BRD4 inhibitor IBET upregulates p27kip/cip protein stability in neuroendocrine tumor cells.
The prevalence of neuroendocrine tumors (NETs) has recently been increasing. Although various drugs such as Octreotide and its analogs show certain efficacy, NETs in many patients progress and metastasize. It is desirable to develop new interventions to improve the therapy. Here we show that human neuroendocrine tumor BON cells are resistant to several drugs commonly used for NET therapy, including Octreotide that activates somatostatin receptor-induced anti-proliferation, and Capecitabine and Temozolimide that damage DNA. In contrast, an inhibitor (IBET) to an epigenetic regulator, Brd4 that binds acetylated histones and upregulates transcription of multiple genes including protooncogene c-Myc, potently inhibited the NET cells. We found that IBET increased the protein levels of cyclin-dependent kinase (CDK) inhibitor p27kip/cip (or p27), but not its mRNA levels. Moreover, the p27 induction at protein level by IBET was at least partly through increasing the protein stability of p27. The increased protein stability of p27 likely resulted from IBET-mediated suppression of Skp2, an E3 ligase that can mediate p27 degradation by increasing its ubiquitinylation. These findings unravel a new mechanism whereby the IBET-induced repression of proliferation of neuroendocrine cells.


Simulated gastrointestinal conditions increase adhesion ability of Lactobacillus paracasei strains isolated from kefir to Caco-2 cells and mucin.
Gastrointestinal conditions along the digestive tract are the main stress to which probiotics administrated orally are exposed because they must survive these adverse conditions and arrive alive to the intestine. Adhesion to epithelium has been considered one of the key criteria for the characterization of probiotics because it extends their residence time in the intestine and as a consequence, can influence the health of the host by modifying the local microbiota or modulating the immune response. Nevertheless, there are very few reports on the adhesion properties to epithelium and mucus of microorganisms after passing through the gastrointestinal tract. In the present work, we evaluate the adhesion ability in vitro of L. paracasei strains isolated from kefir grains after acid and bile stress and we observed that they survive simulated gastrointestinal passage in different levels depending on the strain. L. paracasei CIDCA 8339, 83120 and 83123 were more resistant than L. paracasei CIDCA 83121 and 83124, with a higher susceptibility to simulated gastric conditions. Proteomic analysis of L. paracasei subjected to acid and bile stress revealed that most of the proteins that were positively regulated correspond to the glycolytic pathway enzymes, with an overall effect of stress on the activation of the energy source. Moreover, it is worth to remark that after gastrointestinal passage, L. paracasei strains have increased their ability to adhere to mucin and epithelial cells in vitro being this factor of relevance for maintenance of the strain in the gut environment to exert its probiotic action.


Improved Performance of Glucose Bioanodes Using Composites of (7,6) Single-Walled Carbon Nanotubes and a Ferrocene-LPEI Redox Polymer.
The effect of incorporating different types of carbon nanotubes into composite films of a redox polymer (FcMe2-C3-LPEI) and glucose oxidase (GOX) was investigated. The composite films were constructed by first forming a high-surface area network film of either single-walled carbon nanotubes (SWNTs) or multiwalled carbon nanotubes (MWNTs) on a glassy carbon electrode (GCE) by solution casting of a suspension of Triton-X-100 dispersed SWNTs. Next a glucose responsive redox hydrogel was formed on top of the nanotube-modified electrode by cross-linking FcMe2-C3-LPEI with glucose oxidase via ethylene glycol diglycidyl ether (EGDGE). Electrochemical and enzymatic measurements showed that composite films made with (7,6) SWNTs produced a higher response (3.3 mA/cm2) to glucose than films made with (6,5) SWNTs (1.8 mA/cm2) or MWNTs (1.2 mA/cm2) or films made without SWNTs (0.7 mA/cm2). We also show that the response of the composite films could be systematically varied by fabricating SWNT films with different weight ratios of (7,6) and (6,5) SWNTs. Optimization of the (7,6) SWNTs loading and the redox polymer-enzyme film produced a glucose response of 11.2 mA/cm2. Combining the optimized glucose films with a platinum oxygen breathing cathode into a biofuel cell produced a maximum power density output of 343 μW/cm2.


Social, cultural and economic factors associated with self-medication.
Self-medication is an increasingly frequent phenomenon worldwide; some studies suggest that there is a relationship with socio-economic and cultural factors. To determine the prevalence of self-medication and its related factors in a Colombian city. Cross-sectional descriptive study, in Pereira, Colombia. We selected 414 adults using simple randomization sampling with houses used as the observational unit. The IRIS-AM instrument was used to collect the information required. Four hundred and fourteen (414) people were interviewed, 62.6% were females, and mean age was 44 years; 77.5% of the sample had self-medicated at least once in their life and 31.9% during the last month. The most commonly used medications were: analgesics and antipyretics (44.3%), non-steroidal anti-inflammatory drugs and anti-rheumatic medication (36.4%), and anti-histamine medication (8.5%). The most commonly self-medicated symptoms were: headache (55.7%), cold (16.2%) and muscular pain (13.2%). Multivariate analysis revealed an association between self-medication throughout life and storing medications at home, and between a high level of education and having a favorable opinion of self-medication. Storing medications at home and recommending them to others were associated with self-medication during the previous 30 days. Self-medication rates were found to be similar to those reported globally, but there is not an established pattern for this practice. Associations were found between social and demographic variables and self-medication, which require further characterization. Intention to self-medicate has not been well-described in other studies, and may be an important indicator which will contribute to future understanding of this phenomenon.


Nailfold Capillaroscopy With USB Digital Microscopy in Connective Tissue Diseases: A Comparative Study of 245 Patients and Healthy Controls.
Background: Nailfold capillaroscopy (NFC) is a valuable tool to detect microcirculation abnormalities in connective tissue diseases (CTDs). However, whether the universal serial bus (USB) digital microscopy used as onychoscopy is as effective as the videocapillaroscopy in determining the diagnostic and prognostic values of CTDs remains to be determined. Objective: This study aims to investigate NFC features of systemic lupus erythematosus (SLE), dermatomyositis (DM), and systemic sclerosis (SSc) patients and compare with normal controls as well as examine which feature could differentiate among CTDs. Furthermore, we aim to explore different capillaroscopic abnormalities and their association with disease activity. Methods: Nailfold images were taken from patients and healthy controls using a USB digital microscopy. Patterns on the capillary morphology, diameter, architecture, and density were recorded and compared. We further determined the NFC findings in SLE, DM, and SSc and corresponded to their respective disease activity scoring system. Results: A total of 245 participants, consisting of 54 SLE, 32 DM, and 51 SSc patients, as well as 108 controls, were enrolled. All capillaroscopic features, except for tortuous capillaries, were significantly more common in CTDs than healthy control (all p < 0.05). A multinomial logistic regression analysis revealed that bushy capillaries had significantly higher odds for both SLE and DM than SSc (OR: 4.10, 95% confidence interval (CI): 1.71-9.81, p = 0.002 and OR: 7.82, 95% CI, 2.86-21.38, p < 0.001, respectively). Elongated capillaries demonstrated significant odds for SLE compared with SSc (OR: 3.35, 95% CI: 1.005-11.20, p = 0.049), while prominent subpapillary plexus showed greater odds for SLE compared with both DM and SSc (OR: 2.75, 95% CI: 1.07-7.02, p = 0.03 and OR: 5.78, 95% CI: 2.29-14.58, p < 0.001, respectively). The presence of hemorrhage, enlarged capillaries, and the low-density index had significantly higher odds in favor of SSc than SLE. Bushy capillaries were the only pattern with a strong association for DM over SSc. The presence of enlarged capillaries indicated higher SLE severity, but no specific finding was related to DM or SSc skin scores. Conclusions: Nailfold capillaroscopic examination using a digital microscope is a valuable method for the diagnosis of SLE, DM, and SSc. Several morphologic patterns can help differentiate among CTDs; however, the prognostic significance of this method requires further investigations.


Caffeic acid phenethyl ester protects 661W cells from H2O2-mediated cell death and enhances electroretinography response in dim-reared albino rats.
Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, has a wide range of beneficial properties. The purpose of this study was to test the protective role of CAPE in 661W cells (in vitro) against H(2)O(2)-mediated cell death and in albino rats (in vivo) against various light conditions. The 661W cells were pretreated with CAPE and then stressed with H(2)O(2). Cell death was measured with lactate dehydrogenase (LDH) release assay, and mRNA and proteins were analyzed. Sprague Dawley rats were raised on either a control or CAPE (0.02%) diet and exposed to various light conditions for short or long periods. Retinal histology, mRNA, protein, lipid composition, and retinal function by electroretinography (ERG) were measured at the end of feeding. Pretreatment of 661W cells with CAPE reduced H(2)O(2)-mediated cell death in a dose-dependent manner and induced expression of heme oxygenase-1 (Ho1). Albino rats fed with CAPE had greater expression of Ho1 and intercellular adhesion molecule 1 (Icam1), less expression of FOS-like antigen (Fosl) and lipoxygenase 12 (Lox12) genes in the retina, less translocation of nuclear factor kappaB protein to the nucleus, and a lower molar ratio of n-3 polyunsaturated fatty acids. Further, the ERGs of the retinas of CAPE-fed rats were significantly higher than those of the control-fed rats when raised in dim light. CAPE can activate the antioxidative gene expression pathway in retinal cells in vitro and in vivo. Feeding CAPE to albino rats can enhance ERG responses and change the lipid profile in the rats' retinas.


Serum regulation of in vitro lymphocyte responses in early experimental syphilis.
Sera from rabbits with early experimental syphilis were tested for their effect on in vitro lymphocyte transformation responses to related specific antigens (sonicated T. pallidum), unrelated specific antigens (sheep erythrocytes), and the T cell mitogen, concanavalin A. Results were compared with responses in preinfection sera and in sera from sham-infected rabbits. Titration experiments in which normal serum was used indicated that optimal lymphocyte responsiveness is obtained with a final serum concentration of 1%. Under these conditions, no differences in concanavalin A stimulation were observed in cultures with syphilitic sera. Responses to sonicated T. pallidum were inhibited, but only by 17 to 25% when compared with the response in preinfection sera. In cultures containing 10% serum, inhibition of lymphocyte proliferation to sonicated T. pallidum antigens was evident with sera from all syphilitic animals from day 10 (55% inhibition) through day 31 (80% inhibition) of infection. Responses to concanavalin A and sheep erythrocytes were significantly inhibited by day 10 sera; only 20% of the sera tested demonstrated substantial nonspecific inhibitory capacity. No differences were evident among sera from any of the sham-infected animals or among the preinfection sera from either group. Pooled serum with high inhibitory activity was fractionated by ammonium sulfate precipitation, DEAE ion exchange chromatography, and Sephadex G-200 gel filtration. Two separate inhibitors were identified: (i) a low-molecular-weight, ammonium sulfate-soluble, nonspecific inhibitory fraction containing albumin and alpha-globulins with the capacity to inhibit both antigen and mitogen responses and (ii) a high-molecular-weight, ammonium sulfate-precipitable, inhibitory fraction containing alpha-globulin and FTA-ABS-reactive immunoglobulin M which affected only the antigen-specific response to sonicated T. pallidum. Immunodiffusion failed to detect immunoglobulin or T. pallidum antigens in either fraction. DEAE-purified immunoglobulin G from immune serum was not inhibitory.


Androgen and progesterone effects on follicle-stimulating hormone and luteinizing hormone secretion in anestrous mares.
Anestrous lighthorse mares were treated in December with dihydrotestosterone (DHT; 150 micrograms/kg of body weight), progesterone (P; 164 micrograms/kg), both DHT and P (DHT+P), testosterone (T; 150 micrograms/kg), or vehicle (n = 4/group). Daily blood sampling was started on Day 1, and on Day 4 all mares were administered a pretreatment injection of gonadotropin-releasing hormone (GnRH) and were bled frequently to characterize the responses of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations. Treatment injections were given on Day 4 and then daily through Day 17. On Day 18, all mares were again administered GnRH and were bled frequently. Treatment of mares with DHT, P, or T increased (p less than 0.01) plasma concentrations of these steroids to approximately 1.5 ng/ml during the last 10 days of treatment. There was no effect (p greater than 0.10) of treatment on LH or FSH concentrations in daily blood samples. Relative to the pretreatment GnRH injection, mares treated with T or DHT+P secreted approximately 65% more (p less than 0.01) FSH in response to the post-treatment GnRH injection; FSH response to the second GnRH injection was not altered (p greater than 0.10) in control mares or in DHT- or P-treated mares. There was no effect of any steroid treatment on LH secretion after administration of GnRH (p greater than 0.10). Averaged over all mares, approximately 94 times more FSH than LH was secreted in response to injection of GnRH.(ABSTRACT TRUNCATED AT 250 WORDS)


Upregulation of S100A6 in patients with endometriosis and its role in ectopic endometrial stromal cells.
S100 calcium-binding protein A6 (S100A6) is up-regulated in many malignancies and overexpression of S100A6 has been identified associated with proliferation, migration and invasion phenotype in several cancer cells. In the present study, we explored whether S100A6 plays a role in the development of endometriosis. Significantly higher levels of mRNA and protein expression of S100A6 were observed in ectopic endometrial tissues compared to eutopic and normal endometrial tissues. Silencing of S100A6 in ectopic endometrial stromal cells (ESCs) significantly inhibited cell viability, migration and invasion. Moreover, knockdown of S100A6 suppressed p38/MAPK activity in ectopic ESCs, which can be partially attenuated by CacyBP/SIP phosphorylation inhibitor. In conclusion, our results suggest that the abnormal expression of S100A6 may contribute to the pathogenesis of endometriosis and the S100A6/CacyBP/p38 signaling may provide as a promising treatment target.


Spartin regulates synaptic growth and neuronal survival by inhibiting BMP-mediated microtubule stabilization.
Troyer syndrome is a hereditary spastic paraplegia caused by human spartin (SPG20) gene mutations. We have generated a Drosophila disease model showing that Spartin functions presynaptically with endocytic adaptor Eps15 to regulate synaptic growth and function. Spartin inhibits bone morphogenetic protein (BMP) signaling by promoting endocytic degradation of BMP receptor wishful thinking (Wit). Drosophila fragile X mental retardation protein (dFMRP) and Futsch/MAP1B are downstream effectors of Spartin and BMP signaling in regulating microtubule stability and synaptic growth. Loss of Spartin or elevation of BMP signaling induces age-dependent progressive defects resembling hereditary spastic paraplegias, including motor dysfunction and brain neurodegeneration. Null spartin phenotypes are prevented by administration of the microtubule-destabilizing drug vinblastine. Together, these results demonstrate that Spartin regulates both synaptic development and neuronal survival by controlling microtubule stability via the BMP-dFMRP-Futsch pathway, suggesting that impaired regulation of microtubule stability is a core pathogenic component in Troyer syndrome.


Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures.
Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h following injury and suggest increased calpain activity and membrane disruption as potential underlying mechanisms.


The role of fear-avoidance beliefs in patients with neck pain: relationships with current and future disability and work capacity.
To investigate the relationship between fear-avoidance beliefs and future disability and work capacity in patients with neck pain. A prospective observational study. Physiotherapy outpatient departments. One hundred and twenty patients with neck pain intensity sufficient to affect their work capacity. Patients participated in either six-week conventional physiotherapy or an exercise training programme to test whether the type of treatment received by the patients together with other outcome measures affected the predictive power of fear-avoidance beliefs. Patients underwent examination of the active neck range of movements and neck muscle strength and completed the Fear-Avoidance Beliefs Questionnaire, the Northwick Park Neck Pain Questionnaire, the Medical Outcomes 36-Item Short-Form Health Survey and the 11-point pain numerical rating scale. These were assessed at the beginning and at week 6 of the rehabilitation programme. Patients' work capacity was assessed at week 6 and three months after the six-week rehabilitation programme. Spearman's correlation coefficients between fear-avoidance beliefs and initial and week 6 disability levels were 0.47 and 0.48, respectively. Regression analysis showed that the fear-avoidance beliefs significantly improved the goodness of fit of the model for predicting week 6 disability levels and return to complete work capacity at week 6 and three months after the rehabilitation programme, even after controlling for the physical impairments, the health status, the pain intensity and the type of treatment received. The fear-avoidance beliefs factor is an important biopsychosocial variable in predicting future disability level and return to complete work capacity in patients with neck pain.


A candidate multi-epitope vaccine against SARS-CoV-2.
In the past two decades, 7 coronaviruses have infected the human population, with two major outbreaks caused by SARS-CoV and MERS-CoV in the year 2002 and 2012, respectively. Currently, the entire world is facing a pandemic of another coronavirus, SARS-CoV-2, with a high fatality rate. The spike glycoprotein of SARS-CoV-2 mediates entry of virus into the host cell and is one of the most important antigenic determinants, making it a potential candidate for a vaccine. In this study, we have computationally designed a multi-epitope vaccine using spike glycoprotein of SARS-CoV-2. The overall quality of the candidate vaccine was validated in silico and Molecular Dynamics Simulation confirmed the stability of the designed vaccine. Docking studies revealed stable interactions of the vaccine with Toll-Like Receptors and MHC Receptors. The in silico cloning and codon optimization supported the proficient expression of the designed vaccine in E. coli expression system. The efficiency of the candidate vaccine to trigger an effective immune response was assessed by an in silico immune simulation. The computational analyses suggest that the designed multi-epitope vaccine is structurally stable which can induce specific immune responses and thus, can be a potential vaccine candidate against SARS-CoV-2.


[Impact of sperm function on the fertilization rate of IVF].
To analyze sperm function-related risk factors and their value in predicting the fertilization rate (FR) of in vitro fertilization (IVF). This retrospective study included 668 cases of IVF performed in the Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology from July 2018 to April 2021, which were divided into a low-FR group (FR ≤ 65%, n = 107) and a high-FR group (FR > 65%, n = 561). We compared the sperm volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), acrosome reaction rate, acrosin activity and DNA fragmentation index (DFI) between the two groups, analyzed the correlation between sperm parameters and FR by Spearman's correlation analysis, and the value of sperm function-related risk factors in predicting the FR of IVF using binary logistic regression analysis and receiver-operator characteristic (ROC) curve. There were statistically significant differences in the infertility type of the female patients (P < 0.05) but not in the sperm volume, sperm concentration, PMS, MNS, and acrosome reaction rate (P > 0.05). The DFI was significantly lower in the high-FR than in the low-FR group ([14.31 ± 4.46]% vs [15.35 ± 5.68]%, P = 0.034) and the acrosin activity remarkably higher in the former than in the latter group ([102.11 ± 47.18] vs [91.98 ± 42.61] μIU/106, P = 0.039). Spearman's correlation analysis showed that the FR was correlated negatively with DFI (r = 0.090, P = 0.020) and positively with acrosin activity (r = 0.079, P = 0.042). Primary infertility and DFI were found to be unfavorable factors while acrosin activity a favorable factor for the FR of IVF. The areas under the ROC curve (AUC) of DFI and acrosin activity were 0.571 and 0.562, respectively. DFI and acrosin activity are risk factors and have a predictive value for the fertilization rate of IVF.


Mechanical properties and biological behavior of carbon nanotube/polycarbosilane composites for implant materials.
Multiwalled carbon nanotube/polycarbosilane (MWCNT/PCS) composites were fabricated by the spark plasma sintering (SPS) method. The MWCNT/PCS composites consisted of MWCNTs and nanosized SiC particles pyrolyzed from PCS and possessing good mechanical properties for bone tissue repair or dental implantation. The MWCNT/PCS composites were implanted in the subcutaneous tissue and femur of rats at 1 and 4 weeks after implantation. Histological investigations showed that there was little inflammatory response in the subcutaneous tissue, and newly formed bone tissue was observed in the femur. These results indicated that the MWCNT/PCS composite had little prophlogistic effect and good osteoconductivity. The study suggested the possibility that the MWCNT/PCS composite could be a candidate bone-substitute and dental-implant material in the future.


Nasal biopsy is superior to nasal smear for finding eosinophils in nonallergic rhinitis.
The presence of eosinophils was compared in nasal biopsy and smear. Thirty-two nonallergic rhinitis patients, of whom six had nasal polyps, were included in the study. The specimens were studied light-microscopically after staining with hematoxylin-eosin. The association between the presence of polyps and the finding of eosinophils in the biopsy specimens proved to be significant. Ten normal subjects served as controls. It was far more simple to detect eosinophils in the biopsy samples than in the nasal smears. When we considered biopsies with at least four eosinophils in four fields as hypereosinophilic, our group of patients contained 25% nonallergic rhinitis with eosinophilia syndrome (NARES) patients.


Management of liver disease in dogs and cats.
Liver disease may cause a variety of clinical signs, including depression, anorexia, weakness, weight loss, vomiting, diarrhea, fever, abdominal pain, jaundice, ascites and CNS signs. Treatment is aimed at eliminating the cause, providing supportive care, and preventing secondary complications. Rest facilitates liver regeneration. Hypokalemia, respiratory alkalosis and hypoglycemia may complicate liver disease. Fluids should be given IV rather than SC to severely dehydrated animals. Preferred solutions include Ringer's and half-strength saline with 2.5% dextrose. Solutions containing lactate should not be used. Dietary management includes feeding adequate amounts of protein of high biologic value, carbohydrates, fat, vitamins and minerals.


B cells produce less IL-10, IL-6 and TNF-α in myasthenia gravis.
B cells from myasthenia gravis (MG) patients with autoantibodies (Aab) against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or with no detectable Aab were investigated as cytokine producing cells in this study. B cells were evaluated for memory phenotypes and expressions of IL-10, IL-6 and IL-12A. Induced productions of IL-10, IL-6, IL-12p40, TNF-α and LT from isolated B cells in vitro were measured by immunoassays. MG patients receiving immunosuppressive treatment had higher proportions of memory B cells compared with healthy controls and untreated patients. With CD40 stimulation MG patients produced significantly lower levels of IL-10, IL-6. With CD40 and B cell receptor stimulation of B cells, TNF-α production also decreased in addition to these cytokines. The lower levels of these cytokine productions were not related to treatment. Our results confirm a disturbance of B cell subpopulations in MG subgroups on immunosuppressive treatment. B cell derived IL-10, IL-6 and TNF-α are down-regulated in MG, irrespective of different antibody productions. Ineffective cytokine production by B cells may be a susceptibility factor in dysregulation of autoimmune Aab production.


Isavuconazole-tacrolimus drug-drug interactions in HSCT patients.
Because tacrolimus has a narrow therapeutic window and exhibits both intraindividual and interindividual variability, we attempted to establish the percentage of calcineurin inhibitor (CNI) dose reduction to prevent toxicity and ensure stem cell engraftment when using this immunosuppressant with the antifungal isavuconazole (ISA). By calculating the tacrolimus concentration/dose (C/D) ratio, we expected to demonstrate the magnitude of change in the C/D ratio from baseline after ISA administration. We evaluated the interaction between ISA, a new triazole antifungal used in prophylaxis for invasive fungal infections, and the CNI class of immunosuppressive drugs, specifically tacrolimus, in 11 blood samples from HSCT recipients. The mean tacrolimus C/D ratio increased 1.44-fold from baseline 48 h after ISA administration (P = 0.001). Although further investigation is needed, the results of this study suggest that a reduction of 18% in tacrolimus may be recommended.


The marihuana perception inventory: stage 3--the parent sample.
This article reports the third step in the development of a perceptual inventory of factors associated with marihuana use. Identification of those factors, along with an analysis of demographic characteristics is designed to facilitate the formulation of drug education programs. This third phase was an administration of the inventory to sixty-parents who were also members of a community anti-drug group. Their beliefs are strong, as evidenced by their active association with the group. Factors analysis revealed a five-factor solution that utilized all thirty-four items of the inventory. Scales were again labeled Parental Limitations, Societal Issues, Inherent Predispositions, Rebelliousness, and Maturational Difficulties. Since there was a shift between parents and youths in specific items that made up the scales, it appears that drug educators will need to take parents' perceptions into account when designing programs.


-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia.
To investigate the relationship between the -765G > C COX-2 polymorphism and the development of different gastric lesions: atrophy or intestinal metaplasia and gastric adenocarcinoma. A cross-sectional study was performed involving 320 Portuguese individuals (210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia) using a PCR-RFLP method. -765C allele was overrepresented in the patients with gastric adenocarcinoma (51%) when compared either with the control group (38%) or patients with atrophy or intestinal metaplasia (27%). Callele was found to be very common in our population (0.22), and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele (OR = 2.67, 95% CI = 1.03-6.93; P = 0.04). -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.


Prognostic Significance of Lacunarity in Preoperative Biopsy of Colorectal Cancer.
The quantity and quality of preoperative material in colorectal cancer is often limiting factor in determination of risk factors and therapy planning. The most important negative prognostic factors are intravascular and perineural invasion, as well as tumor budding. Usually, the only parameter available in preoperative biopsy is tumor budding. However, the growing body of evidence suggests that cancer differentiation based on the poorly differentiated clusters has better prognostic value. The limiting factor in applying of these new parameters is reproducible, simple, cheap and fast method of their determination. In this paper we investigated the prognostic value of lacunarity, determined in preoperative biopsy. Lacunarity is a measure of spatial heterogeneity (inhomogeneity) in an image. It quantifies how objects fill the space, and enables analysis of gaps distribution, homogeneity of gaps, and presence of structures. It was shown that lacunarity and the total number of buds could be combined in a model which clearly divides colorectal cancer patients in low, medium and high risk subgroups. The paper also points out that the quantitative numerical methods are superior to semiquantitative methods, and that individual methods should be combined using algorithms to obtain a more accurate prediction. Because the study described is designed as a pilot study, verification is needed on a larger sample of patients from independent researchers.


Bilateral plasma cell granuloma (inflammatory pseudotumour) of the breast.
Plasma cell granuloma of the breast is an extremely rare condition. Only one other case has been reported in the literature. We report here the second case of plasma cell granuloma of the breast. After the initial excision, the lesion recurred in both breasts after 5 months.


Targeting FGFR in Squamous Cell Carcinoma of the Lung.
Unlike for adenocarcinomas of the lung, no molecular targeted therapies have yet been developed for squamous cell lung cancers, because targetable oncogenic aberrations are scarce in this tumor type. Recent discoveries have established that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in cancer development by supporting tumor angiogenesis and cancer cell proliferation via different mechanisms. Through comprehensive genomic studies, aberrations in the FGF pathway have been identified in various tumor types, including squamous cell lung cancer, making FGF receptor (FGFR) a potentially druggable target in this malignancy. Several multi-targeted tyrosine kinase inhibitors include FGFR in their target spectrum and a number of these compounds have been approved for clinical use in different cancers. Novel agents selectively targeting FGFRs have been developed and are currently under investigation in clinical trials, showing promising results. This article reviews FGFR aberrations and the clinical data involving selective and multikinase FGFR inhibitors in squamous cell lung cancer.


Mapping the future for research in emergency medicine palliative care: A research roadmap.
The intersection of emergency medicine (EM) and palliative care (PC) has been recognized as an essential area of focus, with evidence suggesting that increased integration improves outcomes. This has resulted in increased research in EM PC. No current framework exists to help guide investigation and innovation. The objective was to convene a working group to develop a roadmap that would help provide focus and prioritization for future research. Participants were identified based on clinical, operation, policy, and research expertise in both EM and PC and spanned physician, nursing, social work, and patient perspectives. The research roadmap setting process consisted of three distinct phases that were time staggered over 12 months and facilitated through three live video convenings, asynchronous input via an online document, and a series of smaller video convenings of work groups focused on specific topics. Gaps in the literature were identified and informed the four key areas for future research. Consensus was reached on these domains and the associated research questions in each domain to help guide future study. The key domains included work focused on the value imperative for PC in the emergency setting, models of care delivery, disparities, and measurement of impact and efficacy. Additionally, the group identified key methodological considerations for doing work at the intersection of EM and PC. There are several key domains and associated questions that can help guide future research in ED PC. Focus on these areas, and answering these questions, offers the potential to improve the emergency care of patients with PC needs.


Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid.
Pyrazinamide is an important sterilizing drug that shortens tuberculosis (TB) therapy. However, the mechanism of action of pyrazinamide is poorly understood because of its unusual properties. Here we show that pyrazinoic acid, the active moiety of pyrazinamide, disrupted membrane energetics and inhibited membrane transport function in Mycobacterium tuberculosis. The preferential activity of pyrazinamide against old non-replicating bacilli correlated with their low membrane potential and the disruption of membrane potential by pyrazinoic acid and acid pH. Inhibitors of membrane energetics increased the antituberculous activity of pyrazinamide. These findings shed new light on the mode of action of pyrazinamide and may help in the design of new drugs that shorten therapy.


The mitochondrial genome of Prays oleae (Insecta: Lepidoptera: Praydidae).
Prays oleae is one of the most important olive tree pests and a species of interest in evolutionary studies, as it belongs to one of the oldest extant superfamilies of Ditrysian Lepidoptera. We determined its mitogenome sequence, and found it has common features for Lepidoptera, e.g. an >80% A + T content, an apparent CGA start codon for COX1 and an ATAGA(T)n motif in the control region, which also contains several copies of a 163-164 bp repeat. Importantly, the mitogenome displays the Met-Ile-Gln tRNA gene order typical of Ditrysia, consistent with the hypothesis that this is a synapomorphy of that clade.


Triosephosphate metabolism by mature boar spermatozoa.
Boar sperm rapidly interconverted dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, produced fructose-1,6-bisphosphate, approximately equilibrium concentrations of fructose 6-phosphate and glucose 6-phosphate but not glycerol or glycerol 3-phosphate. In the presence of 3-chloro-1-hydroxypropanone, an inhibitor of stage 2 of the glycolytic pathway, the triosephosphates were metabolized faster, produced less fructose-1,6-bisphosphate, fructose 6-phosphate and glucose 6-phosphate, but not glycerol or glycerol 3-phosphate. This suggests that these cells may have the capacity to convert glycolytic intermediates into a storage metabolite to conserve carbon atoms for the eventual synthesis of lactate.


Transit Rider Body Mass Index Before and After Completion of Street Light-Rail Line in Utah.
To determine whether 2012 to 2015 (times 1-3) ridership changes correlated with body mass index (BMI) changes after transit line completion in Salt Lake City, Utah. We used Global Positioning System/accelerometry-measured transit ridership measures in 2012 to 2013 (times 1-2) to compare objective and self-reported ridership. Regression models related changes in objectively measured ridership (times 1-2) and self-reported ridership (times 1-2 and times 1-3) to BMI changes, adjusting for control variables. Objective and self-reported ridership measures were consistent. From time 1 to 2 (P = .021) or to 3 (P = .015), BMI increased among self-reported former riders and decreased among new riders (P = .09 for both times 1-2 and times 1-3), although the latter was nonsignificant. Time 3 attrition adjustment had no effect on results. Adjusting for baseline BMI, the nonsignificant effect for new riders remained nonsignificant, indicating no BMI change; the BMI increase after discontinuing transit remained significant. Observed BMI increases subsequent to stopping transit ridership persisted for more than 2 years (postintervention). These results suggest that transit ridership protects against BMI gains and support the need to provide convenient transit for public health.


'0'- and '8'-shaped complexes generated from a nano-sized oxadiazole-containing organic ligand with CdI2 and CuI.
A new nano-sized rigid double-armed oxadiazole-bridged organic ligand, 2,5-bis{2-methyl-5-[2-(pyridin-3-yl)ethenyl]phenyl}-1,3,4-oxadiazole, C30H20N4O, L or (I), which adopts a cis conformation in the solid state, has been synthesized and used to create the two novel metallocycle complexes (2,5-bis{2-methyl-5-[2-(pyridin-3-yl-κN)ethenyl]phenyl}-1,3,4-oxadiazole)diiodidocadmium(II) dichloromethane monosolvate, [CdI2(C30H20N4O)]·CH2Cl2, (II), and di-μ-iodido-bis[(2,5-bis{2-methyl-5-[2-(pyridin-3-yl-κN)ethenyl]phenyl}-1,3,4-oxadiazole)copper(I)], [Cu2I2(C30H20N4O)2], (III). Molecules of complex (II) adopts a 20-membered `0'-shaped metallocycle structure with crystallographic mirror symmetry. The discrete units are linked into one-dimensional chains through intermolecular π-π and C-H...π interactions. In (III), the two I atoms and two Cu(I) atoms form a {Cu2(μ-I)2} cluster. One {Cu2(μ-I)2} cluster and two L ligands form two 20-membered monometallic rings in a head-to-head fashion, leading to a discrete centrosymmetric `8'-shaped metallocyclic complex. These metallocycles stack together via two kinds of intermolecular π-π interactions to generate a two-dimensional network in the ac plane. The luminescence properties of (I)-(III) were investigated in the solid state at room temperature and displayed an obvious red shift.


Inconsistencies of the evaluation of home advantage in sports competitions under the three points per victory system.
A recent letter sent to the Journal of Human Kinetics' editor (Gómez & Pollard, 2014) warned about a supposed methodology error in the calculation of home advantage in football leagues used in Saavedra et al. (2013) and took the liberty of modifying the research's data. The aim of this letter is to demonstrate that the evaluation system of the home advantage proposed by Pollard (1986) contains serious inconsistencies when applied to competitions which give three points for a win and one point for a draw, as it is the case of the UEFA football leagues in the 21th century.


Long-Term Results of Fixation-Free Incisional Hernia Repair Using a Tentacle-Shaped Implant.
The fixation and the overlap of the mesh represent an open issue in incisional hernia repair. An exclusively designed prosthesis has been developed to assure a suture-free repair and a broader coverage of the abdominal wall. This study describes the long-term results of incisional hernia procedures carried out positioning a tentacle-shaped implant through a specifically developed surgical technique. A proprietary symmetrically-shaped flat mesh constituted by a large central body with integrated radiating arms was used to repair incisional hernias in 68 patients. The prosthesis was placed in preperitoneal/retromuscular sublay. The friction of the straps passing through myotendineal structures of the abdomen was intended to assure an adequate grip to firmly hold the device in place with a broad overlap of the hernia defect in a fixation-free fashion. All tentacle straps were positioned through a special needle passer crossing the abdominal wall laterally from the defect borders then cut short in the subcutaneous layer. In a long-term follow-up of 12 to 96 months (mean 58 months), 11 seromas occurred. No infections, hematomas, chronic pain, mesh dislocation, or recurrence have been reported. The tentacle strap system of the prosthesis effectively ensured reduced skin incision and an easier implant placement avoiding the need for suturing the mesh. Regularly performed computed tomography (CT) and ultrasound (US) investigations proved that the arms of the implant ensured a proper orientation and stabilization of the mesh in association with a broad defect overlap. The specifically developed surgical procedure showed a quick postoperative recovery, a very low complication rate, and no recurrences, even in the long-term.


UGT74AN1, a Permissive Glycosyltransferase from Asclepias curassavica for the Regiospecific Steroid 3-O-Glycosylation.
A permissive steroid glycosyltransferase (UGT74AN1) from Asclepias curassavica exhibited robust capabilities for the regiospecific C3 glycosylation of cardiotonic steroids and C21 steroid precursors, and unprecedented promiscuity toward 53 structurally diverse natural and unnatural compounds to form O-, N-, and S-glycosides, along with the catalytic reversibility for a one-pot transglycosylation reaction. These findings highlight UGT74AN1 as the first regiospecific catalyst for cardiotonic steroid C3 glycosylation and exhibit significant potential for glycosylation of diverse bioactive molecules in drug discovery.


A common metric magnitude system for the perception and production of numerosity, length, and duration.
Numerosity, length, and duration processing may share a common functional mechanism situated within the parietal cortex. A strong parallelism between the processing of these three magnitudes has been revealed by similar behavioral signatures (e.g., Weber-Fechner's law, the distance effect) and reciprocal interference effects. Here, we extend the behavioral evidence for a common magnitude processing mechanism by exploring whether the under- and overestimation patterns observed during numerical perception and production tasks are also present in length and duration perception and production. In a first experiment, participants had to perform two estimation tasks (i.e., perception and production) on three magnitudes (i.e., numerosities, lengths, and durations). The results demonstrate similar patterns for the three magnitudes: underestimation was observed in all perception tasks, whereas overestimation was found in all production tasks. A second experiment ensured that this pattern of under- and over-estimation was not solely generated by the mere process of perceiving or producing something. Participants were required to estimate the alphabetical position of a letter (i.e., perception task) or to produce the letter corresponding to a given position (i.e., production task). No under- or overestimation were observed in this experiment, which suggests that the process of perceiving or producing something alone cannot explain the systematic pattern of estimation observed on magnitudes. Together, these findings strengthen the idea that magnitude estimations share a common metric system, requiring similar mechanisms and/or representations.


Perceptions of Portuguese medical coders on the transition to ICD-10-CM/PCS: A national survey.
In Portugal, trained physicians undertake the clinical coding process, which serves as the basis for hospital reimbursement systems. In 2017, the classification version used for coding of diagnoses and procedures for hospital morbidity changed from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS). To assess the perceptions of medical coders on the transition of the clinical coding process from ICD-9-CM to ICD-10-CM/PCS in terms of its impact on data quality, as well as the major differences, advantages, and problems they faced. We conducted an observational study using a web-based survey submitted to medical coders in Portugal. Survey questions were based on a literature review and from previous focus group studies. A total of 103 responses were obtained from medical coders with experience in the two versions of the classification system (i.e. ICD-9-CM and ICD-10-CM/PCS). Of these, 82 (79.6%) medical coders preferred the latest version and 76 (73.8%) considered that ICD-10-CM/PCS guaranteed higher quality of the coded data. However, more than half of the respondents (N = 61; 59.2%) believed that more time for the coding process for each episode was needed. Quality of clinical coded data is one of the major priorities that must be ensured. According to the medical coders, the use of ICD-10-CM/PCS appeared to achieve higher quality coded data, but also increased the effort. According to medical coders, the change off classification systems should improve the quality of coded data. Nevertheless, the extra time invested in this process might also pose a problem in the future.


Frontotemporal dementia progresses to death faster than Alzheimer disease.
Frontotemporal lobar degeneration (FTLD) is a common cause of non-Alzheimer dementia, but its natural history and the factors related to mortality in affected patients are not well understood. This retrospective, longitudinal study compared survival in FTLD (n = 177) with Alzheimer disease (AD; n = 395). Hazards analysis investigated the contribution of various demographic, neuropsychiatric, and neuropsychological variables and associated neurologic and neuropathologic findings. The frontotemporal dementia (FTD) subtype of FTLD progressed faster than AD (median survival from retrospectively determined symptom onset, 8.7 +/- 1.2 vs 11.8 +/- 0.6 years, p < 0.0001; median survival from initial clinic presentation, 3.0 +/- 0.5 vs 5.7 +/- 0.1 years, p < 0.0001). Survival was similarly reduced in the related conditions corticobasal degeneration and progressive supranuclear palsy. Survival in the semantic dementia subtype of FTLD (11.9 +/- 0.2 years from onset and 5.3 +/- 0.4 years from presentation), however, was significantly longer than in FTD and did not differ from AD. Hazards analysis to determine factors affecting survival in FTLD showed no effect of age at onset, sex, education, family history, or neuropsychiatric profile. Among neuropsychological measures examined, impaired letter fluency had a significant association with reduced survival. Associated ALS significantly reduced survival in FTLD. The presence of tau-positive inclusions was associated with the slowest progression. Frontotemporal lobar degeneration progresses more rapidly than Alzheimer disease, and the fastest-progressing cases are those with the frontotemporal dementia clinical subtype, coexisting motor neuron disease, or tau-negative neuropathology.


High-Throughput and Computational Study of Leaf Senescence through a Phenomic Approach.
Leaf senescence is influenced by its life history, comprising a series of developmental and physiological experiences. Exploration of the biological principles underlying leaf lifespan and senescence requires a schema to trace leaf phenotypes, based on the interaction of genetic and environmental factors. We developed a new approach and concept that will facilitate systemic biological understanding of leaf lifespan and senescence, utilizing the phenome high-throughput investigator (PHI) with a single-leaf-basis phenotyping platform. Our pilot tests showed empirical evidence for the feasibility of PHI for quantitative measurement of leaf senescence responses and improved performance in order to dissect the progression of senescence triggered by different senescence-inducing factors as well as genetic mutations. Such an establishment enables new perspectives to be proposed, which will be challenged for enhancing our fundamental understanding on the complex process of leaf senescence. We further envision that integration of phenomic data with other multi-omics data obtained from transcriptomic, proteomic, and metabolic studies will enable us to address the underlying principles of senescence, passing through different layers of information from molecule to organism.


Liquid-crystalline supramolecular polymers formed through complementary nucleobase-pair interactions.
We report how the placement of nucleobase units, thymine, or N6-(4-methoxybenzoyl)adenine, onto the ends of a mesogenic core, bis-4-alkoxy-substituted bis(phenylethynyl)benzene, affects the properties of these materials. We show that addition of these bulky polar groups significantly reduces the range of liquid-crystalline behavior of these compounds. However, mixing two complementary nucleobase-containing AA- and BB-type monomer units together does result in the formation of stable, thermotropic liquid-crystalline (LC) phases. Hydrogen bonding is shown to play an important role in the formation of these LC phases, consistent with the formation of oligomeric or polymeric hydrogen-bonded aggregates. X-ray analyses of these mixed materials are consistent with the formation of smectic C phases.


Matrigel scaffold combined with Ad-hBMP7-transfected chondrocytes improves the repair of rabbit cartilage defect.
The aim of this study was to explore an effective method for the repair of cartilage defects using chitosan/glycerophosphate (C/GP) gel- and Matrigel-engineered human bone morphogenetic protein 7 (hBMP7)-expressing chondrocytes. Rabbit chondrocytes were obtained, cultured in vitro and transfected with an adenovirus containing hBMP7 and green fluorescent protein (Ad-hBMP7-GFP). The expression of hBMP7 in the transfected cells was tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. The phenotype of the transfected cells was evaluated by detecting the yields of collagen II and hyaluronic acid using RT-PCR and enzyme-linked immunosorbent assay (ELISA). The growth of chondrocytes in the C/GP gel and Matrigel was accessed by measuring the cell growth rate, hematoxylin and eosin (H&E) staining and observation under a scanning microscope. Twelve adult male New Zealand white rabbits were randomly divided into three groups. Two cartilage defects were created in the rabbits' knees by aseptic surgery. Group A (n=4) did not receive any treatment, group B (n=4) were treated with C/GP gel and Matrigel-engineered Ad-mock-GFP-transfected chondrocytes, and group C (n=4) were treated with C/GP gel and Matrigel-engineered Ad-hBMP7-GFP-transfected chondrocytes. Rabbits were sacrificed at 4 weeks after transplantation, and the repair effect was measured by the Wakitani scoring method. On the basis of the RT-PCR and western blot results, hBMP7 was efficiently overexpressed in the Ad-hBMP7-GFP-transfected chondrocytes. The ELISA results showed that the yields of collagen II and hyaluronic acid in Ad-hBMP7-GFP-transfected chondrocytes were significantly higher than those in Ad-mock-GFP-transfected chondrocytes. Chondrocytes have a better morphology and arrangement in a Matrigel scaffold than in C/GP, as assessed by H&E staining and scanning microscopy. According to the Wakitani score, Matrigel combined with Ad-hBMP7-GFP-transfected chondrocytes successfully promoted the repair of cartilage defects in rabbit knees.


Platelet-poor plasma serotonin in normal and preeclamptic pregnancy.
We determined serotonin concentrations in platelet-poor plasma (PPP) from 11 preeclamptic pregnant women and 11 normal pregnant women by HPLC with electrochemical detection after a concentration step. Serotonin concentrations in PPP are very low in comparison with those in platelets, so it is very important to avoid in vitro release of serotonin from platelets. We therefore investigated three types of anticoagulants, the method of blood sampling, and the influence of whether the first or second 10 mL of blood is assayed. The type of anticoagulant proved to be important, K3-EDTA giving the best results. The serotonin concentrations in PPP from the preeclamptic pregnant women were significantly higher (P = 0.0001) than in the normal pregnant women: mean values +/- SD were 27.0 +/- 13.5 and 2.8 +/- 1.4 nmol/L, respectively. We suggest that the measurement of serotonin in PPP might be helpful in study of the role of serotonin in the development of preeclampsia.


Firearm purchasing during the beginning of the COVID-19 pandemic in households with teens: a national study.
To describe and identify the correlates of firearm purchasing at the beginning of the COVID-19 pandemic among US families with teenagers. In June-July 2020, we conducted a national survey of 2924 parents and their teenagers in the US. We report results from this survey to describe firearm purchasing behaviors following the start of the COVID-19 pandemic and investigate correlates of purchasing. Between the beginning of the pandemic and July 2020, 10% of households with teenagers purchased a firearm, and 3% became first-time firearm-owning households. Among firearm-owning households, firearm storage was associated with purchasing such that households that stored at least one firearm loaded and unlocked were more likely to purchase a firearm (OR: 2.02[1.07-3.79]) compared to households that stored all firearms unloaded and/or locked. Firearms purchased at the beginning of the pandemic were more likely to go to homes where at least one firearm was stored loaded and unlocked, which may contribute to increased risk for teen firearm injury and death.


Approaching meV level for transition energies in the radium monofluoride molecule RaF and radium cation Ra+ by including quantum-electrodynamics effects.
Highly accurate theoretical predictions of transition energies in the radium monofluoride molecule, 226RaF, and radium cation, 226Ra+, are reported. The considered transition X2Σ1/2 → A2Π1/2 in RaF is one of the main features of this molecule and can be used to laser-cool RaF for a subsequent measurement of the electron electric dipole moment. For molecular and atomic predictions, we go beyond the Dirac-Coulomb Hamiltonian and treat high-order electron correlation effects within the coupled cluster theory with the inclusion of quadruple and ever higher amplitudes. The effects of quantum electrodynamics (QED) are included non-perturbatively using the model QED operator that is now implemented for molecules. It is shown that the inclusion of the QED effects in molecular and atomic calculations is a key ingredient in resolving the discrepancy between the theoretical values obtained within the Dirac-Coulomb-Breit Hamiltonian and the experiment. The remaining deviation from the experimental values is within a few meV. This is more than an order of magnitude better than the "chemical accuracy," 1 kcal/mol = 43 meV, that is usually considered as a guiding thread in theoretical molecular physics.


CT and PET/CT findings of primary pulmonary diffuse large B-cell lymphoma: One case report and literature review.
Primary pulmonary diffuse large B-cell lymphoma (PPL-DLBCL) is rare and its clinical manifestations lack specificity. In this report, we present one case of PPL-DLBCL with complete clinical and imaging data, including uncontrast-enhanced CT, contrast-enhanced CT, and positron emission tomography (PET)/CT. Previous cases will also be reviewed and summarized. A 62-year-old woman was hospitalized due to a swelling pain located in the right side of her back that persisted for >1 month. Local CT examination indicated a pulmonary infection and anti-infective therapy was administered; however, her symptoms did not improve. In the hospital, a lung CT scan with enhancement showed hyperintensity of the right upper lobe (RUL), ill-defined margins, inhomogeneous density, with air bronchograms, and mild-to-moderate enhancement. PET/CT showed a slight hyperintensity of mass with high uptake (about 14.7 standardized uptake value [SUV]), and no high uptake was found in other locations. A CT-guided percutaneous needle biopsy with Tru-Cut needles was performed. The final diagnosis was PPL-DLBCL. After 4 rounds of chemotherapy using the rituximab-cyclophosphamide hydroxydaunorubicin oncovin prednisolone (R-CHOP) regimen, the patient's pain was significantly relieved. Finally, the PPL-DLBCL manifestation was similar to other types of PPL clinical manifestations and CT manifestations, but the PPL-DLBCL PET/CT showed an apparent, high metabolism. CT-guided percutaneous transthoracic needle biopsy can clearly diagnose the disease.


Nursing intervention in care homes: district nurses' views.
Nursing need within residential care homes has been reported as increasing for the district nursing workforce (Audit Commission, 1999). This report presents the findings from a small exploratory study to discover the views of district nurses regarding a project to provide nursing care to clients in residential care homes. Named nurses work within some of the homes in the city on specified days and are available to carry out nursing interventions required by clients, thus precluding the need for a member of the district nurse team to visit on that day. The background to the study is discussed, followed by the qualitative research methodology used. Three broad themes emerged from the findings: roles and responsibilities, communication and organisational issues. Each of these is discussed and recommendations suggested with a view to enhancing the potential benefit of the project for its users.


Cell-surface antigens of melanoma recognized by human monoclonal antibodies.
Human monoclonal antibodies (mAbs) were derived from lymph node lymphocytes and peripheral blood lymphocytes (PBL) from patients with melanoma. Four methods for generating human mAbs were compared: fusion with human [LICR-LON-HMy-2 (LICR-2)] or mouse (NS-1) cells; transformation by Epstein-Barr virus (EBV); and EBV transformation followed by NS-1 fusion. NS-1 fusion with lymph node lymphocytes resulted in a higher number of growing hybrids than LICR-2 fusion. Virtually no hybrids were obtained from NS-1 or LICR-2 fusions with PBL. EBV transformed lymphocytes from lymph node and peripheral blood with equal efficiency, and the yield of proliferating cultures for antibody screening was more than 10- to 30-fold greater than that obtained by fusion techniques. However, once antibody-producing cultures had been identified, stability and clonability of EBV-transformed cells were poorer than that of NS-1 hybrid cells. To combine the strengths of both methods, cultures of EBV-transformed cells were fused with NS-1; and hybrid clones were isolated that showed vigorous growth, clonability, and stable antibody secretion. Detailed specificity analysis of the mAbs produced by six of these clones indicated detection of a class 1 (unique) melanoma antigen, a class 3 melanoma antigen, and four ganglioside antigens (GD3, GM3, and two other, as yet uncharacterized, heterophile antigens).


[Current status of lung and heart-lung transplantation for pulmonary arterial hypertension].
Lung transplantation (LT) or heart-lung transplantation (HLT) had been a mainstay of treatment for pulmonary arterial hypertension (PAH) since the 1980s. Considerable advances in the medical therapy over the past decade, however, changed the paradigm of treatment algorithm for PAH, and LT in any form became a therapeutic option for patients deteriorating despite the best available medical therapy. On the basis of a shortage of available organs for transplantation, most centers prefer bilateral LT to HLT as the procedure of choice. According to the international registry, survival rates following bilateral LT for PAH are 81% at 1 month, 68% at 1 year, and 50% at 5 years. Improvement in the survival rate in early post-operative periods is a matter of critical concern in LT for PAH.


Eustachian tube dysfunction in allergic rhinitis.
To assess eustachian tube function in patients with allergic rhinitis and compare them with a control group. Tympanometry was performed in 130 patients (260 ears), divided into 2 groups: 80 cases with allergic rhinitis and 50 healthy controls. Cases underwent skin hypersensitivity tests. Cases, age 21.1 +/- 14.9; Controls, age 23.9 +/- 15.6. Most frequent skin hypersensitivity: Dermatophagoides pt (62%), Zea Maiz (44%), and Cockroach (37%). Tympanometry of cases showed negative values of peak tympanometric pressure in both children and adults (P < or = 0.05). Among children under 11 years of age, 15.5% tympanograms showed abnormal curves (13% C curves and 3% B curves); among the control group only normal curves were found (type A). Allergic rhinitis patients have a higher risk of eustachian tube dysfunction, particularly during childhood. Tympanometry is a noninvasive, readily available procedure that may be useful in these patients to prevent chronic middle-ear disease.


Phonomyography of the corrugator supercilii muscle: signal characteristics, best recording site and comparison with acceleromyography.
This study investigated the acoustic signal characteristics and best recording site of phonomyography at the corrugator supercilii muscle and compared phonomyography with acceleromyography. In 12 patients (group I), after induction of anaesthesia and insertion of a laryngeal mask, a microphone (frequency range 2.5 Hz to 10 kHz) was placed on six different areas on the forehead and the peak-to-peak response after single-twitch stimulation of the facial nerve was measured. The microphone was placed where the response was largest and mivacurium 0.2 mg kg(-1) was administered. Fast Fourier transformation was applied to all signals to determine peak frequencies and the power-frequency relationship at different stages of neuromuscular block. In an additional 15 patients (group II), the same microphone and an acceleromyographic probe were placed above the middle portion of the left and right eyebrows respectively. Onset and offset of neuromuscular block were determined after mivacurium 0.2 mg kg(-1). In all seven women and all five men in group I, the best response was obtained just above the middle portion of the eyebrow. Peak frequency was 4.1 (SD 0.9) Hz without neuromuscular block and did not change significantly during onset and offset of neuromuscular block. Ninety per cent of the total signal power was below 40 Hz. In group II, mean onset time and maximum effect measured were 104 (20) s and 76 (10)% respectively using acceleromyography and 134 (30) s and 92 (4)% using phonomyography (P<0.04). Mean time to reach 25, 75 and 90% of control was 9.5 (2.8), 14 (5.1) and 15.1 (5.3) min respectively using acceleromyography and 6.9 (2.8), 12.5 (5.9) and 13.6 (4.9) min using phonomyography (P<0.04). Bland-Altman testing revealed significant bias (precision) for onset time, maximum effect and time to reach 25% of control (acceleromyography minus phonomyography) at -30 (38) s, -16 (11)% and 2.6 (2.8) min respectively. Phonomyography can be used to determine neuromuscular block at the corrugator supercilii muscle. In comparison with acceleromyography, phonomyography tends to measure a longer onset with more pronounced maximum effect and shorter recovery of neuromuscular block.


Epoxyeicosatrienoic acids activate K+ channels in coronary smooth muscle through a guanine nucleotide binding protein.
Epoxyeicosatrienoic acids (EETs) are endothelium-derived arachidonic acid metabolites of cytochrome P450. They dilate coronary arteries, open K+ channels, and hyperpolarize vascular smooth muscles. However, the mechanisms of these smooth muscle actions remain unknown. This study examined the effects of EETs on the large-conductance Ca(2+)-activated K+ channel (KCa) in smooth muscle cells of small bovine coronary arteries. In cell-attached patch-clamp experiments, 11,12-EET produced a 0.5- to 10-fold increase in the activity of the KCa channels when added in concentrations of 1, 10, and 100 nmol/L. In the inside-out excised membrane patch mode, 11,12-EET was without effect on the activity of the KCa channel unless GTP (0.5 mmol/L) or GTP and ATP (1 mmol/L) were added to the bath solution. In the presence of GTP and ATP, the increase in the KCa channel activity with 11,12-EET in inside-out patches was comparable to that in cell-attached patches. This effect of 11,12-EET in inside-out patches was blocked by the addition of GDP-beta-S (100 mumol/L). In outside-out patches, 11,12-EET also increased the KCa channel activity when GTP and ATP were added to the pipette solution. The addition of a specific anti-Gs alpha antibody (100 nmol/L) in the pipette solution completely blocked the activation of the KCa channels induced by 11,12-EET. An anti-G beta gamma or anti-Gi alpha antibody was without effect. We conclude that 11,12-EET activates the KCa channels by a Gs alpha-mediated mechanism. This mechanism contributes to the effects of EETs as endothelium-derived hyperpolarizing factors to hyperpolarize and relax arterial smooth muscle.


Differential Volume Increase of Endolymphatic Compartments in Ménière's Disease Is Inversely Associated With Membrane Thickness.
Our aim in this study was to characterize the morphology of the endolymphatic compartment on histopathology in individuals with Ménière's disease (MD) and to determine why hydrops of the saccule is more pronounced than that of other compartments of the inner ear in MD. Temporal bones from 9 patients with idiopathic MD and from 10 individuals without MD/endolymphatic hydrops were examined. The inner ear fluid compartments in normal ears, and ears with MD were three-dimensionally reconstructed and their volume was calculated. The thickness of the membranes of the labyrinth was measured, and both ruptures of the membranes and patency of the utriculoendolymphatic (UEV; Bast's) valve were assessed. In ears with MD, the saccule and the cochlear duct were most frequently hydropic; the utricle was involved approximately half as frequently. In ears without MD, the Reissner's membrane and the membranous wall of the saccule were thinner than that of the utricle and of the lateral semicircular canal ( p < 0.01). The lateral semicircular canal did not show signs of hydrops. In all ears with MD in which the utricle exceeded the average volume of normals (6 of 12), the UEV was open or there was a rupture in the utricle. Increases in endolymphatic pressure may cause a primary swelling of the apical cochlear duct and saccule, both of which have relatively thin membranes. Hydrops in the utricle may occur less frequently because of a thicker wall, because of a functioning UEV, and when the saccule has already occupied most of the vestibular perilymphatic space.


Fatty acid hydration activity of a recombinant Escherichia coli-based biocatalyst is improved through targeting the oleate hydratase into the periplasm.
Whole-cell biotransformation of fatty acids can be influenced by the activities of catalytic enzymes and by the efficiency of substrate transport into host cells. Here, we improved fatty acid hydration activity of the recombinant Escherichia coli expressing an oleate hydratase of Stenotrophomonas maltophilia by targeting the catalytic enzyme into the periplasm instead of the cytoplasm. Recombinant E. coli producing OhyA in the periplasm under guidance of the PelB signal sequence (E. coli OhyA_PP) exhibited significantly greater hydration activity with oleic acid and linoleic acid compared to a recombinant E. coli producing OhyA in the cytoplasm (E. coli OhyA_CS). For example, the oleate double bond hydration rate of E. coli OhyA_PP was >400 μmol/g dry cells/min (400 U/g dry cells), which is >10-fold higher than that of E. coli OhyA_CS. As the specific activities of the enzymes targeted into the cytoplasm and periplasm were comparable, we assumed that targeting OhyA into the periplasm could accelerate fatty acid transport to the catalytic enzymes by skipping the major mass transport barrier of the cytoplasmic membrane. Our results will contribute to the development of whole-cell biocatalysts for fatty acid biotransformation.


[Results of radiation therapy of nasopharyngeal cancer].
The results of irradiation therapy for nasopharyngeal carcinoma in 49 patients treated at the Department of Radiology, Jikei University of Medicine, between 1968 and 1981 are reviewed. The CR rate increased in proportion to increased dosage, especially in well-differentiated squamous cell carcinoma. The five-year cumulative survival rate was 40% in all stages. Severe late radiation injury occurred in two patients.


[Cryptococcal meningitis in HIV-infected patients at Bobo-Dioulasso hospital (Burkina Faso)].
Cryptococcus neoformans is an important fungal pathogen in immunocompromised patients. A retrospective study was conducted to investigate the occurrence of Cryptococcus neoformans infection in patients admitted to Bobo-Dioulasso Hospital over a 3 year-period. During this period, cryptococcal meningo-encephalitis was diagnosed in 36 individuals. The median age of the patients under study was 34.25 years. There was a male preponderance (24 males/12 females) in our report. Typical presentations were persistent headaches (27 cases/36), neck stiffness (16/36), altered consciousness (14/36), fever (12/36) and convulsions (9/36). Oral candidiasis coexisted with cryptococcal meningitis in 7 patients. HIV serology was positive in all patients. At diagnosis, lymphocytes counts were < 1500/mm3 in 66.66% patients. CSF examination with India ink helped to the diagnosis of cryptococcosis in all cases. Cryptococcus neoformans was associated with Streptococcus pneumoniae in 4 patients. 15/36 patients died within 1 to 29 days after admission. High mortality was related to delayed diagnosis. Cryptococcal meningitis highly contributes to mortality in HIV-infected patients in Burkina Faso and it may occur in patients not severely immunocompromised patients. A need exists to improve strategies for clinical management of AIDS patients in poor African countries.


No effect of the IGF-1 gene rs35767 and rs17032362 polymorphisms in the etiology of idiopathic short stature.
Idiopathic short stature (ISS) refers to pathophysiologically wide and heterogeneous range of disorders, which are considered to involve defects in growth hormone (GH) insulin like growth factor-1 (IGF-1) axis. This study was designed to evaluate GH- IGF-1 axis and investigate IGF-1 gene polymorphisms in ISS.108 patients with a mean age of 11.7±3.6 years constituted the study group, while 108 age and gender matched children with normal stature constituted the control group. Serum IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels and two polymorphisms in IGF-1 gene (rs35767, rs17032362) were investigated.While mean IGF-1 SDS value was lower in study group (p=0.002), no difference was detected between mean IGFBP-3 SDS values. The IGF-1 gene rs35767 polymorphism genotype distribution did not exhibit a statistical difference between study (7.1% wild type, 29.6% heterozygous, 63.3% homozygous) and control groups (3.8% wild type, 39.6% heterozygous, 56.6% homozygous). IGF-1 gene rs17032362 polymorphism genotype distribution was not significantly different either between study (94.8% wild type, 5.2% heterozygous, 0% homozygous) and control groups (97.2% wild type, 2.8% heterozygous, 0% homozygous). Comparing the cases with wild type, homozygous and heterozygous carriers for both polymorphisms with respect to height, weight, BMI, IGF-1 and IGFBP-3 SDS values, no significant difference was detected.IGF-1 SDS levels of patients with ISS were significantly lower compared to control group. There was no difference between IGFBP-3 SDS levels. No effect of IGF-1 gene rs35767 and rs17032362 polymorphisms on stature, IGF-1 and IGFBP-3 levels could be demonstrated.


Adiponectin limits differentiation and trophoblast invasion in human endometrial cells.
Successful human embryo implantation requires a proper differentiation of endometrial stromal cells (ESCs) into decidual cells, during a process called decidualization. ESCs express specific molecules, such as prolactin, insulin-like growth factor-binding protein-1 (IGFBP-1) and connexin-43. Decidual cells are also involved in the control of trophoblast invasion, by secreting various factors, such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Adiponectin is an adipokine with insulin-sensitizing, anti-inflammatory and anti-proliferative effects. At the embryo-maternal interface, adiponectin promotes differentiation and invasion of human trophoblastic cells. We hypothesize that the effects of adiponectin on endometrium could counteract its pro-invasive effects previously described in the human trophoblast. In this context, we have firstly demonstrated that adiponectin downregulates IGFBP-1 and connexin-43 mRNA expressions, as well as prolactin secretion in ESCs, suggesting an anti-differentiative effect of adiponectin. Secondly, we found that invasive capacities of trophoblastic cell line HTR-8/SVneo are reduced in the presence of conditioned media from ESC cultured in the presence of adiponectin. Adiponectin's anti-invasive action is associated with a decreased activity of MMP-2 and MMP-9, and an increased TIMP-3 mRNA expression in ESCs. Finally, adiponectin receptors (ADIPOR1 and ADIPOR2) knockdown abolishes the anti-differentiative and anti-invasive effects of adiponectin in human ESCs. Altogether, our results suggest that adiponectin reduces the decidualization process and inversely induces the production of endometrial factors that limit trophoblast invasion. Thus, through a dual control in trophoblast and endometrial cells, adiponectin appears as a pivotal actor of the embryo implantation process.


Superior Hypogastric Nerve Block for Pain Control after Uterine Artery Embolization: Effect of Addition of Steroids on Analgesia.
Superior hypogastric nerve block (SHNB) decreases pain and use of narcotic pain medication following uterine artery embolization (UAE). The purpose of this retrospective study was to evaluate the effect of the addition of a corticosteroid (triamcinolone) to SHNB on analgesia following UAE. Records of 16 patients were reviewed for when pain occurred or acutely worsened after the procedure. No major complications were identified. Patients reported that pain began or worsened an average of 33.8 hours after the procedure, when their average pain increased from 0.6/10 to 5.9/10 (P < .001). This suggests that addition of triamcinolone to SHNB could result in prolonged analgesia following UAE.


Induction of resistance to Toxoplasma gondii in human macrophages by soluble lymphocyte products.
Autoradiography and light microscopy were used to study the effects of lymphocyte culture supernatants, prepared under a variety of conditions, on the course of intracellular Toxoplasma gondii infection in human monocyte-derived macrophages in vitro. Supernatants prepared by incubating lymphocytes of dye test- (DT) positive subjects with T. gondii lysate antigen (TLA), lymphocytes of DT/negative subjects with streptokinase-streptodornase (SK-SD), or both populations of lymphocytes with concanavalin A (Con A) were capable of activating macrophages to inhibit or kill intracellular T. gondii. Supernatants prepared with the homologous antigen (TLA) to the target organism appeared more active in conferring resistance to infection with T. gondii on macrophages than those prepared with a heterologous antigen (SK-SD) or mitogen (Con A). The number of lymphocytes was critical in preparing active supernatants. These results suggest that soluble lymphocyte mediators can activate human macrophages in vitro to inhibit or kill T. gondii.


Osteitis in Eosinophilic Chronic Rhinosinusitis.
Eosinophilic chronic rhinosinusitis (ECRS) is an allergic inflammatory disease characterized by chronic inflammation of the sinus mucosa, and sometimes, osteitis. This study aimed to investigate the pattern of osteitis in ECRS and the relationship between bony thickening of the middle turbinate and recurrence of ECRS. A total of 246 patients with paranasal diseases were included in the study. The patients' data on bone thickening level, mucosal thickening, polyp score, clinical severity, and laboratory data were retrospectively evaluated. In total, 38, 186, and 22 patients had ECRS, non-ECRS (NECRS), and odontogenic sinusitis, respectively. The Lund-Mackey (LM) score and Global Osteitis Scoring Scale (GOSS) scores in patients with ECRS were higher than those in patients with other paranasal diseases. There was a significant positive correlation between the GOSS score and ECRS clinical disease severity. Postoperative recurrence was significantly increased in patients with ECRS associated with bony thickening of the middle turbinate. Both mucosal inflammation and osteitis were more severe in patients with ECRS than in patients with other diseases, and clinical disease severity was correlated with osteitis. Furthermore, the postoperative recurrence rate tended to increase in patients with ECRS who had bony thickening of the middle turbinate.


Femoral head deformity after open reduction by Ludloff's medial approach.
Ludloff's medial approach has been described as a simple procedure for open reduction of developmental dysplasia of the hip (DDH) requiring minimal dissection and tissue disruption. Many patients undergo subsequent reconstruction of the acetabulum after skeletal maturity for residual dysplasia. Femoral head deformity reportedly influences the long-term outcome of these osteotomies. The literature suggests this deformity may be related to the patient's age at the time of a medial approach. We therefore asked whether femoral head deformity (roundness index, femoral head enlargement) at skeletal maturity correlates with patient age at surgery. We assessed the radiographs of 40 patients (42 hips). Their mean age at surgery was 14.3 months (range, 6-31 months); the minimum followup was 10 years (mean, 15.8 years; range, 10-27 years). The mean roundness index at skeletal maturity correlated with increased age at the time of the operation (mean index, 58.3; range, 47-79) while enlargement did not. Using a medial approach for correction of DDH in older patients increases the risk of femoral head deformity at skeletal maturity.


Clinical experience with Norplant subdermal implant system as long-term contraception during adolescence.
This study was undertaken to assess the efficacy, acceptability and side-effects of the Norplant (Leiras) contraceptive system during adolescence. A total of 13 adolescents were implanted with Norplant immediately after menstruation. Adolescents were advised to present for follow-up visits at 3 days after implantation, at 3, 6 and 12 months and every 1 year thereafter. Blood pressure, menstrual disorders, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose and side-effects were recorded at every visit. The follow-up period was 24 months with a continuation rate of 100% (13/13) for the first 6 months, 92.5% (12/13) for 12 months and 53.8% (7/13) for the whole period. No pregnancies were observed. No infections at the implant site or expulsions were observed. Menorrhagia was observed in 4/13 (30.76%) adolescents in the third month. Thereafter all adolescents were treated with tenoxicam (prostaglandin synthetase inhibitor), so that by the end of the sixth month of treatment menorrhagia was not present in any of the 13 adolescents. No increase of blood pressure was observed. A statistically significant increase (p < 0.01) of triglycerides at 6 months after implantation was found; however, no difference was observed in the values of serum glucose, total cholesterol, HDL and LDL. This preliminary study has shown that Norplant is acceptable as a contraceptive method among adolescents in Greece and can be prescribed safely.


Dietary (+)-catechin and BHT markedly increase alpha-tocopherol concentrations in rats by a tocopherol-omega-hydroxylase-independent mechanism.
The effects of dietary (+)-catechin (CAT) and BHT on plasma and tissue concentrations of alpha-tocopherol (alpha-T), gamma-tocopherol (gamma-T) and cholesterol (C) were studied in male Sprague-Dawley rats. The rats were fed the compounds during a 4-wk period at concentrations of 2 g/kg in standardized diets, low but adequate in vitamin E, with 2 g/kg cholesterol. The CAT-regimen did not affect weight gain, feed intake or organ weights. BHT did not affect feed intake but lowered the body weight and the amount of liver lipids and increased the weights of livers and lungs relative to the body weight. Rats consuming CAT had 2.5-3.5-fold increased plasma, liver and lung alpha-T concentrations, but C concentrations remained unchanged. BHT-feeding resulted in 2.4- and 1.7-fold elevation in alpha-T but approximately 50% decrease in gamma-T concentrations in blood plasma and liver, respectively. BHT also lowered total C in the liver without affecting the concentration of C in the liver lipids. To investigate whether the alpha-T-sparing action of the studied compounds was due to the inhibition of tocopherol-omega-hydroxylase, HepG2 cells were incubated with CAT or BHT in the presence of delta-tocopherol (delta-T) and the 3'- and 5'-delta-carboxychromanol metabolites in the media were analyzed by GC/MS. Neither CAT nor BHT inhibited tocopherol-omega-hydroxylase activity in hepatocyte cultures; CAT was also inactive in a rat microsomal assay. In conclusion, both dietary CAT and BHT markedly increased alpha-T concentrations in plasma and organs of Sprague-Dawley rats by a mechanism that apparently does not involve inhibition of tocopherol-omega-hydroxylase, a key enzyme in tocopherol catabolism.


Satisfaction with medication in older adult patients with chronic respiratory diseases: a multicenter cross-sectional observational study.
To gain insight into medication satisfaction and factors associated with chronic respiratory disease, particularly chronic obstructive pulmonary disease (COPD) in older adults, focusing on public health issues and improving the health of the older adult population. This cross-sectional study was conducted from October 2022 to November 2022 in 24 hospitals in different regions of Hunan Province, China. Older adult patient treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication version II. Multiple regression analysis was used to identify factors independently associated with patient treatment satisfaction. Only 15.9% of all patients scored above 80 in the effectiveness domain, while 11.6 and 16.5% scored above 80 in the convenience and global satisfaction domains, respectively, while 17.3% reported having side effects. Interstitial lung disease was associated with lower drug satisfaction than other disorders (p < 0.05). Multifactorial regression analysis showed that age, education background, profession, and smoking status were independently associated with satisfaction among patients with chronic respiratory diseases (p < 0.05). Education background, profession, CAT score, number of acute exacerbations, duration of home oxygenation and duration of home ventilator use were independently associated with satisfaction in patients with COPD (p < 0.05). Low satisfaction with chronic respiratory drug therapy was associated with age, education background, profession and smoking status. Satisfaction was lower for patients with interstitial lung disease. For COPD, CAT score, education background, profession, number of acute exacerbations, home oxygen and ventilator use influence satisfaction. Clinicians can identify appropriate patients and communicate effectively with them throughout treatment and follow-up, vigorously promote smoking cessation and home oxygen therapy, increase medication satisfaction, especially among older adults, and in turn improve public health and the quality of life of older adults.


Predictors of risk and protection for hypertension in Yup'ik people from Southwest Alaska.
Hypertension (HTN) contributes to vascular disease, and is increasingly common in non-western, rural contexts, such as the Yup'ik people of Southwestern Alaska. While much is known regarding HTN risk factors in western contexts, little is known about their relevance to non-western populations. We explore an American Heart Association risk factor model for HTN in predicting risk and protection from HTN among Yup'ik people. Using data from 1015 Yup'ik individuals residing in remote Southwestern Alaska, we explore age, sex, education, waist circumference, physical activity, tobacco, social support, and cultural identification in multinomial logistic regressions comparing pre-hypertension (pre-HTN; systolic 120 to 129 mm Hg), and hypertension (HTN; systolic > or = 130 mm Hg) to optimal blood pressure (opt-BP; systolic < 120 mm Hg). We find positive associations between age (2%, 5% greater odds respectively), waist circumference (3%, 5% greater odds respectively) and hypertension medication usage (60%, 85% greater odds respectively) with both pre-HTN and HTN. We also find men have 86% greater odds of pre-HTN, people with fasting blood glucose > or = 110 mg/dL have 52% increased odds of pre-HTN, and married persons have 19% lower odds of having pre-HTN compared to having opt-BP. Bicultural identification mitigates age related increases in BP and deleterious effects of low formal education. While model continuities are noted in our Yup'ik study, important points of divergence are also noted. Future research on cultural identification and social support has promising implications for guiding responsive interventions.


MiR-92a Promotes Cell Metastasis of Colorectal Cancer Through PTEN-Mediated PI3K/AKT Pathway.
MicroRNAs regulate gene expression at the posttranscriptional level and play important roles in tumor development, progression, and metastasis. The aim of this study was to investigate the role of microRNA-92a (miR-92a) in metastasis of colorectal cancer (CRC). One hundred fifty-eight CRC patients were enrolled. The expression of miR-92a, PTEN, and E-cadherin was analyzed by real-time PCR. Univariate (Kaplan-Meier) analysis was used to analyze primary outcomes included 5-year overall survival and tumor recurrence. CRC cell model studies were used to analyze the miR-92a-involved CRC metastasis. The expression of miR-92a in tumor tissues was significantly positively correlated with lymph node metastasis in CRC patients (p = 0.012). After adjusting for age, sex, and disease differentiation, this correlation remained significant (p = 0.01). In addition, there was a negative correlation between levels of miR-92a and the PTEN gene (p < 0.0001). No any association of miR-92a and E-cadherin was found (p = 0.128). Patients with high miR-92a/low PTEN had poorer overall survival and disease-free survival rates than those with high miR-92a/high PTEN, low miR-92a/high PTEN, and low miR-92a/low PTEN. The association of levels of miR-92a and PTEN with tumor cell migration in CRC was also confirmed in CRC cell models. We suggest that miR-92a is involved in lymph node metastasis of CRC patients through PTEN-regulated PI3K/AKT signaling pathway.


Comparison of new point-of-care troponin assay with high sensitivity troponin in diagnosing myocardial infarction.
The aim of this study is to compare a new improved point of care cardiac troponin assay (new POC-cTnI) with 1. its predecessor (old POC-cTnI) and 2. a high sensitivity assay (hs-cTnI) for the diagnosis of acute myocardial infarction (AMI) and for major adverse cardiac events (MACE) by 30 days. This is a single centre observational study, set in Christchurch Hospital, New Zealand. Patients presenting to the emergency department with non-traumatic chest pain underwent blood sampling at 0 h and 2h post presentation for analysis with the 3 cTnI assays for the outcome of AMI and for analysis using an accelerated diagnostic protocol (ADP-normal 2h troponins, normal electrocardiograms and Thrombolysis In Myocardial Infarction (TIMI) score of 0 or ≤ 1) for 30 day MACE. Of 962 patients, 220 (22.9%) had AMI. Old POC-cTnI was least sensitive at 70.0% (65.4-73.9%) by 2h (p<0.001). New POC-cTnI, sensitivity 93.6% (89.9-96.2%) had similar sensitivity to hs-cTnI, sensitivity 95.0% (91.5-97.3%) (p = 0.508). There were 231 (24.0%) patients with 30 day MACE. When used as part of the ADP, all assays had 100% (98.0-100%) sensitivity using TIMI = 0. Sensitivities of new POC-cTnI ADP, 98.3% (95.4-99.4%), old POC-cTnI, 96.5% (93.2-98.4%) and hs-cTnI, 98.7% (96.0-99.7%) were similar (p = 0.063-0.375) using TIMI ≤ 1. A new POC-cTnI has improved sensitivity for AMI and MACE compared with its predecessor and comparable sensitivity to a high sensitivity assay. Now that sensitivities of the POC assay are improved, the new assay may be a useful alternative to central laboratory assays when rapid turn-around times are not possible.


Gender differences across race/ethnicity in use of health care among Medicare-aged Americans.
Despite Medicare, medical services are not equally used by elderly women and men in the United States. Our purpose is to examine gender differences in healthcare utilization among older Americans, the persistence of gender differences across race/ethnicity, and the roles of sociodemographic, health, and economic factors to explain differences. Data from the 1998-2000 Health and Retirement Study are used to investigate gender differences in use of hospital, outpatient surgery, home health, and physician services. Analyses are controlled for sociodemographic, health (medical conditions, functional health), and economic (income, wealth, education, health insurance) factors. Women are significantly less likely to use hospital service (odds ratio [OR]=0.83) and outpatient surgery (OR=0.85) but are more likely to use home health care (OR=1.27) and physician services (OR=1.45), controlling for sociodemographics. Differences in health needs and economic resources partially mediate the gender differences in physician and home healthcare utilization but do not explain the gender differences in hospital service and outpatient surgery. Notably, African American, Hispanic, and white women compared with men show significantly less use of hospital services. Gender differences in medical use vary according to the type of services used and are largely consistent across racial/ethnic groups. As the size of the Medicare population increases, promoting equitable use of healthcare resources by both women and men is an important issue in developing healthcare policy and designing public health strategies.


[In vivo effect of nanophase Ti6Al4V on osseointegration: experiment with rabbits].
To evaluate the effect of nanophase Ti6Al4V substrates on the osseointegration in vivo. Novel nanophase Ti6Al4V substrates were prepared according to the severe plastic deformation principle. Eighteen New Zealand white rabbits were randomly divided into 3 equal groups with their trochanters of femur exposed and implanted with titanium substrate with common surface (Ti group), nanophase Ti6Al4V substrate (nano-Ti group), and hydroxyapatite-coated substrate (HA group) respectively. Four, 8, and 12 weeks later X-ray films were taken on 6 rabbits from each group, tetracycline and calcein were injected intramuscularly, and one day later the rabbits were sacrificed. The histological changes of the tissue surrounding the implant including the bone kinesics parameter were evaluated; the bone-implant interfaces were examined with scanning electron microscope (SEM) and transmission electron microscope (TEM) respectively. Radiographic examinations showed that the bone recovery around the implant in the nano-Ti group was earlier compared to that in the Ti group. Histological examination suggested that the interface osseointegration rates 4, 8, and 12 weeks later of the nano-Ti groups were all significantly higher than those of the Ti group ( all P < 0.01). Strong tetracycline labeling and calcein labeling were observed around the implants in the nano-Ti group, indicating the active form action of new bone. The rates of bone mineralization and deposition 4, 8, and 12 weeks later of the nano-Ti group were higher than those of the Ti group. SEM and TEM examinations showed greater degradation of the surface and much more grains in cells in the HA group as compared to those in the nano-Ti group. The bone mineralization and osseointegration rates 4 weeks later of the HA group were significantly higher than those of the nano-Ti group (both P < 0.05), however, there were no significant differences in the bone mineralization and osseointegration rates 8 weeks later between these 2 groups. The bone mineralization and osseointegration rates 12 weeks later of the nano-Ti group were even higher than those of the HA group. The novel nanophase Ti6Al4V substrates improves the bone-implant osseointegration without significant grains of degradation in vivo, suggesting that the novel substrates and nano technology should be further considered for the orthopedic implant applications.


Neuroprotective Effects of Omega-3 Polyunsaturated Fatty Acids in a Rat Model of Anterior Ischemic Optic Neuropathy.
The purpose of this study was to investigate the therapeutic effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration in a rat model of anterior ischemic optic neuropathy (rAION). The level of blood arachidonic acid/eicosapentaenoic acid (AA/EPA) was measured to determine the suggested dosage. The rAION-induced rats were administered fish oil (1 g/day EPA) or phosphate-buffered saline (PBS) by daily gavage for 10 consecutive days to evaluate the neuroprotective effects. Blood fatty acid analysis showed that the AA/EPA ratio was reduced from 17.6 to ≤1.5 after 10 days of fish oil treatment. The retinal ganglion cell (RGC) densities and the P1-N2 amplitude of flash visual-evoked potentials (FVEP) were significantly higher in the ω-3 PUFA-treated group, compared with the PBS-treated group (P < 0.05). The number of apoptotic cells in the RGC layer of the ω-3 PUFA-treated rats was significantly decreased (P < 0.05) compared with that of the PBS-treated rats. Treatment with ω-3 PUFAs reduced the macrophage recruitment at the optic nerve (ON) by 3.17-fold in the rAION model. The M2 macrophage markers, which decrease inflammation, were induced in the ω-3 PUFA-treated group in contrast to the PBS-treated group. In addition, the mRNA levels of tumor necrosis factor-alpha, interleukin-1 beta, and inducible nitric oxide synthase were significantly reduced in the ω-3 PUFA-treated group. The administration of ω-3 PUFAs has neuroprotective effects in rAION, possibly through dual actions of the antiapoptosis of RGCs and anti-inflammation via decreasing inflammatory cell infiltration, as well as the regulation of macrophage polarization to decrease the cytokine-induced injury of the ON.