Benefits Conferred by Peer-Support Nursing Intervention to Pulmonary Function and Quality of Life in Nonsmoking Patients with COPD.
Peer support is a concept of substantial significance to health scientists and practitioners today due to its focus shifting from disease treatment to health promotion. Effective incorporation peer relationships in support-enhancing interventions could improve quality care and health outcomes. More and more cases of chronic obstructive pulmonary disease (COPD) have been diagnosed in nonsmokers. In this study, the effects of peer-support nursing intervention on the pulmonary function and quality of life of nonsmoking patients with COPD were investigated. A total of 100 COPD nonsmoking patients admitted to our hospital from October 2018 to October 2020 were selected as study subjects. All nonsmoking patients were in accordance with the guidelines of COPD diagnosis and treatment issued by the Respiratory Medicine Branch of Chinese Medical Association, and they were not in the habit of smoking. According to the different interventions, the nonsmoking patients were divided into the control group (n = 50) and the observation group (n = 50). Among them, nonsmoking patients in the control group received routine care, and nonsmoking patients in the observation group received routine care and peer-support nursing. The difference on the scores of social support, self-management efficacy, healthy lifestyle, and the distance of six-minute walking were to be compared between the two groups before and after the intervention. There was no significant statistical difference on the general information between the two groups in terms of age, gender, and course of disease (P > 0.05). Before intervention, the social support score involving subjective support, objective support, utilization of support, and total score revealed slight difference between the two groups (P > 0.05). However, after the intervention, the subjective support, utilization of support, and total score remained statistically different between the two groups (P < 0.05), and the objective support showed no significant difference between the two groups (P > 0.05). Before intervention, there was no statistical difference in the self-management efficacy scores such as positive attitude, stress reduction, self-decision-making, and total score between the two groups (P > 0.05). After the intervention, the two groups indicated statistical difference in the self-management efficacy scores (P < 0.05). Before intervention, there was no significant difference between the two groups in the healthy lifestyle score in terms of health responsibility, self-realization, interpersonal support, and stress management (P > 0.05), and the abovementioned outcome measures indicated significant difference between the two groups after intervention (P < 0.05). There was no statistical difference in six-minute walking distance between the two groups before the intervention (P > 0.05), but after the intervention, the observation group revealed a significantly longer distance of six-minute walking compared to the control group (P < 0.05). These data suggest that peer-support nursing intervention can effectively improve pulmonary function and quality of life of nonsmoking patients with COPD.


Genetic diversity and phylogenetic analysis of human immunodeficiency virus type 1 subtypes circulating in French Guiana.
We investigated the characterization of different HIV-1 subtypes present in French Guiana by use of three different methods. Serological methods were used for the initial screening, which were then confirmed by the heteroduplex mobility assay (HMA). The V3 env region was subsequently sequenced for phylogenetic analysis, to confirm the subtype of the samples, and to assign a subtype to samples that gave results that were difficult to interpret or discordant by serology or HMA. A total of 221 HIV-1 seropositive samples were typed; 110 of them were confirmed by HMA and 16 were sequenced. Of the 221 samples tested 210 patients (95%) were found to be infected with subtype B, 10 (4.5%) were infected with subtype A, and one patient was infected with subtype F. Phylogenetic analysis demonstrated that the strains from French Guiana were closely related to the subtype A and B subtypes, and that one strain was closely related to an F subtype (100% bootstrap value). Four strains from French Guiana clustered in the subtype A (99% bootstrap value) and the other strains were associated with subtype B (100% bootstrap value). The geographic position of French Guiana suggested that HIV-1 was probably introduced into the country via several routes, and thus the pattern of the HIV-1 epidemic might evolve in the near future.


Sexually transmitted infections-microbial infections, 2007 update.
Human sexual behavior required for the continuation of humankind nevertheless has its downsides, among them sexually transmitted infections (STIs). The treatment of microbial STIs is challenging but not in itself essentially very difficult. Controlling STIs, on the other hand, is like the task of Sisyphus, a king in Greek mythology who was forced forever to roll a block of stone to the top of a steep hill, only to see it roll back to the valley, where he started the toilsome task again. This is how many a venereologist must view the day's practice, supervising patients with STIs. Yes, there are newcomers, many of them very young, but there are many others, the recidivists, whom the physician and health care staff know only too well. "You don't mind seeing me again, doc. You (collectively) were so good to me last time"--as though catching a chlamydial infection 3 or 4 times, gonorrhea 20 or 30 times, and syphilis on occasion were badges of virility or part of life's natural progression. This is the pattern of STIs in 2007.


Sensitive detection of microRNAs by duplex specific nuclease-assisted target recycling and pyrene excimer switching.
Herein, we develop a simple fluorescence method for the sensitive detection of microRNAs based on duplex specific nuclease-assisted target recycling and pyrene excimer switching. This method is extremely sensitive with a detection limit of 0.58 fM, and it can be applied to absolutely detect endogenous microRNAs in cancer cells, holding great potential for clinical diagnosis and biomedical research studies.


Ototoxicity of Immunosuppressant Drugs: A Systematic Review.
Nowadays, immunosuppressant drugs are widely used to prevent rejection in organ transplantation and to treat autoimmune diseases. Ototoxicity related to immunosuppressant drugs has been anecdotally reported but scarcely investigated. The aim of this investigation was to systematically review the available data on ototoxicity due to immunosuppressant therapy for transplantation or autoimmune disease. A search of electronic databases (PubMed, Web of Science, and Scopus) was performed in order to identify studies concerning otovestibular toxicity due to immunosuppressant therapy for transplantation or autoimmune disease between January 1980 and November 2020. Eighteen articles were considered eligible for the review. Totally 131 patients experienced ototoxicity related to immunosuppressive treatment. Hearing loss was the most common clinical manifestation (128 cases) and was mainly bilateral. Tinnitus was reported in 52 cases and vertigo in 2. The immunosuppressant drugs most frequently involved in ototoxic manifestations were calcineurin inhibitors (cyclosporine and tacrolimus), often related to their high serum levels. Immunosuppressant-related ototoxicity is clinically relevant in uncommon but definitely challenging situations. Clinicians should be aware of this and inquire about hearing impairment symptoms during therapy and refer symptomatic patients to an otolaryngologist/audiologist. Further large-scale, prospective investigations are necessary to better characterize the ototoxicity of each class of immunosuppressants.


Ondansetron-droperidol combination vs. ondansetron or droperidol monotherapy in the prevention of postoperative nausea and vomiting.
Laparoscopic cholecystectomy is associated with a high incidence of postoperative nausea and vomiting. In this study we investigated comparatively the efficacy of combination therapy with ondansetron plus droperidol versus monotherapy with each agent alone in preventing postoperative nausea and vomiting following elective laparoscopic cholecystectomy. One hundred twenty-seven patients who underwent elective laparoscopic cholecystectomy under general anesthesia were included in the study, and assigned to one of the following three groups according to the antiemetic drug given intravenously at the end of the surgery: droperidol 1.25 mg in group D, ondansetron 4 mg in group O, and a combination of droperidol and ondansetron at the doses mentioned above in group D + O. Incidence of postoperative nausea and vomiting, and doses of given rescue antiemetics were recorded during the first postoperative day. The total drug cost per patient spent for postoperative nausea and vomiting management (including prophylactic antiemetics plus rescue postoperative antiemetics) was calculated. Combination therapy significantly reduced postoperative nausea and vomiting at 30 min, 3 h and 6 h after surgery compared with group D (p < 0.01 for all time points) and O (p < 0.01 at 30 min, p < 0.05 at 3 h) and required less rescue antiemetic treatment (p < 0.01). Total antiemetic cost analyses revealed no significant differences among the three groups (p > 0.05). Pretreatment with ondansetron plus droperidol is more effective than monotherapy in preventing postoperative nausea and vomiting following laparoscopic cholecystectomy, without increasing the cost comparatively.


Bouncier Particles at Night: Biogenic Secondary Organic Aerosol Chemistry and Sulfate Drive Diel Variations in the Aerosol Phase in a Mixed Forest.
Aerosol phase state is critical for quantifying aerosol effects on climate and air quality. However, significant challenges remain in our ability to predict and quantify phase state during its evolution in the atmosphere. Herein, we demonstrate that aerosol phase (liquid, semisolid, solid) exhibits a diel cycle in a mixed forest environment, oscillating between a viscous, semisolid phase state at night and liquid phase state with phase separation during the day. The viscous nighttime particles existed despite higher relative humidity and were independently confirmed by bounce factor measurements and atomic force microscopy. High-resolution mass spectrometry shows the more viscous phase state at night is impacted by the formation of terpene-derived and higher molecular weight secondary organic aerosol (SOA) and smaller inorganic sulfate mass fractions. Larger daytime particulate sulfate mass fractions, as well as a predominance of lower molecular weight isoprene-derived SOA, lead to the liquid state of the daytime particles and phase separation after greater uptake of liquid water, despite the lower daytime relative humidity. The observed diel cycle of aerosol phase should provoke rethinking of the SOA atmospheric lifecycle, as it suggests diurnal variability in gas-particle partitioning and mixing time scales, which influence aerosol multiphase chemistry, lifetime, and climate impacts.


Endolymphatic hydrops is prevalent in the first weeks following cochlear implantation.
To explore morphological or electrophysiological evidence for the presence of endolymphatic hydrops (EH) in guinea pig cochleae in the first 3 months after cochlear implantation. Dummy silastic electrodes were implanted atraumatically into the basal turn of scala tympani via a cochleostomy. Round window electrocochleography (ECochG) was undertaken prior to and after implantation. Animals survived for 1, 7, 28 or 72 days prior to a terminal experiment, when ECochG was repeated. The cochleae were imaged using micro-CT after post-fixing with osmium tetroxide to reveal the inner ear soft tissue structure. EH was assessed by visual inspection at a series of frequency specific places along the length of the cochlea, and the extent to which Reissner's membrane departed from its neutral position was quantified. Tissue response volumes were calculated. Using ECochG, the ratio of the summating potential to the action potential (SP/AP ratio) was calculated in response to frequencies between 2 and 32 kHz. There was minimal evidence of electrode trauma from cochlear implantation on micro-CT imaging. Tissue response volumes did not change over time. EH was most prevalent 7 days after surgery in implanted ears, as determined by visual inspection. Scala media areas were increased, as expected in cases of EH, over the first month after cochlear implantation. SP/AP ratios decreased immediately after surgery, but were elevated 1 and 7 days after implantation. EH is prevalent in the first weeks after implant surgery, even in the absence of significant electrode insertion trauma.


Surgical implications of early branching of the left coronary artery in anatomic correction of transposition of the great arteries.
Early branching of the left coronary artery (LCA) may become an additional operative challenge during coronary transfer in anatomic correction of transposition of the great arteries. An early branch of the LCA running in opposite transfer direction was present in 3 out of 25 patients who underwent anatomic correction. By excising a large cuff of aortic sinus wall around the ostium of the LCA enough length was gained for successful coronary transfer without kinking in 2 patients in whom the first branch was arising at the level of the origin of the circumflex artery. In the third patient with the first branch arising proximal to the origin of the circumflex artery an alternative surgical procedure seemed preferable. In such a coronary anomaly optimal visualization of the coronary branching pattern, possibly including selective coronary angiography, is advisable for better planning of the surgical technique.


The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium.
Prostaglandins (PGs) E2 and PGF2α are produced in the endometrium and are important for menstruation and fertility. Dysmenorrhea is associated with increased production of PGF2α relative to PGE2, and the opposite is true for menorrhagia. The pathways leading to PGE2 biosynthesis are well described, but little is known for PGF2α. Aldoketoreductase (AKR)-1C3, the only PGF synthase identified in the human, cannot explain the production of PGF2α by endometrial cells. AKR1B1 appears to be an alternate candidate with promising therapeutic value. The objective of the study was to address whether AKR1B1 (gene ID 231) is a functional PGF2α synthase in the human endometrium and a valid therapeutic target for menstrual pain. The design of the study was basic laboratory analyses to identify gene expression and protein levels associated with PGF2α production in endometrial tissues and endometrial cells from cycling women aged between 23 and 52 yr undergoing biopsies or hysterectomy for diverse gynecological disorders. AKR1B1 is expressed at a high level during the menstrual cycle during the secretory phase and in both epithelial and stromal cells, whereas AKR1C3 was found only in epithelial cells. Purified recombinant AKR1B1 protein, gene silencing, and transient transfection experiments all concur to demonstrate that this enzyme is a functional PGF synthase. Ponalrestat, a specific inhibitor developed to block AKR1B1 activity, reduced PGF2α production in response to IL-1β in both cultured endometrial cells and endometrial explants. The human aldose reductase AKR1B1 currently associated with diabetes complications is also a highly functional PGF synthase responsible for PGF2α production in the human endometrium and a potential target for treatment of menstrual disorders.


Communication in young children with fragile X syndrome: a qualitative study of mothers' perspectives.
To provide descriptive and qualitative information about communication in young children with fragile X syndrome (FXS) and about how families react to and accommodate communication differences in their children. In-depth interviews were conducted with 55 mothers of young children with FXS. Interviewers asked mothers to describe their children's communication, strategies they used to help promote their children's communication, communication-related frustrations, their expectations for their children, and the roles that they perceive for themselves. Over half the children were nonverbal and learning to communicate with augmentative and alternative communication. Mothers reported using strategies that were developmentally appropriate and recommended by early childhood experts, such as reading and talking to their children. Many mothers identified challenges faced in helping their child to communicate, and some cited difficulty obtaining speech-language services as a challenge. Mothers identified their roles as caregiver, teacher, therapist, and advocate. The perspectives offered by mothers are valuable because they indicate how children with FXS communicate in natural contexts. Information about mothers' expectations and roles may help clinicians to be sensitive to variables that will affect working with young children and their families.


Possible inhibitor from traditional Chinese medicine for the β form of calcium-dependent protein kinase type II in the treatment of major depressive disorder.
Recently, an important topic of major depressive disorder (MDD) had been published in 2013. MDD is one of the most prevalent and disabling mental disorders. Consequently, much research is being undertaken into the causes and treatment. It has been found that inhibition of the β form of calcium/calmodulin-dependent protein kinase type II (β-CaMKII) can ameliorate the disorder. Upon screening the traditional Chinese medicine (TCM) database by molecular docking, sengesterone, labiatic acid, and methyl 3-O-feruloylquinate were selected for molecular dynamics. After 20 ns simulation, the RMSD, total energy, and structure variation could define the protein-ligand interaction. Furthermore, sengesterone, the principle candidate compound, has been found to have an effect on the regulation of emotions and memory development. In structure variation, we find the sample functional group of important amino acids make the protein stable and have limited variation. Due to similarity of structure variations, we suggest that these compounds may have an effect on β-CaMKII and that sengesterone may have a similar efficacy as the control. However labiatic acid may be a stronger inhibitor of β-CaMKII based on the larger RMSD and variation.


RADseq-based population genomic analysis and environmental adaptation of rare and endangered recretohalophyte Reaumuria trigyna.
Genetic diversity reflects the survival potential, history, and population dynamics of an organism. It underlies the adaptive potential of populations and their response to environmental change. Reaumuria trigyna is an endemic species in the Eastern Alxa and West Ordos desert regions in China. The species has been considered a good candidate to explore the unique survival strategies of plants that inhabit this area. In this study, we performed population genomic analyses based on restriction-site associated DNA sequencing to understand the genetic diversity, population genetic structure, and differentiation of the species. Analyses of 92,719 high-quality single-nucleotide polymorphisms (SNPs) indicated that overall genetic diversity of R. trigyna was low (HO = 0.249 and HE = 0.208). No significant genetic differentiation was observed among the investigated populations. However, a subtle population genetic structure was detected. We suggest that this might be explained by adaptive diversification reinforced by the geographical isolation of populations. Overall, 3513 outlier SNPs were located in 243 gene-coding sequences in the R. trigyna transcriptome. Potential sites under diversifying selection occurred in genes (e.g., AP2/EREBP, E3 ubiquitin-protein ligase, FLS, and 4CL) related to phytohormone regulation and synthesis of secondary metabolites which have roles in adaptation of species. Our genetic analyses provide scientific criteria for evaluating the evolutionary capacity of R. trigyna and the discovery of unique adaptions. Our findings extend knowledge of refugia, environmental adaption, and evolution of germplasm resources that survive in the Ordos area.


Therapeutic Effects of Dipterocarpus tuberculatus with High Antioxidative Activity Against UV-Induced Photoaging of NHDF Cells and Nude Mice.
To investigate the therapeutic effects of methanol extracts of Dipterocarpus tuberculatus Roxb. (MED) against UV-induced photoaging, we assessed for alterations in the antioxidant activity, anti-apoptotic effects, ECM modulation, skin appearances, and anti-inflammatory response in normal human dermal fibroblast (NHDF) cells and nude mice orally treated with MED. High levels of tannin content and high free radical scavenging activity to DPPH were determined in MED, while seven active components, namely, gallic acid, bergenin, ellagic acid, ε-viniferin, asiatic acid, oleanolic acid, and 2α-hydroxyursolic acid, were identified using LC-MS analyses. UV-induced alterations in the NO concentration, SOD activity, and Nrf2 expression were remarkably recovered in MED-treated NHDF cells. Moreover, the decreased number of apoptotic cells and G2/M phase arrest were observed in the UV + MED-treated groups. Similar recoveries were detected for β-galactosidase, MMP-2/9 expression, and intracellular elastase activity. Furthermore, MED treatment induced suppression of the COX-2-induced iNOS mediated pathway, expression of inflammatory cytokines, and inflammasome activation in UV-radiated NHDF cells. The anti-photoaging effects observed in NHDF cells were subsequently evaluated and validated in UV + MED-treated nude mice through skin phenotypes and histopathological structure analyses. Taken together, these results indicate that MED exerts therapeutic effects against UV-induced photoaging and has the potential for future development as a treatment for photoaging.


Epicardial high-resolution mapping of advanced interatrial block: Relating ECG, conduction abnormalities and excitation patterns.
Impairment of conduction across Bachmann's Bundle (BB) may cause advanced interatrial block (a-IAB), which in turn is associated with development of atrial fibrillation. However, the exact relation between a complete transverse line of conduction block (CB) across BB and the presence of a-IAB has not been studied. The aims of this study are to determine whether (1) a complete transversal line of CB across BB established by high resolution mapping correlates with a-IAB on the surface ECG, (2) conduction abnormalities at the right and left atria correlate with a-IAB, and (3) excitation patterns are associated with ECG characteristics of a-IAB. We included 40 patients in whom epicardial mapping revealed a complete transverse line of CB across BB. Pre-operative ECGs and post-operative telemetry were assessed for the presence of (a) typical a-IAB and de novo early post-operative AF (EPOAF), respectively. Total atrial excitation time (TAET) and RA-LA delay were calculated. Entry site and trajectory of the main sinus rhythm wavefront at the pulmonary vein area (PVA) were assessed. Thirteen patients were classified as a-IAB (32.5%). In the entire atria and BB there were no differences in conduction disorders, though, patients with a-IAB had an increased TAET and longer RA-LA delay compared to patients without a-IAB (90.0 ± 21.9 ms vs. 74.9 ± 13.0 ms, p = 0.017; 160.0 ± 27.0 ms vs. 136.0 ± 24.1 ms, p = 0.012, respectively). Patients with typical a-IAB solely had caudocranial activation of the PVA, without additional cranial entry sites. Prevalence of de novo EPOAF was 69.2% and was similar between patients with and without a-IAB. A transverse line of CB across BB partly explains the ECG characteristics of a-IAB. We found atrial excitation patterns underlying the ECG characteristics of both atypical and typical a-IAB. Regardless of the presence of a-IAB, the clinical impact of a complete transverse line of CB across BB was reflected by a high incidence of de novo EPOAF.


Effect of increasing levels of apparent metabolizable energy on laying hens in barn system.
This experiment was to investigate the effect of increasing levels of apparent metabolizable energy (AMEn) on the laying performance, egg quality, blood parameters, blood biochemistry, intestinal morphology, and apparent total tract digestibility (ATTD) of energy and nutrients in diets fed to laying hens. A total of three-hundred twenty 33-week-old Hy-Line Brown laying hens (Gallus domesticus) were evenly assigned to four experimental diets of 2,750, 2,850, 2,950, and 3,050 kcal AMEn/kg in pens with floors covered with deep litter of rice hulls. There were four replicates of each treatment, each consisting of 20 birds in a pen. AMEn intake was increased (linear, p<0.05) with inclusion level of AMEn in diets increased. Feed intake and feed conversion ratio were improved (linear, p<0.01), but hen-day egg production tended to be increased with an increasing level of AMEn in diets. During the experiment, leukocyte concentration and blood biochemistry (total cholesterol, triglyceride, glucose, total protein, calcium, asparate aminotransferase, and alanine transferase were not influenced by increasing level of AMEn in diets. Gross energy and ether extract were increased (linear, p<0.01) as the inclusion level of AMEn in diets increased. Laying hens fed high AMEn diet (i.e., 3,050 kcal/kg in the current experiment) tended to overconsume energy with a positive effect on feed intake, feed conversion ratio, nutrient digestibility, and intestinal morphology but not on egg production and egg mass.


A five-year follow-up on the temporal stability of the Ego Impairment Index.
This study investigated the temporal stability of the Ego Impairment Index (EII) over a 5-year period. The EII is based on the Comprehensive System (Exner, 1993) and has shown promise as a measure of internal disturbance and psychopathology (Perry & Braff, 1994; Perry & Viglione, 1991; Perry, Viglione, & Braff, 1992). This study successfully recalled 17 subjects from an original sample of 46 who initially suffered from Major Depression, Melancholic-Type 5 years earlier and were treated with antidepressant medication. These subjects did not differ significantly from those Subjects who were not successfully recalled. The Rorschach and a variety of other measures were administered to the subjects. The results revealed impressive temporal consistency over 5 years: a rank-order, test-retest correlation of .68. The EII was also correlated with some of the measures of overall adaptation. These results are consistent with the notion that the EII is a stable trait-measure of psychopathology. Limitations because of the small subgroup of subjects, although not unusual in longitudinal research, are noted.


Association between single-nucleotide polymorphisms of BRAF and papillary thyroid carcinoma in a Chinese population.
Papillary thyroid cancer (PTC) is a common malignancy that frequently harbors a high prevalence of somatic mutations in the oncogenic BRAF gene. As a novel prognostic molecular marker, this gene has drawn much attention in recent years for its potential utility in the risk prognosis and management of PTC. However, the contribution of the germline variants in this gene to PTC remains unclear. The study herein was aimed to investigate the potential association between the inherited BRAF variants and PTC based on a case-control study. We selected four single-nucleotide polymorphisms (SNPs) and took a systematic step to interrogate whether these SNPs of BRAF are associated with PTC risk by genotyping these SNPs from 368 patients with PTC and 564 healthy controls. In comparison of cases and controls for the four SNPs, no differences were observed in the genotypic and allelic frequencies, nor was there evidence of an association between BRAF SNPs and overall risk of PTC. After stratification, however, we found a significantly increased risk of PTC attributed to the SNP variants rs17161747, rs1042179, and rs3748093 for those with a family history of cancer, for smokers, and for both those of age <45 years and nondrinkers, respectively. Further, in the PTC cases, those carrying the rs3748093 variant seemed to be less susceptible to developing lymph node metastases, but more likely to suffer from PTC at an earlier age (<45 years). These preliminary results may provide evidence for the involvement of the common genetic variants scattered throughout the BRAF oncogene in the prediction of PTC onset and progression. In the future, enlarging the number of samples and performing functional studies in this gene may help to validate whether the association truly exists.


Errors in the operating theatre--how to spot and stop them.
The study, first published in 2005, looks at errors made in the operating theatre by observing operations at first hand, recording them for closer scrutiny and evaluation of non-technical skills such as human error, system problems and teamwork, questioning health professionals to assess safety culture, and using computer simulations to study how hospital systems might increase the chances of surgical error.


Serum progranulin levels are elevated in infertile women with obesity.
The aim of the present study was to investigate the changes in serum progranulin and sex hormone levels in infertile women with obesity. A total of 171 infertile women who had fertility desire were included in this cross-sectional study. The initial assessment included measurements of weight, height, waist circumference, and hip circumference to calculate body mass index (BMI) and waist/hip ratio. All participants were categorised into two groups in accordance with BMI as a control group ( < 30 kg/m², n = 135) and a study group (≥ 30 kg/m², n = 36). After anthropometric measurements, venous blood samples were taken for analyses of oestradiol and follicle stimulating hormone (FSH), luteinising hormone, total testosterone (TT), 17-hydroxyprogesterone, dehydroepiandrosterone sulphate, anti-Müllerian hormone, and progranulin. The present study demonstrated that the overweight women had higher FSH levels (p < 0.01). Elevated TT levels were detected in obese women (p < 0.05). Progranulin concentrations were higher in the study group than in the control group (p < 0.05). Regression analysis demonstrated that there was a relationship between the serum progranulin concentrations and BMI (p < 0.05). Our findings support that the elevated progranulin levels are associated with obesity in infertile women. Therefore, infertile and obese patients may benefit if their serum progranulin levels decrease. Further studies are needed to elucidate this issue.


Drp1 Expression and Phosphorylation in Steroidogenic Corpus Luteum during the Estrous Cycle in Rat Ovaries.
In response to luteinizing hormone (LH), a higher concentration of progesterone (P4) is produced in luteal cells of corpus luteum (CL). Mitochondria are an essential cellular organelle in steroidogenesis. The specific engagement of the concept regarding mitochondrial shaping with early stages of steroidogenesis was suggested in reproductive endocrine cells. Although the specific involvement of GTPase dynamin-related protein 1 (Drp1) with steroidogenesis has been demonstrated in luteal cells of bovine CL in vitro, its actual relationship with ovarian steroidogenesis during the estrous cycle remains unknown. In this study, while Fis1 and Opa1 protein levels did not show significant changes during the estrous cycle, Drp1, Mfn1, and Mfn2 proteins exhibited relatively lower levels at proestrus than at estrus or diestrus. 3β-HSD showed higher levels at proestrus than at estrus or diestrus. In addition, Drp1 phosphorylation (s637) was higher in proestrus than in estrus or diestrus. Immune-positive cells for Drp1, pDrp1 (s637), and 3β-HSD were all localized in the cytoplasm of luteal cells in the CL. The immune-positive cells for 3β-HSD were more frequently seen in the CL at proestrus than at estrus or diestrus. Immunoreactivity for Drp1 in luteal cells at proestrus was weaker than that at estrus or diestrus. However, pDrp1 (s637) immune-positive cells were mostly detected in luteal cells at proestrus. These results imply that steroidogenesis (P4 production) in the CL is closely related to phosphorylation of Drp1 at serine 637. Taken together, this study presents evidence that Drp1 phosphorylation at serine 637 is an important step in steroidogenesis in the CL.


Minute synthesis of extremely stable gold nanoparticles.
We describe a rapid environmentally friendly wet-chemical approach to synthesize extremely stable non-toxic, biocompatible, water-soluble monodispersed gold nanoparticles (AuNPs) in one step at room temperature. The particles have been successfully achieved in just a few minutes by merely adding sodium hydroxide (NaOH) acting as an initiator for the reduction of HAuCl(4) in aqueous solution in the presence of polyvinylpyrrolidone (PVP) without the use of any reducing agent. It is also proved to be highly efficient for the preparation of AuNPs with controllable sizes. The AuNPs show remarkable stability in water media with high concentrations of salt, various buffer solutions and physiological conditions in biotechnology and biomedicine. Moreover, the AuNPs are also non-toxic at high concentration (100 microM). Therefore, it provides great opportunities to use these AuNPs for biotechnology and biomedicine. This new approach also involved several green chemistry concepts, such as the selection of environmentally benign reagents and solvents, without energy consumption, and less reaction time.


Self-assembled monolayers of aromatic thiols stabilized by parallel-displaced pi-pi stacking interactions.
Parallel-displaced pi-pi stacking interactions have been known to be the dominant force in stabilizing the double helical structure of DNA and the tertiary structure of proteins. However, little is known about their roles in self-assembled monolayers of other large pi molecules such as aromatic thiols. Here we report on a systematic study of the self-assembled monolayers of four kinds of anthracene-based thiols, 9-mercaptoanthracene (MA), (4-mercaptophenyl) (9-anthryl) acetylene (MPAA), (4-mercaptophenyl) (10-nitro-9-anthryl) acetylene (MPNAA), and (4-mercaptophenyl) (10-carboxyl-9-anthryl) acetylene (MPCAA) on Au(111), in which a spacer and different functional groups (NO2 and COOH) are intentionally designed to introduce and thus allow the investigation of various intermolecular interactions, in addition to pi-pi interactions in the base molecules. We find that all molecules form long-range-ordered monolayers and, more interestingly, that these assembled monolayers exhibit essentially the same fundamental packing structure. On the basis of high-resolution scanning tunneling microscopy observations, we propose the space-filling models for the observed superstructures and demonstrate that all superstructures can be understood in terms of the parallel-displaced pi-pi stacking interactions, despite the presence of competing dipole-dipole and H-bonding interactions associated with these specially designed functional groups.


Index k saddles and dividing surfaces in phase space with applications to isomerization dynamics.
In this paper, we continue our studies of the phase space geometry and dynamics associated with index k saddles (k > 1) of the potential energy surface. Using Poincaré-Birkhoff normal form (NF) theory, we give an explicit formula for a "dividing surface" in phase space, i.e., a codimension one surface (within the energy shell) through which all trajectories that "cross" the region of the index k saddle must pass. With a generic non-resonance assumption, the normal form provides k (approximate) integrals that describe the saddle dynamics in a neighborhood of the index k saddle. These integrals provide a symbolic description of all trajectories that pass through a neighborhood of the saddle. We give a parametrization of the dividing surface which is used as the basis for a numerical method to sample the dividing surface. Our techniques are applied to isomerization dynamics on a potential energy surface having four minima; two symmetry related pairs of minima are connected by low energy index 1 saddles, with the pairs themselves connected via higher energy index 1 saddles and an index 2 saddle at the origin. We compute and sample the dividing surface and show that our approach enables us to distinguish between concerted crossing ("hilltop crossing") isomerizing trajectories and those trajectories that are not concerted crossing (potentially sequentially isomerizing trajectories). We then consider the effect of additional "bath modes" on the dynamics, by a study of a four degree-of-freedom system. For this system we show that the normal form and dividing surface can be realized and sampled and that, using the approximate integrals of motion and our symbolic description of trajectories, we are able to choose initial conditions corresponding to concerted crossing isomerizing trajectories and (potentially) sequentially isomerizing trajectories.


Flowering Mechanisms and Environmental Stimuli for Flower Transition: Bases for Production Scheduling in Greenhouse Floriculture.
The scheduling of plant production is a critical aspect in modern floriculture since nowadays, sales are not oriented toward the recurring holidays as in the past, but always more toward impulse buying, implying a more diverse and constant demand on the market. This requires continuous production, often regulated by precise commercial agreements between growers and buyers, and between buyers and dealers, particularly in large-scale retail trade. In this scenario, diverse techniques to modulate the duration of the growing cycle, by hastening or slowing down plant growth and development, have been developed to match plant flowering to the market demand. Among the numerous approaches, the manipulation of climatic parameters in the growth environment is one of the most common in greenhouse floriculture. In this review, we summarize the physiological and biochemical bases underlying the main mechanisms of flowering, depending on the plant reaction to endogenous signals or environmental stimuli. In addition, the strategies based on the control of temperature (before or after planting) and light environment (as light intensity and spectrum, and the photoperiod) in the scheduling of flower and ornamental crop production are briefly described.


Update of the cholesterol force field parameters in CHARMM.
A modification of the CHARMM36 lipid force field (C36) for cholesterol, henceforth, called C36c, is reported. A fused ring compound, decalin, was used to model the steroid section of cholesterol. For decalin, C36 inaccurately predicts the heat of vaporization (~10 kJ/mol) and molar volume (~10 cc/mol), but C36c resulted in near perfect comparison with experiment. MD simulations of decalin and heptane at various compositions were run to estimate the enthalpy and volumes of mixing to compare to experiment for this simple model of cholesterol in a chain environment. Superior estimates for these thermodynamic properties were obtained with C36c versus C36. These new parameters were applied to cholesterol, and quantum mechanical calculations were performed to modify the torsional potential of an acyl chain torsion for cholesterol. This model was tested through simulations of DMPC/10% cholesterol, DMPC/30% cholesterol, and DOPC/10% cholesterol. The C36 and C36c results were similar for surface areas per lipid, deuterium order parameters, electron density profiles, and atomic form factors and generally agree well with experiment. However, C36 and C36c produced slightly different cholesterol angle distributions with C36c adopting a more perpendicular orientation with respect to the bilayer plane. The new parameters in the C36c modification should enable more accurate simulations of lipid bilayers with cholesterol, especially for those interested in the free energy of lipid flip/flop or transfer of phospholipids and/or cholesterol.


[Is an implant always necessary after enucleation?].
A retrospective study was performed on 114 patients who had received an intraorbital ball implant after removal of an eye: 44 had a primary implant inserted at the time of enucleation and 70 a secondary implant, inserted at a later date. We observed distinct advantages in the primary implantation group. Patients with a primary implant, an acrylic ball covered with sclera inserted within Tenon's capsule, had better cosmetic results and a lower complication rate and fewer needed any other therapeutic measures. Of the patients with primary implants 89% did not require further treatment, as against 51% with secondary implants.


(R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2.
Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid and the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamide. Evaluation of a series of COX-2 inhibitors revealed that many weak competitive inhibitors of arachidonic acid oxygenation are potent inhibitors of endocannabinoid oxygenation. (R) enantiomers of ibuprofen, naproxen and flurbiprofen, which are considered to be inactive as COX-2 inhibitors, are potent 'substrate-selective inhibitors' of endocannabinoid oxygenation. Crystal structures of the COX-2–(R)-naproxen and COX-2–(R)-flurbiprofen complexes verified this unexpected binding and defined the orientation of the (R) enantiomers relative to (S) enantiomers. (R)-Profens selectively inhibited endocannabinoid oxygenation by lipopolysaccharide-stimulated dorsal root ganglion (DRG) cells. Substrate-selective inhibition provides new tools for investigating the role of COX-2 in endocannabinoid oxygenation and a possible explanation for the ability of (R)-profens to maintain endocannabinoid tone in models of neuropathic pain.


A unifying new model of cytokinesis for the dividing plant and animal cells.
Cytokinesis ensures proper partitioning of the nucleocytoplasmic contents into two daughter cells. It has generally been thought that cytokinesis is accomplished differently in animals and plants because of the differences in the preparatory phases, into the centrosomal or acentrosomal nature of the process, the presence or absence of rigid cell walls, and on the basis of 'outside-in' or 'inside-out' mechanism. However, this long-standing paradigm needs further reevaluation based on new findings. Recent advances reveal that plant cells, similarly to animal cells, possess astral microtubules that regulate the cell division plane. Furthermore, endocytosis has been found to be important for cytokinesis in animal and plant cells: vesicles containing endocytosed cargo provide material for the cell plate formation in plants and for closure of the midbody channel in animals. Thus, although the preparatory phases of the cell division process differ between plant and animal cells, the later phases show similarities. We unify these findings in a model that suggests a conserved mode of cytokinesis.


Scaffolding catalysts: highly enantioselective desymmetrization reactions.
Ex-changing places: a highly enantioselective desymmetrization of 1,2-diols has been developed in which the catalyst utilizes reversible covalent bonding to the substrate to achieve both high selectivity and rate acceleration (see scheme, PMP=pentalmethylpiperidine, TBS=tert-butyldimethylsilyl). Induced intramolecularity is responsible for the enhanced rate, thus allowing the reaction to be performed at room temperature.


Functional characteristics of corticolous lichens in the understory of a tropical lowland rain forest.
In tropical lowland forests, corticolous crustose green algal lichens are abundant and highly diverse. This may be related to adaptation to prevailing microenvironmental conditions including, for example, high precipitation and low light intensities. In the understory of a tropical lowland rain forest in French Guiana, we studied the morphology of crustose green algal lichens and measured gas exchange and chlorophyll a fluorescence. We found that (i) periods of thallus suprasaturation with water were reduced by the presence of water-repelling surface structures of mycobiont hyphae at the thallus surface and the medulla; (ii) photosynthesis was adapted to the low light intensities present in the understory; and (iii) photosynthesis was rapidly activated in fluctuating light. The combination of these three mechanisms enables corticolous lichens to implement specific morphological and physiological strategies, which may favour growth in the limiting understory habitat of tropical lowland rain forests.


The 1% of emergency room visits for non-traumatic dental conditions in British Columbia: Misconceptions about the numbers.
In Canada, about 1% of all emergency room (ER) visits in a given year are made by patients with a primary diagnosis of a non-traumatic, non-urgent and yet preventable condition, such as tooth decay. This percentage is typically dismissed as irrelevant. Using 2013-2014 British Columbia data on ER use from the Canadian Institute for Health Information, however, we argue that the 1% figure (and its associated cost) has to be considered beyond its percentage value. In 2013-2014 alone, 12 357 non-traumatic dental visits were made to ERs in BC representing 1% of the total number of ER visits at a cost of $154.8 million to the taxpayers (across Canada, all visits to ER cost $1.8 billion/year). But the vast majority of these dental visits are discharged while the oral problem likely persists, hence taxpayer dollars are wasted. The belief that these dental-related ER visits are insignificant within the total cost for the health care system is misleading: treatment is not given, the problem is not resolved, and yet there is a high cost to taxpayers and to the society at large. Public health resources should be reallocated.


Current findings and gaps in early initiation of breastfeeding practices in sub-Saharan African countries: A scoping review.
Early initiation of breastfeeding (EIBF) plays an important role in reducing neonatal and infant mortality. Sub-Saharan African countries have high rates of neonatal and infant mortality, as well as a low prevalence of EIBF. By conducting a scoping review, we aimed to determine the gaps and current understandings of EIBF in Sub-Saharan Africa. We conducted this scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) reporting guidelines, focusing on primary studies published from 2008 to 2021. We reviewed their titles and abstracts against the eligibility criteria, selecting the relevant ones to this study's criteria for a further full-text review. The identified determinants can be categorized into household, maternal, and health service characteristics. Regarding health service characteristics, many studies reported that cesarean section was strongly associated with the delayed initiation of breastfeeding. Institutional delivery and delivery by skilled birth attendants were also reported to be associated with the early initiation of breastfeeding. Others pointed out that place of residence and wealth index as two household characteristics that were strongly associated with EIBF, as well as maternal characteristics such as older maternal age and higher education status. We found that only eleven studies on the early initiation of breastfeeding have been conducted in Central and West Africa. Household, maternal, and health service factors have been reported to be associated with the early initiation of breastfeeding across many countries. More studies are needed to fill the current geographic gaps and investigate determinants that have not been examined. Future research should also cover interventions that have been effective in improving EIBF for women after caesarean sections in sub-Saharan Africa. Interventions that promote institutional delivery and deliveries by skilled attendants have the potential to improve the practice.


Breast Density Should Play a Greater Role in MRI Screening Guidelines.
Guidelines for breast cancer screening with MRI were first proposed in 2007, only a few years after its clinical introduction. Those initial guidelines, which were generated by a committee sponsored by the American Cancer Society (ACS), have served as the template for similar recommendations by several organizations, with a singular goal regarding patient candidacy for MRI screening, a qualifying threshold based on risk stratification. Higher risk in those patients recommended for MRI screening translates to higher cancer detection rates, which in turn impacts cost-effectiveness. But there is another variable that should be as important as risk stratification in selecting patients for MRI screening: the probability that screening mammography will fail to detect developing cancer. That failure rate is a function of breast density, included in the MRI screening guidelines as a traditional risk factor but neglected when one considers its role as the primary cause of false-negative mammograms. The two implications of dense mammograms are essentially independent: (1) refining risk stratification and (2) predicting the "miss rate" of mammography. In the 2007 guidelines, indications for annual screening MRI, in addition to mammography, were based on patients having a calculated probability of "greater than 20-25% lifetime risk" for developing breast cancer. Other categorical risks, such as BRCA positivity, are listed in the ACS guidelines, but in effect, the threshold for adding MRI to the screening regimen has been a 20% lifetime risk for the development of breast cancer. While risk stratification in the original MRI screening guidelines had a number of inconsistencies, the focus herein is the questionable placement of high-density patients into the category described as "no policy for or against MRI, more research needed," a category where lifetime risks were grouped as 15-19%. Thus, mammographic density was relegated to its role as a traditional risk factor, while its potentially more significant impact, predicting the "miss rate" of mammography, had no role in patient selection for screening MRI. The 2007 ACS guideline committee was limited by the lack of available data, and since there was no evidence for mortality reduction at the time, the decision was made to follow the patient selection criteria that had been used in the six international MRI screening trials, even though there was little consistency among those trials. Since then, the number of screening MRI trials has more than doubled, and new trials are being designed and implemented with a focus on both features of density: risk and cancer camouflage. Enough evidence has accumulated during the 16 years subsequent to the original ACS high-risk screening guidelines to consider a complete revision that accounts for both numerical risk levels and density levels, much like what was used in the ACRIN 6666 trial. In establishing a new set of guidelines, our first question should be: What is the "miss rate" of mammography in this patient? If the chance of a false-negative mammogram is as high as we see with Level D density, then the decision to include MRI becomes straightforward. The traditional risk assessment would then be used to help determine the optimal interval between MRI screens while maintaining cost-effective cancer detection rates.


Mechanism of formation of (deoxy)guanosine adducts derived from peroxidase-catalyzed oxidation of the carcinogenic nonaminoazo dye 1-phenylazo-2-hydroxynaphthalene (Sudan I).
We investigated peroxidase-mediated oxidation of and the formation of the (deoxy)guanosine adduct by 1-phenylazo-2-hydroxynaphthalene (Solvent Yellow 14, Sudan I), a liver and urinary bladder carcinogen for rodents and a potent contact allergen and sensitizer for humans. Using thin layer chromatography (TLC) and/or high performance liquid chromatography (HPLC) combined with mass and/or nuclear magnetic resonance (NMR) spectrometry, we characterized the structures of two major peroxidase-mediated Sudan I metabolites and those of the adducts of (deoxy)guanosine that are formed during Sudan I oxidation. Peroxidase oxidizes Sudan I to radical species that react with another Sudan I radical to form the Sudan I dimer, or in the presence of (deoxy)guanosine, the oxidized Sudan I can attack the exocyclic amino group of guanine, forming the 4-[(deoxy)guanosin-N(2)-yl]Sudan I adduct. The reaction product with a second Sudan I radical results in a dimer where the oxygen 2 radical of Sudan I reacted with carbon 1 in the second Sudan I skeleton. The Sudan I dimer is unstable and decomposes spontaneously to the second oxidation product. This compound consists of the 4-oxo-Sudan I skeleton connected via the oxygen of its 2-hydroxyl group and nitrogen of its azo group with carbon 1 of 2-oxonaphthalene, having a unique spironaphthooxadiazine structure. If (deoxy)guanosine is present during the formation of this Sudan I metabolite, an adduct, in which this Sudan I metabolite is bound to the exocyclic amino group of guanine, is generated. This (deoxy)guanosine adduct is again unstable and decomposes spontaneously to the same adduct that is formed by the direct reaction of oxidized Sudan I, the 4-[(deoxy)guanosin-N(2)-yl]Sudan I adduct. The results presented here are the first structural characterization of Sudan I-(deoxy)guanosine adducts formed during the oxidation of this carcinogen by peroxidase.


[Нospital outcomes of coronary artery bypass grafting in patients with coronary heart disease with previous percutaneous coronary intervention].
Evaluation of the frequency hospital cardiovascular events in groups of patients with stable angina who underwent percutaneous coronary interventions (PCI) with stenting of the arteries before coronary bypass surgery, or who did not have previous myocardial revascularization. The 120 patients with stable angina who underwent routine coronary artery bypass grafting were examined. Group composition: Men 80.8%, age 587.6, duration of coronary heart disease 65.7 years, history of myocardial infarction (MI) 77.5%. Arterial hypertension was present in 92.5%, diabetes mellitus in 12.5% of patients. Multivessel coronary artery disease in 72.5% of patients. 28 (23.4%) patients had previously undergone PCI with stenting of the coronary arteries. The period from PCI to coronary bypass surgery was 2032.6 months. Coronary bypass surgery on-pump was performed in 88.3%, coronary bypass surgery on off-pump in 11.7%. The number of distal anastomoses ranged from 1 to 4. There were no differences in clinical and angiographic indicators, pharmacotherapy, and operation characteristics between the groups of patients who were subjected to or did not have PCI before coronary bypass surgery. There were no differences between the analyzed groups of patients in the frequency of cardiac death (0 and 1.1%, p=0.58), non-fatal MI (3.6% and 9.8%, p=0.29), stroke (0 and 1.1%, p=0.58), acute heart failure (11.7% and 34.8%, p=0.06), the number of patients with paroxysms of atrial fibrillation (28.6% and 17.4%, p=0.94), the proportion of patients with resternotomies (3.6% and 3.3%, p=0.94) and gastrointestinal bleeding (3.6% and 4.3%, p=0.86). PCI with coronary artery stenting, prior to coronary bypass surgery, does not affect the frequency of post-operative hospital cardiovascular and hemorrhagic complications.


Acetaminophen by infusion.
Acetaminophen is a nonsteroidal, nonsalicylate analgesic and antipyretic that is, today, the most common medication ingredient found in oral and rectal over-the-counter and prescription drugs. However, it was not until 2010 that Ofirmev (acetaminophen), an injection form of acetaminophen, was approved for treating mild to moderate pain, as an adjunct to opioids for severe pain, and reduction of fever in those younger than 2 years. Thus, intravenous acetaminophen may be appropriately used in a wide variety of settings and nurses who are knowledgeable and informed about the correct use of intravenous acetaminophen will be able to reduce the potential for medication misadventures. In this article, the uses and cautions for Ofirmev are discussed.


MD simulations of spontaneous membrane protein/detergent micelle formation.
The in vitro study of membrane proteins for the purpose of physicochemical analysis or structure determination often relies upon successful reconstitution into detergent micelles. Moreover, a number of biological processes such as membrane protein folding and transport rely on lipid interactions which may resemble the micellar environment. Little is known about the structures of these micelles or the processes which lead to their formation. We therefore present two 50 ns all-atom molecular dynamics simulations of spontaneous dodecylphosphocholine micelle formation around representatives of the two major families of membrane proteins, a small beta-barrel protein, OmpA, and a model alpha-helical protein, glycophorin A. Despite differences in protein architecture, we highlight common mechanistic pathways in micelle formation, which are consistent with experimental studies. We characterize the exponential kinetics of detergent-protein adsorption and suggest a simple model which may explain the aggregation process. We also compare the results with 25 and 50 ns simulations of preformed micelles containing the same proteins. We confirm that the end structures of the self-assembled micelles are similar to those from their preformed counterparts, with each micelle presenting a bilayerlike environment to the enclosed protein.


Tumor necrosis factor-alpha upregulates angiopoietin-2 in human umbilical vein endothelial cells.
The angiopoietin-Tie2 system is an important regulator of vasculogenesis and vascular integrity. Angiopoietin-2 (Ang2) disrupts blood vessel formation in the developing embryo by antagonizing the effects of angiopoietin-1 (Ang1) on the Tie2 receptor. In this study, we examined the effect of a well-known proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), on Ang2 expression in human umbilical vein endothelial cells. Reverse transcriptase-polymerase chain reaction and Northern blot analyses indicated that TNF-alpha induced Ang2 mRNA expression in a time- and dose-dependent manner. Western blot analyses revealed that TNF-alpha treatment increased cellular Ang2 protein. TNF-alpha induced less Ang2 mRNA expression in the presence of nuclear factor-kappaB (NF-kappaB) inhibitor. These results suggest that TNF-alpha-induced inflammatory angiogenesis might be facilitated by the induction of Ang2.


Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain.
Pain is a subjective experience that alerts an individual to actual or potential tissue damage. Through mechanisms that are still unclear, normal physiological pain can lose its adaptive value and evolve into pathological chronic neuropathic pain. Chronic pain is a multifaceted experience that can be understood in terms of somatosensory, affective, and cognitive dimensions, each with associated symptoms and neural signals. While there have been many attempts to treat chronic pain, in this article we will argue that feedback-controlled 'closed-loop' deep brain stimulation (DBS) offers an urgent and promising route for treatment. Contemporary DBS trials for chronic pain use "open-loop" approaches in which tonic stimulation is delivered with fixed parameters to a single brain region. The impact of key variables such as the target brain region and the stimulation waveform is unclear, and long-term efficacy has mixed results. We hypothesize that chronic pain is due to abnormal synchronization between brain networks encoding the somatosensory, affective and cognitive dimensions of pain, and that multisite, closed-loop DBS provides an intuitive mechanism for disrupting that synchrony. By (1) identifying biomarkers of the subjective pain experience and (2) integrating these signals into a state-space representation of pain, we can create a predictive model of each patient's pain experience. Then, by establishing how stimulation in different brain regions influences individual neural signals, we can design real-time, closed-loop therapies tailored to each patient. While chronic pain is a complex disorder that has eluded modern therapies, rich historical data and state-of-the-art technology can now be used to develop a promising treatment.


Learning by doing: teaching critical appraisal of randomized trials by performing an in-class randomized trial.
Our medical students often encounter difficulty because many have trouble appreciating the relative merits and limitations of clinical research design. In order to remedy these deficits, we developed a novel in-class simulated randomized trial in which students were blinded to their treatment assignment. Specifically, our goals for the session were to demonstrate the importance of randomization of subject populations, to define and use basic terminology such as relative risk reduction along with absolute risk reduction, and to demonstrate the strengths and pitfalls of analysis of subsets of subjects. We proposed the study of a hypothetical new drug, "Flunkimmune," which was claimed to prevent students from failing tests. Students received a random assignment to either the "Flunkimmune" or the placebo group. Students then received an opaque plastic egg appropriate for their randomization. We had prepared the eggs a-priori to each contain a piece of candy, and some to contain a blue dot. The flavor of the candy signified whether a particular student was in the treatment or control group. After all students had received their eggs, we "unblinded" the study by having the students open their eggs and learn to which treatment they had received. We then used an audience response system to construct a demographics table commonly known as Table 1 for the randomized trial-based characteristics of the students' choosing (e.g., "drinks Diet cola," "over six feet tall," "birth weight under seven pounds"). We asked the class to critique their own Table 1 and to comment on the adequacy of the randomization. Students were then informed that the presence of the blue dot signified a "failing" grade on a hypothetical exam to test the efficacy of "Flunkimmune." The eggs had been loaded so that the treatment group had a relative risk reduction of failure rates of 50% compared with the control group and an absolute risk reduction of 20%. This result prompted a debate among students about the relative merits of absolute or relative risk reduction in reporting the results of the study. Students also performed subgroup analyses by determining the failure rates for treatment and control students seated in particular aisles of the lecture hall. This enhanced discussion about the processes of bias and confounding inherent in subgroup analyses. This experiential teaching method allowed students to participate directly in a simulated randomized controlled trial, thereby facilitating understanding of this type of study. Students reported that the experience was enjoyable and stimulated active engagement with critical appraisal of randomized trials. Students' subsequent homework assignments, in which they were asked to critically appraise a randomized trial, demonstrated a depth of understanding not previously encountered at this level. We plan to develop and rigorously evaluate additional experiential activities that expose students to the role of the research investigator.


Effect of diode laser and topical fluoride applications on white-spot lesions in bovine enamel.
This study evaluated the effectiveness of diode laser irradiation combined with topical fluoride application for increasing the hardness of demineralized bovine enamel and esthetically improving white-spot lesions (WSLs). In addition, the study evaluated intrapulpal temperature changes during laser irradiation. One hundred twenty bovine incisors with 4 × 4-mm artificial WSLs were randomly assigned to 8 groups (n = 15): untreated control; fluoride only; LF1, LF2, and LF3, fluoride plus 2-W laser for 15, 30, and 60 seconds, respectively; and LF4, LF5, and LF6, fluoride plus 5-W laser for 15, 30, and 60 seconds, respectively. The Vickers hardness number, CIE L*a*b color space values, and visual analog scale ratings for color improvement were recorded at baseline, after demineralization to create the WSLs, and after treatment. The intrapulpal temperature changes were recorded at completion of irradiation for 30 bovine teeth that were assigned to 6 groups (n = 5) to receive doses of irradiation equivalent to the treatment of the corresponding laser groups described previously. Statistical analysis included 1-way analysis of variance and Tukey multiple comparison tests (α = 0.05) The mean Vickers hardness numbers were significantly greater for the laser groups, and mean visual analog scale scores were significantly greater for all the treatment groups (P < 0.05). The fluoride group had a significantly lower mean color change (ΔE*) value (P < 0.05). The mean intrapulpal temperature changes in the 5-W laser groups were significantly greater than those in the 2-W groups (P < 0.05). Diode laser irradiation combined with topical fluoride application significantly increased the hardness and improved the esthetic appearance of WSLs compared to no treatment (control) and fluoride treatment alone. Intrapulpal temperature changes indicated that diode laser irradiation is safer at a 2-W setting than a 5-W setting.


Targeted ultra-deep sequencing unveils a lack of driver-gene mutations linking non-hereditary gastrointestinal stromal tumors and highly prevalent second primary malignancies: random or nonrandom, that is the question.
The association of non-hereditary (sporadic) gastrointestinal stromal tumors (GISTs) and second primary malignancies is known to be nonrandom, although the underlying molecular mechanisms remain unknown. In this study, 136 of 749 (18.1%) patients with sporadic GISTs were found to have additional associated cancers, with gastrointestinal and genitourinary/gynecologic/breast cancers being the most prevalent. Gene mutations in GISTs and their associated colorectal cancers (CRCs) (n=9) were analyzed using a panel of 409 cancer-related genes, while a separate group of 40 sporadic CRCs not associated with GISTs served as controls. All 9 of the GISTs had either KIT (8 of 9) or PDGFRA (1 of 9) mutations that were not present in their associated CRCs. Conversely, all but one of the 9 GIST-associated CRCs exhibited an APC mutation, a TP53 mutation or both, while none of their corresponding GISTs harbored either APC or TP53 mutations. The genetic profile of CRCs with and without associated GISTs did not differ. Although population-based studies and case series worldwide, including ours, have unanimously indicated that the GIST-CRC association is nonrandom, our targeted ultra-deep sequencing unveiled a lack of driver-gene mutations linking sporadic GISTs to highly prevalent second primaries. Further studies are needed to elucidate other genetic alterations that may be responsible for this puzzling contradiction.


Acral angiokeratoma-like pseudolymphoma: one adolescent and two adults.
In 1988, Ramsay et al proposed an entity of acral pseudolymphomatous angiokeratoma of children (with an abbreviation of APACHE) for the unilateral multiple angiomatous papules affecting the acral region of the extremities of children. We report here similar lesions that developed in the acral portions of 1 female adolescent and 2 women. Histopathologically, they showed pseudolymphomatous features rather than those of angiokeratoma. Thus, the term should be acral angiokeratoma-like pseudolymphoma would be more appropriate than APACHE originally proposed.


Chemical Analysis and Multi-Component Determination in Chinese Medicine Preparation Bupi Yishen Formula Using Ultra-High Performance Liquid Chromatography With Linear Ion Trap-Orbitrap Mass Spectrometry and Triple-Quadrupole Tandem Mass Spectrometry.
Bupi Yishen Formula (BYF), a Chinese medicine preparation, has been clinically applied for the recovery of chronic kidney disease and for delaying its progress. Nevertheless, the chemical components in BYF have yet to be fully clarified. Ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MSn) and triple-quadrupole tandem mass spectrometry (UHPLC-TQ-MS/MS) methods were developed for qualitative chemical profiling and multi-components quantitative analysis in BYF. The chromatographic separation was performed on a Phenomenex Kinetex C18 column (2.1 × 100 mm i.d., 1.7 μm) using gradient elution of water (A) and acetonitrile (B) both containing 0.1% formic acid. Eighty-six compounds, including flavones, saponins, phenolic acids, and other compounds were authenticated or temporarily deduced according to their retention behaviors, mass mensuration, and characteristic fragment ions with those elucidated reference substances or literatures. Among the herbal medicinal materials of the formula, Astragali Radix, Codonopsis Radix, Salviae Miltiorrhizae Radix Rhizoma, and Polygoni Multiflori Radix Praeparata contributed to the bulk of the dissolved metabolites of the formula extraction. In addition, seven analytes were simultaneously determined by UHPLC-TQ-MS/MS, which was validated and has managed to determine major components in BYF. The study indicated that the established qualitative and quantitative methods would be potent and dependable analytical tools for characterizing multi-constituent in complex prescriptions decoction and provided a basis for the evaluation of bioactive components in BYF.


Health lifestyle patterns of U.S. adults.
Reaching national health objectives depends upon our ability to encourage the performance of multiple good health behaviors. There are cognitive, social, and biological reasons for expecting health behaviors to cluster. However, few studies have found significant associations among health behaviors, with the exception of the documented link between smoking and alcohol consumption. We used cluster analysis to identify population subgroups with similar patterns of diet quality, physical activity, alcohol consumption, and cigarette smoking. This is the first study of health behavior interrelationships to include a measure of overall diet quality and a large sample from a nationally representative survey of U.S. adults. We identified seven health behavior typologies: 10% of the sample (health promoting lifestyle) had an overall healthy lifestyle, 25% had a good diet but sedentary activity level, 18% had fair diet but high activity level (fitness lifestyle). Individuals in the passive lifestyle cluster (25%) had no active health promoting activities but did avoid risk taking health behaviors. Six percent of the sample were in a drinking cluster, 15% in a smoking cluster, and 2% had a hedonic lifestyle characterized by heavy drinking and smoking. These lifestyle clusters could be characterized by demographic and socioeconomic factors. This research indicates that it is possible to identify a discrete number of health lifestyles in a population sample of U.S. adults. Understanding past, present, and changing health lifestyles may provide insights for health behavior research and information for the development and targeting of public health programs that can impact on multifactorial chronic diseases.


First records of the genus Pelionella Kaydan, 2015 in East Asia, with description of a new species (Hemiptera, Coccomorpha, Pseudococcidae).
Two mealybug species (Hemiptera: Coccomorpha: Pseudococcidae), Pelionella osakaensissp. n. and P. manifecta (Borchsenius, 1949), are described and illustrated based on adult female specimens collected in Japan, on the Japanese mugwort Artemisia indica Willd. var. maximowiczii (Nakai) H. Hara (Asteraceae). These are the first records of the occurrence of Pelionella species in East Asia. The new species is similar to P. grassiana (Goux, 1989) and P. proeminens (Goux, 1990), but differs in lacking multilocular pores with double loculi rings on the venter and in possessing dorsal cerarii and a circulus. The Japanese population of P. manifecta is morphologically slightly different from the Azerbaijani and French populations in lacking large-type oral-collar tubular ducts associated with clusters formed by multilocular pores and oral-collar ducts on ventral abdominal segments III and IV. A modified key to species of the genus Pelionella Kaydan, 2015, is provided.


Impaired production of burst promoting activity by blood mononuclear cells from chronic uremic patients.
The ability of blood mononuclear cells (MNC) to produce burst promoting activity (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells from uremic patients, with or without hemodialysis, was consistently lower than that of 17 normal donors (mean 64%, P less than 0.01). Coculture of MNC with recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five of 31 patients received in vivo treatment with rEpo (1,500 units x3/week) and showed therapeutic benefit, but in all patients the BPA production remained low. On the other hand, in four patients who were on a hemodialysis protocol and subsequently underwent renal transplantation, impaired BPA production was resolved quickly, and at the same time the number of circulating BFU-E and the hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA production was not observed in patients receiving continuous ambulatory peritoneal dialysis. These observations suggest that decreased production of BPA may play a role in the development of anemia associated with chronic uremic patients, and the correction of BPA production by the improvement of hemodialysis procedure may result in more effective therapy with rEpo for those patients.


Evaluations of land cover risk factors for canine leptospirosis: 94 cases (2002-2009).
Associations of land cover/land use variables and the presence of dogs in urban vs. rural address locations were evaluated retrospectively as potential risk factors for canine leptospirosis in Kansas and Nebraska using Geographic Information Systems (GIS). The sample included 94 dogs positive for leptospirosis predominantly based on a positive polymerase chain reaction test for leptospires in urine, isolation of leptospires on urine culture, a single reciprocal serum titer of 12,800 or greater, or a four-fold rise in reciprocal serum titers over a 2-4 weeks period; and 185 dogs negative for leptospirosis based on a negative polymerase chain reaction test and reciprocal serum titers less than 400. Land cover features from 2001 National Land Cover Dataset and 2001 Kansas Gap Analysis Program datasets around geocoded addresses of case/control locations were extracted using 2500m buffers, and the presence of dogs' address locations within urban vs. rural areas were estimated in GIS. Multivariate logistic models were used to determine the risk of different land cover variables and address locations to dogs. Medium intensity urban areas (OR=1.805, 95% C.I.=1.396, 2.334), urban areas in general (OR=2.021, 95% C.I.=1.360, 3.003), and having urban address locations (OR=3.732, 95% C.I.=1.935, 7.196 entire study region), were significant risk factors for canine leptospirosis. Dogs regardless of age, sex and breed that live in urban areas are at higher risk of leptospirosis and vaccination should be considered.


Use of the lidocaine patch 5% in reducing intensity of various pain qualities reported by patients with low-back pain.
To determine the impact of the lidocaine patch 5% on pain qualities associated with low-back pain (LBP) through use of the Neuropathic Pain Scale (NPS). Patients were enrolled in an open-label, non-randomized, prospective, 6-week study involving 8 clinical trial sites in the United States. Eligible patients had non-radicular LBP and reported moderate-to-severe pain on the NPS at study enrollment. Patients were stratified to 3 groups based on the duration of their LBP, defined as acute/sub-acute (< 3 months), short-term chronic (3-12 months), or long-term chronic LBP (> 12 months). The lidocaine patch 5% was applied to the area of maximal pain, using no more than a total of 4 patches changed every 24 h. Effectiveness was measured by change from baseline to Week 2 and Week 6 in 4 composite measures of the NPS: NPS-10, NPS-4, NPS-8, and NPS-non-allodynia. Safety was assessed by adverse events (AEs), dermal assessment of application site(s), and skin sensory testing. In the combined patient population (n = 71), 6 weeks of treatment with lidocaine patch 5% significantly improved all 4 NPS composite measures at both Week 2 and Week 6 (p < 0.001). Separate analyses by subgroups revealed differential improvements in the 4 composite measures. Eleven patients (15.5%) experienced treatment-related AEs that were primarily mild-to-moderate and dermal in nature. In patients with moderate-to-severe LBP, 2 weeks and 6 weeks of treatment with the lidocaine patch 5% significantly reduces the intensity of pain qualities as measured by all 4 NPS composite measures. Lidocaine patch 5% is well tolerated with few systemic AEs and may provide beneficial pain relief for patients receiving multidisciplinary treatment without increasing risks for adverse drug interactions. Pain scales such as the NPS offer the ability to measure various pain qualities experienced by LBP patients and may allow clinicians to assess the treatment impact of different medications.


A 2-Year Longitudinal Study of Physical Activity and Cardiovascular Risk in Survivors of Stroke.
The purpose of this study was to explore associations between physical activity, cardiovascular risk factors, mobility, mood, fatigue, and cognition over 2 years following stroke rehabilitation discharge. In this longitudinal observational study, survivors of first-ever stroke were evaluated at rehabilitation discharge and 6, 12, and 24 months later. Moderate to vigorous physical activity (MVPA) duration (minutes/day) assessed with an electronic monitor was the primary outcome. Further outcomes included step count, the number and duration of MVPA and sedentary bouts, cardiovascular risk factors (eg, blood pressure, fasting lipid profile, body mass index [BMI]), gait speed and endurance, mood, fatigue, and cognition. Associations between physical activity and cardiovascular risk factors over time were assessed with random-effects regression modeling. Associations between baseline characteristics and physical activity at 2 years were explored using regression modeling. Seventy-nine participants (68.4% men) with a mean age of 65 years (SD = 14) and a median gait speed of 1.2 m/s (interquartile range = 0.8 to 1.4) were included at baseline. Associations were found between higher physical activity (MVPA duration, number and duration of MVPA bouts) and lower BMI. Better gait speed, endurance, and cognition at baseline were associated with higher MVPA and step count at 2 years. Duration and bouts of MVPA are associated with BMI. Increasing MVPA and bouts of MVPA may be a valuable treatment goal to reduce cardiovascular risk in survivors of stroke. This 2-year study found that MVPA is associated with important cardiovascular risk factors in people who have survived stroke. Understanding these associations could be useful for developing effective treatments to prevent recurrent stroke. Performing MVPA and accumulating in bouts of at least 10 minutes might be challenging, but it could be an important component of treatments to reduce cardiovascular risk after stroke.


Free Radical Scavenging and Some Pharmaceutical Utilities of Nanoparticles in the Recent Scenario.
Nanopharmaceuticals have rapidly emerged as a means to cure several diseases. There are numerous reports describing the development and application of nanopharmaceuticals. Here, we discussed nanoparticle synthesis and the mechanisms to scavenge free radicals. We also discuss their major properties and list several commercially available nanomedicines. Reactive oxygen and hydrogen species are formed during normal metabolism, and excessive reactive species can damage proteins, lipids, and DNA and cause disease. Plant- and microbe-based nanoparticles, which can protect tissues from free radical damage, have recently gained research momentum because they are inexpensive and safe. Synthetic and biocompatible nanoparticles exhibit antioxidant, antidiabetic, anti-inflammatory, and anticancer properties, which can be used to treat several diseases. Further studies are needed to investigate their sizes, dose-dependent activities, and mechanisms of action.


[The socio-economic impact of asthmatic disease at Bamako about 131 cases].
With an aim of evaluating the socio-economic impact of the asthmatic disease in Mali, a cross-sectional study was carried out of July 1st to September 30, 2006 in the district of Bamako. The study proceeded with the service of Pneumo-phthisiology of the CHU of the point G and in 4 of the 6 drawn health center of reference of the district to the fate. 131 asthmatic patients were indexed on 1595 consultations is a frequency of 8, 24%. The average age was 31 years, the sex-ratio was of 1,2 in favour of the men. August recorded the greatest number of consultation is 50.4%. The antecedent of family asthma was found in 46, 6% of the cases, the nicotinism in 13% of the cases. The average therapeutic cost per annum rose of 75.750 is 115, 47 EUROS without hospitalization with 222.750 FCFA (339, 57 EUROS) FCFA with hospitalization. The hospital expenses rose on average to. 147000 FCFA (224, 09 EUROS) that is to say 66, 21% of the costs of assumption of responsibility. The intermediate duration of hospitalization was 5,5 days 1 to 4 days without activity was noted at 50.4% of the cases, on average 312 days of absence. The professional damage was announced in 13, 7%. The economic burden was supported by the father in 29% of the cases. In 42% of the cases in charge one of expenditure was civil servant. Asthma is a social disease from its impact on the family economy.


Treatment patterns, healthcare resource utilization, and costs in patients with moderate-to-severe psoriasis treated with systemic therapy in Japan: A retrospective claims database study.
The real-world treatment landscape for patients with moderate-to-severe psoriasis receiving systemic therapies in Japan is not well understood. This study describes the demographic and clinical characteristics, treatment patterns, healthcare resource utilization, and psoriasis-associated costs in these patients. This retrospective observational study used data from the Japan Medical Data Center database between January 2016 and December 2020. Eligible patients had a confirmed diagnosis of psoriasis, ≥1 claim for a systemic treatment of interest, medical history for ≥6 months, and follow-up data for ≥12 months. Systemic therapies comprised biologics (tumor necrosis factor and interleukin inhibitors) and oral treatments (a phosphodiesterase-4 inhibitor, immunosuppressants, and vitamin A). Patient demographics and clinical characteristics, treatment patterns, healthcare resource utilization, and costs were evaluated. The study identified 1770 patients satisfying all inclusion criteria. The mean age was 49.0 years, with 68% of patients aged 20-54 years. Overall, 90.6% and 9.4% of patients received oral medications and biologics as index treatment, respectively. Treatment patterns, healthcare resource utilization, and costs were assessed for treatments received by ≥20 patients (n = 1730). During the 12-month follow-up period, 1102/1730 patients (63.7%) discontinued index treatment, of whom 9.9% switched to alternative systemic treatments. The persistence rate was ≥70% for most biologics and <50% for oral systemic treatments. All 1730 patients had ≥1 all-cause outpatient visit (2.0 visits per person per month) and hospitalization frequency was ≤0.01 per person per month. Persistent patients incurred inflation-adjusted costs of Japanese Yen (JPY) 88 667 per person per month. Treatment switching was associated with an increase in total cost: JPY 128 039 per person per month after switching versus JPY 117 504 before switching. This study of Japanese patients with moderate-to-severe psoriasis demonstrated low persistence, high discontinuation, and low rates of treatment switching with systemic therapies. Switching was associated with increased total cost. These results indicate unmet needs for new treatments.


Influence of gamma irradiation of aflatoxin B1 production by Aspergillus flavus growing on some Nigerian foodstuffs.
Spores of Aspergillus flavus (UI, 81) inoculated into some local food materials were irradiated at 62.5, 125.0, 250.0 and 500.0 krad, and the effect on aflatoxin B1 production on subsequent incubation was measured. The results show that aflatoxin B1 production decreased with increasing gamma irradiation dose in soya bean, groundnut, palm juice, while paw paw mash showed a relatively high yield of aflatoxin at 125.0 krad as compared to other irradiation levels tested except for the control. Irradiation of soya bean and groundnut inoculated with spores of Aspergillus flavus at 500.0 krad (pre-irradiation incubation period of 2 h) inhibited aflatoxin B1 production. Analysis of variance showed that media, pre-irradiation incubation periods and irradiation levels affected the total amounts of aflatoxin produced.


A new karyotype of Oligoryzomys (Sigmodontinae, Rodentia) from central Brazil.
A new karyotype of the genus Oligoryzomys was described for specimens collected in Brazilian Cerrado in Tocantins and Goiás States. Conventional staining, G-, C-banding, and Ag-NOR staining techniques were used for describe this karyotype with 2n=70, AN=74 or 76. The chromosome complement, with the highest diploid number known among Oligoryzomys species, differs from all others previously reported. This small sized Oligoryzomys species can be differentiated from other Brazilian Oligoryzomys not only by chromosomal complement, but also in some morphological attributes. The new species is apparently restricted in distribution and endemic of Brazilian Cerrado, occurring only in Rio Tocantins basin.


Abolishment of the positive feedback mechanism: a criterion for temporary medical hypophysectomy by LH-RH agonist.
The hypothalamic pituitary axis was studied in patients with an abnormal pattern of gonadotropin release during chronic treatment with LH-RH agonist. Two patients had PCOD and the third demonstrated the early luteinization phenomenon. Following a well-defined gonadotropin rise with initiation of LH-RH treatment, no further response was noted. Stabilization of the LH:FSH ratio in PCOD patients was noted after 4 weeks of treatment. Administration of both native LH-RH (100 micrograms) and intravenous pulsatile LH-RH did not evoke any rise in LH. In addition to the above LH-RH challenges, the positive feedback was examined by administration of estradiol benzoate (EB). The study demonstrated that, although the pituitary did not respond to any LH-RH challenge, it may still respond by a rise in LH following EB administration. Both functions of the hypothalamic pituitary axis should be examined in order to determine the state of medical hypophysectomy.


Aspiration of middle ear effusions prior to grommet insertion an etiological factor in tympanosclerosis.
Fifty-five children with bilateral middle ear effusions were entered into a prospective randomized double blind trial to determine whether aspiration of middle ear effusions prior to ventilation tube insertion influences ventilation tube extrusion time or the development of tympanosclerosis. Following myringotomy, aspiration of the left or right ear only was performed randomly prior to ventilation tube insertion. The tympanic membranes were inspected six-monthly to determine whether ventilation tube extrusion had occurred, and at 24 months after surgery for the presence of tympanosclerosis. Results showed no significant difference in extrusion time between aspirated and non-aspirated ears. Aspiration was found to be a factor in the development of tympanosclerosis. We conclude that routine aspiration of the middle ear effusion prior to ventilation tube insertion is associated with an increased risk of tympanosclerosis.


A functionally relevant conformational epitope on the CD9 tetraspanin depends on the association with activated beta1 integrin.
Tetraspanins associate on the cell membrane with several transmembrane proteins, including members of the integrin superfamily. The tetraspanin CD9 has been implicated in cell motility, metastasis, and sperm-egg fusion. In this study we characterize the first CD9 conformation-dependent epitope (detected by monoclonal antibody (mAb) PAINS-13) whose expression depends on changes in the activation state of associated beta(1) integrins. MAb PAINS-13 precipitates CD9 under conditions that preserve the association of this tetraspanin with integrins, but not under conditions that disrupt these interactions. Induction of activation of beta(1) integrins by temperature, divalent cation Mn(2+), or mAb TS2/16 correlated with enhanced expression of the PAINS-13 epitope on a variety of cells. Through the use of different K562 myeloid leukemia transfectant cells expressing specific members of the beta(1) integrin subfamily we show that the expression of the PAINS-13 epitope depends on CD9 association with alpha(6)beta(1) integrin. The mAb PAINS-13 reactivity has been mapped to the CD9 region comprising residues 112-154 in the NH(2) half of the large extracellular loop. Also, we show that the CD9 conformation recognized by mAb PAINS-13 is functionally relevant in beta(1) integrin-mediated cellular processes including wound healing migration, tubular morphogenesis, cell adhesion and spreading and in signal transduction involving phosphatidylinositol 3-kinase activation.


Uromodulin and chronic kidney disease.
Uromodulin (Tamm-Horsfall protein) is produced in the kidney by cells of the thick ascending limb and distal tubule. Recent genetic studies suggest a role of uromodulin in chronic kidney disease. Mutations in the UMOD gene cause uromodulin storage disease. They code for amino acid substitutions that lead to misfolding of the molecule and its retention in the endoplasmic reticulum. Single nucleotide polymorphisms in the region of the UMOD gene have been shown to be associated with chronic kidney disease and reduced glomerular filtration rate. These polymorphisms affect uromodulin concentration in the urine, and lower genetically determined urinary uromodulin concentrations seem to protect against renal disease. Chronic kidney disease is associated with higher serum levels of uromodulin. From animal experiments and human studies it is hypothesized that uromodulin entering the renal interstitium either by basolateral secretion or urinary back-leakage in damaged tubuli interacts with and stimulates cells of the immune system and thereby causes inflammation and progression of chronic kidney disease.


Comparison of Comet assay dose-response for ethyl methanesulfonate using freshly prepared versus cryopreserved tissues.
The National Toxicology Program (NTP) is using the Comet assay to evaluate genotoxic potential, and is investigating the integration of this assay into repeat-dose toxicity studies. To reduce sample-to-sample variability, address logistical concerns associated with evaluating multiple tissues from many animals, and accommodate sample collection at geographically distant testing facilities, tissue samples collected for Comet analysis by the NTP are routinely flash-frozen in liquid nitrogen and stored in a -80°C freezer until evaluation. To compare data obtained from frozen tissues to data from freshly isolated tissues, we conducted a dose-response study in male Sprague Dawley rats. Rats (5 per treatment group) were administered ethyl methanesulfonate (EMS; 0, 25, 50, 100, or 200 mg/kg) by gavage twice at an interval of 21 hr; blood, liver, stomach, and colon tissues were harvested 3 hr after the second treatment. Single-cell preparations from each of the four tissues were put into Hank's balanced salt solution with 10% fresh dimethyl sulfoxide. One aliquot of each tissue preparation was used for immediate analysis, while additional aliquots were flash-frozen in liquid nitrogen and stored in a -80°C freezer for 1 or 8 weeks. One set of 8-week frozen samples was shipped roundtrip via air courier from Research Triangle Park, NC to Rochester, NY prior to analysis. For all four tissues, results from frozen, nontransported samples showed a similar dose-response pattern for EMS-induced genotoxicity. We also demonstrated that for three tissues (blood, liver, stomach), air transport did not alter the sensitivity of the Comet assay for detecting DNA damage.


Analysis on the polarization property of the eigenmodes in a nonplanar ring resonator.
Based on the theory of the Abeles matrix, the reflections from the multilayer dielectric mirrors in a nonplanar ring resonator are discussed in detail considering the imperfect layer thickness and the incident angle errors. The polarization of Gaussian beams in nonplanar ring resonators are analyzed by using a statistical method and the way to analyze the stability of a nonplanar ring resonator in the perspective of polarization is also presented. The results show that a nonlanar ring resonator with a finite mode size may not have the reasonable polarization performances sometimes; the eigenmodes might be right- and left-handed elliptically polarized instead of circularly polarized, and they also have different ellipticity and round trip losses, which are critical for a nonplanar ring resonator. These interesting findings are important to the cavity designs of ring resonators with a nonplanar structure.


Development of a toxicity evaluation program for dental materials and products. II. Screening for systemic toxicity.
A series of systemic toxicity tests for various types of compounds are presented with illustrative data and discussed in regard to their relevance as potential screening tests for dental compounds and products. In developing and marketing a new dental material, it is important not only to ensure safety for the patient but also for the dentist, dental assistant, and laboratory worker who routinely handles and uses the product. Data are presented on a number of commercially available dental products as well as various chemical entities, which were tested by one or more of the methods described.


Microclimate Classification of Bologna (Italy) as a Support Tool for Urban Services and Regeneration.
A microclimate classification of the entire Bologna Municipality has been carried out in order to give a tool to the local administration in the drafting of the General Urbanistic Plan (PUG). The city was classified considering the variation of air temperature as a function of the surface characteristics, the vegetation fraction, the building density and the H/W ratio (height to width). Starting from the microclimate analysis carried out with fluid-dynamic modeling (Envi-met) for some areas of the city of urban interest, the air temperature variation was correlated to the physiological equivalent temperature (PET) in order to make a classification of physiological well-being for the resident population. An urban map of a normalized microclimate well-being index (BMN) has been obtained to give support when private, and public actors want to regenerate part of the city, taking into account the climate-centered approach for the development of a sustainability city.


Dax1 up-regulates Oct4 expression in mouse embryonic stem cells via LRH-1 and SRA.
Dax1 (Nr0b1) is an atypical orphan nuclear receptor that has recently been shown to play a role in mouse embryonic stem (mES) cell pluripotency. Here we describe a mechanism by which Dax1 maintains pluripotency. In steroidogenic cells, Dax1 protein interacts with the NR5A nuclear receptor steroidogenic factor 1 (Nr5a1) to inhibit transcription of target genes. In mES cells, liver receptor homolog 1 (LRH-1, Nr5a2), the other NR5A family member, is expressed, and LRH-1 has been shown to interact with Dax1. We demonstrate by coimmunoprecipitation that Dax1 is, indeed, able to form a complex with LRH-1 in mES cells. Because Dax1 was historically characterized as an inhibitor of steroidogenic factor 1-mediated transcriptional activation, we hypothesized that Dax1 would inhibit LRH-1 action in mES cells. Therefore, we examined the effect of Dax1 on the LRH-1-mediated activation of the critical ES cell factor Oct4 (Pou5f1). Chromatin immunoprecipitation localized Dax1 to the Oct4 promoter at the LRH-1 binding site, and luciferase assays together with Dax1 overexpression and knockdown experiments revealed that, rather than repress, Dax1 accentuated LRH-1-mediated activation of the Oct4 gene. Similar to our previously published studies that defined the RNA coactivator steroid receptor RNA activator as the critical mediator of Dax1 coactivation function, Dax1 augmentation of LRH-1-mediated Oct4 activation is dependent upon steroid receptor RNA activator. Finally, utilizing published chromatin immunoprecipitation data of whole-genome binding sites of LRH-1 and Dax1, we show that LRH-1 and Dax1 commonly colocalize at 288 genes (43% of LRH-1 target genes), many of which are involved in mES cell pluripotency. Thus, our results indicate that Dax1 plays an important role in the maintenance of pluripotency in mES cells through interaction with LRH-1 and transcriptional activation of Oct4 and other genes.


The Role of Nutrients and Diet Characteristics in the Management of Diabetic Foot Ulcers: A Systematic Review.
Diabetic foot ulcers (DFUs) are common complications of diabetes mellitus that affect patients' quality of life and pose a burden on the healthcare system. Although malnutrition and specific nutritional deficiencies can seriously impact wound healing in patients with chronic nonhealing wounds, the role of nutrition in the prevention and management of DFUs is still not clear. This review discusses the significance of frequent diet assessment and nutritional education of patients with DFUs with individualized correction of deficiencies and emphasis on adequate protein intake along with correction of vitamins D, C, E, and selenium status. Future research should clarify the impact of nutritional interventions, potentially involving the use of probiotics, zinc, and omega-3 fatty acids, and successfully translating the findings into practical guidelines for use in everyday clinical practice.