Leflunomide in psoriatic arthritis.
Psoriatic arthritis (PsA) is a common unique form of inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown but 5-30% of the 2-3% of subjects of the general population affected with psoriasis are developing PsA. Typically PsA presents as an oligoarticular asymmetrical arthritis with predominant distal finger joint pattern, presence of spinal involvement enthesitis and dactylitis. There is evidence that T-cells play a key role in the immunopathology of PsA as well as Psoriasis. Leflunomide, a selective pyrimidine synthesis inhibitor with the property to inhibit T-cell activation and proliferation has been shown to improve both joint and skin symptoms in patients with PsA. Significant response rates have been observed for Psoriatic Arthritis Response Criteria (PsARC), modified ACR20 and PASI 50 after 24 weeks of treatment with 20 mg/d Leflunomide orally in a randomised, placebo controlled multicenter trial (TOPAS Study). Leflunomide treatment also improved quality of life and showed a favourable safety profile. It is therefore concluded that Leflunomide offers an efficacious, well tolerated, safe, and relatively inexpensive therapeutic option for the treatment of actively inflamed joints and psoriatic skin lesions in patients with PsA.


Increased transcription in hydroxyurea-treated root meristem cells of Vicia faba.
Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, prevents cells from progressing through S phase by depletion of deoxyribonucleoside triphosphates. Concurrently, disruption of DNA replication leads to double-strand DNA breaks. In root meristems of Vicia faba, HU triggers cell cycle arrest (preferentially in G1/S phase) and changes an overall metabolism by global activation of transcription both in the nucleoplasmic and nucleolar regions. High level of transcription is accompanied by an increase in the content of RNA polymerase II large subunit (POLR2A). Changes in transcription activation and POLR2A content correlate with posttranslational modifications of histones that play a role in opening up chromatin for transcription. Increase in the level of H4 Lys5 acetylation indicates that global activation of transcription following HU treatment depends on histone modifications.


One-pot synthesis of 2,2'-dipicolylamine derived highly photoluminescent nitrogen-doped carbon quantum dots for Fe3+ detection and fingermark detection.
The novel nitrogen-doped carbon quantum dots (N-CQDs) with high fluorescence quantum yield of 23.2% were successfully prepared via a simple hydrothermal reaction with citric acid and 2,2'-dipicolylamine. The as-prepared blue fluorescent N-CQDs had excellent water dispersibility, and showed pH and excitation-dependent emission behaviors. Noticeably, owing to the strong interaction between the residual 2,2'-dipicolylamine group on the surface of N-CQDs and Fe3+, the N-CQDs could be used as a turn off fluorescence probe for Fe3+ sensing through an electron transfer process. Moreover, the photoluminescent N-CQDs/poly(vinyl alcohol) film was further applied for latent fingermark imaging.


The effects of cued UCS rehearsal on the retention of differential 'fear' conditioning: an experimental analogue of the 'worry' process.
This study describes a human electrodermal conditioning experiment in which subjects were asked to mentally rehearse the UCS in a period following initial fear conditioning and prior to a test period involving nonreinforced presentations of the CS. Subjects who were asked to rehearse the UCS retained a differential fear CR during subsequent unreinforced presentations of the CS, but control subjects who were asked to rehearse either a nonaversive event or an aversive event unrelated to the UCS failed to retain the differential CR they had acquired during conditioning. These results suggest that rehearsal of the UCS during periods when CS and UCS are absent can aid the persistence of a fear CR in the absence of further pairings of the CS and UCS. It is argued that these effects can be explained in terms of the effect of UCS rehearsal on the strength and evaluation of the UCS representation. It is also suggested that cued UCS rehearsal might provide a useful procedure for understanding clinical incubation effects and for understanding how the 'worry' process contributes to the maintenance and incubation of fear.


The enhancer of the human transferrin gene is organized in two structural and functional domains.
We previously identified a 300-base pair long enhancer, located 3.6 kilobases upstream of the cap site of the human transferrin gene. A 5' deletion up to position 86 of the enhancer resulted in complete loss of the enhancer activity. Here we show by competition footprint analysis, gel retardation assays, and transient expression studies in hepatoma and HeLa cells that the enhancer is composed of two distinct structural and functional domains, A (nucleotides 1-86) and B (nucleotides 87-291). Each domain is a proto-enhancer of a different type. Domain A is a proto-enhancer that, when multimerized, is able by itself to stimulate transcription from the heterologous SV40 promoter, both in Hep3B and HeLa cells. It contains the octanucleotide TGTTTGCT sequence and is the binding site of two liver-specific nuclear factors and of a different HeLa nuclear factor. Domain B contains four binding sites interacting with several liver nuclear proteins. In order to bind, any of these proteins requires the presence of all the others. This domain is able to block the activity of a downstream negative element, but it has no enhancer activity by itself. In the presence of the transferrin promoter, full enhancer activity requires the association of the two domains A and B.


Quantitative visual pathway abnormalities predict visual field defects in patients with pituitary adenomas: a diffusion spectrum imaging study.
This study was to investigate clinical applicability of diffusion spectrum imaging (DSI) for quantitative detection of visual pathway abnormalities to predict the degree of visual field defects (VFD) in patients with pituitary adenomas. Sixty-five patients with pituitary adenomas and 33 healthy controls underwent conventional MRI and DSI scanning that allowed high-angular-resolution fiber tracking. Optic chiasmal compression and VFD were confirmed in all patients via radiological and neuro-ophthalmological examinations. Quantitative assessments of chiasmal lift, VFD, and DSI parameters from the optic nerve, optic tract, and optic radiation were performed. Group comparisons and correlation analyses were conducted in patients and controls. Using the 5-fold cross-validation method, the support vector machine classifiers were constructed to predict the degree of visual defects. The mean values of quantitative anisotropy and generalized fractional anisotropy in optic nerve and optic tract showed significant differences between patients and controls (p < 0.05). These parameters were also significantly correlated with the chiasmal lift distance and degree of visual defects (p < 0.05). All patients were divided into mild (n = 42) and severe (n = 23) VFD groups, using the mean deviation value of -8 dB as the threshold. The classifiers achieved an accuracy of 0.83, sensitivity of 0.78, and specificity of 0.86 to discriminate patients with mild and severe visual defects. Using high-angular-resolution fiber tracking, DSI may provide quantitative information to detect visual pathway abnormalities and be a potential diagnostic tool for determining the degree of visual field defects in pituitary adenomas. • Abnormal QA and GFA values of optic nerve and optic tract in adenoma patients • Close relationship between DSI parameters and VFD degree in adenoma patients • The classifiers achieved an accuracy of 0.83, sensitivity of 0.78, and specificity of 0.86 to discriminate patients with mild and severe VFD.


Effect of crown margins on periodontal conditions in regularly attending patients.
Subgingival margins of cast restorations have been associated with increased gingival inflammation and probing depth, but it is not known if such effects would be seen among patients receiving regular professional care. In this study, 831 regularly attending patients in 35 North Carolina dental practices were examined. Plaque, gingival inflammation, calculus, and probing depth were assessed on facial and mesiofacial surfaces of the Ramfjord teeth. Surface-specific analyses showed significantly greater (p less than 0.05) gingival inflammation and deeper probing depths with subgingival cast restoration margins for nearly all surfaces examined. Less frequently, decreases in plaque and calculus were associated with the presence of crowns. Intact surfaces in patients with cast restorations were not significantly different from the same surfaces in patients without cast restorations. Even among patients receiving regular preventive dental care, subgingival margins are associated with unfavorable periodontal reactions.


Impacts of Fungicide Treatment and Conventional Fertilization Management on the Potato Metabolome (Solanum tuberosum L.) Evaluated with UPLC-IMS-QToF.
Two field trials were conducted to investigate the influence of fungicide and fertilization management on the potato tubers' metabolome (Solanum tuberosum L.). Thereby, fungicides and conventional fertilizers were varied in terms of quantities, number and date of applications, physical state, and product composition. Following a water-methanol-based extraction, samples were analyzed using an UPLC-IMS-QToF and multivariate data analysis. Fungicide application led to significant changes in the tubers' metabolome. Flavonoids were increasingly expressed as a natural response to impending fungal or viral infections in an untreated group, while the phytoalexin rishitinol was highly abundant in groups with fungicide application. In contrast to fungicides, the application of conventional fertilizers did not cause significant alterations in the tubers' compound composition. Consequently, the impact of fungicide application could be rated as more important than the fertilization-derived influence, which might be because of a gentler adaption to fertilization than to the acute stress of fungicide applications.


Long term outcomes of transcutaneous non-image guided bleomycin sclerotherapy in orbital/adnexal lymphatic malformations: a protocol-based management in 69 eyes.
To study the efficacy and the long-term outcomes of treating micro and macrocystic orbital and/or adnexal lymphatic malformations (OA-LM) with protocol-based bleomycin sclerotherapy. A retrospective interventional study of 69 eyes having OA-LM treated with non-image guided transcutaneous or transconjunctival bleomycin sclerotherapy (1IU/ml aqueous solution) between December 2014 and December 2018. Based on clinical regression, the outcomes were classified as excellent, good, fair and poor. The mean age at presentation was 20 ± 16 years (median 16; range 1 month to 70 years). The orbital-palpebral variant was the most common presentation, seen in 29 patients (42%). Microcystic morphology was seen in 34(49%), macrocystic in 22 (32%) and mixed cyst in 13 (19%) patients. Mean units of bleomycin injected per patient were 9 ± 8 IU (median 5.5 IU, range 1-38 IU). Mean number of treatment sessions required were 2 ± 1 (median 2, range 1-6). The response was excellent in 43 (62%), good in 12 (17%), fair in 9 (13%) and poor in 5 (7%) patients. These responses were comparable across the morphological subgroups (p = 0.24, chi-square test). Adverse reactions noted were inflammation in 11 eyes (16%) and peri-ocular pigmentation in 15 (22%). There was a sustained tumour regression over a mean follow-up duration of 3.5 years (median 3; range 1.5-5 years). Seventy-nine percent of eyes with OA-LM showed a good outcome with transcutaneous and/or transconjunctival non-image guided bleomycin sclerotherapy with no serious adverse events. The results were promising over long-term follow-up.


Development and validation of a UHPLC-ESI-QTOF mass spectrometry method to analyze opines, plant biomarkers of crown gall or hairy root diseases.
Opines are low-molecular-weight metabolites specifically biosynthesized by agrobacteria-transformed plant cells when plants are struck by crown gall and hairy root diseases, which cause uncontrolled tissue overgrowth. Transferred DNA is sustainably incorporated into the genomes of the transformed plant cells, so that opines constitute a persistent biomarker of plant infection by pathogenic agrobacteria and can be targeted for crown gall/hairy root disease diagnosis. We developed a general, rapid, specific and sensitive analytical method for overall opine detection using ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-MS-QTOF), with easy preparation of samples. Based on MS, MS/MS and chromatography data, the detection selectivity of a wide range of standard opines was validated in pure solution and in different plant extracts. The method was successfully used to detect different structural types of opines, including opines for which standard compounds are unavailable, in tumors or hairy roots induced by pathogenic strains. As the method can detect a wide range of opines in a single run, it represents a powerful tool for plant gall analysis and crown gall/hairy root disease diagnosis. Using an appropriate dilution of plant extract and a matrix-based calibration curve, the quantification ability of the method was validated for three opines belonging to different families (nopaline, octopine, mannopine), which were accurately quantified in plant tissue extracts.


Dietary cytidine (5')-diphosphocholine supplementation protects against development of memory deficits in aging rats.
The present study was designed to assess the effect of supplementation with dietary cytidine (5')-diphosphocholine (CDP-choline), a source of cytidine and choline, on memory in young and older rats. Although the hippocampal-dependent memory deficits in aged rats are well documented, cognitive functioning in early aging has not been as thoroughly evaluated. Female Sprague-Dawley rats (3 or 15 months of age) consumed either a control diet or a diet supplemented with CDP-choline (approximately 500 mg/kg/day) for 8 weeks, after which they were trained to perform spatial and cued versions of the Morris water maze. Compared with young rats, aged rats exhibited a selective deficit in spatial memory tasks that required rats to retain information for 24 h or longer. CDP-choline supplementation protected against the development of this deficit, but had no memory-enhancing effect in normal young rats. These findings suggest that early-aged rats display a selective impairment in hippocampal-dependent long-term memory, and that dietary CDP-choline supplementation can protect against this deficit.


Corticostriatal Activity Driving Compulsive Reward Seeking.
Activation of the mesolimbic dopamine system is positively reinforcing. After repeated activation, some individuals develop compulsive reward-seeking behavior, which is a core symptom of addiction. However, the underlying neural mechanism remains elusive. We trained mice in a seek-take chain, rewarded by optogenetic dopamine neuron self-stimulation. After compulsivity was evaluated, AMPA/NMDA ratio was measured at three distinct corticostriatal pathways confirmed by retrograde labeling and anterograde synaptic connectivity. Fiber photometry method and chemogenetics were used to parse the contribution of orbitofrontal cortex afferents onto the dorsal striatum (DS) during the behavioral task. We established a causal link between DS activity and compulsivity using optogenetic inhibition. Mice that persevered when seeking was punished exhibited an increased AMPA/NMDA ratio selectively at orbitofrontal cortex to DS synapses. In addition, an activity peak of spiny projection neurons in the DS at the moment of signaled reward availability was detected. Chemogenetic inhibition of orbitofrontal cortex neurons curbed the activity peak and reduced punished reward seeking, as did optogenetic hyperpolarization of spiny projection neurons time-locked to the cue predicting reward availability. Our results suggest that compulsive individuals display stronger neuronal activity in the DS during the cue predicting reward availability even when at the risk of punishment, nurturing further compulsive reward seeking.


Surgical outcomes of retrograde nailing enhanced with minimally invasive cerclage cable fixation for infra-isthmal femoral fracture.
Infra-isthmal femoral fracture has been known as one of the risk factors for femoral nonunion. Retrograde intramedullary nailing can provide reliable stability of the distal fragment in infra-isthmal femoral fracture, but adequate reduction is required to achieve a successful outcome. This study aimed to evaluate the surgical outcomes of retrograde nailing enhanced with minimally invasive cerclage cable fixation for infra-isthmal femoral fracture. Between March 2013 and July 2017, 15 patients with infra-isthmal fractures treated with retrograde nailing and minimally invasive cerclage cable fixation were included in this study. Cerclage cable was applied for reduction aid (reduction cable) or prevention of further displacement in non-displaced extension of the distal spiral fracture (prevention cable). Number and function of cerclage cables, operation time, additional surgery, and complications were assessed. Further displacement of the wedge after nailing, coronal and sagittal alignment, displacement of the main fragment, and time from injury to union were evaluated as radiologic outcomes. Of the 15 patients in this study, 14 were treated with reduction cables. Average postoperative coronal and sagittal angulation was 1.7° (1° varus to 4° valgus) and 1.6° (2° flexion to 11° extension). Mean displacement between the main fragments was 3.5 mm (range 0-22 mm). Four of the 14 cases used additional prevention cables combined with reduction cable. Only one case was treated solely with a prevention cable. A total of five prevention cables were maintained without further displacement. All patients achieved bone union, and the average time to union was 22.7 weeks (range 9-44 weeks). There were no complications as a result of surgery, such as infection or major neurovascular injury. The minimally invasive cerclage cable technique could be a useful and safe enhancement in retrograde nailing for infra-isthmal femoral fracture in order to prevent further displacement and to reduce the main fracture.


Analyses of ligand binding in five endothiapepsin crystal complexes and their use in the design and evaluation of novel renin inhibitors.
Five renin inhibitors were cocrystallized with endothiapepsin, a fungal enzyme homologous to renin. Crystal structures of inhibitor-bound complexes have provided invaluable insight regarding the three-dimensional structure of the aspartic proteinase family of enzymes, as well as the steric and polar interactions that occur between the proteins and the bound ligands. Beyond this, subtleties of binding have been revealed, including multiple subsite binding modes and subsite interdependencies. This information has been applied in the design of novel potent renin inhibitors and in the understanding of structure-activity relationships and enzyme selectivities.


Instructors' and classroom characteristics associated with exercise enjoyment by females.
The purpose of this study was to examine the relationships between exercise enjoyment and participant's perceptions of selected characteristics of the exercise instructor and exercise class. Women (N=296) attending aerobics classes at a university fitness center were surveyed. Analysis yielded significant correlations among exercise enjoyment and the four characteristics of instructor and five for classroom. Correlations ranged from .16 to .32. Stepwise regression analysis was also conducted. Three of the nine characteristics entered into the model: (1) instructor's personal fitness, (2) instructor's ability to communicate instruction, and (3) liking of other participants in the class. The three variables combined accounted for only 17% of the variability for enjoyment of exercise.


Neurobiological mechanisms in addictive and psychiatric disorders.
The studies reviewed indicate that brain stress system play an important role in the acquisition and maintenance of drugs of abuse that target the brain's reward centers. In doing so, they may destabilize these areas, making the perception of pleasure more elusive and difficult to attain. Withdrawal from drugs of abuse leads to the activation of brain CRF systems that may produce the anxiogenic response associated with drug withdrawal. More research, however, is needed to investigate the role of brain stress systems and neuropeptides in other drug withdrawal symptoms such as anhedonia. A better understanding of the brain systems underlying drug withdrawal may help in the development of improved pharmacotherapies that can alleviate drug withdrawal symptoms. The second part of the article indicated that there is a very high comorbidity between depression and drug dependence. The reviewed studies suggest that depressed patients initiate drug-taking behavior to self-medicate the symptoms associated with their psychiatric disorder. Chronic use of drugs of abuse, however, may exacerbate the symptoms of pre-existing mental disorders and subsequently increase drug-taking behavior. Conversely, professional treatment of pre-existing psychiatric disorders may decrease the use of illicit substances.


Inhibition of peroxisomal degradation by 3-methyladenine (3MA) in primary cultures of rat hepatocytes.
A significant reduction in peroxisomes has been demonstrated in primary cultures of rat hepatocytes. This report demonstrates that 3-methyladenine (3MA), a potent inhibitor of autophagy, inhibits this effect. Hepatocytes from male Wistar rats were isolated by a two-step in situ perfusion technique using collagenase and were cultured in Williams E medium. After a 2-hr attachment period (day 0 of culture), the cells were treated with 200 microM bezafibrate (BF), a peroxisome proliferator, and 5 mM 3MA for 3 days. The cells in the culture dish were fixed in situ, stained for catalase, and embedded in Poly/Bed 812. The number and size of peroxisomes in electron micrographs were analyzed morphometrically. After 3 days of culture, the number of peroxisomes had decreased to 30% of the day 0 level. However, the day 0 level was maintained by treatment with 3MA. In BF-treated cells, many autophagosomes were observed, and peroxisomes had proliferated significantly, although they did not exceed the day 0 level. In cells treated with a combination of 3MA and BF, the number and size of peroxisomes had increased remarkably. These results suggest that 3MA is effective in maintaining both the number and size of peroxisomes in the course of primary cultures of rat hepatocytes. Suppression of peroxisome proliferation by treatment with BF may be regulated by autophagic/lysosomal degradation.


[Large-fractional preoperative irradiation combined with organ-sparing operations in stage I and II cancer of the breast].
A method of combined organ-sparing treatment for first- or second-stage breast cancer has been developed. It includes large-fraction preoperative radiation (28.5 Gy in 5 daily fractions) and segmental mastectomy with axillary lymphadenectomy. The method has been used in 25 patients. Mean follow-up time is 23 months. No local or regional relapses have been recorded. Total relapse-free survival is 92%. The cosmetic and functional effect is satisfactory.


Identification of potential metabolic biomarkers in predicting esophageal varices needing treatment in patients with liver cirrhosis.
The goal of this study was to determine the diagnostic performance of in vivo quantitative proton magnetic resonance spectroscopy (1H-MRS) to identify the presence of esophageal varices needing treatment (VNT), as well as investigate its correlation with clinical characteristics in patients with liver cirrhosis. Forty cirrhotic patients without VNT showing the negative red color sign, and 40 cirrhotic patients with VNT showing positive red color sign underwent laboratory tests, esophago-gastro-duodenoscopy, and 1H-MRS with single-voxel localization in the cirrhotic liver parenchyma. The levels of lactate + triglyceride (TG) and choline in cirrhotic patients with VNT were significantly higher than those in cirrhotic patients without VNT. In multivariate analysis, spleen diameter, platelet count, and platelet count/spleen diameter ratio, as well as lactate + TG, and choline were associated with the presence of VNT. Moreover, lactate + TG and choline levels were positively correlated with spleen diameter and negatively correlated with platelet count in the combined group of cirrhotic patients with and without VNT. Our study demonstrated that higher hepatic lactate + TG and choline levels in cirrhotic patients in conjunction with longer spleen diameter, lower platelet counts, and lower ratios of platelet count to spleen diameter were associated with the presence of esophageal VNT and the risk of developing variceal bleeding. Therefore, in vivo 1H-MRS might be an effective tool for diagnosing and predicting esophageal VNT in patients with liver cirrhosis.


Electric fan use for cooling during hot weather: a biophysical modelling study.
In hot weather, electric fans can potentially provide effective cooling for people, with lower greenhouse gas emissions and cost than air conditioning. However, international public health organisations regularly discourage fan use in temperatures higher than 35°C, despite little evidence. We aimed to determine humidity-dependent temperature thresholds at which electric fans would become detrimental in different age groups. We used biophysical modelling to determine the upper humidity-dependent temperature thresholds at which fan use would become detrimental (ie, worsen heat stress) for healthy young adults (aged 18-40 years), healthy older adults (aged ≥65 years), and older adults taking anticholinergic medication. We also obtained hourly environmental data for the period Jan 1, 2007, to Dec 31, 2019, for 108 populous cities to determine the number of days fan use would be effective for cooling, standardised to a 31-day hot weather month. We established simplified temperature thresholds for future fan use recommendations on the basis of temperatures below which fan use would never have been detrimental between Jan 1, 2007, and Dec 31, 2019, across all prevailing levels of ambient humidity. According to our model, fan use would have been beneficial on 30·0 (96·6%) of 31 hot weather days for healthy young adults and 29·4 (94·9%) of 31 hot weather days for both older adults and older adults taking anticholinergic medication between Jan 1, 2007, and Dec 31, 2019. Adherence to the current WHO recommendation of fan use below temperatures of 35°C only, fan use would have been recommended on 27·2 days (87·7%) of 31 hot weather days. According to our simplified thresholds for fan use (at temperatures <39·0°C for healthy young adults, <38·0°C for healthy older adults, and <37·0°C for older adults taking anticholinergic medication), fan use would have been recommended on 29·6 (95·5%) of 31 hot weather days in healthy young adults, 29·4 (94·8%) days in healthy older adults, and 28·8 (93·0%) days in older adults taking anticholinergic medication between Jan 1, 2007, and Dec 31, 2019. Electric fan use, particularly for healthy young adults, would not have worsened heat stress on the majority of study days between 2007 and 2019. Our newly proposed thresholds for fan use provide simple guidelines that improve future heatwave fan use recommendations. None.


Commentary: management of children with severe vesicoureteral reflux.
The main findings of the IRSC after 5 years of observation are summarized. Of the 434 children entered 128 were from centers in America and 306 from Europe. They were randomly allocated and stratified to a medical or surgical regimen. Of the children 50% had scarred kidneys at entry evenly distributed between the groups. After 5 years of observation there was no difference in outcome between the 2 treatment groups in terms of renal size and growth, the development of new radiological renal scars or areas of parenchymal thinning, or of progression of established scarring. In Europe infection recurred in equal numbers of children but pyelonephritic symptoms were more common in the medical group. Nevertheless, new scars developed in 19 of 155 children treated medically and 20 of 151 children treated surgically, including 5 and 7, respectively, with previously normal kidneys. Factors influencing the choice of treatment include patient age, availability of expert surgical care and experienced medical supervision, parental choice and compliance. Followup studies indicate that renal scarring rather than persistence of reflux determines the prognosis and, therefore, emphasis should be placed on the prevention of scarring.


Cellular benefits of single-use negative pressure wound therapy demonstrated in a novel ex vivo human skin wound model.
Negative pressure wound therapy is a widely used treatment for chronic, nonhealing wounds. Surprisingly, few studies have systematically evaluated the cellular and molecular effects of negative pressure treatment on human skin. In addition, no study to date has directly compared recently available single-use negative pressure modalities to traditional negative pressure devices in a controlled setting. Here we developed a novel large-scale ex vivo human skin culture system to effectively evaluate the efficacy of two different negative pressure wound therapy modalities. Single-use and traditional negative pressure devices were applied to human ex vivo wounded skin sheets cultured over a period of 48 hours. Cellular tissue response to therapy was evaluated via a combination of histological analysis and transcriptional profiling, in samples collected from the wound edge, skin adjacent to the wound, and an extended skin region. Single-use negative pressure wound therapy caused less damage to wound edge tissue than traditional application, demonstrated by improved skin barrier, reduced dermal-epidermal junction disruption and a dampened damage response. Transcriptional profiling confirmed significantly less activation of multiple pro-inflammatory markers in wound edge skin treated with single-use vs traditional negative pressure therapy. These findings may help to explain the greater efficacy of sNPWT in the clinic, while offering a noninvasive system to develop improved NPWT-based therapies.


Multistate outbreak of Escherichia coli O157:H7 infection associated with consumption of packaged spinach, August-September 2006: the Wisconsin investigation.
Escherichia coli O157:H7 infection often causes hemorrhagic colitis and hemolytic uremic syndrome. In 2006, the Wisconsin Division of Public Health and the Wisconsin State Laboratory of Hygiene, in cooperation with other local, state, and federal partners, investigated an outbreak of E. coli O157:H7 infection. In September 2006, the Wisconsin Division of Public Health and the Wisconsin State Laboratory of Hygiene were able to link geographically dispersed E. coli O157:H7 isolates recovered from the stool samples of ill persons, all of which had the same pulsed-field gel electrophoresis pattern (i.e., outbreak pattern). Investigators conducted a case-control study with control subjects (n = 86) matched to case patients (n = 49) by age, sex, and residential location. All case patients' onsets of illness occurred during the period from 20 August through 14 September 2006. Illness was associated with spinach consumption (matched odds ratio, 82.1; 95% confidence interval, 14.7 to >1000). Of the 49 case patients, 26 (53%) recalled eating brand A spinach. On multibrand analysis, only brand A was associated with illness (undefined matched odds ratio; 95% confidence interval, 6.8-infinity). Wisconsin's agriculture laboratory isolated E. coli O157:H7 with the outbreak pattern from spinach in 2 brand A packages, both produced on 15 August 2006. The rapid multijurisdictional epidemiologic and laboratory response, including timely pulsed-field gel electrophoresis pattern analysis and PulseNet posting, facilitated prompt voluntary recall of brand A spinach.


The water-soluble fraction of potentially toxic elements in contaminated soils: relationships between ecotoxicity, solubility and geochemical reactivity.
To better understand the impacts posed by soil contamination to aquatic ecosystems it is crucial to characterise the links between ecotoxicity, chemical availability and geochemical reactivity of potentially toxic elements (PTE's) in soils. We evaluated the adverse effects of water extracts obtained from soils contaminated by chemical industry and mining, using a test battery including organisms from different trophic levels (bacteria, algae and daphnids). These tests provided a quick assessment of the ecotoxicity of soils with respect to possible adverse effects on aquatic organisms although the ecotoxicological responses could be related to the solubility of PTE's only to a limited extent. The analysis of results of bioassays together with the chemical characterisation of water extracts provided additional relevant insight into the role of conductivity, pH, Al, Fe, and Mn of soil extracts on toxicity to organisms. Furthermore, an important conclusion of this study was that the toxicity of extracts to the aquatic organisms could also be related to the soil properties (pH, Org C and Fe(ox)) and to the reactivity of PTE's in soils which in fact control the soluble fraction of the contaminants. The combined assessment of ecotoxicity in water fractions, solubility and geochemical reactivity of PTE's in soils provided a more comprehensive understanding of the bioavailability of inorganic contaminants than ecotoxicological or chemical studies alone and can therefore be most useful for environmental risks assessment of contaminated soils.


Transcranial direct current stimulation over the motor association cortex induces plastic changes in ipsilateral primary motor and somatosensory cortices.
This study was performed to elucidate whether transcranial direct current stimulation (tDCS) over the motor association cortex modifies the excitability of primary motor (M1) and somatosensory (S1) cortices via neuronal connectivity. Anodal, cathodal, and sham tDCS (1 mA) over the left motor association cortex was applied to 10 subjects for 15 min using electrodes of two sizes (9 and 18 cm(2)). Both motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) were recorded before, immediately after, and 15 min after tDCS. Electrode positions were confirmed by overlaying them on MRI anatomical surface images of two individuals. After applying anodal tDCS using the large electrode, amplitudes of MEP components significantly decreased, whereas those of early SEP components (N20 and P25) increase. Opposite effects were observed on MEPs and SEPs after cathodal tDCS. However, a small electrode did not significantly influence either MEPs or SEPs, irrespective of polarity. The small electrode covered mainly the dorsal premotor cortex (PMd) while the large electrode involved the supplementary motor area (SMA) in addition to PMd. These results suggest that anodal tDCS over PMd together with SMA enhanced the inhibitory input to M1 and excitatory input to S1, and that cathodal tDCS might lead to an opposite effect. The finding that only the large electrode modulated M1 and S1 implies that activation of PMd together with SMA by tDCS can induce plastic changes in primary sensorimotor areas.


Agreement between rebound (Icare ic200) and applanation tonometry (Perkins) in patients with primary congenital glaucoma.
To examine agreement between intraocular pressure (IOP) measurements made using the rebound tonometer Icare ic200 (RT200) and the Perkins handheld applanation tonometer (PAT) in patients with primary congenital glaucoma (PCG). The impacts of several covariables on measurements using the two devices were also assessed. Intraocular pressure measurements were made in a single session in 86 eyes of 86 patients with PCG (46 under anaesthesia, 40 in the office). The order was RT200 then PAT. The variables age, central corneal thickness (CCT), corneal state and anaesthesia were recorded in each patient. Data were compared by determining interclass correlation coefficients (ICC) for each tonometer and representing the differences detected as Bland-Altman plots. Effects of covariables were assessed through univariate and multivariate regression. Mean IOP difference between tonometers (RT200 minus PAT) was 1.26 mmHg (95%: 0.22-2.31). Absolute agreement (ICC) was 0.73 (95% CI: 0.62-0.82). Lower and upper limits of agreement (95%) were -8.06 mmHg (95% CI: -9.87 to -6.25) and 10.59 mmHg (95% CI: 8.77-12.40), respectively. The tonometers showed systematic differences (a = -4.63 mmHg; 95% CI: -9.11 to -1.44) and proportional differences; for each mmHg increase in PAT-IOP, the RT200 reading increased by 1.28 mmHg (b = 1.28; 95% CI: 1.12-1.53). None of the variables tested as predictors were able to explain differences between the tonometers. Despite the good overall agreement between both tonometers, caution should be taken in high values of IOP, considering the interchangeability of its readings as systematic and proportional differences appear to exist between both methods.


The postauricular cutaneous advancement flap for repairing ear rim defects.
Due to the ear's complicated anatomy and closely adherent anterior skin, repairing ear rim defects is often difficult. We describe a simple postauricular cutaneous advancement flap for correcting ear rim defects of varying sizes. Skin tumors involving the ear rims of 12 patients were excised. A postauricular cutaneous advancement flap was designed to correct the resulting defects. The postauricular cutaneous advancement flap provided excellent cosmetic results in our 12 patients. Minimal superficial necrosis of the flap was observed in one patient. Utilizing relatively loose postauricular skin, this postauricular advancement flap can cover helical rim defects of varying sizes with excellent cosmetic results and low complication rates.


A 2D cobalt based coordination polymer constructed from benzimidazole and acetate ion exhibiting spin-canted antiferromagnetism.
A coordination polymer, [Co(II)(bIM)(acetate)] (bIM = benzimidazole) was synthesized using a solvothermal method; the complex has a two dimensional non-interpenetrated network structure and exhibits a spin-canted antiferromagnetic behaviour at low temperature and a high coercive field.


Methane and nitrous oxide emissions from rice seedling nurseries under flooding and moist irrigation regimes in Southeast China.
Measurements of methane (CH(4)) and nitrous oxide (N(2)O) fluxes have been extensively taken following rice seedlings transplanted into paddy fields, while little is known about CH(4) and N(2)O fluxes from rice seedling nurseries. Fluxes of CH(4) and N(2)O were simultaneously measured in rice seedling nurseries under the water regimes of continuous flooding and moist irrigation without waterlogging in Southeast China in 2010. Fluxes of CH(4) and N(2)O from continuously flooded nurseries averaged 10.33-14.84 mg m(-2) h(-1) and 28.64-34.35 μg N(2)O-Nm(-2) h(-1) for the different fertilizer applied plots, respectively. Relative to continuous flooding, moist irrigation decreased total CH(4) by 14-50% but increased N(2)O by 72-186%, dependent on the fertilizer types. Compared with inorganic N fertilizer, organic manure application increased CH(4) by 44% and 148% in the continuously flooded and moist irrigation nurseries, respectively. Rice seedling growth parameters were the greatest in moist irrigation nurseries with inorganic N fertilizer application. Moist irrigation instead of continuous waterlogging and shifts from organic manure to combined organic/inorganic N fertilizer inputs have been increasingly experienced in Chinese rice seedling nurseries, which would benefit for mitigating the combined global warming potentials of CH(4) and N(2)O from rice seedling nurseries in China.


Subjective cognitive decline and subsequent dementia: a nationwide cohort study of 579,710 people aged 66 years in South Korea.
Subjective cognitive decline (SCD) is a potential risk factor for dementia. We aimed to investigate the association between SCD and subsequent dementia in a nationwide population-based cohort in South Korea. This cohort included 579,710 66-year-old adults who were followed for a total of 3,870,293 person-years (average 6.68 ± 1.33 years per person). All subjects completed a questionnaire about subjective memory impairment, the Pre-screening Korean Dementia Screening Questionnaire (KDSQ-P), which included a validated 5-item derivative, and were determined to have SCD based on a single question assessing memory decline. Depressive symptoms were assessed in all subjects using a 3-item modified geriatric depression scale. Hazard ratios were estimated using the Cox proportional hazards model and compared between subjects with and without SCD. Compared to subjects without SCD, those with SCD were more likely to develop dementia (incidence per 1000 person-years: non-SCD, 5.66; SCD, 8.59). After adjusting for potential confounding factors, the risk of subsequent dementia significantly increased in subjects with SCD, with an adjusted hazard ratio (aHR) of 1.38 (95% confidence interval [CI] 1.34 to 1.41). The risk of subsequent dementia was greatly increased in subjects with higher KDSQ-P scores (aHR = 2.77, 95% CI 2.35 to 3.27). A significant association between SCD and dementia was observed in both depressive and non-depressive symptom groups (aHR = 1.50, 95% CI 1.42 to 1.57 in subjects with depressive symptoms; aHR = 1.33, 95% CI 1.29 to 1.37 in subjects without depressive symptoms; P = 0.001). In this population of 66-year-old individuals, SCD was significantly associated with an increased risk of subsequent dementia. This association was found in both depressive and non-depressive groups, with an increased risk of dementia in the presence of depressive symptoms. Our findings suggest that SCD indicates a risk for dementia. Further studies are needed to delineate potential approaches to preventing the development of dementia in individuals with SCD.


Generic and health-related quality of life in patients with seasonal and nonseasonal depression.
Although a relatively large body of research has now accumulated concerning the relationship between quality of life (QoL) and nonseasonal depression, there is a dearth of information about QoL in seasonal affective disorder (SAD). The aim of this study was to compare perceived levels of broad ('generic') and health-related QoL in patients with seasonal and nonseasonal depression. Participants were 72 patients with SAD enrolled in an on-going multicentre study in Canada, and 72 patients with nonseasonal major depressive disorder (MDD) matched for severity of depression attending an outpatient psychiatric clinic in Vancouver, British Columbia. All participants completed two measures of QoL (the 20-item Medical Outcomes Study [MOS] Short-Form General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q]) at baseline prior to treatment. The results of the study indicated that both generic and health-related QoL were compromised in patients with SAD compared with general population norms. For example, mean Q-LES-Q scores (range 0-100, where higher scores indicate better QoL) were 44%, compared with scores of 83% reported for the general population. Patients with nonseasonal depression showed significantly poorer functioning in several domains on the SF-20, but no significant differences in Q-LES-Q scores emerged. Perceived QoL is impaired in patients with SAD. Degree of impairment between seasonal and nonseasonal depressives is equivalent when assessed using the Q-LES-Q, but significant inter-group differences are apparent in SF-20 domain scores. Future research is required to determine whether perceived QoL is improved by treatment interventions for seasonal depression such as light therapy or antidepressant medication.


Structural basis of 3' end RNA recognition and exoribonucleolytic cleavage by an exosome RNase PH core.
The exosome is a macromolecular complex that plays fundamental roles in the biogenesis and turnover of a large number of RNA species. Here we report the crystal structures of the Rrp41-Rrp42 core complex of the S. solfataricus exosome bound to short single-stranded RNAs and to ADP. The RNA binding cleft recognizes four nucleotides in a sequence-unspecific manner, mainly by electrostatic interactions with the phosphate groups. Interactions at the 2' hydroxyls of the sugars provide specificity for RNA over DNA. The structures show both the bound substrate and the cleaved product of the reaction, suggesting a catalytic mechanism for the 3'-5' phosphorolytic activity of the exosome.


Could junctional problems at the end of a long construct be addressed by providing a graduated reduction in stiffness? A biomechanical investigation.
The effect of long, rigid fixation on adjacent level hypermobility was investigated in a human cadaver model with and without a transitional posterior dynamic stabilization (PDS) device placed at the last caudal level. To evaluate if PDS devices are useful in the setting of spinal deformities to restore increased adjacent level motions, which occur in long constructs. The hypothesis is that load-sharing benefits of these devices will be most suitable in long constructs and may reduce thoracolumbar junctional effects. The PDS device evaluated has a compressive spacer and flexion-dampening bumper. Mechanical factors such as excessive mobility, increased disc height due to instrumentation, and abnormal loading are thought to accentuate distal level problems, which occur in extended instrumentation. Specifically adjacent level degeneration and distal junctional kyphosis are known to occur in these cases. Seven cadaver spines were tested from T7 to L3. Long instrumentation was applied in 2 rigid groups, R1: Rigid (T8-L2) and R2: Rigid (T8-L1), and PDS to the last caudal level of each, RP1: Rigid (T8-L1) + PDS (L1-L2), and RP2: Rigid (T8-T12) + PDS (T12-L1). Range of motion was evaluated at surgical and distal adjacent levels after displacement controlled loading in a spine tester. Distal adjacent level motion was increased after 5- and 6-level rigid fixation in flexion-extension, lateral bending, and axial rotation. Most of the increases were seen in axial rotation and lateral bending. Replacing the last caudal instrumented level with the PDS test device was able to alleviate hypermobile conditions of the adjacent noninstrumented level, closer to intact (24%, 12% reduction in RP2, RP1, respectively). Reduction of hypermobility caused by extended arthrodesis may represent a new and ideally suited function for PDS devices. Mechanically, the devices were seen to kinematically restore abnormal distal motion, especially with placement of the PDS at the thoracolumbar junction.


Sickle cell disease: a case report of renal amyloidosis.
The development of proteinuria and reduced glomerular filtration rate is associated with higher mortality among patients with sickle cell disease (SCD). AA amyloidosis, also associated with increased mortality, in SCD is rare. We present a case of a woman with homozygous sickle cell disease with nephrotic syndrome and antibodies to double stranded DNA without clinical features of systemic lupus erythematosus. Kidney biopsy reveals AA amyloidosis and is the first report of concomitant AA amyloidosis with antibodies to double stranded DNA in SCD. A 40-year-old Central African woman with homozygous sickle cell disease and history of vaso-occlusive pain crises undergoes kidney biopsy for nephrotic-range proteinuria. Kidney biopsy reveals AA type amyloidosis, which is a rare manifestation of SCD in the kidney. Her anemia worsens with an ACE inhibitor, initiated to reduce proteinuria and limit GFR decline, so it was discontinued. Hydroxyurea, shown to decrease the frequency of vaso-occlusive crises and lower proteinuria, was subsequently initiated but then discontinued due to worsening anemia. Unfortunately, her glomerular filtration rate worsens. AA amyloidosis and antibodies to double stranded DNA can occur in sickle cell disease. ACE inhibition and hydroxyurea decrease proteinuria so they may limit progression of chronic kidney disease. Hydroxyurea also decreases frequency of vaso-occlusive pain crises so it might be helpful in limiting progression of renal AA amyloidosis. However, further studies are needed to determine optimal treatment strategies for AA amyloidosis in sickle cell disease.


Heteropore covalent organic framework-based composite membrane prepared by in situ growth on non-woven fabric for sample pretreatment of food non-targeted analysis.
A heteropore covalent organic framework (COF)-based composite membrane material was prepared and proved to have a satisfactory effect on the pretreatment of vegetable samples. The composite membrane was fabricated by in situ growth of a dual-pore COF on the surface of polydopamine (PDA)-aminated non-woven (NW) fabric. Due to the difference in the strength of the interaction between the phytochromes/COF and the pesticides/COF, the removal of phytochromes and the recovery of pesticides can be achieved by adjusting the composition of the solution. Through a simple immersion or filtration operation, NW@PDA@COF composite membrane can quickly and almost completely remove interfering phytochromes in the samples. The recovery of pesticides was determined by HPLC-MS/MS, and the recovery efficiencies were 72.3~101.7% and 67.3~106.7% for immersion and filtration modes of five different vegetable samples, respectively; the RSD is between 1.1 and 19% (n = 3). The limits of detection and quantification for the 13 pesticides investigated were 0.08 μg·L-1 and 0.23 μg·L-1, respectively. A wide linear range of 1~1000 μg·L-1 was observed with R2 values from 0.9774 to 0.9998. The membrane can be repeatedly used for at least 10 times by using a facile elution treatment. Compared to other commonly used sample pretreatment materials, heteropore COF-based composite membrane is superior in terms of sorbent amount, treatment time, operation simplicity, and material reusability.


An In-hospital Pathway for Acute Coronary Syndrome Patients During the COVID-19 Outbreak: Initial Experience Under Real-World Suboptimal Conditions.
Owing to the COVID-19 outbreak in Lombardy, Italy) there is an urgent need to manage cardiovascular emergencies, including acute coronary syndrome (ACS), with appropriate standards of care and dedicated preventive measures and pathways against the risk of SARS-CoV-2 infection. For this reason, the Government of Lombardy decided to centralize the treatment of ACS patients in a limited number of centers, including our university cardiology institute, which in the past 4 weeks became a cardiovascular emergency referral center in a regional hub-and-spoke system. Therefore, we rapidly developed a customized pathway to allocate patients to the appropriate hospital ward, and treat them according to ACS severity and risk of suspected SARS-CoV-2 infection. We present here the protocol dedicated to ACS patients adopted in our center since March 13, 2020, and our initial experience in the management of ACS patients during the first 4 weeks of its use. Certainly, the protocol has room for further improvement as everyone's experience grows, but we hope that it could be a starting point, adaptable to different realities and local resources.


Pacemaker endocarditis due to Propionibacterium acnes.
Propionibacterium acnes belongs to the cutaneous flora of humans; it is often considered to be contaminant but has also been found to be a pathogen in human diseases. It is an uncommon causal agent in infective endocarditis and appears to have a predilection for prosthetic valves and foreign bodies. We describe a case of pacemaker endocarditis which shows that so-called harmless bacteria like P. acnes must be considered to be potential pathogens.


Template-based recognition of protein fold within the midnight and twilight zones of protein sequence similarity.
Most homologous pairs of proteins have no significant sequence similarity to each other and are not identified by direct sequence comparison or profile-based strategies. However, multiple sequence alignments of low similarity homologues typically reveal a limited number of positions that are well conserved despite diversity of function. It may be inferred that conservation at most of these positions is the result of the importance of the contribution of these amino acids to the folding and stability of the protein. As such, these amino acids and their relative positions may define a structural signature. We demonstrate that extraction of this fold template provides the basis for the sequence database to be searched for patterns consistent with the fold, enabling identification of homologs that are not recognized by global sequence analysis. The fold template method was developed to address the need for a tool that could comprehensively search the midnight and twilight zones of protein sequence similarity without reliance on global statistical significance. Manual implementations of the fold template method were performed on three folds--immunoglobulin, c-lectin and TIM barrel. Following proof of concept of the template method, an automated version of the approach was developed. This automated fold template method was used to develop fold templates for 10 of the more populated folds in the SCOP database. The fold template method developed three-dimensional structural motifs or signatures that were able to return a diverse collection of proteins, while maintaining a low false positive rate. Although the results of the manual fold template method were more comprehensive than the automated fold template method, the diversity of the results from the automated fold template method surpassed those of current methods that rely on statistical significance to infer evolutionary relationships among divergent proteins.


Tick-over-mediated complement activation is sufficient to cause basal deposit formation in cell-based models of macular degeneration.
Despite numerous unsuccessful clinical trials for anti-complement drugs to treat age-related macular degeneration (AMD), the complement system has not been fully explored as a target to stop drusen growth in patients with dry AMD. We propose that the resilient autoactivation of C3 by hydrolysis of its internal thioester (tick-over), which cannot be prevented by existing drugs, plays a critical role in the formation of drusenoid deposits underneath the retinal pigment epithelium (RPE). We have combined gene editing tools with stem cell technology to generate cell-based models that allow the role of the tick-over in sub-RPE deposit formation to be studied. The results demonstrate that structurally or genetically driven pathological events affecting the RPE and Bruch's membrane can lead to dysregulation of the tick-over, which is sufficient to stimulate the formation of sub-RPE deposits. This can be prevented with therapies that downregulate C3 expression. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Biparietal diameter-to-crown-rump length disproportion in first-trimester fetuses with holoprosencephaly.
To determine whether the biparietal diameter measurement is altered in first-trimester fetuses with holoprosencephaly. Cases of holoprosencephaly were collected retrospectively from 4 fetal medicine centers, and first-trimester biparietal diameter measurements were reviewed. The diagnosis of holoprosencephaly was established sonographically by the detection of abnormal choroid plexus morphologic characteristics (absent "butterfly" sign) and the identification of a monoventricular cerebral cavity on axial views of the fetal brain. The proportion of fetuses with biparietal diameter measurements below the 5th percentile for crown-rump length was determined. Among 45 cases of holoprosencephaly reviewed, 43 had information on both biparietal diameter and crown-rump length measurements. The biparietal diameter was below the 5th percentile for crown-rump length in 14 (32.6%) fetuses. Chromosomal analysis was available in 41; no statistically significant difference in biparietal diameter measurement between those with associated chromosomal anomalies and those without anomalies was noted. A supplementary analysis using head circumference measurement showed an even greater proportion of fetuses with holoprosencephaly with measurements below the 5th percentile for crown-rump length (18 of 42 [42.9%]). One-third of first-trimester fetuses with a sonographic diagnosis of holoprosencephaly had a biparietal diameter that was smaller than expected for crown-rump length. In this subset of fetuses, the evaluation of intracranial anatomy for signs of holoprosencephaly may be more difficult to perform due to the smaller size of the brain. Therefore, the detection of a biparietal diameter below the 5th percentile as expected from crown-rump length on the first-trimester scan may be a warning sign of holoprosencephaly and should prompt a detailed examination of the intracranial anatomy.


Rhemium-186-monoaminemonoamidedithiol-conjugated bisphosphonate derivatives for bone pain palliation.
To develop a radiopharmaceutical for the palliation of painful bone metastases based on the concept of bifunctional radiopharmaceuticals, we synthesized a bisphosphonate derivative labeled with rhenium-186 (186Re) that contains a hydroxyl group at the central carbon of its bisphosphonate structure, we attached a stable 186Re-MAMA chelate to the amino group of a 4-amino butylidene-bisphosphonate derivative [N-[2-[[4-[(4-hydroxy-4,4-diphosphonobutyl)amino]-4-oxobutyl]-2-thioethylamino]acetyl]-2-aminoethanethiolate] oxorhenium (V) (186Re-MAMA-HBP) and we investigated the effect of a hydroxyl group at the central carbon of its bisphosphonate structure on affinity for hydroxyapatite and on biodistribution by conducting a comparative study with [N-[2-[[3-(3,3-diphosphonopropylcarbamoyl)propyl]-2-thioethylamino]acetyl]-2-aminoethanethiolate] oxorhenium (V) (186Re-MAMA-BP). The precursor of 186Re-MAMA-HBP, trityl (Tr)-MAMA-HBP, was obtained by coupling a Tr-MAMA derivative to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. 186Re-MAMA-HBP was prepared by a reaction with 186ReO(4-) and SnCl2 in citrate buffer after the deprotection of the Tr groups of Tr-MAMA-HBP. After reversed-phase high-performance liquid chromatography, 186Re-MAMA-HBP had a radiochemical purity of over 95%. Compared with 186Re-MAMA-BP, 186Re-MAMA-HBP showed a greater affinity for hydroxyapatite beads in vitro and accumulated a significantly higher level in the femur in vivo. Thus, the introduction of a hydroxyl group into 186Re complex-conjugated bisphosphonates would be effective in enhancing accumulation in bones. These findings provide useful information on the design of bone-seeking therapeutic radiopharmaceuticals.


A comparison of mandated versus volunteer adolescent participants in youth tobacco cessation programs.
A national evaluation of community-based youth cessation programs delivered in group format provided the opportunity to compare mandated and volunteer program participants on demographics, smoking patterns, other health behaviors and motivation to quit. A total of 857 youth participants completed surveys prior to the start of their treatment program. Mandated youth comprised 24% of the sample (n=202). Both bivariate and multivariate comparisons were conducted. Mandated participants reported lower levels of stress, higher extrinsic motivation and lower intrinsic motivation to quit, and were more likely to be in the earlier (precontemplation) stage of readiness to quit. Mandated and volunteer smokers did not differ in their smoking patterns, school-related smoking behaviors, or binge drinking. Rates of smoking, school problems, and binge drinking were higher among cessation program participants than in general samples of youth. Programs with mixed voluntary-mandatory participation may benefit from extra attention to motivational issues.


A cross-sectional study of the prevalence and clinical management of atherosclerotic cardiovascular diseases in patients with type 2 diabetes across the Middle East and Africa (PACT-MEA): Study design and rationale.
To investigate the epidemiology and clinical management of patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (eASCVD) or high/very high ASCVD risk, defined by the 2021 European Society of Cardiology Guidelines, in seven countries in the Middle East and Africa (PACT-MEA; NCT05317845), and to assess physicians' attitudes and the basis for their decision-making in the management of these patients. PACT-MEA is a cross-sectional, observational study undertaken in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa and the United Arab Emirates based on a medical chart review of approximately 3700 patients with T2D in primary and secondary care settings, and a survey of approximately 400 physicians treating patients with T2D. The primary and secondary objectives are to determine the prevalence of eASCVD and high/very high ASCVD risk in patients with T2D. Current treatment with cardioprotective antidiabetic medication, the proportion of patients meeting the treatment criteria for reimbursement in the study countries where there is an applicable reimbursement guideline, and physician-reported factors in clinical decision-making in T2D management, will also be assessed. This large cross-sectional study will establish the estimated prevalence and management of eASCVD and high/very high ASCVD risk in patients with type 2 diabetes across the Middle East and Africa.


Snoring in primary school children and domestic environment: a Perth school based study.
The home is the predominant environment for exposure to many environmental irritants such as air pollutants and allergens. Exposure to common indoor irritants including volatile organic compounds, formaldehyde and nitrogen dioxide, may increase the risk of snoring for children. The aim of this study was to investigate domestic environmental factors associated with snoring in children. A school-based respiratory survey was administered during March and April of 2002. Nine hundred and ninety six children from four primary schools within the Perth metropolitan area were recruited for the study. A sub-group of 88 children aged 4-6 years were further selected from this sample for domestic air pollutant assessment. The prevalences of infrequent snoring and habitual snoring in primary school children were 24.9% and 15.2% respectively. Passive smoking was found to be a significant risk factor for habitual snoring (odds ratio (OR) = 1.77; 95% confidence interval (CI): 1.20-2.61), while having pets at home appeared to be protective against habitual snoring (OR = 0.58; 95% CI: 0.37-0.92). Domestic pollutant assessments showed that the prevalence of snoring was significantly associated with exposure to nitrogen dioxide during winter. Relative to the low exposure category (<30 microg/m3), the adjusted ORs of snoring by children with medium (30 - 60 microg/m3) and high exposures (> 60 microg/m3) to NO2 were 2.5 (95% CI: 0.7-8.7) and 4.5 (95% CI: 1.4-14.3) respectively. The corresponding linear dose-response trend was also significant (P = 0.011). Snoring is common in primary school children. Domestic environments may play a significant role in the increased prevalence of snoring. Exposure to nitrogen dioxide in domestic environment is associated with snoring in children.


Non-volatile and volatile metabolic profiling of tomato juice processed by high-hydrostatic-pressure and high-temperature short-time.
High hydrostatic pressure (HHP) processing has become a commercial success in fruit and vegetable processing. Herein, the effects of HHP and high-temperature short-time (HTST) processing on metabolic profiling in tomato juice was evaluated by UPLC-MS/MS, HPLC, and GC-MS; a total of 425 metabolites, 14 carotenoids, and 56 volatile compounds were identified in tomato juice. HHP processing affects the composition of the juice less than HTST processing, considering 4 and 33 differential metabolites discriminated after HHP and HTST processing, respectively. The total lycopene and carotenoid contents in tomato juice increased after HHP processing, while the β-carotene and lycopene contents decreased after HTST processing. Further, more volatile compounds and higher contents of aldehydes that contribute to green aroma and lower contents of alcohols were observed after HHP and HTST processing, respectively. These findings provide a comprehensive understanding of the advantages of HHP processing on metabolite profiles in tomato juice.


Boundary lubrication and maxillofacial prosthetic polydimethylsiloxanes.
Polydimethylsiloxanes exhibit hydrophobic behaviour and poor wettability. These features impose some problems with the clinical performance of the material when used for the construction of intraoral and extraoral facial prostheses. Surface active agents were added to modify the surface energy of the polydimethylsiloxane and contact angle measurements were carried out to observe wetting characteristics. Five siloxane-alkene oxide block copolymers, one organosilicon quaternary ammonium chloride and an epoxyalkyl silane ester were used as surfactants. The best surfactant in terms of permanency and contact angle lowering achieved a value of 24 degrees when added at 10% level compared with 57 degrees for the unmodified silicone. The fairly high viscosity, combined with a comb-like structure, together with the high hydroxyl number of 75 provided the correct balance of permanence and wetting characteristics.


Hereditary red cell enzymopathies.
The hereditary red cell enzymopathies are an uncommon but important cause of chronic haemolytic anaemia. Their clinical diversity is mirrored by increasingly evident heterogeneity at the molecular level. The structure, function, and expression of the genes encoding red cell enzymes and the nature of the gene defects in the deficient state are examined.


Psychological aspects of insulin-induced thirst.
Fifteen normal volunteers received one insulin injection or saline in two nonconsecutive days. At 0', 30', 60' and 90' water intake was measured. Simultaneously subjective thirst and hunger were recorded by running a set of psychological tests. Water intake was higher after insulin than saline at 60' and 90'. Insulin increases thirst sensation even before the sensation of hunger.


Can databasing optimise patient care?
Long-term, prospective databasing of multiple sclerosis (MS) information provides a useful resource for natural history studies. Furthermore, it is the only way to address the question of whether early treatment eliminates or delays the inevitable and irreversible clinical worsening that is the hallmark of the late phase of the illness. Due to the variable nature of MS, it is useful to monitor large numbers of individuals over time. The limitations of single databases may be overcome by regional, national or international pooling of data. In this paper, the Italian Multiple Sclerosis Database Network (MSDN) and the international web-based MSBase registry are described.


Circadian covariation of norepinephrine and serotonin in the locus coeruleus and dorsal raphe nucleus in the rat.
We report robust correlations between concentrations of the neurotransmitters norepinephrine and serotonin in the locus coeruleus and the dorsal raphe nucleus of the brainstem in rats analyzed at 7 different time points over 24 h. We found similar circadian rhythmicities for both monoamines with acrophases just before the onset of the dark period. The monoamine concentrations diminished and the significant intercorrelation between norepinephrine and serotonin in the locus coeruleus disappeared during the night suggestive of a noradrenergic stimulation of dorsal raphe serotonin during the day. Timing of experiments is crucially important in studies on brain monoaminergic indices and their interrelationships.


Programmed cell death induced by modified clay in controlling Prorocentrum donghaiense bloom.
Modified clay (MC), an effective material used for the emergency elimination of algal blooms, can rapidly reduce the biomass of harmful algal blooms (HABs) via flocculation. After that, MC can still control bloom population through indirect effects such as oxidative stress, which was initially proposed to be related to programmed cell death (PCD) at molecular level. To further study the MC induced cell death in residual bloom organisms, especially identifying PCD process, we studied the physiological state of the residual Prorocentrum donghaiense. The experimental results showed that flocculation changed the physiological state of the residual cells, as evidenced by growth inhibition and increased reactive oxygen species production. Moreover, this research provides biochemical and ultrastructural evidence showing that MC induces PCD in P. donghaiense. Nuclear changes were observed, and increased caspase-like activity, externalization of phosphatidylserine and DNA fragmentation were detected in MC-treated groups and quantified. And the mitochondrial apoptosis pathway was activated in both MC-treated groups. Besides, the features of MC-induced PCD in a unicellular organism were summarized and its concentration dependent manner was proved. All our preliminary results elucidate the mechanism through which MC can further control HABs by inducing PCD and suggest a promising application of PCD in bloom control.


Wearable system for outdoor air quality monitoring in a WSN with cloud computing: Design, validation and deployment.
Breathing poor-quality air is a global threat at the same level as unhealthy diets or tobacco smoking, so the availability of affordable instrument for the measurement of air pollutant levels is highly relevant for human and environmental protection. We developed an air quality monitoring platform that comprises a wearable device embedding low-cost metal oxide semiconductor (MOS) gas sensors, a PM sensor, and a smartphone for collecting the data using Bluetooth Low Energy (BLE) communication. Our own developed app displays information about the air surrounding the user and sends the gathered geolocalized data to a cloud, where the users can map the air quality levels measured in the network. The resulting device is small-sized, light-weighted, compact, and belt-worn, with a user-friendly interface and a low cost. The data collected by the sensor array are validated in two experimental setups, first in laboratory-controlled conditions and then against referential pollutant concentrations measured by standard instruments in an outdoor environment. The performance of our air quality platform was tested in a field testing campaign in Barcelona with six moving devices acting as wireless sensor nodes. Devices were trained by means of machine learning algorithms to differentiate between air quality index (AQI) referential concentration values (97% success in the laboratory, 82.3% success in the field). Humidity correction was applied to all data.


On a model of human bioenergetics.
A three component hydraulic model has been proposed to represent the energy flows during human exercise and recovery. This model was accompanied by a sketch indicative of the graphical solution but had not been solved mathematically. This paper describes the model and demonstrates the method of mathematical solution, illustrated with a numerical example. Plotted graphically, this particular solution differs from both the "sketch solution" and from what actually happens under experimental conditions. These points of discrepancy are discussed with a view to their rectification and the development of a refined model.


Instruments measuring practitioner performance of the complete examination and screening of neonates: A systematic review.
The complete examination and screening of the neonate is a recommended assessment of neonatal well-being conducted by appropriately trained medical, midwifery and nursing personnel at specific intervals during the first 6-week post-birth. Our aim was to identify and critically evaluate instruments that measure practitioner performance of this important assessment of neonatal health. Using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology, a systematic review was undertaken. Four studies were identified as suitable for data extraction and analysis. This paper briefly describes the four instruments, discusses and compares the COSMIN analysis and ratings of each instrument. A recommendation for the instrument identified as the most suitable to measure practitioner performance is provided. Most instruments were designed by educators to measure the performance of practitioners developing competence in the complete examination and screening of the neonate. Further development and piloting of instruments designed to measure the performance and continuing competence of qualified practitioners of the newborn examination are required.


Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: Data from a Real-World Study in Spain.
This study aimed to describe utilization patterns, persistence, resource utilization and costs in patients with type 2 diabetes mellitus initiating treatment with glucagon-like peptide 1 receptor agonists in routine clinical practice in Spain. This retrospective study of medical records in the Big-Pac database identified adults starting treatment with once-weekly (QW) dulaglutide, exenatide-QW or once-daily liraglutide between 1 November 2015 and 30 June 2017. Patients were followed for up to 18 months from treatment initiation. Data on clinical characteristics of patients, treatment patterns, average daily dose and costs were obtained for the three cohorts. Persistence over the 18-month period was evaluated using Kaplan-Meier curves. All analyses were descriptive. A total of 1402 patients were included in this study (dulaglutide [n = 492], exenatide-QW [n = 438] or liraglutide [n = 472]); 52.8% were men, and the mean (SD) age was 62 (11) years, glycated haemoglobin (HbA1c) was 8.1% (1.2) and body mass index was 35.5 (3.2) kg/m2 at treatment initiation. Persistence at 18 months was 59.1% (95% confidence interval [CI] 54.8-63.4) for dulaglutide, 45.7% (95% CI 41.0-50.4) for exenatide-QW and 46.6% (95% CI 42.1-51.1) for liraglutide. The average (SD) dose was 1.2 (0.4) mg/week for dulaglutide, 1.9 (0.3) mg/week for exenatide-QW and 1.1 (0.3) mg/day for liraglutide. The average reduction in HbA1c levels at 1 year was - 0.68% for patients who initiated dulaglutide, - 0.54% for patients who initiated exenatide-QW and - 0.50% for patients who initiated liraglutide. The mean (SD) total annual health care costs were €4072 (1946) for dulaglutide, €4418 (2382) for exenatide-QW and €4382 (2389) for liraglutide. Results suggest that patients who started treatment with dulaglutide had higher persistence over 18 months, presented lower HbA1c levels at 12 months and incurred lower annual total healthcare costs than patients who initiated exenatide-QW or liraglutide.


[The interaction between the judge and doctors with court-ordered therapy].
Faced with the increase in convictions for sex offences, legislators in the 1990s studied the possibility of monitoring these criminals and offenders, considered to be among the most dangerous, following their imprisonment. This resulted in the law of 17th June 1998, establishing socio-judicial supervision. Inspired by several high-profile cases, the resulting changes to the legislation have reinforced judicial measures aimed at preventing repeat offending with regard to the most serious crimes. Socio-judicial supervision in particular is routinely ordered as part of certain safety measures while court-ordered therapy has become a cornerstone in the management of the most dangerous prisoners. An analysis of the connection between the judge and court-ordered therapy enables its role to be better understood.


Problems in evaluating the consequences of disabling illness: the case of multiple sclerosis.
There is a need for a method, useful both to the clinician and to the research worker which can assess both the 'quantity' and the 'quality' of daily life. In this paper two 'diary' methods are described for obtaining accounts of daily activities, social contacts and patterns of interaction from people diagnosed as having multiple sclerosis. The information obtained is compared with that derived from a major decennial national survey of the population aged over 4 years and from a selected group of matched non-patient controls. The paper is divided into two parts, each concentrating on one of the techniques. The first is a postal 24-hour written account; the second a detailed tape-recorded interview known as the 'Standard Day Interview'. Difficulties and advantages in using these approaches to assess both the quantitative and the qualitative changes during disabling illness are discussed and proposals for developing the methods are presented. Indications of substantive variation in the use of time by samples drawn from the 'healthy' and from populations with multiple sclerosis are reported.


The impact of 18F-FDG PET on initial staging and therapy planning of pediatric soft-tissue sarcoma patients.
Soft-tissue sarcomas in children are a histologically heterogenous group of malignant tumors accounting for approximately 7% of childhood cancers. There is a paucity of data on the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for initial staging and whether PET influenced management of these patients. The aim of this analysis is to assess the use of 18F-FDG PET exclusively, and as a supplement to cross-sectional imaging in comparison to typical imaging protocols (CT and magnetic resonance imaging [MRI]) for initial staging as well as therapy planning in pediatric soft-tissue sarcoma patients. The list of 18F-FDG PET/CT performed for soft-tissue sarcoma between March 2007 and October 2017 was obtained from the Hospital Information System database. Twenty-six patients who had received 18F-FDG PET, MRI and/or CT at initial diagnosis were included in the study. 18F-FDG PET and concurrent diagnostic CT and MRI at initial staging were independently reviewed to note the number of primary and metastatic lesions detected by each modality. A chart review was conducted to collect information on final diagnosis, staging and treatment plan. During the study period, 26 patients (15 females) ages 1.3-17.9 years (median age: 6 years) had received 18F-FDG PET/CT at initial diagnosis of soft-tissue sarcoma. Diagnostic CT was available for comparison in all 26 patients and MRI was available in 18 patients. The mean interval between cross-sectional imaging and 18F-FDG PET was 5.9 days (range: 0-30 days). All 26 primary lesions were equally detected by 18F-FDG PET compared to CT and MRI. From 84 metastatic lesions, 16 were detected by PET as well as CT and MRI, 12 by 18F-FDG PET only (included mainly lymph node metastases) and 56 by CT and MRI only (included mainly lung metastases). 18F-FDG PET changed therapy planning in 5 patients out of 26 (19%) by showing additional lesions not detected by CT and MRI. 18F-FDG PET proved to be a valuable tool for precise initial staging of pediatric soft-tissue sarcoma patients, especially in detecting lymph node metastasis, and could be included in their initial work-up. Given the relative rarity and heterogeneity of this group of tumors, additional investigations are required to definitely establish a role for 18F-FDG PET in the initial staging and therapy planning of soft-tissue sarcoma in the pediatric population.


Combined intake of astaxanthin, β-carotene, and resveratrol elevates protein synthesis during muscle hypertrophy in mice.
The antioxidant factors, astaxanthin, β-carotene, and resveratrol, have a potential effect on protein synthesis in skeletal muscle and a combined intake may have a greater cumulative effect than individual intake. The aim of this study was to investigate the combined effects on skeletal muscle mass and protein metabolic signaling during the hypertrophic process from atrophy in mice. Male ICR mice were divided into five dietary groups consisting of seven animals each: normal, astaxanthin, β-carotene, resveratrol, and all three antioxidants. Equal concentrations (0.06% [w/w]) of the respective antioxidants were included in the diet of each group. In the mixed group, three antioxidants were added in equal proportion. One leg of each mouse was casted for 3 wk to induce muscle atrophy. After removal of the cast, the mice were fed each diet for 2 wk. The muscle tissues were collected, weighed, and examined for protein metabolism signaling and oxidative damage. The weight of the soleus muscle was increased in the astaxanthin, β-carotene, and resveratrol groups to a greater extent than in the normal group; this was accelerated by intake of the mixed antioxidants (P = 0.007). Phosphorylation levels of mammalian target of rapamycin and p70 S6 K in the muscle were higher in the mixed antioxidant group than in the normal group (P = 0.025; P = 0.020). The carbonylated protein concentration was lower in the mixed antioxidant group than in the normal group (P = 0.021). These results suggested that a combination of astaxanthin, β-carotene, and resveratrol, even in small amounts, promoted protein synthesis during the muscle hypertrophic process following atrophy.


[Eradication of Helicobacter pylori in patients with recurrent abdominal pain using a triple drug treatment].
Different antibiotics, antagonist H2 and others have been used for elimination and/or eradication of Helicobacter pylori. Evaluate elimination of Helicobacter pylori with amoxicillin, bismuth subsalicylate and ranitidine; and the improvement of recurrent abdominal pain. 20 children with recurrent abdominal pain associated to gastritis and histologic identification of Helicobacter pylori were studied under a period of 18 months (January 1992 to June 1993), at Instituto Nacional de Pediatría, México, D.F. All children were treated simultaneously with: Amoxicillin, 15 days, plus ranitidine and bismuth subsalicylate for one month. Helicobacter pylori was eliminated in 14 of 20 children studied. All these children had an important improvement of recurrent abdominal pain. Elimination of Helicobacter pylori and clinical improvement was present in 14 of 20 children studied (70%).


Influence of negative pressure applied to the upper airway on the breathing pattern in unanesthetized awake dogs.
We examined the influence of changes in upper airway pressure on the breathing pattern in 5 unanesthetized awake dogs. The dogs breathed through an endotracheal tube or through a comfortably fitting fiberglass snout mask. With matched resistances and volume of the dead space, the inspiratory duration, tidal volume, and minute ventilation were higher during nasal breathing compared to tracheal breathing. Nasal and tracheal occlusion produced prolongation of inspiration in the first occluded breathing attempt, but the prolongation was more marked in nasal occlusion tests. Augmentation of genioglossus muscle activity occurred on the first occluded breath in nasal but not tracheal occlusion. In another series of experiments, negative pressure was applied to the isolated upper airway while the dog breathed through a tracheostomy tube. Negative pressure caused a prolongation of inspiratory duration which was proportional to the level of the applied pressure. However, the prolongation of inspiratory duration was significantly more marked when application of negative pressure was timed simultaneously with tracheal occlusion. Our results demonstrate that the upper airway has a powerful effect on the control of breathing, which becomes more evident during tracheal occlusion.


Immunohistological studies of skin biopsies from patients with lepromatous leprosy.
Forty-six skin biopsies from lepromatous leprosy patients were examined for immunoglobulin and complement deposits as well as mycobacterial antigens. Rabbit anti-human immunoglobulin, rabbit anti-human C3, and rabbit anti-Mycobacterium bovis (BCG) were used as the primary antigen-detecting antibodies in a peroxidase antiperoxidase technique. Of the 26 biopsies from active erythema nodosum leprosum lesions, 6 were positive for immunoglobulin or complement deposits. These deposits were found in the dermoepidermal junction, within the foamy cells, and, in one patient, around a blood vessel. Five of twenty patients with lepromatous leprosy without erythema nodosum leprosum showed similar deposits in the dermoepidermal junction and within foamy cells. None of these patients had these deposits around blood vessels. Mycobacterial antigens were seen in all biopsies studied. The presence of acute inflammatory infiltrates did not correlate with the presence or absence of immunoglobulin or complement deposits. It is felt that immunoglobulin or complement deposits are not a constant feature of early erythema nodosum leprosum lesions and that these deposits may be secondary rather than primary in these lesions.


Genetic analysis of type 2 tri-allelic pattern at TPOX locus in the Chinese Han population.
Tri-allelic patterns can occasionally be observed during the profiling of short tandem repeats (STRs) in routine forensic practice. In previous studies, the Type 2 tri-allelic pattern at TPOX has been widely studied in African and Brazilian populations. In this study, we investigated the incidence, rearrangement, and inheritance of the Type 2 tri-allelic pattern at the TPOX locus in a Chinese Han population. The frequency of the Type 2 pattern at TPOX was approximately 0.0189%, and the major extra allele was allele 11 in the Chinese Han population. Two major allelic combinations, 8/11 and 11/12, were observed, which are different from the configuration of that in both African and Brazilian populations. Tight linkage between alleles 11 and 12 was observed in the majority of the Type 2 pattern at TPOX in the Chinese Han population, while the location of the extra copy on chromosome 2 was validated, which shows an identical ancestral origin. The excess allelic combination 8/11 implies a homogeneous origin and tight linkage relationship. However, the rearrangement in the Type 2 pattern with the 8/11 allelic combination remained unknown. Altogether, these results show the configuration of the Type 2 tri-allelic pattern at the TPOX locus in the Chinese Han population, which will assist in the understanding of the Type 2 tri-allelic pattern at the TPOX locus in the global population.


Educational outreach visits: effects on professional practice and health care outcomes.
Educational outreach visits (EOVs) have been identified as an intervention that may improve the practice of healthcare professionals. This type of face-to-face visit has been referred to as university-based educational detailing, academic detailing, and educational visiting. To assess the effects of EOVs on health professional practice or patient outcomes. For this update, we searched the Cochrane EPOC register to March 2007. In the original review, we searched multiple bibliographic databases including MEDLINE and CINAHL. Randomised trials of EOVs that reported an objective measure of professional performance or healthcare outcomes. An EOV was defined as a personal visit by a trained person to healthcare professionals in their own settings. Two reviewers independently extracted data and assessed study quality. We used bubble plots and box plots to visually inspect the data. We conducted both quantitative and qualitative analyses. We used meta-regression to examine potential sources of heterogeneity determined a priori. We hypothesised eight factors to explain variation across effect estimates. In our primary visual and statistical analyses, we included only studies with dichotomous outcomes, with baseline data and with low or moderate risk of bias, in which the intervention included an EOV and was compared to no intervention. We included 69 studies involving more than 15,000 health professionals. Twenty-eight studies (34 comparisons) contributed to the calculation of the median and interquartile range for the main comparison. The median adjusted risk difference (RD) in compliance with desired practice was 5.6% (interquartile range 3.0% to 9.0%). The adjusted RDs were highly consistent for prescribing (median 4.8%, interquartile range 3.0% to 6.5% for 17 comparisons), but varied for other types of professional performance (median 6.0%, interquartile range 3.6% to 16.0% for 17 comparisons). Meta-regression was limited by the large number of potential explanatory factors (eight) with only 31 comparisons, and did not provide any compelling explanations for the observed variation in adjusted RDs. There were 18 comparisons with continuous outcomes, with a median adjusted relative improvement of 21% (interquartile range 11% to 41%). There were eight trials (12 comparisons) in which the intervention included an EOV and was compared to another type of intervention, usually audit and feedback. Interventions that included EOVs appeared to be slightly superior to audit and feedback. Only six studies evaluated different types of visits in head-to-head comparisons. When individual visits were compared to group visits (three trials), the results were mixed. EOVs alone or when combined with other interventions have effects on prescribing that are relatively consistent and small, but potentially important. Their effects on other types of professional performance vary from small to modest improvements, and it is not possible from this review to explain that variation.


Multiple Endocrine Neoplasia Type 2B Presents Early in Childhood but Often Is Undiagnosed for Years.
We describe the presenting symptoms and signs of multiple endocrine neoplasia type 2B in a cohort of children. Improved awareness of the early nonendocrine signs of multiple endocrine neoplasia type 2B could lead to earlier diagnosis before the development of medullary thyroid cancer and possibly its metastasis.


Revision rotator cuff repair.
The management of patients with a failed rotator cuff repair is challenging. Revision arthroscopic repairs can be entertained in select patients when realistic outcomes are understood. Complete evaluation of the shoulder is needed to identify and treat potential confounding pain generators. The ability to determine if a recurrent tear is repairable is difficult, because there are no established criteria to make this determination. If a recurrent tear is found to be repairable, the results of the surgery are encouraging, although persistent limitations in shoulder function are common. Strategies to improve the rates of tendon healing should be used and include the use of stronger repair constructs, when possible, and implementation of a slower rehabilitation progression.


miEAA 2.0: integrating multi-species microRNA enrichment analysis and workflow management systems.
Gene set enrichment analysis has become one of the most frequently used applications in molecular biology research. Originally developed for gene sets, the same statistical principles are now available for all omics types. In 2016, we published the miRNA enrichment analysis and annotation tool (miEAA) for human precursor and mature miRNAs. Here, we present miEAA 2.0, supporting miRNA input from ten frequently investigated organisms. To facilitate inclusion of miEAA in workflow systems, we implemented an Application Programming Interface (API). Users can perform miRNA set enrichment analysis using either the web-interface, a dedicated Python package, or custom remote clients. Moreover, the number of category sets was raised by an order of magnitude. We implemented novel categories like annotation confidence level or localisation in biological compartments. In combination with the miRBase miRNA-version and miRNA-to-precursor converters, miEAA supports research settings where older releases of miRBase are in use. The web server also offers novel comprehensive visualizations such as heatmaps and running sum curves with background distributions. We demonstrate the new features with case studies for human kidney cancer, a biomarker study on Parkinson's disease from the PPMI cohort, and a mouse model for breast cancer. The tool is freely accessible at: https://www.ccb.uni-saarland.de/mieaa2.


Prostacyclin and human foetal circulation.
Tissues from human umbilical cord arteries and placental veins generated much greater prostacyclin activity than vessels from normal adults. High prostacyclin generation could contribute to maintaining the low peripheral vascular resistance typical of foetal circulation in which blood pressure is low despite very high cardiac output.


Synergistic interactions of fine particles and radiative effects in modulating urban heat islands during winter haze event in a cold megacity of Northeast China.
Severe air pollution and urban heat islands (UHI) intensity (UHII) are two challenging problems that have attracted wide attention in populated cities. However, previous studies mostly focused on the relationship between fine particulate matter (PM2.5) and UHII, but how UHII responds to the interactions between radiative effects (direct effect (DE), indirect effect (IDE) with slope and shading effects (SSE)) and PM2.5 during heavy pollution is still unclear, especially in the cold region. Therefore, this study explores the synergistic interactions between PM2.5 and radiative effects in influencing UHII during a heavy pollution event in the cold-megacity of Harbin-China. Hence, we designed four scenarios: non-aerosol radiative feedback (NARF), DE, IDE, and combined effects (DE + IDE + SSE) in December 2018 (clear-episode) and December 2019 (heavy-haze-episode) using numerical modeling. The results showed that the radiative effects influenced the spatial distribution of PM2.5 concentration leading to a mean drop in 2-m air-temperature by approximately 0.67 °C (downtown) and 1.48 °C (satellite-town) between the episodes. The diurnal-temporal variations revealed that the daytime and nighttime UHIIs were strengthened in the downtown during the heavy-haze-episode, while a reverse effect was observed in the satellite-town. Interestingly, during the heavy-haze-episode, the considerable difference between excellent and heavily polluted PM2.5 levels showed a decrease in UHIIs (1.32 °C, 1.32 °C, 1.27 °C, and 1.20 °C) due to the radiative effects (NARF, DE, IDE, and (DE + IDE + SSE)), respectively. In assessing other pollutants' interactions with the radiative effects, PM10 and NOx had a considerable impact on the UHII during the heavy-haze episode while O3 and SO2 were discovered to be very low in both episodes. Moreover, the SSE has uniquely influenced UHII, especially during the heavy-haze-episode. Therefore, insight from this study provides an understanding of how UHII responds uniquely in the cold region, which in turn could help to formulate effective policies and co-mitigation strategies for air pollution and UHI problems.


Automatic and sensitive detection of West Nile virus non-structural protein 1 with a portable SERS-LFIA detector.
A portable surface-enhanced Raman scattering (SERS)-lateral flow immunoassay (LFIA) detector has been developed for the automatic and highly sensitive detection of West Nile virus (WNV) non-structural protein 1 (NS1) and actual WNV samples. Au@Ag nanoparticles (Au@Ag NPs) labeled with double-layer Raman molecules were used as SERS tags to prepare WNV-specific SERS-LFIA strips. On this platform, the WNV-specific antigen NS1 protein was quantitatively and sensitively detected. The detection limit for the WNV NS1 protein was 0.1 ng/mL, which was 100-fold more sensitive than visual signals. The detection limit for inactivated WNV virions was 0.2 × 102 copies/μL. The sensitivity of the SERS-LFIA detector was comparable to that of the fluorescence quantitative reverse transcription-polymerase chain reaction assay. The prepared SERS-LFIA strips exhibited high sensitivity and good specificity for WNV. Thus, the strips developed herein have clinical application value. Moreover, the portable SERS-LFIA detector enabled automatic and rapid detection of the SERS-LFIA strips. The platform established herein is expected to make a substantial contribution to the diagnosis and control of outbreaks of emerging infectious diseases, including WNV.


Urologic abdominal masses in infants and children.
A series of 167 infants and children presenting with palpable urologic abdominal masses from 1960 to 1973 has been reviewed. The groupings by age at presentation and type of urologic lesion enable us to make certain general statements. Emphasis is placed upon adequate preoperative evaluation in any child with an abdominal mass to avoid unnecessary laparotomy and morbidity.


Modeling the mechanics of fibrous-porous scaffolds for skeletal muscle regeneration.
The scaffolds for skeletal muscle regeneration are designed to mimic the structure, stiffness, and strains applied to the muscle under physiologic conditions. The external strains are also used to stimulate myogenesis of the (stem) cells seeded on the scaffold. The time- and location-dependent mechanics inside the scaffold determine the microenvironment for the seeded cells. Here, fibrous-porous cylindrical scaffolds under the action of external cyclic strains are considered. The scaffold mechanics are described as two-phase (poroelastic) where the solid phase is associated with the fibers and the fluid phase is associated with the liquid-containing pores. In response to an applied cyclic strain, pressure oscillates and fluid moves radially toward and away from the axis of the scaffold. We compute the directions and magnitudes of the radial gradients of the poroelastic characteristics (solid-phase displacement, strain, and velocity; fluid-phase pressure and velocity; relative fluid-solid-phase velocity) determined by the boundary conditions and geometry of the scaffold. Several kinds of the external cyclic strain are analyzed and the resulting poroelastic functions are found. The poroelastic characteristics are obtained in closed form which is convenient for further consideration of myogenesis of the seeded cells and ultimately for the design of the scaffolds for skeletal muscle regeneration. Graphical abstract.