Tailoring the refractive index of Ge-S based glass for 3D embedded waveguides operating in the mid-IR region.
The photosensitivity of GeS(x) binary glasses in response to irradiation to femtosecond pulses at 800 nm is investigated. Samples with three different molecular compositions were irradiated under different exposure conditions. The material response to laser exposure was characterized by both refractometry and micro-Raman spectroscopy. It is shown that the relative content of sulfur in the glass matrix influences the photo-induced refractive index modification. At low sulfur content, both positive and negative index changes can be obtained while at high sulfur content, only a positive index change can be reached. These changes were correlated with variations in the Raman response of exposed glass which were interpreted in terms of structural modifications of the glass network. Under optimized exposure conditions, waveguides with positive index changes of up to 7.8 x 10(-3)and a controllable diameter from 14 to 25 μm can be obtained. Direct inscription of low insertion losses (IL = 3.1 - 3.9 dB) waveguides is demonstrated in a sample characterized by a S/Ge ratio of 4. The current results open a pathway towards the use of Ge-S binary glasses for the fabrication of integrated mid-infrared photonic components.


[Historical outline on malaria and the struggle against it in Venezuela].
The paper presents a synthesis of the history of malaria: the ancient origins of disease, the parasites which produce it, and its vectors. Emphasis is given to its existence in Venezuela, the struggle against its endemic character during the decades of the XXth century and its almost total eradication from malarial areas during the fifties. Reference is also made to current research of an anti-malarial vaccine and its application in a rural area of this country.


A Tunable Optofluidic Microlaser in a Photostable Conjugated Polymer.
The optofluidic laser has become an important platform for biological sensing and medical diagnosis. To date, fluorescent dyes and proteins have been widely utilized as gain materials for biological analysis due to their good biocompatibility, but the limited photostability restricts their reliability and sensitivity. Here, an optofluidic microlaser with an ultralow threshold down to 7.8 µJ cm-2 in the ultrahigh-Q whispering-gallery microcavity, which is filled with a biocompatible conjugated polymer, is demonstrated. This conjugated polymer exhibits a significant enhancement in the lasing stability compared with a typical laser dye (Nile red). In the experiment, after 20 min of illumination with the excitation intensity of 23.2 MW cm-2 , the lasing intensity of the conjugated polymer experiences a decrease of less than 10%, while the lasing feature of Nile red completely disappears. Additionally, by mechanically stretching the resonator, the lasing frequency can be fine-tuned with the range of about 2 nm, exceeding the free spectral range of the resonator.


Retrograde transport of the lectin Phaseolus vulgaris leucoagglutinin in frog central nervous system.
The transport properties of the lectin Phaseolus vulgaris leucoagglutinin (PHA-L) were tested in the frog central nervous system. After delivery of the lectin to the lower brainstem by iontophoresis, stained axons and axon terminals, as well as neurons with richly arborizing dendrites, were observed indifferent regions of the brain and spinal cord even far away from the site of application. The large number and the Golgi-like appearance of labeled neurons situated rostral and caudal to the site of PHA-L deposit indicate that PHA-L is transported equally in both the anterograde and the retrograde direction in the central nervous system of the frog. This is in contrast with the mammalian nervous system, in which PHA-L is transported predominantly in the anterograde direction and the retrograde transport is poor.


[Ischemic hepatitis in an 81 year old patient with congenitally corrected transposition of the great arteries].
The congenitally corrected transposition of the great arteries is a rare form of congenital heart disease, with survival beyond the 6th decade of life being rare. Even more unusual is its presentation alone, without any other form of congenital heart disease. Ischemic hepatitis is a rare entity characterized by an elevation of transaminasas and a centrilobular necrosis due to a reduction in hepatic blood flow, generally of reversible evolution. The authors present a case of ischemic hepatitis in an 81-year-old patient with congenitally corrected transposition of the great arteries. The fatal evolution of the episode and the longevity of the patient are both notable. We comment on the clinical and diagnostic aspects of both entities.


An exploratory study into the health beliefs and behaviours of British Indians with type II diabetes.
Aim To explore the influence of health beliefs and behaviours on diabetes management in British Indians, as successful management of diabetes is dependent on underlying cultural beliefs and behaviours. British South Asians are six times more likely to suffer from type II diabetes than those in the general population. Yet, little research has been carried out into beliefs about diabetes among the British Indian population. The study used semi-structured interviews, a structured vignette and a pile-sorting exercise. In all, 10 British Indians were interviewed at a General Practice in North West London. Findings Those interviewed were informed about their diabetes but had difficulties in adapting their diet. Themes identified included causal beliefs of diabetes, use of alternative therapies, moderation of food, adaption of exercise regimes and sources of information. All were aware of avoiding certain foods yet some still continued to consume these items. Participants expressed the need for culturally sensitive forums to help manage their diabetes.


Validation of the Wexner scale in a Hebrew-speaking population.
The Cleveland Clinic Incontinence Score, known as the Wexner Score (WS), is a simple, disease-specific questionnaire for anal incontinence (AI) assessment. We aimed to translate and validate a Hebrew version of the WS. Between November 2018 and December 2019, the WS was back translated and reviewed by a multidisciplinary pelvic floor team. The questionnaire was filled out by patients visiting the urogynecology and surgical pelvic floor clinics. Two weeks after completion, the patients were contacted using telephone surveys to assess the test-retest reliability examination. Construct validity was assessed by comparing the WS to the Colorectal-Anal Distress Inventory 8 (CRADI-8), a part of the validated Hebrew version of the Pelvic Floor Distress Inventory questionnaire (PFDI-20). Overall, 91 female patients completed the WS questionnaire. Eighty-five percent (n = 78) responded to the re-test WS questionnaire. A high intraclass coefficient of 0.87 was found in the WS total score, with a range from 0.82 to 0.86 for its subscales. A significant positive relationship between the Hebrew versions of the WS and CRADI-8 scores was established (r = 0.66, p < 0.0001). A new, Hebrew-translated version of the WS is a reliable and valid instrument for assessing AI.


Nuclear magnetic resonance-based tissue metabolomic analysis clarifies molecular mechanisms of gastric carcinogenesis.
Gastric cancer (GC) is one of the deadliest cancers worldwide, and the progression of gastric carcinogenesis (GCG) covers multiple complicated pathological stages. Molecular mechanisms of GCG are still unclear. Here, we undertook NMR-based metabolomic analysis of aqueous metabolites extracted from gastric tissues in an established rat model of GCG. We showed that the metabolic profiles were clearly distinguished among 5 histologically classified groups: control, gastritis, low-grade gastric dysplasia, high-grade gastric dysplasia (HGD), and GC. Furthermore, we carried out metabolic pathway analysis based on identified significant metabolites and revealed significantly disturbed metabolic pathways closely associated with the 4 pathological stages, including oxidation stress, choline phosphorylation, amino acid metabolism, Krebs cycle, and glycolysis. Three metabolic pathways were continually disturbed during the progression of GCG, including taurine and hypotaurine metabolism, glutamine and glutamate metabolism, alanine, aspartate, and glutamate metabolism. Both the Krebs cycle and glycine, serine, and threonine metabolism were profoundly impaired in both the HGD and GC stages, potentially due to abnormal energy supply for tumor cell proliferation and growth. Furthermore, valine, leucine, and isoleucine biosynthesis and glycolysis were significantly disturbed in the GC stage for higher energy requirement of the rapid growth of tumor cells. Additionally, we identified potential gastric tissue biomarkers for metabolically discriminating the 4 pathological stages, which also showed good discriminant capabilities for their serum counterparts. This work sheds light on the molecular mechanisms of GCG and is of benefit to the exploration of potential biomarkers for clinically diagnosing and monitoring the progression of GCG.


Human Locomotion Databases. A Systematic Review.
The analysis of human locomotion is highly dependent on the quantity and quality of available data to obtain reliable evidence, due to the great variability of gait characteristics between subjects. Researchers usually have to make significant efforts to generate well-structured and trustworthy datasets. This situation is aggravated when patients are involved, due to experimental, privacy, and safety constraints. The availability of public datasets can facilitate this process. In this work, we systematically review the scientific and technical literature to identify the human locomotion databases publicly available nowadays. Within the 93 datasets identified, we observed that the most basic motor skills, e.g., flat or sloped walking, are well covered, whereas many other daily-life motor skills are poorly represented. The most common sensors used to record gait are optical motion capture systems, followed by RGB cameras and inertial sensors. We observed a lack of consistency in the data formats and limited sample size in most reviewed datasets. These issues hinder researchers from systematically standing on previous research results and represent a major barrier to using Artificial Intelligence and Big Data algorithms. With this work, we aim to provide the scientific community with a comprehensive, critical, and efficient guide to human locomotion datasets across different application domains.


Aortic valve replacement.
From hospital to home care, patients receiving prosthetic valves benefit from nurses who understand their condition and know the essentials for avoiding complications of the procedure--and the anticoagulant therapy they may be on for a lifetime.


Genome Engineering and Agriculture: Opportunities and Challenges.
In recent years, plant biotechnology has witnessed unprecedented technological change. Advances in high-throughput sequencing technologies have provided insight into the location and structure of functional elements within plant DNA. At the same time, improvements in genome engineering tools have enabled unprecedented control over genetic material. These technologies, combined with a growing understanding of plant systems biology, will irrevocably alter the way we create new crop varieties. As the first wave of genome-edited products emerge, we are just getting a glimpse of the immense opportunities the technology provides. We are also seeing its challenges and limitations. It is clear that genome editing will play an increased role in crop improvement and will help us to achieve food security in the coming decades; however, certain challenges and limitations must be overcome to realize the technology's full potential.


Investigation of iron status and markers of inflammation in anaemic and non-anaemic hospitalised cats.
To measure iron parameters and markers of inflammation in anaemic cats presented for intensive care unit hospitalisation, and to compare these to cohorts of non-anaemic hospitalised cats and cats that develop hospital-acquired anaemia. Blood samples were collected for measurement of iron panel and serum amyloid A in addition to routine investigation in cats admitted to the intensive care unit. Medical records were reviewed to determine how many of the Systemic Inflammatory Response Syndrome criteria were met and to assign Acute Patient Physiologic and Laboratory Evaluation scores as a measure of illness severity. Seventy-eight cats were enrolled. Anaemia was documented in 34·6% of cats on presentation and another 10·3% developed anaemia during hospitalisation. Compared with non-anaemic cats, animals that were anaemic on presentation had higher neutrophil and white blood cell counts, and longer hospitalisation. Iron status was consistent with anaemia of inflammation in most anaemic patients. Iron status, serum amyloid A concentration, and prevalence of systemic inflammatory response syndrome did not differ between anaemic and non-anaemic cohorts. All cause mortality was higher in anaemic cats. Anaemia is common in cats hospitalised in the intensive care unit. Systemic inflammation is also common in these cats. Iron status in anaemic cats suggests that anaemia of inflammatory disease may be a significant contributor to anaemia in this patient population.


Dopamine transporter mutant animals: a translational perspective.
The dopamine transporter (DAT) plays an important homeostatic role in the control of both the extracellular and intraneuronal concentrations of dopamine, thereby providing effective control over activity of dopaminergic transmission. Since brain dopamine is known to be involved in numerous neuropsychiatric disorders, investigations using mice with genetically altered DAT function and thus intensity of dopamine-mediated signaling have provided numerous insights into the pathology of these disorders and novel pathological mechanisms that could be targeted to provide new therapeutic approaches for these disorders. In this brief overview, we discuss recent investigations involving animals with genetically altered DAT function, particularly focusing on translational studies providing new insights into pathology and pharmacology of dopamine-related disorders. Perspective applications of these and newly developed models of DAT dysfunction are also discussed.


The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes.
The unique properties of embryonic stem cells (ESCs), including unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of transcriptional factors and epigenetic modulators. However, the molecular mechanisms underlying the function of these regulators are not fully elucidated. Chromodomain helicase DNA-binding protein 4 (Chd4), an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in ESC regulation remains elusive. Here we report that Chd4 is required for the maintenance of ESC self-renewal. RNAi-mediated silencing of Chd4 disrupted self-renewal and up-regulated lineage commitment-associated genes under self-renewal culture conditions. During ESC differentiation in embryoid body formation, we observed significantly stronger induction of differentiation-associated genes in Chd4-deficient cells. The phenotype was different from that caused by the deletion of Mbd3, another subunit of the NuRD complex. Transcriptomic analyses revealed that Chd4 secured ESC identity by controlling the expression of subsets of pluripotency- and differentiation-associated genes. Importantly, Chd4 repressed the transcription of T box protein 3 (Tbx3), a transcription factor with important functions in ESC fate determination. Tbx3 knockdown partially rescued aberrant activation of differentiation-associated genes, especially of endoderm-associated genes, induced by Chd4 depletion. Moreover, we identified an interaction of Chd4 with the histone variant H2A.Z. This variant stabilized Chd4 by inhibiting Chd4 protein degradation through the ubiquitin-proteasome pathway. Collectively, this study identifies the Chd4-Tbx3 axis in controlling ESC fate and a role of H2A.Z in maintaining the stability of Chd4 proteins.


Evolution of concept, but not action, in addiction treatment.
The Western approach to addiction treatment involves a medical or disease orientation to understanding the onset, course, and management of addiction, and a clinical goal of abstinence or very significant reductions in drug use, usually with a combination of behavioral and pharmacological interventions. Even within this Western approach, and despite several consensually accepted features of addiction, a significant mismatch remains between what this culture has come to accept as the nature of the disease and how that same culture continues to treat the disease. This paper discusses the evolution of these Western concepts over the past decade without a corresponding evolution in the nature, duration, or evaluation standards for addiction treatment. (1) Here, we take the position that continuing care and adaptive treatment protocols, combining behavioral therapies, family and social supports, and, where needed, medications show much promise to address the typically chronic, relapsing, and heterogeneous nature of most cases of serious addiction. By extension, methods to evaluate effectiveness of addiction treatment should focus upon the functional status of patients during the course of their treatment instead of post-treatment, as is the evaluation practice used with most other chronic illnesses.


Catastrophic anoxia in the chesapeake bay in 1984.
In 1984, four climatic sequences combined to produce what may be a major anoxic catastrophe in the northern Chesapeake Bay, sufficient to severely threaten the major benthic species. These sequences are (i) the highest late-winter streamflow on record from the Susquehanna River watershed; (ii) streamflows from the Susquehanna River for the consecutive months of June, July, and August that are higher by 2 standard deviations than the respective monthly mean values measured over the last 34 years; (iii) a stationary high in August off the Atlantic Coast; and (iv) an absence of strong storm events in summer. An empirical equation is proposed for the prediction of the monthly trend of dissolved oxygen decrease in terms of a temperature-dependent subpycnoclinal respiration and a modified estuarine Richardson number. As of 23 August 1984, the summer pycnocline of the northern bay had eroded upward from its historically recorded depth below 10 meters to an abnormally shallow 5 meters, with higher stratification than in earlier years. Dissolved oxygen concentrations directly below the pycnocline decreased to zero during June, 2 months earlier than for previous wet years. At present, oxygen-deficient waters containing significant concentrations of hydrogen sulfide have penetrated into Eastern Bay and the Choptank and Potomac rivers. Because most remaining shellfish-spawning and seed-bed areas in these tributaries are located at depths between 4 and 8 meters, the continued absence of major destratifying events will prolong the present anoxic trend and may result in high benthic mortalities.


Postprandial Metabolism and Appetite Do Not Differ between Lean Adults that Eat Breakfast or Morning Fast for 6 Weeks.
It remains unknown whether sustained daily feeding-fasting patterns modify the acute response to specific feedings on a given day. We conducted a randomized controlled trial to establish if daily breakfast consumption or fasting until noon modifies the acute metabolic and appetitive responses to a fixed breakfast and ad libitum lunch. With the use of a parallel group design, we randomly assigned 31 healthy, lean men and women (22-56 y) to 6 wk of either consuming ≥700 kcal of self-selected items before 1100 or fasting (0 kcal) until 1200 daily. Following 48 h of diet and physical activity standardization, we examined metabolic and appetite responses to a standardized breakfast and ad libitum lunch before and after the intervention. Data were analyzed using 3- and 2-way ANCOVA. Systemic concentrations of energy balance regulatory hormones total and acylated ghrelin, leptin, and peptide tyrosine-tyrosine) responded similarly to breakfast and lunch before and after 6 wk of either morning fasting or regular breakfast, with the exception of a tendency for increased glucagon-like peptide-1 concentrations from baseline to follow-up in the Breakfast Group compared with a decrease over that period in the Fasting Group [P = 0.06, partial eta squared value (ƞ2) = 0.16]. Subjective appetite sensations also did not differ over the course of the day, and ad libitum energy intake at lunch was not systematically affected by either intervention, decreasing by 27 kcal (95% CI: -203, 149 kcal) with fasting and by 77 kcal (95% CI: -210, 56 kcal) with breakfast. Similarly, glycemic, insulinemic, lipemic, and thermogenic responses to breakfast and lunch were very stable at baseline and follow-up and, thus, did not differ between treatment groups. Our results indicate that a sustained period of either extended morning fasting or eating a daily breakfast has minimal effect upon acute metabolic and appetite responses in lean adults. This trial was registered at www.isrctn.org as ISRCTN31521726.


External electrostatic interaction versus internal encapsulation between cationic dendrimers and negatively charged drugs: which contributes more to solubility enhancement of the drugs?
Relationships of electrostatic interaction and encapsulation between poly(amidoamine) (PAMAM) dendrimers and negatively charged drug molecules have been investigated by aqueous solubility and NMR ( (1)H NMR and two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY)) studies. PAMAM dendrimers significantly increased the solubilities of phenobarbital and sulfamethoxazole, but scarcely influenced those of primidone and trimethoprim. Moreover, (1)H NMR and 2D-NOESY measurements indicated that few phenobarbital or sulfamethoxazole molecules were entrapped in the cavities of low-generation dendrimers (generation 3, G3). These results suggest that external electrostatic interaction contributes more to the solubility enhancement of drugs than internal encapsulation.


Construction and characterization of a monomeric insulin receptor.
A mutant insulin receptor was constructed by replacing cysteine residues Cys(524), Cys(682), Cys(683), and Cys(685) with serine. The mutant was expressed in COS7 and Chinese hamster ovary cells, did not form covalently linked dimers, and was present at the cell surface. There was half as much insulin binding activity at the cell surface in cells expressing the mutant compared with that in cells expressing the wild type receptor. The intracellular processing of the mutant receptor was affected, since its beta-subunit migrated more slowly than that of the wild type receptor on SDS-PAGE. The mutant was capable of insulin-dependent autophosphorylation and phosphorylation of insulin receptor substrate-1 in vivo and could be cross-linked into receptor dimers when membrane-bound. The amount of insulin-dependent autophosphorylation of the mutant receptor was half that of the wild type receptor. However, after solubilization the monomeric insulin receptor had minimal autophosphorylation activity, and, unlike the naturally occurring monomeric receptor tyrosine kinases, the solubilized monomeric insulin receptor did not dimerize in response to insulin binding as determined by sucrose density gradient centrifugation.


Controlling the anaphylatoxin C5a in diseases requires a specifically targeted inhibition.
The terminal complement split product C5a has been described as an important mediator in inflammatory diseases. C5a is generated upon cleavage of C5 and earlier research suggests that, besides the known C5 convertases formed upon activation of the complement pathways, various enzymes could activate C5 directly. We demonstrate that eculizumab effectively blocks C5 activation when mediated by C5-convertase formation, but fails to block C5a generation resulting from direct enzymatic cleavage by trypsin and thrombin. C5a generated by these enzymes is shown to be fully biologically functional and can be blocked by IFX-1, a specific monoclonal anti-human C5a antibody. We further report clinical cases of atypical hemolytic uremic syndrome (aHUS) and C3 Glomerulonephritis (C3GN) patients under treatment with eculizumab presenting substantially elevated C5a levels. Thus, blocking the C5 convertase mediated activation of C5 may not be efficient to control C5a-mediated effects in human disease and that a targeted approach is warranted.


Assessment of Fusarium pseudograminearum and F. culmorum Biomass in Seedlings of Potential Host Cereal Species.
Fusarium crown rot is a major disease of wheat and barley worldwide, with the most frequently isolated causal agents being Fusarium pseudograminearum and F. culmorum. This study has successfully designed a quantitative polymerase chain reaction assay that is specific for F. culmorum, which has been used in conjunction with a previously established F. pseudograminearum-specific assay to compare the location and extent of infection by each fungus across a range of potential hosts, including six winter and three summer cereal species. All common winter cereals, excluding oat, demonstrated a similar range of visual and fungal biomass results when inoculated with either F. pseudograminearum or F. culmorum. Oat exhibited the lowest visual disease ratings and fungal biomass values of the winter cereals, while the sorghum, maize, and rice cultivars returned the lowest values overall. The ranking of host species according to visual discoloration was strongly correlated for both pathogens. Visual reactions to F. pseudograminearum were greater than those caused by F. culmorum in all potential hosts trialed; however, fungal biomass results only indicated this trend for barley. These results demonstrate significant variation in the ability of these pathogens to colonize the range of cereal species examined and also suggest differences between the pathogens in their patterns of host colonization.


Targeted Sos1 deletion reveals its critical role in early T-cell development.
Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development. Sos1 was required for pre-T-cell receptor (pre-TCR)- but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR-stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development.


Transitions between inherent structures in water.
The energy landscape approach has been useful to help understand the dynamic properties of supercooled liquids and the connection between these properties and thermodynamics. The analysis in numerical models of the inherent structure (IS) trajectories-the set of local minima visited by the liquid-offers the possibility of filtering out the vibrational component of the motion of the system on the potential energy surface and thereby resolving the slow structural component more efficiently. Here we report an analysis of an IS trajectory for a widely studied water model, focusing on the changes in hydrogen bond connectivity that give rise to many IS's separated by relatively small energy barriers. We find that while the system travels through these IS's, the structure of the bond network is continuously modified, exchanging linear bonds for bifurcated bonds and usually reversing the exchange to return to nearly the same initial configuration. For the 216-molecule system we investigate, the time scale of these transitions is as small as the simulation time scale ( approximately 1 fs). Hence, for water, the transition between each of these IS's is relatively small and eventual relaxation of the system occurs only by many of these transitions. We find that during IS changes the molecules with the greatest displacements move in small "clusters" of 1-10 molecules with displacements of approximately 0.02-0.2 nm, not unlike simpler liquids. However, for water these clusters appear to be somewhat more branched than the linear "stringlike" clusters formed in a supercooled Lennard-Jones system found by Glotzer and her collaborators.


Space-time variability of citrus leprosis as strategic planning for crop management.
Citrus leprosis is the most important viral disease of citrus. Knowledge of its spatiotemporal structure is fundamental to a representative sampling plan focused on the disease control approach. Such a well-crafted sampling design helps to reduce pesticide use in agriculture to control pests and diseases. Despite the use of acaricides to control citrus leprosis vector (Brevipalpus spp.) populations, the disease has spread rapidly through experimental areas. Citrus leprosis has an aggregate spatial distribution, with high dependence among symptomatic plants. Temporal variation in disease incidence increased among symptomatic plants by 4% per month. Use of acaricides alone to control the vector of leprosis is insufficient to avoid its incidence in healthy plants. Preliminary investigation into the time and space variation in the incidence of the disease is fundamental to select a sampling plan and determine effective strategies for disease management. © 2018 Society of Chemical Industry.


Assessing afebrile malaria and bed-net use in a high-burden region of India: Findings from multiple rounds of mass screening.
A key obstacle in the fight against malaria is afebrile malaria. It remains undiagnosed and, therefore, is invisible to the health system. Apart from being a serious illness, it contributes to increased transmission. Existing studies in India have not adequately reported afebrile malaria and its determinants, including the use of long-lasting insecticide-treated nets (LLINs). This study used six waves of mass screening, which were conducted by the state government in the high-malaria-burden region of Chhattisgarh, a state in India, in 2020, 2021, and 2022. Each round of data collection included more than 15000 individuals. Descriptive statistics were used to analyse key indicators of malaria prevalence and LLIN use. Multivariate analyses were performed to identify the determinants of afebrile malaria and LLIN use. Malaria prevalence in the afebrile population varied from 0.6% to 1.4% across the different waves of mass screening. In comparison, malaria positivity among febrile individuals was greater than 33% in each wave. Afebrile malaria contributed to 19.6% to 47.2% of the overall malaria burden in the region. Indigenous communities (scheduled tribes) were more susceptible to malaria, including afebrile malaria. Individuals using LLINs were less likely to be affected by afebrile malaria. Overall, 77% of the individuals used LLINs in early monsoon season, and in winter the rate was lower at 55%. LLIN use was significantly associated with the number of LLINs the households received from the government. Although fever continues to be a primary symptom of malaria, afebrile malaria remains a significant contributor to the malaria burden in the region. The free distribution of LLINs should be expanded to include high-burden populations. Global policies must include strategies for surveillance and control of afebrile malaria in high-burden areas.


Improved focus assay of reticuloendotheliosis virus in a quail fibroblast cell line (QT35).
Reticuloendotheliosis virus (REV) strains T and CS consistently induced focus formation in a quail fibroblast cell line designated QT35 that was maintained under agarose overlay following inoculation of REV. The foci were more distinct and better circumscribed than those that developed in QT35 cultures under fluid medium. The focus formation in QT35 cultures under agarose overlay was inhibited by REV antiserum, and there were a highly significant correlation (r = 0.966, P less than 0.005) and a linear relationship between the number of foci that developed and relative virus concentration inoculated. This provides a valid focus assay for REVs.


Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment.
Nowadays, the Nuclear Magnetic Resonance (NMR) techniques are tested for metabolomic urine profile in order to detect early damage of kidney. The purpose of this investigation was the initial assessment of two-dimensional J-resolved NMR urine spectra analysis usability for early kidney injuries detection. The amino acids (AA) and acids profile change after the exposure to nephrotoxic agent (the cisplatin infusion) was examined. The material was the urine of patients with non-small-cell lung cancer, treated with cisplatin in Pulmonology and Lung Cancers Clinic in Wrocław. The urine of healthy volunteers was also examined. The identification of metabolites in urine was based on two-dimensional JRES signals in spectra, described in Human Metabolites Database (HMD). The molar concentration of metabolites was calculated from the volume under the signals. The analysis was focused on amino acids and organic acids (lactid acid and pyruvic acid) profiles. Any specific amino acids were identified after cisplatin infusion in comparison to the state before infusion. However, the differences in concentration were observed over 2-fold increase in valine, isoleucine and leucine, over 3-fold in alanine. Also, the concentration of pyruvic and lactic acids increased significantly (p≤0.05, p≤0.01). There were no specific amino acids identified in response to the infusion of cisplatin; however, some changes in the concentrations of amino acids and other small molecules were found. The analysis of two-dimensional JRES spectra showed an increase of alanine, leucine, isoleucine and valine concentration after the application of cisplatin. It seems that it is worth developing the JRES method based on special computer program.


Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size.
Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 wk of age. LLC animals were allowed to develop tumors for 4 wk to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs, which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs, and functions of miRNAs were analyzed by Ingenuity Pathway Analysis. LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared with PBS. We found 371 miRNAs to be present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3, and others. These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia.


Midwifery in New Zealand 1904-1971.
Childbirth for European women in early twentieth century New Zealand was family centred. The majority of births took place in the home, accepted as a difficult but natural part of a woman's role in life. Midwives were mostly married women who worked autonomously and had usually borne children themselves. By the 1970s this picture had dramatically changed. Virtually all births took place in hospital and were under the control of medical men and women. When legislation was passed (the Nurses Act 1971) that removed the right of New Zealand midwives to practice autonomously, New Zealand midwifery had largely been subsumed by nursing, controlled by medicine and displaced from a community based profession into a hospital based workforce. This article examines how the trends of medicalisation, hospitalisation, and nursification changed the New Zealand maternity services from 1900 to 1971, outlining the effect those changes had on the midwifery profession. The changes described here were also common to other western societies; examining how they occurred provides a context for understanding the history of midwifery in New Zealand.


A Three-Dimensional-Printed Recyclable, Flexible, and Wearable Device for Visualized UV, Temperature, and Sweat pH Sensing.
Wearable devices are now recognized as a powerful tool to collect physiological and environmental information in a smart, noninvasive, and real-time manner. Despite the rapid progress of wearable devices especially wearable electronic devices, there are still several challenges that limit their further development, for example, a complicated electrical signal acquisition and processing process to eliminate the interference from the surrounding signals, bulky power supply, inevitable e-waste, and environmental pollution. Herein, we report a 3D-printed recyclable, flexible, and wearable device for visualized UV, temperature, and sweat pH sensing. Compared with wearable electronic devices, our visualized wearable device senses environmental (UV light, ambient temperature), biophysical (skin temperature), and biochemical (sweat pH) signals via stimuli-responsive color change, which does not require complicated electronic circuit design/assembly, time-consuming data processing and additional power source. In addition, this visualized wearable device is fabricated via a 3D support bath printing technology by printing UV-, temperature-, and sweat pH-sensing inks containing photochromic, thermochromic, and pH-chromic materials, respectively, into/onto sustainable starch solution, resulting in a multi-functional, recyclable, and flexible sensing device with high reproducibility. Our results reveal that UV light intensities under sunlight (0-2500 μW/cm2), ambient, and skin temperatures (0-38 °C) as well as sweat pH (4.0-7.0) can be successfully monitored.


Implication of RAS in Postnatal Cardiac Remodeling, Fibrosis and Dysfunction Induced by Fetal Undernutrition.
Fetal undernutrition is a risk factor for cardiovascular diseases. Male offspring from rats exposed to undernutrition during gestation (MUN) exhibit oxidative stress during perinatal life and develop cardiac dysfunction in ageing. Angiotensin-II is implicated in oxidative stress-mediated cardiovascular fibrosis and remodeling, and lactation is a key developmental window. We aimed to assess if alterations in RAS during lactation participate in cardiac dysfunction associated with fetal undernutrition. Control dams received food ad libitum, and MUN had 50% nutrient restriction during the second half of gestation. Both dams were fed ad libitum during lactation, and male offspring were studied at weaning. We assessed: ventricular structure and function (echocardiography); blood pressure (intra-arterially, anesthetized rats); collagen content and intramyocardial artery structure (Sirius red, Masson Trichromic); myocardial and intramyocardial artery RAS receptors (immunohistochemistry); plasma angiotensin-II (ELISA) and TGF-β1 protein expression (Western Blot). Compared to Control, MUN offspring exhibited significantly higher plasma Angiotensin-II and a larger left ventricular mass, as well as larger intramyocardial artery media/lumen, interstitial collagen and perivascular collagen. In MUN hearts, TGF-β1 tended to be higher, and the end-diastolic diameter and E/A ratio were significantly lower with no differences in ejection fraction or blood pressure. In the myocardium, no differences between groups were detected in AT1, AT2 or Mas receptors, with MrgD being significantly lower in the MUN group. In intramyocardial arteries from MUN rats, AT1 and Mas receptors were significantly elevated, while AT2 and MrgD were lower compared to Control. Conclusions. In rats exposed to fetal undernutrition, RAS disbalance and associated cardiac remodeling during lactation may set the basis for later heart dysfunction.


Performance of mammalian cell culture bioreactor with a new impeller design.
To improve the oxygen transfer in a mammalian cell bioreactor, a new type of impeller consisting of a double-screen concentric cylindrical cage impeller (annular cage impeller in short) was designed and its mass transfer rate evaluated. This new impeller design increases the specific screen area, and the convective mass transfer rate through the annular cage was significantly increased. The oxygen transfer rates with the new impeller and the commercially available cell-lift impeller (CelliGen by New Brunswick Scientific Co.) were evaluated and their performance compared at various rates of aeration and agitation. The results showed that with the new impeller, the oxygen transfer rate was increased by 19% in water and 21% in cell-free culture medium supplemented with 10% horse serum, the total hybridoma cell concentration was increased to 3.4 x 10(7) cells/mL, and the IgG(1) subtype monoclonal antibody (MAb) product concentration was also increased to 512 mg/L in perfusion culture of murine hybridoma cell line 62'D3. These improvements in oxygen transfer rate, cell concentration, and MAb product concentration are all very significant. The mass transfer resistance in the cell-lift impeller system was found to be mainly due to the surface area of the single-screen cage impeller. The new annular cage impeller not only provided the increased surface area for convective oxygen transfer but also protected cells from hydrodynamic shear damage, thereby achieving a significant bioprocess improvement in terms of higher viable cell concentration, higher product concentration, and higher oxygen transfer rate in the mammalian cell bioreactor system.


Association between serum lipid levels and periodontal infection.
The aim of the study was to investigate the association between serum lipids and periodontal infection and the role of serum lipids in the association between body weight and periodontal infection. The Health 2000 Health Examination Survey, which included 8028 subjects aged 30 or older living in continental Finland. This study was based on a subpopulation of dentate, non-diabetic subjects who had never smoked and were aged under 50 years (n=1297). Periodontal infection was defined as the presence of teeth with deepened periodontal pockets. Serum levels of triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol were analysed enzymatically. We found no consistent association between serum lipid levels and periodontal infection among normoweight subjects. There was an association of high serum triglycerides and low HDL with periodontal infection among obese subjects. The association between body mass index and periodontal infection was not essentially affected by serum lipids. In this study population serum lipid levels were not associated with periodontal infection among normoweight subjects. Obese subjects with a high serum triglyceride level and/or a low HDL-cholesterol level could be at higher risk of periodontal infection. Our results suggest that the association between body weight and periodontal infection was mainly mediated through a mechanism other than serum lipids.


The complex of flavivirus envelope polypeptide with meningococcal proteosomes elicits formation of virus-neutralizing antibodies.
Polypeptide E of tick-borne encephalitis virus was isolated in sucrose density gradient and mixed with equal weight portion of meningococcal proteosomes in the presence of N-dodecyl-N,N-dimethylglycine. Mutual complexing of viral and bacterial molecules occurred after removal of detergent by dialysis. Complexed particles appeared in the electron microscope as 40-50 microns thick short-rod structures covered on their surface with both, delicate poppy-like grains, or envelope subunit-like clustered molecules. Even when applied without adjuvant, the complex of tick-borne encephalitis virus polypeptide E with meningococcal proteosomes elicited in mice a marked antiviral as well as antibacterial humoral response.


Intraocular fluid-air exchange reduces retinal ganglion cell activity.
To demonstrate the influence of intraocular fluid-air exchange on retinal ganglion cell activity. In two cats lensectomy and vitrectomy were performed in a two-step approach 2 weeks prior to recording experiments. To measure retinal activity, up to two fiber microelectrodes were inserted via a scleral port. Precise micromanipulator positioning of the electrodes' tips onto the inner retinal surface were verified by ophthalmoscopy and simultaneous electrical recording. Neuronal activity of the retina was continuously recorded with or without visual stimulation. We maintained the intraocular pressure constant at 29 mm Hg. Fluid-air exchange and fluid refill were performed with an infusion tube integrated in the manipulator and slowly to avoid direct mechanical/stream-based damage of the retina. We found that fluid-air exchange leads to a rapid reduction of spontaneous as well as visually evoked retinal ganglion cell activity. The activity started to diminish within few minutes, and then it halved approximately every 3 min. Even 1 h after eye fluid refill, the retinal activity recovered only partially. Decrease in retinal activity after fluid-air exchange can be explained by mechanical stress-induced drying of the inner retinal surface and by potential changes of extracellular ion concentration. Since even moderate airstream-based fluid-air exchanges can lead to retinal damage, the surgeon should minimize the quantity of air passing open sclerotomy sites until a better understanding of the retinal effects of this essential technique in modern vitrectomy is available.


Psychosocial profile of cultists in a Nigerian university: a preliminary report.
To help stem cult activities on campuses by identifying motives for joining cult groups and highlighting psychosocial attributes/profile of a potential or already initiated cult member. Using snow-balling method, 25 consecutive consenting cult members of University of Ilorin were interviewed over a six month period using a semi-structured questionnaire. Those who had symptoms suggestive of psychiatric disorders were further assessed based on ICD-10 criteria. All patients with previous psychiatric illness were excluded. A significant proportion of the respondents were first year, male, previously shy students from high socioeconomic background. There was a significant increase in the proportion of respondents who had palpitation, sweated more, felt bolder, and became current users of alcohol and tobacco after initiation. Also, there was a significant decrease in the proportion of respondents who slept well, felt accepted by friends and performed well in academic activities after initiation. In spite of the small sample size and method of data collection, the preliminary findings in this study, could be useful in stemming the increasing menace of cultism among students in tertiary institutions. It was suggested that control of cult activities should be multidimensional with students, parents and university administration taking active parts. Establishment of 'Help Centres' on campuses was suggested.


Synthesis and fasciolicidal activity of 5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole.
The synthesis and fasciolicidal activity of 5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole (6) is described. Compound 6 showed 100% activity in vitro at 146.70 and 29.34 microM concentrations. It also completely removed 3-d and 10-week-old Fasciola hepatica in sheep at a dose of 15 mg/kg.


Evaluation of Military Recruits With Complaints of Palpitations After Physical Training: A Study From Turkey.
Objective Recruits undergo medical examination before mandatory service. After enlistment, if recruits have health problems, they are sent to a medical board to establish fitness for their duties. We aimed to analyze the complaints of palpitations after physical training in recruits without a known history of cardiovascular disease (CVD) and determine whether the diagnoses were suitable for duty. Methods This cross-sectional descriptive study was conducted among 25,666 participants who were admitted to an outpatient cardiology clinic due to complaints of palpitations between August 2016 and June 2022. Information regarding socio-demographic characteristics was collected. Laboratory test results and electrocardiography (ECG) were analyzed. The diagnoses were evaluated. Results In total, 582 patients who were dismissed from the military were included in the study. The mean age of patients was 19.23±2.02 years. Among the patients, drug use (26; 6.2%) and history of addictive substance use (178; 30.6%) were low. The number of days of service under 10 was high (450; 77.3%). The prevalence of sleep disturbance (122; 21%) and hydration habits (154; 26.5%) were low. According to ECG findings, premature atrial contractions were high (250; 42.9%). There was a significant correlation between the ECG findings and seasons (p<0.001).Rheumatic valve disease (83; 14.26%) and supraventricular tachycardia (77; 13.23%) were the most common diagnoses. Conclusion 2.2 percent of all participants admitted to the hospital due to palpitations were dismissed from the military service, and 0.7 percent of them were diagnosed with cardiac conduction system disease.


Paraoxonase 1 (PON1) is a more potent antioxidant and stimulant of macrophage cholesterol efflux, when present in HDL than in lipoprotein-deficient serum: relevance to diabetes.
The present study analyzed serum paraoxonase 1 (PON1) distribution among HDL and lipoprotein-deficient serum (LPDS) in atherosclerotic patients, and compared PON1 biological functions in these fractions. Serum HDL and LPDS fractions were isolated from control healthy subjects, diabetic and hypercholesterolemic patients. PON1 activities and protein in HDL/LPDS, as well as its ability to protect against lipid peroxidation and to stimulate HDL/LPDS-mediated macrophage cholesterol efflux were measured. In LPDS from controls, PON1 protein and a significant paraoxonase activity were found, whereas arylesterase and lactonase activities were substantially reduced compared to HDL, by 78% and 88%, respectively. In diabetic patients, PON1 protein and paraoxonase activity in HDL were significantly decreased by 2.8- and 1.7-fold, respectively, compared with controls' HDL. In parallel, in these patient's LPDS, PON1 protein and paraoxonase activity were markedly increased by 3.7- and 1.7-fold, respectively, compared with controls' LPDS. PON1 in HDL (but not PON1 in LPDS) significantly decreased AAPH-induced lipid peroxides formation by 33%, and increased macrophage cholesterol efflux by 31%. We conclude that PON1 is less antiatherogenic when present in LPDS than in HDL. The abnormal serum PON1 distribution in diabetic patients, could be responsible for the accelerated atherosclerosis development in these patients.


[COPD--chronic obstructive pulmonary disease and its implications for the human organism].
Chronic obstructive pulmonary disease (COPD) belongs next to bronchial asthma to the most important diseases of the respiratory tract in terms of its socio-economic impact. Especially exacerbations of COPD and clinical end-stages exert extremely negative effects on the global burden of disease. This article analyses current aspects of COPD regarding epidemiology, pathogenesis, pathophysiology and diagnosis of the disease. Given the estimation that COPD will be the third most common cause of death in the year 2020, the high socio-economic costs and the primary cause tobacco smoke exposure, the disease can be regarded as extremely relevant for numerous aspects of insurance medicine.


Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents.
To evaluate the effects of a multidisciplinary obesity treatment programme on fecal microbiota composition and immunoglobulin-coating bacteria in overweight and obese adolescents and their relationship to weight loss. Longitudinal intervention study based on both a calorie-restricted diet (calorie reduction=10-40%) and increased physical activity (calorie expenditure=15-23 kcal/kg body weight per week) for 10 weeks. Thirty-nine overweight and obese adolescents (BMI mean 33.1 range 23.7-50.4; age mean 14.8 range, 13.0-16.0). BMI, BMI z-scores and plasma biochemical parameters were measured before and after the intervention. Fecal microbiota was analyzed by fluorescent in situ hybridization. Immunoglobulin-coating bacteria were detected using fluorescent-labelled F(ab')2 antihuman IgA, IgG and IgM. Reductions in Clostridium histolyticum and E. rectale-C. coccoides proportions significantly correlated with weight and BMI z-score reductions in the whole adolescent population. Proportions of C. histolyticum, C. lituseburense and E. rectale-C. coccoides dropped significantly whereas those of the Bacteroides-Prevotella group increased after the intervention in those adolescents who lost more than 4 kg. Total fecal energy was almost significantly reduced in the same group of adolescents but not in the group that lost less than 2.5 kg. IgA-coating bacterial proportions also decreased significantly in participants who lost more than 6 kg after the intervention, paralleled to reductions in C. histolyticum and E. rectale-C. coccoides populations. E. rectale-C. coccoides proportions also correlated with weight loss and BMI z-score reduction in participants whose weight loss exceeded 4 kg. Specific gut bacteria and an associated IgA response were related to body weight changes in adolescents under lifestyle intervention. These results suggest interactions between diet, gut microbiota and host metabolism and immunity in obesity.


General Synthesis of Carbon Dot-Based Composites with Triple-Mode Luminescence Properties and High Stability.
Carbon dot (CD)-based luminescent materials have attracted great attention in optical anti-counterfeiting due to their excellent photophysical properties in response to ultraviolet-to-visible excitation. Hence, there is an urgent need for the general synthesis of CD-based materials with multimode luminescence properties and high stability; however, their synthesis remains a formidable challenge. Herein, CDs were incorporated into a Yb,Tm-doped YF3 matrix to prepare CDs@YF3:Yb,Tm composites. The YF3 plays a dual role, not only serving as a host for fixing rare earth luminescent centers but also functioning as a rigid matrix to stabilize the triplet state of the CDs. Under the excitation of 365 nm ultraviolet light and 980 nm near-infrared light, CDs@YF3:Yb,Tm exhibited blue fluorescence and green room-temperature phosphorescence of CDs and upconversion luminescence of Tm3+, respectively. Due to the strong protection of the rigid matrix, the stability of CDs@YF3:Yb,Tm is greatly improved. This work provides a general synthesis strategy for achieving multimode luminescence and high stability of CD-based luminescent materials and offers opportunities for their applications in advanced anti-counterfeiting and information encryption.


Determinants of specificity of transactivation by the mineralocorticoid or glucocorticoid receptor.
Glucocorticoids and mineralocorticoids have distinct in vivo roles despite close structural homology and similarities in vitro. Known mechanisms of specificity focus on factors extrinsic to the receptor; interactions that directly regulate the receptor to confer specificity are less well understood, particularly for the mineralocorticoid receptor (MR). To examine relative MR vs. glucocorticoid receptor (GR) function in a more physiological context, we compared transactivation by GR and MR in the standard experimental fibroblast CV-1 cell line, the renal epithelial LLC-PK1 line, and neuronal medullary raphe RN33B cells. Maximal transactivational activity mediated by MR, relative to that mediated by GR, is enhanced in both of these cell lines and is primarily conferred by an N-terminal-mediated enhancement of the MR response. In addition, the ligand concentration required for maximal transcriptional activity of the GR varies significantly between cell lines. This is independent of binding affinity or 11beta-hydroxysteroid dehydrogenase-mediated inactivation and may contribute to in vivo tissue-specific differences in responses to the GR. Although ligand binding affinity is clearly conferred by the LBD, receptor-specific variations between cell lines in transcriptional sensitivity to ligand appear, rather, to be associated with the N-terminus. These studies demonstrate that the specificity of the MR vs. the GR response may be mediated via unique cellular factors, as well as suggesting a novel means of expanding the cellular response to cortisol.


The effect of anthelmintic treatment on coccidia oocyst shedding in a wild mammal host with intermittent cestode infection.
While hosts are routinely exploited by a community of parasite species, the principles governing host responses towards parasites are unclear. Identifying the health outcomes of coinfections involving helminth macroparasites and microparasites is one area of importance for public and domestic animal health. For instance, it is controversial how deworming programmes affect incidence and severity of such important microparasite diseases as malaria. One problem is that most study systems involve domestic and laboratory animals with conditions hardly comparable to those of free-living animals. Here, we study the effect of anthelmintic treatment on coccidia infection intensity in wild Alpine marmots, M. marmota. Our results lend support to the hypothesis that helminth infection has a positive effect on concurrent microparasite infection. However, our work also points to the fact that within-host interactions between helminths and microparasites are context-dependent and can turn to negative ones once helminth burdens increase. Our study suggests that coccidia benefit from intermittent helminth infection in marmots due to the protective effects of helminth infection only during the early phase of the host's active season. Also, the marmot's response towards coccidia infection appears optimal only under no helminth infection when the host immune response towards coccidia would not be compromised, thereby pointing to the importance of regular intestinal helminth elimination by marmots just before hibernation.


Agitated psychotic depression associated with severe hypomanic episodes: a rare syndrome.
The authors present detailed clinical and follow-up data on 12 patients with agitated psychotic depressions who developed serious hypomanic or manic episodes. In six patients, each type of affective episode seemed to merge into the others, while in the other patients there was always a clear temporal distinction between each type of episode. The authors suggest that the older ages of their patients may have contributed to the syndrome. They also offer several possible theoretical explanations: the patients 1) had mixed affective states and were trapped in the "switch" state from depression to mania, 2) inherited both unipolar and bipolar diseases, 3) represent a subgroup of bipolar patients, and 4) were schizoaffective.


Implant surface analysis and microbiologic evaluation of failed implants retrieved from smokers.
The aim of this study was to evaluate the microbiota and surface of failed titanium dental implants from 4 manufacturers. Twelve mobile dental implants were retrieved from 10 smokers after 3 to 10 years of functional loading. Before implant removal, microbial samples were taken and evaluated using polymerase chain reaction. After implant removal, analyses of the failed implant surfaces were performed using scanning electron microscopy and energy-dispersive spectrometer x-ray. Periodontal pathogens such as Aggregactibacter actinomycetemcomitans, Campylobacter rectus, Eikenella corrodens, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola were detected in all implants in different proportions. Surface analysis showed varying degrees of surface roughness between the samples and the presence of proteinaceous material, appearing mainly as dark stains. Foreign carbon, oxygen, sodium, calcium, aluminum, and silicon elements were also found. Although no material-related causes of implant failure were detected, several periodontal pathogens were identified independently of the surface topography or manufacturer.


Cataloguing Treatments Discussed and Used in Online Autism Communities.
A large number of patients discuss treatments in online health communities (OHCs). One research question of interest to health researchers is whether treatments being discussed in OHCs are eventually used by community members in their real lives. In this paper, we rely on machine learning methods to automatically identify attributions of mentions of treatments from an online autism community. The context of our work is online autism communities, where parents exchange support for the care of their children with autism spectrum disorder. Our methods are able to distinguish discussions of treatments that are associated with patients, caregivers, and others, as well as identify whether a treatment is actually taken. We investigate treatments that are not just discussed but also used by patients according to two types of content analysis, cross-sectional and longitudinal. The treatments identified through our content analysis help create a catalogue of real-world treatments. This study results lay the foundation for future research to compare real-world drug usage with established clinical guidelines.


A randomized, double-blind, placebo-controlled study to determine the safety and efficacy of cultured and expanded autologous fibroblast injections for the treatment of interdental papillary insufficiency associated with the papilla priming procedure.
The aim of this study was to assess the efficacy and safety of using autologous fibroblast injections following a minimally invasive papilla priming procedure to augment open interproximal spaces. Twenty-one patients with open interproximal spaces were enrolled in this study, with 20 patients retained to study completion. Two primary sites were selected and randomized to receive autologous fibroblast injections or placebo injections beginning 1 week following the papilla priming procedure; two additional injections were performed 7 to 14 days following the initial injections. Up to seven additional sites could be treated per patient, and the analyses were conducted for the primary and secondary sites. The primary efficacy parameter was the percentage change in papillary height of the primary treatment areas from baseline to the 4-month visit, as measured by a periodontal probe from the base of the contact area to the tip of the interproximal papilla. Digital image analysis and diagnostic models were used to confirm clinical measurements. A visual analog scale (VAS) was used by the examiner and subject to assess the defect change from baseline to 2, 3, and 4 months. Tissue texture also was assessed by the examiner. The primary efficacy analysis failed to show a significant treatment effect at 4 months, but the treatment areas showed a statistically significant mean percentage increase from baseline in papillary height (P = 0.0067; signed-rank test) at 2 months. The difference between test and placebo sites in papillary height at 2 months approached statistical significance (P = 0.0730), suggesting that the test treatment was superior to the placebo treatment. The examiner and subject VASs were statistically significantly different from baseline for both treatment groups, and the VAS was superior for the test sites over the placebo. Based on safety data, the test treatment was deemed safe. This early-phase study using cell transplantation of autologous cultured and expanded fibroblasts following a papilla priming procedure suggests that the treatment is safe and may be efficacious for treating papillary insufficiency, especially in the early phases (2 months) of healing. The analysis of the investigator and subject VAS assessments indicates that the test treatment was superior to the placebo treatment. The finite measurement required to detect a change creates a problem that needs to be addressed in future studies.


Acute haemodynamic profile of celiprolol in patients with coronary heart disease and hypertension: a double-blind comparison with metoprolol.
Celiprolol is a 'third generation' beta-blocking agent which is claimed to avoid problems associated with simpler beta-blockers, such as vasoconstriction, bronchoconstriction and myocardial depression. A double-blind randomized study was undertaken in 30 patients with coronary artery disease and hypertension to compare the haemodynamic effects of single intravenous doses of 0.15 mg kg-1 celiprolol (N = 16) and metoprolol (N = 14). Following celiprolol administration, the tendency was for myocardial function to improve or remain unchanged; left ventricular end-systolic volume and ejection fraction improved significantly (P less than 0.05). However, following metoprolol administration, the tendency was for myocardial function to deteriorate, with significant falls in cardiac output (P less than 0.05), ejection fraction (P less than 0.05) and velocity of circumferential shortening (P less than 0.01). There was a tendency for peripheral resistance to fall slightly with celiprolol but to rise markedly with metoprolol (pNS). Left ventricular pressure-volume loops showed improved performance with celiprolol and deterioration with metoprolol. Both drugs resulted in increases in coronary flow and myocardial oxygen consumption (P less than 0.05). Metoprolol, but not celiprolol, resulted in some deterioration in regional left ventricular wall motion (P less than 0.05). Celiprolol appears to be haemodynamically advantageous compared to metoprolol in patients with coronary artery disease and hypertension.


Zinc oxide based nanocomposite thin film electrodes and the effect of D.C. plasma oxidation power on discharge capacity for lithium ion batteries.
Zinc oxide based thin films have been grown on glass and stainless steel substrates in two steps; thermal evaporation from high purity metallic zinc and D.C. plasma oxidation. X-ray diffraction has shown that the films were polycrystalline nature and small predominant orientation at some specific planes. Analysis showed that plasma oxidation starts from the thermally evaporated leaf-like surfaces and produces a core-shell structure of ZnO on the metallic Zn. Increasing plasma oxidation power causes increased amount of ZnO volume and resistivity. Coin-type (CR2016) test cells were assembled in an argon-filled glove box and cyclically tested. The electrochemical performance of the films has been studied by cyclic voltammetry. The dependence of converted Li-ions on voltage profile of the films has been determined. It was found that the Zn/ZnO films exhibited highest the number of converted Li-ions at 175 W plasma oxidation conditions. Discharge capacity measurements revealed the double phase structures of Zn/ZnO exhibited significantly high reversible capacities. The high capacity and low capacity fade values were attributed to the high electrical conductivity and buffering ability of metallic Zn in the anodes.


Study on clinical and biochemical toxicity biomarkers in a zinc-lead mine workers.
The aim of this study was to determine oxidative stress status as well as blood lead (Pb) and zinc (Zn) levels and clinical markers in workers of a Zn-Pb mine. A comparative cross-sectional analysis was performed in 67 mine workers who have been in contact with Zn and Pb in comparison to a control group containing 67 healthy subjects with the same age and sex. Lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, myleoperoxidase, DNA damage, total antioxidant capacity, Zn, and Pb levels were measured in blood of workers and controls. Clinical examination was accomplished to record any abnormal sign or symptoms. Comparing with controls, the workers showed higher blood levels of superoxide dismutase, myleoperoxidase, glutathione reductase, lipid peroxidation, Pb, and Zn. Workers showed lower DNA-damage as compared with controls. Workers showed clinical symptoms such as memory impairment, less of concentration, insomnia, headache, claudication, epigasteric, inappetence, agitation, tremor, decreasing of reflection of deep tendon, conduction deafness of ear, and fatigue. The workers had extra normal levels of Pb (0.9-3 microg/dL) and showed oxidative stress. Taken together, the results indicate that exposure to combination of Pb and Zn in mine elevates total antioxidant capacity of body in a reflex to overcome to oxidative stress. Especially, in the present case, it seems that toxic effect of Pb has been greater than positive effects of Zn, but the combination exposure has resulted in not such a critical toxicity situation.


Croatian bibliometric analysis, 2000-2007.
To develop search filters and retrieve information estimating the Croatian scientific output (SO) focusing on Public Health (PH) and Preventive Medicine (PM) in MEDLINE. A PubMed search of the MEDLINE database was performed to retrieve articles added to this database between 2000 and 2007. Search filters inspired by previous strategies were applied involving 'geographical', 'place of publication', 'subject' and 'language of publication' aspects. An evaluation of the geographical filter performance was done and sensitivity and specificity were calculated. There were obtained publications in several languages, originated in Croatia, published in Croatia and/or abroad. The Croatian SO in the field of PH-PM was obtained for the same period of time by combining search filters. The evaluation of the filter performance showed sensitivity 95.56% and specificity 100%. The filters constructed permitted the retrieval of the Croatian eight years research output. Increased tendency was observed in the global SO evolution and in the PH-PM area as well. The main languages of publication were English and Croatian. This study is a contribution to research in the field of scientific documentation and further analysis is recommended in constructing and developing search filters to retrieve and focus on specific information.


Evaluation of various serum and animal protein free media for the production of a veterinary rabies vaccine in BHK-21 cells.
We have carried out the adaptation of BHK-21 cells to two serum free (Ex Cell 520 and HyQ PF CHO) and three animal protein free media: Ex Cell 302, HyQ PF CHO MPS and Rencyte BHK. After a direct switch or a gradual adaptation, we have achieved BHK-21 cells growth in the following media: HyQ PF CHO, HyQ PF CHO MPS, Rencyte BHK and Ex Cell 302. The most suitable media for BHK-21 cells growth, with respect to cell density and specific growth rate, were HyQ PF CHO and HyQ PF CHO MPS. Hence we have selected these media to study cell growth and the production of rabies virus. Kinetic studies of cell growth in spinner flasks using the selected media have shown that a maximal cell density of 2x10(6) cells x ml(-1) was reached in both media. For rabies virus production, the viral titer obtained was 1.7x10(6) FFU x ml(-1) in HyQ PF CHO as well as in HyQ PF CHO MPS medium. The optimization of rabies virus production by BHK-21 cells grown in a 2 l bioreactor using the selected media, pointed to the following parameters: culture mode, perfusion rate and multiplicity of infection (MOI), as being the critical factors for achieving a good virus yield. When tested in mice, the activity of the experimental vaccines prepared on HyQ PF CHO MPS medium has shown a protective activity that meets WHO requirements.


DeepX: Deep Learning Accelerator for Restricted Boltzmann Machine Artificial Neural Networks.
Although there have been many decades of research and commercial presence on high performance general purpose processors, there are still many applications that require fully customized hardware architectures for further computational acceleration. Recently, deep learning has been successfully used to learn in a wide variety of applications, but their heavy computation demand has considerably limited their practical applications. This paper proposes a fully pipelined acceleration architecture to alleviate high computational demand of an artificial neural network (ANN) which is restricted Boltzmann machine (RBM) ANNs. The implemented RBM ANN accelerator (integrating network size, using 128 input cases per batch, and running at a 303-MHz clock frequency) integrated in a state-of-the art field-programmable gate array (FPGA) (Xilinx Virtex 7 XC7V-2000T) provides a computational performance of 301-billion connection-updates-per-second and about 193 times higher performance than a software solution running on general purpose processors. Most importantly, the architecture enables over 4 times (12 times in batch learning) higher performance compared with a previous work when both are implemented in an FPGA device (XC2VP70).


Residual thermal stress simulation in three-dimensional molar crown systems: a finite element analysis.
To simulate coefficient of thermal expansion (CTE)-generated stress fields in monolithic metal and ceramic crowns, and CTE mismatch stresses between metal, alumina, or zirconia cores and veneer layered crowns when cooled from high temperature processing. A 3D computer-aided design model of a mandibular first molar crown was generated. Tooth preparation comprised reduction of proximal walls by 1.5 mm and of occlusal surfaces by 2.0 mm. Crown systems were monolithic (all-porcelain, alumina, metal, or zirconia) or subdivided into a core (metallic, zirconia, or alumina) and a porcelain veneer layer. The model was thermally loaded from 900°C to 25°C. A finite element mesh of three nodes per edge and a first/last node interval ratio of 1 was used, resulting in approximately 60,000 elements for both solids. Regions and values of maximum principal stress at the core and veneer layers were determined through 3D graphs and software output. The metal-porcelain and zirconia-porcelain systems showed compressive fields within the veneer cusp bulk, whereas alumina-porcelain presented tensile fields. At the core/veneer interface, compressive fields were observed for the metal-porcelain system, slightly tensile for the zirconia-porcelain, and higher tensile stress magnitudes for the alumina-porcelain. Increasingly compressive stresses were observed for the metal, alumina, zirconia, and all-porcelain monolithic systems. Variations in residual thermal stress levels were observed between bilayered and single-material systems due to the interaction between crown configuration and material properties.


Analysis of clinical manifestations of symptomatic acquired jejunoileal diverticular disease.
To analyze systematically our experience over 22 years with symptomatic acquired diverticular disease of the jejunum and ileum, exploring the clinical manifestations and diagnosis of this rare but life-threatening disease. The medical records of patients with surgically confirmed symptomatic jejunoileal diverticular disease were retrospectively reviewed. Data collected included demographic data, laboratory results, clinical course (acute or chronic), preoperative diagnosis, and operative findings. Inclusion criteria were as follows: (1) surgical confirmation of jejunoileal diverticular disease and (2) exclusion of congenital diverticula (e.g. Meckel's diverticulum). From January 1982 to July 2004, 28 patients with a total of 29 operations met the study criteria. The male:female ratio was 14:14, and the mean age was 62.6+/-3.5 years. The most common manifestation was abdominal pain. In nearly half of the patients, the symptoms were chronic. Two patients died after surgery. Only four cases were correctly diagnosed prior to surgery, three by small bowel series. Symptomatic acquired small bowel diverticular disease is difficult to diagnose. It should be considered in older patients with unexplained chronic abdominal symptoms. A small bowel series may be helpful in diagnosing this potentially life-threatening disease.


Automated Cough Assessment on a Mobile Platform.
The development of an Automated System for Asthma Monitoring (ADAM) is described. This consists of a consumer electronics mobile platform running a custom application. The application acquires an audio signal from an external user-worn microphone connected to the device analog-to-digital converter (microphone input). This signal is processed to determine the presence or absence of cough sounds. Symptom tallies and raw audio waveforms are recorded and made easily accessible for later review by a healthcare provider. The symptom detection algorithm is based upon standard speech recognition and machine learning paradigms and consists of an audio feature extraction step followed by a Hidden Markov Model based Viterbi decoder that has been trained on a large database of audio examples from a variety of subjects. Multiple Hidden Markov Model topologies and orders are studied. Performance of the recognizer is presented in terms of the sensitivity and the rate of false alarm as determined in a cross-validation test.


-463 G/A myeloperoxidase promoter polymorphism is associated with clinical manifestations and the course of disease in MPO-ANCA-associated vasculitis.
Wegener's granulomatosis, microscopic polyangiitis, and Churg Strauss syndrome are forms of systemic vasculitides in which neutrophils and monocyte macrophages infiltrate the walls of small blood vessels, leading to destruction and occlusion. These diseases are associated with autoantibodies directed against granular components of neutrophils and monocytes, i.e., antineutrophil cytoplasmic antibodies (ANCA). The most common target antigens of ANCA in these vasculitides are myeloperoxidase (MPO) and proteinase 3 (PR3). ANCA-stimulated neutrophils injure endothelial cells, a process that is dependent upon the production of reactive oxygen radicals and the release of granular components such as MPO and PR3. Here we investigate whether a common functional MPO promoter polymorphism (-463 G/A) is associated with increased incidence and clinical aspects of ANCA-associated small vessel vasculitis. Genotyping was carried out for 142 patients with ANCA-associated small vessel vasculitis and 129 ethnically matched controls. The GG genotype was found to be associated with an increased risk for MPO-ANCA-associated vasculitis in females (86% GG, P = 0.045), but not males (64% GG, P = 1.0). Interestingly, the MPO A allele is associated with an increased incidence of relapses (P = 0.012) and an earlier age at diagnosis (P = 0.03) of MPO-ANCA-associated vasculitis. Both these associations are specific for MPO-ANCA and are not observed in patients with PR3-ANCA-associated vasculitis. These findings suggest that MPO expression levels influence the disease course of MPO-ANCA-associated vasculitis and further support the view that genetic factors are involved in the pathophysiology of this autoimmune disease.


[Chinese multi-disciplinary consensus on the diagnosis and treatment of hyperuricemia and its related diseases].
The prevalence of hyperuricemia (HUA) in China has been increasing rapidly during the past decade and this disease has stepped up to the second most common metabolic disease following diabetes mellitus. Different disciplinary panels have developed guidelines and consensus on hyperuricemia and gout in respective fields. However, hyperuricemia has been well illustrated to be related to multiple organ disorders such as kidney injuries, endocrine and metabolic abnormalities, and cardiocerebrovascular diseases etc. A multi-disciplinary expert consensus on hyperuricemia and its related diseases will therefore provide a more comprehensive understanding in the diagnosis and treatment of the diseases. The following manuscript is the first consensus established by a task force including rheumatologists, nephrologists, endocrinologists, cardiologists, neurologists, urologists and traditional Chinese medicine experts. This consensus aims at promoting multi-disciplinary collaboration and providing guidelines in clinical practice for general practitioners, doctors from different disciplines at different levels.


Rodent whole embryo culture.
The direct effects of chemical exposures, environmental extremes, and nutrient quality/quantity have been very difficult to study in mammalian embryos due to their anatomical inaccessibility, paucity of tissues, and other factors such as real ethical concerns in human studies. Many acute and chronic developmental anomalies can trace their origins to postimplantation phases of gestation where the organs are first being established and growth and differentiation are in highly active states of flux. Most agents and conditions that produce birth defects are believed to act during this period of organogenesis. The evolution of rodent whole embryo culture (WEC) techniques has provided a valuable experimental model where physiological conditions and exposures can be carefully controlled and manipulated to test hypotheses and explore biochemical and molecular mechanisms of action. Exposure to chemical agents can be controlled through their direct addition to the culture medium. Optimal in vitro culture conditions support the growth of intact, viable conceptuses (embryo and associated extraembryonic membranes) from early egg cylinder stages through establishment of the neural plate, gastrulation, neural tube closure, onset of active heartbeat and circulation, and the initial formation of all major organ systems that occur prior to the establishment of a functional placenta. Detailed comparisons of in vivo and in vitro growth show that conceptuses grown in WEC are nearly identical, structurally and functionally, to conceptuses of the same developmental stage that are allowed to develop normally in vivo. Culture conditions and mechanical apparatus can be modified to suit a large number of different experimental approaches and paradigms.


Hyperopia-Correcting Phototherapeutic Keratectomy and Its Comparison With Conventional Phototherapeutic Keratectomy.
To evaluate hyperopia-correcting phototherapeutic keratectomy (HC-PTK) and to compare the visual and refractive outcomes of HC-PTK and conventional PTK. This study comprised a total of 72 eyes of 72 consecutive patients who underwent HC-PTK and conventional PTK for granular corneal dystrophy or band-shaped keratopathy. Preoperatively and 6 months postoperatively, we assessed visual acuity, manifest refraction, and mean keratometry, as well as postoperative corneal higher-order aberrations and adverse events in each PTK group, and compared these metrics between the two groups. LogMAR BSCVA significantly improved from 0.43 ± 0.47 preoperatively to 0.21 ± 0.38 postoperatively in the HC-PTK group (Wilcoxon signed-rank test, p < 0.001). It was also significantly improved from 0.22 ± 0.21 preoperatively to 0.15 ± 0.12 postoperatively in the conventional PTK group (p = 0.031). Mean refraction significantly changed from 0.27 ± 1.55 diopter (D) preoperatively to 0.50 ± 1.77 D postoperatively, in the HC-PTK group (p = 0.313). By contrast, it was significantly hyperopic from -0.15 ± 2.41 D preoperatively to 1.45 ± 2.46 D postoperatively, in the conventional PTK group (p < 0.001). No significant complications occurred in any case during the follow-up period. Both HC-PTK and conventional PTK showed a significant improvement of BSCVA and no vision-threatening complications at any time in this series. HC-PTK significantly reduced a hyperopic shift in refraction compared with conventional PTK, suggesting its viability for patients requiring PTK, especially in consideration of preventing this hyperopic issue.


Excretion of alkaloids by malpighian tubules of insects.
Nicotine is transported at high rates by Malpighian tubules of larvae of Manduca sexta, Pieris brassicae and Rhodnius prolixus and the transport persists in the absence of alkaloid from the diet. In the fluid-secreting portion of Rhodnius tubules this transport is not coupled to ion transport, nor is it dependent on the physiological state of the animal. The transport, which can occur against a steep electrochemical gradient, shows saturation kinetics with a maximal rate of 700 pmol. min-1 per tubule and is half saturated at 2-3 mM. Nicotine transport independent of ion movements also occurs in the lower resorptive parts of Rhodnius tubules. Both portions of Rhodnius tubules can transport morphine and atropine. These alkaloids and nicotine compete with one naother and are presumed to be carried by the smae transport system. Nicotine transport in Rhodnius was unaffected by organic anions, such as amaranth and benzyl penicillin, or by the organic anion transport inhibitor, probenecid. Fluid secretion in 5-HT-stimulated tubules was reduced by atropine and nicotine, probably by blocking the 5-HT receptors. The Malpighian tubules of adult Calliphora erythrocephala and Musca domestica remove nicotine from bathing solutions, an unknown metabolic accumulating in the tubules. Adult P. brassicae and M. sexta do not exhibit transport of nicotine by their Malpighian tubules.


[Materials for the paediatric resuscitation trolley or backpack: Expert recommendations].
Cardio-respiratory arrest (CPA) is infrequent in children, but it can occur in any place and at any time. This fact means that every health care facility must always have the staff and material ready to resuscitate a child. These recommendations are the consensus of experts of the Spanish Paediatric and Neonatal Resuscitation Group on the material and medication for paediatric and neonatal resuscitation and their distribution and use. CPR trolleys and backpacks must include the essential material to quickly and efficiently perform a paediatric CPR. At least one CPR trolley must be available in every Primary Care facility, Paediatric Intensive Care Unit, Emergency Department, and Pre-hospital Emergency Areas, as well as in paediatric wards, paediatric ambulatory areas, and radiology suites. This trolley must be easily accessible and exclusively include the essential items to perform a CPR and to assist children (from newborns to adolescents) who present with a life-threatening event. Such material must be familiar to all healthcare staff and also include the needed spare parts, as well as enough drug doses. It must also be re-checked periodically. The standardisation and unification of the material and medication of paediatric CPR carts, trolleys, and backpacks, as well as the training of the personnel in their use are an essential part of the paediatric CPR.


Meeting the bilingual learning needs of Tibetan minority students in Qinghai Province: A multiple perspective investigation into problems and solutions.
Using student and teacher open-ended questionnaires, and interviews with teachers and school principals and administrators, this study examined the bilingual learning difficulties faced by the Tibetan minority students in Qinghai Province, China, the challenges in meeting their needs, and the suggestions for coping with these challenges. The participants included 200 Tibetan minority students, 20 classroom teachers, and 10 school principals and administrators randomly selected from eight secondary schools located in eight different counties, where there are the most Tibetan minority students in Qinghai Province. The results showed that they experienced considerable difficulties in both spoken and written Chinese, which had prevented them from understanding the lectures, answering questions, interacting with peers in the classroom, and communicating with friends and classmates outside of classroom. The challenges in meeting their bilingual learning needs include: (a) a language choice dilemma for parents, (b) insufficient training of bilingual education teachers, (c) lack of bilingual education resources; (d) short of qualified teachers; (e) lack of parent-school communication; and (f) insufficient training of principals and administrators. Suggestions for coping with these challenges and educational implications are discussed.


[Case of portal venous gas and pneumatosis cystoides intestinalis occurring during chemotherapy for a castration-resistant prostate cancer].
Portal venous gas is a rare complication. We present a case of hepatic portal venous gas (HPVG) and pneumatosis cystoides intestinalis (PCI) in a patient treated with docetaxel for prostate cancer. An 80-year-old man with castration-resistant prostate cancer received 5 cycles of docetaxel. Diarrhea and vomiting appeared on the 4th day of the 5th cycle. An abdominal computed tomography (CT) scan revealed HPVG and PCI. Since there were neither peritoneal irritation signs nor intestinal necrosis, we performed conservative management. The HPVG and PCI were no longer detected in the abdominal CT scan on the 18th day. Mucosal injury of the bowel wall by docetaxel might have caused HPVG and PCI. This case report is the first description of HPVG and PCI in a patient with castration-resistant prostate cancer in Japan.


Cutting edge: microRNA regulation of macrophage fusion into multinucleated giant cells.
Cellular fusion of macrophages into multinucleated giant cells is a distinguishing feature of the granulomatous response to inflammation, infection, and foreign bodies (Kawai and Akira. 2011. Immunity 34: 637-650). We observed a marked increase in fusion of macrophages genetically deficient in Dicer, an enzyme required for canonical microRNA (miRNA) biogenesis. Gene expression profiling of miRNA-deficient macrophages revealed an upregulation of the IL-4-responsive fusion protein Tm7sf4, and analyses identified miR-7a-1 as a negative regulator of macrophage fusion, functioning by directly targeting Tm7sf4 mRNA. miR-7a-1 is itself an IL-4-responsive gene in macrophages, suggesting feedback control of cellular fusion. Collectively, these data indicate that miR-7a-1 functions to regulate IL-4-directed multinucleated giant cell formation.


Microstructure Evolution of the Near-Surface Deformed Layer and Corrosion Behavior of Hot Rolled AA7050 Aluminum Alloy.
The current study investigates the influence of hot rolling on the microstructure evolution of the near-surface region on AA7050 aluminum alloy and the corrosion performance of the alloy. It is revealed that hot rolling resulted in grain refinement in the near-surface region, caused by dynamic recrystallization, and equiaxed grains less than 500 nm can be clearly observed. Fibrous grains were evident in the hot rolled AA7050 aluminum alloy with relatively lower rolling temperature or larger rolling reduction, caused by the more severe elemental segregation at grain boundaries, which inhibited the progression of dynamic recrystallization. The density of the precipitates in the fibrous grain layer was higher, compared with those in the equiaxed grain layer, due to the increased dislocation density, combined with more severe elemental segregation, which significantly promoted the nucleation of precipitates. With the co-influence exerted by low density of precipitates and dislocations on the improvement of the corrosion performance of the alloy, the rolled AA7050 alloy with decreased density of precipitates and dislocations exhibited better corrosion resistance.


Effect of the environment on participation in spinal cord injuries/disorders: The mediating impact of resilience, grief, and self-efficacy.
The objective of the study was to test the hypothesis that the influence of environmental barriers on participation will be fully mediated by psychosocial factors (resilience, grief or loss, and self-efficacy) among individuals with spinal cord injuries and disorders. This was a cross-sectional mailed survey with a national sample of veterans with spinal cord injuries and disorders (n = 565), which included measures of demographics, perceived environmental barriers, participation, resilience, grief or loss, and self-efficacy. Data were analyzed using a latent variable path analysis; the model fit was assessed using χ2, normed χ2, root mean square error of approximation (RMSEA; <0.07), Comparative Fit Index (CFI; ≥0.95), and Tucker-Lewis Index (TLI; ≥0.95). Participants were mostly male (93.9%), Caucasian or White (74.2%), and, on average, 62.4 years of age (SD = 10.48). Almost 62% had paraplegia, and 38.3% had a motor or sensory complete injury. The hypothesized model showed excellent fit, χ2(42) = 153.40, normed χ2 = 3.65, RMSEA = 0.07, CFI = 0.96, TLI = 0.95. To assess for full mediation, a direct path was added from environment to participation. This model showed nearly identical fit, χ2(41) = 153.39, normed χ2 = 3.74, RMSEA = 0.07, CFI = 0.96, TLI = 0.95; the path from environment to participation was not significant, unstandardized coefficient = -0.04, p = .92. Examination of indirect effects of the hypothesized model demonstrated that environment significantly influences participation through psychosocial factors, unstandardized coefficient = -4.85, p < .001. Together these results support full mediation. In conclusion the present study expands upon past research by suggesting that perceived environmental barriers play a role in internal factors, such as resilience and self-efficacy, which in turn influence participation. Interventions to improve environmental barriers may be warranted, but attention must also be paid to resilience, grief or loss, and self-efficacy to increase participation. (PsycINFO Database Record


Conditional Molecular Generation Net Enables Automated Structure Elucidation Based on 13C NMR Spectra and Prior Knowledge.
Structure elucidation of unknown compounds based on nuclear magnetic resonance (NMR) remains a challenging problem in both synthetic organic and natural product chemistry. Library matching has been an efficient method to assist structure elucidation. However, it is limited by the coverage of libraries. In addition, prior knowledge such as molecular fragments is neglected. To solve the problem, we propose a conditional molecular generation net (CMGNet) to allow input of multiple sources of information. CMGNet not only uses 13C NMR spectrum data as input but molecular formulas and fragments of molecules are also employed as input conditions. Our model applies large-scale pretraining for molecular understanding and fine-tuning on two NMR spectral data sets of different granularity levels to accommodate structure elucidation tasks. CMGNet generates structures based on 13C NMR data, molecular formula, and fragment information, with a recovery rate of 94.17% in the top 10 recommendations. In addition, the generative model performed well in the generation of various classes of compounds and in the structural revision task. CMGNet has a deep understanding of molecular connectivities from 13C NMR, molecular formula, and fragments, paving the way for a new paradigm of deep learning-assisted inverse problem-solving.


Identification of Epigenetically Modified Hub Genes and Altered Pathways Associated With Retinoblastoma.
Retinoblastoma (Rb) is the most common childhood malignancy initiated by biallelic mutation in RB1 gene and driven by various epigenetic events including DNA methylation and microRNA dysregulation. Hence, understanding the key genes that are critically modulated by epigenetic modifications in RB1 -/- cells is very important to identify prominent biomarkers and therapeutic targets of Rb. In this study, we for the first time have integrated various Rb microarray NCBI-GEO datasets including DNA Methylation (GSE57362), miRNA (GSE7072) and mRNA (GSE110811) to comprehensively investigate the epigenetic consequences of RB loss in retinoblastoma tumors and identify genes with the potential to serve as early diagnostic markers and therapeutic targets for Rb. Interestingly, the GEO2R and co-expression network analysis have identified three genes namely E2F3, ESR1, and UNC5D that are significantly deregulated by modified DNA methylation, mRNA and microRNA expression in Rb tumors. Due to their recognition in all epigenetic, transcriptomic, and miRNA datasets, we have termed these genes as "common genes". The results of our integrative bioinformatics analysis were validated in vitro by studying the gene and protein expression of these common genes in Y79, WERI-Rb-1, Rb cell lines and non-tumorigenic retinal pigment epithelial cell line (hTERT-RPE). The expression of E2F3 and UNC5D were up-regulated and that of ESR1 was down-regulated in Rb tumor cells when compared to that in non-tumorigenic hTERT-RPE cells. More importantly, UNC5D, a potent tumor suppressor gene in most cancers is significantly up-regulated in Y79 and Weri Rb1 cells, which, in turn, questions its anti-cancer properties. Together, our study shows that E2F3, ESR1, and UNC5D may be crucially involved in Rb tumorigenesis and possess the potential to act as early diagnostic biomarkers and therapeutic targets of Rb.