Use of the McIsaac Score to Predict Group A Streptococcal Pharyngitis in Outpatient Nurse Phone Triage and Electronic Visits Compared With In-Person Visits: Retrospective Observational Study.
The McIsaac criteria are a validated scoring system used to determine the likelihood of an acute sore throat being caused by group A streptococcus (GAS) to stratify patients who need strep testing. We aim to compare McIsaac criteria obtained during face-to-face (f2f) and non-f2f encounters. This retrospective study compared the percentage of positive GAS tests by McIsaac score for scores calculated during nurse protocol phone encounters, e-visits (electronic visits), and in person f2f clinic visits. There was no difference in percentages of positive strep tests between encounter types for any of the McIsaac scores. There were significantly more phone and e-visit encounters with any missing score components compared with f2f visits. For individual score components, there were significantly fewer e-visits missing fever and cough information compared with phone encounters and f2f encounters. F2f encounters were significantly less likely to be missing descriptions of tonsils and lymphadenopathy compared with phone and e-visit encounters. McIsaac scores of 4 had positive GAS rates of 55% to 68% across encounter types. There were 4 encounters not missing any score components with a McIsaac score of 0. None of these 4 encounters had a positive GAS test. McIsaac scores of 4 collected during non-f2f care could be used to consider empiric treatment for GAS without testing if significant barriers to testing exist such as the COVID-19 pandemic or geographic barriers. Future studies should evaluate further whether non-f2f encounters with McIsaac scores of 0 can be safely excluded from GAS testing.


Intradiscal therapies for discogenic pain.
Since the first injection of chymopapain in 1963, percutaneous intradiscal therapies have been used to treat discogenic back and leg pain. The percutaneous discectomy techniques treat contained disc herniations not by resecting the prolapsed disc material but rather through central decompression of the disc. By removing a small volume of tissue from the disc nucleus, a large reduction in overall disc pressure is achieved with consequent relief of neural compression. DISC Nucleoplasty and Dekompressor are the two leading percutaneous discectomy technologies currently. Although rigorous clinical testing of their efficacy is ongoing, there has now been a 40-year history confirming the concept of percutaneous disc decompression, and initial results are very promising. Discogenic low back pain can also arise from annular tears and other forms of internal disc derangement (IDD). Annuloplasty techniques, such as IntraDiscal Electrothermal Therapy (IDET) and discTRODE, have been developed over the past decade that thermally treat the lesions of IDD. Although the therapeutic mechanisms of thermal annuloplasty have yet to be fully elucidated, research studies demonstrate that the procedure can be effective for appropriately selected patients with degenerative disc disease characterized by discographically proven painful annular fissures. Other novel intradiscal therapies are emerging for percutaneous treatment of discogenic pain and await more widespread clinical evaluation.


Realization of high-quality optical nanoporous gradient-index filters by optimal combination of anodization conditions.
High-quality nanoporous anodic alumina gradient-index filters (NAA-GIFs) are realized by sinusoidal pulse anodisation (SPA) of aluminum. A three-level factorial design of experiments is used to determine the effect of three critical anodization parameters -electrolyte temperature, concentration of the electrolyte and anodization time- on the quality of light control in these photonic crystal (PC) structures. Quantitative analysis of the effect of these anodization parameters on the quality of the characteristic photonic stopband (PSB) of NAA-GIFs reveals that all three anodization parameters and their respective combinations have statistically significant effects. However, anodization time is found to have the highest impact on the quality of light control in NAA-GIFs, followed by the electrolyte concentration and its temperature. Our findings demonstrate that NAA-GIFs fabricated under optimal conditions achieve an outstanding quality factor of ∼86 (i.e.∼18% superior to that of other NAA-based PCs reported in the literature). This study provides new insight into optimal anodization conditions to fabricate high-quality NAA-based PC structures, opening new exciting opportunities to integrate these nanoporous PCs as platform materials for light-based technologies requiring a precise control over photons such as ultra-sensitive optical sensors and biosensors, photocatalysts for green energy generation and environmental remediation, optical encoding and lasing.


Inflammasome Activation Mediates Apoptotic and Pyroptotic Death in Astrocytes Under Ischemic Conditions.
Inflammation is a hallmark mechanism of ischemic stroke-induced brain injury. Recent studies have shown that an intracellular multimeric protein complex known as an inflammasome is a key factor for inducing an inflammatory response, and apoptotic and pyroptotic cell death in ischemic stroke. Inflammasome assembly leads to the activation of pro-inflammatory caspases, and the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18. While the role of inflammasomes in ischemic stroke-induced neuronal death, and microglial activation and cell death have been established, little is known about the role of inflammasomes in astrocytes under ischemic conditions. In this study, we investigated the expression and activation of inflammasome components in protoplasmic and fibrous astrocytes under ischemic conditions. We found that both protoplasmic and fibrous astrocytes expressed a differential increase in inflammasome protein components, and that their activation promoted maturation of IL-1β and IL-18, and secretion of IL-1β, as well as initiating apoptotic and pyroptotic cell death. Pharmacological inhibition of caspase-1 decreased expression of cleaved caspase-1 and production of mature IL-1β, and protected against inflammasome-mediated apoptotic and pyroptotic cell death. Overall, this study provides novel insights into the role of inflammasome signaling in astrocytes under ischemic conditions.


Effect of doxazosin on blood pressure and renal haemodynamics of hypertensive patients with renal failure.
Doxazosin, a quinazoline derivative, has alpha 1- adrenoreceptor antagonist properties similar to those of prazosin. This antihypertensive agent has a longer elimination half-life than prazosin. The pharmacokinetic properties of doxazosin are not significantly different in patients with renal insufficiency compared with healthy controls. In this study eight hypertensive patients with renal insufficiency were studied during a two week washout period, followed by a two week single blind placebo phase and an eight week open doxazosin treatment period. Doxazosin was commenced in a dose of 1 mg daily and titrated if necessary, with the dose being doubled every two weeks. In all but one patient doxazosin was successful in controlling the blood pressure. Treatment with doxazosin for eight weeks had no adverse effects on the effective renal plasma flow or glomerular filtration rate of these patients. Six of the eight patients suffered side effects attributable to doxazosin.


Interventions by Virginia's colleges to respond to student mental health crises.
This study examined interventions by colleges in 2008-2009 to respond to students during mental health crises. Public (N=15) and private (N=25) four-year colleges and two-year community colleges (N=23) in Virginia were surveyed about academic policies governing responses to apparent mental health crises among students and how often they were invoked. Procedures used most often by public and private colleges, respectively, were parental notification (six and 25 per 10,000 students); voluntary medical withdrawal, usually linking readmission to treatment (29 and 25 per 10,000 students); mandatory treatment following disciplinary sanction (302 and 1,704 per 10,000 students); and monitoring by a campus threat assessment team (15 and 51 per 10,000 students). Procedures for involuntary hospitalization and involuntary medical withdrawal were rarely invoked. Community colleges were much less likely than four-year colleges to use any of these procedures. Most four-year colleges in Virginia, both public and private, occasionally invoke a variety of protective interventions to respond to apparent mental health crises experienced by students, but the number of students annually affected by these policies is generally small. The main value of procedures for mandated or leveraged treatment in college may be to motivate students with mental illness to seek treatment voluntarily. Aside from sporadic use of threat assessment teams in extreme instances, community colleges, which do not have counseling centers, lack the capacity to undertake these interventions.


The effect of positive psychology interventions on well-being and distress in clinical samples with psychiatric or somatic disorders: a systematic review and meta-analysis.
Although positive psychology interventions (PPIs) show beneficial effects on mental health in non-clinical populations, the current literature is inconclusive regarding its effectiveness in clinical settings. We aimed to examine the effects of PPIs on well-being (primary outcome), depression, anxiety, and stress (secondary outcomes) in clinical samples with psychiatric or somatic disorders. A systematic review and meta-analysis was conducted following PRISMA guidelines. PsycINFO, PubMed, and Scopus were searched for controlled studies of PPIs in clinical samples between Jan 1, 1998 and May 31, 2017. Methodological quality of each study was rated. We used Hedges' adjusted g to calculate effect sizes and pooled results using random-effect models. Thirty studies were included, representing 1864 patients with clinical disorders. At post-intervention, PPIs showed significant, small effect sizes for well-being (Hedges' g = 0.24) and depression (g = 0.23) compared to control conditions when omitting outliers. Significant moderate improvements were observed for anxiety (g = 0.36). Effect sizes for stress were not significant. Follow-up effects (8-12 weeks), when available, yielded similar effect sizes. Quality of the studies was low to moderate. These findings indicate that PPIs, wherein the focus is on eliciting positive feelings, cognitions or behaviors, not only have the potential to improve well-being, but can also reduce distress in populations with clinical disorders. Given the growing interest for PPIs in clinical settings, more high quality research is warranted as to determine the effectiveness of PPIs in clinical samples. PROSPERO CRD42016037451.


Macroscopic optical imaging technique for wide-field estimation of fluorescence depth in optically turbid media for application in brain tumor surgical guidance.
A diffuse imaging method is presented that enables wide-field estimation of the depth of fluorescent molecular markers in turbid media by quantifying the deformation of the detected fluorescence spectra due to the wavelength-dependent light attenuation by overlying tissue. This is achieved by measuring the ratio of the fluorescence at two wavelengths in combination with normalization techniques based on diffuse reflectance measurements to evaluate tissue attenuation variations for different depths. It is demonstrated that fluorescence topography can be achieved up to a 5 mm depth using a near-infrared dye with millimeter depth accuracy in turbid media having optical properties representative of normal brain tissue. Wide-field depth estimates are made using optical technology integrated onto a commercial surgical microscope, making this approach feasible for real-world applications.


Whole-exome sequencing in multiplex preeclampsia families identifies novel candidate susceptibility genes.
Preeclampsia is a common and serious heritable disorder of human pregnancy. Although there have been notable successes in identification of maternal susceptibility genes a large proportion of the heritability of preeclampsia remains unaccounted for. It is has been postulated that rare variation may account for some of this missing heritability. In this study, we performed whole-exome sequencing (WES) in multiplex families to identify rare exonic risk variants. We conducted WES in 244 individuals from 34 Australian/New Zealand multiplex preeclampsia families. Variants were tested for association with preeclampsia using a threshold model and logistic regression. We found significant association for two moderately rare missense variants, rs145743393 (Padj = 0.0032, minor allele frequency = 0.016) in the chromosome 1 open reading frame 35 (C1orf35) gene, and rs34270076 (Padj = 0.0128, minor allele frequency = 0.024) in the pyroglutamylated RFamide peptide receptor (QRFPR) gene. To replicate these associations we performed imputation in our Australian genome wide association scan for preeclampsia and found no significant exonic variants in either C1orf35 or QRFPR. However, 11 variants demonstrating nominal significance (P < 0.05) in the genomic region between QRFPR and annexin A5 (ANXA5) were identified. We further leveraged publicly available genome-wide available summary data from the UK Biobank to investigate association of these two variants with the underlying clinical phenotypes of preeclampsia and detected nominal association of the QRFPR variant (rs34270076, P = 0.03) with protein levels in females. The study represents the first to use WES in multiplex families for preeclampsia and identifies two novel genes (QRFPR and C1orf35) not previously associated with preeclampsia and find nominal association of rs34270076 with protein levels, a key clinical feature of preeclampsia. We find further support for ANXA5 previously associated with pregnancy complications, including preeclampsia.


Covalent triazine framework supported non-noble metal nanoparticles with superior activity for catalytic hydrolysis of ammonia borane: from mechanistic study to catalyst design.
Development of non-noble metal catalysts with similar activity and stability to noble metals is of significant importance in the conversion and utilization of clean energy. The catalytic hydrolysis of ammonia borane (AB) to produce 3 equiv. of H2, as an example of where noble metal catalysts significantly outperform their non-noble peers, serves as an excellent test site for the design and optimization of non-noble metal catalysts. Our kinetic isotopic effect measurements reveal, for the first time, that the kinetic key step of the hydrolysis is the activation of H2O. Deducibly, a transition metal with an optimal electronic structure that bonds H2O and -OH in intermediate strengths would favor the hydrolysis of AB. By employing a covalent triazine framework (CTF), a newly developed porous material capable of donating electrons through the lone pairs on N, the electron densities of nano-sized Co and Ni supported on CTF are markedly increased, as well as their catalytic activities. Specifically, Co/CTF exhibits a total turnover frequency of 42.3 molH2 molCo-1 min-1 at room temperature, which is superior to all peer non-noble metal catalysts ever reported and even comparable to some noble metal catalysts.


Evaluation of the pol/S Gene Overlapping Mutations in Chronic Hepatitis B Patients in Northern Cyprus.
Mutations associated with the pol and the S gene can emerge as a consequence of the high replication capacity and proofreading deficiencies of hepatitis B virus during replication. The current study was constructed to evaluate primary, partial, compensatory and the escape mutations in chronic hepatitis B patients in Northern Cyprus. The samples of HBsAg positive treatment naïve 100 patients were involved in this study. HBV pol gene region was sequenced, amplified and HBV pol/S gene mutations were determined. The samples of thirty-two patients were excluded because of their low viral load (HBV < 1000 ıu/ml). Among the sequenced 68 samples, there was a partial mutation (1.5%) and 36.7% displayed a resistance profile to lamivudine, adevofir, and telbivudine. Immune response escape, vaccine escape, HBIg and diagnosis escape mutations were determined in 24%, 10%, 6%, and 4% samples of the patients, respectively. Additionally, there were six different combined mutations. These data underscored that there is no concern for primary mutations in Northern Cyprus, however, we have identified a compensatory mutation (rtV173M) that may have primary mutation characteristics by combining with other mutation patterns. Additionally, HBsAg escape mutants demonstrated that detection of the S gene together with the pol gene mutations might be beneficial and important to monitor the surveillance of S variants. Mutations associated with the pol and the S gene can emerge as a consequence of the high replication capacity and proofreading deficiencies of hepatitis B virus during replication. The current study was constructed to evaluate primary, partial, compensatory and the escape mutations in chronic hepatitis B patients in Northern Cyprus. The samples of HBsAg positive treatment naïve 100 patients were involved in this study. HBV pol gene region was sequenced, amplified and HBV pol/S gene mutations were determined. The samples of thirty-two patients were excluded because of their low viral load (HBV < 1000 ıu/ml). Among the sequenced 68 samples, there was a partial mutation (1.5%) and 36.7% displayed a resistance profile to lamivudine, adevofir, and telbivudine. Immune response escape, vaccine escape, HBIg and diagnosis escape mutations were determined in 24%, 10%, 6%, and 4% samples of the patients, respectively. Additionally, there were six different combined mutations. These data underscored that there is no concern for primary mutations in Northern Cyprus, however, we have identified a compensatory mutation (rtV173M) that may have primary mutation characteristics by combining with other mutation patterns. Additionally, HBsAg escape mutants demonstrated that detection of the S gene together with the pol gene mutations might be beneficial and important to monitor the surveillance of S variants.


Further challenges to medical dominance? The case of nurse and pharmacist supplementary prescribing.
Doctors have traditionally been viewed as the dominant healthcare profession, with the authority to prescribe medicines, but recent non-medical prescribing initiatives have been viewed as possible challenges to such dominance. Using the example of the introduction of supplementary prescribing in the UK, this study sought to explore whether such initiatives represent a challenge to medical authority. Ten case study sites in England involving primary and secondary care and a range of clinical areas were used to undertake a total of 77 observations of supplementary prescribing consultations and interviews with 28 patients, 11 doctors and nurse and pharmacist prescribers at each site. Supplementary prescribing was viewed positively by all participants but several doctors and patients appeared to lack awareness and understanding of supplementary prescribing. Continued medical authority was supported empirically in five areas: patients' and supplementary prescribers' perception of doctors as being hierarchically superior; doctors legitimation of nurses' and pharmacists' prescribing initially; doctors' belief that they could control (particularly nurses') access to prescribing training; supplementary prescribers' frequent recourse to use doctors' advice, coupled with doctors' encouragement of such 'knock on door' prescribing advice policies; doctors' denigration of most routine prescribing but claims that diagnosis was more skilled and key to medicine. Supplementary prescribing appeared to be successfully accomplished in practice in a range of clinical settings and was acceptable to all involved but did not ultimately challenge medical dominance. However, more recent nurse and pharmacist independent prescribing (involving diagnosis) may represent a more significant threat.


A field size specific backscatter correction algorithm for accurate EPID dosimetry.
Portal dose images acquired with an amorphous silicon electronic portal imaging device (EPID) suffer from artifacts related to backscattered radiation. The backscatter signal varies as a function of field size (FS) and location on the EPID. Most current portal dosimetry algorithms fail to account for the FS dependence. The ramifications of this omission are investigated and solutions for correcting the measured dose images for FS specific backscatter are proposed. A series of open field dose images were obtained for field sizes ranging from 2 x 2 to 30 x 40 cm2. Each image was analyzed to determine the amount of backscatter present. Two methods to account for the relationship between FS and backscatter are offered. These include the use of discrete FS specific correction matrices and the use of a single generalized equation. The efficacy of each approach was tested on the clinical dosimetric images for ten patients, 49 treatment fields. The fields were evaluated to determine whether there was an improvement in the dosimetric result over the commercial vendor's current algorithm. It was found that backscatter manifests itself as an asymmetry in the measured signal primarily in the inplane direction. The maximum error is approximately 3.6% for 10 x 10 and 12.5 x 12.5 cm2 field sizes. The asymmetry decreased with increasing FS to approximately 0.6% for fields larger than 30 x 30 cm2. The dosimetric comparison between the measured and predicted dose images was significantly improved (p << .001) when a FS specific backscatter correction was applied. The average percentage of points passing a 2%, 2 mm gamma criteria increased from 90.6% to between 96.7% and 97.2% after the proposed methods were employed. The error observed in a measured portal dose image depends on how much its FS differs from the 30 x 40 cm2 calibration conditions. The proposed methods for correcting for FS specific backscatter effectively improved the ability of the EPID to perform dosimetric measurements. Correcting for FS specific backscatter is important for accurate EPID dosimetry and can be carried out using the methods presented within this investigation.


Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is an untreatable lung disease with a median survival of only 3-5 years that is diagnosed using a combination of clinical, radiographic and pathologic criteria. Histologically, IPF is characterised by usual interstitial pneumonia (UIP), a fibrosing interstitial pneumonia with a pattern of heterogeneous, subpleural regions of fibrotic and remodelled lung. We hypothesised that gene expression profiles of lung tissue may identify molecular subtypes of disease that could classify subtypes of IPF/UIP that have clinical implications. We collected transcriptional profiles on lung tissue from 119 patients with IPF/UIP and 50 non-diseased controls. Differential expression of individual transcripts was identified using an analysis of covariance (ANCOVA) model incorporating the clinical diagnosis of each patient as well as age, gender and smoking status. Validation was performed in an independent cohort of 111 IPF/UIP and 39 non-diseased controls. Our analysis identified two subtypes of IPF/UIP based on a strong molecular signature associated with expression of genes previously associated with fibrosis (matrix metalloproteinases, osteopontin, keratins), cilium genes and genes with unknown function. We demonstrate that elevated expression of cilium genes is associated with more extensive microscopic honeycombing and higher expression of both the airway mucin gene MUC5B and the metalloproteinase MMP7, a gene recently implicated in attenuating ciliated cell differentiation during wound repair. Expression of cilium genes appears to identify two unique molecular phenotypes of IPF/UIP. The different molecular profiles may be relevant to therapeutic responsiveness in patients with IPF/UIP.


[The danger present to the spinal cord arterial vasculature during surgery of nerve-tissue tumors of the posterior mediastinum].
The authors report one case of posterior mediastinal neurinoma with a Adamkiewicz artery arising at an atypical site. They stress the spinal cord complications following thoracic surgery. The value of spinal cord arteriography during preoperative examinations and for prevention of complications is discussed.


Internalization of intact poliovirus by HeLa cells as shown by subcellular fractionation in isoosmotic Nycodenz gradients.
HeLa cells were infected with radiolabelled poliovirus at different temperatures, and the intracellular distribution of input radioactivity was studied. To this end, homogenates were fractionated by rate zonal centrifugation in linear isoosmotic (2 to 30%) Nycodenz gradients. Further purification of subcellular fractions was achieved by recentrifugation to equilibrium in 10 to 30% Nycodenz. Temperatures were kept below 30 degrees C to prevent virus capsid modification. Under these conditions, the cell-associated virions remained fully infectious. Below 18 degrees C, most of the viral label was recovered from a bottom region (BR) of the rate zonal gradients. Marker enzyme analysis and antibody accessibility showed that the BR consisted of virions bound to the plasma membrane. Between 18 degrees C and 26 degrees C, viral label also accumulated in a top region (TR) of the rate zonal gradients. According to the criterion of antibody accessibility, the virions associated with the TR were present within intracellular structures, probably lipid membranes. Electron microscopy confirmed the presence of vesicles and tubules in this region of the gradient. No correlation was found between the TR and endosomal, lysosomal or plasma membrane markers. The TR equilibrated at low density (1.10 g/ml) in Nycodenz (free virus, 1.31 g/ml). The results confirm that intact poliovirions can enter the cell and do so via lipid-bound vesicles.


A high bone marrow plasma cell labeling index in stable plateau-phase multiple myeloma is a marker for early disease progression and death.
The plasma cell labeling index (PCLI) is a measure of plasma cell proliferative activity and is an important prognostic factor in newly diagnosed multiple myeloma (MM). Occasionally patients have been observed with stable, plateau phase MM with minimal numbers of residual light-chain-restricted monoclonal plasma cells, but a high PCLI. No data are available on the outcomes for such patients. Data from 57 patients with plateau phase MM and a marrow PCLI of more than 1.0% were compared with 105 matched control patients with MM with a marrow PCLI of less than 1.0%. All patients had less than 10% total plasma cells on marrow aspirate and biopsy. The median time to progression and overall survival were 8 months and 20 months, respectively, in the high PCLI group versus 39 months and 56 months, respectively, in the low PCLI group (P < .0001). These findings suggest that a high PCLI in patients with apparently stable, plateau phase MM is an adverse parameter that may predict a short time to disease progression and death.


Hospitals in Cape Town during the Anglo-Boer War.
The choice of Cape Town as the site for the base hospitals during the Anglo-Boer War was for many reasons a logical one. The hospitals that existed in the city at the time were inadequate in size and lacked the required facilities. The unexpectedly large number of wounded and the epidemics of typhoid and plague demanded an ever-increasing number of hospital beds. These demands were met by expanding existing hospitals making use of temporary hospitals and converting other buildings into hospitals. Eventually more than 3,000 beds were made available by the 10 hospitals in Cape Town and the system, despite continuing problems, provided a reasonable service under difficult circumstances.


[Stillbirth as a perinatal health indicator].
The authors carried out a literature review of the subject "stillbirth", with special emphasis on its conceptual and epidemiological features, aimed at highlighting its importance as a perinatal health indicator.


EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors.
Glioblastomas often show activation of epidermal growth factor receptor (EGFR) and loss of PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor, but it is not known if these two genetic lesions act together to transform cells. To answer this question, we infected PTEN-/- neural precursor cells with a retrovirus encoding EGFRvIII, which is a constitutively activated receptor. EGFRvIII PTEN-/- cells formed highly mitotic tumors with nuclear pleomorphism, necrotic areas, and glioblastoma markers. The transformed cells showed increased cell proliferation, centrosome amplification, colony formation in soft agar, self-renewal, expression of the stem cell marker CD133, and resistance to oxidative stress and ionizing radiation. The RAS/mitogen-activated protein kinase (ERK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways were activated, and checkpoint kinase 1 (Chk1), the DNA damage regulator, was phosphorylated at S280 by Akt, suppressing Chk1 phosphorylation at S345 in response to ionizing irradiation. The PTEN-/- cells showed low levels of DNA damage in the absence of irradiation, which was increased by EGFRvIII expression. Finally, secondary changes occurred during tumor growth in mice. Cells from these tumors showed decreased tumor latencies and additional chromosomal aberrations. Most of these tumor lines showed translocations of mouse chromosome 15. Intracranial injections of one of these lines led to invasive, glial fibrillary acidic protein-positive, nestin-positive tumors. These results provide a molecular basis for the occurrence of these two genetic lesions in brain tumors and point to a role in induction of genomic instability.


The hybrid approach for the surgical treatment of lone atrial fibrillation: one-year results employing a monopolar radiofrequency source.
The hybrid technique combines a mono or bilateral epicardial approach with a percutaneous endocardial ablation in a single-step procedure. We present our early results with this technique employing a monopolar radiofrequency source through a right thoracoscopy in patients with lone atrial fibrillation (LAF). Between June 2009 and December 2010 nineteen consecutive patients (mean 60.8 ± 8.6 years, 84.2% male) underwent right unilateral minimally invasive hybrid procedure for LAF at our Institution. Ten patients (52.6.6%) had long-standing persistent AF while four (21.1%) had persistent and five (26.3%) paroxysmal AF. All patients were followed-up according the Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society (HRS/EHRA/ECA) and Society of Thoracic Surgeon (STS) guidelines. There were neither early nor late deaths. It was possible to complete all the procedures as planned without any conversion to cardiopulmonary bypass. No patient died during the follow up. At one year, 7/19 (36.8%) patients were in sinus rhythm with no episode of AF and off antiarrhythmic drugs (AAD). Time-related prevalence of postoperative AF peaked at 44.4% (41.3-47.4) at two weeks, was 30.4% (27.3-34.9) at three months, fell to 14.2% (11.6-18.1) by 6 months and was 13.3% (11.0-17.4) at 12 months Among patients with long-standing persistent (LSP) AF, 20% (2/10) were in Sinus rythm and off AAD. One-year success rates were 50% (2/4) in persistent and 60% (3/5) in paroxysmal AF. At 12 months estimated prevalence of antyarrhythmic drugs and Warfarin use were 26% (22.4-33.1) and 48% (37.2-53.2), respectively. One year results combining the percutaneous endocardial with the right thoracoscopic epicardial technique were, in our experience, not satisfactory, particularly in patients with LSP and persistent AF. Our findings need to be confirmed by larger studies.


Multiple Introductions of Tomato Pathogen Clavibacter michiganensis subsp. michiganensis into Iran as Revealed by a Global-Scale Phylogeographic Analysis.
Tomato bacterial canker caused by Clavibacter michiganensis subsp. michiganensis is one of the most important seed-borne tomato diseases around the globe. The disease was initially reported in 1993 in Iran, and it became a rising threat for the multibillion dollar tomato industry of the country during the last decade. In this study, using phylogeographic analyses, we determined genetic diversity and geographic distribution of C. michiganensis subsp. michiganensis in Iran. Our field surveys showed that the pathogen is expanding into the southern and eastern areas of the country. Furthermore, multilocus sequence analysis and typing (MLSA/MLST) using the sequences of five housekeeping genes (atpD, gyrB, ppk, recA, and rpoB) revealed that 37 C. michiganensis subsp. michiganensis strains isolated in Iran had high genetic diversity and placed in 15 sequence types (STs), while all the available 184 worldwide C. michiganensis subsp. michiganensis sequences were placed in 43 STs. MLSA divided the worldwide C. michiganensis subsp. michiganensis strains into two phylogroups (I and II). Among the 37 strains isolated in Iran, 30 strains clustered in phylogroup I, while 7 strains clustered in phylogroup II. Phylogeographic data inferred from the allelic profile of the five housekeeping genes suggested multiple introductions of C. michiganensis subsp. michiganensis inoculum into Iran, while the geographic origin of the Iranian C. michiganensis subsp. michiganensis strains remains undetermined. Further analyses using higher numbers of strains are warranted to decipher the evolutionary history of C. michiganensis subsp. michiganensis in Iran. Additionally, stricter seed/transplant inspections are recommended to reduce the risk of pathogen expansion to areas with no history of the disease.IMPORTANCEClavibacter michiganensis subsp. michiganensis, the causal agent of tomato bacterial canker disease, is one of the economically important pathogens of solanaceous crops (e.g., eggplant, pepper, and tomato) around the world. The disease occurs in many countries, with a particular importance in regions characterized by high precipitation and humid environmental conditions. As a seed-borne pathogen, C. michiganensis subsp. michiganensis is included in the A2 (high risk) list of quarantine pathogens by the European and Mediterranean Plant Protection Organization (EPPO). Bacterial canker disease was reported for the first time in 1993 in Iran, while the geographic distribution, genetic diversity, and phylogenetic position of the causal agent remain undetermined. In this study, using the multilocus sequence analysis and typing (MLSA/MLST) approach, we provided a phylogeographic scheme for the C. michiganensis subsp. michiganensis strains isolated in Iran. Furthermore, global-scale phylogenetic analyses led to determination of phylogenetic position of Iranian C. michiganensis subsp. michiganensis strains among worldwide population of the pathogen. Based on diversity parameters and population structure, we suggest relatively higher genetic diversity of the bacterial canker pathogen in Iran than has so far been observed in the other areas of the world. Results obtained in this study provide a novel insight into the genetic diversity and population structure of the bacterial canker pathogen on a global scale.


Spelling ability selectively predicts the magnitude of disruption in unspaced text reading.
We examined the effect of individual differences in written language proficiency on unspaced text reading in a large sample of skilled adult readers who were assessed on reading comprehension and spelling ability. Participants' eye movements were recorded as they read sentences containing a low or high frequency target word, presented with standard interword spacing, or in one of three unsegmented text conditions that either preserved or eliminated word boundary information. The average data replicated previous studies: unspaced text reading was associated with increased fixation durations, a higher number of fixations, more regressions, reduced saccade length, and an inflation of the word frequency effect. The individual differences results provided insight into the mechanisms contributing to these effects. Higher reading ability was associated with greater overall reading speed and fluency in all conditions. In contrast, spelling ability selectively modulated the effect of interword spacing with poorer spelling ability predicting greater difficulty across the majority of sentence- and word-level measures. These results suggest that high quality lexical representations allowed better spellers to extract lexical units from unfamiliar text forms, inoculating them against the disruptive effects of being deprived of spacing information. (PsycINFO Database Record


[Clinicomorphological diagnosis and surgical treatment of complicated gastroesophageal reflux disease].
Biopsy and surgery specimens taken from 224 patients with gastroesophageal reflux disease were clinically and morphologically analyzed. The morphological diagnosis of this condition is of more informative value than endoscopy and X-ray study. Malignization occurs in 25% of patients with Barrett oesophagus. One case of surgical treatment for gastroesophageal reflux disease yielding a good outcome is described.


Breach of autoreactive B cell tolerance by post-translationally modified proteins.
Over 50% of patients with rheumatoid arthritis (RA) harbour a variety of anti-modified protein antibodies (AMPA) against different post-translationally modified (PTM) proteins, including anti-carbamylated protein (anti-CarP) antibodies. At present, it is unknown how AMPA are generated and how autoreactive B cell responses against PTM proteins are induced. Here we studied whether PTM foreign antigens can breach B cell tolerance towards PTM self-proteins. Serum reactivity towards five carbamylated proteins was determined for 160 patients with RA and 40 healthy individuals. Antibody cross-reactivity was studied by inhibition experiments. Mass spectrometry was performed to identify carbamylated self-proteins in human rheumatic joint tissue. Mice were immunised with carbamylated or non-modified (auto)antigens and analysed for autoantibody responses. We show that anti-CarP antibodies in RA are highly cross-reactive towards multiple carbamylated proteins, including modified self-proteins and modified non-self-proteins. Studies in mice show that anti-CarP antibody responses recognising carbamylated self-proteins are induced by immunisation with carbamylated self-proteins and by immunisation with carbamylated proteins of non-self-origin. Similar to the data observed with sera from patients with RA, the murine anti-CarP antibody response was, both at the monoclonal level and the polyclonal level, highly cross-reactive towards multiple carbamylated proteins, including carbamylated self-proteins. Self-reactive AMPA responses can be induced by exposure to foreign proteins containing PTM. These data show how autoreactive B cell responses against PTM self-proteins can be induced by exposure to PTM foreign proteins and provide new insights on the breach of autoreactive B cell tolerance.


Pathobiology of actinic keratosis: ultraviolet-dependent keratinocyte proliferation.
Actinic keratoses are proliferations of transformed neoplastic keratinocytes in the epidermis that are the result of cumulative ultraviolet (UV) radiation from sun exposure. They are commonly found on sites of sun-exposed skin such as the face, balding scalp, and back of the hand. Although UV exposure does exert certain beneficial effects on the skin, excessive exposure to UV radiation induces multiple cascades of molecular signaling events at the cellular level that produce inflammation, immunosuppression, failure of apoptosis, and aberrant differentiation. Cumulatively, these actions result in mutagenesis and, ultimately, carcinogenesis. This article provides a brief overview of the key mediators that are implicated in the pathobiology of actinic keratosis. Three evolutionary possibilities exist for these keratoses in the absence of treatment: (1) spontaneous remission, which can be common; (2) remaining stable, without further progression; or (3) transformation to invasive squamous cell carcinoma, which may metastasize. Because the effects of UV radiation on the skin are complex, it is not yet fully clear how all of the mediators of actinic keratosis progression are interrelated. Nonetheless, some represent potential therapeutic targets, because it is clear that directing therapy to the effects of UV radiation at a number of different levels could interrupt and possibly reverse the mechanisms leading to malignant transformation.


Non-invasive assessment of sciatic nerve stiffness during human ankle motion using ultrasound shear wave elastography.
Peripheral nerves are exposed to mechanical stress during movement. However the in vivo mechanical properties of nerves remain largely unexplored. The primary aim of this study was to characterize the effect of passive dorsiflexion on sciatic nerve shear wave velocity (an index of stiffness) when the knee was in 90° flexion (knee 90°) or extended (knee 180°). The secondary aim was to determine the effect of five repeated dorsiflexions on the nerve shear wave velocity. Nine healthy participants were tested. The repeatability of sciatic nerve shear wave velocity was good for both knee 90° and knee 180° (ICCs ≥ 0.92, CVs ≤ 8.1%). The shear wave velocity of the sciatic nerve significantly increased (p<0.0001) during dorsiflexion when the knee was extended (knee 180°), but no changes were observed when the knee was flexed (90°). The shear wave velocity-angle relationship displayed a hysteresis for knee 180°. Although there was a tendency for the nerve shear wave velocity to decrease throughout the repetition of the five ankle dorsiflexions, the level of significance was not reached (p=0.055). These results demonstrate that the sciatic nerve stiffness can be non-invasively assessed during passive movements. In addition, the results highlight the importance of considering both the knee and the ankle position for clinical and biomechanical assessment of the sciatic nerve. This non-invasive technique offers new perspectives to provide new insights into nerve mechanics in both healthy and clinical populations (e.g., specific peripheral neuropathies).


Remarkable performance of Ir1/FeO(x) single-atom catalyst in water gas shift reaction.
High specific activity and cost effectiveness of single-atom catalysts hold practical value for water gas shift (WGS) reaction toward hydrogen energy. We reported the preparation and characterization of Ir single atoms supported on FeO(x) (Ir1/FeO(x)) catalysts, the activity of which is 1 order of magnitude higher than its cluster or nanoparticle counterparts and is even higher than those of the most active Au- or Pt-based catalysts. Extensive studies reveal that the single atoms accounted for ∼70% of the total activity of catalysts containing single atoms, subnano clusters, and nanoparticles, thus serving as the most important active sites. The Ir single atoms seem to greatly enhance the reducibility of the FeO(x) support and generation of oxygen vacancies, leading to the excellent performance of the Ir1/FeO(x) single-atom catalyst. The results have broad implications on designing supported metal catalysts with better performance and lower cost.


Hello again.
'I have to keep fishing them out of the bin,' said the doctor. There was a supply problem with our disposable instruments, so we had reverted to the old method of sterilising and reusing, but we were still forgetting and throwing them away.


Influenza immunization: the impact of notifying patients of high-risk status.
The influenza immunization rate in the high-risk military and retired military population has not been reported. To determine this rate, and to test whether the rate could be improved by notifying patients of their high-risk status, a clinical trial was conducted using a postcard reminder as an intervention. All 1068 high-risk patients enrolled in a large, residency-affiliated, military family practice department were identified. Of these, 519 patients were randomly selected to receive a reminder postcard; the remainder (549) were not sent a card. The immunization rates of each group were compared. A significantly higher percentage of those to whom postcards were sent received an influenza immunization (25.2% vs 9.1%, P less than .001). This difference was significant in all demographic groups except in those less than 21 years of age and those 21 to 40 years of age, in which very few patients presented for immunization. In those in the study group aged 65 years and over, 46.7% were immunized vs 20% of controls (P less than .001). Those aged 65 years and older and those in the higher income group had higher immunization rates, while those aged 40 years and under had very low immunization rates. The influenza immunization rate among military beneficiaries in high-risk groups is low, but can be significantly improved with a reminder postcard. This intervention may be more effective in the older and higher-income segments of the high-risk population. The low immunization rates of the lower-income group and the younger age groups have significant public health implications and should be studied further.


Mitochondrial Dysfunction and α-Synuclein Synaptic Pathology in Parkinson's Disease: Who's on First?
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Its characteristic neuropathological features encompass the loss of dopaminergic neurons of the nigrostriatal system and the presence of Lewy bodies and Lewy neurites. These are intraneuronal and intraneuritic proteinaceous insoluble aggregates whose main constituent is the synaptic protein α-synuclein. Compelling lines of evidence indicate that mitochondrial dysfunction and α-synuclein synaptic deposition may play a primary role in the onset of this disorder. However, it is not yet clear which of these events may come first in the sequel of processes leading to neurodegeneration. Here, we reviewed data supporting either that α-synuclein synaptic deposition precedes and indirectly triggers mitochondrial damage or that mitochondrial deficits lead to neuronal dysfunction and α-synuclein synaptic accumulation. The present overview shows that it is still difficult to establish the exact temporal sequence and contribution of these events to PD.


Black lipid membranes stabilized through substrate conjugation to a hydrogel.
Recent research in stabilizing lipid bilayer membranes has been directed toward tethering the membrane to a solid surface or contacting the membrane with a solid support such as a gel. It is also known that the solvent annulus plays an important role in lipid bilayer stability. In this work, the authors set out to stabilize the solvent annulus. Glass substrates with approximately 500 mum apertures were functionalized with 3-methacryloxypropyltrimethoxysilane to allow cross-linking with a surrounding polyethyleneglycol dimethacrylate hydrogel. The hydrogel makes a conformal mold around both the lipid bilayer and the solvent reservoir. Since the hydrogel is covalently conjugated with the glass substrate via vinyl groups, the solvent annulus is prevented from leaving the aperture boundary. Measurements of a membrane created with this approach showed that it remained a stable bilayer with a resistance greater than 1 GOmega for 12 days. Measurements of the ion channel gramicidin A, alpha-hemolysin, and alamethicin incorporated into these membranes showed the same conductance behavior as conventional membranes.


Oral contraceptive use and breast cancer: a prospective study of young women.
Previous studies convincingly showed an increase in risk of breast cancer associated with current or recent use of oral contraceptives from the 1960s to 1980s. The relation of contemporary oral contraceptive formulations to breast cancer risk is less clear. We assessed lifetime oral contraceptive use and the specific formulations used among 116,608 female nurses ages 25 to 42 years at enrollment in 1989, and subsequently updated this information every 2 years. We related this information to risk of breast cancer up to June 1, 2001. During 1,246,967 person-years of follow-up, 1,344 cases of invasive breast cancer were diagnosed. Past use of any oral contraceptive was not related to breast cancer risk [multivariate relative risk (RR), 1.12; 95% confidence interval 0.95-1.33]. Current use of any oral contraceptive was related to a marginally significant higher risk (multivariate RR, 1.33; 95% CI, 1.03-1.73). One specific formulation substantially accounted for the excess risk: the RR for current use of triphasic preparations with levonorgestrel as the progestin was 3.05 (95% CI, 2.00-4.66; P < 0.0001). Current use of oral contraceptives carries an excess risk of breast cancer. Levonorgestrel used in triphasic preparations may account for much of this elevation in risk. Different oral contraceptive formulations might convey different risks of breast cancer; ongoing monitoring of these associations is necessary as oral contraceptive formulations change.


The Effects of Poor Neonatal Health on Children's Cognitive Development.
We make use of a new data resource--merged birth and school records for all children born in Florida from 1992 to 2002--to study the relationship between birth weight and cognitive development. Using singletons as well as twin and sibling fixed effects models, we find that the effects of early health on cognitive development are essentially constant through the school career; that these effects are similar across a wide range of family backgrounds; and that they are invariant to measures of school quality. We conclude that the effects of early health on adult outcomes are therefore set very early.


Human infection with avian influenza A H7N9 virus: an assessment of clinical severity.
Characterisation of the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with avian influenza A H7N9 virus, which emerged in China in early 2013. We obtained information about laboratory-confirmed cases of avian influenza A H7N9 virus infection reported as of May 28, 2013, from an integrated database built by the Chinese Center for Disease Control and Prevention. We estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit for patients who required hospital admission for medical reasons. We also used information about laboratory-confirmed cases detected through sentinel influenza-like illness surveillance to estimate the symptomatic case fatality risk. Of 123 patients with laboratory-confirmed avian influenza A H7N9 virus infection who were admitted to hospital, 37 (30%) had died and 69 (56%) had recovered by May 28, 2013. After we accounted for incomplete data for 17 patients who were still in hospital, we estimated the fatality risk for all ages to be 36% (95% CI 26-45) on admission to hospital. Risks of mechanical ventilation or fatality (69%, 95% CI 60-77) and of admission to an intensive care unit, mechanical ventilation, or fatality (83%, 76-90) were high. With assumptions about coverage of the sentinel surveillance network and health-care-seeking behaviour for patients with influenza-like illness associated with influenza A H7N9 virus infection, and pro-rata extrapolation, we estimated that the symptomatic case fatality risk could be between 160 (63-460) and 2800 (1000-9400) per 100,000 symptomatic cases. Human infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection. Chinese Ministry of Science and Technology; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; US National Institute of Allergy and Infectious Disease; and the US National Institutes of Health.


Expressed emotion as an assessment of family environment with mothers and fathers of 1-year-old children.
High levels of expressed emotion (EE) in parents have been found to put children at risk for emotional and behavioural problems. However, the majority of existing studies have focused on mothers of school-aged children and adolescents rather than younger children, and have only rarely included fathers. The present study examined the reliability of EE in mothers and fathers of 1-year old children. It also investigated whether depression and marital problems in the postnatal period predicted EE toward the child at 12 months. EE was assessed with the Preschool Five Minute Speech Sample in 163 families. The rater-interrater and code-recode reliability was high for most EE dimensions. Mothers and fathers were found to display quite similar EE scores. Regression analyses showed that depression and couple relationship significantly predicted EE in mothers, but not fathers. The findings suggest that EE provides a reliable and useful assessment of the family environment in families of young children.


Potential prevention strategies for Alzheimer disease.
Primary prevention trials for Alzheimer disease (AD) should be considered because of the substantial cost of caring for AD patients. Current clues to possible treatments include the potential use of antioxidants, estrogens, anti-inflammatory drugs, drugs designed to alter apolipoprotein E4 status, and compounds altering amyloid metabolism. Because of the expense of primary prevention trials, resources should be devoted to developing epidemiological clues for environmental loss in vivo and searching for additional epidemiological clues for environmental factors that may protect individuals from AD. A primary prevention trial would involve the recruitment of 4,000-5,000 subjects followed for 3-5 years at a cost of approximately $20 million. Alternatively, a primary prevention trial could be performed as an "add on" study to an existing clinical trial of a compound of interest currently being tested in an elderly population at substantially less cost.


Eight different highly specific nucleosome phases on alpha-satellite DNA in the African green monkey.
The question of nucleosome phasing on African Green Monkey (AGM) alpha-satellite DNA has been addressed by employing a new approach. Nucleosome cores were prepared from AGM nuclei with micrococcal nuclease, exonuclease III and nuclease S1. The core DNA population derived from alpha-satellite DNA containing chromatin was purified from total core DNA by denaturation of the DNA, reassociation to a low Cot value, and hydroxyapatite chromatography to separate the renatured satellite fraction. After end-labeling the termini of the alpha-satellite containing core DNA fragments were mapped by high resolution gel electrophoresis relative to known restriction sites along the 172 bp repeat unit of the satellite DNA. The results show that nucleosomes occupy eight strictly defined positions on the alpha-satellite DNA which could be determined with an accuracy of +/- 1 base pair. Approximately 35% of all nucleosomes are organized in one of these frames while the other seven registers contribute about 10% each.


Lesion area detection using source image correlation coefficient for CT perfusion imaging.
Computer tomography (CT) perfusion imaging is widely used to calculate brain hemodynamic quantities such as cerebral blood flow, cerebral blood volume, and mean transit time that aid the diagnosis of acute stroke. Since perfusion source images contain more information than hemodynamic maps, good utilization of the source images can lead to better understanding than the hemodynamic maps alone. Correlation-coefficient tests are used in our approach to measure the similarity between healthy tissue time-concentration curves and unknown curves. This information is then used to differentiate penumbra and dead tissues from healthy tissues. The goal of the segmentation is to fully utilize information in the perfusion source images. Our method directly identifies suspected abnormal areas from perfusion source images and then delivers a suggested segmentation of healthy, penumbra, and dead tissue. This approach is designed to handle CT perfusion images, but it can also be used to detect lesion areas in magnetic resonance perfusion images.


Outcome in ulcerative colitis after switch from adalimumab/golimumab to infliximab: A multicenter retrospective study.
Anti-TNF therapies infliximab (IFX), adalimumab (ADA), and golimumab (GOL) are approved for treating moderate to severe ulcerative colitis (UC). In UC, only the switch from IFX to ADA has been investigated, reaching no more than 10-43% remission rates at 12 months. Of the present study was to investigate disease outcome after a switch from subcutaneous (SC) agents to the intravenous (IV) agent (IFX). In this retrospective multicentre study, we analysed the charts of UC patients unresponsive/intolerant or with secondary loss of response (LOR) to ADA or GOL who were switched to IFX. We evaluated clinical response and remission together with adverse events at 3, 6, and 12 months follow-up. Seventy-six patients were included; 38 patients started ADA and 38 started GOL for a mean therapy duration of 6 ± 6 months. Indications for switch were adverse events in 3%, primary failure in 79%, and LOR in 18% of patients. Clinical remission was reached by 47%, 50%, and 77% of patients, respectively. Patients that switched for LOR did numerically, but not statistically, better than patients who switched for primary failure. Our data show a superior remission rate in SC to IV anti-TNF switch in UC compared to the IV to SC switch reported in literature.


Elevated plasma concentrations of interferon (IFN)-gamma and the IFN-gamma-inducing cytokines interleukin (IL)-18, IL-12, and IL-15 in severe melioidosis.
Interferon (IFN)-gamma plays an important role in the pathogenesis of sepsis. Production of IFN-gamma is stimulated by synergistic effects of interleukin (IL)-18, IL-12, and IL-15. To investigate the regulation of IFN-gamma production during severe gram-negative infection, the plasma concentrations of IFN-gamma, IL-18, IL-12, and IL-15 were measured in 83 patients with suspected melioidosis. The diagnosis was confirmed in 62 patients, 31 of whom had blood cultures positive for Burkholderia pseudomallei, of whom 12 died. Compared with healthy controls, patients had elevated levels of IFN-gamma, IL-18, IL-12p40, and IL-15 on admission, with significantly higher levels in blood culture-positive patients, and these levels remained elevated during the 72-h study period. In whole blood stimulated with heat-killed B. pseudomallei, anti-IL-12 had a stronger inhibitory effect than anti-IL-18 and anti-IL-15 on IFN-gamma production. This effect of anti-IL-12 was further enhanced by anti-IL-18. These data suggest that during gram-negative sepsis, IFN-gamma production is controlled at least in part by endogenous IL-18, IL-12, and IL-15.


[Beta thalassemia: molecular pathogenesis and clinical variability].
Clinically, homozygous beta-thalassaemia is characterised by a severe anaemia requiring regular transfusion therapy in most patients. However, there is a marked clinical variability ranging from this severe picture to the virtual absence of symptoms and haematological abnormalities. Biochemically, beta-globin synthesis in the erythroid precursors of the bone marrow is reduced or absent resulting in a relative excess of insoluble alpha-globin chains and dyserythropoiesis. The molecular genetics of this disorder is highly variable involving a multitude of different mutations of the beta-globin gene. These mutations can inactivate gene expression at all levels on its way from DNA to mature haemoglobin. The clinical picture is largely determined by the type of mutations inherited. Additionally the degree of alpha-globin chain excess can be influenced by the co-inheritance of alpha-thalassaemia or mutations resulting in the hereditary persistence of fetal globin synthesis (HPFH). This review discusses the relationship between the molecular defect and the clinical picture of patients with beta-thalassaemia.


Patient Safety Errors: Leveraging Health Information Technology to Facilitate Patient Reporting.
Patient safety continues to be a national challenge not only for providers but for patients and families as well. In an attempt to standardize processes and systems, we have lost opportunities for improvement. For instance, current patient safety reporting systems tend to favor capturing details around events that are classified as highly clinically significant (i.e., sentinel-level and never events); yet little to no effort is spent on capturing information about less evident errors or near misses, nor simply about concerns that are more experiential in nature. As a result, patients' experiences and observations are relegated to the notion of satisfaction, real-time reporting remains illusive, and the ability to learn across incidents remains anecdotal rather than systematic. Herein we propose an alternative, real-time, innovative model that merges syndromic surveillance and patient engagement to embrace patient-initiated reporting of patient safety events and concerns. The result would be a patient safety system where patients are partners, in both the conduct of their care, and in the quality of the healthcare delivered.


Alteration of a novel dispensable mitochondrial ribosomal small-subunit protein, Rsm28p, allows translation of defective COX2 mRNAs.
Mutations affecting the RNA sequence of the first 10 codons of the Saccharomyces cerevisiae mitochondrial gene COX2 strongly reduce translation of the mRNA, which encodes the precursor of cytochrome c oxidase subunit II. A dominant chromosomal mutation that suppresses these defects is an internal in-frame deletion of 67 codons from the gene YDR494w. Wild-type YDR494w encodes a 361-residue polypeptide with no similarity to proteins of known function. The epitope-tagged product of this gene, now named RSM28, is both peripherally associated with the inner surface of the inner mitochondrial membrane and soluble in the matrix. Epitope-tagged Rsm28p from Triton X-100-solubilized mitochondria sedimented with the small subunit of mitochondrial ribosomes in a sucrose gradient containing 500 mM NH4Cl. Complete deletion of RSM28 caused only a modest decrease in growth on nonfermentable carbon sources in otherwise wild-type strains and enhanced the respiratory defect of the suppressible cox2 mutations. The rsm28 null mutation also reduced translation of an ARG8m reporter sequence inserted at the COX1, COX2, and COX3 mitochondrial loci. We tested the ability of RSM28-1 to suppress a variety of cox2 and cox3 mutations and found that initiation codon mutations in both genes were suppressed. We conclude that Rsm28p is a dispensable small-subunit mitochondrial ribosomal protein previously undetected in systematic investigations of these ribosomes, with a positive role in translation of several mitochondrial mRNAs.


[Use of molybdenum media with glycerin and admixtures of unassimilated polyols for differentiating actinomycetes].
Actinomycetes were cultivated in a medium containing from 0.15 to 0.2% of ammonium molybdate, glycerol and from 0.25 to 1% of polyol which was not assimilated by the cultures and inhibited the production of molybdenum blue in many actinomycetes. The cultures differed in their susceptibility to the inhibition by various polyols. There were not two polyols that would produce an identical effect on all of the cultures. Correlations were established in the action of polyols. The differences in the formation of molybdenum blue can be used for the differentiation and identification of actinomycetes to subdivide them into groups according to their sensitivity to inositol, mannitol, D-arabitol, xylitol, sorbitol, L-arabitol and dulcitol and according to their resistance to dulcitol (minimal, average and maximal resistance). The paper presents schemes for subdividing groups into subgroups and for establishing the properties.


The co-occurrence of myocardial dysfunction and peripheral insensate neuropathy in a streptozotocin-induced rat model of diabetes.
Cardiomyopathy and distal symmetrical polyneuropathy (DSPN), including sensory and autonomic dysfunction, often co-occur in diabetic mellitus (DM) patients. However, the temporal relationship and progression between these two complications has not been investigated. Using a streptozotocin DM animal model that develops insensate neuropathy, our aim was to examine in parallel the development of DSPN and DM-associated changes in cardiac structure and function as well as potential mechanisms, such as autonomic dysfunction, evaluated by changes in urinary and myocardial norepinephrine content and myocardial neuronal markers. Sensory neuropathy was measured by behavioral tests using Von Frey filaments and Hargreaves methods. Echocardiography was used to evaluate myocardial structure and function. Autonomic function was evaluated by measuring urinary and myocardial norepinephrine (NE) levels by enzyme-linked immunosorbent assay and high-performance liquid chromatography/mass spectrometry. Quantitative immunohistochemistry was used to measure the myocardial neuronal markers, calcitonin gene-related peptide (CGRP) and general neuronal protein gene product 9.5 (PGP 9.5). The DM group developed tactile and thermal insensate neuropathy 4-5 weeks after DM onset. Cardiovascular changes were found between 4 and 12 weeks after DM onset and included bradycardia, diastolic and systolic dysfunction and cardiac dilation. There was a 2.5-fold reduction in myocardial NE levels and a 5-fold increase in urinary NE levels in the DM group. Finally, there was a 2.3-fold increase in myocardial CGRP levels in the DM group and no change in PGP9.5 levels. Cardiovascular structural and functional changes developed early in the course of DM and in combination with insensate neuropathy. In parallel, signs of cardiac autonomic dysfunction were also found and included decreased myocardial NE levels and altered CGRP levels. These results may indicate the need for early cardiovascular evaluation in DM patients with insensate neuropathy.


Childhood femoral fracture can lead to premature knee-joint arthritis. 21-year follow-up results: a retrospective study.
During the past decades, treatment of pediatric femoral fractures in Finland has changed from mostly non-operative to more operative. In this retrospective study, we analyzed the long-term results of treatment. 74 patients (mean age 7 (0-14) years) with a femoral fracture were treated in Aurora City Hospital in Helsinki during the period 1980-89. 52 of 74 patients participated in this clinical study with a mean follow-up of 21 (16-28) years. Fracture location, treatment mode, time of hospitalization, and fracture alignment at union were assessed. Subjective assessment and range of motion of the hip and knee were evaluated. Leg-length discrepancy and alignment of the lower extremities were measured both clinically and radiographically. Of the 52 children, 28 had sustained a shaft fracture, 13 a proximal fracture, and 11 a distal fracture. 44 children were treated with traction, 5 by internal fixation, and 3 with cast-immobilization. Length of the hospital treatment averaged 58 (3-156) days and the median traction time was 39 (3-77) days. 21 of the 52 patients had angular malalignment of more than 10 degrees at union. 20 patients experienced back pain. Limping was seen in 10 patients and leg-length discrepancy of more than 15 mm was in 8 of the 52 patients. There was a positive correlation between angular deformity and knee-joint arthritis in radiographs at follow-up in 6 of 15 patients who were over 10 years of age at the time of injury. Angular malalignment after treatment of femoral fracture may lead to premature knee-joint arthritis. Tibial traction is not an acceptable treatment method for femoral fractures in children over 10 years of age.


Critical design issues in the targeted molecular imaging of cell surface receptors.
The imaging of cell-surface receptors can be achieved using several methods, including single photon emission tomography (SPECT) positron emission tomography (PET), optical imaging and magnetic resonance imaging (MRI). The application of targeted MRI contrast agents is particularly well-suited to this task, provided that the agents reach the desired site efficiently and selectively. In addition, they should bind reversibly to the cell-surface receptor and give rise to a large change in cellular relaxation rate, in competition with binding to the natural substrate. Such approaches offer promise in the molecular imaging of neurotransmission in the brain, using conjugates that selectively target dopamine or glutamate receptor sub-types. Strategies based on the use of competitive antagonist vectors offer particular scope, as such conjugates are generally not taken into the target cell following cell surface receptor binding, in contrast to the use of MRI contrast agents based on agonists that tend to be internalised quickly or are designed to target intracellular sites.


Does one day of drinking matter? 21st birthday drinking predicts subsequent drinking and consequences.
There has been ample research on college student risks and consequences related to 21st Birthday Drinking. To date, no studies we are aware of have examined how 21st birthday drinking impacts subsequent drinking and related consequences. This study evaluates the effect of a single night of drinking on peak drinking, heavy drinking, and negative consequences over 12months following the event. Furthermore, we examine if typical drinking behavior prior to 21st birthday moderates the relationship between the event drinking and subsequent use. Participants included 599 college students (46% male) who intended to consume at least five/four drinks (men/women respectively) on their 21st birthday. Screening and baseline assessments were completed approximately four weeks before turning 21. A follow-up assessment was completed approximately one week after students' birthdays and every 3months for one year thereafter. Those who drank more on their 21st birthday, also reported higher peak consumption, increased likelihood of consequences, and increased number of consequences throughout the year. Additionally, baseline peak drinking moderated the relationship such that those who drank less at peak occasion prior to turning 21 showed the strongest effects of 21st BD drinking on subsequent consumption. 21st BD drinking could impact subsequent choices and problems related to alcohol. Interventions are warranted and implications discussed.


Positive endocochlear potential: mechanism of production by marginal cells of stria vascularis.
The positive endocochlear potential (EP+) and high K+ concentration of the endolymph in the scala media of the mammalian cochlea are unusual. They have long been assumed to be due to a putative K-pump in the luminal membrane of the marginal cells of the stria vascularis, which were believed to have a negative internal potential. We show that the cell potential is more positive than the EP+, and that the ion pump is conventional Na,K-ATPase, probably in the basolateral membrane. The latter was determined from experiments in which the ionic environment of the strial cells was controlled by perfusion of the perilymphatic space of the cochlea, in the absence of vascular circulation. While the usual EP+ was maintained by normal perfusate, replacement of Na+ by choline resulted in a negative EP, showing that Na,K-ATPase is necessary for the production of EP+. Elimination of K+ as well as Na+ from the perfusate did not change the value of the negative EP, showing that no K-ATPase is involved.


Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: A longitudinal study.
Transgenic animals expressing mutant human amyloid precursor protein (APP) are used as models for Alzheimer disease (AD). Ideally, behavioral tests improve the predictive validity of studies on animals by mirroring the functional impact of AD-like neuropathology. Learning and memory studies in APP transgenic models have been difficult to replicate. Standardization of procedures, automatization or improved protocol design can improve reproducibility. Here the IntelliCage, an automated system, was used for behavioral testing of APP female transgenic mice with both the Arctic and Swedish mutations, the tg-ArcSwe model. Protocols covering exploration, operant learning, place learning and extinction of place preference as well as passive avoidance tests were used for longitudinal characterization of behavior. Differences in exploratory activity were significant at four months of age, when plaque-free tg-ArcSwe mice visited less frequently the IntelliCage corners and initially performed fewer visits with licks compared to non-tg animals, inside the new environment. Fourteen months old tg-ArcSwe mice required a longer time to re-habituate to the IntelliCages than non-tg mice. At both ages tg-ArcSwe mice perseverated in place preference extinction test. Fourteen months old tg-ArcSwe mice were impaired in hippocampus-dependent spatial passive avoidance learning. This deficit was found to inversely correlate to calbindin-D28k immunoreactivity in the polymorphic layer of the dentate gyrus. Reduced water intake and body weight were observed in 4 months old tg-ArcSwe animals. The body weight difference increased with age. Thus behavioral and metabolic changes in the tg-ArcSwe APP model were detected using the IntelliCage, a system which provides the opportunity for standardized automated longitudinal behavioral phenotyping.


Specificity of postural sway to the demands of a precision task at sea.
Mariners actively adjust their body orientation in response to ship motion. On a ship at sea, we evaluated relations between standing postural activity and the performance of a precision aiming task. Standing participants (experienced mariners) maintained the beam from a handheld laser on a target. Targets were large or small, thereby varying the difficulty of the aiming task. Targets were located in front of the participant or to the participant's right (requiring participants to look over the right shoulder), thereby varying the functional consequences (for the aiming task) of postural activity in different body axes. The torso was oriented toward the bow or toward the ship's side (athwartship), thereby varying the effects on postural activity of differential motion of the ship in its different axes. The weather was rough, producing high magnitudes of ship motion, which sometimes caused participants to step or stagger. Our manipulations influenced the magnitude and dynamics of head and torso movements, as well as the organization of movement in different axes. The results provide the first empirical confirmation that postural activity can be influenced by orientation of the torso relative to a ship. Despite powerful effects of ship motion, postural activity was influenced by variations in target location and in the difficulty of the aiming task, replicating subtle effects that have been observed on land. We discuss implications for hull design and the placement of workstations on ships.


Improvement of Foxp3 stability through CNS2 demethylation by TET enzyme induction and activation.
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine. TET-CD over-expression in iTregs resulted in partial demethylation of CNS2 and stable Foxp3 expression. We also discovered that TET expression was enhanced under low oxygen (5%) culture conditions, which facilitated CNS2 DNA demethylation and stabilization of Foxp3 expression in a TET2- and TET3-dependent manner. In combination with vitamin C treatment, which has been reported to enhance TET catalytic activity, iTregs generated under low oxygen conditions retained more stable Foxp3 expression in vitro and in vivo and exhibited stronger suppression activity in a colitis model compared with untreated iTregs. Our data indicate that the induction and activation of TET enzymes in iTregs would be an effective method for Treg-mediated adoptive immunotherapy.


The protease-activated receptor-2-specific agonists 2-aminothiazol-4-yl-LIGRL-NH2 and 6-aminonicotinyl-LIGRL-NH2 stimulate multiple signaling pathways to induce physiological responses in vitro and in vivo.
Protease-activated receptor-2 (PAR(2)) is one of four protease-activated G-protein-coupled receptors. PAR(2) is expressed on multiple cell types where it contributes to cellular responses to endogenous and exogenous proteases. Proteolytic cleavage of PAR(2) reveals a tethered ligand that activates PAR(2) and two major downstream signaling pathways: mitogen-activated protein kinase (MAPK) and intracellular Ca(2+) signaling. Peptides or peptidomimetics can mimic binding of the tethered ligand to stimulate signaling without the nonspecific effects of proteases. The most commonly used peptide activators of PAR(2) (e.g. SLIGRL-NH(2) and SLIGKV-NH(2)) lack potency at the receptor. However, although the potency of 2-furoyl-LIGRLO-NH(2) (2-f-LIGRLO-NH(2)) underscores the use of peptidomimetic PAR(2) ligands as a mechanism to enhance pharmacological action at PAR(2), 2-f-LIGRLO-NH(2) has not been thoroughly evaluated. We evaluated the known agonist 2-f-LIGRLO-NH(2) and two recently described pentapeptidomimetic PAR(2)-specific agonists, 2-aminothiazol-4-yl-LIGRL-NH(2) (2-at-LIGRL-NH(2)) and 6-aminonicotinyl-LIGRL-NH(2) (6-an-LIGRL-NH(2)). All peptidomimetic agonists stimulated PAR(2)-dependent in vitro physiological responses, MAPK signaling, and Ca(2+) signaling with an overall rank order of potency of 2-f-LIGRLO-NH(2) ≈ 2-at-LIGRL-NH(2) > 6-an-LIGRL-NH(2) ≫ SLIGRL-NH(2). Because PAR(2) plays a major role in pathological pain conditions and to test potency of the peptidomimetic agonists in vivo, we evaluated these agonists in models relevant to nociception. All three agonists activated Ca(2+) signaling in nociceptors in vitro, and both 2-at-LIGRL-NH(2) and 2-f-LIGRLO-NH(2) stimulated PAR(2)-dependent thermal hyperalgesia in vivo. We have characterized three high potency ligands that can be used to explore the physiological role of PAR(2) in a variety of systems and pathologies.


Measures of functional status in older patients treated with palbociclib for advanced breast cancer.
Limited data are available on the effects of treatment for advanced breast cancer (ABC) in older patients because this population has limited enrollment in clinical trials. Data generated from the prospective, noninterventional POLARIS study of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative ABC may help bridge the gap in our understanding of the tolerability and outcomes in this vulnerable population. We evaluated measures of geriatric impairments and activities of daily living in patients with ABC aged ≥70 years in POLARIS to evaluate the change within six months of palbociclib initiation. Geriatric impairments and activities of daily living (functional) status were assessed using the Geriatric 8 (G8) and Activities of Daily Living (ADL) screening tools. The G8, ADL, and Eastern Cooperative Oncology Group performance status (ECOG PS) scores were assessed at baseline and month six through end of treatment with palbociclib. ECOG PS scores were also stratified by G8 and ADL score severity subgroups (G8: ≤14 = impaired subgroup; >14 = not at all impaired subgroup; ADL: <18 = dependent subgroup, 18 = independent subgroup). At data cutoff in November 2020, of 1282 POLARIS patients of all ages, 287 (22.4%) were ≥ 70 years old and completed ≥6 months of palbociclib therapy. At baseline, 117 (45%; n = 260) of these patients had an ECOG PS score of 0, 143 (55%; n = 260) had ECOG PS score > 0, 248 (86%) had G8 scores (mean [SD] 13.6 [2.14]), and 256 (89%) had ADL scores (17.7 [1.03]) among the available 287 patients. At six months, 102 (40%; n = 255) had an ECOG PS score of 0, 153 (60%; n = 255) had ECOG PS score > 0, 198 (69%) had G8 scores (13.6 [1.99]), and 211 (74%) had ADL scores (17.6 [1.22]) among the 287 available patients. There was no mean change (standard deviation) from baseline to 6 months in mean ECOG PS scores (0.0 [0.61], P = 0.24), G8 scores (0.0 [2.17], P = 0.89), or ADL scores (0.0 [1.00], P = 0.62). In this subgroup analysis of older patients with ABC from POLARIS, functional status and impairment outcomes were preserved in older patients receiving palbociclib. G8, ADL, and ECOG PS scores were generally maintained during the first six months of palbociclib therapy. govidentification number. NCT03280303.


Attribute-Driven Granular Model for EMG-Based Pinch and Fingertip Force Grand Recognition.
Fine multifunctional prosthetic hand manipulation requires precise control on the pinch-type and the corresponding force, and it is a challenge to decode both aspects from myoelectric signals. This paper proposes an attribute-driven granular model (AGrM) under a machine-learning scheme to solve this problem. The model utilizes the additionally captured attribute as the latent variable for a supervised granulation procedure. It was fulfilled for EMG-based pinch-type classification and the fingertip force grand prediction. In the experiments, 16 channels of surface electromyographic signals (i.e., main attribute) and continuous fingertip force (i.e., subattribute) were simultaneously collected while subjects performing eight types of hand pinches. The use of AGrM improved the pinch-type recognition accuracy to around 97.2% by 1.8% when constructing eight granules for each grasping type and received more than 90% force grand prediction accuracy at any granular level greater than six. Further, sensitivity analysis verified its robustness with respect to different channel combination and interferences. In comparison with other clustering-based granulation methods, AGrM achieved comparable pinch recognition accuracy but was of lowest computational cost and highest force grand prediction accuracy.


Clinical Impact of Intravascular Ultrasound Guidance During Endovascular Treatment of Subclavian Artery Disease.
To evaluate the short- and long-term efficacy of intravascular ultrasound (IVUS) guidance during endovascular treatment (EVT) of subclavian artery disease. The multicenter SCALLOP registry (SubClavian Artery disease treated with endovascuLar therapy; muLticenter retrOsPective registry) was interrogated to identify 542 patients who underwent successful EVT for SCAD between January 2003 and December 2012. Lesions were classified according to the use of IVUS guidance: 177 patients (mean age 68.9±8.6 years; 149 men) with and 373 patients (mean age 69.9±8.7 years; 275 men) without. The main outcome was the difference in primary patency; secondary outcomes were differences in assisted primary patency, secondary patency, overall survival, freedom from major adverse cardiovascular events [MACE; all-cause mortality, myocardial infarction (MI), and stroke], and freedom from major adverse events (MAE). Multivariate analysis of the IVUS+ group was performed to identify predictors of failure; results are presented as the hazard ratio (HR) and 95% confidence interval (CI). In total, 538 (97.8%) lesions were treated with stents and 12 lesions by balloon angioplasty alone. Periprocedural and in-hospital overall complication rates did not differ significantly between IVUS+ (10.2%) and IVUS- (8.8%, p=0.617). Long-term follow-up demonstrated no significant difference between IVUS+ and IVUS- groups in 5-year all-cause mortality (p=0.37), MI (p=0.07), stroke (p=0.31), or MACE (p=0.07). However, 5-year primary patency was significantly higher in the IVUS+ group (88.5% vs 77.7%, p=0.03). There were no group differences in 5-year assisted primary patency (90.4% vs 89.9%, p=0.81) or secondary patency (99.4% vs 97.1%, p=0.25). Multivariate analysis of the IVUS+ group identified in-hospital stroke (HR 16.92, 95% CI 3.60 to 79.42, p<0.01) and combined use of balloon-expandable and self-expanding stents (HR 5.59, 95% CI 1.22 to 25.65, p=0.02) as independent negative predictors of primary patency. These results suggest that IVUS guidance can significantly improve long-term primary patency following endovascular treatment of subclavian artery disease.


Secondary capsule-supported intraocular lens implantation in children.
To evaluate surgical problems, postoperative complications, and visual results of secondary posterior chamber intraocular lens (IOL) implantation in children. L.V. Prasad Eye Institute, Hyderabad, India. A retrospective study was done of secondary IOL implantation in 27 children (35 eyes) who were not satisfied with aphakic glasses and were intolerant of or reluctant to use contact lenses. The extent of posterior capsular support was assessed prior to surgery. Additional surgical procedures were posterior synechiolysis (11 eyes), anterior vitrectomy (8 eyes), pupilloplasty (2 eyes), and membranectomy (2 eyes). Postoperative complications included wound leak (1 eye), uveitis (5 eyes), peripheral anterior synechias (2 eyes), and retinal detachment (1 eye). Visual acuity improved or remained at the preoperative level in 34 eyes. Secondary posterior chamber IOL implantation is an effective optical modality for managing pediatric aphakia. Observation must continue to determine the long-term safety of the procedure.


Improving medical student attitudes toward older patients through a "council of elders" and reflective writing experience.
In an effort to reduce "agism" which is prevalent among medical trainees, a new geriatrics educational experience for medical students aimed at improving attitudes toward older patients was developed. Each 90-minute Older Adult Session included four components: initial reflective writing exercise; introduction to the session; 75-minute dialogue with the "Council of Elders," a group of active, "well" older adults; and final reflective writing exercise. The new session was provided to 237 first- and second-year medical students during the 2006/07 academic year at Indiana University School of Medicine. Session evaluation included comparing scores on the 14-item Geriatrics Attitude Scale administered before and after the session, identifying attitude changes in the reflective writing exercises, and a student satisfaction survey. Student responses on the Geriatrics Attitude Scale after the session were significantly improved in seven of 14 items, demonstrating better attitudes toward being with and listening to older people and caring for older patients. Analysis of the reflective writings revealed changing of negative to positive or reinforced positive attitudes in 27% of medical students, with attitudes not discernable in the remaining 73% (except one student, in whom positive attitudes changed to negative). Learner satisfaction with the Older Adult Session was high, with 98% agreeing that the session had a positive effect on insight into the care of older adults. A Council of Elders coupled with a reflective writing exercise is a promising new approach to improving attitudes of medical students toward their geriatric patients.


Vasculoprotective properties of plasma lipoproteins from brown bears (Ursus arctos).
Plasma cholesterol and triglyceride (TG) levels are twice as high in hibernating brown bears (Ursus arctos) than healthy humans. Yet, bears display no signs of early stage atherosclerosis development when adult. To explore this apparent paradox, we analyzed plasma lipoproteins from the same 10 bears in winter (hibernation) and summer using size exclusion chromatography, ultracentrifugation, and electrophoresis. LDL binding to arterial proteoglycans (PGs) and plasma cholesterol efflux capacity (CEC) were also evaluated. The data collected and analyzed from bears were also compared with those from healthy humans. In bears, the cholesterol ester, unesterified cholesterol, TG, and phospholipid contents of VLDL and LDL were higher in winter than in summer. The percentage lipid composition of LDL differed between bears and humans but did not change seasonally in bears. Bear LDL was larger, richer in TGs, showed prebeta electrophoretic mobility, and had 5-10 times lower binding to arterial PGs than human LDL. Finally, plasma CEC was higher in bears than in humans, especially the HDL fraction when mediated by ABCA1. These results suggest that in brown bears the absence of early atherogenesis is likely associated with a lower affinity of LDL for arterial PGs and an elevated CEC of bear plasma.


[Effect of triethylenethiophosphoramid on the spermatozoa of rabbits].
Under study were effects of triethylenthiophosphoramid (thioTEP) on mature gametes of rabbits, their impregnating capacity and embryonic development. When treated with thioTEP in non-toxic concentration the spermatozoa did not change their mobility, vitality in vitro and impregnation capacity. However, investigation of early postnatal development showed a delay of the beginning of cleavage and death at early stages due to thioTEP effects; the number of formed blastocysts was observed to decrease from 76% to 61%, i.e. by a statistically significant value 15 +/- 6,5%. A greater number of zigotes of delayed development was found in a group of experimental animals (39%), as compared with controls (24%), when females were dissected on the 4th-5th days after impregnation. DNA content in spermatozoa treated with the chem-mutagen remained unchanged.


Fluoride release and uptake capacities of fluoride-releasing restorative materials.
Many fluoride-releasing dental materials are being sold on the basis of their cariostatic properties. However, the amount fluoride release of these materials is still uncertain. This study investigated the fluoride release and uptake characteristics of four flowable resin composites (Heliomolar Flow, Tetric Flow, Wave, Perma Flo), one flowable compomer (Dyract flow), one conventional glass ionomer cement mixed with two different powder/liquid ratios (ChemFlex Syringeable and ChemFlex Condensable), one packable resin composite (SureFil), one ion-releasing composite (Ariston pHc) and one resin-modified glass ionomer cement (Vitremer). Seven discs (6-mm diameter and 1.5-mm height) were prepared for each material. Each disc was immersed in 3.5 ml of deionized water within a plastic vial and stored at 37 degrees C. The deionized water was changed every 24 hours and the release of fluoride was measured for 30 days. At the end of this period, the samples were recharged with 2 ml of 1.23% acidulated phosphate fluoride (APF) gel for four minutes. Then, all samples were reassessed for an additional 10 days. The fluoride release of all samples was measured with a specific fluoride electrode and an ionanalyzer. Statistical analyses were conducted using two-way repeated measure ANOVA and Duncan's multiple range tests. For all tested materials, the greatest fluoride release was observed after the first day of the study (p<0.01) but gradually diminished with time. During the test period, Tetric Flow released the lowest amount of fluoride; however, no statistically significant difference was found from Wave and Heliomolar Flow (p>0.05). Ariston pHc released the highest amount of fluoride, followed by ChemFlex Syringeable, Vitremer and ChemFlex Condensable. There were statistically significant differences among these materials (p<0.05). Fluoride release of all materials were significantly increased after the first day following refluoridation and Ariston pHc released the greatest among all materials (p<0.01). At the end of two days of refluoridation, the fluoride release rate for each material dropped quickly and stabilized within three days.


Flexible, diagnosticity-driven, rather than fixed, perceptually determined scale selection in scene and face recognition.
Different classifications of an identical visual stimulus may require different perceptual properties from the visual input. How do processes of object and scene categorisation use the information associated with different perceptual spatial scales? One scenario suggests that recognition should use coarse blobs before fine-scale edges because scale usage is perceptually determined. However, perceptual determination neglects one important aspect of any recognition task: the information demands of the considered classification of the input. Evidence is reviewed suggesting that scale usage could be flexibly determined by the diagnosticity of scale-specific cues for different categorisations of scenes and faces.


Are overground or treadmill runners more likely to sustain tibial stress fracture?
Repetitive high bone strain and/or strain rates, such as those that occur during running, contribute to stress fractures as well as promoting maintenance of or increase in bone mass. Kinematic differences are known to exist between overground and treadmill running and these may be reflected in different bone strains and strain rates during the two running techniques. To measure in vivo strains and strain rates in human tibia during treadmill and overground running and determine if there are significant differences in strain and strain rate levels between the two running techniques. A strain gauged bone staple was mounted percutaneously along the axial direction in the mid diaphysis of the medial tibia in three subjects, and in vivo tibial strains were measured during treadmill and overground running at 11 km/h. Axial compression strains (p<0.0001), tension strains (p<0.001), compression strain rates (p<0.0001), and tension strain rates (p<0.0001) were 48-285% higher during overground running than during treadmill running. On the basis of lower in vivo strains and strain rates, treadmill runners are at lower risk of developing tibial stress fractures, but less likely to achieve tibial bone strengthening, than overground runners.


Algorithms and complexity of enumerating minimal precursor sets in genome-wide metabolic networks.
In the context of studying whole metabolic networks and their interaction with the environment, the following question arises: given a set of target metabolites T and a set of possible external source metabolites , which are the minimal subsets of that are able to produce all the metabolites in T. Such subsets are called the minimal precursor sets of T. The problem is then whether we can enumerate all of them efficiently. We propose a new characterization of precursor sets as the inputs of reaction sets called factories and an efficient algorithm to decide if a set of sources is precursor set of T. We show proofs of hardness for the problems of finding a precursor set of minimum size and of enumerating all minimal precursor sets T. We propose two new algorithms which, despite the hardness of the enumeration problem, allow to enumerate all minimal precursor sets in networks with up to 1000 reactions. Source code and datasets used in our benchmarks are freely available for download at http://sites.google.com/site/pitufosoftware/download. email@example.com, firstname.lastname@example.com or email@example.com.


The Use of the Nursing Interventions Classification in Identifying the Workload of a Nursing Team in a Pediatric Oncology Center.
The activities/interventions performed by the nursing team and the time required for their performance have become a widely discussed topic due to their impact on the quality of patient safety and staff working conditions. Nursing Interventions Classification (NIC) was used as a more accurate indicator as it identified activities/interventions. This study analyzed the workload distribution of nursing team in a pediatric oncology center.


The close association of pi-class glutathione S-transferase with drug sensitivity to alkylating agents and cisplatin in human cancer cells.
Buthionine sulfoximine (BSO) is a synthetic amino acid that irreversibly inhibits glutathione biosynthesis. A BSO-resistant line, KB/BSO3, was established from human epidermoid cancer KB cells; and other BSO-resistant lines, HLE/BSO1 and HLE/BSO2, were from human hepatic cancer HLE cells. Cellular level of pi-class glutathione S-transferase (GSTP1) in KB/BSO3 was less than 10% of the parental KB, and those in HLE/BSO1 and HLE/BSO2 wa 30-40% of the parental HLE cells. KB/BSO3, HLE/BSO1 and HLE/BSO2 had collateral sensitivities to a potent anticancer agent, cisplatin, and alkylating agents including melphalan and nitrosourea. The GSTP1 cDNA transfectant KB/BSO3-pi established from KB/BSO3, and also HLE/BSO1-pi and HLE/BSO2-pi established from HLE/BSO1 and HLE/BSO2, restored cellular sensitivities to cisplatin and alkylating agents to similar levels as KB and HLE cells. Our present results indicate that GSTP1 levels apparently limit cellular sensitivities to cisplatin and alkylating agents, suggesting that GSTP1 is a useful diagnostic marker for drug sensitivities to these agents in human cancer cells.