Cell wall-related genes and lignin accumulation contribute to the root resistance in different maize (Zea mays L.) genotypes to Fusarium verticillioides (Sacc.) Nirenberg infection.
The fungal pathogen Fusarium verticillioides (Sacc.) Nirenberg (Fv) causes considerable agricultural and economic losses and is harmful to animal and human health. Fv can infect maize throughout its long agricultural cycle, and root infection drastically affects maize growth and yield. The root cell wall is the first physical and defensive barrier against soilborne pathogens such as Fv. This study compares two contrasting genotypes of maize (Zea mays L.) roots that are resistant (RES) or susceptible (SUS) to Fv infection by using transcriptomics, fluorescence, scanning electron microscopy analyses, and ddPCR. Seeds were infected with a highly virulent local Fv isolate. Although Fv infected both the RES and SUS genotypes, infection occurred faster in SUS, notably showing a difference of three to four days. In addition, root infections in RES were less severe in comparison to SUS infections. Comparative transcriptomics (rate +Fv/control) were performed seven days after inoculation (DAI). The analysis of differentially expressed genes (DEGs) in each rate revealed 733 and 559 unique transcripts that were significantly (P ≤0.05) up and downregulated in RES (+Fv/C) and SUS (+Fv/C), respectively. KEGG pathway enrichment analysis identified coumarin and furanocoumarin biosynthesis, phenylpropanoid biosynthesis, and plant-pathogen interaction pathways as being highly enriched with specific genes involved in cell wall modifications in the RES genotype, whereas the SUS genotype mainly displayed a repressed plant-pathogen interaction pathway and did not show any enriched cell wall genes. In particular, cell wall-related gene expression showed a higher level in RES than in SUS under Fv infection. Analysis of DEG abundance made it possible to identify transcripts involved in response to abiotic and biotic stresses, biosynthetic and catabolic processes, pectin biosynthesis, phenylpropanoid metabolism, and cell wall biosynthesis and organization. Root histological analysis in RES showed an increase in lignified cells in the sclerenchymatous hypodermis zone during Fv infection. These differences in the cell wall and lignification could be related to an enhanced degradation of the root hairs and the epidermis cell wall in SUS, as was visualized by SEM. These findings reveal that components of the root cell wall are important against Fv infection and possibly other soilborne phytopathogens.


Degradation of an ubiquitin-conjugated protein is associated with myoblast differentiation in primary cell culture.
At the early stages of myogenesis, myoblasts fuse to form multinucleated myotubes. This morphological differentiation is the result of dynamic changes in gene regulation and expression. The ubiquitin proteasome-dependent pathway has been reported to play an important role in many aspects of cellular functions such as regulation of growth and cell cycle progression. In this study, we showed that the amount of mRNA's corresponding to the iota subunit of the 20S proteasome, the level of the S4 subunit of the 19S complex and the 20S and 26S proteasomes peptidase activities increased during myoblast fusion. Cell permeable 20S proteasome inhibitor prevented fusion with concomitant accumulation of ubiquitin-conjugated protein. On the other hand, inhibition of ubiquitin ligase E3 enzymes prevented the formation of ubiquitin conjugate and decreased the fusion process. These results strongly support the involvement of the ubiquitin-proteasome proteolytic pathway in the events leading to myoblast fusion.


Physiological effects of dietary cadmium acclimation and waterborne cadmium challenge in rainbow trout: respiratory, ionoregulatory, and stress parameters.
A suite of respiratory, acid-base, ionoregulatory, hematological, and stress parameters were examined in adult rainbow trout (Oncorhynchus mykiss) after chronic exposure to a sublethal level of dietary Cd (500 mg/kg diet) for 45 days and during a subsequent challenge to waterborne Cd (10 microg/L) for 72 h. Blood sampling via an indwelling arterial catheter revealed that dietary Cd had no major effects on blood gases, acid-base balance, and plasma ions (Ca(2+), Mg(2+), K(+), Na(+), and Cl(-)) in trout. The most notable effects were an increase in hematocrit (49%) and hemoglobin (74%), and a decrease in the plasma total ammonia (43%) and glucose (49%) of the dietary Cd-exposed fish relative to the nonexposed controls. Dietary Cd resulted in a 26-fold increase of plasma Cd level over 45 days (approximately 24 ng/mL). The fish exposed to dietary Cd showed acclimation with increased protection against the effects of waterborne Cd on arterial blood P(aCO2) and pH, plasma ions, and stress indices. After waterborne Cd challenge, nonacclimated fish, but not Cd-acclimated fish, exhibited respiratory acidosis. Plasma Ca(2+) levels declined from the prechallenge level, but the effect was more pronounced in nonacclimated fish (44%) than in Cd-acclimated fish (14%) by 72 h. Plasma K(+) was elevated only in the nonacclimated fish. Similarly, waterborne Cd caused an elevation of all four traditional stress parameters (plasma total ammonia, cortisol, glucose, and lactate) only in the nonacclimated fish. Thus, chronic exposure to dietary Cd protects rainbow trout against physiological stress caused by waterborne Cd and both dietary and waterborne Cd should be considered in determining the extent of Cd toxicity to fish.


A case of tracheobronchopathia ostochondorplastica.
Tracheobronchopathia osteochondroplastica (TO) is a disorder caused by the accumulation of calcium phosphate in the submucosa of large airways. Benign proliferation of bone and cartilage lead to the narrowing of airways. Bronchoscopy is the diagnostic test for TO. It shows characteristic smooth nodules emerging from tracheal rings that never involves the posterior membranous wall.


Inorganic Ferrocene Analogue [Fe(P4)2]2.
Inorganic metallocene derivatives containing only cyclo-Pn ligands have been targeted for more than 20 years, but their syntheses have never been achieved by pursuing the conventional route of using P4 phosphorus except for the generation of [Ti(η5-P5)2]2-. Herein, we report a facile one-step method for the synthesis of the homoleptic iron complex [Fe(P4)2]2- by the Zintl-phase-type precursor KP. 31P NMR analyses indicate that upon dissolving the KP phase in ethylenediamine P42- was generated only in the presence of 2,2,2-crypt. The amounts of cation-sequestering agents, the type of iron precursor, and their consuming ratio have a decisive impact on the yield of [Fe(P4)2]2-. Both the FeII and the FeIII precursors can oxidize P42- to give a concomitant product [(P7)Fe(P4)]3-, which can be partially inhibited by the addition of potassium to produce relatively pure crystalline [K(2,2,2-crypt)]2[Fe(P4)2].


Dysregulation of microRNA-214 and PTEN contributes to the pathogenesis of hypoxic pulmonary hypertension.
Hypoxia-induced pulmonary hypertension, which is characterized by vascular remodeling of blood vessels, is an important complication in COPD. In this study, we found that the expression of miR-214 was differentially expressed by screening 13 candidate miRNAs in pulmonary artery smooth muscle cells (PASMCs). Additionally, using luciferase assay in PASMCs, we found that phosphatase-and-tensin homolog (PTEN) was a target of miR-214. Furthermore, the expression of PTEN was found to be substantially downregulated in PASMCs from COPD patients with pulmonary hypertension (PH) compared with normal controls by using real-time polymerase chain reaction (PCR), immunohistochemistry, and Western blot. In addition, we transfected PASMCs with miR-214 mimics, using real-time PCR and Western blotting, to confirm the miRNA/mRNA relationship. Furthermore, the introduction of miR-214 significantly promoted the proliferation of PASMCs by suppressing apoptosis of the cells, which was mediated by the downregulation of PTEN. Exposure to hypoxia significantly increased the expression of miR-214 and decreased the expression of PTEN in PASMCs, and its proliferation was significantly promoted. Such effects could be significantly attenuated by the introduction of miR-214 inhibitors, which significantly downregulated miR-214 expression and upregulated the expression of PTEN. In conclusion, hypoxia-induced upregulation of miR-214 was found to promote PH development by targeting PTEN in PASMCs, and miR-214 could be a promising diagnostic tool and novel therapeutic target in the management of hypoxia-induced PH in COPD.


Evaluation of Three Commercial Handheld Ultra-Low-Volume Foggers with Aqualure® 20-20 Against Adult Aedes albopictus.
The Anastasia Mosquito Control District (AMCD) tests all equipment before field use to determine if machines are suitable for the needs of the district. Three handheld ultra-low-volume (ULV) foggers--the American LongRay (ULV) Fogger Model 3600B with rechargeable lithium battery (DC model), American LongRay ULV Fogger Model 3600E with 110V or 220V AC power (AC model), and Boston Fog Battery Motorized Fogger (Boston Fogger)--were compared to determine which fogger would be most suitable for use by AMCD. Mortality of caged Aedes albopictus was analyzed after 24 h to determine the success of a single application. All 3 foggers resulted in 100% mortality after 24 h using the insecticide Aqualuer 20-20 (active ingredients permethrin 20.6% and piperonyl butoxide 20.6%) 1:5 dilution with reverse osmosis water. Based on operator safety, robustness, and operational performance, the American LongRay DC model was found to be the most suitable at administering Aqualuer 20-20 against caged adult Ae. albopictus.


Transcription Factor OsDOF18 Controls Ammonium Uptake by Inducing Ammonium Transporters in Rice Roots.
Nitrogen is one of the most important mineral elements for plant growth. We studied the functional roles of Oryza sativa DNA BINDING WITH ONE FINGER 18 (OsDOF18) in controlling ammonium uptake. The growth of null mutants of OsDOF18 was retarded in a medium containing ammonium as the sole nitrogen source. In contrast, those mutants grew normally in a medium with nitrate as the sole nitrogen source. The gene expression was induced by ammonium but not by nitrate. Uptake of ammonium was lower in osdof18 mutants than in the wild type, while that of nitrate was not affected by the mutation. This indicated that OsDOF18 is involved in regulating ammonium transport. Among the 10 ammonium transporter genes examined here, expression of OsAMT1;1, OsAMT1;3, OsAMT2;1, and OsAMT4;1 was reduced in osdof18 mutants, demonstrating that the ammonium transporter genes function downstream of OsDOF18. Genes for nitrogen assimilation were also affected in the mutants. These results provide evidence that OsDOF18 mediates ammonium transport and nitrogen distribution, which then affects nitrogen use efficiency.


Growth, biochemical response and nutritional status of Angico-Vermelho (Parapiptadenia rigida (Bentham) Brenan) under the application of soil amendment in Cu-contaminated soil.
Forest species Angico-Vermelho (Parapiptadenia rigida (Bentham) Brenan) is an alternative for the revegetation of areas contaminated with high levels of heavy metals such as copper (Cu). However, excess Cu may cause toxicity to plants, which is why the use of soil amendments can facilitate cultivation by reducing the availability of Cu in the soil. The aim of this study was to assess how the use of amendment can contribute to growth and nutritional status as well as reduce oxidative stress in Angico-Vermelho grown in Cu-contaminated soil. Samples of a Typic Hapludalf soil containing high Cu content were used for the application of four amendments (limestone, organic compost, Ca silicate and zeolite), in addition to a control treatment. The treatments were arranged in a completely randomized design, with four replicates. The use of amendments decreased Cu content available in soil and contributed to improve both plant nutritional status and its antioxidant response expressed by enzymatic activity. The application of the amendments, especially zeolite and Ca silicate, increased dry matter yield of Angico-Vermelho. Thus, the results presented here suggest that the use of amendments contributes to improving Cu-contaminated soils and favors revegetation with Angico-Vermelho.


A novel coupled enzyme assay reveals an enzyme responsible for the deamination of a chemically unstable intermediate in the metabolic pathway of 4-amino-3-hydroxybenzoic acid in Bordetella sp. strain 10d.
2-amino-5-carboxymuconic 6-semialdehyde is an unstable intermediate in the meta-cleavage pathway of 4-amino-3-hydroxybenzoic acid in Bordetella sp. strain 10d. In vitro, this compound is nonenzymatically converted to 2,5-pyridinedicarboxylic acid. Crude extracts of strain 10d grown on 4-amino-3-hydroxybenzoic acid converted 2-amino-5-carboxymuconic 6-semialdehyde formed from 4-amino-3-hydroxybenzoic acid by the first enzyme in the pathway, 4-amino-3-hydroxybenzoate 2,3-dioxygenase, to a yellow compound (epsilonmax = 375 nm). The enzyme in the crude extract carrying out the next step was purified to homogeneity. The yellow compound formed from 4-amino-3-hydroxybenzoic acid by this purified enzyme and purified 4-amino-3-hydroxybenzoate 2,3-dioxygenase in a coupled assay was identified as 2-hydroxymuconic 6-semialdehyde by GC-MS analysis. A mechanism for the formation of 2-hydroxymuconic 6-semialdehyde via enzymatic deamination and nonenzymatic decarboxylation is proposed based on results of spectrophotometric analyses. The purified enzyme, designated 2-amino-5-carboxymuconic 6-semialdehyde deaminase, is a new type of deaminase that differs from the 2-aminomuconate deaminases reported previously in that it primarily and specifically attacks 2-amino-5-carboxymuconic 6-semialdehyde. The deamination step in the proposed pathway differs from that in the pathways for 2-aminophenol and its derivatives.


Cardiopulmonary resuscitation alone vs. cardiopulmonary resuscitation plus automated external defibrillator use by non-healthcare professionals: a meta-analysis on 1583 cases of out-of-hospital cardiac arrest.
Out-of-hospital cardiac arrest (OHCA) accounts for 250.000-350.000 sudden cardiac deaths per year in the United States. The availability of automated external defibrillators (AEDs) promoted the implementation of public access defibrillation programs based on out-of-hospital early defibrillation by non-healthcare professionals. To perform a systematic review and a meta-analysis of the pooled effect of studies comparing the outcome of pts receiving cardiopulmonary resuscitation plus AED therapy (CPR+AED) vs. cardiopulmonary resuscitation (CPR) alone, both delivered by non-healthcare professionals, for the treatment of OHCA. We performed a search of the relevant literature exploring major scientific databases, carrying out a hand search of key journals, analysing conference proceedings and abstracts and discussing the topic with other researchers. Two analyses were planned to assess the outcomes of interest (survival to hospital admission and survival to hospital discharge). Three studies were selected for the meta-analysis. The first meta-analysis evidenced a RR of 1.22 (95% C.I.: 1.04-1.43) of surviving to hospital admission for people treated with CPR+AED as compared to CPR-only. The second meta-analysis showed a RR of 1.39 (95% C.I.: 1.06-1.83) of surviving to hospital discharge for people treated with CPR+AED as compared to CPR-only. The results of our meta-analysis demonstrate that programs based on CPR plus early defibrillation with AEDs by trained non-healthcare professionals offer a survival advantage over CPR-only in OHCA. The conclusions of our meta-analysis add to previous evidence in favour of developing public-health strategies based on AED use by trained layrescuers.


[Persistent pulmonary hypertension in the newborn infant caused by aneurysm of the vein of Galen].
A male full-term neonate is described in whom cardiac insufficiency developed within 24 hours post partum. Ultrasound revealed an arterio-venous fistula of the vein of Galen. The patient's condition did not allow surgical correction and he died on the 22nd day of life. Persistent pulmonary hypertension was an important accompanying feature. The literature is reviewed with respect to the prognosis and the up to now seldom reported complication of persistent pulmonary hypertension of the newborn (PPHN).


Antibiotic Impregnated Beads, Indications in musculoskeletal infection.
The management of musculoskeletal infection as a result of acute extremity injury remains a challenge to the experienced surgeon. The current treatment of acute debridement and wound irrigation remain the most important factors in the prevention of acute or chronic infection. Skeletal stabilisation and appropriate soft tissue coverage are also imperative in the standard care of these complicated traumatic wounds. Once stabilised, severe open fractures remain at risk as a result of the compromised vascularity of the bone and soft tissue. Parenteral broad-spectrum antibiotics are recommended as a prophylaxis to the open wound contamination. In such injuries the therapeutic levels of the antibiotics are frequently diminished by the impaired tissue perfusion, vasospasm, edema and vascular damage.


Cyclic Disilylated and Digermylated Germylenes.
The preparation of triethylphosphine adducts of cyclic disilylated or digermylated germylenes was achieved by reaction of 1,4-dipotassio-1,1,4,4-tetrakis(trimethylsilyl)tetramethyltetrasilane with GeBr2·(dioxane) and PEt3. Phosphine abstraction with B(C6F5)3 allowed formation of the base-free germylenes, which undergo 1,2-trimethylsilyl shifts to the germylene atom to form the respective silagermene or digermene, which further dimerize in [2 + 2] cycloadditions to tricyclic compounds. The reasons responsible for the germylenes' completely different reactivities in comparison to the previously studied analogous stannylenes and plumbylenes were elucidated in a theoretical study.


Legal and ethical considerations of artificial intelligence in skin cancer diagnosis.
Artificial intelligence (AI) technology is becoming increasingly accurate and prevalent for the diagnosis of skin cancers. Commercially available AI diagnostic software is entering markets across the world posing new legal and ethical challenges for both clinicians and software companies. Australia has the highest rates of skin cancer in the world and is poised to be a significant benefactor and pioneer of the technology. This review describes the legal and ethical considerations raised by the emergence of artificial intelligence in skin cancer diagnosis and proposes recommendations for best practice.


Do predictive mechanisms improve the angular vestibulo-ocular reflex in vestibular neuritis?
Recovery from vestibular neuritis (VN) is often incomplete which leads to persistent vestibular imbalance during rapid head movements. Patients with unilateral vestibular lesions have a larger gain of the horizontal vestibulo-ocular reflex during active compared to passive head movements. To test whether this gain increase is related to predictive mechanisms we studied 15 patients with VN and 14 control subjects during predictable and unpredictable passive horizontal head impulses in the light and darkness. The vestibulo-ocular reflex showed a significantly shorter latency and higher gain in the light for predictable head impulses towards the ipsilesional side. However, this effect is small and might contribute but cannot exclusively account for the gain increase during active head movements.


Ferritin is used for iron storage in bloom-forming marine pennate diatoms.
Primary productivity in 30-40% of the world's oceans is limited by availability of the micronutrient iron. Regions with chronically low iron concentrations are sporadically pulsed with new iron inputs by way of dust or lateral advection from continental margins. Addition of iron to surface waters in these areas induces massive phytoplankton blooms dominated primarily by pennate diatoms. Here we provide evidence that the bloom-forming pennate diatoms Pseudo-nitzschia and Fragilariopsis use the iron-concentrating protein, ferritin, to safely store iron. Ferritin has not been reported previously in any member of the Stramenopiles, a diverse eukaryotic lineage that includes unicellular algae, macroalgae and plant parasites. Phylogenetic analyses suggest that ferritin may have arisen in this small subset of diatoms through a lateral gene transfer. The crystal structure and functional assays of recombinant ferritin derived from Pseudo-nitzschia multiseries reveal a maxi-ferritin that exhibits ferroxidase activity and binds iron. The protein is predicted to be targeted to the chloroplast to control the distribution and storage of iron for proper functioning of the photosynthetic machinery. Abundance of Pseudo-nitzschia ferritin transcripts is regulated by iron nutritional status, and is closely tied to the loss and recovery of photosynthetic competence. Enhanced iron storage with ferritin allows the oceanic diatom Pseudo-nitzschia granii to undergo several more cell divisions in the absence of iron than the comparably sized, oceanic centric diatom Thalassiosira oceanica. Ferritin in pennate diatoms probably contributes to their success in chronically low-iron regions that receive intermittent iron inputs, and provides an explanation for the importance of these organisms in regulating oceanic CO(2) over geological timescales.


GUBS: Graph-Based Unsupervised Brain Segmentation in MRI Images.
Brain segmentation in magnetic resonance imaging (MRI) images is the process of isolating the brain from non-brain tissues to simplify the further analysis, such as detecting pathology or calculating volumes. This paper proposes a Graph-based Unsupervised Brain Segmentation (GUBS) that processes 3D MRI images and segments them into brain, non-brain tissues, and backgrounds. GUBS first constructs an adjacency graph from a preprocessed MRI image, weights it by the difference between voxel intensities, and computes its minimum spanning tree (MST). It then uses domain knowledge about the different regions of MRIs to sample representative points from the brain, non-brain, and background regions of the MRI image. The adjacency graph nodes corresponding to sampled points in each region are identified and used as the terminal nodes for paths connecting the regions in the MST. GUBS then computes a subgraph of the MST by first removing the longest edge of the path connecting the terminal nodes in the brain and other regions, followed by removing the longest edge of the path connecting non-brain and background regions. This process results in three labeled, connected components, whose labels are used to segment the brain, non-brain tissues, and the background. GUBS was tested by segmenting 3D T1 weighted MRI images from three publicly available data sets. GUBS shows comparable results to the state-of-the-art methods in terms of performance. However, many competing methods rely on having labeled data available for training. Labeling is a time-intensive and costly process, and a big advantage of GUBS is that it does not require labels.


Could proximal white subungual onychomycosis be a complication of systemic spread? The lessons to be learned from Maladie Dermatophytique and other deep infections.
There are several published cases where dermatophyte infections have spread systemically, resulting in widespread internal dissemination as well as spread to local lymphatics and lymph nodes. The best example is provided by the condition known as Maladie Dermatophytique. In this commentary the arguments are discussed for a potential role of lymphatic dissemination in the development of proximal white subungual onychomycosis, where invasion of the nail plate by fungi proceeds from the proximal nail fold.


Antiplatelet drug resistance: not ready for prime time.
Antiplatelet drug therapy reduces vascular events in a wide range of patients. Although antiplatelet drug resistance is becoming well documented, a universal definition has not been established. This lack and the lack of standardized measures of platelet function make estimation of the prevalence of antiplatelet drug resistance difficult. Mounting evidence suggests that antiplatelet drug resistance is associated with adverse clinical outcomes, which have been assessed in patients with coronary artery disease, myocardial infarction, cerebrovascular disease, and peripheral vascular disease. Patients with antiplatelet drug resistance have significantly more vascular events than patients without such resistance. However, there are no guidelines for the treatment of antiplatelet drug resistance. Although point-of-care platelet-function testing makes screening for resistance feasible, routine screening should not be standard practice until data regarding the management of antiplatelet drug resistance are available.


[Heterogeneity of the iron status in the woman population during the pregnancy in Côte-d'Ivoire].
The iron deficiency is a major problem of public health in the African countries, particularly in pregnant women population. The aim of our study was to appreciate the iron status during the pregnancy period (first, second and three trimesters); to realize an evaluation and to characterize the biological indicators of pregnant women. Our study was carried out in four medical and urban units of Abidjan in Côte-d'Ivoire with 531 pregnant women. The biological parameters significantly reduced in the third trimester of the pregnancy. But, an enhancement of the transferrin and the total iron binding capacity was observed. Moreover, 66 % of pregnant women presented iron deficiency anaemia (p < 0.01). In conclusion, the study shows that no pregnant woman presented iron normal status in the third trimester of the pregnancy.


A history of the early days of personality testing in American industry: an obsession with adjustment.
Objective personality testing began with Woodworth's Personal Data Sheet in 1917. That test was developed to identify soldiers prone to nervous breakdowns during enemy bombardment in World War I (WWI). Soon after, many competing personality tests were developed for use in industry. Many of these tests, like Woodworth's, focused on the construct of employee maladjustment and were deemed important in screening out applicants who would create workplace disturbances. In this article, the authors review the history of these early personality tests, especially the Bernreuter Personality Inventory and the Humm-Wadsworth Temperament Scale, and discuss the implications of personality testers' obsession with the construct of employee maladjustment. In addition, the authors discuss the industry's obsession with emotional maladjustment and how this obsession coincided with a cultural shift in norms relating to cultural expression.


Subchondral bone of the human knee joint in aging and osteoarthritis.
Although most research investigating the pathogenesis of osteoarthritis (OA) has focused on cartilage, it has been suggested that the subchondral bone (SCB) plays an important role in the development of OA. The relationships between aging, severity of OA change and the SCB thickness and density in the human knee joint specimens from a wide range of ages were examined. One hundred forty knee joints from 72 individuals (25 females, 45 males and 2 unknowns; average age 54.8 years, range 17 to 91 years) were obtained. The surface of the articular cartilage of both the femur and tibia was evaluated for gross morphological changes with a 4-point grading scale. The lateral and medial femoral condyles were cut along a sagittal plane and the tibia along a coronal plane to make bone and cartilage strip specimens. The strips were X-rayed onto mammography film and then scanned into a computer for assessment of SCB thickness and density using image analysis software. Medial tibial SCB thickness was significantly lower among the elderly (age>69 years) than among the young (age<40) or the middle-aged (40 to 69) (P< 0.001 via ANOVA). Lateral tibial SCB thickness also showed the same trend of decreasing thickness with increasing age, but differences between age groups were not statistically significant. Tibial SCB thicknesses were significantly lower in arthritic grades compared to normal grades (P=0.008 in lateral and 0.017 in medial via ANOVA); in contrast, no significant differences between normal and arthritic were found in femoral SCB thicknesses. The arthritic group tended to have lower SCB densities than the normal group, but this was statistically significant in only the lateral femoral condyle. The results obtained in the present study are not consistent with generally accepted notions of the relationship between subchondral bone thickness or density and OA. Subchondral bone changes are not etiologic for OA but, more likely, are secondary to loss of articular cartilage which precedes the appearance of subchondral sclerosis.


Pharmacovigilance with Transformers: A Framework to Detect Adverse Drug Reactions Using BERT Fine-Tuned with FARM.
Adverse drug reactions (ADRs) are the undesirable effects associated with the use of a drug due to some pharmacological action of the drug. During the last few years, social media has become a popular platform where people discuss their health problems and, therefore, has become a popular source to share information related to ADR in the natural language. This paper presents an end-to-end system for modelling ADR detection from the given text by fine-tuning BERT with a highly modular Framework for Adapting Representation Models (FARM). BERT overcame the predominant neural networks bringing remarkable performance gains. However, training BERT is a computationally expensive task which limits its usage for production environments and makes it difficult to determine the most important hyperparameters for the downstream task. Furthermore, developing an end-to-end ADR extraction system comprising two downstream tasks, i.e., text classification for filtering text containing ADRs and extracting ADR mentions from the classified text, is also challenging. The framework used in this work, FARM-BERT, provides support for multitask learning by combining multiple prediction heads which makes training of the end-to-end systems easier and computationally faster. In the proposed model, one prediction head is used for text classification and the other is used for ADR sequence labeling. Experiments are performed on Twitter, PubMed, TwiMed-Twitter, and TwiMed-PubMed datasets. The proposed model is compared with the baseline models and state-of-the-art techniques, and it is shown that it yields better results for the given task with the F-scores of 89.6%, 97.6%, 84.9%, and 95.9% on Twitter, PubMed, TwiMed-Twitter, and TwiMed-PubMed datasets, respectively. Moreover, training time and testing time of the proposed model are compared with BERT's, and it is shown that the proposed model is computationally faster than BERT.


Incidence Trend and Epidemiology of Common Cancers in the Center of Iran.
Cancer is a major public health problem in Iran and many other parts of the world. The cancer incidence is different in various countries and in country provinces. Geographical differences in the cancer incidence lead to be important to conduct an epidemiological study of the disease. This study aimed to investigate cancer epidemiology and trend in the province of Qom, located in center of Iran. This is an analytical cross-sectional study carried out based on re-analysis cancer registry report and the disease management center of health ministry from 2004 to 2008 in the province of Qom. To describe incidence time trends, we carried out join point regression analysis using the software Join point Regression Program, Version 126.96.36.199. There were 3,029 registered cases of cancer during 5 years studied. Sex ratio was 1.32 (male to female). Considering the frequency and mean standardized incidence, the most common cancer in women were breast, skin, colorectal, stomach, and esophagus, respectively while in men the most common cancers included skin, stomach, colorectal, bladder, and prostate, respectively. There was an increasing and significant trend, according to the annual percentage change (APC) equal to 8.08% (CI: 5.1-11.1) for all site cancer in women. The incidence trend of all cancers was increasing in this area. Hence, planning for identifying risk factors and performing programs for dealing with the disease are essential.


Breaking new ground--are changes in immunization services needed for the introduction of future HIV/AIDS vaccines and other new vaccines targeted at adolescents?
A safe, effective and accessible preventive vaccine is our best long-term hope for the control of the HIV/AIDS pandemic. Once the first generation of HIV vaccines are developed, many questions remain unanswered regarding their administration. For instance, which vaccines should be given to whom at what age and how many doses? We argue that pre- and early-adolescents will be one of the main target groups for future HIV vaccines, that is, before the age of exposure to the virus. Historically, immunization has mainly focused on infants. Indeed, vaccines have only occasionally been systematically targeted at adolescents, even in industrialized countries. Delivering vaccines to pre-adolescents and adolescents in developing countries would, to a great extent, be a new challenge. But it is not just HIV/AIDS vaccines that are coming down the pipeline. Herpes simplex type2 (HSV-2) and human papillomavirus (HPV) vaccines are also among the exciting candidate vaccines that may be the agents of change needed to encourage even the poorest countries to develop strategies for reaching adolescents with vaccines and other health services in the coming decade. Together, they may also provide the impetus for changing the paradigm for how vaccines are administered. Not only will more antigens be included in national immunization schedules, but the age of target groups will range much more widely than at present, encompassing older children, adolescents and young adults. While presenting major difficulties for delivery, these new ingredients also offer stimulating opportunities to completely rethink how vaccines are presented, administered and delivered. We predict that even the poorest countries will be looking to developing integrated, sustainable strategies for reaching pre-adolescents and adolescents with vaccines in the coming decade.


[Zinc finger protein 521 suppresses osteogenic differentiation of rat mesenchymal stem cells by inhibiting the Wnt/beta-catenin signaling pathway].
Zinc finger protein 521 (Zfp521) is involved in a number of cellular processes in a variety of cells and tissues. In the present study, the effects of Zfp521 on osteogenic differentiation of rat mesenchymal stem cells (MSCs) were investigated. The results showed that, in rat MSCs, knocking down cellular Zfp521 by short hairpin RNA (shRNA) decreases cell proliferation while promoting ALP activity, calcium accumulation, and the expression of mRNA that encodes bone sialoprotein (BSP), osteocalcin (OCN) and Runx2. Furthermore, in Zfp521-depleted cells, the up-regulation of phospho-Wnt (p-Wnt) and beta-catenin expression levels was detected. However, over-expression of Zfp521 played the opposite role in proliferation and osteogenic differentiation of rat MSCs. To further demonstrate the functions of the Wnt/beta-catenin signaling in Zfp521 regulated-osteogenic differentiation, the activation of Wnt/beta-catenin was blocked with IWP-2 inhibitor. The suppression of the Wnt/beta-catenin pathway completely abrogated the effects of Zfp521 knockdown on osteogenic differentiation of rat MSCs. Therefore, we conclude that Zfp521 regulates osteogenic differentiation of rat MSCs through the suppression of the Wnt/beta-catenin signaling pathway.


Studies on the transmembrane disposition of the neural cell adhesion molecule N-CAM. The use of liposome-inserted radioiodinated N-CAM to study its transbilayer orientation.
The transmembrane orientation of the polypeptide chains present in preparations of adult and neonatal mouse N-CAM was studied using, as a model system, liposome-inserted purified N-CAM preparations. N-CAM purified from adult or neonatal mouse brain was 125I-labeled and reconstituted into artificial lipid vesicles. After trypsin digestion, the peptides that remained associated with the liposomes were isolated by floatation of the vesicles on sucrose gradients. In control experiments the liposomes were lysed before trypsin treatment. Large, overlapping peptides were obtained after this treatment, several of which were protected by the liposome membrane. Sialic-acid-bearing peptides were revealed by their sensitivity to neuraminidase. To distinguish between peptides corresponding to intracellular or extracellular domains use was made of the P61 and H28.123 monoclonal antibodies, which recognize determinants located on the cytoplasmic and the extracellular part of the molecules respectively. There was no indication that the N-CAM chains were inserted in an inside-out configuration. Peptides protected from trypsin attack by the liposomes and recognized only by P61 had Mr values of 92 000, 42 000 and 35 000. The H28.123 determinant could be mapped to a 32 000-Mr peptide located close to the membrane at the vesicle's exterior. The bulk of the sialic acid seemed to be carried by a rather short sequence distal to the H28.123-reactive peptide but at some distance from the N terminus. Fragments of very similar Mr were generated from young and adult material. However, a 45 000-Mr peptide from neonatal N-CAM appeared to migrate in the higher-Mr region of sodium dodecyl sulfate/polyacrylamide gels in its fully sialylated form. It is concluded that (a) identical polypeptide chains are present in young and adult preparation, (b) the 180 000-Mr, 140 000-Mr and 120 000-Mr chains differ by the length of their cytoplasmic extensions and (c) the largest cytoplasmic sequences have a Mr close to 90 000. A tentative linear model of the transmembrane topography of the N-CAM polypeptides is presented.


Making the case for caregiver research in geriatric psychiatry.
Research on caregiver health has seen a groundswell of interest in the last few years. Unfortunately, most of this literature has appeared in venues not usually seen by psychiatrist-geriatricians. In this article, the authors argue that caregiver research is not only relevant to the geriatric mental health community, but it is especially important to geriatric psychiatry. To do this, they focus on five areas: 1) an overview of caregiver outcomes and metaanalysis of relationships of caregiver distress/psychiatric morbidity with physiological/physical indices; 2) definitions and examples of moderators and mediators of relationships of caregiver status with health indices, including comorbidity of caregiving with psychiatric/medical illnesses; 3) caregiver/care-recipient trajectories and reciprocal relationships among dyads; 4) prospective studies; and, 5) areas to consider in caregiver interventions. Great strides have been made in caregiver research, but much more needs to be done. Psychiatric geriatricians are well placed to advance caregiver research because of their unique training in medicine, psychotherapy, pharmacology, and aging. They hope the discussion of this research will encourage work in this important area.


Subtypes of renal cell carcinoma: MRI and pathological features.
Renal cell carcinoma (RCC) is the most common malignant tumor involving the kidney. Determining the subtypes of renal cell carcinoma is among the major goals of preoperative radiological work-up. Among all modalities, magnetic resonance imaging (MRI) has several advantages, such as inherent soft tissue contrast, detection of lipid and blood products, and excellent sensitivity to detect small amounts of intravenous contrast, which facilitate the discrimination of subtypes of RCC. In this article, we review MRI and pathological features used for determining the main histologic subtypes of RCC, including clear cell, papillary, collecting duct, chromophobe, multilocular cystic, and unclassified RCC.


Deletion or substitution within the alpha platelet-derived growth factor receptor kinase insert domain: effects on functional coupling with intracellular signaling pathways.
The tyrosine kinase domains of the platelet-derived growth factor (PDGF) and colony-stimulating factor-1 (CSF-1)/c-fms receptors are interrupted by kinase inserts (ki) which vary in length and amino acid sequence. To define the role of the ki in the human alpha PDGF receptor (alpha PDGFR), we generated deletion mutants, designated alpha R delta ki-1 and alpha R delta ki-2, which lacked 80 (710 to 789) and 95 (695 to 789) amino acids of the 104-amino-acid ki region, respectively. Their functional characteristics were compared with those of the wild-type alpha PDGFR following introduction into a naive hematopoietic cell line, 32D. Biochemical responses, including PDGF-stimulated PDGFR tyrosine phosphorylation, phosphatidylinositol (PI) turnover, and receptor-associated PI-3 kinase activity, were differentially impaired by the deletions. Despite a lack of any detectable receptor-associated PI-3 kinase activity, 32D cells expressing alpha R delta ki-1 showed only partially impaired chemotactic and mitogenic responses and were capable of sustained proliferation in vitro and in vivo under conditions of autocrine stimulation by the c-sis product. 32D transfectants expressing the larger ki deletion (alpha R delta ki-2) showed markedly decreased or abolished biochemical and biological responses. However, insertion of the highly unrelated smaller c-fms (685 to 750) ki domain into alpha R delta ki-2 restored each of these activities to wild-type alpha PDGFR levels. Since the CSF-1R does not normally induce PI turnover, the ability of the c-fms ki domain to reconstitute PI turnover in the alpha R delta ki-2 transfectant provides evidence that the ki domain of the alpha PDGFR does not directly couple with this pathway. Taken together, all od these bindings imply that their ki domains have evolved to play very similar roles in the known signaling functions PDGF and CSF-1 receptors.


[Sleeping disorders can imitate attention deficit/hyperactivity disorder].
Attention deficit/hyperactivity disorder (ADHD) is often associated with anxiety, depression, oppositional defiant disorder and sleeping difficulties. Sleeping disorders are reported in more than 50% of children with ADHD. On the other hand, symptoms of sleep disorder, inattention, hyperactivity and impulsiveness can imitate the symptoms of ADHD. We describe a 5(1/2)-year-old boy with symptoms of attention deficit and social withdrawal. His sleep was disturbed, with late sleep onset and frequent awakening during the night. After correction of his sleep pattern, the symptoms of attention deficit and social withdrawal disappeared.


Process-based modeling of species' distributions: what limits temperate tree species' range boundaries?
Niche-based models are widely used to understand what environmental factors determine species' distributions, but they do not provide a clear framework to study the processes involved in defining species' ranges. Here we used a process-based model to identify these processes and to assess the potential distribution of 17 North American boreal/temperate tree species. Using input of only climate and soil properties, the model reproduced the 17 species' distributions accurately. Our results allowed us to identify the climatic factors as well as the biological processes involved in limiting species' ranges. The model showed that climatic constraints limit species' distributions mainly through their impact on phenological processes, and secondarily through their impact on drought and frost mortality. The northern limit of species' ranges appears to be caused mainly by the inability to undergo full fruit ripening and/or flowering, while the southern limit is caused by the inability to flower or by frost injury to flowers. These findings about the ecological processes shaping tree species' distribution represent a crucial step toward obtaining a more complete picture of the potential impact of climate on species' ranges.


Efficacy and safety of manual acupuncture manipulations with different frequencies on epigastric pain syndrome (EPS) in functional dyspepsia (FD) patients: study protocol for a randomized controlled trial.
Manual acupuncture (MA) manipulations are one of the key factors influencing acupuncture effects in traditional Chinese medicine theory. Different MA manipulations contain different stimulating parameters, thus generating different acupuncture responses or effects. Evidence has demonstrated that acupuncture is effective for functional dyspepsia (FD). However, the effects of different stimulating parameters of MA manipulations on FD remain unclear. This study is a randomized controlled trial with a four-arm, parallel-group structure. Patients with FD with epigastric pain syndrome (EPS) will be included and randomly allocated into four groups: three MA manipulation groups (separately treated with a frequency of 1 Hz, 2 Hz, or 3 Hz) and a control group. All groups will receive omeprazole as a basic treatment and acupuncture: in the MA manipulation groups, the needles will be manipulated manually with three different frequencies on the basis when de qi is reached, while in the control group, the needles will be inserted without any manipulation. All patients will receive acupuncture treatment of five consecutive sessions per week for 2 weeks and be followed up at 4, 8, and 12 weeks. The primary outcomes of the study include patients' response to the treatment. The secondary outcomes include dyspeptic symptoms, quality of life, mental status, fasting serum gastrin, motilin, and ghrelin concentrations, and adverse events. The protocol was approved by the Ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (2016-K-057-01). The aim of this study is to evaluate the efficacy and safety of MA manipulations with different stimulating parameters (different frequencies) on EPS in patients with FD. Chinese Clinical Trial Registry, ChiCTR-IOR-16008189 . Registered on 30 March 2016.


Differences in faecal bacterial communities in coeliac and healthy children as detected by PCR and denaturing gradient gel electrophoresis.
Coeliac disease (CD) is a chronic inflammatory disorder of the small intestinal mucosa. Scientific evidence supports a role of the gut microbiota in chronic inflammatory disorders; yet information is not specifically available for CD. In this study, a comparative denaturing gradient gel electrophoresis analysis of faecal samples from coeliac children and age-matched controls was carried out. The diversity of the faecal microbiota was significantly higher in coeliac children than in healthy controls. The presence of the species Lactobacillus curvatus, Leuconostoc mesenteroides and Leuconostoc carnosum was characteristic of coeliac patients, while that of the Lactobacillus casei group was characteristic of healthy controls. The Bifidobacterium population showed a significantly higher species diversity in healthy children than in coeliacs. In healthy children, this population was characterized by the presence of Bifidobacterium adolescentis. Overall, the results highlighted the need for further characterization of the microbiota in coeliac patients, and suggested a potential role of probiotics and/or prebiotics in restoring their gut microbial balance.


Investigation of biochemical factors related to non-bothersome nocturnal urination.
We investigated the factors related to nocturnal urination that was not considered bothersome by comparing various parameters between subjects who felt nocturnal urination as bothersome and those who did not. A total of 94 persons (50 males and 44 females) were enrolled. They urinated >or= once per night. Each subject's perception of nocturnal urination was examined, and the subjects were divided into a bothersome group and a non-bothersome group. Blood biochemical data and urinary condition were compared between the two groups and various subgroups. There were 60 subjects (56 +/- 17 years old) in the non-bothersome group, and 34 subjects (57 +/- 17 years old) in the bothersome group. The serum melatonin level was significantly lower and the total score of the International Prostatic Symptom Score questionnaire (IPSS) and the quality of life (QOL) score were significantly higher in the bothersome group than in the non-bothersome group. Among 50 subjects with nocturnal urination >or= twice per night, the serum melatonin level was also significantly lower and the QOL score was significantly higher in the bothersome group than in the non-bothersome group. In conclusion, nocturnal urination might be not considered bothersome when subjects maintain sufficient levels of melatonin.


Pure red cell aplasia with malignant thymoma: a rarity.
Pure red cell aplasia sometimes accompanies thymoma. Herein we report a PRCA patient with malignant thymoma. Only two Indian cases of PRCA with malignant thymoma have been reported so far and six cases in the world literature, to the best of our knowledge. This paper describes a malignant thymoma in a 40 year old male who later on developed pure red cell aplasia 7 months after thymectomy.


Charge-transfer complexes of N-methyl-and N-ethylcarbazole with 3,5-dinitrobenzonitrile.
In the two title compounds, N-methylcarbazole-3,5-dinitrobenzonitrile (1/1), C(13)H(11)N.C(7)H(3)N(3)O(4), (I), and N-ethylcarbazole-3,5-dinitrobenzonitrile (1/1), C(14)H(13)N.C(7)H(3)N(3)O(4), (II), the donor and acceptor molecules are stacked alternately to form one-dimensional columns. In (I), the N-methyl group of the donor is nearly eclipsed with respect to one of the nitro groups of the neighboring acceptor in a column, whereas the N-ethyl group is anti with respect to the cyano group of the neighboring acceptor in (II).


Identification of cow and buffalo milk based on Beta carotene and vitamin-A concentration using fluorescence spectroscopy.
The current study presents the application of fluorescence spectroscopy for the identification of cow and buffalo milk based on β-carotene and vitamin-A which is of prime importance from the nutritional point of view. All samples were collected from healthy animals of different breeds at the time of lactation in the vicinity of Islamabad, Pakistan. Cow and buffalo milk shows differences at fluorescence emission appeared at band position 382 nm, 440 nm, 505 nm and 525 nm both in classical geometry (right angle) setup as well as front face fluorescence setup. In front face fluorescence geometry, synchronous fluorescence emission shows clear differences at 410 nm and 440 nm between the milk samples of both these species. These fluorescence emissions correspond to fats, vitamin-A and β-carotene. Principal Component Analysis (PCA) further highlighted these differences by showing clear separation between the two data sets on the basis of features obtained from their fluorescence emission spectra. These results indicate that classical geometry (fixed excitation wavelength) as well as front face (synchronous fluorescence emission) of cow and buffalo milk nutrients could be used as fingerprint from identification point of view. This same approach can effectively be used for the determination of adulterants in the milk and other dairy products.


High prevalence of Salmonella and IMP-4-producing Enterobacteriaceae in the silver gull on Five Islands, Australia.
The objective of this study was to investigate the silver gull as an indicator of environmental contamination by salmonellae and carbapenemase-producing Enterobacteriaceae (CPE) in south-east Australia. A total of 504 cloacal samples were collected from gull chicks at three nesting colonies in New South Wales, Australia [White Bay (n = 144), Five Islands (n = 200) and Montague Island (n = 160)] and were examined for salmonellae and CPE. Isolates were tested for carbapenemase genes and susceptibility to 14 antibiotics. Clonality was determined by PFGE and MLST. Genetic context and conjugative transfer of the carbapenemase gene were determined. A total of 120 CPE of 10 species, mainly Escherichia coli (n = 85), carrying the gene blaIMP-4, blaIMP-38 or blaIMP-26 were obtained from 80 (40%) gulls from Five Islands. Thirty percent of birds from this colony were colonized by salmonellae. Most isolates contained the gene within a class 1 integron showing a blaIMP-4-qacG-aacA4-catB3 array. The blaIMP gene was carried by conjugative plasmids of variable sizes (80-400 kb) and diverse replicons, including HI2-N (n = 30), HI2 (11), A/C (17), A/C-Y (2), L/M (5), I1 (1) and non-typeable (6). Despite the overall high genetic variability, common clones and plasmid types were shared by different birds and bacterial isolates, respectively. Our data demonstrate a large-scale transmission of carbapenemase-producing bacteria into wildlife, likely as a result of the feeding habits of the birds at a local waste depot. The isolates from gulls showed significant similarities with clinical isolates from Australia, suggesting the human origin of the isolates. The sources of CPE for gulls on Five Islands should be explored and proper measures applied to stop the transmission into the environment.


Characterizing the 'feel-good experience' in multiple sclerosis patients treated with natalizumab or other therapies.
Aim: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with natalizumab have anecdotally reported a 'feel-good experience' (FGE). The authors characterized the FGE using survey data from patients with RRMS treated with natalizumab or other disease-modifying therapies (other-DMT). Methods: Questionnaire data from RRMS patients who use MyMSTeam, an online patient social network, were analyzed. Results: The survey included 347 patients (95 natalizumab; 252 other-DMT). More natalizumab than other-DMT patients self-reported having an FGE (62.1 vs 44.8%; p = 0.001) as well as other physical, emotional and cognitive benefits. Conclusion: This study demonstrates that physical, emotional and cognitive benefits were more commonly reported by patients treated with natalizumab than those treated with other disease-modifying therapies and helps characterize patient-reported factors associated with the FGE.


Circular RNA circ_0111277 attenuates human trophoblast cell invasion and migration by regulating miR-494/HTRA1/Notch-1 signal pathway in pre-eclampsia.
Mounting evidence has revealed that impaired spiral artery remodeling, placental dysfunction, and inadequate trophoblast invasion are closely correlated with the etiology and pathogenesis of pre-eclampsia (PE). Moreover, defective trophoblast invasion may trigger poor maternal-fetal circulation and placental hypoxia, leading to PE. However, the detailed molecular pathology of PE remains unclear. Although circRNAs, as a new type of stable and abundant endogenous noncoding RNA, have been proven to be essential to the pathogenesis of various diseases, their role in PE requires further verification. In this context, it is necessary to unveil the roles of circRNAs in regulating the migration and invasion of extravillous trophoblasts. In this study, using quantitative real-time PCR, we confirmed that hsa_circ_0111277 was upregulated in PE placentas relative to the level in normal pregnancy placentas. In addition, positive correlations between hsa_circ_0111277 expression and PE-related factors (proteinuria level at 24 h and placental weight) were identified by Pearson's analysis based on the clinical data of 25 PE patients. Moreover, fluorescence in situ hybridization analysis illustrated that circ_0111277 was preferentially localized within the cytoplasm. Mechanistically, circ_0111277 sponged hsa-miR-494-3p in trophoblast cells to attenuate the latter's repression by regulating HTRA1/Notch-1 expression. In conclusion, trophoblast cell migration and invasion were shown to be promoted and modulated by the hsa_circ_0111277/miR-494-3p/HTRA1/Notch-1 axis, which provides useful insight for exploring a new therapeutic approach for PE.


Synthesis of the [126.96.36.199] Tetracyclic Core of Calyciphylline N via a Boc-Mediated Oxidative Dearomatization/Diels-Alder Approach.
A sequential process involving Boc-mediated oxidative dearomatization and inter/intramolecular Diels-Alder reaction was investigated. Based on an intermolecular Diels-Alder reaction and subsequently a radical 7-endo-trig type cyclization, the [18.104.22.168] tetracyclic core of Calyciphylline N was assembled.


Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories.
Ebola virus (EBOV) infection induces the formation of membrane-less, cytoplasmic compartments termed viral factories, in which multiple viral proteins gather and coordinate viral transcription, replication, and assembly. Key to viral factory function is the recruitment of EBOV polymerase, a multifunctional machine that mediates transcription and replication of the viral RNA genome. We show that intracellularly reconstituted EBOV viral factories are biomolecular condensates, with composition-dependent internal exchange dynamics that likely facilitates viral replication. Within the viral factory, we found the EBOV polymerase clusters into foci. The distance between these foci increases when viral replication is enabled. In addition to the typical droplet-like viral factories, we report the formation of network-like viral factories during EBOV infection. Unlike droplet-like viral factories, network-like factories are inactive for EBOV nucleocapsid assembly. This unique view of EBOV propagation suggests a form-to-function relationship that describes how physical properties and internal structures of biomolecular condensates influence viral biogenesis.


Solitary Celiac Lymph Node Metastasis Has a Better Long-Term Survival Compared With Solitary Mediastinal Lymph Node Metastasis in Esophagectomy of Esophageal Squamous Cell Cancer: A Propensity Score Matching Analysis.
The prognostic benefit of extensive lymphadenectomy remains controversial in esophageal squamous cell carcinoma (ESCC). The purpose of this retrospective study was to investigate the potential effect of solitary mediastinal (SM) lymph node metastasis and solitary celiac (SC) lymph node metastasis on the short- and long-term outcomes for patients who underwent minimally invasive McKeown esophagectomy. From September 2009 to December 2020, a total of 934 cases were diagnosed with ESCC and underwent minimally invasive McKeown esophagectomy in our department; 223 cases met the inclusion and exclusion criteria. Propensity score matching (PSM) was utilized to contrast the postoperative results and long-term survival of Group 1 (SM) and Group 2 (SC). Univariate and multivariate Cox proportional hazards regression analyses were used on possible predictors of survival. One hundred forty-seven patients were available for outcome comparison after PSM. The postoperative results were not significantly different between the two groups. In terms of long-term survival, the 5-year disease-free survival (DFS) was 37.6% and 57.3% (p = 0.191) and 5-year disease-specific survival (DSS) was 39.7% and 68.4% (p = 0.028) for Group 1 (SM) and Group 2 (SC), respectively. Univariate and multivariate Cox proportional hazards regression analyses showed that body mass index (BMI), pathologic stage (pStage), and SC/SM grouping had significant hazard ratios (HRs), which suggested that SC is associated with better DSS. This cohort study showed that SC lymph node metastasis has a better long-term survival compared with SM lymph node metastasis in esophagectomy of ESCC. The results challenge the current understanding and need confirmation in further research.


Oral nafazatrom in man: effect on inhaled antigen challenge.
The effect of oral nafazatrom (Bay g6575, 2 X 3 g) or placebo on inhaled antigen challenge was assessed in a double-blind study. In four subjects antigen challenge resulted in an immediate fall of 93.2 +/- 3.36% in airflow at 40% of vital capacity (Vp40) and a 45.85 +/- 4.95% reduction in forced partial expiratory volume at one second (FEV1). Neither nafazatrom nor placebo had any effect on baseline lung function or that after challenge. Leukotriene B4 was generated by ex vivo stimulus of blood with ionophore A23187, and quantified by high performance liquid chromatography (h.p.l.c.)-radioimmunoassay. No inhibition of LTB4 formation occurred ex vivo following oral nafazatrom, although addition of 10(-5) M nafazatrom to blood in vitro significantly inhibited LTB4 release. Peak plasma nafazatrom levels during the study ranged from 3.3 X 10(-7) M to 1.47 X 10(-6) M which are below the concentration (10(-5) M) at which significant 5-lipoxygenase inhibition occurs in vitro. Oral nafazatrom is ineffective as a 5-lipoxygenase inhibitor in man, probably because of poor bioavailability after administration.


Potent suppressive effects of 3-O-methylquercetin 5,7,3',4'-O-tetraacetate on ovalbumin-induced airway hyperresponsiveness.
We investigated the suppressive effects of 3-O-methylquercetin 5,7,3',4'- O-tetraacetate (QMTA), a more-potent phosphodiesterase (PDE)3/4 inhibitor than quercetin 3-O-methyl ether (3-MQ), which has been reported to have the potential for treating asthma, against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR). The IC50 value of QMTA for PDE3 was significantly less than that for PDE4. According to the Lineweaver-Burk analysis, QMTA (1-10 microM) competitively inhibited PDE3 and PDE4 activities. The Ki values were 0.9+/-0.3 (n=5) and 3.9+/-0.5 (n=5) microM, respectively, which significantly differed from each other, suggesting that QMTA has higher affinity for PDE3 than for PDE4. QMTA (3-10 microM) concentration-dependently relaxed the baseline level, and significantly inhibited cumulative OVA (10-100 microg/mL)-induced contractions in isolated sensitized guinea pig trachealis suggesting that QMTA has bronchodilator and inhibiting effects on mast cell degranulation. After the secondary challenge, the AHR was measured in unrestrained OVA-sensitized mice, with nebulized methacholine (MCh, 6.25-50 mg/mL), by barometric plethysmography using a whole-body plethysmograph. In the present results, QMTA (3-10 micromol/kg, I. P.) dose-dependently attenuated the enhanced pause (Penh) value induced by MCh (25-50 mg/mL). QMTA (3-10 micromol/kg, I. P.) also significantly inhibited total inflammatory cells, macrophages, neutrophils, lymphocytes, and eosinophils in BALF after determination of Penh values. It also significantly suppressed the release of interleukin (IL)-2, IL-4, IL-5, IFN-gamma, and TNF-alpha, with the exception that 3 micromol/kg QMTA did not suppress the releases of IL-5. QMTA even at 1 micromol/kg significantly inhibited eosinophils, IL-2, and TNF-alpha. In conclusion, our results strongly suggest that QMTA has greater potential than 3-MQ for the treatment of asthma.


Production of inhibin A and inhibin B in boars: changes in testicular and circulating levels of dimeric inhibins and characterization of inhibin forms during testis growth.
We investigated the production of inhibin in boars from the infantile to pubertal periods by: (1) measurement of testicular and circulating levels of inhibin, (2) characterization of inhibin forms and (3) localization of inhibin alpha subunits in the testis. Total inhibin levels in the testis increased until 8 weeks of age but then declined to much lower values at 15 weeks. Testicular inhibin A and inhibin B were high until 8 weeks. Circulating levels of total inhibin and inhibin A were also high until 8 weeks, then declined from 10 weeks; inhibin B was not detected, because of low sensitivity of the inhibin B assay. Analyses of inhibin A and inhibin B levels in the eluted fractions obtained from testes after immunoaffinity chromatography and SDS-PAGE showed the presence of a peak of approximately 45 kDa until 10 weeks of age. As the boars aged, the levels of inhibin A and inhibin B increased in the molecular weight region of 29-31 kDa. The fractions corresponding to 29 and 30 kDa suppressed FSH release from rat pituitary cells, but the 45 kDa fraction had no FSH-suppressing activity. Total amounts of inhibin A isolated from the SDS gels were similar to those of inhibin B until 10 weeks of age, but were three times higher than those of inhibin B between 15 and 25 weeks. Further fractionation by reverse phase high-performance liquid chromatography revealed that the 29-31 kDa immunoreactive material was composed of mature forms of inhibin A and inhibin B, in addition to a 26 kDa alpha monomer. Immunohistochemistry indicated that positive immunostaining for the alpha subunits was observed in Sertoli cells from the infantile to pubertal periods. Elongated spermatids also showed positive signals at age 25 weeks. These results clearly indicated that: (1) the boar testis has the ability to produce inhibin A and inhibin B during the infantile period but inhibin A is the predominant form towards puberty and (2) the molecular weight forms of inhibin and the sites of production of inhibin change with testicular development.


Differences in productivity and collaboration patterns on spine-related research between neurosurgeons and orthopedic spine surgeons: Bibliometric analysis.
Spinal surgeries are commonly performed by neurosurgeons and orthopedic spine surgeons, with many spine-related articles published by them. However, there has been limited research that directly compares their research achievements. This article conducted a comparative analysis of spine-related research achievements between neurosurgeons and orthopedic spine surgeons. This study examines differences in productivity and impact on spine-related research between them using these measures, particularly with a novel clustering algorithm. We gathered 2148 articles written by neurosurgeons and orthopedic spine surgeons from the Web of Science core collections, covering the period from 2013 to 2022. To analyze author collaborations, we employed the follower-leader clustering algorithm (FLCA) and conducted cluster analysis. A 3-part analysis was carried out: cluster analysis of author collaborations; mean citation analysis; and a category, journal, authorship, L-index (CJAL) score based on article category, journal impact factors, authorships, and L-indices. We then utilized R to create visual displays of our findings, including circle bar charts, heatmaps with dendrograms, 4-quadrant radar plots, and forest plots. The mean citations and CJAL scores were compared between neurosurgeons and orthopedic spine surgeons. When considering first and corresponding authors, orthopedics authors wrote a greater proportion of the articles in the article collections, accounting for 75% (1600 out of 2148). The CJAL score based on the top 10 units each also favored orthopedic spine surgeons, with 71% (3626 out of 6139) of the total score attributed to them. Using the FLCA, we observed that orthopedic spine surgeons tended to have more collaborations across countries. Additionally, while citation per article favored orthopedic spine surgeons with standard mean difference (= -0.66) and 95%CI: -0.76, -0.56, the mean CJAL score in difference (= 0.34) favored neurosurgeons with 95%CI: 0.24 0.44. Orthopedic spine surgeons have a higher number of publications, citations, and CJAL scores in spine research than those in neurosurgeons. Orthopedic spine surgeons tend to have more collaborations and coauthored papers in the field. The study highlights the differences in research productivity and collaboration patterns between the 2 authors in spine research and sheds light on potential contributing factors. The study recommends the use of FLCA for future bibliographical studies.


Characterization of low-affinity binding sites for glibenclamide on the Kir6.2 subunit of the beta-cell KATP channel.
The ATP-sensitive K+ channel, an octameric complex of two structurally unrelated types of subunits, SUR1 and Kir6.2, plays a central role in the physiological regulation of insulin secretion. The sulfonylurea glibenclamide, which trigger insulin secretion by blocking the ATP-sensitive K+ channel, interacts with both high and low affinity binding sites present on beta-cells. The high affinity binding site has been localized on SUR1 but the molecular nature of the low affinity site is still uncertain. In this study, we analyzed the pharmacology of glibenclamide in a transformed COS-7 cell line expressing the rat Kir6.2 cDNA and compared with that of the MIN6 beta cell line expressing natively both the Kir6.2 and the SUR1 subunits. Binding studies and Scatchard analysis revealed the presence of a single class of low affinity binding sites for glibenclamide on the COS/Kir6.2 cells with characteristics similar to that observed for the low affinity site of the MIN6 beta cells.


A randomized double blind trial of verbal NSAID education compared to verbal and written education.
We performed a double blind randomized controlled trial to investigate whether patients taking nonsteroidal antiinflammatory drugs (NSAID) knew more about these drugs at followup depending on whether they were randomized to receiving or not receiving an NSAID information sheet. The patients were unaware they were in a study. All patients received verbal education on the side effects of NSAID that was standardized and always given by the same rheumatologist. Thirty patients randomly received an NSAID information sheet and 26 patients did not. At next clinic followup, after reading a letter of explanation about the study and signing a consent form, patients completed a questionnaire asking about their knowledge of NSAID. Outcome variables assessed within the questionnaire included whether NSAID : (1) can decrease inflammation; (2) help with pain; (3) cause stomach upset and bleeding in the bowels. None of these variables were statistically significant. The only variable that was statistically significantly different between the groups was their report of whether they had received an information sheet about NSAID (p<0.00004). A greater proportion of patients who received the NSAID information sheet correctly reported they had received one compared to those who had not received one and who said they had not received one (85% in the former group, 70% in the latter group). The group who received the NSAID information sheet were more apt to say that NSAID can help with their pain (odds ratio 6.1, p<0.05). Education level was positively correlated with knowledge (p<0.04). However, level of education explained only 11% of the variance in overall knowledge scores (r=0.34) among all patients. An information sheet may not add educational value over verbal information by a physician in a clinic setting.


Crystal Crosslinked Gels for the Deposition of Inorganic Salts with Polyhedral Shapes.
Biomineralization has been given a great deal of attention by materials chemists because of its low environmental load and sustainability. With the goal of synthesizing such processes, various methods have been developed, especially for inorganic salts of calcium. In this report, we focused on the deposition of inorganic salts, such as calcium carbonate and calcium phosphate using crystal crosslinked gels (CCG), which are prepared by crystal crosslinking of metal-organic frameworks (MOFs). Due to the crystalline nature of MOFs, CCGs intrinsically possess polyhedral shapes derived from the original MOF crystals. As the result of deposition, the obtained inorganic salts also exhibited a polyhedral shape derived from the CCG. The deposition mainly occurred near the surface of the CCG, and the amorphous nature of the deposited inorganic salts was also confirmed.


Huntington's disease: N-methyl-D-aspartate receptor coagonist glycine is increased in platelets.
Experiments in vertebrates and striatal tissue cultures have provided evidence for a neuroexcitotoxic cause for the neurodegeneration in Huntington's disease (HD), via N-methyl-D-aspartate (NMDA) receptors. Glycine in vitro increases the response of NMDA receptors to its agonists via the NMDA receptor-associated glycine receptor, and the same effect has been observed in vivo. Significantly increased levels of glycine have previously been found in the cerebrospinal fluid of patients with HD. In this present study glycine was measured in platelets and plasma of patients with HD and in controls by high-pressure liquid chromatography. Mean glycine concentration was significantly increased (P < or = 0.01) in platelets in HD compared to controls, though plasma glycine was normal. A possible role for glycine in the pathogenesis of HD, based on the excitotoxicity hypothesis of HD, is discussed.


Protective effect of loratadine on specific conjunctival provocation test.
The protective effect of loratadine (anti-H1 antagonist) on clinical and cellular processes following the early phase of specific conjunctival provocation test was assessed in 20 patients affected by seasonal allergic rhinoconjunctivitis, in a double-blind, randomized, placebo-controlled, parallel-group study. Patients were randomly assigned to two treatment groups, each being given a single daily dose of loratadine 10 mg or placebo, for 7 days, out of pollen season. Pretreatment with Loratadine resulted in a significant higher allergen threshold dose than placebo (p less than 0.01). Patients treated with loratadine experienced a significant reduction (p less than 0.01) in conjunctival symptom severity as compared with placebo, following conjunctival challenge. Finally, the number of inflammatory cells was lower in the loratadine-treated patients compared to the placebo group (p less than 0.01). In conclusion, loratadine exerts a significant protective effect on the early phase cellular and clinical events of conjunctival reaction induced by allergen challenge in atopic patients.


Anisotropic limit of the bond-percolation model and conformal invariance in curved geometries.
We investigate the anisotropic limit of the bond-percolation model in d dimensions, which is equivalent to a (d-1) -dimensional quantum q-->1 Potts model. We formulate an efficient Monte Carlo method for this model. Its application shows that the anisotropic model fits well with the percolation universality class in d dimensions. For three-dimensional rectangular geometry, we determine the critical point as t(c) =8.6429(4), and determine the length ratio as alpha(0) =1.5844(3), which relates the anisotropic limit of the percolation model and its isotropic version. On this basis, we simulate critical systems in several curved geometries including a spheroid and a spherocylinder. Using finite-size scaling and the assumption of conformal invariance, we determine the bulk and surface magnetic exponents in two and three dimensions. They are in good agreement with the existing results.


Family history of autoimmune diseases in psychosis.
The mothers of 101 psychotic patients and 116 normal controls were interviewed using a semi-structured questionnaire designed to determine the presence or absence of autoimmune disorders in first degree relatives of the probands. Thyrotoxicosis and insulin-dependent diabetes mellitus were significantly more common in the relatives of the psychotic patients than in the control relatives; in particular thyrotoxicosis was more frequent in the mothers of patients (11%) than the mothers of controls (2.6%). None of the examined characteristics of the patients, including RDC-diagnosis, family history of psychosis, age at onset of psychosis and winter birth, was predictive of thyrotoxicosis and insulin-dependent diabetes mellitus in relatives.


The use of citrullinated peptides for the diagnosis and prognosis of rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint inflammation and extra-articular manifestations. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing RA. ACPAs may be detected several years before symptoms appear, and their presence at disease onset is a good predictor of the development of erosive joint lesions. Synthetic peptides can replace cognate proteins in solid-phase assays for specific autoantibody recognition in RA patients. The use of synthetic peptides instead of proteins represents an advantage in terms of the reproducibility of such immunoassays. They give absolute control over the exact epitopes presented. Furthermore, it is difficult to prepare sufficient amounts of high-quality antigenic proteins with a well-defined degree of citrullination. Synthetic citrullinated peptides, in contrast, are easily obtained in a pure form with a well-defined chemical structure and the epitopes can be precisely oriented in the plate by covalent binding of the peptides. We have recently obtained and highlighted the application of chimeric peptides bearing different citrullinated protein domains for the design of RA diagnosis systems. Our results indicate that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported (fibrin, vimentin and filaggrin) helps to identify a particular subset of RA patients.


Acute Alcohol Binge Deteriorates Metabolic and Respiratory Compensation Capability After Blunt Chest Trauma Followed by Hemorrhagic Shock-A New Research Model.
The clinical relevance of blunt (thoracic) chest trauma (TxT) and hemorrhagic shock is indisputable due to the high prevalence of this injury type, as well as its close association with mortality and/or preventable deaths. Furthermore, there is an ongoing discussion about the influence of alcohol in trauma patients. Thus, we established a model of TxT followed by hemorrhagic shock with resuscitation (H/R) in alcohol-intoxicated rats. Depending on group allocation, 12 (subacute) or 2 (acute) hours before experimentation, the animals received a single oral dose of alcohol (ethanol [EtOH]) or saline (NaCl) followed by TxT, hemorrhagic shock (35 ± 3 mm Hg), and resuscitation (TxT + H/R). Arterial blood gas analyses and continuous monitoring of blood pressure were performed during the experimentation period. Survival during the experimentation procedure was determined. Subacute and acute EtOH group exhibited lower baseline mean arterial blood pressure values compared with the corresponding NaCl group, respectively. Both EtOH groups showed lower maximal bleed-out volume, which was necessary to induce hemorrhagic shock compared to NaCl groups, and the recovery during the resuscitation period was attenuated. During the experimentation in all groups, a trend to acidic pH was observed. Acute EtOH group showed lowest pH values compared to all other groups. Higher pCO2 values were observed in both EtOH groups. All groups developed negative base excess and decreasing HCO3- values until the end of hemorrhagic shock and showed increasing base excess and HCO3- values during resuscitation. Significantly higher mortality rate was found in the acute EtOH group. This study indicates that alcohol limits the metabolic and respiratory compensation capability, thereby promoting mortality.


[Health and socio-economic condition of certified Minamata disease patients, 1999].
To clarify the needs and to consider establishing a social support system for patients with Minamata disease (MD), or methylmercury poisoning, by investigating their health and socioeconomic conditions. The total number of people certified as having MD in May 1999 by the Kumamoto and Kagoshima Prefecture Government Committees on MD was 2265. We sent two questionnaires to 917 individuals who were surviving at that time, which corresponded to 40.5% of the total number of MD patients. The first survey sought information on the individual's health-seeking behavior, and the second survey was about their socio-economic conditions and requirements for welfare and medical care in the future. The average age among male patients was 68.0 +/- 13.2 yrs (n = 477) and that among female patients was 71.2 +/- 13.0 yrs (n = 440). The response rates were 45.7% (n = 416) for the first questionnaire and 38.6% (n = 354) for the second questionnaire. Among the MD patients, 71.7% judged their health condition to be 'bad' or 'very bad', and 97.4% received medical treatments that included acupuncture or moxacautery and massage. Regarding the activity of daily living (ADL), which includes 'communicating', 'walking', 'eating', 'use of toilet', 'dressing' and 'taking a bath', the rates of 'independent' were relatively low among those under 49 yrs and those over 75 yrs compared with the other age groups. Many individuals emphasized that they had anxiety about their health and health care in the future. We concluded that the quality of life (QOL) of MD patients was low. It is important to consider developing a social support system for MD patients.


Code Red: Explaining Average Age of Death in the City of Hamilton.
The aim of this study is to identify the underlying factors that explain the average age of death in the City of Hamilton, Ontario, Canada, as identified in the Code Red Series of articles that were published in the city's local newspaper in 2010. Using a combination of data from the Canadian Census, the Government of Ontario and the Canadian Institute for Health Information, factor analysis was performed yielding three factors relating to poverty, working class, and health and aging. In a regression analysis these factors account for 42% of the total variability in the average ages of death observed at the census tract level of geography within the city.


A nonacoordinated bridging selenide in a tricapped trigonal prismatic geometry identified in undecanuclear copper clusters: syntheses, structures, and DFT calculations.
Undecanuclear copper clusters, [Cu(11)(micro(9)-Se)(micro(3)-Br)(3)[Se(2)P(OR)(2)](6)] (R = Et, Pr, (i)Pr) (1a-c), were isolated along with closed-shell ion-centered cubes, [Cu(8)(micro(8)-Br)[Se(2)P(OR)(2)](6)] (PF(6)) (2a-c) and [Cu(8)(micro(8)-Se)[Se(2)P(OR)(2)](6)] (3a-c), from the reaction of [Cu(CH(3)CN)(4)](PF(6)), NH(4)[Se(2)P(OR)(2)], and Bu(4)NBr in a molar ratio of 2:3:2 in CH(2)Br(2). The molecular formulations of these clusters were confirmed by elemental analysis, positive FAB mass spectrometry, and multinuclear NMR ((1)H, (31)P, and (77)Se). (77)Se NMR spectra of Cu(11) clusters (1a-c) are of special interest as two inequivalent selenium nuclei of the diselenophosphate (dsep) ligand exhibit different scalar coupling patterns with the adjacent phosphorus nuclei. X-ray analysis of 1c reveals a Cu(11)Se core stabilized by three bromide and six dsep ligands. The central core adopts the geometry of a 3,3,4,4,4-pentacapped trigonal prism with a selenium atom in the center. The coordination geometry for the nonacoordinate selenium atom is tricapped trigonal prismatic. The X-ray structure 2a or 2c consists of a cationic cluster in which eight copper ions are linked by six diselenophosphate ligands with a central micro(8)-Br ion. The shape of the molecule is a bromide-centered distorted Cu(8) cube. Each diselenophosphate ligand occupies square faces of the cube and adopts a tetrametallic tetraconnective coordination pattern. Each copper atom of the cube is coordinated by three selenium atoms with a strong interaction with the central bromide ion. Molecular orbital calculations at the B3LYP level of the density functional theory have been carried out to study the Cu-micro(9)-Se interactions for clusters [Cu(11)(micro(9)-Se)(micro(3)-X)(3)[Se(2)P(OR)(2)](6)] (X = Br, I). Calculations show that the formal bond order of each Cu-micro(9)-Se bond is slightly smaller than half of those calculated for the terminal Cu-micro(2)-Se bonds.


Exercise-induced adaptations of rat soleus muscle grafts.
In female Wistar rats (n = 316) under pentobarbital sodium anesthesia, the soleus muscle was autografted with its nerve reimplanted. One purpose was to characterize the chronological development of graft innervation and recruitment during locomotion. Furthermore, we tested hypotheses regarding the efficacy of run conditioning of different intensities, durations, and postgrafting initiation times to alter mass and pyruvate-malate oxidation capacity of grafts. Choline acetyltransferase activity of grafts increased from 10% of control value at 7 days postgrafting to 55 and 100% at days 28 and 56, respectively. Running-induced glycogen depletion occurred in grafts; this is consistent with graft recruitment during locomotion. There was a threshold of conditioning intensity below which no improvements occurred and above which there were improvements. Spring (50 m/min) and endurance (30 m/min) conditioning of a duration of at least 28 days that was initiated at 28 or 56 days postgrafting increased mass of grafts by 30% compared with grafts from nonconditioned rats. Easy conditioning (15 m/min) had no effect on graft mass. Changes in graft total protein content paralleled those of mass. Oxidation capacity of grafts increased significantly with some conditioning protocols, but not to the same extent as mass. The exercise-induced adaptations should improve graft function in the host organism.


Dynamics of cutaneous atmospheric oxygen uptake in response to mechanical stretch revealed by optical fiber microsensor.
Skin expands and regenerates in response to mechanical stretch. This important homeostasis process is critical for skin biology and can be exploited to generate extra skin for reconstructive surgery. Atmospheric oxygen uptake is important in skin homeostasis. However, whether and how cutaneous atmospheric oxygen uptake changes during mechanical stretch remains unclear, and relevant research tools to quantify oxygen flux are limited. Herein, we used the scanning micro-optrode technique (SMOT), a non-invasive self-referencing optical fiber microsensor, to achieve real-time measurement of cutaneous oxygen uptake from the atmosphere. An in vivo mechanical stretch-induced skin expansion model was established, and an in vitro Flexcell Tension system was used to stretch epidermal cells. We found that oxygen influx of skin increased dramatically after stretching for 1 to 3 days and decreased to the non-stretched level after 7 days. The enhanced oxygen influx of stretched skin was associated with increased epidermal basal cell proliferation and impaired epidermal barrier. In conclusion, mechanical stretch increases cutaneous oxygen uptake with spatial-temporal characteristics, correlating with cell proliferation and barrier changes, suggesting a fundamental mechanistic role of oxygen uptake in the skin in response to mechanical stretch. Optical fiber microsensor-based oxygen uptake detection provides a non-invasive approach to understand skin homeostasis.


Miscalibration and severe complications after diode laser cyclophotocoagulation: two case reports.
Because two similar transscleral cyclophotocoagulation diode lasers with identical power & duration settings induced significantly different postoperative inflammation, we wanted to compare the real output of both lasers. Using a Power/Energy Meter (Fieldmaster) we compared the output of the two lasers (the Iridis [Quantel Medical] and the Iris Medical [OcuLight SLx]) at different energy levels. At a setting of 600, 1000, 1400, 1700, 2000 and 2500 mW, the measured output for the Iridis and Iris Medical diode laser were respectively 685 and 400 mW, 970 and 650 mW, 1470 and 875 mW, 1700 and 1000 mW, and 1990 compared to 1000 mW. On the average the output of the Iridis laser was correct and the output of the Iris Medical laser was 40% lower than the setting. Overtreatment and severe complications occurred with the Iridis laser because the manufacturer recommended using wrong power settings based on the Iris Medical laser, which was undercalibrated. The calibration of cyclophotocoagulation diode lasers should be performed prior to use when changing to a new device and whenever over- or undertreatment is observed.


CD1c as a target recognition structure for human T lymphocytes: analysis with peripheral blood gamma/delta cells.
It has been shown recently that one gamma/delta cell line, termed IDP2, derived from a immunodeficient patient recognizes the CD1c molecule on the surface of target cells. In light of these data, we have tested 43 cloned and 11 polyclonal gamma/delta cell lines derived from peripheral blood of 19 donors following nonspecific mitogenic stimulation. In this panel, which included lymphocytes expressing various combinations of gamma and delta chains, only one clone, termed J2B7, was found to interact with target cells via a CD1c-dependent recognition pathway. These J2B7 lymphocytes have, like IDP2, a delta chain which results from the frequent V1/J1 rearrangement while they use a distinct V gamma gene segment. The data support the view that the CD1c major histocompatibility complex "class I-like" gene product does not have a pivotal contribution to the repertoire of peripheral blood gamma/delta cells in adult individuals.


Use of the sit-to-stand task to evaluate motor function of older adults using telemetry.
Physical exercises are widely used in community programs, but not all older adults are willing to participate. Information and communication technology may solve this problem by allowing older people to participate in fitness programs at home. Use of remote instruction will facilitate physical exercise classes without requiring that participants gather at one place. The aim of this study was to examine use of a sit-to-stand task in evaluating motor function using conventional video communication in a telemetry system to enable real-time monitoring, and evaluation in physical performance of older adults at home. The participants were 59 older individuals and 81 university students. Three physical exercise batteries were used: arm curl, figure-of-eight walk test, and functional reach. The knee extension maximum angular velocity (KEMAV) and the iliac elevation maximum velocity (IEMV) during standing up from a chair and the heel rise frequency were used in the motion-capture measurements. The results were assessed using multi-group structural equation modeling (SEM) for the young and older groups. Young participants consistently performed better than their older counterparts on all items. Analyses with multi-group SEM based on correlations between items yielded a good model-fit for the data. Among all path diagrams for IEMV and KEMAV in the older and young groups, paths from muscular strength to skillfulness showed significant effects. The path from the IEMV to muscular strength was also significant in the older group. Multi-group SEM suggested that video-based measurements of IEMV during sit-to-stand motion can estimate muscular strength, which suggests that remote monitoring of physical performance can support wellness of community-dwelling older adults.


Maternal thyroid hormone is required for parvalbumin neurone development in the anterior hypothalamic area.
Thyroid hormone (TH) is crucial for brain development and function. This becomes most evident in untreated congenital hypothyroidism, leading to irreversible mental retardation. Likewise, maternal hypothyroxinaemia, a lack of TH during pregnancy, is associated with neurological dysfunction in the offspring, such as autism and reduced intellectual capacity. In the brain, TH acts mainly through TH receptor α1 (TRα1). Consequently, mice heterozygous for a dominant-negative mutation in TRα1 display profound neuroanatomical abnormalities including deranged development of parvalbumin neurones. However, the exact timing and orchestration of TH signalling during parvalbumin neurone development remains elusive. In the present study, we dissect the development of parvalbumin neurones in the anterior hypothalamic area (AHA) in male mice using different mouse models with impaired pre- and postnatal TH signalling in combination with bromodeoxyuridine birth dating and immunohistochemistry. Our data reveal that hypothalamic parvalbumin neurones are born at embryonic day 12 and are first detected in the AHA at postnatal day 8, reaching their full population number at P13. Interestingly, they do not require TH postnatally because their development is not impaired in mice with impaired TH signalling after birth. By contrast, however, these neurones crucially depend on TH through TRα1 signalling in the second half of pregnancy, when the hormone is almost exclusively provided by the mother. For the first time, our findings directly link a maternal hormone to a neuroanatomical substrate in the foetal brain, and underline the importance of proper TH signalling during pregnancy for offspring mental health. Given the role of hypothalamic parvalbumin neurones in the central control of blood pressure, the present study advocates the inclusion of cardiovascular parameters in the current discussion on possible TH substitution in maternal hypothyroxinaemia.


Corepressor required for adenovirus E1B 55,000-molecular-weight protein repression of basal transcription.
Adenovirus E1B 55,000-molecular-weight protein (55K) binds to host cell p53, stabilizing it, greatly increasing its affinity for its cognate DNA-binding site, and converting it from a regulated activator to a constitutive repressor. Here we analyzed the mechanism of repression by the p53-E1B 55K complex. E1B 55K repression requires that 55K be tethered to the promoter by binding directly to DNA-bound p53. Transcription from an assembled, p53-activated preinitiation complex was not repressed by the subsequent addition of E1B 55K, suggesting that either sites of 55K interaction with p53 or targets of 55K in the preinitiation complex are blocked. Specific E1B 55K repression was observed in reactions lacking TFIIA and with recombinant TATA-binding protein in place of TFIID, conditions under which p53 does not activate transcription. Thus, E1B 55K does not simply inhibit a p53-specific activation mechanism but rather blocks basal transcription. As a consequence, E1B 55K may repress transcription from any promoter with an associated p53-binding site, no matter what other activators associate with the promoter. E1B 55K did not repress basal transcription in reactions with recombinant and highly purified general transcription factors and RNA polymerase II but rather required a corepressor that copurifies with the polymerase.


Corporate influence and conflicts of interest: assessment of veterinary medical curricular changes and student perceptions.
The ethics document of the Association of American Veterinary Medical Colleges provides guiding principles for veterinary schools to develop conflict of interest policies. These policies regulate faculty and student interactions with industry, potentially reducing the influence companies have on students' perceptions and future prescribing practices. This paper examines the implementation of a conflict of interest policy and related instructional activities at one veterinary college in the US. To inform policy and curricular development, survey data were collected regarding veterinary students' attitudes toward pharmaceutical marketing, including their perceptions of their own susceptibility to bias in therapeutic decisions. Responses from this group of students later served as control data for assessing the effectiveness of educational programs in the content area. A conflict of interest policy was then implemented and presented to subsequent classes of entering students. Classroom instruction and relevant readings were provided on ethics, ethical decision making, corporate influences, and the issue of corporate influence in medical student training. Within seven days of completing a learning program on conflict of interest issues, another cohort of veterinary students (the treatment group) were administered the same survey that had been administered to the control group. When compared with the control group who received no instruction, survey results for the treatment group showed moderate shifts in opinion, with more students questioning the practice of industry-sponsored events and use of corporate funds to reduce tuition. However, many veterinary students in the treatment group still reported they would not be personally influenced by corporate gifts.


Continuous positive airway pressure treatment in patients with sleep apnoea: does it really improve glucose metabolism?
Obstructive Sleep Apnoea Syndrome (OSAS) is a common disorder, characterised by repetitive episodes of partial or complete obstruction of the upper airway during sleep and associated with increasing respiratory efforts. These perturbations lead, in turn, to oxyhaemoglobin desaturation, sleep fragmentation, and daytime symptoms, mainly excessive sleepiness. Accumulating evidence suggests that intermittent hypoxia and oxyhaemoglobin desaturation may result, independently of obesity, in impaired glucose metabolism, as well as insulin resistance even in non-diabetic patients with OSAS. Additionally, OSAS has been proposed as an independent risk factor for type 2 diabetes mellitus. Continuous Positive Airway Pressure (CPAP) is the treatment of choice for OSAS, since it eliminates upper airway collapse during sleep and also improves sleep fragmentation, daytime symptoms and quality of life. Moreover, it has been proposed that the amelioration of breathing disturbances during sleep can improve several markers of glucose metabolism and insulin resistance, such as glycated haemoglobin, fasting glucose, insulin, and insulin resistance. Indeed, some studies have reported improvements in these parameters especially in compliant patients. However, other works failed to confirm this beneficial effect. The present article reviews the issue whether CPAP treatment exerts a beneficial effect on glucose metabolism and insulin resistance.