[Value of serum galactomannan assay in the diagnosis of pediatric invasive pulmonary aspergillosis].
Galactomannan (GM) is a major aspergilli cell-wall constituent released into circulation during the early stage of invasive disease, and can be detected. Many studies suggest that serum galactomannan assay has an excellent sensitivity and specificity for the early diagnosis of adult invasive aspergillosis (IA). However, there have been few studies on serum galactomannan assay in pediatric patients. Therefore, we evaluate the value of serum galactomannan assay in the diagnosis of pediatric invasive pulmonary aspergillosis in this study. Blood samples were obtained from 88 children, of whom 14 had definitive or possible invasive pulmonary aspergillosis (IPA), 16 had other invasive pulmonary fungal infection and 58 had pulmonary non-fungal infection. Of the 58 patients, 23 had bacterial pneumonia, 20 had mycoplasma pneumonia and 15 had pulmonary tuberculosis. A double-direct sandwich ELISA was employed to detect GM optical density index (ODI) in the serum sample. GM ODI were observed before and after treatment in six children with IPA. Measurement data followed the Gaussian distribution were expressed as x(-) +/- s; differences among groups were tested using a single factor analysis of variance. If the s>1/3 x(-), measurement data were expressed as M [minimum, maximum], and the differences among groups were tested by a rank sum test. P < 0.05 was considered to be statistically significant. The serum GM ODI in IPA group [1.03 (0.16 - 3.73)] was significantly higher than that in the other invasive pulmonary fungal infection group [0.30 (0.04 - 1.28)] and pulmonary non-fungal infection group [0.24 (0.08 - 0.69)] (P < 0.05). If the cut-off GM ODI was set at 0.5, the sensitivity and specificity of the assay for IPA were 71.4% and 91.9% respectively. The accuracy rate for IPA was 88.6%. If the cut-off GM ODI was set at 0.8, the sensitivity, specificity and accuracy rate for IPA were 64.2%, 98.6% and 93.2% respectively. Of 6 children whose GM were observed serially, GM ODI declined consistently with the clinical remission in 3 children. GM ODI raised in 2 children corresponding to clinical exacerbation. Whereas GM ODI elevated paradoxically regardless of clinical remission in the remaining one patient. Serum GM detection was an effective method for the diagnosis of pediatric IPA.


Training health personnel in the area of breast-feeding.
One of the key factors in the prevalence and duration of breastfeeding is the position taken by health personnel, and the practices adopted in hospitals and health centers. It is thus important that health personnel be made aware of their crucial influence in this domain, and be prepared to provide the necessary information and support 1st to pregnant women in their choice of mode of infant feeding, and then to those who choose to breastfeed. The author analyzes the moments which are critical in the decision to breastfeed and in successful lactation, and recommends on this basis the various elements which should be included in the training of the different categories of health personnel. The successful promotion of breastfeeding depends not only on their acquisition of knowledge in the management of breastfeeding, but also on their attitudes.


Synthesis of medium-bridged twisted lactams via cation-pi control of the regiochemistry of the intramolecular Schmidt reaction.
Medium-bridged twisted amides can be synthesized by the intramolecular Schmidt reaction of 2-azidoalkyl ketones. In these reactions, the regiochemistry of the Schmidt reaction is diverted into a typically disfavored pathway by the presence of an aromatic group at the alpha-position adjacent to the ketone, which stabilizes the predominantly reactive conformation of the azidohydrin intermediate by engaging in a nonbonded cation-pi interaction with the positively charged diazonium cation. This results in the rarely observed rearrangement of the C-C bond distal to the azidoalkyl chain. This reaction pathway also requires the azide-containing tether to be situated in the axial orientation in the key azidohydrin intermediate. Examination of the effect of substitution of aromatic rings on the regiochemistry of the Schmidt reaction shows an increase in the migratory selectivity with more electron-rich aromatic groups. The selectivity is lower when an electron-withdrawing substituent is placed on the aromatic ring. The ability of cation-pi interactions to act as a controlling element decreases when Lewis acids coordinate to substituents on the aromatic ring. The developed version of the Schmidt reaction provides a direct access to a family of medium-bridged twisted amides with a [4.3.1] bicyclic system, compounds which are very difficult to access with use of other currently available methods.


Streptococcal IdeS: therapeutic potential for Guillain-Barré syndrome.
Plasma exchange and intravenous immunoglobulin are effective in treating Guillain-Barré syndrome (GBS) probably because the former removes IgG autoantibodies and complement and the latter inhibits complement activation subsequent to the autoantibody binding to peripheral nerve antigens. IgG degrading enzyme of Streptococcus pyogenes (IdeS) can cleave the pathogenic autoantibodies into F(ab')2 and Fc. The purpose of this study is to show whether IdeS has novel therapeutic potential for GBS. Sera with anti-ganglioside IgG antibodies from 15 patients with GBS or Miller Fisher syndrome were used. We tested whether IdeS cleaved the anti-ganglioside IgG antibodies and inhibited deposition of activated complement component on ELISA plates. IdeS efficiently cleaved IgG and blocked complement activation mediated by anti-GM1, anti-GD1a and anti-GQ1b IgG antibodies. IdeS has therapeutic potential for GBS and related conditions.


Cotyledonoid dissecting leiomyoma: an uncommon form of a common disease.
Leiomyomas are benign uterine smooth muscle neoplasms with varied morphology that are well known to undergo secondary changes. Cotyledonoid dissecting leiomyoma is a rare and distinct form of leiomyoma that poses a diagnostic challenge for clinicians, radiologists, and pathologists and can be confused with malignant uterine neoplasms. Only a few cases have been reported so far in the literature. Here we report a case of a cotyledonoid dissecting leiomyoma in a 60-year-old woman, emphasize its gross and histological features, and provide a review of the literature.


Determination of size and mass-and number-based concentration of biogenic SeNPs synthesized by lactic acid bacteria by using a multimethod approach.
Selenium nanoparticles (SeNPs) were synthesized by a green technology using lactic acid bacteria (LAB, Lactobacillus acidophilus, L. delbrueckii subsp. bulgaricus and L. reuteri). The exposure of aqueous sodium selenite to LAB led to the synthesis of SeNPs. Characterization of SeNPs by transmission electron microscopy with energy dispersive X-ray spectrum (EDXS) analysis revealed the presence of stable, predominantly monodispersed and spherical SeNPs of an average size of 146 ± 71 nm. Additionally, SeNPs hydrodynamic size was determined by dispersive light scattering (DLS) and nanoparticle tracking analysis (NTA). For this purpose, a methodology based on the use of surfactants in basic medium was developed for isolating SeNPs from the bacterial pellet. The hydrodynamic size values provided by DLS and NTA were 258 ± 4 and 187 ± 56 nm, respectively. NTA measurements of number-based concentration reported values of (4.67±0.30)x109 SeNPs mL-1 with a relative standard deviation lower than 5% (n = 3). The quantitative results obtained by NTA were supported by theoretical calculations. Asymmetrical flow field flow fractionation (AF4) on line coupled to the inductively couple plasma mass spectrometry (ICP-MS) and off-line coupled to DLS was further employed to characterize biogenic SeNPs. The distribution of the particle size for the Se-containing peak provide an average size of (247 ± 14) nm. The data obtained by independent techniques were in good agreement and the developed methodology could be implemented for characterizing NPs in complex matrices such as biogenic nanoparticles embedded inside microbial material.


Accuracy of thymine-thymine dimer bypass by Saccharomyces cerevisiae DNA polymerase eta.
The Saccharomyces cerevisiae RAD30 gene functions in error-free replication of UV-damaged DNA. RAD30 encodes a DNA polymerase, Pol eta, which inserts two adenines opposite the two thymines of a cis-syn thymine-thymine (T-T) dimer. Here we use steady-state kinetics to determine the accuracy of DNA synthesis opposite the T-T dimer. Surprisingly, the accuracy of DNA synthesis opposite the damaged DNA is nearly indistinguishable from that opposite nondamaged DNA, with frequencies of misincorporation of about 10(-2) to 10(-3). These studies support the hypothesis that unlike most DNA polymerases, Pol eta is able to tolerate distortions in DNA resulting from damage, which then enables the polymerase to utilize the intrinsic base pairing ability of the T-T dimer.


The influence of family's cohesion and adaptability in family satisfaction of parents with a child with autism spectrum disorder.
The current study examined whether there was significant relationship among family functioning (cohesion and adaptability) and overall family satisfaction in parents with a child with autism spectrum disorder. It was predicted that poor family adaptive functioning, poor family cohesion along with other family-related variables (child diagnosis, parents' marital status, and other siblings in the family) would predict lower levels of family satisfaction. 73 mothers and 27 fathers of a child with ASD participated in this study. Google forms were used in this electronic web research. Data were collected using the Family Adaptability and Cohesion Evaluation Scale (FACES-III) and the Family satisfaction scale (FSS). This study's results demonstrate that family adaptability along with a child's autism spectrum disorder diagnosis may be significant predictors of family satisfaction. Findings report the significance of identifying discrepancies in family functioning as they provide an insight into how family members not only view but also how they interact with each other which in turn can inform clinical interventions and the therapeutic work.


An analysis of 372 patients with anterior uveitis in a large Ibero-American cohort of spondyloarthritis: the RESPONDIA Group.
This study analysed the frequency of anterior uveitis (AU) and its correlations in a large cohort of patients with spondyloarthritis (SpA). A common protocol of investigation was prospectively applied to 2012 SpA patients in 85 centres from 10 Ibero-American countries. Clinical and demographic variables and disease indexes were investigated. Categorical variables were compared by χ2 and Fisher's exact test, and continuous variables were compared by ANOVA or Kruskal-Wallis test. A value of p<0.05 was considered significant. AU was referred by 372 SpA patients (18.5%). AU was statistically associated with inflammatory low back pain (p<0.001), radiographic sacroiliitis (p<0.001), enthesopathies (p=0.004), urethritis/acute diarrhoea (p<0.001), balanitis (p=0.002), hip involvement (p=0.002), HLA-B27 (p=0.003), and higher C-reactive protein (p=0.001), whilst it was negatively associated with the number of painful (p=0.03) and swollen (p=0.005) peripheral joints, psoriatic arthritis (p<0.001), psoriasis (p<0.001), nail involvement (p<0.001), and dactilitis (p=0.062; trend). No association with gender, race, and indices (disease activity, functionality and quality of life) was observed. Logistic regression showed that ankylosing spondylitis (p=0.001) and HLA-B27 (p=0.083; trend) was significantly associated with AU, while extra-articular manifestations (predominantly psoriasis) were negatively associated (p=0.016). Anterior uveitis is a frequent extra-articular manifestation in SpA patients, positively associated with axial involvement and HLA-B27 and negatively associated with peripheral involvement and psoriatic arthritis.


Evaluation of industrial local exhaust hood efficiency by a tracer gas technique.
Efficiency of industrial local exhaust ventilation is defined as the ratio of air contaminant quantity captured by the system per unit time to the total contaminant quantity produced by the process per unit time. To date, no direct method exists for this evaluation. This paper describes a tracer gas technique, using sulfur hexafluoride (SF6), which has been developed for the evaluation of local exhaust system efficiency. SF6 was discharged at a known rate into the industrial process generation area. Then, by comparing this quantity to that captured by the exhaust system, as measured in the exhaust duct, hood efficiency is determined. Major advantages of this technique are: The tracer gas technique is able to evaluate directly the hood efficiency. The tracer gas technique is not affected by cross-contamination from nearby industrial processes. The tracer gas technique can be conducted "on site" with minimal interruption of industrial process or interference with workers' duties. The tracer gas, using SF6 is non-toxic. Since SF6 is a gas, this technique may be limited to efficiency evaluation of hoods associated with gases, fumes, vapors, or fine particles.


Binding affinity and kinetic analysis of targeted small molecule-modified nanoparticles.
Nanoparticles bearing surface-conjugated targeting ligands are increasingly being explored for a variety of biomedical applications. The multivalent conjugation of targeting ligands on the surface of nanoparticles is presumed to enhance binding to the desired target. However, given the complexities inherent in the interactions of nanoparticle surfaces with proteins, and the structural diversity of nanoparticle scaffolds and targeting ligands, our understanding of how conjugation of targeting ligands affects nanoparticle binding remains incomplete. Here, we use surface plasmon resonance (SPR) to directly and quantitatively study the affinity and binding kinetics of nanoparticles that display small molecules conjugated to their surface. We studied the interaction between a single protein target and a structurally related series of targeting ligands whose intrinsic affinity varies over a 4500-fold range and performed SPR at protein densities that reflect endogenous receptor densities. We report that even weak small molecule targeting ligands can significantly enhance target-specific avidity (by up to 4 orders of magnitude) through multivalent interactions and also observe a much broader range of kinetic effects than has been previously reported. Quantitative measurement of how the affinity and kinetics of nanoparticle binding vary as a function of different surface conjugations is a rapid, generalizable approach to nanoparticle characterization that can inform the design of nanoparticles for biomedical applications.


The dual effect of epidermal growth factor upon human chorionic gonadotropin secretion by the first trimester placenta in vitro.
Epidermal growth factor (EGF) is believed to play an important role in the regulation of placental function. We have examined the effect of EGF upon first trimester (7-10 gestational weeks) placental hCG secretion and cellular differentiation using both static (explants and isolated cells) and kinetic (superfusion of explants) culture methods. In superfused explants, short (1-4 min) pulses of EGF increased both the rate and amplitude of spontaneous pulsatility of hCG. The frequency increased from 3/h to 5/h, and the amplitude increased compared to the control channels as calculated by the area under the curve. This effect was dose dependent and the concentration of 50 ng/ml, which was the lowest dose tested, was the most effective. In explants cultured for 24 h, EGF caused a 2-fold increase in hCG secretion, compared to control, P less than 0.05. In two different dispersed trophoblastic cell cultures, EGF added daily for the first week caused a 180% increase in hCG secretion, P less than 0.05. However, according to morphological criteria, i.e. light microscopy and vital staining, no significant effect upon the rate of differentiation to syncytiotrophoblast was observed in long-term cultures of one of these preparations. In conclusion, EGF plays a dual trophic role in stimulating hCG secretion in the first trimester. However, this effect is not dependent on cellular differentiation.


Paraneoplastic neurological autoimmunity associated with ANNA-1 autoantibody and thymoma.
Neurologic autoimmunity frequently occurs with thymoma, particularly myasthenia gravis and skeletal muscle-specific autoantibodies. Type 1 antineuronal nuclear antibody (ANNA-1/"anti-Hu"), which is recognized as an immunoglobulin G marker of small-cell lung carcinoma, has not been reported with thymoma. The authors identified four patients (three under age 40) with ANNA-1 and a paraneoplastic neurologic complication of thymoma. Retrospective testing of stored serum from 172 patients with thymoma revealed ANNA-1 in 3%. This report extends the oncologic implications of ANNA-1 seropositivity.


Perceptions of another person's heavy drinking as a function of one's relationship to the drinker a pilot study.
Of 301 participants in a telephone survey, 201 could identify a problem drinker within their social networks. In 67 cases the drinker was a partner, in 45 another family member, in 61 a friend, and in 28 a work colleague. Another person's heavy drinking was reported as most disrupting to one's life when that person was a partner or other family member or if one was living in the same residence as the drinker. The exception to this was that reported disruption to respondents' work life was greatest when the drinker was a work colleague. While there appear to be problems for friends and work colleagues, partners and other family members appear to report the most disruption so providing services to family members seems appropriate.


Judging the subjective difficulty of different kinds of tasks.
People judge the relative difficulty of different kinds of tasks all the time, yet little is known about how they do so. We asked university students to choose between tasks that taxed perceptual-motor control and memorization to different degrees. Our participants decided whether to carry a box through a wide (81 cm) or narrow (36 cm) gap after memorizing six, seven, or eight digits. The model that maximized the likelihood of observing the choice data treated the extra physical demand of passing through the narrow gap as functionally equivalent to memorizing an extra .55 digits. Substantively, the model suggested that participants judged the difficulty of the compound tasks in terms of separate resources. The approach introduced here may help interrelate different kinds of task difficulty. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Left anterior fascicular block: an ischaemic response during treadmill testing.
A patient in whom exercise induced reversible ischaemic left anterior fascicular block is reported. Glyceryl trinitrate relieved the fascicular block. Coronary angiography showed a 90% obstruction of the left anterior descending artery. The left anterior fascicular block induced by exercise disappeared after a successful coronary angioplasty.


Interneurons containing calretinin are specialized to control other interneurons in the rat hippocampus.
Spine-free calretinin-immunoreactive (CR-IR) interneurons form a subpopulation of GABAergic cells in the rat hippocampus. A characteristic feature of these cells--located in all areas and layers--is the frequent dendro-dendritic and axo-dendritic contacts they form with each other. In this study we examined in detail the connectivity of these neurons by reconstructing their dendritic and axonal arbor and by identifying their postsynaptic targets. Radially running dendrites of CR-IR cells, located in different layers, intermingled into long braids. An average cell was in contact with dendrites of three to seven other CR-IR cells. Reconstruction of the dendritic trees from six consecutive sections demonstrated that at least 15 cells may participate in a dendro-dendritically connected cluster. Electron microscopical examination revealed that regularly spaced zonula adherentia connect the touching dendrites. The postsynaptic targets of CR-IR neurons have been examined using postembedding immunogold staining for GABA. CR-containing GABA-immunoreactive axons of local origin formed multiple symmetrical synaptic contacts (two to five) exclusively on GABAergic dendrites (CR-negative as well as CR-positive). Two to 10 CR-IR axons may converge onto a single CR-IR neuron, often from cells belonging to the same dendro-dendritically connected cluster. Using double immunocytochemistry, CR-IR cells were shown to heavily innervate calbindin D28k-containing interneurons and VIP-containing basket cells but avoided the parvalbumin-containing basket and axo-axonic cells. The unique connectivity of CR-IR cells may enable them to play a crucial role in the generation of synchronous, rhythmic hippocampal activity by controlling other interneurons terminating on different dendritic and somatic compartments of principal cells.


Assessment of Oral Conditions and Quality of Life in Morbid Obese and Normal Weight Individuals: A Cross-Sectional Study.
The aim of this study was to identify the impact of oral disease on the quality of life of morbid obese and normal weight individuals. Cohort was composed of 100 morbid-obese and 50 normal-weight subjects. Dental caries, community periodontal index, gingival bleeding on probing (BOP), calculus, probing pocket depth, clinical attachment level, dental wear, stimulated salivary flow, and salivary pH were used to evaluate oral diseases. Socioeconomic and the oral impacts on daily performances (OIDP) questionnaires showed the quality of life in both groups. Unpaired Student, Fisher's Exact, Chi-Square, Mann-Whitney, and Multiple Regression tests were used (p<0.05). Obese showed lower socio-economic level than control group, but no differences were found considering OIDP. No significant differences were observed between groups considering the number of absent teeth, bruxism, difficult mastication, calculus, initial caries lesion, and caries. However, saliva flow was low, and the salivary pH was changed in the obese group. Enamel wear was lower and dentine wear was higher in obese. More BOP, insertion loss, and periodontal pocket, especially the deeper ones, were found in obese subjects. The regression model showed gender, smoking, salivary pH, socio-economic level, periodontal pocket, and periodontal insertion loss significantly associated to obesity. However, both OIDP and BOP did not show significant contribution to the model. The quality of life of morbid obese was more negatively influenced by oral disease and socio-economic factors than in normal weight subjects.


Disposition of some sulphur-containing hexachlorobenzene (HCB) metabolites: affinity of methylsulphonylpentachlorobenzene for the gray matter of brain, the lungs and the adrenal zona reticularis.
The distribution of methylsulphonylpentachloro-[14C]benzene (I), methylthiopentachloro-[14C]benzene (II), 1,4-bis(methylthio)tetrachloro-[14C]benzene (III) and 1,2,4-tris(methylthio)trichloro[14C]benzene (IV) was studied after intravenous injection in mice. The administration of I resulted in a rapid and selective accumulation of radioactivity in the gray matter of the brain, the lung and the zona reticularis of the adrenal cortex. In mice pretreated with metyrapone, or with high dose of unlabelled I, the radioactivity in the tissues was increased, whereas pretreatment with diethyl maleate did not change the disposition of I. In mice injected with II-IV no site of selective accumulation in the tissues was observed. Similarly to I, compounds II-IV were rapidly excreted in bile/faeces and urine. It is proposed that the sulphone group is essential for the high affinity of I for the brain, lung and adrenal cortex.


Fetal Cartilage-Derived Cells Have Stem Cell Properties and Are a Highly Potent Cell Source for Cartilage Regeneration.
Current strategies for cartilage cell therapy are mostly based on the use of autologous chondrocytes or mesenchymal stem cells (MSCs). However, these cells have limitations of a small number of cells available and of low chondrogenic ability, respectively. Many studies now suggest that fetal stem cells are more plastic than adult stem cells and can therefore more efficiently differentiate into target tissues. However, the characteristics and the potential of progenitor cells from fetal tissue remain poorly defined. In this study, we examined cells from human fetal cartilage at 12 weeks after gestation in comparison with bone marrow-derived MSCs or cartilage chondrocytes from young donors (8-25 years old). The fetal cartilage-derived progenitor cells (FCPCs) showed higher yields by approximately 24 times than that of chondrocytes from young cartilage. The morphology of the FCPCs was polygonal at passage 0, being similar to that of the young chondrocytes, but it changed later at passage 5, assuming a fibroblastic shape more akin to that of MSCs. As the passages advanced, the FCPCs showed a much greater proliferation ability than the young chondrocytes and MSCs, with the doubling times ranging from 2∼4 days until passage 15. The surface marker profile of the FCPCs at passage 2 was quite similar to that of the MSCs, showing high expressions of CD29, CD90, CD105, and Stro-1. When compared to the young chondrocytes, the FCPCs showed much less staining of SA-β-gal, a senescence indicator, at passage 10 and no decrease in SOX9 expression until passage 5. They also showed a much greater chondrogenic potential than the young chondrocytes and the MSCs in a three-dimensional pellet culture in vitro and in polyglycolic acid (PGA) scaffolds in vivo. In addition, they could differentiate into adipogenic and osteogenic lineages as efficiently as MSCs in vitro. These results suggest that FCPCs have stem cell properties to some extent and that they are more active in terms of proliferation and chondrogenic differentiation than young chondrocytes or MSCs.


Ultrasound-guided modified serratus anterior plane block for perioperative analgesia in breast oncoplastic surgery: A case series.
Ultrasound-guided serratus anterior plane (SAP) block has been described to provide complete anaesthesia and analgesia to the lateral thoracic wall. Its use has been recently reported in breast reconstruction surgeries. We present a series of 11 patients where ultrasound-guided SAP block was used as part of multimodal analgesia in breast reconstruction surgery using latissimus dorsi (LD) myocutaneous flap after mastectomies. This resulted in excellent analgesia in the perioperative period and minimal use of intravenous analgesics. The SAP block technique described here is safe and also provides effective analgesia in breast reconstruction surgery with LD flap.


An analysis of an optimal selection process for characteristics and technical performance of baseball pitchers.
Selection of a qualified pitcher has relied previously on qualitative indices; here, both quantitative and qualitative indices including pitching statistics, defense, mental skills, experience, and managers' recognition were collected, and an analytic hierarchy process was used to rank baseball pitchers. The participants were 8 experts who ranked characteristics and statistics of 15 baseball pitchers who comprised the first round of potential representatives for the Chinese Taipei National Baseball team. The results indicated a selection rate that was 91% consistent with the official national team roster, as 11 pitchers with the highest scores who were recommended as optimal choices to be official members of the Chinese Tai-pei National Baseball team actually participated in the 2009 Baseball World Cup. An analytic hierarchy can aid in selection of qualified pitchers, depending on situational and practical needs; the method could be extended to other sports and team-selection situations.


[Cerebrovascular disorders--clinical aspects and follow-up].
The observation of the spontaneous course of the extracranial vascular process as a characteristic cause of cerebral ischemia has shown that vascular changes occur largely independently from the appearance of cerebral functional disturbances in the associated vascular territory. Hemodynamic factors play a minor role; while with the present standard methods available, embolic mechanisms can be insufficiently analyzed. The prospective developmental observations of morphologic and fluid-dynamic aspects and supplemental cell biology and metabolic analysis provide new criteria for an individual risk evaluation of the various mechanisms causing pathologically different cerebral function disturbances, and their analysis has crucial significance for a therapy plan.


Visible-blind ultraviolet narrowband photomultiplication-type organic photodetector with an ultrahigh external quantum efficiency of over 1 000 000.
A visible-blind ultraviolet (UV) photodetector can detect UV signals and is not interfered with by visible light or infrared light in the environment. In order to realize high-performance visible-blind UV organic photodetectors (OPDs), we design photomultiplication-type (PM-type) OPDs by using a novel strategy. Firstly, wide bandgap organic semiconductor materials, which do not absorb visible light, are selected as donors to absorb UV light. Secondly, a very small amount of C60 is used as an acceptor to trap photogenerated electrons. These accumulating electrons near the Al electrode form a potential, which leads to band bending and narrowing of the interface barrier, thereby assisting hole-tunneling injection to form a multiplication. The fabricated visible-blind UV PM-type OPDs with donor/acceptor doping ratio of 50 : 1 exhibit a narrowband response with full-width at half-maximum (FWHM) of approximately 36 nm, an ultrahigh external quantum efficiency of 1.08 × 106% and a remarkable specific detectivity of 1.28 × 1014 jones at 335 nm wavelength under -14 V bias. The UV-to-visible rejection ratio exceeds 103 by adjusting the donor/acceptor mixing ratios. The devices made with other wide bandgap organic materials also showed similar performance, indicating that this device structure provides an effective method for the preparation of high-performance visible-blind UV PM-type OPDs. In addition, we prepared a flexible visible-blind UV PM-type OPD based on a PET substrate and integrated it with a flexible OLED to fabricate a wearable UV monitor, which can visually detect the intensity of UV light.


[The incidence of clinical forms of female endocrine sterility in 1990-1993 at the III Gynecological Clinic of the Maternity Home of the State Institutional Hospital].
The high frequency of the female endocrine sterility and the favorable therapy results are showing categorically the importance of the endocrine sterility as a medical and a social problem. For the period 1990-1993 in Third Gynaecological clinic--Sector of Gynaecological Endocrinology, were observed 584 patients with proved endocrine sterility. The present research has the goal to discuss the frequency of the different clinical forms of the endocrine sterility. The most frequent one is PCO--30.59%, followed by corpus luteum insufficiency--23.58%, and hyperprolactinaemia--20.05%. The results are interpreted on the basis of similar research for the period 1976-1985 with analog contingent. Conclusions are made for the essential directions of the diagnostic and therapy process in the clinic.


Assessing the impact of a research funder's recommendation to consider core outcome sets.
Core outcome sets (COS) have the potential to reduce waste in research by improving the consistency of outcomes measured in trials of the same health condition. However, this reduction in waste will only be realised through the uptake of COS by clinical trialists. Without uptake, the continued development of COS that are not implemented may add to waste in research. Funders of clinical trials have the potential to have an impact on COS uptake by recommending their use to those applying for funding. The aim of our study was to assess the extent to which applicants followed the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme's recommendation to search for a COS to include in their clinical trial. We examined the outcomes section and detailed project descriptions of all 95 researcher-led primary research applications submitted to the NIHR HTA between January 2012, when the recommendation to search for a COS was included in the guidance for applicants, and December 2015 for evidence that a search for a COS had taken place and rationale for outcome choice in the absence of COS. A survey of applicants was conducted to further explore their use of COS and choice of outcomes with a response rate of 49%. Nine out of 95 applicants (10%) stated in their application that they had searched the COMET (Core Outcome Measures for Effectiveness Trials) Initiative database for a COS and another nine referred to searching for a COS using another method, e.g. a review of the literature. Of the 77 (81%) applicants that did not mention COMET or COS in their application, eight stated in the survey that they had searched the COMET database and ten carried out a search using another method. Some applicants who did not search for a COS gave reasons for their choice of outcomes including taking advice from patients and the public and choosing outcomes used in previous trials. A funding body can have an impact on COS uptake by encouraging trialists to search for a COS. Funders could take further steps by putting processes in place to prompt applicants to be explicit about searching for COS in their application and notifying the funding board if a search has not taken place. The sources of information used by trialists to make decisions about outcomes in the absence of COS may suggest methods of dissemination for COS.


Laccomimus xikrin sp. nov. and new records of other species of Laccomimus Toledo & Michat, 2015 (Coleoptera: Dytiscidae: Laccophilinae) from Brazil.
The genus Laccomimus Toledo & Michat, 2015 was recently erected for small drop-shape Dytiscidae beetles commonly found in Tropical South America associated with lentic waters. In the present paper a new species, Laccomimus xikrin sp. nov., is described and illustrated. New records from Brazil are presented for Laccomimus alvarengi Toledo & Michat, 2015 from Amazonas state, L. bordoni Toledo & Michat, 2015 from São Paulo state and L. variegatus Toledo & Michat, 2015 from Pará state.


Angiotensin converting enzyme from capacitated rabbit spermatozoa: two distinct forms.
Angiotensin converting enzyme (ACE) is present in high concentration in the sperm cells of the rabbit. The enzyme is released during in vitro capacitation of the spermatozoa. It has been purified from the released proteins in the minimum capacitation medium after in vitro capacitation of the spermatozoa and is found to exist in two forms. One is of higher molecular weight and has low enzyme activity but the other one is of low molecular weight and has higher activity. Conversion of the higher molecular weight form to the lower molecular weight my be taking place during the capacitation of the spermatozoa.


Metastatic prostatic adenocarcinoma to the brain and spinal cord: a contemporary clinicopathologic analysis of 30 cases.
Metastatic prostatic adenocarcinoma (PCa) to lymph nodes and bone is well documented in the literature, however only case reports and small series of metastatic PCa to the brain and spinal cord with clinicopathologic analysis have been published. We identified 30 cases of metastatic PCa to the brain and spinal cord. The mean patient age was 67 years (range: 50 to 87 years). Thirteen (43%) cases involved the brain and 17 (57%) cases involved the spinal cord. Most of the cases (60%) were a single mass. Of the 13 cases involving the brain, the temporal lobe 6 (46%) was the most common site and the spinal cord lesions involved the thoracic region in 13/17 (76%) cases. All patients had one or more metastases to other organs. In 8 patients, the brain or spinal cord metastasis was the initial diagnosis of PCa. In the patients that had prior prostate biopsy specimens available, the Gleason score ranged from 3+3=6 (Grade group 1: indicating unsampled higher grade PCa) to Gleason score 4+5=9 (Grade group 5). Follow-up was available in 21 cases with a mean duration of 20 months (range: 1 to 130 months). This is one of the largest clinicopathologic studies to date of metastatic PCa to the brain and spinal cord. Although rare, metastatic PCa should be considered in the differential diagnosis of a solitary brain or spinal cord mass in male patients, even over a decade after the initial diagnosis of PCa.


Optical-Tactile Sensor for Lump Detection Using Pneumatic Control.
Soft tactile sensors are an attractive solution when robotic systems must interact with delicate objects in unstructured and obscured environments, such as most medical robotics applications. The soft nature of such a system increases both comfort and safety, while the addition of simultaneous soft active actuation provides additional features and can also improve the sensing range. This paper presents the development of a compact soft tactile sensor which is able to measure the profile of objects and, through an integrated pneumatic system, actuate and change the effective stiffness of its tactile contact surface. We report experimental results which demonstrate the sensor's ability to detect lumps on the surface of objects or embedded within a silicone matrix. These results show the potential of this approach as a versatile method of tactile sensing with potential application in medical diagnosis.


Maternal activity budgets: feasibility of exclusive breastfeeding for six months among urban women in Honduras.
Although exclusive breastfeeding for 6 months is likely to be beneficial for infant health, mothers often cite time pressures as a reason to introduce other foods. Using 12-hr in-home observations at 19 and 24 wk postpartum, we compared maternal activity budgets and time spent breastfeeding among low-income, urban mothers not employed outside the home who exclusively breastfed (EBF) or gave other foods in addition to breast milk (BF+SF). Breastfeeding time was similar between groups (averaging approx 75 min/12 hr) except that multiparous EBF mothers at 24 wk spent more time breastfeeding their infants than did BF+SF mothers. However, total time devoted to infant feeding (including preparation and feeding of solids in the BF+SF group) was significantly greater in the BF+SF group than in the EBF group (except among multiparous women at 24 wk). Feeding frequency per 12-hr averaged 6.7-8.9 in the EBF group and 5.4-8.1 BF + 1.8 meals in the BF+SF group. Both EBF and BF+SF mothers had considerable 'free' time; they spent, on average, 2-3 hr during each 12-hr period resting, chatting or watching TV. Primiparous women tended to spend less time at household chores and child care than multiparous women. Of the BF+SF mothers, 60% said that breastfeeding was 'somewhat' or 'very' time-demanding (vs 15% of EBF mothers), 49% said that it interfered with other activities (vs 6% of EBF mothers), and 26% said that they gave other foods to extend the time between breastfeeds. Although many of the BF+SF mothers knew that giving foods may increase infant illness, there were cultural pressures not to exclusively breastfeed. For example, many introduced solids to their infants prior to 6 months because they believed that infants should 'learn' how to eat other foods, to 'acclimate' the stomach and learn to differentiate flavors. We conclude that time constraints are not a barrier to exclusive breastfeeding in this population, although they may be perceived as a barrier.


Medicare and Medicaid programs; requirements for long-term care facilities: delay in effective date of regulations--HCFA. Final rule; delay of effective date.
This rule changes the effective date of regulations issued in the Federal Register on February 2, 1989 (54 FR 5316), as amended by a rule published on July 14, 1989 (54 FR 29717), that contained new and revised requirements for long-term care facilities (skilled nursing facilities, intermediate care facilities, and effective October 1, 1990, nursing facilities) that participate in the Medicare and Medicaid programs. The effective date of January 1, 1990 is changed to October 1, 1990.


Functional overlap of IP(3)- and cADP-ribose-sensitive calcium stores in guinea pig myenteric neurons.
In myenteric neurons two different receptor subtypes govern the intracellular Ca(2+) stores: the inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) and the ryanodine receptor (RyR). Their degree of functional overlap was determined by examining Ca(2+) release in these cells through both superfusion techniques and intracellular microinjection. Microinjection of IP(3) (50 microM) and cADP-ribose (cADPr, 50 microM), specific ligands for the IP(3)R and RyR, respectively, demonstrated mobilization of intracellular Ca(2+) stores. Perfusion with cinnarizine (50 microM) or dantrolene (10 microM), antagonists of the IP(3)R and RyR, respectively, eliminated the Ca(2+) response to microinjected IP(3) and cADPr. Superfusion of the neurons with 100 microM ATP, an IP(3)-mediated Ca(2+)-mobilizing agonist, caused intracellular Ca(2+) increments, which were antagonized by cinnarizine, and the RyR antagonists dantrolene, procaine (5 mM), and ryanodine (1 microM). Caffeine (10 mM) was applied repetitively in Ca(2+)-free conditions to deplete RyR-sensitive stores; subsequent perfusion with ATP demonstrated a Ca(2+) response. Conversely, caffeine caused a Ca(2+) response after repetitive ATP exposures. The internal Ca(2+) stores of myenteric neurons are governed by two receptor subtypes, IP(3)R and RyR, which share partial functional overlap.


Sleep deprivation decreases glycogen in the cerebellum but not in the cortex of young rats.
We tested whether brain glycogen reserves were depleted by sleep deprivation (SD) in Long-Evans rats 20-59 days old. Animals were sleep deprived beginning at lights on and then immediately killed by microwave irradiation. Glycogen and glucose levels were measured by a fluorescence enzymatic assay. In all age groups, SD reduced cerebellar glycogen levels by an average of 26% after 6 h of SD. No changes were observed in the cortex after 6 h of SD, but in the oldest animals, 12 h of SD increased cortical glycogen levels. There was a developmental increase in basal glycogen levels in both the cortex and cerebellum that peaked at 34 days and declined thereafter. Robust differences in cortical and cerebellar glycogen levels in response to enforced waking may reflect regional differences in energy utilization and regulation during wakefulness. These results show that brain glycogen reserves are sensitive to SD.


Concurrent High Condylectomy and Orthognathic Surgery for Treatment of Patients With Unilateral Condylar Hyperplasia.
Facial asymmetry from unilateral condylar hyperplasia (UCH) may be definitively treated in the presence of active disease (with high condylectomy and concurrent orthognathic surgery) or after waiting for disease inactivity (orthognathic surgery alone). There is currently no consensus on the standard of care. In this study, we sought to compare functional and esthetic outcomes, as well as treatment duration, between these 2 management options. Patients who underwent treatment for UCH were identified through retrospective review. Pre- and postoperative 3-dimensional (3D) images were obtained. Short- and long-term operative outcomes of those treated during the active (group 1) were compared to those treated in the inactive phase (group 2). Total treatment time, operative time, and length of hospital stay were evaluated. Facial asymmetry was also assessed by laypersons using a Likert scale. Fifteen patients (mean 25.6 years, range 14-56) were included: 6 in group 1 and 9 in group 2. All surgical outcomes were statistically independent of procedure type. Treatment time was significantly longer in the group 2 (P = 0.03). Both groups demonstrated significant improvement in facial asymmetry scores postoperatively with no significant difference in pre- or postoperative asymmetry between groups (P = 0.64). In patients with active UCH, high condylectomy and orthognathic surgery is a procedure that restores facial symmetry and improves jaw function while halting mandibular growth. Good esthetic and functional outcomes, as well as reduced treatment time and disease burden, support the use of this treatment option for this population.


The flavonoid baicalin improves glucose metabolism by targeting the PH domain of AKT and activating AKT/GSK3β phosphorylation.
Baicalin is one of the main flavonoids of the dried root of Scutellaria baicalensis Georgi and is reported to exert beneficial effects on the regulation of glucose/lipid metabolism. However, understanding its specific target and unique mechanism for improving glucose utilization is a challenge. In this paper, target fishing with a baicalin probe reveals that baicalin interacts with AKT. An immunofluorescence assay further demonstrates the colocalization of baicalin with AKT in the cytoplasm. A competitive test and virtual docking show that baicalin might bind to the pleckstrin homology domain of AKT. This specific binding hampers AKT membrane translocation, activates the phosphorylation of AKT on Ser473, induces the downstream glycogen synthase kinase 3β activation, and affects glycogen synthesis.


Interrupting Intergenerational Cycles of Maternal Obesity.
Factors operating in the preconception and prenatal periods, such as maternal obesity, excessive gestational weight gain and gestational diabetes, predict a substantial fraction of childhood obesity as well as lifelong adverse health consequences in the mother. These periods may lend themselves to successful intervention to reduce such risk factors because parents may be especially willing to change behavior if it confers health advantages to their children. If effective interventions started before or during pregnancy can be maintained after birth, they have the potential to lower the risk of both maternal obesity in the next pregnancy and obesity in the growing child, thus helping to interrupt maternal and child intergenerational vicious cycles of obesity, diabetes and related cardiometabolic health consequences. While this paradigm is appealing, challenges include determining the magnitude, causality and modifiability of these risk factors, and quantifying any adverse consequences of intervention.


Melatonin as a pro-osteogenic agent in oral implantology: a systematic review of histomorphometric outcomes in animals and quality evaluation using ARRIVE guidelines.
The aim of this review was to evaluate the outcomes of preclinical trials that assessed the use of melatonin as a pro-osteogenic agent in the field of oral implantology. Melatonin is a hormone that has been shown to have beneficial antioxidant and bone-metabolic effects. A number of experimental studies have analysed its effect in promoting osseointegration around dental implants in animals. A bibliographic search in PubMed, Scopus and EBSCOhost was performed. Animal studies that quantitatively analysed the pro-osteogenic effect of melatonin were included. Quality assessment of the included studies was performed using the ARRIVE guidelines. Eight studies met the inclusion criteria. The experimental animals used were dogs, rabbits and rats. Melatonin was used in a lyophilized powdered form, an injectable form or as a dipping solution. Six of the eight studies included showed a statistically significant positive effect of melatonin on bone-implant contact and various other histomorphometric parameters. The ARRIVE criteria were generally well reported by the included studies (17.5 ± 1.60/24), although several criteria (including randomization and blinding) were poorly documented, with most of the studies showing a high/unclear risk of bias. The majority of the studies included showed a statistically significant positive effect of melatonin on bone formation around implants. However, the clinical significance of this effect was unclear given the high/unclear risk of bias in the majority of included studies. Given the limited amount of data available, further research should be conducted to evaluate the clinical potential of this pineal hormone in clinically relevant situations, such as compromised sites or patients.


Regulation of cell growth by estrogen signaling and potential targets in thyroid cancer.
Thyroid cancer occurs three times more frequently in females than in males, and in females the incidence decreases after menopause. This gender difference suggests that the growth and progression of thyroid cancer may be influenced by female sex hormones, particularly estrogens. Experimental data have clearly demonstrated that estrogens can influence cancer cell growth. The action of estrogens on target sites is mediated through related but distinct estrogen receptors, designated estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), both of which are known to be expressed in thyroid cancer cells. The proliferation of thyroid cancer cells is promoted by an ERalpha agonist, whereas the proliferation is reduced by the enhanced expression of ERbeta or by an ERbeta agonist. When ERbeta is down-regulated, the proliferation of thyroid cells is significantly increased. Studies have shown that the expression of ERalpha in thyroid cancer cells is increased while the expression of ERbeta is either very low or absent. In conclusion, it appears that estrogens have opposite effects on the growth of thyroid cancer cells, depending on the balance between ERalpha and ERbeta in the cells. The modulation of ERalpha and ERbeta and the intervention of their pathways may open up new potential targets for the treatment of thyroid cancer.


Is microparticle enzyme-linked immunoassay (MEIA) reliable for use in tacrolimus TDM? Comparison of MEIA to liquid chromatography with mass spectrometric detection using longitudinal trough samples from transplant recipients.
In the larger transplant centers where technical expertise is available, liquid chromatography with mass spectrometric detection (LC-MS) for tacrolimus therapeutic drug monitoring is replacing the popular microparticle enzyme-linked immunoassay (MEIA) as a cost-effective alternative technology. As more labs convert to LC-MS, the accuracy, precision, selectivity, and sensitivity of the tacrolimus MEIA are being challenged, using data from large populations of clinical samples. However, little attention has been paid to how the results of particular procedures may differ within and among individual patients and to how such differences may relate to patients' characteristics or to relevant biochemical parameters. So, after validation of an LC/MS procedure and verification of an LC/MS/MS procedure, the author analyzed 552 serial trough blood tacrolimus samples, collected from 38 patients over a 3-month period, by controlled MEIA and LC-MS procedures. Corresponding hematocrit and serum albumin level data were obtained. In an attempt to investigate whether the observations of others who studied population-based data could be illustrated for individuals, longitudinal data from several patients were plotted to visually elucidate any relations between the tacrolimus concentration and biochemical data. Finally tacrolimus concentration, hematocrit, and serum albumin data were compared using data stratified by transplant type, in-/outpatient status, male/female gender, or period elapsed since transplant surgery. The validated/verified LC-MS procedures were shown to be much better controlled than the MEIA during the 3-month parallel comparison study period. The longitudinal data of several individuals who experienced wide changes in the biochemical parameters clearly illustrated the relation between the difference in tacrolimus concentrations determined by MEIA and LC-MS and hematocrit (and sometimes albumin). Differences between the MEIA- and LC-MS-determined tacrolimus concentration data were strongly correlated to transplant type, in-/outpatient status, gender, time elapsed since liver transplant surgery, hematocrit, and weakly to serum albumin levels. In summary, the LC-MS methods provide highly reliable and reproducible estimates of tacrolimus concentrations, whereas the performance of MEIA technology did not provide reliable long-term performance for longitudinal therapeutic drug monitoring of tacrolimus because it was effected by several inherent demographic factors and by factors that can change over time in transplant recipients.


Co-overexpression of two Heat Shock Factors results in enhanced seed longevity and in synergistic effects on seedling tolerance to severe dehydration and oxidative stress.
We have previously reported that the seed-specific overexpression of sunflower (Helianthus annuus L.) Heat Shock Factor A9 (HaHSFA9) enhanced seed longevity in transgenic tobacco (Nicotiana tabacum L.). In addition, the overexpression of HaHSFA9 in vegetative organs conferred tolerance to drastic levels of dehydration and oxidative stress. Here we found that the combined overexpression of sunflower Heat Shock Factor A4a (HaHSFA4a) and HaHSFA9 enhanced all the previously reported phenotypes described for the overexpression of HaHSFA9 alone. The improved phenotypes occurred in coincidence with only subtle changes in the accumulation of small Heat Shock Proteins (sHSP) that are encoded by genes activated by HaHSFA9. The single overexpression of HaHSFA4a in vegetative organs (which lack endogenous HSFA9 proteins) did not induce sHSP accumulation under control growth conditions; neither it conferred thermotolerance. The overexpression of HaHSFA4a alone also failed to induce tolerance to severe abiotic stress. Thus, a synergistic functional effect of both factors was evident in seedlings. Our study revealed that HaHSFA4a requires HaHSFA9 for in planta function. Our results strongly support the involvement of HaHSFA4a and HaHSFA9 in transcriptional co-activation of a genetic program of longevity and desiccation tolerance in sunflower seeds. These results would also have potential application for improving seed longevity and tolerance to severe stress in vegetative organs.


Population and development within the ecosphere: one view of the literature.
"Contemporary academic economists, unlike those of the nineteenth century, find that although population growth and density can have bad effects on development, these will only be severe with wrong economic policies. Technical advance and substitution in free markets avoid major difficulties, for example shortage of materials. But ecologists see the poor cutting trees for firewood, the rich pouring carbon in to the atmosphere, and doubt the capacity of the environment to absorb the effects of dense and growing populations and their present technologies. On both sides are distinguished scholars, whose writings cannot here be covered exhaustively, but only enough said for background to the question posed to demographers: Should this central population issue not be on our research agendas?"


Treatment charges, payment sources, and disability from alcohol-related trauma.
We examined treatment charges and who paid them and disability for work, school, household activities, and activities of daily living according to identified use of alcohol before injury among 2,416 patients age 15 years or older from 22 northwestern Vermont communities. Over 90% received emergency department treatment only. Among patients reported to have consumed this drug mean hospital and physician charges, respectively, were $2,482 and $565; 31.7% did not pay any portion of their hospital bills, and 27.8% of their total bills were unpaid. Among patients not known to have consumed alcohol, mean hospital and physician charges were $601 and $158, respectively; 10.7% made no payments and 11.3% of their bills were unpaid. Bills of alcohol users more often were paid by Medicaid and less often by Workmen's Compensation or commercial insurance than were those of patients without alcohol. Users also were less likely than the nonalcohol group to pay physicians' bills for hospital care. Alcohol users experienced longer postinjury disability than did persons not known to have been drinking.


A surgical model to increase the intestinal absorptive surface: intestinal lengthening and growing neomucosa in the same approach.
Despite numerous investigations short bowel syndrome (SBS) is still an unsolved clinical problem. The purpose of this study was to develop a new surgical approach that combines both intestinal lengthening and growing neomucosa. The operative principle is based on a longitudinal division of an intestinal segment antimesenterically and a formation of two intestinal tubes out of bowel halves anastomosing one cutting edge to the incised mucosal midline and the other to the antimesenteric side of the constructed first intestinal tube, so that a common wall between the two hemiloops was created which leads to grow neomucosa. This procedure was applied to 11 rabbits. The hemiloops and neomucosa were investigated for its feasibility and morphologic characteristics. Gross and microscopic examinations at 8 weeks revealed that all the intestinal tubes were viable and patent. No anastomotic leakage was present. In all animals, the serosal surfaces of the common walls were covered with neomucosa that resembles the mucosa of the existing intestine morphologically; there was no significant difference in villus height, villus width at base, crypt depth, number of villi per unit serosal length, villus surface, and villus surface per unit serosa. The growth of neomucosa was completely a result of epithelialization without any evidence of contraction. The quantity and rate of neomucosal growth seems unaffected by intestinal segment length. Finally a two times increase in intestinal length, whereas the diameter halved and a statistically significant increase (P < 0.001) in total villus surface via growing neomucosa was obtained. This model might be useful in the management of SBS when supported by clinical and functional investigations.


Do clinical characteristics predict the cognitive course in early-onset schizophrenia-spectrum disorders?
Being in a period with extensive brain maturation, adolescents with early-onset schizophrenia-spectrum disorders (EOS) provide unique neurodevelopmental data that may contribute to a better understanding of schizophrenia at all ages. Cognitive dysfunction is a central feature of schizophrenia and is more pronounced in EOS than in later onset illness. However, there is limited research on both the long-term course of global cognition in EOS, and how cognition over time is influenced by clinical characteristics during the early illness period. Thirty-one EOS patients and 73 controls (age 12-18) were assessed on clinical variables at baseline (PANSS, duration of untreated psychosis [DUP], hospitalizations, suicide attempts, and remission). Neuropsychological assessments with the MATRICS Consensus Cognitive Battery (MCCB) were conducted at baseline and after both 1 and 2 years, and composite scores of total performances were calculated. The analyses were performed with a linear mixed model. The present study found that global cognition followed a stable course over the first years of the disease in EOS, though at a significantly lower level in EOS compared with the controls. We did not detect a relationship between DUP, remission, positive/negative symptoms, and hospitalizations on one hand, and long-term cognition on the other hand, but PANSS-general and suicide attempt history at baseline were identified as risk factors of longitudinal cognitive function. Though at different levels, the EOS group and the controls had a similar cognitive course over 2 years. Some baseline characteristics (psychotic symptoms, DUP, remission, and hospitalization) had no influence on cognition within the first 2 years of illness. In contrast, general symptoms and a history of suicide attempts at baseline were more potent risk factors of the cognitive course than the psychotic-specific symptoms, and should, therefore, be subject to specific attention in the evaluation and treatment of patients with early-onset psychosis.


Ancient myths with perennial question.
Even though myths have an imaginative component that frequently clashes with logical thinking, their symbolism often resonates with our collective unconscious. The divine inspiration that propels mythological heroes towards the noblest and highest ideals also carries the risk of taunting the jealousy of the gods. This may culminate in fatal results as has happened to Remus when he overstepped the newly defined boundaries set by his twin Romulus when outlining the future city of Rome. Fortunately, mythological heroes often enjoyed the benefit of having wise advisors. These were generally able to counsel their charges against yielding to the sin of pride so as to avoid triggering the anger of the gods. But when deprived of such advisors - as we are - how are we to place legitimate boundaries to our citadel of growing medical knowledge lest we scoff at limits and pay the penalty exacted from Remus?


Intravenous reproductive and developmental toxicity studies of cimadronate (YM175), a novel bisphosphonate, in rats and rabbits.
Cimadronate (YM175) is a novel bisphosphonate with potent inhibitory activity on bone resorption under development for the treatment of tumor-induced hypercalcemia, metastatic bone disease and osteoporosis. We conducted intravenous reproductive toxicity and teratology studies (Segment I, II and III) of this compound in rats and teratology study in rabbits. The test compound was dissolved in physiological saline, which was also given as the vehicle control. Rats were administered at a dosage of 0.06, 0.16 and 0.62 mg/kg/day in the male Segment I study. Dose levels in the other studies in rats including the female Segment I were 0.16, 0.31 and 0.62 mg/kg/day. In the Segment I study, no treatment-related abnormalities were observed in reproductive parameters or fetuses. In the Segment II study, slightly retarded fetal ossification was noted at 0.31 mg/kg/day or more, but the incidence of malformation did not increase. In the Segment III study, death of the dams and abnormal tooth growth of offspring were observed at 0.16 mg/kg/day or more. Further Segment III study showed that the no toxic effect level was 0.003 mg/kg/day. In the rabbit teratology study, dose levels were 0.01, 0.025 or 0.05 mg/kg/day. No toxic effects on pregnant females or their litters were observed at up to 0.05 mg/kg/day.


SF5- and SCF3-substituted tetrahydroquinoline compounds as potent bactericidal agents against multidrug-resistant persister Gram-positive bacteria.
Bacteria persister cells are immune to most antibiotics and hence compounds that are active against persister bacteria are needed. We screened a chemical library of SF5- and SCF3-substituted tetrahydroquinoline compounds, synthesized via the Povarov reaction, for antibacterial activity and identified active compounds that displayed good activities against many Gram-positive bacteria, including persisters. The most potent of these compounds, HSD1835, inhibited the growth of drug-resistant Gram-positive bacterial pathogens (including clinical strains) at concentrations ranging from 1 μg mL-1 to 4 μg mL-1. Several of the SCF3- and SF5-containing compounds were active against methicillin-resistant Staphylococcus aureus (MRSA) and against the two most fatal strains of vancomycin-resistant Enterococcus (VRE), VRE faecalis and VRE faecium. The compounds showed bactericidal activity against stationary phase persister MRSA in time-kill assays. Mechanistic studies showed that HSD1835 acts by disrupting bacterial membranes. Scanning electron microscopy (SEM) was used to confirm bacterial membrane disruption. Interestingly, in a 30 day serial exposure experiment, MRSA remained susceptible to low-dose HSD1835 whilst resistance to ciprofloxacin and mupirocin emerged by day 10. Analogs of HSD1835, which did not bear the SF5 or SCF3 moieties, were inactive against bacteria. Recent reports (G. A. Naclerio, N. S. Abutaleb, K. I. Onyedibe, M. N. Seleem and H. O. Sintim, RSC Med. Chem. 2020, 11, 102-110 and G. A. Naclerio, N. S. Abutaleb, D. Li, M. N. Seleem and H. O. Sintim, J. Med. Chem. 2020, 63(20), 11934-11944) also demonstrated that adding the SF5 or SCF3 groups to a different scaffold (oxadiazoles) enhanced the antibacterial properties of the compounds, so it appears that these groups are privileged moieties that enhance the antimicrobial activities of compounds.


A measure of knowledge flow between specific fields: Implications of interdisciplinarity for impact and funding.
Encouraging knowledge flow between mutually relevant disciplines is a worthy aim of research policy makers. Yet, it is less clear what types of research promote cross-disciplinary knowledge flow and whether such research generates particularly influential knowledge. Empirical questions remain as to how to identify knowledge-flow mediating research and how to provide support for this research. This study contributes to addressing these gaps by proposing a new way to identify knowledge-flow mediating research at the individual research article level, instead of at more aggregated levels. We identify journal articles that link two mutually relevant disciplines in three ways-aggregating, bridging, and diffusing. We then examine the likelihood that these papers receive subsequent citations or have funding acknowledgments. Our case study of cognitive science and educational research knowledge flow suggests that articles that aggregate knowledge from multiple disciplines are cited significantly more often than are those whose references are drawn primarily from a single discipline. Interestingly, the articles that meet the criteria for being considered knowledge-flow mediators are less likely to reflect funding, based on reported acknowledgements, than were those that did not meet these criteria. Based on these findings, we draw implications for research policymakers.


SREBP-1c overactivates ROS-mediated hepatic NF-κB inflammatory pathway in dairy cows with fatty liver.
Dairy cows with fatty liver are characterized by hepatic lipid accumulation and a severe inflammatory response. Sterol receptor element binding protein-1c (SREBP-1c) and nuclear factor κB (NF-κB) are components of the main pathways for controlling triglyceride (TG) accumulation and inflammatory levels, respectively. A previous study demonstrated that hepatic inflammatory levels are positively correlated with hepatic TG content. We therefore speculated that SREBP-1c might play an important role in the overactivation of the hepatic NF-κB inflammatory pathway in cows with fatty liver. Compared with healthy cows, cows with fatty liver exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6 and IL-1β. Hepatic SREBP-1c-mediated lipid synthesis and the NF-κB inflammatory pathway were both overinduced in cows with fatty liver. In vitro, treatment with non-esterified fatty acids (NEFA) further increased SREBP-1c expression and NF-κB pathway activation, which then promoted TG and inflammatory cytokine synthesis. SREBP-1c overexpression overactivated the NF-κB inflammatory pathway in hepatocytes by increasing ROS content and not through TLR4. Furthermore, SREBP-1c silencing decreased ROS content and further attenuated the activation of the NEFA-induced NF-κB pathway, thereby decreasing TNF-α, IL-6 and IL-1β synthesis. SREBP-1c-overexpressing mice exhibited hepatic steatosis and an overinduced hepatic NF-κB pathway. Taken together, these results indicate that SREBP-1c enhances the NEFA-induced overactivation of the NF-κB inflammatory pathway by increasing ROS in cow hepatocytes, thereby further increasing hepatic inflammatory injury in cows with fatty liver.


Do synaesthetic colours act as unique features in visual search?
For individuals with grapheme-colour synaesthesia, letters, numbers and words elicit vivid and highly consistent colour experiences. A critical question in determining the mechanisms underlying the phenomenon is whether synaesthetic colours arise early in visual processing, prior to the allocation of focused attention, or at some later stage following explicit recognition of the inducing form. If the synaesthetic colour elicited by an achromatic target emerges early in visual processing, then the target should be relatively easy to find in an array of achromatic distractor items, provided the target and distractors elicit different synaesthetic colours. Here we present data from 14 grapheme-colour synaesthetes and 14 matched non-synaesthetic controls, each of whom performed a visual search task in which a target digit was distinguished from surrounding distractors either by its unique synaesthetic colour or by its unique display colour. Participants searched displays of 8, 16 or 24 items for a specific target. In the chromatic condition, target and distractor digits were presented in different colours (e.g., a yellow '2' amongst blue '5's). In the achromatic condition, all digits in the display were black, but targets elicited a different synaesthetic colour from that induced by the distractors. Both synaesthetes and controls showed the expected efficient (pop-out) search slopes when the target was defined by a unique display colour. In contrast, search slopes for both groups were equally inefficient when the target and distractors were achromatic, despite eliciting distinct colours for the synaesthetes under normal viewing conditions. These results indicate that, at least for the majority of individuals, synaesthetic colours do not arise early enough in visual processing to guide or attract focal attention. Our findings are consistent with the hypothesis that graphemic inducers must be selectively attended to elicit their synaesthetic colours.


Common genetic variants in the plasminogen activation pathway are not associated with multiple sclerosis.
Matrix metalloproteinase 9 (MMP9) is involved in multiple sclerosis (MS) aetiology. Previously, we identified differential gene expression of plasminogen activation cascade genes in MS patients. Based on our gene expression results, we wanted to identify whether polymorphisms in the genes associated with the plasminogen pathway could predict MS risk. We genotyped 1153 trio families, 727 MS cases and 604 healthy controls for 17 polymorphisms in MMP9, plasminogen activator urokinase (PLAU), PLAU receptor (PLAUR) and serpin peptidase inhibitor/clade 2/member B2 (SERPINB2) genes. No associations were found between the 17 polymorphisms and MS. Also, gene expression levels were analysed according to genotype: no associations were observed. In conclusion despite the consistent evidence for the role of MMP9 and the plasminogen activation cascade in MS, we found no associations between genotype nor gene expression. This suggested there are other potentially modifiable factors influencing gene expression in MS.


RNA-catalyzed amino acid activation.
We have selected RNAs that perform a new reaction that chemically activates amino acids, paralleling mixed phosphate anhydride synthesis by protein aminoacyl-transfer RNA synthetases. Care with recovery of the unstable reaction product was apparently essential to this selection. The best characterized RNA, KK13, requires only Ca2+ for reaction and is optimally active at low pH with KM = 50 mM and kcat = 1.1 min(-1) for activation of leucine. In conjunction with previous RNA-catalyzed aminoacyl-RNA synthesis, peptide bond formation, and RNA-based coding, these amino acid-activating RNAs complete an experimental demonstration that the four fundamental reactions of protein biosynthesis can be RNA-mediated. The appearance of translation in an RNA world is therefore supported.


Therapeutic jurisprudence: integrated inquiry and instrumental prescriptions.
This paper considers the manner in which one could apply a therapeutic jurisprudence (TJ) analysis to a controversial approach to the treatment of sex offenders. Rather than attempting to resolve the difficult questions regarding this form of intervention, however, this paper uses this issue as an opportunity to examine some theoretical concerns about the nature and limits of the TJ research program. As interpreted here, TJ consists of a program of scholarship and law reform intended to promote integration of conceptual, empirical, and normative inquiry. TJ does not in itself resolve normative issues, but it promotes integrated analysis that can sharpen our ability to articulate and examine those normative concerns. TJ remains normatively neutral at the levels of value and theoretical neutrality. Prescriptively, it cannot generate principled normative prescriptions, but it can generate instrumental prescriptions. The long-term measure of the TJ program rests upon its success in promoting innovative and integrated interdisciplinary scholarship and law reform.


Complete Genome Sequence of the Neonatal Meningitis-Causing Escherichia coli Strain NMEC O18.
Neonatal meningitis Escherichia coli (NMEC) is a common agent of neonatal bacterial meningitis, causing high neonatal mortality and neurologic sequelae in its victims. Here, we present the complete genome sequence of NMEC O18 (also known as NMEC 58), a highly virulent (O18ac:K1, ST416) strain.


The Effects of a Daily Skincare Regimen on Maintaining the Benefits Obtained from Previous Chemical Resurfacing Treatments.
Chemical peels are versatile treatments that involve chemical exfoliation of the skin for cosmetic improvement. Deeper peels produce more significant results, but can be associated with longer healing time and potential complications. Novel chemical resurfacing treatments (AGE and MELA) were developed in Europe to produce skin resurfacing via controlled inflammation to promote cell regeneration with minimum negative effects associated with conventional peelings. The AGE Resurfacing regimen is indicated for the treatment of photoaging, and consists of multi-ingredient peeling solution with trichloroacetic acid, pyruvic acid, salicylic acid, mandelic acid, and lactobionic acid. The MELA Resurfacing regimen addresses hyperpigmentation concerns and contains mandelic acid, potassium azeloyl diglycinate, retinol, salicylic acid, phytic acid, lactobionic acid, and lactic acid. Results of previously conducted US clinical experience trial of AGE and MELA resurfacing protocols rated 81% of subjects with some level of improvement according to physician assessment.
 To evaluate whether a daily skin care regimen used for 12 weeks could maintain the benefits achieved with AGE and MELA chemical resurfacing treatments.
 Subjects who completed participation in the AGE and MELA skin resurfacing clinical trial were recruited to participate in a continuation trial and used a daily regimen of MDRejuvena facial products for 12 weeks. No other facial products were permitted. Physicians assessed the severity of individual skin parameters at baseline and week 12 and provided global assessment. Subjects assessed improvement of individual skin parameters at week 12 and provided an overall assessment.
 Thirteen subjects participated in the 12-week continuation trial. According to the physician's global assessment, all subjects demonstrated some level of improvement at week 12 compared to baseline. Physician assessment showed a decrease in severity of all skin parameters assessed at week 12 compared to baseline. According to the subject overall assessment at week 12, 11 of 12 subjects noted some level of improvement, 1 subject saw no improvement, and 1 subject did not provide an overall assessment. Mild to moderate improvement was observed by subjects in all individual skin parameters assessed except for skin discoloration.
 The results of the continuation study demonstrate that use of a daily skin care regimen, which include combination of 2 various strengths of MDRejuvena Rejuvaphyl® Rejuvenating Complex: low strength (LS) and high strength (HS), not only maintains but can enhance the beneficial effects of skin resurfacing treatments for at least 12 weeks.

 J Drugs Dermatol. 2016;15(9):1145-1150.


The maturation of motor dexterity: or why Johnny can't go any faster.
The speed of alternating movements at the ankle, metacarpophalangeal and wrist joints in 11 healthy children and 13 adults doubled between age 3 and 11 years, despite a 32-fold increase in limb-segment inertia produced by the doubling in limb length over the same period. The data for the children showed little or no practice effect. The speeds for the adults, though faster than those for the children, were more widely dispersed, indicating the possibility that training might increase the speed of the slowest adult. The findings are consistent with a previous report demonstrating a parallel increase in the speed of calf muscles over the first 10 years of life and it is inferred that the increase in dexterity at the wrist and metacarpophalangeal joints also depends on an increase in muscle speed with age. Muscle maturation may impose a rate-limiting envelope for all motor tasks which is particularly evident in rapidly alternating movements. These findings have implications for training in sport and music and for the understanding of motor delay, clumsiness and speech difficulties.


Estimated 24-hour urine sodium excretion is correlated with blood pressure in Korean population: 2009-2011 Korean National Health and Nutritional Examination Survey.
No large-scale studies have investigated the association between salt intake and hypertension in Korean population. To investigate the relationship of blood pressure to salt consumption, we analyzed data from 19,476 participants in the 2009-2011 Korean National Health and Nutritional Examination Survey (KNHANES). Urinary sodium excretion over 24-hr (24HUNa) was estimated from spot urine tests using Tanaka's equation. The study subjects were stratified into hypertensive and normotensive groups. Hypertensive participants (n=6,552, 33.6%) had higher estimated 24HUNa, 150.4±38.8 mEq/day, than normotensive participants, 140.5±34.6 mEq/day (P<0.001). The association between 24HUNa and blood pressure outcomes was not affected by adjustment for other risk factors for hypertension (odds ratio 0.001; 95% confidence interval 0.001-0.003; P<0.001). Increases in 24HUNa of 100 mEq/day were associated with a 6.1±0.3/2.9±0.2 mmHg increase in systolic/diastolic blood pressure in all participants. This effect was stronger in hypertensive participants (increase of 8.1±0.5/3.4±0.3 mmHg per 100 mEq/day) and smaller in normotensive participants (2.9±0.3/1.3±0.2 mmHg). These results support recommendations for low salt intake in Korean population to prevent and control adverse blood pressure levels.


Twist constraints on linker DNA in the 30-nm chromatin fiber: implications for nucleosome phasing.
Previous work has shown that nucleosome repeat lengths, and hence linker DNA lengths, are preferentially quantized to a set of values differing by integral multiples of the helical twist of DNA. An explanation was proposed in which this preferential quantitation is due to twist constraints on linker DNA arising from nucleosome-nucleosome interactions in folded chromatin. Here we report the results of a study, using ethidium intercalation, designed to test whether twist constraints do indeed exist. Electron microscopy reveals that ethidium intercalation causes decondensation of dinucleosomes. Direct measurement of the free energy of intercalation by fluorescence spectroscopy reveals competition between chromatin folding and ethidium intercalation. Results from other laboratories establish that these effects of ethidium are due to ethidium-induced changes in the twist of linker DNA, and not to a variety of other possible effects. We conclude that twist constraints on linker DNA do exist. These may explain the observation of preferentially quantized linker DNA lengths. Implications of these results for mechanisms of nucleosome phasing and the mechanisms of drug action are discussed.


[Tuberculosis Annual Report 2008--Series 9. Treatment of TB (2)].
The standard treatment for tuberculosis (TB) is the key to its control. Here we report on the statistics of treatment status and the duration of hospitalization/treatment. The place of initial treatment was observed among newly notified TB patients (n = 24,760) in 2008. Of those, the proportion receiving treatment in hospital among sputum smear positive pulmonary TB patients was the most (91.7%), including 2.1% hospitalized mainly due to other diseases. The proportion receiving treatment in hospital among bacteriologically negative pulmonary TB cases was the least (25.8%), including 10.3% hospitalized mainly due to other diseases. This proportion of patients receiving treatment in hospital did not differ with age, among sputum smear positive pulmonary TB cases. But, this proportion differed greatly in their age groups (e.g. 9.9% in their 20s, 25.7% in their 50s and 50.0% in their 80s), among bacteriologically negative pulmonary TB cases. The duration of hospitalization for TB treatment among newly notified cases in 2007 was observed at the end of 2008. The median hospitalization periods were 69 days, 74 days, 45 days, 38 days and 45 days, among new sputum smear positive pulmonary TB cases, retreatment sputum smear positive pulmonary TB cases, other bacillary positive pulmonary TB cases, bacilli negative pulmonary TB cases and extra-pulmonary TB cases, respectively. The duration of TB treatment among newly notified cases in 2007 was observed at the end of 2008. The median treatment duration among all forms of TB was 273 days. The longest median treatment duration was 298 days for retreatment sputum smear positive pulmonary TB cases and the shortest was 204 days for bacteriologically negative pulmonary TB cases.


[Classification of lymphomas].
A new classification of lymphoma has been published in 2001 under the direction of the World Health Organisation. This classification is based on a consensus between experts in haematopathology, haematology and oncology involved in management of lymphoma. Around 40 entities are described on the basis of morphology, immunophenotype, genetic and clinical presentation. Lymphomas and lymphoid leukaemias are gathered because tumour masses and leukaemic phases are present in numerous entities. This classification differentiates B-cell lymphomas from T/NK (natural killer) cell lymphomas. Grading the different lymphomas into low grade or high grade is no more required in this classification.


Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis.
Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells. HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease.


Contribution to the knowledge of the bumblebee fauna of Afghanistan (Hymenoptera, Apidae, Bombus Latreille).
Bumblebees (Hymenoptera: Apidae: genus Bombus Latreille, 1802) constitute an important group of pollinators for many wild plants and crops in north temperate regions and South America. Although knowledge of these insects has been increasing over the last decades, some geographic areas remain poorly studied and additions to the knowledge of their faunas are infrequent. Afghanistan is one example of a country that is currently underrepresented in the scientific literature despite its high species diversity. For this study, more than 420 new occurrence records were gathered for 17 bumblebee species belonging to all eight subgenera recorded in the country, including the first record of a species closely related to the B longipennis group. Additionally, the first standardized database for Afghan bees is launched, which we hope will be enriched in the future to allow further assessments of population trends for the bumblebees of Afghanistan. Finally, the previously published species records for the country are discussed considering the most recent taxonomic revisions of the genus and key perspectives are highlighted for further work in this understudied country and neighboring regions.


Document analysis of sports literature for individuals with disabilities.
A document analysis was conducted on published articles (data-based and review) relative to sports for individuals with disabilities. Data were directly compared to those published from a 10-year (1986 to 1996) document analysis by Reid and Prupas (1998). The current analysis consisted of the recent 10-year time period (2001 to 2011). Retrieved articles were assigned into one of eight categories. Reliability checks resulted in 90% for inter-rater and 93% for intra-rater agreement. The period 2001 to 2011 resulted in the greatest number of data-based articles published while the period 1986 to 1996 resulted in the greatest number of review articles published. Similarities and differences were discussed relative to the timeframes used as well as the method used to retrieve publications. Results were provided information for future research and writing in the area of sport for individuals with disabilities.


PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies.
Indication biopsies for deterioration of kidney allograft function often require follow-up biopsies to assess treatment response or lack of improvement. Immune-mediated injury, namely borderline rejection (BLR), T-cell mediated rejection (TCMR), or antibody-mediated rejection (ABMR), results from preformed or de novo alloreactivity due to donor and recipient HLA-mismatches. The impact of HLA-mismatches on alloreactivity is determined by highly immunogenic HLA-epitopes. We analyzed 123 kidney transplant recipients (KTRs) from 2009 to 2019 who underwent a first indication and a follow-up biopsy. KTRs were divided into three groups according to the first biopsy: No rejection (NR)/BLR (n=68); TCMR (n=21); ABMR (n=34). The HLA-derived epitope-mismatches were calculated using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm. Group NR/BLR: KTRs with higher total PIRCHE-II scores were more likely to develop TCMR in the follow-up biopsy (p=0.031). Interestingly, these differences were significant for both HLA-class I- (p=0.017) and HLA-class II-derived (p=0.017) PIRCHE-II scores. Group TCMR: KTRs with ongoing TCMR in the follow-up biopsy were more likely to show higher total PIRCHE-II scores (median 101.50 vs. 74.00). Group ABMR: KTRs with higher total PIRCHE-II scores were more likely to show an increase in the microvascular inflammation score in the follow-up biopsy. This difference was more pronounced for the HLA-class II-derived PIRCHE-II scores (median 70.00 vs. 31.76; p=0.086). PIRCHE-II scores may prove useful as a biomarker to predict the histopathological changes of immune-related injury from a first indication to a follow-up biopsy. This immunological risk stratification may contribute to individualized treatment strategies.


Prediction of rotator cuff repair results by magnetic resonance imaging.
Thirty chronic rotator cuff tears were repaired consecutively and evaluated prospectively using a precise anatomic description of the tear that included the rotator interval, the Constant functional score, and an assessment of the tendon state and the atrophy of the supraspinatus muscle by preoperative and postoperative magnetic resonance imaging. Early correlations (mean followup, 21.1 months) attempted to define predictive factors of the final outcome of the repair, physical factors indicative of final tendon state, and postoperative evolution of supraspinatus atrophy. Magnetic resonance imaging oblique sagittal views showed that supraspinatus atrophy correlated with the sagittal and coronal extent of the tear and represented a strong predictive factor of postoperative retearing. At followup, 15 (50%) cuffs were continuous and thick, seven (23%) were continuous but thin, and six (20%) were retorn. Two (7%) cuffs had been repaired only partly. In the group with a persistent tear, flexion strength and differential Constant score were correlated with the final tendon state with no excellent or good results, and with less than 4 kg of strength. Supraspinatus atrophy improved in 18 of the 22 postoperative continuous cuffs, but never decreased in persistent tears, although there was pain relief and functional gain.


Dental prosthetic status and prosthetic need of the institutionalized elderly living in geriatric homes in mangalore: a pilot study.
Introduction. To promote oral health among the elderly, we need to know their prosthetic status and prosthetic need. Hence, a survey of prosthetic status and need of elderly inmates of old age homes in Mangalore was done. Materials and Methods. A cross-sectional study was undertaken, and 133 subjects aged 60 years and above were examined (54.9% males and 45.1% females). Results. Eighty-eight percent of those examined were fully edentulous, and only 12% had complete dentures; none of the study subjects had partial dentures. Prosthetic status was significantly associated with gender (P = .024), while prosthetic need and gender were not significantly associated (P = .395). Conclusions. A high unmet need for prosthetic care existed among the institutionalized elderly surveyed.


Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine. ME/CFS patients were heterogeneous for genetic background, trigger, start mode, symptoms, and evolution. ME/CFS patients had higher levels of IL-17A (p = 0.018), FABP-2 (p = 0.002), and 3-hydroxykynurenine (p = 0.037) and lower levels of kynurenine (p = 0.012) and serotonin (p = 0.045) than controls. Changes in kynurenine and 3-hydroxykynurenine were associated with increased kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine ratios, indirect measures of kynurenine aminotransferases and kynurenine 3-monooxygenase enzymatic activities, respectively. No correlation was found among cytokines, FABP-2, and tryptophan metabolites, suggesting that inflammation, anomalies of the intestinal barrier, and changes of tryptophan metabolism may be independently associated with the pathogenesis of the disease. Interestingly, patients with the start of the disease after infection showed lower levels of kynurenine (p = 0.034) than those not starting after an infection. Changes in tryptophan metabolites and increased IL-17A levels in ME/CFS could both be compatible with anomalies in the sphere of energy metabolism. Overall, clinical traits together with serum biomarkers related to inflammation, intestine function, and tryptophan metabolism deserve to be further considered for the development of personalized medicine strategies for ME/CFS.


Characterization of INCB086550: A Potent and Novel Small-Molecule PD-L1 Inhibitor.
Blocking the activity of the programmed cell death protein 1 (PD-1) inhibitory receptor with therapeutic antibodies against either the ligand (PD-L1) or PD-1 itself has proven to be an effective treatment modality for multiple cancers. Contrasting with antibodies, small molecules could demonstrate increased tissue penetration, distinct pharmacology, and potentially enhanced antitumor activity. Here, we describe the identification and characterization of INCB086550, a novel, oral, small-molecule PD-L1 inhibitor. In vitro, INCB086550 selectively and potently blocked the PD-L1/PD-1 interaction, induced PD-L1 dimerization and internalization, and induced stimulation-dependent cytokine production in primary human immune cells. In vivo, INCB086550 reduced tumor growth in CD34+ humanized mice and induced T-cell activation gene signatures, consistent with PD-L1/PD-1 pathway blockade. Preliminary data from an ongoing phase I study confirmed PD-L1/PD-1 blockade in peripheral blood cells, with increased immune activation and tumor growth control. These data support continued clinical evaluation of INCB086550 as an alternative to antibody-based therapies. We have identified a potent small-molecule inhibitor of PD-L1, INCB086550, which has biological properties similar to PD-L1/PD-1 monoclonal antibodies and may represent an alternative to antibody therapy. Preliminary clinical data in patients demonstrated increased immune activation and tumor growth control, which support continued clinical evaluation of this approach. See related commentary by Capparelli and Aplin, p. 1413. This article is highlighted in the In This Issue feature, p. 1397.


[Features of lipogenesis of basidiomycetes Pleurotus ostreatus and Flammulina velutipes in cultures on various media].
The compositions of free fatty acids (FA) in the mycelia of oyster cap (Pleurotus ostreatus (Jacq. ex Fr.) Kumm.) and honey mushroom (Flammulina velutipes (Curt. ex Fr.) Sing.) and the effect of mycelium cultivation conditions on the composition and proportions of individual FA were investigated. Palmitic and linoleic acids were found to be major acids produced by P. ostreatus growing on solid agar medium and in a submerged culture with a synthetic medium. The composition of minor FA in P. ostreatus was dependent on cultivation conditions. Surface cultivation of its mycelium yielded pentadecanoic, octadecenoic, and stearic acids. Submerged cultivation additionally yielded undecanoic, myristic, hexadecenoic, and lignoceric acids. The composition of free FA in F. velutipes showed no significant differences from that of P. ostreatus. Variation in the C/N ratio in the cultivation medium affected both the FA composition in P. ostreatus and F. velutipes and the relationship between saturated and unsaturated FA.