPT, while registering in the app and watching a yoga video were highly intuitive. Additionally, 12 (75%) of the 16 participants completed the German version of MARS. The quality of YogiTherapy was rated with an average MARS score of 3.79 (SD 0.51) from a maximum score of 5. Furthermore, results from the MARS questionnaire demonstrated a positive evaluation regarding functionality and aesthetics. The refined and tested YogiTherapy app showed promising results among most participants. In the future, the app could serve its function as a complementary treatment for patients with AS. For this purpose, surveys with a larger number of patients should still be conducted. As a substantial advancement, we made the app free and openly available on the iOS App and Google Play stores.


Fluorescein angioscopy: techniques of partial fluorescence, permanent drawing record and photocoagulation.
Fluorescein angioscopy with the indirect ophthalmoscope might be the preferred technique for evaluating and treating certain lesions, particularly those in the retinal periphery. Three techniques which are helpful in extending the advantages of angioscopy are described. (1) Partial fluorescence is achieved with careful adjustment of the cobalt blue filter which relates the fluorescence to retinal landmarks, ie, color angioscopy. (2) A permanent record of angioscopy in different phases can be made with tracing paper over the retinal drawing. (3) Correct localization of lesions to be coagulated is achieved with blue filters over the coagulator beam following fluorescein injection. The filter is removed during coagulation.


How legislation and health systems can promote adolescent health.
This chapter focuses on some of the laws and regulations that could make it easier for adolescents to adopt health-promoting and disease-preventing behaviors, or that have minimized the dangers that might be caused by their behaviors. It also reviews some of the aspects of health care systems that may present barriers to health-promoting behaviors and suggests how they might be changed.


Predictors of regained occupational functioning after electroconvulsive therapy (ECT) in patients with major depressive disorder--a population based cohort study.
The aim of the present study is to investigate the rate of regained occupational functioning among patients treated with electroconvulsive therapy (ECT) for major depression and to define predictors of time to regained occupational functioning. A nested cohort study was performed of patients treated by ECT for unipolar major depressive disorder registered in the Quality register for ECT and in the Swedish Social Insurance Agency registry. Predictive values of single clinical variables and their relative importance were tested with Cox regression analysis. 394 patients were identified. Of those, 266 were on non-permanent sick leave and 128 on disability pension during ECT. Within 1 year post-ECT, 71% of the patients with non-permanent sick leave regained occupational functioning. Factors independently associated with a statistically significant increased time to regained occupational functioning were longer duration of sick leave pre-ECT, milder depression pre-ECT, less complete improvement with ECT, benzodiazepine treatment after ECT and co-morbid substance dependence. A large proportion of the patients do not return to work within several months post-ECT. Paradoxically, patients with more severe depression pre-ECT had a reduced time to regained occupational functioning, indicating a larger effect in this patients group of the treatment. Moreover, the period with sick leave compensation might be reduced if ECT is initiated within the first 3 months of sick leave. Most patients on non-permanent sick leave regain occupational functioning after ECT. However, it usually takes a few months even in symptomatically improved patients.


A scanned, focused, multiple transducer ultrasonic system for localized hyperthermia treatments.
A commercial diagnostic ultrasound scanner (Octoson) was modified for performing hyperthermia treatments. The temperature elevations were induced in tissues by four large, focused ultrasonic transducers whose common focal zone was scanned along a computer controlled path as determined from B-scan images. The system is described and the results of preliminary tests demonstrating some of its capabilities are given. Extensive tests with canine thighs and kidneys were performed. The blood flow to the kidneys was controllable, and thus tumours having different blood perfusion rates could be simulated. The results showed that the system is capable of inducing a local temperature maximum deep in tissues (up to 10 cm was tested) and that tissues with high perfusion rates could be heated.


Abiraterone in metastatic salivary duct carcinoma.
Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy with limited evidence guiding standard treatment. SDC is known to overexpress the androgen receptor, with only a handful of cases reporting responses to androgen blockade. This report presents a case of SDC responding to multiple lines of androgen blockade, including a rapid response to abiraterone, a CYP17 inhibitor effective in prostate cancer. This case represents the first published report of SDC responding to abiraterone and illustrates that androgen receptor expressing SDC may be treated with multiple lines of androgen blockade, including newer agents such as abiraterone. This case suggests that SDC may continue to be androgen-dependent after progression on androgen deprivation, which is analogous to prostate cancer.


Body weight, gender and response to TNF-α blockers in axial spondyloarthritis.
The objective of this study was to determine whether BMI and gender could lead to a different response rate to anti-TNF agents in patients affected by axial SpA. One hundred and seventy patients with active axial SpA (defined as a BASDAI ≥ 4) treated with an anti-TNF agent [adalimumab (ADA), etanercept (ETA), infliximab (IFX)] were retrospectively evaluated. Patients were divided according to the baseline BMI as normal weight (BMI < 25), overweight (BMI 25-30) and obese (BMI ≥ 30). After 12 months of treatment a 50% improvement of the initial BASDAI (BASDAI50) was the primary end point and BASDAI ≤ 1 was the secondary end point. After 12 months of anti-TNF treatment, 67.8% of men and 46.2% of women reached the BASDAI50 (P = 0.01). According to BMI categories, the rate of BASDAI50 achievement decreased from 72.8% in normal weight subjects to 54.5% in overweight and 30.4% in obese subjects (P < 0.001). In the logistic regression analysis, the best independent predictors of failure to obtain a BASDAI50 response at the 12th month of therapy in axial SpA patients were female gender [odds ratio (OR) 3.23 (95% CI 1.52, 7.14)] and a BMI ≥ 30 [OR 3.57 (95% CI 1.15, 11.11)]. Analysing outcomes based on IFX therapy (the larger subgroup), the BASDAI50 response rate fell from 79.0% in normal weight subjects to 56.7% in overweight and 16.7% in obese subjects (P < 0.001). No significant differences were observed with ADA and ETA. Data suggest that being female, overweight and mostly obese is associated with a lower rate of success in obtaining response status in axial SpA patients treated with anti-TNF drugs. Body weight could represent a modifiable factor to reach the best outcome in axial SpA patients treated with TNF blockers.


Ovine luteinizing hormone-induced steroid and luteinizing hormone secretion, and ovulation in intact and pregnant mare serum gonadotropin-primed hens.
Studies were conducted to investigate the effect of ovine luteinizing hormone (LH) treatment on steroid and LH secretion and ovulation in intact, saline-primed hens and in pregnant mare serum gonadotropin (PMSG)-primed hens. Intact, saline-primed hens, injected 12 hr prior to the first (C1) ovulation of the sequence, responded with fully potentiated preovulatory surges of progesterone (P4) (peak value was 371% above preinjection values), estradiol-17 beta (E2) (117% above baseline), LH (220% above baseline), and premature ovulation. By comparison, those hens injected at the same time prior to the second (C2) ovulation responded with a lesser increase in plasma P4 (peak value was 305% above baseline) and E2 (72% above baseline), and there was no significant increase in plasma LH. Within this group, 4 of 5 hens failed to ovulate prematurely. All groups of PMSG-primed hens had significantly higher preinjection concentrations of P4 and E2, and lower basal concentrations of LH, compared to saline-primed hens. Subsequent to treatment of PMSG-primed hens with 25 or 100 micrograms ovine LH, there was a significant increase in plasma P4 to approximately 200% above preinjection concentrations. By contrast, there was a nonsignificant increase in plasma LH (50% above baseline values) and no significant increase in plasma E2. The ovulatory response following PMSG-priming was greatest in hens injected with 100 micrograms ovine LH (5 of 5 hens ovulated), while 3 of 5 hens injected with 25 micrograms ovine LH and 6 of 6 saline-challenged hens failed to ovulate.(ABSTRACT TRUNCATED AT 250 WORDS)


Production of Phytochromes by High-Cell-Density E. coli Fermentation.
Phytochromes are important photoreceptors of plants, bacteria, and fungi responsive to light in the red and far-red spectrum. For increasing applications in basic research, synthetic biology, and materials sciences, it is required to recombinantly produce and purify phytochromes in high amounts. An ideal host organism for this purpose is E. coli due to its widespread use, fast growth, and ability for high-cell-density fermentation. Here, we describe the development of a generic platform for the production of phytochromes in E. coli that is compatible with high-cell-density fermentation. We exemplify our approach by the production of the photosensory domains of phytochrome B (PhyB) from A. thaliana and of the cyanobacterial phytochrome 1 (Cph1) from Synechocystis PCC 6803 in the multigram scale per 10 L fermentation run.


Treatment of psoriasis with cyclosporin. Experience at Johannesburg Hospital.
Ten patients with moderate to severe plaque psoriasis were treated with cyclosporin A (CyA) for 2-19 months (mean 12 months). Initial dosages were 2.5 mg/kg/d in 6 patients and 5.0 mg/kg/d in 4. At 3 months the dosage was increased from 2.5 to 5.0 mg/kg/d in 4 patients in accordance with the study protocol. Subsequent dosages were adjusted according to clinical response and side-effects. Treatment was stopped owing to raised serum creatinine levels in 4 patients on the higher dose; levels returned to normal soon after this. The only other important side-effect was hypertension, which developed in 4 patients, in 2 of whom serum creatinine levels were raised. In all patients the psoriasis improved markedly within 2 months but relapsed, either while the dose of CyA was being tapered off or after treatment with the drug was stopped. Relapse was most rapid in patients with severe initial involvement. On a dosage of 2.5 mg/kg/d there was at least 50% clearance of the psoriasis and no evidence of renal side-effects.


The prognostic utility of the Silicone Study Classification System. Silicone Study Report 9. Silicone Study Group.
To evaluate the reproducibility and the prognostic utility of the Retina Society and Silicone Study Classification Systems in eyes after surgery for severe proliferative vitreoretinopathy (PVR). Subgroup analysis of the Silicone Study--a randomized, multicentered, surgical trial. Community and university-based ophthalmology clinics. Three hundred forty eyes with preoperative and intraoperative evaluations using both systems of grading PVR (reproducibility study), and 287 eyes with preoperative and intraoperative evaluations using both systems of grading PVR and with a 24-month follow-up examination (prognosis study). Vitrectomy for PVR with long-acting perfluoropropane gas or silicone oil as the intraocular tamponade. Retinal reattachment, visual acuity ( > or = 5/200), intraocular pressure, corneal clarity, and the need for reoperation. The reproducibility of the Silicone Study Classification System was 64% (type of contraction), 77% (number of clock hours), 67% (posterior PVR), 88% anterior and posterior PVR), and 94% (anterior, posterior, and subretinal PVR). The reproducibility of the Retina Society Classification System was 99%. Using the Silicone Study Classification System, location of PVR predicted visual acuity (P=.004, chi 2 test for trend) and hypotony (P=.03, chi 2 test for trend). Using the Retina Society Classification System, the grade of PVR predicted only visual acuity (P=.01, chi 2 test for trend). For eyes with anterior and posterior PVR, there was a decreasing trend in successful visual acuity outcome with increasing severity of PVR (from C-3 to D-3, P=.02, chi 2 test for trend). Although the classification of PVR using the Silicone Study classification System was not reproducible for the type of contraction or for posterior PVR, identification of the anteroposterior extent of the PVR was prognostic of visual acuity and hypotony at 24 months. The joint knowledge of the location of PVR (using the Silicone Study Classification System) and the tightness of the funnel for retinas with 9 to 12 clock hours involved by fixed folds (using the Retina Society Classification System) has prognostic utility for eyes with anterior and posterior PVR.


What's the place of immunotherapy in malignant mesothelioma treatments?
Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura with a very poor prognosis. Treatments evaluated for malignant mesothelioma, including chemotherapy, radiotherapy and surgery are of limited efficacy. However, the fact that the tumors of some patients with MPM regress spontaneously or respond to immunotherapy suggests that the immune system may respond to MPM under some circumstances. In this respect, animal studies have demonstrated immunoreactivity of MPM to different immunotherapies. In the case of MPM, several clinical studies have demonstrated a correlation between the presence of a lymphocyte infiltrate and a better prognosis and humoral response directed against specific antigens related to tumor. Thus, MPM immunotherapy is undoubtedly a highly promising but also very challenging approach to the treatment of this disease that has slipped through the defense lines of the immune system. This article reviews past and recent developments of the clinical strategies that concern immunotherapy of mesothelioma.


On the analysis of rotational symmetric microstructured surfaces.
A previous paper [2] presented an analysis of a class of microstructured optical surfaces in two dimensions, in which a classification of the microstructures was obtained (regular and anomalous) and a concept of 2D ideal microstructures was introduced. In this paper the study of those microstructured optical surfaces is extended to three dimensions with rotational symmetry. As a starting point, non-microstructured rotational optical systems in the First Order Approximation are also classified as point-spot type and ring-spot type, with remarkable perfect particular cases. This classification is also extended to the case in which ideal microstructured rotational surfaces are used, for both regular and anomalous type. The case of perfect ring-spot type system with an odd number of rotational, anomalous, ideal microstructures enables the definition of an anomalous aplanatic system that has direct application for mixing spatially and angularly the light emitted by several sources.


Pregnancy rates after artificial insemination with cooled stallion spermatozoa either with or without single layer centrifugation.
A successful outcome after artificial insemination with cooled semen is dependent on many factors, the sperm quality of the ejaculate being one. Previous studies have shown that spermatozoa with good motility, normal morphology, and good chromatin integrity can be selected by means of colloid centrifugation, particularly single layer centrifugation (SLC) using species-specific colloids. The purpose of the present study was to conduct an insemination trial with spermatozoa from "normal" ejaculates, i.e., from stallions with no known fertility problem, to determine whether the improvements in sperm quality seen in SLC-selected sperm samples compared with uncentrifuged controls in laboratory tests are reflected in an increased pregnancy rate after artificial insemination. In a multicentre study, SLC-selected sperm samples and uncentrifuged controls from eight stallions were inseminated into approximately 10 mares per treatment per stallion. Ultrasound examination was carried out approximately 16 days after insemination to detect an embryonic vesicle. The pregnancy rates per cycle were 45% for controls and 69% for SLC-selected sperm samples, which is statistically significant (P < 0.0018). Thus, the improvement in sperm quality reported previously for SLC-selected sperm samples is associated with an increase in pregnancy rate, even for ejaculates from stallions with no known fertility problem.


Jumping from the couch: an essay on phantasy and emotional structure.
This paper addresses two questions: first, how do phantasies work? Second, how do these mental activities affect a person's overall emotional life? The first question tends to be overlooked since those who accept, for example, projective identification as a basic mental activity tend also to treat it as an explanatory primitive. On this view, there is no further question to ask about how projective identification itself works; rather, other psychological and emotional phenomena are explained in terms of it. By contrast, this paper asks, how does projective identification itself work? The aim is not to provide a reductive explanation but to ask how it is that phantasies have the efficacy they have. To that end, one moment in the analysis of the Rat Man is re-examined. There is then an attempt to show the difficulties involved in weaving an account of phantasy into the broader-scale interpretation of emotional life.


Use of lumboperitoneal shunts with the Strata NSC valve: a single-center experience.
The lumboperitoneal (LP) shunt with the adjustable PS Medical Strata NSC LP valve and small lumen peritoneal catheter was introduced in the authors' unit in 2007. The object of this study was to audit the unit's experience with this new shunt system. The authors performed a retrospective review of the clinical records of patients who underwent Strata NSC LP shunt insertion. Demographic and clinical data as well as information about complications and revisions were reported. Between August 2007 and November 2009, 20 patients underwent placement of an LP shunt with an adjustable Strata NSC valve and small lumen peritoneal catheter at the authors' institution. Their mean age was 40.3 years and the mean duration of follow-up was 12 months. Preoperatively, 18 patients had headache and 15 patients had visual signs and symptoms. Fourteen of the 18 patients with preoperative headache did not complain of headache postoperatively, and 4 had headache that was found not to be related to shunt function. Two of the patients with preoperative visual complaints had ongoing visual problems postoperatively. None of the patients had infection or subdural hematoma. The only overdrainage symptoms occurred in association with spontaneous readjustment of the valve and resolved when the valve was reset. Thirteen patients (65%) did not require shunt revision. Seven patients (35%) required 13 shunt exploration or revision procedures, mainly due to distal obstruction. Placement of an LP shunt failed to completely resolve the raised intracranial pressure problem in 2 patients. The use of the Strata NSC valve and small lumen peritoneal catheter is effective in treating pseudotumor cerebri and is beneficial in terms of markedly reducing overdrainage complications compared with other reported series of cases in which an LP shunt has been placed. However, the use of the Strata NSC valve and small lumen peritoneal catheter did not have a marked impact on other causes of shunt failure, particularly distal obstruction.


A new thermoplastic splint for proximal interphalangeal joint flexion contractures.
Aim of this technical note is to describe the fabrication procedure of a new thermoplastic static-progressive hand-based splint for PIP joint flexion contractures, and report its effects in the treatment of a small group of sportsmen. The serial-static splint consists of a short metacarpal gauntlet base, with a hole for the thumb and a dorsal finger gutter that extends to the distal extremity. A low-temperature thermoplastic material, two loop fastener straps, three small pieces of self-adhesive hook fastener and cooling spray are required. The orthosis has been tested on four professional volleyball players (3 females and 1 male), aged 18-24 years, suffering from PIP joint flexion contractures after traumatic hand injuries occurred 2 to 3 months before. Patients wore the splint for 1 hour followed by 1 hour of rest (6 times per day), for 2 to 3 weeks. During the resting periods patients performed a few sets of active ROM exercises at their PIP joint. This new splint design demonstrated to be effective in early recovery of complete PIP joint extension and subjects resumed soon their sports activity. Our device is easy to fabricate and to use and comfortable for patients.


Evaluating the Need for Palliative Care Services at a General Hospital in Israel.
Most hospitals in Israel do not provide palliative care beds and only few general hospitals have palliative consultation services. To date there are no data on the rate of hospitalizations and the need for palliative care in general hospitals in Israel. The objective was to characterize patients in need of palliative treatment during hospitalization in a general hospital in Israel. A retrospective review was performed of a random sample of files of patients admitted to the Internal Medicine Department at the Soroka University Medical Center (SUMC) between May 2007 and April 2008. Patients were defined as in need of palliative care if they had a CARING score ≥13. The data were collected using a structured questionnaire that included sociodemographic data and data on comorbid conditions, main complaints, primary diagnosis, duration of hospitalization, and hospitalization outcome. We reviewed 2795 hospitalizations. Of these, 14.9% were defined as in need of palliative care. Fourteen percent of the patients died during hospitalization and 47% died over the six-month follow-up period. The most common primary diagnosis was malignancy (61%), followed by end-stage pulmonary disease (19%) and Alzheimer's and other causes of dementia (9%). In only 12 hospitalizations (3.5%) was palliative care arranged for patients at discharge. A high percentage of patients hospitalized in internal medicine divisions could benefit from palliative care. The data presented here could aid hospitals in the integration of palliative care services.


Association between back and neck pain and workplace absenteeism in the USA: the role played by walking, standing, and sitting difficulties.
There is a paucity of literature identifying factors that influence the back and neck pain (BNP)-workplace absenteeism relationship. Therefore, this study aimed to investigate the association between BNP and workplace absenteeism and potential mediating variables in a large sample of the US population. Nationally representative data collected in 2019 from the RAND American Life Panel (ALP) were used for this retrospective study. Workplace absenteeism was defined as the number of days of absence in the past 12 months for health-related reasons (count variable), while BNP corresponded to the presence of back pain due to spinal stenosis, back pain due to other causes, or neck pain (dichotomous variable). Control variables included sex, age, ethnicity, marital status, education, occupation, annual family income, health insurance, obesity, and diabetes. There were eight influential variables (depression, anxiety, sleep disorder, alcohol dependence, opioid dependence, walking difficulty, standing difficulty, and sitting difficulty). The association between BNP and workplace absenteeism was analyzed using a negative binomial regression model. There were 1,471 adults aged 22-83 years included in this study (52.9% of men; mean [standard deviation] age 44.5 [13.0] years). After adjusting for control variables, BNP was positively and significantly associated with workplace absenteeism (incidence rate ratio = 1.40, 95% confidence interval: 1.07-1.83). Walking, standing, and sitting difficulties individually explained between 24 and 43% of this association. Workplace interventions focusing on the management of BNP and overcoming difficulties in walking, standing, and sitting, potentially utilizing exercise, therapy, and ergonomic interventions, may prevent absenteeism.


Antifungal Tc17 cells are durable and stable, persisting as long-lasting vaccine memory without plasticity towards IFNγ cells.
Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen. Memory Tc17 cells were canonical CD8+ T cells with phenotypic features distinct from Tc1 cells, and were Ror(γ)thi, TCF-1hi, T-betlo and EOMESlo. In investigating the bases of Tc17 persistence, we observed that memory Tc17 cells had much higher levels of basal homeostatic proliferation than did Tc1 cells. Conversely, memory Tc17 cells displayed lower levels of anti-apoptotic molecules Bcl-2 and Bcl-xL than Tc1 cells, yet were resistant to apoptosis. Tc1 cells required Bcl-2 for their survival, but Bcl-2 was dispensable for the maintenance of Tc17 cells. Tc17 and Tc1 cells displayed different requirements for HIF-1α during effector differentiation and sustenance and memory persistence. Thus, antifungal vaccination induces durable and stable memory Tc17 cells with distinct requirements for long-term persistence that distinguish them from memory Tc1 cells.


Conformational states of the (Na+ + K+)-transporting ATPase. Formation of 240 000-Mr and 116 000-Mr polypeptides in the presence of a bifunctional thiol probe.
Interpeptide cross-linking of alpha-subunits with concomitant loss of Na+ + K+-transporting ATPase (Na+, K+-ATPase) activity was found when the purified lamb kidney enzyme was treated with the bifunctional thiol reagent 4,4'-difluoro-3,3'-dinitrodiphenyl sulphone (F2DNS). Several forms of the enzyme could be clearly distinguished: one binding ATP (non-phosphorylated enzyme, E1 X ATP), a phosphorylated form (E2-P) and a phosphoenzyme-ouabain complex (E2P X ouabain). A polypeptide of approx. Mr 240 000 and probable alpha 2 composition comprised up to 5-20% of the total polypeptides after reaction of the lamb kidney Na+, K+-ATPase with F2DNS. The amount of this polypeptide formed was related to the conformational state of the enzyme. The presence of adenine nucleotide greatly diminished the amount of 240 000-Mr polypeptide formed and provides evidence for an enzyme-adenine-nucleotide complex under conditions where the enzyme is not phosphorylated. F2DNS reacted with the enzyme in the presence of Mg2+, Pi and ouabain to form a new polypeptide with an approx. Mr of 116 000, and comprised 23% of the total, whereas the 240 000-Mr polypeptide comprised 9% of the total. This suggests that the 116 000-Mr polypeptide is a characteristic marker of the E2P X ouabain complex. By using specific antibodies it was established that both the 240 000- and 116 000-Mr polypeptides contained alpha-, but not beta-, subunits of the Na+, K+-ATPase.


Mitophagy in viral infections.
Antiviral innate immune responses and apoptosis are the two major factors limiting viral infections. Successful viral infection requires the virus to take advantage of the cellular machinery to bypass cellular defenses. Accumulated evidences show that autophagy plays a crucial role in cell-to-virus interaction. Here, we focus on how viruses subvert mitophagy to favor viral replication by mitigating innate immune responses and apoptotic signaling.


Nationwide survey of pregnancy and delivery in patients with coronary arterial lesions caused by Kawasaki disease in Japan.
Our purpose was to determine the outcome of pregnancy and delivery in patients with coronary arterial lesions caused by Kawasaki disease. We surveyed by mail the Japanese national experience of pregnancy and delivery in patients known to have Kawasaki disease. The first questionnaire was returned by 154 of 207 (74%) institutions, and 16 of the 154 had knowledge of deliveries in their patients. Based on a second questionnaire, and previous Japanese case reports, we identified 46 deliveries in 30 patients from 16 institutions. The age at delivery ranged from 18 to 35 years, with a median of 27 years. Of the patients, 4 had undergone coronary arterial bypass grafting. Low-dose aspirin was given in 16 patients. The deliveries, 27 in all, had been vaginal in 20 patients, albeit that 7 required assistance by forceps or vacuum extraction under epidural anesthesia. Caesarean section had been performed in 11 patients, 3 for obstetric indications, and 1 for chest discomfort in the third trimester. Although there were no cardiac events, obstetric complications occurred in 2. The results of pregnancy and delivery were favourable. The mode of delivery should be primarily determined by obstetrical considerations, rather than the coronary arterial lesions caused by Kawasaki disease. Excessive anticoagulant therapy may not be needed for this population.


The N-terminus of fission yeast DNA polymerase alpha contains a basic pentapeptide that acts in vivo as a nuclear localization signal.
The N-terminal sequence of the catalytic subunit of fission yeast DNA polymerase alpha (pol alpha) contains two putative nuclear localization signals (NLS). To check the functionality of these signals in vivo, the N-terminal sequence was experimentally divided into three amino acid blocks, two of which contain a distinct presumptive NLS. Each block was deleted, either individually or in combination with one of the two others. The deleted gene products were expressed in fission yeast, and assayed by indirect immunofluorescence for their aptitude to localize to the cell nucleus. Block II, which contains the putative NLS pentapeptide 97RKRKK, was both necessary and sufficient to promote nuclear import of pol alpha, as well as of a pyruvate kinase fusion protein. Precise excision of the NLS pentapeptide from block II inhibited the nuclear import of pol alpha, thus confirming the role of this sequence as the functional NLS of the fission yeast enzyme.


Endoscopic retrograde cholangiopancreatography associated pancreatitis: A 15-year review.
The aim of this article is to review the literature regarding post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We searched for and evaluated all articles describing the diagnosis, epidemiology, pathophysiology, morbidity, mortality and prevention of post-ERCP pancreatitis (PEP) in adult patients using the PubMed database. Search terms included endoscopic retrograde cholangiopancreatography, pancreatitis, ampulla of vater, endoscopic sphincterotomy, balloon dilatation, cholangiography, adverse events, standards and utilization. We limited our review of articles to those published between January 1, 1994 and August 15, 2009 regarding human adults and written in the English language. Publications from the reference sections were reviewed and included if they were salient and fell into the time period of interest. Between the dates queried, seventeen large (> 500 patients) prospective and four large retrospective trials were conducted. PEP occurred in 1%-15% in the prospective trials and in 1%-4% in the retrospective trials. PEP was also reduced with pancreatic duct stent placement and outcomes were improved with endoscopic sphincterotomy compared to balloon sphincter dilation in the setting of choledocholithiasis. Approximately 34 pharmacologic agents have been evaluated for the prevention of PEP over the last fifteen years in 63 trials. Although 22 of 63 trials published during our period of review suggested a reduction in PEP, no pharmacologic therapy has been widely accepted in clinical use in decreasing the development of PEP. In conclusion, PEP is a well-recognized complication of ERCP. Medical treatment for prevention has been disappointing. Proper patient selection and pancreatic duct stenting have been shown to reduce the complication rate in randomized clinical trials.


Evaluation of flow cytometric and automated methods for detection of activated platelets in dogs with inflammatory disease.
To evaluate platelet surface-associated P-selectin, mean platelet component concentration (MPC), mean platelet component distribution width (MPCDW), mean platelet volume (MPV), and platelet distribution width (PDW) for detection of activated platelets in dogs with septic and nonseptic inflammatory disease. 20 healthy dogs and 20 dogs with septic and nonseptic inflammatory disease. Procedures-Platelet surface-associated P-selectin (expressed as the median fluorescence intensity [MFI] of the platelet population), MPC, MPCDW, MPV, and PDW were determined in 20 healthy adult dogs, and reference ranges were calculated. These parameters were also determined in 11 dogs with nonseptic and 9 dogs with septic inflammatory disease and evaluated to determine which parameters were useful for detection of activated platelets. Results-12 dogs with inflammatory disease had P-selectin greater than the upper limit of the reference range, whereas 16 dogs with inflammatory disease had MPC lower than the lower limit of the reference range. All dogs in which P-selectin was greater than the upper limit of the reference range had MPC lower than the lower limit of the reference range. The correlation coefficient for P-selectin and MPC was 0.62. Differences in the MPCDW, MPV, and PDW in most dogs with inflammatory disease (compared with healthy dogs) were found; however, the correlation coefficients for P-selectin and MPCDW, MPV, and PDW were low. Platelet surface-associated P-selectin and MPC appeared to be useful to detect activated platelets in most dogs with septic and nonseptic inflammatory disease.


Cytochrome P450 CYP1B1 interacts with 8-methoxypsoralen (8-MOP) and influences psoralen-ultraviolet A (PUVA) sensitivity.
There are unpredictable inter-individual differences in sensitivity to psoralen-UVA (PUVA) photochemotherapy, used to treat skin diseases including psoriasis. Psoralens are metabolised by cytochrome P450 enzymes (P450), and we hypothesised that variability in cutaneous P450 expression may influence PUVA sensitivity. We previously showed that P450 CYP1B1 was abundantly expressed in human skin and regulated by PUVA, and described marked inter-individual differences in cutaneous CYP1B1 expression. We investigated whether CYP1B1 made a significant contribution to 8-methoxypsoralen (8-MOP) metabolism, and whether individuality in CYP1B1 activity influenced PUVA sensitivity. We used E. coli membranes co-expressing various P450s and cytochrome P450 reductase (CPR) to study 8-MOP metabolism and cytotoxicity assays in CYP1B1-expressing mammalian cells to assess PUVA sensitivity. We showed that P450s CYP1A1, CYP1A2, CYP1B1, CYP2A6 and CYP2E1 influence 8-MOP metabolism. As CYP1B1 is the most abundant P450 in human skin, we further demonstrated that: (i) CYP1B1 interacts with 8-MOP (ii) metabolism of the CYP1B1 substrates 7-ethoxyresorufin and 17-β-estradiol showed concentration-dependent inhibition by 8-MOP and (iii) inhibition of 7-ethoxyresorufin metabolism by 8-MOP was influenced by CYP1B1 genotype. The influence of CYP1B1 on PUVA cytotoxicity was further investigated in a Chinese hamster ovary cell line, stably expressing CYP1B1 and CPR, which was more sensitive to PUVA than control cells, suggesting that CYP1B1 metabolises 8-MOP to a more phototoxic metabolite(s). Our data therefore suggest that CYP1B1 significantly contributes to cutaneous 8-MOP metabolism, and that individuality in CYP1B1 expression may influence PUVA sensitivity.


Integrated Network Pharmacology and GC-MS-Based Metabolomics to Investigate the Effect of Xiang-Su Volatile Oil Against Menopausal Depression.
Menopausal depression perplexes a great number of women in later life. Xiangfu-Zisu (Xiang-Su), a traditional Chinese herbal pair composed of rhizomes of Cyperus rotundus L. (Xiangfu) and leaves of Perilla frutescens (L.) Britt. (Zisu), is frequently reported with antidepressant-like effects. The volatile oil from Xiangfu and Zisu has shown good antidepressant action, but its mechanism is still unclear. This study aimed to investigate the pharmacological mechanism of Xiang-Su (XS) volatile oil against menopausal depression through gas chromatography-mass spectrometry (GC-MS)-based network pharmacology and metabolomics. First, ADME screening was performed on actual detected components of XS volatile oil to obtain active constituents, and then duplicates of active constituent-related targets and menopausal depression-related targets were collected. These duplicates were considered as targets for XS volatile oil against menopausal depression, followed by GO and KEGG enrichment analyses. It showed that a total of 64 compounds were identified in XS volatile oil, and 38 active compounds were screened out. 42 overlapping genes between 144 compound-related genes and 780 menopausal depression-related genes were obtained. Results showed that targets of SLC6A4 and SLC6A3, regulation of serotonergic and dopaminergic synapses, were involved in the antidepressant mechanism of XS volatile oil. Next, antidepressant-like effect of XS volatile oil was validated in menopausal rats by ovariectomy (OVX) combined with chronic unpredictable mild stress (CUMS). Behavioral tests, biochemical analysis, and GC-MS-based non-targeted plasma metabolomics were employed to validate the antidepressant effect of XS volatile oil. Experimental evidence demonstrated that XS volatile oil reversed behavioral parameters in the sucrose preference test (SPT), open-field test (OFT), forced swim test (FST), and serum estradiol levels in OVX rats. Furthermore, results of metabolomics indicated that XS volatile oil mainly acts on regulating metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and tryptophan metabolism, which were corresponding with the above-predicted results. These data suggest that network pharmacology combined with metabolomics provides deep insight into the antidepressant effect of XS volatile oil, which includes regulating key targets like SLC6A4 and SLC6A3, and pathways of serotonergic and dopaminergic synapses.


Observation of Age-Related Decline in the Performance of the Transverse Abdominis Muscle.
Previous research has shown that the performance of skeletal muscle declines with advancing age. Coordination of the transverse abdominis (TrA), a deep postural muscle, has been shown to be reduced in persons with low back pain. No previous research has studied the effect of age on the activation on this muscle. To assess the effect of age on TrA activation in response to rapid arm abduction. Cross-sectional cohort study. University exercise physiology laboratory. A total of 18 adult men (aged 27 ± 7.0 years) for the younger group and 11 older adults (5 men and 6 women, aged 59.6 ± 4.0 years) were recruited for this study. Participants were positioned on a treatment table and performed a series of rapid arm abduction movements with their right arm while the activation of the TrA muscle was recorded using ultrasound imaging. Onset of arm abduction was measured using surface electromyography and synchronized with the ultrasound through the ultrasound unit's electrocardiogram channel. The mean time difference between the 2 events was calculated during post-hoc analysis. A Mann-Whitney test was performed to test for differences in the onset performance of the TrA muscle between the 2 groups. Results showed that the older group was significantly slower than the younger group in engaging their TrA in response to the rapid arm abduction (P = .036). A separate analysis of the older group data showed that no significant differences existed between the male and female participants that could potentially have acted as a confounding factor for the main finding (P = .126). This study shows that older adults were slower than younger adults in activating their TrA muscle in response to rapid arm abduction. This delay has the potential to lead to increased occasions when the low back is unprotected, increasing the likelihood of injury or low back pain.


Whole-genome resequencing reveals candidate genes associated with milk production trait in Guanzhong dairy goats.
Milk production is one of the most important economic utility of goats. Guanzhong dairy goat is a local dairy goat in Shaanxi Province of China and has high milk yield and quality. However, there are relatively few studies on molecular markers of milk production traits in Guanzhong dairy goats. In this study, we sequenced the whole genomes of 20 Guanzhong dairy goats, 10 of which had high milk yield (HM) and 10 of which had low milk yield (LM). We detected candidate signatures of selection in HM goats using Fst and π-ratio statistics and identified several candidate genes including ANPEP, ADRA1A and PRKG1 associated with milk production. Our results provide the basis for molecular breeding of milk production traits in Guanzhong dairy goats.


Numerical model of light propagation through Fabry-Perot etalons composed of interfaces with non-planar surface topography.
We present a model that calculates optical fields reflected and transmitted by a Fabry-Perot (FP) etalon composed of interfaces with non-planar surface topography. The model uses the Rayleigh-Rice theory, which predicts the fields reflected and transmitted by a single interface, to account for the non-planar surface topography of each interface. The Rayleigh-Rice theory is evaluated iteratively to account for all round trips that light can take within the FP etalon. The model predictions can then be used to compute Interferometer transfer function (ITF)s, by performing wavelength or angle resolved simulations enabling predictions of the bandwidth, peak transmissivity, and sensitivity of FP etalons. The model was validated against the Pseudospectral time-domain (PSTD) method, which resulted in good agreement. Since the model accuracy is expected to reduce as the Root mean square (RMS) of the topographic map increases, the error in the model's predictions was studied as a function of topographic map RMS. Finally, application of the model was exemplified by predicting the impact of roughness on ITFs and computing the changes in FP etalon transmissivity as cavity thickness is modulated by an ultrasonic wave.


[Effects of regulator peptides on expression of mannose-containing membrane structures in leukocytes in acute stress].
We have investigated the influence of regulative peptides (oxytocin, pituitrin, thyroid-releasing hormone and SNC) on the expression of mannose-containing membrane structures (MCMS) of lymphocytes and neutrophils in acute stress (3-hour immobilization on the back). MCMS were assayed by the indirect lectin-peroxidase test. We have found that MCMS-expression of lymphocytes significantly decreased but neutrophil MCMS-expression changed in different directions. SNC and thyroid-releasing hormone decreased and MCMS expression increased, respectively. Acute stress activated MCMS expression of lymphocytes. This activation was uncorrectable by the investigated peptides, MCMS expression of neutrophils was corrected by oxytocin, thyroid-releasing hormone and pituitrin. Thus, MCMS expression of leukocytes changed as a multimodal system by acute stress and peptide administration. This system may take part in pathogenesis of the stress reaction.


MALDI-IMS combined with shotgun proteomics identify and localize new factors in male infertility.
Spermatogenesis is a complex multi-step process involving intricate interactions between different cell types in the male testis. Disruption of these interactions results in infertility. Combination of shotgun tissue proteomics with MALDI imaging mass spectrometry is markedly potent in revealing topological maps of molecular processes within tissues. Here, we use a combinatorial approach on a characterized mouse model of hormone induced male infertility to uncover misregulated pathways. Comparative testicular proteome of wild-type and mice overexpressing human P450 aromatase (AROM+) with pathologically increased estrogen levels unravels gross dysregulation of spermatogenesis and emergence of pro-inflammatory pathways in AROM+ testis. In situ MS allowed us to localize misregulated proteins/peptides to defined regions within the testis. Results suggest that infertility is associated with substantial loss of proteomic heterogeneity, which define distinct stages of seminiferous tubuli in healthy animals. Importantly, considerable loss of mitochondrial factors, proteins associated with late stages of spermatogenesis and steroidogenic factors characterize AROM+ mice. Thus, the novel proteomic approach pinpoints in unprecedented ways the disruption of normal processes in testis and provides a signature for male infertility.


Biodiversity conservation in tropical agroecosystems: a new conservation paradigm.
It is almost certainly the case that many populations have always existed as metapopulations, leading to the conclusion that local extinctions are common and normally balanced by migrations. This conclusion has major consequences for biodiversity conservation in fragmented tropical forests and the agricultural matrices in which they are embedded. Here we make the argument that the conservation paradigm that focuses on setting aside pristine forests while ignoring the agricultural landscape is a failed strategy in light of what is now conventional wisdom in ecology. Given the fragmented nature of most tropical ecosystems, agricultural landscapes should be an essential component of any conservation strategy. We review the literature on biodiversity in tropical agricultural landscapes and present evidence that many tropical agricultural systems have high levels of biodiversity (planned and associated). These systems represent, not only habitat for biodiversity, but also a high-quality matrix that permits the movement of forest organisms among patches of natural vegetation. We review a variety of agroecosystem types and conclude that diverse, low-input systems using agroecological principles are probably the best option for a high-quality matrix. Such systems are most likely to be constructed by small farmers with land titles, who, in turn, are normally the consequence of grassroots social movements. Therefore, the new conservation paradigm should incorporate a landscape approach in which small farmers, through their social organizations, work with conservationists to create a landscape matrix dominated by productive agroecological systems that facilitate interpatch migration while promoting a sustainable and dignified livelihood for rural communities.


Indication of spatially random occurrence of Chlamydia-like organisms in Bufo bufo tadpoles from ponds located in the Geneva metropolitan area.
Occurrence of bacteria belonging to the order Chlamydiales was investigated for the first time in common toad (Bufo bufo) tadpole populations collected from 41 ponds in the Geneva metropolitan area, Switzerland. A Chlamydiales-specific real-time PCR was used to detect and amplify the Chlamydiales 16S ribosomal RNA-encoding gene from the tails of 375 tadpoles. We found the studied amphibian populations to host Chlamydia-like organisms (CLOs) attributable to the genera Similichlamydia, Neochlamydia, Protochlamydia and Parachlamydia (all belonging to the family Parachlamydiaceae), Simkania (family Simkaniaceae) and Estrella (family Criblamydiaceae); additionally, DNA from the genus Thermoanaerobacter (family Thermoanaerobacteriaceae) was detected. Global autocorrelation analysis did not reveal a spatial structure in the observed CLOs occurrence rates, and association tests involving land cover characteristics did not evidence any clear effect on CLOs occurrence rates in B. bufo. Although preliminary, these results suggest a random and ubiquitous distribution of CLOs in the environment, which would support the biogeographical expectation 'everything is everywhere' for the concerned microorganisms.


Pregnancy-related anxiety and depressive symptoms are associated with visuospatial working memory errors during pregnancy.
Cognitive deficits, especially in memory and concentration, are often reported during pregnancy. Similar cognitive dysfunctions can also occur in depression and anxiety. To date, few studies have investigated the associations between cognitive deficits and psychiatric symptoms during pregnancy. This field is of interest because maternal cognitive functioning, and particularly its higher-order aspects are related to maternal well-being and caregiving behavior, as well as later child development. Pregnant women (N =230), reporting low (n =87), moderate (n =97), or high (n =46) levels of depressive, general anxiety and/or pregnancy-related anxiety symptoms (assessed repeatedly with EPDS, SCL-90/anxiety subscale, PRAQ-R2, respectively) were tested in mid-pregnancy for their cognitive functions. A computerized neuropsychological test battery was used. Pregnant women with high or moderate level of psychiatric symptoms had significantly more errors in visuospatial working memory/executive functioning task than mothers with low symptom level. Depressive symptoms throughout pregnancy and concurrent pregnancy-related anxiety symptoms were significant predictors of the performance in the task. General anxiety symptoms were not related to visuospatial working memory. Cognitive functions were evaluated only at one time-point during pregnancy precluding causal conclusions. Maternal depressive symptoms and pregnancy-related anxiety symptoms were both associated with decrements in visuospatial working memory/executive functioning. Depressive symptoms seem to present more stable relationship with cognitive deficits, while pregnancy-related anxiety was associated only concurrently. Future studies could investigate, how stable these cognitive differences are, and whether they affect maternal ability to deal with demands of pregnancy and later parenting.


Use of immobilized L-asparaginase in acrylic microparticles in an extracorporeal hollow-fiber dialyzer.
L-asparaginase was immobilized under aseptic conditions in spherical microparticles of polyacrylamide. To avoid direct contact between blood and enzyme, we have applied the immobilized L-asparaginase in microparticles on the outer surface of the capillary fibers of a hemofilter. The hemofilters were very efficient in the transformation of L-asparagine to L-aspartic acid, both in vitro and in vivo. L-Asparagine in buffer (50 microM in 5 liters) was converted to L-aspartic acid within 60 min after circulation through a hemofilter containing 2000 I.U. of L-asparaginase. Circulating L-asparagine in healthy sheep (about 40-50 microM was reduced to low levels after 2 to 3 hr of perfusion with a unit containing 2000 I.U. of L-asparaginase. The reduction persisted for 3 to 4 hr after terminated treatment. Repeated, extracorporeal treatments in sheep showed that the L-asparagine decrease induced an increased resynthesis of L-asparagine, probably due to the action of the L-asparagine synthetase.


Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study.
Elucidating gut microbiota among gallstone patients as well as the complex bacterial colonization of cholesterol gallstones may help in both the prediction and subsequent lowered risk of cholelithiasis. To this end, we studied the composition of bacterial communities of gut, bile, and gallstones from 29 gallstone patients as well as the gut of 38 normal individuals, examining and analyzing some 299, 217 bacterial 16S rRNA gene sequences from 120 samples. First, as compared with normal individuals, in gallstone patients there were significant (P < 0.001) increases of gut bacterial phylum Proteobacteria and decreases of three gut bacterial genera, Faecalibacterium, Lachnospira, and Roseburia. Second, about 70% of gut bacterial operational taxonomic units (OTUs) from gallstone patients were detectable in the biliary tract and bacteria diversity of biliary tract was significantly (P < 0.001) higher than that of gut. Third, analysis of the biliary tract core microbiome (represented by 106 bacteria OTUs) among gallstone patients showed that 33.96% (36/106) of constituents can be matched to known bacterial species (15 of which have publicly available genomes). A genome-wide search of MDR, BSH, bG, and phL genes purpotedly associated with the formation of cholesterol gallstones showed that all 15 species with known genomes (e.g., Propionibacterium acnes, Bacteroides vulgates, and Pseudomonas putida) contained at least contained one of the four genes. This finding could potentially provide underlying information needed to explain the association between biliary tract microbiota and the formation of cholesterol gallstones. To the best of our knowledge, this is the first study to discover gut microbiota dysbiosis among gallstone patients, the presence of which may be a key contributor to the complex bacteria community assembly linked with the presence of cholesterol gallstones. Likewise, this study also provides the first large-scale glimpse of biliary tract microbiota potentially associated with cholesterol gallstones. Such a characterization of the biliary tract core microbiome has potentially important biological and medical implications regarding the role of bacteria in the formation cholesterol gallstones.


The certainty factor-based neural network in continuous classification domains.
The integration of certainty factors (CFs) into the neural computing framework has resulted in a special artificial neural network known as the CFNet. This paper presents the cont-CFNet, which is devoted to classification domains where instances are described by continuous attributes. A new mathematical analysis on learning behavior, specifically linear versus nonlinear learning, is provided that can serve to explain how the cont-CFNet discovers patterns and estimates output probabilities. Its advantages in performance and speed have been demonstrated in empirical studies.


Dissociation of catalase. A correlation between changes in sedimentation and spectroscopic properties accompanying dissociation of bacterial catalase in alkaline solution.
1. At high concentrations, in 10mm-phosphate buffer, pH7.0, the sedimentation coefficient of bacterial catalase varies with concentration according to: [Formula: see text] with S(0) (20,w)=11.30S and k(s)=6.29x10(-3)ml mg(-1). Sedimentation-equilibrium experiments yield a molecular weight of 240000. 2. Parallel studies of changes in sedimentation-velocity behaviour and in electronic spectra of bacterial catalase at pH>11 were made. Dissociation is indicated by the appearance of a slow-moving (2.9S) component in sedimentation patterns and this is accompanied by marked changes in absorption spectrum in the Soret region. Values of R=E(406)/E(355) show a theoretically predictable near-linear dependence on alpha, the degree of dissociation calculated from ultracentrifuge data. 3. The Soret absorption of bacterial catalase subunits is much lower than that of the native enzyme, and it is suggested that dissociation produces an environmental constraint on the prosthetic group that results in distortion of the porphyrin ring.


Population genetic dynamics of three-spined sticklebacks (Gasterosteus aculeatus) in anthropogenic altered habitats.
In industrialized and/or agriculturally used landscapes, inhabiting species are exposed to a variety of anthropogenic changes in their environments. Genetic diversity may be reduced if populations encounter founder events, bottlenecks, or isolation. Conversely, genetic diversity may increase if populations adapt to changes in selective regimes in newly created habitats. With the present study, genetic variability of 918 sticklebacks from 43 samplings (21.3 ± 3.8 per sample) at 36 locations from cultivated landscapes in Northwest Germany was analyzed at nine neutral microsatellite loci. To test if differentiation is influenced by habitat alterations, sticklebacks were collected from ancient running waters and adjacent artificial stagnant waters, from brooks with salt water inflow of anthropogenic and natural origin and adjacent freshwater sites. Overall population structure was dominated by isolation by distance (IBD), which was significant across all populations, and analysis of molecular variance (AMOVA) revealed that 10.6% of the variation was explained by river catchment area. Populations in anthropogenic modified habitats deviated from the general IBD structure and in the AMOVA, grouping by habitat type running/stagnant water explained 4.9% of variation and 1.4% of the variation was explained by salt-/freshwater habitat. Sticklebacks in salt-polluted water systems seem to exhibit elevated migratory activity between fresh- and saltwater habitats, reducing IBD. In other situations, populations showed distinct signs of genetic isolation, which in some locations was attributed to mechanical migration barriers, but in others to potential anthropogenic induced bottleneck or founder effects. The present study shows that anthropogenic habitat alterations may have diverse effects on the population genetic structure of inhabiting species. Depending on the type of habitat change, increased genetic differentiation, diversification, or isolation are possible consequences.