Advances in treatment of pulmonary arterial hypertension: patent review.
Current therapeutic approaches for pulmonary arterial hypertension (PAH) commonly include use of prostacyclins, endothelin pathway antagonists or NO (nitric oxide) pathway modulators. These agents are non-specific and suffer from several important shortcomings including short half-lives, invasive routes of administration, higher dose and frequency requirements, and several dose-related systemic side effects. Hence, discovery of novel agents with improved therapeutic efficacy with respect to survival benefits and the development of non-invasive routes of administration are in critical need. Current research aimed at developing more selective therapies for PAH are focused both on agents acting on novel molecular targets, as well as, novel compounds acting on conventional pathways with improved characteristics. Area covered: The present review covers recently filed (issued/application) patents (2010-2016) describing novel agents acting on investigational targets as well as novel compounds with improved characteristics acting on established targets. Patents describing combinations of conventional and investigational compounds are also discussed. Expert opinion: PAH has recently been considered as cancer-like disease with over-proliferation of pulmonary arterial smooth muscle cells and endothelial cells. New cellular and molecular biological advances have revealed novel target/pathways involved in the pathogenesis and progression of PAH. Thus, discovery of agents that act on these novel pathways provides a promising avenue of research for improving therapeutic approaches for PAH.


Relationship between dietary macronutrient intake and the risk of age-related cataract in middle-aged and elderly patients in northeast China.
To examine the association between dietary macronutrient intake and the risk of age-related cataract (ARC) in middle-aged and elderly men. A hospital-based case-control study was conducted from December 2009 to November 2011. Cases (n=360) were patients with cataract aged 45-85 years old, and controls (n=360) were patients who had been admitted to the same hospital for diseases not related with cataract. All subjects were interviewed using a structured interviewer-administrated questionnaire that included information on socio-demographic characteristics, lifestyle habits and detailed medical history, simultaneously, the dietary intakes of nutrients were collected via a valid semi-quantitative food frequency questionnaire (FFQ). The odds ratios (OR) and corresponding 95% confidence intervals (CI) of three types of ARC were estimated using multiple logistic regression models. After adjusting for multiple potential confounders, total dietary intake of carbohydrate was positively associated with cortical cataract, compared to controls in the lowest quartile, and the OR for cases in the highest quartile of intake was 2.471 (95%CI: 1.348-6.043, P=0.027). Higher dietary intakes of protein were protective for posterior subcapsular cataract (PSC) (OR=0.528, 95%CI: 0.148-0.869, P=0.023). Dietary fat intake was not associated with any type of cataract, however, participants in the highest quartile of polyunsaturated fatty acids intake had 2.7 times the risk of nuclear cataract as did those in the lowest quartile (OR=2.742, 95%CI: 1.790-4.200, P=0.033). A high intake of carbohydrate and polyunsaturated fatty acid may increase the odds of cortical and nuclear cataract, respectively, whereas high intake of protein, especially animal protein, may protect against PSC cataract. It is possible that dietary changes of target population may reduce the risk of ARC.


Optimizing Fixation Protocols to Improve Molecular Analysis from FFPE Tissues.
Most Departments of Pathology around the world have a considerable archive of formalin-fixed paraffin-embedded (FFPE) tissue suitable for molecular assessment. This article points out the potential DNA damage that may occur if basic steps are not followed during processing and storage of these samples. Furthermore, it hopes to establish parameters to optimize quality and quantity of DNA extracted from FFPE tissues.


Study on Personality Types of Dentists in different Disciplines of Dentistry.
The purpose of this study was to determine the most common personality type among dentists in seven selected clinical dentistry specialties using the Myers-Briggs Type Indicator (MBTI) and to compare between these different types of personalities. A survey containing the MBTI and demographic and practice questions was used to assess the personality styles of 243 dental specialists in Riyadh, Saudi Arabia. The survey results were analyzed using descriptive statistics. The results of the MBTI for 243 specialist dentists revealed, generally, a higher percentage of scoring for introversion (I) with an average of 65% than extroversion (E). The study identified 10 common personality types among these specialists: ISTJ, ISFJ, INFJ, ISTP, INFP, INTP, ENFP, ENTP, ENFJ, and ENTJ (extraversion-introversion (E-I), sensing-intuition (S-N), thinking-feeling (T-F), and judging-perception (J-P)). The dominant personality type in all seven clinical specialties in dentistry was ISTJ, with an average of 54%. The personality types showed variation among the seven clinical dentistry specialties. However, among these seven clinician's specialties in dentistry, more than 50% of the individuals shared one common type of personality (ISTJ). The identification of the personality type might help in their association with coworkers, students, and patients as well as knowing the individual preferences toward different specialties in dentistry.


Effects of eggshell and seashell powder as natural dietary calcium supplements on growth, molting frequency, and carapace calcium composition of juvenile red claw crayfish, Cherax quadricarinatus.
The growth performance of red claw crayfish, Cherax quadricarinatus, fed diets with different sources and concentrations of natural calcium was evaluated. Formulated diets containing 30% protein and 8% lipid were prepared using supplementation of 0 (control), 3%, 6%, 9% eggshell, and 6% seashell. C. quadricarinatus juveniles with an average total weight of 0.21 ± 0.01 g and length of 25.0 ± 0.10 mm were obtained from ten ovigerous females bred in captivity. An aquarium with a size of 0.72 m² was divided into eight compartments with an area of 0.09 m² per compartment and was individually stocked with juvenile crayfish. A total of eight juvenile crayfish were used per dietary treatment. There were five dietary treatments in total and each of these treatments were replicated three times. The addition of eggshell and seashell powder exerted positive effects on the growth performance, molting frequency, and survival of the crayfish. Crayfish fed with a 6% eggshell-supplemented diet exhibited the best overall growth performance. The calcium percentage of the carapace increased with the increase in calcium content of the diets. Meanwhile, the performance of diets comprising eggshells and seashells was not significantly different (P > 0.05). Considering the low cost and abundance of eggshells, the addition of 6% of this product to the diet is recommended for the best growth of juvenile C. quadricarinatus.


TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB/PI3K/AKT signaling pathway.
Ovarian cancer (OV) is the deadliest gynecological cancer. Transmembrane protein 119 (TMEM119) has been reported as oncogene in several human cancers. However, the function of TMEM119 in OV is still poorly known. Western blot and qRT-PCR were used to analyze TMEM119 levels. Transwell assays, wound healing assays, CCK-8 assays and EdU cell proliferation assays were designed to explore the function and potential mechanism of TMEM119 in malignant biological behaviors in OV. TMEM119 was observed to be overexpressed in OV tissues and associated with poor survival in OV patients. Knockdown and overexpression experiments demonstrated that TMEM119 promoted proliferation, invasion, and migration in OV cells in vitro. TMEM119 mRNA expression was related to the pathways of focal adhesion according to Gene Set Enrichment Analyses and was correlated with the mRNA expression level of platelet-derived growth factor receptor beta (PDGFRB). TMEM119 exerted oncogenic effects partially by regulating the expression of PDGFRB and by activating the PI3K/AKT signaling pathway. Collectively, our findings highlight the potential role of TMEM119 in the malignant biological behavior of OV, which may serve as a potential biomarker and a therapeutic candidate for OV.


Implementing a Pain Self-Management Protocol in Home Care: A Cluster-Randomized Pragmatic Trial.
To determine the effectiveness of a cognitive-behavioral pain self-management (CBPSM) protocol delivered by physical therapists (PTs) for use by older adults with activity-limiting pain receiving home care. A randomized pragmatic trial comparing delivery of the intervention plus usual care with usual care alone. Community. Individuals aged 55 and older admitted with orders for physical therapy who endorsed activity-limiting pain and reported pain scores of 3 or greater on a scale from 0 to 10 (N = 588). A CBPSM protocol delivered by PTs. Primary outcomes were assessed at 60 days using validated measures of pain-related disability, pain intensity, gait speed, and number of activity of daily living (ADL) deficits. Of 588 participants, 285 received care from a PT randomized to the intervention and 303 from a PT randomized to the usual care group. Both groups had significant reductions in pain-related disability, pain intensity, and ADL limitations and improved gait speed. No significant treatment differences were identified. There were no consistent treatment differences when interactions and subgroups were examined. This real-world pragmatic trial found no effect of implementation of a pain self-management intervention in a home care setting. Despite the lack of positive findings, future studies are indicated to determine how similar protocols that have been found to be effective in efficacy studies can be successfully implemented in routine clinical care.


Enhanced transfection efficiency and improved cell survival after electroporation of G2/M-synchronized cells and treatment with sodium butyrate.
To achieve high transfection efficiency in human fibroblasts with good preservation of proliferative capacity we developed an electroporation procedure that combines two distinct modalities: use of recipient cells synchronized in the late G2/mitotic phase of the cell cycle and treatment of cells post-electroporation with 5 mM butyrate. This combination enabled reduction of plasmid DNA concentration and electroporation voltage, both associated with cytotoxicity, while greatly enhancing transfection efficiencies. Although the method was primarily developed for transient expression it was also found to improve stable expression. This procedure should have wide applicability, particularly in studies seeking to identify DNA sequences that lead to inhibition of DNA synthesis and proliferation in human fibroblasts and other cells refractory to transfection.


Video-assisted open thyroid lobectomy through a small incision.
To examine if postoperative morbidity may occur in gasless video-assisted thyroid lobectomy, 111 patients with solitary nodules were treated either by gasless video-assisted lobectomy or by conventional lobectomy. Operating time needed for video-assisted lobectomy significantly exceeded that needed for conventional surgery. No death, massive hemorrhage, wound hematoma, wound infection, or permanent recurrent laryngeal nerve injury occurred in patients treated by either video-assisted or conventional lobectomy. Damage to the external branch of the superior laryngeal nerve occurred in 6 (10.2%) patients following conventional surgery but in no patients following video-assisted lobectomy (P = .0289). Transient recurrent laryngeal nerve palsy occurred in 5 (8.5%) patients after conventional surgery and in 3 (5.8%) patients after video-assisted surgery (P = .7209). It is noteworthy that morbidity occurs in video-assisted lobectomy. The general principles of thyroid surgery should be followed to avoid the occurrence of complications.


Physical and sensory properties of gelatin from seabass (Lates calcarifer) as affected by agar and κ-carrageenan.
Physical and sensory properties of gelatin from skin and swim bladder of seabass (SK and SW, respectively) as affected by agar or κ-carrageenan at 10 and 20% substitution were investigated. Hardness of both SK and SW gels containing agar increased with increasing level of agar. However, the addition of κ-carrageenan lowered hardness of mixed gels. Springiness and cohesiveness of either SK or SW gels decreased as the level of both agar or κ-carrageenan increased. Gelling and melting temperatures generally increased when the level of hydrocolloids was increased. The highest gelling (∼36C) and melting temperatures (∼43C) were obtained for SK added with 20% agar and 20% κ-carrageenan, respectively. However, the addition of both hydrocolloids at 10% affected gel microstructure differently. Furthermore, the addition of agar at 10% could increase the likeness score of sensory properties of gelatin gel. Therefore, the addition of hydrocolloids with appropriate level could improve the texture and sensory properties of gelatin from seabass. Due to the poor gelling property of fish gelatin, compared to its mammalian counterpart, improvement of this property using the selected hydrocolloids can be a promising means. In this work, it was found that agar or κ-carrageenan can be incorporated to fish gelatin to improve gelling, textural and sensory properties of gelatin from skin of seabass (Lates calcarifer). Both agar and κ-carrageenan could increase gelling and melting temperatures of seabass gelatin. The incorporation of hydrocolloids (agar and κ-carrageenan) could also improve the quality of fish gelatin gel, which in turn can widen the applications of fish gelatin in the food and other industries.


Comparison of thoroughbred and Arabian horses using RAPD markers.
We compared pools of DNA from 10 Thoroughbred horses and 10 Arabian horses for the presence of randomly amplified polymorphic DNA (RAPD) markers which might be useful in distinguishing between the breeds. Using 212 decamer oligonucleotides and our polymerase chain reaction (PCR) conditions, 173 of the primers produced scoreable bands. The number of bands ranged from 0 to 9 with an average of 3.6. In family studies using 11 arbitrarily selected primers, five of the 11 primers produced polymorphic bands which exhibited Mendelian inheritance as dominant markers. When comparing the pooled DNA from Thoroughbred and Arabian horses we found 10 primers which identified markers present in the pooled DNA from one breed but absent in the pool from the other breed. Testing individual horses revealed that only two markers were wholly absent for one group while being present among members of the other. Primer UBC-85 (5'-GTGCTCGTGC-3') detected a pair of markers absent in Thoroughbred horses but present among 11 of 31 Arabian horses. These markers were 1500 and 1700 base pairs (bp) long and designated UBC-85C and UBC-85D, respectively. Primer UBC-126 (5'-CTTTCGTGCT-3') detected a 1000 bp marker (designated UBC-126C) absent in 20 of 20 Thoroughbred horses but present in 31 of 31 Arabian horses.(ABSTRACT TRUNCATED AT 250 WORDS)


Relationship Between Multidrug-Resistant Enterobacterales and Obesity in Older Adults.
The objective of our study was to determine if obesity is associated with the presence of multidrug-resistant (MDR) bacteria among Enterobacterales. This two-center cohort study included adult hospitalized patients with at least one specimen sampled from any site for bacterial culture yielding an Enterobacterales bacterial species from November 2016 to May 2017. Study groups were stratified by obesity status based on body mass index <30 kg/m2 (non-obese) and ≥30 kg/m2 (obese). The primary outcome was the presence of gram-negative MDR bacteria defined as presumptive extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ceftriaxone resistance) or carbapenem-resistant Enterobacterales (CRE). A multivariable logistic regression model was fit to estimate the adjusted odds ratio while controlling for potential confounders. A total of 366 patients, 238 non-obese and 128 obese, were included. The most common gram-negative bacterial species identified was Escherichia coli (64.2%). There was a higher proportion of gram-negative MDR bacteria in obese versus non-obese patients (18.8 versus 11.3%, P=0.057). Obesity was independently associated with gram-negative MDR bacteria after controlling for confounders (adjusted odds ratio, 1.92; 95% CI 1.03-3.60). The association did not significantly vary by diabetes status (interaction term P=0.792). Among older adult hospitalized patients, obesity was independently associated with the presence of a gram-negative MDR bacteria (presumptive ESBL or CRE) in a culture.


The effects of hyperbaric oxygen therapy on experimental colon anastomosis after preoperative chemoradiotherapy.
The aim of the present study was to investigate the effect of hyperbaric oxygen therapy (HBOT) on colon anastomosis after chemoradiotherapy (CRT). Sixty female Wistar-Albino rats were divided into 5 groups and underwent left colon resection and end-to-end anastomosis. CRT simulation was performed on 2 sham groups before the anastomosis, and 1 of these groups was administered additional postoperative HBOT. Two groups were administered CRT before the anastomosis, and 1 of them received additional postoperative HBOT. On postoperative day 5, all groups underwent relaparotomy; burst pressure was measured and samples were obtained for histopathologic and biochemical analysis. There was a significant weight loss in the CRT groups and postoperative HBOT had an improving effect. Significantly decreased burst pressure values increased up to the levels of the controls after HBOT. Hydroxyproline levels were elevated in all groups compared to the control group. Hydroxyproline levels decreased with HBOT after CRT. No significant difference was observed between the groups regarding fibrosis formation at the anastomosis site. However, regression was observed in fibrosis in the group receiving HBOT after CRT. Preoperative CRT affected anastomosis and wound healing unfavorably. These unfavorable effects were alleviated by postoperative HBOT. HBOT improved the mechanical and biochemical parameters of colon anastomosis in rats.


QA binding in reaction centers of the photosynthetic purple bacterium Rhodobacter sphaeroides R26 investigated with electron spin polarization spectroscopy.
The relation between quinone (QA) binding and electron transport in reaction centers (RCs) of photosynthetic purple bacteria is investigated, using electron spin polarization (ESP) X-band (9 GHz) EPR as a tool to probe for structural changes resulting from charge separation and stabilization and from replacing the native QA molecule with other quinones. We present a study of possible changes in QA-binding that might be responsible for the remarkably prolonged lifetime of the charge-separated state at cryogenic temperatures for RCs of Rhodobacter sphaeroides R26 cooled under illumination [Kleinfeld, D., et al. (1984) Biochemistry 23, 5780-5786]. It is shown that this effect is not caused by a major reorientation of the chromophores. Furthermore, we studied the effects of structurally different quinones functioning as primary electron acceptor in different purple bacteria. With simulations of ESP X-band spectra of the spin-polarized secondary radical pair P.+QA.+- in menaquinone-reconstituted, Zn(2+)-substituted RCs of Rb. sphaeroides R26, we show that quinone reconstitution is highly selective for site and orientation. Furthermore, we find that a very small exchange interaction between P.+ and QA.+- (magnitude of JPQ approximately 1 microT) is needed to account accurately for the observed relative line intensities at X-band, without affecting the accuracy of the simulations of reported ESP K-band spectra [Füchsle, G., et al. (1993) Biochim. Biophys. Acta 1142, 23-35; Van der Est, A., et al. (1993) Chem. Phys. Lett. 212, 561-568]. This pronounced influence of small values for JPQ on the X-band ESP line shape results from cancellation effects of absorptive and emissive contributions to the spectrum, such that small shifts can be observed. The exchange interaction has opposite sign for the native, ubiquinone-containing RC [viz. JP.UQ = (-0.8 +/- 0.2) microT] and the menaquinone-substituted RC [JP.MK = (+0.3 +/- 0.2) microT]. The implications of these observations for electron-transport theory are discussed.


Clinical correlates of early onset antipsychotic treatment resistance.
There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. This study investigates sociodemographic and clinical correlates of early onset of TRS. Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.


Commercial use of evidence in public health policy: a critical assessment of food industry submissions to global-level consultations on non-communicable disease prevention.
Ultra-processed food industry (UPFI) actors have consistently opposed statutory regulation in health policy debates, including at the WHO. They do so most commonly with claims that regulatory policies do not work, will have negative consequences or that alternatives such as self-regulation work well or better. Underlying this are often assertions that industry is aligned with principles of evidence-based policymaking. In this study, we interrogate if this holds true by exploring the extent and quality of the evidence UPFI respondents employed to support claims around regulatory policy, and how they did this. First, we identified all submissions from organisations who overtly represent UPFI companies to consultations held by the WHO on non-communicable disease policy between 2016 and 2018. Second, we extracted all relevant factual claims made in these submissions and noted if any evidence was referenced in support. Third, we assessed the quality of evidence using independence from UPFI, nature, and publication route as indicators. Lastly, where peer-reviewed research was cited, we examined if the claims made could be justified by the source cited. Across 26 included consultation responses, factual claims around regulation were made in 18, although only 10 referenced any evidence at all. Of all 114 claims made, 39 pieces of identifiable evidence were cited in support of 56 claims. Of the 39 distinct pieces of evidence, two-thirds were industry-funded or industry-linked, with only 16 externally peer-reviewed. Over half of industry-funded or industry-linked academic articles failed to declare a conflict of interest (COI). Overall, of only six claims which drew on peer-reviewed and independent research, none appropriately represented the source. UPFI respondents made far-reaching claims which were rarely supported by high-quality, independent evidence. This indicates that there may be few, if any, benefits from consulting actors with such a clear COI.


Interpreting 16S rDNA T-RFLP Data: Application of Self-Organizing Maps and Principal Component Analysis to Describe Community Dynamics and Convergence.
Interpreting the large amount of data generated by rapid profiling techniques, such as T-RFLP, DGGE, and DNA arrays, is a difficult problem facing microbial ecologists. This study compares the ability of two very different ordination methods, principal component analysis (PCA) and self-organizing map neural networks (SOMs), to analyze 16S-DNA terminal restriction-fragment length polymorphism (T-RFLP) profiles from microbial communities in glucose-fed methanogenic bioreactors during startup and changes in operational parameters. Our goal was not only to identify which samples were similar, but also to decipher community dynamics and describe specific phylotypes, i.e., phylogenetically similar organisms, that behaved similarly in different reactors. Fifteen samples were taken over 56 volume changes from each of two bioreactors inoculated from river sediment (S2) and anaerobic digester sludge (M3) and from a well-established control reactor (R1). PCA of bacterial T-RFLP profiles indicated that both the S2 and M3 communities changed rapidly during the first nine volume changes, and then became relatively stable. PCA also showed that an HRT of 8 or 6 days had no effect on either reactor communtity, while an HRT of 2 days changed community structure significantly in both reactors. The SOM clustered the terminal restriction fragments according to when each fragment was most abundant in a reactor community, resulting in four clearly discernible groups. Thirteen fragments behaved similarly in both reactors, eight of which composed a significant proportion of the microbial community as judged by the relative abundance of the fragment in the T-RFLP profiles. Six Bacteria terminal restriction fragments shared between the two communities matched cloned 16S rDNA sequences from the reactors related to Spirochaeta, Aminobacterium, Thermotoga, and Clostridium species. Convergence also occurred within the acetoclastic methanogen community, resulting in a predominance of Methanosarcina siciliae-related organisms. The results demonstrate that both PCA and SOM analysis are useful in the analysis of T-RFLP data; however, the SOM was better at resolving patterns in more complex and variable data than PCA ordination.


MEpurity: estimating tumor purity using DNA methylation data.
Tumor purity is a fundamental property of each cancer sample and affects downstream investigations. Current tumor purity estimation methods either require matched normal sample or report moderately high tumor purity even on normal samples. It is critical to develop a novel computational approach to estimate tumor purity with sufficient precision based on tumor-only sample. In this study, we developed MEpurity, a beta mixture model-based algorithm, to estimate the tumor purity based on tumor-only Illumina Infinium 450k methylation microarray data. We applied MEpurity to both The Cancer Genome Atlas (TCGA) cancer data and cancer cell line data, demonstrating that MEpurity reports low tumor purity on normal samples and comparable results on tumor samples with other state-of-art methods. MEpurity is a C++ program which is available at https://github.com/xjtu-omics/MEpurity. Supplementary data are available at Bioinformatics online.


Stereotactic body radiotherapy for patients with non-small-cell lung cancer using RapidArc delivery and a steep dose gradient: prescription of 60% isodose line of maximum dose fitting to the planning target volume.
We retrospectively investigated outcomes, including pulmonary toxicities, of stereotactic body radiation therapy using RapidArc and a risk-adapted 60% isodose plan for early-stage non-small-cell lung cancer patients. We evaluated patients staged as cT1a-2bN0M0 between 2011 and 2017 and treated with a total dose of 40-60 Gy in five fractions to the 60% isodose line of the maximum dose encompassing the planning target volume with curative intent. Comorbidities and age were rated using an age-adjusted Charlson comorbidity index (AACCI). Factors associated with overall survival (OS) were investigated. A total of 237 patients with 250 lesions were eligible. The median follow-up was 28.0 months. The local recurrence rate at 3 years was 0.8%; none of the patients developed isolated local recurrence. OS, deaths from lung cancer, and deaths from intercurrent disease at 3 years were 72.7%, 8.2% and 19.1%, respectively. On multivariate analysis for correlating factors with OS, AACCI and maximal standardized uptake value on [18F]-fluorodeoxyglucose positron emission tomography/computed tomography remained significant. Grade ≥3 toxicities were limited to radiation pneumonitis in six (2.4%) patients (Grade 3 in four patients and Grade 5 in two patients). Among those, three patients had idiopathic interstitial pneumonia. The total dose was unrelated to the incidence of Grade ≥3 radiation pneumonitis (P = 0.69). Using the 60% isodose prescription and RapidArc, maximal local control was achieved with acceptable toxicities. Although the OS may depend on patient background, dose escalation aiming at higher local control can be beneficial for medically inoperable patients.


[Under the aegis of urgency: management practices by public hospital directors in Rio de Janeiro, Brazil].
This article discusses management practices in public hospitals (general hospitals with emergency services) in the city of Rio de Janeiro, Brazil, based on a psychosociological approach to organizational analysis. Of the 12 existing hospitals, 8 were included in the current study, conducted from July 2003 to April 2004. The research, drawing on hospital directors' narratives, identified three management models. The first focuses on processes of change, highlighting symbolic and imaginative elements for building a vision of the future for the hospitals. The second concentrates on specific projects, which absorbs all the management efforts. A third pattern (predominant in the study) is marked by the struggle to keep the hospital working, with the image of urgency as the driving force. The imposition of continuous action leaves no room for reflection. The crisis in Rio de Janeiro's public hospitals has led to a "wartime" environment and thus the dissemination of the urgency-based model.


An integrated system of community services for the rehabilitation of chronic psychiatric patients in Shenyang, China.
The evolution of the Zhengyang Community Mental Health Rehabilitation Centre described in this paper proves that community-based mental health services initiated and developed by enthusiastic and committed community members can be successful in the Chinese setting. The most important step is to utilise community resources to secure a stable source of income, preferably by establishing a profitable welfare enterprise that can both finance the provision of other services and provide work for mentally ill clients who cannot obtain regular employment. The ultimate goal is to reintroduce as many clients back into the community as possible, so a range of services is needed: supervision of medication, social skills training, occupational rehabilitation, and, most importantly, work placement. The vitality of the organisation depends on its flexibility and responsiveness to the changing needs of patients; it must use its experience to guide policy decisions about the development of new services and the alteration or termination of existing services.


A new furanoid diterpene from Caesalpinia pulcherrima.
A new cassane-type diterpene isovouacapenol E (1) was isolated from the leaves of Caesalpinia pulcherrima, together with the known compounds caesaldekarin A (3), spathulenol (4), caryophyllene oxide (5), phytol, and sitosterol. The structure of 1 was elucidated by spectral data interpretation.


Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women.
Controversy exists as to whether lipoprotein(a), a lipoprotein with homology to plasminogen, is a clinically meaningful cardiovascular risk marker in women. There is also poor agreement among lipoprotein(a) levels obtained by different assays. To determine the association of lipoprotein(a) levels, measured with an assay independent of apolipoprotein(a) isoform size, with the incidence of future cardiovascular events. Prospective study of 27,791 initially healthy women in the Women's Health Study, enrolled between November 1992 and July 1995 and followed up for 10 years. Lipoprotein(a) level was measured in blood samples obtained at baseline with an assay independent of apolipoprotein(a) isoform size. Hazard ratios (HRs) for first-ever major cardiovascular events (nonfatal myocardial infarction, nonfatal cerebrovascular event, coronary revascularization, or cardiovascular deaths). During follow-up, there were 899 incident cardiovascular events. After adjusting for age, smoking, blood pressure, body mass index, total cholesterol, high-density lipoprotein cholesterol, diabetes, hormone use, C-reactive protein, and randomization treatment groups, women in the highest quintile of lipoprotein(a) (> or =44.0 mg/dL) were 1.47 times more likely (95% CI, 1.21-1.79; P for trend <.001) to develop cardiovascular events than women in the lowest quintile (< or =3.4 mg/dL). This association, however, was due almost entirely to a threshold effect among those with the highest lipoprotein(a) levels. After adjusting for all of the variables listed above, the HR associated with lipoprotein(a) levels exceeding the 90th percentile (> or =65.5 mg/dL) was 1.66 (95% CI, 1.38-1.99); 95th percentile (> or =83 mg/dL), 1.87 (95% CI, 1.50-2.34); and 99th percentile (> or =130.7 mg/dL), 1.99 (95% CI, 1.32-3.00), with almost no risk gradient at lower levels. Associations were strongest among women with low-density lipoprotein cholesterol (LDL-C) above the median level. In this subgroup, the adjusted HR associated with lipoprotein(a) levels exceeding the 90th percentile was 1.81 (95% CI, 1.48-2.23); 95th percentile, 1.93 (95% CI, 1.51-2.48); and 99th percentile, 1.93 (95% CI, 1.21-3.05) (P value for interaction with LDL-C = .001). In this cohort of initially healthy women, extremely high levels of lipoprotein(a) (> or =90th percentile), measured with an assay independent of apolipoprotein(a) isoform size, were associated with increased cardiovascular risk, particularly in women with high levels of LDL-C. However, the threshold and interaction effects observed do not support routine measurement of lipoprotein(a) for cardiovascular stratification in women.


Microsatellite instability at chromosome 8p in non-small cell lung cancer is associated with lymph node metastasis and squamous differentiation.
Genetic alterations at chromosome arm 8p are associated with advanced disease and poor patient outcome in several types of malignant tumors. We studied the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosome 8p in early stage non-small cell lung cancer (NSCLC) of 47 patients with stage I or II disease (25 squamous cell carcinomas and 22 adenocarcinomas). Microsatellite analysis was performed after laser microdissection using 5 polymorphic tetranucleotide microsatellite markers and 4 dinucleotide markers at chromosome 8p. A pentanucleotide repeat marker at the chromosomal locus 17p13.1 (TP53.Alu) was also analyzed. Expression of the mismatch repair (MMR) proteins hMSH2, hMSH6 and hMLH1 was evaluated by immunohistochemistry. Microsatellite instability (MSI) in at least 2 markers was detected in 9 of 47 patients (19.1%) and was predominantly found at tetranucleotide repeats. Sixteen of 47 (34.0%) NSCLC demonstrated LOH at chromosome 8p. All MSI-positive tumors showed normal expression of the MMR proteins. The presence of MSI at chromosome 8p was associated with lymph node metastasis (p=0.02), squamous differentiation (8/25; 32%-p=0.03), and the presence of LOH at the p53 locus (p=0.06). None of the other investigated clinical, pathologic or molecular factors correlated with MSI. Our study showed that an elevated MSI at selected tetranucleotide sequences (EMAST) on chromosome 8p is frequent in early stage squamous cell carcinomas of the lung with lymphatic spread. The tetranucleotide marker panel used in this study was able to indicate lymph node metastasis and high risk disease in patients with resectable squamous cell lung cancer.


Co-inhibitory blockade while preserving tolerance: checkpoint inhibitors for glioblastoma.
The introduction of immunotherapy with checkpoint receptor blockade has changed the treatment of advanced cancers, at times inducing prolonged remission. Nevertheless, the success rate of the approach is variable across patients and different tumor types, and treatment is often accompanied by severe immune-related side effects, suggesting the importance of co-inhibitory pathway for both prevention of autoimmunity and failure of tumor rejection. A better understanding of how to uncouple anti-tumor activity from loss of self-tolerance is necessary to increase the therapeutic efficacy of checkpoint immunotherapy. In this review, we describe basic concepts of T-cell exhaustion that occur in cancer, highlighting the role of co-inhibitory receptors in contributing to this process while preventing immunopathology. By providing an overview of the current therapeutic success and immune-related burden of secondary effects of checkpoint immunotherapy, we illustrate the "double-edged sword" related to interference with immune-regulatory pathways. Finally, since achieving tumor rejection while preserving self-tolerance is particularly important for the central nervous system, we analyze the case for checkpoint immunotherapy in glioblastoma, the most common adult brain tumor.


Low flow velocity in the middle cerebral artery predicting infarction after bypass surgery in adult moyamoya disease.
OBJECTIVE Direct and indirect bypass surgeries are recognized as the most effective treatments for preventing further stroke in adults with moyamoya disease (MMD). However, the risk factors for postoperative infarction after bypass surgery for MMD are not well established. Therefore, the objective of this study was to investigate the risk factors for postoperative infarction. In particular, the authors sought to determine whether transcranial Doppler (TCD) ultrasonography measurements of mean flow velocity (MFV) in the middle cerebral artery (MCA) could predict postrevascularization infarction. METHODS The medical records of patients with MMD who underwent direct bypass surgery at the authors' institution between July 2012 and April 2015 were reviewed. The MFV in the MCA was measured with TCD ultrasonography and categorized as high (> 80 cm/sec), medium (40-80 cm/sec), and low (< 40 cm/sec). Postoperative MRI, including diffusion-weighted imaging, was performed for all patients within a week of their surgery. Angiographic findings were classified according to the Suzuki scale. Postrevascularization infarction was defined as any diffusion restriction on postoperative MRI scans. Postoperative neurological status was assessed through a clinical chart review, and the modified Rankin Scale was used to evaluate clinical outcomes. RESULTS Of 43 hemispheres in which bypass surgery for MMD was performed, 11 showed postrevascularization infarction. Ten of these hemispheres had low MFV and 1 had medium MFV in the ipsilateral MCA. In both univariate and multivariate analyses, a low MFV was associated with postrevascularization infarction (adjusted OR 109.2, 95% CI 1.9-6245.3). A low MFV was also statistically significantly associated with more advanced MMD stage (p = 0.02). CONCLUSIONS A low MFV in the ipsilateral MCA may predict postrevascularization infarction. Bypass surgery for MMD appears to be safe in early-stage MMD. Results of TCD ultrasonography provide clinical data on the hemodynamics in MMD patients before and after revascularization.


The genetic basis of systemic lupus erythematosus.
Although cumulative evidence suggests that a genetic predisposition plays a major role in the development of systemic lupus erythematosus (SLE), the susceptibility genes are mostly unknown. The difficulty in identifying susceptibility genes is due in part to the inherent nature of this polygenic complex disease and the diverse genetic backgrounds of human populations. Murine SLE models that have homogenous genetic backgrounds are less complex for genetic dissection. Genome-wide linkage studies of murine SLE have mapped the position of a number of susceptibility loci. Recently, several of these major murine loci have been shown to link to different clinical and laboratory features of lupus-like phenotypes. In addition, evidence for additional genetic contributions via interaction between murine loci has been reported. In human SLE, many polymorphic genes (which have potential roles in SLE, as suggested by their known functions) have been associated with SLE or SLE subsets by population-based case-control or within-case studies. Because more compelling genetic evidence includes linkage analysis, our group has used the identified murine susceptibility loci as a guide and conducted linkage analysis of genetic markers located within a specific, possibly syntenic human chromosomal region. Evidence for linkage of a chromosome 1q41-42 region was observed in SLE-affected sibling pairs from multiple ethnic groups. This article summarizes recent developments and outlines possible future directions in delineating the genetic basis of SLE.


Endovascular treatment of a true posterior communicating artery aneurysm.
Posterior communicating artery (PCoA) aneurysms are most commonly located at the junction of the internal carotid artery and the PCoA. "True" PCoA aneurysms, which originate from the PCoA itself, are rarely encountered. Most previously reported cases were treated surgically mainly before the endovascular option became available. A 53-year-old male presented with sudden onset of right hemiparesis and aphasia. Left middle cerebral artery stroke was diagnosed. Further studies revealed a 3 mm left PCoA aneurysm arising from the PCoA itself, attached to neither the internal carotid artery nor the posterior cerebral artery. Endovascular treatment was performed and the aneurysm was coiled completely. Technical advances in endovascular interventional technology have permitted an additional approach to these lesions. The possible endovascular significance of the treatment of true PCoA aneurysms is discussed.


Simultaneous transplantation of the kidney and pancreas for end-stage diabetic nephropathy.
The surgical techniques involved in the simultaneous harvesting of the pancreas and kidneys from a cadaveric donor and the subsequent transplantation of the organs are presented in detail. The advantages of synchronous transplantation of the pancreas and kidneys in the treatment of end-stage diabetic nephropathy are also discussed.


Effects of eye gaze cues provided by the caregiver compared to a stranger on infants' object processing.
Previous research has shown that eye gaze affects infants' processing of novel objects. In the current study we address the question whether presenting a highly familiar face vs. a stranger enhances the effects of gaze cues on object processing in 4-month-olds. Infants were presented pictures of the infant's caregiver and another infant's caregiver (stranger) either turning eye gaze toward an object next to the face or looking away from the object. Then objects were presented again without the face and event-related potentials (ERP) were recorded. An enhanced positive slow wave (PSW) was found for objects that were not cued by the caregiver's eye gaze, indicating that these objects required increased encoding compared to objects that were cued by the caregiver's gaze. When a stranger was presented, a PSW was observed in response to objects regardless of whether the objects were gaze-cued or not. Thus, the caregiver's eye gaze had a larger effect on infants' object processing than the stranger's gaze. This suggests that at 4 months of age the caregiver's eye gaze is easier to process for infants, more salient, or both. The findings are discussed in terms of early social cognitive development and face processing models.


When and how to excise vaginal mesh.
Since 2011, there has been increasing attention paid to the use of synthetic grafts (mesh) in pelvic reconstructive surgery. Although synthetic grafts are considered permanent implants to improve outcomes, the use of this material has created inadvertent complications such as erosion, chronic pain, and dyspareunia. Patient evaluation is complex and surgical techniques carry risks not yet completely understood. This review summarizes current opinions in synthetic graft excision for the treatment of mesh-related complications. Recent studies reveal excisions are being increasingly performed and graft placement is decreasing. Patients of lower-volume surgeons have a higher risk of complication and need for excisional procedures. Pain is becoming the most common indication for vaginal mesh excision and that pain is mostly elicited with palpation of the mesh arms. Explantation is technically challenging and carries significant risks. Vaginal synthetic graft complications are increasingly being managed by surgical excision. Careful evaluation of patient symptoms and objective findings should help guide management. Surgeons considering operative management should counsel patients regarding the risks of excision including but not limited to hemorrhage, nerve damage, muscular injury, and recurrent symptoms.


Antimicrobial prophylaxis for major head and neck surgery in cancer patients.
A total of 113 patients were randomly allocated to receive either ticarcillin plus clavulanic acid (total dose, 20.8 g) or clindamycin (total dose, 2.4 g) plus amikacin (total dose, 1 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, prior antineoplastic treatment (surgery, chemotherapy, and radiotherapy) or tracheostomy, and the various types of surgery including radical neck dissection. The wound infection rate was 10% in the group of patients receiving clindamycin plus amikacin and 36% in the group receiving ticarcillin plus clavulanic acid (P less than 0.05). Initiation of systemic antibiotic therapy within 15 days of surgery was necessary for 20 and 45% of these patients, respectively (P less than 0.05). The distribution of microorganisms causing wound infections was comparable in both groups, except for anaerobes, which were isolated predominantly from patients who had received ticarcillin plus clavulanic acid.


Correlations of life form, pollination mode and sexual system in aquatic angiosperms.
Aquatic plants are phylogenetically well dispersed across the angiosperms. Reproductive and other life-history traits of aquatic angiosperms are closely associated with specific growth forms. Hydrophilous pollination exhibits notable examples of convergent evolution in angiosperm reproductive structures, and hydrophiles exhibit great diversity in sexual system. In this study, we reconstructed ancestral characters of aquatic lineages based on the phylogeny of aquatic angiosperms. Our aim is to find the correlations of life form, pollination mode and sexual system in aquatic angiosperms. Hydrophily is the adaptive evolution of completely submersed angiosperms to aquatic habitats. Hydroautogamy and maleflower-ephydrophily are the transitional stages from anemophily and entomophily to hydrophily. True hydrophily occurs in 18 submersed angiosperm genera, which is associated with an unusually high incidence of unisexual flowers. All marine angiosperms are submersed, hydrophilous species. This study would help us understand the evolution of hydrophilous pollination and its correlations with life form and sexual system.


Nominate an outstanding vet for a BVA award.
One of the highlights of the BVA year is the presentation of our awards at Members' Day. Public affairs manager Helena Cotton invites members to nominate outstanding vets to be considered for a BVA award.


Self-reported sleep disorder symptoms in epilepsy.
Three groups of adult epileptic subjects with simple partial, complex partial, and generalized seizures and normal control subjects completed a brief self-report sleep questionnaire. The simple partial and complex partial groups indicated significantly more sleep disorder symptoms, especially frequent night awakenings. The generalized group was most similar to the controls. Irrespective of seizure type, the epileptic patients with the most frequent seizures also had the most sleep disturbances. Sleep disorder symptoms did not increase with age in the seizure groups. It would thus seem that epileptic patients with partial seizures and those with more frequent seizures are at risk for developing sleep disorders.


Analytical technique to recover the third dimension in planar imaging of inhaled aerosols: (1) impact on spatial quantification.
An analytical algorithm is described for converting planar scintigraphic images of aerosol distributions in the lungs to an equivalent three-dimensional (3D) representation. The recovery of volumetric information should benefit regional quantification. The technique has been validated using simulated planar images of eleven known aerosol distributions in ten realistic lungs. Global and regional 3D parameters, such as the total activity deposition (A), the penetration index (PI) and the relative penetration index (rPI), were quantified on the planar images and on their 3D representation. Random and systematic errors of the estimation were measured. Finally, the performance of planar imaging was compared with that of single-photon emission computed tomography (SPECT). SPECT images were simulated for the same aerosol distributions in the same subjects and quantified for A, PI, and rPI. The systematic errors in A, PI and rPI obtained from planar imaging were 8.9%, 64.8%, and 54.1%, respectively, using the two-dimensional (2D) analysis; they improved significantly to 4.4%, 19.0%, and 25.5% with the 3D analysis (p < 0.01). The corresponding values for SPECT were 5.2%, 9.8%, and 15.7%, significantly better for PI and rPI (p < 0.01). The random errors of A were similar for all techniques being about 5%; those of PI and rPI measurements were significantly higher for planar imaging (<or=14%) than SPECT (<or=8%). In conclusion, 3D spatial parameters can be derived from planar imaging that are significantly more accurate in characterizing different aerosol depositions than their 2D counterpart. However, the errors remain significantly higher than with SPECT.


Evaluation of the effects of various factors on the serum triglyceride level in young adults.
The life style of young adults has been receiving attention with a view to its improvement to preventing coronary heart diseases (CHD) in later life. In this study, for determining the influence of different life styles on the serum triglyceride level, we carried out surveys and laboratory studies on the relationships of the nutritional intake, physical activity, and cigarette smoking and alcohol consumption of young adults with their serum triglyceride levels. The nutritional survey indicated a significant correlation between the serum triglyceride level and carbohydrate intake (p < 0.01). In the survey of physical activity, a significant inverse correlation was found between the energy expenditure per kg body weight and the serum triglyceride level (p < 0.05). No significant relationship was found of smoking or drinking with the serum triglyceride level. The body mass index was found to have effects on both the serum triglyceride and total cholesterol levels. Of the factors examined, carbohydrate intake and energy expenditure per kg body weight had the greatest effects on the serum triglyceride level. Considering the trend for young people to consume large quantities of carbonated drinks, in which most of carbohydrate is sucrose, we tested the affect of a high carbohydrate diet on one group of subjects and found that it caused a significant increase in the serum triglyceride level (p < 0.05). Another group for whom a mild exercise regimen was prescribed showed slight, but not significant decrease in the serum triglyceride level. These results suggest that at least optimal nutrition and physical activity including weight control during adolescence are important for preventing CHD.


Top-down design of magnonic crystals from bottom-up magnetic nanoparticles through protein arrays.
We show that chemical fixation enables top-down micro-machining of large periodic 3D arrays of protein-encapsulated magnetic nanoparticles (NPs) without loss of order. We machined 3D micro-cubes containing a superlattice of NPs by means of focused ion beam etching, integrated an individual micro-cube to a thin-film coplanar waveguide and measured the resonant microwave response. Our work represents a major step towards well-defined magnonic metamaterials created from the self-assembly of magnetic nanoparticles.


The Use of Neural Network Modeling Methods to Determine Regional Threshold Values of Hydrochemical Indicators in the Environmental Monitoring System of Waterbodies.
The regulation of the anthropogenic load on waterbodies is carried out based on water quality standards that are determined using the threshold values of hydrochemical indicators. These applied standards should be defined both geographically and differentially, taking into account the regional specifics of the formation of surface water compositions. However, there is currently no unified approach to defining these regional standards. It is, therefore. appropriate to develop regional water quality standards utilizing modern technologies for the mathematical purpose of methods analysis using both experimental data sources and information system technologies. As suggested by the use of sets of chemical analysis and neural network cluster analysis, both methods of analysis and an expert assessment could identify surface water types as well as define the official regional threshold values of hydrochemical system indicators, to improve the adequacy of assessments and ensure the mathematical justification of developed standards. The process for testing the proposed approach was carried out, using the surface water resource objects in the territory of the Republic of Tatarstan as our example, in addition to using the results of long-term systematic measurements of informative hydrochemical indicators. In the first stage, typing was performed on surface waters using the neural network clustering method. Clustering was performed based on sets of determined hydrochemical parameters in Kohonen's self-organizing neural network. To assess the uniformity of data, groups in each of the selected clusters were represented by specialists in this subject area's region. To determine the regional threshold values of hydrochemical indicators, statistical data for the corresponding clusters were calculated, and the ranges of these values were used. The results of testing this proposed approach allowed us to recommend it for identifying surface water types, as well as to define the threshold values of hydrochemical indicators in the territory of any region with different surface water compositions.


Frameworks for selecting appropriate rural sanitation technology options in low- and middle-income countries: a critical review.
Several rural technology options exist on the sanitation market with different characteristics, yet project failures in some developing countries were attributable to inappropriate technology choices. Frameworks that are used to select sanitation technology options (hard copy, computer programmes) were developed by researchers and project implementers. They vary in design and application as there is no standard format. This appears to create a gap between science and practice. Frameworks should have some key elements needed to select appropriate sanitation technologies. We evaluated 12 available frameworks (2000-2019) used to select sanitation technologies in rural communities of low- and middle-income countries against 22 assessment criteria derived from literature. Criteria that were not fully addressed by some of the reviewed frameworks (scores of 8-50%) included equity, sanitation demand, sanitation behaviour change, ongoing contact, replicability, framework limitations, personnel selection and flexibility. Addressing such limitations may assist in future framework development.


A systems biology and proteomics-based approach identifies SRC and VEGFA as biomarkers in risk factor mediated coronary heart disease.
Coronary heart disease (CHD) is the most common cause of death worldwide. The burden of CHD increases with risk factors such as smoking, hypertension, obesity and diabetes. Several studies have demonstrated the association of these classical risk factors with CHD. However, the mechanisms of these associations remain largely unclear due to the complexity of disease pathophysiology and the lack of an integrative approach that fails to provide a definite understanding of molecular linkage. To overcome these problems, we propose a novel systems biology approach that relates causative genes, interactomes and pathways to elucidate the risk factors mediating the molecular mechanisms and biomarkers for feasible diagnosis. The literature was mined to retrieve the causative genes of each risk factor and CHD to construct protein interactomes. The interactomes were examined to identify 298 common molecular signatures. The common signatures were mapped to the tissue network to synthesize a sub-network consisting of 82 proteins. Further, the dissection of the sub-network provides functional modules representing a diverse range of molecular functions, including the AKT/p13k, MAPK and wnt pathways. Also, the prioritization of functional modules identifies SRC, VEGFA and HIF1A as potential candidate markers. Further, we validate these candidates with the existing markers CRP, NOS3 and VCAM1 in the serum of 63 individuals, 33 with CHD and 30 controls, using ELISA. SRC, VEGFA, H1F1A, CRP and NOS3 were significantly altered in patients compared to controls. These results support the utility of these candidate markers for the diagnosis of CHD. Overall, our molecular observations indicate the influence of risk factors in the pathophysiology of CHD and identify serum markers for diagnosis.


Spring-Mediated Cranioplasty in Sagittal Synostosis: Does Age at Placement Affect Expansion?
The aim of this study is to evaluate the effect of timing of surgery and spring characteristics on correction of scaphocephalic deformity in patients undergoing spring-mediated cranioplasty (SMC) for sagittal craniosynostosis. The authors conducted a review of patients with sagittal craniosynostosis who underwent SMC at a tertiary referral center between July 2011 and March 2017, with a primary outcome measure of head shape, both preoperatively and postoperatively, determined by cephalic index (CI). Patient demographics and operative details including timing of surgery and spring characteristics were collected. Differences in CI preoperation and postoperation were compared using Wilcoxon signed-rank test. Ordinary least-squares linear regression was used to assess the impact of timing, number of springs, maximum single spring force, and total spring force on postoperative change in CI. Thirty-six subjects (12 males and 24 females) were included in the study. Mean age at spring placement was 3.9 months (range: 1.9-9.2) with a mean follow-up of 1.4 years (range: 0.3-5.2). The mean number of springs used was 3 (range: 2-4). The mean maximum single spring force was 9.9 Newtons (N) (range: 6.9-13.0) and the mean total spring force was 24.6 N (range: 12.7-37.0). Mean CI increased from 70 ± 0.9 preoperatively to 77 ± 1.0 postoperatively (P < 0.001). Age at spring placement was significantly associated with change in CI: for every month increase in age, the change in CI decreased by 1.3 (P = 0.03). The number of springs used, greatest single spring force, and total spring force did not correlate with changes in CI (P = 0.85, P = 0.42, and P = 0.84, respectively). In SMC, earlier age at time of surgery appears to correlate with greater improvement in CI, at least in the short-term. While spring characteristics did not appear to affect head shape, it is possible that the authors were underpowered to detect a difference, and spring-related variables likely deserve additional study.


Prevention of Stroke in Rheumatoid Arthritis.
The risk of cerebrovascular disease is increased among rheumatoid arthritis (RA) patients and remains an underserved area of medical need. Only a minor proportion of RA patients achieve suitable stroke prevention. Classical cardiovascular risk factors appear to be under-diagnosed and undertreated among patients with RA. Reducing the inflammatory burden is also necessary to lower the cardiovascular risk. An adequate control of disease activity and cerebrovascular risk assessment using national guidelines should be recommended for all patients with RA. For patients with a documented history of cerebrovascular or cardiovascular risk factors, smoking cessation and corticosteroids and non-steroidal anti-inflammatory drugs at the lowest dose possible are crucial. Risk score models should be adapted for patients with RA by introducing a 1.5 multiplication factor, and their results interpreted to appropriately direct clinical care. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers are preferred treatment options. Biologic and non-biologic disease-modifying anti-rheumatic drugs should be initiated early to mitigate the necessity of symptom control drugs and to achieve early alleviation of the inflammatory state. Early control can improve vascular compliance, decrease atherosclerosis, improve overall lipid and metabolic profiles, and reduce the incidence of heart disease that may lead to atrial fibrillation. In patients with significant cervical spine involvement, early intervention and improved disease control are necessary and may prevent further mechanical vascular injury.


Synchronization, phase locking, and metachronal wave formation in ciliary chains.
Synchronization and wave formation in one-dimensional ciliary arrays are studied analytically and numerically. We develop a simple model for ciliary motion that is complex enough to describe well the behavior of beating cilia but simple enough to study collective effects analytically. Beating cilia are described as phase oscillators moving on circular trajectories with a variable radius. This radial degree of freedom turns out to be essential for the occurrence of hydrodynamically induced synchronization of ciliary beating between neighboring cilia. The transitions to the synchronized and phase-locked state of two cilia and the formation of metachronal waves in ciliary chains with different boundary conditions are discussed.


Acute coronary syndrome, comorbidity, and mortality in geriatric patients.
Morbidity and mortality rates from heart diseases are highly represented in geriatric-aged patients, but these patients also have supporting diseases. Acute coronary syndrome includes unstable angina and acute myocardial infarction with and without ST elevation. The aim of this study was to make a retrospective morbidity analysis of patients admitted to the emergency department. The study is made for a period of three years (from 1998 to 2000). It includes 588 patients divided by age (395 were 65-75 years old; 193 were older than 75 years) and sex (there were 326 men and 262 women). Comorbidity and mortality were investigated. Patients with one, two, three, and more than three supporting diseases were 6.29%, 23.13%, 68.53%, and 2.04%, respectively, of the total number. The most frequent geriatric patients had heart failure, followed by endocrinological diseases (type 2 diabetes, obesity, struma), neurological diseases (insultus, paresis), and chronic kidney diseases (pielonephritis, nephrolithiasis). The combination of hypertension, heart failure, and type 2 diabetes had the highest comorbidity frequency. The mortality rate for 1998 was 8.81%, for 1999 7.74%, and for 2000 13.41%. The mortality rate at the first 12 hours at the beginning of the acute coronary syndrome was 66.6%. Geriatric patients suffer from many diseases, and at the beginning of the onset of acute coronary syndrome they have multiorganal failure. Elderly patients are a high-risk contingent in intensive coronary care units.


[Malignant thymoma with intracranial metastases].
Malignant thymomas usually proliferate invasively and rarely metastasize to other organs. Since the metastases occur predominantly to the liver and kidneys, there have been only 16 cases with metastatic spreads of malignant thymomas to the central nervous system reported in the literature. A 59-year-old man was admitted with complaints of dizziness and vomiting. Three years and three months ago, he had been operated upon for mediastinal tumor, which was diagnosed as a predominantly lymphocytic type thymoma, and then followed by irradiation therapy of 3800 rads. The size of the tumor decreased markedly after the irradiation. Nine months after the operation, he complained again of dizziness and vomiting. Computed tomography scans showed a tumorous lesion in the right cerebellar hemisphere, which was thought to be a metastasis from the thymoma. He received radiotherapy of 4000 rads directed to the intracranial metastatic tumor, with the reduction of the tumor size and the relief of symptoms. On the present admission, he had cerebellar signs and symptoms. Neuroradiologically, there was a hypervascular tumor in the left cerebellar hemisphere and a hypovascular one in the right. At operation, a vascular and solid tumor with small necrotic areas were found in the left cerebellum, and a tumor with large liquefied clot within it in the right cerebellum. Pathologically, bilateral cerebellar tumors were confirmed as the metastases from the thymoma in the epithelial type.


Refractive predictability in eyes with intraocular gas tamponade - results of a prospective controlled clinical trial.
To determine the postoperative refractive error in eyes with intraocular gas tamponade in combined phacovitrectomy using a Z-haptic intraocular lens (IOL). This prospective non-randomized case-control study compared patients with combined phacovitrectomy with or without intraocular gas tamponade to cataract surgery-only. The main outcome measure was the IOL power prediction error (PE). Secondary outcome measures were spherical equivalent, anterior chamber depth (ACD), and axial length. Thirty-four patients with epiretinal membranes and 18 patients with cataract only were enrolled. There were no statistically significant (P>0.05) differences of IOL power PE or postoperative ACDs (P=0.952-1.00). Nevertheless, IOL power PE indicated a myopic shift in cases with phacovitrectomy independent of gas tamponade (P=1.00). No statistically significant between-group differences between secondary outcome measures were observed. A myopic shift after phacovitrectomy seems to be independent of the use of intraocular gas tamponade. When using a Z-haptic IOL, aiming for slight residual hyperopia (+0.50 D) is suggested in patients having phacovitrectomy.


Sex differences in hepatic regulation of cholesterol homeostasis.
Physiological sex differences may influence metabolic status and then alter the onset of some diseases. According to recent studies, it is now well established that females are more protected from hypercholesterolemia-related diseases, such as cardiovascular diseases until menopause. Female protection from hypercholesterolemia is mediated by the hypolipidemic properties of estrogens, even if mechanisms underlying this protection remain still debated. Even though the regulatory mechanisms of cholesterol homeostasis maintenance are well known, few data are available on the supposed differences between male and female in these processes. So, the aim of this work was to define, through an in vivo study, the putative sex-dependent regulation of the processes underlying cholesterol homeostasis maintenance. We examined 3-hydroxy 3-methylglutaryl coenzyme A reductase and its regulatory protein network as well as the amount of low-density lipoprotein receptor and cholesterol. The study was conducted in the liver and plasma of male and female rats, on adults and during postnatal development, and on 17-beta-estradiol-treated male rats. Our data support that physiological differences in proteins involved in cholesterol balance are present between the sexes and, in particular, 3-hydroxy 3-methylglutaryl coenzyme A reductase shows lower activity and expression in female and 17-beta-estradiol-treated male rats than in adult untreated male. Our data suggest that sex differences in enzyme expression depend on variation in regulatory proteins and seem to be related to estrogen presence. This work adds new evidence in the complicated picture of sex-dependent cellular physiology and establishes a new role for reductase regulatory proteins as a link between estrogen protective effects and cholesterol homeostasis.


Action of carbamate biocides on sterols, gibberellin and aflatoxin formation.
An interrelationship between primary and secondary metabolites of a toxigenic mould (Aspergillus parasiticus var. globosus IMI 120920) was obtained in liquid broth containing various concentrations of dithane Z-78 and propoxur. The results show that a stimulatory response was recorded in gibberellin, protein, sterol and aflatoxin yield in cultures treated with 15, 30, 50 and 100 ppm a.i. of dithane Z-78. On the other hand, propoxur reduced the yield of gibberellin, amino acids, protein, sterol and aflatoxin. In comparison to its effect on the mycelial growth, gibberellin and aflatoxin activity is inhibited more severely than dry weight increase, thus leading to the assumption that there is a specific effect of the inhibitor on both gibberellin and aflatoxin synthesis.


Factors associated with delayed diagnosis of appendicitis in adults: A single-center, retrospective, observational study.
Appendicitis is one of the most common causes of acute abdominal pain; yet the risk of delayed diagnosis remains despite recent advances in abdominal imaging. Understanding the factors associated with delayed diagnosis can lower the risk of diagnostic errors for acute appendicitis. These factors, including physicians' specialty as a generalist or non-generalist, were evaluated through a retrospective, observational study of adult acute appendicitis cases at a single center, between April 1, 2014, and March 31, 2021. The main outcome was timely diagnosis, defined as "diagnosis at the first visit if the facility had computed tomography (CT) capability" or "referral to an appropriate medical institution promptly after the first visit for a facility without CT capability," with all other cases defined as delayed diagnosis. The frequency of delayed diagnosis was calculated and associated factors evaluated through multivariate and exploratory analyses. The overall rate of delayed diagnosis was 26.2% (200/763 cases). Multivariate analysis showed that tenderness in the right lower abdominal region, absence of diarrhea, a consultation of ≤6 h after symptom onset, and consultation with a generalist were associated with a decreased risk of delayed diagnosis of acute appendicitis. Exploratory analysis found that generalists performed more physical findings related to acute appendicitis, suggesting that this diagnostic approach may be associated with timely diagnosis. Future studies should adjust for other potential confounding factors, including patient complexity, consultation environment, number of physicians, diagnostic modality, and physician specialties.


Poisonous Spiders: Bites, Symptoms, and Treatment; an Educational Review.
More than 40,000 species of spiders have been identified in the world. Spider bites is a common problem among people, however few of them are harmful but delay in treatment can cause death. Since the spider bites are risk full to human, they should be taken seriously, especially in endemic areas. Our objective in this review was to study about poisonous spiders and find out treatments of them. Therefore, we collected related articles from PubMed database and Google Scholar. Three important syndromes caused by spider bites are loxoscelism, latrodectism and funnel web spider syndrome. Many treatments are used but much more studies should have done to decrease the mortality. In this review, we describes different venomous spiders according to their appearance, symptoms after their bites and available treatments.


The bioavailability of ethinyloestradiol and levonorgestrel in patients with an ileostomy.
The bioavailability of ethinyloestradiol and levonorgestrel has been studied in 5 young women with an ileostomy following surgery for ulcerative colitis and compared to that in 5 control subjects. Single i.v. and oral doses of both drugs were administered and the bioavailability calculated from the ratio of the two areas under the plasma concentration versus time curve for the two drugs. The mean bioavailability of ethinyloestradiol in the patients with an ileostomy was 55.4 +/- 10.9% (+/- S.D.) compared to a control value of 45.0 +/- 6.1% (p greater than or equal to 0.1). The mean bioavailability of levonorgestrel in the ileostomy patients was 85.2 +/- 13.1% compared to 104.6 +/- 22.3% in the controls (p greater than or equal to 0.1). Women who have an ileostomy following lower bowel surgery can rely on their oral contraceptive preparations being absorbed in the normal way.


Polyphosphonium-based bipolar membranes for rectification of ionic currents.
Bipolar membranes (BMs) have interesting applications within the field of bioelectronics, as they may be used to create non-linear ionic components (e.g., ion diodes and transistors), thereby extending the functionality of, otherwise linear, electrophoretic drug delivery devices. However, BM based diodes suffer from a number of limitations, such as narrow voltage operation range and/or high hysteresis. In this work, we circumvent these problems by using a novel polyphosphonium-based BM, which is shown to exhibit improved diode characteristics. We believe that this new type of BM diode will be useful for creating complex addressable ionic circuits for delivery of charged biomolecules.


Study of the stability and the kinetics of hydrolysis on the new potential antiarrhythmic "substance H + B".
"Substance H + B", N-[2-(2-heptyloxyphenylcarbamoyloxy)-ethyl]-N- benzylpiperidine chloride (1) is a new potential antiarrhythmic, prepared by quarternization of the local anesthetic, antiarrhythmic and antimicrobial heptacaine, N-[2-(2-heptyloxyphenylcarbamoyloxy)-ethyl]-piperidine chloride. The content of the work was a study of the stability of 1 based on the short-time stability tests of aqueous solutions, the observation of long-time storing of the substance and study of the kinetics of hydrolysis in aqueous, ethanolic buffer solutions. The conclusions of the presented results are: 1 is stable in acidic and neutral media, the alkaline hydrolysis is faster from the start compared to the hydrolysis of heptacaine, but later obtains an equilibrium character.


Correlates of stimulant use among people who use heroin undergoing treatment in out-patient facilities in France, 2010-2020.
Background: Polydrug use has been implicated in driving a "fourth wave" of the overdose crisis in North America, specifically through concurrent use of stimulants and opioids, especially fentanyl. In France, however, heroin has historically been and remains the easiest-to-access opioid, accounting for most drug treatment demand. Whether similar polydrug use is increasing in Western Europe remains understudied, despite severe health implications and potential inadequate public health responses.Methods: We take advantage of a nation-wide dataset containing information on all patients serviced in treatment centers in France from 2010 to 2020. We conduct Poisson regression to determine the main predictors of stimulant use among people who use heroin (PWUH) and opioids (PWUO) generally.Results: Heroin remains the primary opioid within drug treatment in France. A decreasing number of out-patients seeking treatment for heroin use has been accompanied by an increasing trend of stimulant use over time, most commonly with powder cocaine. Our results suggest a significant increase of crack cocaine use among the most vulnerable PWUH. Concurrent use of stimulants among PWUH was positively associated with use of alcohol, cannabis, unprescribed psychotropics and hallucinogens, and negatively with tobacco. Similar results were found for all in-treatment PWUO.Conclusions: Our results uncover heterogeneity in the profiles of PWUH that should be fully acknowledged to ensure better efficiency in substance use clinical practices and policy, while simultaneously drawing attention to trends in concurrent opioid-stimulant use outside North America. We advocate for an extension of the generalized risk framework and its implementation in prevention programs.


Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons.
The characterization of acid-sensing ion channel (ASIC)-like currents has been reported in hippocampal neurons in primary culture. However, it is suggested that the profile of expression of ASICs changes in culture. In this study, we investigated the properties of proton-activated current and its modulation by extracellular Ca(2+) and Zn(2+) in neurons acutely dissociated from the rat hippocampal CA1 using conventional whole-cell patch-clamp recording. A rapidly decaying inward current and membrane depolarization was induced by exogenous application of acidic solution. The current was sensitive to the extracellular proton with a response threshold of pH 7.0-6.8 and the pH(50) of 6.1, the reversal potential close to the Na(+) equilibrium potential. It had a characteristic of acid-sensing ion channels (ASICs) as demonstrated by its sensitivity to amiloride (IC(50)=19.6+/-2.1 microM). Either low [Ca(2+)](o) or high [Zn(2+)](o) increased the amplitude of the current. All these characteristics are consistent with a current mediated through a mixture of homomeric ASIC1a and heteromeric ASIC1a+2a channels and closely replicate many of the characteristics that have been previously reported for hippocampal neurons cultured for a week or more, indicating that culture artifacts do not necessarily flaw the properties of ASICs. Interestingly, we found that high [Zn(2+)](o) (>10(-4) M) slowed the decay time constant of the ASIC-like current significantly in both acutely dissociated and cultured hippocampal neurons. In addition, the facilitating effects of low [Ca(2+)](o) and high [Zn(2+)](o) on the ASIC-like current were not additive. Since tissue acidosis, extracellular Zn(2+) elevation and/or Ca(2+) reduction occur concurrently under some physiological and/or pathological conditions, the present observations suggest that hippocampal ASICs may offer a novel pharmacological target for therapeutic invention.


Ambulatory care research in the VA: present status and recommendations for the future.
The growth of ambulatory care delivery in the Department of Veterans Affairs (VA) has been accompanied by increasing interest in and need for ambulatory care research. Results from a national survey of academic general internal medicine units suggest that those that share VA and university affiliation tend to be more successful than those that are unaffiliated. The VA must strive to improve the environment for ambulatory care research. Among other things, this will entail providing adequate protected time to ambulatory care faculty and developing a uniform ambulatory care database to facilitate longitudinal, population-based research. Extended fellowships in ambulatory care and faculty development programs for existing staff will be required to create a core of competent investigators. The VA must also provide increased funding to the Health Services Research and Development and Cooperative Studies programs. Special funding programs targeted to key areas such as quality assurance, medical education, and direct patient care should be established. In addition, the VA should seek to develop joint ventures with other funding agencies for innovative ambulatory care initiatives.


FGF21 ameliorates diabetic cardiomyopathy by activating the AMPK-paraoxonase 1 signaling axis in mice.
The aim of the present study is to explore the molecular mechanism of fibroblast growth factor 21 (FGF21) in protecting against diabetic cardiomyopathy (DCM). Streptozotocin/high-fat diet (STZ/HFD) was used to induced diabetes in FGF21-deficient mice and their wild-type littermates, followed by evaluation of the difference in DCM between the two genotypes. Primary cultured cardiomyocytes were also used to explore the potential molecular mechanism of FGF21 in the protection of high glucose (HG)-induced cardiomyocyte injury. STZ/HFD-induced cardiomyopathy was exacerbated in FGF21 knockout mice, which was accompanied by a significant reduction in cardiac AMP-activated protein kinase (AMPK) activity and paraoxonase 1 (PON1) expression. By contrast, adeno-associated virus (AAV)-mediated overexpression of FGF21 in STZ/HFD-induced diabetic mice significantly enhanced cardiac AMPK activity, PON1 expression and its biological activity, resulting in alleviated DCM. In cultured cardiomyocytes, treatment with recombinant mouse FGF21 (rmFGF21) counteracted HG-induced oxidative stress, mitochondrial dysfunction, and inflammatory responses, leading to increased AMPK activity and PON1 expression. However, these beneficial effects of FGF21 were markedly weakened by genetic blockage of AMPK or PON1. Furthermore, inactivation of AMPK also markedly blunted FGF21-induced PON1 expression but significantly increased HG-induced cytotoxicity in cardiomyocytes, the latter of which was largely reversed by adenovirus-mediated PON1 overexpression. These findings suggest that FGF21 ameliorates DCM in part by activation of the AMPK-PON1 axis.


Supplementary Motor Area and Superior Parietal Lobule Restore Sensory Facilitation Prior to Stepping When a Decrease of Afferent Inputs Occurs.
The weighting of the sensory inputs is not uniform during movement preparation and execution. For instance, a transient increase in the transmission to the cortical level of cutaneous input ~700 ms was observed before participants initiated a step forward. The sensory facilitation occurred at a time when feet cutaneous information is critical for setting the forces to be exerted onto the ground to shift the center of mass toward the supporting side prior to foot-off. Despite clear evidence of task-dependent modulation of the early somatosensory signal transmission, the neural mechanisms are mainly unknown. One hypothesis suggests that during movement preparation the premotor cortex and specifically the supplementary motor area (SMA) can be the source of an efferent signal that facilitates the somatosensory processes irrespectively of the amount of sensory inputs arriving at the somatosensory areas. Here, we depressed mechanically the plantar sole cutaneous transmission by increasing pressure under the feet by adding an extra body weight to test whether the task-dependent modulation is present during step preparation. Results showed upregulation of the neural response to tactile stimulation in the extra-weight condition during the stepping preparation whereas depressed neural response was still observed in standing condition. Source localization indicated the SMA and to a lesser extent the superior parietal lobule (SPL) areas as the likely origin of the response modulation. Upregulating cutaneous inputs (when mechanically depressed) at an early stage by efferent signals from the motor system could be an attempt to restore the level of sensory afferents to make it suitable for setting the anticipatory adjustments prior to step initiation.


Mechanisms for Lactobacillus rhamnosus treatment of intestinal infection by drug-resistant Escherichia coli.
The development of probiotics as therapeutic drugs is greatly important for the protection against threats of drug-resistant pathogen infection in both humans and animals. This study showed that Lactobacillus rhamnosus SHA113, previously isolated from breast milk of healthy humans, showed efficient therapeutic effects on infection by drug resistant Escherichia coli QBQ009. In addition to protecting the intestinal barrier via up-regulating the expression of tight junction proteins ZO-1 and occludin, it was also found that (1) both L. rhamnosus SHA113 and E. coli QBQ009 cells caused changes of the epithelial cell cytoskeleton and up-regulated the expression of phagocytosis-related proteins MYH2 in Caco-2 cells; however, only E. coli QBQ009 caused a strong decrease of cell viability. L. rhamnosus SHA113 treatment after E. coli QBQ009 infection significantly restored the damaged intestinal barrier and the changes of the epithelial cell cytoskeleton caused by E. coli QBQ009. (2) L. rhamnosus SHA113 showed a much higher adhesion rate to the intestinal tract and Caco-2 cells than E. coli QBQ009. The presence of E. coli QBQ009 significantly decreased the adhesion rate of L. rhamnosus SHA113, but not in reverse. (3) L. rhamnosus SHA113 had much higher self-coagulation than E. coli, and could strongly co-coagulate with E. coli QBQ009. The viability of E. coli QBQ009 greatly decreased after co-coagulation, while that of L. rhamnosus SHA113 was not influenced. (4) The polysaccharides produced by L. rhamnosus SHA113 significantly decreased the permeability of the intestinal tract and Caco2 cells, but had no remarkable influence on the adhesion rate of E. coli QBQ009. (5) Feeding L. rhamnosus SHA113 caused a significant reduction of Proteobacteria in the cecum of healthy mice, which was not significant in infected and treated mice. In summary, the decreased live pathogen amounts might be one of the decisive factors for the efficient cure of E. coli QBQ009 infection by L. rhamnosus SHA113, and the restoration of the intestinal barrier might be caused by the reduction of pathogens.


Newtonian Equivalence Principles.
The equivalence principle has constituted one of the cornerstones of discussions in the foundations of spacetime theories over the past century. However, up to this point the principle has been considered overwhelmingly only within the context of relativistic physics. In this article, we demonstrate that the principle has much broader, super-theoretic significance: to do so, we present a unified framework for understanding the principle in its various guises, applicable to both relativistic and Newtonian contexts. We thereby deepen significantly our understanding of the role played by the equivalence principle in a broad class of spacetime theories.


Antisecretory agents, peptic secretion and serum pepsinogen in man.
Less attention has been devoted to the effects of antisecretory agents on pepsin secretion than to those on gastric acid secretion, particularly in human subjects. Moreover, comparison of the various trials is far from being simple and straightforward owing to the fact that the studies available present substantial variability in terms of types of subjects (controls, DU patients), gastric secretion (basal, stimulated), type of stimulation (pentagastrin, histamine, insulin, meals, sham feeding) antisecretory drug administration route (oral, i.v.) and considered parameters (concentration, output). This review of the published data reveals that all antisecretory agents reduce pepsin output, regardless of their sometimes very different mechanism of action. Despite this, there are differences in antisecretory effects according to the agent used to stimulate gastric secretion. Even within a single drug class (H2-antagonists, prostaglandins) there may be differences depending on the potency of the compound used.


A natural language processing approach towards harmonisation of European medicinal product information.
Product information (PI) is a vital part of any medicinal product approved for use within the European Union and consists of a summary of products characteristics (SmPC) for healthcare professionals and package leaflet (PL) for patients, together with the product packaging. In this study, based on the English corpus of the EMA product information documents for all centrally approved medicinal products within the EU, a BERT sentence embedding model was used together with clustering and dimensional reduction techniques to identify sentence similarity clusters that could be candidates for standardization. A total of 1258 medicinal products were included in the study. From these, a total of 783 K sentences were extracted from SmPC and PL documents which were aggregated into a total of 284 and 129 semantic similarity clusters, respectively. The spread distribution among clusters shows separation into different cluster types. Examples of clusters with low spread include those with identical word embeddings due to current standardization, such as section headings and standard phrases. Others show minor linguistic variations, while the group with the largest variability contains variable wording but with significant semantic overlap. The sentence clusters identified could serve as candidates for further standardization of the PI. Moving from free text human wording to auto-generated text elements based on multiple-choice input for appropriate parts of the package leaflet and summary of product characteristics, could reduce both time and complexity for applicants as well as regulators, and ultimately provide patients and prescribers with documents that are easier to understand and better adapted for search availabilities.


Fatigue and stroke.
Under disabling conditions such as stroke, fatigue may worsen other symptoms and impede full participation in a rehabilitation program. The functional improvement needed to regain mobility and independence may be impacted significantly by fatigue. This article explores the symptom of fatigue and its relation to stroke from a rehabilitation perspective. It examines theoretical models, operational definitions, fatigue as a response to stroke, assessment and measurement instruments, symptom management strategies, and future research directions.


Assessing the association between omalizumab and arteriothrombotic events through spontaneous adverse event reporting.
Omalizumab is a monoclonal antibody, indicated for the treatment of severe allergic asthma. In Europe, there have been concerns about the cardiovascular safety of omalizumab. The objective of this study was to analyze the association between omalizumab and arterial thrombotic events in a spontaneous adverse drug reaction reporting database in the US. Reports of arterial thrombotic events submitted to the US Food and Drug Administration's Adverse Event Reporting System (AERS) between 2004 and 2011 were retrieved and analyzed by the reporting odds ratio data mining algorithm. The reporting odds ratio of arterial thrombotic events for omalizumab was compared with specific asthma medications and all drugs in the AERS. Values ≥2 were considered significant safety signals. The Medical Dictionary for Regulatory Activities Preferred Terms were used to identify arterial thrombotic events (eg, stroke, myocardial infarction). In total, 293,783 reports of arterial thrombotic events were retrieved (about 2% of all adverse drug reaction reports), corresponding to 2274 asthma drug-arterial thrombotic events pairs (omalizumab, 222; inhaled corticosteroids [ICS], 131; long-acting beta-agonists [LABA], 102; single-device combination ICS-LABA, 506; inhaled short-acting beta-agonists [SABA], 475; oral SABA, 6; inhaled antimuscarinics [AMC], 477; single-device combination AMC-SABA, 127; xanthines, 50; leukotriene modifiers, 174; and mast cell stabilizers, 4). Reporting odds ratio and 95% confidence interval values for omalizumab compared with other asthma drugs and all drugs in AERS were 2.75 (2.39-316) and 1.09 (0.95-1.24), respectively. Omalizumab ranked second after ICS in the risk of arterial thrombotic events, followed by AMC, AMC-SABA, and ICS-LABA. Omalizumab is associated with higher than expected reporting of arterial thrombotic events in asthmatic patients. This hypothesis needs further testing in robust epidemiological studies.


Characteristics of patients with bleeding peptic ulcer requiring emergency endoscopy and aggressive treatment.
Patients with an ulcer and active bleeding or a nonbleeding, visible vessel are high-risk for further bleeding and should receive aggressive therapy. In this study, we tried to identify clinical parameters that predict these high-risk groups. Over a 7-month period, 16 clinical parameters were analyzed prospectively in 316 patients with bleeding peptic ulcer. A multivariate analysis was used to find the independent predictors for the high-risk patients. A total of 114 patients (36%) was found to have a spurting hemorrhage (eight patients), oozing hemorrhage (27 patients), or a nonbleeding visible vessel (79 patients). Using an univariate analysis, a statistically significant predictor was the appearance of coffee ground fluid or blood from the nasogastric tube. This predictor also emerged as an independent factor (odds ratio, 0.4333; 95% confidence interval, 0.263-0.714). Patients with bleeding peptic ulcer who have coffee ground fluid or blood from the nasogastric tube should receive an emergency endoscopy and aggressive treatment.


The communication skills and the empathic tendency levels of nursing students: a cross-sectional study.
The most basic component of communication skills is the complex and multidimensional skill of empathy. This study was conducted to assess the communication skills and empathic tendency levels of female nursing students Turkish university. This cross-sectional study sample consisted of 342 nurse student. There was a significant difference between the classes in terms of communication skills (0.021, p < .05) but no significant difference in terms of the empathic tendency levels (0.712, p > .05). The mean communication skills score increased in the final year but empathic tendency levels did not increase with increasing school years. This result suggests that the empathic tendency level could not be increased with the courses in the curriculum in our study. The results suggest that empathic tendency levels were not increased with subsequent nursing coursework. Determining empathic predisposition levels prior to entry into nursing programs should therefore be considered.


The impact of basketball on the social adjustment of Chinese middle school students: the chain mediating role of interpersonal relationships and self-identity.
This study examines the effects of 12 weeks of basketball on interpersonal relationships, self-identity and social adjustment of middle school students, as well as exploring the mediating role of interpersonal relationships and self-identity in basketball's influence on social adjustment. A total of 87 students from a middle school in Jiangsu Province, China, were selected to participate in this study. A 12-week basketball intervention experiment was conducted, and questionnaires were administered to measure the study variables. Common method bias test, normality test, ANOVA and Pearson correlation analysis were used to analyze the study variables. The theoretical model of this study was also validated using the Process plug-in developed by Hayes, setting p < 0.05 (two-tail) as statistically significant. After a 12-week basketball intervention experiment, the interpersonal relationships, self-identity and social adjustment of the middle school students in the experimental and control groups showed improvement, with the experimental group showing significantly more significant improvement than the control group. A 12-week basketball intervention can positively impact the social adjustment of middle school students, with interpersonal relationships and self-identity acting as a chain mediator in the impact process.


Abietane diterpenoids from Salvia pachyphylla and S. clevelandii with cytotoxic activity against human cancer cell lines.
A phytochemical study has been carried out on the aerial parts of Salvia pachyphylla and S. clevelandii. From S. pachyphylla, the known diterpenes carnosol (2), rosmanol, 20-deoxocarnosol (3), carnosic acid, isorosmanol (4), 7-methoxyrosmanol, 5,6-didehydro-O-methylsugiol (5), 8beta-hydroxy-9(11),13-abietadien-12-one (6), 11,12-dioxoabieta-8,13-diene, and 11,12-dihydroxy-20-norabieta-5(10),8,11,13-tetraen-1-one were isolated, together with the new diterpene pachyphyllone (1). From S. clevelandii, the known diterpenes rosmadial (7), 16-hydroxycarnosol (8), abieta-8,11,13-triene, and taxodone were obtained, together with carnosol (2), rosmanol, and carnosic acid. The structure of the new compound (1) was identified on the basis of spectroscopic data analysis. Several of these compounds (1-8) were evaluated against a small panel of human cancer cell lines.