Anthropogenic activities affecting metal transfer and health risk in plastic-shed soil-vegetable-human system via changing soil pH and metal contents.
Accumulation and concomitant risk of metals in plastic-shed soil (PSS)-vegetable system around industrial areas have attracted growing public concern recently, while limited studies have focused on human bioaccessible metals in various plastic-shed vegetables and health risk calculated using bioaccessible metals. Previous studies showed that intensive farming and industrial activities could prominently affect metal migration from PSS to vegetables via altering PSS pH, total and bioavailable metal contents. In contrast, whether changes in PSS pH and metal contents control bioaccessible metals in vegetables and health risk is still unknown. For PSS management and sustainable plastic-shed vegetable production in the areas with rapid industrialization, 41 PSS and 32 plastic-shed vegetable samples were sampled from the industrial areas of Yangtze River Delta, China to systematically clarify the specific connections among anthropogenic activities, soil pH and metal contents, and metal transfer and health risk in PSS-vegetable-human system. The results indicated that Cr and Cd contents in 15.6% and 9.38% of vegetable samples exceeded the allowable limits in China. Tolerable cancer risk existed and was mainly induced by bioaccessible Cr in vegetables. Decreased PSS pH mainly caused by heavy use of nitrogen fertilizers increased bioavailable Ni, Cd, Zn, Pb, and Cu in PSS and subsequently enhanced their total and bioaccessible contents in vegetables. Prominent Cr accumulation in PSS induced by industrial wastewater irrigation exacerbated Cr uptake by vegetables, which increased bioaccessible Cr in vegetables and contributed greatly to cancer risk. To reduce transfer and health risk especially of Cd and Cr in the food chain, some appropriate measures related to source control and remediation should be proposed for preventing and mitigating PSS acidification and Cr accumulation.


Cadmium sorption to plasma membrane isolated from barley roots is impeded by copper association onto membranes.
The present study was designed to examine the effect of copper (Cu) on sorption of cadmium (Cd) to plasma membrane (PM) preparations as one of the models of competition between metals on root PM. Plasma membrane preparations were obtained from roots of barley (Hordeum vulgare L. cv. Minorimugi) and 50 μM CdSO₄ with or without 50 μM CuSO₄ were added to the PM suspensions. The sorption of Cd to PM vesicles increased with time within 15 min while Cu sorption to the PM occurred instantaneously. The sorption of Cd to PM vesicles was inactivated immediately after the addition of Cu into the reaction mixture. Results indicate that Cu association to PM vesicles occurs quicker than Cd, and, as a result, impedes the access of Cd to PM vesicles. The present study suggests that the competition between Cd and other minerals at root PM of plants can be demonstrated by employing isolated PM preparations. We consider that the difference in the capacity among some minerals for impeding Cd sorption to PM may also be characterized by investigating the interaction between Cd and other minerals on the PM.


Role of plasma lipids and lipoproteins in predicting amphotericin B-induced nephrotoxicity in pediatric oncology patients.
The objective of this study was to determine if total plasma and lipoprotein cholesterol (C) and triglyceride (TG) concentrations could predict the degree of nephrotoxicity caused by the antifungal agent amphotericin B (AmpB); and to use the average amount of potassium supplementation received daily as a indicator of nephrotoxicity in pediatric oncology patients. Plasma samples from 18 patients (ages < 17 years) who were receiving AmpB due to suspected or confirmed fungal infection at British Columbia Children's Hospital were analyzed for lipid concentrations. The high density lipoprotein (HDL) fractions were separated by precipitation; total (TOT) plasma and fraction C and TG concentrations were measured by enzymatic colorimetric assays; and low density lipoprotein (LDL) C levels were determined by Friedewald's formula. Changes in serum creatinine levels from baseline and amounts of potassium supplementation were used as indicators of nephrotoxicity; both were obtained from patients' medical charts. Pearson correlation coefficients (r) were determined and considered significant if P < 0.05. The total cumulative AmpB dose, adjusted for weight, does not seem to predict AmpB-induced nephrotoxicity. Positive but relatively weak correlations were found between total potassium supplementation and LDL C (r = 0.489, P < 0.02); and TOT C (r = 0.551, P < 0.01). In addition, a positive but relatively weak correlation between the average amount of potassium supplementation per day above baseline and HDL C (r = 0.407; P < 0.02) was observed. Differences in total plasma and LDL cholesterol concentrations may be used as predictors of AmpB-induced nephrotoxicity in pediatric oncology patients.


Impact of screening between the ages of 60 and 64 on cumulative rates of cervical cancer to age 84y by screening history at ages 50 to 59: A population-based case-control study.
There is little empirical data on the absolute benefit of cervical screening between ages 60-64y on subsequent cancer risk. We estimate the incidence of cervical cancer up to age 84y in women with and without a cervical cytology test at age 60-64y, by screening histories aged 50-59y. The current study is a population based case-control study of women born between 1928 and 1956 and aged 60-84y between 2007 and 2018. We included all such women diagnosed with cervical cancer in England and an aged-matched random sample without cancer. Women with a hysterectomy were excluded. Exposure was cervical cytology between ages 50-64y. The main outcome was 25y cumulative risk of cervical cancer between ages 60-84y. We found that eight in every 1000 (8.40, 95%CI: 7.78 to 9.07) women without a screening test between age 50-64y develop cervical cancer between the ages of 60-84y. The risk is half: 3.46 per 1000 (95%CI: 2.75 to 4.36) among women with a test between age 60-64y but no cervical screening test at age 50-59y. The absolute difference in risk is equivalent to one fewer cancer for every 202 such women screened. The highest risk (10.01, 95%CI:6.70 to 14.95) was among women with abnormal screening at ages 50-59y and no tests 60-64y. 25y risk among women with a screening test every five years between age 50-64y was just under two in a 1000 (1.59, 95%CI:1.42 to 1.78). Results suggest the upper age of screening should be dependent on previous screening participation and results.


Cannula Wound Closure with the Laurus PC Suture Device
The Laurus PC suturing device closes cannula wounds of 10 mm diameter and larger. It uses a special suture-needle combination that is double armed on either absorbable or nonabsorbable suture. One end of the suture is loaded into the device and placed through the wound into the peritoneal cavity. With a single push of a button, the needle is driven through the peritoneum and rectus fascia and is captured within the device, forming a suture loop. The device is withdrawn, reloaded with the other needle end of the suture and fired through the opposing side of the wound. The suture is tied and the skin is closed with adhesive strips. The closure time is less than 1 minute.


Syringomyelia as a sequel to traumatic paraplegia.
Ten cases of post-traumatic paraplegia are described in whom syringomyelia symptoms have supervened. Five patients have been operated upon after investigation. Operative results have been encouraging. A discussion of likely pathogenetic mechanisms is presented.


Effects of conversion of coastal marshes to aquaculture ponds on sediment anaerobic CO2 production and emission in a subtropical estuary of China.
The extensive conversion of carbon-rich coastal wetland to aquaculture ponds in the Asian Pacific region has caused significant changes to the sediment properties and carbon cycling. Using field sampling and incubation experiments, the sediment anaerobic CO2 production and CO2 emission flux were compared between a brackish marsh and the nearby constructed aquaculture ponds in the Min River Estuary in southeastern China over a three-year period. Marsh sediment had a higher total carbon and lower C:N ratio than aquaculture pond sediment, suggesting the importance of marsh vegetation in supplying labile organic carbon to the sediment. Conversion to aquaculture ponds significantly decreased sediment anaerobic CO2 production rates by 69.2% compared to the brackish marsh, but increased CO2 emission, turning the CO2 sink (-490.8 ± 42.0 mg m-2 h-1 in brackish marsh) into a source (6.2 ± 3.9 mg m-2 h-1 in aquaculture pond). Clipping the marsh vegetation resulted in the highest CO2 emission flux (382.6 ± 46.7 mg m-2 h-1), highlighting the critical role of marsh vegetation in capturing and sequestering carbon. Sediment anaerobic CO2 production and CO2 uptake (in brackish marsh) and emission (in aquaculture ponds) were highest in the summer, followed by autumn, spring and winter. Redundancy analysis and structural equation modeling showed that the changes of sediment temperature, salinity and total carbon content accounted for more than 50% of the variance in CO2 production and emission. Overall, the results indicate that vegetation clearing was the main cause of change in CO2 production and emission in the land conversion, and marsh replantation should be a primary strategy to mitigate the climate impact of the aquaculture sector.


Ca2+/calmodulin-dependent protein kinase IIdelta orchestrates G-protein-coupled receptor and electric field stimulation-induced cardiomyocyte hypertrophy.
1. G-Protein-coupled receptors (GPCR) and electrical field stimulation (EFS) regulate cardiac function and pathological remodelling, including cardiac hypertrophy. Cardiac Ca(2+)/calmodulin-dependent protein kinase (CaMK) IIdelta expression and activity are altered in cardiac hypertrophy and heart failure. The aim of the present study was to determine the effects of CaMKIIdelta isoforms on neonatal rat cardiomyocyte hypertrophy induced by GPCR and EFS. 2. Cardiac hypertrophy was induced by angiotensin II, phenylephrine or EFS and was confirmed by increases in cell volume, [(3)H]-leucine incorporation, sarcomere assembly and mRNA expression of atrial natriuretic factor and beta-myosin heavy chain. The effects of the CaMKII inhibitors KN93 and autocamtide 2-related inhibitory peptide (AIP) on cardiomyocyte hypertrophy were investigated, as was the effect of overexpression of dominate negative CaMKIIdelta. 3. Cardiomyocyte hypertrophy was inhibited by the CaMKII inhibitors KN93 and AIP and by overexpression of dominate negative CaMKIIdelta, but was potentiated by overexpression of wild-type CaMKIIdeltaB or CaMKIIdeltaC. Activation of CaMKII by GPCR agonists or EFS was inhibited by the CaMKII inhibitors. 4. The GPCR agonists and EFS synergistically activated CaMKII and upregulated CaMKIIdeltaB and CaMKIIdeltaC mRNA expression and protein synthesis. All these effects were abolished by the CaMKII inhibitors. 5. The findings of the present study indicate that CaMKII orchestrates additive prohypertrophic factors between GPCR agonists and EFS. Thus, CaMKII may be a useful target in the clinical treatment of hypertrophy and cardiac remodelling.


From linked marker to gene.
An area of increasing importance in human genetics research is the strategy of 'reverse genetics' or 'positional cloning', whereby a gene associated with a genetic disease is isolated on the basis of its approximate chromosomal position. This article and the accompanying centrepage diagram describe the main features of this strategy and outline the techniques involved; they are designed to be used for teaching purposes and as a general reference for those from other fields of genetics research.


Neurologic disease activity in people with multiple sclerosis treated with immune checkpoint inhibitors.
There is concern that immune checkpoint inhibitors (ICPIs) can provoke relapses in people with multiple sclerosis (pwMS). Analyze outcomes of pwMS who received ICPI treatment for malignancy. We electronically identified pwMS who received ICPI treatment at Mass General Brigham hospital system. We retrospectively obtained information about patients' MS, cancer, treatment, and outcomes. Sixteen patients were identified with an average (standard deviation (SD)) age of 67.4 (11.9) years. Eleven (68.8%) had no relapses since MS diagnosis. None had MS relapses after ICPI treatment or new MS lesions. ICPI use was not associated with increased clinical disease activity in this cohort of older patients with inactive MS.


The association between mobile devices use and behavior problems among fourth grade children in Japan.
Previous studies showed mixed evidence on the association between duration of mobile devices usage and behavior problems among children. We aimed to examine this association using a large population-based sample of fourth grade children (i.e. aged 9-10 years old), stratified by gender. Questionnaires with anonymous unique identifiers were distributed to 4th grade students (aged 9-10 years old) at all public schools in Adachi City, Tokyo (n = 4,105). Duration of mobile devices usage was self-reported, and behavior problems were assessed by the Strengths and Difficulties Questionnaire by caregivers. Multiple regression analyses were performed, adjusting for potential confounders such as socioeconomic status, family social capital, and number of friends. Among boys, U-shape association was found between duration of mobile devices usage and behavior problems; boys with usage time of less than 1 h showed 0.88 [95% confidence interval (CI) -1.50 to -0.27] point lower total difficulty score in comparison with boys who do not use mobile devices, and total difficulty score among boys with usage time of 1 h or more was not different with non-users. Among girls, dose-response positive association was found between duration of mobile devices usage and total difficulty score (P for trend: <0.001). Among children aged 9-10 years old, mobile devices usage time of less than 1 h was a protective factor for behavior problems in boys, while usage time of 1-h or more was a risk factor in girls. Further longitudinal study is warranted to confirm the findings.


Mercury speciation in meconium and associated factors.
Meconium is formed early in gestation and it is normally not excreted until after birth. Thus it may provide a longer and cumulative record of exposure to mercury (Hg). The present study aims to speciate Hg in meconium samples (N = 488) from Slovenian and Croatian new-borns prenatally exposed to low levels of methyl-Hg (MeHg) from maternal seafood intake and to Hg0 from maternal dental amalgam fillings. We had complete data of total Hg (THg) and MeHg in meconium and THg in maternal hair (MH), while THg and MeHg in maternal blood (MB) were available only for Croatian mothers. Personal data namely maternal seafood intake, age, pre-pregnancy BMI, parity, smoking, estimated gestational age at birth, sex, and birth weight were available for the majority of participants, except the number of dental amalgams which was in most cases missing for Croatian mothers. The median THg concentration in meconium was 11.1 (range: 0.41-375.2) ng/g and inorganic Hg (Hg(II)) presented 98.8% (range: 82%-100%, CV: 2%) of THg. We observed significant correlation between meconium and MH Hg levels, with the highest correlation between hair THg and meconium MeHg. Correlation analysis including MB (available only for Croatian population) showed a significant positive correlation between THg in meconium and THg in MB (Rs = 0.642). Additionally, MeHg from MB was correlated with MeHg in meconium (Rs = 0.898), while the correlation between Hg(II) in MB and meconium was positive, but not significant. Maternal seafood intake was significantly correlated with meconium MeHg (Rs = 0.498) and Hg(II) (Rs = 0.201). Multiple linear regression (performed on the Slovenian population, N = 143) confirmed a positive association between meconium MeHg and seafood intake. Furthermore, meconium Hg(II) was positively associated with the number of maternal dental amalgam fillings, but linear regression models did not confirm correlation between seafood intake and meconium Hg(II) levels. We assume that Hg0 released from maternal dental amalgam fillings and MeHg from seafood intake were both transported through the placental barrier and portioned between different foetal compartments including meconium. Weak correlation between maternal seafood intake and Hg(II) levels in meconium suggests that there is certain evidence of MeHg demethylation. However, because this correlation was not confirmed by the multiple regression, MeHg demethylation during prenatal life cannot be neither confirmed nor excluded. Further investigations at higher level of exposure are needed to confirm this observations. We can conclude that meconium is a suitable biomarker for MeHg and Hg0 exposure during pregnancy. However, comparability of the results reported in meconium in different studies is hindered by a lack of standardized sampling protocols, storage, and analysis.


The effect of prophylaxis with low dose heparin on blood coagulation parameters. A double blind study in connection with transvesical prostatectomy.
Heparin was administered subcutaneously 5.000 IU twice daily using a double blind method to ten of twenty-one patients undergoing transvesical prostatectomy. Platelet count, APTT, throbin time, Reptilase time, Normotest, fibrinogen, Factor-VIII, ethanol gelation test, antithrombin III, fibrinolytic degradation products, alpha1-antitrypsin and alpha2-macroglobulin were studied pre- and postoperatively up to the 10th postoperative day. Statistical analysis of parameters of blood coagulation and fibrinolysis showed no significant difference between the two groups. The mechanism by which low dose heparin exerts its thromboprophylactic effect could not be elucidated from the study of the investigated parameters. The laboratory data gave no indication to a possible increased risk of postoperative hemorrhage.


Synergistic strengthening mechanism of hydraulic selection pressure and poly aluminum chloride (PAC) regulation on the aerobic sludge granulation.
This study aimed to enhance aerobic granulation by the integration of hydraulic selection pressure (HSP) and poly aluminum chloride (PAC) regulation. Based on an investigation of sludge characteristics, microbial aggregation and extracellular polymeric substances (EPS) secretion, the synergistic mechanisms of HSP and PAC regulation were revealed. For granule formation, HSP primarily improved the cell hydrophobicity and extracellular protein production, while PAC regulation markedly neutralized the surface charge of cells and reduced the interaction energy between them. In addition, biomass retention was also facilitated by the PAC dosing. Notably, the results of total interaction energy and flocculating ability imply that prior HSP screening could significantly promote PAC regulation on microbial aggregation. To optimize the balance between granule formation and reactor performances, five kinds of integrated strategies for HSP and PAC regulation were conducted in batch test. According to the results, 4.3 g/L initial mixed liquor volatile suspended solids (MLVSS) was preferred before the addition of PAC.


Medico-Legal Cases Involving Cardiologists and Cardiac Test Underuse or Overuse.
Evidence-based campaigns are available to support appropriate diagnostic testing in cardiology, but medico-legal concerns can impede implementation. We conducted a retrospective descriptive analysis of medico-legal cases (civil legal, regulatory authority, hospital matters) involving cardiologists in Canada. For eligibility, cases must have closed at the Canadian Medical Protective Association between January 1, 2009 and December 31, 2018. We defined test underuse and overuse using criticisms in the medico-legal record from peer experts, regulatory authorities, or hospitals. We used a contributing factors framework and descriptive statistics for analysis. From 2009 to 2018, the Canadian Medical Protective Association closed 60,598 cases with 368 (0.6%) involving a cardiologist. Within those cases, there was no criticism of cardiac diagnostic test overuse and 15 cases (4.1%) with criticism of underuse (tests not ordered, not expedited, delayed). In 12 of 15 cases of underuse (80.0%), the patient experienced severe harm or death. Of 8 civil legal cases, 6 were decided in favour of the plaintiff (75.0%) and 2 were dismissed by consent before proceeding to trial (25.0%). Decisions on regulatory authority matters did not favour the cardiologist (7 of 7 cases). In all cases of underuse, there was need for focused testing to investigate new or worsening symptoms. The most common contributing factors included clinical decision-making, situational awareness, and communication with teams and patients. Medico-legal cases involving cardiologists and the overuse or underuse of cardiac diagnostic tests were extremely rare in Canada, despite the potential for harm. The criticisms of cardiac diagnostic test underuse related to issues with diagnosing symptomatic patients.


Association of deprivation, ethnicity, and sex with quality indicators for diabetes: population based survey of 53,000 patients in primary care.
To determine the effect of deprivation and ethnicity on the achievement of quality indicators for patients with diabetes and the extent of any inequalities between the sexes. Population based cross sectional survey using electronic general practice records. 237 UK practices contributing to the QRESEARCH database. 54,180 patients with diabetes, derived from a population of 1.8 million patients. Adjusted odds ratios for 18 indicators for diabetes from the new general medical services contract for UK general practitioners and comparisons between patients from the most deprived and most affluent fifths (areas of high and low ethnicity) and between men and women. The prevalence of diabetes was 3.0%, and there was a large variation between practices in achievement of indicators. Compared with patients from affluent areas, those from deprived areas were less likely to have body mass index and smoking status recorded. They were also less likely to have records for HbA1c concentration; an HbA1c value < 7.5% or < 10%; retinal screening; blood pressure; testing for neuropathy or microalbuminuria, or flu vaccination. Compared with patients from areas of low ethnicity those from areas of high ethnicity were less likely to have many measures recorded. Women were significantly less likely to have records for body mass index; pulses; blood pressure values below 145/85 mm Hg; testing for microalbuminuria; serum cholesterol concentration; serum cholesterol values < 5 mmol/l; and angiotensin converting enzyme inhibitors given in the presence of proteinuria or microalbuminuria. Practices in areas of high deprivation and high ethnicity will have to work harder to achieve the quality indicators for diabetes, and it is possible that those practices that most need the resources are the ones least likely to get them.


Muscle transpositions in the shoulder and upper arm for sequelae of brachial plexus palsy.
Permanent deficiency in abduction and external rotation of the arm seen after brachial plexus injury may be corrected by a levator scapulae transposition onto the supraspinatus, while the teres major, associated or not with latissimus dorsi, is transferred onto the infraspinatus muscle. Transposed in a bipolar manner, the latissimus may compensate the deltoid muscle. Associated measures have to be carried out in children with deformities caused by obstetrical palsy. A paralysed serratus anterior is best compensated by a transfer of the pectoralis major together with pectoralis minor muscle.


Determination of zearalenone and its metabolites in endometrial cancer by coupled separation techniques.
This study presents a selective method of isolation of zearalenone (ZON) and its metabolite, α-zearalenol (α-ZOL), in neoplastically changed human tissue by accelerated solvent and ultrasonic extractions using a mixture of acetonitrile/water (84/16% v/v) as the extraction solvent. Extraction effectiveness was determined through the selection of parameters (composition of the solvent mixture, temperature, pressure, number of cycles) with tissue contamination at the level of nanograms per gram. The produced acetonitrile/water extracts were purified, and analytes were enriched in columns packed with homemade molecularly imprinted polymers. Purified extracts were determined by liquid chromatography (LC) coupled with different detection systems (diode array detection--DAD and mass spectrometry--MS) involving the Ascentis RP-Amide as a stationary phase and gradient elution. The combination of UE-MISPE-LC (ultrasonic extraction--molecularly imprinted solid-phase extraction--liquid chromatography) produced high (R≈95-98%) and repeatable (RSD<3%) recovery values for ZON and α-ZOL.


A Renal-Clearable Duplex Optical Reporter for Real-Time Imaging of Contrast-Induced Acute Kidney Injury.
Despite its high morbidity and mortality, contrast-induced acute kidney injury (CIAKI) remains a diagnostic dilemma because it relies on in vitro detection of insensitive late-stage blood and urinary biomarkers. We report the synthesis of an activatable duplex reporter (ADR) for real-time in vivo imaging of CIAKI. ADR is equipped with chemiluminescence and near-infrared fluorescence (NIRF) signaling channels that can be activated by oxidative stress (superoxide anion, O2.- ) and lysosomal damage (N-acetyl-β-d-glucosaminidase, NAG), respectively. By virtue of its high renal clearance efficiency (80 % injected doses after 24 h injection), ADR detects sequential upregulation of O2.- and NAG in the kidneys of living mice prior to a significant decrease in glomerular filtration rate (GFR) and tissue damage in the course of CIAKI. ADR outperforms the typical clinical assays and detects CIAKI at least 8 h (NIRF) and up to 16 h (chemiluminescence) earlier.


Visible-Light-Enabled Carboxylation of Benzyl Alcohol Derivatives with CO2 Using a Palladium/Iridium Dual Catalyst.
Invited for this month's cover is the group of Nobuharu Iwasawa at Tokyo Institute of Technology. The image shows a switchable site-selective carboxylation between benzylic C-O and aryl C-Cl moieties enabled by a palladium/iridium dual catalyst under visible light irradiation. The Communication itself is available at 10.1002/cssc.202102095.


Tuning protein autoinhibition by domain destabilization.
Activation of many multidomain signaling proteins requires rearrangement of autoinhibitory interdomain interactions that occlude activator binding sites. In one model for activation, the major inactive conformation exists in equilibrium with activated-like conformations that can be stabilized by ligand binding or post-translational modifications. We established the molecular basis for this model for the archetypal signaling adaptor protein Crk-II by measuring the thermodynamics and kinetics of the equilibrium between autoinhibited and activated-like states. We used fluorescence and NMR spectroscopies together with segmental isotopic labeling by means of expressed protein ligation. The results demonstrate that intramolecular domain-domain interactions both stabilize the autoinhibited state and induce the activated-like conformation. A combination of favorable interdomain interactions and unfavorable intradomain structural changes fine-tunes the population of the activated-like conformation and allows facile response to activators. This mechanism suggests a general strategy for optimization of autoinhibitory interactions of multidomain proteins.


Antibody repertoire development in teleosts--a review with emphasis on salmonids and Gadus morhua L.
The group of teleosts is highly diverse, comprising more than 23000 extant species. Studies of the teleost antibody repertoire have been conducted in many different species within different orders, though some species and families have been better characterised than others. The Atlantic cod (Gadus morhua L.) and several species within the Salmoninae (e.g. Salmo salar and Oncorynchus mykiss) are among the best-studied teleosts in terms of the antibody repertoire. The estimated size of the repertoire, the organisation of immunoglobulin (IG) gene segments, the expressed IG repertoire, the IgM serum concentration, and the serum antibody responses reveal some fundamental differences between these species. The serum IgM concentration of G. morhua is some ten times higher than that of S. salar, though G. morhua is characterised as a 'low' (or 'non') responder in terms of specific antibody production. In contrast, an antibody response is readily induced in S. salar, although the response is strongly regulated by antigen induced suppression. The IGHD gene of G. morhua has a unique structure, while the IGHM and IGHD genes of S. salar have a characteristic genomic organisation in two parallel loci. In addition, salmonids, express a broad repertoire of IGH and IGI V-region gene segments, while a single V gene family dominates the expressed heavy and light chain repertoire of G. morhua. Little is known about the developing antibody repertoire during ontogeny, in different stages of B-cell maturation, or in separate B-cell subsets. Information on the establishment of the preimmune repertoire, and the possible role of environmental antigens is also sparse.


Patterns of exploration in rats distinguish lisuride from lysergic acid diethylamide.
In order to further validate a previously proposed animal model of the effects of LSD in humans, doses of 5, 15, 30 and 60 micrograms/kg lisuride (a non-hallucinogenic congener of LSD) were studied using a behavioral pattern monitor (BPM). The BPM provided both quantitative measures of crossovers, rearings, and holepokes and qualitative measures of spatial patterns of locomotion. A holeboard chamber connected to a homecage provided two test situations. Rats were tested either with (free exploration) or without access to the homecage (forced exploration). In both situations, lisuride exhibited a biphasic dose-response curve for horizontal locomotion (low dose suppression and high dose enhancement), while rearing was significantly reduced at all doses. Lisuride also produced a dose-dependent increase in the perseverative quality of locomotor patterns. A comparison of these results with our previous studies with lysergic acid diethalmide (LSD) indicate that, with the exception of rearings, lisuride fails to mimic LSD's characteristic effects on exploratory activity. Rather, lisuride exhibited many similarities to the dopamine angonist apomorphine.


Responses of Teretrius nigrescens toward the dust and frass of its prey, Prostephanus truncatus.
Teretrius nigrescens is considered to be a specialized predator of Prostephanus truncatus, a serious pest of stored maize and dried cassava roots. Using a bait-bag behavioral bioassay, this investigation found T nigrescens to be strongly arrested by dust and frass produced by P. truncatus on maize, whereas responses to maize flour were weak. Attempts to increase the arrestiveness of flour by altering its physical properties (coarseness or particle size range) were unsuccessful. The arrestive property of dust/frass did not degrade with long-term storage nor did it volatilize or degrade with oven baking up to 150 degrees C. However, extraction with methanol and reapplication was successful in transferring the arrestive property from the dust/frass onto maize flour. The prey dust/frass also induced more oviposition than did maize flour, as judged by production of F1 offspring. The results provide strong evidence for the existence of a high boiling point compound(s) in P. truncatus dust/frass that acts as a contact kairomone for T nigrescens. This, or another compound(s) also seems to act as an oviposition stimulant for female T. nigrescens.


Why Do Older Korean Adults Respond Differently to Activities of Daily Living and Instrumental Activities of Daily Living? A Differential Item Functioning Analysis.
Culture-based gender norms regarding who performs daily activities can bias the assessment of instrumental activities of daily living (IADL). This study evaluated item-response biases in the activities of daily living (ADL) and IADL among community-living Korean older adults. The subjects included older Korean participants of the Korean Longitudinal Study of Ageing baseline survey (n=4,164). We performed differential item functioning (DIF) analysis of these data using the Mantel-Haenszel method. We observed different reported levels of disability for eight IADL items among gender, age, and educational level subgroups. After matching for overall functional disability, men were more likely to report limitations in performing various household activities, compared to cognitive activities in women. Cross-national comparisons of ADL and IADL disabilities need to consider item response bias stemming from culture-based gender norms regarding who performs different household activities.


Burnout, workplace violence and social support among drivers and conductors in the road passenger transport sector in Maputo City, Mozambique.
Workplace violence is a work stressor which is presumed to lead to burnout, whereas social support is hypothesized to buffer the impact of such a stressor on health outcomes. In this study the association between burnout and workplace violence was investigated, and the role played by social support in moderating the relationship assessed. The study group consisted of workers in the road passenger transport sector in Maputo City, Mozambique. A random sample of 504 participants was selected from a register of 2,618 drivers and conductors working with road passenger transport. The study design was cross-sectional. Previously validated measures of burnout, workplace violence and social support were used. The prevalence of severe burnout was 3.6% and of mild burnout 30.1%. Workplace violence was significantly associated with burnout after control for potential confounders. Burnout was more common among workers lacking social support following workplace violence than among peers who had received supported following an incident of violence. The study suggests that burnout is a public health problem among workers in the road passenger transport sector, and may be closely and independently linked to workplace violence. Social support appears to buffer or moderate the effect of workplace violence on burnout. This has implications for policy in the workplace. Strategies and guidelines are needed to support workers following workplace violence, since these may prove vital in reducing burnout and other psychosocial consequences.


A split luciferase complementation assay for studying in vivo protein-protein interactions in filamentous ascomycetes.
Protein-protein interactions play important roles in controlling many cellular events. To date, several techniques have been developed for detection of protein-protein interactions in living cells, among which split luciferase complementation has been applied in animal and plant cells. Here, we examined whether the split luciferase assay could be used in filamentous ascomycetes, such as Gibberella zeae and Cochliobolus heterostrophus. The coding sequences of two strongly interacting proteins (the F-box protein, FBP1, and its partner SKP1) in G. zeae, under the control of the cryparin promoter from Cryphonectria parasitica, were translationally fused to the C- and N-terminal fragments of firefly luciferase (luc), respectively. Each fusion product inserted into a fungal transforming vector carrying the gene for resistance to either geneticin or hygromycin B, was transformed into both fungi. We detected complementation of split luciferase proteins driven by interaction of the two fungal proteins with a high luminescence intensity-to-background ratio only in the fungal transformants expressing both N-luc and C-luc fusion constructs. Using this system, we also confirmed a novel protein interaction between transcription factors, GzMCM1 and FST12 in G. zeae, which could hardly be proven by the yeast two-hybrid method. This is the first study demonstrating that monitoring of split luciferase complementation is a sensitive and efficient method of studying in vivo protein-protein interactions in filamentous ascomycetes.


Isolation of D-myo-inositol 1:2-cyclic phosphate 2-inositolphosphohydrolase from human placenta.
We have isolated D-myo-inositol 1:2-cyclic phosphate 2-inositolphosphohydrolase (EC 220.127.116.11) from human placenta. This enzyme catalyzes the conversion of inositol 1:2-cyclic phosphate to inositol 1-phosphate. The enzyme was purified 1300-fold to apparent homogeneity from the soluble fraction of human placenta. The enzyme requires Mn2+ or Mg2+ ions for activity, has an apparent Km for inositol 1:2-cyclic phosphate of 0.15 mM and forms 2.2 mumol of inositol 1-phosphate/min/mg protein. The enzyme does not utilize the cyclic esters of inositol polyphosphates as substrates. The molecular weight determined by gel filtration chromatography is approximately 55,000. Upon electrophoresis in polyacrylamide gels in sodium dodecyl sulfate, the molecular weight was found to be 29,000 both in the presence and absence of beta-mercaptoethanol. The enzyme was inhibited by inositol 2-phosphate (IC50 = 4 microM) and to a lesser degree by inositol 1-phosphate (IC50 = 2 mM) and inositol (IC50 = 4 mM). Zn2+ is a potent inhibitor of enzyme activity (IC50 = 10 microM). Neither Li+ nor Ca2+ had any effect on enzyme activity. This enzyme may serve to generate inositol from inositol cyclic phosphate metabolites produced by the phosphoinositide signaling pathway in cells.


Five new records of bee flies (Bombyliidae, Diptera) from Saudi Arabia with zoogeographical remarks.
Five bee-fly species (Bombyliidae, Diptera) have been listed in this paper as new to the Kingdom of Saudi Arabia. Four of the recorded species have been identified to the level of species, namely: Bombomyiadiscoidea (Fabricius, 1794), Spogostylumcandidum (Sack, 1909), Exoprosopalinearis Bezzi, 1924, and Exoprosopaminos (Meigen, 1804), while the fifth one only to genus, Desmatoneura sp. The species have been collected from Al-Baha and Asir Provinces in the south-western part of the Kingdom. One of the four identified species, Exoprosopalinearis, has an Afrotropical affinity, and another two, Spogostylumcandidum and Bombomyiadiscoidea, have considerable Afrotropical distributions, and this result agrees to some extent with studies considering these parts of the Arabian Peninsula, including Al-Baha and Asir Provinces, having Afrotropical influences and may be included in the Afrotropical Region rather than in the Palaearctic Region or the Eremic zone.


Comparison of two injectable anaesthetic protocols in Egyptian fruit bats (Rousettus aegyptiacus) undergoing gonadectomy.
Egyptian fruit bats have gained increasing interest being a natural reservoir for emerging zoonotic viruses. Anaesthesia is often required to allow safe handling of bats. We aimed to compare the sedative and cardiopulmonary effects of two balanced anaesthetic protocols in bats undergoing gonadectomy. Group DK (n = 10) received intramuscular dexmedetomidine (40 µg/kg) and ketamine (7 mg/kg), whereas group DBM (n = 10) received intramuscular dexmedetomidine (40 µg/kg), butorphanol (0.3 mg/kg) and midazolam (0.3 mg/kg). Induction time and cardiopulmonary parameters were recorded. If anaesthetic plan was inadequate, isoflurane was titrated-to-effect. At the end of surgery venous blood gas analysis was performed and atipamezole or atipamezole-flumazenil was administered for timed and scored recovery. In DBM group heart rate and peripheral oxygen saturation were significantly higher (p = 0.001; p = 0.003 respectively), while respiratory rate was significantly lower (p = 0.001). All bats required isoflurane supplementation with no significant differences between groups. Induction and recovery times showed no significant differences. In group DK a better recovery was scored (p = 0.034). Sodium and chloride were significantly higher in DBM group (p = 0.001; p = 0.002 respectively). Both anaesthetic protocols were comparable and can be recommended for minor procedures in bats.


Observing backfolded and unfolded acoustic phonons by broadband optical light scattering.
We use broadband time domain Brillouin scattering to observe coherently generated phonon modes in bulk and nanolayered samples. We transform the measured transients into a frequency-wavevector diagram and compare the resulting dispersion relations to calculations. The detected oscillation amplitude depends on the occupation of phonon modes induced by the pump pulse. For nanolayered samples with an appropriately large period, the whole wavevector range of the Brillouin zone becomes observable by broadband optical light scattering. The backfolded modes vanish, when the excitation has passed the nanolayers and propagates through the substrate underneath.


Paramagnetic signals in the globus pallidus as late radiographic sign of juvenile-onset GM1 gangliosidosis.
The juvenile form of GM1 gangliosidosis lacks specific physical findings and thus is often a diagnostic challenge for clinicians. T2 hypodensity in the globus pallidus is a characteristic radiographic sign of neurodegeneration with iron accumulation in the brain that is observed in GM1 gangliosidosis, but the exact timing when this radiographic sign becomes apparent remains to be elucidated. Two male siblings had normal development until 2 years of age and then developed psychomotor regression with dystonia. Their neuroimaging studies indicated progressive global cerebral atrophy. Exome sequencing identified compound heterozygous missense mutations in GLB1, leading to a diagnosis of GM1 gangliosidosis. A retrospective review of neuroimaging studies revealed that the two patients had strikingly similar clinical courses and radiographic progressions with cortical atrophy that preceded the T2 hypointensity in the globus pallidus. Paramagnetic signals in the globus pallidus become apparent relatively late during the disease course, once cerebral atrophy has already become prominent. A comprehensive diagnostic approach involving clinical, radiographic, and genetic testing is necessary for the early identification of affected individuals.


Anticancer properties of curcumin-treated Lactobacillus plantarum against the HT-29 colorectal adenocarcinoma cells.
Probiotic bacteria with functions of importance to the health and well-being of the host exhibit various medicinal properties including anti-proliferative properties against cancer cells. There are observations demonstrating probiotic bacteria and their metabolomics can be different in various populations with different eating habits. Here, Lactobacillus plantarum was treated with curcumin (the major compound of turmeric), and its resistance to the curcumin was determined. After then the cell-free supernatants of untreated bacteria (CFS) and bacteria treated with curcumin (cur-CFS) were isolated and their anti-proliferative properties against HT-29 colon cancer cells were compared. The ability of L. plantarum treated with curcumin to combat a variety of pathogenic bacterial species and its ability to survive in acidic conditions were evidence that the probiotic properties of the bacterium were unaffected by the curcumin treatment. L. plantarum treated with curcumin and intact L. plantarum were both able to live in acidic conditions, according to the results of the resistance to low pH test. The MTT result showed that CFS and cur-CFS dose-dependently decreased the growth of HT29 cells with a half-maximal inhibitory concentration of 181.7 and 116.3 µL/mL at 48 h, respectively. Morphological alteration of DAPI-stained cells also exhibited significant fragmentation in the chromatin within the nucleus of cur-CFS-treated cells compared to CFS-treated HT29 cells. Moreover, flow cytometry analyses of apoptosis and cell cycle confirmed DAPI staining and MTT assay results and stipulated the increased occurrence of programmed cell death (apoptosis) in cur-CFS-treated cells (~ 57.65%) compared to CFS-treated cells (~ 47%). These results were more confirmed with qPCR and exhibited the upregulation of Caspase 9-3 and BAX genes, and downregulation of the BCL-2 gene in cur-CFS- and CFS-treated cells. In conclusion, turmeric spice and curcumin may affect the metabolomics of probiotics in intestinal flora which could subsequently influence their anticancer properties.


Genetic Information Insecurity as State of the Art.
Genetic information is being generated at an increasingly rapid pace, offering advances in science and medicine that are paralleled only by the threats and risk present within the responsible systems. Human genetic information is identifiable and contains sensitive information, but genetic information security is only recently gaining attention. Genetic data is generated in an evolving and distributed cyber-physical system, with multiple subsystems that handle information and multiple partners that rely and influence the whole ecosystem. This paper characterizes a general genetic information system from the point of biological material collection through long-term data sharing, storage and application in the security context. While all biotechnology stakeholders and ecosystems are valuable assets to the bioeconomy, genetic information systems are particularly vulnerable with great potential for harm and misuse. The security of post-analysis phases of data dissemination and storage have been focused on by others, but the security of wet and dry laboratories is also challenging due to distributed devices and systems that are not designed nor implemented with security in mind. Consequently, industry standards and best operational practices threaten the security of genetic information systems. Extensive development of laboratory security will be required to realize the potential of this emerging field while protecting the bioeconomy and all of its stakeholders.


Autism spectrum disorders in children and adolescents with Moebius sequence.
Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups. The primary caregivers of all children and adolescents with Moebius sequence aged 6-17 years known to the German Moebius foundation were anonymously asked to complete two screening measures of ASD [Behavior and Communication Questionnaire (VSK); Marburger Asperger's Syndrome Rating Scale (MBAS)]. For those who reached the cut-off for ASD, well standardized diagnostic instruments (Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, WISC-III, and Kinder-DIPS) should be administered. Minimal diagnostic criteria for Moebius sequence were congenital facial weakness (uni- or bilateral) and impairment of ocular abduction (uni- or bilateral). Familiar cases should be excluded. The primary caregivers of 35/46 children and adolescents (18 males, 17 females, mean age 11.5 years) sent back completed questionnaires, but only 27 subjects met inclusion criteria. According to the primary caregivers, none of these subjects showed mental retardation. Two probands (both males 9 and 16 years old) reached the cut-off of the MBAS whereas the results of the VSK did not indicate ASDs in any of the patients. The 9 year old boy could be examined personally and did not meet diagnostic criteria of ASD. ASDs might be not as frequent as reported in previous studies on patients with Moebius sequence, at least not in patients without mental retardation.


Squamous epithelial cancer in metaplastic pleura following extrapleural pneumothorax for pulmonary tuberculosis.
During the period 1947-1955, 148 patients underwent extrapleural pneumolysis for pulmonary tuberculosis in Stockholm City Chest Hospital at Söderby. In 121 tuberculosis healed following operation. Ten of these later developed pain and a feeling of tension on the operated side and were operated upon with evacuation of the extrapleural sac. In four of them a highly differentiated keratinizing aquamous cell carcinoma had developed. In addition, two more cases of carinomas of the same type operated on at other hospitals are described. Five of the six patients died of cancer. Squamous cell carcinoma occurring in metaplastic mesothelial cells has hitherto not been reported on and the phenomenon is discussed and compared with the more common scar cancers within lung tissue caused by damage from tuberculosis.


Interaction of male sensory cues and estradiol in the induction of estrus in the prairie vole.
In the prairie vole, estrus and ovulation are induced by stimulation from a male, which also increases the female's gonadal weight and serum estradiol level. It is not known whether the induction of receptivity is dependent solely on an endogenous increase in circulating estradiol or an interaction of increased estradiol and male sensory stimulation. Using a dose response paradigm, we examined if a dose of estradiol within physiological range was sufficient to induce receptivity. We also examined if extended male contact could induce receptivity in ovariectomized females tested either without estradiol replacement or with a subthreshold dose of estradiol. We found that elevating blood levels of estradiol to those found during estrus was sufficient to induce sexual receptivity; male contact was not necessary. Extended male cohabitation did induce estrus in ovariectomized females treated with a subthreshold dose of estradiol, a dose which without male contact did not support sexual receptivity. In these same females, the extended male contact elevated circulating estradiol levels; the source of the estradiol is unknown.


Uridine correlates with the concentration of fructosamine and HbA1c in children with type 1 diabetes.
Treating uridine as a product of UTP degradation and hypoxanthine as a degradation product of ATP, we assessed the concentration of uridine and hypoxanthine in the blood of children with newly diagnosed type 1 diabetes. We also sought to define the relationship between indicators of the degree of metabolic control of diabetes (fructosamine, HbA1c) and the concentration of the tested catabolites. This study was carried out on 33 children aged 12.26 ± 4.49 with newly diagnosed type 1 diabetes during their first hospitalization. The concentration of uridine and hypoxanthine was determined by high-performance liquid chromatography (HPLC). The results showed significantly elevated levels of hypoxanthine and uridine in the blood. We further show that blood uridine level is associated with purine metabolism and hyperglycaemia, and we demonstrate a significant positive correlation between the concentration of uridine and (i) the percentage of HbA1c and (ii) fructosamine levels, which indicate the role of hyperglycaemia in the pathogenesis of pyrimidine nucleotide metabolism in type 1 diabetes prior to diagnosis. The results confirm the existence of a relationship between the degree of metabolic control of diabetes and pyrimidine metabolism. Presumably, the analysis of uridine could be used as an adjunct marker of the severity of diabetic complications in newly diagnosed patients.


Ultrasonic-assisted precolumn derivatization-HPLC determination of acrylamide formed in Radix Asparagi during heating process.
An ultrasonic-assisted precolumn derivatization-HPLC method was established and validated for the determination of acrylamide formed in traditional Chinese herb Radix Asparagi during heating process. This method entails extraction with water, ultrasonic-assisted derivatization with 2-mercaptobenzoic acid. The final extracted acrylamide derivative was separated on C(18) column by using a mixture of acetonitrile and acetic acid (1 gL(-1) water solution) (20:80, v/v) as mobile phase. The flow rate was 0.7 mL min(-1) and the detection wavelength was set at 238 nm. Factors influencing the derivative reaction were evaluated and the optimum derivatization conditions were as follows: molar ratio of derivative reagent to acrylamide was 35:1, pH 8-12, ultrasonic-assisted reaction time was 100 min. The calibration curve of acrylamide showed good linearity in the range of 0.015-4.5 microg mL(-1) with correlation coefficient of 0.9999. The limit of detection was estimated to be 25 microg kg(-1) based on the signal-to-noise ratio of 3 recorded at 238 nm. Recovery of acrylamide from the sample was 106.6+/-6.6%. Relative standard deviation of five duplicate determinations for the same sample solution was 1.59%.


Model based analysis of carbon fluxes within microalgae-bacteria flocs using respirometric-titrimetric data.
With the emerging need of nutrient recycling in resource recovery facilities, the use of microalgae-bacteria flocs has received considerable attention in the past few years. However, although the main biological processes are already known, the complex interactions occurring between algae and bacteria are not fully understood. In this work, a combined respirometric-titrimetric unit was used to assess the microorganisms' kinetics within microalgae-bacteria flocs under different growth regimes (i.e. photoautotrophic, heterotrophic and mixotrophic) and different ratios of inorganic (IC) to organic carbon (OC) (IC:OC-ratios). Using this respirometric-titrimetric data, a new model was developed, calibrated and successfully validated. The model takes into account the heterotrophic growth of bacteria, the photoautotrophic, heterotrophic and mixotrophic growth of algae and the production and consumption of extracellular polymeric substances (EPS) by both bacteria and algae. As such, the model can be used for detailed analysis of the carbon fluxes within microalgae-bacteria flocs in an efficient way. Model analysis revealed the high importance of the EPS regulatory mechanism. Firstly, under heterotrophic growth conditions, OC-uptake occurred during the first 10-15 min. This was linked with internal OC storage (49% of added OC) and EPS production (40%), as such providing carbon reserves which can be consumed during famine conditions. Moreover, the algae were able to compete with bacteria for OC. Secondly, under photoautotrophic conditions, algae used the added IC to grow (57% of added IC) and to produce EPS (29%), which consecutively stimulated heterotrophic bacteria growth (20%). Finally, under mixotrophic conditions, low IC:OC-ratios resulted in an extensive OC-storage and EPS production (50% of added C) and an enhanced microalgal CO2 reuse, resulting in an increased algal growth of up to 29%.


Effects of atropine on the release of newly synthesized acetylcholine from rat striatal slices at various concentrations of calcium ions.
The release of acetylcholine (ACh) from brain tissue is known to be inhibited by muscarinic autoreceptors on cholinergic nerve terminals but the mechanism of the inhibition is not understood. Atropine brings about an increase of ACh release by removing the inhibitory action of autoreceptors. We investigated whether the effect of atropine on the release of [14C]ACh newly synthesized during incubations from [U-14C] glucose depends on the concentration of Ca2+ in the medium. In rat striatal slices incubated in the presence of an inhibitor of cholinesterases and of 30 mmol/l K+, significant increases in the release of [14C]ACh elicited by atropine were only observed during incubations with very low concentrations of Ca2+. This finding supports the view that the activation of presynaptic muscarinic autoreceptors in the brain affects the release of ACh by reducing the availability of Ca2+ that is required for transmitter liberation.


The closure of a major psychiatric hospital. Reactions of the psychogeriatric nursing staff.
A political decision to decentralize psychiatric care in a province in Sweden was arrived at in October 1984, leading to the closing down of the only psychiatric hospital in the area (290,000 inh.). The hospital is of the traditional type with 490 beds and 1,294 staff. It has units for long-term care, short-term care and rehabilitation, as well as a unit for research and education. The psychogeriatric patients are to be transferred to their home districts. All of the psychogeriatric staff have been guaranteed new jobs under the auspices of the County Council's medical services. This study is concerned with the nursing staff's reactions to the decentralization and the kind of problems they were faced with. A questionnaire was sent to all nursing staff, and for the psychogeriatric unit (199 patients) the personnel turnover was also registered. The results show that the greatest problems for the nursing staff were the splitting up of their working teams and having to establish relations with new colleagues. They were also worried about longer and more expensive journeys to new places of work. Most of the nursing staff considered the information given about the consequences of the political decision very poor. More than half of the nursing staff (54%) thought the patients would be provided with better care by decentralized psychiatric health services. Many stated that the decision had affected them so that their interest in further education (37%) and in working in a new type of psychiatric care (43%) had increased.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduction of central line infections in Veterans Administration intensive care units: an observational cohort using a central infrastructure to support learning and improvement.
Elimination of hospital-acquired infections is an important patient safety goal. All 174 medical, cardiac, surgical and mixed Veterans Administration (VA) intensive care units (ICUs). A centralised infrastructure (Inpatient Evaluation Center (IPEC)) supported the practice bundle implementation (handwashing, maximal barriers, chlorhexidinegluconate site disinfection, avoidance of femoral catheterisation and timely removal) to reduce central line-associated bloodstream infections (CLABSI). Support included recruiting leadership, benchmarked feedback, learning tools and selective mentoring. Sites recorded the number of CLABSI, line days and audit results of bundle compliance on a secure website. CLABSI rates between years were compared with incidence rate ratios (IRRs) from a Poisson regression and with National Healthcare Safety Network referent rates (standardised infection ratio (SIR)). Pearson's correlation coefficient compared bundle adherence with CLABSI rates. Semi-structured interviews with teams struggling to reduce CLABSI identified common themes. From 2006 to 2009, CLABSI rates fell (3.8-1.8/1000 line days; p<0.01); as did IRR (2007; 0.83 (95% CI 0.73 to 0.94), 2008; 0.65 (95% CI 0.56 to 0.76), 2009; 0.47 (95% CI 0.40 to 0.55)). Bundle adherence and CLABSI rates showed strong correlation (r = 0.81). VA CLABSI SIR, January to June 2009, was 0.76 (95% CI 0.69 to 0.90), and for all FY2009 0.88 (95% CI 0.80 to 0.97). Struggling sites lacked a functional team, forcing functions and feedback systems. Capitalising on a large healthcare system, VA IPEC used strategies applicable to non-federal healthcare systems and communities. Such tactics included measurement through information technology, leadership, learning tools and mentoring.


Pharmacokinetics of oral cyclosporin A (Sandimmun) in healthy subjects.
Extensive pharmacokinetic (PK) profiles after oral dosing of 300 mg cyclosporin A (CsA) were determined in whole blood by radioimmunoassay (RIA) in 14 healthy male volunteers, using two-compartment models with either first order (M1) or zero order (M0) absorption. According to zero order absorption the mean of the following PK parameters was determined: terminal half-life = 12.1 +/- 5.0 h, apparent volume of distribution at steady-state = 5.6 +/- 2.11 X kg-1, apparent clearance = 0.51 +/- 0.11 l X h-1 X kg-1. The time lag between drug ingestion and first blood level was short, 0.38 +/- 0.11 h. Drug absorption lasted for 2.8 +/- 1.6 h. The end of absorption was indicated in each individual by a sharp drop in blood levels. The observations support the assumption that CsA is absorbed in the upper part of the small intestine with a clear-cut termination (absorption window). This assumption may explain the high degree of variability in the bioavailability of CsA.


Chemical Composition of Magonia pubescens Essential Oils and Gamma-Radiation Effects on Its Constituents and Cytotoxic Activity in Leukemia and Breast Cancer Model.
Magonia pubescens A. St.-Hil. is a Brazilian species often used in ethnopharmacology for wound and pain healing and seborrhea treatment. For the first time, essential oils (EOs) obtained from M. pubescens inflorescences were studied. The plant materials (Montes Claros, Brazil, 2018) were submitted to different gamma-radiation doses and their chemical compositions were analyzed by GC/MS and GC-FID. The cytotoxic activity of the EOs was evaluated against K562 and MDA-MB-231 cancer cell lines. A total of 30 components were identified, being 24 compounds detected for the first time in M. pubescens. The main obtained components were hotrienol (35.9 %), cis-linalool oxide (17.0 %) and trans-linalool oxide (10.2 %). The chemical composition of the EO was slightly affected by the applied radiation doses. Irradiated and non-irradiated EOs showed cytotoxic activity against both cell lines and the non-irradiated EO sample was the most active against the K562 cell lines (IC50 =22.10±1.98).


Supercutaneous locking compression plate in the treatment of infected non-union and open fracture of the leg.
Salvage of infected tibia and fibula non-union and severe open fractures is challenging and often requires staged treatment. We describe all cases that underwent supercutaneous plating of the leg as external fixation technique and assessed union rate, time to union, rate of infection clearance, and patient-reported outcome measures. This is a retrospective cohort study from a single level 1 trauma center. We included 19 patients that underwent supercutaneous plating-locking compression plate applied as external fixator-of the leg. Indications were: infected non-union of a pilon, cruris, or ankle fracture (n = 13); post-traumatic fistula draining osteomyelitis of the tibia (n = 3); infected mal-reduced subacute cruris fracture (n = 1); acute open pilon fracture (n = 1); and acute open cruris fracture (n = 1). Outcome measures were: union, time to union, infection clearance, the 36-item Short Form (SF-36) physical component summary scale (PCS) and mental component summary scale (MCS), and NRS pain scores. Union was achieved in 88% of the patients after a median of 279 days [interquartile range (IQR) 154-440]. Infection clearance was achieved in 94% of the patients. The PCS (median 51, IQR 46-56, p = 0.903) and MCS (median 57, IQR 50-60, p = 0.241) do not differ from normative population values. NRS Pain score at rest was 0 on average (IQR 0-1), 2 on average when walking (IQR 0-4), and 1 on average when climbing stairs (IQR 0-2). Supercutaneous plating is a simple and reliable technical trick to bridge and stabilize a nonunion or fracture site while clearing an infection and have soft-tissues heal before subsequent definitive (internal)fixation and/or cancellous bone grafting. Reasonable union and infection clearance rates are achieved, and good functional outcome can generally be expected. Therapeutic level III.


Liposomes as biocompatible and smart delivery systems - the current state.
Liposomes are self-assembled, closed spherical systems with a lipid bilayer, composed of i.a. one or more amphiphilic phospholipids, and widely used in the pharmaceutical, cosmetic and food industries. Whether composed of natural or synthetic lipids, liposomal vehicles are biocompatible, biodegradable, non-toxic and non-immunogenic carriers of active substances, both hydrophilic and hydrophobic by nature. Progress in liposome technology, modulation of the lipid composition, size and charge of the vesicle and modification of their surface has enabled the shift from conventional vesicles to "smart-generation" liposomes. Currently, liposomal vesicles are applied to improve the therapeutic effect of active substances and to provide the controlled release of drugs, thus prolonging the biological half-life or reducing toxicity of the actives. This paper reviews the recent process developments in liposomal systems, especially over the past decade. The methods of the systems preparation, characterisation and application are described. Additionally, methods of liposome surface modification and the mechanism of active substances delivery are outlined.


Short- and long-term results of colonoscopic polypectomy in children.
Eighty-four colorectal polyps of up to 3.3 cm in diameter were removed with the diathermy snare during 48 colonoscopies on 42 children, aged 2 to 18 years (mean, 7.4 years). Most polyps were juvenile and the majority were located in the sigmoid colon (55%) or rectum (37%). No complications related to medication, colonoscopy, or snare polypectomy were observed. The two presenting symptoms, rectal bleeding and anemia, disappeared soon after polypectomy in all but one patient with adenomatous polyposis coli, subsequently operated upon. Follow-up examinations, including total colonoscopy, performed 4 months to 7 years (mean, 25 months) later did not reveal abnormalities in any of the 37 children whose previously removed polyps were juvenile. The authors conclude that endoscopic snare polypectomy is an effective and safe treatment for colorectal polyps in the pediatric age group.


A Simple Preheating-Pyrolysis Strategy Leading to Superior Oxygen Reduction Reaction Activity in Fe-N/Carbon Black.
Maintaining the high catalytic activity of the oxygen reduction reaction (ORR) while reducing costs is a long-standing effort to promote the application of polymer electrolyte fuel cells. Here, the binding of nitrogen-containing ligands and carbon black is enhanced by controlling the pyrolysis conditions of a FeSO4 , 1,10-phenanthroline (phen), carbon black mixture, which significantly improves the ORR catalytic activity of the pyrolysis products. Preheating is proposed as a process improvement method using a heat treatment at a temperature between the melting and boiling points of phen before high-temperature pyrolysis, which achieves an effective combination of phen and carbon black, and enhances the interaction between phen and ferrous ions. This method substantially increases the number of FeNx active centers in the pyrolysis product, resulting in an impressive Fe-N/C catalyst with half-wave potential (E1/2 ) up to 0.93 V and a diffusion-limited current density (jL ) of 5.9 mA cm-2 and no obvious decay after 20 000 cyclic voltammetry cycles in 0.1 m KOH, which are all among the best-reported data known to date. The interaction between the ratio of Fe/phen and the pyrolysis conditions is also investigated. Under the right conditions, cheap raw materials can also generate highly catalytically active sites.


The higher plant plastid NAD(P)H dehydrogenase-like complex (NDH) is a high efficiency proton pump that increases ATP production by cyclic electron flow.
Cyclic electron flow around photosystem I (CEF) is critical for balancing the photosynthetic energy budget of the chloroplast by generating ATP without net production of NADPH. We demonstrate that the chloroplast NADPH dehydrogenase complex, a homolog to respiratory Complex I, pumps approximately two protons from the chloroplast stroma to the lumen per electron transferred from ferredoxin to plastoquinone, effectively increasing the efficiency of ATP production via CEF by 2-fold compared with CEF pathways involving non-proton-pumping plastoquinone reductases. By virtue of this proton-pumping stoichiometry, we hypothesize that NADPH dehydrogenase not only efficiently contributes to ATP production but operates near thermodynamic reversibility, with potentially important consequences for remediating mismatches in the thylakoid energy budget.


Antioxidant, anti-inflammatory, and wound healing effects of topical silver-doped zinc oxide and silver oxide nanocomposites.
Silver nanoparticles (Ag-NPs), silver oxide nanoparticles (AgO-NPs), and zinc oxide nanoparticles (ZnO-NPs) have healing, antibacterial, and antioxidant properties. Furthermore, Ag-NPs and ZnO-NPs also have anti-inflammatory properties. In this study, we synthesized a nanocomposite using Ag-ZnO and AgO-NPs (Ag-ZnO/AgO NPs). The structural and morphological properties of nanocrystals and nanocomposite were investigated by X-ray diffraction and scanning electronics microscopic. The wurtzite crystalline structure of Ag-ZnO and two morphologies for the nanocomposite (nanorods and nanoplatelets) were determined. Topical treatment with 1% Ag-ZnO/AgO NPs was compared to untreated wounds (control group). Wounds were induced in the dorsal region of BALB/c mice and evaluated after 3, 7, 14, and 21 days of treatment. The nanocomposite demonstrated anti-inflammatory and antioxidant capacities. In addition, wounds treated with Ag-ZnO/AgO NPs showed accelerated closure, non-cytotoxicity, especially on keratinocytes and collagen deposition, and increased metalloproteinases 2 and 9 activity. The nanocomposite improved healing by reducing the inflammatory process, protecting tissues from damage caused by free radicals, and increasing collagen deposition in the extracellular matrix. These characteristics contributed to the accelerated wound closure process. Thus, Ag-ZnO/AgO NPs show potential for can be a strategy for topical use in formulations of new drugs to treat wounds.


Effects of increased plastic film residues on soil properties and crop productivity in agro-ecosystem.
Intensive use of low-density polyethylene (LDPE) plastic films in agro-ecosystems has raised considerable concerns due to the increasing film residues in soils. It is unclear how the increased film residues affect soil properties and crop productivity and whether biodegradable (Bio) film can substitute LDPE. To address the issue, we designed a landfill experiment with different addition levels of plastic residue into soils of maize (Zea mays L.) field from 2018 to 2019. Six treatments were arranged as PMT1-T3/BioT1-T3, representing the low, medium, and high-level application of LDPE / Bio film fragments, with no residual film, applied as CK. Results show that, soil bulk density was significantly increased from 1.19 to 1.31 g/cm3 regardless of residue types. In contrast, soil porosity was lowered from 58.03% in CK to 57.36% in Bio and 56.12% in LDPE significantly (P < 0.05). Increased residues improved soil nitrogen level and lowered the C/N ratio significantly. Also, it decreased microbial biomass C and N levels but with no change in C/N (P < 0.05). Maize yield and WUE decreased, while soil water storage increased significantly. LDPE residues affected soil properties and productivity partly lower than Bio ones did, but the negative effects of them were similar in the maize field.


Pulsed dye laser double-pass treatment of patients with resistant capillary malformations.
The pulsed dye laser is an effective and established treatment for port-wine stains and has become the generally accepted standard of care. However, in many cases, complete clearance cannot be achieved as a significant proportion of lesions become resistant to treatment. Multiple passes or pulse-stacking techniques have been used to improve the extent and rate of fading, but concerns over increased adverse effects have limited this clinical approach. In this work, a double-pass technique with the pulsed dye laser has been described, which may allow for increased depth of vascular injury, greater efficacy, and an acceptable risk profile. Our aim was to determine the efficacy and the rate of side-effects for a double-pass protocol with a pulsed dye laser (PDL) to treat patients previously treated with PDL and/or other laser modalities. A retrospective chart review was conducted of 26 patients treated with a minimum of three double-pass treatments alone, or in combination, with single pass conventional PDL. Almost half of the patients (n = 12) showed either a moderate or significant improvement in fading compared to pre-treatment photographs with the double-pass technique. In a further 12 patients, there was a mild improvement. In two patients, there was no change. Sixteen patients developed mild side-effects: blisters (n = 5), dry scabs (n = 11) and transient hyperpigmentation (n = 4). This preliminary experience suggests that a double-pass technique at defined intervals between the first and second treatment with PDL can further lighten some port-wine stains, which are resistant to conventional single-pass treatments. This technique may be a useful addition to the laser treatment of PWS and deserves further scrutiny with randomized prospective studies and histological analysis to confirm the increased depth of vascular injury.


Blocking effect of salvianolic acid A on calcium channels in isolated rat ventricular myocytes.
To study the effect of salvianolic acid A (SAA) on L-type calcium current (I-CaL) in isolated ventricular myocytes of Sprague-Dawley rats. SAA powder was dissolved in normal Tyrode's solution to reach the concentrations of 1, 10, 100, and 1000 μmol/L. The traditional whole-cell patch-clamp recording technique was employed to evaluate the effects of SAA on I-CaL in single ventricular myocytes which were prepared by Langendorff perfusion apparatus from Sprague-Dawley rats. SAA (1, 10, 100, and 1000 μmol/L) inhibited I-CaL peak value by 16.23%±1.3% (n=6, P<0.05), 22.9%±3.6% (n=6, P<0.05), 53.4%±3.0% (n=8, P<0.01), and 62.26%±2.9% (n=6, P<0.01), respectively. SAA reversibly inhibited I-CaL in a dose-dependent manner and with a half-blocking concentration (IC(50)) of 38.3 μmol/L. SAA at 100 μmol/L elevated the I-V curve obviously, and shifted the half-active voltage (V(0.5)) from (-15.78±0.86) mV to (-11.24 ±0.77) mV (n=6, P<0.05) and the slope (K) from 5.33±0.74 to 4.35±0.74 (n=6, P>0.05). However, it did not alter the shapes of I-V curve, steady-state inactivation curve, or recovery from inactivation curve. SAA inhibited I-CaL in a dose-dependent manner. It shifted the steady-state activation curve to a more positive voltage, which indicated that the drug affected the activated state of calcium channels, and suggested that the Ca(2+) antagonistic effect of SAA be beneficial in the treatment of myocardial ischemia reperfusion injury.


Standardized wording to improve efficiency and clarity of GRADE EtD frameworks in health guidelines.
Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision (EtDs) frameworks are increasingly applied by health guideline developers to improve the use of evidence and transparency of health recommendations. Typically, EtDs include 12 criteria but these are flexible and EtDs have been adapted to different types of health decisions. However, developers of health recommendations struggle with the content that they should include in the EtD. The goal of this work was to provide a standardized template that facilitate the development of GRADE EtDs in health guidelines and examples for practical training. We began by establishing the need for standardized wording templates in 10 American Society of Hematology guidelines with over 250 recommendations. We drafted template wording, and examples, and sought iterative feedback from methodologists and guideline panels in this guideline and two additional guidelines. We generated templates for all EtD criteria describing the type of research evidence considered, ideally based on systematic reviews, using standardized reporting of effect size, integrating the certainty of evidence and additional considerations. We also produced templates to inform the completion of the EtD conclusions section that includes recommendations, justification, implementation considerations, monitoring and evaluation and research priorities. We developed a pragmatic and useful tool to support clarity, transparency, and efficiency of the guideline EtD process.


The influence of depression on treatment for methamphetamine use.
To determine whether the presence of comorbid depression influences response to psychological treatment for methamphetamine use. Randomised controlled clinical trial. Our study was conducted between 2001 and 2005 at two sites in Australia: the Hunter Region of New South Wales and the city of Brisbane, Queensland. The 214 participants, who were all using methamphetamine at least once a week in the month prior to the study, were self-referred or referred from health services or drug and alcohol clinical services. Participants were divided into two groups based on whether or not they had depressive symptoms at baseline. The control group received only a self-help booklet; the two treatment groups received either two or four counselling sessions involving cognitive behaviour therapy and motivational interviewing techniques to manage methamphetamine use. Changes in methamphetamine use and depression at 5 weeks and 6 months after baseline. Over 70% of participants met criteria for depression at baseline, and depression was associated with significantly greater severity of methamphetamine use and related issues. Benzodiazepine use was significantly higher among depressed than non-depressed participants. Reductions in methamphetamine use between baseline and 5 weeks were independently predicted by comorbid depression, in favour of increased change among those with baseline depression. Depressed participants who received three or four counselling sessions showed a significant reduction in depression at 5 weeks. However, reductions in methamphetamine use and depression compared with baseline were no longer evident at 6 months. Over the short term, comorbid depression did not negatively affect response to treatment, with some evidence of a dose-response treatment effect for reduction in depression. This was not maintained at 6 months, indicating that methamphetamine-focused treatment may not enable people with comorbid depression to make sustained improvement at the level of their counterparts without depression. ACTRN12611000355976.


Determination of lesion to normal bone uptake ratios of skeletal radiopharmaceuticals by QARG (quantitative autoradiography).
An animal model was developed to determine the ratio of uptake of different bone seeking radiotracers in skeletal lesions relative to normal bone in rats by dual tracer quantitative autoradiography (QARG). The lesion to normal bone uptake ratios (L/NB ratios) of 99mTc-MDP, 99mTc-HDP and 99mTc-DMAD were compared using 153Sm-EDTMP as an internal standard. The results from these studies demonstrated that the L/NB ratio of 99mTc-DMAD was an average of 54 and 71% higher than 99mTc-MDP and 99mTc-HDP, respectively and 79% higher than measured for 153Sm-EDTMP.


Corrosion of tungsten microelectrodes used in neural recording applications.
In neuroprosthetic applications, long-term electrode viability is necessary for robust recording of the activity of neural populations used for generating communication and control signals. The corrosion of tungsten microwire electrodes used for intracortical recording applications was analyzed in a controlled bench-top study and compared to the corrosion of tungsten microwires used in an in vivo study. Two electrolytes were investigated for the bench-top electrochemical analysis: 0.9% phosphate buffered saline (PBS) and 0.9% PBS containing 30 mM of hydrogen peroxide. The oxidation and reduction reactions responsible for corrosion were found by measurement of the open circuit potential and analysis of Pourbaix diagrams. Dissolution of tungsten to form the tungstic ion was found to be the corrosion mechanism. The corrosion rate was estimated from the polarization resistance, which was extrapolated from the electrochemical impedance spectroscopy data. The results show that tungsten microwires in an electrolyte of PBS have a corrosion rate of 300-700 μm/yr. The corrosion rate for tungsten microwires in an electrolyte containing PBS and 30 mM H₂O₂ is accelerated to 10,000-20,000 μm/yr. The corrosion rate was found to be controlled by the concentration of the reacting species in the cathodic reaction (e.g. O₂ and H₂O₂). The in vivo corrosion rate, averaged over the duration of implantation, was estimated to be 100 μm/yr. The reduced in vivo corrosion rate as compared to the bench-top rate is attributed to decreased rate of oxygen diffusion caused by the presence of a biological film and a reduced concentration of available oxygen in the brain.


Serum reactions. An analysis of commercial antivenoms and the possible role of anticomplementary activity in de-novo reactions to antivenoms and antitoxins.
Infusion of concentrated heterologous serum proteins may precipitate severe reactions in humans. Some of these reactions are not due to a preexisting hypersensitivity to the foreign protein, but rather to the strongly anticomplementary activity (ACA) of the infused protein. The latter mechanism could account for the occasional anaphylactoid reaction seen in a patient who has had no known previous exposure to the foreign protein. Similarly, it could account for the patient who fails to react to a preliminary subcutaneous trial dose, but then collapses when he is infused later with the same preparation. Nine commercial antivenoms from nine countries were examined and most were found to have high levels of anticomplementary activity. Considerable variation was found in both the immunochemical properties and the anticomplementary activity of these antivenoms. Antitoxins of equine origin to the toxins of diphtheria, tetanus and gas gangrene were also found to have high anticomplementary activity. Because of this activity these preparations should always be diluted and infused slowly. Lack of reaction to a test dose will never guarantee an uneventful infusion, and thus all infusions of heterologous immunoglobulin should be undertaken with the greatest caution and vigilance.


Dysregulated by stigma: Cortisol responses to repeated psychosocial stress in gay and heterosexual men.
Research on pathways linking stigma with health inequalities affecting sexual minority populations, focused predominantly on exploring the hypothalamic-pituitary-adrenocortical (HPA) dysregulation profiles associated with chronic stress. One of such profiles reflecting a state of increased susceptibility to disease, and not yet studied among sexual minority individuals, is impaired habituation to repeated stress of the same type. In this study we explored whether sexual identity modulates endocrine stress responses and stress responses habituation in healthy heterosexual and gay men. We also explored the associations between perceived sexual minority stigma and cortisol response to stress in the latter group. Gay (N = 49) and heterosexual (N = 40) men, aged 24.4 years, were confronted twice with the Trier Social Stress Test and provided 5 salivary cortisol samples for each of the two testing sessions. A multilevel mixed-effects approach was used to model the cortisol curve throughout the two-day procedure. Habituation to repeated stress was conceptualized as the decrease in the total cortisol levels as well as the change in the cortisol curvilinearity between the first and the second testing session. Gay participants were characterized by significantly higher cortisol levels throughout both laboratory visits. Their cortisol levels were also predicted by perceived rejection from family due to minority sexual identity, and stigma-related vicarious trauma. Although neither group showed habituation defined as the decrease in cortisol level, the shape of the cortisol curve changed between both visits only in the heterosexual participants. Increased cortisol levels observed in gay men are predicted by minority stressors. Combined with non-habituation, the upregulation of the HPA axis may constitute a physiological pathway linking stigma to adverse health outcomes.


4-Hydroxy-pyran-2-one and 3-hydroxy-N-methyl-2-oxindole derivatives of Salinispora arenicola from Brazilian marine sediments.
Three new 3-hydroxy-N-methyl-2-oxindole (1 and 2) and 4-hydroxy-pyran-2-one (3) derivatives, along with the known 3-hydroxy-N-methyl-2-oxindole (4) and 6-methoxy-N-methylisatin (5) were isolated from a marine Salinispora arenicola strain from sediments of the St. Peter and St. Paul Archipelago, Brazil. The structures of the new compounds were elucidated by a combination of spectroscopic (1D and 2D NMR and HR-ESIMS) data, including single-crystal X-ray diffraction analysis for 2 and 3. Compounds 1 to 5 were assayed for their antimicrobial properties, but only 4 and 5 were active against Enterococcus faecalis with MIC value of 15.6 μg/mL.


Evidence for two pitch encoding mechanisms using a selective auditory training paradigm.
The neural mechanisms underlying the perception of pitch, a sensory attribute of paramount importance in hearing, have been a matter of debate for over a century. A question currently at the heart of the debate is whether the pitch of all harmonic complex tones can be determined by the auditory system's using a single mechanism, or whether two different neural mechanisms are involved, depending on the stimulus conditions. When the harmonics are widely spaced, as is the case at high fundamental frequencies (FOs), and/or when the frequencies of the harmonics are low, the frequency components of the sound fall in different peripheral auditory channels and are then "resolved" by the peripheral auditory system. In contrast, at low F0s, or when the harmonics are high in frequency, several harmonics interact within the passbands of the same auditory filters, being thus "unresolved" by the peripheral auditory system. The idea that more than one mechanism mediates the encoding of pitch depending on the resolvability status of the harmonics was investigated here by testing for transfer of learning in F0 discrimination between different stimulus conditions involving either resolved or unresolved harmonics after specific training in one of these conditions. The results, which show some resolvability-specificity of F0-discrimination learning, support the hypothesis that two different underlying mechanisms mediate the encoding of the F0 of resolved and unresolved harmonics.


Management of atraumatic shoulder instability in physiotherapy (MASIP): a survey of physiotherapy practice.
The impact of atraumatic shoulder instability (ASI) on patients can be extensive, its management complex, with a biopsychosocial approach recommended. Currently how physiotherapists manage ASI is unknown or the extent to which current clinical practice aligns with existing evidence. At the time of this study no national guidelines or consensus to direct practice existed. A cross-sectional electronic survey was distributed between July-September 2018, targeting UK-based physiotherapists managing shoulder pathology. Respondents were invited to describe their management of ASI, and rate their awareness and utilisation of various treatment techniques on a Likert-scale; median and interquartile ranges were calculated. Free text survey items were analysed using quantitative content analysis (QCA) to identify codes and categories. Means and percentages were calculated to summarise QCA and descriptive data. Valid survey responses were analysed (n = 135). Respondents had between 2 and 39 years of physiotherapy experience (mean = 13.9 years); the majority (71.1 %) reported that ASI made up < 10 % of their caseload. Only 22.9 % (n = 31/135) of respondents reported feeling 'very confident' in managing ASI; the majority feeling 'somewhat confident' (70.4 %, n = 95/135) or 'not confident' (6.7 %, n = 9/135). The majority of respondents (59.3 %) used an ASI classification system, > 90 % citing the Stanmore Classification. Physiotherapists adapted their management according to clinical presentation, responding to differing biopsychosocial needs of the patient scenario. Most respondents (> 80 %) did not use a protocol to guide their management. Exercise was the most utilised management approach for ASI, followed by education; novel treatment strategies, including cortical rehabilitation, were also reported. Findings indicate physiotherapists utilise a wide range of treatment strategies and respond to biopsychosocial cues when managing patients with ASI. The majority reported not being very confident in managing this condition, however only a minority use rehabilitation protocols to support their management. Some interventions that respondents reported using lacked evidence to support their use in ASI management and further research regarding effectiveness is required. Guidelines have been published since this survey; the impact of these will need evaluating to determine their effectiveness in the future.


How old is old for implant therapy in terms of early implant losses?
To assess, retrospectively, whether older age has an impact on implant osseointegration when compared with younger age. All patients ≥65 years old at implant installation, in an university setting over a time-period of 11.5 years, with complete anamnestic data and follow-up until prosthetic restoration were included, and any early implant loss (EIL; i.e. lack of osseointegration prior to or at the time-point of prosthetic restoration) was recorded. Further, one implant, from each of the elderly patients, was attempted matched to one implant in a younger patient (35 to <55 years old at implant installation) from the same clinic based on (a) gender, (b) implant region, (c) smoking status and (d) bone grafting prior to/simultaneously with implant installation. The potential impact of various local and systemic factors on EIL in the entire elderly population, and in the matched elderly and younger patient group was statistically assessed. Four hundred forty-four patients ≥65 years old (range 65.1-91.3; 56.8% female) receiving 1,517 implants were identified; 10 patients had one EIL each (implant/patient level: 0.66/2.25%). Splitting this patient cohort additionally into four age groups [65-69.9 (n = 213), 70-74.9 (n = 111), 75-79.9 (n = 80) and ≥80 (n = 40)], EIL was on the implant level 0.41, 0.83, 0.34 and 2.26%, respectively, (p = .102) and on the patient level 1.41, 2.70, 1.25 and 7.50%, respectively, (p = .104); multilevel analysis showed weak evidence of association of increasing age with higher EIL rate (p = .090). Matching was possible in 347 cases, and 5 (1.44%) and 9 (2.59%) EIL in the elderly and younger patients, respectively, were observed (p = .280). EIL could not be associated with any systemic condition or medication intake. Elderly patients ≥65 years old presented a similarly low EIL rate as younger patients 35 to <55 years old, while patients ≥80 years old may have a slight tendency for a higher EIL rate. Hence, ageing does not seem to compromise osseointegration, and if at all, then only slightly and at a later stage of life.


Size and density dependent sedimentation analysis of advanced nanoparticle systems.
Various functional colloidal systems like polymer grafted inorganic particles, complex multi-component mixtures, organic-inorganic hybrid particles, inorganic-inorganic core-shell particles and swellable particles were characterized by sedimentation coefficient analysis in analytical ultracentrifuge owing to the accurate correlation of the sedimentation coefficient with variations in size and density of the materials. The sedimentation coefficient is absolute in nature and does not require any property information beforehand. By following the changes in the sedimentation coefficient and its distribution, it could be established if the polymer grafting on the surface of the inorganic particles took place or if the organic-inorganic or inorganic-inorganic hybrid was formed or if the particles were strongly crosslinked or swellable. The complex particle mixtures were also quantified for the number of components contained in them and their exact amounts by following the sedimentation coefficient distributions.


Exploratory RNA-seq analysis in healthy subjects reveals vulnerability to viral infections during a 12- month period of isolation and confinement.
Exposure to stressful environments weakens immunity evidenced by a detectable reactivation of dormant viruses. The mechanism behind this observation remains unclear. We performed next generation sequencing from RNA extracted from blood samples of 8 male subjects collected before, during and after a 12-month stay at the Antarctic station Concordia. RNA-seq data analysis was done using QIAGEN Ingenuity Pathway Analysis (IPA) software. Data revealed the inactivation of key immune functions such as chemotaxis and leukocyte recruitment which persisted after return. Next to the activation of the stress response eIF2 pathway, interferon signaling was predicted inactivated due to a downregulation of 14 downstream genes involved in antiviral immunity. Among them, the interferon stimulated genes (ISGs) IFITM2 and 3 as well as IFIT3 exhibited the strongest fold changes and IFIT3 remained downregulated even after return. Impairment of antiviral immunity in winter-over crew can be explained by the downregulation of a battery of ISGs.


Clinical and epidemiological features of patients colonised by different types of carbapenemase-producing Enterobacterales.
The aim of this study was to compare the epidemiological and clinical characteristics of hospitalised patients colonised or infected by different types of carbapenemase-producing Enterobacterales (CPE) and to analyse the differences in their outcome. This was a retrospective comparative study of all patients colonised or infected by KPC-, NDM- or OXA-48-producing CPE who were hospitalised between 1 January 2018 and 30 June 2019. Microbiological, demographic and clinical data were collected from the patients' computerised files. One type of CPE was isolated in 285 patients, including 138 with KPC-CPE, 94 with NDM-CPE and 53 with OXA-48-CPE. The most common CPE types were KPC-Klebsiella pneumoniae (n = 47), OXA-48-Escherichia coli (n = 38), NDM-Enterobacter cloacae complex (n = 35) and KPC-Citrobacter freundii (n = 37). All three groups of patients were similar with respect to their risk factors, with the exception of previous exposure to antimicrobials that was more common in patients with KPC-CPE compared with OXA-48-CPE. Also, these patients were more likely to be co-infected by other multidrug-resistant bacteria. Clinical infections were more common in KPC-CPE than in OXA-48-CPE carriers (9.9% vs. 1.9%; P = 0.033). No other demographic or clinical variables were found to be correlated with clinical infections. Our study suggests that colonisation by OXA-48-CPE might be less risky compared with KPC-CPE.


Human Dickkopf-1 (huDKK1) protein: characterization of glycosylation and determination of disulfide linkages in the two cysteine-rich domains.
Human Dickkopf-1 (huDKK1), an inhibitor of the canonical Wnt-signaling pathway that has been implicated in bone metabolism and other diseases, was expressed in engineered Chinese hamster ovary cells and purified. HuDKK1 is biologically active in a TCF/lef-luciferase reporter gene assay and is able to bind LRP6 coreceptor. In SDS-PAGE, huDKK1 exhibits molecular weights of 27-28 K and 30 K at ∼ 1:9 ratio. By MALDI-MS analysis, the observed molecular weights of 27.4K and 29.5K indicate that the low molecular weight form may contain O-linked glycans while the high molecular weight form contains both N- and O-linked glycans. LC-MS/MS peptide mapping indicates that ∼ 92% of huDKK1 is glycosylated at Asn²²⁵ with three N-linked glycans composed of two biantennary forms with 1 and 2 sialic acid (23% and 60%, respectively), and one triantennary structure with 2 sialic acids (9%). HuDKK1 contains two O-linked glycans, GalNAc (sialic acid)-Gal-sialic acid (65%) and GalNAc-Gal[sialic acid] (30%), attached at Ser³⁰ as confirmed by β-elimination and targeted LC-MS/MS. The 10 intramolecular disulfide bonds at the N- and C-terminal cysteine-rich domains were elucidated by analyses including multiple proteolytic digestions, isolation and characterization of disulfide-containing peptides, and secondary digestion and characterization of selected disulfide-containing peptides. The five disulfide bonds within the huDKK1 N-terminal domain are unique to the DKK family proteins; there are no exact matches in disulfide positioning when compared to other known disulfide clusters. The five disulfide bonds assigned in the C-terminal domain show the expected homology with those found in colipase and other reported disulfide clusters.


Insights into the role of energy source in hormesis through diauxic growth of bacteria in mixed cultivation systems.
Hormesis, a biphasic dose-response relationship characterized by low-dose stimulation and high-dose inhibition, has been reported to be closely related to energy sources in cultivation systems. However, few studies have clarified how the energy source influences hormesis. In this study, based on the typical diauxic patterns of Escherichia coli (E. coli) growth in mixed cultivation media containing 1.0 g L-1 glucose and Luria-Bertani broth, the hormetic response of sulfonamides (SAs) to E. coli growth was investigated under this diauxic growth condition to thoroughly explain the close relationship between hormesis and energy sources in cultivation systems. The results indicated that SAs trigger time-dependent hormetic effects on E. coli growth over the span of 24 h, in which the biphasic dose-response occurs only during the second lag and the earlier stage of the second log phase of diauxic growth. Mechanistic exploration reveals that SAs can bind with adenylate cyclase at a low dose and dihydropteroate synthase at a high dose, respectively, activating the stimulatory and inhibitory signaling pathway to influence carbon catabolite repression in diauxic growth, which can interfere with the metabolism of tryptone and yeast extract to ultimately trigger hormesis. Moreover, the stimulatory and inhibitory effects of SAs are changed by the variations in metabolic status at different growth phases, resulting in time-dependent hormesis. This study proposes an induced mechanistic explanation of hormesis in mixed cultivation media based on the energy source's metabolism, which may not only reflect the generalizability of hormesis but also further promote its application in production activities.