Transferrin Receptor Targeted Polyplexes Completely Comprised of Sequence-Defined Components.
Human transferrin protein (Tf) modified polyplexes have already displayed encouraging potential for receptor-mediated nucleic acid delivery into tumors. The use of a blood-derived targeting protein and polydisperse macromolecular cationic subunits however presents a practical challenge for pharmaceutical grade production. Here, Tf receptor (TfR) targeted small interfering RNA (siRNA) polyplexes are designed that are completely composed of synthetic, monodisperse, and sequence-defined subunits generated by solid-phase supported synthesis. An optimized cationizable lipo-oligoaminoamide (lipo-OAA) is used for siRNA core polyplex formation, and a retro-enantio peptide (reTfR) attached via a monodisperse polyethylene glycol (PEG) spacer via click chemistry is applied for targeting. Improved gene silencing is demonstrated in TfR-expressing KB and DU145 cells. Analogous plasmid DNA (pDNA) polyplexes are successfully used for receptor-mediated gene delivery in TfR-rich K562 cells and Neuro2a cells. Six lipo-OAAs differing in their lipidic domain and redox-sensitive attachment of lipid residues are tested in order to evaluate the impact of core polyplex stability on receptor-dependent gene transfer.


A Case-Control Study of Serum and Tissue Catalase among Morphological Variants of Vitiligo.
Role of oxidative stress in the pathogenesis of vitiligo. Estimation of serum and tissue catalase levels in morphological variants of vitiligo. A prospective case-control study was conducted in the outpatient department of Dermatology in Safdarjung hospital. We estimated levels of serum and tissue catalase in 30 vitiligo patients and 30 matched healthy controls. The data analysis was done in Statistical Package for Social Sciences (SPSS) version 21.0. Normality of data was tested by Kolmogorov-Smirnov test. Serum and tissue catalase was lower in vitiligo patients than controls. Serum catalase was lowest in vulgaris type, whereas in the acrofacial type had lowest tissue catalase levels. Vitiligo patients have a generalized oxidative stress functioning at a higher pace as seen with decreased serum and tissue CAT which can well be taken as a marker of active disease and they can be helped with topical pseudoCAT preparations.


Disparity between perceived needs and service provision: a cross-sectional study of Italians with multiple sclerosis.
Assessing the coverage by public or private resources in meeting health-related and social-related needs may be useful for service planning and guide optimization of care, important especially in view of an increase in the prevalence of multiple sclerosis (MS). An ad hoc questionnaire assessed satisfaction of health-related and social care-related needs in a cross-sectional study of 1014 people with MS identified through MS outpatient clinics and local branches and social media channels of the Italian MS Society. 87.1% and 79.8% of the responders had experienced at least one health-related or social-related need, respectively. The study demonstrated significant gaps between perceived needs and service provision. Rehabilitation, residential care, and psychological support were most frequently unsatisfied health-related needs, while the more commonly unmet social-related needs were financial support, elimination of architectural barriers, workplace adaptations, and career guidance. The multivariate analysis highlighted that the satisfaction of health-related needs was primarily associated with geographic area of residence. Social-related needs correlated with both clinical and sociodemographic aspects. The results provide insight into the range of interventions, care, and support people with MS report to be important to them at different points in their disease trajectory. More emphasis should be put on the inequitable distribution of NHS services in different geographic areas of Italy as well as on particularly fragile subgroups of the MS population (older individuals, and those with higher levels of disability) because the care of these individuals continues to be assumed by the family.


The National Institute for Health and Clinical Excellence (NICE) guidelines for caesarean section, 2011 update: implications for the anaesthetist.
In 2004 the first National Institute for Health and Clinical Excellence guidelines on caesarean section were published with the aim of providing evidence-based recommendations for best practice. With the publication of new evidence, the guidelines have been revised with the second edition released in 2011. This review highlights the changes that have been made which are of specific relevance to obstetric anaesthetists including planned caesarean section compared with vaginal birth in healthy women with an uncomplicated pregnancy; management of the morbidly adherent placenta; mother-to-child transmission of maternal infections; maternal request for caesarean section; decision-to-delivery interval for emergency caesarean section; timing of antibiotic administration and childbirth after caesarean section.


Anti-HIV drugs: comparative toxicities in murine fetal liver and bone marrow erythroid progenitor cells.
The toxicity of anti-HIV drugs, 3'-azido-3'-deoxythymidine (zidovudine, AZT), 2',3'-dideoxycytidine (DDC), 2',3'-dideoxy-2',3'-didehydrothymidine (d4T) and ribavirin was studied in vitro in murine fetal liver cells (FLC) and in bone marrow cells. These studies indicate that d4T is the least toxic drug and ribavirin is the most toxic agent in both models. However, the murine FLC system was found to be a more sensitive model for the assessment of toxicity of anti-HIV agents towards erythroid progenitor cells as indicated by the IC50 values.


Physics of pure and non-pure positron emitters for PET: a review and a discussion.
With the increased interest in new PET tracers, gene-targeted therapy, immunoPET, and theranostics, other radioisotopes will be increasingly used in clinical PET scanners, in addition to (18)F. Some of the most interesting radioisotopes with prospective use in the new fields are not pure short-range β(+) emitters but can be associated with gamma emissions in coincidence with the annihilation radiation (prompt gamma), gamma-gamma cascades, intense Bremsstrahlung radiation, high-energy positrons that may escape out of the patient skin, and high-energy gamma rays that result in some e (+)/e (-) pair production. The high level of sophistication in data correction and excellent quantitative accuracy that has been reached for (18)F in recent years can be questioned by these effects. In this work, we review the physics and the scientific literature and evaluate the effect of these additional phenomena on the PET data for each of a series of radioisotopes: (11)C, (13)N, (15)O, (18)F, (64)Cu, (68)Ga, (76)Br, (82)Rb, (86)Y, (89)Zr, (90)Y, and (124)I. In particular, we discuss the present complications arising from the prompt gammas, and we review the scientific literature on prompt gamma correction. For some of the radioisotopes considered in this work, prompt gamma correction is definitely needed to assure acceptable image quality, and several approaches have been proposed in recent years. Bremsstrahlung photons and (176)Lu background were also evaluated.


Effects of local handwashing agents on microbial contamination of the hands in a rural setting in Northwest Ethiopia: a cluster randomised controlled trial.
To evaluate the effectiveness of handwashing with water and wood ash in reducing faecal contamination of the hands. A cluster randomised controlled trial was employed with two arms: handwashing with water and wood ash versus handwashing with water alone. Rural households of East Dembiya District, Central Gondar Zone, Amhara National Regional State, Ethiopia. 440 mothers and caregivers of children younger than 5 years assigned (1:1, 220 in each group) in clusters, with buffer zones between each cluster. Health education on effective handwashing was given to the intervention and control groups. Participants in the intervention group used wood ash of the same quantity (ie, one closed palm). The primary outcome was microbial contamination of the hands, measured by means of Escherichia coli counts before and after handwashing. At baseline, 75.9% and 67.7% of the participants in the intervention and control groups, respectively, had dirt on their fingernails, and the hands of all participants in both groups were contaminated with E. coli. The mean E. coli counts recovered at baseline were 3.07 log10 colony forming unit (CFU)/swab in the intervention group and 3.03 log10 CFU/swab in the control group, while at endline it was 1.4 log10 CFU/swab in the intervention group and 3.02 log10 CFU/swab in the control group. The mean E.coli counts was reduced by 1.65 log10 due to the intervention (difference-in-differences: β= -1.65, 95% CI= -1.84 to -1.46). Two-thirds of the swab samples tested positive for E. coli after handwashing with water and wood ash, which indicates wood ash is not very effective in terms of completely removing micro-organisms on the hands. However, wood ash was significantly better than water alone in reducing the concentration of faecal coliform organisms on the hands. Local health authorities should primarily promote handwashing with soap. However, in the absence of soap, use of wood ash over water alone might be appropriate. PACTR202011855730652.


Usefulness of the HE4 biomarker as a second-line test in the assessment of suspicious ovarian tumors.
The aim of our study was the evaluation of HE4 usefulness as a test in assessment of ovarian tumors which are suspicious and difficult to classify correctly via subjective ultrasound examination. In this retrospective cohort study 253 women diagnosed with adnexal masses were examined preoperatively. Suspicious tumors (n = 145) were divided into groups of: "probably benign" (n = 70), "uncertain" (n = 34), and "probably malignant" (n = 41). "Uncertain" tumors were also assessed as "benign" (n = 11) or "malignant" (n = 23). The logistic regression model was performed to analyze if the serum marker improves the prediction of a malignant finding and net reclassification improvement (NRI) was calculated to measure diagnostic improvement. Within the analyzed group 85 (58.6%) benign and 60 (41.4%) malignant tumors were confirmed histopathologically. The comparison of HE4 with subjective ultrasound assessment showed lowered NRI in the entire analyzed group as well as in the groups of tumors classified as "probably benign" or "probably malignant" (NRI = -0.16; P = 0.0139 and NRI = -0.133; P = 0.0489, respectively). The analysis of logistic regression model confirmed that biomarkers do not improve diagnostic accuracy. The difference between areas under ROC for HE4 (0.891) and CA125 (0.902) was not statistically significant (P = 0.760). After subjective ultrasound assessment, the addition of the second-line test-HE4 as well as CA125 serum level does not improve diagnostic performance. However, HE4 evaluation satisfies the clinical expectations of diagnostic tools for ovarian tumors and, thus, may be useful to less experienced sonographers.


Rapid Rule-Out of Myocardial Infarction After 30 Minutes as an Alternative to 1 Hour: The RACING-MI Cohort Study.
The aim of this study was to investigate whether myocardial infarction can be safely ruled in or out after 30 minutes as an alternative to 1 hour. This was a prospective, single-center clinical study enrolling patients admitted to the emergency department. Patients with chest pain suggestive of myocardial infarction were eligible for inclusion. There was no walk-in to the emergency department, and patients with highly elevated out-of-hospital troponin were transferred directly to an invasive heart center. High-sensitivity troponin I was measured at admission (0 hour), 30 minutes, 1 hour, and 3 hours. Diagnostic performance was assessed using the sensitivity and negative predictive value (primary endpoints) as measures of ability to rule out myocardial infarction. Specificity and positive predictive value of myocardial infarction were used as measures for the ability to rule in myocardial infarction (secondary endpoints). In total, 1,003 patients qualified for analysis. Median age was 64 (interquartile range 52 to 74) years, and 42% were women. Myocardial infarction was confirmed in 9% of patients. In the validation cohort (n=503), the 0-h/30-min algorithm assigned 242 (48%) patients to rule out, 54 (11%) to rule in, and 207 (41%) to the observational zone. This resulted in a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (95% confidence interval 98.5% to 100%), specificity of 96.7% (94.7% to 98.2%), and positive predictive value of 72.2% (58.4% to 83.5%). In comparison, the 0-h/1-h algorithm performed with a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (98.5% to 100%), specificity of 97.2% (95.2% to 98.5%), and positive predictive value of 75.5% (61.7% to 86.2%). The accelerated 0-h/30-min algorithm allowed for safe rule-out of myocardial infarction 30 minutes after admission. The rule-in ability of the 0-h/30-min algorithm was comparable to that of the 0-h/1h algorithm.


Subcompartmentalization and Pseudo-Division of Model Protocells.
Membrane enclosed intracellular compartments have been exclusively associated with the eukaryotes, represented by the highly compartmentalized last eukaryotic common ancestor. Recent evidence showing the presence of membranous compartments with specific functions in archaea and bacteria makes it conceivable that the last universal common ancestor and its hypothetical precursor, the protocell, may have exhibited compartmentalization. To the authors' knowledge, there are no experimental studies yet that have tested this hypothesis. They report on an autonomous subcompartmentalization mechanism for protocells which results in the transformation of initial subcompartments to daughter protocells. The process is solely determined by the fundamental materials properties and interfacial events, and does not require biological machinery or chemical energy supply. In the light of the authors' findings, it is proposed that similar events may have taken place under early Earth conditions, leading to the development of compartmentalized cells and potentially, primitive division.


Initial analysis of variability among basal hormone biomarkers of ovarian reserve.
The most commonly used biomarker tests of ovarian reserve are basal hormone measurements during the early follicular phase, including mainly FSH but also oestradiol, FSH:LH ratio, and inhibin B. This study was designed to assess prospectively the intra- and inter-cycle variability of serum values of those hormone biomarkers in the early follicular phase of consecutive cycles in a group of women candidates for assisted reproduction. Fifty eumenorrhoeic women underwent blood sampling for hormone measurement on cycle day 3 for three consecutive cycles, and during the first study cycle, daily samples were obtained on cycle days 2, 3, 4 and 5. No significant difference was detected among FSH concentrations and FSH:LH ratios during cycle days 2-5; in contrast, oestradiol and inhibin B were not constant through the early follicular phase. No difference in FSH or inhibin B serum concentrations and FSH:LH ratio on cycle day 3 during three consecutive cycles was noted; however, significant inter-cycle variability for oestradiol serum concentration on cycle day 3 was detected. FSH and inhibin serum concentrations, and FSH:LH ratio varied significantly less than oestradiol on cycle day 3, but inter-cycle variability was similar for the first three hormonal biomarkers of ovarian reserve. There was significantly less intra-cycle variability of FSH serum concentration and FSH:LH ratio than oestradiol and inhibin B serum concentrations. Basal FSH serum concentrations (or FSH:LH ratio) during the early follicular phase showed neither significant inter-cycle nor intra-cycle variability when measured during 3 consecutive months in an assisted reproduction patient population, thus offering greater flexibility of pretreatment sampling.


The single-layer continuous polypropylene colon anastomosis. A prospective assessment using water-soluble contrast enemas.
Fifty consecutive unselected patients with anastomoses to the left side of the colon were studied. Each patient had an anastomosis constructed with a single layer of continuous 4-0 polypropylene. On the seventh postoperative day, or sooner, a water-soluble contrast enema was obtained to evaluate the integrity of the anastomosis. Two patients developed radiographic and clinical evidence of anastomotic leakage, and one patient developed a late pelvic abscess and colocutaneous fistula. The documented leak rate of 6 percent attests to the safety of this method of colonic anastomosis.


Fungi in libraries: an aerometric survey.
The possible role of fungi as allergic contaminants in book collections has been investigated in eleven University of Michigan Libraries. Air in the stacks of each of the eleven libraries was sampled on three occasions (2 or 4--10 minute samples on each occasion) with Andersen Volumetric viable particle samplers. Books were handled during sampling in half the samples each day. In addition on each sampling day a location in the same building away from book storage and an outdoor location were sampled. Library spore levels were generally low. Outdoor levels consistently exceeded indoor levels. Air conditioned (AC) libraries had lower spore levels and indoor/outdoor ratios than conventionally ventilated (CV) libraries. Handling books during sampling increased spore counts in all libraries, but strikingly in CV libraries. Fungus taxa recovered were similar to those encountered in domestic interiors and outside locations in our area. The overall low spore levels and lack of a distinctive library mycoflora suggest that other sources should be sought for library-based respiratory symptoms.


The outcome of oral appliance therapy on position-dependent obstructive sleep apnea: A multicenter randomized controlled trial.
This multicenter trial on patients with obstructive sleep apnea (OSA) treated with an oral appliance aimed to determine the effect of sleeping positions. A cohort of 314 patients with OSA were enrolled and evaluated at 8 weeks and 1 year, focusing on treatment effects. At baseline and the 2 follow-ups, new polygraphic registration comparing the proportion of treatment responders without position-dependent OSA (non-position-dependent OSA [non-POSA]) and with POSA was used. At the 8-week and 1-year follow-up, 205 and 139 patients were included, respectively. The proportion of responders (apnea-hypopnea index [AHI] <10 and/or ≥50% reduction in AHI) was 56% for the non-POSA group and 69% for the POSA group (not significant [NS]). The responders increased at the 1-year follow-up: 68% and 77% for the non-POSA and POSA groups (NS), respectively. The absolute change in AHI in all sleeping positions at 8 weeks was -12.9 (interquartile range, -25.0 to -0.5) in the non-POSA group and -10.5 (interquartile range, -19.9 to -5.3; NS) in the POSA group. However, the decrease in supine AHI was significantly greater among subjects with POSA. In contrast, the decrease in nonsupine AHI was significantly greater in the non-POSA group, an effect that remained at the 1-year follow-up. Our hypothesis that subjects with POSA at baseline would have a higher treatment response rate after oral appliance treatment compared with subjects without POSA was rejected. However, those with POSA had a significantly higher supine AHI decrease, and those without POSA had significantly less nonsupine AHI.


Virtual surgical planning: Balancing esthetics, practicality, and anticipated stability in a complex Class III patient.
The treatment of skeletal Class III malocclusion with anterior open bite is a complex and challenging aspect of orthodontics. Facial esthetic factors, practicality and the anticipated stability of a provisional surgical plan must all be factored into the final decision of the actual orthodontic-orthognathic treatment. This case report presents the multidisciplinary treatment of a 39-year-old female patient with skeletal Class III, severe open bite with first dental contact being on the second molars, lateral crossbite, and crowding in both arches. The nonextraction treatment started with aligning and leveling of the teeth in both arches followed by an initial surgical plan based on the clinical evaluation of the smile esthetics. Precise surgical planning information was imported into the Virtual Surgica (VSP Orthognathics) workflow to visualize the direction and amount of movement necessary. The final plan was adjusted because of anticipated practical limitations of the surgery as well as to insure the stability. LeFort I, bilateral sagittal split osteotomies, and setback genioplasty were thus performed. After the surgery, the treatment concluded with the fine adjustment of the occlusion. In the end, good esthetic and functional outcomes with long-term stability were achieved as a result of this delicate multidisciplinary approach.


Modulation of ochratoxin A induced DNA-damage in urothelial cell cultures.
Despite good evidence for a genotoxic potential of ochratoxin A (OTA), the mechanism of OTA-induced genotoxicity (direct or indirect?) is still unclear. This calls for a further characterization of OTA-related DNA damage, and investigations of factors that may modulate dose-effect relationships in cells.Since bladder epithelium is a target tissue for the toxicity of OTA, its effects were studied in cultures of human bladder carcinoma (H5637) cells. Cytotoxicity of OTA, assessed by Neutral red (NR) uptake or Alamar-Blue assay, is concentration- and time-dependent: Upon 24 h treatment of 5637 cells, NR uptake is reduced by 50% with OTA concentrations of ≥0.2 microM, but not with 3 h treatment of the cells. Since cytotoxicity of OTA was not affected by addition of xenobiotic metabolizing enzymes (S-9 mix), it appears to be unrelated to biotransformation of the mycotoxin. Also, addition of S-9 mix did not significantly affect the genotoxicity of OTA as studied by alkaline single cell gel electrophoresis (Comet assay). DNA damage was detectable after 3 h treatment of cells at OTA concentrations between 0.1 and 1 microM, and increased further at higher concentrations. The magnitude of OTA-induced DNA damage did not increase with longer treatment times (18, 24 h), probably due to repair processes in the cells. Repair of OTA-induced lesions is quite efficient in kidney (Arch Toxicol 2002, 75, 734-741) and in porcine bladder cells (Föllmann and Lebrun, 2005, Mycotoxin Research, this volume). Interestingly, the genotoxicity of OTA is modulated by the pH of the culture medium, with higher damage at pH 5 compared to pH 7.5. In line with this, uptake studies with tritiated OTA show a higher cellular accumulation of the mycotoxin at pH 5 than in buffer of pH 7.5. Thus, bladder cells exposed to OTA in slightly acidic urine (which facilitates reabsorption) may be at higher risk.


Definition and application of proximal-distal gradient finger perfusion in systemic sclerosis by laser speckle contrast analysis.
In patients with systemic sclerosis (SSc) the perfusion of the fingers shows an alteration of the physiological proximal-distal gradient (PDG). The aim of this study is to provide a generalizable definition of PDG, applying it in a cohort of SSc patients and healthy controls (HC) using laser speckle contrast analysis (LASCA). Adult consecutive SSc patients and HC were enrolled. Peripheral blood perfusion of the hands was evaluated by LASCA, subsequently obtaining 3 different regions of interest: from the distal interphalangeal joint to the fingertip (DIST), from the metacarpophalangeal joint to the distal interphalangeal joint (PROX), and of the whole finger (TOT). A PDG formula independent of both intra- and inter-personal factors was then built. The PDG formula so obtained was: [(DIST × 2.63) - PROX]/TOT. Ninety-four SSc patients (79.8% female, mean age 58.7 years) were enrolled. Applying the PDG formula, SSc patients revealed mean PDG values significantly lower than HC (1.82 ± 0.44 PU vs 2.70 ± 0.38 PU; p < 0.0001). Patients with a previous history of digital ulcers presented significant lower PDG values (p = 0.002). The ROC curve analysis identified in 2.28 PU the best PDG cut-off value between SSc and HC, with 86% sensibility and 90% specificity. This study provided a PDG formula generalizable to all kind of subjects, applying it in SSc with great sensibility and specificity using LASCA, the best non-invasive imaging technique for the dynamical evaluation of peripheral perfusion. LASCA-PDG appears also as a tool able to identify a subclinical microangiopathic impairment.


Nanovaccines and their mode of action.
Nanosized particles including nanovaccines are a novel approach to the development of vaccines to combat diseases. Nanovaccines have the promise to utilize the immune system to cure infections and to prevent infections and diseases from spreading. Rational vaccine development requires an understanding of vaccine mediated stimulation of the immune system. We review here immunostimulatory properties of nanovaccines including their immunogenicity, adjuvant properties, inflammatory responses and the mechanisms of uptake and stimulation of immune cells. Examples of various nanoparticles currently being developed as vaccines are also provided.


Obtaining a sexual history from adolescent girls. A preliminary report of the influence of age and ethnicity.
This preliminary study was undertaken to explore the hypothesis that socioeconomic and racial, as well as medical, factors influence the physician's decision about obtaining a sexual history from an adolescent female. Sixty consecutive medical records of adolescent-age emergency room patients with acute abdominal pain were classified according to ethnic group and socioeconomic status and searched for evidence that a sexual history had been taken. The study revealed a much higher number of recorded sexual histories among blacks and Hispanics. Although the absence of such a history seemed to have little relationship to diagnostic accuracy, a sensitive selectivity in exposing acutely ill teenagers to possible embarrassing questions appeared to be reserved for white, middle-class teenagers.


Management of myopic astigmatism with phakic intraocular lens implantation.
A 48-year-old woman presented with a manifest refraction of -9.25 -2.25 x 98 that resulted in a best corrected visual acuity (BCVA) of 20/20(-2) in the right eye. She was contact lens intolerant but was not a good candidate for laser in situ keratomileusis because of a thin cornea. A phakic posterior chamber intraocular lens (IOL) with a toric optic was implanted with no operative complications. One day after surgery, the uncorrected visual acuity (UCVA) was 20/15. Five months postoperatively, the UCVA in the operated eye was 20/15 with a manifest refraction of +0.25 -0.25 x 60 and a BCVA of 20/15. No changes to the crystalline lens or anterior lens capsule were seen. This is the first report of implantation of a toric phakic IOL in North America.


Development of an electrochemical RNA-aptasensor to detect human osteopontin.
Electrochemical aptasensors may be used to detect protein biomarkers related to tumor activity. Osteopontin (OPN), a protein present in several body fluids, has been suggested as a potential biomarker since its overexpression seems to be associated with breast cancer progression and metastasis. In this work, a simple and label-free voltammetric aptasensor for the detection of OPN, using an RNA aptamer previously reported to have affinity for human OPN as the molecular recognition element, and the ferro/ferricyanide solution as a redox probe, was developed. The RNA aptamer was synthetized and immobilized in a working microelectrode gold surface (diameter of 0.8mm) of a screen-printed strip with a silver pseudo-reference electrode and a gold counter electrode. The electrochemical behavior of the electrode surface after each preparation step of the aptasensor was studied using cyclic voltammetry and square wave voltammetry. The resulting voltammetric aptasensor was used to detect OPN in standard solutions. Cyclic voltammetry results showed that the aptasensor has reasonable detection and quantification limits (3.7 ± 0.6 nM and 11 ± 2 nM, respectively). Indeed, the detection limit falls within the osteopontin levels reported in the literature for patients with metastatic breast cancer. Moreover, the aptasensor is able to selectively detect the target protein in the presence of other interfering proteins, except for thrombin. Considering the overall results, a possible application of the aptasensor for cancer prognosis may be foreseen in a near future.


Infant rats: sensorimotor ontogeny and effects of substantia nigra destruction.
The ontogeny of sensorimotor behaviors of albino rats were evaluated from birth through adulthood (Experiment 1). Sensorimotor behaviors (e.g., visual and tactile orientation, forelimb and hindlimb hopping, righting reflexes) achieved mature (adultlike) characteristics at various ages during ontogeny and a rostral-caudal developmental pattern was revealed. In Experiment 2, the substantia nigra was bilaterally or unilaterally destroyed in rats at 10 or 25 days of age and the ontogeny of sensorimotor and regulatory (feeding, drinking, body weight regulation) behaviors were evaluated. Bilateral destruction of the substantia nigra, zona compacta, at 10 and 25 days of age resulted in transient cessation of suckling and/or feeding and drinking followed by recovery. Male brain-damaged rats had reduced body weight through 150-170 days of age. Specific feeding and drinking tests revealed the presence of residual regulatory deficits which seemed permanent. Sensorimotor testing revealed transient dysfunction for a variety of sensorimotor behaviors, with eventual recovery of normal sensorimotor capacity. The results are related to sensorimotor ontogeny and recovery from infant brain damage.


Discovery of unique CYP716C oxidase involved in pentacyclic triterpene biosynthesis from Camptotheca acuminata.
Dozens of triterpenes have been isolated from Camptotheca acuminata, however, triterpene metabolism in this plant remains poorly understood. The common C28 carboxy located in the oleanane-type and ursane-type triterpenes indicates the existence of a functionally active triterpene, C28 oxidase, in this plant. Thorough mining and screening of the CYP716 genes were initiated using the multi-omics database for C. acuminata. Two CYP716A (CYP716A394 and CYP716A395) and three CYP716C (CYP716C80-CYP716C82) were identified based on conserved domain analyses and hierarchical cluster analyses. CYP716 microsomal proteins were prepared and their enzymatic activities were evaluated in vitro. The CYP716 classified into the CYP716C subfamily displays β-amyrin oxidation activity, and CYP716A displays α-amyrin and lupeol oxidation activity, based on gas chromatography-mass spectrometry analyses. The oxidation products were determined based on their mass and nuclear magnetic resonance spectrums. The optimum reaction conditions and kinetic parameters for CYP716C were determined, and functions were verified in Nicotiana benthaminana. Relative quantitative analyses revealed that these CYP716C genes were enriched in the leaves of C. acuminata plantlets after 60 d. These results indicate that CYP716C plays a dominant role in oleanane-type triterpene metabolism in the leaves of C. acuminata via a substrate-specific manner, and CYP716A is responsible for ursane- and lupane-type triterpene metabolism in fruit. This study provides valuable insights into the unique CYP716C-mediated oxidation step of pentacyclic triterpene biosynthesis in C. acuminata.


Seroprevalence of HBV/HCV coinfection among patients with HCV screened during the national campaign for HCV eradication in Egypt.
Little is known about the true prevalence of hepatitis B virus (HBV) coinfection in patients with hepatitis C virus (HCV). This multicenter nationwide study aimed to assess the seroprevalence of HBV among Egyptian patients with HCV and its possible risk factors. This is a cross-sectional, multicenter, nationwide study. Data were extracted from the National Network of Viral Hepatitis Treatment Centers database. Baseline data of patients proved to be viremic during the national campaign for HCV eradication (October 2018-April 2019) were retrieved. Data included demographics, laboratory tests (HBsAg, CBC, liver biochemical profile, creatinine, AFP, HbA1c, and viral load), FIB-4 score calculation, and abdominal ultrasound results. Results of 297,965 patients showed that HBsAg was positive in 2,347 (0.8%) patients. Patients with HBV/HCV were 57% females and had a mean age of 51 ± 13 years. Patients with positive HBsAg showed significantly more tobacco consumption, intravenous drug abuse, hypertension, and diabetes. No significant difference was noted in HCV viremia between patients with HCV and those with HBV/HCV. Only 14% of patients with HBV/HCV had cirrhosis compared with the 9% of those with HCV; two of them had HCC. Although Egypt has a heavy HCV burden, the overall prevalence of HBV is low among patients with HCV infection. Comorbid conditions seem to favor coinfection.


Molecular diagnosis and genetic counseling for spinal muscular atrophy (SMA).
Spinal muscular atrophy (SMA) is a neuromuscular autosomal recessive disorder caused by bi-allelic pathogenic variants in the SMN1 gene. 95% of SMA patients have a SMN1 homozygous deletion. In the 5% remaining affected patients, a heterozygous SMN1 deletion is associated with an intragenic SMN1 rare inactivating pathogenic variant on the other allele. The clinical phenotype of SMA is heterogeneous and severity is inversely correlated with the number of SMN2 copies, a non-functional SMN1 copy. The development of new treatments leads to the generalization of carrier and newborn screening in many countries and new robust and low cost methods for large population-based screening have been developed. It is important that all diagnosed patients and relatives receive appropriate genetic counseling, taking into account the great complexity of SMA region to avoid pitfalls. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.


Italian recommendations on dental support in the treatment of adult obstructive sleep apnea syndrome (OSAS).
The aim of the present article is to present a set of proposed clinical recommendations aimed at Italian dentists involved in the management of patients with obstructive sleep apnea syndrome or snoring. With the purpose of creating a study group, some of the most important Italian scientific societies operating in fields relevant to the issue of sleep medicine in dentistry were asked to appoint a representative. Each member of the study group was required to answer questions regarding the clinical management of OSAS and snoring. Oral appliances can be used to treat: - simple snoring, in patients who do not respond to, or do not appear to be suitable candidates for behavioral measures such as weight loss or positional therapy; - mild or moderate OSAS, in patients who prefer OAs to continuous positive airway pressure (CPAP) or who are not suitable candidates for CPAP, because of its failure or failure of behavioral approaches like weight loss or positional therapy; - severe OSAS, in patients who do not respond to or do not tolerate CPAP and in whom no indication for either maxillofacial or ENT surgery appears applicable. The application of oral appliances is highly desirable in cases of simple snoring or mild to moderate OSAS, whereas considerable caution is warranted when treating severe OSAS. It is fundamental to ensure that the patient understands his problem and, at the same time, to present all the various treatment options.


Early steps in oxidation-induced SOD1 misfolding: implications for non-amyloid protein aggregation in familial ALS.
Among the diseases of protein misfolding, amyotrophic lateral sclerosis (ALS) is unusual in that the proteinaceous neuronal inclusions that are the hallmark of the disease have neither the classic fibrillar appearance of amyloid by transmission electron microscopy nor the affinity for the dye Congo red that is a defining feature of amyloid. Mutations in the Cu, Zn superoxide dismutase (SOD1) cause the largest subset of inherited ALS cases. The mechanism by which this highly stable enzyme misfolds to form non-amyloid aggregates is currently poorly understood, as are the stresses that initiate misfolding. The oxidative damage hypothesis proposes that SOD1's normal free radical scavenger role puts it at risk of oxidative damage and that it is this damage that triggers the misfolding primed by mutation. Here, we present evidence that hydrogen peroxide treatment, which generates free radical species at the SOD1 active site, causes oxidative damage to active-site histidine residues, leading to major structural changes and non-amyloid aggregation similar to that seen in ALS. Time-resolved measurements of release of bound metal ligands, exposure of hydrophobic surface area, and alterations in the SOD1 proton NMR spectrum have allowed us to model the early structural changes occurring as SOD1 misfolds, prior to aggregation. ALS-causing SOD1 mutations apparently alter this pathway by increasing exposure of buried epitopes in misfolded species populated at endpoint. We have identified a well-populated early misfolding intermediate that could serve as a target for therapies designed to block downstream misfolding and aggregation events and thereby treat SOD1-associated ALS.


Changing dynamics in lower-extremity amputation in China.
To evaluate the current pattern of lower-extremity amputation (LEA) in a Chinese population and to identify independent risk factors for failure to ambulate in the community after LEA. Retrospective study. Tertiary hospital. Consecutive Chinese adults (N=189) who underwent LEA from 1995 to 1997. Not applicable. Pattern of LEA in comparison with previous data and risk factors for failure to ambulate in the community after LEA. The mean age at amputation was 74.1 years. Vascular occlusive disease and infection accounted for most of the reasons for the LEA. The pattern of LEA had changed significantly. The proportion of patients who were able to ambulate in the community decreased from 66.1% before the LEA to 29.9% 12 months after LEA. Logistic regression analysis showed that major amputation level, presence of diabetes mellitus, hypertension, inability to ambulate in the community before LEA, and failed use of prosthesis were significant independent risk factors for failure to ambulate in the community after LEA. A more aggressive rehabilitation approach, together with efforts targeted at various levels is required to achieve better functional ambulation level and to improve reintegration into the community after LEA.


Lymphoid aggregates in Crohn's colitis and mucosal immunity.
Under normal conditions, the colorectal mucosa exhibits small numbers of scattered lymphocytes and plasma cells in the lamina propria and only few mucosal lymphoid aggregates (MLAs). In Crohn's colitis, the number of lymphocytes and plasma cells in the lamina propria and of MLA is substantially increased. In addition, multiple lymphoid aggregates are newly formed in the submucosa (submucosal lymphoid aggregate (SLA)) and deeper. The aim of the present study was to investigate the cellular immune response in MLA, in SLA, and in the lamina propria in Crohn's colitis. Fifty-nine colorectal biopsies/surgical specimens with or without inflammatory diseases were challenged with multiple myeloma 1 (MUM1) that highlights activated T cells, committed B cells, and plasma cells (aT/cB/PC). The number of MUM1-positive aT/cB/PC per high-power field (HPF) in MLA and in SLA was significantly lower in Crohn's colitis than in controls (p < 0.05). In contrast, the number of MUM1-positive aT/cB/PC per HPF in the lamina propria was significantly higher in Crohn's colitis and in other forms of chronic colitis than in controls (p < 0.05). The paucity of MUM1-positive cells in MLA and in SLA in Crohn's colitis might be caused by an increased number of MUM1-negative precursors. These precursors would eventually migrate into the lamina propria to differentiate into aT/cB/PC, complying thereby with the immunological mucosal demands generated by the on-going chronic inflammation.


Microscale process evaluation of recombinant biocatalyst libraries: application to Baeyer-Villiger monooxygenase catalysed lactone synthesis.
Microscale processing techniques are rapidly emerging as a cost- effective means for parallel experimentation and hence the evaluation of large libraries of recombinant biocatalysts. In this work, the potential of an automated microscale process is demonstrated in a linked sequence of operations comprising fermentation, enzyme induction and bioconversion using three whole-cell biocatalysts each expressing cyclohexanone monoxygenase (CHMO). The biocatalysts, Escherichia coli TOP 10 [pQR239], E. coli JM107 and Acinetobacter calcoaceticus NCIMB 9871, were first produced in 96-deep square well fermentations at various carbon source concentrations (10 and 20 g L(-1) glycerol). Following induction of CHMO activity biomass concentrations of up to 6 gDCW L(-1) were obtained. Cells from each fermentation were subsequently used for the Baeyer-Villiger oxidation of bicyclo[3.2.0]hept-2-en-6-one, cyclohexanone and cyclopentanone. Each bioconversion was performed at two initial substrate concentrations (0.5 and 1.0 g L(-1)) in order to simultaneously explore both substrate specificity and inhibition. The microscale process sequences yielded quantitative and reproducible data for each biocatalyst on maximum growth rate, biomass yield, initial rate of lactone formation, specific biocatalyst activity and bioconversion yield. E. coli TOP 10 [pQR239] was demonstrated to be an efficient biocatalyst showing substrate specificities and substrate inhibition effects in line with previous studies. Finally, in order to show that the data obtained with E. coli TOP 10 [pQR239] at microwell scale (1,000 microL) could be related to larger scales of operation, the process was performed in a 2-L stirred-tank bioreactor. Using conditions designed to enable microwell kinetic measurements under none oxygen-limited conditions, the fermentation and bioconversion data obtained at the two scales showed good quantitative agreement. This study therefore confirms the potential of automated microscale experimentation for the whole-process evaluation of recombinant biocatalyst libraries and the specification of pilot and process scale operating conditions.


Preparation and in vivo evaluation of PCADK/PLGA microspheres for improving stability and efficacy of rhGH.
The goal of this research is to prepare poly(cyclohexane-1,4 diyl acetone dimethylene ketal) (PCADK)/poly(D,L-lactide-co-glycolide) (PLGA) blend microspheres loaded with recombinant human growth hormone (rhGH). The effect of PCADK degradation products on the structural integrity, secondary and tertiary structure and pharmacodynamics of rhGH was evaluated by native-polyacrylamide gel electrophoresis (Native-PAGE), size-exclusion high performance liquid chromatography (SEC-HPLC), circular dichroism (CD), fluorescence spectroscopy and in hypophysectomized rat models. Compared with PLGA degradation products, rhGH was found to be more stable in the presence of PCADK degradation products. PCADK/PLGA blend microspheres were then prepared and the morphology, encapsulation efficiency, release behavior and rhGH stability were investigated. PCADK/PLGA microspheres had regular shapes and smooth surfaces when the proportion of PCADK was less than 50%. The late-releasable amount of rhGH in PCADK/PLGA microspheres was greater than that in PLGA microspheres. In addition, the PCADK/PLGA microspheres showed larger AUC and improved therapeutic effects on rats than PLGA microspheres. Furthermore, the pH inside the microspheres was detected by CLSM to explain the improved rhGH stability in the PCADK/PLGA microspheres. In conclusion, PCADK/PLGA blend microspheres showed potential to improve rhGH stability and the efficacy of sustained-release of rhGH compared with PLGA microspheres.


Resilience and coping strategies of older adults in Hong Kong during COVID-19 pandemic: a mixed methods study.
Despite the adverse physical health impact of COVID-19 on older adults, whether they are psychosocially vulnerable under the pandemic remains debatable. In this mixed methods study, we examined the psychosocial vulnerability of older adults relative to their younger counterparts and explored how they coped with the pandemic. From September to October 2020, 1067 adults in Hong Kong were randomly sampled and completed a telephone survey, whereas 10 older adults were recruited for individual interviews between September 2020 and April 2021. Quantitative measurements included subjective well-being, worries about COVID-19, and changes in social capital and social interaction since the pandemic. The transcribed qualitative data were closely read and summarized using thematic analyses. Compared with younger adults, older adults tended to be less worried about COVID-19 infection and economic activity/livelihood, despite being slightly more worried about supplies of personal protective equipment. They also had better subjective well-being in terms of happiness and life satisfaction, with their social capital and social interaction less affected. In addition, five themes emerged from the qualitative interviews: (1) life philosophy; (2) economic security; (3) telecommunication; (4) role of community organizations and social workers; and (5) positive coping strategies. Older adults in this study showed better psychosocial well-being than their younger counterparts under the COVID-19 pandemic, which challenged the deeply rooted societal stereotype about the vulnerability of older adults. The stronger resilience for positive coping, technological assistance, and targeted government and community support may have protected older adults from distress during the pandemic.


Successfully treated Hodgkin's disease followed by mycosis fungoides: case report and review of the literature.
We report the case of a 30-year-old man who had Hodgkin's disease of the nodular sclerosing type and subsequently developed mycosis fungoides. The Hodgkin's disease was treated with radiation therapy and chemotherapy, and the patient was in complete remission. Seven years later mycosis fungoides occurred and rapidly became progressive. Autopsy revealed that the mycosis fungoides involved multiple organs without any evidence of Hodgkin's disease. The possible significance of the association of these two diseases is presented.


Importance of circadian rhythms in animal cell cultures.
Circadian rhythms are a characteristic feature of many cell and organ cultures. Such rhythms may be important in the interpretation of data from cells in culture. More examples of circadian rhythms in tissue culture are badly needed to understand this phenomena. However, they will only be expressed under optimum and well-understood conditions.


Inferential processing of context: studies of cognitively impaired subjects.
Language comprehension tasks involving pronoun coreference were administered to a group of demented patients, a group of patients with cardiac disease, and groups of normal elderly persons and young adults. Pronoun coreference was constrained by either lexical, syntactic, or contextual cues. No differences were found between old and young subjects for any task. While the demented patients were impaired on all tasks, the cardiac patients were specifically impaired in the inferential processing of context.


A review on management of waste three-way catalysts and strategies for recovery of platinum group metals from them.
Platinum group metals (PGMs), especially platinum (Pt), palladium (Pd), and rhodium (Rh), are widely used in automotive three-way catalysts (TWCs). PGM resources are scarce and unevenly distributed, with global reserves of 69,000 t in 2020, of which more than 99% are concentrated in South Africa, Russia, Zambia, and the United States. However, the demand for PGMs worldwide is growing continually, especially in China. The recovery of PGMs from spent TWCs not only can alleviate the contradiction between supply and demand but also have good economic and environmental benefits. This paper briefly analyzes the market demand for Pt, Pd, and Rh in the global automotive industry in recent years, emphasizing the importance of waste TWC recycling. It also presents the current status of waste TWC management in some countries, especially China, and critically reviews the main recycling strategies for waste TWCs. On this basis, suggestions for strengthening the management of waste TWCs in China are put forward, and the future development trend of recycling technology is foreseen. The purpose of this paper is to provide some valuable references for the decision-makers of waste TWC management, and hopefully to provide inspiration for related scholars on the future research direction of waste TWC recycling technology.


Minimally Invasive Surgical Approach for Treatment of Chronic Subdural Hematoma, Outcome in 1079 Patients.
To present the authors' experience in treatment of chronic subdural hematoma (CSDH) by a minimally surgical percutaneous approach. We relate our experience of mini-invasive evacuation of chronic subdural hematoma. Between May 2006 and December 2017, 1079 patients have been operated for percutaneous evacuation of chronic subdural hematoma. Prior to operation, the volume of hematoma was measured quantitatively by using a software for CT scan. From May 2006 to December 2017, 1079 patients underwent mini-invasive percutaneous evacuation (MIPE). Of the 1079 patients, 994 (92.12%) became asymptomatic or improved clinically. Six weeks later, the scan revealed the hematoma had wholly disappeared in 699 (64.78%) of the cases. We had one postoperative abscess. Treatment of CSDH using our MIPE technique is a safe method with satisfactory outcome and a good therapeutic alternative to the craniostomy.


Effect of environment, conformation, sequence and base substituents on the imino proton exchange rates in guanine and inosine-containing DNA, RNA, and DNA-RNA duplexes.
High-resolution 1H nuclear magnetic resonance in H2O has been used to study the effect of sequence, conformation, environmental factors and base substituents on the exchange behavior of the hydrogen-bonded imino protons of guainine X cytosine and inosine X cytosine base-pairs in DNA, RNA, and DNA-RNA duplexes. The exchange rates were determined by measurement of the spin-lattice relaxation rates of the imino protons as a function of temperature. The exchange was not altered by the presence of high concentrations of salt, and the inability of phosphate to catalyze the exchange indicates that the exchange is limited by formation of a solvent-accessible "open" state. The exchange behavior depends on the duplex conformation and sequence. Exchange from the Z form polymers was orders of magnitude slower than the corresponding duplexes in the B conformation, and the A form RNA duplexes exchanged more slowly than the B form DNA polymers with the same sequence. The exchange behavior of the DNA-RNA hybrids was dependent on whether the purine or the pyrimidine strand contained the deoxyribose sugar. For both the guanine and inosine-containing duplexes, the homopolymer duplexes exchange more slowly than the more stable alternating copolymers. For the alternating duplexes, substitution of cytosine with 5-bromo- or 5-methylcytosine slowed the exchange and increased the activation energy for exchange. The inosine-containing duplexes exchanged more rapidly than the guanosine-containing duplexes, but both showed similar changes in exchange behavior in response to changes in sequence and base substituents. The activation energies for base-pair opening in B form DNA are correlated with the van der Waals contribution to the base-base interaction energy, suggesting that the purine base is partially unstacked in the open state. Using the relaxation measurements to set an upper limit on the exchange rate in poly(dG-dC) and the tritium exchange behavior at low temperature, we find that even though Z-DNA exchanges very slowly, the activation energy is similar to that observed in the A and B form duplexes, suggesting that exchange occurs from a similar open state.


[The leukocyte migration inhibition test (LMIT) in recurrent herpes simplex labialis. Comparison of the results of treatment with BCG and Levamisole (author's transl)].
Forty six patients suffering from recurrent herpes simplex labialis (HSLR) have been treated by either BCG or Levamisole. Therapy was equally successful in both groups: 10 patients remained free of symptoms during the observation period, 11 patients improved clearly and 2 patients did not respond to the therapy. Sensitization of lymphocytes toward herpes simplex virus antigen (HVS-AG) was determined in vitro by means of the leukocyte migration inhibition test (LMIT); test were performed before therapy and in certain intervals after the end of it. While lymphocytes of 10 control persons could be stimulated by HSV-AG, those of patients suffering from HSLR did not react to this antigen before onset of any therapy. Clinical success of therapy correlated well with the in vitro results of the LMIT: after therapy, the lymphocytes of symptom-free and improved patients also reacted in vitro to the antigen added.


Degradation of polychlorinated biphenyls using mesoporous iron-based spinels.
A series of mesoporous iron-based spinel materials were synthesized to degrade polychlorinated biphenyls (PCBs), with CB-209 being used as a model compound. The materials were characterized by X-ray powder diffraction (XRD), pore structure analysis, and X-ray photoelectron spectroscopy (XPS). A comparison of the dechlorination efficiencies (DEs) of the materials revealed that NiFe2O4 had the highest DE, followed by Fe3O4. Newly produced polychlorinated biphenyls, chlorinated benzenes, hydroxyl species and organic acids were detected by gas chromatography-mass spectrometry, high performance liquid chromatography-mass spectrometry and ion chromatograph. Identification of the intermediate products indicates that three degradation pathways, hydrodechlorination, the breakage of CC bridge bond and oxidative reaction, accompanied by one combination reaction, are competitively occurring over the iron-based spinels. The relative amounts of produced three NoCB isomers were illustrated by the CCl BDEs of CB-209 at meta-, para- and ortho-positions, and their energy gap between HOMO and LUMO. The consumption of the reactive oxygen species caused by the transformation of Fe3O4 into Fe2O3 in the Fe3O4 reaction system, and the existence of the highly reactive O2(-) species in the NiFe2O4 reaction system, could provide a reason why the oxidation reaction was more favored over NiFe2O4 than Fe3O4.


Generation of an affinity matrix useful in the purification of natural inhibitors of plasmepsin II, an antimalarial-drug target.
An affinity matrix containing the antimalarial drug target Plm II (plasmepsin II) as ligand was generated. This enzyme belongs to the family of Plasmodium (malarial parasite) aspartic proteinases, known as Plms (plasmepsins). The procedure established to obtain the support has two steps: the immobilization of the recombinant proenzyme of Plm II to NHS (N-hydroxysuccinimide)-activated Sepharose and the activation of the immobilized enzyme by incubation at pH 4.4 and 37 degrees C. The coupling reaction resulted in a high percentage immobilization (95.5%), and the matrices obtained had an average of 4.3 mg of protein/ml of gel. The activated matrices, but not the inactive ones, were able to hydrolyse two different chromogenic peptide substrates and haemoglobin. This ability was completely blocked by the addition of the general aspartic-proteinase inhibitor, pepstatin A, to the reaction mixture. The matrices were useful in the affinity purification of the Plm II inhibitory activity detected in marine invertebrates, such as Xestospongia muta (giant barrel sponge) and the gorgonian (sea-fan coral) Plexaura homomalla (black sea rod), with increases of 10.2- and 5.9-fold in the specific inhibitory activity respectively. The preliminary K(i) values obtained, 46.4 nM (X. muta) and 1.9 nM (P. homomalla), and the concave shapes of the inhibition curves reveal that molecules are reversible tight-binding inhibitors of Plm II. These results validated the use of the affinity matrix for the purification of Plm II inhibitors from complex mixtures and established the presence of Plm II inhibitors in some marine invertebrates.


Influence of atmospheric pressure low-temperature plasma treatment on the shear bond strength between zirconia and resin cement.
Zirconia exhibits excellent strength and high biocompatibility in technological applications and it is has therefore been investigated for clinical applications and research. Before setting prostheses, a crown prosthesis inner surface is sandblasted with alumina to remove contaminants and form small cavities. This alumina sandblasting causes stress-induced phase transition of zirconia. Atmospheric-pressure low-temperature plasma has been applied in the dental industry, particularly for adhesives, as a surface treatment to activate the surface energy and remove contaminants. The purpose of this study was to examine the influence of atmospheric-pressure low-temperature plasma treatment on the shear bond strength between zirconia and adhesive resin cement. The surface treatment method was classified into three groups: untreated (Cont group), alumina sandblast treatment (Sb group), and atmospheric-pressure low-temperature plasma treatment (Ps group). Adhesive resin cement was applied to stainless steel and bonded to zirconia. Shear adhesion tests were performed after complete hardening of the cement. Multiple comparisons were performed using a one-way analysis of variance and the Bonferroni method. X-ray diffractometry was used to examine the change in zirconia crystal structure. Statistically significant differences were noted between the control and Sb groups and between the control and Ps groups. In contrast, no statistically significant differences were noted for the Ps and Sb bond strength. Atmospheric-pressure low-temperature plasma treatment did not affect the zirconia crystal structure. Atmospheric-pressure low-temperature plasma treatment improves the bonding strength of adhesive resin cement as effectively as alumina sandblasting, and does not alter the zirconia crystal structure.


Inhibition of jet fuel aliphatic hydrocarbon induced toxicity in human epidermal keratinocytes.
Jet propellant (JP)-8, the primary jet fuel used by the U.S. military, consists of hydrocarbon-rich kerosene base commercial jet fuel (Jet-A) plus additives DC1-4A, Stadis 450 and diethylene glycol monomethyl ether. Human epidermal keratinocytes (HEK) were exposed to JP-8, aliphatic hydrocarbon (HC) fuel S-8 and aliphatic HC pentadecane (penta), tetradecane (tetra), tridecane (tri) and undecane (un) for 5 min. Additional studies were conducted with signal transduction pathway blockers parthenolide (P; 3.0 microm), isohelenin (I; 3.0 microm), SB 203580 (SB; 13.3 microm), substance P (SP; 3.0 microm) and recombinant human IL-10 (rHIL-10; 10 ng ml(-1)). In the absence of inhibitors, JP-8 and to a lesser extent un and S-8, had the greatest toxic effect on cell viability and inflammation suggesting, as least in vitro, that synthetic S-8 fuel is less irritating than the currently used JP-8. Each inhibitor significantly (P < 0.05) decreased HEK viability. DMSO, the vehicle for P, I and SB, had a minimal effect on viability. Overall, IL-8 production was suppressed at least 30% after treatment with each inhibitor. Normalizing data relative to control indicate which inhibitors suppress HC-mediated IL-8 to control levels. P was the most effective inhibitor of IL-8 release; IL-8 was significantly decreased after exposure to un, tri, tetra and penta but significantly increased after JP-8 exposure compared with controls. Inhibitors were not effective in suppressing IL-8 release in JP-8 exposures to control levels. This study shows that inhibiting NF-kappa B, which appears to play a role in cytokine production in HC-exposed HEK in vitro, may reduce the inflammatory effect of HC in vivo.


Universal neonatal hearing screening and delayed hearing loss or late-developmental hearing loss.
To determine the percentage of children with permanent bilateral postnatal hearing loss in order to study its incidence, related risk factors, diagnosis and treatment. Retrospective study to collect data on children diagnosed with hearing loss outside the neonatal period in the Hearing Loss Unit of the Hospital Universitario Central de Asturias, from April 2014 to April 2021. 52 cases met the inclusion criteria. The detection rate of congenital hearing loss in the neonatal screening programme in the same study period was 1.5 children per thousand newborns per year, adding postnatal hearing loss results in a rate of infant bilateral hearing loss of 2.7 children per thousand (55.5% and 44.4% respectively). Thirty-five children presented risk factors for hearing loss, of which 23 were at retrocochlear risk. The mean age at referral was 91.9 (18-185) months. Hearing aid fitting was indicated in 44 cases (84.6%). Cochlear implantation was indicated in eight cases (15.4%). Although congenital hearing loss accounts for the majority of childhood deafness, postnatal hearing loss has a significant incidence. This may be mainly due to: (1) that hearing impairment may arise in the first years of life, (2) that mild hearing loss as well as hearing loss in severe frequencies are undetectable by neonatal screening in some cases, (3) that some children may have false negative results. postnatal hearing loss requires identification of risk factors and long-term follow-up of children with hearing loss, as it needs to be detected and treated early.


Role of calcineurin in angiotensin II-induced cardiac myocyte hypertrophy of rats.
The present study investigated the role of calcineurin in angiotensin II(AngII) -induced cardiac myocyte hypertrophy of rats. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII-treated cardiomyocytes was tested by using PNPP; protein synethsis rate was assessed by 3H-leucine incorporation; atrial natriuretic factor(ANF) mRNA level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase (LDH) levels in cultured medium and by dyed cell numbers. After stimulation of 10, 100 and 1 000 nmol/L of AngIi, calcineurin activities in the cardiomyocytes were increased by 13%, 57% (P < 0.05) and 228% (P < 0.01) respectively, compared with control group. Cyclosporin A(CsA), a specific inhibitor of calcineurin, markedly inhibited the calcineurin activity and decreased the 3H-leucine incorporation in AngII-treated cardiomyocytes in a dose-dependent manner. It was also found that CsA slightly reduced the mRNA level of ANF gene in AngII-stimulated cardiomyocytes. During AngII-induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII-induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII-induced myocardial hypertrophy of rats.


Adhesion molecules in lymphoma metastasis.
Lymphoma cells are derived from normal lymphocytes and therefore their metastatic behavior is probably based on mechanisms of migration of these normal progenitors. Several adhesion molecules that are involved in this normal migration, have been identified. These include the 'lymph node homing receptors' and the leukocyte (beta 2) integrins. The limited evidence available for a role of these molecules in lymphoma metastasis is reviewed here. Recently, the regulation of the activity of adhesion molecules was shown to be of pivotal importance for the control of leukocyte traffic. The implications of these findings for lymphoma metastasis are discussed.


Mojonnier method as reference for infrared determination of fat in meat products.
The Mojonnier method was compared with the conventional Soxhlet method for the determination of fat in 7 different meat products to assess its use as a standard reference method for calibration of commercial quantitative infrared transmission analyzers (e.g., Multispec M, Milkoscan 300 or 104). Results for the meat samples obtained by the Mojonnier method did not differ significantly from those obtained by the Soxhlet method. In addition, the Mojonnier method was less time-consuming and more precise than the Soxhlet; therefore, it can be used as a standard reference procedure for the calibration and assessment of infrared milk analyzers in their potential application to the rapid determination of fat in meat and meat products.


Higher subjective socioeconomic status is linked to increased charitable giving and mentalizing-related neural value coding.
Socioeconomic status (SES), a concept related to an individual's economic and social position relative to others, can shape social interactions like altruistic behaviors. However, little is known about the exact neurocognitive mechanisms that link SES with altruism. Our study aimed to provide a comprehensive account of the sociocognitive and neural mechanisms through which SES affects charitable giving - an important variant of human altruism. To this end, participants completed a charitable donation task while their brain activity was measured using functional magnetic resonance imaging (fMRI). We also assessed participants' socio-cognitive ability to infer other people's mental states (i.e., mentalizing) - a driver of prosocial behavior - in an independent social task. Behaviorally, we found that both charitable giving and social cognition were status-dependent, as subjective SES positively predicted donations and mentalizing capacity. Moreover, the link between SES and charitable giving was mediated by individuals' mentalizing capacity. At the neural level, a multivariate pattern analysis of fMRI data revealed that higher subjective SES was associated with stronger value coding in the right temporoparietal junction (rTPJ). The strength of this value representation predicted charitable giving and was linked to mentalizing. Furthermore, we observed an increased negative functional coupling between rTPJ and left putamen with higher SES. Together, increased charitable giving in higher-status individuals could be explained by status-dependent recruitment of mentalizing-related value coding and altered functional connectivity in the brain. Our findings provide insights into the socio- and neurocognitive mechanisms explaining why and when higher SES leads to prosociality, which might ultimately inform targeted interventions to promote prosocial behavior in human societies.


[Adaptation of Rhodopseudomonas palustris to changes in atmospheric conditions].
The high level of delta-aminolaevulinate synthetase (ALA-S) in Rhodopseudomonas palustris cells grown under photosynthetic conditions decreased when they were vigorously aerated; moreover, the bacteriochlorophyll synthesis suddenly stopped. When aeration was interrupted, enzymatic level increased notably, but bacteriochlorophyll level did not. Chloramphenicol added to cultures when aeration was interrupted did not affect the increase of enzymic level. When it was added as the aeration started, the enzymic level decayed, but did not increase as notably when the aeration was interrupted. ALA-S in extracts of aerated cells underwent spontaneous activation when homogenates were stored at 4 degrees C. The effect of several activators on different forms of ALA-S is postulated in order to explain these findings.


Pulmonary artery replacement for pulmonary Takayasu's arteritis.
Takayasu's arteritis is a chronic inflammatory disease that affects the pulmonary artery, as well as the aorta and its major branches. A 59-year-old man presented with a 2-month history of progressive exertional dyspnea. Further examination revealed marked wall thickening of the pulmonary trunk and bilateral proximal pulmonary artery, resulting in severe stenoses with high pressure gradient of 60 mmHg. The patient underwent graft replacement of the bilateral pulmonary artery and the pulmonary trunk with a 16-mm ring-supported extended polytetrofluoroethylene graft under extracorporeal circulation. Histopathological findings were consistent with Takayasu's arteritis with pulmonary artery involvement. After the operation, the pressure gradient decreased to 6 mmHg and the patient was free from exertional dyspnea.


The Influence of Missed Canals on the Prevalence of Periapical Lesions in Endodontically Treated Teeth: A Cross-sectional Study.
Untreated root canals may have a direct impact on the prognosis of root canal treatment. The objective of this cross-sectional study was to evaluate the association of missed canals with periapical lesions in endodontically treated teeth. One thousand one hundred sixty preexisting cone-beam computed tomographic scans from 8 different health centers were assessed between January 2018 and December 2018 by 5 independently calibrated observers. Two thousand three hundred five endodontically treated teeth were identified in a sample of 20,836 teeth (27,046 roots). All endodontically treated teeth were evaluated for the presence or absence of missed root canals and periapical lesions. The z test for proportions was used to analyze differences between groups, and an odds ratio was calculated in order to analyze the association between missed canals and lesions. P < .05 was considered statistically significant. The prevalence of missed canals was 12.0%, and teeth with untreated canals were associated with periapical pathology in 82.6% of the cases. The root presenting with the highest percentage of missed canals (62.8%) was the mesiobuccal root of the maxillary first molar, being associated with periapical lesions in 75.2% of cases. Maxillary molar mesiobuccal roots presenting with a missed canal were 3.1 times more likely to be associated with periapical pathology than maxillary molars with all canals identified and treated. The association between untreated root canals and the presence of periapical lesions noted in the present study shows that missed canals have a significant impact on treatment prognosis.


Measuring urban food-energy-water nexus sustainability: Finding solutions for cities.
A city is the place where food, energy, and water consumption happen. This consumption leads to challenges and has a strong impact on natural sources. Although researchers broadly agree on the importance of incorporating the concept of the food, energy, and water nexus into policy strategies and decision-making, the assessment system for how governance methods can improve the provision of these three essential services is relatively blank. To clarify the policy mechanisms and heterogeneity of sustainability issues related to the food, energy and water nexus at the city level, this study develops an indicator system to guide the implementations and optimize urban sustainability. A qualitative approach is employed to form the priority strategies in in four selected cities: Amsterdam, Eindhoven, Taipei, and Tainan. The results show that renewable energy plays an essential role in the food-energy-water nexus. In addition, we also observed that future work should focus on technological innovation. These observations imply that the unique combination of influence factors in food-energy-water sustainability offers a comprehensive outlook of the broad and complex challenges that a city faces due to resource limitations, which can help inform future governance practices. Finally, some policy recommendations are made for highlighting and the activities needed to work. The results of the present evaluation could be used as a tool to strengthen food-energy-water management in the future. They can guide managers to develop possible solutions that ensure resources are applied successfully according to the visions of multiple perspectives and help the relevant ministries to improve future consultation plans.


Combining RNA interference and kinase inhibitors against cell signalling components involved in cancer.
The transcription factor activator protein-1 (AP-1) has been implicated in a large variety of biological processes including oncogenic transformation. The tyrosine kinases of the epidermal growth factor receptor (EGFR) constitute the beginning of one signal transduction cascade leading to AP-1 activation and are known to control cell proliferation and differentiation. Drug discovery efforts targeting this receptor and other pathway components have centred on monoclonal antibodies and small molecule inhibitors. Resistance to such inhibitors has already been observed, guiding the prediction of their use in combination therapies with other targeted agents such as RNA interference (RNAi). This study examines the use of RNAi and kinase inhibitors for qualification of components involved in the EGFR/AP-1 pathway of ME180 cells, and their inhibitory effects when evaluated individually or in tandem against multiple components of this important disease-related pathway. AP-1 activation was assessed using an ME180 cell line stably transfected with a beta-lactamase reporter gene under the control of AP-1 response element following epidermal growth factor (EGF) stimulation. Immunocytochemistry allowed for further quantification of small molecule inhibition on a cellular protein level. RNAi and RT-qPCR experiments were performed to assess the amount of knockdown on an mRNA level, and immunocytochemistry was used to reveal cellular protein levels for the targeted pathway components. Increased potency of kinase inhibitors was shown by combining RNAi directed towards EGFR and small molecule inhibitors acting at proximal or distal points in the pathway. After cellular stimulation with EGF and analysis at the level of AP-1 activation using a beta-lactamase reporter gene, a 10-12 fold shift or 2.5-3 fold shift toward greater potency in the IC50 was observed for EGFR and MEK-1 inhibitors, respectively, in the presence of RNAi targeting EGFR. EGFR pathway components were qualified as targets for inhibition of AP-1 activation using RNAi and small molecule inhibitors. The combination of these two targeted agents was shown to increase the efficacy of EGFR and MEK-1 kinase inhibitors, leading to possible implications for overcoming or preventing drug resistance, lowering effective drug doses, and providing new strategies for interrogating cellular signalling pathways.


Comparative genomic analysis of a Shiga toxin-producing Escherichia coli (STEC) O145:H25 associated with a severe pediatric case of hemolytic uremic syndrome in Davidson County, Tennessee, US.
Shiga toxin-producing E. coli (STECs) are foodborne pathogens associated with bloody diarrhea and hemolytic uremic syndrome (HUS). Although the STEC O157 serogroup accounts for the highest number of infections, HUS-related complications and deaths, the STEC non-O157, as a group, accounts for a larger proportion of STEC infections and lower HUS cases. There is limited information available on how to recognize non-O157 serotypes associated with severe disease. The objectives of this study were to describe a patient with STEC non-O157 infection complicated with HUS and to conduct a comparative whole genome sequence (WGS) analysis among the patient's STEC clinical isolate and STEC O157 and non-O157 strains. The STEC O145:H25 strain EN1I-0044-2 was isolated from a pediatric patient with diarrhea, HUS and severe neurologic and cardiorespiratory complications, who was enrolled in a previously reported case-control study of acute gastroenteritis conducted in Davidson County, Tennessee in 2013. The strain EN1I-0044-2 genome sequence contained a chromosome and three plasmids. Two of the plasmids were similar to those present in O145:H25 strains whereas the third unique plasmid EN1I-0044-2_03 shared no similarity with other STEC plasmids, and it carried 23 genes of unknown function. Strain EN1I-0044-2, compared with O145:H25 and O157 serogroup strains shared chromosome- and plasmid-encoded virulence factors, including Shiga toxin, LEE type III secretion system, LEE effectors, SFP fimbriae, and additional toxins and colonization factors. A STEC O145:H25 strain EN1I-0044-2 was isolated from a pediatric patient with severe disease, including HUS, in Davidson County, TN. Phylogenetic and comparison WGS analysis provided evidence that strain EN1I-0044-2 closely resembles O145:H25, and confirmed an independent evolutionary path of STEC O145:H25 and O145:H28 serotypes. The strain EN1I-0044-2 virulence make up was similar to other O145:H25 and O157 serogroups. It carried stx2 and the LEE pathogenicity island, and additional colonization factors and enterotoxin genes. A unique feature of strain EN1I-0044-2 was the presence of plasmid pEN1I-0044-2_03 carrying genes with functions to be determined. Further studies will be necessary to elucidate the role that newly acquired genes by O145:H25 strains play in pathogenesis, and to determine if they may serve as genetic markers of severe disease.


Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients.
The optimal procedure for resection of malignant pleural mesothelioma is controversial, partly because previous analyses include small numbers of patients. We performed a multi-institutional study to increase statistical power to detect significant differences in outcome between extrapleural pneumonectomy and pleurectomy/decortication. Patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at 3 institutions were identified. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis. From 1990 to 2006, 663 consecutive patients (538 men and 125 women) underwent resection. The median age was 63 years (range, 26-93 years). The operative mortality was 7% for extrapleural pneumonectomy (n = 27/385) and 4% for pleurectomy/decortication (n = 13/278). Significant survival differences were seen for American Joint Committee on Cancer stages 1 to 4 (P < .001), epithelioid versus non-epithelioid histology (P < .001), extrapleural pneumonectomy versus pleurectomy/decortication (P < .001), multimodality therapy versus surgery alone (P < .001), and gender (P < .001). Multivariate analysis demonstrated a hazard rate of 1.4 for extrapleural pneumonectomy (P < .001) controlling for stage, histology, gender, and multimodality therapy. Patients who underwent pleurectomy/decortication had a better survival than those who underwent extrapleural pneumonectomy; however, the reasons are multifactorial and subject to selection bias. At present, the choice of resection should be tailored to the extent of disease, patient comorbidities, and type of multimodality therapy planned.


Evaluation of ulnar styloid length.
General awareness of the ulnar styloid impaction syndrome is low and often is neglected. Radiographic evaluation of the ulnar styloid length generally includes an x-ray of the posteroanterior view. This study analyzed the effect of different radiographic views to assess the length of the ulnar styloid. The ulnar styloid-capitate ratio (SCR) expresses the relative length of the ulnar styloid, and we compare this ratio with the ulnar styloid process index (USPI). To evaluate the ulnar styloid and to analyze the effect of different radiographic views on measurement outcome, measurements were performed in 7 different radiographic positions of both wrists of 69 patients. To assess the relative size of the ulnar styloid and its impaction potential the USPI was calculated, re-evaluated, and compared with the SCR, in which the length of the ulnar styloid is divided by the length of the capitate bone. The mean ulnar styloid length in all standard posteroanterior radiographs is 4.4 +/- 1.2 mm. In our population the average USPI was 0.21 +/- 0.11 and the average SCR was 0.18 +/- 0.05. The SCR has a stronger correlation with the length of the ulnar styloid than the USPI. Furthermore this new ratio eliminates differences related to gender, whereas the USPI does not. To identify ulnar impaction potential we recommend using the USPI, but to compare ulnar styloid between patients we recommend using the SCR obtained from neutral posteroanterior radiographs. For white patients we suggest defining a long ulnar styloid as having an SCR greater than 0.18 +/- 0.05 and/or an overall styloid length greater than 6 mm.


Corneal Ulcers in Critically Ill Foals in Intensive Care: Case Series of Standard Treatment and Corneal Cross-Linking.
Riboflavin/UV-A corneal cross-linking (CXL) has been applied to treat corneal ulcers in adult horses, but its use in critically ill neonatal foals has not been described. Five cases of hospitalized, critically ill neonatal foals that were in intensive care with corneal ulcers, the ophthalmic treatment, and their outcome up to 1 year are described. A single treatment of CXL phototherapy was performed in three of five foals (five eyes). The application of a riboflavin ophthalmic solution for 20 minutes was followed by the UV-A light irradiation at 30 mW/cm2 for 3 minutes. Topical antibiotic administration was withdrawn after CXL. Two other foals received standard treatment. Descriptions of ocular lesions, fluorescein staining, and photographic documentation were recorded. The visual outcome, corneal transparency, and aesthetics, as well as healing time were evaluated in the follow-up. The frequency of topical medication considerably decreased in cases treated with CXL. Corneal opacity and pain decreased within 3 days following CXL. In the foals treated with CXL, the ulcers healed (fluorescein stain negative) in 24, 28, and 35 days after the onset of clinical signs and 10, 15, and 21, after CXL. No fibrosis or corneal scars were found in the cases treated with CXL. The two standard treatment cases healed after 26 and 36 days respectively. Corneal cross-linking may be an additional or alternative treatment of corneal ulcers in critically ill neonatal foals and may reduce the use of antibiotics.


Mercaptopropionylglycine: a progress in cystine stone therapy.
During a 4-year period 9 cases of severe recurrent cystine stones and cystinuria were treated with mercaptopropionylglycine. The oral long-term administration revealed the high effectiveness of the drug and resulted in no further stone formation. Mercaptopropionylglycine is free of side effects and more effective than D-penicillamine.


International society of oncology pharmacy practitioners (ISOPP) position statement: The role of oncology pharmacy practitioners in immunotherapy treatment with immune checkpoint inhibitors for malignant conditions.
Oncology pharmacists, pharmacy technicians and assistants are key members of the multidisciplinary health care team (MHT) caring for patients receiving immunotherapy with immune checkpoint inhibitors. The International Society of Oncology Pharmacy Practitioners (ISOPP) developed this position statement to provide guidance on the role of oncology pharmacy practitioners in caring for patients receiving immune checkpoint inhibitors.Four key recommendations were identified: 1) participation as an integrated, collaborative member of the MHT;2) provision of education and training for patients, students, residents, fellows and other members of the MHT;3) involvement in clinical governance to optimise the use of immune checkpoint inhibitors and4) involvement in research and development in the field of immunotherapy.In summary, oncology pharmacy practitioners play essential roles within the MHT in caring for patients receiving immune checkpoint inhibitors.


Benefits for African American and white low-income 7-10-year-old children and their parents taught together in a community-based weight management program in the rural southeastern United States.
Low-income children and parents are at increased risk for developing overweight and obesity. Therefore, the purpose of this exploratory study was to compare whether African American and white children and parents benefitted equally from a community-based weight management intervention delivered in two rural counties in southeastern North Carolina (N.C.). We compared the efficacy of the Family Partners for Health intervention for African American and white children and their parents by testing the three-way interaction of the intervention group according to visit and race. African American children in the intervention group weighed significantly (P = 0.027) less than those in the control group, while white children in the intervention group weighed less than those in the control group, but the difference did not reach statistical significance. African American and white parents in the intervention group weighed less than their respective control groups across all three data collections, but the difference was only significant in the group of white parents (P = 0.010) at the completion of the study. At the completion of the study, African American children in the intervention group received significantly (P = 0.003) more support for physical activity than African American children in the control group. At both time points, white children in the intervention group were not significantly different from those in the control group. African American parents in the intervention group scored slightly worse in the stress management assessment compared to those in the control group, while white parents in the intervention group showed a significantly (P = 0.041) better level of stress management than those in the control group. At the completion of the study, African American parents in the intervention group scored somewhat worse in emotional eating self-efficacy compared to the scores of the African American parents in the control group, while white parents in the intervention group scored significantly (P < 0.001) better than those in the control group. We were successful in affecting some outcomes in both African American and white children and parents using the same intervention. NCT01378806 Registered June 22, 2011.


Light competition drives herbivore and nutrient effects on plant diversity.
Enrichment of nutrients and loss of herbivores are assumed to cause a loss of plant diversity in grassland ecosystems because they increase plant cover, which leads to a decrease of light in the understory1-3. Empirical tests of the role of competition for light in natural systems are based on indirect evidence, and have been a topic of debate for the last 40 years. Here we show that experimentally restoring light to understory plants in a natural grassland mitigates the loss of plant diversity that is caused by either nutrient enrichment or the absence of mammalian herbivores. The initial effect of light addition on restoring diversity under fertilization was transitory and outweighed by the greater effect of herbivory on light levels, indicating that herbivory is a major factor that controls diversity, partly through light. Our results provide direct experimental evidence, in a natural system, that competition for light is a key mechanism that contributes to the loss of biodiversity after cessation of mammalian herbivory. Our findings also show that the effects of herbivores can outpace the effects of fertilization on competition for light. Management practices that target maintaining grazing by native or domestic herbivores could therefore have applications in protecting biodiversity in grassland ecosystems, because they alleviate competition for light in the understory.


A binational survey of smartphone activated volunteer responders for out-of-hospital cardiac arrest: Availability, interventions, and post-traumatic stress.
Responder smartphone apps use global positioning data to enable emergency medical services to alert volunteer responders of nearby potential out-of-hospital cardiac arrests (OHCA). To assess volunteer availability, interventions provided and frequency of probable post traumatic stress disorder (PTSD) experienced by responders receiving a smartphone alert. A web-based survey was emailed to alerted responders at week-two post-alert and a PTSD screening survey at week-six, in Victoria, Australia (1/08/2019-8/11/2020), and in New Zealand (18/02/2020-28/10/2020). We received 1,985 responses to the week-two survey and 1,443 responses to the week-six survey. Of the 1,985 responders, 1,744 (87.9%) had completed cardiopulmonary resuscitation (CPR) training in the last twelve months, and 1,514 (76.3%) had performed CPR at least once. The alert was seen by 1,501 (75.6%) responders, 749 (37.7%) accepted the alert, 538 (27.1%) arrived on scene, and 283 (14.3%) provided care to the patient. In the multivariable analysis, CPR training within twelve months was associated with increased odds of responders accepting alerts (AOR 1.41, 95%CI: 1.02-1.96; p=0.040). Responders who had performed CPR before, were more than twice as likely to provide patient care compared to responders who had not (AOR 2.54, 95%CI: 1.56-4.12; p<0.001). One responder screened positive for probable PTSD. Acceptance rates in Australia and New Zealand were consistent with other smartphone apps. Responder recruitment should be targeted at those with medical backgrounds who have prior CPR experience, as they are more likely to provide care. The very low risk of PTSD is reassuring information when recruiting volunteers.


Metallosis: A diagnosis not only in patients with metal-on-metal prostheses.
Although the real actual incidence of metallosis is unknown, it is described as a rare diagnosis with a 5% estimated incidence in the hip prosthetic replacements. The adoption of non-metallic articular prosthetic devices, made of polyethylene and ceramic, is the main reason to the diminishing number of reported cases. We present a case of metallosis with a clinical systemic presentation in a patient with a non-metallic hip prosthesis, which occurred due to a fracture of the acetabular liner component, leading to abnormal metal-metal contact. The metallic debris leads to a massive local and systemic release of cytokines. Revision is necessary whenever osteolysis and loosening of the prosthesis occur. Imaging evaluation, especially CT, has a central role in diagnosis and planning the surgical treatment.


Post-operative circulating cytokine patterns--the influence of infection.
To study post-operative plasma concentrations of tumor necrosis factor alpha (TNF), interleukin-1 beta (IL-1) and interleukin-6 (IL-6) in infected and non-infected patients. Prospective controlled clinical study. The intensive care unit (ICU) of a university hospital. The study comprised 20 patients, 9 infected and 11 non-infected, consecutively admitted to the ICU after moderate or major surgery. Twelve healthy volunteers were used as controls. Leucocyte count, CRP and the plasma TNF, IL-1 and IL-6 concentrations were studied 24-48 h after the start of surgery. Axillary temperature, the duration of surgery, the number of packed red cells transfused, the APACHE II score and outcome were registered. Both infected and non-infected patients had higher plasma concentrations of IL-6 than the controls (p < 0.001 and p < 0.01 respectively). Patients with infection had a higher plasma IL-6 concentration than non-infected patients (p < 0.05). Similar analyses of plasma TNF concentrations revealed no differences between infected and non-infected patients. Plasma IL-1 was detected only occasionally. Non-survivors (n = 4) had higher plasma concentrations of TNF and IL-6 than survivors (p < 0.05 and p = 0.05 respectively). In non-infected patients a correlation between the number of units of packed red cells transfused and the plasma IL-6 concentration was observed (r = 0.73, p < 0.05). No specific plasma cytokine pattern for infected patients subjected to surgery was observed. The effect of surgery and infection on the plasma IL-6 concentration seemed to be additive. Transfusion of packed red cells appeared to elevate the post-operative plasma IL-6 concentration.


Acceptance of elective bradypacing by patients: an African perspective.
In our practice, we noticed that patients respond differently when pacemaker insertion is recommended to them. We then saw the need to study how African patients accept elective pacemaker implantation. The study was conducted to determine African patients' responses to elective pacemaker insertion. We recruited patients who reported at our outpatient clinic with indications for elective pacemaker insertion. The study period lasted 64 months from September 1999. The patients were counseled before insertion and we sought their consent before being recruited for the study. Five possible responses were used to grade acceptance. They were followed up for 12 months each. Patients who were brought in emergency and those who refused participation were excluded. Those who missed follow-up were also dropped. Ninety-two patients (n = 92) met our study criteria after dropping eight patients who missed follow-up clinic attendance. Most of the candidates (71.7%) felt they had no options but to accept pacemakers at the time of operation. The remaining candidates either accepted the procedure with hope or wholeheartedly. Most of the candidates migrated up the ladder of acceptance over the 12-month period. We concluded that most patients would accept pacemakers wholeheartedly over time.


Influence of the type and degree of left ventricular hypertrophy on the prevalence of ventricular arrhythmias in patients with hypertensive heart disease.
To investigate the correlation between the prevalence of ventricular arrhythmias (VA) and the type and degree of left ventricular hypertrophy (LVH) in hypertensive patients using exercise testing and Holter monitoring. A total of 192 patients (87 men and 105 women) without coronary disease were divided into three groups according to type of LVH (concentric, eccentric, and asymmetric) and three subgroups in relation to the degree of hypertrophy (mild, moderate, and severe). In all subjects blood pressure was measured, electrocardiographic and echocardiographic data obtained and the prevalence of VA determined by Holter monitoring and bicycle ergometry. The most frequent LVH type was the concentric (63%), followed by eccentric (28%) and asymmetric (9%). Severe LVH was found in 10% of patients. Complex VA during Holter monitoring were identified in > 40% of patients. During the stress test this percentage increased by additional 7.4%. There was no statistically significant difference between groups in frequency of simple (p = 0.757) and complex (p = 0.657, p = 0.819, p = 0.617, for polytopic, pairs and ventricular tachycardia, respectively) VA. Increased prevalence of VA was found for the moderate and severe degree in all types. In the concentric type the difference was statistically significant for simple VA (p = 0.042). : There was no correlation between type of LVH and prevalence of VA. The severity of hypertrophy contributes more to a greater prevalence of VA than the LVH pattern. The combination of severe degree and concentric type carries the greatest cardiovascular risk.


Suppression of calcium release by calcium or procaine in voltage clamped rat skeletal muscle fibres.
1. Calcium transients were measured in fast-twitch rat skeletal muscle fibres stretched to 3.7-4.0 microns per sarcomere, and voltage clamped at a holding potential of -80 mV using the double-seal Vaseline gap technique. Resting calcium was monitored with fura-2 and the calcium transients were measured with antipyrylazo III. The rate of release of calcium from the sarcoplasmic reticulum was calculated from the calcium transient records. The temperature was 14-17 degrees C. 2. The steady-state calcium dependence of inactivation of release was studied with a two-pulse protocol in which 200 ms prepulses of different amplitudes elevated the internal calcium concentration to various levels. The inactivation of release was then measured in the test pulse that followed the prepulses. The calcium concentration at which the inactivation of release are half-maximal was approximately 0.22 microM, the average number of bound calcium ions needed to cause inactivation was about three per release channel and the amount of release that could be inactivated was, on average, 2.48 times the steady level of release during the test pulses. 3. Procaine (0.3mM) reversibly decreased the amplitude and the rate of rise of the calcium transient. Both the peak and the steady level of release were decreased by about 50%. The shape of the release waveform was not modified.


Pb detoxification in Equisetum diffusum.
Current research highlights the use of aquatic macrophyte Equisetum diffusum (Himalayan horsetail) for lead detoxification. This plant species can grow in waste cathode ray tube (CRT) powder and absorbs its Pb. X-ray fluorescence spectroscopy (XRF) analysis of plant ash shows that 68 mg/kg lead concentration in the untreated plant was improved to 7600 mg/kg in CRT powder after 90 days. The role of monosilicic and/or monoplumbic acid as reaction intermediates for Pb detoxification and associated bioaccumulation is proposed. Pb detoxification in E. diffusum is mainly rendering around the iso-electronic nature of Pb and Si and forms similar phytochelatin (PC) complexes with available family of peptide ligands. The study focuses on the underlying functions of silicon containing plants in metal detoxification.