The Design, Characterization and Antibacterial Activity of Heat and Silver Crosslinked Poly(Vinyl Alcohol) Hydrogel Forming Dressings Containing Silver Nanoparticles.
The prompt treatment of burn wounds is essential but can be challenging in remote parts of Africa, where burns from open fires are a constant hazard for children and suitable medical care may be far away. Consequently, there is an unmet need for an economical burn wound dressing with a sustained antimicrobial activity that might be manufactured locally at low cost. This study describes and characterizes the novel preparation of a silver nitrate-loaded/poly(vinyl alcohol) (PVA) film. Using controlled heating cycles, films may be crosslinked with in situ silver nanoparticle production using only a low heat oven and little technical expertise. Our research demonstrated that heat-curing of PVA/silver nitrate films converted the silver to nanoparticles. These films swelled in water to form a robust, wound-compatible hydrogel which exhibited controlled release of the antibacterial silver nanoparticles. An optimal formulation was obtained using 5% (w/w) silver nitrate in PVA membrane films that had been heated at 140 °C for 90 min. Physical and chemical characterization of such films was complemented by in vitro studies that confirmed the effective antibacterial activity of the released silver nanoparticles against both gram positive and negative bacteria. Overall, these findings provide economical and simple methods to manufacture stable, hydrogel forming wound dressings that release antibiotic silver over prolonged periods suitable for emergency use in remote locations.


Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome.
Robinow syndrome is a short-limbed dwarfism characterized by abnormal morphogenesis of the face and external genitalia, and vertebral segmentation. The recessive form of Robinow syndrome (RRS; OMIM 268310), particularly frequent in Turkey, has a high incidence of abnormalities of the vertebral column such as hemivertebrae and rib fusions, which is not seen in the dominant form. Some patients have cardiac malformations or facial clefting. We have mapped a gene for RRS to 9q21-q23 in 11 families. Haplotype sharing was observed between three families from Turkey, which localized the gene to a 4. 9-cM interval. The gene ROR2, which encodes an orphan membrane-bound tyrosine kinase, maps to this region. Heterozygous (presumed gain of function) mutations in ROR2 were previously shown to cause dominant brachydactyly type B (BDB; ref. 7). In contrast, Ror2-/- mice have a short-limbed phenotype that is more reminiscent of the mesomelic shortening observed in RRS. We detected several homozygous ROR2 mutations in our cohort of RRS patients that are located upstream from those previously found in BDB. The ROR2 mutations present in RRS result in premature stop codons and predict nonfunctional proteins.


Analysis of TSC cortical tubers by deep sequencing of TSC1, TSC2 and KRAS demonstrates that small second-hit mutations in these genes are rare events.
Tuberous sclerosis complex (TSC) is an often severe neurocutaneous syndrome. Cortical tubers are the predominant neuropathological finding in TSC, and their number and location has been shown to correlate roughly with the severity of neurologic features in TSC. Past studies have shown that genomic deletion events in TSC1 or TSC2 are very rare in tubers, and suggested the potential involvement of the MAPK pathway in their pathogenesis. We used deep sequencing to assess all coding exons of TSC1 and TSC2, and the activating mutation hot spots within KRAS in 46 tubers from TSC patients. Germline heterozygous mutations were identified in 81% of tubers. The same secondary mutation in TSC2 was identified in six tuber samples from one individual. Further study showed that this second hit mutation was widely distributed in the cortex from one cerebral hemisphere of this individual at frequencies up to 10%. No other secondary mutations were found in the other 40 tubers analyzed. These data indicate that small second hit mutations in any of these three genes are very rare in TSC tubers. However, in one TSC individual, a second hit TSC2 point mutation occurred early during brain development, and likely contributed to tuber formation.


Enucleation in pancreatic surgery: indications, technique, and outcome compared to standard pancreatic resections.
Pancreatic surgery is a technically challenging intervention with high demands for preoperative diagnostics and perioperative management. A perioperative mortality rate below 5% is achieved in high-volume centers due to the high level of standardization in surgical procedures and perioperative care. Besides standard resections, certain indications may require individualized surgical concepts such as tumor enucleations. The aim of the study was to evaluate the indications, technique, and outcome of this limited local approach compared to major resections. Data from patients undergoing pancreatic surgery were prospectively recorded. All patients with tumor enucleations were compared with classical resections (pancreaticoduodenectomy or left resection) in a matched-pair analysis (1:2). Tumor type, localization, operative parameters, complications, and outcome were evaluated. Fifty-three patients underwent pancreatic tumor enucleation between October 2001 and December 2009. Indications included cystic lesions, IPMNs, and neuroendocrine pancreatic tumors. Enucleations were associated with shorter operation time, less blood loss as well as shorter ICU and hospital stay compared to pancreaticoduodenectomy and left resections. The overall surgical morbidity of enucleations was 28.3% without major complications. Leading clinical problems were ISGPF type A fistulas (20.8%) requiring prolonged primary drainage. No surgical revisions were necessary, and no deaths occurred. Pancreatic tumor enucleations can be carried out with good results and no mortality. Decisions regarding enucleations are highly individual compared to standard resections, underlining the importance of treatment in experienced high-volume institutions. Enucleations should be carried out whenever possible and oncologically feasible to prevent the typical complications of major pancreatic resection.


The Association between Fatalistic Beliefs and Late Stage at Diagnosis of Lung and Colorectal Cancer.
Fatalistic beliefs may be implicated in longer help-seeking intervals, and consequently, greater risk of advanced stage at cancer diagnosis. We examined associations between fatalism and stage at diagnosis in a population-based cohort of 4,319 U.S. patients with newly diagnosed lung or colorectal cancer participating in the Cancer Care Outcomes and Research Surveillance (CanCORS) study. Fatalistic beliefs were assessed with an established measure. A fatalism score (range, 4-16) was created by summing Likert scale responses to four items. Cancer stage at diagnosis was abstracted from medical records by trained staff. Logistic regression was used to assess the association between fatalism score and advanced stage at diagnosis (IV vs. I-III), adjusting for sociodemographic and clinical characteristics. Overall, 917 (21%) patients had stage IV cancers (lung: 28%, colorectal: 16%). The mean fatalism score was 10.7 (median = 11; interquartile range, 9-12). In adjusted analyses, a higher fatalism score was associated with greater odds of stage IV diagnosis (OR per unit increase in fatalism = 1.05; 95% confidence interval 1.02-1.08; P = 0.003). Patients with the highest fatalism score had an adjusted 8.9% higher frequency of stage IV diagnosis compared with patients with the lowest score (25.4% vs. 16.5%). In this large and socioeconomically, geographically, and ethnically diverse population of patients with lung and colorectal cancer, fatalistic beliefs were associated with higher risk of advanced stage at diagnosis. Longitudinal studies are needed to confirm causation. These findings support the value of incorporating information about the curability of early-stage cancers in public education campaigns.


In situ measurements of radiofrequency exposure levels in Greece from 2008 to 2013: a multi-parametric annual analysis.
From 2008 through 2013, more than 6,000 in situ frequency selective audits, in the proximity of base stations, were conducted throughout Greece by the Greek Atomic Energy Commission (EEAE), in order to verify exposure limit compliance. EEAE is the competent national authority for protection of the general public against artificially produced non-ionizing radiation. This paper presents the first post processing and multi-parametric year statistical analysis of in situ measurement data corresponding to 4,705 audits in the whole country, compared to general public exposure levels, according to Greek legislation. The aim is to derive nationwide conclusions for the characterization of general public exposure to radiofrequency electromagnetic fields, during the last 6 years. The results' presentation includes electric field exposure ratios referring to broadband and frequency selective measurements at the highest exposure measurement point. Statistical analysis is applied to assist the data presentation and evaluation, based on selected criteria and classification parameters, including: (i) year (2008-2013); (ii) environment (urban/suburban/rural); (iii) frequency bands of selected common telecommunication services (e.g., TV, FM, GSM, DCS, UMTS); and (iv) number of service providers installed at the same site. In general, measurement results revealed that the vast majority of exposure values were below reference levels for general public exposure, as defined by Greek legislation. Data are constantly updated with the latest measurements, including emerging wireless technologies.


Impact of urinary and climacteric symptoms on social and sexual life after surgical treatment of stress urinary incontinence in women: a long-term outcome.
The aim of the present study was to evaluate the long-term results of surgical treatment of stress urinary incontinence (SUI) using both subjective and objective methods. Few studies have focused on the influence of biological and social changes in a woman's life on the long-term outcome of surgical treatment of stress urinary incontinence. The study included 45 women with genuine SUI treated with either retropubic urethrocystopexy (n=30) or puboccocygeal repair (n=15). The assessment included interviews, questionnaires, urinary diary, pad test, continence test and urodynamic investigation. The results were evaluated at intervals of 3 months, 1 year and 5--7 years after the treatment. One year after the surgical treatment 71% of the women in the urethrocystopexy group and 80% in the pubococcygeal repair group were subjectively cured, while 5--7 years after surgery the corresponding values were 43% vs. 60%. However, according to pad test a 67% of the women in the urethrocystopexy group and 47% in the pubococcygeal repair group had ceased to leak urine 1 year after the operation whereas at the long-term follow-up the corresponding values were 64% vs. 71%. According to the questionnaire at the long-term follow-up only 35% of the women in the whole group had genuine SUI whereas 21% had urge-incontinence. Moreover, 37% experienced sweating, 23% flushing and 44% vaginal dryness. The number of women with adiposity had increased significantly (P < 0.001) at the long-term follow-up. Twenty-eight per cent of the women decreased their activities whereas the majority experienced no impediment. Seventy-nine per cent reported that they were sexually active and the majority reported satisfaction with their sexual lives. Accurate assessment of postoperative results of SUI demands rigorous recording of subjective and objective data taking into consideration psychological and social factors, otherwise there is a high risk of bias in the interpretation of the results of the treatment for SUI. This study indicates that, in order to give women with SUI adequate treatment the nursing care should comprehend the women's divergent experiences of urinary incontinence and its impact on social and sexual life.


Isolation of a mycoplasma from sarcoid tissue.
Using a modified cell-free culture medium, a mycoplasma was isolated from sarcoid lymph nodes in two cases and from sarcoid skin lesions in four out of seven cases of chronic sarcoidosis. Growth inhibition tests showed that the isolates were related to Mycoplasma orale type 1. By the indirect haemagglutination method, 244 cases of definite or probable sarcoidosis, 160 patients with other diseases, and 355 blood donors were tested for antibodies against an isolated mycoplasma (strain 215-M). Titres [unk] 16 were found in 14% of the patients with sarcoidosis and in 8% of the patients with other diseases but only in 0.6% of the blood donors. The proportion of patients with high antibody titres among those with sarcoidosis and erythema nodosum was smaller (8%) than among those with other forms of sarcoidosis (17%). The role of the mycoplasmas isolated from sarcoid tissues remains obscure, but it is possible that these organisms are only an expression of altered immunity in sarcoidosis.


The case for diet: a safe and efficacious strategy for secondary stroke prevention.
Diet is strongly associated with risk for first stroke. In particular, observational and experimental research suggests that a Mediterranean-type diet may reduce risk for first ischemic stroke with an effect size comparable to statin therapy. These data for first ischemic stroke suggest that diet may also be associated with risk for recurrent stroke and that diet modification might represent an effective intervention for secondary prevention. However, research on dietary pattern after stroke is limited and direct experimental evidence for a therapeutic effect in secondary prevention does not exist. The uncertain state of science in this area is reflected in recent guidelines on secondary stroke prevention from the American Heart Association, in which the Mediterranean-type diet is listed with only a class IIa recommendation (level of evidence C). To change guidelines and practice, research is needed, starting with efforts to better define current nutritional practices of stroke patients. Food frequency questionnaires and mobile applications for real-time recording of intake are available for this purpose. Dietary strategies for secondary stroke prevention are low risk, high potential, and warrant further evaluation.


Accuracy of Consumer Monitors for Estimating Energy Expenditure and Activity Type.
Increasing use of consumer-based physical activity (PA) monitors necessitates that they are validated against criterion measures. Thus, the purpose of this study was to examine the accuracy of three consumer-based PA monitors for estimating energy expenditure (EE) and PA type during simulated free-living activities. Twenty-eight participants (mean ± SD: age, 25.5 ± 3.7 yr; body mass index, 24.9 ± 2.6 kg·m) completed 11 activities ranging from sedentary behaviors to vigorous intensities. Simultaneous measurements were made with an Oxycon portable calorimeter (criterion), a Basis Peak and Garmin Vivofit on the nondominant wrist, and three Withings Pulse devices (right hip, shirt collar, dominant wrist). Repeated-measures ANOVA were used to examine differences between measured and predicted EE. Intraclass correlation coefficients were calculated to determine reliability of EE predictions between Withings placements. Paired samples t tests were used to determine mean differences between observed minutes and Basis Peak predictions during walking, running, and cycling. On average, the Basis Peak was within 8% of measured EE for the entire PA routine (P > 0.05); however, there were large individual errors (95% prediction interval, -290.4 to +233.1 kcal). All other devices were significantly different from measured EE for the entire PA routine (P < 0.05). For activity types, Basis Peak correctly identified ≥92% of actual minutes spent walking and running (P > 0.05), and 40.4% and 0% of overground and stationary cycling minutes, respectively (P < 0.001). The Basis Peak was the only device that did not significantly differ from measured EE; however, it also had the largest individual errors. Additionally, the Basis Peak accurately predicted minutes spent walking and running, but not cycling.


Mobility of NMDA autoreceptors but not postsynaptic receptors at glutamate synapses in the rat entorhinal cortex.
NMDA receptors (NMDAr) are known to undergo recycling and lateral diffusion in postsynaptic spines and dendrites. However, NMDAr are also present as autoreceptors on glutamate terminals, where they act to facilitate glutamate release, but it is not known whether these receptors are also mobile. We have used functional pharmacological approaches to examine whether NMDA receptors at excitatory synapses in the rat entorhinal cortex are mobile at either postsynaptic sites or in presynaptic terminals. When NMDAr-mediated evoked EPSCs (eEPSCs) were blocked by MK-801, they showed no evidence of recovery when the irreversible blocker was removed, suggesting that postsynaptic NMDAr were relatively stably anchored at these synapses. However, using frequency-dependent facilitation of AMPA receptor (AMPAr)-mediated eEPSCs as a reporter of presynaptic NMDAr activity, we found that when facilitation was blocked with MK-801 there was a rapid (approximately 30-40 min) anomalous recovery upon removal of the antagonist. This was not observed when global NMDAr blockade was induced by combined perfusion with MK-801 and NMDA. Anomalous recovery was accompanied by an increase in frequency of spontaneous EPSCs, and a variable increase in frequency-facilitation. Following recovery from blockade of presynaptic NMDAr with a competitive antagonist, frequency-dependent facilitation of AMPAr-mediated eEPSCs was also transiently enhanced. Finally, an increase in frequency of miniature EPSCs induced by NMDA was succeeded by a persistent decrease. Our data provide the first evidence for mobility of NMDAr in the presynaptic terminals, and may point to a role of this process in activity-dependent control of glutamate release.


Predictive value of CT angiography source image ASPECTS in patients with anterior circulation acute ischemic stroke after endovascular treatment: ultimate infarct size and clinical outcome.
The objective of this study was to investigate the predictive value of computed tomographic angiography (CTA) source image Alberta Stroke Program Early CT Score (ASPECTS) on clinical outcome and final infarction extent after endovascular treatment (EVT) in patients with acute ischemic stroke (AIS). M: ethods : All eligible patients from January 2014 to March 2018 undergoing EVT due to anterior circulation AIS were retrospectively reviewed. The baseline ASPECTS on initial noncontrast CT (NCCT) and the CTA source image were compared with the follow-up MR diffusion-weighted imaging (DWI) ASPECTS. Receiver operating characteristic (ROC) curve analysis was used to assess the predictive value of CTA ASPECTS for prediction of final infarct extent and good clinical outcome. Our sample included a total of 122 eligible patients (64 males, mean age 70 years) with a median baseline National Institute of Health Stroke Scale (NIHSS) score of 12. Baseline ASPECTS on the CTA source image correlated with follow-up MR DWI ASPECTS better than NCCT ASPECTS (P<0.001). ROC curve analysis revealed baseline CTA ASPECTS (area under the curve [AUC] =0.74, 95% CI: 0.65 to 0.83, P<0.001) can better predict favorable functional outcome than NCCT ASPECTS (AUC=0.64, 95% CI: 0.54 to 0.74, P=0.008). Baseline NIHSS score <15, CTA ASPECTS≥8, and successful recanalization were independent predictors of good clinical outcomes. The ASPECTS on the CTA source image provides more information in the prediction of good clinical outcome and final infarction size than NCCT in patients with AIS treated with EVT.


Yokoyama procedure for cyclic strabismus with axial high myopia:a case report.
It is a very rare form of ocular motility characterized by alternating strabismus and orthotropia. We report a patient with a 48-h cycle of esohypotropia associated with axial high myopia that resolved by Yokoyama procedure. A 43-year-old female patient who underwent left medial rectus muscle recession and lateral rectus muscle resection elsewhere due to highly myopic strabismus 2 years ago. The patient experienced a recurrence of left esohypotropia 12 months after undergoing surgery, exhibiting a 48-hour cycle. The cycle is one full day of esohypotropia and one day of orthotropia. The patient exhibited a case of high myopia in the left eye, characterized by a diopter measurement of -24.00DS and an eye axis measurement of 28.43 mm. Orbital CT showed supertemporal dislocation of the posterior portion of the elongated globe out from the muscle cone. Based on these observations, we performed Yokoyama procedure by uniting the muscle bellies of the superior rectus(SR) and lateral rectus (LR) muscles to restoring the dislocated globe back into the muscle cone. When cyclic strabismus is combined with axial high myopia, the Yokoyama procedure was effective and cycles are successfully terminated without overcorrection on no squint days. The purpose of this procedure is to put the dislocated globe back into its muscle cone by uniting the muscle bellies of the superior rectus and lateral rectus.


[Investigation of bacterial and viral etiology in community acquired central nervous system infections with molecular methods].
In this multicenter prospective cohort study, it was aimed to evaluate the bacterial and viral etiology in community-acquired central nervous system infections by standart bacteriological culture and multiplex polymerase chain reaction (PCR) methods. Patients hospitalized with central nervous system infections between April 2012 and February 2014 were enrolled in the study. Demographic and clinical information of the patients were collected prospectively. Cerebrospinal fluid (CSF) samples of the patients were examined by standart bacteriological culture methods, bacterial multiplex PCR (Seeplex meningitis-B ACE Detection (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Group B streptococci) and viral multiplex PCR (Seeplex meningitis-V1 ACE Detection kits herpes simplex virus-1 (HSV1), herpes simplex virus-2 (HSV2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus 6 (HHV6)) (Seeplex meningitis-V2 ACE Detection kit (enteroviruses)). Patients were classified as purulent meningitis, aseptic meningitis and encephalitis according to their clinical, CSF (leukocyte level, predominant cell type, protein and glucose (blood/CSF) levels) and cranial imaging results. Patients who were infected with a pathogen other than the detection of the kit or diagnosed as chronic meningitis and other diseases during the follow up, were excluded from the study. A total of 79 patients (28 female, 51 male, aged 42.1 ± 18.5) fulfilled the study inclusion criteria. A total of 46 patients were classified in purulent meningitis group whereas 33 were in aseptic meningitis/encephalitis group. Pathogens were detected by multiplex PCR in 41 patients. CSF cultures were positive in 10 (21.7%) patients (nine S.pneumoniae, one H.influenzae) and PCR were positive for 27 (58.6%) patients in purulent meningitis group. In this group one type of bacteria were detected in 18 patients (14 S.pneumoniae, two N.meningitidis, one H.influenzae, one L.monocytogenes). Besides, it is noteworthy that multiple pathogens were detected such as bacteria-virus combination in eight patients and two different bacteria in one patient. In the aseptic meningitis/encephalitis group, pathogens were detected in 14 out of 33 patients; single type of viruses in 11 patients (seven enterovirus, two HSV1, one HSV2, one VZV) and two different viruses were determined in three patients. These data suggest that multiplex PCR methods may increase the isolation rate of pathogens in central nervous system infections. Existence of mixed pathogen growth is remarkable in our study. Further studies are needed for the clinical relevance of this result.


Neuromodulation Induced by Sitagliptin: A New Strategy for Treating Diabetic Retinopathy.
Diabetic retinopathy (DR) involves progressive neurovascular degeneration of the retina. Reduction in synaptic protein expression has been observed in retinas from several diabetic animal models and human retinas. We previously reported that the topical administration (eye drops) of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, prevented retinal neurodegeneration induced by diabetes in db/db mice. The aim of the present study is to examine whether the modulation of presynaptic proteins is a mechanism involved in the neuroprotective effect of sitagliptin. For this purpose, 12 db/db mice, aged 12 weeks, received a topical administration of sitagliptin (5 μL; concentration: 10 mg/mL) twice per day for 2 weeks, while other 12 db/db mice were treated with vehicle (5 μL). Twelve non-diabetic mice (db/+) were used as a control group. Protein levels were assessed by western blot and immunohistochemistry (IHC), and mRNA levels were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Our results revealed a downregulation (protein and mRNA levels) of several presynaptic proteins such as synapsin I (Syn1), synaptophysin (Syp), synaptotagmin (Syt1), syntaxin 1A (Stx1a), vesicle-associated membrane protein 2 (Vamp2), and synaptosomal-associated protein of 25 kDa (Snap25) in diabetic mice treated with vehicle in comparison with non-diabetic mice. These proteins are involved in vesicle biogenesis, mobilization and docking, membrane fusion and recycling, and synaptic neurotransmission. Sitagliptin was able to significantly prevent the downregulation of all these proteins. We conclude that sitagliptin exerts beneficial effects in the retinas of db/db mice by preventing the downregulation of crucial presynaptic proteins. These neuroprotective effects open a new avenue for treating DR as well other retinal diseases in which neurodegeneration/synaptic abnormalities play a relevant role.


Risk factor management in survivors of stroke: a double-blind, cluster-randomized, controlled trial.
Comprehensive community care has the potential to improve risk factor management of patients with stroke or transient ischaemic attack. The primary aim is to determine the effectiveness of an individualized management program on risk factor management for patients discharged from hospital after stroke. Multicentre, cluster-randomized, controlled trial, with clusters by general practice. Participants are randomized to receive intervention or control after a baseline assessment undertaken after discharge from hospital. The general practice they attend is marked as an intervention or control accordingly. All subsequent participants attending those practices are automatically assigned as intervention or control. Baseline and all outcome assessments, including an analysis of risk factors, are undertaken by assessors blinded to patient randomization. Based on the results of blinded assessments, the individualized management program group will receive targeted advice on how to manage their risk factors using a standardized, evidence-based template to communicate 'ideal' management with their general practitioner. In addition, patients randomized to the individualized management program group will receive counselling and education about stroke risk factor management by an intervention study nurse. Individualized management programs will be reviewed at three-months, six-months, 12 months, and 18 months after stroke, at which times they will be modified if appropriate. Stroke risk management will be evaluated using changes in the Framingham cardiovascular risk score. Analysis will be on an intention-to-treat basis using analysis of covariance or generalized linear model to adjust for baseline risk score and other relevant confounding factors.


Localization of genes encoding egg modifiers of paternal genome function to mouse chromosomes one and two.
It is now well established that genomic imprinting effects in mammals require a combination of epigenetic modifications imposed during gametogenesis and additional modifications imposed after fertilization. The earliest post-fertilization modifications to be imposed on the genome are those thought to be mediated by factors in the egg cytoplasm. Strain-dependent differences in the actions of these egg modifiers in mice reveal an important potential for genetic variability in the imprinting process, and also provide valuable genetic systems with which to identify some of the factors that participate in imprinting. Previous studies documented a strain-dependent difference in the modification of paternal genome function between the C57BL/6 and DBA/2 mouse strains. This difference is revealed as a difference in developmental potential of androgenetic embryos produced with eggs from females of the two strains by nuclear transplantation. The specificity of the effect for the paternal genome is consistent with an effect on imprinted genes. The egg phenotype is largely independent of the genotype of the fertilizing sperm, and the C57BL/6 phenotype is dominant in reciprocal F1 hybrids. Genetic studies demonstrated that the difference in egg phenotypes between the two strains is most likely controlled by two independently segregating loci. We now report the results of experiments in which the egg phenotypes of the available BxD recombinant inbred mouse strains have been determined. The results of the analysis are consistent with the two locus model, and we have identified candidate chromosomal locations for the two loci. These data demonstrate clearly that differences in how the egg cytoplasm modifies the incoming paternal genome are indeed genetically determined, and vary accordingly.


Treatment Algorithm for Surgical Site Infections Following Extensor Mechanism Repair.
Despite general agreement regarding techniques for extensor mechanism repair, there is very limited guidance in the literature for the management of surgical site infections (SSIs) that may occur after these procedures. Early or mild superficial SSIs, such as cellulitis, can be managed on an outpatient basis while monitoring for improvement, with escalated intervention if the symptoms do not resolve within 1 week. Deep SSIs should be managed more aggressively with surgical irrigation and debridement (I&D), including the knee joint, depending on the results of the aspiration, removal of all braided nonabsorbable suture (if necessary) with immediate or delayed exchange with monofilament suture, and the administration of parenteral antibiotics based on culture results and an infectious disease consult. Arthrocentesis should be performed early to monitor for the spread of infection to the joint space, and diagnosis of a septic knee joint should be immediately followed by arthroscopic or open I&D. For refractory cases (i.e., wound coverage issues or persistent infections despite multiple attempts at debridement), a consult with a plastic surgeon for consideration of a gastrocnemius flap is recommended, and surgeons should remain suspicious of the possibility of the contiguous spread of osteomyelitis.


Ventricular tachycardia ablation.
The role of catheter ablation in the treatment of ventricular arrhythmias has been changing in the last decade, and this form of therapy now aims at curing multiple ventricular tachycardia morphologies and complex substrates in patients with structural heart disease (post-infarction and idiopathic dilated cardiomyopathy). Under these circumstances, conventional mapping is not feasible and accurate, and the development of new diagnostic methods has become necessary. The non-contact mapping system has been introduced to study the activation pattern of any ventricular arrhythmia by a "single-cycle" analysis, and has brought to the characterization of unstable and of non-sustained forms of arrhythmia. The evaluation of the arrhythmogenic substrate has similarly become more precise by the more common use of the electroanatomic mapping (CARTO), which is being applied to identify areas of scarred tissue responsible for ventricular arrhythmias, to map stable tachycardias and to validate the creation of a line of block. By means of this technological advancement, the identification of critical isthmi and deep intramural circuits has also led to new ablation strategies, frequently simplifying the procedure and minimizing complications.


Psychosocial Response to New-Onset Diabetes as a Long-Term Effect of Allogeneic Hematopoietic Stem Cell Transplantation.
Currently, little information is available to guide health care practitioners on how to facilitate positive outcomes in individuals who develop new-onset diabetes after allogeneic hematopoietic stem cell transplantation (allo HSCT) for treatment of hematological cancers. Results from this constructivist grounded theory study provide a theoretical framework explaining the psychosocial process of change that middle-age and older adults experience when developing new-onset diabetes in this context. Two predominant factors influenced this change: treatment burden and perception of diabetes. Key findings were that participants with ongoing complications, primarily graft-versus-host disease, experienced a high degree of treatment-related burden and unclear perceptions of diabetes when compared with those with no or few post-allo-HSCT complications. These factors limited their capacity to positively respond to and self-manage their condition. Implications for practice are to thoroughly consider these two factors when developing patient-centered interventions for middle-age and older adults with new-onset diabetes after allo HSCT.


Incidence of Respiratory Syncytial Virus Infection in Older Adults: Limitations of Current Data.
Respiratory syncytial virus (RSV) is an important cause of severe respiratory illness in older adults and adults with respiratory or cardiovascular comorbidities. Published estimates of its incidence and prevalence in adult groups vary widely. This article reviews the potential limitations affecting RSV epidemiology studies and suggests points to consider when evaluating or designing them. Studies reporting the incidence or prevalence of RSV infection in adults in high-income Western countries from 2000 onwards were identified via a rapid literature review. Author-reported limitations were recorded, together with presence of other potential limitations. Data were synthesized narratively, with a focus on factors affecting incidence estimates for symptomatic infection in older adults. A total of 71 studies met the inclusion criteria, most in populations with medically attended acute respiratory illness (ARI). Only a minority used case definitions and sampling periods tailored specifically to RSV; many used influenza-based or other criteria that are likely to result in RSV cases being missed. The great majority relied solely on polymerase chain reaction (PCR) testing of upper respiratory tract samples, which is likely to miss RSV cases compared with dual site sampling and/or addition of serology. Other common limitations were studying a single season, which has potential for bias due to seasonal variability; failure to stratify results by age, which underestimates the burden of severe disease in older adults; limited generalizability beyond a limited study setting; and absence of measures of uncertainty in the reporting of results. A significant proportion of studies are likely to underestimate the incidence of RSV infection in older adults, although the effect size is unclear and there is also potential for overestimation. Well-designed studies, together with increased testing for RSV in patients with ARI in clinical practice, are required to accurately capture both the burden of RSV and the potential public health impact of vaccines.


The persistence of bovine gamma-globulin injected as an antigen into rabbits; a comparison with its previously studied persistence in mice.
A sensitive biological test has been used to detect the persistence of minute traces of a foreign protein, bovine gamma-globulin, in the blood and livers of rabbits intravenously injected with it, as an antigen. At various intervals after injecting these rabbits (donors) serum or liver tissue was transferred from them to the peritoneal cavities of normal or unilaterally adrenalectomized mice (recipients) with the aim of rendering the latter hypersensitive to the antigen that might be persisting in the transferred materials; a state of affairs detectable, 2 days later, by the appearance of signs of reversed passive anaphylaxis when the recipient mice were intravenously challenged with a strong anti-bovine gamma-globulin rabbit serum. The protein persisted in the blood of the donor rabbits, in readily demonstrable amounts for 1 month, and in the blood of one animal, in minute traces, or as long as 6 weeks. It was detectable in the livers for 8 weeks. The persistence of bovine gamma-globulin in rabbits, which form circulating antibodies to it well, is not as long as that in mice, which form antibodies to it poorly, since in previous work with the mouse the antigen was found (1) in the blood after 8 weeks and in the liver for 14 weeks. Nevertheless the antigen persists in the rabbit much longer than is generally supposed. Indeed it can be found in the liver all through the period in which circulating antibody is demonstrable in the blood. Explanations for the phenomenon have been suggested. Its significance in relation to the mechanisms of antibody formation is obvious.


Time-Dependent Image Restoration of Low-SNR Live-Cell Ca2 Fluorescence Microscopy Data.
Live-cell Ca2+ fluorescence microscopy is a cornerstone of cellular signaling analysis and imaging. The demand for high spatial and temporal imaging resolution is, however, intrinsically linked to a low signal-to-noise ratio (SNR) of the acquired spatio-temporal image data, which impedes on the subsequent image analysis. Advanced deconvolution and image restoration algorithms can partly mitigate the corresponding problems but are usually defined only for static images. Frame-by-frame application to spatio-temporal image data neglects inter-frame contextual relationships and temporal consistency of the imaged biological processes. Here, we propose a variational approach to time-dependent image restoration built on entropy-based regularization specifically suited to process low- and lowest-SNR fluorescence microscopy data. The advantage of the presented approach is demonstrated by means of four datasets: synthetic data for in-depth evaluation of the algorithm behavior; two datasets acquired for analysis of initial Ca2+ microdomains in T-cells; finally, to illustrate the transferability of the methodical concept to different applications, one dataset depicting spontaneous Ca2+ signaling in jGCaMP7b-expressing astrocytes. To foster re-use and reproducibility, the source code is made publicly available.


Lessons from a patient partnership intervention to prevent adverse drug events.
Patient safety 'best practices' that call for patient participation to prevent adverse drug events have not been rigorously evaluated. To consider lessons learned from a patient partnership intervention to prevent adverse drug events among medical in-patients. Prospective randomized, controlled pilot trial. Boston teaching hospital. Patients. Two hundred and nine adult in-patients on a general medicine unit. Intervention patients (n = 107) received drug safety information and their medication list; controls (n = 102) received drug safety information only. Measurements. Adverse drug events and close-call drug errors were identified using chart review and incident reports from nurses, pharmacists, and physicians. Patients and clinicians were surveyed about the intervention. In 1053 patient-days at risk, 11 patients experienced 12 adverse drug events and 16 patients experienced 18 close calls. There was a non-significant difference between intervention patients and controls in survey responses and in the adverse drug event rate (8.4% versus 2.9%, P = 0.12) and close-call rate (7.5% versus 9.8%, P = 0.57). Eleven percent of patients were aware of drug-related mistakes during the hospitalization. Among nurse respondents, 29% indicated that at least one medication error was prevented when a patient or family member identified a problem. Partnering with in-patients to prevent adverse drug events is a promising strategy but requires further study to document its efficacy.


Reduction of endocytic activity accelerates cell elimination during tissue remodeling of the Drosophila epidermal epithelium.
Epithelial tissues undergo cell turnover both during development and for homeostatic maintenance. Cells that are no longer needed are quickly removed without compromising the barrier function of the tissue. During metamorphosis, insects undergo developmentally programmed tissue remodeling. However, the mechanisms that regulate this rapid tissue remodeling are not precisely understood. Here, we show that the temporal dynamics of endocytosis modulate physiological cell properties to prime larval epidermal cells for cell elimination. Endocytic activity gradually reduces as tissue remodeling progresses. This reduced endocytic activity accelerates cell elimination through the regulation of Myosin II subcellular reorganization, junctional E-cadherin levels, and caspase activation. Whereas the increased Myosin II dynamics accelerates cell elimination, E-cadherin plays a protective role against cell elimination. Reduced E-cadherin is involved in the amplification of caspase activation by forming a positive-feedback loop with caspase. These findings reveal the role of endocytosis in preventing cell elimination and in the cell-property switching initiated by the temporal dynamics of endocytic activity to achieve rapid cell elimination during tissue remodeling.


Phagosome fusion vesicles of Paramecium. II. Freeze-fracture evidence for membrane replacement.
Phagosome fusion vesicles (PFVs), a new population of relatively large granules in Paramecium caudatum which fuse with the first stage of digestive vacuoles (DV-I) shortly after these vacuoles are released from the cytopharynx (their site of formation), have been studied by using the freeze-fracture technique. Identification of PFVs is possible in the resulting replicas at all sites where they are commonly found in thin sections, at the cytopharynx, bound but not fused with nascent digestive vacuoles and fused with released vacuoles in the cell's posterior end. These PFVs have membranes which do not resemble the membranes of the forming digestive vacuole membrane or the discoidal vesicle membranes from which vacuole membrane is derived. Their smooth E-fracture face with only 50 to 100 intramembrane particles (IMPs) per micrometers 2 and particulate P-face (approximately 2500 IMPs/micrometers) do resemble the second vacuole stage (DV-II) which is characterized by a smaller diameter and acid pH. Evidence is presented for PFV fusion with the DV-I and for membrane replacement, at least in part, as the DV-I becomes a DV-II. Membrane replacement entails first adding PFVs to the DV-I and then removing the original discoidal vesicle-derived membrane as tubules as the vacuole condenses. Implications of the possible role of PFVs in forming intravacuolar symbiotic relationships are also discussed.


Protein Kinase CK2 Acts as a Molecular Brake to Control NADPH Oxidase 1 Activation and Colon Inflammation.
NADPH oxidase 1 (NOX1) has emerged as a prime regulator of intestinal mucosa immunity and homeostasis. Dysregulation of NOX1 may cause inflammatory bowel disease (IBD). It is not clear how NOX1 is regulated in vivo under inflammatory conditions. We studied the role of CK2 in this process. The NOX1 organizer subunit, NADPH oxidase organizer 1 (NOXO1), was immunoprecipitated from cytokine-treated colon epithelial cells, and bound proteins were identified by mass spectrometry analysis. Sites on NOXO1 phosphorylated by CK2 were identified by nanoscale liquid chromatography coupled to tandem mass spectrometry. NOX1 activity was determined in colon epithelial cells and colonoids in the presence or absence of CX-4945, a CK2 specific inhibitor. Acute colitis was induced by administration of trinitrobenzenesulfonic acid in mice treated or not with CX-4945. Colon tissues were analyzed by histologic examination, quantitative polymerase chain reaction, and Western blots. CK2 activity, markers of inflammation, and oxidative stress were assessed. We identified CK2 as a major partner of NOXO1 in colon epithelial cells under inflammatory conditions. CK2 directly binds NOXO1 at the C-terminus containing the Phox homology domain and phosphorylates NOXO1 on several sites. CX-4945 increased ROS generation by NOX1 in human colon epithelial cells and organoids. Strikingly, CK2 activity was reduced in trinitrobenzenesulfonic acid-induced acute colitis, and CX-4945 exacerbated colitis inflammation as shown by increased levels of CXCL1, ROS generation, lipid peroxidation, and colon damage. The ubiquitous protein kinase CK2 limits NOX1 activity via NOXO1 binding and phosphorylation in colonic epithelial cells and lessens experimental colitis. Loss of CK2 activity during acute colitis results in excessive ROS production, contributing to the pathogenesis. Strategies to activate CK2 could be an effective novel therapeutic approach in IBD.


Intestinal transplantation: an update.
As outcomes with intestinal transplantation continue to improve, its role in the management of intestinal failure patients becomes clearer. Some intestinal failure patients do well with long-term total parenteral nutrition (TPN), while others develop life-threatening complications and need to be evaluated for intestinal transplants (ITs). The purpose of this review is to update the current status of intestinal transplantation and its role in the management of intestinal failure patients. Current outcomes indicate that intestinal transplants should be considered earlier in intestinal failure patients that develop liver injury, to prevent irreversible liver disease that would mandate a simultaneous liver transplant. Due to the small bowel (SB) graft's unique immunobiologic features, it is especially challenging to transplant successfully. Although new immunosuppressive strategies have been developed that appear to improve short-term results, their impact on long-term outcomes has yet to be shown. A better understanding of the interactions that occur between the SB's inherent immune system and its luminal flora may be required to devise strategies that will significantly curtail the SB graft's immunogenicity. Intestinal transplantation remains a significant challenge. Ongoing efforts to better define the parameters that best predict total parenteral nutrition failure and the unique mechanisms that influence small bowel allograft outcomes are necessary before a broader application of small bowel transplantation can be indicated.


EGFR testing and erlotinib use in non-small cell lung cancer patients in Kentucky.
This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from 0.1% to 10.6% over the evaluated period while erlotinib use ranged from 3.4% to 5.4%. Factors associated with no EGFR testing were older age, male gender, enrollment in Medicaid or Medicare, smoking, and geographic region. Factors associated with not receiving erlotinib included older age, male gender, enrollment in Medicare or Medicaid, and living in moderate to high poverty. Survival analysis demonstrated EGFR testing or erlotinib use was associated with a higher likelihood of survival. EGFR testing and erlotinib prescribing were slow to be implemented in our predominantly rural state. While population-level factors likely contributed, patient factors, including geographic location (areas with high poverty rates and rural regions) and insurance type, were associated with lack of use, highlighting rural disparities in the implementation of cancer precision medicine.


Inorganic polyphosphate interacts with nucleolar and glycosomal proteins in trypanosomatids.
Inorganic polyphosphate (polyP) is a polymer of three to hundreds of phosphate units bound by high-energy phosphoanhydride bonds and present from bacteria to humans. Most polyP in trypanosomatids is concentrated in acidocalcisomes, acidic calcium stores that possess a number of pumps, exchangers, and channels, and are important for their survival. In this work, using polyP as bait we identified > 25 putative protein targets in cell lysates of both Trypanosoma cruzi and Trypanosoma brucei. Gene ontology analysis of the binding partners found a significant over-representation of nucleolar and glycosomal proteins. Using the polyphosphate-binding domain (PPBD) of Escherichia coli exopolyphosphatase (PPX), we localized long-chain polyP to the nucleoli and glycosomes of trypanosomes. A competitive assay based on the pre-incubation of PPBD with exogenous polyP and subsequent immunofluorescence assay of procyclic forms (PCF) of T. brucei showed polyP concentration-dependent and chain length-dependent decrease in the fluorescence signal. Subcellular fractionation experiments confirmed the presence of polyP in glycosomes of T. brucei PCF. Targeting of yeast PPX to the glycosomes of PCF resulted in polyP hydrolysis, alteration in their glycolytic flux and increase in their susceptibility to oxidative stress.


Extraction and Characterization of Inulin-Type Fructans from Artichoke Wastes and Their Effect on the Growth of Intestinal Bacteria Associated with Health.
Globe artichoke is an intriguing source of indigestible sugar polymers such as inulin-type fructans. In this study, the effect of ultrasound in combination with ethanol precipitation to enhance the extraction of long chain fructans from artichoke wastes has been evaluated. The inulin-type fructans content both from bracts and stems was measured using an enzymatic fructanase-based assay, while its average degree of polymerization (DP) was determined by HPLC-RID analysis. Results show that this method provides artichoke extracts with an inulin-type fructans content of 70% with an average DP between 32 and 42 both in bracts and in stems. The prebiotic effect of long chain inulins from artichoke extract wastes was demonstrated by its ability to support the growth of five Lactobacillus and four Bifidobacterium species, previously characterized as probiotics. Besides, we considered the possibility to industrialize the process developing a simpler method for the production of inulin-type fructans from the artichoke wastes so that the artichoke inulin preparation could be suitable for its use in synbiotic formulations in combination with different probiotics for further studies including in vivo trials.


Immunopathogenesis of HIV infection in cocaine users: role of arachidonic acid.
Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE2), thromboxane A2 receptor (TBXA2R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), 14-3-3 ζ/δ and 5-lipoxygenase (5-LOX) mediated induction of IDC immune dysfunctions in cocaine using HIV positive patients. The plasma levels of AA, PGE2, 15d-PGJ2, 14-3-3 ζ/δ and IDC intracellular COX-2 and 5-LOX expression were assessed in cocaine users, HIV positive patients, HIV positive cocaine users and normal subjects. Results showed that plasma concentration levels of AA, PGE2 and COX-2, TBXA2R and 5-LOX in IDCs of HIV positive cocaine users were significantly higher whereas 15d-PGJ2 and 14-3-3 ζ/δ were significantly reduced compared to either HIV positive subjects or cocaine users alone. This report demonstrates that AA metabolites are capable of mediating the accelerative effects of cocaine on HIV infection and disease progression.


Differences in the electrophysiological response of canine ventricular epicardium and endocardium to ischemia. Role of the transient outward current.
Acute ischemia is known to produce more severe electrophysiological disturbances in canine ventricular epicardium than endocardium, although the mechanism for the differential sensitivity is still unresolved. Recent studies have demonstrated the presence of a prominent transient outward current (Ito) in ventricular epicardium but not endocardium. The present study was designed to test the hypothesis that the differential sensitivity of these two tissues to ischemia results, at least in part, from a more prominent Ito in epicardium than in endocardium. Isolated canine ventricular epicardial and endocardial tissues and myocytes were studied by standard microelectrode techniques. Simulated ischemia (hyperkalemia, hypoxia, and acidosis) abolished the action potential plateau and caused a 50% to 60% shortening of action potential duration in epicardium but only a 10% to 20% shortening in endocardium. 4-Aminopyridine, an Ito inhibitor, restored the plateau in epicardium and reduced the dispersion of action potential duration between epicardium and endocardium. Stimulation protocols that minimized the contribution of Ito, such as acceleration of the stimulation rate or introduction of early premature beats, produced a paradoxical prolongation of the epicardial response caused by restoration of the action potential dome. Thus, ischemia-induced dispersion of repolarization was greatly diminished at rapid rates and after premature beats. Similar results were obtained in tissues and myocytes obtained from the same myocardial layers, suggesting that the differential sensitivities of epicardium and endocardium to ischemia are largely a result of inherent differences in cellular properties. Our data suggest that the presence of a prominent Ito in epicardium but not endocardium contributes importantly to the selective electrical depression of epicardium by simulated ischemia. The repolarizing influence of Ito serves to amplify the ischemia-induced changes in inward (ICa and INa) and outward (calcium-activated) currents. By facilitating loss of the dome in epicardium, Ito contributes to the development of a marked dispersion of repolarization between normal and ischemic epicardium and between epicardium and endocardium, thereby providing the electrophysiological substrate for the genesis of reentrant arrhythmias.


Mitochondrial genome of the entomophthoroid fungus Conidiobolus heterosporus provides insights into evolution of basal fungi.
Entomophthoroid fungi represent an ecologically important group of fungal pathogens on insects. Here, the whole mitogenome of Conidiobolus heterosporus, one of the entomophthoroid fungi, was described and compared to those early branching fungi with available mitogenomes. The 53,364-bp circular mitogenome of C. heterosporus contained two rRNA genes, 14 standard protein-coding genes, 26 tRNA genes, and three free-standing ORFs. Thirty introns interrupted nine mitochondrial genes. Phylogenetic analysis based on mitochondrion-encoded proteins revealed that C. heterosporus was most close to Zancudomyces culisetae in the Zoopagomycota of basal fungi. Comparison on mitogenomes of 23 basal fungi revealed great variabilities in terms of mitogenome conformation (circular or linear), genetic code (codes 1, 4, or 16), AT contents (53.3-85.5%), etc. These mitogenomes varied from 12.0 to 97.3 kb in sizes, mainly due to different numbers of genes and introns. They showed frequent DNA rearrangement events and a high variability of gene order, although high synteny and conserved gene order were also present between closely related species. By reporting the first mitogenome in Entomophthoromycotina and the second in Zoopagomycota, this study greatly enhanced our understanding on evolution of basal fungi.


On Calculating Free Energy Differences Using Ensembles of Transition Paths.
The free energy of a process is the fundamental quantity that determines its spontaneity or propensity at a given temperature. In particular, the binding free energy of a drug candidate to its biomolecular target is used as an objective quantity in drug design. Recently, binding kinetics-rates of association (k on) and dissociation (k off)-have also demonstrated utility for their ability to predict efficacy and in some cases have been shown to be more predictive than the binding free energy alone. Some methods exist to calculate binding kinetics from molecular simulations, although these are typically more difficult to calculate than the binding affinity as they depend on details of the transition path ensemble. Assessing these rate constants can be difficult, due to uncertainty in the definition of the bound and unbound states, large error bars and the lack of experimental data. As an additional consistency check, rate constants from simulation can be used to calculate free energies (using the log of their ratio) which can then be compared to free energies obtained experimentally or using alchemical free energy perturbation. However, in this calculation it is not straightforward to account for common, practical details such as the finite simulation volume or the particular definition of the "bound" and "unbound" states. Here we derive a set of correction terms that can be applied to calculations of binding free energies using full reactive trajectories. We apply these correction terms to revisit the calculation of binding free energies from rate constants for a host-guest system that was part of a blind prediction challenge, where significant deviations were observed between free energies calculated with rate ratios and those calculated from alchemical perturbation. The correction terms combine to significantly decrease the error with respect to computational benchmarks, from 3.4 to 0.76 kcal/mol. Although these terms were derived with weighted ensemble simulations in mind, some of the correction terms are generally applicable to free energies calculated using physical pathways via methods such as Markov state modeling, metadynamics, milestoning, or umbrella sampling.


Chronic breathlessness associated with poorer physical and mental health-related quality of life (SF-12) across all adult age groups.
Little is known about the impact of chronic breathlessness (modified Medical Research Council (mMRC) score ≥2 for most days, at least three of the last six months) on health-related quality of life (Short Form-12 (SF-12)). 3005 adults from randomly selected households were interviewed face-to-face in South Australia. mMRC ≥2 community prevalence was 2.9%. Adjusted analyses showed clinically meaningful and statistically significant decrements of physical and mental components of SF-12 (mean SF-12 summary scores in physical (-13.0 (-16.0 to -10.2)) and mental (-10.7 (-13.7 to -7.8)) components compared with people with mMRC=0) as chronic breathlessness severity increased, across five age groupings.


Removal of Metabolic Liabilities Enables Development of Derivatives of Procaspase-Activating Compound 1 (PAC-1) with Improved Pharmacokinetics.
Procaspase-activating compound 1 (PAC-1) is an o-hydroxy-N-acylhydrazone that induces apoptosis in cancer cells by chelation of labile inhibitory zinc from procaspase-3. PAC-1 has been assessed in a wide variety of cell culture experiments and in vivo models of cancer, with promising results, and a phase 1 clinical trial in cancer patients has been initiated (NCT02355535). For certain applications, however, the in vivo half-life of PAC-1 could be limiting. Thus, with the goal of developing a compound with enhanced metabolic stability, a series of PAC-1 analogues were designed containing modifications that systematically block sites of metabolic vulnerability. Evaluation of the library of compounds identified four potentially superior candidates with comparable anticancer activity in cell culture, enhanced metabolic stability in liver microsomes, and improved tolerability in mice. In head-to-head experiments with PAC-1, pharmacokinetic evaluation in mice demonstrated extended elimination half-lives and greater area under the curve values for each of the four compounds, suggesting them as promising candidates for further development.


Intensity of parasitic infestation in silver carp, Hypophthalmichthys molitrix.
Silver carp, Hypopthalmichthys molitrix is one of the most economically valuable fish species in Bangladesh. However, its production is often hindered by parasite-induced mortality. The present study reports the intensity of parasitic infestation in 216 specimens of H. molitrix collected from different fish markets in Rajshahi City, Bangladesh. Nine different parasite species (Trichodina pediculatus, Dactylogyrus vastator, Ichthyophthirius multifilis, Gyrodactylus elegans, Lernaea sp., Apiosoma sp., Myxobolus rohitae, Camallanus ophiocephali, and Pallisentis ophiocephali) were recovered from the gill, skin, stomach, and intestine of host fish. The highest level of infection was observed for host skin, while lower levels were observed for host gill, stomach, and intestine. The results also revealed that the intensity of parasite infection in different organs of H. molitrix varied with the season. In particular, the highest levels of infection were recorded during the winter period (November-February), when fish are most susceptible to parasites. The findings of the study will help in the management and conservation of H. molitrix.


Acupuncture pain management for patients with cystic fibrosis: a pilot study.
Cystic fibrosis is the most commonly occurring genetic disorder among Caucasians. The purpose of this study was to evaluate the effects of acupuncture for pain management in patients with cystic fibrosis; clinical data was obtained regarding the integration of acupuncture into the management of pain in patients with cystic fibrosis. Visual analog scales were used for pain measurement. Acupuncture was found to be effective in decreasing pain complaints in patients with cystic fibrosis. No side effects or complications were reported in relation to the acupuncture treatment. Acupuncture is effective for managing symptoms and illnesses associated with cystic fibrosis. Further randomized controlled trials will be necessary to evaluate additional efficacy in pain management and the improvement of the quality of life of patients with cystic fibrosis.


Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer.
Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, the prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC. We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwestern China. Univariate and multivariate Cox proportional-hazards models were used to determine associations between serum GGT and OS in metastatic PDAC. Controlled for possible confounding factors, serum GGT was significantly associated with OS: serum GGT > 48 U/L yielded a hazard ratio of 1.53 (95% CI: 1.19-1.97) for mortality risk. A significant dose-response association between serum GGT and OS was also observed. Subgroup analysis showed a possible interaction between GGT and blood glucose level. Serum GGT could be a potential indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.


Clinical efficacy of endoscopic treatment for benign colorectal stricture: balloon dilatation versus stenting.
There has been a lack of research comparing balloon dilatation and self-expandable metal stent (SEMS) placement to determine which is better for long-term clinical outcomes in patients with benign colorectal strictures. We aimed to compare the clinical efficacy and complication rates of balloon dilatation and SEMS placement for benign colorectal strictures from a variety of causes. Between January 1999 and January 2012, a total of 43 consecutive patients who underwent endoscopic treatment for benign colorectal stricture (balloon only in 29 patients, SEMS only in seven patients, and both procedures in seven patients) were retrospectively reviewed. Thirty-six patients underwent endoscopic balloon dilatation, representing 65 individual sessions, and 14 patients received a total of 17 SEMS placements. The initial clinical success rates were similar in both groups (balloon vs SEMS, 89.1% vs 87.5%). Although the reobstruction rates were similar in both groups (balloon vs SEMS, 54.4% vs. 57.1%), the duration of patency was significantly longer in the balloon dilatation group compared with the SEMS group (65.5±13.3 months vs. 2.0±0.6 months, p=0.031). Endoscopic balloon dilatation is safe and effective as an initial treatment for benign colorectal stricture and as an alternative treatment for recurrent strictures.


Increase in cellular cyclic AMP concentrations reverses the profibrogenic phenotype of cardiac myofibroblasts: a novel therapeutic approach for cardiac fibrosis.
Tissue fibrosis is characterized by excessive production, deposition, and contraction of the extracellular matrix (ECM). The second messenger cAMP has antifibrotic effects in fibroblasts from several tissues, including cardiac fibroblasts (CFs). Increased cellular cAMP levels can prevent the transformation of CFs into profibrogenic myofibroblasts, a critical step that precedes increased ECM deposition and tissue fibrosis. Here we tested two hypotheses: 1) myofibroblasts have a decreased ability to accumulate cAMP in response to G protein-coupled receptor (GPCR) agonists, and 2) increasing cAMP will not only prevent, but also reverse, the myofibroblast phenotype. We found that myofibroblasts produce less cAMP in response to GPCR agonists or forskolin and have decreased expression of several adenylyl cyclase (AC) isoforms and increased expression of multiple cyclic nucleotide phosphodiesterases (PDEs). Furthermore, we found that forskolin-promoted increases in cAMP or N(6)-phenyladenosine-cAMP, a protein kinase A-selective analog, reverse the myofibroblast phenotype, as assessed by the expression of collagen Iα1, α-smooth muscle actin, plasminogen activator inhibitor-1, and cellular contractile abilities, all hallmarks of a fibrogenic state. These results indicate that: 1) altered expression of AC and PDE isoforms yield a decrease in cAMP concentrations of cardiac myofibroblasts (relative to CFs) that likely contributes to their profibrotic state, and 2) approaches to increase cAMP concentrations not only prevent fibroblast-to-myofibroblast transformation but also can reverse the profibrotic myofibroblastic phenotype. We conclude that therapeutic strategies designed to enhance cellular cAMP concentrations in CFs may provide a means to reverse excessive scar formation following injury and to treat cardiac fibrosis.


Antenatal diagnosis of postductal coarctation of the aorta. A case report.
Fetal echocardiography can be used to detect congenital heart disease prenatally with a high degree of accuracy, and complex heart malformations have also been clearly described in the fetus. However, it is difficult to diagnose correctly or to exclude definitely aortic coarctation by fetal echocardiography. A 23-year-old woman was referred for fetal echocardiographic examination at 21 weeks' gestation after discovery of hydrops fetalis (nonimmune) on an obstetric ultrasound examination. Aortic isthmus appeared hypoplastic with a diameter < or = 3rd percentile for gestational age. There was a narrowing within the descending aorta immediately distal to the origin of the ductus arteriosus. Color flow imaging demonstrated acceleration and turbulent flow and the peak pressure gradient was measured 83 mmHg by continuous wave Doppler in the same area. The pregnancy terminated in spontaneous abortion at 22 weeks' gestation. The fetus was stillborn. The autopsy findings confirmed the prenatal diagnosis. We conclude that together with the quantitative estimation of the aortic arch, color Doppler and continuous wave Doppler are helpful in diagnosis and estimation of the pressure gradient.


Dietary protein intake and skeletal-muscle protein metabolism in rats. Studies with the ammonium chloride-wash fraction from crude polyribosomes of well-nourished and protein-depleted rats.
1. Crude polyribosomes from skeletal muscle of the hind leg of rats fed on a low-protein diet for 10 days are less active in cell-free protein synthesis than are polyribosomes obtained from well-nourished control rats. 2. The polyribosomes were salt-washed (0.5m-NH(4)Cl) and the wash extract was examined for its amino acid incorporating activity and for EF (elongation factor) 1 and EF 2 activities. 3. Compared with preparations from control rats, the salt-wash fraction from protein-depleted rats was less active and showed lower EF 1 and EF 2 activity. 4. The ribosomes were rendered equal in activity by salt-washing, but no inhibitor was detected in the salt wash. 5. Differences in the incorporating activity of crude polyribosomes from the diet groups persisted in the presence of saturating amounts of partially purified EF 1 and EF 2. 6. It is concluded that the lowered protein-synthetic activity of crude polyribosomes caused by restricted protein intake is not causally related to the lower activities of EF 1 and EF 2 in the polyribosome preparations. 7. The possible nature of the change in crude polyribosome activity due to low-protein feeding is discussed.


Drug Targeting and Biomarkers in Head and Neck Cancers: Insights from Systems Biology Analyses.
The head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, but robust biomarkers and diagnostics are still not available. This study provides in-depth insights from systems biology analyses to identify molecular biomarker signatures to inform systematic drug targeting in HNSCC. Gene expression profiles from tumors and normal tissues of 22 patients with histological confirmation of nonmetastatic HNSCC were subjected to integrative analyses with genome-scale biomolecular networks (i.e., protein-protein interaction and transcriptional and post-transcriptional regulatory networks). We aimed to discover molecular signatures at RNA and protein levels, which could serve as potential drug targets for therapeutic innovation in the future. Eleven proteins, 5 transcription factors, and 20 microRNAs (miRNAs) came into prominence as potential drug targets. The differential expression profiles of these reporter biomolecules were cross-validated by independent RNA-Seq and miRNA-Seq datasets, and risk discrimination performance of the reporter biomolecules, BLNK, CCL2, E4F1, FOSL1, ISG15, MMP9, MYCN, MYH11, miR-1252, miR-29b, miR-29c, miR-3610, miR-431, and miR-523, was also evaluated. Using the transcriptome guided drug repositioning tool, geneXpharma, several candidate drugs were repurposed, including antineoplastic agents (e.g., gemcitabine and irinotecan), antidiabetics (e.g., rosiglitazone), dermatological agents (e.g., clocortolone and acitretin), and antipsychotics (e.g., risperidone), and binding affinities of the drugs to their potential targets were assessed using molecular docking analyses. The molecular signatures and repurposed drugs presented in this study warrant further attention for experimental studies since they offer significant potential as biomarkers and candidate therapeutics for precision medicine approaches to clinical management of HNSCC.


Longitudinal changes in movement-related functional MRI activity in Parkinson's disease patients.
Functional brain imaging has shown alterations in the basal ganglia, cortex and cerebellum in Parkinson's disease patients. However, few functional imaging studies have tested how these changes evolve over time. Our study aimed to test the longitudinal progression of movement-related functional activity in Parkinson's disease patients. At baseline, 48 Parkinson's disease patients and 16 healthy controls underwent structural and functional magnetic resonance imaging during a joystick motor task. Patients had repeated imaging after 18-months (n = 42) and 36-months (n = 32). T-tests compared functional responses between Parkinson's disease patients and controls, and linear mixed effects models examined longitudinal differences within Parkinson's disease. Correlations of motor-activity with bradykinesia, rigidity and tremor were undertaken. All contrasts used whole-brain analyses, thresholded at Z > 3.1 with a cluster-wise P < 0.05. Baseline activation was significantly greater in patients than controls across contralateral parietal and occipital regions, ipsilateral precentral gyrus and thalamus. Longitudinally, patients showed significant increases in cerebellar activity at successive visits following baseline. Task-related activity also increased in the contralateral motor, parietal and temporal areas at 36 months compared to baseline, however this was reduced when controlling for motor task performance. We have shown that there are changes over time in the blood-activation level dependent response of patients with Parkinson's disease undertaking a simple motor task. These changes are observed primarily in the ipsilateral cerebellum and may be compensatory in nature.


Activating mGlu3 Metabotropic Glutamate Receptors Rescues Schizophrenia-like Cognitive Deficits Through Metaplastic Adaptations Within the Hippocampus.
Polymorphisms in GRM3, the gene encoding the mGlu3 metabotropic glutamate receptor, are associated with impaired cognition and neuropsychiatric disorders such as schizophrenia. Limited availability of selective genetic and molecular tools has hindered progress in developing a clear understanding of the mechanisms through which mGlu3 receptors regulate synaptic plasticity and cognition. We examined associative learning in mice with trace fear conditioning, a hippocampal-dependent learning task disrupted in patients with schizophrenia. Underlying cellular mechanisms were assessed using ex vivo hippocampal slice preparations with selective pharmacological tools and selective genetic deletion of mGlu3 receptor expression in specific neuronal subpopulations. mGlu3 receptor activation enhanced trace fear conditioning and reversed deficits induced by subchronic phencyclidine. Mechanistic studies revealed that mGlu3 receptor activation induced metaplastic changes, biasing afferent stimulation to induce long-term potentiation through an mGlu5 receptor-dependent, endocannabinoid-mediated, disinhibitory mechanism. Selective genetic deletion of either mGlu3 or mGlu5 from hippocampal pyramidal cells eliminated effects of mGlu3 activation, revealing a novel mechanism by which mGlu3 and mGlu5 interact to enhance cognitive function. These data demonstrate that activation of mGlu3 receptors in hippocampal pyramidal cells enhances hippocampal-dependent cognition in control and impaired mice by inducing a novel form of metaplasticity to regulate circuit function, providing a clear mechanism through which genetic variation in GRM3 can contribute to cognitive deficits. Developing approaches to positively modulate mGlu3 receptor function represents an encouraging new avenue for treating cognitive disruption in schizophrenia and other psychiatric diseases.


Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma.
Neuroblastoma (NB) tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Thirty-five NB tumours from patients diagnosed at < 18 months (25 stage 4 and 10 stage 4s), were evaluated by allelic and gene expression analyses. All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36), 23% 11q and/or 14q LOH (27%) and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 < 12 months tumours revealed distinct gene expression profiles. A significant portion of genes mapped to chromosome 1 (P < 0.0001), 90% with higher expression in stage 4s, and chromosome 11 (P = 0.0054), 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 < 18m, yet, association with chromosomes 1 (P < 0.0001) and 11 (P = 0.005) was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 < 18 months without MYCN amplification. Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour.


Physical activity and self-perceived health status.
Recently more attention has been focused on the impact of physical activity on modification of self-perceived heath status in adults. The objective of the study was to evaluate the level of occupational and non-occupational physical activities and their correlation with self-perceived heath status among economically productive individuals. Physical activity of the subjects studied was evaluated by the Seven Day Physical Activity Recall (SDPAR) questionnaire among randomly chosen residents of the city of Lódź (n = 598, including 299 women and 299 men). The examination of the subjective health assessment was conducted based on the analogue visual scale. The multifactorial logistic regression analysis indicated that weekly energy expenditure on occupational physical activity (kcal/week) did not play a significant role in self-perception of health status among men or women. Neither did the outcome of the study provide evidence for the significant effect of housework load on self-perceived health status among the study participants. However, a sufficient level of leisure-time physical activity in a beneficial way affects health-related self-perception of the examined subjects. In the group of men expending 1000 kcal/week or more on leisure-time physical activity, the risk for poor health-related self-report was significantly lower than among men declaring no energy expenditure on this activity (adjusted odds ratio (OR = 0.29, 95% CI: 0.13-0.66). Among females not taking up any recreational physical activity, the risk of low self-perceived health status was also higher than in females reaching a satisfactory level of recreational physical activity (adjusted OR = 0.38, 95% CI: 0.17-0.87). Preventive programs aimed at improving subjective health assessment through the increased leisure-time physical activity should be addressed to all economically productive individuals and particularly to people of older age groups and above all to females.


Regulation of gene expression during swarmer cell differentiation in Proteus mirabilis.
The gram-negative bacterium Proteus mirabilis can exist in either of two cell types, a vegetative cell characterized as a short rod and a highly elongated and hyperflagellated swarmer cell. This differentiation is triggered by growth on solid surfaces and multiple inputs are sensed by the cell to initiate the differentiation process. These include the inhibition of flagellar rotation, the accumulation of extracellular putrescine and O-antigen interactions with a surface. A key event in the differentiation process is the upregulation of FlhD(2)C(2), which activates the flagellar regulon and additional genes required for differentiation. There are a number of genes that influence FlhD(2)C(2) expression and the function of these genes, if known, will be discussed in this review. Additional genes that have been shown to regulate gene expression during swarming will also be reviewed. Although P. mirabilis represents an excellent system to study microbial differentiation, it is largely understudied relative to other systems. Therefore, this review will also discuss some of the unanswered questions that are central to understanding this process in P. mirabilis.


Spleen cells from animals tolerant to a thymus-dependent antigen can be activated by lipopolysaccharide to synthesize antibodies against the tolerogen.
Immunological tolerance was induced in adult mice by the injection of 5 mg of deaggregated hapten-protein conjugate. The tolerant state was confirmed 4-19 days later by the failure of such animals to mount an immune response against an aggregated form of the same thymus-dependent hapten-protein conjugate as well as by the inability of spleen cells from tolerant animals to respond to a thymus-independent hapten-carrier conjugate. Even though the animals were fully tolerant, their spleen cells were activated by lipopolysaccharide (LPS) in vitro to produce normal numbers of plaque-forming cells against the hapten. The finding that spleen cells from tolerant animals could be activated by LPS into synthesis of antibodies against the tolerogen indicates that tolerance to thymus-dependent antigens does not affect B cells, but presumably only T cells. It is suggested that the only stringent test for the existence of B-cell tolerance is the inability of polyclonal B-cell activators to activate antibody synthesis against the tolerogen. The findings make it unlikely that B-cell tolerance to autologous thymus-dependent antigens exists and further indicate that such antigens cannot deliver activating or tolerogenic signals to B cells, although they are competent to combine with and block the Ig receptors.


Trends in African Americans' Attitudes and Behaviors About Living Donor Kidney Transplantation.
Due to marginal efforts to increase living donor kidney transplantation, it is unclear whether interventions to improve African Americans' interest and pursuit of living donation should be tailored to address patients' exposure to or familiarity with dialysis or transplant settings. We conducted a cross-sectional secondary analysis of baseline data from 3 separate randomized clinical trials among African Americans with varying degrees of experience with dialysis or transplantation (predialysis, on dialysis but not on transplant list, and on transplant wait-list) settings. Interest in living donation was described using a 0 to 10 scale and pursuit of living donor kidney transplantation by achievement of at least 1 pursuant behavior. In multivariable logistic regression analyses, we assessed the association of knowledge, health literacy, and trust in health care with interest in or pursuit of living donation. Interest among the 3 study cohorts was high (predialysis, 62.9%; dialysis, 67.4%; and transplant wait-list, 74.2%). The dialysis and transplant wait-list study cohorts pursued living donation more readily than those not on dialysis (73%, 92%, and 45%, respectively). Interest and pursuit were not statistically significantly associated with knowledge, health literacy, or the 3 factors reflecting medical mistrust. Interest and pursuit of living donation were greater among study participants with greater exposure to dialysis or transplant settings. Efforts to promote patients' early interest and pursuit of living donor transplants may consider novel strategies to educate patients with less experience about the benefits of living donor kidney transplantation.


Characterization and polyanion-binding properties of purified recombinant prion protein.
Certain polysulphated polyanions have been shown to have prophylactic effects on the progression of transmissible spongiform encephalopathy disease, presumably because they bind to prion protein (PrP). Until now, the difficulty of obtaining large quantities of native PrP has precluded detailed studies of these interactions. We have over-expressed murine recombinant PrP (recPrP), lacking its glycophosphoinositol membrane anchor, in modified mammalian cells. Milligram quantities of secreted, soluble and partially glycosylated protein were purified under non-denaturing conditions and the identities of mature-length aglycosyl recPrP and two cleavage fragments were determined by electrospray MS. Binding was assessed by surface plasmon resonance techniques using both direct and competitive ligand-binding approaches. recPrP binding to immobilized polyanions was enhanced by divalent metal ions. Polyanion binding was strong and showed complex association and dissociation kinetics that were consistent with ligand-directed recPrP aggregation. The differences in the binding strengths of recPrP to pentosan polysulphate and to other sulphated polyanions were found to parallel their in vivo anti-scrapie and in vitro anti-scrapie-specific PrP formation potencies. When recPrP was immobilized by capture on metal-ion chelates it was found, contrary to expectation, that the addition of polyanions promoted the dissociation of the protein.


Use of an Early Labor Lounge to Promote Admission in Active Labor.
Professional maternity care organizations within the United States are aligned in the goal to prevent the first cesarean birth in nulliparous women with a term, singleton, vertex fetus. Currently, one in 3 women are at risk for having a cesarean birth. The most common reason for cesarean in the United States is labor dystocia. The evidence supports delaying admission to the birthing unit until active labor is established, thereby minimizing the inadvertent diagnosis of labor dystocia. Providers are familiar with the rationale supporting delayed admission to the birthing unit until active labor is established; however, there is very little evidence on how to effectively promote this delay. Provider apprehension and the lack of early labor support are challenges to sending women home to await the onset of active labor. Maternal anxiety, fear, pain, and unpreparedness also play a part in this reluctance. To address these obstacles, South Shore Hospital created an early labor lounge with stations aimed at instilling confidence in the birth team, promoting teamwork, facilitating relaxation, and reducing anxiety for laboring women. A literature review focusing on women's perceptions of promoting admission in active labor, maternal anxiety, and nonpharmacologic strategies for managing early labor are discussed within the context of the creation, implementation, and evaluation of an early labor lounge.


Downregulation of lncRNA APCDD1L-AS1 due to DNA hypermethylation and loss of VHL protein expression promotes the progression of clear cell renal cell carcinoma.
Background: The current studies only indicated that long non-coding RNA (lncRNA) APCDD1L-AS1, as a novel lncRNA, may play a role in oral squamous cell carcinoma and lung cancer. However, its potential role in clear cell renal cell carcinoma (ccRCC) and its possible mechanism of action remain vague. Methods: TCGA-KIRC and GEO data and qRT-PCR and pyrosequencing results of clinical specimens were used to identify the expression level and DNA methylation status of APCDD1L-AS1. The effects of APCDD1L-AS1 overexpression on ccRCC growth and metastasis were determined by function experiments. Western blot and Tandem mass tags (TMT) were utilized to explore the relationship between APCDD1L-AS1 and VHL expression and its downstream underlying mechanisms. Results: The expression of APCDD1L-AS1 was downregulated in ccRCC. Decreased APCDD1L-AS1 expression was related to higher tumor stage and histological grade and shorter RFS (Relapse-free survival). Besides, APCDD1L-AS1 overexpression restrained the growth and metastasis of ccRCC cells in vitro and in vivo. Moreover, reduced APCDD1L-AS1 expression could be caused by DNA hypermethylation and loss of von Hippel Lindau (VHL) protein expression. Furthermore, the dysregulation of histones expression caused by APCDD1L-AS1 overexpression may be one of the important mechanisms to suppress the progression of ccRCC. Conclusion: APCDD1L-AS1 was able to inhibit the progression of ccRCC, and its decreased expression could be caused by DNA hypermethylation and loss of VHL protein expression. Therefore, APCDD1L-AS1 may serve as a new therapeutic target in the treatment of ccRCC.


Epistemic sabotage: The production and disqualification of evidence in disability benefit claims.
Disability benefits function by demarcating categories of need (the administrative category of disability) and determine eligibility using assessments of functioning. In the UK, these assessments are the Work Capability Assessment and PIP assessment. Inherently technical and abstruse processes, these assessments have been opportune sites for welfare reform in recent years. Disability benefits have also been a central point of contention between disability studies and sociology. Sociology has traditionally favoured an 'incomes approach' and called for more adequate financial support from the state. Early figures in the disabled people's movement rejected this position, and aligned with an oppression paradigm, argued for a more radical economic and social inclusion. We contend that this divide, set out in the Fundamental Principles of Disability, remains relevant for researching welfare reform today. This article treats benefits assessments as epistemic practices-interactional processes wherein claimants, their personal health professionals and commercial assessment providers come together in the production of knowledge about disability. Data include 50 in-depth interviews with benefit claimants and a discourse analysis of official texts directed at claimants, personal health professionals and commercial assessment providers. We outline a phenomenon we term 'epistemic sabotage', whereby the knowledge claims of claimants and their health professionals are systemically disqualified.


[A current model for predicting the risk of cardiovascular diseases in patients with type 2 diabetes mellitus].
Type 2 diabetes mellitus (T2DM) is a severe progressive disease complicating the development of micro- and macrovascular complications that result in early disability, including that in able-bodied persons, a reduction in the patients' life, and its worse quality. The author discusses the new scale developed according to the results of the ADVANCE trial for predicting the cardiovascular risk in patients with T2DM which may be used widely in these patients to estimate the risk of cardiovascular events and as a tool to assist in determining the intensity of treatment. She considers current approaches to treating T2DM, by using the results of the ADVANCE trial.


Egyptian propolis: 1-antimicrobial activity and chemical composition of Upper Egypt propolis.
The antimicrobial activity of four propolis samples collected from Upper Egypt against Staphylococcus aureus; Escherichia coli and Candida albicans was evaluated. There was a variation in the antimicrobial activity according to the propolis origin. Banisweif propolis showed the highest antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans, but Fayoum propolis had moderate activity against all tested pathogens. Propolis collected from Assiut and Souhag gave lower antimicrobial activity. Propolis samples were investigated by GC/MS, 71 compounds were identified, 14 being new for propolis. Banisweif propolis is characterized by the presence of 7 caffeate esters and 4 triterpenoids. Fayoum propolis showed the highest amount of lactic acid and the presence of 3 chalcones. But Assiut propolis is characterized by the presence of 4 prenylated coumarates. Souhag propolis is characterized by the presence of 5 aliphatic dicarboxylic acids and some other new compounds to propolis.


Hole-Type Spacers for More Stable Shale Gas-Produced Water Treatment by Forward Osmosis.
An appropriate spacer design helps in minimizing membrane fouling which remains the major obstacle in forward osmosis (FO) systems. In the present study, the performance of a hole-type spacer (having holes at the filament intersections) was evaluated in a FO system and compared to a standard spacer design (without holes). The hole-type spacer exhibited slightly higher water flux and reverse solute flux (RSF) when Milli-Q water was used as feed solution and varied sodium chloride concentrations as draw solution. During shale gas produced water treatment, a severe flux decline was observed for both spacer designs due to the formation of barium sulfate scaling. SEM imaging revealed that the high shear force induced by the creation of holes led to the formation of scales on the entire membrane surface, causing a slightly higher flux decline than the standard spacer. Simultaneously, the presence of holes aided to mitigate the accumulation of foulants on spacer surface, resulting in no increase in pressure drop. Furthermore, a full cleaning efficiency was achieved by hole-type spacer attributed to the micro-jets effect induced by the holes, which aided to destroy the foulants and then sweep them away from the membrane surface.


Cancer chemotherapy associated symptomatic stomatitis: role of Herpes simplex virus (HSV).
The relationship between oral shedding of Herpes simplex virus (HSV) and cytotoxic cancer chemotherapy was studied. HSV seropositive outpatients receiving cytotoxic chemotherapy had HSV recovered from throat washings in eight of 114 patients (7.0%), significantly more often than HSV seropositive outpatients with malignancy who were not receiving cytotoxic chemotherapy (one of 91 patients; 1.1%; P = 0.04). Twenty-eight HSV seropositive chemotherapy patients and 11 HSV seropositive healthy hospital personnel were studied serially 2-3 times per week over a 3-4 week period for oral HSV shedding. Although a comparable percentage of each group shed HSV at least once (57.1% of chemotherapy patients versus 36.4% of controls), chemotherapy patients had a strikingly higher incidence of multiple positive cultures: 40/218 attempts (18.7%) versus 4/156 attempts (2.6%) for controls (P less than 10(-5)). Among chemotherapy patients who developed clinically evident stomatitis, 12 of 14 (85.7%) had HSV recovered compared to four of 14 (28.6%) without lesions (P = 0.004). We conclude that while oral mucosal HSV infection is associated with symptomatic stomatitis following chemotherapy, HSV does not account for all mucosal lesions in chemotherapy patients.


Growth inhibition of Rhodopseudomonas capsulata by methylmercury acetate.
Growth of Rhodopseudomonas capsulata was inhibited in a bacteriostatic manner by as little as 10-minus 8 M methylmercury acetate (MeHgAc) in unsupplemented synthetic liquid medium or when cells were exposed to 8.0 nm of MeHgAc per mg of cell protein in a single exposure.


Patterns with different phases but same statistics.
Many successful methods in various vision tasks rely on statistical analysis of visual patterns. However, we are interested in covering the gap between the underlying mathematical representation of the visual patterns and their statistics. With this general trend, in this paper a relationship between phase structure of a class of patterns and their moments after and before filtering have been considered. First, a general formula between the phase structure and moments of the images is obtained. Second, a theorem is developed that states under which conditions two visual patterns with the same frequencies but different phases have the same moments up to a certain moment. Finally, a theorem is developed that explains, given a set of filters, under which conditions two visual patterns with both different frequencies and different phases have the same subband statistics.