Immunofluorescence patterns in sun-exposed and not-sun-exposed skin of healthy individuals.
Immunofluorescence studies were performed on the sun-exposed (S) and not-sun-exposed (N) skin of 25 healthy volunteers regarding the incidence of the five Ig classes, albumin, fibrinogen, C1q, C4, C3B, C3c, C3d, C5, C3PA and properdin. In addition a comparative study of two so-called anti-complement antisera was made, one (CI) containing anti-(C4+C3a+C3d), the other (CII) anti-(C3B+C3c). In all biopsies the epidermal basement membrane (BM) was stained positively with anti-C3d in a fibrillar, interrupted linear, or granular pattern. A band-like picture of the BM was observed with anti-IgG , anti-albumin and anti-fibrinogen in three biopsies of the S skin. In two other S skin biopsies a lichenoid pattern was found with anti-fibrinogen, anti-C3d and IgM. The latter antiserum caused a weakly positive band-like picture of the BM, occasionally together with granular deposits, more often in the S skin (11) than in the N skin (4). In the capillary walls, granular deposits of IgM, C3d and occasionally C3c were seen in both the S skin (7) and the N skin (13). In the subjacent vessels, globular deposits positive with anti-C3d, C5 and C3c were found predominantly in the S skin. In the M. arrector pili, granular deposits of C3d and, less obviously, C5, properdin and IgM were frequently observed. A band-like, linear, or granular picture of the BM of the adnexal structures was caused by anti-C3d. IgG was found around the sweat gland in about 30%, but the other serum proteins were only rarely present. The IF patterns of the two so-called anti-complement sera showed marked differences, which were apparently caused by the presence of anti-C3d in the CI serum. The significance of these findings for the diagnostic and pathogenetic interpretation of IF results in pathology are outlined briefly.


The politics of mad femme disclosure.
This essay imagines mad femme politics as an intervention and as a strategy that moves disabled, chronically ill, and mad educators and learners toward collective access and liberation. Using personal narrative, femme theory, and mad studies as reference points, the essay explores how a queering of tenderness and vulnerability can empower and embolden the process of disclosure.


Biotic interactions of marine algae.
Marine algae encompass lineages that diverged about one billion years ago. Recent results suggest that they feature natural immunity traits that are conserved, as well as others that appear to be phylum- or environment-specific. In particular, marine plants resemble terrestrial plants and animals in their basic mechanisms for pathogen recognition and signaling, suggesting that these essential cell functions arose in the sea. Specific traits are based on the synthesis of unique secondary defense metabolites, often making use of the variety of halides found in the sea.


Neuropsychological Differences Related to Age in Dementia with Lewy Bodies.
To examine the influence of age on neuropsychological performances in dementia with Lewy bodies (DLB) and Alzheimer disease (AD) patients. We examined memory, executive, and visuo-constructional performances in 202 DLB patients and 236 AD patients. We divided the subjects into three age groups (65-74, 75-84, and 85-95 years old), and evaluated the differences in neuropsychological performances. Recent memory in the DLB group was significantly better than that in the age-matched AD group when comparing the age groups 65-74 years and 75-84 years; however, memory impairment in the DLB patients in the age group 85-95 years was comparable with that in the age-matched AD patients. In contrast to recent memory, the other assessed neuropsychological performances, such as visuospatial and executive functions, showed no significant change in differences between the DLB and AD groups with advancing age. Our study revealed that the nature of memory impairment in DLB patients changes according to age. DLB patients in the young-old and old-old age groups showed significantly better memory performance than the age-matched AD patients, whereas memory performance of the DLB patients in the oldest-old age group was similar to that of the age-matched AD patients. This may be associated with the increased rate of coexisting AD pathology in DLB patients with older age.


The role of polarity in the development of the hydrozoan planula larva.
These experiments were done in order to define the role that polarity plays during embryogenesis in hydrozoans.Parts of hydrozoan embryos isolated at different developmental stages from early cleavage to postgastrula will regulate to form normal planulae. During this process, the original anterior-posterior axis of the part is conserved. In normal embryos the posterior pole of the anterior-posterior axis is congruent with the site where the polar bodies are given off and with the site where the first cleavage is initiated. By centrifuging fertilized eggs, it is possible to create embryos in which the first cleavage initiation site does not correspond to the site where the polar bodies are given off. In these embryos the posterior pole of the anterior-posterior axis corresponds to the first cleavage initiation site. When parts of these embryos are isolated at different stages they also regulate to form normal planulae. The axial properties of these planulae are determined by the site of first cleavage initiation.The interactions between regions of the embryo with different axial properties were studied by grafting together parts in such a way as to create embryos with abnormal axial arrangements. Following gastrulation interactions take place between the grafted parts leading to the formation of normal planulae with a new set of axial properties.Blastula stage embryos can be dissociated into single cells and the cells can be reaggregated. These reaggregates form normal planulae. Polarity can be entrained in the reaggregates by grafting a small piece of tissue from any part of an intact blastula to the reaggregate. These cells organize the formation of an axis of symmetry with an appropriate orientation with respect to the graft.


[Reduction of radiological exposure time during radiofrequency catheter ablation procedures using a novel intracardiac localization system based on the Ohm's law].
Three-dimensional nonfluoroscopic system may be helpful to guide radiofrequency catheter ablation procedures and to reduce the radiological exposure. A new intracardiac navigation and multicatheter visualization system based on Ohm's law (LocaLisa, Medtronic, Minneapolis, MN, USA) has been recently introduced. The aim of our study was to assess the efficacy of the Loca-Lisa system in comparison to fluoroscopy-based approach in reducing the radiological exposure time required for radiofrequency catheter ablation procedures. One hundred and thirty-seven consecutive patients underwent LocaLisa-based radiofrequency catheter ablation procedures in our cardiac electrophysiology laboratory during 19 months of LocaLisa utilization (from October 2001 to April 2003): 46 atrial flutter, 44 atrioventricular node reentrant tachycardia, 16 atrioventricular reentry tachycardia due to atrioventricular accessory pathway, 14 atrial fibrillation, 11 ectopic atrial tachycardia, and 6 atrioventricular node modulation. We retrospectively compared the radiological exposure times of this group of patients to those of the last 137 patients undergone fluoroscopy-based radiofrequency catheter ablation procedures for curing the same index arrhythmia by the same procedural protocol. The mean radiological exposure time was significantly shorter for the LocaLisa-based radiofrequency catheter ablation procedures (16 +/- 12 vs 34 +/- 17 min; reduction of 53%, p < 0.01) and it occurred for all the arrhythmia types. The reduction was of 64% (from 39 +/- 18 to 14 +/- 12 min, p < 0.01) for atrial flutter, 42% (from 24 +/- 10 to 14 +/- 11 min, p < 0.01) for atrioventricular nodal reentrant tachycardia, 30% (from 40 +/- 14 to 28 +/- 14 min, p = 0.02) for atrioventricular reentry tachycardia, 57% (from 49 +/- 12 to 21 +/- 13 min, p < 0.01) for atrial fibrillation (right atrial linear lesions), 50% (from 38 +/- 12 to 19 +/- 8 min, p < 0.01) for ectopic atrial tachycardia and 42% (from 12 +/- 11 to 7 +/- 5 min, p = NS) for atrioventricular node modulation. The reduction in the radiological exposure time progressively increased as our team got used with the nonfluoroscopic navigation system. Overall and single arrhythmia-divided mean radiological exposure times can be significantly reduced by the LocaLisa system during radiofrequency catheter ablation procedures. The reduction of radiation increases progressively by becoming friendly to the system with a very short duration of learning curve phase.


Structure-Based Design of First-Generation Small Molecule Inhibitors Targeting the Catalytic Pockets of AID, APOBEC3A, and APOBEC3B.
Activation-induced cytidine deaminase (AID) initiates antibody diversification by mutating immunoglobulin loci in B lymphocytes. AID and related APOBEC3 (A3) enzymes also induce genome-wide mutations and lesions implicated in tumorigenesis and tumor progression. The most prevalent mutation signatures across diverse tumor genomes are attributable to the mistargeted mutagenic activities of AID/A3s. Thus, inhibiting AID/A3s has been suggested to be of therapeutic benefit. We previously used a computational-biochemical approach to gain insight into the structure of AID's catalytic pocket, which resulted in the discovery of a novel type of regulatory catalytic pocket closure that regulates AID/A3s that we termed the "Schrodinger's CATalytic pocket". Our findings were subsequently confirmed by direct structural studies. Here, we describe our search for small molecules that target the catalytic pocket of AID. We identified small molecules that inhibit purified AID, AID in cell extracts, and endogenous AID of lymphoma cells. Analogue expansion yielded derivatives with improved potencies. These were found to also inhibit A3A and A3B, the two most tumorigenic siblings of AID. Two compounds exhibit low micromolar IC50 inhibition of AID and A3A, exhibiting the strongest potency for A3A. Docking suggests key interactions between their warheads and residues lining the catalytic pockets of AID, A3A, and A3B and between the tails and DNA-interacting residues on the surface proximal to the catalytic pocket opening. Accordingly, mutants of these residues decreased inhibition potency. The chemistry and abundance of key stabilizing interactions between the small molecules and residues within and immediately outside the catalytic pockets are promising for therapeutic development.


In silico analysis of single nucleotide polymorphism (rs34377097) of TBXA2R gene and pollen induced bronchial asthma susceptibility in West Bengal population, India.
Prevalence of asthma is increasing steadily among general population in developing countries over past two decades. One of the causative agents of broncho-constriction in asthma is thromboxane A2 receptor (TBXA2R). However few studies of TBXA2R polymorphism were performed so far. The present study aimed to assess potential association of TBXA2R rs34377097 polymorphism causing missense substitution of Arginine to Leucine (R60L) among 482 patients diagnosed with pollen-induced asthma and 122 control participants from West Bengal, India. Also we performed in-silico analysis of mutated TBXA2R protein (R60L) using homology modeling. Clinical parameters like Forced expiratory volume in 1 second (FEV1), FEV1/Forced vital capacity (FVC) and Peak expiratory flow rate (PEFR) were assessed using spirometry. Patients' sensitivity was measured by skin prick test (SPT) against 16 pollen allergens. Polymerase chain reaction-based Restriction fragment length polymorphism was done for genotyping. Structural model of wild type and homology model of polymorphic TBXA2R was generated using AlphaFold2 and MODELLER respectively. Electrostatic surface potential was calculated using APBS plugin in PyMol. Genotype frequencies differed significantly between the study groups (P=0.03). There was no significant deviation from Hardy-Weinberg equilibrium in control population (χ2=1.56). Asthmatic patients have significantly higher frequency of rs34377097TT genotype than control subjects (P=0.03). SPT of patients showed maximum sensitivity in A. indica (87.68%) followed by C. nusifera (83.29%) and C. pulcherima (74.94%). Significant difference existed for pollen sensitivity in adolescent and young adult (P=0.01) and between young and old adult (P=0.0003). Significant negative correlation was found between FEV1/FVC ratio and intensity of SPT reactions (P<0.0001). Significant association of FEV1, FEV1/FVC and PEFR was observed with pollen-induced asthma. Furthermore, risk allele T was found to be clinically correlated with lower FEV1/FVC ratio (P=0.015) in patients. Our data showed R60L polymorphism, which was conserved across mammals, significantly reduced positive electrostatic charge of polymorphic protein in cytoplasmic domain thus altered downstream pathway and induced asthma response. The present in-silico study is the first one to report association of TBXA2R rs34377097 polymorphism in an Indian population. It may be used as prognostic marker of clinical response to asthma in West Bengal and possible target of therapeutics in future.


Effect of carbon nanotube addition on the wear behavior of basalt/epoxy woven composites.
The effect of acid-treated carbon nanotube (CNT) addition on the wear and dynamic mechanical thermal properties of basalt/epoxy woven composites was investigated in this study. Basalt/CNT/epoxy composites were fabricated by impregnating woven basalt fibers into epoxy resin mixed with 1 wt% CNTs which were acid-treated. Wear and DMA (dynamic mechanical analyzer) tests were performed on basalt/epoxy composites and basalt/CNT/epoxy composites. The results showed that the addition of the acid-treated CNTs improved the wear properties of basalt/epoxy woven composites. Specifically, the friction coefficient of the basalt/epoxy composite was stabilized in the range of 0.5-0.6 while it fell in the range of 0.3-0.4 for basalt/CNT/epoxy composites. The wear volume loss of the basalt/CNT/epoxy composites was approximately 68% lower than that of the basalt/epoxy composites. The results also showed that the glass transition temperature of basalt/CNT/epoxy composites was higher than that of basalt/epoxy composites. The improvement of wear properties of basalt/epoxy composites by the addition of acid-treated CNTs was caused by the homogeneous load transfer between basalt fibers and epoxy matrix due to the reinforcement of CNTs.


Exposure to a Glyphosate-based Herbicide Alters the Expression of Key Regulators of Mammary Gland Development on Pre-pubertal Male Rats.
We previously reported that exposure during gestation and lactation to a low dose of glyphosate-based herbicide (GBH) reduced the area and perimeter of male offspring mammary gland at postnatal day 60 (PND60), whereas a higher dose increased the longitudinal growth of the gland. Here, our aim was to assess whether perinatal exposure to GBH exhibits endocrine disruptive action in male mammary gland at an early time point (pre-puberty), which could be related to the changes observed after puberty. We also wanted to explore whether an early evaluation of the male rat mammary gland is appropriate to assess exposure to potential endocrine disrupting chemicals (EDCs). Pregnant rats were orally exposed, through the diet, to vehicle (saline solution), 3.5 or 350 mg/kg/day of GBH from gestational day 9 until weaning. At PND21, the male offspring were euthanized, and mammary gland samples were collected. The histology and proliferation index of the mammary glands were evaluated, and the mRNA expression of estrogen (ESR1) and androgen (AR) receptors, cyclin D1 (Ccnd1), amphiregulin (Areg), insulin-like growth factor 1 (IGF1), epidermal growth factor receptor (EGFR) and IGF1 receptor (IGF1R) were assessed. Moreover, the phosphorylated-Erk1/2 (p-ERK1/2) protein expression was determined. No differences were observed in mammary epithelial structures and AR expression between experimental groups; however, the proliferation index was reduced in GBH3.5-exposed males. This result was associated with decreased ESR1, Ccnd1, Areg, IGF1, EGFR and IGF1R mRNA expressions, as well as reduced p-Erk1/2 protein expression in these animals. ESR1, Ccnd1, IGF1R and EGFR expressions were also reduced in GBH350-exposed males. In conclusion, the mammary gland development of pre-pubertal male rats is affected by perinatal exposure to GBH. Although further studies are still needed to understand the molecular mechanisms involved in GBH350 exposure, the present results may explain the alterations observed in mammary gland growth of post-pubertal males exposed to low doses of GBH. Our results also suggest that early evaluation of the male rat mammary gland is useful in assessing exposure to potential EDCs. However, analysis of EDCs effects at later time points should not be excluded.


The Challenges and Advances in Diagnosis of Vector-Borne Diseases: Where Do We Stand?
Vector-borne diseases (VBD) are of major importance to human and animal health. In recent years, VBD have been emerging or re-emerging in many geographical areas, alarming new disease threats and economic losses. The precise diagnosis of many of these diseases still remains a major challenge because of the lack of comprehensive data available on accurate and reliable diagnostic methods. Here, we conducted a systematic and in-depth review of the former, current, and upcoming techniques employed for the diagnosis of VBD.


Drought tolerance of Aspergillus violaceofuscus and Bacillus licheniformis and their influence on tomato growth and potassium uptake in mica amended tropical soils under water-limiting conditions.
Drought is a significant abiotic stress that alters plant physiology and ultimately affects crop productivity. Among essential plant nutrients, potassium (K) is known to mitigate the deleterious effect of drought on plant growth. If so, K addition or inoculation of potassium solubilizing microorganisms (KSMs) that are tolerant to drought should promote plant growth during water stress. Therefore, in this study, K solubilizing Aspergillus violaceofuscus and Bacillus licheniformis, isolated from saxicolous environments, were tested for their capacity to tolerate drought using different molecular weights (~4000, 6000, and 8000 Da), and concentrations (0, 250, 500, 750, 1000, and 1250 mg/L) of polyethylene glycol (PEG) under in vitro conditions. The results showed that high concentrations (750 and 1000 mg/L) of PEG with different molecular weight considerably improved bacterial cell numbers/fungal biomass and catalase (CAT) and proline activities. Moreover, the ability of KSMs alone or in combination to impart drought tolerance and promote plant growth in the presence and absence of mica (9.3% K2O) supplementation was tested in Alfisol and Vertisol soil types under greenhouse conditions. The results revealed that the tomato plants inoculated with KSMs individually or dually with/without mica improved the physiological and morphological traits of the tomato plants under drought. Generally, tomato plants co-inoculated with KSMs and supplemented with mica were taller (2.62 and 3.38-fold) and had more leaf area (2.03 and 1.98-fold), total root length (3.26 and 8.86-fold), shoot biomass (3.87 and 3.93-fold), root biomass (9.00 and 7.24-fold), shoot K content (3.08 and 3.62-fold), root K content (3.39 and 2.03-fold), relative water content (1.51 and 1.27-fold), CAT activity (2.11 and 2.14-fold), proline content (3.41 and 3.28-fold), and total chlorophyll content (1.81 and 1.90-fold), in unsterilized Alfisol and Vertisol soil types, respectively, than uninoculated ones. Dual inoculation of the KSMs along with mica amendment, also improved the endorrhizal symbiosis of tomato plants more than their individual inoculation or application in both soil types. These findings imply that the A. violaceofuscus and B. licheniformis isolates are promising as novel bioinoculants for improving crop growth in water-stressed and rainfed areas of the tropics in the future.


Work-related stress, reason for consultation and diagnosis-specific sick leave: How do they add up?
Work-related stress is common in Western society and disorders associated with stress are often managed in primary health care. This study was set to increase the understanding of the relationship between reason for consultation, work-related stress and diagnosis-specific sick leave for primary health care patients. The longitudinal observational study included 232 employed non-sick listed patients at seven primary health care centres in Sweden. Of these patients, 102 reported high work-related stress, as measured with the Work Stress Questionnaire, and 84 were on registered sick leave within one year after inclusion. The study showed that, compared to those who did not report high work-related stress, highly stressed patients more often sought care for mental symptoms (60/102 versus 24/130), sleep disturbance (37/102 versus 22/130) and fatigue (41/102 versus 34/130). The risk for sick leave with a mental diagnosis within a year after base-line was higher among patients reporting high work-related stress than among those who did not (RR 2.97, 95% CI 1.59;5.55). No such association was however found for the risk of sick leave with a musculoskeletal diagnosis (RR 0.55, 95% CI 0.22;1.37). Seeking care for mental symptoms, sleep disturbance and fatigue were associated with having a future mental sick leave diagnosis (p-values < 0.001), while seeking care for musculoskeletal symptoms was associated with having a future musculoskeletal sick leave diagnosis (p-value 0.009). In summary, compared to those who did not report high work-related stress, patients with high work-related stress more often sought care for mental symptoms, sleep disturbance and fatigue which lead to a mental sick leave diagnosis. Reporting high work-related stress was, however, not linked to having sought care for musculoskeletal symptoms nor future sick leave due to a musculoskeletal diagnosis. Hence, both patients and general practitioners seem to characterize work-related stress as a mental complaint.


Comparing performance of Tabriz obstetrics and gynaecology hospitals managed as autonomous and budgetary units using Pabon Lasso method.
Considering governmental scrutiny and financial constraints in medicine, the need for improved performance, which can provide acceptable care for medical consumers, leads to the conduct of new managerial methods to improve effectiveness. This study aimed to compare performance indicators of obstetrics and gynaecology teaching hospitals in Tabriz. A longitudinal, retrospective study was conducted to compare performance indexes of Tabriz obstetrics and gynaecology teaching hospitals during 2010-2012. Al-Zahra is Tabriz's central teaching hospital in obstetrics and gynaecology that is authorised under a board of trustees as an autonomous hospital and Taleghani hospital is managed under centralised administration. Study variables included: Average Length of Stay (ALOS), Bed Occupancy Rate (BOR), and Bed Turnover Ratio (BTR). The data was extracted via the Hospital Information Systems (HIS) within the hospitals' admission and discharge units. Pabon Lasso model was used to assess hospital performance. Data was analysed and graphs were plotted using the SPSS-17 software package. According to study findings, overall ALOS in Al-Zahra hospital is 3.15 (2.15) days (1.88 (0.97) days for prenatal wards and 6.13 (0.97) days for neonatal wards) and ALOS in Taleghani Hospital is 3.37 (3.09) days (1.74 (0.14) days for perinatal wards and 5.96 (3.55) days for neonatal wards). In this regard, Al-Zahra hospital holds the maximum BOR with 86.92 per cent and the minimum BOR was attributed to Taleghani hospital at 68.44 per cent (P<0.001). Study findings indicate that BOR in neonatal wards is greater than prenatal wards. On the other hand, BOR in Al-Zahra is greater than Taleghani (P<0.001), whereas BOR trend shows an increasing pattern in both hospitals. Results of this study showed that the performance of Al- Zahra Hospital is better than Taleghani Hospital. These two hospitals are similar in different aspects except Al-Zahra is under a board of trustees and Taleghani is not. We should also consider that Al-Zahra Hospital has more facilities than Taleghani.


The mechanistic basis for higher-order interactions and non-additivity in competitive communities.
Motivated by both analytical tractability and empirical practicality, community ecologists have long treated the species pair as the fundamental unit of study. This notwithstanding, the challenge of understanding more complex systems has repeatedly generated interest in the role of so-called higher-order interactions (HOIs) imposed by species beyond the focal pair. Here we argue that HOIs - defined as non-additive effects of density on per capita growth - are best interpreted as emergent properties of phenomenological models (e.g. Lotka-Volterra competition) rather than as distinct 'ecological processes' in their own right. Using simulations of consumer-resource models, we explore the mechanisms and system properties that give rise to HOIs in observational data. We demonstrate that HOIs emerge under all but the most restrictive of assumptions, and that incorporating non-additivity into phenomenological models improves the quantitative and qualitative accuracy of model predictions. Notably, we also observe that HOIs derive primarily from mechanisms and system properties that apply equally to single-species or pairwise systems as they do to more diverse communities. Consequently, there exists a strong mandate for further recognition of non-additive effects in both theoretical and empirical research.


Direct monitoring of lipid transfer on exposure of citrem nanoparticles to an ethanol solution containing soybean phospholipids by combining synchrotron SAXS with microfluidics.
Lipid exchange among citrem nanoparticles and an ethanol micellar solution containing soy phosphatidylcholine was investigated in situ by coupling small angle X-ray scattering with a microfluidic device. The produced soy phosphatidylcholine/citrem nanoparticles have great potential in the development of hemocompatible nanocarriers for drug delivery.


Profiling and bioinformatics analyses reveal differential circular RNA expression in hypertensive patients.
CircRNAs, a novel class of noncoding RNAs, have been reported in many diseases. However, their role in hypertension remains unclear. Here, we aimed to determine the circRNA expression profile in hypertension patients and further construct a circRNA-miRNA-mRNA network for mechanism exploration. Plasma circRNA expression profiles were screened by circRNA microarrays and verified by qRT-PCR method. CircRNA-miRNA-mRNA network was established to predict the circRNA targets. Gene ontology (GO) analysis and KEGG pathway analysis were applied for further enrichment of mRNA data. CircRNA microarrays study identified 13 downregulated and 46 upregulated circRNAs in hypertension patients, where four circRNAs (hsa-circ-0000437, hsa-circ-0008139, hsa-circ-0005870 and hsa-circ-0040809) showed significantly difference. By further validation, hsa-circ-0005870 exhibited significant downregulation in hypertensive patients. Then, we constructed a network of hsa-circ-0005870-targeted miRNAs, including hsa-miR-6807-3p, hsa-miR-5095, hsa-miR-1273g-3p, hsa-miR-5096, hsa-miR-619-5p, and their corresponding mRNAs. Gene oncology and KEGG pathway analysis enriched from specific mRNAs indicated the involvement of hsa-circ-0005870 in hypertension. In summary, hsa-circ-0005870 may represent a novel biomarker for the diagnosis of hypertension, and hsa-circ-0005870-miRNA-mRNA network may provide potential mechanism for hypertension.


[Using multiplex PCR to analyze the breakpoint of a severe Y-chromosome deletion].
To elucidate the relationship between azoospermia factor(AZF) microdeletion of Y chromosome and azoospermia, the exact breakpoint of a severe Y-chromosome deletion was determined according to the physical map of AZF. Multiplex polymerase chain reaction was used to amplify fifteen sequence tagged sites (STS), namely sY82, sY84, sY86 in AZFa, sY124, sY127, sY128, sY133, sY134, sY143 in AZFb, sY239, sY242 sY254, sY255 in AZFc, and sY145, sY152 in AZFd; sex-determining region Y(SRY) was taken as an internal control. And then sY82,sY86,sY85,sY84 were further analyzed using the sample of the patient who had Y-chromosome deletion by G band analysis to map the breakpoint at molecular level. All 15 STS and sY85 were amplified in positive control while only sY82, sY86 were amplified in the clinical sample, thus the breakpoint was found to be between sY86 and sY85. This study on the patient provided the direct biomolecular evidence of the exact breakpoint of the severe Y-chromosome deletion and established the deletion map of acrocentric chromosome. It also proved that the patient's azoospermia was due to the deletion of AZF.


Cooperative Bond Activation and Catalytic CO2 Functionalization with a Geometrically Constrained Bis(silylene)-Stabilized Borylene.
Metal-ligand cooperativity has emerged as an important strategy to tune the reactivity of transition-metal complexes for the catalysis and activation of small molecules. Studies of main-group compounds, however, are scarce. Here, we report the synthesis, structural characterization, and reactivity of a geometrically constrained bis(silylene)-stabilized borylene. The one-pot reaction of [(SiNSi)Li(OEt2)] (SiNSi = 4,5-bis(silylene)-2,7,9,9-tetramethyl-9H-acridin-10-ide) with 1 equiv of [BBr3(SMe2)] in toluene at room temperature followed by reduction with 2 equiv of potassium graphite (KC8) leads to borylene [(SiNSi)B] (1), isolated as blue crystals in 45% yield. X-ray crystallography shows that borylene (1) has a tricoordinate boron center with a distorted T-shaped geometry. Computational studies reveal that the HOMO of 1 represents the lone pair orbital on the boron center and is delocalized over the Si-B-Si unit, while the geometric perturbation significantly increases its energy. Borylene (1) shows single electron transfer reactivity toward tris(pentafluorophenyl)borane (B(C6F5)3), forming a frustrated radical pair [(SiNSi)B]•+[B(C6F5)3]•-, which can be trapped by its reaction with PhSSPh, affording an ion pair [(SiNSi)BSPh][PhSB(C6F5)3] (3). Remarkably, the cooperation between borylene and silylene allows the facile cleavage of the N-H bond of aniline, the P-P bond in white phosphorus, and the C═O bond in ketones and carbon dioxide, thus representing a new type of main-group element-ligand cooperativity for the activation of small molecules. In addition, 1 is a strikingly effective catalyst for carbon dioxide reduction. Computational studies reveal that the cooperation between borylene and silylene plays a key role in the catalytic chemical bond activation process.


Inequality in child mortality across different states of India: a comparative study.
The burden of social inequality falls disproportionately on child health and survival. This inequality raises the question of how wide this gap is, or what its relation is with the level of child mortality. Whether these disparities are increasing or declining with the development and how they differ from region to region or from state to state within the country needs to be looked into. As a measure of inequality and to compare the disparities between different states of India, concentration curves and indices are constructed from infant and under five mortality data classified under different quintiles of wealth index from the National Family Health Survey (NFHS-3) data of India. Inequality measures indicate that inequality in child mortality is more concentrated in the comparatively developed states than the poorer states in India.


Fanconi anemia pathway--the way of DNA interstrand cross-link repair.
The study of rare genetic diseases usually inspires the research of cancer biology. Fanconi anemia (FA), is a rare cancer susceptibility syndrome with an incidence of only 1 per 350,000 births. FA is an autosomal recessive disease with three main features: chromosome instability, hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), cisplatin and so on, and susceptible to a number of cancer types, mainly leukemia and squamous cell carcinomas of the head and neck or gynecologic system. DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking. However, FA pathway is closely linked with carcinogenesis and tumor drug resistance. This paper mainly focuses on the FA pathway and its progress in cancer research.


Serum levels of creatine kinase and its isoenzymes during the 1st postpartum day in healthy newborns delivered vaginally or by cesarean section.
The purpose of this study is to investigate the relationship of creatine kinase (CK) and its isoenzyme levels in the newborn to the mode of delivery, time interval from birth (divided in four 6-hour time periods), parity and sex of the neonates. During the 1st postpartum day, serum levels of CK and its isoenzymes (CK-MM, CK-MB, CK-BB) were determined from 115 healthy full-term neonates born consecutively either by spontaneous vaginal delivery (VD, n = 85) or by elective cesarean section (CS, n = 30). The multiple regression analysis was applied. Total CK levels were positively correlated with VD (p < 0.0003). This was mainly attributed to a rise in the CK-MM activity which presented a similar pattern to CK. CK-MB activity was also positively correlated with VD. In contrast, CK-BB was negatively correlated to the postpartum time period. Neonatal sex and parity did not influence CK and its isoenzyme levels significantly. In conclusion, VD contributes significantly to an increase in CK levels during the 1st day of extrauterine life.


Transient ischemic attack and coronary artery disease: a two-sample Mendelian randomization analysis.
Although observational studies have shown that patients who experienced transient ischemic attacks (TIAs) had a higher risk of coronary artery disease (CAD), the causal relationship is ambiguous. We conducted a two-sample Mendelian randomization (MR) study to analyze the causal relationship between TIA and CAD using data from the FinnGen genome-wide association study. Analysis was performed using the inverse-variance weighted (IVW) method. The robustness of the results was evaluated using MR-Egger regression, the weighted median, MR pleiotropy residual sum, and outlier (MR-PRESSO) and multivariable MR analysis. Results from IVW random-effect model showed that TIA was associated with an increased risk of coronary artery atherosclerosis (OR 1.17, 95% CI 1.06-1.28, P = 0.002), ischemic heart disease (OR 1.15, 95% CI 1.04-1.27, P = 0.007), and myocardial infarction (OR1.15, 95% CI 1.02-1.29, P = 0.025). In addition, heterogeneity and horizontal pleiotropy were observed in the ischemic heart disease results, while the sensitivity analysis revealed no evidence of horizontal pleiotropy in other outcomes. This MR study demonstrated a potential causal relationship between TIA and CAD. Further research should be conducted to investigate the mechanism underlying the association.


Catastrophic misinterpretation of bodily sensations and external events in panic disorder, other anxiety disorders, and healthy subjects: A systematic review and meta-analysis.
The catastrophic misinterpretation model of panic disorder (PD) predicts that the catastrophic misinterpretation of bodily sensations is a distinctive characteristic of PD. Existing research on this prediction has produced mixed findings. This paper presents a systematic review and meta-analysis of studies comparing the strength of catastrophic misinterpretation of bodily sensations and external events in patients with PD, patients with other anxiety disorders, and healthy controls. Following a systematic screening, seven studies were included in the meta-analysis. For the catastrophic misinterpretation of bodily sensations, analyses showed medium to large effects between patients with PD and healthy controls and between patients with PD and patients with other anxiety disorders. For the catastrophic misinterpretation of external events, analyses showed medium to large effects between patients with PD and healthy controls and a small negative effect between patients with PD and patients with other anxiety disorders. The findings support the assumption that the catastrophic misinterpretation of bodily sensations is a distinctive characteristic of panic disorder and thus lend support to the catastrophic misinterpretation model of PD.


Therapeutic Evaluation of Topical Retinoic Acid in Acne Vulgaris.
A clinical trial with topical retinoic acid 0.05% was undertaken on 43 patients with acne vulgarism. The response was assessed over a 12 weeks period. Drug proved very effective giving excellent to good response in 83.3% of cases. Local reaction was temporary and in most cases the treatment could be successfully continued with reduced frequency of applications. The drug was well accepted by patients.


Statins and the neuromuscular system: a neurologist's perspective.
Statins intolerance is mainly due to their side effects on the neuromuscular system (primarily muscle). It has become an important issue because of the major cardiovascular risk reduction of this class of drugs. However, the facts related to these side effects are sometimes under-recognized or controversial. A literature review of the recent developments in the field is given. The clinical definition of statin myopathy and its presentation are not suitable for the myology field. Management and prevention are not validated. More genetic risk factors need to be established. Neurologists should become more involved in statin intolerance evaluation and management.


Modification of cell membrane composition by dietary lipids and its implications for atherosclerosis.
Dietary lipids can modify the properties of cell membranes, including membrane fluidity and membrane permeability. The saturation and isomerization of dietary fatty acids may affect the pattern of fatty acids acylated to glycerol in phospholipids. Oxidized sterols may affect membrane properties directly by their insertion in the membrane or indirectly through their effects on lipid metabolism. The flow of calcium and other nutrients into the cells appears to be a major property affected by those changes in lipid composition of membranes and may be important in the onset of atherosclerosis. The factors that alter the character of the lipids in cell membranes should receive increased study in both in vitro and in vivo systems to clarify their role in diseases processes.


Methods for studying protein synthesis and degradation in liver and skeletal muscle.
Different methods used for measuring protein turnover in liver and skeletal muscle are described, with special emphasis on technical and practical aspects and the advantages and limitations of different techniques. In the first part of the review, the concept of precursor specific radioactivity and its importance for accurate determination of protein synthesis rate is discussed. In the second part, different in vivo techniques for protein turnover measurements are reviewed, including continuous administration of tracer amino acid, flooding dose technique, indirect measurement of protein synthesis, and estimation of protein degradation in vivo. In the third part of the report, in vitro techniques are described, including measurement of protein turnover in incubated liver slices, perfused liver, isolated hepatocytes, incubated isolated muscles or muscle biopsies, and perfused rat hemicorpus. In vivo techniques are preferred when accurate absolute values of protein turnover rates are desired. In vitro techniques offer the advantage of standardized conditions, maintaining strict control of substrate and hormone concentrations, and eliminating complicating interactions with other tissues. For several in vitro techniques, a good correlation has been demonstrated between relative changes in protein turnover in vitro and in vivo in different conditions.


Unique Conformation in a Natural Interruption Sequence of Type XIX Collagen Revealed by Its High-Resolution Crystal Structure.
Naturally occurring interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. We determined the crystal structures of the host-guest peptide (GPO)3-GPOALO-(GPO)4 to 1.03 Å resolution in two crystal forms. In these structures, the interruption zone brings localized disruptions to the triple helix and introduces a light 6-8° bend with the same directional preference to the whole molecule, which may correspond structurally to the first physiological kink site in type XIX collagen. Furthermore, at the G5G interruption site, the presence of Ala and Leu residues, both with free N-H groups, allows the formation of more direct and water-mediated interchain hydrogen bonds than in the related Gly → Ala structure. These could partly explain the difference in thermal stability between the different interruptions. In addition, our structures provide a detailed view of the dynamic property of such an interrupted zone with respect to hydrogen bonding topology, torsion angles, and helical parameters. Our results, for the first time, also identified the binding of zinc to the end of the triple helix. These findings will shed light on how the interruption sequence influences the conformation of the collagen molecule and provide a structural basis for further functional studies.


Block copolymers containing organic semiconductor segments by RAFT polymerization.
Approaches to the synthesis of block copolymers containing organic semiconductor segments (polythiophene, perylene diimide) by RAFT polymerization have been explored. A method involving transformation of a vinyl derivative to a macro-RAFT agent provides for the synthesis of block copolymers which are joined by a short non-hydrolysable linkage.


[Tauopathy and Alzheimer disease: a full degenerating process].
Neurofibrillary degeneration is well correlated to the clinical signs of Alzheimer disease. However, the amyloid cascade is so well established in the scientific and medical community that the role of neurofibrillary degeneration in Alzheimer's disease etiopathogenesis is often underestimated. However, neuronal vulnerability is clearly a key factor for facilitating the amyloid pathology which allows the propagation of the degenerating process. In the present work, the role of tau pathology as both diagnostic marker and therapeutic target is highlighted in Alzheimer disease and related disorders.


Environmental variability and population dynamics: do European and North American ducks play by the same rules?
Density dependence, population regulation, and variability in population size are fundamental population processes, the manifestation and interrelationships of which are affected by environmental variability. However, there are surprisingly few empirical studies that distinguish the effect of environmental variability from the effects of population processes. We took advantage of a unique system, in which populations of the same duck species or close ecological counterparts live in highly variable (north American prairies) and in stable (north European lakes) environments, to distinguish the relative contributions of environmental variability (measured as between-year fluctuations in wetland numbers) and intraspecific interactions (density dependence) in driving population dynamics. We tested whether populations living in stable environments (in northern Europe) were more strongly governed by density dependence than populations living in variable environments (in North America). We also addressed whether relative population dynamical responses to environmental variability versus density corresponded to differences in life history strategies between dabbling (relatively "fast species" and governed by environmental variability) and diving (relatively "slow species" and governed by density) ducks. As expected, the variance component of population fluctuations caused by changes in breeding environments was greater in North America than in Europe. Contrary to expectations, however, populations in more stable environments were not less variable nor clearly more strongly density dependent than populations in highly variable environments. Also, contrary to expectations, populations of diving ducks were neither more stable nor stronger density dependent than populations of dabbling ducks, and the effect of environmental variability on population dynamics was greater in diving than in dabbling ducks. In general, irrespective of continent and species life history, environmental variability contributed more to variation in species abundances than did density. Our findings underscore the need for more studies on populations of the same species in different environments to verify the generality of current explanations about population dynamics and its association with species life history.


Effect of glucose concentrations on functional maturation of monolayer-cultured B cells from the rat pancreas.
The effect of two concentrations of glucose on the maturation of the response of B cells was studied in pancreatic monolayer cultures of the neonatal rat using a perifusion system. After exposure for the initial 3 days to a medium with 5.5 mmol glucose/l and 10 mumol iodoacetic acid/l (day 3), in order to delete fibroblasts selectively, monolayer cultures were kept for a total of 12 days in medium with either 5.5 or 16.7 mmol glucose/l alone. On day 3, B cells responded in a monophasic fashion, with no significant second phase, to acute challenge with 16.7 mmol glucose/l. At a concentration of 10 mmol/l, leucine and 2-ketoisocaproate both produced only minimal increases in the second phase of secretion above the basal level. In contrast, B cells on day 7 cultured in 5.5 mmol glucose/l showed a biphasic response to glucose, leucine and 2-ketoisocaproate. The magnitude in response to glucose was well preserved at day 15 of culture, whereas the stimulatory effects of leucine and 2-ketoisocaproate decreased to 24-57% of that of B cells on day 7. Moreover, B cells on day 7 cultured in 16.7 mmol glucose/l responded in a biphasic manner to glucose, the response being 65% of that of B cells in 5.5 mmol glucose/l. Additionally, the response to leucine and 2-ketoisocaproate still appeared to be monophasic. At day 15 of culture, however, the response of B cells in 16.7 mmol glucose/l to glucose was 105%, to leucine 245% and to 2-ketoisocaproate 127% of that of B cells in 5.5 mmol glucose/l.(ABSTRACT TRUNCATED AT 250 WORDS)


Noninvasive assessments of skin glycated proteins by fluorescence and Raman techniques in diabetics and nondiabetics.
Diabetes is a complex metabolic disease and has chronic complications. It has been considered a serious public health problem. The aim of the current study was to evaluate skin glycated proteins through fluorescence and Raman techniques. One hundred subjects were invited to participate in the study. Six volunteers did not attend due to exclusion criteria or a change of mind about participating. Therefore, 94 volunteers were grouped according to age range (20-80 years), health condition (nondiabetic, with insulin resistance [IR] and/or diabetic) and Fitzpatrick skin type (I-VI). The fluorescence spectrometer and the portable Raman spectroscopy system were used to measure glycated proteins from the skin. There was elevated skin autofluorescence in healthy middle-aged and elderly subjects, as well as in patients with IR and/or diabetes. Regarding Raman spectroscopy, changes in the skin hydration state, degradation of type I collagen and greater glycation were related for diabetes and chronological aging. Weak and positive correlation between the skin autofluorescence and the Raman peaks ratio (855/876) related to the glycated proteins was also found. Raman spectroscopy shows several bands for spectral analyses, complementing the fluorescence data. Therefore, this study contributes to understanding of the optical of human skin for noninvasive diabetes screening.


Very distal vein bypass in patients with thromboangiitis obliterans.
Surgical revascularization for chronic critical limb ischaemia in patients with thromboangiitis obliterans (TAO) still remains controversial. Generally, besides cessation of smoking, conservative treatment supported by intravenous administration of vasoactive agents is regarded as the treatment of choice, in combination with local wound therapy or minor amputation. In four male patients (42-47 years) surgical revascularization was chosen as therapy for established gangrene or non-healing ulceration after unsuccessful conservative treatment and cessation of smoking. Angiography was able to identify a suitable distal arterial segment for the bypass which was revascularized by means of an autologous vein graft. Grafts were followed with repetitive duplex ultrasound. Revision of the bypass graft was initiated if indicated by pathological duplex findings. In all cases a bypass could be constructed with either the ipsilateral greater saphenous vein or arm veins. A distal origin configuration was possible in three cases with popliteo-pedal or cruro-pedal bypasses. In the fourth case the distal superficial femoral artery was used for inflow. Two early graft thromboses underwent successful revision. During follow-up, duplex ultrasound identified graft stenoses in three bypasses which were successfully treated with endovascular techniques. All grafts are patent with complete resolution of ischaemic symptoms after 46, 42, 32, and 29 months. The patients remained non-smokers and returned to a professional life. Surgical therapy with distal vein bypass for persistent ischaemic symptoms after definitive cessation of smoking seems feasible in selected cases with TAO and a suitable distal artery. Close follow-ups of the patients with duplex ultrasound are necessary to identify developing vein graft stenoses. Angioplasty seems to be an important part of the long-term therapeutic concept.


p.Val452Ile mutation of the SLC25A13 gene in a Turkish patient with citrin deficiency.
Şeker-Yılmaz B, Kör D, Tümgör G, Ceylaner S, Önenli-Mungan N. p.Val452Ile mutation of the SLC25A13 gene in a Turkish patient with citrin deficiency. Turk J Pediatr 2017; 59: 311-314. Citrin deficiency is an autosomal recessive metabolic disorder, which is caused by pathogenic mutations in the SLC25A13 gene on chromosome 7q21.3, as the causative gene that encodes the liver type aspartate/glutamate carrier isoform 2 (AGC2). One of the main clinical presentations is neonatal intrahepatic cholestatic hepatitis caused by citrin deficiency. We report a Turkish child presented with prolonged neonatal jaundice associated with elevated plasma citrulline and galactosuria. NICCD was suspected at this point and mutation study of SLC25A13 showed that she was homozygous for the missense NM_014251.2:c.1354G > A (NP_055066.1:p.Val452Ile) (dbSNP: rs143877538) mutation. Dramatic response was observed to the dietary treatment with medium-chain triglycerides containing formula, ursodeoxycholic acid and fat-soluble vitamin supplementation. The minor allele frequency of this variant was given as nearly as 0.01 in the South Asian population; it seems like a disease causing variant. This is the first report of this variant in the Turkish and European population.


Tricuspid valve surgery.
The tricuspid valve has been taken as a non-critical valve in terms of acute or late mortality in a number of conditions. Tricuspid functional regurgitation is a cause of late operations with an increased morbidity. A number of techniques have been described and used in clinical practice in the past forty years and include simple suture techniques and the use of support for annuloplasty with the use of different types of prosthetic rings. The experience accumulated over the years indicates that tricuspid annuloplasty is mandatory to improve late results, which are superior, in general, to replacement of the valve. The role of echocardiography in defining surgical planning, intraoperative results and follow-up is reviewed as echocardiography is a fundamental tool in cardiac surgery. Surgery for isolated lesions of the tricuspid valve has not received much attention and herein we report the results of the follow-up of a limited series of patients undergoing isolated tricuspid surgery. The correlation between echocardiographic measurements and surgical measurements was confirmed and was helpful at the time of the confirmation of repair (r=0.53). Forty-seven patients (18 repair, 29 replacement) underwent isolated surgery. Results of isolated tricuspid repair seemed to be superior when compared to those of tricuspid replacement. Survival was 20.7% for tricuspid valve replacement (N=18) and 50% for tricuspid valve repair (N=29) (p=0.04). Freedom from reoperation was 94.4±5.4% for repair and 67.3±12.1% for replacement (p= 0.0011). The tricuspid valve continues to be a surgical challenge.


Which MR-derived perfusion parameters are the best predictors of infarct growth in hyperacute stroke? Comparative study between relative and quantitative measurements.
To compare predictors of infarct growth in hyperacute stroke from a retrospective review of various relative and quantitative parameters calculated at perfusion-weighted magnetic resonance (MR) imaging performed within 6 hours after ictus. Fluid-attenuated inversion recovery and diffusion- and perfusion-weighted images were obtained in 66 patients. The initial infarct was delineated on diffusion-weighted images; the hemodynamic disturbance, on apparent mean transit time (MTT) maps; and the final infarct, on follow-up fluid-attenuated inversion recovery images. Relative (without and with deconvolution) and quantitative values of the bolus arrival time, time to peak (TTP), apparent MTT or MTT, cerebral blood volume (CBV), peak height, and cerebral blood flow (CBF) index or CBF were calculated for initial infarct, infarct growth (final minus initial infarct contour), viable hemodynamic disturbance (apparent MTT minus final infarct contour), and contralateral mirror regions. Univariate and multivariate analyses (receiver operating characteristic curves and discriminant analysis) were performed to compare the diagnostic performance of these parameters for predicting infarct growth. At univariate analysis, relative peak height and quantitative CBF were the best predictors of infarct growth; at multivariate analysis, a function of peak height and TTP for relative measurements and CBF alone for quantitative measurements. Quantitative and relative measurements (without or with deconvolution) worked equally well. A combined relative peak height or TTP threshold (<54% or >5.2 seconds, respectively) had a sensitivity of 71% and a specificity of 98%. A quantitative CBF threshold (<35 mL/min/100 g) had a sensitivity of 69% and a specificity of 85%. A combination of relative peak height and TTP measurements allowed the best prediction of infarct growth, which obviates more complex quantitative calculation.


Application of bioluminescence resonance energy transfer to quantitate cell-surface expression of membrane proteins.
We report a bioluminescence resonance energy transfer (BRET) assay to quantitate the fraction of an engineered membrane protein at the cell surface versus inside the cell. As test cases, we engineered two different G protein-coupled receptors (GPCRs) in which a NanoLuc luciferase (NLuc) and a HaloTag are fused to the extracellular amino-terminal tail of the receptors. We then employed a pulse-chase labeling approach relying on two different fluorescent dyes with distinctive cell permeability properties. The dyes are efficiently excited by luminescence from NLuc, but are spectrally distinct. Measuring BRET from the chemiluminescence of the NLuc to the fluorophores bound to the HaloTag minimizes the limitations of in-cell fluorescence resonance energy transfer (FRET)-based approaches such as photobleaching and autofluorescence. The BRET surface expression assay can quantitatively differentiate between the labeling of receptors at the cell surface and receptors inside of the cell. The assay is shown to be quantitative and robust compared with other approaches to measure cell surface expression of membrane proteins such as enzyme-linked immunosorbent assay or immunoblotting, and significantly increases the throughput because the assay is designed to be carried out in microtiter plate format.


Enhanced environmental disinfection systems. Can they help you reduce infection rates?
Enhanced environmental disinfection systems are designed to disinfect surfaces of patient rooms using vaporized agents, UV light, or other techniques. But just how effective are they at reducing healthcare-associated infection rates? The jury is still out.


Contact System Activation and Cancer: New Insights in the Pathophysiology of Cancer-Associated Thrombosis.
Cancer induces a systemic hypercoagulable state that elevates the baseline thrombotic risk of affected patients. This hypercoagulable state reflects a complex interplay between cancer cells and host cells and the coagulation system as part of the host response to cancer. Although the tissue factor (TF)/factor VIIa pathway is proposed to be the principal initiator of fibrin formation in cancer patients, clinical studies have not shown a consistent relationship between circulating TF levels (often measured as plasma microvesicle-associated TF) and the risk of thrombosis. A renewed interest in the role of the contact pathway in thrombosis has evolved over the past decade, raising the question of its role in the pathogenesis of thrombotic complications in cancer. Recent observations have documented the presence of activation of the contact system in gastrointestinal, lung, breast and prostate cancers. Although the assays used to measure contact activation differ, and despite the absence of standardization of methodologies, it is clear that both the intrinsic and extrinsic pathways may be activated in cancer. This review will focus on recent findings concerning the role of activation of the contact system in cancer-associated hypercoagulability and thrombosis. An improved understanding of the pathophysiology of these mechanisms may lead to personalized antithrombotic protocols with improved efficacy and safety compared with currently available therapies.


Asymmetric trehalose analogues to probe disaccharide processing pathways in mycobacteria.
The uptake and metabolism of the disaccharide trehalose by Mycobacterium tuberculosis is essential for the virulence of this pathogen. Here we describe the chemoenzymatic synthesis of new azido-functionalised asymmetric trehalose probes that resist degradation by mycobacterial enzymes and are used to probe trehalose processing pathways in mycobacteria.


Comparison of pre- and post-ischemic treatment of telmisartan and nimodipine combination in experimentally induced cerebral ischemia.
Time dependent intervention plays a crucial role in preventing neurodegeneration after ischemic insult. The intensity of excitotoxicity is greater in the secondary reperfusion phase (2-4 h) compared to the primary occlusion phase (2 h), which could be attributed to secondary elevation of excitatory amino acids (EAA) in cerebral ischemia. In the present study, we tried to assess the neuroprotective effects of telmisartan and nimodipine (TM-NM) combination on the secondary reperfusion phase. The drug treatments were made immediately after reperfusion and their effects were compared with pre-treatment. The neuroprotective effect was studied using middle cerebral artery occlusion (MCAo) transient ischemic model in rats. On the 7th day after reperfusion, the rats were subjected to behavioral studies. The brain was dissected out on the 9th day to measure neurobiochemical alterations and for histopathological observations. The results have shown that TM-NM (5 mg/kg) attenuated the EAA release in different brain regions with partial restoration of energy levels in secondary reperfusion phase. Similarly, it normalized the behavioral alteration and the effect was comparable to pre-ischemic treatment (2.5 mg/kg). Pre-ischemic treatment of TM-NM (2.5 mg/kg) protected the neurons from ischemic reperfusion injury by energy dependent EAA regulation. It can be concluded from the study that, even though the pre- and post-treatment of TM-NM show similar results, the post-ischemic treatment of TM-NM combination is beneficial due to better EAA control. Since hypertension is the primary risk factor for stroke, clinical incidents of stroke in hypertensive patients receiving angiotensin receptor blockers (ARBs) can be further investigated to understand the present study in the clinical situation.


Effect of hog pancreatic kallikrein on blood pressure in rats.
In all mammals investigated so far, an amount of 0.1 - 1 biological unit (KU) of hog pancreatic kallikrein per kg body weight injected intravenously caused a fast reduction in blood pressure with one exception, the rat. Even 1000 times higher doses of hog pancreatic kallikrein did not reduce the blood pressure in this animal. In spite of many experiments performed with rats using hog pancreatic kallikrein to influence various metabolic pathways, there has been no proof, to date, that this enzyme also causes kallikrein-specific effects via kinin liberation in rats. We found only a slow and weak reduction of rat blood pressure after injection of 100 KU hog pancreatic kallikrein per rat, when the endogenous kininases had been previously inactivated by the kininase II inhibitor captopril. However, a fast reduction in blood pressure, similar to the response observed after kinin injection, could be recorded if 90 microliter rat blood, previously incubated for a few minutes with a least 20 k.u. hog pancreatic kallikrein in the presence of captopril, was reinjected. Hence, kinin liberation from rat kininogens by hog pancreatic kallikrein does occur, but proceeds so slowly that the fast kinin degradation by kininases can prevent the typical blood pressure effect of kinin in vivo.


Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis.
T-cell proliferation and generation of protective memory during chronic infections depend on Interleukin-7 (IL-7) availability and receptivity. Regulation of IL-7 receptor (IL-7R) expression and signalling are key for IL-7-modulated T-cell functions. Aberrant expression of soluble (s) and membrane-associated (m) IL-7R molecules is associated with development of autoimmunity and immune failure in acquired immune deficiency syndrome (AIDS) patients. Here we investigated the role of IL-7/IL-7R on T-cell immunity in human tuberculosis. We performed two independent case-control studies comparing tuberculosis patients and healthy contacts. This was combined with follow-up examinations for a subgroup of tuberculosis patients under therapy and recovery. Blood plasma and T cells were characterised for IL-7/sIL-7R and mIL-7R expression, respectively. IL-7-dependent T-cell functions were determined by analysing STAT5 phosphorylation, antigen-specific cytokine release and by analysing markers of T-cell exhaustion and inflammation. Tuberculosis patients had lower soluble IL-7R (p < 0.001) and higher IL-7 (p < 0.001) plasma concentrations as compared to healthy contacts. Both markers were largely independent and aberrant expression normalised during therapy and recovery. Furthermore, tuberculosis patients had lower levels of mIL-7R in T cells caused by post-transcriptional mechanisms. Functional in vitro tests indicated diminished IL-7-induced STAT5 phosphorylation and impaired IL-7-promoted cytokine release of Mycobacterium tuberculosis-specific CD4+ T cells from tuberculosis patients. Finally, we determined T-cell exhaustion markers PD-1 and SOCS3 and detected increased SOCS3 expression during therapy. Only moderate correlation of PD-1 and SOCS3 with IL-7 expression was observed. We conclude that diminished soluble IL-7R and increased IL-7 plasma concentrations, as well as decreased membrane-associated IL-7R expression in T cells, reflect impaired T-cell sensitivity to IL-7 in tuberculosis patients. These findings show similarities to pathognomonic features of impaired T-cell functions and immune failure described in AIDS patients.


Ruptured abdominal aortic aneurysm: long-term survival after operation.
The long-term follow-up of 65 patients surviving surgery for ruptured abdominal aortic aneurysms is presented. Fifty-six per cent of these patients were alive at the time of review, having survived for a mean period of 36 months. The majority were enjoying a quality of life similar to that experienced before operation. Preexisting ischaemic heart disease did not alter the long-term prognosis. Cumulative survival curves for this group of survivors approximated both the survival curve for the average matched Australian population and similar curves constructed for patients operated upon electively for abdominal aortic aneurysms.


[The risk of diabetic complications in older elderly diabetic patients].
We examined the risk of the diabetic complications among older elderly diabetic patients. We compared the HbA1c levels of 117 type 2 diabetic patients ≥ 75 years old over a 5-year period, before patients received a diagnosis of diabetic complications, with those of diabetic patients without diabetic complications. The HbA1c levels of diabetic retinopathy patients were significantly higher than those of patients without diabetic retinopathy (7.9% vs. 6.8%, p<0.01). Similarly, the HbA1c levels of patients with diabetic nephropathy were significantly higher than those of patients without diabetic nephropathy (7.3% vs. 6.7%, p<0.01). The HbA1c levels of diabetic patients with cerebral infarction or ischemic heart disease were also higher than those in diabetic patients without these vascular complications (7.7% vs. 7.0%, p<0.05). The current findings emphasize the importance of careful glycemic control for the prevention of diabetic complications in older elderly patients.


Transcription factor FOXO1 promotes cell migration toward exogenous ATP via controlling P2Y1 receptor expression in lymphatic endothelial cells.
Sprouting migration of lymphatic endothelial cell (LEC) is a pivotal step in lymphangiogenic process. However, its molecular mechanism remains unclear including effective migratory attractants. Meanwhile, forkhead transcription factor FOXO1 highly expresses in LEC nuclei, but its significance in LEC migratory activity has not been researched. In this study, we investigated function of FOXO1 transcription factor associated with LEC migration toward exogenous ATP which has recently gathered attentions as a cell migratory attractant. The transwell membrane assay indicated that LECs migrated toward exogenous ATP, which was impaired by FOXO1 knockdown. RT-PCR analysis showed that P2Y1, a purinergic receptor, expression was markedly reduced by FOXO1 knockdown in LECs. Moreover, P2Y1 blockage impaired LEC migration toward exogenous ATP. Western blot analysis revealed that Akt phosphorylation contributed to FOXO1-dependent LEC migration toward exogenous ATP and its blockage affected LEC migratory activity. Furthermore, luciferase reporter assay and ChIP assay suggested that FOXO1 directly bound to a conserved binding site in P2RY1 promoter and regulated its activity. These results indicated that FOXO1 serves a pivotal role in LEC migration toward exogenous ATP via direct transcriptional regulation of P2Y1 receptor.


Improving ondansetron use and oral rehydration instructions for pediatric acute gastroenteritis.
In paediatric patients with acute gastroenteritis (AGE), ondansetron use decreases the need for intravenous fluids, reduces hospitalisations and shortens illness duration. Oral rehydration is also known to have excellent outcomes for mild to moderate dehydration secondary to AGE. Although these interventions are recommended in guidelines from international professional societies, baseline data at our clinic showed that <2% of these patients were offered ondansetron, and that few patients received appropriately detailed rehydration instructions. Therefore, we engaged residents and fellows as teachers and leaders in our university clinic's quality improvement programme to promote evidence-based practice for paediatric AGE. Our gap analysis identified opportunities for interventions including educating paediatricians and paediatrics residents on the safety and utility of the medication. We created standardised oral rehydration after-visit instructions and implemented a trainee-led educational approach that encouraged appropriate medication use. We used a follow-up survey to uncover provider concerns and tailor future interventions. The process metrics included: proportion of paediatric patients appropriately treated with ondansetron (goal of 80%), and proportion of patients given appropriate oral rehydration instructions. The outcome metric was 7-day representation rates. To achieve sustainability, we restructured our process to have senior residents take ownership of teaching and data collection. Trainee-driven interventions increased ondansetron prescription rates to a median of 66.6%. Patients prescribed ondansetron were less likely to represent to care, although representation rate was low overall. Postintervention data suggests that prescription rates decreased without continued interventions and additional systems redesign may help sustain impact.


Psychiatric Diagnoses and Treatment Preceding Schizophrenia in Adolescents Aged 9-17 Years.
Our study aimed to examine psychiatric diagnoses and treatment preceding a schizophrenia diagnosis in adolescents, stratified by sex and race/ethnicity. Using Medicaid physical and behavioral health and pharmacy claims data, we identified 1,459 adolescents who were aged 9-17 years and diagnosed with schizophrenia between January 2006 through June 2009. Psychiatric diagnosis, mental health service use including psychiatric hospitalization, residential treatment and outpatient therapy and psychotropic medication use preceding schizophrenia were identified. Forty-five percent of the adolescents were diagnosed with one or more psychiatric conditions. More than 40% of the adolescents were hospitalized or placed in a residential treatment facility for other psychiatric conditions preceding schizophrenia. Overall, 72% of the adolescents were prescribed with one or more psychotropic medications and 22% were prescribed with three or more psychotropic medications in the year prior to their first schizophrenia diagnosis. We found that sex and race/ethnicity influence preceding psychiatric conditions and psychiatric treatment use. Careful screening and evaluation to validate diagnoses is important as the presence of certain psychiatric morbidity is common among adolescents with schizophrenia during the prodromal period. Developing acceptable and accessible interventions that will reduce psychiatric hospitalization and residential treatment care and improve care connection for schizophrenia treatment is important to mitigate complexity in treatment for adolescents and reduce cost burden for families and the society. Integrating health claims data in the development of schizophrenia risk conversion models can be useful in effectively predicting ideal timing of tailored interventions for adolescents with preceding psychiatric conditions.


[Ascites due to hypothyroidism].
A 77-year-old man presented with ascites which was due to hypothyroidism. After the ascites had been brought into remission by salt restriction, diuretics and paracentesis, monotherapy with levothyroxine prevented recurrence. Ascites reappeared as soon as levothyroxine was withdrawn due to the patient's non-compliance. Distinctive aspects of this type of ascites are the high concentration of total protein in the ascites and the high serum-to-ascites albumin gradient (SAAG). The pathogenesis of ascites in hypothyroidism is unknown. Possible hypotheses include increased capillary permeability, obstruction to lymphatic flow caused by hyaluronic acid-albumin complexes, and diminished water diuresis due to excess antidiuretic hormone. A patient with unexplained ascites should be tested for hypothyroidism, especially when the SAAG is high (> 11 g/l).


Differences among human immunodeficiency virus strains in their capacities to induce cytolysis or persistent infection of a lymphoblastoid cell line immortalized by Epstein-Barr virus.
Four strains of human immunodeficiency virus (HIV) manifest consistent differences in biologic behavior after infection of the X50-7 line of human umbilical cord lymphocytes immortalized by Epstein-Barr virus (EBV). Some dilutions of the first strain examined, human T-cell lymphotropic virus type III B, which is derived from a pool of patient isolates propagated in H9 cells, caused transient cytopathic effects (CPE) followed by recovery of a subpopulation of X50-7 cells which became virus carrier cultures. Other dilutions of the same virus stock completely lysed X50-7 cells. Two other strains, RF2 and YW, both from individual patients with acquired immune deficiency syndrome, always induced complete cytolysis of X50-7 cells at all dilutions which infected the cells. However, RF2 did establish persistent infection of H9 cells. A fourth strain, PH1-MN, from a child with acquired immune deficiency syndrome-related complex, induced only transient CPE in X50-7 and H9 cells, which thereafter always recovered to form carrier cultures. For all four strains, the dilutions of HIV stocks which caused CPE corresponded to dilutions which resulted in the detection of HIV polypeptides by immunoblot. Cytolysis in HIV-infected X50-7 cells was accompanied by a decrease in the amount of EBV nuclear antigen; however, HIV infection did not induce EBV replication. Thus CPE in X50-7 cells is due to replication of HIV per se and not to activation of EBV. The observations indicate that there are differences in the cytolytic properties of HIVs and that these differences are influenced by the target cell.


Genetic screening for iron overload: No evidence of discrimination at 1 year.
This study measured the extent of insurance and employment problems associated with population screening for hereditary hemochromatosis and iron overload. 101,168 primary care patients from the US and Canada were screened for iron phenotypes and HFE genotypes associated with hemochromatosis. Those identified to be at risk (2253) were offered a clinical examination, which 1677 (74%) accepted, and the 1154 of these who responded to an initial questionnaire about psychosocial issues were surveyed 1 year later about whether they had experienced problems with insurance or employment that they attributed to hereditary hemochromatosis and iron overload. 832 (72.1%) of the 1154 participants surveyed after 1 year responded to the second survey. Three (0.4%) had verified problems with insurance or employment that they believed were related to hereditary hemochromatosis and iron overload. Two had problems with life insurance, and one with long-term care insurance. All 3 had elevated iron levels but not a relevant HFE genotype. One of the life insurance problems was resolved; the second one was not serious. The participant who was denied long-term care insurance had other health conditions unrelated to hereditary hemochromatosis and iron overload that could have contributed to the denial. No problems were verified for health insurance or employment, or from any of the comparison group participants (controls and those with inconclusive screening results). The risk of insurance or employment problems 1 year after phenotype and genotype screening for hereditary hemochromatosis and iron overload is very low.


Upfront immunotherapy leads to lower brain metastasis velocity in patients undergoing stereotactic radiosurgery for brain metastases.
While immunotherapy has been shown to improve survival and decrease neurologic death in patients with brain metastases, it remains unclear whether this improvement is due to prevention of new metastasis to the brain. We performed a retrospective review of patients presenting with brain metastases simultaneously with the first diagnosis of metastatic disease and were treated with upfront immunotherapy as part of their treatment regimen and stereotactic radiosurgery (SRS) to the brain metastases. We compared this cohort with a historical control population (prior to the immunotherapy era) who were treated with pre-immunotherapy standard of care systemic therapy and with SRS to the brain metastases. Median overall survival time was improved in the patients receiving upfront immunotherapy compared to the historical cohort (48 months vs 8.4 months, p=0.001). Median time to distant brain failure was statistically equivalent (p=0.3) between the upfront immunotherapy cohort and historical control cohort (10.3 vs 12.6 months). Brain metastasis velocity was lower in the upfront immunotherapy cohort (median 3.72 metastases per year) than in the historical controls (median 9.48 metastases per year, p=0.001). Cumulative incidence of neurologic death at one year was 12% in the upfront immunotherapy cohort and 28% in the historical control cohort (p=0.1). Upfront immunotherapy appears to improve overall survival and decrease BMV compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent immunotherapy with SRS.


[Development over 3 years of asthma recently diagnosed in a cohort of children (ASMA study). Factors related to improvement in clinical status].
The objective of the ASMA study was to describe the evolution of light to moderate asthma, newly or recently (12 Pounds months) diagnosed in private pneumology centers, and to search for the predictive factors. In 1995, 251 private pneumologists, throughout Metropolitan France, recruited 396 asthmatic children, 6 to 12 years old (64% boys). The 334 patients eligible for the study were examined every 4 months during 3 years (a mean of 6 controls were conducted out of the expected 9). The data were collected on standardized questionnaires completed by the physicians and notebooks filled-in by the patients the week before each control. This questionnaire comprised two asthma 'control' criteria: "control" of the clinical state, defined as asthma attacks < 1 per week AND nocturnal awakening < 1 per week AND absence of asthma symptoms between attacks on every control visit; "control" of the need for b2 mimetics on request, defined as the non-use throughout the week preceding the control visit. The global clinical state of the cohort rapidly improved once care was initiated: the proportion of children exhibiting at least one attack of asthma per week rapidly dropped to 43% on inclusion and to 13% on the first control visit (4 months), 10% on the second control visit, and then fluctuated at around 8% up until the last control visit. A similar evolution was noted regarding nocturnal asthma attacks. The proportion of patients with prescriptions for inhaled corticosteroids and long-lasting b2-mimetics increased over the three years of follow-up. Analysis of the factors related to the individual 'control' of the clinical state showed a negative effect in family histories of asthma (father) and the presence of smokers in the home, but above all a positive effect of compliance to treatment and particularly its understanding (OR = 2.5; p = 0.03) and respect of the doses (OR = 2.7; p < 0.01). The positive effect of compliance was confirmed by analysis of the factors related to the use of b2 mimetics on request. Smoking should be avoided in the home. Compliance to treatment could be improved by making sure that the patients and their parents fully understand the disease and its treatment, and by persuading them to strictly follow the treatments prescribed.


A pulse sequence for directly measuring the anharmonicities of coupled vibrations: Two-quantum two-dimensional infrared spectroscopy.
We have experimentally demonstrated a pulse sequence for the acquisition of heterodyned two-dimensional infrared (2D IR) spectra that correlates the overtone and combination bands to the fundamental frequencies. The spectra are generated by Fourier transforming the time domain signal that is allowed to evolve during one- and two-quantum coherence times. In this manner, the overtone and combination bands appear along the two-quantum axis, resulting in a direct determination of the diagonal and off-diagonal anharmonicities. To demonstrate this pulse sequence, we have collected two-quantum 2D IR spectra of a ruthenium dicarbonyl complex, extracted the diagonal and off-diagonal anharmonicities, and simulated the spectra using an exciton model. Several polarization conditions are presented that suppress the diagonal or cross peaks and we have used them to improve the accuracy of the measurement.


Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women.
Adequate folate intake may be important for breast cancer prevention. Its protective effect may be influenced by factors associated with folate metabolism. We sought to evaluate folate intake in relation to breast cancer risk and examine whether the relation is affected by alcohol and intake of vitamin B(2) and B(12). A prospective cohort analysis of folate intake was conducted among 62,739 postmenopausal women in the French E3N cohort who had completed a validated food frequency questionnaire in 1993. During nine years' follow-up, 1,812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized in quintiles and energy-adjusted using the regression-residual method. Cox model-derived relative risks (RRs) were adjusted for known breast cancer determinants. The multivariate RR for extreme quintiles of folate intake was 0.78 (95% CI: 0.67-0.90; p-trend = 0.001) [Median intake for Q(1) = 296 microg/day and Q(5) = 522 microg/day]. There was no evidence to support effect modification by alcohol or B(2) intake. The decreasing trend was most marked in women with higher folate and vitamin B(12 )intake. However, test for interaction was not statistically significant (p = 0.29). High folate intake was associated with decreased breast cancer risk. Vitamin B(12) intake may modify this association.


Interest in smoking cessation among methadone maintained outpatients.
The prevalence of cigarette smoking among opiate abusers is extremely high and tobacco related diseases are a major factor associated with morbidity and mortality for this group. Yet, many treatment providers remain reluctant to address smoking cessation with their clients due in part to the belief that substance abusers are not interested in quitting smoking. The present study examined self-reported interest in smoking cessation among methadone maintenance clients (N = 120) in four clinics in Los Angeles. Fifty-eight percent of subjects rated themselves as 'Somewhat' or 'Very Interested' in a smoking cessation program. Overall subjects appeared to accurately perceive the personal risks from tobacco smoking. In conclusion we find that clients in methadone maintenance treatment programs evidence a high level of interest in quitting smoking and may well be suited for a highly structured smoking cessation intervention.


Concise preparation of tetra-orthogonally protected (2S,6R)-lanthionines.
Lantibiotics are antimicrobial peptides containing the unique bis-amino acids lanthionine and beta-methyllanthionine. While previous syntheses of lanthionine have often involved the coupling of precursors derived from D-serine and L-cysteine, we here report an inverted strategy whereby D-cysteine and L-serine are employed as building blocks. This approach provides for a concise preparation of tetra-orthogonally protected (2R,6S)-lanthionines while allowing convenient introduction of orthogonal protecting groups not previously incorporated into lanthionines.


High Incidence of Intra-articular Injuries With Segond Fractures of the Tibia in the Pediatric and Adolescent Population.
Segond fractures (avulsion fractures of the proximal lateral tibia) are highly associated with anterior cruciate ligament (ACL) tears in adult patients. This large case series of pediatric Segond fractures describes the associated intra-articular knee injuries to determine if these fractures have a high incidence of ACL tears or its equivalent injury in young patients. Institutional review board approved retrospective study at a tertiary children's hospital of patients under 19 years who were diagnosed with a Segond fracture between 2009 and 2019 was conducted. Demographics, clinical data, imaging features, associated injuries, and treatment information were collected. Fifty-three patients (44 males and 9 females) with median age 15.4 (11.8 to 19) years with Segond fractures of the proximal tibia on radiographic imaging were included. Diagnosis of associated injuries was established based on clinical examination, radiology report, and arthroscopic findings. Median Segond fracture size was 2.0×9.0 mm measured on standard anteroposterior knee radiographs. Magnetic resonance imaging (MRI) was obtained in 49/53 (92.5%) patients. Associated injuries included ACL tears (39 patients, 73.6%), tibial spine fractures (9, 17.0%), and other injuries (5, 9.4%). 37/53 (69.8%) patients had meniscal injury. Three (5.7%) patients sustained multiligament injuries. All associated injuries were confirmed by either MRI/computerized tomography or direct operative examination. Among Segond fractures found with ACL tears, 12 (30.8%) were contact injuries, 30 (76.9%) were sports injuries. In associated tibial spine fractures, 7 (78%) injuries were contact in nature and were sports related. There was a statistically significant difference (P=0.013) in age, patients with tibial spine fractures (median 13.6 y) being younger than those with ACL tears (median 15.4 y). 12/53 (22.6%) had associated articular cartilaginous injuries, 3 of which were treated surgically. Overall, 81.1% of patients were treated operatively for associated intra-articular injuries. This large case series of Pediatric Segond fractures suggests a high association with intra-articular injuries, specifically, ACL tears and its equivalent injury, that is, tibial spine fractures, the later more common in the younger patient population. An MRI is recommended in patients with a Segond fracture for characterizing the exact intra-articular injury to help plan the appropriate management. Level IV-prognostic.


Anticardiolipin antibodies in giant cell arteritis and polymyalgia rheumatica: a study of 40 cases.
The occurrence and clinical value of anticardiolipin antibodies (aCL) were studied in 33 patients with giant cell arteritis (GCA) and in seven patients with polymyalgia rheumatica (PMR), at onset and during follow-up. aCL were present in 19/40 (47.5%) GCA/PMR cases, most of them of the IgG isotype, whereas all controls (21 subjects) were aCL negative. The presence of aCL was not associated with inflammatory parameters or clinical signs of arteritis; however, they disappeared in a significant percentage (56%) of patients during steroid therapy. No correlation was found between ischaemic events and aCL, suggesting that they are not important for the development of vascular complications in GCA/PMR patients. Moreover, a retrospective evaluation of our data showed a correlation between aCL positivity and anaemia, whose significance remains to be elucidated.


Political, administrative, and economic resources for the control of poliomyelitis.
Control of any major childhood disease in developing countries is dependent on the ability of health services to reach the susceptible population and to administer appropriate therapy or preventive action. Both of these needs are addressed by the development of primary health-care services. The vaccine-preventable diseases, including poliomyelitis, are likely to be controlled only through programs that are executed through the primary health-care system. The implications of the technical aspect of poliomyelitis control on economic resources are secondary to the administrative capability of the programs to manage these technical facilities effectively. The first prerequisite of any health program is the political will on the part of the decision makers to carry it through effectively. This will be reflected in the strength of the administrative structures and the economic resources made available. At present poliomyelitis, with its clinical visibility and its appeal to humanitarian instincts, has an importance as a leader for immunization programs and thus, for primary health care.


Replication of single-stranded DNA templates by primase-polymerase complexes of the yeast, Saccharomyces cerevisiae.
A partially purified primase-polymerase complex from the yeast, Saccharomyces cerevisiae, was capable of replicating a single stranded circular phage DNA into a replicative form with high efficiency. The primase-polymerase complex exhibited primase activity and polymerase activity on singly primed circular ssDNA as well as on gapped DNA. In addition, it was able to replicate an unprimed, single-stranded, circular phage DNA through a coupled primase-polymerase action. On Biogel A-O.5m filtration the primase-polymerase activities appeared in the void volume, demonstrating a mass of greater than 500 kilodaltons. Primase and various primase-polymerase complexes synthesized unique primers on single stranded DNA templates and the size distribution of primers was dependent on the structure of the DNA and the nature of the primase-polymerase assembly.


MicroRNAs in placental health and disease.
MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are encoded by the genomes of most organisms. They regulate gene expression through posttranscriptional mechanisms to attenuate protein output in various genetic networks. The discovery of miRNAs has transformed our understanding of gene regulation and sparked intense efforts intended to harness their potential as diagnostic markers and therapeutic tools. Over the last decade, a flurry of studies has shed light on placental miRNAs but has also raised many questions regarding the scope of their biologic action. Moreover, the recognition that miRNAs of placental origin are released continually in the maternal circulation throughout pregnancy suggested that circulating miRNAs might serve as biomarkers for placental function during pregnancy. Although this generated much enthusiasm, recently recognized challenges have delayed the application of miRNA-based biomarkers and therapeutics in clinical practice. In this review, we summarize key findings in the field and discuss current knowledge related to miRNAs in the context of placental biology.


ACR Appropriateness Criteria® Hemoptysis.
Hemoptysis, the expectoration of blood, ranges in severity from nonmassive to massive. This publication reviews the literature on the imaging and treatment of hemoptysis. Based on the literature, the imaging recommendations for massive hemoptysis are both a chest radiograph and CT with contrast or CTA with contrast. Bronchial artery embolization is also recommended in the majority of cases. In nonmassive hemoptysis, both a chest radiograph and CT with contrast or CTA with contrast is recommended. Bronchial artery embolization is becoming more commonly utilized, typically in the setting of failed medical therapy. Recurrent hemoptysis, defined as hemoptysis that recurs following initially successful cessation of hemoptysis, is best reassessed with a chest radiograph and either CT with contrast or CTA with contrast. Bronchial artery embolization is increasingly becoming the treatment of choice in recurrent hemoptysis, with the exception of infectious causes such as in cystic fibrosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Low-CD weakly-coupled FMF for short-reach IM/DD MDM transmission.
Weakly-coupled mode division multiplexing (MDM) technique is a promising candidate for capacity enhancement of short-reach optical interconnections, for which the multiple-ring-core few-mode fiber (MRC-FMF) has been proven to be an effective design method to suppress distributed modal crosstalk. Similar to low chromatic-dispersion (CD) O-band transmission based on single-mode fibers (SMF), all the mode channels in a weakly-coupled FMF for short-reach applications should achieve low CD to support intensity-modulation/direct-detection (IM/DD) transmission. In this paper, we propose, for the first time to the best of our knowledge, an index perturbation method to adjust both effective index and CD of each mode in an MRC-FMF. Firstly, an accurate modeling method to model the relationship between SiO2-GeO2 material index and the germanium concentration at different wavelengths is proposed by analyzing the index characteristics of 4 kinds of germanium-doped fused silica SMFs at the same fabrication processing, which could be utilized to calculate the CD characteristics for an MRC-FMF with perturbed index profile. Then, based on the perturbation method considering the influences on both effective index and CD, a weakly-coupled low-CD MRC-FMF supporting 4 linearly-polarized (LP) modes is designed and fabricated. The measured minimum effective index difference min|Δneff| among all modes is larger than 1.3 × 10-3, and the CD values of all the modes lie between -6 and +6 ps/km/nm ranging from 1280 to 1320 nm, which agree well with the design. The 2-km transmission experiment indicates that the fabricated MRC-FMF could support stable digital-signal-processing (DSP)-free IM/DD transmission for all the 4 LP modes. This work is beneficial to the application of short-reach weakly-coupled MDM systems.


Is information on genetic determinants of obesity helpful or harmful for obese people?--A randomized clinical trial.
Although more and more genetic information is available, it is unclear whether this information is helpful for patients. Therefore, we assessed the positive and negative effects of informing obese people about the genetic etiology of being overweight. Two hundred ninety-four obese people were randomized to 2 interventions (a 1-session consultation for obese people on how to manage obesity either including genetic information or not); their results were compared to a control group (116). Subjects were assessed before and after consultation and 6 months later. Weight, scales on feeling guilty for being overweight, self-control, negative mood (primary endpoint), body acceptance, restraint eating. Both types of consultations were considered helpful by the participants, and had comparable effects on body weight. The consultation with genetic information was rated superior in terms of leading to new insights (advantage for consultation with genetic information, even 6 months later; p = 0.046). No negative effects (e.g., loss of self-efficacy/self-control, increase of body weight; all p > 0.20 for interaction consultation x time) were observed for informing obese people about the genetic etiology of being overweight. The consultation resulted in long-term improvement of negative mood if it included genetic information in the case of participants with a family history of obesity and if it included no genetic information in the case of obese people without a family history of obesity (p = 0.03 for interaction of group, intervention, and time). Consultations in obesity can be helpful in general. These consultations should include genetic information if people have a family history of obesity.


Which Factors Control the Nucleophilic Reactivities of Enamines?
Changes in rate constants, equivalent to changes in Gibbs energies of activation ΔG≠ , are commonly referred to as kinetic effects and differentiated from thermodynamic effects (Δr G°). Often, little attention is paid to the fact that structural effects on ΔG≠ are composed of a thermodynamic (Δr G°) and a truly kinetic (intrinsic) component (ΔG0≠ ), as expressed by the Marcus equation. Rate and equilibrium constants have been determined for a number of reactions of enamines with benzhydrylium ions (Aryl2 CH+ ), which has allowed the determination of Marcus intrinsic barriers and a differentiated analysis of structure-reactivity relationships. To our knowledge, this is the first report in which the Lewis basicity of a πCC bond towards carbon-centered Lewis acids (for example, carbenium ions) has quantitatively been determined. The synthesis, structures, and properties of deoxybenzoin-derived enamines ArCH=C(Ph)NR2 , which have been designed as reference nucleophiles for the future quantification of electrophilic reactivities, are explicitly described.