Purification and biochemical characterization of statin, a nonproliferation specific protein from rat liver.
The nuclear protein statin, detectable with specific monoclonal antibodies, is found mostly in nonproliferating cells (Wang, E. (1985) J. Cell Biol. 100, 545-551). In the rat liver a 57-kDa protein designated as rat liver protein 57 (RLp57) was recently identified to carry the epitope for the anti-statin-specific monoclonal antibody, S-44 (Sester, U., Moutsatsos, I. K., and Wang, E. (1989) Exp. Cell Res. 182, 550-558). To characterize further the RLp57 protein, in the present study a polyclonal antibody was raised to the RLp57 protein eluted from polyacrylamide gel. Similar to the anti-statin monoclonal antibody, this polyclonal antibody recognizes a nuclear antigen in nonproliferating fibroblasts and reacts with a 57-kDa protein in rat liver and nonproliferating cells strongly suggesting that RLp57 is a statin protein from rat liver. Two isoforms of RLp57 (isoelectric points between 6.5 and 7.0) were detected after two-dimensional gel electrophoresis and immunoblotting. RLp57 was purified using multiple chromatographic steps, including ion-exchange and affinity chromatography followed by chromatofocusing. These results show that RLp57, a statin protein found in liver, has two isoelectric variants and can be purified to apparent homogeneity by sequential steps of chromatographic procedures.


Who is eating what: diet assessment using next generation sequencing.
The analysis of food webs and their dynamics facilitates understanding of the mechanistic processes behind community ecology and ecosystem functions. Having accurate techniques for determining dietary ranges and components is critical for this endeavour. While visual analyses and early molecular approaches are highly labour intensive and often lack resolution, recent DNA-based approaches potentially provide more accurate methods for dietary studies. A suite of approaches have been used based on the identification of consumed species by characterization of DNA present in gut or faecal samples. In one approach, a standardized DNA region (DNA barcode) is PCR amplified, amplicons are sequenced and then compared to a reference database for identification. Initially, this involved sequencing clones from PCR products, and studies were limited in scale because of the costs and effort required. The recent development of next generation sequencing (NGS) has made this approach much more powerful, by allowing the direct characterization of dozens of samples with several thousand sequences per PCR product, and has the potential to reveal many consumed species simultaneously (DNA metabarcoding). Continual improvement of NGS technologies, on-going decreases in costs and current massive expansion of reference databases make this approach promising. Here we review the power and pitfalls of NGS diet methods. We present the critical factors to take into account when choosing or designing a suitable barcode. Then, we consider both technical and analytical aspects of NGS diet studies. Finally, we discuss the validation of data accuracy including the viability of producing quantitative data.


Unexplained lower abdominal pain associated with sacroiliac joint dysfunction: report of 2 cases.
A 25-year-old woman and a 31-year-old man presented with chronic lower back pain and unexplained lower abdominal pain. Both patients had groin tenderness at the medial border of the anterior superior iliac spine. The results of radiographical and physical examinations suggested sacroiliac joint dysfunction. Sacroiliac joint injection relieved their symptoms, including groin tenderness. In our experience, groin tenderness is highly specific for sacroiliac joint dysfunction. We speculate that spasm of the iliac muscle can cause groin pain and tenderness. Groin pain and a history of unexplained abdominal pain, with lower back pain, are symptoms that suggest sacroiliac joint dysfunction. Additionally, compression of the iliac muscle is a simple and useful maneuver; therefore, it can be used as a screening test for sacroiliac joint dysfunction, alongside other provocation tests.


The OTUD1-Notch2-ICD axis orchestrates allogeneic T cell-mediated graft-versus-host disease.
Disorders of the ubiquitin-proteasome system (UPS) are known to influence the incidence and mortality of various diseases. It remains largely unknown whether and how the UPS affects the onset and progression of acute graft-verus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study demonstrated that the deubiquitinase OTUD1 is an essential regulator of aGVHD. Activation of CD4+ T cells after allo-HSCT, elevated the protein levels of OTUD1, which in turn interacted with the Notch2-ICD (NICD) to cleave the ubiquitin of NICD at the K1770 site, thereby inducing NICD protein accumulations in T cells. OTUD1-driven NICD signaling promoted the differentiation and functions of Th1 and Th17 cells and amplified the cascade of aGVHD. Moreover, by screening a FDA-approved drugs library the study identified dapagliflozin as an inhibitor targeting the OTUD1/NICD axis. Dapagliflozin administration significantly prolonged the survival of aGVHD mice. This study characterized a previously unknown role of OTUD1 in T cell-mediated allogeneic responses and provided a promising therapeutic strategy to target OTUD1 for the alleviation of aGVHD.


Transvaginal needle suspension procedures for recurrent stress incontinence.
The results of transvaginal needle suspension in 36 patients with stress urinary incontinence who failed previous operation were reviewed. Eighteen patients underwent a Stamey endoscopic needle suspension, and a Peyrera-Raz cystourethropexy was performed on the remainder. Recurrent stress incontinence was confirmed by history, physical examination, and urodynamic studies. Cure rates of 78 percent for the Stamey procedure and 83 percent for the Raz operation were achieved. Excluding patients with voiding dysfunction or urge incontinence postoperatively due to bladder instability, the failure rates were 6 percent and 11 percent, respectively. Analysis of the results according to the preoperative maximal urethral pressures demonstrated that low-pressure urethras if accompanied with urethrovesical hypermobility have no impact on the results if the anatomic abnormality was corrected adequately by the needle suspension. Thus, the transvaginal needle suspension was found to be highly effective in patients with low-pressure urethras, who failed previous operation, but had persistent bladder neck hypermobility, and suggests that this method of surgical repair should be the first choice in this selected group.


Prognosis and risk factors in patients with asymptomatic aortic stenosis and their modulation by atorvastatin (20 mg).
The aim of the prospective, randomized, placebo-controlled Tyrolean Aortic Stenosis Study (TASS) was to characterize the natural history and risk factors and their possible modulation by new-onset atorvastatin treatment (20 mg/day vs placebo) in patients with asymptomatic calcified aortic stenosis. Forty-seven patients without previous lipid-lowering therapy or indications for it according to guidelines at study entry were randomized to atorvastatin treatment or placebo and prospectively followed for a mean study period of 2.3 +/- 1.2 years. Patients' prognoses were worse than expected, with 24 (51%) experiencing major adverse clinical events, in most cases the new onset of symptoms followed by aortic valve replacement. In multivariate regression analysis, independent risk factors for worse clinical outcomes were aortic valve calcification, as assessed by multidetector computed tomography, and plasma levels of C-reactive protein. In univariate analysis, mean systolic pressure gradient or an increased N-terminal-pro-B-type natriuretic peptide plasma level allowed the prediction of major adverse clinical events as well, whereas concomitant coronary calcification, age, and the initiation of atorvastatin treatment had no significant prognostic implication. As shown in a subgroup of 35 patients (19 randomly assigned to atorvastatin and 16 to placebo), annular progression in aortic valve calcification and hemodynamic deterioration were similar in both treatment groups. In conclusion, TASS could demonstrate a poor clinical outcome in patients with asymptomatic calcified aortic stenosis which can be predicted by new risk factors such as strong AVC or increased plasma levels of CRP or NT-proBNP. The study does not support the concept that treatment with a HMG-CoA reductase inhibitor (20 mg atorvastatin once daily) halts the progression of calcified aortic stenosis.


The Effect of Mid-to-Long-Term Hospitalization on the Catastrophic Health Expenditure: Focusing on the Mediating Effect of Earned Income Loss.
Mid-to-long-term hospitalization (MLTH) can threaten the household economy with high medical costs and loss of income. Therefore, it could increase the catastrophic health expenditure (CHE), measured as the ratio of medical expenses to the ability to pay. This study aimed to determine the effect of MLTH on the incidence of CHE and the mediating effect of earned income reduction rate (EIRR). We used 2015 to 2017 data from the Korean Welfare Panel Study and selected households with earned income through work. The final samples were 1671 households in the database. This study applied three-step regression analyses for estimating mediation effects. First, MLTH affected CHE increases; second, MLTH increased EIRR; third, both EIRR and MLTH increased CHE at the same time. Additionally, the bootstrapping results were 0.364 to 0.644 in the 95% confidence interval, which suggested that EIRR mediated the effects of MLTH on CHE. Previous studies have only focused on medical costs when interpreting CHE; however, it is also essential to recognize that the MLTH can have a negative effect on the EIRR. This study contributed to the literature by giving another insight into interpreting the cause of CHE, focusing on income loss factors.


Echocardiographic features in patients with ANCA-associated vasculitis within 3 months before and after diagnosis.
We investigated the all-inclusive echocardiographic features in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) within 3 months before and after diagnosis. We reviewed the medical records of 89 AAV patients taking echocardiography and 35 age- and gender-matched controls. We collected clinical and laboratory data and echocardiographic results. We compared the variables between patients with AAV of each variant and controls and among those with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). The mean age and period from diagnosis to echocardiography were 54.5 years (30 men) and 1.4 months. The mean age of controls was 51.6 years. AAV patients exhibited lower mean left ventricle ejection fraction (LVEF) (64.0 vs. 69.1%, P = 0.002) and higher mean E/E' ratio (11.7 vs. 8.8, P = 0.001) and right ventricle systolic pressure (RVSP) (30.2 vs. 23.2 mm Hg, P < 0.001) than the controls. Each variant of AAV presented a different pattern of echocardiographic features in comparison with controls. MPA patients exhibited systolic and diastolic dysfunctions and pulmonary arterial hypertension more often than controls. Meanwhile, GPA patients exhibited only diastolic dysfunction, and EGPA patients had systolic dysfunction and pulmonary arterial hypertension more frequently than controls. No meaningful differences in echocardiographic features appeared among AAV variants. AAV patients exhibited reduced systolic function and advanced diastolic dysfunctions and pulmonary arterial hypertension near the time of diagnosis compared with controls. Each variant of AAV presented a different pattern in echocardiographic features.


Visual Decision-Making in an Uncertain and Dynamic World.
The right decision today may be the wrong decision tomorrow. We live in a world in which expectations, contingencies, and goals continually evolve and change. Thus, decisions do not occur in isolation but rather are tightly embedded in these streams of temporal dependencies. Accordingly, even relatively straightforward visual decisions must take into account not just the immediate sensory input but also past experiences and future goals and expectations. Here, we evaluate recent progress in understanding how the brain implements these dependencies. We show that visual decision-making relies on mechanisms of evidence accumulation and commitment that have been studied extensively under relatively static, isolated conditions but in general can operate much more flexibly. A deeper understanding of these mechanisms will require identifying the principles that govern this flexibility, which must operate across different timescales to produce effective decisions in uncertain and dynamic environments.


Stage-specific characterization of the vascular endothelial growth factor axis in prostate cancer: expression of lymphangiogenic markers is associated with advanced-stage disease.
The vascular endothelial growth factor (VEGF) family plays a critical role in tumor angiogenesis and lymphangiogenesis. We characterized, at the mRNA and protein levels, the expression of VEGF-A and VEGF-D and their cognate receptors, VEGFR-1, VEGFR-2, and VEGFR-3 in early- and advanced-stage prostate cancer specimens. The levels of VEGF-A and VEGF-D mRNA in early- and advanced-stage specimens were compared using an angiogenic gene array and were confirmed by quantitative real-time PCR. Receptor protein levels and activation status were determined by immunoblotting. Spatial expression of the proteins was evaluated using immunohistochemistry with fresh and archival tissues from benign prostatic hypertrophy specimens, early-stage prostate specimens, and advanced-stage metastatic specimens. Circulating plasma levels of these growth factors were measured using ELISAs. We observed that expression patterns of VEGF isotypes corresponded to the prostate cancer stage: high expression of angiogenic growth factor VEGF-A was observed in early-stage prostate specimens, whereas high expression of lymphangiogenic growth factor VEGF-D was associated with advanced-stage metastatic disease. All VEGF receptors were present at variable levels in all specimens, but their activation states varied in a stage-specific manner. VEGFR-1 and, to a limited extent, VEGFR-2 were activated in early-stage specimens, whereas VEGFR-2 and VEGFR-3 were activated in advanced-stage specimens. Our results suggest that lymphangiogenic markers, such as VEGF-D and VEGFR-2 and VEGFR-3, may be better than angiogenic markers as targets of therapeutic intervention in advanced-stage prostate disease.


Hydrogen peroxide accumulation and transcriptional changes in grapevines recovered from flavescence dorée disease.
Flavescence dorée (FD) is considered one of the most severe phytoplasma diseases affecting grapevine. The spontaneous, complete, and stable remission of the symptoms of FD (recovery) is a phenomenon that may occur in infected grapevines. The molecular bases of this phenomenon are still unclear, although some works suggest that recovery could be linked to the accumulation of hydrogen peroxide (H2O2). Several genes coding for enzymes involved in H2O2 metabolism, in the ascorbate-glutathione cycle, defense responses, and the biosynthesis of hormones were identified. The H2O2 content was biochemically determined and the expression levels of 44 genes were analyzed through quantitative real-time reverse-transcription polymerase chain reaction in healthy (H), infected by FD-associated phytoplasma (I), and 2-years-recovered (R) plants of Vitis vinifera 'Barbera'. In tissues of R plants, large amounts of H2O2 were detected, essentially linked to an upregulation of genes involved in the production of H2O2 (germin-like protein and glycolate oxidase); whereas, in I grapevines, the overexpression of some scavenging genes reduced the quantity of H2O2. The recovery state was characterized by the activation of ethylene biosynthesis and of defense genes not linked to salicylic acid (SA) signaling, such as the WRKY2 transcription factor. Conversely, I plants reacted to phytoplasma with SA-mediated signaling, even though this response does not appear to be effective against the pathogen.


Tentorium schwannoma mimicking meningioma: an unusual location.
A 60-year-old female was admitted to our clinic complaining of a long-lasting headache. Cranial magnetic resonance imagining examination of the patient revealed a 22x24 mm extra-axial, well-demarcated, mass lesion based on the left tentorium. The patient underwent a craniotomy and the tumor was totally excised with the adjacent tentorium. The histopathological examination of the tumor complied with the diagnosis of schwannoma. The rest of the clinical course was uneventful and the patient was released from the hospital without any neurological deficit. Intracranial schwannomas can rarely originate from atypical dural locations and radiological techniques are not always helpful in distinguishing tentorial schwannoma from tentorial meningioma. We presented a patient with a tentorium schwannoma mimicking meningioma and discussed the current literature.


[Self-stigma, self-esteem and self-efficacy of mentally ill].
The way that the social stigma of mental illness is related with the self-stigma, which in turn affects self-esteem and self-efficacy of mental patients was investigated. A sample of 66 patients in the Adult Psychiatric Clinic of the Thessaloniki General Hospital "G. Papanikolaou" was participated in this descriptive association study, with cross-sectional comparisons. The sample comprised of patients who were hospitalized or visited the Clinic as out-patients during the period that the study was undertaken. A tool for measuring the basic demographic, social and clinical characteristics of the participants was designed and used. Additionally, the Self-Stigma of Mental Illness Scale, SSMIS, Rosenberg's Self-Esteem Scale, RSE and the General Self-Efficacy Sherer Scale, GSESH were used for measuring self-stigma, self-esteem and self-efficacy respectively. Results showed that self-esteem and self-efficacy were highly associated with each another. Self-esteem and self-efficacy co varied. Greater self-stigma was associated with lower self-esteem and selfefficacy confirming the power of this relationship which is connected with patients' psychological empowerment and acts as mediator between patients' self-categorization as "mentally ill" and their self-esteem and self-efficacy. Additionally, a mild negative association between self-esteem, self-efficacy and age was found while higher educational level was associated with greater selfefficacy. Greater self-stigma along with lower educational level were the most significant predictors of both self-esteem and self-efficacy of mental patients, as shown by regression analysis. Some of our results, such as the percentage of low self-esteem (30.3%), were different from previous relevant data (9.1-24%), probably due to differences in sample's cultural characteristics and composition, research tools used, and the degree of mentally ill patients' reaction to social stigma perception. Despite its methodological limitations, the present study showed that self-stigma contributes to low self-efficacy and self-esteem of the mentally ill. It is thus a fair objective on the one hand to reduce stigmatization for the benefit of patients, and secondly, to raise public awareness in order to minimize the overall stigmatization towards mental illness, which is the primary cause of self-stigma.


What Should Guide Health Policy? A Perspective Beyond Politics.
As the U.S. electorate has become increasingly polarized, these divisions are poised to shape legislative and regulatory work in the years ahead. For those whose focus is on the public goods of health care for all, the advancement of science through rigorous research, and the contribution of higher education to the continual improvement of the nation's workforce, there is profound uncertainty about the future. There are several pressing questions facing the nation and academic medicine, including the future of affordable, accessible insurance; acceptance of scientific evidence; sustainable learning and teaching methodologies; and the well-being and preparation of the nation's health workforce to care for an increasingly diverse nation. For those in academic medicine and policy making alike, the authors propose a framework, grounded in scientific evidence and guided by clinical ethics, for designing and evaluating health policy solutions for these and other pressing questions.


3D-printed Handheld Models Do Not Improve Recognition of Specific Characteristics and Patterns of Three-part and Four-part Proximal Humerus Fractures.
Reliably recognizing the overall pattern and specific characteristics of proximal humerus fractures may aid in surgical decision-making. With conventional onscreen imaging modalities, there is considerable and undesired interobserver variability, even when observers receive training in the application of the classification systems used. It is unclear whether three-dimensional (3D) models, which now can be fabricated with desktop printers at relatively little cost, can decrease interobserver variability in fracture classification. Do 3D-printed handheld models of proximal humerus fractures improve agreement among residents and attending surgeons regarding (1) specific fracture characteristics and (2) patterns according to the Neer and Hertel classification systems? Plain radiographs, as well as two-dimensional (2D) and 3D CT images, were collected from 20 patients (aged 18 years or older) who sustained a three-part or four-part proximal humerus fracture treated at a Level I trauma center between 2015 and 2019. The included images were chosen to comprise images from patients whose fractures were considered as difficult-to-classify, displaced fractures. Consequently, the images were assessed for eight fracture characteristics and categorized according to the Neer and Hertel classifications by four orthopaedic residents and four attending orthopaedic surgeons during two separate sessions. In the first session, the assessment was performed with conventional onscreen imaging (radiographs and 2D and 3D CT images). In the second session, 3D-printed handheld models were used for assessment, while onscreen imaging was also available. Although proximal humerus classifications such as the Neer classification have, in the past, been shown to have low interobserver reliability, we theorized that by receiving direct tactile and visual feedback from 3D-printed handheld fracture models, clinicians would be able to recognize the complex 3D aspects of classification systems reliably. Interobserver agreement was determined with the multirater Fleiss kappa and scored according to the categorical rating by Landis and Koch. To determine whether there was a difference between the two sessions, we calculated the delta (difference in the) kappa value with 95% confidence intervals and a two-tailed p value. Post hoc power analysis revealed that with the current sample size, a delta kappa value of 0.40 could be detected with 80% power at alpha = 0.05. Using 3D-printed models in addition to conventional imaging did not improve interobserver agreement of the following fracture characteristics: more than 2 mm medial hinge displacement, more than 8 mm metaphyseal extension, surgical neck fracture, anatomic neck fracture, displacement of the humeral head, more than 10 mm lesser tuberosity displacement, and more than 10 mm greater tuberosity displacement. Agreement regarding the presence of a humeral head-splitting fracture was improved but only to a level that was insufficient for clinical or scientific use (fair to substantial, delta kappa = 0.33 [95% CI 0.02 to 0.64]). Assessing 3D-printed handheld models adjunct to onscreen conventional imaging did not improve the interobserver agreement for pattern recognition according to Neer (delta kappa = 0.02 [95% CI -0.11 to 0.07]) and Hertel (delta kappa = 0.01 [95% CI -0.11 to 0.08]). There were no differences between residents and attending surgeons in terms of whether 3D models helped them classify the fractures, but there were few differences to identify fracture characteristics. However, none of the identified differences improved to almost perfect agreement (kappa value above 0.80), so even those few differences are unlikely to be clinically useful. Using 3D-printed handheld fracture models in addition to conventional onscreen imaging of three-part and four-part proximal humerus fractures does not improve agreement among residents and attending surgeons on specific fracture characteristics and patterns. Therefore, we do not recommend that clinicians expend the time and costs needed to create these models if the goal is to classify or describe patients' fracture characteristics or pattern, since doing so is unlikely to improve clinicians' abilities to select treatment or estimate prognosis. Level III, diagnostic study.


The Promise of the Internet of Things in Healthcare: How Hard Is It to Keep?
Internet of Things is starting to be implemented in healthcare. An example is the automated monitoring systems that are currently being used to provide healthcare workers with feedback regarding their hand hygiene compliance. These solutions seem effective in promoting healthcare workers self-awareness and action regarding their hand hygiene performance, which is still far from desired. Underlying these systems, an indoor positioning component (following Internet of Things paradigm) is used to collect data from the ward regarding healthcare workers' position, which will be later used to make some assumptions about the usage of alcohol-based handrub dispensers and sinks. We found that building such a system under the scope of the healthcare field is not a trivial task and it must be subject to several considerations, which are presented, analyzed and discussed in this paper. The limitations of present Internet of Things technologies are not yet ready to address the demanding field of healthcare.


Comparison of Freshwater Diatom Assemblages from a High Arctic Oasis to Nearby Polar Desert Sites and Their Application to Environmental Inference Models.
Arctic oases are regions of atypical warmth and relatively high biological production and diversity. They are small in area (<5 km(2) ) and uncommon in occurrence, yet they are relatively well studied due to the abundance of plant and animal life contained within them. A notable exception is the lack of research on freshwater ecosystems within polar oases. Here, we aim to increase our understanding of freshwater diatom ecology in polar oases. Diatoms were identified and enumerated from modern sediments collected in 23 lakes and ponds contained within the Lake Hazen oasis on Ellesmere Island, and compared with diatom assemblages from 29 sites located outside of the oasis across the northern portion of the island. There were significant differences in water chemistry variables between oasis and northern sites, with oasis sites having higher conductivity and greater concentrations of nutrients and related variables such as dissolved organic carbon (DOC). Taxa across all sites were typical of those recorded in Arctic freshwaters, with species from the genera Achnanthes sensu lato, Fragilaria sensu lato, and Nitzschia dominating the assemblages. A correspondence analysis (CA) ordination showed that oasis sites generally plotted separately from the northern sites, although the sites also appear to plot separately based on whether they were lakes or ponds. Canonical correspondence analysis (CCA) identified specific conductivity, DOC, and SiO2 as explaining significant (P < 0.05) and additional amounts of variation in the diatom data set. The most robust diatom-based inference model was generated for DOC, which will provide useful reconstructions on long-term changes in paleo-optics of high Arctic lakes.


Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison.
A double-blind, multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in outpatients with major depressive episode; 184 patients were randomised to fluvoxamine (100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale (HAMD) total score. However, the percentage of HAMD responders (>or= 50% decrease in HAMD total score) at week 2, the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability, depression and anxiety scale at weeks 1, 2 and 4, all showed significant advantages for fluvoxamine. During the last 2 weeks, fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale. Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs. Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality.


Real-Time and Offline Evaluation of Myoelectric Pattern Recognition for the Decoding of Hand Movements.
Pattern recognition algorithms have been widely used to map surface electromyographic signals to target movements as a source for prosthetic control. However, most investigations have been conducted offline by performing the analysis on pre-recorded datasets. While real-time data analysis (i.e., classification when new data becomes available, with limits on latency under 200-300 milliseconds) plays an important role in the control of prosthetics, less knowledge has been gained with respect to real-time performance. Recent literature has underscored the differences between offline classification accuracy, the most common performance metric, and the usability of upper limb prostheses. Therefore, a comparative offline and real-time performance analysis between common algorithms had yet to be performed. In this study, we investigated the offline and real-time performance of nine different classification algorithms, decoding ten individual hand and wrist movements. Surface myoelectric signals were recorded from fifteen able-bodied subjects while performing the ten movements. The offline decoding demonstrated that linear discriminant analysis (LDA) and maximum likelihood estimation (MLE) significantly (p < 0.05) outperformed other classifiers, with an average classification accuracy of above 97%. On the other hand, the real-time investigation revealed that, in addition to the LDA and MLE, multilayer perceptron also outperformed the other algorithms and achieved a classification accuracy and completion rate of above 68% and 69%, respectively.


Diet Plus Inositols, α-Lactalbumin and Gymnema sylvestre: The Successful Combo to Restore Body Weight and Metabolic Profile in Obese and Dysmetabolic Patients.
The primary control of dysmetabolic patients is extremely challenging worldwide, with inadequate dietary habits and sporadic physical activity among the key risk factors for metabolic syndrome onset. Nowadays, there is no exclusive treatment for this condition, and considering that preventive measures usually fail, new therapeutic approaches need to be proposed and investigated. This present pilot study compared the effects of diet alone and in association with a combination of myo-inositol and d-chiro-inositol in their 40:1 ratio, α-lactalbumin, and Gymnema sylvestre on different metabolic parameters in obese dysmetabolic patients. To this purpose, 37 patients with BMI between 30 and 40 and fasting blood glucose between 100 and 125 mg/dL were divided into two groups: (i) the control group followed a hypocaloric Mediterranean diet, (ii) while the study group was also supplemented with a daily dosage of two sachets, each one containing 1950 mg myo-inositol, 50 mg d-chiro-inositol, 50 mg α-lactalbumin, and 250 mg Gymnema Sylvestre. After a 6-month treatment, all parameters improved in both groups. Nevertheless, the treated group experienced a greater improvement, especially concerning the variation from the baseline of HOMA index, triglycerides, BMI, body weight, and waist circumference. These findings support the supplementation with myo-inositol and d-chiro-inositol in the 40:1 ratio, α-lactalbumin, and Gymnema sylvestre as a therapeutical strategy to potentiate the beneficial effects induced via dietary programs in dysmetabolic patients.


Cochlear Implant Outcomes: Quality of Life in Prelingually Deafened, Late-Implanted Patients.
Reevaluating and expanding cochlear implantation's (CI) indication while measuring the quality of life (QoL) outcomes regarding the parent's point of view of prelingually deafened, late-implanted patients, which are widely known to showcases a limited improvement in speech recognition. A retrospective descriptive and analytic study to assess QoL outcomes from CI in 64 early deafened, late-implanted patients, according to their parent's perspective, between January 2009 and December 2019, using the Nottingham Pediatric Cochlear Implant Program (Nottingham University Hospital, Nottingham, United Kingdom) "Children with cochlear implantation: parents perspective." The most represented age interval is the 5 and 7 interval and the mean age is 10.09 years. There was no sex predominance, with rural origin and high school academicals level preponderance. Fourteen children had experienced neonatal icterus, eight had meningitis, and seven were the result of related marriage. The age of the first consultation was typically over 2 years old, with only 45 schooled children. Age had a significantly statistic correlation between Self-reliance and Well-being and happiness subscales. History of receiving aid and speech therapy has a clear correlation with Self-reliance, Well-being and happiness, and Communication and Education. Schooling statuses, sex, age of appearance, and communication mode were not correlated to any subscale score, and with the exception of Effect of implantation, all the other "Children with cochlear implantation: parent's perspective" subscales were intercorrelated. Properly validated QoL assessments for CI are a must, as outcomes of CI expand beyond audiometric performances to include the improvement of QoL.


Effects of lattice polarity on interfacial space charges and defect disorder in ionically conducting AgI heterostructures.
Heterostructured (β/γ)-AgI exhibits a spontaneous lattice polarization not accounted for in standard space-charge models. This polarization field dominates the positional variation of energies of isolated defects, and Ag(+) vacancies and interstitials are stabilized at alternate [β/γ] interfaces. This suggests enhanced Frenkel pair separation, analogous to electronic charge separation in polar semiconductor heterostructures. Stoichiometric systems are, however, characterized by associated Frenkel pairs due to strong V(Ag)-Ag(i) interactions and show no enhancement of defect numbers. In nonstoichiometric systems, lattice polarization does direct the distribution of the excess defect species, and defect-defect interactions enhance local Frenkel pair concentrations at interfaces, suggesting that nonstoichiometry is critical to the extreme room-temperature ionic conductivities observed in heterostructured AgI nanoplates.


[Comparative analysis of the action of 2 calmodulin inhibitors on the contractile function of the isolated heart].
Ca2+-complexon EGTA and two calmodulin inhibitors: metaphenazine and trifluoperazine, induced similar effects on the cardiac contractile function: they diminished cardiac output, decelerated left ventricle pressure fall and increased both minimal--and end-diastolic pressure. Changes in the left ventricular pressure and its time course were more obvious during calmodulin inhibitor action as compared to EGTA at equal diminution of cardiac output. Trifluoperazine decreased left ventricular systolic pressure and resistance of coronary arteries to a greater extent than metaphenazine. The findings suggest participation of calmodulin in the regulation of myocardial relaxation mainly.


Potential Roles of microRNAs for Assessing Cardiovascular Risk in Pre-Eclampsia-Exposed Postpartum Women and Offspring.
Pre-eclampsia, which is part of the spectrum of hypertensive pregnancy disorders, poses a significant health burden, contributing to maternal and infant morbidity and mortality. Pre-eclampsia is widely associated with persistent adverse effects on the cardiovascular health of women with a history of pre-eclampsia. Additionally, there is increasing evidence demonstrating that offspring of pre-eclamptic pregnancies have altered cardiac structure and function, as well as different vascular physiology due to the decrease in endothelial function. Therefore, early detection of the likelihood of developing pre-eclampsia-associated cardiovascular diseases is vital, as this could facilitate the undertaking of the necessary clinical measures to avoid disease progression. The utilisation of microRNAs as biomarkers is currently on the rise as microRNAs have been found to play important roles in regulating various physiological and pathophysiological processes. In regard to pre-eclampsia, recent studies have shown that the expression of microRNAs is altered in postpartum women and their offspring who have been exposed to pre-eclampsia, and that these alterations may persist for several years. This review, therefore, addresses changes in microRNA expression found in postpartum women and offspring exposed to pre-eclampsia, their involvement in cardiovascular disease, and the potential role of microRNAs to be used as predictive tools and therapeutic targets in future cardiovascular disease research.


Future Newborns with Opioid-Induced Neonatal Abstinence Syndrome (NAS) Could Be Assessed with the Genetic Addiction Risk Severity (GARS) Test and Potentially Treated Using Precision Amino-Acid Enkephalinase Inhibition Therapy (KB220) as a Frontline Modality Instead of Potent Opioids.
In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn-parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids.


Adaptive behaviour and learning in slime moulds: the role of oscillations.
The slime mould Physarum polycephalum, an aneural organism, uses information from previous experiences to adjust its behaviour, but the mechanisms by which this is accomplished remain unknown. This article examines the possible role of oscillations in learning and memory in slime moulds. Slime moulds share surprising similarities with the network of synaptic connections in animal brains. First, their topology derives from a network of interconnected, vein-like tubes in which signalling molecules are transported. Second, network motility, which generates slime mould behaviour, is driven by distinct oscillations that organize into spatio-temporal wave patterns. Likewise, neural activity in the brain is organized in a variety of oscillations characterized by different frequencies. Interestingly, the oscillating networks of slime moulds are not precursors of nervous systems but, rather, an alternative architecture. Here, we argue that comparable information-processing operations can be realized on different architectures sharing similar oscillatory properties. After describing learning abilities and oscillatory activities of P. polycephalum, we explore the relation between network oscillations and learning, and evaluate the organism's global architecture with respect to information-processing potential. We hypothesize that, as in the brain, modulation of spontaneous oscillations may sustain learning in slime mould. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.


Ice shelf microbial ecosystems in the high arctic and implications for life on snowball earth.
The Ward Hunt Ice Shelf (83 degrees N, 74 degrees W) is the largest remaining section of thick (> 10 m) land-fast sea ice along the northern coastline of Ellesmere Island, Canada. Extensive meltwater lakes and streams occur on the surface of the ice and are colonized by photosynthetic microbial mat communities. This High Arctic cryo-ecosystem is similar in several of its physical, biological and geochemical features to the McMurdo Ice Shelf in Antarctica. The ice-mats in both polar regions are dominated by filamentous cyanobacteria but also contain diatoms, chlorophytes, flagellates, ciliates, nematodes, tardigrades and rotifers. The luxuriant Ward Hunt consortia also contain high concentrations (10(7)-10(8) cm-2) of viruses and heterotrophic bacteria. During periods of extensive ice cover, such as glaciations during the Proterozoic, cryotolerant mats of the type now found in these polar ice shelf ecosystems would have provided refugia for the survival, growth and evolution of a variety of organisms, including multicellular eukaryotes.


Binding of bovine T194A PrP(C) by PrP(Sc)-specific antibodies: potential implications for immunotherapy of familial prion diseases.
Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that are based on the misfolding of a cellular prion protein (PrP(C)) into an infectious, pathological conformation (PrP(Sc)). There is proof-of-principle evidence that a prion vaccine is possible but this is tempered with concerns of the potential dangers associated with induction of immune responses to a widely-expressed self-protein. By targeting epitopes that are specifically exposed upon protein misfolding, our group developed a vaccine that induces PrP(Sc)-specific antibody responses. Here we consider the ability of this polyclonal antibody (SN6b) to bind to a mutant of PrP(C) associated with spontaneous prion disease. Polyclonal antibodies were selected to mimic the vaccination outcome and also explore all possible protein conformations of the recombinant bovine prion protein with mutation T194A [bPrP(T194A)]. This mutant is a homolog of the human T183A mutation of PrP(C) that is associated with early onset of familial dementia. With nanopore analysis, under non-denaturing conditions, we observed binding of the SN6b antibody to bPrP(T194A). This interaction was confirmed through ELISAs as well as immunoprecipitation of the recombinant and cellularly expressed forms of bPrP(T194A). This interaction did not promote formation of a protease resistant conformation of PrP in vitro. Collectively, these findings support the disease-specific approach for immunotherapy of prion diseases but also suggest that the concept of conformation-specific immunotherapy may be complicated in individuals who are genetically predisposed to PrP(C) misfolding.


Association of Treatment Modality, Functional Outcomes, and Baseline Characteristics With Treatment-Related Regret Among Men With Localized Prostate Cancer.
Treatment-related regret is an integrative, patient-centered measure that accounts for morbidity, oncologic outcomes, and anxiety associated with prostate cancer diagnosis and treatment. To assess the association between treatment approach, functional outcomes, and patient expectations and treatment-related regret among patients with localized prostate cancer. This population-based, prospective cohort study used 5 Surveillance, Epidemiology, and End Results (SEER)-based registries in the Comparative Effectiveness Analysis of Surgery and Radiation cohort. Participants included men with clinically localized prostate cancer from January 1, 2011, to December 31, 2012. Data were analyzed from August 2, 2020, to March 1, 2021. Prostate cancer treatments included surgery, radiotherapy, and active surveillance. Patient-reported treatment-related regret using validated metrics. Regression models were adjusted for demographic and clinicopathologic characteristics, treatment approach, and patient-reported functional outcomes. Among the 2072 men included in the analysis (median age, 64 [IQR, 59-69] years), treatment-related regret at 5 years after diagnosis was reported in 183 patients (16%) undergoing surgery, 76 (11%) undergoing radiotherapy, and 20 (7%) undergoing active surveillance. Compared with active surveillance and adjusting for baseline differences, active treatment was associated with an increased likelihood of regret for those undergoing surgery (adjusted odds ratio [aOR], 2.40 [95% CI, 1.44-4.01]) but not radiotherapy (aOR, 1.53 [95% CI, 0.88-2.66]). When mediation by patient-reported functional outcomes was considered, treatment modality was not independently associated with regret. Sexual dysfunction, but not other patient-reported functional outcomes, was significantly associated with regret (aOR for change in sexual function from baseline, 0.65 [95% CI, 0.52-0.81]). Subjective patient-perceived treatment efficacy (aOR, 5.40 [95% CI, 2.15-13.56]) and adverse effects (aOR, 5.83 [95% CI, 3.97-8.58]), compared with patient expectations before treatment, were associated with treatment-related regret. Other patient characteristics at the time of treatment decision-making, including participatory decision-making tool scores (aOR, 0.80 [95% CI, 0.69-0.92]), social support (aOR, 0.78 [95% CI, 0.67-0.90]), and age (aOR, 0.78 [95% CI, 0.62-0.97]), were significantly associated with regret. Results were comparable when assessing regret at 3 years rather than 5 years. The findings of this cohort study suggest that more than 1 in 10 patients with localized prostate cancer experience treatment-related regret. The rates of regret appear to differ between treatment approaches in a manner that is mediated by functional outcomes and patient expectations. Treatment preparedness that focuses on expectations and treatment toxicity and is delivered in the context of shared decision-making should be the subject of future research to examine whether it can reduce regret.


Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis.
Although prolactin is reported to counteract the immunosuppressive effects of glucocorticoids, cyclosporine, and morphine, it remains unknown whether prolactin has any salutary effects on the depressed immune responses following severe hemorrhage. To study this, mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 min, then adequately resuscitated and divided into two groups. One group received saline vehicle, while the other group received prolactin (100 micro g/25 g body weight, s.c.) immediately before resuscitation. Two hours thereafter, peritoneal (pMphi) and splenic macrophages (sMphi) were harvested and assessed not only for their ability to release IL-1 and IL-6, but also for cytokine gene expression using semiquantitative reverse transcription and PCR. In an additional group, mice were subjected to sepsis by cecal ligation and puncture 3 days after hemorrhage. Hemorrhage markedly decreased the ability of pMphi and sMphi to release IL-1 and IL-6. This was, however, associated with increased mRNA expression for IL-1beta and IL-6 and increased serum corticosterone levels. Following prolactin treatment of hemorrhaged mice, IL-1beta and IL-6 mRNA levels as well as cytokine release capacity and blood corticosterone levels were comparable to the values in sham animals. Prolactin also improved the survival of animals subjected to sepsis after hemorrhage. Thus, the immunosuppression following hemorrhage appears to be mediated and modulated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, prolactin represents a novel immunomodulating hormone for the treatment of immunodepression encountered after hemorrhagic shock and for decreasing the mortality from subsequent sepsis under those conditions.


Clinical effectiveness and cost-effectiveness of drotrecogin alfa (activated) (Xigris) for the treatment of severe sepsis in adults: a systematic review and economic evaluation.
To assess the clinical and cost-effectiveness of drotrecogin alfa (activated) for the treatment of adults with severe sepsis in a UK context. Electronic databases. Data from the commercial use of the drug up to April 2002. Data from the manufacturer submission to the National Institute for Clinical Excellence (NICE). A systematic review of the literature and an economic evaluation were undertaken. Data were synthesised through a narrative review with full tabulation of results from included studies. The evidence on the effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis came primarily from one large pivotal randomised controlled trial, the PROWESS study. This study demonstrated a statistically significant absolute reduction in 28-day mortality of 6.5%. Longer term survival benefit was maintained to 90 days. By 9 months, the trend towards increased median survival was non-significant, although the survival curves did not cross. Results presented by the number of organ dysfunctions were not statistically significant, but when mortality rates for those with two or more organ failures were combined, the relative risk of death was significantly lower in those treated with drotrecogin alfa (activated) compared with placebo. However, this report highlights a number of considerations relevant to the subgroup analyses reported for the PROWESS study. Published cost-effectiveness studies of treatment with drotrecogin alfa (activated) have applied a range of methods to the estimation of benefits, estimating an incremental gain per treated patient of between 0.38 and 0.68 life-years (for patients with severe sepsis). For patients with severe sepsis and multiple organ dysfunction, the manufacturer (Eli Lilly) estimated an incremental gain of 1.115 life-years per treated patient, compared to 1.351 life-years per treated patient estimated by the Southampton Health Technology Assessments Centre (SHTAC). These latter UK analyses are based on a patient group that is more severely affected by disease, where effectiveness is greater and the baseline risk of all-cause mortality is much higher (SHTAC analysis), these factors are associated with the noted difference in effect. The three published cost-effectiveness studies report cost for US and Canadian patient groups; for those patients with severe sepsis they report the additional cost per patient treated in a range around 10,000-16,000 dollars. The manufacturer's submission reports analysis for the UK, based on 28-day survival data in patients with severe sepsis and multiple organ dysfunction (the European licence indication), with the additional mean cost per treated patient estimated to be 5106 pounds. The analysis undertaken by SHTAC, for a UK group of patients with severe sepsis and multiple organ dysfunction, estimates an additional mean cost per patient treated of 6661 pounds. The manufacturer's submission to NICE presents cost-effectiveness estimates for drotrecogin alfa (activated) in the UK, in patients with severe sepsis and multiple organ dysfunction, at 6637 pounds per quality-adjusted life-year (QALY) based on 28-day effectiveness data, and 10,937 pounds per QALY based on longer term follow-up data. SHTAC developed an independent cost-effectiveness model and estimated a base-case cost per QALY of 8228 pounds in patients with severe sepsis and multiple organ failure (based on 28-day survival data). Simulation results indicate that where the NHS is willing to pay 20,000 pounds per QALY, drotrecogin alfa (activated) is a cost-effective use of resources in 98.7% of cases. Published economic evaluations report various sensitivity analyses, with results sensitive to changes in the measure of treatment effect, but otherwise studies reported that results were robust to variations in most assumptions used in the cost-effectiveness analysis. Drotrecogin alfa (activated) plus best supportive care appears clinically and cost-effective compared with best supportive care alone, in a UK cohort of severe sepsis patients, and in the subgroup of more severely affected patients with severe sepsis and multiple organ failure. The introduction of drotrecogin alfa (activated) will involve a substantial additional cost to the NHS. The treatment-eligible population in England and Wales may comprise up to 16,570 patients, with an estimated annual drug acquisition cost of over 80 million pounds, excluding VAT. Further research is required on the longer term impact of drotrecogin alfa (activated) on both mortality and morbidity in UK patients with severe sepsis, on the clinical and cost-effectiveness of drotrecogin alfa (activated) in children (under 18 years) with severe sepsis, and on the effect of the timing of dosage and duration of treatment on outcomes in severe sepsis.


Development of a rapid DNA extraction method and one-step nested PCR for the detection of Naegleria fowleri from the environment.
Naegleria fowleri is a small free-living amoebo-flagellate found in natural and manmade thermal aquatic habitats worldwide. The organism is pathogenic to man causing fatal primary amoebic meningoencephalitis (PAM). Infection typically results from bathing in contaminated water and is usually fatal. It is, therefore, important to identify sites containing N. fowleri in the interests of preventive public health microbiology. Culture of environmental material is the conventional method for the isolation of N. fowleri but requires several days incubation and subsequent biochemical or molecular tests to confirm identification. Here, a nested one-step PCR test, in conjunction with a direct DNA extraction from water or sediment material, was developed for the rapid and reliable detection of N. fowleri from the environment. Here, the assay detected N, fowleri in 18/109 river water samples associated with a nuclear power plant in South West France and 0/10 from a similar site in the UK. Although culture of samples yielded numerous thermophilic free-living amoebae, none were N. fowleri or other thermophilic Naegleria spp. The availability of a rapid, reliable and sensitive one-step nested PCR method for the direct detection of N. fowleri from the environment may aid ecological studies and enable intervention to prevent PAM cases.


New paradigms in chemokine receptor signal transduction: Moving beyond the two-site model.
Chemokine receptor (CKR) signaling forms the basis of essential immune cellular functions, and dysregulated CKR signaling underpins numerous disease processes of the immune system and beyond. CKRs, which belong to the seven transmembrane domain receptor (7TMR) superfamily, initiate signaling upon binding of endogenous, secreted chemokine ligands. Chemokine-CKR interactions are traditionally described by a two-step/two-site mechanism, in which the CKR N-terminus recognizes the chemokine globular core (i.e. site 1 interaction), followed by activation when the unstructured chemokine N-terminus is inserted into the receptor TM bundle (i.e. site 2 interaction). Several recent studies challenge the structural independence of sites 1 and 2 by demonstrating physical and allosteric links between these supposedly separate sites. Others contest the functional independence of these sites, identifying nuanced roles for site 1 and other interactions in CKR activation. These developments emerge within a rapidly changing landscape in which CKR signaling is influenced by receptor PTMs, chemokine and CKR dimerization, and endogenous non-chemokine ligands. Simultaneous advances in the structural and functional characterization of 7TMR biased signaling have altered how we understand promiscuous chemokine-CKR interactions. In this review, we explore new paradigms in CKR signal transduction by considering studies that depict a more intricate architecture governing the consequences of chemokine-CKR interactions.


Relation of serum ascorbic acid to serum lipids and lipoproteins in US adults.
To examine the relation of serum ascorbic acid level to serum lipid and lipoprotein levels among a random sample of the US adult population. Using linear regression, the relation of serum ascorbic acid level to serum lipid and lipoprotein levels was examined among 5,412 women and 5,116 men enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), 1976-1980. Age, race, body mass index, level of physical activity, level of education, alcohol intake, and dietary energy, cholesterol, and fat intakes, and other potential confounders were included in the multivariate models. Serum ascorbic acid level was independently associated with high-density lipoprotein cholesterol (HDL-C) among women; each 1 mg/dl increase in serum ascorbic acid level (range 0.1 to 2.7 mg/dl) was associated with a 2 mg/dl increase in HDL-C level (p = 0.001). Because other investigators have demonstrated an inverse relation between ascorbic acid intake or blood levels and total serum cholesterol in individuals with elevated total serum cholesterol levels, we analyzed four subgroups of NHANES II participants with total serum cholesterol levels > 200 mg/dl. Among women with total serum cholesterol levels > or = 200 mg/dl, each 1 mg/dl increase in serum ascorbic acid level was independently associated with an increase of 2 to 3 mg/dl in HDL-C level (p < or = 0.05). Serum ascorbic acid level was not significantly associated with other serum lipids or lipoproteins. If the observed associations are linked causally, they would suggest that ascorbic acid is a factor in cholesterol homeostasis among women and may be particularly important for women at increased risk for coronary heart disease.


[A case of rhabdomyosarcoma of the parotid region].
The present paper reports a case of rhabdomyosarcoma in a 4-year-old patient, the rapidity with which it spread and the intensity of its extension bringing the case under observation. It is, in fact, a case of embryonal rhabdomyosarcoma localized in the right parotid area with an extension to the temporal fossa, to the epi-oro-hypopharynx as far as the lateral vertebral region with C5-C6 involvement and penetrating the medium cranialis fossa. Initially the child showed signs of tissue growth at the right parotid site, originating without symptoms and rapidly increasing in volume. As exploratory surgery revealed that it would be impossible to achieve radical removal of the growth, the authors opted for radio-chemotherapy treatment. This type of approach, however, gives short lived results, in this case evidenced by recurrences within six months and leading to the patient's death after just eight months. It is important to stress the rapid evolution of this neoplasm, its tendency to recur and metastasize as well as its poor prognosis in general.


The socioeconomic impact of equine epizootic lymphangitis in working equids in low and middle-income countries: a scoping review.
Equine epizootic lymphangitis (EEL) is a very infectious and contagious fungal disease that, with its ocular, respiratory and skin forms, causes severe effects on the health and welfare of working equids. Treatment is expensive and rarely available in low and middle-income countries (LMICs). Epidemiological data is lacking in most countries where the disease is known to exist. The purpose of this scoping review is to identify the current knowledge on the socioeconomic impact of EEL in working equids in LMICs, to highlight knowledge gaps and provide recommendations for future research. Seven eligible papers were obtained from the search of four databases and backward citation searching. The review showed that the available research on this subject is very scarce and restricted to Ethiopia. From the results it emerged that EEL causes detrimental socioeconomic effects on working equids' owners, compromising their health and livelihood. Its economic consequences were attributed to the reduced working capacity and loss of sick animals. Among the social impacts, authors highlighted the stigma around sick equids and their owners. Further studies on the socioeconomic impact of EEL conducted in endemic areas are highly required. The integration of epidemiological data with socioeconomic impact studies from LMICs may promote funding allocation for the development of cost-effective treatments and vaccines and for implementing disease prevention and control programmes. Future research would gain from applying the One Health approach to better examine the multiplicity of the disease socioeconomic effects, therefore increasing the potential of research to orientate policy.


Applicability of an exposure model for the determination of emissions from mobile phone base stations.
Applicability of a model to estimate radiofrequency electromagnetic field (RF-EMF) strength in households from mobile phone base stations was evaluated with technical data of mobile phone base stations available from the German Net Agency, and dosimetric measurements, performed in an epidemiological study. Estimated exposure and exposure measured with dosemeters in 1322 participating households were compared. For that purpose, the upper 10th percentiles of both outcomes were defined as the 'higher exposed' groups. To assess the agreement of the defined 'higher' exposed groups, kappa coefficient, sensitivity and specificity were calculated. The present results show only a weak agreement of calculations and measurements (kappa values between -0.03 and 0.28, sensitivity between 7.1 and 34.6). Only in some of the sub-analyses, a higher agreement was found, e.g. when measured instead of interpolated geo-coordinates were used to calculate the distance between households and base stations, which is one important parameter in modelling exposure. During the development of the exposure model, more precise input data were available for its internal validation, which yielded kappa values between 0.41 and 0.68 and sensitivity between 55 and 76 for different types of housing areas. Contrary to this, the calculation of exposure-on the basis of the available imprecise data from the epidemiological study-is associated with a relatively high degree of uncertainty. Thus, the model can only be applied in epidemiological studies, when the uncertainty of the input data is considerably reduced. Otherwise, the use of dosemeters to determine the exposure from RF-EMF in epidemiological studies is recommended.


Developing Appropriateness Criteria for Pediatric Vascular Access.
To describe the methodology undertaken to provide guidance on the appropriateness, as well as inappropriateness, of vascular access device selection, characteristics, and insertion technique for pediatric patients. The RAND Corporation-University of California, Los Angeles Appropriateness Method was used. After definition of key terms and scope, a systematic review of the pediatric vascular access literature was undertaken. Clinical scenarios were developed to reflect the common indications for vascular access across pediatric health care. These were sectioned according to (1) device selection, (2) device characteristics, and (3) insertion technique. An interdisciplinary panel of experts (N = 14) consisting of leading experts representing diverse pediatric clinical disciplines including anesthesiology, cardiology and cardiac surgery, critical care and emergency, general surgery, hematology and oncology, hospital medicine, infectious disease, interventional radiology, pharmacology, regional pediatric hospitalist, and vascular access nursing specialties was convened. The scenarios were rated for appropriateness by the panel over 2 rounds (1 [highly inappropriate] to 9 [highly appropriate]). Round 1 ratings were completed anonymously and independently by panel members and classified into 3 levels of appropriateness: appropriate, uncertain, and inappropriate, or disagreement. For round 2, panelists met in-person to discuss the round 1 ratings and independently rerated the indications. All indications were reclassified into 3 levels of appropriateness or disagreement. The RAND Corporation-University of California, Los Angeles Appropriateness Method provides a rigorous, in-depth and transparent methodology to develop the first appropriateness criteria for the selection of pediatric vascular access devices in a range of patient groups.


The power of mumps virus: Matrix protein activates apoptotic pathways in human colorectal cell lines.
New therapeutic approaches can significantly impact the control of colorectal cancer (CRC), which is increasing worldwide. In this study, we investigated the potential of targeting viral proteins to combat cancer cells. Specifically, we examined the anticancer potential of the matrix (M) protein of the mumps virus Hoshino strain in SW480 CRC cell lines. To begin, we individually transfected SW480 cells with pcDNA3 plasmids containing the mumps virus M gene. We then investigated the percentage of cell death, caspase activity, and the expression levels of genes involved in apoptosis pathways. Following this, we performed bioinformatics analysis on the M protein to identify any similarities with Bcl-2 family members and their viral homologs. Our diagnostic methods showed that treatment with the mumps M protein induced apoptosis and upregulated the expression and activity of pro-apoptotic proteins in SW480 CRC cells compared to the control and vector groups. Based on our bioinformatics studies, we proposed that the BH3 motif in the M protein may trigger apoptosis in CRC cells by interacting with cellular Bax. Overall, our study showed for the first time that the mumps virus M protein could be considered as a targeted treatment for CRC by inducing apoptotic pathways.


Initial evidence of religious practice and belief in depressed african american cancer patients.
This study examined spiritual coping (beliefs and practices) of depressed African American cancer patients through a comparison with depressed White cancer patients and non-depressed African American cancer patients. Using mixed methods, 74 breast (n=41) and prostate (n=33) cancer survivors including 34 depressed and 23 nondepressed African Americans and 17 depressed Whites were interviewed. The interviews were audiotaped and transcribed. Qualitative data analysis identified themes that were coded. The codes were entered into SPSS software. The Fisher's exact test was performed to examine group differences in self-reported spiritual coping. Significantly more depressed African Americans questioned God when learning of a cancer diagnosis than the non-depressed African Americans (p=.03), but they did not differ from the depressed Whites in this regard (p=.70). Significantly more depressed African Americans reported having faith in God (p=.04), reading the bible (p=.02), and conversing with God (p=.01) than did the depressed Whites. They also reported praying alone (p=.01) more frequently than the depressed Whites who, on the other hand, reported praying with others (non-family members) together for one's own health more frequently (p=.04). Depression is associated with a deepening need for spirituality and it affects religious beliefs and practices more in African American than White cancer patients. Given its important role in the lives of African American cancer patients, spirituality may be utilized as a reasonable, culturally-based approach to better assess and treat depression in these patients.


What Determines Whether a Pain is Rated as Mild, Moderate, or Severe? The Importance of Pain Beliefs and Pain Interference.
Reliable and valid measures of pain intensity are needed to accurately evaluate the efficacy of pain treatments. Perhaps with the exception of faces pain intensity scales, which are thought to reflect both pain intensity and pain affect, the other most commonly used pain intensity scales-Numerical Rating Scales (NRSs), Visual Analog Scales, and Verbal Rating Scales (VRSs)-are all thought to reflect primarily pain intensity or the magnitude of felt pain. However, to our knowledge, this assumption has not been directly tested for VRSs. We evaluated whether VRS pain severity ratings are influenced by pain beliefs, catastrophizing, or pain interference over and above any effects of pain intensity, as measured by a NRS, in 4 samples of individuals with physical disabilities and chronic pain. As hypothesized, and while controlling for pain intensity as measured by a NRS, higher scores on factors representing pain interference with function, pain catastrophizing, and a number of pain-related beliefs were all associated with a tendency for the study participants to rate their pain as more severe on a VRS. These findings indicate VRSs of pain severity cannot necessarily be assumed to measure only pain intensity; they may also reflect patient perceptions about pain interference and beliefs about their pain. Clinicians and researchers should take these findings into account when selecting measures and when interpreting the results of studies using VRSs as outcome measures.


Enzyme immunoassay for detection of human immunodeficiency virus antigens in cell cultures.
A sensitive and specific avidin-biotin enzyme immunoassay that uses immunoreagents from naturally infected individuals was formulated for the detection of human immunodeficiency virus (HIV) antigens. A total of 500 cell culture samples from 111 cultures were tested in this assay and in a reverse transcriptase (RT) assay. Of 353 samples that were positive in the immunoassay, 174 were positive and 179 were negative in the RT assay. The specificity of the immunoassay results was supported by the failure of samples to react with nonimmune serum, by the ability of an anti-HIV type 1 monoclonal antibody to block the reactivity of selected samples, and by the appearance of RT activity in samples drawn from some cultures after a longer period of cultivation. HIV antigens were detected in 174 of 176 RT-positive samples (sensitivity, 98.9%). A comparison of the kinetics of antigen production and RT activity revealed that detectable antigen levels frequently preceded the appearance of RT activity. Thus, 50% of virus-containing cultures were identified within 9 days by immunoassay compared with 14 days by RT assay. In addition, RT activity was often detected intermittently in cultures sampled on several days, whereas antigen levels did not decline after initial appearance. Enzyme immunoassays for HIV antigen detection that use easily obtained reagents and simple technologies could facilitate laboratory and clinical research which requires cultivation of viruses.


Successful pregnancy in an adolescent with metastatic undifferentiated sarcoma. A case report.
An adolescent with metastatic sarcoma conceived after chemotherapy and delivered a normal but premature infant. Therapeutic intervention during the first trimester was avoided. This case emphasizes the need for intensive birth control counseling among adolescent oncology patients, the ethical problems associated with treatment of cancer during pregnancy and the potential neonatal problems, such as prematurity and hypothyroidism, arising from such pregnancies.


HIV/AIDS and the legislature: an international comparison.
This paper examines the legislative response to the AIDS epidemic. It goes beyond a mere overview and tries to give an insight into the chronology of the legislative reaction as well as its contents. For this, the legal instruments of 217 jurisdictions were analyzed. A global chronological pattern of legislative reaction could be observed. Concerning the contents of legislation, legislatures seem to combine the public health interests with the interests, rights and responsibilities of individuals. This insight into the legislative reaction to AIDS can help us to predict and understand legislative responses to future epidemics.


Security and privacy qualities of medical devices: an analysis of FDA postmarket surveillance.
Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients' stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting. We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices. Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism. Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware.


Thermal-Assisted Multiscale Patterning of Nonplanar Colloidal Nanostructures for Multi-Modal Anti-Counterfeiting.
Nanotransfer printing of colloidal nanoparticles is a promising technique for the fabrication of functional materials and devices. However, patterning nonplanar nanostructures pose a challenge due to weak adhesion from the extremely small nanostructure-substrate contact area. Here, the study proposes a thermal-assisted nonplanar nanostructure transfer printing (NP-NTP) strategy for multiscale patterning of polystyrene (PS) nanospheres. The printing efficiency is significantly improved from ≈3.1% at low temperatures to ≈97.2% under the glass transition temperature of PS. Additionally, the arrangement of PS nanospheres transitioned from disorder to long-range order. The mechanism of printing efficiency enhancement is the drastic drop of Young's modulus of nanospheres, giving rise to an increased contact area, self-adhesive effect, and inter-particle necking. To demonstrate the versatility of the NP-NTP strategy, it is combined with the intaglio transfer printing technique, and multiple patterns are created at both micro and macro scales at a 4-inch scale with a resolution of ≈2757 pixels per inch (PPI). Furthermore, a multi-modal anti-counterfeiting concept based on structural patterns at hierarchical length scales is proposed, providing a new paradigm of imparting multiscale nanostructure patterning into macroscale functional devices.


Levels of DNA damage are unaltered in mice overexpressing human catalase in nuclei.
Two types of transgenic mice were generated to evaluate the role of hydrogen peroxide in the formation of nuclear DNA damage. One set of lines overexpresses wild-type human catalase cDNA, which is localized to peroxisomes. The other set overexpresses a human catalase construct that is targeted to the nucleus. Expression of the wild-type human catalase transgene was found in liver, kidney, skeletal muscle, heart, spleen, and brain with muscle and heart exhibiting the highest levels. Animals containing the nuclear-targeted construct had a similar pattern of expression with the highest levels in muscle and heart, but with lower levels in liver and spleen. In these animals, immunofluorescence detected catalase present in the nuclei of kidney, muscle, heart, and brain. Both types of transgenic animals had significant increases of catalase activities compared to littermate controls in most tissues examined. Despite enhanced activities of catalase, and its presence in the nucleus, there were no changes in levels of 8OHdG, a marker of oxidative damage to DNA. Nor were there differences in mutant frequencies at a Lac Z reporter transgene. This result suggests that in vivo levels of H(2)O(2) may not generate 8OHdG or other types of DNA damage. Alternatively, antioxidant defenses may be optimized such that additional catalase is unable to further protect nuclear DNA against oxidative damage.


Intracranial arteriovenous malformations: an 11-year experience.
A consecutive series of 107 patients with an intracranial arteriovenous malformation who were considered for surgical treatment over the 11-year period between 1974 and 1985 is analysed. In 71 (66.4%) patients complete obliteration (which in some cases was combined with pre- or peroperative embolization) by surgery was attempted and was achieved in all but two patients. Five patients were treated by embolization alone and three patients by radiotherapy alone. Twenty-eight patients were managed conservatively for one of four reasons: an expectation of a good outcome without treatment (six patients); the refusal of recommended surgical treatment (five patients); poor condition at presentation (eight patients); or the risks of operative treatment were thought to be too great (nine patients). There was a 9.9% mortality in the surgically-treated series and significant morbidity in 16 (22.3%) patients. In all but two of these 16 patients, morbidity was related directly to the initial intracerebral haemorrhage. The one-year mortality in the group that did not undergo operation was significantly higher than in those patients who were treated surgically. Some general guide-lines for the management of intracranial arteriovenous malformations are proposed.


Tocilizumab treatment in neuromyelitis optica spectrum disorders: Updated meta-analysis of efficacy and safety.
This systematic review and meta-analysis summarize the efficacy and safety of Tocilizumab (TCZ) in treating NMOSD and investigates the factors that affect its efficacy. TCZ is the first monoclonal antibody against the IL-6 receptor for treating NMOSD, and its efficacy and safety vary in different studies. We collected English-language research literature until January 1, 2023, by searching databases such as PubMed, MEDLINE, Embase, Cochrane Library, and clinicaltrials.gov, and identified 9 studies involving 153 patients (139 female and 14 male) that met our inclusion criteria. In these studies, the average ARR ratio and EDSS score reduction values in the TCZ treatment group were -1.34 (95 % CI, -1.60 to -1.09) and -0.81 (95 % CI, -1.04 to -0.58), respectively. Based on the data we have collected, compared to the AQP4-IgG negative NMOSD patients, TCZ demonstrates a more pronounced effectiveness in AQP4-IgG positive NMOSD patients. The study also found that the effectiveness of TCZ in reducing NMOSD patients' ARR ratio was related to gender, race, and TCZ dosage, while the effectiveness of reducing EDSS score was not related to these factors. Among the 153 patients receiving TCZ treatment, 101 (66 %) experienced mild adverse reactions, and one patient experienced a severe adverse reaction (facial cellulitis). The comprehensive data indicate that TCZ treatment can reduce the frequency of NMOSD relapses, improve patients' neurological function, and have good safety. The effectiveness of TCZ in reducing NMOSD patients' ARR ratio is related to multiple factors.


Impact of cell-free hemoglobin on contracting skeletal muscle microvascular oxygen pressure dynamics.
Free hemoglobin (Hb) associated with hemolysis extravasates into vascular tissue and depletes nitric oxide (NO), which leads to impaired vascular function and could impair skeletal muscle metabolic control during exercise. We tested the hypothesis that: 1) free Hb would extravasate into skeletal muscle tissue, reducing the contracting skeletal muscle O2 delivery/O2 utilization ratio (microvascular PO2, PO2mv) to a similar extent as that observed following NO synthase (NOS) blockade, and 2) that the Hb scavenging protein haptoglobin (Hp) would prevent Hb extravasation and inhibit these skeletal muscle tissue effects. PO2mv was measured in eight rats (phosphorescence quenching) at rest and during 180 s of electrically induced (1-Hz) twitch spinotrapezius muscle contractions (experiment 1). A second group of seven rats was also used to investigate the effects of Hb + Hp (experiment 2). For both experiments, measurements were made: 1) during control conditions, 2) following a bolus infusion of either Hb (50 mg/kg) or Hb + Hp (50 mg/kg), and 3) following local superfusion of NG-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg). Additional experiments were completed to visualize Hb extravasation into the muscular tissue using Click chemistry techniques. There were no significant differences in the PO2mv observed at rest for any condition in either experiment (p > 0.05 for all). In experiment 1, both Hb and L-NAME reduced the PO2mv significantly during the steady-state of muscle contractions when compared to control conditions with no differences between Hb and L-NAME (control: 24 ± 1, Hb: 21 ± 1, L-NAME: 20 ± 1 mmHg, p < 0.05). In experiment 2, only L-NAME resulted in a significantly lower PO2mv during the steady-state of muscle contractions (control: 25 ± 1, Hb + Hp: 22 ± 2, L-NAME: 18 ± 1 mmHg, p < 0.05). Free Hb lowered the blood-myocyte O2 driving force to a level not significantly different from L-NAME. However, infusing Hb bound to Hp resulted in no significant differences in steady-state PO2mv during muscle contractions when compared to control. Surprisingly, we did not observe Hb accumulation in skeletal muscle tissue. Taken together these data suggests that free Hb impairs O2 delivery/utilization via a NO scavenging effect. Furthermore, the unchanged PO2mv steady-state observed following Hb + Hp further indicates that vascular compartmentalization of Hb by the scavenger protein haptoglobin may improve skeletal muscle metabolic control and potentially exercise tolerance in those afflicted with hemolytic diseases.


Green-to-red photoconvertible fluorescent proteins: tracking cell and protein dynamics on standard wide-field mercury arc-based microscopes.
Green fluorescent protein (GFP) and other FP fusions have been extensively utilized to track protein dynamics in living cells. Recently, development of photoactivatable, photoswitchable and photoconvertible fluorescent proteins (PAFPs) has made it possible to investigate the fate of discrete subpopulations of tagged proteins. Initial limitations to their use (due to their tetrameric nature) were overcome when monomeric variants, such as Dendra, mEos, and mKikGR were cloned/engineered. Here, we report that by closing the field diaphragm, selective, precise and irreversible green-to-red photoconversion (330-380 nm illumination) of discrete subcellular protein pools was achieved on a wide-field fluorescence microscope equipped with standard DAPI, Fluorescein, and Rhodamine filter sets and mercury arc illumination within 5-10 seconds. Use of a DAPI-filter cube with long-pass emission filter (LP420) allowed the observation and control of the photoconversion process in real time. Following photoconversion, living cells were imaged for up to 5 hours often without detectable phototoxicity or photobleaching. We demonstrate the practicability of this technique using Dendra2 and mEos2 as monomeric, photoconvertible PAFP representatives fused to proteins with low (histone H2B), medium (gap junction channel protein connexin 43), and high (alpha-tubulin; clathrin light chain) dynamic cellular mobility as examples. Comparable efficient, irreversible green-to-red photoconversion of selected portions of cell nuclei, gap junctions, microtubules and clathrin-coated vesicles was achieved. Tracking over time allowed elucidation of the dynamic live-cycle of these subcellular structures. The advantage of this technique is that it can be performed on a standard, relatively inexpensive wide-field fluorescence microscope with mercury arc illumination. Together with previously described laser scanning confocal microscope-based photoconversion methods, this technique promises to further increase the general usability of photoconvertible PAFPs to track the dynamic movement of cells and proteins over time.


Synthesis, Molecular Docking and Biological Characterization of Pyrazine Linked 2-Aminobenzamides as New Class I Selective Histone Deacetylase (HDAC) Inhibitors with Anti-Leukemic Activity.
Class I histone deacetylases (HDACs) are key regulators of cell proliferation and they are frequently dysregulated in cancer cells. We report here the synthesis of a novel series of class-I selective HDAC inhibitors (HDACi) containing a 2-aminobenzamide moiety as a zinc-binding group connected with a central (piperazin-1-yl)pyrazine or (piperazin-1-yl)pyrimidine moiety. Some of the compounds were additionally substituted with an aromatic capping group. Compounds were tested in vitro against human HDAC1, 2, 3, and 8 enzymes and compared to reference class I HDACi (Entinostat (MS-275), Mocetinostat, CI994 and RGFP-966). The most promising compounds were found to be highly selective against HDAC1, 2 and 3 over the remaining HDAC subtypes from other classes. Molecular docking studies and MD simulations were performed to rationalize the in vitro data and to deduce a complete structure activity relationship (SAR) analysis of this novel series of class-I HDACi. The most potent compounds, including 19f, which blocks HDAC1, HDAC2, and HDAC3, as well as the selective HDAC1/HDAC2 inhibitors 21a and 29b, were selected for further cellular testing against human acute myeloid leukemia (AML) and erythroleukemic cancer (HEL) cells, taking into consideration their low toxicity against human embryonic HEK293 cells. We found that 19f is superior to the clinically tested class-I HDACi Entinostat (MS-275). Thus, 19f is a new and specific HDACi with the potential to eliminate blood cancer cells of various origins.


Single center experience with treatment of spinal dural arteriovenous fistulas.
Spinal dural arteriovenous fistulas (SDAVFs) are rare pathologies with a yearly incidence of 5-10 new cases/million, constituting 60-80 % of spinal arteriovenous malformations. Clinical symptoms include progressive paraparesis, paresthesias, bladder, and bowel disturbances. The pathophysiology of SDAVFs is not well elucidated. Microneurosurgery and endovascular techniques are established treatment modalities for permanent fistula occlusion, which are oftentimes accompanied by an amelioration of neurological deficits in the long run. Here, we report our interdisciplinary neurosurgical/neuroradiological management strategy of SDAVFs in 32 patients who were evaluated retrospectively. We focused on clinical presentation, microneurosurgical and interventional technique, early, and late neurological results. Quality of life (QoL) was additionally assessed in 12 patients at last follow-up. We discuss the results against the background of the current literature. Our series and the literature indicate that clinical outcome after treatment of SDAVF is favorable in general. Both neurosurgical and neurointerventional therapies appear to be safe and effective, but short-term neurological deterioration after the intervention constitutes an as-of-yet unsolved problem. Beyond age and preoperative neurological state, presence of comorbidities had a significant influence on neurological outcome in our study sample. Self-assessed physical and mental QoL at long-term follow-up was reduced in quite a number of patients and was associated with a poorer neurological result as well as presence of comorbidities. The patients' perspective in terms of QoL was first investigated in this study, but further research on QoL and psychosocial impairment of SDAVF patients is needed to enable individualized counseling and rehabilitation strategies.


The microbiology of biological phosphorus removal in activated sludge systems.
Activated sludge systems are designed and operated globally to remove phosphorus microbiologically, a process called enhanced biological phosphorus removal (EBPR). Yet little is still known about the ecology of EBPR processes, the microbes involved, their functions there and the possible reasons why they often perform unreliably. The application of rRNA-based methods to analyze EBPR community structure has changed dramatically our understanding of the microbial populations responsible for EBPR, but many substantial gaps in our knowledge of the population dynamics of EBPR and its underlying mechanisms remain. This review critically examines what we once thought we knew about the microbial ecology of EBPR, what we think we now know, and what still needs to be elucidated before these processes can be operated and controlled more reliably than is currently possible. It looks at the history of EBPR, the currently available biochemical models, the structure of the microbial communities found in EBPR systems, possible identities of the bacteria responsible, and the evidence why these systems might operate suboptimally. The review stresses the need to extend what have been predominantly laboratory-based studies to full-scale operating plants. It aims to encourage microbiologists and process engineers to collaborate more closely and to bring an interdisciplinary approach to bear on this complex ecosystem.


The effects of probiotic and synbiotic supplementation on metabolic syndrome indices in adults at risk of type 2 diabetes: study protocol for a randomized controlled trial.
The incidence of type 2 diabetes, cardiovascular diseases, and obesity has been rising dramatically; however, their pathogenesis is particularly intriguing. Recently, dysbiosis of the intestinal microbiota has emerged as a new candidate that may be linked to metabolic diseases. We hypothesize that selective modulation of the intestinal microbiota by probiotic or synbiotic supplementation may improve metabolic dysfunction and prevent diabetes in prediabetics. In this study, a synthesis and study of synbiotics will be carried out for the first time in Iran. In a randomized triple-blind controlled clinical trial, 120 adults with impaired glucose tolerance based on the inclusion criteria will be selected by a simple random sampling method and will be randomly allocated to 6 months of 6 g/d probiotic, synbiotic or placebo. The fecal abundance of bacteria, blood pressure, height, weight, and waist and hip circumferences will be measured at baseline and following treatment. Also, plasma lipid profiles, HbA1C, fasting plasma glucose, and insulin levels, will be measured and insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) will be calculated at baseline and will be repeated at months 3, 6, 12, and 18. The data will be compared within and between groups using statistical methods. The results of this trial could contribute to the evidence-based clinical guidelines that address gut microbiota manipulation to maximize health benefits in prevention and management of metabolic syndrome in prediabetes. Iranian Registry of Clinical Trials: IRCT201511032321N2 . Registered on 27 February 2016.


Mechanisms of coronary flow reserve impairment in human hypertension. An integrated approach by transthoracic and transesophageal echocardiography.
The purpose of this study was to investigate the different mechanisms responsible for an impairment of coronary vasodilator capacity in hypertensive subjects by an integrated echocardiographic approach, including transesophageal Doppler echocardiography, which allows noninvasive monitoring of coronary flow velocity in the left anterior descending artery during pharmacological vasodilation. The study population consisted of 17 healthy control subjects and 33 hypertensive subjects: 10 without hypertrophy, 16 with mild to moderate hypertrophy, and 7 with severe left ventricular hypertrophy. Mean systolic and diastolic flow velocities were monitored basally (together with indexes of myocardial oxygen demand, such as heart rate, myocardial inotropism, and left ventricular wall stress) and during infusion of low-dose (0.56 mg/kg per 4 minutes) and high-dose (0.84 mg/kg per 9 minutes) dipyridamole. Coronary reserve was assessed as the ratio of mean diastolic velocity after high-dose dipyridamole and basal diastolic velocity, and minimum coronary resistance as the ratio of diastolic blood pressure and diastolic velocity after high-dose dipyridamole. Compared with the control group, in all hypertensive groups, coronary reserve was similarly decreased (3.54 +/- 0.84 versus 2.59 +/- 0.42, 2.29 +/- 0.46, and 2.43 +/- 0.71; P < .01) and minimum resistance increased (0.56 +/- 0.15 versus 0.75 +/- 0.31, 0.75 +/- 0.19, and 0.78 +/- 0.21 mm Hg.s-1.cm-1; P = NS). These results confirm that coronary reserve in hypertensive individuals is reduced even before the occurrence of left ventricular hypertrophy. The reduction in coronary reserve depends on both an increase in resting coronary flow and an impairment in maximal vasodilator capacity. An increase in resting flow is dependent on higher heart rate and wall stress in hypertensive subjects without ventricular hypertrophy and on increased myocardial mass in hypertensive subjects with hypertrophy. Hypertensive subjects with ventricular hypertrophy also demonstrated a significantly blunted response to low-dose dipyridamole.


Temporal and spatial regulation of pectic (1-->4)-beta-D-galactan in cell walls of developing pea cotyledons: implications for mechanical properties.
Modifications in cell wall pectic polysaccharides are thought to influence cell-cell adhesion and the mechanical properties of plant tissues. Monoclonal antibodies to epitopes occurring in homo- galacturonan and side chains of rhamnogalacturonan I have been used in an immunolocalization study of cell wall architecture of developing pea cotyledons. Pectic (1-->4)-beta-D-galactan appears in cotyledon cell walls at a defined stage late in development (approximately 26-30 days after anthesis), whereas homogalacturonan and pectic (1-->5)-alpha-L-arabinan are present in cotyledon cell walls throughout development. (1-->4)-beta-galactan was restricted to a distinct thin layer at the plasma membrane face of the cell wall. Anion exchange and immunoaffinity chromatography indicated that the (1-->4)-beta-galactan was associated with acidic pectic components. Mechanical compressive testing of pea cotyledons, before and after (1-->4)-beta-galactan appearance, indicated that the cotyledons with the galactan-rich cell wall layer were twice as firm as those with no detectable (1-->4)-beta-galactan.


[Psychological effects of road accidents: a challenge for public health].
The authors discuss psychological consequences of road accidents and the need for providing support for the victims and their families. The most common psychological effects include mental health problems, increased use of psychotropic drugs, and difficulty in performing occupational functions. Therefore, it is necessary to remodel the system of traffic safety and supplement it with a comprehensive system of support for both direct victims of accidents and their close relatives. To reach this goal, we need to develop optimal conditions for multidisciplinary research to investigate the effects of road accidents in Poland. This would make it possible to design effective psychological treatment and develop an institutional system for relevant support. However, some preventive measures can be taken right now, e.g., early intervention for severely injured victims during their hospital stay or providing support for non-injured victims and their families.


Managing discrimination in selection: the influence of directives from an authority and social dominance orientation.
The authors examined one manner in which to decrease the negative impact of social dominance orientation (SDO), an individual difference variable that indicates support for the "domination of 'inferior' groups by 'superior' groups" (J. Sidanius & F. Pratto, 1999, p. 48), on the selection of candidates from low-status groups within society. Consistent with the tenets of social dominance theory, in 2 studies we found that those high in SDO reported that they were less likely to select a potential team member who is a member of a low-status group (i.e., a White female in Study 1 and a Black male in Study 2) than those low in SDO. However, explicit directives from an authority moderated this effect such that those high in SDO were more likely to select both candidates when authority figures clearly communicated that job performance indicators should be used when choosing team members. Thus, our studies suggest that the negative effects of SDO may be attenuated if those high in SDO are instructed by superiors to use legitimate performance criteria to evaluate job candidates.