Cell-free production of a functional oligomeric form of a Chlamydia major outer-membrane protein (MOMP) for vaccine development.
Chlamydia is a prevalent sexually transmitted disease that infects more than 100 million people worldwide. Although most individuals infected with Chlamydia trachomatis are initially asymptomatic, symptoms can arise if left undiagnosed. Long-term infection can result in debilitating conditions such as pelvic inflammatory disease, infertility, and blindness. Chlamydia infection, therefore, constitutes a significant public health threat, underscoring the need for a Chlamydia-specific vaccine. Chlamydia strains express a major outer-membrane protein (MOMP) that has been shown to be an effective vaccine antigen. However, approaches to produce a functional recombinant MOMP protein for vaccine development are limited by poor solubility, low yield, and protein misfolding. Here, we used an Escherichia coli-based cell-free system to express a MOMP protein from the mouse-specific species Chlamydia muridarum (MoPn-MOMP or mMOMP). The codon-optimized mMOMP gene was co-translated with Δ49apolipoprotein A1 (Δ49ApoA1), a truncated version of mouse ApoA1 in which the N-terminal 49 amino acids were removed. This co-translation process produced mMOMP supported within a telodendrimer nanolipoprotein particle (mMOMP-tNLP). The cell-free expressed mMOMP-tNLPs contain mMOMP multimers similar to the native MOMP protein. This cell-free process produced on average 1.5 mg of purified, water-soluble mMOMP-tNLP complex in a 1-ml cell-free reaction. The mMOMP-tNLP particle also accommodated the co-localization of CpG oligodeoxynucleotide 1826, a single-stranded synthetic DNA adjuvant, eliciting an enhanced humoral immune response in vaccinated mice. Using our mMOMP-tNLP formulation, we demonstrate a unique approach to solubilizing and administering membrane-bound proteins for future vaccine development. This method can be applied to other previously difficult-to-obtain antigens while maintaining full functionality and immunogenicity.


Examining the Acute Effects of Classroom-Based Physical Activity Breaks on Executive Functioning in 11- to 14-Year-Old Children: Single and Additive Moderation Effects of Physical Fitness.
Objective: Research supports the efficacy of acute, classroom-based, physical activity breaks on executive functioning in children. However, research pertaining to the effect of physical fitness on the acute physical activity-executive functioning relationship remains limited. The primary purpose of this study was to investigate the acute effects of classroom-based, teacher-delivered, physical activity breaks on executive functioning in 11-14-year-old children. We also investigated the potential moderating effects of both aerobic and musculoskeletal fitness on the acute physical activity-executive functioning relationship. Method: Participants (N = 116) completed pre- and post-test assessments of executive functioning (i.e., inhibition, switching, and updating) separated by a classroom-based physical activity break or sedentary classroom work. We manipulated the dose (i.e., length) and type of physical activity breaks. With regards to dose, participants in the experimental conditions engaged in 5-, 10-, or 20-min of physical activity whereas controls completed sedentary classroom math work at their desk. With regards to type, one experimental condition completed traditional physical activity breaks whereas the other experimental condition completed academic physical activity breaks (i.e., performed mental math and physical activity). Participants' mood, motivation, and self-efficacy were also assessed following the experimental manipulations. Results: Overall, executive function scores improved across each assessment following the physical activity breaks when compared to sedentary classroom work regardless of dose and type. Participants also reported more positive mood states, higher motivation to complete the executive function tests, and higher self-efficacy to perform the executive functions tests following the physical activity breaks. Single moderation analyses showed that low-moderate levels of aerobic fitness moderated the acute physical activity-executive functioning relationship. Additive moderation analysis showed, collectively, that both aerobic and musculoskeletal fitness moderated the acute physical activity-executive functioning relationship. Conclusion: Findings from the present study provide evidence for the acute effects of short (i.e., 5-20 min) classroom-based physical activity breaks on executive functioning and psychological states in children. Results also suggest levels of both aerobic and musculoskeletal fitness moderate these effects, however future research is needed to further elucidate this complex relationship.


The advantages of the disease model.
Health care professionals are interested in practical definitions that provide solutions to problems. There are many advantages to defining chemical dependence as a disease. This paper gives a health care professional clear directions regarding identifying the problem of chemical dependence and specifying a specific treatment plan for patients. We review the issues of personal responsibility, the moral model of addictions, and the neuropharmacology of the disease process, and advocate for the disease model as an effective, practical method for treating alcoholism and drug dependence.


From Vineyard Soil to Wine Fermentation: Microbiome Approximations to Explain the "terroir" Concept.
Wine originally emerged as a serendipitous mix of chemistry and biology, where microorganisms played a decisive role. From these ancient fermentations to the current monitored industrial processes, winegrowers and winemakers have been continuously changing their practices according to scientific knowledge and advances. A new enology direction is emerging and aiming to blend the complexity of spontaneous fermentations with industrial safety of monitored fermentations. In this context, wines with distinctive autochthonous peculiarities have a great acceptance among consumers, causing important economic returns. The concept of terroir, far from being a rural term, conceals a wide range of analytical parameters that are the basis of the knowledge-based enology trend. In this sense, the biological aspect of soils has been underestimated for years, when actually it contains a great microbial diversity. This soil-associated microbiota has been described as determinant, not only for the chemistry and nutritional properties of soils, but also for health, yield, and quality of the grapevine. Additionally, recent works describe the soil microbiome as the reservoir of the grapevine associated microbiota, and as a contributor to the final sensory properties of wines. To understand the crucial roles of microorganisms on the entire wine making process, we must understand their ecological niches, population dynamics, and relationships between 'microbiome- vine health' and 'microbiome-wine metabolome.' These are critical steps for designing precision enology practices. For that purpose, current metagenomic techniques are expanding from laboratories, to the food industry. This review focuses on the current knowledge about vine and wine microbiomes, with emphasis on their biological roles and the technical basis of next-generation sequencing pipelines. An overview of molecular and informatics tools is included and new directions are proposed, highlighting the importance of -omics technologies in wine research and industry.


[Level of serum phosphorus and adult type 2 diabetes mellitus].
To determine effects of the serum levels of phosphorus, calcium and magnesium on patients with type 2 diabetes mellitus. A total of 244 hospitalized patients were enrolled from 2014 to 2015, and they were assigned into a type 2 diabetic group (n=162) and control group (n=82). The serum levels of phosphorus, calcium and magnesium were determined. The correlations between blood levels of glucose and the serum levels of phosphorus, calcium or magnesium were analyzed. The serum level of phosphate in type 2 diabetic group was significantly lower than that in the control group (P<0.05). There was no significant difference in the level of serum calcium and magnesium between the two groups. In the type 2 diabetic group, there was no significant correlation between the level of blood glucose and the serum level of phosphorus, calcium or magnesium. In the control group, the blood glucose and serum levels of phosphorus were positively correlated (r=0.226, P=0.042), but there was no significant correlation between the level of blood glucose and the serum level of calcium or magnesium. Serum level of phosphorus is obviously decreased in type 2 diabetes patients, indicating that they may have a disorder in phosphorus metabolism.


Dissipation of contractile forces: the missing piece in cell mechanics.
Mechanical forces are key regulators of cell and tissue physiology. The basic molecular mechanism of fiber contraction by the sliding of actin filament upon myosin leading to conformational change has been known for decades. The regulation of force generation at the level of the cell, however, is still far from elucidated. Indeed, the magnitude of cell traction forces on the underlying extracellular matrix in culture is almost impossible to predict or experimentally control. The considerable variability in measurements of cell-traction forces indicates that they may not be the optimal readout to properly characterize cell contractile state and that a significant part of the contractile energy is not transferred to cell anchorage but instead is involved in actin network dynamics. Here we discuss the experimental, numerical, and biological parameters that may be responsible for the variability in traction force production. We argue that limiting these sources of variability and investigating the dissipation of mechanical work that occurs with structural rearrangements and the disengagement of force transmission is key for further understanding of cell mechanics.


Fate of Carbohydrates and Lignin during Composting and Mycelium Growth of Agaricus bisporus on Wheat Straw Based Compost.
In wheat straw based composting, enabling growth of Agaricus bisporus mushrooms, it is unknown to which extent the carbohydrate-lignin matrix changes and how much is metabolized. In this paper we report yields and remaining structures of the major components. During the Phase II of composting 50% of both xylan and cellulose were metabolized by microbial activity, while lignin structures were unaltered. During A. bisporus' mycelium growth (Phase III) carbohydrates were only slightly consumed and xylan was found to be partially degraded. At the same time, lignin was metabolized for 45% based on pyrolysis GC/MS. Remaining lignin was found to be modified by an increase in the ratio of syringyl (S) to guaiacyl (G) units from 0.5 to 0.7 during mycelium growth, while fewer decorations on the phenolic skeleton of both S and G units remained.


In silico designing of a new cysteine analogue of hirudin variant 3 for site specific PEGylation.
Hirudin is an anticoagulant agent of the salivary glands of the medicinal leech. Recombinant hirudin (r-Hir) displays certain drawbacks including bleeding and immunogenicity. To solve these problems, cysteine-specific PEGylation has been proposed as a successful technique. However, proper selection of the appropriate cysteine residue for substitution is a critical step. This study has, for the first time, used a computational approach aimed at identifying a single potential PEGylation site for replacement by cysteine residue in the hirudin variant 3 (HV3). Homology modeling (HM) was performed using MODELLER. All non-cysteine residues of the HV3 were replaced with the cysteine. The best model was selected based on the results of discrete optimized protein energy score, PROCHECK software, and Verify3D. The receptor binding was investigated using protein-protein docking by ClusPro web tool which was then visualized using LigPlot+ software and PyMOL. Finally, multiple sequence alignment (MSA) using ClustalW software and disulfide bond prediction were performed. According to the results of HM and docking, Q33C, which was located on the surface of the protein, was the best site for PEGylation. Furthermore, MSA showed that Q33 was not a conserved residue and LigPlot+ software showed that it is not involved in the hirudin-thrombin binding pocket. Moreover, prediction softwares established that it is not involved in disulfide bond formation. In this study, for the first time, the utility of the in silico approach for creating a cysteine analogue of HV3 was introduced. Our study demonstrated that the substitution of Q33 by cysteine probably has no effect on the biological activity of the HV3. However, experimental analyses are required to confirm the results.


[Bioavailability of minerals. 1. Determination methods].
Minerals have a important role in metabolism. Only a little is known on the recommended intake for maintenance of body function. Supplying depends on the bioavailability. Methods for experimental determination are described and limits and possibilities are discussed.


Effects of 4 weeks of β-alanine supplementation on aerobic fitness in water polo players.
The purpose of the present study was to investigate the ergogenic effects of 4 weeks of β-alanine supplementation on peak oxygen uptake ([Formula: see text]) and force associated with [Formula: see text] ([Formula: see text]) during a tethered swimming graded exercise test, and a three-minute all-out effort (3minALL-OUT) in water polo players. Twenty-two male national competitive level water polo players were randomly assigned to receive either 4 weeks of β-alanine (n = 11) or a placebo (n = 11) (i.e., 4.8 g·day-1 for 10 days, then6.4 g·day-1 for 18 days, resulting in 163.2 g over 28 days). The participants performed the TSGET and 3minALL-OUT before and after the supplementation period. There were no significant interaction effects between-groups for any variable, however, the magnitude-based inferences analyses showed a possibly beneficial effect (74%) of β-alanine supplementation on [Formula: see text] compared to placebo treatment (Δ% [post-pre] for Placebo group = -5.2%; Δ% [post-pre] for β-alanine group = +0.7%). Only the β-alanine group presented a significant reduction in [Formula: see text] expressed in absolute values (PRE = 3.3±0.6L·min-1; POST = 3.0±0.4L·min-1; p = .021). Similarly, only the β-alanine group presented a significant increase in critical force (PRE = 51.2±10.4N; POST = 56.5±13.1N; p = .044) and a reduction in the curvature constant parameter (W'; PRE = 2998.0±1103.7N·s; POST = 2224.6±1058.9N·s; p = .049). Thus, we can conclude that 4 weeks of β-alanine supplementation presented mixed results in water polo players, indicating that this nutritional strategy may not be effective in improving parameters of the TSGET and 3minALL-OUT .


Coordination-driven self-assembly of functionalized supramolecular metallacycles.
Coordination-driven self-assembly that combines rigid ditopic Pt(II) metal acceptors and bis-pyridyl organic donors provides a facile means of synthesizing well-defined metallacycles of predetermined size and geometry. Functionalization of the component acceptor or donor building blocks allows for the preparation of multifunctional supramolecular materials wherein the stoichiometry and position of individual functional moieties can be precisely controlled. The design, self-assembly, and applications of polyfunctional supramolecules incorporating functional moieties with host-guest, photonic, materials, and self-organizational properties is discussed.


Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin.
The methyl-CpG dinucleotide containing a symmetrical 5-methylcytosine (mC) is involved in gene regulation and genome stability. We report here that methylation-mediated transcriptional repressor methylated DNA-binding domain 1 (MBD1) interacts with methylpurine-DNA glycosylase (MPG), which excises damaged bases from substrate DNA. MPG itself actively represses transcription and has a synergistic effect on gene silencing together with MBD1. Chromatin immunoprecipitation analysis reveals the molecular movement of MBD1 and MPG in vivo: (i) The MBD1-MPG complex normally exists on the methylated gene promoter; (ii) treatment of cells with alkylating agent methylmethanesulfonate (MMS) induces the dissociation of MBD1 from the methylated promoter, and MPG is located on both methylated and unmethylated promoters; and (iii) after completion of the repair, the MBD1-MPG complex is restored on the methylated promoter. Mobility-shift and structural analyses show that the MBD of MBD1 binds a methyl-CpG pair (mCpG x mCpG) but not the methyl-CpG pair containing a single 7-methylguanine (N) (mCpG x mCpN) that is known as one of the major lesions caused by MMS. We further demonstrate that knockdown of MBD1 by specific small interfering RNAs significantly increases cell sensitivity to MMS. These data suggest that MBD1 cooperates with MPG for transcriptional repression and DNA repair. We hypothesize that MBD1 functions as a reservoir for MPG and senses the base damage in chromatin


[Distribution and patterns of tobacco consumption in Germany].
Tobacco consumption increases the risk of many chronic degenerative diseases and causes considerable social follow-up costs. The ongoing high tobacco consumption in the population, therefore, highlights an area in which health policy action is urgently required. According to the Telephone Health Survey 2003, about 37% of men aged 18 years and older and 28% of women of the same age are smokers. Almost half of the male daily smokers and a third of the female daily smokers consume 20 or more cigarettes a day, thus exposing themselves to a serious health risk. Among persons of socially disadvantaged groups, smoking prevalence is particularly high; they are also more likely to be heavy smokers and less likely to stop smoking. In the last 20 years, tobacco consumption has only declined slightly among men, while it has increased among women. These results underline the necessity for comprehensive tobacco prevention and tobacco control, and this means not only general measures but also initiatives focusing on specific target groups.


The Predictive Value of Different Nutritional Indices Combined with the GRACE Score in Predicting the Risk of Long-Term Death in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.
Nutritional status is associated with prognosis in acute coronary syndrome (ACS) patients. Although the Global Registry of Acute Coronary Events (GRACE) risk score is regarded as a relevant risk predictor for the prognosis of ACS patients, nutritional variables are not included in the GRACE score. This study aimed to compare the prognostic ability of the Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) in predicting long-term all-cause death in ACS patients undergoing percutaneous coronary intervention (PCI) and to determine whether the GNRI or PNI could improve the predictive value of the GRACE score. A total of 799 patients with ACS who underwent PCI from May 2018 to December 2019 were included and regularly followed up. The performance of the PNI in predicting all-cause death was better than that of the GNRI [C-index, 0.677 vs. 0.638, p = 0.038]. The addition of the PNI significantly improved the predictive value of the GRACE score for all-cause death [increase in C-index from 0.722 to 0.740; IDI 0.006; NRI 0.095; p < 0.05]. The PNI was superior to the GNRI in predicting long-term all-cause death in ACS patients undergoing PCI. The addition of the PNI to the GRACE score could significantly improve the prediction of long-term all-cause death.


Lossless Monochromator in an Ultrafast Electron Microscope Using Near-Field THz Radiation.
The ability to form monoenergetic electron beams is vital for high-resolution electron spectroscopy and imaging. Such capabilities are commonly achieved using an electron monochromator, which energy filters a dispersed electron beam, thus reducing the electron flux to yield down to meV energy resolution. This reduction in flux hinders the use of monochromators in many applications, such as ultrafast transmission electron microscopes (UTEMs). Here, we develop and demonstrate a mechanism for electron energy monochromation that does not reduce the flux-a lossless monochromator. The mechanism is based on the interaction of free-electron pulses with single-cycle THz near fields, created by nonlinear conversion of an optical laser pulse near the electron beam path inside a UTEM. Our experiment reduces the electron energy spread by a factor of up to 2.9 without compromising the beam flux. Moreover, as the electron-THz interaction takes place over an extended region of many tens of microns in free space, the realized technique is highly robust-granting uniform monochromation over a wide area, larger than the electron beam diameter. We further demonstrate the wide tunability of our method by monochromating the electron beam at multiple primary electron energies from 60 to 200 keV, studying the effect of various electron and THz parameters on its performance. Our findings have direct applications in the fast-growing field of ultrafast electron microscopy, allowing time- and energy-resolved studies of exciton physics, phononic vibrational resonances, charge transport effects, and optical excitations in the mid IR to the far IR.


Methylated DNA markers for plasma detection of ovarian cancer: Discovery, validation, and clinical feasibility.
Aberrant DNA methylation is an early event in carcinogenesis which could be leveraged to detect ovarian cancer (OC) in plasma. DNA from frozen OC tissues, benign fallopian tube epithelium (FTE), and buffy coats from cancer-free women underwent reduced representation bisulfite sequencing (RRBS) to identify OC MDMs. Candidate MDM selection was based on receiver operating characteristic (ROC) discrimination, methylation fold change, and low background methylation among controls. Blinded biological validation was performed using methylated specific PCR on DNA extracted from independent OC and FTE FFPE tissues. MDMs were tested using Target Enrichment Long-probe Quantitative Amplified Signal (TELQAS) assays in pre-treatment plasma from women newly diagnosed with OC and population-sampled healthy women. A random forest modeling analysis was performed to generate predictive probability of disease; results were 500-fold in silico cross-validated. Thirty-three MDMs showed marked methylation fold changes (10 to >1000) across all OC subtypes vs FTE. Eleven MDMs (GPRIN1, CDO1, SRC, SIM2, AGRN, FAIM2, CELF2, RIPPLY3, GYPC, CAPN2, BCAT1) were tested on plasma from 91 women with OC (73 (80%) high-grade serous (HGS)) and 91 without OC; the cross-validated 11-MDM panel highly discriminated OC from controls (96% (95% CI, 89-99%) specificity; 79% (69-87%) sensitivity, and AUC 0.91 (0.86-0.96)). Among the 5 stage I/II HGS OCs included, all were correctly identified. Whole methylome sequencing, stringent filtering criteria, and biological validation yielded candidate MDMs for OC that performed with high sensitivity and specificity in plasma. Larger plasma-based OC MDM studies, including testing of pre-diagnostic specimens, are warranted.


[Wild birds--a reservoir for influenza A virus].
Influenza A viruses, in particular the H5 and H7 subtypes, have caused epizootic diseases in poultry for a long time. Wild aquatic birds and shorebirds form the natural virus reservoir. All influenza virus subtypes and almost all possible haemagglutinin/neuraminidase combinations have been detected in wild birds, whereas relatively few have been detected in humans and other mammals. In 1997, the emerging and spreading of the highly pathogenic strain H5N1 within Asia was supported by lack of hygiene in commercial poultry units and by the existence of live bird markets. During autumn 2005, migratory birds have been accused for spreading the infection along their flyways to Europe including Switzerland. For early detection of introduction to Europe, many countries have initiated surveillance programs for avian influenza in wild birds. Vaccines against influenza A viruses are existing for birds and are widely used to protect domestic fowl in endemic regions of Asia as well as valuable birds in zoos worldwide. Subtype H5N1 could be the progenitor virus of a new pandemic influenza virus. Therefore, the World Organisation for Animal Health (OIE, Paris) as well as the Food and Agriculture Organisation of the United Nations (FAO, Rome) will need to increase their efforts to assist countries to combat the disease in the field.


Suggested guidelines for immunohistochemical techniques in veterinary diagnostic laboratories.
This document is the consensus of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) Subcommittee on Standardization of Immunohistochemistry on a set of guidelines for immunohistochemistry (IHC) testing in veterinary laboratories. Immunohistochemistry is a powerful ancillary methodology frequently used in many veterinary laboratories for both diagnostic and research purposes. However, neither standardization nor validation of IHC tests has been completely achieved in veterinary medicine. This document addresses both issues. Topics covered include antibody selection, fixation, antigen retrieval, antibody incubation, antibody dilutions, tissue and reagent controls, buffers, and detection systems. The validation of an IHC test is addressed for both infectious diseases and neoplastic processes. In addition, storage and handling of IHC reagents, interpretation, quality control and assurance, and troubleshooting are also discussed. Proper standardization and validation of IHC will improve the quality of diagnostics in veterinary laboratories.


Sirtuin 1 and oral cancer.
The sirtuins (SIRTs) are a family of highly conserved histone deacetylases (HDACs) consisting of seven members (SIRT1-SIRT7). Over the past few decades, SIRT1 has been the most extensively studied and garnered tremendous attention in the scientific community due to its emerging role in cancer biology. However, its biological role in the regulation of oral cancer is not yet fully understood. Owing to contradictory findings regarding the role of SIRT1 in oral cancer, debate about it continues. The present study discusses the biological roles and potential therapeutic implications of SIRT1 in precancerous oral lesions and oral cancer.


Stabilization of juvenile metachromatic leukodystrophy after bone marrow transplantation: a 13-year follow-up.
A 29-year-old female patient with juvenile metachromatic leukodystrophy diagnosed at age 14 years received a bone marrow transplant at age 16 years. A report was published 6 years after bone marrow transplantation concluding that the disease had slowly progressed in the 2 years following bone marrow transplantation. We now report on a further 7-year follow-up, typified by a steady state of spastic paraplegia and mild dementia. Neurophysiological, neuroradiological, and psychological status also remained stable. In the patient's leukocytes, the activity of arylsulfatase A, the enzyme deficient in untreated metachromatic leukodystrophy, was within the normal range whereas urinary sulfatides remained elevated. Data on the natural course of juvenile metachromatic leukodystrophy are rare, so in the present case it is difficult to establish whether the rather favorable course can be attributed with certainty to bone marrow transplantation. The long-term stabilization in this patient, however, suggested that bone marrow transplantation may halt the progression of juvenile metachromatic leukodystrophy.


How long may a breath sample be stored for at -80 °C? A study of the stability of volatile organic compounds trapped onto a mixed Tenax:Carbograph trap adsorbent bed from exhaled breath.
Thermal desorption is used extensively in exhaled breath volatile organic compound (VOC) analysis, and it is often necessary to store the adsorbent tube samples before analysis. The possible introduction of storage artefacts is an important potential confounding factor in the development of standard methodologies for breath sampling and analysis. The stability of VOCs trapped from breath samples onto a dual bed Tenax(®) TA:Carbograph adsorbent tube and stored -80°C was studied over 12.5 month. 25 samples were collected from a single male participant over 3 h and then stored at -80 °C. Randomly selected adsorbent tubes were subsequent analysed by thermal desorption-gas chromatography-mass spectrometry at 5 times points throughout the 12.5 month of the study. Toluene-d8, decane-d22 and hexadecane-d34 internal standards were used to manage the instrument variability throughout the duration of the study. A breath-matrix consisting of 161 endogenous and 423 exogenous VOC was created. Iterative orthogonal partial least squared discriminant analysis (OPLS-DA) and principal components analysis (PCA) indicated that it was not possible to detect storage artefacts at 1.5 month storage. By 6 month storage artefacts were discernible with significant changes observed for 27% of the recovered VOC. Endogenous VOC were observed to be more susceptible to storage. A paired two-tailed t-test on the endogenous compounds indicated that the maximum storage duration under these conditions was 1.5 month with 94% of the VOCs stable. This study indicates that a prudent approach is best adopted for the storage of adsorbent samples; storage times should be minimised, and storage time examined as a possible discriminatory factor in multivariate analysis.


[Molecular mechanism involved in adhesion of monocytes to endothelial cells induced by nicotine and Porphyromonas gingivalis-LPS].
To investigate molecular mechanism involved in nicotine in combination with Porphyromonas gingivalis (P.g) caused monocyte-endothelial cell adhesion. The effect of nicotine, P.g-lipopolysaccharide (P.g-LPS) and their combination on the proliferation of U937 cells was determined by CCK-8 method. Interleukin-6 (IL-6) expression was investigated by real-time PCR after U937 cells were treated with nicotine, P.g-LPS and their combination. In human umbilical vein endothelial cells (HUVECs), the expressions of monocyte chemoattractant protein CCL-8 and adhesion molecules including vascular cell adhesion molecule 1 (Vcam-1), very late antigen 4 alpha (VLA4α), tumor necrosis factor receptor superfamily member 4 (OX40) and OX40 ligand (OX40L) were detected by real-time PCR or Western blotting assays after HUVEC cells were treated with nicotine, P.g-LPS and their combination. Adhesion of monocytes to endothelial cells was detected after the HUVECs and U937 cells were stimulated with nicotine, P.g-LPS and their combination, respectively. P.g-LPS did not affect the proliferative ability of nicotine in U937 cells. However, the ability of P.g-LPS induced IL-6 expression was inhibited by 100 μmol/L nicotine in U937 cells. In HUVECs, the expressions of CCL-8, Vcam-1, VLA4α, OX40 and OX40L were significantly up-regulated by nicotine and P.g-LPS combination compared with nicotine alone, P.g-LPS alone and the untreated control. Adhesion of monocytes to HUVECs results showed that the two types of cells treated with nicotine in combination with P.g-LPS could markedly increase the adhesion ability of monocytes to HUVECs. P.g-LPS in combination with nicotine could recruit monocytes to endothelial lesion through up-regulation of CCL-8, and promote adhesion of monocytes to endothelial cells through enhancement of Vcam-1/VLA4α and OX40/OX40L interactions, which could be involved in the initiation and development of atherosclerosis.


A convergent approach to the total synthesis of telmisartan via a Suzuki cross-coupling reaction between two functionalized benzimidazoles.
A direct and efficient total synthesis has been developed for telmisartan, a widely prescribed treatment for hypertension. This approach brings together two functionalized benzimidazoles using a high-yielding Suzuki reaction that can be catalyzed by either a homogeneous palladium source or graphene-supported palladium nanoparticles. The ability to perform the cross-coupling reaction was facilitated by the regio-controlled preparation of the 2-bromo-1-methylbenzimidazole precursor. This convergent approach provides telmisartan in an overall yield of 72% while circumventing many issues associated with previously reported processes.


Scleral buckle removal following retinal reattachment surgery: clinical and microbiologic aspects.
Scleral buckle infection following retinal reattachment surgery is infrequent but not rare. We identified 45 cases among approximately 3000 scleral buckling procedures performed at our institution between July 1, 1985 and July 1, 1991. The scleral buckle was exposed in all 45, and the subsequent microbiologic culture was positive in 33. The most common causative organism was coagulase negative staphylococci (17 of 33 cases with positive cultures). Risk factors for an adverse outcome included positive culture, preoperative vision < or = 20/200, and preoperative retinal detachment. Broad spectrum antibiotics covered organism sensitivity profiles in 16 of the 18 cases tested. Prompt removal of infected buckles and treatment with broad-spectrum topical antibiotics are important for maintaining vision.


Molecular characterization of Aspergillus fumigatus TcsC, a characteristic type III hybrid histidine kinase of filamentous fungi harboring six HAMP domains.
The type III hybrid histidine kinase (HHK) TcsC enables the pathogenic mold Aspergillus fumigatus to thrive under hyperosmotic conditions. It is, moreover, of particular interest, since it is the target of certain antifungal agents, such as fludioxonil. This study was aimed at a functional characterization of the domains that constitute the sensing and the kinase module of TcsC. The sensing module consists of six HAMP domains, an architecture that is commonly found in type III HHKs of filamentous fungi. To dissect the functional role of the individual domains, we have analyzed a set of truncated derivatives of TcsC with respect to their impact on fungal growth and their ability to respond to hyperosmotic stress and fludioxonil. Our data demonstrate that the TcsC kinase module per se is constitutively active and under the control of the sensing module. We furthermore found that the sixth HAMP domain alone is sufficient to arrest the kinase module in an inactive state. This effect can be partially lifted by the presence of the fifth HAMP domain. Constructs harboring more than these two HAMP domains are per se inactive and all six HAMP domains are required to enable a response to fludioxonil or hyperosmotic stress. When expressed in an A. fumigatus wild type strain, the construct harboring only the sixth HAMP domain exerts a strong dominant negative effect on the native TcsC. This effect is successively reduced in other constructs harboring increasing numbers of HAMP domains. To our knowledge, this is the first molecular characterization of a type III HHK containing six HAMP domains. Our data strongly suggest that TcsC is a positive regulator of its MAPK SakA and thereby differs fundamentally from the prototypic yeast type III HHK DhNik1 of Debaryomyces hansenii, which harbors only five HAMP domains and acts as a negative regulator of its MAPK.


Cognitive effects of antipsychotic agents in persons with traumatic brain injury.
Over 1 million survivors of traumatic brain injury receive maintenance pharmacotherapy, of which a substantial number receive antipsychotic agents for the treatment of psychoses, agitation and aggression, and other maladaptive behaviours. In spite of the common clinical uses of antipsychotics, the cognitive risks versus benefits are unclear. The purpose of this study was to assess differences in cognitive functioning before, during, and after discontinuation of antipsychotic agents in inpatients undergoing rehabilitation for traumatic brain injury. Neuropsychiatric tests (Reys Auditory-Verbal Learning, Trail Making A&B, Digit Span Forwards and Backward) evaluating cognitive skills of verbal ability, visuomotor speed, memory, learning, attention, and spatial ability were administered to each subject at baseline (immediately prior to tapering or discontinuing antipsychotic), when taper reached 50% of baseline dose, 1 week after antipsychotic discontinuation, and 3 weeks after discontinuation. These data suggest that select areas of cognition improve after antipsychotic discontinuation in subjects with traumatic brain injury. The magnitude of improvement appeared to be greater after discontinuation with thioridazine, a low-potency agent, compared to haloperidol, a high-potency agent. Results, although very preliminary, support the hypothesis of cholinergic involvement in regulating cognitive processes, and this underscores the need for more systematic research in this area.


[Synergism of selected pesticides. 1. Acute oral toxicity in combined administration].
Comparative studies with male rats were performed to investigate the coergism of single oral doses of selected pesticides, the comparison being based on the lethal effects observed. The quantitative analysis of the dose-mortality relationship and the determination of the coergistic index evidenced a slight increase of the lethal effect with lindane-phosmet and lindane-carbaryl combinations. The combined administration of lindane and ethylenethiourea resulted in an additive lethal effect.


Renal replacement treatment for diabetic nephropathy in Northern Ireland 1979-1987.
Twenty-three patients with end-stage renal failure due to diabetic nephropathy received renal replacement treatment. All patients had insulin-dependent diabetes mellitus. Nineteen transplants were performed in seventeen patients. Two-year graft survival for all transplants was 74% with a two-year patient survival post-transplantation of 81%. Overall two-year patient survival was 73%, compared with 82% in non-diabetic patients receiving renal replacement treatment. In diabetic patients accepted for treatment there was a high incidence of non-renal complications, particularly vascular disease. An aggressive approach to the treatment of vascular disease in these patients may improve overall survival rates.


Effects of radiation therapy on neuropsychological functioning in patients with nasopharyngeal carcinoma.
Sixteen patients who had a nasopharyngeal carcinoma (NPC) who were treated with radiation therapy were followed up after a median duration of 5.5 years and given a battery of neuropsychological tests. Results were compared with a comparable group of newly diagnosed NPC patients awaiting radiation therapy. The irradiated group was significantly poorer in overall IQ, non-verbal memory recall, and reported a substantially greater number of memory related complaints. These results contrast with the complacent general assumption that radiation therapy has a negligible effect on adult functioning.


Eye Disorders among Adult People Diagnosed with Infantile Autism in Childhood: A Longitudinal Case Control Study.
The objective of this study was to compare the prevalence and types of eye disorders in a clinical sample of 118 adult people diagnosed with infantile autism (IA) during childhood with 336 sex- and age-matched controls from the general population. All participants were screened through the nationwide Danish National Hospital Register. The average observation time of both groups was 37.2 years, and mean age was 49.6 years, by the end of the observation period. The overall prevalence of any eye disorder was 15.3% (18/118) in cases with IA, compared to 10.1% (34/336) in controls (p = 0.18). Refraction and accommodation disorders were significantly associated with IA: 7.6% (9/118) vs 1.2% (4/336) (p = 0.001). The rate of eye disorder was particularly high (24.5%) in those with a co-occurring profound or severe learning disability (IQ < 50). Refraction and accommodation disorders were more frequently present in Danish adults with IA, particularly when a profound or severe learning disability was co-present. The increased prevalence of eye disorders in participants with a severe or profound learning disability, and the fact that people with IA do not necessarily realize the presence of a vision deficit, necessitates increased ophthalmological attention.


Oxonitridosilicate Oxides RE26Ba6[Si22O19N36]O16:Eu2+ (RE = Y, Tb) with a Unique Layered Structure and Orange-Red Luminescence for RE = Y.
The oxonitridosilicate oxides RE26Ba6[Si22O19N36]O16:Eu2+ (RE = Y, Tb) were synthesized by high-temperature reaction in a radiofrequency furnace starting from REF3, RE2O3 (RE = Y, Tb), BaH2, Si(NH)2, and EuF3. The structure elucidation is based on single-crystal X-ray data. The isotypic materials crystallize in the monoclinic space group Pm (no. 6) [Z = 3, a = 16.4285(8), b = 20.8423(9), c = 16.9257(8) Å, β = 119.006(3)° for RE = Y and a = 16.5465(7), b = 20.9328(9), c = 17.0038(7) Å, β = 119.103(2)° for RE = Tb]. The unique silicate layers are made up from Q1-, Q2-, and Q3-type Si(O/N)4- as well as Q4-type SiN4-tetrahedra, forming three slightly differing types of cages. The corresponding 3-fold superstructure as well as pronounced hexagonal pseudosymmetry complicated the structure elucidation. Rietveld refinement on powder X-ray diffraction data, energy-dispersive X-ray spectroscopy and infrared spectroscopy support the findings from single-crystal X-ray data. When excited with UV to blue light, Y26Ba6[Si22O19N36]O16:Eu2+ shows broad orange-red luminescence (λem = 628 nm, fwhm ≈ 125 nm/3130 cm-1). An optical band gap of 4.2 eV was determined for the doped compound by means of UV/vis spectroscopy.


A prescription that addresses the decline of basic science education in medical school.
Over 30 years ago a cry rang out through the proverbial halls of academia; "The clinician scientist is an endangered species." These prophetic words have been reverberated in the ears of every specialty and every general medical organization in deafening tones. Why is the role of the clinician scientist or clinician investigator so important that this phrase has been repeated subsequently in medical and educational journals? Simply put, the clinician scientist bridges the ravine between the ever-growing mountain of scientific knowledge and the demanding patient centered clinical care. Here, we describe the current educational model established by the University of Calgary, Leaders in Medicine Program. Our program seeks to train future physicians and clinician scientists by incorporating training in basic science, translational and clinical research with clinical and medical education in a longitudinal program to students of traditional MD/PhD, MD/MSc or MD/MBA stream as well as interested Doctor of Medicine students.


Amplifier Hosts May Play an Essential Role in Tomato Begomovirus Epidemics in Brazil.
Current control of tomato golden mosaic disease, caused in Brazil predominantly by tomato severe rugose virus (ToSRV), is dependent on both, planting resistant/tolerant hybrids and intensive insecticide sprays (two to three per week) for controlling Bemisia tabaci, the vector of ToSRV. Resistant hybrids only confer moderate resistance to infection by ToSRV and some tolerance to the disease. Insecticide sprays, although widely used, have failed in most tomato production areas in Brazil, as they are unable to reduce primary spread, i.e., infection caused by the influx of viruliferous whiteflies coming from external sources of inoculum. Severe epidemics are recurrently observed in some tomato fields in several Brazilian regions, which prompted us to postulate the existence in the agroecosystem, in some places and time, of amplifier hosts that provide the necessary force of infection for epidemics to occur, even in the absence of secondary spread in the target crop. Amplifier hosts are ideally asymptomatic, occur in high density near the target crop, and support growth of both virus and vector. Soybean and common bean are potential amplifier hosts for begomovirus in tomato crops. Our results support the hypothesis that soybean plants may play an important role as an amplifier host of ToSRV for tomato crops in the field, although this does not seem to be a frequent phenomenon. Successful amplification will depend on several factors, including the soybean cultivar, the soybean stage of development at the moment of infection, the ToSRV isolate, and the perfect synchrony between the beginning of a soybean field and the end of a ToSRV-infected crop, and, later, between the senescence of the ToSRV-infected soybean plants and the new tomato crop. The concept of amplifier hosts has been widely used in ecology of zoonoses but, to our knowledge, has never been used in botanical epidemiology.


Activity of two synthetic amphiphilic peptides and magainin-2 against herpes simplex virus types 1 and 2.
The in vitro antiviral activity of two amphiphilic synthetic peptides, modelin-1 (mod-1) and modelin-5 (mod-5), and of the natural antibacterial peptide magainin-2 (mag-2) against herpes simplex viruses type 1 (HSV-1) and 2 (HSV-2) were evaluated. The peptides were incubated with the virus, i.e. direct inactivation, and their effects examined by means of plaque reduction assay and/or reduction in virus yield. Only mod-1 displayed a strong antiviral effect against HSV-1 and HSV-2, with 50% effective dose (ED50) values of 4.6 and 4.1 micrograms/mL, respectively. Mag-2, mod-5 and a mixture of both had no significant inhibitory effect. Addition of mod-1 up to a concentration of 100 micrograms/mL to the culture medium had no significant cytotoxic effect on host vero cells, as measured by the trypan blue-exclusion method. It showed, however, considerable hemolytic activity against human red blood cells. Experiments including acyclovir (ACV) as a reference viral inhibitor indicated that the mode of action of mod-1 is different from that of ACV. In contrast to ACV, the peptide inactivates the virus following a very short incubation before vero cell infection, suggesting some kind of direct interaction of the peptide with the viral envelope, rather than inhibition of viral DNA replication or gene expression. Our results suggest that mod-1 may be an effective topical antiviral agent against herpes viruses.


Biosynthesis of sterols by a yeast homogenate. Incorporation of mevalonic acid into cholesta-5,7,24-trien-3beta-ol and 5alpha-cholesta-7,24-dien-3beta-ol.
Incubation of (3RS,2R)-[2-14C,2-3H]mevalonic acid and (3RS, 2S)-[2-14C,2-3H]mevalonic acid with mechanically disrupted yeast cells resulted in C27-metabolites. Two (14C5, 3H4)-metabolites, cholesta-5,7,24-trien-3beta-ol and 5 alpha-cholesta-7,24-dien-3beta-ol, were isolated and characterized. The impairment of the 24-methyl transferase system was confirmed by the lack of incorporation of 14C into the sterol fraction on incubation of S-adenosyl-L-[methyl-14C]methionine with the yeast homogenate. The results indicate that interference with the (C-24)-alkylating system did not prevent the transformation of lanosterol to the cholesta-5,7,24-trien-3beta-ol and to 5 alpha-cholesta-7,24-dien-3beta-ol. It can therefore be inferred that transformations of the nucleus and of the side chain can function independently. However our results do not provide a definition of the actual sequence of the metabolic events between lanosterol and ergosterol.


Alterations in the expression of the NF-κB family member RelB as a novel marker of cardiovascular outcomes during acute exacerbations of chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) exacerbations are acute events of worsened respiratory symptoms and enhanced inflammation partly mediated by NF-κB activation. RelB, an NF-κB family member, suppresses cigarette smoke-induced inflammation but its expression in COPD is unknown. Moreover, there is no information on its association with clinical features of COPD. The objectives of this study were to assess RelB expression relative to markers of inflammation as well as its association with cardiovascular and pulmonary features of COPD patients at stable-state and exacerbation. Data from 48 COPD patients were analyzed. Blood samples were collected from stable-state and exacerbating patients. After RNA isolation, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess RelB, Cox-2, IL-8 and IL-1β mRNA expression and their associations with measured clinical variables. Of the 48 COPD subjects, 18 were in stable-state and 30 were in exacerbation. RelB mRNA expression was lower than that of Cox-2, IL-8, and IL-1β in all cases (all p<0.001, except for IL-8 at exacerbation (p = 0.22)). Cox-2, IL-8 and IL-1β were significantly associated with clinical features of patients in both stable-state and at exacerbation. There was no association with RelB expression and any clinical features in COPD subjects at stable-state. RelB mRNA levels were significantly associated with cardiovascular events such as systolic blood pressure during exacerbation. RelB mRNA expression is lower than that of the other inflammatory mediators. Expression of Cox-2, IL-8 and IL-1β were related to clinical features in both stable-state and at exacerbation. However, RelB expression was associated with clinical features of patients only during exacerbation, suggesting that RelB may represent a novel marker of health outcomes, in particular cardiovascular, during exacerbation in COPD.


[Relationship between hyperuricemia and adverse events in patients aged 40 years or older receiving rheumatic aortic valve replacement].
To explore the prognostic value of hyperuricemia for adverse events in patients >40 years old receiving valve replacement surgery for rheumatic aortic valve disease. Consecutive middle-aged and elderly patients receiving aortic valve replacement surgery for rheumatic aortic valve disease between March, 2009 and July, 2013 were recruited in this study. The patients were divided into hyperuricemic group and normouricemic group based on their serum levels of uric acid, and the clinical data and adverse events within 1 year after the surgery were compared between the 2 groups. A total of 632 consecutive patients were recruited, including 381 patients with hyperuricemia and 251 with normouricemia. The in-hospital mortality rate was significantly higher in hyperuricemic group than in normouricemic group (7.6% vs 2.0%, P=0.002). Serum uric acid levels were negatively correlated with eGFR (r=-0.421, P<0.001) and positively correlated with C-reactive protein level (r=0.093, P=0.025). Multivariate analysis showed that hyperuricemia was independently associated with the in-hospital mortality (OR=3.07, 95%CI: 1.13-8.37, P=0.028) and mortality at 1 year after the surgery (HR=3.14, 95%CI: 1.30-7.62, P=0.011) after adjusting for potential risk factors including age, NYHA III-IV and postoperative acute kidney injury (AKI). Kaplan-Meier analysis showed that the cumulative rate of 1-year mortality after surgery was significantly higher in patients with hyperuricemia (Log-rank=11.73, P=0.001). Hyperuricemia is a predictor of in-hospital and one-year mortality in middle-aged and elderly patients following aortic valve replacement surgery for rheumatic aortic valve disease.


ATP is stored in lysosomes of greater epithelial ridge supporting cells in newborn rat cochleae.
Adenosine triphosphate (ATP), which plays a crucial role in both developing and mature cochleae, is released from greater epithelial ridge (GER) supporting cells of the rat cochlea, but the organelles in which ATP is stored have not yet been identified. Thus, we studied the organelles involved in ATP storage and suggest that lysosomes provide this function. GER supporting cells of newborn rats were isolated, purified, and cultured, and labeled vesicles within the supporting cells were identified via confocal microscopy and transmission electron microscopy (TEM). ATP release from GER supporting cells after glycyl-L-phenylalanine-β-naphthylamide (GPN) treatment was measured. The specifically labeled organelles observed by confocal microscopy and TEM were lysosomes, and GPN treatment enhanced ATP luminescence in the extracellular fluid of the supporting cells. The release of ATP from supporting cells was affected by changes in intra- and extracellular Ca2+ concentrations. In addition, changes in the intracellular Ca2+ caused by inhibiting the phospholipase signaling pathway affected the release of ATP from supporting cells. We demonstrated that ATP is stored in the lysosomes of GER supporting cells within newborn rat cochleae and that ATP release from GER supporting cells may be Ca2+ -dependent.


Mucormycosis in a patient with acute myeloid leukemia successfully treated with liposomal amphotericin B associated with deferasirox and hyperbaric oxygen.
We report a 38-year-old woman presenting with febrile neutropenia, acute myeloid leukemia (AML) and invasive mucormycosis. Bone marrow aspirate was characteristic of AML minimally differentiated (WHO classification 2008). Flow cytometric immunophenotyping analysis showed blasts positive for CD7, CD33, CD34, CD71, CD117, HLA-DR, MPO, and TdT, with normal karyotype (46, XX), and the absence of the FLT3-ITD and NPM1 mutations. The patient's management included chemotherapy with cytarabine and idarubicin, and treatment with liposomal amphotericin B, deferasirox, hyperbaric oxygen therapy, and antibiotics. Nowadays, she is in complete hematological remission, and CT images of control are normal. Invasive mucormycosis is an uncommon and severe condition, which involves diagnosis and treatment challenges. Clinical features and predisposing factors should be highlighted in order to enhance the suspicion index, contributing to early diagnosis and disease control. Our aim is to report classical features of this uncommon condition and to emphasize usual management challenges.


Tunable poly(lauryl methacrylate) surface grafting via SI-ATRP on a one-pot synthesized cellulose nanofibril macroinitiator core as a shear-thinning rheology modifier and drag reducer.
The optimally one-pot synthesized 2-bromoproponyl esterified cellulose nanofibril (Br-CNF) has been validated as a robust macroinitiator for self-surface-initiated atom transfer radical polymerization (SI-ATRP) of lauryl methacrylate (LMA) in tunable graft lengths and high conversions of up to 92.7%. SI-ATRP of LMA surface brushes on Br-CNF followed first order kinetics in lengths at up to 46 degree of polymerization (DP) based on mass balance or 31 DP by solution-state 1H NMR in DMSO-d6. With increasing PLMA graft lengths, Br-CNF-g-PLMA cast films exhibited increasing hydrophobicity with water contact angles from 80.9° to 110.6°. The novel Br-CNF-g-PLMA exhibited dual shear thinning behavior of the Br-CNF core as evident by n < 1 flow behavior index and drag reducing properties of PLMA grafts with increased viscosity at up to 21 071×. Br-CNF-g-PLMA with 46 DP could be fully dispersed in silicon pump oil to function as a drag reducer to enhance viscosity up to 5× at 25, 40, and 55 °C. The novel macroinitiator capability of Br-CNF in SI-ATRP of vinyl monomers and the bottlebrush-like LMA surface grafted Br-CNF as highly effective viscosity modifier and drag reducer further demonstrate the versatile functionality of Br-CNF beyond hydrophobic coatings and reactive polyols previously reported.


Expression of transferrin receptors on mitogen-stimulated human peripheral blood lymphocytes: relation to cellular activation and related metabolic events.
Mitogen-activated normal human peripheral blood lymphocytes bind transferrin to specific membrane receptors. In this study, lymphocytes stimulated with phytohaemagglutinin for 0-66 hr were examined to determine the relation of this phenomenon to cellular activation and related metabolic events. Transferrin receptors were first detected at 20-24 hr. This event was consistently preceded by RNA and protein turnover which commenced during the first 6 hr of culture, whereas initiation of DNA synthesis was detected concurrently with the appearance of receptors or slightly later (24-30 hr). Exposure of cells to inhibitors of RNA and protein synthesis early during culture (at 0 or 24 hr) prevented the expression of transferrin receptors, but also caused generalized metabolic failure, and abrogated cellular activation. In contrast, later addition of these agents at 48 hr did not interfere significantly with the process of activation, but did suppress the terminal increase in receptor-bearing cells observed during the final 18 hr in control cultures lacking inhibitor. After deliberate thermal stripping of receptors from activated cells, the reappearance of membrance binding sites which normally occurred within 30 min, was also blocked by cycloheximide, puromycin and actinomycin D. However, similar inhibition of DNA which was induced by hydroxyurea had much less effect upon both the initial appearance of receptors and their reappearance after ligand-induced depletion. These results demonstrate that the appearance of transferrin receptors upon human lymphocytes is dependent upon cellular activation and requires synthesis of protein and RNA.


The role of the ICRP in radiation protection--a view from industry.
It is the objective of this paper to discuss some aspects concerning the role and importance of the ICRP. Here, this is done with a background of practical radiation protection in industry. The author organises and controls radiation protection for a worldwide operating company, for which efficiently realised radiation safety is as relevant for its workplaces as for its products and services. According to the author's subjective observation, the ICRP has a decreasing importance in operational radiation protection. However, there are growing demands on the ICRP as it is the only basis for internationally compatible regulations and standards. It is the merit of the ICRP that an international comparison of legal protection systems and concepts should give a much more homogeneous picture than that for any other safety and protection issue. The most valuable asset of the ICRP is its credibility as a scientific authority solely committed to the effective protection of people. But its success also brings with it an obligation: there is an increasing need for more effective communication to non-experts. This and other expectations for the future are briefly discussed.


A guide for mental health clinicians to develop and undertake benchmarking activities.
There is a growing expectation for staff to participate in benchmarking activities. If benchmarking projects are to be successful, managers and clinicians need to be aware of the steps involved. In this article, we identify key aspects of benchmarking and consider how clinicians and managers can respond to and meet contemporary requirements for the development of sound benchmarking relationships. Practicalities and issues that must be considered by benchmarking teams are also outlined. Before commencing a benchmarking project, ground rules and benchmarking agreements must be developed and ratified. An understandable benchmarking framework is required: one that is sufficiently robust for clinicians to engage in benchmarking activities and convince others that benchmarking has taken place. There is a need to build the capacity of clinicians in relation to benchmarking.


Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer.
One hundred twenty pathologically confirmed operable Stage III (T3N0-2) breast cancer patients were randomized to receive either postoperative radiotherapy or chemotherapy, or a combination of these, with or without levamisole immunotherapy. Radiotherapy was given to regional lymph node areas and chest wall. Chemotherapy consisted of 6 cycles of Adriamycin (doxorubicin) (45 mg/m2), vincristine (1.2 mg/m2) intravenously, and cyclophosphamide (200 mg/m2 for 5 days) perorally every 4 weeks. Peroral levamisole, 150 mg a day, 2 days weekly, was given as an immunotherapy. The 3-year results are described in this article. The effect of levamisole on the prognosis cannot be evaluated yet because of the short follow-up period. The disease-free survival was almost equal in each patient group, however, some benefit was achieved by levamisole (a shift of disease-free survival from 12 to 18 months). The patients receiving radiotherapy alone had the poorest prognosis: 68% had a recurrent tumor, and 57% were alive. In the chemotherapy group, the figures were 53% and 72%, respectively. Patients who received a combined treatment had the best prognosis: 13% had a recurrent tumor, and 90% survived 3 years. There was a statistically significant difference in the recurrence rate between any single therapy and the combined treatment (radiotherapy to combined treatment, P less than 0.001, chemotherapy to combined treatment, P less than or equal to 0.01 chi-square test). In overall survival, a statistically significant difference was reached between radiotherapy and combination treatment groups (P less than 0.01, chi-square test). Radiotherapy gave a good local control of the tumor, and chemotherapy decreased the number of metastases. The nonmetastatic axillary lymph node status and secondary amenorrhea or severe menstrual disturbances were of positive prognostic value. The side effects due to radiotherapy and chemotherapy were moderate and tolerable. The dose of Adriamycin had to be reduced only in four patients. All of the patients receiving chemotherapy had a transient total alopecia. Three of them had nonlethal arrhythmias, and one had skin rash. Levamisole was found very toxic with 9 cases of transient agranulocytosis, leading to the discontinuation of immunotherapy in 22 of 59 patients. Our results show that radiotherapy controls the tumor only locally and chemotherapy systematically, but the best patient-saving results are achieved with a combination of radiotherapy and chemotherapy. The disease-free and overall survival are statistically significant, and favor the combined therapy.


The Gray Mold Spore Detection of Cucumber Based on Microscopic Image and Deep Learning.
Rapid and accurate detection of pathogen spores is an important step to achieve early diagnosis of diseases in precision agriculture. Traditional detection methods are time-consuming, laborious, and subjective, and image processing methods mainly rely on manually designed features that are difficult to cope with pathogen spore detection in complex scenes. Therefore, an MG-YOLO detection algorithm (Multi-head self-attention and Ghost-optimized YOLO) is proposed to detect gray mold spores rapidly. Firstly, Multi-head self-attention is introduced in the backbone to capture the global information of the pathogen spores. Secondly, we combine weighted Bidirectional Feature Pyramid Network (BiFPN) to fuse multiscale features of different layers. Then, a lightweight network is used to construct GhostCSP to optimize the neck part. Cucumber gray mold spores are used as the study object. The experimental results show that the improved MG-YOLO model achieves an accuracy of 0.983 for detecting gray mold spores and takes 0.009 s per image, which is significantly better than the state-of-the-art model. The visualization of the detection results shows that MG-YOLO effectively solves the detection of spores in blurred, small targets, multimorphology, and high-density scenes. Meanwhile, compared with the YOLOv5 model, the detection accuracy of the improved model is improved by 6.8%. It can meet the demand for high-precision detection of spores and provides a novel method to enhance the objectivity of pathogen spore detection.


Paraspinal Muscle Degeneration as an Independent Risk for Loss of Local Alignment in Degenerative Lumbar Scoliosis Patients After Corrective Surgery.
Retrospective study. To investigate the effect of paraspinal muscle degeneration on the maintenance of local and global alignment among degenerative lumbar scoliosis (DLS) patients after corrective surgery. 98 DLS patients with a mean follow-up period of 38.3 months after corrective surgery were included. The T1 pelvic angle (TPA), lumbar lordosis (LL), pelvic incidence were measured preoperatively, immediate postoperatively and at last follow-up. All patients were divided into LL maintenance group (n = 21) and LL loss group (n = 77). For patients with well-aligned correction (immediate postoperative TPA ≤ 20°, n = 73), they were divided into TPA maintenance group (last follow-up TPA ≤ 20°) and TPA loss group (last follow-up TPA > 20°). The relative gross cross-sectional area (rGCSA) and fat infiltration (FI) of multifidus (MF) and erector spinae (ES), and the relative functional CSA (rFCSA) of psoas major (PS) were measured at L3, L4 and L5 on preoperative magnetic resonance imaging. MF rGCSA were significantly smaller in LL loss group than in LL maintenance group. Both MF rGCSA and PS rFCSA were significantly smaller and MF FI was significantly higher in TPA loss group than in TPA maintenance group. Binary logistic regression revealed that the MF rGCSA was an independent factor of LL loss; Large immediate postoperative TPA was an independent risk factor of TPA loss, but not the parameters of paraspinal muscles. The effect of paraspinal muscles in lower lumbar segments might be mainly focused on the maintenance of local alignment rather than the global alignment.


Volar Distal Radius Anatomy Applied to the Treatment of Distal Radius Fracture.
Volar locking plate (VLP) fixation has become the standard surgical treatment for distal radius fractures. However, flexor tendon rupture is one of the major complications following volar plating. This detailed review on the anatomy and morphology of the volar distal radius might facilitate appropriate placement of the volar plate and thereby avoid flexor tendon rupture. We introduce safe and secure VLP fixation along standard surgical procedures to avoid complications based on anatomy of the volar surface of the distal radius.


Mg1.8La0.2Ni-xNi nanocomposites for electrochemical hydrogen storage.
Mg1.8La0.2Ni hydrogen storage alloy was ball-milled with Ni powder, leading to the formation of a nanocrystalline and amorphous microstructure with particle sizes less than 50 nm in diameter. Each sample was examined by transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS), and X-ray diffraction (XRD). This structure was beneficial for the reduction of electrochemical impedance, as well as significant improvement of its discharge capacity, cycle life, and rate capability for electrochemical hydrogen storage in an alkaline solution. When the molar ratio (x) of Ni over Mg1.8La0.2Ni was equal to 2, the dehydriding capacity reached 2.55 wt % from electrochemical pressure-temperature isotherms (P-C-T). It was in good agreement with its initial discharge capacity, 716 mA*h/[g of (Mg1.8La0.2Ni)], observed from the electrochemical charge and discharge process. After 50 cycles, its discharge capacity still reached 381 mA*h/[g of (Mg1.8La0.2Ni)]. Further results showed that this composite had a promising high rate capability. At the current density of 1200 mA/g its discharge capacity reached 48% of its initial capacity.


Formulation and characterization of lutetium-177-labeled stannous (tin) colloid for radiosynovectomy.
Easy large-scale production, easy availability, cost-effectiveness, long half-life, and favorable radiation characteristics have made lutetium-177 (Lu) a preferred radionuclide for use in therapy. Lutetium-177-labeled stannous (Lu-Sn) colloid particles were formulated for application in radiosynovectomy, followed by in-vitro and in-vivo characterization. Stannous chloride (SnCl2) solution and Lu were heated together, the pH was adjusted, and the particles were recovered by centrifugation. The heating time and amount of SnCl2 were varied to optimize the labeling protocol. The labeling efficiency (LE) and radiochemical purity (RCP) of the product were determined. The size and shape of the particles were determined by means of electron microscopy. In-vitro stability was tested in PBS and synovial fluid, and in-vivo stability was tested in humans. LE and RCP were greater than 95% and ∼99% (Rf=0-0.1), respectively. Aggregated colloidal particles were spherical (mean size: 241±47 nm). The product was stable in vitro for up to 7 days in PBS as well as in synovial fluid. Injection of the product into the infected knee joint of a patient resulted in its homogenous distribution in the intra-articular space, as seen on the scan. No leakage of activity was seen outside the knee joint even 7 days after injection, indicating good tracer binding and in-vivo stability. Lu-Sn colloid was successfully prepared with a high LE (>95%) and high RCP (99%) under optimized reaction conditions. Because of the numerous benefits of Lu and the ease of preparation of tin colloid particles, Lu-Sn colloid particles are significantly superior to its currently available counterparts for use in radiosynovectomy.


[A case of brucellosis presenting with urinary tract infection].
In this report an acute brucellosis case presenting with the symptoms of urinary tract infection (UTI) has been discussed. A 29 years old male patient was admitted to the emergency service of our hospital with the complaints of acute UTI. His complaints were persisting for five days before admission. His physical examination was normal but there were fever (39 degrees C) and costovertebral angle tenderness. His medical history revealed that multiple stones in the lower pole of the right kidney and paranchyme loss were detected by IVP two years ago. The bacteria that were isolated from blood and urine cultures were identified as Brucella melitensis by conventional methods. Rose Bengal test was found positive, and standard tube agglutination test was positive at a titer of 1/640. The patient was treated with oral ciprofloxacin (1000 mg/day) and rifampicin (600 mg/day) combination for six weeks. The aim of this presentation was to draw attention to this uncommon condition, as UTI symptoms are not the first symptoms of acute brucellosis. UTI symptoms should be carefully considered as a presentation of brucellosis especially in regions where brucellosis is endemic.


Diagnostic significance of excretory urography and ultrasonography in renal diseases.
A comparative study of intravenous urography (IVU) and ultrasonography (USG) was performed in 100 patients of all age groups, having symptoms and signs of various renal diseases. Sonography was found to be 100% sensitive and diagnostic in approximately 74% of renal pathologies included in this study, namely calculous disease (excluding midureteric calculi), obstructive lesions of pelvicalyceal system (PCS), cystic diseases, gross congenital lesions, traumatic lesions and neoplasms. It also provided information about the complications of long standing obstruction to PCS such as non-functional and atrophied kidneys, infection, etc. IVU proved better in midureteric calculi (100%), 88.2% of all congenital lesions including the major as well as minor variations. Both modalities proved to be of poor help in diffuse parenchymal diseases (IVU-40% and USG-50%) and renal tuberculosis (IVU-18.2% and USG-45.5%). Sonography was able to delineate the cause of obstruction to PCS in only 72.3% of cases as compared to 88% by IVU.


Need for velopharyngeal management following palatoplasty: an outcome analysis of syndromic and nonsyndromic patients with Robin sequence.
The Robin sequence is a pathogenetically and etiologically heterogeneous condition that can be a nonsyndromic anomaly or one feature of many syndromes. Little information is available regarding the distribution of patients having Robin sequence, with or without associated syndromes, who develop velopharyngeal dysfunction. In order to discern whether patients with Robin sequence, nonsyndromic and/or syndromic, have different velopharyngeal dysfunction rates from those observed among all patients undergoing palatoplasty during the same time period, a retrospective study was undertaken. The charts of 873 patients with overt clefts of the secondary palate managed at a single cleft center between 1978 and 1992 were reviewed. Diagnostic criteria for Robin sequence included cleft palate without cleft lip, microretrognathia, and perinatal respiratory and/or feeding difficulties; 79 such patients (9 percent) were identified from the initial group of 873. Of these, 58 patients (7 percent) were at least 3 years of age and had sufficient follow-up to allow for evaluation of speech outcome by an experienced speech pathologist through a variety of methodologies (videonasendoscopy, speech videofluoroscopy, perceptual speech characteristics). This group comprised the Robin sequence study population. All Robin sequence patients' charts were reviewed by a medical geneticist to confirm the presence or absence of a syndrome. Of the original 873 patients, there were 127 non-Robin sequence patients who were sufficiently cooperative in diagnostic testing to yield definitive information. This group comprised the non-Robin sequence study population. Among nonsyndromic Robin sequence patients, 15 of 34 (44 percent) developed velopharyngeal dysfunction and required velopharyngeal management, while 2 of 24 syndromic patients (8 percent) developed velopharyngeal dysfunction (p = 0.003). Of the 127 non-Robin sequence isolated cleft palate patients, 113 were nonsyndromic, of whom 18 percent (20 of 113) required velopharyngeal dysfunction management, and 14 were syndromic, of whom 64 percent (9 of 14) required velopharyngeal dysfunction management (p = 0.00009). We conclude that nonsyndromic Robin sequence patients have a higher rate of postpalatoplasty velopharyngeal dysfunction than the nonsyndromic non-Robin sequence cleft population. Outcome analysis of velopharyngeal function in cleft patients should take into account patients who have cleft palate in association with Robin sequence, with or without a recognizable syndrome.


Chronic granulomatous disease presenting with small bone osteomyelitis in a young child: A case report.
Chronic granulomatous disease (CGD) is a life threatening inherited disorder with varied clinical presentations often characterized by recurrent bacterial and fungal infections along with widespread granulomatous tissue response. The disease results from phagocytic defects characterized by deficiencies in oxidative burst of neutrophils. Nitroblue tetrazolium reduction test (NBT) and Dihydrorhodamine (DHR) with PMA stimulation by flow cytometry are quick, simple, sensitive and specific laboratory tests that help establish early and reliable diagnosis of CGD with an overall improvement in survival and disease prognosis. We report a case of 2-year old child who presented with small bone osteomyelitis involving bilateral feet and was later diagnosed to have autosomal recessive CGD due to mutation in NCF1 gene.


[Autologous bone marrow transplantation in children with acute leukemia or non-Hodgkin's lymphoma].
More than 95% of children with acute lymphoblastic leukemia (ALL) achieve complete remission with conventional chemotherapy and 60 to 70% are cured. In contrast, only 70 to 80% of children with acute myeloid leukemia (AML) achieve remission and 30 to 40% are cured. In acute leukemia, ALL and AML, high initial white blood cell counts, poor initial response to therapy, certain structural chromosomal abnormalities, and diagnosis under 1 year of age indicate an increased risk of relapse. Prognosis is poor in children, who relapse during treatment. If no bone marrow donor is available, high dose chemo(radio)therapy and autologous stem cell rescue can be applied in these children to consolidate second remission. Furthermore, autologous bone marrow transplantation may be used to consolidate first remission of individual children, who suffer from acute leukemia with high risk criteria. 19 children with a median age of 8 years (0.5 to 19 years) underwent high dose chemo(radio)therapy and autologous bone marrow and/or blood derived stem cell rescue. 11 suffered from ALL, 4 had AML, and 4 suffered from Non Hodgkin's lymphoma (NHL). 7/13 children (54%), who were in first or second remission after early relapse, are alive in continued remission for median 24 months (9 to 44) after autografting. Children in more advanced stage of disease had no benefit from high dose therapy and autologous stem cell rescue.


Association of the 276G->T polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans.
The adiponectin gene is known to modulate adiponectin concentrations and diabetes mellitus development. We assessed whether adiponectin gene variants contribute to circulating adiponectin, insulin resistance (IR), or cardiovascular disease risk factors. Nondiabetic subjects [n = 902; x +/- SE age: 42.5 +/- 0.53 y; body mass index (BMI; in kg/m2): 24.7 +/- 0.11] were genotyped for 2 single-nucleotide polymorphisms (SNPs), 45T-->G and 276G-->T. After adjustment for age, sex, and BMI, subjects with the G allele for the SNP 276 had significantly higher concentrations of triacylglycerol and small dense LDL (sdLDL) and smaller LDL particle size than did T/T subjects. G/G subjects at SNP 276 had significantly lower plasma adiponectin and higher homeostasis model assessment (HOMA) of IR and urinary prostaglandin F2alpha than did T/T subjects. In the SNP 45-276 haplotype test, we also observed that subjects with the X/X haplotype had significantly higher plasma adiponectin after adjustment than did TG/TG or TG/X haplotype subjects. In the highest BMI group (BMI > or = 26), T/T subjects had lower HOMA-IR (P = 0.011) and higher plasma adiponectin (P = 0.026) at SNP 276 than did G/G or G/T subjects. These patterns were also seen for adiponectin in haplotype groups. However, no significant genotype effect for SNP 45T-->G was observed. The 276G-->T polymorphism of the adiponectin gene modulates circulating adiponectin and IR, particularly in obese states. G allele carriers also have higher oxidative stress, higher sdLDL concentrations, and smaller LDL particle size. Therefore, the presence of the G allele in the adiponectin gene at SNP 276 could be a significant contributor to higher cardiovascular disease risk in Koreans, independent of common environmental factors.


Cardiovascular risk in young Finns, results from the second follow-up study.
A comprehensive study of coronary heart disease (CHD) risk factors and their determinants in children and adolescents in Finland was initiated in the late 1970's. The main cross-sectional study was undertaken in 1980, with 3596 subjects aged from 3 to 18 years participating. The first follow-up study was carried out in 1983, and the second in 1986. The present report describes briefly some findings in 2746 children and young adults, aged 9, 12, 15, 18, 21 and 24 years, participating in 1986. Serum total cholesterol concentrations, mean (SD), ranged between 4.31 (0.73) and 4.91 (0.81) mmol/l in boys, and between 4.73 (0.85) and 5.09 (0.82) mmol/l in girls, respectively. Mean serum cholesterol values had fallen from 1980 to 1986 by 5.4% in such age cohorts, which had been included in all three studies. Fat content in the diet remained unchanged (38 E %), whereas the mean P/S ratio increased from 0.24 in 1980 to 0.31 in 1986. Young Finns from East Finland had a higher somatic risk index than those from West Finland (P greater than 0.001). The clustering of somatic risk factors was stable between 1980 and 1986. Further follow-up of the cohorts will, we hope, provide the tools for implementing primary prevention of CHD in Finland.


Transient dimerization of human MxA promotes GTP hydrolysis, resulting in a mechanical power stroke.
Myxovirus resistance (Mx) proteins restrict replication of numerous viruses. They are closely related to membrane-remodeling fission GTPases, such as dynamin. Mx proteins can tubulate lipids and form rings or filaments that may interact directly with viral structures. GTPase domain dimerization is thought to allow crosstalk between the rungs of a tubular or helical assembly, facilitating constriction. We demonstrate that the GTPase domain of MxA dimerizes to facilitate catalysis, in a fashion analogous to dynamin. GTP binding is associated with the lever-like movement of structures adjacent to the GTPase domain, while GTP hydrolysis returns MxA to its resting state. Dimerization is not significantly promoted by substrate binding and occurs only transiently, yet is central to catalytic efficiency. Therefore, we suggest dimerization functions to coordinate the activity of spatially adjacent Mx molecules within an assembly, allowing their mechanical power strokes to be synchronized at key points in the contractile cycle.


Security Services for the HemaCAM Project.
Within the HemaCAM project which deals with automated differential white blood cell count by image processing, a security infrastructure has been integrated. The security services for this demonstrator have been derived from the German health network ONCONET that enables a trustworthy framework for both health professionals and patients as well as supports clinical studies. For the solution, services assuring both communication security and application security have to be provided. This task has been realised by the use of the security token Health Professional Card and an appropriate Trusted Third Party infrastructure.


[Soluble and membrane-bound neutral alpha-glucosidase from the human kidney].
In human kidney cortex neutral alpha-glucosidases 1 and 2 are represented by two forms, soluble (cytosolic) and membrane-bound (brush border) ones. It has been shown that the soluble enzyme preexists in human kidney but does not derive from the membrane-bound form. Similar to the membrane-bound enzyme the soluble form is a glycoprotein. Both enzyme forms possess identical electrophoretic mobility, pH-optimum, heat sensibility and Km values for maltose (0.7 mM) and 4-methylumbelliferyl-alpha-D-glucopyranoside (0.57 mM), but differ by molecular weights as determined by gel filtration chromatography. The molecular weights of the soluble neutral alpha-glucosidases 1 and 2 are lower than those of the comparable brush border enzymes (470 000, 360 000, 520 000 and 440 000, correspondingly). Neutral membrane-bound alpha-glucosidase 1 is a sialylated enzyme with a pI of 4.10 +/- 0.02. The soluble enzyme contains no or only traces of neuraminic acid and has a pI 4.40 +/- 0.03. The soluble and membrane-bound neutral alpha-glucosidases are apparently independent forms of the enzyme, differing by the degree of sialylation and by the presence of an "anchor" in the membrane-bound enzyme. The synthesis of both forms is presumably coded by the same structural gene.


Impact of quality of the image, orientation, and similarity of the stimuli on visual search for faces.
Evidence from a series of visual-search experiments suggests that detecting an upright face amidst face-like distractors elicits a pattern of reaction times that is consistent with serial search. In four experiments the impact of orientation, number of stimuli in the display, and similarity of stimuli on search rates was examined. All displays were homogeneous. Trials were blocked by distractor type for three experiments. In the first experiment search rates for faces amidst identical faces rotated by 180 degrees were examined. No advantage was evidenced in searching for an upright face. The impact of the quality of the face representation was examined in the second experiment. Search rates are reported for a line-drawn and a digitized image of a face amidst identical faces rotated by 180 degrees. Search was faster for digitized than for line-drawn faces. The findings of the first experiment for orientation were replicated. In the third and fourth experiments the impact of disrupting the facial configuration in distractors was examined and performance was contrasted for blocked and mixed trials, respectively, with the same stimulus set. Reaction times increased with the number of distractors in the display in all but the nonface condition, which produced a shallow slope suggestive of parallel search. Search amidst other distractors appeared to involve the conjoining of a specific set of features with specific spatial relations. The hierarchy of relevant configural dimensions was inconsistent across these two experiments, suggesting that the symmetry, top-down order of features, orientation of the face, and predictability of the distractor type may have an interactive effect on search strategies.


How to raise children's self-esteem? Comment on Orth and Robins (2022).
Since the 1960s, self-esteem has become a cornerstone of Western child-rearing. After reviewing a large body of rigorous longitudinal research, Orth and Robins (2022) conclude that self-esteem brings modest but significant benefits across all ages. However, the authors did not intend to suggest strategies for raising children's self-esteem. The aim of my commentary is to identify such strategies. Without guidance on how to raise children's self-esteem safely and sustainably, well-intentioned strategies, such as inflated praise, may inadvertently undermine self-esteem or even breed narcissism. Instead, interventions should be based on a theoretically informed and empirically supported understanding of the determinants of self-esteem. By targeting these determinants, interventions may be able to raise children's self-esteem safely (i.e., without breeding narcissism) and sustainably (i.e., leading to lasting improvements in self-esteem and its presumed outcomes). Evaluating these interventions through randomized controlled trials will help build a theory of when and why self-esteem interventions work. Ultimately, this work will provide nuanced and dependable guidance to parents, teachers, and professionals on how to raise children's self-esteem. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Novel trends in extraction and optimization methods of bioactives recovery from pomegranate fruit biowastes: Valorization purposes for industrial applications.
Pomegranate biowastes present potential economic value worldwide owing to their several health benefits mediated by a complex mixture of unique bioactives. The exploitation of these bioactives has motivated the exploration of eco-friendly, efficient, and cost-effective extraction techniques to maximize their recovery. The current review aims to provide updated technical information about bioactives extraction mechanisms from pomegranate wastes (seeds and peel), their advantages and disadvantages, and factors towards optimization. A comparative overview of the modern green extraction techniques viz., supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, pressurized liquid extraction, and eutectic solvent mixture as alternatives to conventional extraction methods for seeds and peel is presented. Approaches focused on biowastes modification for properties improvement are also discussed. Such comprehensive review shall provide the best valorization practices of pomegranate biowastes and its application in food and non-food areas focusing on original methods, innovation, protocols, and development to be considered for other fruit biowastes.


Community responses to violence.
Community level efforts are effective in the reduction of violence. Community-level interventions have three goals: to prevent the escalation of risk for violence among the families in the community, to assist families at risk of or using violence, and to protect victims of abuse. To prevent violence or reduce its prevalence, community groups need to collaborate to reduce the community-level risk factors. Assisting families and protecting victims of violence requires coordination of community services, including law enforcement, schools, therapists, courts, child care, and social services. All of these goals can best be achieved through the efforts of a community level, multidisciplinary council or board that directs the programs. A community process to establish an integrated program involves several steps. The leaders that are identified need to represent all the disciplines and the entire geographic area involved in the project. Once the leaders start meeting, the baseline information and plan can be developed. Then the project itself can be undertaken, with the support of the media and other appropriate organizations. Several examples of effective projects document this process and its success; the best efforts involve coalitions of private and governmental agencies working together. Physicians are integral to this process. The practice of medicine provides opportunities every day to prevent and intervene in potential cases of abuse and violence. Also, by participating actively in the community, physicians can be effective leaders to change attitudes and behaviors and institute programs toward reducing violence.


Immunomodulation and mechanisms of fucoidan from Cladosiphon okamuranus ameliorates atopic dermatitis symptoms.
Atopic dermatitis (AD) is a long-term allergic skin disorder that occurs most frequently in children. Currently, the common treatment of AD is corticosteroids; however, the drugs cause serious side effects. Therefore, there are many patients who seek complementary and alternative treatments such as healthy food. We report that fucoidan from Cladosiphon okamuranus (COP) exhibit exceptional immuno-modulatory effects significantly improving atopic dermatitis (AD) at both in vitro and in vivo levels: First, we performed the P815 cell degranulation assay, of which the results revealed that COP possesses anti-degranulation activity suggesting COP is very conducive to relieving allergic reactions of AD. Next, we performed the animal model examination, of which AD was significantly improved, suggesting COP can focally and globally modulate the immune systems of animals. The systemic improvements were manifested clearly by decreased epidermal hyperplasia, reduced infiltration of eosinophils, and decreased expression of AD-associated cytokines. Notably, COP reduced epidermal hyperplasia by downregulating the expression of IL-22. COP displayed therapeutic effects, which is comparable to corticosteroids but lack corticosteroid side effects, such as weight loss in our animal study. COP is multitudinous immunomodulatory abilities to serve as a healthy food supplement at the current stage, not least beneficial to atopic dermatitis.


Identification of proteins encoded by the L1 and L2 open reading frames of human papillomavirus 1a.
The human papillomavirus 1 (HPV-1) virion is composed of two virally encoded proteins: a 57,000-molecular-weight polypeptide (57K polypeptide), which is the product of the L1 open reading frame (ORF), and a 78K polypeptide, which is derived from the L2 ORF. The 57K (L1) product, which represents the major structural component, appears to be disulfide cross-linked in virus particles. The 78K (L2) protein is a minor component of the virion and does not appear to be disulfide linked either to the L1 gene product or to itself. Analysis of virus particles banding at different buoyant densities revealed differences in the L2 content of heavy-full and light-full virions. Antiserum prepared against a bacterially expressed fragment of the L1 ORF was found by immunofluorescence to cross-react with HPV-2 and bovine papillomavirus 1 virions in wart sections. No cross-reactivity was observed with antisera prepared against either the N- or C-terminal halves of the L2-encoded protein. Similarly, antisera prepared against purified virus particles (disrupted and nondisrupted) reacted only with an expressed fragment of the L1 ORF and not with either L2-encoded polypeptides or proteins derived from the E1, E2, E4, E6, or E7 ORFs. This indicates that the L1 protein contains the papillomavirus common antigens.


[Transvaginal sonography in diagnosis of the female pelvis].
Transvaginal ultrasound has become an important tool in diagnosing conditions in the female pelvis. The application of higher frequencies allows better resolution to be obtained than with the percutaneous technique, so the ratio between transvaginal and percutaneous ultrasound is now 70:30. Transvaginal ultrasound is used for the diagnosis of uterine malformations, tumors of the uterus, the cervix, the ovaries, for follow-up after a hysterectomy or radiotherapy, for diagnosis of the pelvic floor, as well as for additional information concerning the urinary bladder, bowel and pelvic vessels. In addition, a typical gynecological application of transvaginal ultrasound is the diagnosis of infertility and gravidity. Newer developments are emerging with ultrasound contrast media and Doppler as well as color flow Doppler sonography.


[Treatment of hypertension and cardiovascular complications].
The three approaches (physiopathological, epidemiological and pharmacological) to the management of hypertension should converge to provide a personalized prescription of the most appropriate treatment to prevent and/or cure the cardiovascular complications of hypertension: hypertensive left ventricular hypertrophy and the risks directly related to it (haemodynamic, arrhythmic, ischaemic) may be corrected by certain antihypertensive agents (methyldopa, ACE inhibitors, some calcium antagonists) although there is no proof as yet of the benefits of this intervention (which could suppress the adaptation to the increased wall stress of the left ventricle); malignant hypertension and its cardiovascular complications have almost disappeared with modern antihypertensive therapy. Cardiac failure can be effectively prevented and cured when exclusively related to hypertension. When diastolic pressures are lowered by 8-10 mmHg cerebrovascular risk is reduced by a half and coronary risk by a quarter. Cardiovascular mortality related to hypertension is thus reduced by 20% and total mortality is thereby significantly decreased; the large scale clinical trials which provided these data were performed in the years 1965-1985 with diuretic therapy relayed by (or compared with) betablockers from 1980 onwards. These two families remain the drugs of reference in the prevention and treatment of the cardiovascular complications of hypertension. Personalized description of antihypertensive therapy should take into account the degree of risk and previous cardiovascular complications of the hypertensive patient: betablockers eventually associated with calcium antagonists are to be preferred in cases of hypertension with coronary artery disease and/or arrhythmias, severe hypertension and hypertension complicated by cardiac failure are good indications for ACE inhibitors without prejudicing other therapeutic options necessary in certain contexts, in particular aspirin therapy in patients with previous transient ischemic cerebral attacks.(ABSTRACT TRUNCATED AT 250 WORDS)


Father involvement, maternal depression and child nutritional outcomes in Soweto, South Africa.
Father involvement in South Africa is low, despite evidence that it can improve maternal and child health and wellbeing. Within a larger randomised controlled trial, we assessed whether father involvement during and after pregnancy increased birth weight and exclusive breastfeeding through improved maternal mental health. At 6-week postnatal, mothers completed questionnaires on birth, feeding practices, social support, father involvement and postnatal depression. Father involvement during pregnancy was measured by their attendance at antenatal care and the study intervention, whereas postnatal involvement was measured by attendance at antenatal care and type of paternal support provided. Structural equation modelling was used to identify associations between father involvement, maternal depression, low birth weight and exclusive breastfeeding. Among the 212 mother-baby pairs, father involvement was very low with only 43%, 33% and 1% of partners attending early ultrasound, antenatal care and the birth of the child, respectively. Twenty-nine percent of the mothers showed signs of depression during pregnancy, compared with 7% after birth. Eighteen percent of the infants were born low birth weight, and 57% of mothers reported exclusively breastfeeding at 6 weeks. Father involvement was directly associated with postnatal depression, but it did not directly or indirectly impact exclusive breastfeeding or low birth weight. We conclude that postnatal father involvement can improve postnatal maternal depression and that men would benefit from specific guidance on how they can support mothers during and after pregnancy.


Changes in forage quality, ingestive mastication, and digesta kinetics resulting from switchgrass maturity.
Five maturities of switchgrass hay harvested at 14-d intervals (vegetative through 20% heading) were fed to Hereford steers (297 kg) in a 5 x 5 Latin square. Relationships with switchgrass maturity were negative and quadratic (P < .05) for DMI and cubic (P < .05) for digestible DMI. Declines in apparent digestibilities of DM, ADF, and cellulose were cubic (P < .05), whereas these were quadratic (P < .05) for NDF, hemicellulose, and CP. Whole masticates from the least, mid, and most mature hays showed linear (P < .05) declines in DM concentration and IVDMD with increasing maturity, whereas NDF concentrations increased linearly (P < .05). Mean retention time of gastrointestinal DM increased linearly (P < .01) from 64 to 94 h from the least to the most mature hay, and the associated rate of passage declined linearly (P < .01) from 3.3 to 2.1%/h. Sieving of masticate DM showed a reduced proportion of large particles (> or = 2.8 mm) and an increased proportion of small particles (< or = .5 mm) with advancing forage maturity. More than 94% of the sieved fecal DM passed a 1.0-mm sieve, but particle sizes showed the same relationship with forage maturity as noted for masticate DM. This occurred despite the comminution from the rumination and digestive processes.