Defluorination study of spent carbon cathode by microwave high-temperature roasting.
Spent carbon cathode (SCC) produced in the process of aluminum electrolysis is a typical toxic and hazardous solid waste. Therefore, the harmless treatment of SCC is extremely important for the green development of aluminum electrolysis industry. In this paper, the microwave-assisted high-temperature roasting technology was developed to remove fluorides in SCC for recycling of this cathode. The melting point, dielectric parameter, crystalline structure, surface chemical property, elemental composition, morphological structure, carbon graphitization and surface area were characterized using thermogravimetric analysis and differential scanning calorimetry, high-temperature composite conductivity analyzer, X-ray diffraction, X-ray fluorescence, X-ray photoelectron spectroscopy, scanning electronic microscopy, transmission electron microscopy, Raman spectroscopy and isothermal N2 adsorption-desorption method. The content of fluorides in raw and treated SCC was measured by ion activity meter. The results showed that the phase of sodium fluoride and cryolite would transform from solid to liquid when the temperature was higher than 1098.5 °C, and the SCC exhibited good performance on wave absorption with the action depth of 1 cm. The SCC was mainly composed of 57.94 wt% C, 14.23 wt% NaF, 1.80 wt%, CaF2, 15.06 wt% Na3AlF6, and 10.97 wt% Other. After treatment under microwave, the graphite carbon exhibited pitting structure and the fluorides could be effectively removed. In addition, the average layer spacing of graphite was increased from 0.34 to 0.36 nm. The defluorination of SCC could be enhanced with the increase of roasting temperature, which would attain 95.4% at 1500 °C. Compared with the traditional roasting method, the process under microwave showed more defects, which would provide a new guidance for the treatment and recycling of spent SCC.


piRNA-Guided CRISPR-like Immunity in Eukaryotes.
Eukaryotic genomes contain virus-derived sequences called endogenous virus elements (EVEs). The majority of EVEs are related to retroviruses, which integrate into the host genome in order to replicate. Some retroviral EVEs encode a function; for example, some produce proteins that block infection by related viruses. EVEs derived from nonretroviral viruses - also recently found in many eukaryotic genomes - are more enigmatic. Here, we summarize the evidence that EVEs can act as templates to generate Piwi-interacting RNAs (piRNAs), whose canonical function is sequence-specific silencing of transposable elements (TEs) to maintain genomic integrity. We argue that EVEs may thus enable heritable, sequence-specific antiviral immune memory in eukaryotes - analogous to CRISPR-Cas immunity in prokaryotes.


Endothelial function and outdoor temperature.
Studies within populations consistently showed that cardiovascular mortality increases with hot weather. However, the biological mechanisms underlying this association remain largely unknown. Endothelial function plays a pivotal role in the pathogenesis of cardiovascular disease. Therefore, we investigated the association between endothelial function and outdoor temperature. We measured flow-mediated vasodilatation (FMD) as index of endothelial function in 274 randomly recruited subjects (50% women, mean age 40.6 year). Both before (partial r = -0.14, p = 0.017) and after adjustment (partial r = -0.17, p = 0.006) for sex, age, body mass index, brachial artery diameter and current smoking, FMD was negatively associated with mean daily temperature. The odds of endothelial dysfunction increased by 58% (95% CI: 4-141%; p = 0.03) for each 10 degrees C increment in mean daily temperature during the week before the examination. Our findings suggest that endothelial dysfunction might contribute to the increase in cardiovascular morbidity and mortality associated with hot weather.


Assessment of lithium bioaccumulation by quinoa (Chenopodium quinoa willd.) and its implication for human health.
Lithium (Li) is the lightest alkali metal and 27th most abundant element in the earth crust. In traces, the element has medicinal value for various disorders in humans, however, its higher concentrations may lead to treatment-resistant depression and altered thyroid functioning. Quinoa (Chenopodium quinoa) has gained popularity owing to its halophytic nature and its potential use as an alternative to the traditional staple foods. However, quinoa response to Li-salt in terms of growth, Li accumulation potential and health risks associated with consumption of the quinoa seeds grown on Li-contaminated soils has not been explored yet. During this study, quinoa was exposed to various concentrations of Li (0, 2, 4, 8 and 16 mM) at germination as well as seedling stages. The results showed that seed germination was the highest (64% higher than control) at Li concentration of 8 mM. Similarly, at 8 mM doses of Li shoot length, shoot dry weight, root length, root dry weight and grain yield were increased by 130%, 300%, 244%, 858% and 185% than control. It was also revealed that Li increased the accumulation of calcium and sodium in quinoa shoots. Carotenoids contents were increased, but chlorophyll contents remained un-changed under Li application. The activities of antioxidants viz. Peroxide dismutase, catalase and super oxide dismutase were also increased with an increase in the levels of Li in the soil. Estimated daily intake and hazard quotient of Li in quinoa were less than the threshold level. It was concluded that Li concentration of 8 mM is useful for quinoa growth and it can be successfully grown on Li contaminated soils without causing any human health risks.


Assessment of disease severity on capsule endoscopy in patients with small bowel villous atrophy.
There is a lack of uniformity of reporting on features of celiac disease (CD) on small bowel capsule endoscopy (SBCE). This makes determining extent of disease and comparison of severity of disease challenging. De-identified SBCEs of 300 patients (78 CD [26%], 18 serology negative villous atrophy [6%], and 204 controls with normal duodenal histology [68%]) were included. Videos were reviewed by two experts. All patients had duodenal histology taken within 2 weeks of SBCE. The degree of agreement in CD features and extent of disease was then determined. The resulting score for each factor was used to determine overall severity of disease. There was substantial agreement in the kappa coefficient for the detection of CD features between reviewers (0.67). Agreement for extent of affected small bowel (SB) mucosa was high (0.97). On multiple regression analysis, several features of CD correlated with extent of affected SB mucosa for both reviewers. The odds ratios derived from this analysis were then used to score features of CD, enabling scores of severity to be calculated for each patient. The median overall scores for patients increased significantly according to the independent classification of severity by the capsule reviewers: mild (20, 0-79), moderate (45, 25-123), and severe (89, 65-130) (P = 0.0001). The good correlation of CD scores between expert reviewers confirms the validity of features of CD on SBCE. An objective score of CD features in the SB is useful in the follow up of patients with CD and serology negative villous atrophy.


Brentuximab vedotin in the treatment of paediatric patients with relapsed or refractory Hodgkin's lymphoma: Results of a real-life study.
Brentuximab vedotin (BV) is an antibody drug-conjugated anti-CD30 approved for the treatment of adult classical Hodgkin's lymphoma (HL), whereas it is considered as off-label indication in paediatrics. The aim of the study was to evaluate the safety and efficacy of BV to treat patients aged less than 18 years with refractory/relapsed HL. In this multicentre, retrospective study, 68 paediatric patients who received at least one dose of BV between November 2011 and August 2020 were enrolled. A median of nine doses of BV were administered as monotherapy (n = 31) or combined with other therapies (n = 37). BV was administrated alone as consolidation therapy after stem cell transplantation (SCT) in 12 patients, before SCT in 18 patients, whereas in 15 patients it was used before and after SCT as consolidation therapy. Median follow-up was 2.8 years (range: 0.6-8.9 years). The best response was observed in the 86% of patients; the overall response rate was 66%. The 3-year progression-free survival was 58%, whereas the overall survival was 75%. No statistically significant differences between patients treated with BV monotherapy or combination were highlighted. In multivariate analysis, patients with non-nodular sclerosis HL and not transplanted had an increased risk of failure. Overall, 46% of patients had grade 3-4 adverse events that led to BV discontinuation in five of them. In conclusion, our study confirms that BV was a safe and effective drug, able to induce complete remission, either as monotherapy or in association with standard therapy.


[The acceptance of personal responsibility as a criterion in assigning health care benefits. An empirical study].
In order to accomplish broad acceptance of priority setting in healthcare, a public debate seems essential, in particular, including the preferences of the general public. In Germany, objections to public involvement are to some extent based on the perception that individuals have an inherent personal bias and cannot represent interests other than their own. The following excerpt from a more comprehensive study reports on the acceptance of personal responsibility as a criterion for prioritizing. A mixed-methods design is used for combining a qualitative interview study and a quantitative survey representative of the German public. Both the interview study and the survey demonstrate that behavior that is harmful to one's health is generally accepted as a criterion for posteriorizing patients, mostly regardless of self interest. In addition, the interview study shows reasons for acceptance or refusal of the self-inflicted behavior criterion.


Development and practical applications of a method for repeated transvaginal, ultrasound-guided biopsy collection of the bovine ovary.
In response to the increasing research into primordial and preantral follicular dynamics, a device for transvaginal, ultrasound-guided biopsy collection of the bovine ovary was developed and tested. The new device is based upon a commercially available Ovum Pick-up instrument and consists of a modified needle guidance system, which has been equipped with a trocar needle and caries a 60 cm long true-cut biopsy needle. Biopsies are captured in a 20mm long and 2mm wide specimen notch. In the present experiment, 10 cows were subjected to a twice weekly biopsy regime over a four-week period. A total of 208 attempts at biopsy collection were made, and 141 tissue samples collected (success rate of 68%). Through histological and immunological analyses, these tissue samples have been shown to contain primordial and preantral follicles. At the end of the trial period, several of the donor cows were slaughtered at timed intervals, and the ovaries were harvested for assessment of the damage inflicted by the repeated biopsy procedure. Post mortem ovaries were inspected macroscopically and examined by conventional histological staining. In ovaries retrieved 2 days after the last biopsy session, blood clots were macroscopically apparent throughout the ovaries. Histological examination showed increased infiltration of red blood cells in the ovarian stroma. Analysis from ovaries collected at subsequent slaughter points revealed reduced infiltration of blood, and clear indications of resumed antral follicle development were apparent towards the end of the first month after the trial period. We conclude that the biopsy sampling technique is a repeatable procedure which could serve as a renewable source of primordial and preantral follicles for culture, and as an in vitro model for the study of preantral follicular dynamics.


Pectin/poly(lactide-co-glycolide) composite matrices for biomedical applications.
The aim of the research was to develop matrices for the delivery of biologically active substances for tissue regeneration. To this end, a new biodegradable matrix composed of a hydrophobic porous poly(lactide-co-glycolide), p(LGA), network entangled with another network of hydrophilic pectin was fabricated in the presence of calcium chloride. The calcium salts function as both a pore forming reagent and cross-linker for the formation of pectin networks; the method combines creating pores and cross-linking polymers in one step. Microscopic imaging and dynamic mechanical analysis revealed a double-network structure of the composite matrices. The pectin enables the composite to carry signal molecules. This is accomplished by linking signal molecules to pectin by physical adsorption or by chemical reaction. The p(LGA) networks in the composite impart mechanical properties comparable to p(LGA) alone. The mechanical properties of the composite are far superior to matrices containing only pectin. Furthermore, the pectin-containing matrices improved cell adhesion and proliferation when compared to plain p(LGA) matrices, as determined in vitro by osteoblast culture.


Computationally characterizing and comprehensive analysis of zinc-binding sites in proteins.
Zinc is one of the most essential metals utilized by organisms, and zinc-binding proteins play an important role in a variety of biological processes such as transcription regulation, cell metabolism and apoptosis. Thus, characterizing the precise zinc-binding sites is fundamental to an elucidation of the biological functions and molecular mechanisms of zinc-binding proteins. Using systematic analyses of structural characteristics, we observed that 4-residue and 3-residue zinc-binding sites have distinctly specific geometric features. Based on the results, we developed the novel computational program Geometric REstriction for Zinc-binding (GRE4Zn) to characterize the zinc-binding sites in protein structures, by restricting the distances between zinc and its coordinating atoms. The comparison between GRE4Zn and analogous tools revealed that it achieved a superior performance. A large-scale prediction for structurally characterized proteins was performed with this powerful predictor, and statistical analyses for the results indicated zinc-binding proteins have come to be significantly involved in more complicated biological processes in higher species than simpler species during the course of evolution. Further analyses suggested that zinc-binding proteins are preferentially implicated in a variety of diseases and highly enriched in known drug targets, and the prediction of zinc-binding sites can be helpful for the investigation of molecular mechanisms. In this regard, these prediction and analysis results should prove to be highly useful be helpful for further biomedical study and drug design. The online service of GRE4Zn is freely available at: http://biocomp.ustc.edu.cn/gre4zn/. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications. Guest Editor: Yudong Cai.


Oryctes virus--time for a new look at a useful biocontrol agent.
The introduction of Oryctes virus into outbreak areas of the rhinoceros beetle, Oryctes rhinoceros (Coleoptera: Scarabaeidae), has been a major success for "classical" biocontrol with a virus and has led to a dramatic reduction in palm damage in many areas of the Asia/Pacific region. In recent years, however, there have been new reports of high levels of rhinoceros beetle damage to palms. Damage has been especially intense in SE Asia following the introduction of no-burn polices for land clearance and replanting, but outbreaks have also been reported from some Pacific Islands where control seems to have diminished over time. SE Asian studies show that there is considerable genetic variation among endemic Oryctes virus isolates and studies in new island release areas have shown rapid evolution of the virus. The consequences of such genetic variation are in need of further study. Furthermore, the taxonomic position of the virus is unclear, with its removal from the Baculoviridae to an "unassigned' virus, reflecting its novel characteristics. Genomic sequencing could help resolve the taxonomy of the virus and provide a basis for studying strain variation. Oryctes virus has achieved wide success in the past without the benefit of molecular analysis and identification techniques. In order to fully take advantage of this unique pathogen for protection of palms, a renewed, coordinated effort centered on genetic selection and distribution of effective strains is required.


Zoom Objective Structured Clinical Exams: Virtually the Same as the Real Thing?
Objective structured clinical exams (OSCE) are used to train and assess resident foundational family-centered communication skills incorporating key stakeholders. In 2020 encounters were conducted virtually. We sought to compare standardized patient (SP) and family faculty (FF) assessment across OSCE and virtual OSCE (VOSCE) formats. The intern classes of 2019 and 2020 completed a live OSCE and VOSCE respectively where they disclosed an error to an SP. The 10 minute encounter was observed by an FF and facilitator followed by a 20 minute debrief. The SP and FF completed a behavioral checklist to evaluate skill mastery. Eighteen (90%) of the 20 interns completed the encounter each year. Total mastery scores were significantly higher for SP assessment than for FF assessment in both OSCE [68% vs 46% (z = -3.005, P < .05)] and VOSCE formats [68% vs 53% (z = -2.105, P < .05)]. Total mastery scores of SPs across OSCE and VOSCE formats did not significantly differ, nor did FF scores based on evaluation format. Our current experience suggests VOSCEs are a viable alternative to in person sessions given the comparable assessment across the two modalities. The ease of participating in virtual sessions may provide a way to more easily partner with key stakeholders.


Comparative efficacy of radiofrequency denervation in chronic low back pain: A systematic review and network meta-analysis.
Facet joint pain is a common cause of chronic low back pain (CLBP). Radiofrequency (RF) denervation is an effective treatment option. A systematic review and network meta-analysis (NMA) was performed to evaluate and compare the efficacy and effectiveness of different RF denervation treatments in managing facet joint-derived CLBP. The Cochrane Library, Embase, PubMed, and China Biology Medicine were searched to identify eligible randomized controlled trials (RCTs) from January 1966 through December 2021. Interventions included conventional radiofrequency denervation (CRF), pulsed radiofrequency denervation (PRF), pulsed radiofrequency treatment of the dorsal root ganglia (PRF-DRG), radiofrequency facet capsule denervation (RF-FC), and radiofrequency ablation under endoscopic guidance (ERFA). The outcome was the mean change in visual analog scale (VAS) score from baseline. A random-effects NMA was used to compare the pain relief effects of the interventions over the short term (≤6 months) and long term (12 months). The rank of effect estimation for each intervention was computed using the surface under the cumulative ranking curve. A total of 10 RCTs with 715 patients met the inclusion criteria. Moderate evidence indicated that CRF denervation had a greater effect on pain relief than sham control in the short term (standardized mean difference (SMD) -1.58, 95% confidence intervals (CI) -2.98 to -0.18) and the long term (SMD -4.90, 95% CI, -5.86 to -3.94). Fair evidence indicated that PRF denervation was more effective than sham control for pain over the long term (SMD -1.30, 95% CI, -2.17 to -0.43). Fair evidence showed that ERFA denervation was more effective for pain relief than sham control in the short term (SMD -3.07, 95% CI, -5.81 to -0.32) and the long term (SMD -4.00, 95% CI, -4.95 to -3.05). Fair evidence showed that RF-FC denervation was more effective for pain relief than sham control in the long term (SMD -1.11, 95% CI, -2.07 to -0.15). A fair level of evidence indicated that PRF-DRG denervation was more effective for pain relief than sham control in the short term (SMD -5.34, 95% CI, -8.30 to -2.39). RF is an effective option for patients diagnosed with facet joint-derived CLBP.Systematic Review Registration: Identifier: CRD42022298238.


Genetic screen for regulators of ind expression identifies shrew as encoding a novel twisted gastrulation-like protein involved in Dpp signaling.
Initiation and refinement of expression of the Ind homeodomain protein in the Drosophila embryo is coordinately regulated by global dorsoventral patterning pathways Dorsal, Egfr, and Dpp, and well as by Vnd, which positions the ventral boundary of Ind. Therefore, we set out to look for novel regulators of dorsoventral patterning by screening the Exelixis deficiency collection for modified expression of Ind. Indeed, we found deficiencies that remove components of the known signaling pathways had altered or lost ind expression. These findings included deficiencies that remove screw, dpp, and egfr as well as deficiencies that remove ind itself. In addition, we found several deficiencies that had altered or loss of ind expression. We also observed phenotypes suggestive of dorsoventral patterning defects such as twisting during gastrulation, and defects associated with loss of dorsal specification. These include a pair of overlapping deficiencies that produced ventralized embryos. We find that transheterozygotes of these two deficiencies are also ventralized. There are seven genes common to both deficiencies, including CG11582, which encodes a twisted gastrulation-like protein. These two deficiencies are also allelic with shrew mutations. Here, we present data supporting the conclusion that CG11582 is the gene affected in shrew mutants.


Inhibition of amyloid fibril formation and cytotoxicity by a chemical analog of Curcumin as a stable inhibitor.
Clinical application of curcumin for Alzheimer's disease treatment is severely limited with regard to its poor bioavailability, high rate of metabolism, and instability under neutral condition. In the current study, we designed three compounds in which the diketone moiety of curcumin was replaced by cyclohexanone. In these compounds, the linker length of the molecules was optimal; and substitution of dioxolane for hydroxyl groups on compound 3 should prevent metabolic inactivation. The inhibitory effect of the compounds was investigated against hen egg white lysozyme (HEWL) fibrillation using AFM (atomic force microscope), ThT (thioflavin T) and MTT assay. We found that all three compounds were able to inhibit HEWL aggregation in a dose-dependent manner and inhibit the cytotoxic activity of aggregated HEWL. Docking results demonstrated that the compounds could bind into lysozyme and occupy the whole active site groove. In conclusion, we present chemical analogs of curcumin with various modifications in the spacer and the phenolic rings as improved inhibitors of amyloid aggregation.


Epidemiological Factors Associated with Gross Diagnosis of Pulmonary Pathology in Feedyard Mortalities.
Respiratory disease continues to be the major cause of mortality in feedyard cattle, with bronchopneumonia (BP) and acute interstitial pneumonia (AIP) as the two most common syndromes. Recent studies described a combination of these pathological lesions with the presence of AIP in the caudodorsal lungs and BP in the cranioventral lungs of necropsied cattle. This pulmonary pathology has been described as bronchopneumonia with an interstitial pneumonia (BIP). The epidemiological characteristics of BIP in U.S. feedyard cattle are yet to be described. This study's objectives were to describe the agreement between feedyard clinical and necropsy gross diagnosis and to characterize epidemiological factors associated with four gross pulmonary diagnoses (AIP, BIP, BP, and Normal pulmonary tissue) observed during feedyard cattle necropsies. Systemic necropsies were performed at six feedyards in U.S. high plains region, and gross pulmonary diagnoses were established. Historical data were added to the dataset, including sex, days on feed at death (DOFDEATH), arrival weight, treatment count, and feedyard diagnosis. Generalized linear models were used to evaluate epidemiological factors associated with the probability of each pulmonary pathology. Comparing feedyard clinical diagnosis with gross pathological diagnosis revealed relatively low agreement and the frequency of agreement varied by diagnosis. The likelihood of AIP at necropsy was higher for heifers than steers and in the 100-150 DOFDEATH category compared with the 0-50 DOFDEATH (p = 0.05). The likelihood of BIP increased after the first treatment, whereas the DOFDEATH 0-50 category had a lower likelihood compared with the 150-200 category (p = 0.05). These findings highlight the importance of necropsy for final diagnosis and can aid the development of future diagnosis and therapeutic protocols for pulmonary diseases.


Randomized trial of efficacy and safety of dornase alfa delivered by eRapid nebulizer in cystic fibrosis patients.
Dornase alfa administered via jet nebulizer is indicated as a chronic respiratory medication for cystic fibrosis (CF) patients. Efficacy and safety of dornase alfa via an electronic nebulizer with vibrating membrane technology have not been formally assessed in randomized clinical trials. 87 CF patients (≥6 years) were randomized in a crossover study to receive dornase alfa 2.5 mg/d in 2-week periods with the Pari eRapid and Pari LC Plus jet nebulizers. The primary end point was comparison of forced expiratory volume in the first second. Safety, quality of life, and treatment satisfaction/preference were also compared between devices. Lung function was equivalent between nebulizers. Most domain scores from the Cystic Fibrosis Questionnaire-Revised and Treatment Satisfaction Questionnaire for Medication instruments were similar but patients strongly preferred the eRapid. Mean patient-reported administration times were shorter with the eRapid vs the LC Plus (2.7 vs 10.2 min). Adverse events were similar between devices. Administration of dornase alfa via the eRapid nebulizer resulted in comparable efficacy and safety, shorter nebulization times, and higher patient preference.


Corneal keratocyte apoptosis following topical intraoperative mitomycin C in rabbits.
To determine the soaking duration and concentration effect of mitomycin C (MMC) on the corneal keratocyte following single intraoperative application. Two hundred ten pigmented rabbit eyes underwent mechanical epithelium debridement of the central 10-mm comea followed by soaking of six different solutions: MMC1A: 0.01% MMC x 1 minute; MMC1B: 0.01% MMC x 2 minutes; MMC2A: 0.02% MMC x 1 minute; MMC2B: 0.02% MMC x 2 minutes; BSS1: balanced salt solution (BSS) x 1 minute; and BSS2: BSS x 2 minutes. Thirty-five eyes were allocated into each group. Changes of the central comeal thickness, corneal clarity score, and keratocyte apoptosis were examined on days 0, 1, 2, 3, 5, 7, and 14. A significant increase of central corneal thickness and corneal clarity score was noted in all MMC treated groups. The central corneal thickness recovered to its baseline level whereas the corneal clarity score remained increased at 2 weeks. The changes were more significant in MMC2 than in MMC1 corneas. However, changes of central corneal thickness and corneal clarity score were more significant in MMC1B than in MMC1A, whereas no difference was noted between MMC2A and MMC2B. Significantly higher stromal keratocyte loss and keratocyte apoptosis, from superficial to deep corneal stroma, was noted in MMC1 and MMC2 groups up to 14 days postoperatively, in a soaking duration and dose-dependent manner. Single application of MMC on the corneal surface caused soaking concentration and duration dependent corneal edema and keratocyte apoptosis in this rabbit model.


Idiopathic nephrotic syndrome in children: role of regulatory T cells and gut microbiota.
We investigated whether an association exists between regulatory T cells (Tregs) during initial presentation in children with idiopathic nephrotic syndrome (INS) and later development of frequently relapsing INS. Blood samples were obtained at onset and at remission from 25 patients (median age, 4.0 years) with INS; eight did not show relapse after initial response (non-relapsing [NR]), whereas 17 showed frequent relapses (frequently relapsing [FR]). Tregs were measured by flow cytometry; increases were compared between groups. Fecal samples were obtained at onset from 20 patients with INS, as well as from 20 age-matched healthy children. Gut microbiota composition was assessed using 16S ribosomal RNA (rRNA) sequencing (ion PGM). The rate of increase in Tregs from onset to remission was significantly lower in the FR group (124.78%) than in the NR group (879.16%; P < 0.001). Additionally, 16S rRNA sequencing of gut microbiota showed that the proportion of butyric acid-producing bacteria was significantly lower in the FR group (7.08%) than in the healthy children (17.45%; P < 0.001). In children with INS, small increases in Tregs in response to steroid treatment were associated with subsequent increased risk of frequent relapses. In addition, the FR group had a greater degree of dysbiosis at onset. A low rate of Tregs increase is associated with subsequent frequent relapses of INS. The increase in Tregs in response to steroid treatment was small when dysbiosis was present in patients with INS, particularly when the proportion of butyrate-producing bacteria was considerably reduced We presume that improvement of dysbiosis by administration of probiotics and prebiotics may enhance the rate of Tregs' increase, thus preventing frequent relapse.


The effectiveness of the BuzzyⓇ device to reduce or prevent pain in children undergoing needle-related procedures: The results from a prospective, open-label, randomised, non-inferiority study.
Pain from needle-related procedures in children can alter pain perception, increase pain sensitivity, and generate inappropriate pain responses. Currently pain management includes the use of lidocaine-containing patches, which is complicated to manage in a busy medical setting such as a vaccination centre. We assessed the BuzzyⓇ device, which combines vibration and cold, to manage pain in children undergoing a needle-related procedure, compared to the standard lidocaine patch. Prospective, open-label, non-inferiority trial. The vaccination centres of three university hospitals in France. French speaking children aged 4-15 requiring a needle-related procedure (vaccination or venepuncture) were eligible. Principal exclusion criteria were allergy or sensitivity to the lidocaine patch. Children were randomly allocated (1:1) to use either the BuzzyⓇ device or the lidocaine patch during the needle-related procedure. The lidocaine patch was applied to the puncture site for the hour prior to the intervention. The BuzzyⓇ device was applied to the puncture site for 30 s and then moved 5 cm along the limb during the procedure. The refrigerated wings were detached if they bothered the child. The child assessed their pain using the validated Revised Faces Pain Scale. The revised faces pain scale comprised six facial expressions from 0, normal "no pain" to 10, a screaming face "severe pain" (2 points/face). The primary endpoint was the average pain score recorded by the child. The study aimed to test the non-inferiority of BuzzyⓇ. Overall 219 participants were randomised. The primary outcome was assessed in 215 children: 108 in the BUZZY group (43% asked for the refrigerated wings were de to be detatched before the end of the procedure) and 107 in the PATCH group. The baseline characteristics were similar between the study groups with an average age of 9 (range: 4.08-15.81). The average needle-related pain was 2.04 in the BUZZY group and 1.42 in the PATCH group. The average difference between the children's assessments in the groups was 0.62, thus faling to demonstrate non-inferiority. Our study failed to show that the BuzzyⓇ device was not inferior to the lidocaine patch in managing pain in children undergoing needle-related procedures. Tweetable abstract: Pain management in children undergoing a needle-related procedure vaccination: which efficacy for BuzzyⓇ device as an alternative to lidocaine patch? A prospective, randomised study.


The accuracy of radiologic identification of humans using skeletal landmarks: a contribution of forensic pathology.
The radiologic identification of humans, using skeletal landmarks in the thorax, is a potentially reliable method and its applicability to problems in forensic pathology is emphasized. This method was used in a case of homicide in which the identity of the victim required confirmation.


The role of sonolysis and sonothrombolysis in acute ischemic stroke: a systematic review and meta-analysis of randomized controlled trials and case-control studies.
To assess the evidence on the safety and efficacy of sonothrombolysis in acute stroke. Electronic databases and grey literature were searched under different MeSH terms from 1970 to present. Randomized control trials (RCTs) and case control studies (CCSs) on sonolysis and sonothrombolysis alone or with microsphere in acute stroke patients (>18 old). Outcome measures included complete recanalization (CR) at 1-2 and 24 hours, 3 months modified Rankin Scale (mRS), and symptomatic intracerebral hemorrhage (sICH). Data was extracted to Review Manager software. Fifty-seven studies were retrieved and analyzed. Ten studies (7 RCTs and 3 CCSs) were included in our meta-analysis, which revealed that sonolysis and sonothrombolysis are safe (OR of sICH: 1.14; 95% confidence interval (CI): 0.56- 2.34;P=0.71) and effective (OR of CR at 1-2 hours: 2.95;95% CI: 1.81-4.81;P<0.00001) and have more than two-fold higher likelihood of favourable long-term outcome (3-month mRS 0-2; OR: 2.20; CI:1.52-3.19;P<0.0001). Further subgroup analysis based on the presence of microsphere revealed that it is safe (OR of sICH: 1.18; CI:0.433.24;P=0.75) and effective (OR of CR: 2.61; CI: 1.36-4.99;P=0.004). Subgroup analysis based on sonolysis revealed to be safe and effective. This novel treatment appears safe and effective. The evidence of microsphere as an enhancement of sonothrombolysis is evolving.


Governing the Majority World? Critical reflections on the role of occupation technology in international contexts.
Within occupational therapy, increasing attention has been focussed on international development work. However, many have critiqued the focus of knowledge development within occupational therapy and occupational science, arguing that it is focussed on Western values. Questions arise about how occupational therapy and occupational science, and the knowledge and therapeutic technologies that are associated with these communities, will affect the 'developing' world, which, recently, some have described as the Majority World. Using Foucauldian analytical tools, this paper reflects on specific discourses that are foundational for development work. Specifically, this paper attempts to better understand how concepts like 'occupational justice' and the 'occupational being' are presented in the literature and relate to practices in international contexts. Within this analysis, attention is focussed on how practices associated with occupational development work might also be enmeshed in power dynamics. This paper outlines how occupational discourses may shape and order life in particular ways and challenges researchers and practitioners to develop a better understanding of how power can operate through occupational discourses and occupational therapy practices. This paper also adds to the literature through the interpretation and explication of various theories that may underpin work in international contexts. Suggestions for future directions that will enable the development of more politically and culturally sensitive knowledge and practices are also explored. It is crucial that as a community we become more aware of how our theoretical frameworks may impact and shape practice.


Preliminary results indicate that regular training induces high protection against oxidative stress in basketball players compared to soccer.
In elite athlete several metabolic changes occur during regular training. These modifications are associated with changes in blood metabolic profile and can lead to adaptive mechanisms aimed at establish a new dynamic equilibrium, which guarantees better performance. The goal of this study was to characterize the plasma metabolic profile and redox homeostasis, in athletes practicing two different team sports such as soccer and basketball in order to identify potential metabolic pathways underlying the differences in training programs. A cohort of 30 male, 20 professional players (10 soccer and 10 basketballs) and 10 sedentary males as control were enrolled in the study. Plasma redox balance, metabolites and adiponectin were determined. The results show low levels of oxidative species (25.5%), with both high antioxidant capacity (17.6%) and adiponectin level (64.4%) in plasma from basketball players, in comparison to soccer players. Metabolic analysis indicates in basketball players a significant high plasma level of amino acids Valine and Ornithine both involved in redox homeostasis and anti-inflammatory metabolism.


The role of cosmetologists as health promoters in the prevention of infant mortality.
Safe sleep practices reduce an infant's risk for sudden infant death syndrome and sleep-related death. While rates of infants placed on their back to sleep are high, other safe sleep practices are less widely implemented. Our objective was to evaluate the feasibility of using cosmetologists as health promoters for infant safe sleep to reduce infant mortality. In this descriptive study, a 27-item survey was mailed to the 405 licensed cosmetologists residing in the five zip codes with the highest infant mortality rates in the county. Of 149 completed surveys (36.8 %), 103 cosmetologists (69.1 %) were currently working. Most were comfortable (68.9 %) promoting health topics with their clients. Popular health-related topics currently discussed included: diet/weight control, healthy eating, and physical activity. Few (≤13 %) were interested in discussing infant mortality prevention or safe sleep promotion. Most respondents were either unsure (56 %) or did not feel infant mortality was a problem in their community (41 %); however, more than half (53 %) knew someone who had experienced an infant death. Cosmetologists were not highly interested in providing safe sleep education; however they engaged in diet and exercise talk already. Cosmetologists may be more appropriate for obesity-prevention programs to reduce infant mortality than safe sleep promotion.


Remodeling of motor units after nerve regeneration studied by quantitative electromyography.
Peripheral nerve has the capacity to regenerate after nerve lesions; during reinnervation of muscle motor units are gradually reestablished. The aim of this study was to follow the time course of reestablishing and remodeling of motor units in relation to recovery of force after different types of nerve repair. Reinnervation of muscle was compared clinically and electrophysiologically in complete median or ulnar nerve lesions with short gap lengths in the distal forearm repaired with a collagen nerve conduit (11 nerves) or nerve suture (10 nerves). Reestablishment of motor units was studied by quantitative EMG and recording of evoked compound muscle action potential (CMAP) during a 24-month observation period after nerve repair. Force recovered partially to about 80% of normal. Denervation activity gradually decreased during reinnervation though it was still increased at 24 months. Nascent motor unit potentials (MUPs) at early reinnervation were prolonged and polyphasic. During longitudinal studies, MUPs remained prolonged and their amplitudes gradually increased markedly. Firing of MUPs was unstable throughout the study. CMAPs gradually increased and the number of motor units recovered to approximately 20% of normal. There was weak evidence of CMAP amplitude recovery after suture ahead of conduit repair but without treatment related differences at 2 years. Surgical repair of nerve lesions with a nerve conduit or suture supported recovery of force and of motor unit reinnervation to the same extent. Changes occurred at a higher rate during early regeneration and slower after 12 months but should be followed for at least 2 years to assess outcome. EMG changes reflected extensive remodeling of motor units from early nascent units to a mature state with greatly enlarged units due to axonal regeneration and collateral sprouting and maturation of regenerated nerve and reinnervated muscle fibers after both types of repair. Remodeling of motor units after peripheral nerve lesions provides the basis for better recovery of force than the number of motor axons and units. There were no differences after repair with a collagen nerve conduit and nerve suture at short nerve gap lengths. The reduced number of motor units indicates that further improvement of repair procedures and nerve environment is needed.


Elevated frequency of micronucleated cells in the buccal mucosa of individuals at high risk for oral cancer: betel quid chewers.
The micronucleus test was applied to buccal mucosa cells of 2 population groups at high risk for oral cancer: Khasis of the northeastern hill region of India, who eat raw betel nuts together with betel leaves and lime, and residents of the state of Orissa (India), who chew betel quids consisting mainly of perfumed tobacco, dried betel nut, betel leaf, lime and several spices. Micronuclei were scored on Feulgen/fast green-stained smear preparations of exfoliated cells obtained by scraping the surface of the buccal mucosa. All 17 raw betel nut eaters and all 20 chewers of betel quids had significantly elevated frequencies of micronucleated mucosa cells over nonchewing controls of comparable ethnic background and dietary habits. The frequencies of micronucleated exfoliated cells were higher at the site within the oral cavity where the quid was kept compared to those at the opposite buccal wall. The micronuclei frequency was lower among individuals chewing a raw betel nut, betel leaf and lime mixture compared to those using tobacco,-betel nut-, lime- and betel leaf-containing quids. Micronuclei frequencies in exfoliated human cells seem to represent a useful 'internal dosimeter' for estimating exposure to genotoxic, and by implication, carcinogenic agents in the tissue from which cancers will develop.


Botulinum toxin A versus electrogalvanic stimulation for levator ani syndrome: is one a more effective therapy?
Levator ani syndrome (LAS) is a functional disorder that can be a challenge to treat. LAS that is refractory to medical management may be treated with electrogalvanic stimulation (EGS) or Botulinum toxin A (BTX) injection. The aim of the present study was to evaluate the outcomes associated with both EGS and BTX in patients with medically refectory LAS to determine if either demonstrate a long-term benefit or whether one treatment is better than the other. A retrospective study was performed on consecutive patients with LAS treated with BTX or EGS at our institute. Patients were identified from a prospectively maintained database. The study time frame was 6 years. One hundred and twenty patients [80 females, mean age 52 years (range 21-84, SD 15.8)] were treated for medically refractory LAS: 102 with BTX and 18 with EGS. With EGS, 28.6% of patients reported a complete response, 14.3% reported a partial response and 57.1% reported no response to treatment. With BTX, 35.5% of patients reported a complete response, 19.7% reported a partial response and 44.7% reported no response to treatment. There was no difference between BTX and EGS with regard to treatment response. Patients who had BTX were more likely to report a short-term benefit in treatment when compared to those patients who had EGS (p = 0.002). This difference between reported outcome to BTX and EGS treatments did not sustain in the long term (p = 0.2). Both BTX and EGS are to some extent effective at resolving symptoms of LAS. In the short term, BTX appears to be more effective. Neither treatment sustains its benefit in the long term.


Radiation risk to patients from nuclear medicine in Poland (1981).
This paper presents the method and results of an estimation of radiation risk to the patients subjected to in vivo diagnostic radio-isotopic procedures in Poland in 1981. The qualitative and quantitative structure of these examinations is also presented. The estimation of an expected number of the stochastic effects caused by the internal exposure to ionizing radiation from the administered radionuclides have been performed for the patients according to ICRP recommendations. The conclusion was that 33 fatal radiation induced cancers, caused mainly by thyroid procedures with 131I, may be expected in the future in the population of about 80,000 patients who were subjected to radioisotopic procedures in Poland in 1981.


Nerve growth factor mediates peripheral mechanical hypersensitivity that accompanies experimental cystitis in mice.
Increased sensitivity to somatic stimuli has been noted in the presence of visceral inflammation. Cystitis was induced by intraperitoneal injection of cyclophosphamide (CYP) in female mice. Sensitivity of hind paws to mechanical stimuli was determined prior to and 4, 9 and 24 h after CYP, and sensitivity of the tail to thermal stimuli was determined prior to, 4 and 24 h after CYP treatment. To investigate the role of nerve growth factor (NGF) in these processes, other groups of mice received NGF antiserum, normal serum, or K252a intravenously 30 min after CYP administration. CYP induced bladder inflammation that was not ablated by treatment with NGF antiserum or K252a. Sensitivity to mechanical stimuli was increased 4 and 9 h after CYP administration. This was reversed by NGF antiserum or K252a but not by normal serum. After 24 h, no differences were observed in withdrawal threshold among groups. None of the treatments had any effect on sensitivity to thermal stimuli. To further investigate the role of NGF in this process, NGF was instilled into the bladders of mice in the presence or absence of intravenous NGF antiserum. Four hours after intravesical instillation of NGF, the threshold of the hind paws to mechanical stimulation was significantly decreased, and this effect was reversed by prior treatment with NGF antiserum. This model of visceral pain causes increased sensitivity to peripheral application of mechanical stimuli. This effect is at least partially mediated by NGF, and the bladder may be the source of NGF in this process.


Survival, growth and physiology of marine bivalve (Sinonovacula constricta) in long-term low-salt culture.
In this study, we investigated the possibility of rearing and breeding the razor clam (Sinonovacula constricta) in inland low salinity water or freshwater. Long-term low salinity (LS) rearing was performed for 3 months to determine the effects of LS on the survival rate, growth rate, and the activities of critical enzymes in juvenile S. constricta (JSC). The survival rate in the LS group was only 15.67% at the end of the LS rearing test. In the first month, the survival rate in the LS group was significantly lower than that in the control group (P < 0.001). The growth rate (shell length growth rate and weight gain rate) was significantly lower in the LS group than the control group in the first month (P < 0.001 for length and weight). However, the growth rates in the two groups differed little during the second and third months. The oxygen consumption and ammonia excretion rates by JSCs were significantly higher in the LS group than the control group during the first month, but they decreased gradually during the following 2 months. The Na+/K+ ATPase and superoxide dismutase activities were significantly higher in the LS group than the control group during the first month, but they then decreased gradually until there were no significant differences between the groups. However, the aspartate aminotransferase activity was higher in the LS group than the control group during all 3 months. Most of the JSCs died due to LS but the survival of some JSCs suggests the possibility of breeding LS resistant or freshwater S. constricta.


Correction to: The Effects of Lifestyle and/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have we Learned from the DALI Studies?
The original version of this review article unfortunately contained a mistake.


Analysis of epigenetic modifications of DNA in human cells.
Epigenetics, the study of somatically heritable changes in gene expression not related to changes in the DNA sequence, is a rapidly expanding research field that plays important roles in healthy as well as in diseased cells. DNA methylation and hydroxymethylation are epigenetic modifications found in human cells, which are deeply implicated in normal cellular processes as well as in several major human diseases. Here, a range of different methods for the analyses of DNA methylation and hydroxymethylation at locus-specific and genome-wide scales is described.


Tuneable separation of gold by selective precipitation using a simple and recyclable diamide.
The efficient separation of metals from ores and secondary sources such as electronic waste is necessary to realising circularity in metal supply. Precipitation processes are increasingly popular and are reliant on designing and understanding chemical recognition to achieve selectivity. Here we show that a simple tertiary diamide precipitates gold selectively from aqueous acidic solutions, including from aqua regia solutions of electronic waste. The X-ray crystal structure of the precipitate displays an infinite chain of diamide cations interleaved with tetrachloridoaurate. Gold is released from the precipitate on contact with water, enabling ligand recycling. The diamide is highly selective, with its addition to 29 metals in 2 M HCl resulting in 70% gold uptake and minimal removal of other metals. At 6 M HCl, complete collection of gold, iron, tin, and platinum occurs, demonstrating that adaptable selective metal precipitation is controlled by just one variable. This discovery could be exploited in metal refining and recycling processes due to its tuneable selectivity under different leaching conditions, the avoidance of organic solvents inherent to biphasic extraction, and the straightforward recycling of the precipitant.


The economic benefits of rainwater-runoff reduction by urban green spaces: a case study in Beijing, China.
Urbanization involves the replacement of vegetated surfaces with impervious built surfaces, and it often results in an increase in the rate and volume of rainwater surface runoff. Urban green spaces play a positive role in rainwater-runoff reduction. However, few studies have explored the benefits of rainwater-runoff reduction by urban green spaces. Based on inventory data of urban green spaces in Beijing, the paper evaluated the economic benefits of rainwater-runoff reduction by urban green spaces, using the rainwater-runoff-coefficient method as well as the economic valuation methods. The results showed that, 2494 cubic meters of potential runoff was reduced per hectare of green area and a total volume of 154 million cubic meters rainwater was stored in these urban green spaces, which almost corresponds to the annual water needs of the urban ecological landscape in Beijing. The total economic benefit was 1.34 billion RMB in 2009 (RMB: Chinese currency, US$1=RMB6.83), which is equivalent to three-quarters of the maintenance cost of Beijing's green spaces; the value of rainwater-runoff reduction was 21.77 thousand RMB per hectare. In addition, the benefits in different districts and counties were ranked in the same order as urban green areas, and the average benefits per hectare of green space showed different trends, which may be related to the impervious surface index in different regions. This research will contribute to an understanding of the role that Beijing's green spaces play in rainwater regulation and in the creation and scientific management of urban green spaces.


In Vitro Anthelmintic Assay.
Nematodes are believed to have originated 1000 million years ago as free living anaerobic benthic organisms. Modern anthelmintic drugs have been in use but the worms have created resistance to most of the broad spectrum anthelmintics such as benzimidazoles, levamisole, avermectins, etc. However, these drugs cause side effects. More recently, plant extracts have been reported as having developed resistance against anthelmintics. A study using earthworms to determine the activity has been developed and explained in a well-defined manner in this chapter.


Atypical ductal hyperplasia of the breast: the controversial management of a borderline lesion: experience of 47 cases diagnosed at vacuum-assisted biopsy.
The present paper describes our experience of 47 cases of atypical ductal hyperplasia (ADH) diagnosed at vacuum-assisted biopsy. From June 1999 to December 2003, 47 consecutive diagnoses of non-palpable ADH of the breast were made by 11-gauge vacuum-assisted biopsy (Mammotome). Of these, 17 were subjected to surgical excision and 11 underwent a second Mammotome at the site of the previous vacuum-assisted biopsy. Diagnostic underestimation occurred in only two cases, with a surgical diagnosis of ductal carcinoma in situ. In both patients, aged between 46 and 55 years, the radiological images showed microcalcifications of >20 mm, and the lesions were not completely removed by Mammotome. Despite the obvious limitations of the present study, it can be concluded that the probability of underestimating ADH diagnosis by Mammotome appears to be related to the radiological features of the lesion (>20 mm) and to the adequacy of specimens.


[The coexistence of 2 different neuroendocrine tumors of the upper gastrointestinal tract and pancreas].
A 41-year-old obese patient presented with cramp-like abdominal pain, watery diarrhoea with partly digested food particles, projectile vomiting and newly diagnosed diabetes mellitus. For the preceding 6 years he had been treated for recurrent gastric and duodenal ulcers. Although the fasting gastrin level was raised and Zollinger-Ellison syndrome suspected, computed tomography (CT), magnetic resonance imaging (MRI) and coeliac angiography at another hospital had failed to discover a tumor. Biochemical tests were unremarkable except for an increased GPT concentration, slight fasting hyperglycemia and hypertriglyceridemia. The gastrin and chromogranin A levels were markedly elevated (15,590 pg/ml and 584.2 U/l, respectively). Gastroscopy revealed, in addition to multiple small duodenal ulcers, a round polypoid mass (diameter of 0.7 cm) lateral to the papilla of Vater, histologically an APUDoma. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a 0.5 cm long compression of the duct of Wirsung in the region of the head of the pancreas. Liver metastases were excluded by magnetic resonance imaging and computed tomography. Endosonography showed a ca. 4 mm space-occupying lesion in the region of the body of the pancreas. Octreotide scintigraphy demarcated two foci at the level of the head of the pancreas (somatostatin-receptor positive). After a pylorus-preserving partial duodenopancreatectomy with lymph node dissection N1/N2, histology confirmed a gastrinoma of the duodenum and a glucagonoma of the pancreas (pT3pN1pMx). Postoperatively the patient became symptom-free and both the blood sugar level and the tumor marker were normal. Combined ERCP, endosonography and scintigraphy are more sensitive than other radiological examinations (CT and MRI) in diagnosing and localizing neuroendocrine tumours of the gastrointestinal tract. Despite the low incidence of such tumours, the possible synchronous occurrence of several such tumour should not be ignored.


Gradient effects in extravascular water determination using 15O-labelled water under steady state conditions: theory and error sensitivity.
Steady state tracer measurements with short-lived isotopes allow the determination of dynamic and static physiological functions and parameters. Both types of measurements are affected by the gradient effects which result from the decay of the tracer through the volume observed. Using 15O-labelled compounds and positron emission tomography (PET), dynamic functions like flow are quite sensitive to variations in extraction fraction and distribution coefficient. In the operational equation for the determination of distribution volumes the gradient effect can be reduced to correction terms which are governed by the mean transit time of the tracer through the observed volume. Because mean transit times can be measured independently they allow a reasonable correction of gradient effects in distribution volume determinations, even if deviations of extraction fraction and distribution coefficient from unity must be considered.


Melatonin ameliorates histone modification disorders in mammalian aged oocytes by neutralizing the alkylation of HDAC1.
Aging-associated histone modification changes in oocytes have been sporadically reported, but the underlying mechanisms remain elusive. Here, we systematically characterize multiple histone modifications in oocytes during aging. We find that maternal and postovulatory aging markedly alter the status of histone modifications, specifically H4K12ac and H3K4me3, in both mouse and porcine oocytes. Meanwhile, we identify a substantial reduction in HDAC1 (histone deacetylase 1) protein in aged oocytes, which contributes to the changes in H4K12ac and H3K4me3. Moreover, by employing methylglyoxal (MG) and site-directed mutagenesis, we demonstrate that the elevated reactive carbonyl species (RCS) level induces HDAC1 degradation, likely through attacking the cysteine residues, thereby influences histone modification state. Importantly, supplementation of melatonin not only prevents the loss of HDAC1 protein, but also partially corrects the H4K12ac and H3K4me3 status in aged oocytes. To sum up, this study established the link between redox disequilibrium and histone modification alterations during mammalian oocyte aging.


Monoclonal antibody successes in the clinic.
Most monoclonal antibodies in clinical trials are owned by small biotech companies. But with blockbuster-sized revenues and approval rates higher than those for small-molecule drugs, that all may be set to change.


Change in reciprocity as a predictor of depressive symptoms: a prospective cohort study of Finnish women and men.
The purpose of the study was to examine gender differences in the association between changes in the balance of give and take in close relationships and depressive symptoms. Data from a 5-year prospective cohort study in Finland (HeSSup Study) (N=18,445) were analyzed. After adjustment for demographic characteristics, recent negative life events, baseline depressive symptoms, hostility, and the supportiveness of social network, a shift of balance toward support receiving was a significant risk factor for future depressive symptoms among women. In contrast, men whose balance of give and take had moved toward support giving had a higher risk of future depressive symptoms than other men. When the analyses were replicated in a sub-cohort of initially non-depressed participants who lived in reciprocal relationships and had no recent life events, the results became even more pronounced among women, although not among men. We conclude that, for women, a shift in their close relationships toward support receiving may lead to increased risk of depressive symptoms, whereas for men a shift toward giving may have a parallel though less evident impact.


Autologous Infant and Allogeneic Adult Red Cells Demonstrate Similar Concurrent Post-Transfusion Survival in Very Low Birth Weight Neonates.
Based on the hypothesis that neonatal autologous red blood cell (RBC) survival (RCS) is substantially shorter than adult RBC, we concurrently tracked the survival of transfused biotin-labeled autologous neonatal and allogeneic adult RBC into ventilated, very low birth weight infants. RBC aliquots from the first clinically ordered, allogeneic adult RBC transfusion and from autologous infant blood were labeled at separate biotin densities (biotin-labeled RBC [BioRBC]) and transfused. Survival of these BioRBCs populations were concurrently followed over weeks by flow cytometric enumeration using leftover blood. Relative tracking of infant autologous and adult allogeneic BioRBC was analyzed by linear mixed modeling of batched weekly data. When possible, Kidd antigen (Jka and Jkb) mismatches between infant and donor RBCs were also used to track these 2 populations. Contrary to our hypothesis, concurrent tracking curves of RCS of neonatal and adult BioRBC in 15 study infants did not differ until week 7, after which neonatal RCS became shortened to 59%-79% of adult enumeration values for uncertain reasons. Analysis of mismatched Kidd antigen RBC showed similar results, thus, confirming that BioRBC tracking is not perturbed by biotin RBC labeling. This study illustrates the utility of multidensity BioRBC labeling for concurrent measurement of RCS of multiple RBC populations in vivo. The similar RCS results observed for neonatal and adult BioRBCs transfused into very low birth weight infants provides strong evidence that the circulatory environment of the newborn infant, not intrinsic infant-adult RBC differences, is the primary determinant of erythrocyte survival. Clinicaltrials.gov: NCT00731588.


Characterization of the effect of ganstigmine (CHF2819) on amyloid precursor protein metabolism in SH-SY5Y neuroblastoma cells.
We have investigated the effect of ganstigmine (CHF2819), a novel geneserine derived acetylcholinesterase (AChE) inhibitor, on the expression and metabolism of the amyloid precursor protein (APP) in neuroblastoma cell line SH-SY5Y. The rationale was based on the suggestion that cholinergic activity may also be involved in the regulation of APP metabolism. We studied the acute effect on APP metabolism following the secretion of sAPPalpha in the conditioned medium of cells. Following short term treatment (2h), ganstigmine promoted a slight increase in the release of sAPPalpha, the maximal effect approaching on average 1.5 fold baseline value. The data obtained in the long term experiments demonstrate that continuous inhibition of AchE obtained with 100 nM ganstigmine following an exposure of 24 hours did not influence APP isoforms expression. However, the compound appeared to increase the constitutive release of sAPPalpha, with a mechanism that is derived from an indirect cholinergic stimulation.


Transition from the classroom to the Web: successful strategies for teaching online.
Online courses are an integral part of nursing education programs.The responsibility for developing and teaching asynchronous online courses can be challenging, especially for neophyte educators. Two experienced educators discuss strategies for developing and enhancing selected aspects of asynchronous online courses. Practical, evidence-based aspects of designing, conducting, and evaluating web-based courses are presented. Examples from courses using WebCT are shown.


Development of a Consensus Syllabus of Palliative Medicine for Physicians in Japan Using a Modified Delphi Method.
Although palliative care is rapidly being disseminated throughout Japan as a result of government policy, a systematic syllabus of palliative medicine for physicians has not been developed. This study aimed to develop a Japanese national consensus syllabus of palliative medicine for physicians. We used a modified Delphi method to develop the consensus syllabus. We created a Delphi panel by selecting 20 expert eligible panelists consisting of Diplomate or Faculty of the Specialty Board of Palliative Medicine and certified by the Japanese Society for Palliative Medicine. We inducted external reviewers from 11 palliative care-related organizations. Among 20 experts surveyed, 20 (100%) responded over all rounds. Ten (50%) participated in a panel meeting. In the first round, 179 of 179 (100%) learning objectives were judged to be appropriate and 5 of 179 (3%) learning objectives were judged to be too difficult. In the panel meeting, 25 learning objectives were excluded, three new learning objectives were added, and 15 learning objectives were reworded. In the second round, 18 of 18 (100%) learning objectives were judged to be appropriate. The final version of the syllabus developed consists of 157 specific behavioural objectives and 22 general instructional objectives across 22 courses. We have developed the first national consensus syllabus of palliative medicine for physicians in Japan. Based on this syllabus, a training program on palliative medicine will be established by training facilities in Japan, and physicians will be able to practice specific palliative care.


Development of a multilocus variable-number of tandem repeat typing method for Listeria monocytogenes serotype 4b strains.
Listeria monocytogenes serotype 4b strains have been identified as the causative agent in many human listeriosis epidemics as well as in a considerable number of sporadic cases. Due to the genetic homogeneity of serotype 4b isolates, development of rapid subtyping methods with high discriminatory power for serotype 4b isolates is required to allow for improved outbreak detection and source tracking. In this study, multilocus variable-number tandem repeat analysis (MLVA) was developed and used to characterize 60 serotype 4b isolates from various sources. All isolates were also characterized by automated EcoRI ribotyping, single enzyme pulsed-field gel electrophoresis (PFGE) with ApaI, and a multilocus sequence typing (MLST) scheme targeting six virulence and virulence-associated genes. Discriminatory power of MLVA (as determined by Simpson Index of Discrimination) was higher than the discriminatory power of any of the other three methods. MLVA markers targeted were found to be stable and did not change when three isolates were passaged daily for 70 days. Cluster analyses of MLVA, PFGE and MLST consistently grouped the same isolates into three major clusters, each of which includes one of the three major L. monocytogenes epidemic clones (i.e., ECI, ECIa and ECII). We conclude that the MLVA method described here (i) provides for more discriminatory subtyping of L. monocytogenes serotype 4b strains than the other three methods, (ii) identifies three major groups within the serotype 4b, which are consistent with the groups identified by other subtyping methods, and (iii) is easy to interpret. Use of MLVA may thus be recommended for subtyping of serotype 4b isolates, including as a secondary more discriminatory subtyping method that could be used after initial isolate characterization by PFGE or ribotyping.


Increased numbers of CD68 antigen positive dendritic epidermal cells and upregulation of CLA (cutaneous lymphocyte-associated antigen) expression on these cells in various skin diseases.
CD68 is a myelomonocytic marker identified in human dermal macrophages. Although the existence of CD68 + dendritic epidermal cells has been reported, their characteristics have not been well elucidated. Cutaneous lymphocyte-associated antigen (CLA) is a homing receptor of cutaneous inflammatory T cells. Our recent report suggested that CLA was a homing molecule of CD1a+ Langerhans cells (LC) in the skin. In the present study we tested whether CD68 and CLA+ dendritic epidermal cells were present in skin specimens of normal skin and diseased skin such as lichen planus (LP), psoriasis vulgaris (PS), discoid lupus erythematosus (DLE), basal cell epithelioma (BCE), squamous cell carcinoma (SCC), irritated seborrheic keratosis (iSK), and Bowen's disease (BD). CD68+ dendritic epidermal cells were identified in normal skin and consisted of half the population of CD1a+ LC. These data indicate that CD68+ dendritic epidermal cells constitute a subpopulation of CD1a+ LC. CLA was expressed on a small percentage of CD68+ dendritic epidermal cells in normal skin. A remarkably increased number of CD68+ dendritic epidermal cells and upregulation of CLA on CD68+ dendritic epidermal cells were observed in diseased skin. The percentage of CLA+ cells among all CD68+ dendritic epidermal cells was less than that of CLA+ cells among all CD1a+ LC in diseased skin. The percentage of CLA+ cells among all CD68+ dendritic dermal cells was much less than that of CLA+ cells among all CD1a+ dendritic dermal cells. In normal skin, the epidermis showed minimal expression of monocyte chemoattractant protein (MCP)-1 and TGF-beta2, and no expression of TGF-beta1. In diseased skin, the epidermis showed elevated, but still moderate immunoreactivity for MCP-1. Slightly enhanced immunoreactivity for TGF-beta2, but not for TGF-beta1, was observed in the epidermis of diseased skin. Increased epidermal MCP-1 immunohistochemical staining was associated with the increased number of CD68 dendritic epidermal cells. These data suggest the possibility that MCP-1 secretion from the epidermis can affect the migration of CD68; Cutaneous lymphocyte-associated antigen; Monocyte chemoattractant protein-1; TAF-beta.


Discovery and SAR of novel tetrahydropyrrolo[3,4-c]pyrazoles as inhibitors of the N-type calcium channel.
A novel series of substituted tetrahydropyrrolo[3,4-c]pyrazoles were investigated as blockers of the N-type calcium channel (Cav2.2 channels), a chronic pain target.


Methylglyoxal and other carbohydrate metabolites induce lanthanum-sensitive Ca2+ transients and inhibit growth in E. coli.
The results here are the first demonstration of a family of carbohydrate fermentation products opening Ca2+ channels in bacteria. Methylglyoxal, acetoin (acetyl methyl carbinol), diacetyl (2,3 butane dione), and butane 2,3 diol induced Ca2+ transients in Escherichia coli, monitored by aequorin, apparently by opening Ca2+ channels. Methylglyoxal was most potent (K(1/2) = 1 mM, 50 mM for butane 2,3 diol). Ca2+ transients depended on external Ca2+ (0.1-10 mM), and were blocked by La3+ (5 mM). The metabolites affected growth, methylglyoxal being most potent, blocking growth completely up to 5 h without killing the cells. But there was no affect on the number of viable cells after 24 h. These results were consistent with carbohydrate products activating a La3+-sensitive Ca2+ channel, rises in cytosolic Ca2+ possibly protecting against certain toxins. They have important implications in bacterial-host cell signalling, and where numbers of different bacteria compete for the same substrates, e.g., the gut in lactose and food intolerance.


A survey on the availability of geriatric-friendly protocols, equipment and physical environment across emergency departments in Flanders, Belgium.
The acquisition of geriatric-friendly resources is an important part of adapting emergency department (ED) care to the needs of vulnerable older patients. The aim of this study was to explore the availability of geriatric-friendly protocols, equipment and physical environment criteria in EDs and to identify related improvement opportunities. The head nurse of 63 EDs in Flanders and Brussels Capital Region was invited to complete a survey in collaboration with the chief physician of the ED. The questionnaire was inspired by the American College of Emergency Physicians Geriatric ED Accreditation Program and explored the availability, relevance and feasibility of geriatric-friendly protocols, equipment and physical environment. Descriptive analyses were performed. A region-wide improvement opportunity was defined as a resource that was never to occasionally (0-50%) available on Flemish EDs and was scored (rather or very) relevant by at least 75% of respondents. A total of 32 questionnaires were analysed. The response rate was 50.8%. All surveyed resources were available in at least one ED. Eighteen out of 52 resources (34.6%) were available in more than half of EDs. Ten region-wide improvement opportunities were identified. These comprised seven protocols and three physical environment characteristics: 1) a geriatric approach initiated from physical triage, 2) elder abuse, 3) discharge to residential facility, 4) frequent geriatric pathologies, 5) access to geriatric specific follow-up clinics, 6) medication reconciliation, 7) minimising 'nihil per os' designation, 8) a large-face, analogue clock in each patient room, 9) raised toilet seats and 10) non-slip floors. Currently available resources supporting optimal ED care for older patients in Flanders are very heterogeneous. Researchers, clinicians and policy makers need to define which geriatric-friendly protocols, equipment and physical environment criteria should become region-wide minimum operational standards. Findings of this study are relevant to facilitate the development process of this endeavour.


Difficult airways: a 3D printing study with virtual fibreoptic endoscopy.
Head and neck cancer patients present unique airway challenges, and oropharyngeal, laryngeal, and hypopharyngeal tumours considerably distort and narrow the anatomy of the airway. We describe the use of 3D augmented reality software combined with 3D printed models to assess the anatomy of difficult airways and to assist in the formulation of the most optimal airway management strategy in such patients. The reported patients had computed tomograms (CT) of the neck prior to their anaesthetic and surgical management. DICOM files of the respective scans were imported to 3D rendering software (OsiriX, Pixmeo). We constructed volume rendered models for initial assessment of the airway then generated serial surface rendered models to create a virtual endoscopic path of the airway to simulate the fibreoptic approach. To further facilitate the study of difficult airways we have subsequently printed 3D models of those that were most difficult using rapid prototyping. Head and neck tumours significantly distort the airway. Thorough study of the relevant anatomy prior to airway management for operating reasons enhances communication between the surgeon and anaesthetist, and aids selection of the most appropriate intubation approach. In conclusion, this paper highlights a useful and novel pre-assessment strategy that allows a virtual, visual, 3-dimensional assessment of the airway anatomy combined with 3D modelling and 3D printing. This enables the airway specialist, anaesthetist, and head and neck surgeon to anticipate any critical steps and adjust the plan accordingly.


Estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast tumors: early prediction of chemosensitivity with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography during neoadjuvant chemotherapy.
The objective of this prospective study was to evaluate the ability of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) to predict chemosensitivity in patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Sixty-four consecutive patients underwent (18)F-FDG PET/CT scanning at baseline and after the second course of neoadjuvant chemotherapy (NAC). The evolution (Δ) between the 2 scans of image parameters (maximum standardized uptake value [SUV(max)], SUV(mean), metabolic tumor volume, and total lesion glycolysis [TLG]) was measured. Correlations between early changes in PET-derived parameters and pathologic response observed in surgical specimens after the completion of 8 courses of NAC were estimated with Mann-Whitney U tests. Response prediction on the basis of clinical data, histologic type, or molecular markers also was assessed (Fisher exact test). Receiver operating characteristic (ROC) analysis was used to compare the area under the curve (AUC) of each parameter. The best prediction of chemosensitivity was obtained with ΔTLG (-49% ± 31% in nonresponders vs -73% ± 25% in responders; P < .0001). Among the biologic parameters, only negative progesterone receptor status (57% responders vs 31% nonresponders; P = .04) and luminal B subtype (63% responders vs 22% nonresponders; P = .02) were predictive of a pathologic response. ROC analysis resulted in an AUC of 0.81, 0.73, 0.71, and 0.63 for ΔTLG, ΔSUV(max), luminal subtype, and progesterone receptor status, respectively. When patients responded to NAC, the majority of ER-positive/HER2 negative tumors exhibited partial tumor shrinkage; and the PET parameters that combined volume and activity measurements, such as TLG, offered better accuracy for early prediction than the SUV(max). Negative progesterone receptor status and luminal B subtype had weaker predictive power than PET-derived parameters.


The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Intracranial pressure treatment threshold.
An absolute ICP threshold that is uniformly applicable is unlikely to exist. Current data, however, support 20-25 mm Hg as an upper threshold above which treatment to lower ICP should generally be initiated.


How can biochar-based metal oxide nanocomposites counter salt toxicity in plants?
Application of biochar-based metal oxide nanocomposites can acquire new composites and combine the benefits of biochar with nanomaterials. For the first time, this research was conducted to evaluate the possible effects of solid biochar (25 g biochar kg-1 soil) and biochar-based nanocomposites (BNCs) of magnesium oxide (25 g BNC-MgO kg-1 soil), manganese oxide (25 g BNC-MnO biochar kg-1 soil) and combined use of these nanocomposites (12.5 g BNC-MgO + 12.5 g BNC-MnO kg-1 soil) on salt (non-saline, 6 and 12 dSm-1 NaCl salinities) tolerance of safflower plants (Carthamus tinctorius L.). Salinity reduced potassium, magnesium and manganese contents in root and leaf tissues, chlorophyll content index, photosynthetic pigments, maximum quantum yield of photosystem II (Fv/Fm) and relative photosynthetic electron transport rate (RETR), leaf water content and plant biomass, but increased the sodium content, reactive oxygen species generation (ROS), oxidative stress and antioxidants and ROS detoxification potential of safflower roots and leaves. Application of biochar and BNCs increased the contents of potassium, manganese and magnesium in plant tissues, photosynthetic pigments, Fv/Fm and RETR, leaf water content and reduced sodium accumulation, ROS generation and oxidative stress under saline conditions, leading to a higher plant biomass in comparison with control. The BNC-MgO + BNC-MnO was the superior treatment on reducing salt toxicity. This treatment reduced oxidative stress by enhancing photosynthetic pigments, Fv/Fm and RETR of safflower under salt stress. These results revealed that BNCs have a great potential for improving salt tolerance of plants through increasing RETR and decreasing sodium accumulation and ROS generation.


Attachment Ability of Human Apical Papilla Cells to Root Dentin Surfaces Treated with Either 3Mix or Calcium Hydroxide.
Tissue regeneration and root continuation are the ultimate goals in regenerative endodontics. Apical papilla cells (APCs) have been hypothesized to play roles in those processes. Therefore, preservation of cell vitality and promoting initial cell attachment seem to be crucial steps. The purposes of this study were to investigate the attachment ability and morphology of viable human APCs by using fibronectin immunofluoresence, alamarBlue assay, and scanning electron microscopy, when APCs were grown on human root dentin surfaces treated with 3Mix or calcium hydroxide (Ca(OH)2) at different concentrations. Human root dentin slices were divided into 6 groups: (1) control, (2) 3Mix 0.39 μg/mL, (3) 3Mix 100 μg/mL, (4) 3Mix paste, (5) Ca(OH)2 1 mg/mL, and (6) Ca(OH)2 1000 mg/mL. All samples were separately treated for 7 days and final rinsed with 17% EDTA. Then primary human APCs were seeded. Fibronectin immunofluorescence was used to evaluate the attachment ability of APCs on treated dentin. A vitality assay by using alamarBlue was monitored at specific time intervals. The morphology of the cells on the dentin was observed under scanning electron microscopy. The lowest number of fibronectin-positive cells was observed on root dentin treated with 3Mix paste (P < .05). The 3Mix at 0.39 and 100 μg/mL did not affect the amount of APC attachment, whereas the viability of APCs on the dentin surface was significantly lower in the 100-μg/mL 3Mix-treated group than in the negative control group (P < .05). Both concentrations of Ca(OH)2 induced APC attachment (P < .05). Moreover, only cells grown on the surfaces treated with Ca(OH)2 exhibited cytoplasmic processes. Human root dentin treated with 3Mix paste had significantly lower APC attachment. The 3Mix at 0.39 μg/mL and 100 μg/mL had no significant negative effect on APC attachment on dentin. Higher numbers of cells attaching on dentin were observed in calcium hydroxide-treated groups.


Location of substance P-, bombesin-gastrin-releasing peptide, [Met5]enkephalin- and [Met5]enkephalin-Arg6-Phe7-like immunoreactivities in adult human sympathetic ganglia.
Indirect immunofluorescent methods were used to study peptides in human paravertebral sympathetic ganglia. [Met5]enkephalin, [Met5]enkephalin-Arg6-Phe7 and bombesin-gastrin-releasing peptide-like immunoreactivities were localized in varicose nerve fibers, which often formed basket-like networks around principal ganglion cells. Substance P-like immunoreactivity appeared frequently as solitary varicose nerve fibers and occasionally as networks. No immunolabeled cell bodies were discovered with any of the antisera used, including antibodies raised against molluscan cardioexcitatory peptide Phe-Met-Arg-Phe-NH2. The results demonstrate the presence of peptides within nerve fibers and terminals but not cell bodies of human paravertebral sympathetic ganglia. The localization suggests that the peptides have neurotransmitter or neuromodulator roles in the ganglia.


Recent discoveries in physiology of insulin-like growth factor-1 and its interaction with gonadotropins in folliculogenesis.
Ovarian follicular development is under the influence of gonadotrophins. The manner by which gonadotrophins achieve their role in cell replication and hormone production is through other specialized molecules. Insulin-like growth factor-1 (IGF-1) is considered to be one of the most important of these molecules. IGF-1 is present in relatively large amounts in the ovary and the IGF-1 gene is expressed in the graafian follicle. IGF-1 binding proteins modulate the action of IGF-1 and are influenced by gonadotrophins. Null mutations of genes encoding IGF-1 and type-1 IGF receptor have demonstrated the obligatory role of IGF-1 in folliculogenesis. It was proposed that IGF-1 may be an obligatory mediator of gonadotrophin-induced folliculogenesis and that the interaction is synergistic. From this point, one group embarked on a series of physiological studies to further elucidate the interaction of these molecules. We discovered that, according to circumstances, follicle stimulating hormone (FSH) may act with IGF-1 synergistically (as was postulated before), additively, independently, or even antagonistically. We discovered that granulosa cells must first be exposed to FSH and then they respond well to IGF-1. All previous studies of granulosa cells were done on mural granulosa cells. We subsequently showed that cumulus type of granulosa cells (adjacent to the oocyte) behave differently in their responses to gonadotrophins and IGF-1.


Utility of Glasgow Microenvironment Score as a prognostic tool in colorectal carcinoma.
Colorectal carcinoma (CRC) is third most common malignancy in the world. The presence of Lymphocytes particularly at the invasive margin of the tumor have been associated with good immune response indicating better prognosis. The relative tumor stroma is also important in deciding the course of the disease. The Glasgow Microenvironment Score (GMS) comprises of assessment of tumor cell infiltrate using Klintrup-Makinen (KM) grade and tumor stroma percentage. The aim of the present study is to evaluate the utility of GMS score in relation to parameters of adverse histopathological outcome in carcinoma colon that is grading, staging, LVI, PNI and nodal metastasis. Colectomy specimens received over 3 year period were subjected to microscopic evaluation for LVI, PNI, grade, stage & lymph node metastasis. Lymphocytes at the deepest invasive margin of tumor were counted as per KM score in 5 HPF by two independent pathologists . Patients were classified as Low grade (0/1) or high grade (2/3) response. Tumor stroma percentage was calculated as stroma poor (<50%) and stroma rich (>/= 50 %). The GMS was scored by combining the two and scored 0, 1 and 2. Total 37 patients with no prior therapy were included out of which 23 were males and 14 females. 15 patients (40.54%) had GMS of 0, 6 (16.21%) had GMS 1 and 16 (43.24%) had GMS 2. A high GMS was associated with LVI (P = 0.02), PNI (P = 0.01) lymph node metastasis (P = 0.003). However, no significant association was found between GMS with Grade (P = 0.98) and Stage (P = 0.36). Low GMS was associated with good outcome and high GMS with poor outcome. This score can be used for risk stratification, can be of clinical utility and may be applied to pathological descriptions of CRC.


Laser temperature-jump apparatus for the study of force changes in fibers.
An iodine photodissociation laser generates the 1.315-micron infrared light used to heat the fiber and solvent. Heating of the cell contents by the direct absorption of laser energy is complete within the 100-microseconds rise time of the force transducer. A 5 degrees C temperature jump was usual. Interference with the force record by shock waves, electromagnetic disturbances, and uneven heating of fiber and solvent is minimal and close to the normal background noise of the transducer output. The postjump temperature of the cell remains static for a minimum of 400 ms before evidence of cooling is seen. The temperature of the cell could be changed rapidly. The cuvette contents could therefore be rapidly raised to, and lowered from, elevated prejump temperatures. As a result, sensitive biological samples are subjected to potentially denaturing conditions for the minimum length of time required for the temperature jump. Experiments on collagen and muscle fibers in which normal and rubber-like thermoelastic responses are kinetically resolved from each other are presented. The instrument offers substantial improvements in performance over other currently available designs.


A new multi-epitope peptide vaccine induces immune responses and protection against Leishmania infantum in BALB/c mice.
Visceral leishmaniasis (VL) is a tropical and subtropical disease which is endemic in more than eighty countries around the world. Leishmania infantum is one of the main causative agents of VL disease. Currently, there is no approved-to-market vaccine for VL therapy. In this study, we evaluated cellular and humoral immune responses induced by our newly designed multi-epitope vaccine in BALB/c mice. Four antigenic proteins, including histone H1, sterol 24-c-methyltransferase (SMT), Leishmania-specific hypothetical protein (LiHy), and Leishmania-specific antigenic protein (LSAP) were chosen for the prediction of potential immunodominant epitopes. Moreover, to enhance vaccine immunogenicity, two toll-like receptors 4 (TLR4) agonists, resuscitation-promoting factors of Mycobacterium tuberculosis (RpfE and RpfB), were employed as the built-in adjuvants. Immunization with the designed multi-epitope vaccine elicited a robust Th1-type immune response, compared to other groups, as shown by increased levels of IL-2, IFN-γ, TNF-α, and IgG2a. Furthermore, a significant decrease was observed in Th-2-type-related cytokines such as IL-4 in immunized mice. The designed construct also induced a significant reduction in parasite load (p < 0.0001), conferring protection against L. infantum challenge. This study could be promising in gaining insight towards the potential of peptide epitope-based vaccines as effective protective approaches against Leishmania species.


Efficacy of an expanded ventilator bundle for the reduction of ventilator-associated pneumonia in the medical intensive care unit.
The ventilator bundle (VB) includes a group of clinical maneuvers (head-of-bed elevation, "sedation vacation," deep vein thrombosis prophylaxis, and peptic ulcer disease prophylaxis) to improve outcomes in patients undergoing mechanical ventilation. We modified the standard VB in our medical intensive care unit to include a group of respiratory therapist-driven protocols and, postimplementation, observed a statistically significant (P = .0006) reduction in ventilator-associated pneumonia (VAP), from a median of 14.1 cases/10(3) ventilator-days (interquartile range [IQR] = 12.1 to 20.6) to 0 cases/10(3) ventilator-days (IQR = 0 to 1.1).


Cervical vertebral erosion due to tortuous vertebral artery.
A case of cervical vertebral erosion due to tortuous vertebral artery is presented. This entity is rare and only 11 cases have been reported in the literature. The present case is the first to be demonstrated by magnetic resonance imaging. The importance of considering this vascular anomaly in the differential diagnosis of cervical spinal tumors is discussed.


Adamantane-derived scaffolds targeting the sigma-2 receptor; an in vitro and in silico study.
Novel adamantane-based compounds were synthesized and assessed as potential sigma-2 receptor ligands. Molecular docking and 50 ns molecular dynamic simulation were carried out to determine the binding modes, mechanism of interaction, and stability of these compounds within the active site of the sigma-2 receptor. In addition, the ADME-T properties have been explored. The cytotoxicity in cancer cell lines that express sigma-2 receptors was also examined. In addition, the in silico and cytotoxicity data for the new compounds were compared to a reference sigma-2 receptor ligand with high receptor-binding affinity and selectivity. The data suggests that the new compounds interact with the sigma-2 receptor in a comparable manner to the reference compound, and that adamantane can be used as a scaffold to synthesize sigma-2 receptor ligands with useful functional groups that can be used to conjugate moieties for tumor-imaging or cytotoxic cargo delivery.


On some psychometric properties of the questions about behavioral function (QABF) scale.
This study examined certain psychometric properties of the questions about behavioral function (QABF) scale. The QABF was completed on 118 problem behaviours presented by 40 young people with severe intellectual disabilities, and measures of inter-rater reliability, internal consistency, and construct validity were calculated overall and for subgroups of behaviours defined by topography and reported frequency. Levels of inter-rater reliability for both individual items and subscales were generally modest, but inter-rater reliability of rankings of subscale scores exceeded that reported for other comparable assessments. Inter-rater agreement was higher for higher rate behaviours and lower for maladaptive (versus disruptive and destructive) behaviours. Internal consistency was high for all QABF subscales, but also for the scale as a whole. Factor analysis yielded five factors clearly corresponding to the five QABF subscales and a sixth relating to a single item concerning the repetitive nature of the behaviour. Methodological issues which may have reduced levels of reliability are discussed. We conclude that in terms of psychometric properties, the QABF presents some specific advances on previous brief scales assessing behavioural function, but also that it continues to be appropriate to use other observational or experimental methods together with such scales when conducting functional assessments.


Early impairment in dopaminergic neurotransmission in brains of SIV-infected rhesus monkeys due to microglia activation.
Movement disorders are a common neurological complication of immunodeficiency virus infection and are thought to result from dopaminergic dysfunction in the basal ganglia. We measured levels of dopamine, and its metabolites homovanillic acid and 3,4-dihydroxyphenylacetic acid, in the putamen of healthy and simian immunodeficiency virus (SIV)-infected rhesus monkeys from infection until the development of AIDS. Changes in expression levels of cAMP response element binding protein (CREB), a transcription factor involved in the signalling pathway of dopamine, were also examined. Furthermore, we isolated microglia from the same animals and investigated their activation status in order to explore whether neurochemical findings are associated with immune activation. Plasma and CSF viral RNA load, T-cell analysis and basal ganglia histopathology provided information about disease progression in the animals. Putamen dopamine content was significantly reduced within 3 months of SIV infection, due to decreased dopamine synthesis initially, followed by loss of tyrosine hydroxylase-positive cells in substantia nigra, and accompanied by a decrease in total CREB expression. Pharmacological manipulation of dopaminergic tone with L-DOPA and selegiline showed that the reduction in CREB expression was due to reduced levels of dopamine. These neurochemical changes were significantly correlated with microglia activation in the absence of gross histopathological lesions. Our data demonstrate that putamen dopaminergic function is impaired during SIV infection and indicate that microglia may trigger endogenous mechanisms involved in the dysfunction of dopaminergic systems.


Novel Score to Predict Very Late Recurrences After Catheter Ablation of Atrial Fibrillation.
Various predictors of atrial fibrillation (AF) recurrence have been shown based on the baseline characteristics before catheter ablation (CA). This study aimed to develop a novel scoring system for predicting very late recurrences of AF (VLRAFs) after an initial CA, taking the postprocedural clinical data into account and reassessing VLRAFs in 12-month patients' condition using previously known preprocedural predictors of AF recurrences. We retrospectively studied 327 patients who underwent an initial CA with freedom from AF for over 12 months. We elucidated the predictors of VLRAFs and created a new score to predict VLRAFs in the discovery AF cohort (n = 181). Thereafter, we investigated whether the new scoring system could accurately predict VLRAFs in the validation AF cohort (n = 146). In the discovery AF cohort, VLRAFs were observed in 53 patients (29%) during the follow-up period (mean follow-up duration: 55 months). The univariate and multivariate Cox proportional-hazards model demonstrated that non-pulmonary vein foci, early recurrences of AF (ERAFs), atrial premature contraction (APC) burden ≥ 142/24 hours, and minimum prematurity index of the APCs ≤ 48% were associated with VLRAFs after CA. We created a new scoring system to predict VLRAFs, the n-PReDCt score (non-pulmonary vein: 1 point, early recurrences of AFs (Recurrences of AF in early phase after CA): 1 point, APC burden ≥ 142/24 hours: 1 point, and minimum prematurity index (= Coupling interval) of the APCs of ≤ 48%: 1 point). The n-PReDCt score was significantly associated with VLRAFs by a Kaplan-Meier analysis in the discovery AF and validation AF cohorts (p < 0.0001 and p < 0.0001, respectively).


Third Gordon Hamilton-Fairley Memorial Lecture. Tumour markers--where do we go from here?
An overview of the application of markers for solid tumours is presented. Some of the potential problems with general cancer tests are considered as well as the ways in which the more specific markers have been applied. The limited specificities of markers defined so far remain a serious limitation but they have found useful clinical application. Their use in radioimmunolocalisation provides an interesting challenge to the physical methods of tumour localisation and the possibilities of drug targeting by antibodies are as exciting as the difficulties are formidable. It is, I suggest, a field that will continue to evolve and be productive.


Propeller Flaps of the Lower Extremity.
Wounds of the lower extremity involving the distal third of the leg remain a significant challenge due to anatomic location and often poor host physiology. Perforator-based propeller flaps may provide rapid coverage of these wounds with a relatively low rate of major complications and often readily managed minor complications. A thorough vascular evaluation must be performed prior to the procedure to ensure adequate flap design and selection of the correct perforator is performed. They have the added advantage over their soft tissue free flap counterparts in that they have significantly less host morbidity with similar rates of total necrosis.