Complications of Acute and Chronic Otitis Media in a Tertiary Referral Center in Nepal.
The aim of this study was to report the incidence of complications in otitis media and to determine the frequencies of various extracranial and intracranial complications at a tertiary care hospital. We retrospectively reviewed the clinical records of patients of all ages and genders who were treated in a tertiary care hospital in Nepal from May 2015 to May 2020 for complications of acute and chronic otitis media. The complications were broadly classified as extracranial and intracranial. The details of patient profiles, histories, examination findings, investigations and treatments were reviewed from the charts. The mean age of 164 patients with complications of otitis media was 47.44±18.58 years. There were 79 (48.2%) male and 85 (51.8%) female patients. The overall incidence of otitis media complications was 0.78%. The incidences of the complications from acute otitis media, chronic otitis media without cholesteatoma, and chronic otitis media with cholesteatoma were 0.5%, 0.06% and 5.6%, respectively. Extracranial complications, intracranial complications and combined extracranial and intracranial complications were seen in 80%, 11% and 9% of the patients, respectively. The most common extracranial and intracranial complications were subperiosteal abscesses and brain abscesses, respectively. There was one mortality due to complication. The incidences of complications and mortality from otitis media have declined with the availability of suitable antibiotics, improved imaging, and multidisciplinary management. Antibiotic resistance and masking of signs and symptoms, however, could pose challenges in the future.


Ecological network analysis of an urban water metabolic system: model development, and a case study for Beijing.
Using ecological network analysis, we analyzed the network structure and ecological relationships in an urban water metabolic system. We developed an ecological network model for the system, and used Beijing as an example of analysis based on the model. We used network throughflow analysis to determine the flows among components, and measured both indirect and direct flows. Using a network utility matrix, we determined the relationships and degrees of mutualism among six compartments--1) local environment, 2) rainwater collection, 3) industry, 4) agriculture, 5) domestic sector, and 6) wastewater recycling--which represent producer, consumer, and reducer trophic levels. The capacity of producers to provide water for Beijing decreased from 2003 to 2007, and consumer demand for water decreased due to decreasing industrial and agricultural demand; the recycling capacity of reducers also improved, decreasing the discharge pressure on the environment. The ecological relationships associated with the local environment or the wastewater recycling sector changed little from 2003 to 2007. From 2003 to 2005, the main changes in the ecological relationships among components of Beijing's water metabolic system mostly occurred between the local environment, the industrial and agricultural sectors, and the domestic sector, but by 2006 and 2007, the major change was between the local environment, the agricultural sector, and the industrial sector. The other ecological relationships did not change during the study period. Although Beijing's mutualism indices remained generally stable, the ecological relationships among compartments changed greatly. Our analysis revealed ways to further optimize this system and the relationships among compartments, thereby optimizing future urban water resources development.


Patients, Nurses, and Physicians Working Together to Develop a Discharge Entrustable Professional Activity Assessment Tool.
The Accreditation Council for Graduate Medical Education milestones were written by physicians and thus may not reflect all the behaviors necessary for physicians to optimize their performance as a key member of an interprofessional team. From April to May 2013, the authors, Educational Research Outcomes Collaborative leaders, assembled interprofessional team discussion groups, including patients or family members, nurses, physician trainees, physician educators, and other staff (optional), at 11 internal medicine (IM) programs. Led by the site's principal investigator, the groups generated a list of physician behaviors related to the entrustable professional activity (EPA) of a safe and effective discharge of a patient from the hospital, and prioritized those behaviors. A total of 182 behaviors were listed, with lists consisting of between 10 and 29 behaviors. Overall, the site principal investigators described all participants as emerging from the activity with a new understanding of the complexity of training physicians for the discharge EPA. The authors batched behaviors into six components of a safe and effective discharge: medication reconciliation, discharge summary, patient/caregiver communication, team communication, active collaboration, and anticipation of posthospital needs. Specific, high-priority behavior examples for each component were identified, and an assessment tool for direct observation was developed for the discharge EPA. The authors are currently evaluating trainee and educator perceptions of the assessment tool after implementation in 15 IM programs. Additional next steps include developing tools for other EPAs, as well as a broader evaluation of patient outcomes in the era of milestone-based assessment.


The relation of ongoing brain activity, evoked neural responses, and cognition.
Ongoing brain activity has been observed since the earliest neurophysiological recordings and is found over a wide range of temporal and spatial scales. It is characterized by remarkably large spontaneous modulations. Here, we review evidence for the functional role of these ongoing activity fluctuations and argue that they constitute an essential property of the neural architecture underlying cognition. The role of spontaneous activity fluctuations is probably best understood when considering both their spatiotemporal structure and their functional impact on cognition. We first briefly argue against a "segregationist" view on ongoing activity, both in time and space, which would selectively associate certain frequency bands or levels of spatial organization with specific functional roles. Instead, we emphasize the functional importance of the full range, from differentiation to integration, of intrinsic activity within a hierarchical spatiotemporal structure. We then highlight the flexibility and context-sensitivity of intrinsic functional connectivity that suggest its involvement in functionally relevant information processing. This role in information processing is pursued by reviewing how ongoing brain activity interacts with afferent and efferent information exchange of the brain with its environment. We focus on the relationship between the variability of ongoing and evoked brain activity, and review recent reports that tie ongoing brain activity fluctuations to variability in human perception and behavior. Finally, these observations are discussed within the framework of the free-energy principle which - applied to human brain function - provides a theoretical account for a non-random, coordinated interaction of ongoing and evoked activity in perception and behavior.


Understanding and applying regulatory guidance on the nonclinical development of biotechnology-derived pharmaceuticals.
Biotechnology-derived pharmaceuticals are a well established and growing part of the therapeutic armamentarium. Beginning with recombinant versions of products such as insulin that were previously manufactured by extraction from animal and human sources, licensed biotechnology drugs and those in development now span an ever-increasing range of product types and therapeutic categories. As a consequence of this diversity, both general and product class-specific scientific guidelines have been developed on a regional (e.g. EU/US) or international (e.g. ICH - International Conference on Harmonization) basis. The current portfolio of nonclinical guidelines, particularly ICH S6, emphasizes flexibility and adaptability to the specific circumstances of the individual biotechnology product and its intended indication, taking into account factors not generally applicable to small-molecule drugs, such as pharmacodynamic responsiveness of safety and efficacy models, species specificity, and antibody formation. Guidelines developed principally with small-molecule drugs in mind may, nevertheless, have some applicability to biotechnology drugs on issues such as safety pharmacology, as well as on regulatory, procedural and dossier submission requirements. Scientific guidelines, such as those providing nonclinical guidance, are just one, albeit important, component of an increasingly complex legal/scientific environment in drug development.


Diffusing capacity for carbon monoxide. The effects of different derivations of breathhold time and alveolar volume and of carbon monoxide back pressure on calculated results.
The effect of deriving breathhold time and alveolar volume in different ways and of subtracting the back pressure of carbon monoxide on the calculated diffusing capacity (DLCO) was examined in 398 young adult smokers, ex-smokers, and nonsmokers. Significantly higher values were obtained when the recommendations of the ATS-DLD Epidemiology Standardization Project were followed for calculating breathhold time and alveolar volume, respectively, compared to following those of the ECCS Standardized Lung Function Testing Project. We therefore recommend that in reporting DLCO results, an explicit statement be included on the methods used to calculate both. Significantly higher values for DLCO were also obtained when CO back pressure was taken into account. The magnitude of this effect in smokers makes it difficult not to recommend its inclusion in epidemiologic studies. In clinical laboratories, however, when correction for CO back pressure is omitted, it is unlikely to result in an underestimate of DLCO of more than 5%, even in smokers.


Novel N-benzenesulfonyl sophocarpinol derivatives as coxsackie B virus inhibitors.
Novel N-benzenesulfonyl sophocarpinic acid/ester and sophocarpinol derivatives were synthesized and evaluated for their antienteroviral activities against coxsackievirus type B3 (CVB3) from sophocarpine (1), a natural medicine isolated from Chinese herb. Structure-activity relationship (SAR) analysis revealed that the double bond and its geometrical configuration and position at the C-11 attachment did not greatly affect the potency. Among these derivatives, sophocarpinol 24d exerted the promising activities against not only CVB3 but also CVB1, CVB2, CVB5, and CVB6 with IC50 ranging from 0.62 to 3.63 μM (SI from 46 to 275), indicating a broad-spectrum antienteroviral characteristic. The SAR results provided the powerful information for further strategic optimization and development of a novel scaffold of broad-spectrum antiviral candidates against enteroviruses.


Therapeutic Exercise Intervention Using Vibration Platforms for Glycemic Control in Type 2 Diabetes: A Pilot Study.
Diabetes generates a great impact on society, as well as a concern for health professionals due to its high and increasing prevalence; there are several studies that demonstrate the effectiveness of vibration platforms and their benefits at a physiological level. The aim of this study will be to analyze the decrease in glycosylated hemoglobin and glycemia levels after the use of whole-body vibration platforms and the possible inclusion of this therapeutic option within the usual treatments. This is a double-blind, randomized controlled trial with parallel group design in a 1:1 ratio. The sample will be composed of people diagnosed with type 2 diabetes mellitus in in the Plasencia area (Cáceres, Extremadura). Participants will be randomly assigned to the intervention or control group using a randomization list and will follow the inclusion criteria: type 2 diabetics between 50 and 60 years of age and not taking diabetes medication. All participants will undergo a determination of glycosylated hemoglobin, blood pressure, lipid profile, weight and height, and different functional tests such as Time Up and Go, 10 Meters Walk Test, and 5 Sit To Stand. The experimental group will perform a whole-body vibration intervention on an oscillating platform for 12 weeks with a weekly frequency of three nonconsecutive days and a duration of 12 min. The exercises will consist of 60 s of work and 60 s with rest. The control group will carry out their normal life insisting on the importance of glycemic controls before and after their daily physical exercise. This study has been registered at clinical.trial.org, ID: NCT05968222. Whole-body vibration platforms have demonstrated their effectiveness in different pathologies such as stroke, fibromyalgia, sclerosis multiple, or Parkinson's. For that reason, an improvement in glycemic and lipid values and body composition are expected in people with diabetes after a whole-body vibration intervention for 12 weeks' duration. In addition, whole-body vibration platforms could be postulated as an alternative to usual treatments.


[The teaching of the nursing process to undergraduate students].
The authors, instructors of Fundamentals of Nursing, describe two experiments in teaching nursing process, for which two different types of field of practice were used: the nursing personnel of the first hospital did not employ the nursing process in the care of their patients, but on the second hospital the utilization of this process had been adopted. Two outstanding expected results were obtained: 1. The group of students, who practised in the first hospital did not believe the utilization of the nursing process would be possible in professional practices; but the groups who had seen such process being used showed a totally different attitude and agreed about the convenience of the adaption of the nursing process by the hospitals; 2. the students who are taking Fundamentals of Nursing are not get prepared to identify nursing problems and to suggest solution, owing to their lack of knowledge of pathology. The authors recommend the teaching of the nursing process gradually, througout the undergraduate course, in order to secure more effective results.


Bites by the night adder (Causus maculatus) and burrowing vipers (genus Atractaspis) in Nigeria.
Nineteen patients proven to have been bitten by the small African adders Causus maculatus, Atractapis dahomeyensis and A. microlepidota were studied in the Nigerian savanna region. One of the patients bitten by C. maculatus was drowsy, hypotensive and flaccid on admission but recovered without treatment. Mild or moderate local swelling, local lymphadenitis and mild fever were the only other features in this group. None of the patients bitten by Atractaspis had signs of systemic envenoming apart from moderate fever. Local blistering appeared in two cases but did not progress to necrosis. No patient showed any disturbance of blood coagulation, or evidence of spontaneous hemorrhage or of cranial nerve lesions. The small literature on the effects of Causus and Atractaspis venoms in man and in laboratory animals is reviewed. It appears that bites by these species are very unlikely to cause serious ill effects. A few deaths from Atractaspis bites have been reported, but the danger from these species has been exaggerated.


Whole-exome sequencing for prenatal diagnosis of fetuses with congenital anomalies of the kidney and urinary tract.
In the absence of cytogenetic abnormality, fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with/without other structural anomalies show a higher likelihood of monogenic causes; however, defining the underlying pathology can be challenging. Here, we investigate the value of whole-exome sequencing (WES) in fetuses with CAKUT but normal findings upon karyotyping and chromosome microarray analysis. WES was performed on DNA from the cord blood of 30 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 23 cases, sequencing was initially performed on fetal DNA only; for the remaining seven cases, the trio of fetus, mother and father was sequenced simultaneously. Of the 30 cases, pathogenic variants were identified in 4 (13%) (UMOD, NEK8, HNF1B and BBS2) and incidental variants in 2 (7%) (HSPD1 and GRIN2B). Furthermore, two of the above four cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/22 (9.1%) for isolated CAKUT and 2/8 (25%) for CAKUT with other abnormalities. Applying WES to the prenatal diagnostic approach in CAKUT fetuses with or without other anomalies allows for an accurate and early etiology-based diagnosis and improved clinical management. To expedite interpretation of the results, trio sequencing should be employed; however, interpretation may nevertheless be compromised by incomplete coverage of all relevant genes.


Mass spectrometry in sports drug testing: Structure characterization and analytical assays.
Owing to the sensitive, selective, and unambiguous nature of mass spectrometric analyses, chromatographic techniques interfaced to various kinds of mass spectrometers have become the most frequently employed strategy in the fight against doping. To obtain utmost confidence in analytical assays, mass spectrometric characterization of target analytes and typical dissociation pathways have been utilized as basis for the development of reliable and robust screening as well as confirmation procedures. Methods for qualitative and/or quantitative determinations of prohibited low and high molecular weight drugs have been established in doping control laboratories preferably employing gas or liquid chromatography combined with electron, chemical, or atmospheric pressure ionization followed by analyses using quadrupole, ion trap, linear ion trap, or hyphenated techniques. The versatility of modern mass spectrometers enable specific as well as comprehensive measurements allowing sports drug testing laboratories to determine the misuse of therapeutics such as anabolic-androgenic steroids, stimulants, masking agents or so-called designer drugs in athletes' blood or urine specimens, and a selection of recent developments is summarized in this review.


Evaluation of clinical outcomes in patients with dry eye disease using lubricant eye drops containing polyethylene glycol or carboxymethylcellulose.
The purpose of this study was to compare changes in corneal staining in patients with dry eye after 6 weeks of treatment with Systane® Gel Drops or Refresh Liquigel® lubricant eye drops. Patients aged ≥18 years with a sodium fluorescein corneal staining sum score of ≥3 in either eye and best-corrected visual acuity of 0.6 logarithm of the minimum angle of resolution or better in each eye who were using a lubricant eye gel or ointment for dry eye were included in this randomized, parallel-group, multicenter, double-blind trial. Patients were randomized to four times daily Systane® Gel Drops (polyethylene glycol 400 0.4% and propylene glycol 0.3%) or Refresh LiquiGel® Drops (carboxymethylcellulose sodium 1%) for 6 weeks. The primary efficacy outcome was mean change from baseline to week 6 in sodium fluorescein corneal staining. Supportive efficacy outcomes included conjunctival staining, tear film break-up time, Patient Global Assessment of Improvement, Impact of Dry Eye on Everyday Life (IDEEL) Treatment Satisfaction/Treatment Bother Questionnaire, Single Symptom Comfort Scale, and Ocular Symptoms Questionnaire. The safety analysis comprised recording of adverse events. In total, 147 patients (Systane group, n=73; Refresh group, n=74; mean ± standard deviation age, 57±16 years) were enrolled and included in the safety and efficacy analyses. Corneal staining was significantly reduced from baseline to week 6 for Systane and Refresh (-3.4±2.5 and -2.5±2.6 units, respectively; P<0.0001, t-test), with a significantly greater improvement with Systane versus Refresh (P=0.0294). Results for conjunctival staining, tear film break-up time, and patient-reported outcome questionnaires were not statistically different between groups. No safety issues were identified; adverse events were reported by 19% of patients with Systane and 30% of patients with Refresh eye drops. Systane Gel Drops were associated with significantly better corneal staining scores versus Refresh Liquigel eye drops in patients with dry eye. Supportive efficacy outcomes were not significantly different between groups. Both treatments were well tolerated.


Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice.
Exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of cardiovascular diseases such as atherosclerosis. Vascular cell adhesion molecule-1 (VCAM-1) is a critical mediator for adhesion and uptake of monocytes across the endothelium in the early stages of atherosclerosis development. The upregulation of VCAM-1 by PCBs may be dependent on functional membrane domains called caveolae. Caveolae are particularly abundant in endothelial cell membranes and involved in trafficking and signal transduction. The objective of this study was to investigate the role of caveolae in PCB-induced endothelial cell dysfunction. Primary mouse aortic endothelial cells (MAECs) isolated from caveolin-1-deficient mice and background C57BL/6 mice were treated with coplanar PCBs, such as PCB77 and PCB126. In addition, siRNA gene silencing technique was used to knockdown caveolin-1 in porcine vascular endothelial cells. In MAECs with functional caveolae, VCAM-1 protein levels were increased after exposure to both coplanar PCBs, whereas expression levels of VCAM-1 were not significantly altered in cells deficient of caveolin-1. Furthermore, PCB-induced monocyte adhesion was attenuated in caveolin-1-deficient MAECs. Similarly, siRNA silencing of caveolin-1 in porcine endothelial cells confirmed the caveolin-1-dependent VCAM-1 expression. Treatment of cells with PCB77 and PCB126 resulted in phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2), and pharmacological inhibition of ERK1/2 diminished the observed PCB-induced increase in monocyte adhesion. These findings suggest that coplanar PCBs induce adhesion molecule expression, such as VCAM-1, in endothelial cells, and that this response is regulated by caveolin-1 and functional caveolae. Our data demonstrate a critical role of functional caveolae in the activation and dysfunction of endothelial cells by coplanar PCBs.


WikiPathways 2024: next generation pathway database.
WikiPathways (wikipathways.org) is an open-source biological pathway database. Collaboration and open science are pivotal to the success of WikiPathways. Here we highlight the continuing efforts supporting WikiPathways, content growth and collaboration among pathway researchers. As an evolving database, there is a growing need for WikiPathways to address and overcome technical challenges. In this direction, WikiPathways has undergone major restructuring, enabling a renewed approach for sharing and curating pathway knowledge, thus providing stability for the future of community pathway curation. The website has been redesigned to improve and enhance user experience. This next generation of WikiPathways continues to support existing features while improving maintainability of the database and facilitating community input by providing new functionality and leveraging automation.


Microspore reprogramming to embryogenesis induces changes in cell wall and starch accumulation dynamics associated with proliferation and differentiation events.
Plant cell wall polymers are regulated during development, but the specific roles of their different molecular components and the functional meaning of cell wall changes in different cell types and cell processes are still unclear. In the present work the presence and distribution of different cell wall components in Capsicum annuum L. pollen have been analyzed in situ in order to monitor how they change during two developmental programs. These programs are: pollen development, which is a differentiation process, and stress-induced pollen reprogramming to embryogenesis, which involves proliferation followed later by differentiation processes. Specific antibodies recognizing the major cell wall polymers, the major hemicellulose, xyloglucan (XG), the rhamnogalacturonan II (RGII) pectin domain and high- and low-methyl-esterified pectins were used for both dot-blot and immunolocalization assays at light and electron microscopy levels during defined developmental stages. For comparison purposes, a similar approach was also used in zygotic embryogenesis and root apical tip growth. Results showed differences in the distribution pattern of these molecular complexes, in the proportion of esterified and de-esterified pectins in the two pollen developmental pathways, and defined wall changes during microspore reprogramming. These changes were associated with proliferation and differentiation events where highly esterified pectins were characteristic of proliferation, while de-esterified pectins, XG and RGII were abundant in walls of differentiating cells. Starch deposits were also studied and the results revealed changes in starch synthesis dynamics after switching the pollen embryogenic developmental program. These changes occurred together with modifications in the distribution patterns of cell wall polymers, starch accumulation being associated with cell differentiation. As in the case of proliferating cells, esterified pectins were also abundant in the apertures of developing microspores, regions of new cell wall formation. The different distribution patterns of cell wall polymers were common for proliferating cells and differentiating cells in all the plant systems analyzed, including zygotic embryos and root tip cells, suggesting that these patterns are markers of proliferation and differentiation events as well as markers of pollen reprogramming to embryogenesis.


Prediction of recurrent venous thromboembolism by clot lysis time: a prospective cohort study.
Venous thromboembolism (VTE) is a chronic disease, which tends to recur. Whether an abnormal fibrinolytic system is associated with an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic capacity (reflected by clot lysis time [CLT]) and risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 yrs) with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, homozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. Study endpoint was symptomatic recurrent VTE. For measurement of CLT, a tissue factor-induced clot was lysed by adding tissue-type plasminogen activator. Time between clot formation and lysis was determined by measuring the turbidity. 135 (19%) patients had recurrent VTE. For each increase in CLT of 10 minutes, the crude relative risk (RR) of recurrence was 1.13 (95% CI 1.02-1.25; p = 0.02) and was 1.08 (95% CI 0.98-1.20; p = 0.13) after adjustment for age and sex. For women only, the adjusted RR was 1.14 (95% CI, 0.91-1.42, p = 0.22) for each increase in CLT of 10 minutes. CLT values in the 4(th) quartile of the female patient population, as compared to values in the 1(st) quartile, conferred a risk of recurrence of 3.28 (95% CI, 1.07-10.05; p = 0.04). No association between CLT and recurrence risk was found in men. Hypofibrinolysis as assessed by CLT confers a moderate increase in the risk of recurrent VTE. A weak association between CLT and risk of recurrence was found in women only.


Assessment of maternal knowledge of solar exposure and vitamin D in the neonatal period.
To assess mothers' knowledge on sun exposure related to serum vitamin D levels in the neonatal period. Observational, analytical and cross-sectional study, carried out from August 2020 to May 2021 through a questionnaire directed to mothers of newborns, in a maternity hospital in Southern Brazil. From 141 interviewees, 132 (93.6%) believe it is important to expose the neonate to sun, 101 (71.6%) think this exposure can increase vitamin D levels, 86 (61%) received such information from a doctor, 108 (76.6%) believe there are no risks of sun exposure, 88 (62.4%) claim it isn´t necessary to use any kind of protection, 96 (68.1%) said that only exposure to the sun was necessary to maintain adequate levels of vitamin D during the neonatal period. Only two mothers (1.4%) claim that you should not exposure the neonate to the sun, and only one (0.7%) stated that sun expose can cause skin problems. Most mothers lack satisfactory knowledge about sun exposure related to serum vitamin D levels in the neonatal period. The need to inform and clarify the population about sun exposure during this period is remarkable, in addition to disseminating the proper way to maintain serum levels of vitamin D.


Machine learning models accurately predict ozone exposure during wildfire events.
Epidemiologists use prediction models to downscale (i.e., interpolate) air pollution exposure where monitoring data is insufficient. This study compares machine learning prediction models for ground-level ozone during wildfires, evaluating the predictive accuracy of ten algorithms on the daily 8-hour maximum average ozone during a 2008 wildfire event in northern California. Models were evaluated using a leave-one-location-out cross-validation (LOLO CV) procedure to account for the spatial and temporal dependence of the data and produce more realistic estimates of prediction error. LOLO CV avoids both the well-known overly optimistic bias of k-fold cross-validation on dependent data and the conservative bias of evaluating prediction error over a coarser spatial resolution via leave-k-locations-out CV. Gradient boosting was the most accurate of the ten machine learning algorithms with the lowest LOLO CV estimated root mean square error (0.228) and the highest LOLO CV Rˆ2 (0.677). Random forest was the second best performing algorithm with an LOLO CV Rˆ2 of 0.661. The LOLO CV estimates of predictive accuracy were less optimistic than 10-fold CV estimates for all ten models. The difference in estimated accuracy between the 10-fold CV and LOLO CV was greater for more flexible models like gradient boosting and random forest. The order of estimated model accuracy depended on the choice of evaluation metric, indicating that 10-fold CV and LOLO CV may select different models or sets of covariates as optimal, which calls into question the reliability of 10-fold CV for model (or variable) selection. These prediction models are designed for interpolating ozone exposure, and are not suited to inferring the effect of wildfires on ozone or extrapolating to predict ozone in other spatial or temporal domains. This is demonstrated by the inability of the best performing models to accurately predict ozone during 2007 southern California wildfires.


Drug Resistance-Associated Mutations in ERG11 of Multidrug-Resistant Candida auris in a Tertiary Care Hospital of Eastern Saudi Arabia.
Candida auris is an emerging multi-drug resistant pathogen with high mortality rate; nosocomial infections have been reported worldwide, causing a major challenge for clinicians and microbiological laboratories. The study aims to describe new cases of C. auris and detect drug resistance-associated mutations of C. auris by the sequencing of ERG11 and FKS1 genes. A total of six specimens were collected from blood, urine, ear swab, and groin screening samples. Isolates were incubated for 48 h on Sabouraud Dextrose agar (SDA) at 42 °C, then confirmed by MALDI-TOF MS. Furthermore, antifungal susceptibility testing was performed using the Vitek 2 system to detect Minimum Inhibitory Concentrations (MICs) of six antifungals. Sequences of 18S rRNA gene and ITS regions from isolates and phylogenetic analysis were performed. Gene sequencing was analysed to detect drug resistance-associated mutations by FKS1 and ERG11 genes sequencing. All C. auris isolates were confirmed by MALDI-TOF MS, and evolutionary analyses using sequences of 18S rRNA gene and ITS region. Antifungal susceptibility testing showed that all isolates were resistant to fluconazole. Sequencing of ERG11 and FKS1 genes from the isolates revealed the presence of two (F132Y and K143R) drug resistance-associated mutations in ERG11, however, FKS1 gene was devoid of mutations. The study sheds light on a public health threat of an emerging pathogen, and the hospital implemented strict contact screening and infection control precautions to prevent C. auris infection. Finally, there is a critical need to monitor the antifungal resistance in different geographical areas and implementation of efficient guidelines for treatment.


Identifying the science and technology dimensions of emerging public policy issues through horizon scanning.
Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.


Kinetic expression analysis of the cluster mdv1-mir-M9-M4, genes meq and vIL-8 differs between the lytic and latent phases of Marek's disease virus infection.
Marek's disease virus (GaHV-2) is an alphaherpesvirus that induces T-cell lymphoma in chickens. The infection includes both lytic and latent stages. GaHV-2 encodes three clusters of microRNAs (miRNAs) located in the internal (I)/terminal (T) repeat (R) regions. We characterized transcripts encompassing the mdv1-mir-M9-M4 and mir-M11-M1 clusters located in the IR(L)/TR(L) region, upstream and downstream from the meq oncogene, respectively. By 5'- and 3'-RACE-PCR and targeted RT-PCR, we showed that mdv1-mir-M9-M4 could be transcribed from an unspliced transcript or from at least 15 alternatively spliced transcripts covering the IR(L)/TR(L) region, encompassing the meq and vIL-8 genes and localizing the mdv1-mir-M9-M4 cluster to the first intron at the 5'-end. However, all these transcripts, whether spliced or unspliced, seemed to start at the same transcriptional start site, their transcription being driven by a single promoter, prmiRM9M4. We demonstrated alternative promoter usage for the meq and vIL-8 genes, depending on the phase of GaHV-2 infection. During the latent phase, the prmiRM9M4 promoter drove transcription of the meq and vIL-8 genes and the mdv1-mir-M9-M4 cluster in the first intron of the corresponding transcripts. By contrast, during the lytic phase, this promoter drove the transcription only of the mdv1-mir-M9-M4 cluster to generate unspliced mRNA, the meq and vIL-8 genes being transcribed principally from their own promoters. Despite the expression of meq and the mdv1-mir-M9-M4 cluster under two different transcriptional processes during the latent and lytic phases, our data provide an explanation for meq expression and mdv1-mir-M4-5P overexpression in miRNA libraries from GaHV-2-infected cells, regardless of the phase of infection.


Ruthenium-containing P450 inhibitors for dual enzyme inhibition and DNA damage.
Cytochrome P450s are key players in drug metabolism, and overexpression in tumors is associated with significant resistance to many medicinal agents. Consequently, inhibition of P450s could serve as a strategy to restore drug efficacy. However, the widespread expression of P450s throughout the human body and the critical roles they play in various biosynthetic pathways motivates the development of P450 inhibitors capable of controlled local administration. Ruthenium complexes containing P450 inhibitors as ligands were synthesized in order to develop pro-drugs that can be triggered to release the inhibitors in a spatially and temporally controlled fashion. Upon light activation the compounds release ligands that directly bind and inhibit P450 enzymes, while the ruthenium center is able to directly damage DNA.


The Paneth cell and the innate immune response.
Innate immune defense of the small intestine is mediated in part by antimicrobial peptides and proteins secreted by Paneth cells, epithelial cells positioned at the base of the crypts of Lieberkuhn. Recent studies have yielded better understanding of the role that Paneth cells may play in host defense. Emerging data suggest that these cells may contribute to the pathophysiology of several human diseases. A wealth of data has also emerged on the regulatory pathways of Paneth cell functions and structure-function analysis on Paneth cell antimicrobials. This review discusses new reports in these areas. Studies of transgenic and knockout mice have supported a pivotal role of Paneth cell defensins in protection from oral bacterial pathogens. Other studies suggest that Paneth cells may be the targets of virulence mechanisms of bacterial pathogens. New observations also suggest that Paneth cell dysfunction may contribute to the clinical phenotype of Crohn disease, necrotizing enterocolitis, and, perhaps, intestinal manifestations of cystic fibrosis. Paneth cells are emerging as key mediators of innate host defense in the small intestine. The antimicrobial activity of Paneth cell secretory products on transient and resident microbes in the gut may have a profound influence on health. The possible role of Paneth cell dysfunction in human disease and a better understanding of Paneth cell regulatory pathways are areas poised for significant advances in the near future.


Petechial hemorrhages of the tympanic membrane in attempted suicide by hanging: A case report.
It is important to determine whether a person has been strangulated and the diagnosis is not always straightforward since ligature marks are not always present. In forensic medicine the physical examination recommended is careful inspection of the head and neck region, oral cavity, examination of the eyes including the conjunctiva on both the upper and lower eyelids and photo documentation. Petechial hemorrhages of the conjunctiva are considered marker of life threatening hanging or strangulation. Hemorrhage from ears, perforated tympanic membrane and haematotympanum are scarcely described in case reports of strangulated patients. To our knowledge we are the first to report petechial hemorrhages of the tympanic membrane in a patient following attempted suicide by hanging. We believe that the petechial hemorrhages develop from the capillaries located in lamina propria of the epidermal layer above the fibrous layer. This assumption is made on the basis of our assessment of a normal tympanic membrane with light microscopy. Petechial hemorrhages of the tympanic membrane might in fact be the only sign of life threatening pressure applied to the neck. This is a very important finding and prospective studies should be conducted for further clarification on the matter.


Position effect variegation and viability are both sensitive to dosage of constitutive heterochromatin in Drosophila.
The dosage effect of Y-chromosome heterochromatin on suppression of position effect variegation (PEV) has long been well-known in Drosophila. The phenotypic effects of increasing the overall dosage of Y heterochromatin have also been demonstrated; hyperploidy of the Y chromosome produces male sterility and many somatic defects including variegation and abnormal legs and wings. This work addresses whether the suppression of position effect variegation (PEV) is a general feature of the heterochromatin (independent of the chromosome of origin) and whether a hyperdosage of heterochromatin can affect viability. The results show that the suppression of PEV is a general feature of any type of constitutive heterochromatin and that the intensity of suppression depends on its amount instead of some mappable factor on it. We also describe a clear dosage effect of Y heterochromatin on the viability of otherwise wild-type embryos and the modification of that effect by a specific gene mutation. Together, our results indicate that the correct balance between heterochromatin and euchromatin is essential for the normal genome expression and that this balance is genetically controlled.


Development and Characterization of a Scaffold-Free 3D Spheroid Model of Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes.
Cardiomyocytes (CMs) are terminally differentiated cells in the adult heart, and ischemia and cardiotoxic compounds can lead to cell death and irreversible decline of cardiac function. As testing platforms, isolated organs and primary cells from rodents have been the standard in research and toxicology, but there is a need for better models that more faithfully recapitulate native human biology. Hence, a new in vitro model comprising the advantages of 3D cell culture and the availability of induced pluripotent stem cells (iPSCs) of human origin was developed and characterized. Human CMs derived from iPSCs were studied in standard 2D culture and as cardiac microtissues (MTs) formed in hanging drops. Two-dimensional cultures were examined using immunofluorescence microscopy and western blotting, while the cardiac MTs were subjected to immunofluorescence, contractility, and pharmacological investigations. iPSC-derived CMs in 2D culture showed well-formed myofibrils, cell-cell contacts positive for connexin-43, and other typical cardiac proteins. The cells reacted to prohypertrophic growth factors with a substantial increase in myofibrils and sarcomeric proteins. In hanging drop cultures, iPSC-derived CMs formed spheroidal MTs within 4 days, showing a homogeneous tissue structure with well-developed myofibrils extending throughout the whole spheroid without a necrotic core. MTs showed spontaneous contractions for more than 4 weeks that were recorded by optical motion tracking, sensitive to temperature and responsive to electrical pacing. Contractile pharmacology was tested with several agents known to modulate cardiac rate and viability. Calcium transients underlay the contractile activity and were also responsive to electrical stimulation, caffeine-induced Ca(2+) release, and extracellular calcium levels. A three-dimensional culture using iPSC-derived human CMs provides an organoid human-based cellular platform that is free of necrosis and recapitulates vital cardiac functionality, thereby providing a new and promising relevant model for the evaluation and development of new therapies and detection of cardiotoxicity.


[Dynamics of changes in the lipid composition of bile in patients with alimentary obesity during treatment].
In the bile of patients with alimentary obesity, the content of primary (cholic) bile acids is reduced, that of secondary (deoxycholic) acids is increased, and the quota of glycine-bound cholates is lowered. This points to the distress of the cholate-synthesizing, glyco-conjugating, and hydroxylating function of liver cells. In addition, the bile of obese persons is characterized by a low content of free fatty acids associated with an increase in the amount of total lipids, glycerides, and phospholipids. The treatment of obesity by the subcaloric diet and graded physical exercise brings about positive changes in the content of cholic and deoxycholic acids in the bile and gives rise to the enhanced excretion of all lipid fractions, cholesterol in particular, with the bile to the intestine, thereby raising the bile lithogenic potential.


The NCIC-Manitoba Breast Tumor Bank: a resource for applied cancer research.
The NCIC-Manitoba Breast Tumor Bank is one of several tumour banks that have been established through the Molecular Epidemiology Program of the National Cancer Institute of Canada (NCIC). The NCIC-Manitoba Breast Tumor Bank is an example of one model developed to facilitate research designed to translate the findings of basic science into information useful in the clinical arena. The tumour bank's mandate is to provide a national resource that consists of a preassembled dataset of matched samples of paraffin-embedded and frozen tumour tissue with corresponding pathological and clinical data. In the first 3 years the tumour bank has accrued data and samples from over 1800 cases of breast cancer and has provided support for 20 research projects across Canada and the United States.


Vitamin D deficiency remains prevalent despite increased laboratory testing in New South Wales, Australia.
The aim of the present study was to assess the prevalence of vitamin D deficiency and toxicity, the frequency of 25-hydroxyvitamin D (25[OH]D) testing, and 25(OH)D variations with respect to patient gender, patient age and season in New South Wales, Australia. A retrospective analysis of pathology records was performed to ascertain patient age, patient gender, sample collection date, plasma or serum 25(OH)D levels, calcium and parathyroid hormone (PTH) levels, and test numbers between 2001 and 2010. Linear regression with Bonferroni correction was used to calculate and compare age-adjusted mean 25(OH)D levels. Relationships of 25(OH)D with PTH and calcium were tested using Spearman's rank correlation. 25(OH)D testing increased by 730% over the ten-year study period. In 2010, many men (33%) and women (40%) were, to some degree, vitamin D deficient (≤ 50 nmol/L). Vitamin D toxicity was rare, with only one instance noted. 25(OH)D levels correlated positively with calcium and negatively with PTH levels. 25(OH)D levels decreased with age. In 2010, 25(OH)D levels were highest in February and lowest in September/October. Cyclical variation was observed for 25(OH)D levels between 2006 and 2010. We found that vitamin D deficiency was prevalent in both men and women, with a higher prevalence in the latter, despite the substantial increased demand for 25(OH)D testing in our population over the decade. Vitamin D deficiency was associated with elevated PTH levels. Vitamin D toxicity was rare and only observed once during our study period. 25(OH)D levels decreased with age and varied with season, with the highest levels observed in late summer and the lowest in early spring.


Mung Bean Protein Supplement Improves Muscular Strength in Healthy, Underactive Vegetarian Adults.
Although vegetarian diets are considered generally protective against chronic disease, nutrient deficiencies, including protein, are possible due to low bioavailability from plant-based sources. The consequences of inadequate dietary protein include reduced lean body mass (LBM) and muscle weakness. This study examined relationships between protein intake, strength, and LBM in 37 underactive vegetarians and recorded the impact of protein supplementation (18 g/day mung bean protein) on these indices utilizing an eight-week, randomized, controlled, feeding trial. Both handgrip and knee flexor and extensor strength were measured at baseline and week eight. At baseline, LBM was significantly related to grams of protein consumed daily. LBM was also correlated to grip strength (r = 0.569, p < 0.001) and lower body strength (r = 0.763 to 0.784; p < 0.001). Twenty-five vegetarians completed the feeding trial, including 11 in the protein supplementation group (PRO) and 14 in the control group (CON). At the end of the trial, LBM and strength did not differ significantly between groups. However, the average percent change for grip, flexor, and extensor strength did differ between PRO and CON participants (+2.9 ± 7.2% and -2.6 ± 7.3% respectively, p = 0.05). Thus, there were strong associations between dietary protein, LBM, and strength in vegetarians and an indication that supplementary vegetarian protein increased strength in the absence of exercise and independent of LBM.


Bacterial biofilm colonization and succession in tropical marine waters are similar across different types of stone materials used in seawall construction.
Seawalls are important in protecting coastlines from currents, erosion, sea-level rise, and flooding. They are, however, associated with reduced biodiversity, due to their steep orientation, lack of microhabitats, and the materials used in their construction. Hence, there is considerable interest in modifying seawalls to enhance the settlement and diversity of marine organisms, as microbial biofilms play a critical role facilitating algal and invertebrate colonization. We assessed how different stone materials, ranging from aluminosilicates to limestone and concrete, affect biofilm formation. Metagenomic assessment of marine microbial communities indicated no significant impact of material on microbial diversity, irrespective of the diverse surface chemistry and topography. Based on KEGG pathway analysis, surface properties appeared to influence the community composition and function during the initial stages of biofilm development, but this effect disappeared by Day 31. We conclude that marine biofilms converged over time to a generic marine biofilm, rather than the underlying stone substrata type playing a significant role in driving community composition.


Surface-Engineered Black Niobium Oxide@Graphene Nanosheets for High-Performance Sodium-/Potassium-Ion Full Batteries.
Nanoscale surface-engineering plays an important role in improving the performance of battery electrodes. Nb2 O5 is one typical model anode material with promising high-rate lithium storage. However, its modest reaction kinetics and low electrical conductivity obstruct the efficient storage of larger ions of sodium or potassium. In this work, partially surface-amorphized and defect-rich black niobium oxide@graphene (black Nb2 O5- x @rGO) nanosheets are designed to overcome the above Na/K storage problems. The black Nb2 O5- x @rGO nanosheets electrodes deliver a high-rate Na and K storage capacity (123 and 73 mAh g-1 , respectively at 3 A g-1 ) with long-term cycling stability. Besides, both Na-ion and K-ion full batteries based on black Nb2 O5- x @rGO nanosheets anodes and vanadate-based cathodes (Na0.33 V2 O5 and K0.5 V2 O5 for Na-ion and K-ion full batteries, respectively) demonstrate promising rate and cycling performance. Notably, the K-ion full battery delivers higher energy and power densities (172 Wh Kg-1 and 430 W Kg-1 ), comparable to those reported in state-of-the-art K-ion full batteries, accompanying with a capacity retention of ≈81.3% over 270 cycles. This result on Na-/K-ion batteries may pave the way to next-generation post-lithium batteries.


Striatal β-amyloid in dementia with Lewy bodies but not Parkinson's disease.
Professor Jellinger first identified that striatal Aβ deposition at postmortem seemed to differentiate cases of dementia with Lewy bodies (DLB) from those with Parkinson's disease dementia (PDD), a finding subsequently questioned. Our replication study in 34 prospectively studied cases assessed the ability of striatal Aβ deposition to differentiate DLB from PDD, and also assessed the relationship between striatal and cortical Aβ deposition and α-synuclein-immunoreactive pathologies, using previously published protocols. Cases with DLB had significantly shorter durations and greater dementia severities compared with cases with PDD. Striatal Aβ-immunoreactive plaques were only consistently found in cases with DLB and correlated with both the severity (positive correlation) and duration (negative correlation) of dementia. Striatal Aβ-immunoreactive plaques also positively correlated with the severity of α-synuclein-immunoreactive pathologies as well as cortical Aβ-positive plaques. Striatal Aβ deposition positively predicted dementia in Lewy body cases with high specificity and had the greatest sensitivity to differentiate DLB from PDD with 100% negative predictive value. These data suggest that striatal Aβ deposition in Lewy body diseases contributes to early dementia and in these cases may impact on the efficacy of treatments targeting the striatum.


Cysteinyl leukotriene involvement in chronic lung disease in premature infants.
The pathophysiology of chronic lung disease (CLD) in premature infants who require mechanical ventilation and prolonged oxygen supplementation has been well-described but the underlying mechanisms are not understood. Our aim was to test the hypothesis that excess cysteinyl leukotriene (LT) production was a contributing factor in CLD. We compared LT production and lung function, at 7 months of age, in nine premature infants with CLD and in eight control infants without CLD. None of the control infants developed any neonatal respiratory problems, but two subsequently required bronchodilator therapy. Respiratory function was assessed by the measurement of thoracic gas volume (TGV), airways resistance (Raw) and functional residual capacity (FRC). Total cysteinyl LT production was quantified by measurement of leukotriene E4 (LTE4) in a spot urine sample. Although all patients were asymptomatic at follow-up, there was evidence of significant lung function abnormalities in infants with CLD. The CLD infants had significantly elevated TGV, Raw and FRC values reflecting airway obstruction when compared to the controls. Urinary LTE4 levels were significantly higher in the CLD infants when compared to the controls (geometric mean: 741 and 337 pmol.mmol-1 creatinine, respectively). There was no direct correlation between urinary LTE4 levels in the CLD group and TGV, Raw or FRC values. Although this study is small and a direct correlation between lung function and urinary leukotriene E4 was not demonstrated, pathological lung function and an enhanced urinary leukotriene E4 production in infants with chronic lung disease would tend to suggest that the cysteinyl leukotrienes were involved in the sequelae of this disease.


Height measurement of microchip connecting pins by use of stereovision.
A stereovision method for estimating the height of connecting pins on a microchip is described. The technique uses a centroidal method to simplify the calculation. A few seconds are required for a Pentium 586 PC to calculate the heights of 300 connecting pins on a 50 mm x 50 mm microchip. The method is described, and experimental results are presented. The optical system, which consists of two CCD cameras with long-focal-length lenses and a two-channel digital image grabber, is capable of in situ measurement.


Genome-wide association study on differentiated thyroid cancer.
Genome-wide association studies (GWASs) of differentiated thyroid cancer (DTC) have identified associations with polymorphisms at 2q35 (DIRC3), 8p12 (NRG1), 9q22.33 (FOXE1), and 14q13.2 (NKX2-1). However, most of the inherited genetic risk factors of DTC remain to be discovered. Our objective was to identify additional common DTC susceptibility loci. We conducted a GWAS in a high-incidence Italian population of 690 cases and 497 controls and followed up the most significant polymorphisms in 2 additional Italian series and in 3 low-incidence populations totaling 2958 cases and 3727 controls. After excluding the most robust previously identified locus (9q22.33), the strongest association was shown by rs6759952, confirming the recently published association in DIRC3 (odds ratio [OR] = 1.21, P = 6.4 × 10(-10), GWAS and all replications combined). Additionally, in the combined analysis of the Italian series, suggestive associations were attained with rs10238549 and rs7800391 in IMMP2L (OR = 1.27, P = 4.1 × 10(-6); and OR = 1.25, P = 5.7 × 10(-6)), rs7617304 in RARRES1 (OR = 1.25, P = 4.6 × 10(-5)) and rs10781500 in SNAPC4/CARD9 (OR = 1.23, P = 3.5 × 10(-5)). Our findings provide additional insights into the genetic and biological basis of inherited genetic susceptibility to DTC. Additional studies are needed to determine the role of the identified polymorphisms in the development of DTC and their possible use in the clinical practice.


Exiguobacterium enclense sp. nov., isolated from sediment.
A Gram-stain-positive bacterium, designated strain NIO-1109(T), was isolated from a marine sediment sample from Chorao Island, Goa, India. Phenotypic and chemotaxonomic characteristics and data from phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NIO-1109(T) was related to the genus Exiguobacterium . Strain NIO-1109(T) exhibited >98.0% 16S rRNA gene sequence similarity with respect to Exiguobacterium indicum HHS 31(T) (99.5%) and Exiguobacterium acetylicum NCIMB 9889(T) (99.1%); the type strains of other species showed <98% similarity. Levels of DNA-DNA relatedness between strain NIO-1109(T) and E. acetylicum DSM 20416(T) and E. indicum LMG 23471(T) were less than 70% (33.0 ± 2.0 and 37 ± 3.2%, respectively). Strain NIO-1109(T) also differed from these two closely related species in a number of phenotypic traits. Based on phenotypic, chemotaxonomic and phylogenetic data, strain NIO-1109(T) is considered to represent a novel species of the genus Exiguobacterium , for which the name Exiguobacterium enclense sp. nov. is proposed. The type strain is NIO-1109(T) ( =NCIM 5457(T) =DSM 25128(T) = CCTCC AB 2011124(T)).


Ultrasmall iron oxide nanoparticles: synthesis, surface modification, assembly, and biomedical applications.
Ultrasmall iron oxide nanoparticles (USIO NPs) with a size <5nm are a class of emerging nanomaterials. As a result of their intrinsic drawbacks related to poor colloidal stability, low r1 relaxivity, and lack of functionality, various strategies have been adopted to synthesize USIO NPs with controllable sizes, to surface modify the particles with polymers, and to assemble them in combination with other nanoscale platforms. Here, we review recent progresses in the synthesis, surface modification, and self-assembly of USIO NPs to address key issues in their biomedical application in the field of cancer diagnosis and therapy, in particular magnetic resonance (MR) imaging, dual-modal or multimodal imaging, drug delivery, and theranostics.


Potassium secretion by the cortical collecting tubule.
The isolated perfused rabbit cortical collecting tubule has been shown to actively transport K from bath to lumen. The first step in this process is active uptake of K across the basolateral membrane via and Na:K exchange pump as evidenced by: 1) basolateral localization and Na:K exchange properties of the ouabain-sensitive Na,K-ATPase, 2) ouabain sensitivity of the Na and K fluxes, 3) interdependence of the Na and K fluxes, and 4) ouabain-sensitivity of 42K uptake into the cell across the basolateral membrane. At the luminal border, a significant K permeability of the apical cell membrane has been identified using electrophysiological techniques. This K permeability is insensitive to the diuretic amiloride, and, thus, differs from the pathway for Na entry, which is highly amiloride sensitive. A significant K permeability of the paracellular pathway is not apparent. It is concluded that K secretion by the rabbit cortical collecting tubule occurs via a two-step process: active uptake of K across the basolateral membrane via the Na:K exchange pump, followed by passive efflux of K across the apical membrane via an amiloride-insensitive K conductive pathway.


Recovery of evidence-based practice.
Consumer recovery is now enshrined in the national mental health policy of many countries. If this construct, which stems from the consumer/user/survivor movement, is truly to be the official and formal goal of mental health services, then it must be the yardstick against which evidence-based practice (EBP) is judged. From a consumer-recovery perspective, this paper re-examines aspects of services chosen for study, methodologies, outcomes measures, and standards of evidence associated with EBP, those previously having been identified as deficient and in need of expansion. One of the significant differences between previous investigations and the present study is that the work, writing, perspectives, and advocacy of the consumer movement has developed to such a degree that we now have a much more extensive body of material upon which to critique EBP and inform and support the expansion of EBP. Our examination reinforces previous findings and the ongoing need for expansion. The consumer recovery-focused direction, resources, frameworks, and approaches identified through the present paper should be used to expand the aspects of services chosen for study, methodologies, outcomes measures, and standards of evidence. This expansion will ultimately enable services to practice in a manner consistent with the key characteristics of supporting personal recovery.


Why July Matters.
Each July, new graduates from premedical, medical, and residency programs, along with junior and midcareer faculty, acclimatize to their changing roles. During this month, overall efficiency, quality, and patient safety may suffer, a problem dubbed the "July effect." The many transitions that occur in teaching hospitals during July are often implicated as the root cause of this problem. The question, then, of how best to improve the team-based clinical care provided in July remains important. In this Commentary, the authors outline a model that combines the team-based care paradigm with effective leadership, followership, and communication-based strategies and propose some actionable steps.A key first step to enhancing patient safety in July is improving effective leadership through use of a select group of attendings whose teaching style empowers learners within a framework of close supervision. Second, programmatic efforts to pair these leaders with good followers are needed. Senior residents in July should be selected on their ability to mentor, guide, and support interns. Third, a system of free-flowing, bidirectional communication must be nurtured to ensure optimal outcomes. Adapting strategies from the airlines (e.g., interdisciplinary conferences to discuss optimal patient care approaches; checklists for daily activities such as sign-outs; directed feedback and debriefing techniques emphasizing actionable areas for improvement) is promising and worth studying.Available data suggest that the "July effect" is real. Developing new and exploring existing approaches for allaying this phenomenon are important areas of further investigation.


Cohort mortality study of rubber and plastics product makers in Italy.
A retrospective cohort mortality study was carried out in 20 industrial factories in the Local Health Unit Bologna Sud (Emilia Romagna, Italy), where different rubber and plastics products were manufactured. The cohort consisted of 925 subjects (578 males and 347 females) employed for at least six months continuously; follow-up was between the beginning of operation of each factory, ranging between mid fifties and mid seventies, and 31 December 1989. For those exposed more than one year cause specific Standardized Mortality Ratios (SMRs) were computed using regional rates for comparison, 90% confidence intervals (CI) were calculated assuming the Poisson distribution. Among the 748 subjects employed for more than one year (457 males and 291 females) there were no lost to follow-up, 54 individuals were dead (41 males and 13 females) and for three subjects the cause of death was unknown. The results showed that all causes mortality was above expectancy in the total cohort (SMR = 123; 54 Obs; 90% CI = 97-154), among males (SMR = 117; 41 Obs; 90% CI = 89-152) and females (SMR = 143; 13 Obs; 90% CI = 85-228). Increased mortality for all malignant tumours was observed in the total cohort (SMR = 150; 25 Obs; 90% CI = 104-209) and for both genders. All nine lung cancer cases were observed among males, the SMR was equal to 218 and was statistically significant; seven cases occurred at duration of exposure less than 10 years and six at latency up to 20 years. The interpretation in terms of causality of the present investigation is limited by the small number of observations and by exposure definition solely in terms of employment in the study factories; nonetheless the results are indicating the existence, in this group of rubber and plastics product makers, of an adverse health effect which deserve further investigation.


Efficacy and safety of peripherally inserted central venous catheters in acute cardiac care management.
Patients admitted to cardiac intensive care unit need administration of drugs intravenously often in concomitance of therapeutic techniques such as non-invasive ventilation, continuous renal replacement therapy and intra-aortic balloon counterpulsation. Therefore, the insertion of central venous catheters provides a reliable access for delivering medications, laboratory testing and hemodynamic monitoring, but it is associated with the risk of important complications. In our study, we tested the efficacy and safety of peripherally inserted central catheters to manage cardiac intensive care. All patients admitted to cardiac intensive care unit with indication for elective central venous access were checked by venous arm ultrasound for peripherally inserted central catheter's implantation. Peripherally inserted central catheters were inserted by ultrasound-guided puncture. After 7 days from the catheter's placement and at the removal, vascular ultrasound examination was performed searching signs of upper extremity deep venous thrombosis. In case of sepsis, blood cultures peripherally from the catheter and direct culture of the tip of the catheter were done to establish a catheter-related blood stream infection. In our cardiac intensive care unit, 137 peripherally inserted central catheters were placed: 80.3% of patients eligible for a peripherally inserted central catheter were implanted. The rate of symptomatic catheter-related peripheral venous thrombosis was 1.4%. Catheter-related blood stream infection was diagnosed in one patient (0.7%; 5.7 × 1000 peripherally inserted central catheter days). All peripherally inserted central catheters were inserted successfully without other major complications. In patients admitted to cardiac intensive care unit, peripherally inserted central catheters' insertion was feasible in a high percentage of patients and was associated with low infective complications and clinical thrombosis rate.


Morphometric and mating compatibility of Dectes texanus texanus (Coleoptera: Cerambycidae) from soybean and sunflower.
The cerambycid Dectes texanus texanus LeConte that infests soybean, Glycine max (L.) Merr., is thought to be the same Dectes that damages sunflower, Helianthus annuus L. However, morphometric characteristics and mating compatibility between individuals from soybean and sunflower fields have not been assessed. Eight hundred eighty stalks of soybean and sunflower residues infested with Dectes were collected from Texas and Kansas. Outside stalk diameter of sunflower (22.6 mm) was 3.2 times greater than that of soybean. Diameters of tunnels by Dectes in sunflower and soybean were 7.0 and 3.4 mm, respectively. Widths of head capsules and pronotums were approximately 1.3 times greater for Dectes larvae from sunflower than soybean. Larval, pupal, and adult Dectes from sunflower were approximately 2.5 times heavier and 1.3 times longer than from soybean. Adults reared from residues of soybean and sunflower were paired to evaluate mating compatibility. Although individuals collected and reared from different crop residues differed significantly in size, percentage of mating success by Dectes from the two crops (26.2%) did not differ significantly from that by adults from the same kind of crop (34.9%). Results indicated that Dectes that infest soybean and sunflower are the same species and reconfirmed that farmers should not plant soybean and sunflower in rotation or in adjacent fields.


Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study.
After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial). The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).


Protective effect of polyunsaturated fatty acid supplementation in apoferritin induced murine glomerulonephritis.
The effects of increasing two dietary polyunsaturated fatty acids, eicosapentaenoic and linoleic, on the glomerulonephritis induced by repeated injections of apoferritin in the mouse were studied. Urinary protein excretion was measured serially; serum creatinine, aortic and renal production of eicosanoids and kidney histology were measured at sacrifice at 8 weeks. Both high EPA and LA feedings were associated with lesser proteinuria, normalization of renal function and profound changes in the tissue production of prostaglandin and thromboxane, which may explain their protective effect in this model of renal disease.


Endoscopic ultrasound: a review of current diagnostic and therapeutic applications.
Endoscopic ultrasound (EUS) has become important in a variety of clinical settings. Echoendoscopes may be categorised into radial and linear configurations. Radial devices are used for diagnostic imaging, whereas linear echoendoscopes also facilitate image guided tissue sampling and intervention. EUS is an established primary diagnostic tool for a number of conditions including choledocholithiasis and biliary microlithiasis. It is therefore well suited to the investigation of the aetiology of pancreatitis where simpler measures fail to identify the aetiology. It can also be used to identify chronic non-calcific pancreatitis. EUS is important in the secondary evaluation of abnormalities detected by other imaging modalities-for example, cystic pancreatic lesions. The high resolution of EUS allows more detailed image based analysis than other imaging modalities. The ability to sample cyst fluid significantly increases the accuracy of lesion characterisation. Most importantly, EUS has become indispensable in the staging of a variety of upper gastrointestinal tract tumours. If resection is being considered, the high resolution images obtained via EUS are invaluable for local tumour staging. EUS guided tissue sampling permits accurate nodal staging without relying on lymph node size as proxy for malignant infiltration. In patients with contraindications to magnetic resonance imaging, EUS is an alternative for the staging of rectal carcinoma. It is used in the staging of lung cancer, often in combination with endobronchial ultrasound. Finally, EUS is used therapeutically in image guided drainage (such as gastrocystostomy in pancreatic pseudocyst) and coeliac plexus neurolysis in patients with abdominal pain caused by pancreatic cancer or pancreatitis.


Constipation in the cancer patient: causes and management.
Constipation is a distressing symptom with multiple etiologies in the cancer patient. Therapy is based on identification and management of underlying causes combined with symptomatic treatment. A working knowledge of bowel physiology and laxative pharmacology forms the foundation for this approach.


Myometrial invasion of endometrium cancer assessed by transrectal ultrasonography.
Transrectal ultrasonographic examinations before surgery were performed on 27 patients with stage I endometrial cancer to assess myometrial invasion. The findings were compared with the histopathologic data obtained by surgery. Sensitivity and specificity of transrectal ultrasonography in myometrial invasion of endometrium cancer were 82.6 and 100%, respectively. Therefore, transrectal ultrasonography may be a useful diagnostic tool to determine the myometrial invasion, which is the most important prognostic factor in endometrial cancer.


Factor VIIa (recombinant) for acute traumatic hemorrhage.
The use of factor VIIa (recombinant) for the treatment of acute traumatic hemorrhage is reviewed. Factor VIIa (recombinant) has received considerable attention as a hemostatic agent and is increasingly being used for the management of bleeding associated with a variety of conditions. Severely injured trauma patients with uncontrolled bleeding are at high risk for coagulopathy and may benefit from the administration of factor VIIa (recombinant). A literature review was conducted to identify original research in the form of randomized controlled trials investigating the use of factor VIIa (recombinant) for the treatment of traumatic hemorrhage. Due to the paucity of such trials, three retrospective evaluations and three large case series pertaining to this topic were also reviewed. Of the two randomized controlled trials, one found a reduction in red blood cell (RBC) transfusion requirements in patients with blunt traumatic hemorrhage after the administration of factor VIIa (recombinant). This reduction in RBC requirements was not found in the study conducted with patients with penetrating trauma. These trials were not powered to show a mortality difference, and the effect of factor VIIa (recombinant) on survival in blunt and penetrating traumatic hemorrhage is unknown. Ongoing clinical trials may answer questions regarding its effect on mortality and other clinically important outcomes. Factor VIIa (recombinant) reduces RBC transfusion requirements in patients with blunt traumatic hemorrhage, and its effect on mortality is currently being investigated. Adjunctive use of factor VIIa (recombinant) should be considered only after other treatment modalities have been optimized.


The teichuronic acid from the walls of Bacillus licheniformis A.T.C.C. 9945.
The teichuronic acid of Bacillus licheniformis A.T.C.C. 9945 grown under phosphate limitation was isolated from the cell walls and purified by ion-exchange and Sephadex chromatography. The detailed structure of the polysaccharide was established by methylation analysis, periodate oxidation and partial acid hydrolysis. The polymer is composed of tetrasaccharide repeating units with the structure [GlcA beta(1 leads to 4)GlcA beta(1 leads to 3)GalNAc beta(1 leads to 6)GalNAc alpha(1 leads to 4)n. 13C n.m.r. analysis has confirmed most of the structural features of the polysaccharide and, in particular, the anomeric configurations and linkage positions of substituents. The teichuronic acid from glucose-limited cells was identical with that from cells grown under phosphate limitation.


Multi-directional pathways of tobacco and marijuana use, including comorbid use, among a population-based cohort of adolescents in Texas: A six-wave cross-lagged model.
Past 30-day tobacco and marijuana use commonly occur among adolescents. It is unclear whether use of one product precedes the other, especially given the new climate surrounding marijuana legalization and the increasing popularity of e-cigarettes. Six-panel cross-lagged regression models, with six months between each panel/Wave (2014-17), were used to model stability paths, bi-directional paths, and comorbid paths (i.e., correlations) between past 30-day use of marijuana and tobacco products. Data were derived from three cohorts of adolescents (n = 3907; weighted N = 461,069) in 6th, 8th, and 10th grades at baseline. Few bidirectional relationships between past 30-day tobacco and marijuana use were observed in early adolescence (6th grade). During the middle adolescence developmental period (8th grade), past 30-day marijuana use was prospectively associated with greater risk of past 30-day tobacco use. In late adolescence (10th grade), increased odds of past 30-day marijuana use given prior past 30-day e-cigarette use, and vice versa, were observed. For all cohorts, stability paths were common, especially for past 30-day marijuana use. Comorbid use was common in middle adolescence (8th grade) but small in magnitude. This is the first study to longitudinally situate comorbid, past 30-day use of tobacco and marijuana and simultaneously examine bi-directional past 30-day use of these products for adolescents. Marijuana use more often and more strongly predicted subsequent tobacco use than the reverse, especially during middle adolescence (13-15 years old). Marijuana use should be considered when creating interventions that address adolescent e-cigarette use in the U.S.


Modelling of OGTT curve identifies 1 h plasma glucose level as a strong predictor of incident type 2 diabetes: results from two prospective cohorts.
The relevance of the OGTT in predicting type 2 diabetes is unclear. We assessed the performance of 14 OGTT glucose traits in type 2 diabetes prediction. We studied 2,603 and 2,386 Europeans from the Botnia study and Malmö Prevention Project (MPP) cohorts with baseline OGTT data. Over a follow-up period of 4.94 years and 23.5 years, 155 (5.95%) and 467 (19.57%) participants, respectively, developed type 2 diabetes. The main outcome was incident type 2 diabetes. One-hour plasma glucose (1h-PG) was a fair/good predictor of incident type 2 diabetes in the Botnia study and MPP (AUC for receiver operating characteristic [AUCROC] 0.80 [0.77, 0.84] and 0.70 [0.68, 0.73]). 1h-PG alone outperformed the prediction model of multiple clinical risk factors (age, sex, BMI, family history of type 2 diabetes) in the Botnia study and MPP (AUCROC 0.75 [0.72, 0.79] and 0.67 [0.64, 0.70]). The same clinical risk factors added to 1h-PG modestly increased prediction for incident type 2 diabetes (Botnia, AUCROC 0.83 [0.80, 0.86]; MPP, AUCROC 0.74 [0.72, 0.77]). 1h-PG also outperformed HbA1c in predicting type 2 diabetes in the Botnia cohort. A 1h-PG value of 8.9 mmol/l and 8.4 mmol/l was the optimal cut-point for initial screening and selection of high-risk individuals in the Botnia study and MPP, respectively, and represented 30% and 37% of all participants in these cohorts. High-risk individuals had a substantially increased risk of incident type 2 diabetes (OR 8.0 [5.5, 11.6] and 3.8 [3.1, 4.7]) and captured 75% and 62% of all incident type 2 diabetes in the Botnia study and MPP. 1h-PG is a valuable prediction tool for identifying adults at risk for future type 2 diabetes.


Protecting the future of indigenous children and nations: an examination of the Indian Child Welfare Act.
The Indian Child Welfare Act is a landmark piece of legislation, passed in response to a long history of Native American children being alienated from their families and communities. The Act has far reaching implications for social workers and human service professionals who have any involvement with Native American children or families. Still, many professionals are either unaware of the Act all together or do not know how to effectively implement its provisions in their practice. This lack of awareness and other factors such as inadequate funding have meant that the Act has never realized its full potential to reduce the number of children in out-of-home care. In order to increase awareness about the Act and to make its implementation in day to day social services more practical, this article provides background information on the factors leading to the Act, information on the law itself, and recommendations for practitioners, administrators, and students in the human services.


Heart rate and QT variability in children with anxiety disorders: a preliminary report.
This study compared beat-to-beat heart rate and QT variability in children with anxiety disorders (n = 7) and normal controls (n = 15) by using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with a higher risk for sudden cardiac death. A decrease in heart rate variability is also linked to significant cardiovascular events. Supine detrended QT variability, QT variability corrected for mean QT interval, and QTvi (a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) were significantly higher in children with anxiety compared to controls (P < 0.05). The largest Lyapunov Exponent (LLE) of heart rate time series was significantly lower (P < 0.05) in children with anxiety compared to controls. These findings suggest a relative increase in sympathetic activity and a relative decrease in cardiac vagal activity in children with anxiety disorders, and are discussed in the context of the effects of tricyclics on cardiac autonomic function in children, and the rare occurrence of sudden death during tricyclic antidepressant treatment.


The Use of Continuous Glucose Monitors in Sport: Possible Applications and Considerations.
This review discusses the potential value of tracking interstitial glucose with continuous glucose monitors (CGMs) in athletes, highlighting possible applications and important considerations in the collection and interpretation of interstitial glucose data. CGMs are sensors that provide real time, longitudinal tracking of interstitial glucose with a range of commercial monitors currently available. Recent advancements in CGM technology have led to the development of athlete-specific devices targeting glucose monitoring in sport. Although largely untested, the capacity of CGMs to capture the duration, magnitude, and frequency of interstitial glucose fluctuations every 1-15 min may present a unique opportunity to monitor fueling adequacy around competitive events and training sessions, with applications for applied research and sports nutrition practice. Indeed, manufacturers of athlete-specific devices market these products as a "fueling gauge," enabling athletes to "push their limits longer and get bigger gains." However, as glucose homeostasis is a complex phenomenon, extensive research is required to ascertain whether systemic glucose availability (estimated by CGM-derived interstitial glucose) has any meaning in relation to the intended purposes in sport. Whether CGMs will provide reliable and accurate information and enhance sports nutrition knowledge and practice is currently untested. Caveats around the use of CGMs include technical issues (dislodging of sensors during periods of surveillance, loss of data due to synchronization issues), practical issues (potential bans on their use in some sporting scenarios, expense), and challenges to the underpinning principles of data interpretation, which highlight the role of sports nutrition professionals to provide context and interpretation.


Risk Factors for Hypocoagulability After Cardiac Surgery: A Retrospective Study.
Hemostatic disturbances after cardiac surgery can lead to excessive postoperative bleeding. Thromboelastography (TEG) was employed to evaluate perioperative coagulative alterations in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), investigating the correlation between factors concomitant with cardiac surgery and modifications in coagulation. Coagulation index as determined by TEG correlated significantly with postoperative bleeding at 24-72 h after cardiac surgery (P < .001). Among patients with a normal preoperative coagulation index, those with postoperative hypocoagulability showed significantly lower nadir temperature (P = .003), larger infused fluid volume (P = .003), and longer CPB duration (P = .033) than those with normal coagulation index. Multivariate logistic regression showed that nadir intraoperative temperature was an independent predictor of postoperative hypocoagulability (adjusted OR: 0.772, 95% CI: 0.624-0.954, P = .017). Multivariate linear regression demonstrated linear associations of nadir intraoperative temperature (P = .017) and infused fluid volume (P = .005) with change in coagulation index as a result of cardiac surgery. Patients are susceptible to hypocoagulability after cardiac surgery, which can lead to increased postoperative bleeding. Ensuring appropriate temperature and fluid volume during cardiac surgery involving CPB may reduce risk of postoperative hypocoagulability and bleeding.


Interactions of hemopoietic cytokines on differentiation of HL-60 cells. Nerve growth factor is a basophilic lineage-specific co-factor.
Nerve growth factor (NGF) is a neurotropic polypeptide which has broad biological activity other than support of growth and survival of sympathetic, sensory and central neurons. NGF promotes rat mast cell hyperplasia in vivo and human granulopoiesis in vitro, selectively augmenting basophil/mast cell differentiation in the presence of T cells or conditioned medium derived from a human T cell line (Mo-CM), a source of granulocyte-macrophage colony-stimulating factor (GM-CSF). NGF also synergizes with GM-CSF to promote human basophil/mast cell differentiation in both methylcellulose and suspension cultures of myeloid progenitors. In the current studies, we examined the interactions of NGF and several cytokines considered to be involved in human basophil/mast cell and eosinophil growth and differentiation, including interleukin (IL)-3, IL-4, IL-5, GM-CSF and granulocyte colony-stimulating factor (G-CSF). NGF synergistically enhanced IL-5 induced dose-dependent increases in histamine content and basophilic cell differentiation of myeloid leukemic HL-60 cells, but was only additive to similar effects of IL-3. In contrast, IL-4 and G-CSF did not promote basophilic differentiation of HL-60 cells in the presence or absence of NGF. Various combinations of GM-CSF, G-CSF, IL-3, IL-4 and IL-5 could not reproduce the synergy observed between NGF and either IL-5 or GM-CSF. NGF appears to represent a class of lineage-specific co-factors, in this case being involved in GM-CSF- or IL-5-induced basophilic lineage differentiation, thus contributing to tissue inflammation or repair.


Association of Shock Index with Echocardiographic Parameters in Cardiac Intensive Care Unit.
A high shock index (SI), the ratio of heart rate (HR) to systolic blood pressure (SBP), has been associated with unfavorable outcomes. We sought to determine the hemodynamic underpinnings of an elevated SI using 2-D and doppler Transthoracic Echocardiography (TTE) in unselected cardiac intensive care unit (CICU) patients. We included Mayo Clinic CICU admissions from 2007 to 2018 who were in sinus rhythm at the time of TTE. The SI was calculated using HR and SBP at the time of TTE. Patients were grouped according to SI: <0.7, 4012 (64%); 0.7-0.99, 1764 (28%); and ≥ 1.0, 513 (8%). Pearson's correlation coefficient was used to assess associations between continuous variables. We included 6289 unique CICU patients, 58% of whom had acute coronary syndrome. The median age was 67.9 years old and 37.8% were females. The mean SI was 0.67 BPM/mmHg. As the SI increased, markers of left ventricular (LV) systolic function and forward flow decreased, including left ventricular ejection fraction (LVEF), fractional shortening, left ventricular outflow tract (LVOT) velocity time integral (VTI), stroke volume, LV stroke work index, and cardiac power output. Biventricular filling pressures increased, and markers of right ventricular function worsened with rising SI. Most TTE measurements reflecting LV function and forward flow were inversely correlated with SI, including LV stroke work index (r = -0.59) and LVOT VTI (r = -0.41), as were both systemic vascular resistance index (r = -0.43) and LVEF (r = -0.23). CICU patients with elevated SI have worse biventricular function and systemic hemodynamics, particularly decreased stroke volume and related calculated TTE parameters. The SI is an easily available marker that can be used to identify CICU patients with unfavorable hemodynamics who may require further assessment.


[Efficacy of Neoadjuvant Endocrine Therapy for Prostate Ductal Carcinoma with Large Multiple Cysts Prior to Robot-Assisted Laparoscopic Radical Prostatectomy].
A 71-year-old man with gross hematuria and urinary retention showed a 7×8 cm polycystic mass compressing the prostate on the right ventral side on pelvic magnetic resonance imaging (MRI). The prostate specific antigen (PSA) level was 6.47 ng/ml. Prostate biopsy histopathology was consistent with prostate ductal carcinoma. Considering the difficulty of surgical therapy, endocrine therapy was undertaken prior to surgery for seven months. Almost all of the cyst disappeared ; robot-assisted laparoscopic radical prostatectomy was then successfully performed. Prostate ductal carcinoma is a relatively rare pathology for which radical prostatectomy plays an important role if the disease is localized. However, when ductal carcinoma involves large cysts, surgical treatment may be difficult. This report discusses the usefulness of neoadjuvant endocrine therapy to reduce the size of the cystic lesions.


Tunichrome-Inspired Gold-Enrichment Dispersion Matrix and Its Application in Water Treatment: A Proof-of-Concept Investigation.
Tunicate, a filter-feeder in seawater, is able to accumulate high amount of metals using intracellular polymer matrices. The woven pyrogallol structures of tunichrome, a small peptide contained in tunicate's blood cells, is believed to be responsible for selective metal sequestration in tunicates from seawater. However, the intriguing tunichrome matrix is difficult both to harvest from the tunicate and to synthesize massively due to the extreme oxidation sensitivity of the pyrogallol moiety which limits the study scope. Here, we succeeded to mimic tunichrome by conjugating two cheap and naturally occurring components: pyrogallol-5-carboxylic acid (gallic acid) and chitin nanofiber. A tunicate-mimetic infiltration matrix of surface-tailored chitin nanofibers with pyrogallol moieties (CGa) demonstrated the versatility of this strategy in generation of ingenious filtration material, especially for unprecedented fine and clean gold recovery inside of the tunicate-mimetic infiltration matrix (>99%, 533 mg gold per gram weight), which exceeds that of the presently most popular materials. Complexation between pyrogallol on the nanofiber and gold was similar to that of a tunichrome's metal sequestration. Extended X-ray absorption fine structure (EXAFS) spectroscopy and data-fitting elucidated the decreased coordination numbers for Au-Au nearest neighbors, demonstrating that gold coordinated to pyrogallol units, followed by an intramolecular association of Au0. A catalytic reduction of 4-nitrophenol mediated by the tunicate-mimetic matrix with harvested gold revealed excellent recyclability up to 30 cycles (∼95% reduction), which together with methylene blue reduction and antimicrobial performances indicates the versatile characteristics of sustainable processes by the tunichrome mimetics. This strategy opens the door for fast-developing new biomimetic alternatives for precious metal recovery, which is not restricted to gold and can offer a tool for multifaceted soft/hard nanomaterials.


Rhodomyrtone as a New Natural Antibiotic Isolated from Rhodomyrtus tomentosa Leaf Extract: A Clinical Application in the Management of Acne Vulgaris.
Rhodomyrtone, a plant-derived principal compound isolated from Rhodomyrtus tomentosa (Myrtaceae) leaf extract, was assessed as a potential natural alternative for the treatment of acne vulgaris. The clinical efficacy of a 1% liposomal encapsulated rhodomyrtone serum was compared with a marketed 1% clindamycin gel. In a randomized and double-blind controlled clinical trial, 60 volunteers with mild to moderate acne severity were assigned to two groups: rhodomyrtone serum and clindamycin gel. The volunteers were instructed to apply the samples to acne lesions on their faces twice daily. A significant reduction in the total numbers of acne lesions was demonstrated in both treatment groups between weeks 2 and 8 (p < 0.05). Significant differences in acne numbers compared with the baseline were evidenced at week 2 onwards (p < 0.05). At the end of the clinical trial, the total inflamed acne counts in the 1% rhodomyrtone serum group were significantly reduced by 36.36%, comparable to 34.70% in the clindamycin-treated group (p < 0.05). Furthermore, a commercial prototype was developed, and a clinical assessment of 45 volunteers was performed. After application of the commercial prototype for 1 week, 68.89% and 28.89% of volunteers demonstrated complete and improved inflammatory acne, respectively. All of the subjects presented no signs of irritation or side effects during the treatment. Most of the volunteers (71.11%) indicated that they were very satisfied. Rhodomyrtone serum was demonstrated to be effective and safe for the treatment of inflammatory acne lesions.


Isolation and characterization of a sulfated polysaccharide from the brown alga Sargassum patens and determination of its anti-herpes activity.
Bioactivity-guided fractionation of the hot water extract from the brown alga Sargassun patens led to the isolation of a polysaccharide as an antiviral component against herpes simplex viruses which are the cause of cold sores (HSV-1) and genital herpes (HSV-2). The polysaccharide contained a sulfur group that could be present as a sulfate ester. It is thus a sulfated polysaccharide with a molecular mass of about 424 kDa, and is designated SP-2a. Gas chromatographic assay showed that the polysaccharide consisted of fucose, galactose, mannose, xylose, glucose, and galactosamine. The fucose is the major constituent sugar (35.3%), followed by galactose (18.4%). The 50% effective concentration (EC50) against HSV-2, HSV-1, and HSV-1 acyclovir resistant strain was 1.3, 5.5, and 4.1 microg/mL, respectively. The 50% cytotoxic concentration (CC50) of SP-2a on the growth of normal Vero cell line was more than 4000 microg/mL. Therefore SP-2a of S. patens may be a potent agent for treating HSV infections.


Cloning and expression of type III collagen in normal and injured tendons of horses.
To clone the 5' end of type III collagen and describe its pattern of mRNA and protein expression in normal and healing tendons in horses. 14 healthy adult horses. The tensile region of collagenase-injured superficial digital flexor tendons was harvested at intervals from 1 to 24 weeks after injury. Total RNA was reverse-transcribed into cDNA for cloning and sequencing of type III collagen. Equine-specific nucleic acid probes were developed and used for northern blot analysis and in situ hybridization. Type III collagen protein and cyanogen bromide-cleaved collagen peptides were assessedby gel electrophresis. Type III collagen mRNA expression and protein content increased immediately after injury and remained increased. Type III collagen was localized to the endotenon in normal tendon and in injured tendon at 1 week. At 8 and 24 weeks, expression became more widely distributed throughout the tendon parenchyma. Injured tendon contained 6 times more type I than type III collagen mRNA. Quantities of type III collagen protein were maximal in the first 4 weeks after injury (approx 33%) and then began to decrease. Type III collagen expression is increased initially in endotenon and subsequently in parenchyma of healing tendon; however, type III remains the minor collagen throughout the healing process. The role of type III collagen in tendon healing is not fully elucidated.