Poverty rates in Venezuela: getting the numbers right.
This article looks at household and individual poverty rates in Venezuela over the past seven years. For more than a year, the statement that poverty in Venezuela has increased under the government of President Hugo Chávez has appeared in scores of major newspapers, on major television and radio programs, and even in publications devoted to foreign policy. There are no data to support such statements, and in fact the available data show a decline in poverty for both individuals and households over the seven-year period: the percentage of people in poverty declined from 50 percent in the first quarter of 1999 to 43.7 percent in 2005. Further, there is no evidence to suggest any change in the methodology for measuring poverty during this period, as has been alleged in a number of reports. The article also examines briefly the impact of significant changes in non-cash benefits such as free health care, which are not taken into account in the measured poverty rate, on poor people in Venezuela. Finally, the authors look at how the mistakes in reporting on Venezuela's poverty rate were made; an appendix gives examples of mistakes in major media and foreign policy publications.


Modulation of Inter-kingdom Communication by PhcBSR Quorum Sensing System in Ralstonia solanacearum Phylotype I Strain GMI1000.
Ralstonia solanacearum is a ubiquitous soil-borne plant pathogenic bacterium, which frequently encounters and interacts with other soil cohabitants in competition for environmental niches. Ralsolamycin, which is encoded by the rmy genes, has been characterized as a novel inter-kingdom interaction signal that induces chlamydospore development in fungi. In this study, we provide the first genetic evidence that the rmy gene expression is controlled by the PhcBSR quorum sensing (QS) system in strain GMI1000. Mutation of phcB could lead to significant reduction of the expression levels of the genes involved in ralsolamycin biosynthesis. In addition, both the phcB and rmy mutants were attenuated in induction of chlamydospore formation in Fusarium oxysporum f. cubense and diminished in the ability to compete with the sugarcane pathogen Sporisorium scitamineum. Agreeable with the pattern of QS regulation, transcriptional expression analysis showed that the transcripts of the rmy genes were increased along with the increment of the bacterial population density. Taken together, the above findings provide new insights into the regulatory mechanisms that the QS system involves in governing the ralsolamycin inter-kingdom signaling system.


Degradation efficiencies of azo dye Acid Orange 7 by the interaction of heat, UV and anions with common oxidants: persulfate, peroxymonosulfate and hydrogen peroxide.
In this paper, the degradation of azo dye Acid Orange 7 (AO7) by three common peroxides (persulfate (PS), peroxymonosulfate (PMS) or hydrogen peroxide (H(2)O(2))) under various activation conditions, i.e., heat (25-80 degrees C), UV light (254 nm), or anions (SO(4)(2-), NO(3)(-), CO(3)(2-), HCO(3)(-), HPO(4)(2-), and Cl(-)), was investigated. The order of AO7 degradation efficiencies by heat activation is PS>>PMS>H(2)O(2). PS oxidation activated by heat (>50 degrees C) is an effective degradation technology, while PMS and H(2)O(2) are hardly activated. When assisted by UV, peroxides could all be activated and degrade AO7 quickly. The order is PS>H(2)O(2)>PMS. We activated peroxides, for the first time, by using some anions and compared the subsequently degradation efficiencies of AO7. It was found that PMS could be activated by some anions, but PS and H(2)O(2) cannot. The activation efficiencies of PMS by SO(4)(2-) and NO(3)(-) are negligible, whereas remarkable by HCO(3)(-), HPO(4)(2-), Cl(-) and CO(3)(2-). For HCO(3)(-), HPO(4)(2-) and Cl(-), the activation efficiencies become higher with the increase of anion concentration. For CO(3)(2-), however, the activation efficiency is higher at lower concentration.


The outcome of corneal grafting in patients with stromal keratitis of herpetic and non-herpetic origin.
To evaluate the outcome of corneal grafting in patients with stromal keratitis of herpetic (HSK) and non-herpetic origin, using predefined diagnostic criteria and standardised postoperative therapeutic strategies. 384 adult immunocompetent recipients of a corneal graft for herpetic (n = 186) or non-herpetic (n = 198) keratitis were followed up prospectively for up to 5 years. The herpetic group displayed significantly more corneal vascularisation (p = 0.013), more epithelial defects (p = 0.049), lower corneal sensitivity (p <0.001), more graft rejection episodes (p = 0.002), and required larger grafts (p<0.001). However, the postoperative course of visual acuity, endothelial cell numerical density, and rate of graft failures were similar in both groups. After 5 years, cumulative probability of graft survival in HSK patients (40.85%) was similar to that observed in individuals with non-herpetic keratitis (50.15%; log rank = 0.874; relative risk: 1.04). Despite a markedly higher preoperative risk profile in herpetic eyes, the functional outcomes of grafts in individuals with keratitis of herpetic or non-herpetic origin were similar. Probably the most important contribution is a consequent close follow up and a therapeutic strategy including systemic prophylaxis of viral recurrence and of graft rejection by well adopted local steroid therapy.


Performances of five risk algorithms in predicting cardiovascular events in patients with Psoriatic Arthritis: An Italian bicentric study.
In patients with psoriatic arthritis (PsA) an increased cardiovascular (CV) risk has been observed. Recently, a EULAR taskforce suggested to use a multiplication by the factor of 1.5 of CV risk algorithms in patients with inflammatory arthritis. This study aims to evaluate the performance of five original and adapted according to EULAR recommendations CV risk algorithms in PsA: SCORE, CUORE, Framingham Risk Score (FRS), QRISK2, and Reynold's Risk Score (RRS). Prospectively collected data from two Italian cohorts were used. Discriminatory ability for CV risk prediction was evaluated by the area under the ROC curves. Calibration between predicted and observed events was assessed by Hosmer-Lemeshow (HL) tests. Sensibility and specificity were calculated for low-to-intermediate and intermediate-to-high risk cut-offs. One hundred fifty-five patients were enrolled with an observation of 1550 patient/years. Area under the ROC were 0.7679 (95% CI 0.64768 to 0.88812), 0.864 (95% CI 0.79675 to 0.93278), 0.7575 (95% CI 0.65784 to 0.85708), 0.8660 (95% CI 0.79428 to 0.93772), and 0.7183 (95% CI 0.57795 to 0.85862) for SCORE, CUORE, FRS, QRSIK2, and RRS, respectively. HL tests demonstrated poor model fit (p<0.05) for SCORE, CUORE, and RRS. Discriminative ability and calibration were not improved by adaption of the algorithms according to EULAR recommendations. Up to 80% of CV events occurred in patients at "low risk" and up to 93% of CV events in patients at "low-intermediate risk". Adaption of the CV risk algorithms according to EULAR indications did not provide improvement in discriminative ability and calibration in patients with PsA.


Boosting the concordance index for survival data--a unified framework to derive and evaluate biomarker combinations.
The development of molecular signatures for the prediction of time-to-event outcomes is a methodologically challenging task in bioinformatics and biostatistics. Although there are numerous approaches for the derivation of marker combinations and their evaluation, the underlying methodology often suffers from the problem that different optimization criteria are mixed during the feature selection, estimation and evaluation steps. This might result in marker combinations that are suboptimal regarding the evaluation criterion of interest. To address this issue, we propose a unified framework to derive and evaluate biomarker combinations. Our approach is based on the concordance index for time-to-event data, which is a non-parametric measure to quantify the discriminatory power of a prediction rule. Specifically, we propose a gradient boosting algorithm that results in linear biomarker combinations that are optimal with respect to a smoothed version of the concordance index. We investigate the performance of our algorithm in a large-scale simulation study and in two molecular data sets for the prediction of survival in breast cancer patients. Our numerical results show that the new approach is not only methodologically sound but can also lead to a higher discriminatory power than traditional approaches for the derivation of gene signatures.


Free reactive oxygen species and nephrotoxicity of contrast agents.
The nephrotoxicity induced by contrast media remains a serious clinical problem, and the underlying mechanism has not been completely understood. Experimental and clinical investigations suggest that reactive oxygen species (ROS) are critical determinants of radiocontrast nephropathy (RCN), and that antioxidants can prevent this damage. Cultured human proximal renal tubule cells (HK-2) were exposed to hydrogen peroxide (H2O2) at different concentrations. H2O2-induced tubular DNA damage was examined in the presence of the antioxidant MESNA (sodium-2-mercaptoethane sulphonate). The induction of DNA damage was measured with the alkaline comet assay (single cell gel electrophoresis). We also studied 12 patients with stable renal impairment (median baseline creatinine 296 micromol/l; range: 203-495 micromol/l) undergoing cardiac catheterization/intervention prospectively. Patients received 800 mg MESNA intravenously 30 min before exposure to the contrast agent in addition to 0.9% saline hydration. In the cell cultures, oxidative stress on HK-2 cells induced increased DNA migration in the comet assay. Treatment of tubular cells with the antioxidant MESNA prior to the addition of H2O2 significantly reduced DNA migration in the comet assay. In the clinical study, treatment of the patients with MESNA prevented the adverse renal effect of contrast media (median serum creatinine 293; range: 187-433 micromol/l) 48 h after coronary angiography/intervention. Both the in vivo and the in vitro studies suggest that the ROS-mediated renal injury could be inhibited by a potent antioxidant such as MESNA.


Reproducing ear-canal reflectance using two measurement techniques in adult ears.
Clinical diagnostic applications of ear-canal reflectance have been researched extensively in the literature, however, the measurement uncertainty associated with the conventional measurement technique using an insert ear probe is unknown in human ear canals. Ear-canal reflectance measured using an ear probe is affected by multiple sources of error, including incorrect estimates of the ear-canal cross-sectional area and oblique ear-probe insertions. In this paper, ear-canal reflectance measurements are reproduced in an occluded-ear simulator and in 54 adult ear canals using two different measurement techniques: a conventional ear probe and a two-microphone probe that enables the separation of reverse- and forward-propagating plane waves. The two-microphone probe is inserted directly into test subjects' ear canals, and the two-microphone method is distinguished by not requiring the ear-canal cross-sectional area to calculate the ear-canal reflectance. The results show a reasonable agreement between the two measurement techniques. The paper further examines the influence of oblique ear-probe insertions and the compensation for such oblique insertions, which results in an improved agreement between the two measurement techniques.


Integrative Transcriptome Analyses of the Human Fallopian Tube: Fimbria and Ampulla-Site of Origin of Serous Carcinoma of the Ovary.
Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.


Effects of Processing-Induced Contamination on Organic Electronic Devices.
Organic semiconductors are a family of pi-conjugated compounds used in many applications, such as displays, bioelectronics, and thermoelectrics. However, their susceptibility to processing-induced contamination is not well understood. Here, it is shown that many organic electronic devices reported so far may have been unintentionally contaminated, thus affecting their performance, water uptake, and thin film properties. Nuclear magnetic resonance spectroscopy is used to detect and quantify contaminants originating from the glovebox atmosphere and common laboratory consumables used during device fabrication. Importantly, this in-depth understanding of the sources of contamination allows the establishment of clean fabrication protocols, and the fabrication of organic field effect transistors (OFETs) with improved performance and stability. This study highlights the role of unintentional contaminants in organic electronic devices, and demonstrates that certain stringent processing conditions need to be met to avoid scientific misinterpretation, ensure device reproducibility, and facilitate performance stability. The experimental procedures and conditions used herein are typical of those used by many groups in the field of solution-processed organic semiconductors. Therefore, the insights gained into the effects of contamination are likely to be broadly applicable to studies, not just of OFETs, but also of other devices based on these materials.


Lifestyle and osteoporosis.
Osteoporosis is associated with a number of lifestyle factors, including nutritional factors such as intake of calcium, protein, dairy food, fruits and vegetables and vitamin D status, and behavioural factors such as physical activity, smoking and alcohol consumption. Ensuring adequate calcium intake and vitamin D status and having regular weight-bearing physical activity throughout life are important for bone health and the prevention of osteoporosis and related fractures. Studies have shown that smoking and excessive alcohol intake have adverse effects on bone health and increase the risk of fracture. There is evidence suggesting that adequate protein intake and higher intake of fruits and vegetables are beneficial to bone health.


The multistory self: why the self is more than the sum of its autoparts.
A summary is presented of both the theoretical and clinical points made by the contributors to this issue of Journal of Clinical Psychology: In Session on the multiplicity of self. It is argued that there are many theoretical and clinical commonalities in the diverse range of psychotherapies that have been developed and that have been used in work with problems in the self-concept. Core problems encountered in clinical practice include an apparent self-integration that is attained through the exclusion of important parts of the self. The key to opening up clients who present such problems is through the use of experienced emotions and the therapeutic relationship. More extreme problems in the self-concept can be seen in the personality and psychotic disorders, in which the self may be chaotic or disintegrated. Such clients may need help with the development of a reflective self that can integrate and regulate the separate parts of the self-concept.


Transient shifts in bacterial communities associated with the temperate gorgonian Paramuricea clavata in the Northwestern Mediterranean Sea.
Bacterial communities that are associated with tropical reef-forming corals are being increasingly recognized for their role in host physiology and health. However, little is known about the microbial diversity of the communities associated with temperate gorgonian corals, even though these communities are key structural components of the ecosystem. In the Northwestern Mediterranean Sea, gorgonians undergo recurrent mass mortalities, but the potential relationship between these events and the structure of the associated bacterial communities remains unexplored. Because microbial assemblages may contribute to the overall health and disease resistance of their host, a detailed baseline of the associated bacterial diversity is required to better understand the functioning of the gorgonian holobiont. The bacterial diversity associated with the gorgonian Paramuricea clavata was determined using denaturing gradient gel electrophoresis, terminal-restriction fragment length polymorphism and the construction of clone libraries of the bacterial 16S ribosomal DNA. Three study sites were monitored for 4 years to assess the variability of communities associated with healthy colonies. Bacterial assemblages were highly dominated by one Hahellaceae-related ribotype and exhibited low diversity. While this pattern was mostly conserved through space and time, in summer 2007, a deep shift in microbiota structure toward increased bacterial diversity and the transient disappearance of Hahellaceae was observed. This is the first spatiotemporal study to investigate the bacterial diversity associated with a temperate shallow gorgonian. Our data revealed an established relationship between P. clavata and a specific bacterial group within the Oceanospirillales. These results suggest a potential symbiotic role of Hahellaceae in the host-microbe association, as recently suggested for tropical corals. However, a transient imbalance in bacterial associations can be tolerated by the holobiont without apparent symptoms of disease. The subsequent restoration of the Hahellaceae-dominated community is indicative of the specificity and resilience of the bacteria associated with the gorgonian host.


A crossbred reference population can improve the response to genomic selection for crossbred performance.
Breeding goals in a crossbreeding system should be defined at the commercial crossbred level. However, selection is often performed to improve purebred performance. A genomic selection (GS) model that includes dominance effects can be used to select purebreds for crossbred performance. Optimization of the GS model raises the question of whether marker effects should be estimated from data on the pure lines or crossbreds. Therefore, the first objective of this study was to compare response to selection of crossbreds by simulating a two-way crossbreeding program with either a purebred or a crossbred training population. We assumed a trait of interest that was controlled by loci with additive and dominance effects. Animals were selected on estimated breeding values for crossbred performance. There was no genotype by environment interaction. Linkage phase and strength of linkage disequilibrium between quantitative trait loci (QTL) and single nucleotide polymorphisms (SNPs) can differ between breeds, which causes apparent effects of SNPs to be line-dependent. Thus, our second objective was to compare response to GS based on crossbred phenotypes when the line origin of alleles was taken into account or not in the estimation of breeding values. Training on crossbred animals yielded a larger response to selection in crossbred offspring compared to training on both pure lines separately or on both pure lines combined into a single reference population. Response to selection in crossbreds was larger if both phenotypes and genotypes were collected on crossbreds than if phenotypes were only recorded on crossbreds and genotypes on their parents. If both parental lines were distantly related, tracing the line origin of alleles improved genomic prediction, whereas if both parental lines were closely related and the reference population was small, it was better to ignore the line origin of alleles. Response to selection in crossbreeding programs can be increased by training on crossbred genotypes and phenotypes. Moreover, if the reference population is sufficiently large and both pure lines are not very closely related, tracing the line origin of alleles in crossbreds improves genomic prediction.


ATP-dependent degradation of 125I-bovine serum albumin by rabbit reticulocytes does not need repression of an endogenous inhibitor.
The ubiquitin-dependent proteolysis of 125I-bovine serum albumin in rabbit reticulocytes has been investigated. Using various reticulocyte fractions (reticulocyte protease, inhibitor-free protease, "ubiquitin" and "inhibitor") in the presence or absence of ATP, we found that the repression of an endogenous inhibitor, as suggested by others for alpha-casein proteolysis, is unlikely for bovine serum albumin. Therefore, differences exist in the ATP-dependent proteolytic pathway of rabbit reticulocytes depending on the substrate. Fractionation of the reticulocyte ATP-dependent proteolytic system revealed at least two proteolytic and two inhibitory fractions involved in the proteolysis of bovine serum albumin.


THE DUAL ROLE OF SELECTION AND EVOLUTIONARY HISTORY AS REFLECTED IN GENETIC CORRELATIONS.
The patterns of genetic correlations between a series of eye and antenna characters were compared among two sets of spring-dwelling and cave-dwelling populations of Gammarus minus. The two sets of populations originate from different drainages and represent two separate invasions of cave habitats from surface-dwelling populations. Matrix correlations, using permutation tests, indicated significant correlations both between populations in the same basin and from the same habitat. The technique of biplot, which allows for the simultaneous consideration of relationships between different genetic correlations and different populations, was used to further analyze the correlation structure. A rank-3 biplot indicated that spring and cave populations were largely differentiated by eye-antennal correlations, whereas basins were differentiated by both eye-antennal and antennal-antennal correlations. Eye-antennal correlations, which are likely to be subject to selection, were most similar within habitats, which are likely to have similar selective regimes.


[Production and characterization of gold labeled monoclonal antibody against MC-LR].
Production of the gold labeled monoclonal antibody against MC-LR. Study the simple mechanism of the conjugation by the spectral analysis. Production and purification monoclonal antibodies against MC-LR by hybridoma technology. Production the 20nm colloidal gold and label the monoclonal antibody. Study the gold--McAb conjugate by the spectroanalysis. Monoclonal antibody produced by the hybridoma cells were tested for subtypes and designated as IgG2a for 8C11. The titers of antibody in ascites was 108.The IC50 for MC-LR was around 3ng/ml. The IgG molecule weight was 1.5 x 10(5). The structure of the antibody was altered to more tighter and stabler. Product the gold labeled monoclonalantibody against MC-LR conjugate successfully and keep the antige-binding determinant.


A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology.
Candida albicans is an opportunistic pathogen that is commonly found as a member of the human microflora. The ability of C. albicans to alter its cellular morphology has been associated with its virulence; yeast cells are more prevalent in commensal interactions whereas filamentous cells appear important in opportunistic infections. C. albicans encounters a multitude of other microbial species in the host environment and it is likely that they impact the C. albicans transition between virulent and non-virulent states. Here, we report that C. albicans morphology is significantly affected by the presence of Pseudomonas aeruginosa, another opportunistic pathogen. In a screen using a C. albicans HWP1-lacZ strain to indicate regions of filamentous growth, we identified P. aeruginosa mutants incapable of inhibiting C. albicans filamentation. Through these studies, we found that 3-oxo-C12 homoserine lactone, a cell-cell signalling molecule produced by P. aeruginosa, was sufficient to inhibit C. albicans filamentation without affecting fungal growth rates. Both microscopic analysis and real-time reverse transcription polymerase chain reaction analysis of morphology-specific markers confirmed that filamentation was suppressed by 200 microM 3-oxo-C12 homoserine lactone. Structurally related compounds with a 12-carbon chain length, e.g. C12-acyl homoserine lactone and dodecanol also affected C. albicans filamentation at similar concentrations. In contrast, other acylated homoserine lactones of different chain lengths did not affect fungal morphology. The activity of 3OC12HSL is compared with that of farnesol, a C. albicans-produced molecule also with a C12-backbone. The effects that bacteria have on the morphology of C. albicans represents one of the ways by which bacteria can influence the behaviour of fungal cells.


Interleukin-3 receptor α chain (CD123) is preferentially expressed in immature T-ALL and may not associate with outcomes of chemotherapy.
Interleukin-3 (IL-3) receptor α chain (CD123) plays an essential role in regulating the proliferation of hematopoietic stem cells. In the hematopoietic malignancies, CD123 expression has been found in acute myeloid leukemia (AML), B-precursor acute lymphoblastic leukemia (B-ALL), as well as dendritic cell malignancies. However, whether CD123 is also expressed in T-acute lymphoblastic leukemia (T-ALL) remains unknown. Using multi-parameter flow cytometry, we analyzed CD123 expression in 160 consecutive diagnostic T-ALL patients, including 88 pediatric T-ALL cases and 72 adult T-ALL cases. The minimal residual disease (MRD) was detected after one course of induction therapy to evaluate the treatment effects. CD123 expression was detected in 24 out of 88 (27 %) pediatric T-ALLs and 30 out of 72 (42 %) adult T-ALLs. Further analysis revealed that CD123 expression is associated with the maturation stage of T-ALLs. The frequencies of CD123-positive cases decreased from 83 to 40 % and 21 % in early T-precursor ALLs, T-precursor ALLs, and mature T-ALLs, respectively. Interestingly, we detected the CD4+CD8+ double-positive leukemic cells in 22 immature and 34 mature T-ALL patients. Of note, only 4 % of these patients expressed CD123. In addition, we found that 79 % of CD33+ and 64 % of CD117+ immature T-ALL patients also expressed CD123. However, CD123 expression did not predict the outcomes of the first course of induction therapy in T-ALL patients. In conclusion, we found that CD123 is preferentially expressed in immature T-ALL. Moreover, CD123 expression is strongly associated with cross-lineage expression of myeloid markers in early T-precursor ALL.


Clumping distractors around the target facilitates performance on the visual search task in the elderly.
Fifteen elderly participants and 15 young controls were tested on a version of the visual search task to determine if stimulus location had an effect on reaction time (RT). Location was manipulated by presenting the distractors clumped around a target or spread apart on the screen. Elderly participants performed worse overall. Clumping proved to be an important manipulation in the target absent (p < .001), but not the target present, condition. The manipulation of array size (6 versus 12 distractors) proved significant regardless of probe presence (p < .001) or absence (p < .001). Since clumping the distractors significantly improved the search times in the elderly, this suggests that a deficit in attention contributes to an inefficient search strategy in the elderly.


A pilot study of autofluorescence in the diagnosis of pleural disease.
Conventional medical thoracoscopy (MT), routinely performed in patients with pleural disease, does not always lead to a conclusive diagnosis. The endoscopic appearance of pleural diseases under white light could be misleading. Autofluorescence has been shown to be an interesting and effective diagnostic tool. The objective of this study was to evaluate the diagnostic value of autofluorescence imaging during MT. Patients with undiagnosed pleural effusion admitted to our clinical center between August 2013 and February 2014 were enrolled. MT was performed first with white light and then by autofluorescence. Endoscopic results of different diseases were recorded, and biopsy specimens were obtained for pathologic analysis. We calculated the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the two methods by comparing them with the pathologic results. Thirty-seven eligible patients were studied, including 21 with malignancy, nine with tuberculous pleurisy, three with infective pleurisy, and four with no diagnosed condition. Autofluorescence revealed additional malignant lesions, which were missed under white light in five patients. The diagnostic sensitivity and NPV of autofluorescence were 100% (95% CI, 98.5%-100%) and 100% (95% CI, 93.9%-100%), respectively. Autofluorescence was superior to white light, with a sensitivity of 92.8% (95% CI, 89.3%-95.3%) and NPV of 76.8% (95% CI, 67.0%-84.4%). For the specificity and PPV, no significant difference was found. The advantage of autofluorescence is its high sensitivity and NPV. It is useful to detect microlesions and delineate the pathologic margins. Autofluorescence can benefit patients with its better visualization.


An investigational study of a dual-layer, chorion-free amnion patch as a protective barrier following lumbar laminectomy in a sheep model.
The inherent properties of the human amniotic membrane (HAM) suggest its potential for use as a physical barrier during surgery to protect neural elements and vessels from the surrounding environment. The objective of this study was to evaluate the effect of a dual-layer, chorion-free amnion patch (DLAM; ViaShield®, Globus Medical Inc., Audubon, PA, USA) processed from HAM as a protective barrier following lumbar laminectomy in a sheep model. A multiplex immunoassay was performed to quantify the inherent cytokines present in the amnion after processing. Twelve skeletally mature female crossbred Suffolk sheep were randomly divided into two equal post-operative periods (4 and 10 weeks). Each sheep underwent a laminectomy at L3 and L5, and one of the surgical sites randomly received the DLAM treatment. At each postsurgical time point, the extent of epidural fibrosis and neurohistopathological responses at the laminectomy sites was assessed based on epidural fibrosis-dura tenacity scores and decalcified histology, respectively. Immunoassay results showed that inflammatory mediators and immunomodulatory cytokines were present in the amnion after processing, but no proangiogenic cytokines were detected. At 10 weeks, tissue tenacity was significantly less in the DLAM treatment group when compared with the operative control (1.2 ± 0.4 vs. 2.8 ± 0.4, p < 0.05), demonstrating the ability of DLAM to act as a barrier and cover the dura. Gross observations showed fewer fibroblasts in the DLAM group in comparison with the control at both post-operative time points. Fibroblast infiltration analysis indicated that at both 4 and 10 weeks, there were significantly more infiltrated fibroblasts in the operative control sites than in the DLAM-treated sites, expressed as a percentage of the total number of fibroblasts present (4 weeks: 72.3 ± 10.2% vs. 10.8 ± 10.1%, p < .05; 10 weeks: 84.9 ± 15.8% vs. 43.1 ± 11.6%, p < .05). Additionally, fibroblasts travelled further into the dura in the operative control group compared with the DLAM-treated group at both time points. In conclusion, this study found that DLAM reduced fibroblast infiltration and tissue tenacity following lumbar laminectomy in a sheep animal model. These findings support the potential use of DLAM in clinical practice as a protective barrier for neural elements and anterior vessels.


Economic Impact of Insufficient and Disturbed Sleep in the Workplace.
Insufficient and disturbed sleep are associated with significant morbidity among working-age adults. Poor sleep results in negative health outcomes and increases economic costs to employers. The current systematic review surveyed the peer-reviewed scientific literature and aggregated scientific evidence of sleep-related economic burdens borne by employers. A systematic review was performed to identify peer-reviewed, English language studies evaluating the economic impact of insufficient and disturbed sleep among adult employee populations. An exhaustive literature search was performed using keywords related to sleep, economics, and the workplace. Included were scientific studies (randomized controlled trials, cohort and case control studies, cross-sectional and longitudinal studies) examining specific employee populations with relevant sleep and economic outcomes. Each included study was evaluated for risk of bias and relevant data was extracted and summarized. Sleep problems among employee populations are associated with worsened workplace outcomes, such as presenteeism, absenteeism, and accidents. Sleep problems also increased costs to employers, ranging from US$322 to US$1967 per employee. Interventions to improve sleep, such as the use of blue-light filtering glasses, strategic shift scheduling, and targeted interventions to treat insomnia, may improve workplace outcomes and reduce costs. This review synthesizes the existing data regarding the negative impacts of insufficient and disturbed sleep on the workplace, suggesting that employers have an economic stake in their employees' sleep. PROSPERO: CRD42021224212.


Ankylosis of the mouse molar after systemic administration of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP).
The proposed homeostasis between fibroblasts in the periodontal ligament and bone cells lining the inner aspect of the alveolar wall is thought to be responsible for maintaining the width of the periodontal ligament space. In the present study, we attempted to interfere with this cellular balance by systemic administration of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP). The maxillary left molars of mice were extracted. They then received a daily subcutaneous injection of HEBP (10 mg P/kg b.w.) for periods of 10, 30 or 50 days. A 2nd group of animals received HEBP without molar extraction. Control groups were injected with Ringer's solution. The animals were sacrificed after the last injection and the mandibles processed for light and electron microscopy. HEBP treatment caused a significant decrease of the width of the periodontal ligament space which was influenced by time. Ankylosis started to occur after 30 days, predominantly in the interradicular areas and was more common around unopposed teeth. At 50 days, signs of resorption were seen along the acellular cementum layer. During HEBP-administration, extensive deposition of newly formed cementum matrix was observed along the cellular cementum but this activity was not seen along the acellular cementum. It is concluded that HEBP interferes with the mechanisms that mediate preservation of the periodontal ligament width.


Effects of activated T cells on natural killing.
Two populations of human blood lymphocytes--one forming rosettes with sheep erythrocytes, the other non-rosetting--are cytolytic in vitro for several long term cultured tumour-derived cell lines. A particular breast cancer-derived target cell (MDA-157) is only killed by the non-rosetting effector. Rosetting cells from normal donors infected or immunized with influenza virus augment cytolytic activity on MDA-157 targets by non-rosetting effector cells. Similar augmenting activity can be induced by incubating the rosetting population with sources of immune (gamma), but not leucocyte (alpha) interferon in vitro. This augmentation of cytolytic activity does not require compatibility at the major histocompatibility locus between the augmenting and effector populations.


Identification of chemical synapses in the pharynx of Caenorhabditis elegans.
The rhythmic contraction of the Caenorhabditis elegans pharynx is unique in that the network of 12 neurons, including two M3 neurons, that regulate the contraction is known. The neurotransmitters secreted by these cells, and the target cells responding to these chemical signals, are not known. Here, we describe an approach to obtain this missing information and use the M3 cells as an example. Electrical recordings (electropharyngeograms) were used in conjunction with temporally and spatially defined application of neurotransmitters via photolysis of inactive, photolabile precursors. To illustrate the technique we used pharyngeal preparations in which the two M3 neurons are intact and preparations in which they were removed by laser irradiation. Removal of M3 neurons results in the loss of the small negative peaks in the electropharyngeograms and an increase in time during which the pharynx remains contracted. We demonstrate that the application of glutamate by photolysis of caged glutamate to a pharynx from which the two M3 neurons were removed produces effects similar to those observed before removal of the M3 neurons. In control experiments, photolytic release from photolabile precursors of carbamoylcholine, a stable and well characterized analog of acetylcholine, or of gamma-aminobutyric acid, from photolabile precursors did not have this effect. The response depended on the amount of glutamate released. By reducing the size of the photolytic beam, glutamate was released at several different locations of the pharynx. Two areas of the pharynx mainly respond to the application of glutamate; one corresponds to the pm4 muscle cells in the metacorpus, and the other to the junction between muscle cells pm5 in the isthmus and pm6 in the terminal bulb.


Comparative oxidation studies of methionine residues reflect a structural effect on chemical kinetics in rhG-CSF.
The effect of protein conformation on the rate of chemical degradation is poorly understood. To address the role of structure on chemical degradation kinetics, comparative oxidation studies of methionine residues in recombinant human granulocyte colony-stimulating factor (rhG-CSF) were performed. The kinetics of oxidation of methionine residues by hydrogen peroxide (H2O2) in rhG-CSF and corresponding chemically synthesized peptides thereof was measured at different temperatures. To assess structural effects, equilibrium denaturation experiments also were conducted on rhG-CSF, yielding the free energy of unfolding as a function of temperature. A comparison of the relative rates of oxidation of methionine residues in short peptides with those of corresponding methionine residues in rhG-CSF yields an understanding of how protein tertiary structure affects oxidation reactions. For the temperature range that was studied, 4-45 degrees C, the oxidation rate constants followed an Arrhenius equation quite well, suggesting the lack of temperature-induced local structural perturbations that affect chemical degradation rates. One of the four methionine residues, Met 122, exhibited an activation energy significantly different from that of the corresponding peptide. Extrapolation of kinetic data predicts non-Arrhenius behavior around the melting temperature. Three phenomenological models based on different mechanisms are discussed, and an application to shelf life prediction of pharmaceuticals is presented.


Cation exchange--a common mechanism in the storage and release of biogenic amines stored in granules (vesicles)? II. Comparative studies on sodium-induced release of biogenic amines from the synthetic weak cation-exchangers Amberlite IRC-50 and duolite CS-100 and from biogenic (granule-enriched) materials.
Superfusion of phenylethylamine-, noradrenaline- or histamine-charged weak (carboxyl) cation-exchangers (IRC-50 and Duolite CS-100) with isotonic NaCl caused a release of the amines. Similarly, bovine chromaffin granules and nerve granule preparations from bovine splenic nerve, rat vas deferens and rat corpus striatum released their amine(s) upon superfusion with the same solution. The courses of release from the synthetic and biogenic materials showed very similar characteristics and fitted the same exchange equations. The observations support the view that the matrices of the biogenic amine-storing granules have the properties of weak cation-exchanger materials with carboxyls as the cation-binding groups, and that the NaCl-induced release of the biogenic amines is due to cation exchange (Na+ in equilibrium Amine+). The possibility that amine release in vivo is based on cation exchange is discussed.


Immunohistochemical reactions for fibroblast growth factor receptor in arteries of patients with moyamoya disease.
The cause of moyamoya disease remains unknown, and pathophysiological mechanisms remain uncertain. Basic fibroblast growth factor (FGF) is a pluripotent polypeptide that has been shown to play roles in angiogenesis, tumorigenesis and many other processes. In a previous study, we demonstrated immunohistochemically that the amount of basic FGF was increased above normal in the superficial temporal artery (STA) of patients with moyamoya disease. To clarify the function of basic FGF in moyamoya disease, we have performed an immunohistochemical study of the STA using a polyclonal antihuman FGF receptor antibody and also have tested immunohistochemical reactions for basic FGF. Twelve surgical specimens of the STA from patients with moyamoya disease were studied. Twelve specimens of the STA from skin flaps of patients with other neurological diseases were also investigated for comparison. The sections of the STA from patients with moyamoya disease showed dense and strong FGF receptor and basic FGF immunoreactivity in endothelial cells, in cells scattered in the thickened intima, and in smooth muscle cells in the media. In contrast, the sections of the STA of control patients showed faint basic FGF immunoreactivity. The statistical analysis revealed a significant difference of basic FGF immunoreactivity between moyamoya disease and other neurological diseases (chi 2 = 23; P = 0.0001). Moderately intense FGF receptor immunoreactivity was observed in most control patients. However, the statistical analysis revealed a significant difference of FGF receptor immunoreactivity between moyamoya disease and other neurological diseases (chi 2 = 13.382; P = 0.0012).(ABSTRACT TRUNCATED AT 250 WORDS)


Prostaglandin D synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPARγ.
The antitumor activity of prostaglandin (PG) D2 has been demonstrated against some types of cancer, including gastric cancer. However, exogenous PGD2 is not useful from a clinical point of view because it is rapidly metabolized in vivo. The aim of this study was to clarify the antitumor efficacy of an alternative, PGD synthase (PGDS), on gastric cancer cells. The effects of PGD2 and PGDS on the proliferation of gastric cancer cells were examined in vivo and in vitro. The expression levels of PGD2 receptors and peroxisome proliferator-activated receptor γ (PPARγ) were evaluated by RT-PCR. The effects of a PPARγ antagonist or siPPARγ on the proliferation of cancer cells and the c-myc and cyclin D1 expression were examined in the presence or absence of PGD2 or PGDS. PPARγ was expressed in gastric cancer cell lines, but PGD2 receptors were not. PGD2 and PGDS significantly decreased the proliferation of gastric cancer cells that highly expressed PPARγ. PGDS increased the PGD2 production of gastric cancer cells. A PPARγ antagonist and siPPARγ transfection significantly suppressed the growth-inhibitory effects of PGD2 and PGDS. Expression of c-myc and cyclin D1 was significantly decreased by PGD2 ; this inhibitory effect was suppressed by PPARγ antagonist. Both PGD2 and PGDS significantly decreased subcutaneous tumor growth in vivo. Tumor volume after PGDS treatment was significantly less than PGD2 treatment. These findings suggest that PGDS and PGD2 decrease the proliferation of gastric cancer cells through PPARγ signaling. PGDS is a potentially promising therapeutic agent for gastric cancers that express PPARγ.


Effects of antidepressant treatment on heart rate variability in major depression: a quantitative review.
The literature measuring effects of antidepressant and electroconvulsive therapy (ECT) for major depression on heart rate variability (HRV) in medically well individuals was reviewed. Fourteen studies evaluating HRV were included. Twenty three pre-post or within group comparisons were available. Treatment impact on measures of HRV was pooled over studies. We examined different classes of antidepressants, and for short and long electrocardiogram (ECG) recordings separately. Tricyclic antidepressants (TCAs) were associated with declines in most measures of HRV and significant increase in heart rate (HR) in studies with short recording intervals. No significant changes were found for longer recording times.Treatment effects with selective serotonin reuptake inhibitors (SSRIs) were more variable. Short-recording studies revealed a significant decrease in HR and an increase in one HRV measure. In two 24-hour recording studies no significant changes were observed. No relationship between ECT and HRV has been established in the literature. The effects of other drugs are reported. Few studies measure the effects of treatment of depression on HRV. Existing studies have generally used very small samples, employing a variety of measurements and methodologies. We confirm that TCAs are associated with a large decrease in HRV and increase HR. However, data for SSRIs is not clear. Although the effect of SSRIs on HRV is weaker than for TCAs, evidence shows that SSRIs are associated with a small decrease in HR, and an increase in one measure of HRV. The use of TCAs in depression leads to changes in HRV that are associated with increased risk of mortality.


[Development of an automatic pneumatic tourniquet system that determines pressures in synchrony with systolic blood pressure].
The correlation coefficients between arterial occlusion pressure and systolic blood pressure, diastolic blood pressure, limb circumference, body mass etc were obtained through healthy volunteer experiments, in which tourniquet were applied on upper/lower extremities. The prediction equations were derived from the data of experiments by multiple regression analysis. Based on the microprocessor C8051F340, a new pneumatic tourniquet system that can determine tourniquet pressure in synchrony with systolic blood pressure was developed and verified the function and stability of designed system. Results showed that the pneumatic tourniquet which automatically adjusts occlusion pressure in accordance with systolic blood pressure could stop the flow of blood to get a bloodless field.


High dose erythropoietin increases brain tissue oxygen tension in severe vasospasm after subarachnoid hemorrhage.
Vasospasm-related delayed cerebral ischemia (DCI) significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH). Erythropoietin (EPO) may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2). Seven consecutive poor grade SAH patients with multimodal neuromonitoring (MM) received systemic EPO therapy (30.000 IU per day for 3 consecutive days) for severe cerebral vasospasm. Cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), intracranial pressure (ICP), PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model. A total of 22 interventions were analyzed. Median age was 47 years (32-68) and 86 % were female. Three patients (38 %) developed DCI. MAP decreased 2 hours after intervention (P < 0.04) without significantly affecting CPP and ICP. PbtO2 significantly increased over time (P < 0.05) to a maximum of 7 ± 4 mmHg increase 16 hours after infusion. Brain metabolic parameters did not change over time. EPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation.


Implementing interoperable secure health information systems.
Ensuring the privacy and confidentiality of individuals has made security an indispensable component of health information systems. Delivery of healthcare services beyond the enterprise level to the regional, national or cross-border area places new challenges for security implementation. We review the current status and uptake of security measures in healthcare settings across European countries and examine in more detail some of the leading eHealth applications. Drawing on the findings of this analysis, we propose a generic model for streamlining the security implementation process on any level -local, regional, national or cross-border. Finally, we address the future prospects and requirements for advancing secure delivery of healthcare services across European borders.


SIRT6 Depletion Sensitizes Human Hepatoma Cells to Chemotherapeutics by Downregulating MDR1 Expression.
Multidrug resistance (MDR) due to overexpression of MDR1 is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). In this study, we explored the function and underlying molecular mechanism of SIRT6 in MDR of HCC. Chemotherapeutic agents (doxorubicin, cisplatin, and sorafenib) treatment increased SIRT6 mRNA and protein level in two HCC cell lines in a dose-dependent manner. SIRT6 depletion resulted in decreased cell viability and increased apoptosis in HCC cells treated with chemotherapeutic agents. Mechanistically, SIRT6 depletion reduced MDR1 transcription by targeting its promoter in HCC cells treated with chemotherapeutic agents. Consistently, the protein level of MDR1 was also reduced in SIRT6-depleted HCC cells. Further studies indicated that SIRT6 depletion may suppress CCAAT/enhancer binding protein β (C/EBPβ), to act as a transcriptional activator of MDR1 in HCC cells treated with chemotherapeutic agents. Importantly, forced expression of MDR1 could attenuate the apoptosis induced by chemotherapeutic agents in SIRT6-depleted cells. Taken together, these results indicated SIRT6 depletion enhanced chemosensitivity of human hepatoma cells by downregulating MDR1 expression through suppressing C/EBPβ. SIRT6 may serve as a novel target to enhance chemosensitivity in HCC cells.


Light, strong, and stable nanoporous aluminum with native oxide shell.
Aluminum (Al) metal is highly reactive but has excellent corrosion resistance because of the formation of a self-healing passive oxide layer on the surface. Here, we report that this native aluminum oxide shell can also stabilize and strengthen porous Al when the ligament (strut) size is decreased to the submicron or nanometer scale. The nanoporous Al with native oxide shell, which is a nanoporous Al-Al2O3 core-shell composite self-organized in a galvanic replacement reaction, is nonflammable under ambient conditions and stable against coarsening near melting temperatures. This material is stronger than conventional foams of similar density consisting of pure Al or Al-based composites, and also lighter and stronger than most nanoporous metals reported previously. Its light weight, high strength, and excellent stability warrant the explorations of functional and structural applications of this material, if more efficient and scalable synthesis processes are developed in the future.


Imaging elastic waves in solids: how to use laser feedback interferometry to visualize them.
The use of ultrasonic elastic waves is a well established technique for non-destructive testing of materials and structures, in particular to exploit the interaction of waves with structural features to detect and characterize defects. Optical methods offer the advantage of visualising the distribution of elastic waves in a non-contact manner without disturbing the elastic wave. In this work we propose a laser feedback interferometry (LFI) based system as a cost effective, non-contact, alternative to a well established laser Doppler vibrometer technique. We demonstrate the visualization of the elastic waves, using an example of an elastic wave propagating through a prismatic acrylic rod. We show that the ultra-compact and simple implementation of LFI enables accurate visualization of the elastic waves in solids, and opens the pathway to a range of new opportunities in ultrasonic non-destructive testing and evaluation.


Charcot-Marie-Tooth disease and Noonan syndrome with giant proximal nerve hypertrophy.
We report a family with Noonan syndrome (NS), giant proximal nerve hypertrophy, and hereditary motor sensory neuropathy type 1A (HMSN1A). Five members of a family were found to have clinical features of NS. In all cases, NS was associated with giant hypertrophy of proximal nerves and two individuals also exhibited café-au-lait spots. In one case, an 8-to-10-cm diameter pelvic mass was shown to be a grossly hypertrophied nerve, with histologic features of demyelination and remyelination. In addition, four of five family members affected with NS were found to have HMSN1A clinically and by demonstration of constitutional HMSN1A duplication on DNA testing. Linkage analysis for NS ruled out the involvement of the neurofibromatosis type 1 gene and the known NS locus in chromosome 12, supporting the existence of an additional NS locus.


Sexual Transgressions in Couples: The Influence of Dependence and Commitment on their Perception and Handling.
Transgressions occur frequently in romantic relationships, and how they are perceived is influenced by the type of transgression that occurred. By means of an experimental study of 399 participants (75.9% women and 24.1% men) aged 18 to 64 years old (Mage = 31.20, SD = 10.48), we examined the relationship between the type of sexual transgression (infidelity versus coercion), and perceived severity, strategies individuals would use in response to the transgression, and the probability they would leave the relationship, as well as levels of dependence and commitment. Results revealed higher perceived severity (p < .001, η2p = .24) and probability of leaving the relationship (p < .001, η2p = .39) in the infidelity scenario (versus coercion). Meanwhile, women (compared to men) rated sexual transgressions as more severe (p < .001, η2p = .04) and reported a higher probability of leaving the relationship (p < .001, η2p = .03), as well as a higher use of active conflict resolution strategies (exit, p = .048, η2p = .01, and voice, p < .001, η2p = .06) and lower use of passive strategies (loyalty, p < .001, η2p = .08). Finally, high levels of commitment and dependence predicted lower perceived severity (commitment, p < .001, 95% CI [-.72, -.20]; dependence, p < .001, 95% CI [-1.73, -.85]) and lower probability of leaving the relationship (commitment, p = .048, 95% CI [-.55, -.01]; dependence, p < .001, 95% CI [-1.66, -.73]) in coercion (versus infidelity) transgressions. These results highlight the normalization of sexual coercion in romantic relationships, which is not viewed as negatively as infidelity, and that commitment and dependence contribute to minimizing the negative impressions of it.


Molecule Self-Assembly Synthesis of Porous Few-Layer Carbon Nitride for Highly Efficient Photoredox Catalysis.
Polymeric carbon nitride (C3N4) has emerged as the most promising candidate for metal-free photocatalysts but is plagued by low activity due to the poor quantum efficiency and low specific surface area. Exfoliation of bulk crystals into ultrathin nanosheets has proven to be an effective and widely used strategy for enabling high photocatalytic performances; however, this process is complicated, time-consuming, and costly. Here, we report a simple bottom-up method to synthesize porous few-layer C3N4, which involves molecule self-assembly into layered precursors, alcohol molecules intercalation, and subsequent thermal-induced exfoliation and polycondensation. The as-prepared few-layer C3N4 expose more active sites and greatly enhance the separation of charge carriers, thus exhibiting a 26-fold higher hydrogen evolution activity than bulk counterpart. Furthermore, we find that both the high activity and selectivity for the oxidative coupling of amines to imines can be obtained under visible light that surpass those of other metal-free photocatalysts so far.


Early-life fecal microbiome and metabolome dynamics in response to an intervention with infant formula containing specific prebiotics and postbiotics.
This study examined fecal metabolome dynamics to gain greater functional insights into the interactions between nutrition and the activity of the developing gut microbiota in healthy term-born infants. The fecal samples used here originate from a randomized, controlled, double-blind clinical study that assessed the efficacy of infant formula with prebiotics and postbiotics (experimental arm) compared with a standard infant formula (control arm). A group of exclusively breast-fed term infants was used as a reference arm. First, conventional targeted physiological and microbial measurements were performed, which showed differences in fecal Bifidobacterium levels and corresponding activity (e.g., lactate levels). Next, the overall fecal microbiota composition was determined by 16S rRNA gene amplicon sequencing. The microbiota composition profiles showed several bacterial groups in the experimental arm to be significantly different from the control arm and mostly closer to the levels observed in the reference arm. Finally, we applied an untargeted UPLC-MS/MS approach to examine changes in the fecal metabolome. Fecal metabolome profiles showed the most distinct separation, up to 404 significantly different metabolites, between the study arms. Our data reveal that infant formula with specific prebiotics and postbiotics may trigger responses in the intestinal microbiota composition that brings the ensuing fecal metabolite profile of formula-fed infants closer toward those observed in breast-fed infants. Furthermore, our results demonstrate a clear need for establishing an infant gut metabolome reference database to translate these metabolite profile dynamics into functional and physiologically relevant responses.NEW & NOTEWORTHY Untargeted metabolomics techniques can provide a "snapshot" of an ecosystem in response to environmental stimuli, such as nutritional interventions. Our analyses of fecal samples from infants demonstrate the potential of phenotyping by metabolomics while deciphering the complex interactions of early-life nutrition and gut microbiome development.


Epidemiology of latent tuberculosis infection among patients with and without diabetes mellitus.
Individuals with type 2 diabetes mellitus (DM) are at a greater risk of tuberculosis (TB) reactivation. There is a paucity of information about the risk factors associated with latent tuberculosis infection (LTBI) in patients with diabetes. We conducted an observational study to compare the prevalence and risk factors associated with LTBI factors in Malaysian adults with and without DM. Four hundred and four patients with DM and 359 patients with non-DM at a regional primary care clinic were recruited as participants in this case-control study. The tuberculin sensitivity test (TST) was performed. The presence of LTBI was defined by a TST value of 10 mm in DM patients and 10 mm in the non-DM group. A logistic regression model was used to identify variables associated with LTBI. There was no statistical significant difference in the prevalence rates seen between the DM and non-DM group of the study. LTBI prevalence among patients with DM was 28.5%. The proportion of patients in the non-DM group with LTBI was 29.2%. When a critical cut-off of 8 mm was used, the adjusted odds ratio of LTBI in DM patients was 1.88 (95% confidence interval: 1.22-2.82). Smoking was an independent risk factor for LTBI regardless of DM status. HbA1c levels or anthropometric measurements were not associated with LTBI in diabetic patients. There is no significant risk of contracting LTBI in DM patients using the standard 10-mm TST cut-off. Nonetheless, using lower cut-offs in a DM population appear valid. Smoking is an important predictor of LTBI.


Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice.
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by survival motor neuron (SMN) protein deficiency which results in motor neuron loss and muscle atrophy. SMA is caused by a mutation or deletion of the survival motor neuron 1 (SMN1) gene and retention of the nearly identical SMN2 gene. SMN2 contains a C to T change in exon 7 that results in exon 7 exclusion from 90% of transcripts. SMN protein lacking exon 7 is unstable and rapidly degraded. The remaining full-length transcripts from SMN2 are insufficient for normal motor neuron function leading to the development of SMA. Three different therapeutic approaches that increase full-length SMN (FL-SMN) protein production are approved for treatment of SMA patients. Studies in both animal models and humans have demonstrated increasing SMN levels prior to onset of symptoms provides the greatest therapeutic benefit. Treatment of SMA, after some motor neuron loss has occurred, is also effective but to a lesser degree. The SMN∆7 mouse model is a well characterized model of severe or type 1 SMA, dying at 14 days of age. Here we treated three groups of ∆7SMA mice starting before, roughly during, and after symptom onset to determine if combining two mechanistically distinct SMN inducing therapies could improve the therapeutic outcome both before and after motor neuron loss. We found, compared with individual therapies, that morpholino antisense oligonucleotide (ASO) directed against ISS-N1 combined with the small molecule compound RG7800 significantly increased FL-SMN transcript and protein production resulting in improved survival and weight of ∆7SMA mice. Moreover, when give late symptomatically, motor unit function was completely rescued with no loss in function at 100 days of age in the dual treatment group. We have therefore shown that this dual therapeutic approach successfully increases SMN protein and rescues motor function in symptomatic ∆7SMA mice.


Assessment of sewage sludge bioremediation at different hydraulic retention times using mixed fungal inoculation by liquid-state bioconversion.
Sustainable, environmental friendly, and safe disposal of sewage treatment plant (STP) sludge is a global expectation. Bioremediation performance was examined at different hydraulic retention times (HRT) in 3-10 days and organic loading rates (OLR) at 0.66-7.81 g chemical oxygen demand (COD) per liter per day, with mixed filamentous fungal (Aspergillus niger and Penicillium corylophilum) inoculation by liquid-state bioconversion (LSB) technique as a continuous process in large-scale bioreactor. Encouraging results were monitored in treated sludge by LSB continuous process. The highest removal of total suspended solid (TSS), turbidity, and COD were achieved at 98, 99, and 93%, respectively, at 10 days HRT compared to control. The minimum volatile suspended solid/suspended solid implies the quality of water, which was recorded 0.59 at 10 days and 0.72 at 3 days of HRT. In treated supernatant with 88% protein removal at 10 days of HRT indicates a higher magnitude of purification of treated sludge. The specific resistance to filtration (SRF) quantifies the performance of dewaterability; it was recorded minimum 0.049 × 10(12) m kg(-1) at 10 days of HRT, which was equivalent to 97% decrease of SRF. The lower OLR and higher HRT directly influenced the bioremediation and dewaterability of STP sludge in LSB process. The obtained findings imply encouraging message in continuing treatment of STP sludge, i.e., bioremediation of wastewater for environmental friendly disposal in near future.


[Multiple injuries in mass accidents].
The treatment starts with reanimation, managing the shock, followed by life-saving surgery on the central nervous system, chest, abdomen, large blood vessels and the uropoietic system. From the very beginning the therapy should be conducted on an intradisciplinary basis, first with the anaesthesiologist, later with other specialists as required. Once the patient's life has been saved, treatment of eyes, hands and systematic attention to extremities should follow. Shock has to be managed within 24 hours. Luxations of large joints should be reposed on the date of injury, open fractures closed, all fractures immobilized in favourable position. No extension should be applied in patients suffering from brain injuries; fractures of the femur should be fixed surgically by a second team in the course of the neurosurgical operation. A stomatologist's assistance makes general anaesthesia possible even with fractures of the jaw. In mass accidents the therapeutic plan for the polytraumatized should be fixed on the following day. A mass accident involving 35 injured treated within two and a half hours demonstrates this procedure in 7 polytraumatized persons.


[Management of pneumonia in advanced stage dementia].
Alzheimer's dementia is a leading cause of morbidity and mortality with devastating consequences for the affected individuals and their family. Pneumonia is a common complication in patients with advanced dementia that is frequently the direct cause of death. Despite the relatively well-established progressive and non-reversible trajectory of Alzheimer's disease, these patients still frequently receive curative treatments during the last months of their lives and access to palliative care is often delayed. The approach and therapeutic options to manage pneumonia at the advanced stage of Alzheimer's disease are discussed in this article.


A model of the complex between human beta-microseminoprotein and CRISP-3 based on NMR data.
beta-Microseminoprotein (MSP), a 10kDa seminal plasma protein, forms a tight complex with cysteine-rich secretory protein 3 (CRISP-3) from granulocytes. The 3D structure of human MSP has been determined but there is as yet no 3D structure for CRISP-3. We have now studied the complex between human MSP and CRISP-3 with multidimensional NMR. (15)N-HSQC spectra show substantial differences between free and complexed hMSP. Using several 3D-NMR spectra of triply labeled hMSP in complex with a recombinant N-terminal domain of CRISP-3, most of the backbone of hMSP could be assigned. The data show that only one side of hMSP, comprising beta-strands 1, 4, 5, and 8 are affected by the complex formation, indicating that beta-strands 1 and 8 form the main binding surface. Based on this we present a tentative structure for the hMSP-CRISP-3 complex using the known crystal structure of triflin as a model of CRISP-3.


Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1 and NKX6.1 in INS-1 cells.
In the 60% pancreatectomy (Px) rat model of beta-cell adaptation, normoglycemia is maintained by an initial week of beta-cell hyperplasia that ceases and is followed by enhanced beta-cell function. It is unknown how this complex series of events is regulated. We studied isolated islets and pancreas sections from 14-day post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2-fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4-fold increase in beta-cell nuclear Nkx6.1 immunostaining. As PPAR-gamma activation is known to both lower proliferation and have prodifferentiation effects in many tissues, we studied PPAR-gamma actions in INS-1 cells. A 3-day incubation with the PPAR-gamma agonist troglitazone reduced proliferation and increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2. Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. Our results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1. Additional studies are needed to determine whether there is a regulatory role for PPAR-gamma signaling in the beta-cell adaptation following a 60% Px in rats.


Is cholangiography required for ex situ splitting of cadaveric livers?
Anomalous biliary anatomy is encountered frequently and, if not considered at the time of ex situ splitting of a cadaveric liver into left lateral segment and right lobe grafts, right-sided second-order ducts that enter the left system, or the segment IV duct, may be damaged, leading to biliary complications in the recipients. Bench cholangiography facilitates delineation of these anomalies, but if one considers the commonly encountered variations in biliary anatomy, in relation to the correct plane of division of the left hepatic duct (away from the hilum, close to the umbilical fissure), it is possible to avoid inadvertent injury to right-sided sectoral ducts. This approach, combined with careful probing of the ducts and absolute identification of the segment IV duct negates the contribution of cholangiography.


Managing gastroesophageal reflux disease.
A common condition, gastroesophageal reflux disease (GERD) involves the reflux of gastric contents into the esophagus. GERD may contribute to asthma, noncardiac chest pain, and other problems. This article presents trends in GERD management, including pathophysiology, diagnosis, and treatment. The authors also explore lifestyle modifications, pharmacologic therapy, and gastroenterology referral.


Chiral LC-MS/MS method for the discrimination of triiodothyronine enantiomers on a crown ether-based chiral stationary phase.
Considering the greater pharmaceutical and clinical interest of triiodothyronine (T3 ) thyroid hormone, an effective D/L-T3 enantiomer separation was performed on a crown ether-based chiral stationary phase by LC-MS/MS. In optimal analytical condition and selected reaction monitoring mode, the two enantiomers of T3 were baseline separated within 10 min. The limit of detection and limit of quantitation were found to be 0.05 and 0.10 ng/μl; 0.20 and 0.50 ng/μl for D- and L-T3 , respectively. During validation, this method proved to be feasible, accurate as well as enantioselective and sensitive for the resolution of T3 enantiomers. For commercial D- and L-T3 chemicals, the enantiomeric impurities as the other enantiomer were 0.11% and 4.61%. On the other hand, the impurity as D-T3 for commercial pharmaceutical products (liothyronine sodium tablets, two suppliers) was 0.68% and 6.57%.


News in gastroenterology, hepatology and digestive endoscopy.
Gastroenterology, hepatology and digestive endoscopy are rapidly evolving disciplines with significant advances in the diagnostics and treatment in the entire gastrointestinal tract. The aim of our article was to summarize new perspectives on relevant situations in gastroenterology and hepatology like acute pancreatitis, functional dyspepsia, rational indication of proton pump inhibitors, inflammatory bowel diseases (IBD), cholestatic liver diseases, alcohol induced hepatitis, non-alcoholic fatty live disease (NAFLD) and patophysiology of bilirubin and bile acids. Digestive endoscopy represents an interventional part of gastroenterology and key recent topics are mentioned like pancreatic cancer screening, arteficial intelligence, resection of low-risk neoplastic lesions, enteroscopy techniques, cholangio- and pancreatiscopy and extraluminal expansion of endoscopy techniques by means of endoscopic submucosal and transmural dissection, endoscopic myotomy and lumen apposing stents.


Enzyme-linked immunoadsorbent assays for myelin basic protein and antibodies to myelin basic protein.
Enzyme Linked Immunoadsorbent Assays are described for Myelin Basic Protein and antibodies to this protein. Under optimal conditions 30 pg of Basic Protein and 100 pg of antibody can be detected. Both assays are simple to establish, require small volumes of sample, and are highly reproducible. All the necessary reagents are stable indefinitely.


[Frequency of cancer in a specialty hospital in Mexico City. Implications for the development of early detection methods].
Cancer is the second cause of death in Mexico. The Juarez Hospital of Mexico is a highly specialized general hospital in which the frequency of cancer treated at the Oncology Unit is a representative sample of the frequency of cancer in the country. To learn about the frequency of presentation of tumors diagnosed in a third level hospital. We reviewed all the biopsies and surgical specimens diagnosed as cancer or malignant tumors registered in the pathology unit during the years 2006 to 2010. We grouped the cases by age, sex, and anatomic site. We identified the 10 most common cancers for both sexes, age groups and sex affected, raising the chances of early detection campaigns reinforce for the most common cancers and try to increase control and cure rates and improve coverage of the economically weak, for their integration into health systems. Information obtained reflects the reality of the country to the general population without entitlements. That in our country women suffer more than men of cancer that breast neoplasms and genital tract are the most frequent, and timely detection systems exist and should be strengthened to achieve greater eligible for early identification of cases in our population.


[Not Available].
This essay focuses on a moment when in medicine the prevailing static conception of disease was seen from a temporal perspective and conceived as a developmental process. Included in this discourse was Hahnemann's conception of homoeopathy. His conception combined two traditional systems of reading and interpreting signs of illness drawing a direct conclusion from a visible sign to a significant therapy while excluding causal-theoretical reflection about the meaning of signs. The basis of this idea is rooted in the general epistemological structure of the 18th century, in which knowledge was represented in the relation of a sign with meaning or significance. In contrast to the trinary structure of modern semiotics as exemplified by the Peircian terms "object, representamen and interpretant", medical semiotics and knowledge in the 18th century was instituted by the binary semantic relationship of representation. Thus, Hahnemann's roots in the intellectual world of the 18th century not only defined his contribution to the discourse, they may also explain his exclusion after the conceptual change of the early 19th century.


[Influence of the inoculum effect on minimal inhibitory concentrations of 3 derivatives of 5-nitro-imidazole and 11 other antibiotics on Bacteroides fragilis].
Three nitro-imidazole derivatives and eleven other antibiotics were studied for both their antimicrobial activity and the degree to which they produced inoculum effect on twenty strains of Bacteroides fragilis group. Five inocula were studied ranging from 10(5) to 10(9) CFU/ml. Statistical analysis show the significant influence of inoculum and those of strains. Nitro-imidazole derivatives exhibited a large inoculum effect while other antibiotics exhibited only a minimal to-no-inoculum effect.


The effect of stressful life events on the risk for psychosis: differences between Mexican at clinical and familial high risk.
Stressful life events (SLEs) in the development of early psychosis have been little studied in low-income countries. This study examines differences in the prevalence of SLEs in Mexican at clinical high risk (CHR) and those with familial high risk for psychosis who do not meet CHR criteria (non-CHR FHR). We also analyze the association between SLEs and CHR. Participants included 43 persons with CHR and 35 with non-CHR FHR. CHR criteria were assessed with the Comprehensive Assessment of At-Risk Mental State. SLEs were assessed using the Questionnaire of Stressful Life Events. Participants with CHR reported more SLEs associated with negative academic experiences than those in the non-CHR FHR group. Bullying (OR = 7.77, 95% CI [1.81, 33.32]) and low educational level (OR = 21.25, 95% CI [5.19, 46.90]) were the strongest predictors of CHR, while starting to live with a partner (OR = 0.26, 95% CI [0.10, 0.84]) was associated with a lower risk of CHR. Negative school experiences increase the risk of psychosis, particularly bullying, suggesting that schools may be ideal settings for implementing individual preventive strategies to reduce risk factors and increase protective factors to improve the prognosis of those at risk of developing psychosis. In Latin America, there are multiple barriers to early intervention in psychosis. It is thus crucial to identify risk and protective factors at the onset and in the course of psychosis in order to design effective preventive interventions.


Flow cytometric analysis of erythrocyte populations in Tn syndrome blood using monoclonal antibodies to glycophorin A and the Tn antigen.
Flow cytometric analysis employing monoclonal antibodies to the Tn antigen and glycophorin A was used to characterize the erythrocyte populations present in blood samples from individuals with Tn syndrome. Four monoclonal antibodies specific for the Tn antigen, Gal-NAc monosaccharide, on human erythrocytes were obtained from a fusion of splenocytes from a Biozzi mouse immunized with red cells from a Tn individual. These monoclonal antibodies specifically recognize GalNAc monosaccharide sites located on the erythrocyte cell surface sialoglycoproteins, glycophorin A and glycophorin B, and do not bind to fixed normal red cells presenting the Neu-NAc alpha 2-3Gal beta 1-3(NeuNAc alpha 2-6)GalNAc alpha 1-O-Ser(Thr) tetrasaccharide or to fixed neuraminidase-digested cells presenting the Gal-GalNAc disaccharide. The percentages of Tn-positive red cells in samples from six unrelated Tn donors ranged from 28 to 99%. Binding of the glycophorin A-specific monoclonal antibodies showed that the erythrocytes composing the Tn-negative fraction presented normal amounts of the M and N epitopes on glycophorin A. The presumed somatic mutational origin of Tn-positive cells was tested in blood samples from five normal donors; three possible Tn cells were observed after analysis of a total of 1.1 x 10(7) erythrocytes, suggesting that the frequency of such cells in normal individuals is less than 1 x 10(-6).


A histometrical study on the long bones of raccoon dogs, Nyctereutes procyonoides and badgers, Meles meles.
To obtain the data required for identification of skeletal remains excavated from archaeological sites, histometrical observations were made in the cross sections of the mid-shaft of humerus, radius, femur and tibia of raccoon dogs (Nyctereutes procyonoides) and badgers (Meles meles) captured in Kagoshima Prefecture. There were interspecific differences between both animals in the breadth, the depth and the area of medullary cavity at the mid-shaft of the bones, all measurements were greater in male than in female bones. The thickness and the area of compact bones in male raccoon dogs were larger than those of female. No differences in histological structure could be detected among the bones, but an interspecific difference was found in the shape of osteons; round and constant-sized osteons consisting of 3 to 5 lamellae in raccoon dogs, while round or elliptic osteons varying in size from 3 to 8 lamellae in badgers. The ratios, the osteon areas per unit compact bone areas, were higher in all the bones of raccoon dogs. The short diameters of osteons and the ratios were greater in males in both animals. In females, the short diameter of osteons was smaller, and the number of osteons was larger. The results revealed interspecific differences between both animals and sexual dimorphism in each species.


Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7.
LRRK2, a gene relevant to Parkinson's disease, encodes a scaffolding protein with both GTPase and kinase activities. LRRK2 protein is itself phosphorylated and therefore is subject to regulation by cell signalling; however, the kinase(s) responsible for this event have not been definitively identified. Here using an unbiased siRNA kinome screen, we identify and validate casein kinase 1α (CK1α) as being responsible for LRRK2 phosphorylation, including in the adult mouse striatum. We further show that LRRK2 recruitment to TGN46-positive Golgi-derived vesicles is modulated by constitutive LRRK2 phosphorylation by CK1α. These effects are mediated by differential protein interactions of LRRK2 with a guanine nucleotide exchange factor, ARHGEF7. These pathways are therefore likely involved in the physiological maintenance of the Golgi in cells, which may play a role in the pathogenesis of Parkinson's disease.


The Immunosuppressant Fingolimod (FTY720) for the Treatment of Mechanical Force-Induced Abnormal Scars.
Abnormal scars such as hypertrophic scars (HSs) and keloids are excessively growing scars that exhibit chronic inflammation and capillary vasculogenesis. The lipid mediator sphingosine-1-phosphate (S1P) is important in inflammatory cell recruitment and angiogenesis. Fingolimod (FTY720) is an analog of S1P and thus functionally antagonizes S1P receptors and inhibits the enzyme that produces S1P. We examined the effects of topical FTY720 injections on mechanical force-induced HS progression. Mechanical force-induced HSs were generated in C57BL6/J mice by suturing a dorsal incision and applying a stretching device on Days 6, 8, 10, and 12. On Days 8, 10, and 12, intracutaneous FTY720 (10 μM) or control vehicle injections were performed. On Day 14, scar tissues and blood were procured and subjected to histology and flow cytometry. Flow cytometry showed that FTY720 decreased the frequencies of macrophages with M2 predominance in the scars but had no effect on total, CD4+, or CD8a+ T cell frequencies. FTY720 also decreased the vascular endothelial cell frequencies in the scar along with the microvessels, as determined by immunohistochemistry. Compared to the vehicles, FTY720 treatment significantly reduced the gross scar area and the cross-sectional scar area on histology. On the other hand, FTY720 tended to reduce white blood cells and significantly reduced the lymphocyte frequencies in the blood. Topical FTY720 induces M2 predominance and impairs angiogenesis. Therefore, its local immunosuppressive mechanisms differ from those of conventional immunosuppressive agents. Topical FTY720 can be a novel therapeutic option for abnormal scars that are difficult to control with corticosteroids. Its lymphocytopenic effects may be limited by careful optimization of the treatment regimen.


Persistence of histoplasma in adrenals 7 years after antifungal therapy.
Adrenal histoplasmosis is an uncommon cause for adrenal insufficiency. The duration of treatment for adrenal histoplasmosis is not clear. Existing treatment regimens advocate antifungals given for periods ranging from 6 months to 2 years. We report here a rare case who showed persistence of histoplasma in adrenal biopsy 7 years after being initially treated with itraconazole for 9 months. This calls for a prolonged therapy with regular review of adrenal morphology and histology in these patients.


Mutual growth-promoting effect between Bifidobacterium bifidum WBBI03 and Listeria monocytogenes CMCC 54001.
In this study, Bifidobacterium bifidum WBBI03 and Listeria monocytogenes CMCC 54001 were selected to detect the changes in their growth pattern after mutual interaction between them. The proteomic changes after the interaction between the 2 bacteria were detected by the isobaric tags for relative and absolute quantitation method. The proteins related to the biosynthesis and cell reproduction were selected, and their changes at the transcriptional level were monitored by fluorescent quantitative PCR. Also, 3 other types of probiotic organisms and opportunistic pathogens were used to verify the results mentioned above. The results showed that growing the 2 organisms together could promote the growth of each other, resulting in earlier entry into the logarithmic phase. The results also showed that the expression of these proteins mostly tended to be upregulated at the translational and transcriptional level. The increase in the expression of these proteins might help promote the growth and reproduction of B. bifidum WBBI03 and L. monocytogenes CMCC 54001. One aspect of the biological significance of their presence in the normal intestine may be that the opportunistic pathogens promote the growth of the probiotics.


Epidemiology of Zika virus, 1947-2007.
Since 1947, Zika virus has been identified sporadically in humans in Africa and Asia; however, clinically consequential Zika virus disease had not been documented prior to the current outbreak in the Americas. Considering 6 decades have passed since the first identification of the virus, it is perhaps unexpected that Zika virus was recognised only recently as capable of causing disease epidemics. Substantial work on understanding the epidemiology of Zika virus has been conducted since the virus' first outbreak in 2007 in Micronesia; however, there has been little study of the earlier data on Zika virus. A systematic literature search was conducted to identify evidence of Zika virus infection in humans from 1947 to 2007. Data extracted included seroprevalence of Zika virus infection, age distributions of positive test results and serologic test modalities used. Country-level and age-specific seroprevalence was calculated. Estimates of seroprevalence by different serologic test modalities were compared. 12 026 citations were retrieved by the literature search, and 76 articles were included in this review. Evidence of Zika virus infection in humans was found in 29 countries in Africa, 8 countries in Asia and 1 country in Europe. Country-level seroprevalence of Zika virus infection ranged from 0.4% to 53.3%. Seroprevalence of Zika virus infection was found to increase across the lifespan; 15-40% of reproductive-age individuals may have been previously infected. No significant difference was found between estimates of seroprevalence by different serologic test modalities. Zika virus has likely been endemic for decades in certain regions of the world; however, the majority of reproductive-age individuals have likely not been infected. Historical evidence of Zika virus infection exists regardless of the serologic test modality used.


Promoter IV-BDNF deficiency disturbs cholinergic gene expression of CHRNA5, CHRM2, and CHRM5: effects of drug and environmental treatments.
Brain-derived neurotrophic factor (BDNF) promotes maturation of cholinergic neurons. However, how activity-dependent BDNF expression affects specific cholinergic gene expression remains unclear. This study addressed this question by determining mRNA levels of 22 acetylcholine receptor subunits, the choline transporter (CHT), and the choline acetyltransferase (ChAT) in mice deficient in activity-dependent BDNF via promoter IV (KIV) and control wild-type mice. Quantitative RT-PCR revealed significant reductions in nicotinic acetylcholine receptor alpha 5 (CHRNA5) in the frontal cortex and hippocampus and M5 muscarinic acetylcholine receptor (CHRM5) in the hippocampus, but significant increases in M2 muscarinic acetylcholine receptor (CHRM2) in the frontal cortex of KIV mice compared to wild-type mice. Three-week treatments with fluoxetine, phenelzine, duloxetine, imipramine, or an enriched environment treatment (EET) did not affect the altered expression of these genes except that EET increased CHRNA5 levels only in KIV frontal cortex. EET also increased levels of CHRNA7, CHT, and ChAT, again only in the KIV frontal cortex. The imipramine treatment was most prominent among the four antidepressants; it up-regulated hippocampal CHRM2 and frontal cortex CHRM5 in both genotypes, and frontal cortex CHRNA7 only in KIV mice. To the best of our knowledge, this is the first evidence that BDNF deficiency disturbs expression of CHRNA5, CHRM2, and CHRM5. Our results suggest that promoter IV-BDNF deficiency - which occurs under chronic stress - causes cholinergic dysfunctions via these receptors. EET is effective on CHRNA5, while its compensatory induction of other cholinergic genes or drugs targeting CHRNA5, CHRM2, and CHRM5 may become an alternative strategy to reverse these BDNF-linked cholinergic dysfunctions.


Remembering the good times: Herbert Remmer.
In the early 1970s, I experienced the joy of working in Tübingen, Germany with Herbert Remmer. The following brief description of events that occurred reflects personal impressions of those and subsequent interactions with Herbert Remmer. He will be remembered as a man blessed with a good humor, his interest in science and people, a philosophy of responsibility to his fellow man, and his enjoyment of life. The anecdotes presented here offer only a brief glimpse of this remarkable man.


The role of dental plaque in gingivitis and periodontitis.
A dynamic equilibrium between the periodontal microbiota and the host generally results in a clinical state of periodontal health, characterized by minimal inflammatory changes in the marginal gingival tissues. Maintenance of health is most easily achieved by controlling the resident mass of bacteria. In rare instances, control of specific microorganisms may be indicated. Lack of microbial control may lead to an imbalance between the microbiota and the host due to a markedly increased microbial mass and/or increased virulence of the micro-organisms present. Such alterations in the host-parasite equilibrium may result in transient episodes of tissue destruction and, in the long term, to cumulative damage to the periodontal tissues.


[When sex hurts the couple : the case of endometriosis].
Sexual health is a critical aspect of quality of life and is also influenced by medical conditions and health care interventions, particularly when gynaecological disorders are involved. Dyspareunia is a common symptom of endometriosis, a cause of personal distress and a main raison for seeking treatment. Endometriosis negatively affects different domains of sexual function and specific biopsychological variables (chronic pain, recurrence, infertility) may further worsen quality of sexual function and relationship. Consequences of endometriosis treatment on global sexual functioning have not been featured prominently in the available literature, assuming wrongly that sexual pain improvement was always translated into a recovered sexual health.


Avulsion Fracture of the Anterosuperior Iliac Spine: A Case Report.
Avulsion fracture of the anterosuperior iliac spine is a rare injury, typically occurring in adolescents during sports activities. We present a case of a 13-year-old adolescent who experienced recent pelvic trauma, resulting in inguinal pain and functional impairment of the left lower limb. Clinical examination revealed pain upon hip mobilization and extension of the left hip joint. Pelvic X-ray revealed a fracture-avulsion of the anterosuperior iliac spine. The patient was managed conservatively with rest and unloading of the injured lower limb. Follow-up showed resolution of pain within a few weeks and the resumption of sports activities at six months.


[Difficulties of describing human relationships with the help of psychoanalytic descriptive models: a critique of ego-psychology].
Progress of psychotherapy and of related behaviour sciences makes evident the importance of a better understanding of human relations. But psychoanalysis finds it hard to describe interpersonal processes without transference. In order to remain within the conceptional frame of metapsychology it has to see interaction between individuals as the oral, aggressive or sexual cathexis of an object or as satisfaction or denial of the subject by the object. The structure of the "ego", which--in analogy to medical thinking--is conceived as an organ with its functions, is considered to have no interpersonal activities. The "ego" of the classic psychoanalytic theory is chiefly occupied with itself. It has to care for its egoistical interests and to guarantee its self-preservation. As an auxiliary and meanwhile popular concept the "self" has been introduced to describe object-relations. This concept is not sharply defined. Due to its metapsychological implications it produces additional theoretical difficulties. Linguistic studies show that every inventory of words implies a certain insight into reality. For this reason the metapsychological machine-like concept of psychic structures does not permit new ideas about interpersonal relations. If we leave metapsychology and base on colloquial speech we see that the experience of "I" is much more related to persons than the rather autistic concept of the "ego" shows. Further we learn that self-preservation cannot be an egoistical interest; it depends on the attachment to others. All feelings of self-esteem depend much more on interpersonal relations than on "narcissistic regulations". From these experiences three conclusions are derived: a) One of the main qualities of the ego is the relatedness to persons. b) The concept of narcissistic regulation as a successor of primary narcissism is no longer useful. Narcissistic traits develop as the secundary compensations if the individual failed to build up satisfactory interpersonal relations. c) The revision of (a) ego-psychology and (b) theory of narcissism asks for modifications of the therapeutic technique, where now the interest is especially concentrated on interpersonal problems instead on the pathology of the ego.


Three-dimensional-printed cardiac prototypes aid surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases: Early experience and proof of concept in a resource-limited environment.
Three-dimensional. (3D) printing is an innovative manufacturing process that allows computer-assisted conversion of 3D imaging data into physical "printouts" Healthcare applications are currently in evolution. The objective of this study was to explore the feasibility and impact of using patient-specific 3D-printed cardiac prototypes derived from high-resolution medical imaging data (cardiac magnetic resonance imaging/computed tomography [MRI/CT]) on surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases (CHDs). Five patients with complex CHD with previously unresolved management decisions were chosen. These included two patients with complex double-outlet right ventricle, two patients with criss-cross atrioventricular connections, and one patient with congenitally corrected transposition of great arteries with pulmonary atresia. Cardiac MRI was done for all patients, cardiac CT for one; specific surgical challenges were identified. Volumetric data were used to generate patient-specific 3D models. All cases were reviewed along with their 3D models, and the impact on surgical decision-making and preoperative planning was assessed. Accurate life-sized 3D cardiac prototypes were successfully created for all patients. The models enabled radically improved 3D understanding of anatomy, identification of specific technical challenges, and precise surgical planning. Augmentation of existing clinical and imaging data by 3D prototypes allowed successful execution of complex surgeries for all five patients, in accordance with the preoperative planning. 3D-printed cardiac prototypes can radically assist decision-making, planning, and safe execution of complex congenital heart surgery by improving understanding of 3D anatomy and allowing anticipation of technical challenges.


Unusual position-sensitive jaw tremor responsive to botulinum toxin.
We report on a woman with a focal position-sensitive jaw tremor present with the jaw held slightly open or while drinking from a cup. Electromyography demonstrated a rhythmic 5 Hz alternating tremor involving masseter and digastric muscles with normal reciprocal inhibition. The tremor was markedly reduced with botulinum toxin injections.