Feasibility and preliminary efficacy of a school-based health and well-being program for adolescent girls.
The primary aim of this pilot study was to evaluate the feasibility and preliminary efficacy of a school-based health and well-being program (Health and Well-being for Girls: HWBG) on adolescent girls' well-being, mindfulness, screen-time, and physical activity. The HWBG program was evaluated using a group randomized controlled trial (RCT) in one secondary school. A convenience sample of female students in Grade 8 (mean age 14 ± 0.5 years) was recruited for the study (n=4 classes; 89 girls). The 20-week multi-component HWBG program, guided by Self-Determination Theory and Acceptance and Commitment Therapy, was designed and delivered by a member of the research team. Randomization occurred prior to baseline assessments at the class level (n=4 classes) into dose-matched treatment conditions (i.e., two classes received the HWBG intervention and two classes received an alternate elective course as a wait-list control group). Process evaluation measures of recruitment, retention, adherence, and satisfaction were used to determine program feasibility. This study was designed to assess feasibility (primary outcome) and preliminary efficacy (secondary outcomes), rather than effectiveness. Preliminary efficacy of HWBG for improving mental and social health, screen-time, and physical activity were measured and analyzed using linear mixed-models. "The health and well-being program" targeting adolescent girls was found to be feasible for implementation as an elective course in a secondary school setting. Participants in the HWBG program reported high levels of satisfaction, the majority of lessons (45 out of 50), were implemented as planned and adherence to the planned HWBG program content was very high. Medium positive effects on mental health (d=0.45) and social health (d=0.50) were observed. Small effects were observed for physical activity, and no significant intervention effects were found for levels of recreational screen time. Participant ratings showed high levels of perceived benefit and enjoyment as indicated in the evaluation data (mean rating of 4.44 out of a possible 5.0) when asked whether the program was enjoyable. The study provides preliminary support for HWBG as a potentially feasible and enjoyable program suitable for use with adolescent girls in the secondary school setting. Potential of the study for facilitating improvements in pro-social and psychological well-being is also supported. ACTRN12617000157370 . The trial was registered with the Australian New Zealand Clinical Trials Registry.


Quantitative mass spectrometry evaluation of human retinol binding protein 4 and related variants.
Retinol Binding Protein 4 (RBP4) is an exciting new biomarker for the determination of insulin resistance and type 2 diabetes. It is known that circulating RBP4 resides in multiple variants which may provide enhanced clinical utility, but conventional immunoassay methods are blind to such differences. A Mass Spectrometric immunoassay (MSIA) technology that can quantitate total RBP4 as well as individual isoforms may provide an enhanced analysis for this biomarker. RBP4 was isolated and detected from 0.5 uL of human plasma using MSIA technology, for the simultaneous quantification and differentiation of endogenous human RBP4 and its variants. The linear range of the assay was 7.81-500 ug/mL, and the limit of detection and limit of quantification were 3.36 ug/mL and 6.52 ug/mL, respectively. The intra-assay CVs were determined to be 5.1% and the inter-assay CVs were 9.6%. The percent recovery of the RBP4-MSIA ranged from 95 - 105%. Method comparison of the RBP4 MSIA vs the Immun Diagnostik ELISA yielded a Passing & Bablok fit of MSIA = 1.05× ELISA - 3.09, while the Cusum linearity p-value was >0.1 and the mean bias determined by the Altman Bland test was 1.2%. The novel RBP4 MSIA provided a fast, accurate and precise quantitative protein measurement as compared to the standard commercially available ELISA. Moreover, this method also allowed for the detection of RBP4 variants that are present in each sample, which may in the future provide a new dimension in the clinical utility of this biomarker.


Planar cell polarity: moving from single cells to tissue-scale biology.
Planar cell polarity (PCP) reflects cellular orientation within the plane of an epithelium. PCP is crucial during many biological patterning processes and for organ function. It is omnipresent, from convergent-extension mechanisms during early development through to terminal organogenesis, and it regulates many aspects of cell positioning and orientation during tissue morphogenesis, organ development and homeostasis. Suzanne Eaton used the power of Drosophila as a model system to study PCP, but her vision of, and impact on, PCP studies in flies translates to all animal models. As I highlight here, Suzanne's incorporation of quantitative biophysical studies of whole tissues, integrated with the detailed cell biology of PCP phenomena, completely changed how the field studies this intriguing feature. Moreover, Suzanne's impact on ongoing and future PCP studies is fundamental, long-lasting and transformative.


Improving cholecystectomy.
Bacteriologic study of bile in 100 patients undergoing cholecystectomy for various manifestations of choletithiasis yielded 36 per cent positive cultures, with greater frequency in older individuals and those with acute cholecystitis and common duct stone; these results are comparable to those in previous studies and reaffirm the septicity of the bile. Incidence of wound infection, averanging 10 per cent in published series of cholecystectomies, was 0.5 per cent in 200 patients in whom a water-impermeable wound drape was sewn to the peritoneum to prevent contamination by potentially infected bile. This result, in patients with an infectious risk comparable to that in other series, establishes the value of meticulous wound isolation in preventing wound infection.


Nε-Carboxymethyl-Lysine Mediates Vascular Calcification in Diabetes Caused by Impaired Osteoclastic Resorption Activity Through NFATc1-GNPTAB.
Nε-carboxymethyl-lysine (CML) is closely associated with vascular calcification in diabetes. Osteoclasts are the only cells with bone resorption activity that have the potential to reverse calcification. This study aimed to investigate the mechanism of CML in the bone resorption activity of macrophage-derived osteoclasts in diabetic calcified plaques. Macrophage-derived osteoclasts were found to be present in calcified plaques of the anterior tibial artery in patients with diabetic amputation. Furthermore, in vitro studies showed that CML induced the differentiation of macrophages into osteoclasts, although, the bone resorption activity of these macrophage-derived osteoclasts was impaired. CML significantly increased the levels of NFATc1and GNPTAB. In vivo studies showed that there was more calcium deposition and less TRAP was less in the CML group while this effect was reversed after silencing of NFATc1. In conclusion, CML mediates NFATc1-GNPTAB to regulate bone resorption activity of osteoclasts in diabetic calcified plaques. CML promotes macrophage differentiation into osteoclasts, but their function is impaired in diabetic calcified plaques through NFATc1-GNPTAB, which eventually leads to the further progression of vascular calcification in diabetes.


A review of dose calculation approaches with cone beam CT in photon and proton therapy.
The use of cone beam computed tomography (CBCT) for performing dose calculations in radiation therapy has been widely investigated as it could provide a quantitative analysis of the dosimetric impact of changes in patients during the treatment. The aim of this review was to classify different techniques adopted to perform CBCT dose calculation and to report their dosimetric accuracy with respect to the metrics used. A literature search was carried out in PubMed and ScienceDirect databases, based upon the following keywords: "cone beam computed tomography", "CBCT", "cone beam CT", "dose calculation", "accuracy". Sixty-nine peer-reviewed relevant articles were included in this review: thirty-one patient studies, fifteen phantom studies and twenty-three patient & phantom studies. Most studies were found to have focused on head and neck, lung and prostate cancers. The techniques adopted to perform CBCT dose calculation have been grouped in six categories labelled as (1) pCT calibration, (2) CBCT calibration, (3) HU override, (4) Deformable image registration, (5) Dose deformation, and (6) Combined techniques. Differences between CBCT dose and reference dose were reported both for target volumes and OARs. A comparison among the available techniques for CBCT dose calculations is challenging as many variables are involved. Therefore, a set of reporting standards is recommended to enable meaningful comparisons among different studies. The accuracy of the results was strongly dependent on the image quality, regardless of the methods used, highlighting the need for dose validation and quality assurance standards.


Differential gene expression profile from haematopoietic tissue stem cells of red claw crayfish, Cherax quadricarinatus, in response to WSSV infection.
White spot syndrome virus (WSSV) is one of the most important viral pathogens in crustaceans. During WSSV infection, multiple cell signaling cascades are activated, leading to the generation of antiviral molecules and initiation of programmed cell death of the virus infected cells. To gain novel insight into cell signaling mechanisms employed in WSSV infection, we have used suppression subtractive hybridization (SSH) to elucidate the cellular response to WSSV challenge at the gene level in red claw crayfish haematopoietic tissue (Hpt) stem cell cultures. Red claw crayfish Hpt cells were infected with WSSV for 1h (L1 library) and 12h (L12 library), respectively, after which the cell RNA was prepared for SSH using uninfected cells as drivers. By screening the L1 and L12 forward libraries, we have isolated the differentially expressed genes of crayfish Hpt cells upon WSSV infection. Among these genes, the level of many key molecules showed clearly up-regulated expression, including the genes involved in immune responses, cytoskeletal system, signal transduction molecules, stress, metabolism and homestasis related genes, and unknown genes in both L1 and L12 libraries. Importantly, of the 2123 clones screened, 176 novel genes were found the first time to be up-regulated in WSSV infection in crustaceans. To further confirm the up-regulation of differentially expressed genes, the semi-quantitative RT-PCR were performed to test twenty randomly selected genes, in which eight of the selected genes exhibited clear up-regulation upon WSSV infection in red claw crayfish Hpt cells, including DNA helicase B-like, multiprotein bridging factor 1, apoptosis-linked gene 2 and an unknown gene-L1635 from L1 library; coatomer gamma subunit, gabarap protein gene, tripartite motif-containing 32 and an unknown gene-L12-254 from L2 library, respectively. Taken together, as well as in immune and stress responses are regulated during WSSV infection of crayfish Hpt cells, our results also light the significance of cytoskeletal system, signal transduction and other unknown genes in the regulation of antiviral signals during WSSV infection.


Cytokine-producing dendritic cells in the pathogenesis of inflammatory skin diseases.
Inflammatory skin diseases can be examined from many viewpoints. In this review, we consider three distinct cutaneous inflammatory diseases from the point of view of their major lesional dendritic cell (DC) subpopulations. The DC populations considered are Langerhans cells, myeloid DCs, and plasmacytoid DCs (pDCs), with specific attention to the presence and role of the inflammatory counterparts of these cells. From such a "dendritic cell-centric" focus, psoriasis, atopic dermatitis (AD), and cutaneous lupus erythematosus (CLE) are explored. In psoriasis, there is a specific population of myeloid "inflammatory" DCs that appears to play an important pathogenic role, while pDCs have been recently implicated in the initiation of psoriatic lesions. In AD, Langerhans cells may be important during initiation, while "inflammatory dendritic epidermal cells" (IDECs) appear to be abundant in lesional epidermis and dermis and contribute to maintenance of AD. These IDECs may actually be analogous to the myeloid inflammatory DCs found in the epidermal and dermal compartments of the skin in psoriasis, although they express distinct surface markers and induce different T cell polarities as a result of different cytokine milieu in which they develop. CLE has been recently characterized as a type I IFN-mediated disease, and pDCs are integral to the pathogenesis of this disease. Thus, these DC subpopulations and their products will be reviewed in the context of these three cutaneous diseases to provide clinico-pathophysiological correlations between the lesional DCs, their products, and the skin diseases.


Frenular chordee: implications and treatment.
Twenty of 75 male children undergoing elective circumcision demonstrated a ventral glandular chordee produced by an unusually prominent frenulum. Surgical incision of this prominent band of tissue relaxed the glandular traction (chordee), more adequately exposing the ventral inner prepuce, facilitating skin incisions, and permitting an improved cosmetic and functional outcome.


[Clinico-laboratory substantiation of possible use of the indirect hemagglutination test for the interpretation of diagnosis of enteropathogenic E. coli carrier state].
The diagnostic value of the indirect hemagglutination (IHA) test in deciphering the diagnosis of enteropathogenic E. coli carrier state was found in this work; this was done by comparing the specific antibody level in carriers and patients suffering from coli-infection and also by establishing the correlation between the results of the IHA test and the clinical and laboratory examination of carriers.


Circadian nature of immune function.
The primary physiological role of the circadian system is to synchronize and coordinate organ systems, particularly in response to dynamics in the environment. The immune system is under direct circadian control by systemic cues and molecular clocks within immune cells. The master circadian pacemaker called the suprachiasmatic nucleus (SCN) conveys timing information to the immune system through endocrine and autonomic pathways. These signals promote phase coherence of peripheral clocks in the immune system, and also govern daily variations in immune function. The coordination of immune response may compose an anticipatory state for optimal immune response. Interactions between circadian and immune systems are bidirectional, in that immune factors can modulate phasing of circadian clocks. Circadian disruption, such as environmental desynchronization and/or anomalous molecular clock functions, may lead to lack of system coordination, and particular vulnerabilities to infection and disease may develop.


The Micro-Ring for full subperiosteal implant and prosthesis construction.
This technique was developed to overcome some of the difficulties experienced by the dentist in construction and maintenance of an implant denture. Laboratory construction time is greatly reduced in both the subperiosteal and the implant prosthesis. The greatest advantages of the technique are accurate and positive construction and predictable results.


Effects of chronic ethanol administration on rat brain phospholipid metabolism.
Alterations in brain phospholipid metabolism were observed after chronic ethanol administration for 16 days to developing rats. Animals were injected intraperitoneally with 32Pi 16 h prior to killing. Overall uptake of 32Pi by brain did not differ between the control and ethanol-treated groups, which were killed 2 h and 24 h after the last ethanol feeding. Except for an increase in the labeling of myelin after ethanol treatment, the amount of radioactivity recovered in the synaptosomal-mitochondrial and plasma membrane fractions of control and ethanol-treated groups was not different. Relative to the radioactivity of phosphatidylcholines, which indicated no change, there were increases (20-44%) in labeling of ethanolamine plasmalogens, phosphatidic acids, and phosphatidylinositols in cortical synaptosomes from the 2-h ethanol-treated group. In the plasma membrane fractions, however, increases (9-14%) in labeling of phosphatidylserines and phosphatidylinositols were observed in both 2- and 24-h ethanol-treated groups. In both membrane fractions, there was an obvious increase (44-86%) in labeling of polyphosphoinositides at 24 h after withdrawal from ethanol. Results thus indicate an adaptive increase in the biosynthesis of ethanolamine plasmalogen and brain acidic phospholipids due to chronic ethanol administration. Furthermore, the increase in labeling of polyphosphoinositides in the 24-h withdrawal group may reflect the hypoactivity associated with ethanol withdrawal.


Decision-tables for choosing commonly applied inferential statistical tests in comparative and correlation studies.
Nurse researchers are increasingly using a wide variety of inferential statistical tests. However, novice researchers might find choosing tests for their studies difficult, as a result of this variety. To present structured decision-tables to help choose which statistical tests to use in comparative and correlation studies. The wide spectrum of statistical techniques the authors identified in nursing research helped them to construct overview tables that researchers could use as a simple tool to help choose appropriate statistical tests for their studies. The decision-tables provided in this paper are unique in that they are composed of commonly applied statistical techniques identified in nursing studies and structured to simplify the pathway to statistical test decision-making for a broad spectrum of study designs. Novice nurse researchers can use the decision-tables presented in this paper as a starting point to explore with research colleagues or supervisors the appropriate choice of statistical techniques.


An open-label non-inferiority randomised control trial comparing nebulised amphotericin B with oral itraconazole in patients with pulmonary aspergilloma.
Pulmonary aspergilloma (PA) is a common complication seen in patients with pulmonary tuberculosis sequelae. Antifungal therapy, including oral azoles, is commonly used though only surgical resection offers curative benefit. Local administration of amphotericin B, like intracavitary instillation, has been effective in aspergilloma patients though nebulised amphotericin B (nAB) has never been formally assessed. The aim of this prospective, non-inferior, open-label, randomised control trial is to evaluate the efficacy and safety of nebulised amphotericin B compared to oral itraconazole therapy in the treatment of PA. Diagnosed cases of PA (n=33) were randomised into the control group receiving oral itraconazole (n=18) and intervention group receiving nebulised amphotericin B (n = 15). Response to treatment was assessed both clinically and radiologically at the end 6 months. The number of patients showing overall improvement at the end of 6 months in the control arm(oral itraconazole) vs intervention arm(nebulised amphotericin B) was 65% (95% CI 38.3-85.8) and 67%(95% CI 38.4%-88.2%), respectively, in the intention-to-treat and 79% (95% CI 49.2%-95.3%), and 65% (95% CI 38.4%-88.2%), respectively, in the per-protocol analysis. While there was no statistically significant difference between the intervention and control arm in both the analyses, non-inferiority was shown in the per-protocol but not in the intention-to-treat analysis. No major adverse events were noted in either group; however, a significant proportion of patients receiving nAB reported minor cough (40%), which, however, did not lead to discontinuation of therapy in any patients. Nebulised amphotericin B can be an effective therapeutic option for pulmonary aspergilloma patients.


Interferon production and activity in mouse neuroblastoma cells.
Mouse neuroblastoma cells are capable of synthesizing interferon after induction with virus or polynucleotides. Differentiation of neuroblastoma cells depresses interferon synthesis without an apparent effect on sensitivity to interferon.


Luminescent detection of specific DNA sequences.
The process whereby part of the energy evolved in a chemical reaction is emitted as light is known as luminescence. When luminol is oxidized by hydrogen peroxide in the presence of horseradish peroxidase (HRP), light is evolved (1). This is shown in Fig. 1. Luciferin not only enhances the reaction, but prolongs the emission over several minutes (2). The light may be measured in a luminometer or visualized as the blackening of photographic film, as will be described. Fig. 1. Oxidation of luminol in the presence of hydrogen peroxide and HRP (the catalyst).


Differences in Effectiveness and Use of Robotic Surgery in Patients Undergoing Minimally Invasive Colectomy.
We compared patient outcomes of robot-assisted surgery (RAS) and laparoscopic colectomy without robotic assistance for colon cancer or nonmalignant polyps, comparing all patients, obese versus nonobese patients, and male versus female patients. We used the 2013-2015 American College of Surgeons National Surgical Quality Improvement Program data to examine a composite outcome score comprised of mortality, readmission, reoperation, wound infection, bleeding transfusion, and prolonged postoperative ileus. We used propensity scores to assess potential heterogeneous treatment effects of RAS by patient obesity and sex. In all, 17.1% of the 10,844 of patients received RAS. Males were slightly more likely to receive RAS. Obese patients were equally likely to receive RAS as nonobese patients. In comparison to nonRAS, RAS was associated with a 3.1% higher adverse composite outcome score. Mortality, reoperations, wound infections, sepsis, pulmonary embolisms, deep vein thrombosis, myocardial infarction, blood transfusions, and average length of hospitalization were similar in both groups. Conversion to open surgery was 10.1% lower in RAS versus nonRAS patients, but RAS patients were in the operating room an average of 52.4 min longer. We found no statistically significant differences (p > 0.05) by obesity status and gender. Worse patient outcomes and no differential improvement by sex or obesity suggest more cautious adoption of RAS.


Impact of surgical volume and surgical outcome assessing registers on the quality of thyroid surgery.
The available evidence concerning the relationship between volume and outcome for thyroid surgery is assessed in this article. Morbidity forms the principal surrogate marker of thyroid surgery quality for which postoperative hypocalcaemia and recurrent laryngeal nerve injuries are most commonly reported upon. Whilst there is an abundance of published data for these outcomes, interpretation to recommend annual volume thresholds is challenging. This is due to a lack of consensus on definitions not only for outcomes but high and low volume surgeons. The evidence reviewed in this article supports the notion that high volume surgeons achieve superior outcomes in thyroid surgery quality though it is not possible to recommend minimal annual volumes on the basis of this evidence alone. Every thyroid surgeon should know their own outcomes and how they compare with their peers and engagement in thyroid surgery registries can facilitate this.


Ulnar collateral ligament reconstruction in javelin throwers: an analysis of return to play rates and patient outcomes.
Although results after ulnar collateral ligament reconstruction (UCLR) in baseball players have been well documented, the literature is replete regarding the outcomes after UCLR in javelin throwers. To report outcomes after UCLR in javelin throwers. UCLR in javelin throwers will result in a high rate of return to play similar to that of previously published studies from athletes of other sports. All patients who were identified preoperatively as javelin throwers and underwent UCLR between 2011 and 2017 with a minimum 2-year follow-up were eligible for inclusion. Patients were assessed with the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score, Timmerman-Andrews Elbow score, Conway-Jobe score, patient satisfaction, return to sport rate questionnaire, and the occurrence of any postoperative complications. Eighteen patients met the inclusion criteria. Complete follow-up was available in 16 (88.9%) patients. The average age at surgery was 21.2 ± 2.0 (range, 18.6-24.9) years. At the final follow-up, the average Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score and Timmerman-Andrews Elbow score were 77.3 (range, 18.7-98.4) and 91.8 (range, 70.0-100.0), respectively. Outcomes on the Conway-Jobe scale were as follows: excellent (n = 6; 37.5%), good (n = 4; 25%), fair (n = 6; 37.5%). Ten (62.5%) patients returned to play at an average of 12.2 ± 3.6 (range, 6.0-18.0) months after surgery. Two (12.5%) patients sustained a shoulder injury postoperatively; however, neither required surgery. UCLR in javelin throwers results in good outcomes with a low rate of reinjury/reoperation. However, the return to play rate (62.5%) and good/excellent outcomes per the Conway-Jobe scale (68.8%) are lower than what has been previously reported in baseball players and javelin throwers. Further investigation regarding outcomes in javelin throwers after UCLR is warranted.


Association of human immunodeficiency virus (HIV) p24 antigenemia with decrease in CD4+ lymphocytes and onset of acquired immunodeficiency syndrome during the early phase of HIV infection.
Human immunodeficiency virus (HIV) p24 antigenemia was assessed in a longitudinal study of 52 homosexual men who developed serum antibody to HIV. Antibody seroconversion to HIV as defined by a positive HIV enzyme immunoassay (EIA) confirmed by Western (immuno-) blot was associated with three major patterns of HIV antigenemia. In the first pattern, a transient antigenemia was noted 6 (six subjects) and 12 (one subject) months prior to detection of antibody by HIV EIA and Western blot in 7 (13.5%) of the 52 men. Use of an EIA employing a recombinant envelope protein (ENV9) was able to detect antibody in four of these seven men at the time of this early antigenemia. In the second pattern, HIV p24 antigenemia occurred in 8 (15.4%) of the 52 subjects within the first 12 months after HIV antibody seroconversion. No p24 antigen was detected in the 37 (71.1%) remaining subjects. CD4+ cell numbers were lower in antigen-positive men before and after antibody seroconversion. Development of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was strongly associated with evidence of persistent p24 antigenemia during the early, postseroconversion period. HIV p24 antigenemia may be of value in determining appropriate cohorts for drug therapy trials for subjects with early-phase HIV infection.


Long-term survival following kidney transplantation in previous lung transplant recipients-An analysis of the unos registry.
Kidney transplantation has been advocated as a therapeutic option in lung recipients who develop end-stage renal disease (ESRD). This analysis outlines patterns of allograft survival following kidney transplantation in previous lung recipients (KAL). Data from the UNOS lung and kidney transplantation registries (1987-2013) were cross-linked to identify lung recipients who were subsequently listed for and/or underwent kidney transplantation. Time-dependent Cox models compared the survival rates in KAL patients with those waitlisted for renal transplantation who never received kidneys. Survival analyses compared outcomes between KAL patients and risk-matched recipients of primary, kidney-only transplantation with no history of lung transplantation (KTx). A total of 270 lung recipients subsequently underwent kidney transplantation (KAL). Regression models demonstrated a lower risk of post-listing mortality for KAL patients compared with 346 lung recipients on the kidney waitlist who never received kidneys (P<.05). Comparisons between matched KAL and KTx patients demonstrated significantly increased risk of death and graft loss (P<.05), but not death-censored graft loss, for KAL patients (P = .86). KAL patients enjoy a significant survival benefit compared with waitlisted lung recipients who do not receive kidneys. However, KAL patients do poorly compared with KTx patients. Decisions about KAL transplantation must be made on a case-by-case basis considering patient and donor factors.


Outpatient Percutaneous Endovascular Abdominal Aortic Aneurysm Repair: A Single-Center Experience.
To evaluate the safety of outpatient percutaneous endovascular abdominal aortic repair (PEVAR) versus inpatient PEVAR without or with adjunct procedures. Between January 2012 and June 2019, a cohort of 359 patients comprising 168 (46.8%) outpatients and 191 (53.2%) inpatients who had undergone PEVAR were enrolled. All the patients were asymptomatic but had indications for endovascular aortic repair, ie, fit for intravenous anesthesia and anatomically feasible with standard devices. Patient sex, age, comorbidities, smoking status, type of anesthesia, adjunct procedures, type of graft device, operative times, mortality, complications, and readmissions were analyzed. Median follow-up period was 16.5 months (interquartile range, 9-31 months). Except for a higher percentage of tobacco use (42.6% vs 28.8%; P = .04), dyslipidemia (39.7% vs 19.2%; P < .01), and use of local anesthesia (99.4% vs 82.2%; P < .01) in the outpatients, there was no significant difference in the type of graft and adjunct procedures used. No outpatient mortality occurred. There was no difference in the number, severity, and onset of complications (all P > .05). Outpatient unexpected same-day admission, 30-day readmission, and emergency department visit rates were 4.8%, 2.4% (P = .13), and 10% (P < .01), respectively. Operative times for outpatient PEVAR without adjunct procedures were shorter (P < .01). Outpatient PEVAR can be performed with a safety profile similar to that of inpatient PEVAR. The unexpected same-day admission, 30-day readmission, and emergency department visit rates were low. The outpatient PEVARs without adjunct procedures took less time.


First report of Elaphostrongylus cervi in Spanish red deer Cervus elaphus hispanicus.
Elaphostrongylus cervi Cameron, 1931 was identified in six Cervus elaphus hispanicus sampled in Cuenca, central Spain. A total of 23 adult worms were found in the central nervous system with a mean of 3.8. Although E. cervi is reported to be widespread in cervids, this is the first time it has been recorded in Spanish red deer.


[Sleep respiratory disorders, non-invasive ventilation and critical care in Archivos de Bronconeumología (June 2008-November 2009)].
The present study analyses the works published in Archivos de Bronconeumología from June 2008 to November 2009 that mention sleep disorders, non-invasive ventilation and critical care. The methodology used was to analyse the objectives of the works submitted, with their main results and the conclusions suggested by the authors, often putting forward the possibility of conducting new research studies. The review no only includes original articles but is also a reflection on the editorials, special articles and review works.


Distribution, virulence-associated genes and antimicrobial resistance of Aeromonas isolates from diarrheal patients and water, China.
To determine the prevalence of Aeromonas infections in diarrheal patients, the distribution of virulence-associated genes and antibiotic resistance among different Aeromonas species in China. We conducted continual active surveillance aimed on Aeromonas from diarrheal patients and aquatic samples. Aeromonas strains were identified by biochemical tests, further confirmed to species level by a multilocus phylogenetic analysis. Potential virulence genes were detected by PCR. Antibiotics susceptibility testing was carried based on the minimal inhibitory concentration. From 5069 samples (stool specimens, n = 4529; water samples, n = 540) in China, 257 Aeromonas isolates [stools, n = 193 (4.3%); water, n = 64 (11.9%)] were identified by biochemical tests. The most common species from stools and water were Aeromonas veronii (42.5%) and Aeromonas caviae (37.5%), respectively. Distribution of five potential genes were significantly different between stool and water samples, two genes (ast and alt) were higher in stool than in water samples (P < 0.01). Meanwhile, three species (A. veronii, A. caviae and Aeromonas aquariorum) account for the six most prevalent combination patterns of potential genes. Furthermore, strains resistant to nine antibiotics was markedly higher in strains isolated from water than those from stools (P ≤ 0.003); in contrast, resistance to only two antibiotics was higher in strains isolated from stools compared to those from water. In addition, strains containing multiple antibiotic resistance (MAR) from stools (8.6%; 16/187) and water (30.2%; 19/63) were resistant to ten or more antibiotics. Our study highlights the multiple factors involved in the pathogenesis of Aeromonas and reveals that environmental Aeromonas has acquired a wide range of MAR compared to those from clinical sources.


Interest of using genetically manipulated mice as models of depression to evaluate antidepressant drugs activity: a review.
Among the multiple possibilities to study human depressive disorders, animal models remain important preclinical tools. They allow the understanding of the mechanisms of action of antidepressant drugs. Primarily developed in rat, animal models of depression have been adapted to the mouse, an easy-to-use mammal with better genetic possibilities than rats. As an example, genetic manipulation of the serotoninergic 5-hydroxytryptamine-HT; (5-HT) system provided important opportunities to investigate the role of this monoamine in mood disorders. The contribution of either constitutive knockout (KO), tissue specific, or inducible KO mice and animal models in the current knowledge of the pathophysiology and treatment of depression is unanimously recognized. The phenotype of genetically manipulated animals is strongly influenced by both the genetic background of the animal as well as environmental factors. For these reasons, it is necessary to underline that KO mice have been generated on various genetic backgrounds, which strongly influence the behavioral and neurochemical responses to the tests. The present review will thus focus on KO mice lacking G protein-coupled monoaminergic receptors (e.g; 5-HT1B, 5-HT1A, and 5-HT4 receptors) and the 5-HT serotonin transporter, which is the main target of antidepressant drugs (or strategies). The importance of KO mice for neurotrophic factors, particularly for brain-derived neurotrophic factor and its main receptor displaying a tyrosine kinase activity, will also be addressed to illustrate the fact that in preclinical studies, combination of genetic manipulations with pharmacological ones should allow further progress in the field of neuropsychopharmacology.


Rule of five violations among the FDA-approved small molecule protein kinase inhibitors.
Because genetic alterations including mutations, overexpression, translocations, and dysregulation of protein kinases are involved in the pathogenesis of many illnesses, this enzyme family is the target of many drug discovery programs in the pharmaceutical industry. Overall, the US FDA has approved 74 small molecule protein kinase inhibitors, nearly all of which are orally effective. Of the 74 approved drugs, thirty-nine block receptor protein-tyrosine kinases, nineteen target nonreceptor protein-tyrosine kinases, twelve are directed against protein-serine/threonine protein kinases, and four target dual specificity protein kinases. The data indicate that 65 of these medicinals are approved for the management of neoplasms (51 against solid tumors such as breast, colon, and lung cancers, eight against nonsolid tumors such as leukemia, and six against both types of tumors). Nine of the FDA-approved kinase inhibitors form covalent bonds with their target enzymes and they are accordingly classified as TCIs (targeted covalent inhibitors). Medicinal chemists have examined the physicochemical properties of drugs that are orally effective. Lipinski's rule of five (Ro5) is a computational procedure that is used to estimate solubility, membrane permeability, and pharmacological effectiveness in the drug-discovery setting. It relies on four parameters including molecular weight, number of hydrogen bond donors and acceptors, and the Log of the partition coefficient. Other important descriptors include the lipophilic efficiency, the polar surface area, and the number of rotatable bonds and aromatic rings. We tabulated these and other properties of the FDA-approved kinase inhibitors. Of the 74 approved drugs, 30 fail to comply with the rule of five.


Conductive interstitial thermal therapy device for surgical margin ablation: in vivo verification of a theoretical model.
To demonstrate the efficacy and predictability of a new conductive interstitial thermal therapy (CITT) device to ablate surgical margins. The temperature distributions during thermal ablation of CITT were calculated with finite element modelling in a geometrical representation of perfused tissue. The depth of ablation was derived using the Arrhenius and the Sapareto and Dewey (S&D) models for the temperature range of 90 to 150 degrees C. The female pig animal model was used to test the validity of the mathematical model. Breast tissues were ablated to temperatures in the range of 79-170 degrees C, in vivo. Triphenyltetrazolium chloride viability stain was used to delineate viable tissue from ablated regions and the ablation depths were measured using digital imaging. The calculations suggest that the CITT can be used to ablate perfused tissues to a 10-15 mm width within 20 minutes. The measured and calculated depths of ablation were statistically equivalent (99% confidence intervals) within +/- 1mm at 170 degrees C. At lower temperatures the equivalence between the model and the observations was within +/- 2 mm. The CITT device can reliably and uniformly ablate a 10-15 mm wide region of soft tissue. Thus, it can be used to secure negative margins following the resection of a primary tumor, which could impede local recurrences in the treatment of local diseases such as early staged, non-metastatic, breast cancer.


Effects of glucagon like peptide-1 to mediate glycemic effects of weight loss surgery.
To date, weight loss surgeries are the most effective treatment for obesity and glycemic control in patients with type 2 diabetes. Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG), two widely used bariatric procedures for the treatment of obesity, induce diabetes remission independent of weight loss while glucose improvement after adjustable gastric banding (AGB) is proportional to the amount of weight loss. The immediate, weight-loss independent glycemic effect of gastric bypass has been attributed to postprandial hyperinsulinemia and an enhanced incretin effect. The rapid passage of nutrients into the intestine likely accounts for significantly enhanced glucagon like-peptide 1 (GLP-1) secretion, and postprandial hyperinsulinemia after GB is typically attributed to the combined effects of elevated glucose and GLP-1. For this review we focus on the beneficial effects of the three most commonly performed bariatric procedures, RYGB, SG, and AGB, on glucose metabolism and diabetes remission. Central to this discussion will be the extent to which the effects of surgery are mediated by GLP-1. Better understanding of these mechanisms could provide insight to development of novel therapeutic strategies for treatment of diabetes as well as refinement of surgical techniques.


Molecular dynamics simulations of silicon-fluorine etching.
Molecular dynamics simulations of the reactions between gaseous fluorine atoms and (SiFx)n adsorbates on the Si(100) - (2 x 1) surface are performed using the SW potential and compared to simulations with the WWC reparameterization of the SW potential. Theoretical and experimental work has demonstrated that the reactive fluorosilyl layer during silicon-fluorine etching is composed of tower-like adspecies of SiF, SiF2 and SiF3 groups. The objective of the simulations is to determine how the chemical composition, mechanism of formation, and energy distribution of the etched gas-phase products depend on the identity of the reacting adsorbate, the incident kinetic energy, and the parameterization of the potential energy function. Three reactions are simulated: F(g) + SiF3(a), F(g) + SiF2-SiF3(a), and F(g) + SiF2-SiF2-SiF3(a). SiF4 is the major product and Si2F6 and Si3F8 are minor products. In Si2F6 and Si3F8, the silicon-fluorine bond that is formed is stronger than the silicon-silicon bond in the molecule and, therefore, the majority of these products have enough energy to dissociate and will fragment before reaching the detector. An SN2-like mechanism is the primary mechanism responsible for the formation of SiF4, Si2F6, and Si3F8. In addition, at higher energies, the simulations have discovered a previously unknown mechanism for the formation of SiF4, which involves an insertion between a silicon-silicon bond. The results of the simulations with the two potentials differ quite substantially in their prediction of the reactivity of the adsorbates. The SW potential predicts a 2- to 3-eV lower energy threshold for reaction and a much higher reaction cross-section, especially for the SiF4 product. These results are explained in terms of the differences in the potential energy functions used to describe the silicon-fluorine interactions. In addition, the results are compared to experimental data on silicon-fluorine etching.


The modified horn flap for nasal tip reconstruction.
Numerous flap design techniques have been proposed for soft tissue reconstruction of the nasal tip. The modified horn flap based on the superior alar artery and nasalis muscle is the preferred option for defects ranging in size from 1 to 2 cm vertically and 1.5 to 3 cm horizontally after skin cancer excision. This innovative technique is a reliable and versatile island flap for reconstruction of the nasal tip in a one-stage operation, providing successful functional and aesthetic results, as tissues for the flap are generated from the nose. The contribution of the superior alar artery, which forms the vascular axis of the flap, plays a vital role in flap survival - together with part of the nasalis muscle.


Neuroinflammation in Neurodegenerative Disorders-a Review.
The potential for positron emission tomography (PET) to detect neuroinflammation in vivo has sparked a remarkable interest in various disciplines of neuroscience. Early PET radioligands, such as [11C]PK(R)-11195 for the 18-kDa translocator protein (TSPO) and [11C]L-deprenyl for monoamine oxidase B, have been used in studies designed to clarify the role of neuroinflammation in a variety of psychiatric and neurological disorders. Recent years have witnessed the development of several second-generation PET radioligands for TSPO and radioligands to measure endogenous targets that are active in various stages of the inflammatory cascade, such as cyclooxygenase and arachidonic acid. Here, we discuss some of the biomarkers for neuroinflammation that are available for quantification with PET, as well as recent findings from studies where neuroinflammation has been assessed in neurodegenerative disorders. In addition, we highlight the challenges to accurate interpretation of PET studies of neuroinflammation.


Managing geriatric syndromes: what geriatric assessment teams recommend, what primary care physicians implement, what patients adhere to.
To evaluate the responses of primary care physicians and patients to recommendations from a community-based comprehensive geriatric assessment (CGA) program for management of four target conditions: falls, depression, urinary incontinence, and functional impairment. Case series. Senior centers, meal sites, senior housing, and other community sites as screening locations; and a community-bases academic practice as the location for CGA. A total of 150 older patients living in the community who have one or more of the four target conditions and who received CGA. Physician implementation and patient adherence rates were ascertained during a face-to-face structured interview with the patient 3 months after CGA. Two hundred twelve of 528 (40%) CGA recommendations were clearly or possible related to the target or target-related conditions. Of these 212 recommendations, 59% required a physician's order for implementation. The remaining 41% were patient self-care recommendations. Overall physician implementation across conditions was 70%; implementation rates were highest for falls and lowest for functional impairment. Overall patient adherence rate was 85% for physician-implemented recommendations and 46% for self-care recommendations. Patient adherence to recommendations for counseling or support groups and exercise programs was particularly low. When examining the process of care of community-based CGA, patient as well as physician adherence must be considered. Although patient adherence to physician-initiated recommendations was high for all conditions, it varied substantially across target conditions and types of recommendations for self-care recommendations.


Economic evaluations of interventions to prevent and control health-care-associated infections: a systematic review.
Almost 9 million health-care-associated infections have been estimated to occur each year in European hospitals and long-term care facilities, and these lead to an increase in morbidity, mortality, bed occupancy, and duration of hospital stay. The aim of this systematic review was to review the cost-effectiveness of interventions to limit the spread of health-care-associated infections), framed by WHO infection prevention and control core components. The Embase, National Health Service Economic Evaluation Database, Database of Abstracts of Reviews of Effects, Health Technology Assessment, Cinahl, Scopus, Pediatric Economic Database Evaluation, and Global Index Medicus databases, plus grey literature were searched for studies between Jan 1, 2009, and Aug 10, 2022. Studies were included if they reported interventions including hand hygiene, personal protective equipment, national-level or facility-level infection prevention and control programmes, education and training programmes, environmental cleaning, and surveillance. The British Medical Journal checklist was used to assess the quality of economic evaluations. 67 studies were included in the review. 25 studies evaluated methicillin-resistant Staphylococcus aureus outcomes. 31 studies evaluated screening strategies. The assessed studies that met the minimum quality criteria consisted of economic models. There was some evidence that hand hygiene, environmental cleaning, surveillance, and multimodal interventions were cost-effective. There were few or no studies investigating education and training, personal protective equipment or monitoring, and evaluation of interventions. This Review provides a map of cost-effectiveness data, so that policy makers and researchers can identify the relevant data and then assess the quality and generalisability for their setting.


[In vitro antimicrobial susceptibility in Enterococcus faecalis and Enterococcus faecium isolated from hospitalized patients].
Enterococcus spp is currently considered as one of the most important nosocomial pathogens . The antibiotic resistance of this group of bacteria is a particularly important problem in health centers. To characterize the antibiotic resistance of 50 Enterococcus spp strains isolated from hospitalized patients clinical samples. We conducted a cross-sectional descriptive observational study in 50 clinical isolates of Enterococcus spp. Only one isolate per patient was analyzed . The identification and antibiotic susceptibility were studied by conventional and automated methods . The phenotypic analysis of glycopeptide resistance mechanisms was performed as recommended by the Spanish Society of Clinical Microbiology and Infectious Diseases . Of 50 isolates obtained from clinical samples, 30 ( 60.0%) belonged to Enterococcus faecalis and 20 (40.0 %) to Enterococcus faecium . The global resistance expressed by this genre was as follows: Ampicillin, 38/50 ( 76.0%); high-level gentamicin, 33/50 ( 66.0%); high-level streptomycin, 34/50 (68.0 %) ; ciprofloxacin, 26/50 (52.0 %); linezolid, 4/50 (8.0 %); teicoplanin, 17/50 ( 34.0%); vancomycin, 25/50 (50.0 %); minocycline, 31/50 ( 62.0%); tetracycline, 34/50 (68.0 %); nitrofurantoin, 9/50 ( 18.0%). As regards glycopeptides, 25/50 (50.0%) showed a Van A mechanism and 10/50 (20.0 %) a Van B mechanism . The isolates obtained at Hospital Hermanos Ameijeiras showed higher resistance rates than those reported in the consulted literature. The high percentage of vancomycin-resistant strains might have influenced the development of other Gram-positive bacteria resistant to this drug. This is the first report on Enterococcus faecium resistant to linezolid in a Cuban hospital.


The role of claw deformation and claw size on goat lameness.
Lameness due to claw overgrowth remains one of the main welfare challenges in dairy goat farms. Although claw trimming is a crucial part of the solution, most times there is a delay in its implementation, with no perceived consequences. The goal of this cross-sectional study was to assess the correlation between the size and deformation of dairy goats claws with lameness score. The width and length of the claws of 38 adult dairy goats were taken and classified as deformed (DEF) or non-deformed (NO_DEF). Lameness was also scored in the majority of the animals assessed for claw deformation. Deformation of at least one claw was present in 34 animals (89% of the total sample). From the 34 goats with deformed claws, 33 presented at least one deformed rear claw and 18 presented at least one deformed front claw. From the 152 claws assessed 58% were deformed (n = 88), of which 19% (n = 29) were front claws and 39% were rear claws (n = 59). Increased width of the front claws was associated with increased likelihood of having deformation with odds of 1.24, and the increased length explained 16% of the variation in lameness scores. A positive relation between lameness score and the number of deformed claws was also shown. Overall, these results suggest that the size of dairy goats' claws influences the prevalence of deformation and lameness severity and that the number of deformed claws affects goats' gait. They also help to build the argument in favor of regular trimming in dairy goat farms.


Effects of short-term graded dietary carbohydrate intake on intramuscular and whole body metabolism during moderate-intensity exercise.
Altering dietary carbohydrate (CHO) intake modulates fuel utilization during exercise. However, there has been no systematic evaluation of metabolic responses to graded changes in short-term (< 1 wk) dietary CHO intake. Thirteen active men performed interval running exercise combined with isocaloric diets over 3 days before evaluation of metabolic responses to 60-min running at 65% V̇O2max on three occasions. Diets contained lower [LOW, 2.40 ± 0.66 g CHO·kg-1·day-1, 21.3 ± 0.5% of energy intake (EI)], moderate (MOD, 4.98 ± 1.31 g CHO·kg-1·day-1, 46.3 ± 0.7% EI), or higher (HIGH, 6.48 ± 1.56 g CHO·kg-1·day-1, 60.5 ± 1.6% EI) CHO. Preexercise muscle glycogen content was lower in LOW [54.3 ± 26.4 mmol·kg-1 wet weight (ww)] compared with MOD (82.6 ± 18.8 mmol·kg -1 ww) and HIGH (80.4 ± 26.0 mmol·kg-1 ww, P < 0.001; MOD vs. HIGH, P = 0.85). Whole body substrate oxidation, systemic responses, and muscle substrate utilization during exercise indicated increased fat and decreased CHO metabolism in LOW [respiratory exchange ratio (RER): 0.81 ± 0.01] compared with MOD (RER 0.86 ± 0.01, P = 0.0005) and HIGH (RER: 0.88 ± 0.01, P < 0.0001; MOD vs. HIGH, P = 0.14). Higher basal muscle expression of genes encoding proteins implicated in fat utilization was observed in LOW. In conclusion, muscle glycogen availability and subsequent metabolic responses to exercise were resistant to increases in dietary CHO intake from ∼5.0 to ∼6.5 g CHO·kg-1·day-1 (46% to 61% EI), while muscle glycogen, gene expression, and metabolic responses were sensitive to more marked reductions in CHO intake (∼2.4 g CHO·kg-1·day-1, ∼21% EI).NEW & NOTEWORTHY The data presented here suggest that metabolic responses to steady-state aerobic exercise are somewhat resistant to short-term changes in dietary carbohydrate (CHO) intake within the 5-6.5 g CHO·kg-1·day-1 [46-61% energy intake (EI)] range. In contrast, reduction in short-term dietary CHO intake to ∼2.4 g CHO·kg-1·day-1 (21% EI) evoked clear changes indicative of increased fat and decreased CHO metabolism during exercise.


Significance of morphological alteration by portal vein branch ligation in endotoxin-induced liver injury after partial hepatectomy.
Regenerating liver after partial hepatectomy (PH) is susceptible to endotoxin. This study was conducted to investigate how morphological alteration by preoperative portal vein branch ligation (PVL) affects endotoxin-induced liver injury after PH. Male Sprague-Dawley rats were divided into a PVL group undergoing left PVL and into a non-PVL group receiving a sham operation. Seven days later, animals in both groups were subjected to PH (the left lateral, median and caudate lobes). Lipopolysaccharide (LPS) was intravenously administered to both groups 2 days after PH. A significant increase in hepatocyte and sinusoidal endothelial cell proliferation assessed by Ki-67 immunostaining reached a peak at day 2 and 3 after PVL, respectively, in accordance with the changes in plasma interleukin-6 concentrations after PVL. The proliferation response of these cells after PH was observed in both groups, showing a significantly weaker response in the PVL group. The sinusoidal width after PH was significantly reduced in the non-PVL group when compared with that in the PVL group. LPS administration induced a marked elevation of plasma tumour necrosis factor-alpha levels in the non-PVL group compared with the PVL group. PVL before PH significantly attenuated endotoxin-induced functional and structural liver damage with greater hepatic polymorphonuclear leucocyte infiltration and microcirculatory derangement, resulting in an improvement in the 7-day survival rate. Morphological alteration by PVL is of great advantage in preventing the development of endotoxin-induced liver injury in the regeneration process after PH.


Fluorescence imaging of the ILM flap following MH surgery.
To report on the imaging of internal limiting membrane (ILM) flap following macular hole (MH) surgery. Three eyes of 3 patients with baseline Snellen visual acuities (VAs) of 20/250, 20/30, and 20/100 underwent superior wide-base internal limiting membrane flap transposition (SWIFT) for MH. Indocyanine green (ICG) was used for intraoperative staining of the ILM. Following MH surgery, MH closed in all cases and VAs were 20/30, 20/30, and 20/60 respectively. An "en face" ICG fluorescence image of the ILM flap was obtained using infrared confocal scanning laser imaging at 795 nm. ICG fluorescence demonstrated the ILM flap to be intact and in good position with complete coverage of the MH in all cases. An area of hypofluorescence was present superiorly, corresponding to the flap harvest site with absent ILM. ICG hyperfluorescence of varying intensity was present at the MH site in all 3 cases. Folding of the ILM flap was present in one case. Following MH surgery, the status of an ILM flap may be evaluated by an "en face" image of the flap obtained by ICG fluorescence imaging. This imaging modality may be valuable in the study of various ILM flap techniques.


Burden of illness associated with eosinophilic granulomatosis with polyangiitis: a systematic literature review and meta-analysis.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease associated with vascular inflammation and multisystem organ damage. The literature reporting EGPA incidence or prevalence is limited. We performed a systematic literature review and meta-analysis to describe the incidence, prevalence, and disease burden associated with EGPA. Real-world, observational, English-language studies in MEDLINE, MEDLINE In-Process, and Embase up to 6 June, 2019, were included. A single investigator screened all identified titles/abstracts and extracted data; an additional, independent investigator repeated the screening and validated the extracted data. A random-effects meta-analysis was conducted to generate pooled estimates for EGPA incidence and prevalence. Data from 100 eligible publications were extracted (32 with incidence/prevalence data, 65 with morbidity/healthcare resource data; 3 with both types of data). Significant evidence of between-study heterogeneity for reported incidence (p = 0.0013-0.0016) and prevalence (p = 0.0001-0.0006) estimates was observed. Global and European pooled estimates (95% confidence interval) of EGPA incidence were 1.22 (0.93, 1.60) and 1.07 (0.94, 1.35) cases per million person-years, respectively; global and European pooled estimates (95% confidence interval) for EGPA prevalence were 15.27 (11.89, 19.61) and 12.13 (6.98, 21.06) cases per million individuals, respectively. The proportions of patients experiencing relapses, or who had nasal polyps or severe asthma, varied considerably across studies. EGPA healthcare resource use was high, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Our results indicate that although global and European EGPA incidence and prevalence is low, the associated disease burden is substantial. Key points • We performed a systematic literature review and meta-analysis of real-world, observational studies describing the incidence, prevalence, and disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA). • Based on meta-analysis data from 35 eligible studies reporting incidence and prevalence, the incidence and prevalence of EGPA were low (globally 1.22 cases per million person-years and 15.27 cases per million individuals, respectively). • Among the 49 studies with morbidity and/or healthcare resource data, most reported a large proportion of patients with EGPA relapses and comorbidities of nasal polyps and severe asthma. • Healthcare resource use was also high among patients with EGPA in these studies, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Taken together, these data indicate the substantial disease burden associated with EGPA.


Cognitive and neuroimaging outcomes in individuals with benign and low-grade brain tumours receiving radiotherapy: a protocol for a prospective cohort study.
Radiation-induced cognitive decline (RICD) occurs in 50%-90% of adult patients 6 months post-treatment. In patients with low-grade and benign tumours with long expected survival, this is of paramount importance. Despite advances in radiation therapy (RT) treatment delivery, better understanding of structures important for RICD is necessary to improve cognitive outcomes. We hypothesise that RT may affect network topology and microstructural integrity on MRI prior to any gross anatomical or apparent cognitive changes. In this longitudinal cohort study, we aim to determine the effects of RT on brain structural and functional integrity and cognition. This study will enroll patients with benign and low-grade brain tumours receiving partial brain radiotherapy. Patients will receive either hypofractionated (>2 Gy/fraction) or conventionally fractionated (1.8-2 Gy/fraction) RT. All participants will be followed for 12 months, with MRIs conducted pre-RT and 6-month and 12 month post-RT, along with a battery of neurocognitive tests and questionnaires. The study was initiated in late 2018 and will continue enrolling through 2024 with final follow-ups completing in 2025. The neurocognitive battery assesses visual and verbal memory, attention, executive function, processing speed and emotional cognition. MRI protocols incorporate diffusion tensor imaging and resting state fMRI to assess structural connectivity and functional connectivity, respectively. We will estimate the association between radiation dose, imaging metrics and cognitive outcomes. This study has been approved by the Research Subjects Review Board at the University of Rochester (STUDY00001512: Cognitive changes in patients receiving partial brain radiation). All results will be published in peer-reviewed journals and at scientific conferences. ClinicalTrials.gov NCT04390906.


Transcriptome analysis reveals the tolerant mechanisms to cobalt and copper in barley.
Cobalt (Co) and copper (Cu) co-exist commonly in the contaminated soils and at excessive levels, they are toxic to plants. However, their joint effect and possible interaction have not been fully addressed. In this work, a hydroponic experiment was performed to investigate the combined effects of Co and Cu on two barley genotypes at transcriptional level by RNA-seq analysis. The results identified 358 genes inclusively expressed in both genotypes under single and combined treatments of Co and Cu, with most of them being related to metal transport, stress response and transcription factor. The combined treatment induced more differently expressed genes (DEGs) than the single treatment, with Yan66, a metal tolerant genotype having more DEGs than Ea52, a sensitive genotype. The pathways associated with anthocyanin biosynthesis, MAPK signaling, glutathione biosynthesis, phenylalanine metabolism, photosynthesis, arginin biosynthesis, fatty acid elongation, and plant hormone signal transduction biosynthesis were induced and inhibited in Yan66 and Ea52, respectively. Furthermore, flavonoid biosynthesis was much more largely enhanced and accordingly more free flavonoid components (naringin, narirutin and neohesperidin) were accumulated in Yan66 than in Ea52. It may be suggested that high tolerance to both Co and Cu in Yan66 is attributed to its high gene regulatory ability.


New Insights into Cockroach Allergens.
This review addresses the most recent developments on cockroach allergen research in relation to allergic diseases, especially asthma. The number of allergens relevant to cockroach allergy has recently expanded considerably up to 12 groups. New X-ray crystal structures of allergens from groups 1, 2, and 5 revealed interesting features with implications for allergen standardization, sensitization, diagnosis, and therapy. Cockroach allergy is strongly associated with asthma particularly among children and young adults living in inner-city environments, posing challenges for disease control. Environmental interventions targeted at reducing cockroach allergen exposure have provided conflicting results. Immunotherapy may be a way to modify the natural history of cockroach allergy and decrease symptoms and asthma severity among sensitized and exposed individuals. The new information on cockroach allergens is important for the assessment of allergen markers of exposure and disease, and for the design of immunotherapy trials.


Cognitive impairment in Crohn's disease is associated with systemic inflammation, symptom burden and sleep disturbance.
Patients with Crohn's disease (CD) frequently complain of cognitive difficulties such as problems with concentration and clouding of thought, yet this has scarcely been objectively defined and underlying mechanisms remain unknown. The objective of this article is to objectively measure cognitive impairments in patients with CD compared with healthy controls, and if present, to identify potentially modifiable, contributing factors associated with cognitive impairment. CD patients and healthy age-/sex-matched controls completed surveys encompassing clinical, demographic, psychiatric, fatigue and sleep parameters. Contemporaneously, disease activity assessment with serum CRP, faecal calprotectin, Harvey-Bradshaw Index and the Subtle Cognitive Impairment test (SCIT) were performed, with the primary measure of response time (SCIT-RT) compared between groups. Multiple linear regression assessed for factors associated with slower SCIT-RT, denoting subtle cognitive impairment. A total of 49 CD and 31 control individuals participated, with median age 44 years (range 22-65) and 43 years (21-63), respectively. Compared to controls, SCIT-RT was slower across all timepoints in CD patients (ANOVA p < 0.001). In multivariate analysis, serum CRP (standardised beta coefficient 0.27, 95% CI (0.02, 0.51)), abdominal pain (0.43 (0.16, 0.70)), plasma haemoglobin (1.55 (1.42, 1.68)), and concurrent fatigue (0.56 (0.25, 0.88)) were each independently associated with slower SCIT-RT in CD (each p < 0.05), with a trend for poorer sleep quality 0.54 (-0.03, 1.11) (p = 0.06), yet conversely, higher faecal calprotectin titres were associated with faster SCIT-RT (-1.77 (-1.79, -1.76), p < 0.01). Patients with CD demonstrated subtle cognitive impairment utilising the objective SCIT, correlating with systemic inflammation and other disease burden measures, although higher faecal calprotectin titres were unexpectedly associated with less cognitive impairment.


Blomia tropicalis allergen 5 (Blo t 5) T-cell epitopes and their ability to suppress the allergic immune response.
Blomia tropicalis is the major asthma allergen in the tropics comparable to Dermatophagoides pteronyssinus. However, little is known about the B. tropicalis epitopes recognized by T cells. Our aim was to identify the T-cell epitopes in the major B. tropicalis allergen, Blo t 5, and investigate the potential of the corresponding peptides to inhibit the allergic inflammatory lung response. C57BL/6 mice were immunized with plasmid DNA encoding Blo t 5 and T-cell epitopes identified using the interferon-γ ELISPOT assay with 15-mer overlapping peptides. C57BL/6 mice were sensitized with bone-marrow-derived dendritic cells (BMDC) pulsed with Blo t 5 allergen followed by intranasal Blo t 5 challenge. Two H-2b restricted epitopes (Bt576-90 and Bt5106-115 ) were recognized by CD4 T cells specific for Blo t 5, but no CD8 epitopes were identified. In mice sensitized with Blo t 5-pulsed BMDC and challenged with intranasal Blo t 5 Bt576-90 and Bt5106-115 , peptide-specific CD4 T cells were found to secrete the T helper type 2 cytokines interleukin-5 and interleukin-13. Intradermal administration of synthetic peptides encoding the identified T-cell epitopes suppressed allergic airway inflammation to further allergen challenges. Hence, we have identified novel CD4 T-cell epitopes specific for Blo t 5 and demonstrated that these peptides could be employed therapeutically to suppress the T-cell response in a murine model of allergic airway inflammation.


Modulation of carcinogen-induced DNA damage and repair enzyme activity by dietary riboflavin.
Formation of single strand breaks in nuclear DNA induced by hepatocarcinogens aflatoxin B1 and N-nitrosodimethylamine was observed to be more pronounced in rats maintained on a riboflavin-deficient diet compared to that on a normal diet. This increased damage was reversed on riboflavin supplementation. The induction of repair enzymes poly(ADP-ribose) polymerase, DNA polymerase beta and DNA ligase was significantly higher in riboflavin-deficient rats following DNA damage caused by the administration of carcinogens. Riboflavin supplementation brought down the induction to the levels found in rats maintained on normal diet. Since damage to DNA and its altered repair may relate to carcinogenesis, modulation of these parameters by riboflavin suggests a potential chemopreventive role of this vitamin.


Increasing G9a automethylation sensitizes B acute lymphoblastic leukemia cells to glucocorticoid-induced death.
Synthetic glucocorticoids (GCs) are used to treat lymphoid cancers, but many patients develop resistance to treatment, especially to GC. By identifying genes that influence sensitivity to GC-induced cell death, we found that histone methyltransferases G9a and G9a-like protein (GLP), two glucocorticoid receptor (GR) coactivators, are required for GC-induced cell death in acute lymphoblastic leukemia (B-ALL) cell line Nalm6. We previously established in a few selected genes that automethylated G9a and GLP recruit heterochromatin protein 1γ (HP1γ) as another required coactivator. Here, we used a genome-wide analysis to show that HP1γ is selectively required for GC-regulated expression of the great majority of GR target genes that require G9a and GLP. To further address the importance of G9a and GLP methylation in this process and in cell physiology, we found that JIB-04, a selective JmjC family lysine demethylase inhibitor, increased G9a methylation and thereby increased G9a binding to HP1γ. This led to increased expression of GR target genes regulated by G9a, GLP and HP1γ and enhanced Nalm6 cell death. Finally, the KDM4 lysine demethylase subfamily demethylates G9a in vitro, in contrast to other KDM enzymes tested. Thus, inhibiting G9a/GLP demethylation potentially represents a novel method to restore sensitivity of treatment-resistant B-ALL tumors to GC-induced cell death.


Germination of Aspergillus fumigatus conidia in the lungs of normal and cortisone-treated mice.
Inhaled conidia of Aspergillus fumigatus germinated in the lungs of mice at a low rate but both germinated and ungerminated spores were cleared. Spores germinated at a high rate in the lungs of cortisone-treated mice.


[The unstable upper ankle joint. Treatment of acute ligament rupture--a review of the literature].
Acute lateral ankle ligament sprains represent a very frequent examinated and treated injury in the daily traumatological routine. A cursory review of recent articles published on this subject gives a confusing picture regarding diagnosis and treatment of such injuries. An air of controversy surrounds the interpretation of diagnostic x-rays and the management of these common ankle problems. This review article is to summarize current thoughts of different aspects concerning the treatment of acute lateral ankle ligament sprains.


Pulmonary artery aneurysm associated with a nonstenotic bicuspid pulmonic valve: A role for genetics?
Bicuspid pulmonic valves are quite uncommon, being described in only 0.1% of donor's hearts, while pulmonary artery aneurysms (PAAs) are even rarer, having been found in 8 out of 109,571 autopsies. This rarity makes it difficult to characterize the relationship between them. We describe the case of a 66-year-old female who was found to have a bicuspid pulmonic valve and PAA (5.1 cm) on imaging by her cardiologist. This case raises the question of whether the association between bicuspid semilunar valve disease and vascular wall anomalies is more genetic or hemodynamic. Even on the aortic side, despite the robust association between bicuspid aortic valves and thoracic aortic aneurysms, the mechanism still remains unclear. In our patient there was no significant gradient across the bicuspid pulmonic valve, suggesting that hemodynamics are not the primum mobile of this association.


DFT study of cyclic glycine-alanine dipeptide binding to gold nanoclusters.
In this work, we studied the interactions between cyclic glycine-alanine dipeptide c(GA) and gold nanoclusters (AunNCs, where n = 2-10) using density functional theory (DFT), atoms-in-molecules theory (AIM), and natural bond orbital analysis (NBO). This dipeptide (DP) consists of two amino acid residues (glycine and alanine); thus, the preference of both residues for binding to gold atoms was examined. The preference of alanine residue to the studied AunNCs was found to be greater than that of glycine residue. Two types of interactions were exhibited between the AunNCs and c(GA), the partially-covalent partially-electrostatic type and electrostatic interaction. Performance of two DFT functionals and different basis sets is assessed. The results benchmark the importance of the DFT functional with dispersion and long-range corrections, as well as the polarization functions in the basis sets for the gold lusters-peptide binding. The binding energy (ΔEbind) values of the c(GA)-AunNCs complexes in gas and water implicit solvent were compared with those previously published for cyclic glycine-glycine DP-AunNCs complexes. It was found that the ΔEbind values of the former complexes are greater than those of latter ones in water solvent.


Optic neuropathy in Hodgkin's disease.
Hodgkin's disease is a rare cause of infiltrative optic neuropathy, which typically evolves late in the disease course. We managed an unusual case of isolated optic neuropathy in a 21-year-old man occurring during clinical remission from Hodgkin's disease. Radiotherapy and treatment with high-dose systemic corticosteroids resulted in dramatic improvement in vision. Even without other evidence of recurrent disease, acute-onset optic neuropathy in a patient with a history of a lymphoproliferative disorder should raise the question of a reemergence of the malignancy.


Is a switch to a different electronic health record associated with a change in patient satisfaction?
Financial impacts associated with a switch to a different electronic health record (EHR) have been documented. Less attention has been focused on the patient response to an EHR switch. The Mayo Clinic was involved in an EHR switch that occurred at 6 different locations and with 4 different "go-live" dates. We sought to understand the relationship between patient satisfaction and the transition to a new EHR. We used patient satisfaction data collected by Press Ganey from July 2016 through December 2019. Our patient satisfaction measure was the percent of patients responding "very good" (top box) to survey questions. Twenty-four survey questions were summarized by Press Ganey into 6 patient satisfaction domains. Piecewise linear regression was used to model patient satisfaction before and after the EHR switch dates. Significant drops in patient satisfaction were associated with the EHR switch. Patient satisfaction with access (ease of getting clinic on phone, ease of scheduling appointments, etc.) was most affected (range of 6 sites absolute decline: -3.4% to -8.8%; all significant at 99% confidence interval). Satisfaction with providers was least affected (range of 6 sites absolute decline: -0.5% to -2.8%; 4 of 6 sites significant at 99% confidence interval). After 9-15 months, patient satisfaction with access climbed back to pre-EHR switch levels. Patient satisfaction in several patient experience domains dropped significantly and stayed lower than pre-"go-live" for several months after a switch in EHR. Satisfaction with providers declined less than satisfaction with access.


[The value of bone mineral density assessment by dual-energy x-ray absorptiometry for prediction of cardiovascular mortality in patients treated with hemodialysis].
Determine whether bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry can be used as predictor of increased risk of death in hemodialysis patients. A prospective study was performed of 516 patients with chronic kidney disease treated with hemodialysis (men 265, women 251, mean age 44.811.4 years) who were observed for 5.73.2 years. Before inclusion in the study, in all patients was analyzed bone mineral density using dual-energy X-ray absorptiometry in three standard departments: lumbar vertebrae, proximal femur and distal forearm. The probability analysis of the outcome was carried out using the KaplanMeier method and Cox. During follow-up period 111 (21.5%) patients died, 50.5% from cardiovascular events. Survival analysis by KaplanMeier method allowed to prove the increased risk of death from cardiovascular pathology in hemodailysis patients with low bone mineral density of all evaluated areas. Step-by-step multivariate Cox regression analysis showed that the T score of the femur, showing the difference of BMD of the patient with normal value of BMD for young adult, had the greatest prognostic significance. Reduced bone mineral density in patients receiving hemodialysis is associated with an increased risk of death from cardiovascular disease. Dual energy x-ray absorptiometry can be used for assessment of this risk.


Sex differences in left ventricular electrical dyssynchrony and outcomes with cardiac resynchronization therapy.
Women seem to derive more benefit from cardiac resynchronization therapy (CRT) than men, even after accounting for the higher burden of risk factors for nonresponse often observed in men. To assess for sex-specific differences in left ventricular (LV) electrical dyssynchrony as a contributing electrophysiological explanation for the greater degree of CRT benefit among women. We compared the extent of baseline LV electrical dyssynchrony, as measured by the QRS area (QRSA), among men and women with left bundle branch block (LBBB) undergoing CRT at Duke University (n = 492, 35% women) overall and in relation to baseline QRS characteristics using independent sample t tests and Pearson correlation coefficients. Cox regression analyses were used to relate sex, QRSA, and QRS characteristics to the risk of cardiac transplantation, LV assist device implant, or death. Although the mean QRS duration (QRSd) did not differ by sex, QRSA was greater for women vs men (113.8 μVs vs 98.2 μVs, P < .001), owing to differences in the QRSd <150 ms subgroup (92.3 ± 28.7 μVs vs 67.6 ± 26.2 μVs, P < .001). Among those with nonstrict LBBB, mean QRSd was similar but QRSA was significantly greater among women than men (96.0 ± 25.0 μVs vs 63.6 ± 26.2 μVs, P < .001). QRSA was similar among men and women with strict LBBB (P = .533). Female sex was associated with better long-term outcomes in an unadjusted model (hazard ratio 0.623, confidence interval 0.454-0.857, P = .004) but sex no longer predicted outcomes after accounting for differences in QRSA. Our study suggests that sex-specific differences in LV dyssynchrony contribute to greater CRT benefit among women. Standard QRSd and morphology assessments seem to underestimate the extent of LV electrical dyssynchrony among women with LBBB.


Metabonomics techniques and applications to pharmaceutical research & development.
In this review, the background to the approach known as metabonomics is provided, giving a brief historical perspective and summarizing the analytical and statistical techniques used. Some of the major applications of metabonomics relevant to pharmaceutical Research & Development are then reviewed including the study of various influences on metabolism, such as diet, lifestyle, and other environmental factors. The applications of metabonomics in drug safety studies are explained with special reference to the aims and achievements of the Consortium for Metabonomic Toxicology. Next, the role that metabonomics might have in disease diagnosis and therapy monitoring is provided with some examples, and the concept of pharmacometabonomics as a way of predicting an individual's response to treatment is highlighted. Some discussion is given on the strengths and weaknesses, opportunities of, and threats to metabonomics.


Evaluation of the BioFire Blood Culture Identification 2 panel and impact on patient management and antimicrobial stewardship.
Bloodstream infection survival is linked to timely administration of optimal antimicrobial therapy. Commercial multiplex polymerase chain reaction (PCR) assays, such as the BioFire Blood Culture Identification Panel (BCID) used for the rapid diagnosis of bloodstream infections, have significantly improved the turnaround time for optimisation of antimicrobial therapy. Reported concordance with culture-based methods and multiplex PCR analysis is high and only limited by (1) the range of targets available on the multiplex panel; and (2) the complexity of microorganisms present in the blood culture specimen. In this study, we evaluated the use of the BioFire Blood Culture Identification 2 panel (BCID2), including an expanded repertoire of targets for Gram-positive and Gram-negative bacteria, yeast and antimicrobial resistance genes compared to the BCID panel. The BCID2 panel identified microorganisms in 39/42 (92.9%) blood cultures where monomicrobial growth was detected; the three unidentified blood cultures contained organisms not included in the BCID2 panel. Polymicrobial blood culture analysis revealed a lower degree of concordance (28.6%); however, most disagreement was due to the culture-based identification of off-panel microorganisms of low clinical significance. Turnaround time, from blood culture collection to organism identification on the blood cultures correctly identified by BCID2, was 24.6 (±16.8) hours for the BCID2 panel versus 38.2 (±21.9) hours for conventional methods. Analysis of the theoretical impact of the BCID2 identification on clinical management found therapy would be altered in 45.1% (23/51) of patients. The BCID2 panel is anticipated to improve the diagnosis and antimicrobial management of patients with serious bloodstream infections.


The validity of self-reported information about hypertensive disorders of pregnancy in a population-based survey: the Tromsø Study.
To investigate the validity of self-reported information about hypertensive disorders in previous pregnancies among women participating in the fourth survey of the Tromsø Study. Retrospective cohort study with case-control design. Parous women participating in the fourth survey of the Tromsø Study. Medical records including partograms of 200 randomly selected women who had answered positively to whether they had hypertension and/or proteinuria during one or more of their previous pregnancies (cases) and 200 women who had answered negatively (controls) were studied. The cases and controls were matched for age. The investigators were blinded to the allocation of cases and controls until data collection was finished. Self-reported and actual prevalence of hypertensive pregnancy disorders and predictive value of self-reported hypertension and/or proteinuria in previous pregnancies. Clinical data were missing for 23.5% (94/400) of the participants (50 cases and 44 controls). A total of 80% (120/150) of cases and 57.1% (89/156) of controls had answered the question on whether or not they had high blood pressure and/or proteinuria during their pregnancies correctly (positive predictive value 0.800; negative predictive value 0.571). The proportion of false-positive cases declined with increasing age while the proportion of false-negative controls increased until 55 years of age. We found good concordance between self-reported hypertension and/or proteinuria during previous pregnancies and actual clinical findings among the cases. However, there was a tendency towards under-reporting among controls.


Sexual differences and seasonal variations in vasoactive intestinal peptide immunoreactivity in the suprachiasmatic nucleus of jerboa (Jaculus orientalis).
The sexual differences and the seasonal variation in the vasoactive intestinal peptide (VIP) content of the suprachiasmatic nucleus (SCN) of a desert rodent, the jerboa (Jaculus orientalis) were studied using immunocytochemical techniques. During the period of sexual activity (spring-early summer), the VIP immunoreactivity in the SCN was higher in females than in males. In the period of sexual quiescence (autumn), both males and females exhibited an even more intense VIP immunoreaction in the SCN as compared to spring. However, during this period, the sex-related differences in the VIP content of the SCN observed in spring were no longer detectable. The direct possible influence of sex hormones on the VIP content in the SCN, and the physiological significance of the seasonal variation observed in the VIP immunoreactivity in the SCN in this species remains to be determined.


COVID-19 and Pediatric Mental Health Hospitalizations.
To analyze Australian national data to examine the impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health-related hospital presentations among children and adolescents during the pandemic period with restrictions, and the period after the restrictions eased. We analyzed the monthly mental health-related inpatient admissions and emergency department (ED) attendances data from 6 large pediatric hospitals across Australia, using the Bayesian structural time series models. The COVID-19 restriction period was from March 2020 to December 2021 and the COVID-19 restriction-eased period from January to June 2022. A total of 130 801 mental health-related hospital admissions (54 907) and ED attendances (75 894) were analyzed. During the COVID-19 restriction period, there was a significant increase in inpatient admissions related to deliberate self-harm behaviors (82%, 95% credible interval [CrI], 7%-160%) and ED attendances related to overall mental health disorders (15%, 95% CrI, 1.1%-30%) and eating disorders (76%, 95% CrI, 36%-115%). The increase was higher among females and those living in the least socioeconomically disadvantaged areas, suggesting a widening gap between mental health-related presentations by sex and socioeconomic status. After the restrictions eased, there were slight declines in mental health-related hospital presentations; however, the numbers remained higher than the pre-COVID-19 levels. The increase in mental health-related hospital presentations during the COVID-19 period calls for additional support for pediatric mental health care, particularly for eating disorders and deliberate self-harm among female adolescents. It is important to monitor pediatric mental health service use as we enter "COVID-19 normal" period.


Prognosis of functional mitral regurgitation after aortic valve replacement for pure severe aortic stenosis.
Whether patients with severe aortic stenosis (AS) and significant functional mitral regurgitation (MR) should undergo isolated aortic (aortic valve replacement [AVR]) or double aortic-mitral valve procedure (DVP) remains controversial. We sought to determine outcomes of such patients undergoing surgical (surgical aortic valve replacement [SAVR]) and transcatheter AVR (TAVR) or DVP, identify echocardiographic parameters predictive of significant residual MR after isolated AVR, and determine its impact on long-term survival. Data prospectively collected from 736 consecutive patients with severe AS and significant MR undergoing AVR or DVP were retrospectively analyzed. Exclusion of organic MR, other valve diseases and concomitant CABG yielded a final population of 74 patients with significant functional MR (32 TAVR, 23 SAVR, 19 DVP). Demographics, postoperative complications and age-adjusted survival were compared. Echocardiographic predictors of significant residual MR and its impact on survival were analyzed for patients undergoing isolated AVR. In the isolated AVR group, MR improvement occurred in 60% of patients and was associated with a significant increase in survival compared to persistence of significant MR (p = .03). Patients with improved MR had significantly greater preoperative left ventricular dilatation (LVEDD: 49 vs. 43 mm, p = .001; LVESD: 35 vs. 29 mm, p = .03; LVEDV: 101 vs. 71 ml, p = .0003; LVESV: 57 vs. 33 ml, p = .002). There was no significant difference in perioperative mortality (5.3 vs. 4.4 vs. 9.4%, p = .85) or age-adjusted long-term survival between isolated AVR and DVP groups (76.3 vs. 84.2% survival at 2-year follow-up, p = .26), or between SAVR, TAVR and DVP groups (78.2 vs. 75.0 vs. 84.2% survival at 2-year follow-up, p = .13). After isolated AVR, MR improvement occurs in 60% of patients. It is predicted by greater ventricular dimensions and associated with significantly better long-term survival. Whether a staged approach with transcatheter correction of MR should be considered in patients with significant residual MR following AVR remains undetermined.


A method for isolating nonsense suppressors in enterobacteriaceae using an amber mutant of the drug resistance factor R1.
We describe here the isolation of a mutant derivative of the drug resistance factor R1 (Meynell and Datta, 1966) that carries a nonsense mutation in a gene determining resistance to penicillins. We have used this mutant R1 to isolate derivatives of Escherichia coli and Klebsiella pneumoniae that contain nonsense suppressors (Sup- strains) by screening penicillin-resistant revertants of strains containing the mutant R factor for the presence of such suppressors. This obviates the need to have known nonsense mutations in chromosomal genes. Theoretically, suppressor-containing derivatives of any bacterial species that can maintain and express R1 can be constructed.


The potential of mineral weathering of halophilic-endophytic bacteria isolated from Suaeda salsa and Spartina anglica.
Bacteria have the abilities of salt tolerant, mineral weathering and plant growth promoting can promote the growth of plants in saline lands. However, few reports of the mineral weathering capacity of halophilic-endophytic bacteria, raising the question of whether the halophilic-endophytic weathering bacteria are fundamentally distinct from those in plants communities. In this study, we isolated and characterized halophilic bacterial strains from the roots and leaves of Suaeda salsa and Spartina anglica with respect to their mineral weathering pattern, role in the promoting plant growth, community structure, and their changes in these two plants. Using improved Gibbson medium, we obtained 156 halophilic bacterial strains, among which 92 and 64 strains were isolated from the S. salsa and S. anglica samples, respectively. The rock weathering patterns of the isolates were characterized using batch cultures that measure the quantity of Si, Al, K, and Fe released from crystal biotite under aerobic conditions. Significantly, the biomass and capacity of the mineral weathering of the halophilic-endophytic bacteria were different in the plants. The abundance of the halophilic-endophytic bacterials in the Suaeda salsa was significantly greater than Spartina anglica, whereas the mineral weathering bacterial in the Suaeda salsa was similar to the Spartina anglica. Furthermore, the proportion of plant growth-promoting bacteria in the Suaeda salsa was higher than Spartina anglica. Phylogenetic analyses show that the weathered minerals were inhabited by specific functional groups of bacteria (Halomonas, Acinetobacter, Burkholderia, Alcaligenes, Sphingobium, Arthrobacter, Chryseobacterium, Paenibacillus, Microbacterium, Ensifer, Ralstonia and Enterobacter) that contribute to the mineral weathering. The changes in halophilic endophytes weathering communities between the two plants were attributable not only to major bacterial groups but also to a change in the minor population structure.


Pentobarbitone inhibits the stress response to transport in male goats.
Pentobarbitone (20 mg/kg i.v.) blocked plasma cortisol release when administered either before a 20 min journey or during a 2 h journey. This confirms that pentobarbitone can block stimulated, as well as resting, cortisol secretion. In general, blood glucose concentrations were not increased above 90 mg/100 ml until at least 30 min after the start of transport; however, this increase was also blocked by pentobarbitone administered 30 min into the 2 h journey. Significant increases in respiratory and heart rates occurred within 15 min of the start of transport; pentobarbitone caused an immediate decrease in these parameters. In conclusion, pentobarbitone was shown to reverse many metabolic changes induced by transport.


Thermodynamics and kinetics of incorporation into a membrane.
Some very recent work on the equilibrium and rate of incorporation of the pore forming peptide alamethicin into phospholipid bilayers is briefly reviewed. The experimental methods and the proceedings to evaluate and interpret the data are generally applicable analogously to other cases of substrates which somehow associate with a membrane. For the special system under consideration, a very high degree of incorporation is observed, reflecting internal aggregation and thermodynamically non-ideal repulsive interactions. These points are included in a basic model which is shown to provide a quantitative fit of the measured results. Stopped-flow experiments have shown that the overall incorporation occurs as a practically one-step process. Its rate is remarkably fast, only slightly slower than the diffusion controlled upper limit. All the kinetic data can be quite satisfactorily interpreted in terms of a reaction scheme with steady-state intermediates comprising the obvious diffusional translocations as well as the accompanying conformational change. In particular, the special findings for the alamethicin system suggest a most simple working hypothesis of the molecular mechanism underlying the voltage-dependent gating effect.


The origin, emergence and evolutionary genetics of dengue virus.
Dengue is one of the most important emerging viruses, posing a threat to one-third of the global human population. Herein we show how the comparative analysis of gene sequence data has shed light on the origin and spread of dengue virus, as well as on the evolutionary processes that structure its genetic diversity. This reveals that dengue virus has a relatively recent evolutionary history, with the four serotypes originating approximately 1000 years ago and only establishing endemic transmission in humans in the last few hundred years. However, its place of origin remains uncertain as does the extent of genetic and phenotypic diversity present in the sylvatic (primate) transmission cycle. Although there is some evidence that viral strains differ in key phenotypic features such as virulence, and for positive selection at immunologically important sites, it seems likely that stochastic processes also play a major role in shaping viral genetic diversity, with lineage extinction a common occurrence. A more complete understanding of the evolution and epidemiology of dengue virus, particularly with respect to the aetiology of severe disease, will require large-scale prospective studies and the comparative analysis of complete genome sequences.


Radiographic geometry and clinical glenohumeral range of motion after reverse shoulder athroplasty, a retrospective cohort study.
The range of motion (ROM) in reverse shoulder arthroplasty (RSA), is mechanically limited by the surrounding bony obstacles especially in abduction and rotation planes. However, the clinical effect of implant positioning, prosthesis design, and individual differences in bone morphology, on ROM is obscure. The aim of this study was to investigate the correlation between radiographic geometry and clinical glenohumeral (GH) ROM after RSA. RSA patients operated at Turku University Hospital during 2007-2013 were called for radiological and clinical follow-up. Pre- and postoperative true anteroposterior radiographs were obtained and the positioning of the center of rotation (COR) in relation to the surrounding bony structures was measured. Active and passive shoulder and GH abduction, flexion, internal and external rotation ROM were measured with goniometer. The Constant score (CS) and pain visual analogue scale (VAS) were recorded. The correlation between the radiographically measured parameters and the active and passive ROM and clinical outcome was statistically analyzed. 91 shoulders were available for analyses with a mean follow-up of 38.7 months ± SD 20 (range 12-83) months. 77% of the patients were female, the mean age was 73 (SD 9) years. The mean angle between the line of supraspinatus fossa, and the line between COR and lateral edge of the acromion (α-angle) was 127° (SD 14) and the mean angle between the lines from lateral edge of the acromion to COR, and from there to the superior edge of the greater tubercle (β-angle) was 54° (SD 11). The mean active shoulder flexion at follow-up was 118° (SD 26), abduction 104° (SD 32), external rotation 41° (SD 22), internal rotation 77° (SD 21). The mean passive GH flexion was 80° (SD 19), abduction 67° (SD 15), external rotation 31° (SD 16) and internal rotation 34° (SD 14). The mean Constant score at follow-up was 53 (SD 18) and pain VAS 2 (SD 3). The positioning of the radiographically measured COR did not statistically significantly correlate with the ROM or clinical outcome scores. Postoperative radiographically measured two-dimensional geometry and positioning of the COR does not significantly correlate with the glenohumeral range of motion or clinical results after RSA. Level 3, retrospective cohort study.


Determination of hydralazine and metabolites in urine by liquid chromatography with electrochemical detection.
The cyclic voltammetric behavior of hydralazine and its primary metabolites, the pyruvate and acetone hydrazones, was examined in the positive potential range at both conventional and electrochemically pretreated glassy carbon electrodes. The enhanced oxidations observed at the treated surface were used as the basis of amperometric electrochemical detection of the compounds following reversed-phase liquid chromatography. The detection limits so obtained at +0.75 V vs. Ag/AgCl (1, 3, and 5 ng injected, respectively) were comparable to those previously reported for absorption and fluorescence detection approaches employing derivatization/preconcentration procedures. For liquid chromatography with electrochemical detection, however, direct quantitation of all three species in urine samples was readily accomplished without any chemical derivatization or sample treatment operations other than particulate filtration.