Prospective studies of diagnosis and intervention: the Dutch experience.
This prospective multicenter study included 1,205 patients, who were referred for difficult-to-treat hypertension or analysis of possible secondary hypertension. After a standardized selection protocol based on sharply defined drug-resistant hypertension or renal function impairment during angiotensin-converting enzyme inhibition, patients underwent renal scintigraphy and a captopril-renin challenge test. A set of clinical characteristics was also recorded. Sensitivity and specificity of renal scintigraphy for diagnosing renal artery stenosis were 0.72 and 0.90 and of the captopril-renin test 0.77 to 0.91 and 0.69 to 0.75 depending on the criterion used. The clinical characteristics were used to construct a clinical prediction rule for renal artery stenosis, which had a sensitivity of 0.68 and a specificity of 0.87 at a cut-off level of 30% predicted probability. However, with the prediction rule a sensitivity of 0.90 could be reached by performing arteriography only in patients with a predicted probability of stenosis of > or =10%, resulting in a considerable reduction of the number of arteriograms to be made. A diagnostic strategy is advocated starting with drug-resistant hypertension and continuing to renal arteriography only in patients with increased probability of stenosis. Patients with atherosclerotic renal artery stenosis were then randomized to balloon angioplasty (n = 56) versus antihypertensive medication (n = 50). Three months after randomization 22 patients from the medication group underwent balloon angioplasty in second instance. In an intention-to-treat analysis, no difference in blood pressure was found between the groups after 3 months, nor after 12 months of follow-up, although there was a small medication-sparing effect of balloon angioplasty. The lack of a beneficial effect of balloon angioplasty compared with medication could not be attributed to the high stenosis recurrence rate after angioplasty, nor to the fact that the inclusion criterion was set at a stenosis level of > or =50% so that patients with relatively mild stenosis were also included. Renal function after angioplasty was slightly better in the angioplasty group than in the medication group, and improvement of the renal scintigram occurred more often after angioplasty. Apart from the treatment of patients with specific characteristics, the presented therapeutic approach starts with extending the antihypertensive drug therapy to control blood pressure. Only if blood pressure cannot be controlled or if renal function deteriorates, balloon angioplasty (with stent placement) is indicated.


Thoracoscopic Nuss procedure for young adults with pectus excavatum: excellent midterm results and patient satisfaction.
Chest wall remodeling by substernal placement of a Nuss bar is the treatment of choice for children with pectus excavatum; however, it has not yet gained widespread acceptance in adults. We demonstrate that thoracoscopic Nuss bar insertion in young adults is safe and leads to excellent results. Adult patients who underwent thoracoscopic Nuss bar insertion at one institution between 2006 and 2012 were identified. Data on demographics, postoperative outcomes, quality of life, and cosmetic satisfaction was collected. A validated single-step quality of life survey was administered to patients. Student's t test and the Wilcoxon rank sum test were used for statistical analysis. Seventy-three patients (65 male, 8 female) with a median age of 20 years (range, 16 to 51) were included. The median follow-up was 44.6 months (range, 36.9 to 73.26). Most patients (59 of 73, 81%) had one bar placed. The median length of hospital stay was 5 days (range, 3 to 9) and the median duration of epidural anesthesia was 3 days (range, 0 to 7). There were 4 reoperations (5.5%) in the immediate postoperative period: 2 for bar displacement and 2 for poor cosmesis. All reoperations were performed thoracoscopically. Other postoperative complications included pneumothorax (3 of 73, 4.1%) and ileus (1 of 73, 1.3%). Fifty-one patients participated in a quality-of-life survey (73% response rate). The mean self-esteem score improved from 4.6 of 10 preoperatively to 6.5 of 10 postoperatively (p=0.002). The social impact of the pectus deformity became less significant (mean preoperative score 3.6, mean postoperative score 2.8, p=0.02). The severity of initial postoperative pain was much improved on follow-up. The vast majority of patients (41 of 51, 80%) were satisfied with the cosmetic result, and 96% (49 of 51) would opt to have the surgery again. For young adults who wish to correct their pectus deformity, a thoracoscopic Nuss procedure is safe and results in a high rate of patient satisfaction, significant improvement in self-image, and excellent midterm cosmetic results.


Work hours, workload, sleep and fatigue in Australian Rail Industry employees.
Research suggests that less than 5 h sleep in the 24 h prior to work and/or more than 16 h of wakefulness can significantly increase the likelihood of fatigue-related impairment and error at work. Studies have also shown exponential safety declines with time on shift, with roughly double the likelihood of accident or injury after 10 h relative to the first 8h. While it is acknowledged that reduced sleep, increased wakefulness and longer work hours produce work-related fatigue, few studies have examined the impact of workload on this relationship. Studies in the rail industry have focused on drivers. This study investigated fatigue in a large sample of Australian Rail Industry Employees. Participants were from four companies (n = 90: 85m, 5f; mean age 40.2 ± 8.6 y). Data was analysed for a total of 713 shifts. Subjects wore wrist actigraphs and completed sleep and work diaries for 14-days. They also completed the Samn-Perelli Fatigue Scale at the beginning and end of shifts, and the NASA-TLX workload scale at least twice during each shift. Average (±SD) sleep length (7.2 ± 2.6h), prior wake at shift end (12.0 ± 4.7h), shift duration (8.0 ± 1.3) and fatigue (4.1 ± 1.3, "a little tired, less than fresh") were within limits generally considered acceptable from a fatigue perspective. However, participants received 5 h or less sleep in the prior 24 h on 13%, were awake for at least 16 h at the end of 16% and worked at least 10 h on 7% of shifts. Subjects reported that they felt "extremely tired, very difficult to concentrate," or "completely exhausted, unable to function effectively" on 13% of shifts. Sleep length (OR = 0.88, p < 0.01), shift duration (OR = 1.18, p < 0.05), night shift (REF = morning shift, OR = 2.12, p < 0.05) and workload ratings (OR = 1.2, p < 0.05) were significant predictors of ratings of extreme tiredness/exhaustion (yes/no). While on average, sleep loss, extended wakefulness, longer work hours and work-related fatigue do not appear problematic in this sample, there is still a notable percentage of shifts that are likely to be associated with high levels of work-related fatigue. Given the size of the Australian Rail Industry, with thousands of shifts occurring each day, this is potentially of operational concern. Further, results indicate that, in addition to sleep length, wakefulness and work hours, workload significantly influences fatigue. This has possible implications for bio-mathematical predictions of fatigue and for fatigue management more generally.


Mammographic guidewire localization of nonpalpable breast lesions.
Guidewire-directed biopsy is the predominant method of evaluating nonpalpable breast lesions detected by mammography. It is an accurate and safe procedure for obtaining a histologic evaluation of abnormal tissue, leading to early diagnosis and improved survival rates. This report reviews 526 needle localizations and biopsies of nonpalpable breast lesions performed in two community hospitals over a 39-month period and compares early results with those achieved in the last 13 months of the study. This review indicates that as experience in using this modality increased, the cancer detection rate increased and the percentage of invasive cancers decreased. The percentage of cancers detected in the final 13 months of the study (19%, Group II) was higher than in the first 26 months of the study (13%, Group I). Although microcalcifications were found in 24 per cent of the mammograms leading to a diagnosis of cancer, they did not prove to be a reliable indicator of malignancy in this study.


Sensitive determination of acidic drugs and triclosan in surface and wastewater by ion-pair reverse-phase liquid chromatography/tandem mass spectrometry.
A new method is presented for the determination of 12 acidic pharmaceuticals (non-steroidal anti-inflammatory drugs and bezafibrate), including two metabolites from aqueous samples, together with triclosan as a personal care product. Ion-pair liquid chromatography (IP-LC) with electrospray ionisation tandem mass spectrometry (ESI-MS) in the negative ion mode was employed. The ion-pairing agent (tri-n-butylamine) increased the signal intensity for all acidic analytes and detection limits of 6-200 ng/L were obtained by multiple reaction monitoring. This allows analysis of wastewater samples by direct injection into the LC/MS system without the need for a preceding enrichment step. When combined with a solid-phase extraction (SPE) step, limits of quantification between 0.15 and 11 ng/L were obtained from 100-mL sample volumes, which is adequate for most applications. The occurrence of matrix effects was studied and standard addition was required for reliable quantification after SPE from wastewater. The method was finally applied to surface and wastewaters, with analyte concentrations ranging from below the detection limit up to 5.5 microg/L.


Ethnic-specific meta-analyses of association between the OPRM1 A118G polymorphism and alcohol dependence among Asians and Caucasians.
Many studies have investigated the association between the OPRM1 A118G polymorphism (rs1799971) and alcohol dependence, but the results were inconsistent. To better understand this relationship, ethnicity-specific meta-analyses were conducted. We retrieved all eligible studies published up to April 12, 2011 from the PubMed/MEDLINE, EMBASE, and ISI Web of Science databases. Ethnicity-specific meta-analyses were performed using either fixed- or random-effect models as appropriate. Twelve independent studies with 1900 cases and 2382 controls were included. Five studies were conducted in Asians and seven in Caucasians. Ethnicity-specific meta-analyses revealed that the A118G polymorphism was significantly associated with alcohol dependence risk in Asians (GA vs. AA: odds ratio [OR], 1.73; 95% confidence interval [CI], 1.33-2.25; GA+GG vs. AA: OR, 1.57; 95% CI, 1.22-2.02), but not in Caucasians (GA vs. AA: OR, 1.05; 95% CI, 0.75-1.49; GA+GG vs. AA: OR, 1.11; 95% CI, 0.79-1.55). The OPRM1 A118G polymorphism may contribute to the susceptibility of alcohol dependence in Asians but not in Caucasians.


Endogenously expressed IL-13Rα2 attenuates IL-13-mediated responses but does not activate signaling in human lung fibroblasts.
IL-13 can bind to two distinct receptors: a heterodimer of IL-13Rα1/IL-4Rα and IL-13Rα2. Whereas IL-13Rα1/IL-4Rα engagement by IL-13 leads to the activation of STAT6, the molecular events triggered by IL-13 binding to IL-13Rα2 remain incompletely understood. IL-4 can bind to and signal through the IL-13Rα1/IL-4Rα complex but does not interact with IL-13Rα2. Idiopathic pulmonary fibrosis is a progressive and generally fatal parenchymal lung disease of unknown etiology with no current pharmacologic treatment options that substantially prolong survival. Preclinical models of fibrotic diseases have implicated IL-13 activity on multiple cell types, including macrophages and fibroblasts, in initiating and perpetuating pathological fibrosis. In this study, we show that IL-13, IL-4, IL-13Rα2, and IL-13-inducible target genes are expressed at significantly elevated levels in lung tissue from patients with idiopathic pulmonary fibrosis compared with control lung tissue. IL-4 and IL-13 induce virtually identical transcriptional responses in human monocytes, macrophages, and lung fibroblasts. IL-13Rα2 expression can be induced in lung fibroblasts by IL-4 or IL-13 via a STAT6-dependent mechanism, or by TNF-α via a STAT6-independent mechanism. Endogenously expressed IL-13Rα2 decreases, but does not abolish, sensitivity of lung fibroblasts to IL-13 and does not affect sensitivity to IL-4. Genome-wide transcriptional analyses of lung fibroblasts stimulated with IL-13 in the presence of Abs that selectively block interactions of IL-13 with IL-13Rα1/IL-4Rα or IL-13Rα2 show that endogenously expressed IL-13Rα2 does not activate any unique IL-13-mediated gene expression patterns, confirming its role as a decoy receptor for IL-13 signaling.


Prevalence, Awareness, Treatment, Control, and Correlates of Hypertension in the Pars Cohort Study.
High blood pressure is an important risk factor for all-cause mortality and cardiovascular mortality and morbidity among Iranians. We aimed to estimate its prevalence, correlates, and its rate of awareness, treatment, and control in South of Iran. The Pars Cohort Study (PCS) was launched in a district of Fars province. All residents between 40 and 75 years old in the district were recruited from 2012 to 2014. Hypertension was defined as either systolic/diastolic blood pressure ≥ 140/90 mm Hg or taking medications. Logistic regression was used to identify the correlates of hypertension and awareness and its treatment and control. A total of 9264 participants were recruited. Of the total participants, 46.2% were men. The mean age was 52.6 years (SD: 9.7). Prevalence of hypertension was 26.9%. Of the total 2489 hypertensives, 49.6% were aware and 55.7% were under treatment. Blood pressure was controlled in 69.2% of treated hypertensives. In the adjusted model, female sex and history of cardiovascular disease (CVD) were positively associated with having hypertension, higher awareness, and better treatment and control. Older age, being overweight or obese, and having a history of diabetes were also positively associated with having hypertension and higher awareness and treatment; however, being overweight or obese was associated with poorer hypertension control. Older age and having a history of diabetes did not show a statistically significant association with control. Being underweight and higher physical activity were inversely associated with having hypertension but were not associated with awareness, treatment, or control. Prevalence of hypertension is high but the rates of awareness, treatment, and control are not adequate.


The effect of gold loading and particle size on photocatalytic hydrogen production from ethanol over Au/TiO₂ nanoparticles.
Catalytic hydrogen production from renewables is a promising method for providing energy carriers in the near future. Photocatalysts capable of promoting this reaction are often composed of noble metal nanoparticles deposited on a semiconductor. The most promising semiconductor at present is TiO₂. The successful design of these catalysts relies on a thorough understanding of the role of the noble metal particle size and the TiO₂ polymorph. Here we demonstrate that Au particles in the size range 3-30 nm on TiO₂ are very active in hydrogen production from ethanol. It was found that Au particles of similar size on anatase nanoparticles delivered a rate two orders of magnitude higher than that recorded for Au on rutile nanoparticles. Surprisingly, it was also found that Au particle size does not affect the photoreaction rate over the 3-12 nm range. The high hydrogen yield observed makes these catalysts promising materials for solar conversion.


Radio-iodine treatment of hyperthyroid cats.
Thirty-two elderly domestic shorthaired cats (mean age 12.9 years) were treated with radioiodine (131I). The dose of 131I administered ranged from 39 mBq to 134 mBq. Twenty-eight cats became euthyroid after treatment, one became hypothyroid and three remained hyperthyroxaemic. Two of the hyperthyroxaemic cats were successfully re-treated with 131I. Five cats died from concurrent diseases within one year of treatment. The administration of a dose of 131I selected by assessing the severity of the clinical signs, the size of the thyroid gland(s) and the serum level of thyroxine was an effective treatment for hyperthyroidism.


Juvenile periodontitis in Ibadan, Nigeria.
Juvenile periodontitis is a form of periodontitis characterised by a pattern of rapid vertical loss of alveolar bone around the permanent first molars and incisors. In this hospital based retrospective study of juvenile periodontitis in Ibadan, 34 cases in the age range 17-34 years were seen over a period of five years. The mean age was 23.2 years. Diagnosis was made on accepted clinical and radiological parameters. The findings showed a low prevalence of 1.56%, (64.7% of localised juvenile periodontitis, 35.3% of generalised juvenile periodontitis). There was a 2:1 female to male relationship and the oral hygiene status of the subjects was fairly good in most instances. Remarkable symmetrical pattern and relationship was observed. The age of onset or age at presentation was 17 years contrary to reports from other studies which revealed circumpubertal age of onset.


Algal stromatolites: use in stratigraphic correlation and paleocurrent determination.
Algal stromatolites are used for detailed rock-stratigraphic correlation for a distance of 160 kilometers in the Pethei Formation, of Aphebian (Precambrian) age, in the Northwest Territories, Canada. Laterally linked stromatolites are initiated by the draping of successive laminations over intraclasts or other irregularities in the bedding surface. Stromatolite shapes and orientations are related to paleocurrent direction determined from associated sedimentary structures. Thus stromatolite geometry is at least in part environmentally controlled.


Sites of phosphorylation and mutation in regulatory subunit of cyclic AMP-dependent protein kinase from S49 mouse lymphoma cells: mapping to structural domains.
A novel peptide mapping approach has been used to map sites of charge modification to major structural domains of regulatory subunit (R) of type I cAMP-dependent protein kinase from S49 mouse lymphoma cells. Proteolytic fragments of crude, radiolabeled R were purified by cAMP affinity chromatography and displayed by two-dimensional polyacrylamide gel electrophoresis. [35S]methionine-labeled peptides containing sites of mutation or phosphorylation exhibited charge heterogeneity attributable to the modification. Phosphate-containing fragments were also labeled with [32P]orthophosphate to confirm their phosphorylation. Major fragments from [35S]methionine-labeled S49 cell R corresponded in size to carboxyterminal cAMP-binding fragments reported from proteolysis of purified type I Rs from various mammalian species; additional fragments were also visualized. End-specific markers in Rs from some mutant S49 sublines confirmed that cAMP-binding fragments extended to the carboxyterminus of R. Aminoterminal endpoints of fragments could be deduced, therefore, from peptide molecular weights. Clustering of proteolytic cleavage sites within the "hinge-region" separating aminoterminal and carboxyterminal domains of R permitted high resolution mapping in this region: the endogenous phosphate and a "phenotypically-silent" electrophoretic marker mutation fell within a 2.5-kdalton interval at its aminoterminal end. On the other hand, Ka mutations that increase the apparent constant for activation of kinase by cAMP mapped within the large cAMP-binding region of R. A map of charge density distribution within the hinge-region of R was constructed to facilitate structural comparisons between Rs from S49 cells and from other mammalian sources.


Ameliorative effect of methanol extract of Rumex vesicarius on CCl4-induced liver damage in Wistar albino rats.
Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties. This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl4-induced liver damage. The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200 mg/kg, p.o.) for 7 d prior to the induction of liver damage by CCl4. Animals were then sacrificed 24 h after CCl4 administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses. CCl4-induced hepatotoxicity was confirmed by an increase (p < 0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl4-induced hepatotoxicity was also manifested by an increase (p < 0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200 mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01 ± 13.21), serum ALT (82.15 ± 5.01), serum ALP (504.75 ± 19.72), hepatic LPO (3.38 ± 0.33), and increased levels of hepatic glutathione (0.34 ± 0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl4-intoxicated rats. The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl4-induced liver toxicity; hence, it can be used as a hepatoprotective agent.


[Biosocial causes of abnormal behavior in childhood and adolescence (author's transl)].
"Abnormal behavior" is no diagnosis. But this term has been accepted in modern industrial Society. For some time many which at present burden the family, the social environment and structure. The basic causes for decompensation of adaptability of children and adolescents are discussed. 4 factors are considered particularly powerful: a disposition towards behavioral instability, absence of close human links in early childhood, lack of socialisation in the sexual sphere and the inability to identify with the own sez-role. The pathologic symptoms nearly always result from a combination of these four. The decisive causes of behavioral disturbance can, therefore, not be found in actual frustration but in unfavorable conditions of development in early childhood.


Influence of socioeconomic factors on delays, management and outcome amongst patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.
The outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) is strongly affected by time delays. In this study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients undergoing pPCI, who came from a well-defined region of the French part of Switzerland. A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analysed for the following socioeconomic factors: level of education, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment with fibrinolytic agents or patients immediately referred for coronary artery bypass graft surgery. Therefore, 222 patients were finally included. At 1 year, there was no difference in mortality between the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly longer for patients with a low level of education, Swiss citizens and unmarried patients, with median differences of 23 minutes, 18 minutes and 13 minutes, respectively (p <0.05). Nevertheless, no difference was found regarding in-hospital management and clinical outcome. This study demonstrates that symptom-to-first-medical-contact time is longer amongst people with a lower educational level, Swiss citizens and unmarried people. Because of the low mortality rate in general, these differences in delays did not affect clinical outcomes. Still, tertiary prevention measures should particularly focus on these vulnerable populations.


Executive functioning in high-functioning children with autism.
Executive functioning was investigated in 34 children (24 boys and 10 girls) with developmental language disorder (DLD) and 21 children (18 boys and 3 girls) with high-functioning autistic disorder (HAD) matched on Full Scale IQ, Nonverbal IQ, age (mean age 9 year, 1 month), and SES. The DLD group had a Verbal IQ that was 10 points higher than the HAD group. These children were given the Wisconsin Card Sorting Test (WCST), the Mazes subtest from the WISC-R, the Underlining test, and the Rapid Automatized Naming test. In addition, these children were given the Vineland Scales of Adaptive Functioning and the Wing Diagnostic Symptom Checklist in order to assess severity of autistic symptomatology. Results indicated that the only significant difference between the two groups on the cognitive tasks was perseverative errors on the WCST; there was no significant difference on total number of categories achieved or total number of errors on the WCST or on the other executive function measures. There was also significant overlap in the scores between the two groups and the difference in perseverative errors was no longer significant when Verbal IQ was partialled out. Executive functioning was strongly related to all IQ variables in the DLD group and particularly related to Verbal IQ in the HAD group. Although there was a relationship in the HAD group between executive functioning and adaptive functioning, as well as between executive functioning and autistic symptomatology, these relationships were generally no longer significant in the HAD group after the variance due to Verbal IQ was accounted for. The results are interpreted to indicate that although impaired executive functioning is a commonly associated feature of autism, it is not universal in autism and is unlikely to cause autistic behaviors or deficits in adaptive function.


Enhancement of photon intensity in forced coupled quantum wells inside a semiconductor microcavity.
We study numerically the photon emission from a semiconductor microcavity containing N≥2 quantum wells under the influence of a periodic external forcing. The emission is determined by the interplay between external forcing and internal interaction between the wells. While the external forcing synchronizes the periodic motion, the internal interaction destroys it. The nonlinear term of the Hamiltonian supports the synchronization. The numerical results show a jump of the photon intensity to very large values at a certain critical value of the external forcing when the number of quantum wells is not too large. We discuss the dynamics of the system across this transition.


[Anxiety, depression, and stressed life in patients awaiting heart transplantation: are these factors to be considered?].
Heart transplantation is a therapeutic procedure in which biological, psychological, social and ethical aspects play an important role, none of them has to be underestimated. It is known that the waiting period up to heart transplantation is extremely stressful for patients and their families, causing psychopathological and disadaptive reactions. Aim of the present study was to investigate psychological tract characteristics, stress reactions and quality of life in a group of patients registered for heart transplantation. Sixty two patients (47 M, 15 F), with mean age of 53 +/- 9.9 years in NYHA class (16 class II, and 43 class III/IV) and ejection fraction 29 +/- 10 have filled in the following two questionnaires: the Cognitive Behavioural Assessment form H (CBA-H), to measure psychological functioning and/or behaviours at risk for heart disease, and the Short Form 36 (SF-36), to evaluate physical and functional health status. In patients awaiting heart transplantation, the presence of anxiety contributes to reduce physical activity, vitality and mental health. Depressed mood disorders negatively influence physical and mental health and vitality. Perception of stressed life limits role and physical activity, vitality, and emotional status and augments intensity of physical pain. Symptoms of anxiety, depression and stress influence negatively mental health and daily physical activity. These aspects may vary of intensity with progression of the disease and lengthening of waiting. The importance of an early and continuous psychological support to the patient becomes fundamental to individuate and treat these disorders to favour optimal post-transplant outcomes.


Physico-Chemical Characterization of the Interaction of Red Fluorescent Protein-DsRed With Thin Silica Layers.
The Discosoma recombinant red fluorescent (DsRed) protein is the latest member of the family of fluorescent proteins. It holds great promise for applications in biotechnology and cell biology. However, before being used for rational engineering, knowledge on the behavior of DsRed and the underlying mechanisms relating its structural stability and adsorption properties on solid surfaces is highly demanded. The physico-chemical analysis performed in this study reveals that the interaction of DsRed with SiO2 surfaces does not lead to complete protein denaturation after adsorption and dehydration. Nevertheless, the photoluminescence emission of dehydrated DsRed small droplets was found to be slightly red-shifted, peaking at 590 nm. The measured contact angles of droplets containing different concentration of DsRed proteins determine the interaction as hydrophilic one, however with larger contact angles for larger DsRed concentrations. The DsRed protein behavior is not pH-dependent with respect of the contact angle measurements, in agreement with previously reported studies.


Ion concentrations in nasal airway surface liquid: a prediction model for the identification of cystic fibrosis carriers.
Cystic fibrosis (CF) carriers seem to have a higher risk to develop chronic rhino-sinusitis (CRS), although the full underlying mechanisms are unknown. Ion concentrations in nasal airway surface liquid (ASL) may be influenced by the heterozygosity for CF gene mutation, with possible impacts on the development of CRS. A cheap and feasible standardized technique was designed to measure the ion levels in nasal ASL. With this purpose we collected, under basal conditions, samples from the nasal cavity of 165 adults: 14 homozygous for CF, 83 carriers and 68 healthy controls. Sodium (Na) and Chlorine (Cl) concentrations were then evaluated among different groups. Statistical analysis revealed a significant difference of Na and Cl values between controls and carriers and between controls and homozygotes. Receiver operating characteristic (ROC) curves and derived indicators (Youden's index and Area Under the Curve, AUC) were used to further evaluate the diagnostic capability of Na and Cl concentrations to differentiate heterozygotes from controls. ROC curves demonstrated that the optimal diagnostic cut-off value of Na is at 124, and the optimal cut-off value of Cl is at 103,2. ASL sampling can be considered a new diagnostic tool for providing quantitative information on nasal ion composition. According to our findings, Na and Cl concentrations of nasal ASL could represent a useful tool to assess heterozygotes and healthy controls.


The noninferiority of the nonparticulate steroid dexamethasone vs the particulate steroids betamethasone and triamcinolone in lumbar transforaminal epidural steroid injections.
To assess whether a nonparticulate steroid (dexamethasone, 10 mg) is less clinically effective than the particulate steroids (triamcinolone, 80 mg; betamethasone, 12 mg) in lumbar transforaminal epidural steroid injections (TFESIs) in subjects with radicular pain with or without radiculopathy. Retrospective observational study with noninferiority analysis of dexamethasone relative to particulate steroids. Single academic radiology pain management practice. Three thousand six hundred forty-five lumbar TFESIs at the L4-5, L5-S1, or S1 neural foramina, performed on 2,634 subjects. Subjects were assessed with a pain numerical rating scale (NRS, 0-10) and Roland-Morris disability questionnaire (R-M) prior to TFESI, and at 2 weeks and 2 months follow-up. For categorical outcomes, successful pain relief was defined as either ≥50% reduction in NRS or pain 0/10; functional success was defined as ≥40% reduction in R-M score. Noninferiority analysis was performed with δ = -10% as the limit of noninferiority. Continuous outcomes (mean NRS, R-M scores) were analyzed for noninferiority with difference bounds of 0.3 for NRS scores and 1.0 for R-M scores. With categorical outcomes, dexamethasone was demonstrated to be noninferior to the particulate steroids in pain relief and functional improvement at 2 months. Using continuous outcomes, dexamethasone was demonstrated to be superior to the particulate steroids in both pain relief and functional improvement at 2 months. This retrospective observational study reveals no evidence that dexamethasone is less effective than particulate steroids in lumbar TFESIs performed for radicular pain with or without radiculopathy.


TLR7/TLR9- and B Cell Receptor-Signaling Crosstalk: Promotion of Potentially Dangerous B Cells.
B cells are capable of receptor-mediated responses to foreign antigens. Recognition of microbial-derived nucleic acid (NA) by toll-like receptors (TLRs) 7 and 9 in B cells has been substantiated. Endogenous NA released from damaged or dying cells can also be immunogenic in certain contexts and can incite aberrant activation of B cells. When TLR-driven B cell receptor (BCR)-activated B cells are not properly constrained, pathologic autoantibodies are produced. It is also clear that endosomal TLR7/TLR9 can operate in conjunction with BCR. In addition to BCR signaling, a balance between TLR7 and TLR9 is pivotal in the development of B cell autoreactivity. While TLR9 is important in normal memory B cell responses through BCR, TLR9 activation has been implicated in autoantibody production. Paradoxically, TLR9 also plays known protective roles against autoimmunity by directly and indirectly inhibiting TLR7-mediated autoantibody production. Herein, we summarize literature supporting mechanisms underpinning the promotion of pathological BCR-activated B cells by TLR7 and TLR9. We focus on the literature regarding known points of TLR7/TLR9 and BCR crosstalk. Data also suggest that the degree of TLR responsiveness relies on alterations of certain intrinsic B-cell signaling molecules and is also context specific. Because allogeneic hematopoietic stem cell transplantation is a high NA and B cell-activating factor environment, we conclude that B cell studies of synergistic TLR-BCR signaling in human diseases like chronic graft-versus-host disease are warranted. Further understanding of the distinct molecular pathways mediating TLR-BCR synergy will lead to the development of therapeutic strategies in autoimmune disease states.


A decreasing glacier mass balance gradient from the edge of the Upper Tarim Basin to the Karakoram during 2000-2014.
In contrast to the glacier mass losses observed at other locations around the world, some glaciers in the High Mountains of Asia appear to have gained mass in recent decades. However, changes in digital elevation models indicate that glaciers in Karakoram and Pamir have gained mass, while recent laser altimetry data indicate mass gain centred on West Kunlun. Here, we obtain results that are essentially consistent with those from altimetry, but with two-dimensional observations and higher resolution. We produced elevation models using radar interferometry applied to bistatic data gathered between 2011 and 2014 and compared them to a model produced from bistatic data collected in 2000. The glaciers in West Kunlun, Eastern Pamir and the northern part of Karakoram experienced a clear mass gain of 0.043 ± 0.078~0.363 ± 0.065 m w.e. yr-1. The Karakoram showed a near-stable mass balance in its western part (-0.020 ± 0.064 m w.e. yr-1), while the Eastern Karakoram showed mass loss (-0.101 ± 0.058 m w.e. yr-1). Significant positive glacier mass balances are noted along the edge of the Upper Tarim Basin and indicate a decreasing gradient from northeast to southwest.


Assessment of the Angolan (CHERRT) Mobile Laboratory Curriculum for Disaster and Pandemic Response.
As of April 5, 2020, the World Health Organization reported over one million confirmed cases and more than 62,000 confirmed coronavirus (COVID-19) deaths affecting 204 countries/regions. The lack of COVID-19 testing capacity threatens the ability of both the United States (US) and low middle income countries (LMIC) to respond to this growing threat, The purpose of this study was to assess the effectiveness through participant self-assessment of a rapid response team (RRT) mobile laboratory curriculum METHODS: We conducted a pre and post survey for the purpose of a process improvement assessment in Angola, involving 32 individuals. The survey was performed before and after a 14-day training workshop held in Luanda, Angola, in December 2019. A paired t-test was used to identify any significant change on six 7-point Likert scale questions with α< 0.05 (95% confidence interval). All six of the questions - 1) "I feel confident managing a real laboratory sample test for Ebola or other highly contagious sample;" 2) "I feel safe working in the lab environment during a real scenario;" 3) "I feel as if I can appropriately manage a potentially highly contagious laboratory sample;" 4)"I feel that I can interpret a positive or negative sample during a suspected contagious outbreak;" 5) "I understand basic Biobubble/mobile laboratory concepts and procedures;" and 6) "I understand polymerase chain reaction (PCR) principles" - showed statistical significant change pre and post training. Additionally, the final two questions - "I can more effectively perform my role/position because of the training I received during this course;" and "This training was valuable" - received high scores on the Likert scale. This Angolan RRT mobile laboratory training curriculum provides the nation of Angola with the confidence to rapidly respond and test at the national level a highly infectious contagion in the region and perform on-scene diagnostics. This mobile RRT laboratory provides a mobile and rapid diagnostic resource when epidemic/pandemic resource allocation may need to be prioritized based on confirmed disease prevalence.


[Trauma and vulnerability among children. New knowledge necessitates conceptual revision].
How are we to understand a child's development--both the potentiating and inhibiting factors? The past two decades have witnessed intensive research both on mental trauma and its possible effects on the child's developing brain, and on the importance of risk factors and protective factors in children's development and health. Research in these two fields has been conducted concurrently and has yielded new, important, and in many cases complementary, information. To promote the general availability and clinical applicability of these advances in our knowledge, it is necessary to modify our conceptual approach, basing it on the child's perspective instead.


The Food Marketing Defense Model: Integrating Psychological Research to Protect Youth and Inform Public Policy.
Marketing practices that promote calorie-dense, nutrient-poor foods directly to children and adolescents present significant public health risk. Worldwide, calls for government action and industry change to protect young people from the negative effects of food marketing have increased. Current proposals focus on restricting television advertising to children under 12 years old, but current psychological models suggest that much more is required. All forms of marketing pose considerable risk; adolescents are also highly vulnerable; and food marketing may produce far-reaching negative health outcomes. We propose a food marketing defense model that posits four necessary conditions to effectively counter harmful food marketing practices: awareness, understanding, ability and motivation to resist. A new generation of psychological research is needed to examine each of these processes, including the psychological mechanisms through which food marketing affects young people, to identify public policy that will effectively protect them from harmful influence.


Foliar δ(13)C response patterns along a moisture gradient arising from genetic variation and phenotypic plasticity in grassland species of Inner Mongolia.
Plants depend upon both genetic differences and phenotypic plasticity to cope with environmental variation over different timescales. The spatial variation in foliar δ(13)C levels along a moisture gradient represents an overlay of genetic and plastic responses. We hypothesized that such a spatial variation would be more obvious than the variation arising purely from a plastic response to moisture change. Leymus chinensis and Stipa spp. were sampled from Inner Mongolia along a dry-wet transect, and some of these species were transplanted to an area with a moisture gradient. For Stipa spp., the slope of foliar δ(13)C and mean annual precipitation along the transect was significantly steeper than that of foliar δ(13)C and mean annual precipitation after the watering treatment. For L. chinensis, there was a general decreasing trend in foliar δ(13)C under the different (increasing) watering levels; however, its populations showed an irregular relationship between foliar δ(13)C and moisture origin. Therefore, support for our hypothesis was obtained from Stipa spp., but not from L. chinensis.


Programs and Place: Risk and Asset Mapping for Fall Prevention.
Identifying ways to measure access, availability, and utilization of health-care services, relative to at-risk areas or populations, is critical in providing practical and actionable information to key stakeholders. This study identified the prevalence and geospatial distribution of fall-related emergency medical services (EMS) calls in relation to the delivery of an evidence-based fall prevention program in Tarrant County, Texas over a 3-year time period. It aims to educate public health professionals and EMS first respondents about the application of geographic information system programs to identify risk-related "hot spots," service gaps, and community assets to reduce falls among older adults. On average, 96.09 (±108.65) calls were received per ZIP Code (ranging from 0 calls to 386 calls). On average, EMS calls per ZIP Code increased from 30.80 (±34.70) calls in 2009 to 33.75 (±39.58) calls in 2011, which indicate a modest annual call increase over the 3-year study period. The percent of ZIP Codes offering A Matter of Balance/Volunteer Lay Leader Model (AMOB/VLL) workshops increased from 27.3% in 2009 to 34.5% in 2011. On average, AMOB/VLL workshops were offered in ZIP Codes with more fall-related EMS calls over the 3-year study period. Findings suggest that the study community was providing evidence-based fall prevention programming (AMOB/VLL workshops) in higher-risk areas. Opportunities for strategic service expansion were revealed through the identification of fall-related hot spots and asset mapping.


Nonomuraea glycinis sp. nov., a novel actinomycete isolated from the root of black soya bean [Glycine max (L.) Merr].
A novel actinomycete, designated strain NEAU-BB2C19T, was isolated from the root of black soya bean [Glycine max (L.) Merr] collected from Harbin, Heilongjiang Province, China, and characterized using a polyphasic approach. The strain was an aerobic, Gram-stain-positive actinomycete that formed extensively branched substrate mycelium and aerial hyphae. The predominant menaquinones were MK-9(H2) and MK-9(H0). The major cellular fatty acid profile consisted of iso-C16 : 0, 10-methyl C17 : 0 and 10-methyl C18 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, phosphatidylglycerol and glycolipid. The DNA G+C content was 68.2±0.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-BB2C19T should be assigned to the genus Nonomuraea and formed a distinct branch with its closest neighbour Nonomuraea guangzhouensis NEAU-ZJ3T (98.75 % 16S rRNA gene sequence similarity). The morphological and chemotaxonomic properties of the strain were also consistent with those of members of the genus Nonomuraea. A combination of DNA-DNA hybridization results and some phenotypic characteristics indicated that strain NEAU-BB2C19T could be clearly differentiated from its closest phylogenetic relative. Thus, the strain is concluded to represent a novel species of the genus Nonomuraea, for which the name Nonomuraea glycinis sp. nov. is proposed. The type strain is NEAU-BB2C19T (=CGMCC 4.7430T=DSM 104838T).


Electronic reporting of diagnostic laboratory test results from all healthcare sectors is a cornerstone of national preparedness and control of COVID-19 in Denmark.
The COVID-19 pandemic has led to an unprecedented demand for real-time surveillance data in order to inform critical decision makers regarding the management of the pandemic. The aim of this review was to describe how the Danish national microbiology database, MiBa, served as a cornerstone for providing data to the real-time surveillance system by linkage to other nationwide health registries. The surveillance system was established on an existing IT health infrastructure and a close network between clinical microbiologists, information technology experts, and public health officials. In 2020, testing capacity for SARS-CoV-2 was ramped up from none to over 10,000 weekly PCR tests per 100,000 population. The crude incidence data mirrored this increase in testing. Real-time access to denominator data and patient registries enabled adjustments for fluctuations testing activity, providing robust data on crude SARS-CoV-2 incidence during the changing diagnostic and management strategies. The use of the same data for different purposes, for example, final laboratory reports, information to the public, contact tracing, public health, and science, has been a critical asset for the pandemic response. It has also raised issues concerning data protection and critical capacity of the underlying technical systems and key resources. However, even with these limitations, the setup has enabled decision makers to adopt timely interventions. The experiences from COVID-19 may motivate a transformation from traditional indicator-based public health surveillance to an all-encompassing information system based on access to a comprehensive set of data sources, including diagnostic and reference microbiology.


Aerobic exercise interventions for adults living with HIV/AIDS.
The profile of HIV infection is constantly changing. Although once viewed as an illness progressing to death, among those with access to antiretroviral therapy, HIV infection can now present as a disease with an uncertain natural history, perhaps a chronic manageable disease for some. Thus, the needs of persons infected with HIV have increasingly included management of impairments, disabilities and handicaps. Exercise is a key management strategy employed by rehabilitation professionals to address these issues and assist persons living with HIV/AIDS. Exercise has been shown to improve strength, cardiovascular function, and psychological status in seronegative populations (~~Bouchard 1993~~) but what are the effects of exercise for adults living with HIV infection? If the risks and benefits of exercise for people living with HIV infection are better understood, appropriate exercise prescription may be practiced by health care providers, and may enhance the effectiveness of HIV management, thus improving the overall outcome for adults living with HIV infection. To examine the effect of aerobic exercise interventions on cardiopulmonary, immunological/virological and psychological parameters in adults living with HIV infection. To identify the appropriate studies, we conducted a search using MEDLINE, EMBASE, SCIENCE CITATION INDEX, AIDSLINE, CINAHL, HEALTHSTAR, PSYCHLIT, SOCIOFILE, SCI, SSCI, ERIC and DAI. We also reviewed abstracts from international AIDS, ICAAC, and other major meetings. Reference lists from pertinent articles and books and personal contact with authors were also used, as were Collaborative Review Group databases and results of hand searching of targeted journals. All languages were included. Searches for the original review covered the period from 1980 to July 1999. For the purposes of this update, an additional literature search, following the same identification of studies criteria as listed above, was conducted from August 1999 to January 2001. To be selected, studies had to be randomized controlled trials involving HIV+ adults 18 years of age or older and had to include at least one group randomized to receive aerobic exercise performed at least three times/week for at least four weeks. Data on study design, participants, interventions, and outcomes were extracted from the reports onto specifically designed data collection forms by at least two reviewers. A total of eight studies (six from the original search and two from the updated search) were identified that satisfied the eligibility criteria. The main results indicated that performing constant or interval aerobic exercise, or a combination of constant aerobic exercise and progressive resistive exercise for at least 20 minutes, at least three times per week for four weeks appears to be safe and may lead to clinically significant improvements in cardiopulmonary fitness. Furthermore, individual studies suggest that aerobic exercise may improve psychological well-being for adults living with HIV/AIDS. These findings are limited to those who continued to exercise and for whom there was adequate follow-up data. Aerobic exercise appears to be safe and may be beneficial for adults living with HIV/AIDS. These findings are limited by the small sample sizes and large drop-out rates of the included studies. Future research would benefit from an increased attention to participant follow-up and intention-to-treat analysis. Further research is required to determine the optimal parameters of aerobic exercise and stage of disease in which aerobic exercise may be most beneficial for adults living with HIV infection.


Heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 (PF4) and heparin. HIT is frequently considered in the differential diagnosis of thrombocytopenia occurring in patients on heparin therapy. HIT is a challenging diagnosis because of routine heparin use in hospitalized patients, the common occurrence of thrombocytopenia, and high rates of anti-PF4/heparin seroconversions in patients treated with heparin. Our diagnostic approach to HIT is presented here, underscoring critical elements of clinical and laboratory evaluation.


[Preparative isolation of gonadotropin and urokinase on carboxylic cation exchangers].
Low-pressure ion-exchange chromatography was used for sequential isolation of chorionic gonadotropin and urokinase (EC 22.214.171.124) from urine of pregnant women. Theoretical analysis of electrostatic interactions of protein macromolecules with the sorptive surface of a carboxylic cation exchanger was performed. This analysis allowed us to optimize the pH values for selective sorption and reversible desorption of the target component on a cation exchanger with a selected acidity of functional groups. The use of carboxylic cation exchangers KM-2p and Biokarb-GM allowed us to obtain the preparations with purity not inferior to commercially available preparations.


Open-label, randomized study comparing basal insulin peglispro and insulin glargine, in combination with oral antihyperglycemic medications, in insulin-naïve Asian patients with type 2 diabetes.
The present phase 3, randomized, open-label study compared the efficacy and safety of basal insulin peglispro with insulin glargine after 26 weeks of treatment when added to oral antihyperglycemic medications in insulin-naïve Asian patients with type 2 diabetes. The primary objective was to show non-inferiority of the change in glycated hemoglobin from baseline to 26 weeks. At 26 weeks, insulin peglispro was non-inferior to glargine, meeting the primary objective. Patients receiving insulin peglispro (n = 192) showed a greater reduction in glycated hemoglobin from baseline compared with glargine (n = 196); -1.6 vs -1.4%, P = 0.005) and in fasting serum glucose (-61.2 vs -54.8 mg/dL, P = 0.02). A significantly higher proportion of patients receiving insulin peglispro achieved glycated hemoglobin <7% (57 vs 44%, P = 0.012). Insulin peglispro patients showed significantly less weight gain from baseline (1.1 vs 1.6 kg, P = 0.03). Relative rates (insulin peglispro/glargine) of total and nocturnal hypoglycemia through 26 weeks were 1.06 (P = 0.67) and 0.7 (P = 0.10), respectively. Significantly more insulin peglispro-treated patients experienced adverse events compared with glargine-treated patients (P = 0.042). Alanine aminotransferase and aspartate aminotransferase were significantly increased from baseline with insulin peglispro compared with glargine at week 26 (3.5 vs -4.6 IU/L and 2.8 vs -1.5 IU/L, respectively; P < 0.001). The incidence of injection site reactions was low and did not differ between the treatments. Insulin peglispro provided better glycemic control vs glargine with no differences in hypoglycemia and increased aminotransferases in insulin-naïve Asian patients with type 2 diabetes.


A sequentially bioconjugated optofluidic laser for wash-out-free and rapid biomolecular detection.
Microstructures can improve both sensitivity and assay time in heterogeneous assays (such as ELISA) for biochemical analysis; however, it remains a challenge to perform the essential wash process in those microstructure-based heterogeneous assays. Here, we propose a sequential bioconjugation protocol to solve this problem and demonstrate a new type of fiber optofluidic laser for biosensing. Except for acting as an optical microresonator and a microstructured substrate, the miniaturized hollow optical fiber (HOF) is used as a microfluidic channel for storing and transferring reagents thanks to its capability in length extension. Through the capillary action, different reagents were sequentially withdrawn into the fiber for specific binding and washing purposes. By using the sequentially bioconjugated FOFL, avidin molecules are detected based on competitive binding with a limit of detection of 9.5 pM, ranging from 10 pM to 100 nM. It is demonstrated that a short incubation time of 10 min is good enough to allow the biomolecules to conjugate on the inner surface of the HOF. Owing to its miniaturized size, only 589 nL of liquid is required for incubation, which reduces the sample consumption and cost for each test. This work provides a tool to exploit the potential of microstructured optical fibers in high-performance biosensing.


Genetic Variants of the DSF Quorum Sensing System in Stenotrophomonas maltophilia Influence Virulence and Resistance Phenotypes Among Genotypically Diverse Clinical Isolates.
The pathogenicity of Stenotrophomonas maltophilia is regulated in part by its quorum sensing (QS) system. The main QS signaling molecule in S. maltophilia is known as diffusible signal factor (DSF), and the rpf gene cluster is responsible for its synthesis and perception. Two cluster variants have been previously described, rpf-1 and rpf-2, which differ basically in the conditions under which DSF is produced. Here, correlations between the rpf variant and antibiotic susceptibility, LPS electrophoretic profiles and virulence-related phenotypes were evaluated for a collection of 78 geographically and genetically diverse clinical strains of S. maltophilia. In general there were associations between previously established genogroups and the genetic variant of the rpf cluster. However, only few genotype-phenotype correlations could be observed. Resistance to the β-lactam antibiotics ceftazidime and ticarcillin was associated with strains carrying the rpf-1 variant, whereas strains of variant rpf-2, particularly those of genogroup C, showed higher resistance levels to colistin. Strains of variant rpf-2 were also significantly more virulent to Galleria mellonella larvae than those of rpf-1, most likely due to an increased ability of rpf-2 strains to form biofilms. A comparative genomic analysis revealed the presence of proteins unique to individual genogroups. In particular, the strains of genogroup C share an operon that encodes for a new virulence determinant in S. maltophilia related to the synthesis of an alternative Flp/Tad pilus. Overall, this study establishes a link between the DSF-based QS system and the virulence and resistance phenotypes in this species, and identifies potential high-risk clones circulating in European hospitals.


Evaluation of children in six blind schools of Andhra Pradesh.
1. To determine the anatomical site and underlying causes of severe visual impairment and blindness in children in special education in Andhra Pradesh, India. 2. To compare the causes of blindness in two different regions in the state. 3. To evaluate improvement with correction of refractive error and low-vision devices (LVDs). Children in 6 schools for the blind and in 3 integrated education programmes were examined by one ophthalmologist, and were refracted and assessed for LVDs by an optometrist. The major anatomical site and underlying aetiology of severe visual impairment and blindness (SVI/BL; < 6/60 in the better eye) were recorded using the standardised WHO reporting form. Two hundred and ninety one students under 16 years were examined, and after refraction, 267 (91.7%) were classified as being severely visually impaired or blind. The most common anatomical sites of SVI/BL were retina in 31.1% children; cornea in 24.3%; and whole globe in 20.2%. The aetiology was unknown in 38.2%, hereditary in 34.8% and childhood causes in 24%. 114 children (39.2%) had functional low vision (i.e. visual acuity < 6/18 to light perception with navigational vision). In this group, 36 children improved with spectacles and 16 benefited by LVDs. 41 children (15.4%) were able to read N10 point though they were studying Braille. Overall 37.4% of children had "avoidable" causes of blindness. The major avoidable causes were vitamin-A deficiency and cataract. Vitamin-A deficiency and congenital anomalies were more common in the dry plateau areas of the state. One in seven children could read normal print with optical support.


Multifunctional gold nanoparticles for osteoporosis: synthesis, mechanism and therapeutic applications.
Osteoporosis is currently the most prevalent bone disorder worldwide and is characterized by low bone mineral density and an overall increased risk of fractures. To treat osteoporosis, a range of drugs targeting bone homeostasis have emerged in clinical practice, including anti-osteoclast agents such as bisphosphonates and denosumab, bone formation stimulating agents such as teriparatide, and selective oestrogen receptor modulators. However, traditional clinical medicine still faces challenges related to side effects and high costs of these types of treatments. Nanomaterials (particularly gold nanoparticles [AuNPs]), which have unique optical properties and excellent biocompatibility, have gained attention in the field of osteoporosis research. AuNPs have been found to promote osteoblast differentiation, inhibit osteoclast formation, and block the differentiation of adipose-derived stem cells, which thus is believed to be a novel and promising candidate for osteoporosis treatment. This review summarizes the advances and drawbacks of AuNPs in their synthesis and the mechanisms in bone formation and resorption in vitro and in vivo, with a focus on their size, shape, and chemical composition as relevant parameters for the treatment of osteoporosis. Additionally, several important and promising directions for future studies are also discussed, which is of great significance for prevention and treatment of osteoporosis.


Prevalence and Safety of Off-Label Use of Chemotherapeutic Agents in Older Patients With Breast Cancer: Estimates From SEER-Medicare Data.
Prescribing drugs outside of the label indication is legal and may reflect standard practice; however, some off-label use may be inappropriate. This study measured the prevalence and safety of off-label use both in accordance with practice guidelines and inconsistent with practice guidelines in older patients with breast cancer. The SEER-Medicare data set was used to identify women diagnosed with breast cancer. Intravenous chemotherapy was identified using Medicare claims and classified as either on-label, off-label but included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer ("off-label/supported"), or off-label and not included in the NCCN Guidelines ("off-label/unsupported"). Hospitalization/emergency department (ED) admission rates were compared. A total of 13,347 women were treated with 16,127 regimens (12% of women switched regimen); 64% of regimens were off-label/supported, 25% were on-label, and 11% were off-label/unsupported, and hospitalization/ED admission occurred in 27%, 25%, and 32% of regimens, respectively (P<.0001). Drugs never included in the NCCN Guidelines for Breast Cancer accounted for 19% of off-label/unsupported use (1% of total use). Off-label use without scientific support was not common, whereas 64% of use was off-label/supported, reflecting the fact that widely accepted indications are often not tested in registration trials. Off-label/supported use will likely increase as more drugs are expected to have activity across cancer sites, and therefore understanding the implications of such use is critical.


Establishment and characterization of a novel cell line from midgut tissue of Helicoverpa armigera (Lepidoptera: Noctuidae).
The midgut of lepidopteran larvae serves as a target for many pathogens such as Bacillus thuringiensis (Bt). Cell lines originating from midgut tissues will be very helpful tools in many research fields. However, to date, no Bt-susceptible midgut-derived cell lines are available. Here, we reported that a novel cell line, designated as HNU-Ha-MG1, was established from midgut tissue of the fourth instar larvae of Helicoverpa armigera. This cell line grew well in Grace's insect cell culture medium supplemented with 10-15% fetal bovine serum. The shape of the most cells was round or polygonal, and some tended to aggregate to form multiple cell masses. The size of the cells was 13.8 ± 1.8 μm in diameter, and the maximum density reached (2.40 ± 0.15) × 10(6) cells/ml. The population doubling time during logarithmic growth phase was 58.6 ± 7.0 h at 28°C. The number of chromosomes was about 90-130, which exhibited typical chromosome characteristics of lepidopteran cell lines. The patterns of random amplified polymorphic DNA of the cell line were different from those of Sl-HP and Hi5 cell lines which were frequently used in our laboratory. 20-Hydroxyecdysterone induced apoptosis in a very small part of cells at 2 μg/ml but did not affect expression of autophagy-related protein 8 (Atg8) and its lipidation at 36 h post-treatment. The cell line was permissive to Autographa californica nuclear polyhedrosis virus (AcMNPV) and H. armigera nuclear polyhedrosis virus (HaSNPV). This cell line was found to be susceptible to activated Cry1C at the final concentration of 0.5-1.0 μg/ml but not to the activated Cry1Ac.


[Surgical strategies in concurrent closed thoracoabdominal trauma].
The experience of surgical treatment of 393 injured persons with closed thoracoabdominal trauma (CTAT) in an acute period was summarized. The CTAT structure, peculiarities of diagnosis, surgical tactics, complications were regarded and the injured persons deaths causes were analyzed. Operative intervention was performed in 202 (51.4%) injured persons. Mortality was 35.1%.


Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men.
Regular consumption of n-3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk. This study aimed to determine whether eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have differential effects on serum lipids and lipoproteins, glucose, and insulin in humans. In a double-blind, placebo-controlled trial of parallel design, 59 overweight, nonsmoking, mildly hyperlipidemic men were randomly assigned to receive 4 g purified EPA, DHA, or olive oil (placebo) daily while continuing their usual diets for 6 wk. Fifty-six men aged 48.8 +/- 1.1 y completed the study. Relative to those in the olive oil group, triacylglycerols fell by 0.45 +/- 0.15 mmol/L ( approximately 20%; P = 0.003) in the DHA group and by 0.37 +/- 0.14 mmol/L ( approximately 18%; P = 0.012) in the EPA group. Neither EPA nor DHA had any effect on total cholesterol. LDL, HDL, and HDL(2) cholesterol were not affected significantly by EPA, but HDL(3) cholesterol decreased significantly (6.7%; P = 0.032). Although HDL cholesterol was not significantly increased by DHA (3. 1%), HDL(2) cholesterol increased by approximately 29% (P = 0.004). DHA increased LDL cholesterol by 8% (P = 0.019). Adjusted LDL particle size increased by 0.25 +/- 0.08 nm (P = 0.002) with DHA but not with EPA. EPA supplementation increased plasma and platelet phospholipid EPA but reduced DHA. DHA supplementation increased DHA and EPA in plasma and platelet phospholipids. Both EPA and DHA increased fasting insulin significantly. EPA, but not DHA, tended to increase fasting glucose, but not significantly so. EPA and DHA had differential effects on lipids, fatty acids, and glucose metabolism in overweight men with mild hyperlipidemia.


Canadian organ donation organizations' donor audit processes: an environmental scan.
Deceased donor audits (DAs) allow organ donation and transplantation systems to measure and analyze missed donation opportunities (MDOs). Missed donation opportunities can harm both patients/families denied the opportunity to donate and patients on transplant waitlists denied access to lifesaving organs. In Canada, there are no national standards for DAs, data analysis, nor accountability processes surrounding MDOs. Understanding DA current practice in each jurisdicton would facilitate developing a national strategy for DAs. All provincial organ donation organizations (ODOs) were invited to participate in an environmental scan (ES) of current DA practices. The two ES phases were an electronic survey followed by semistructured interviews. We collected information about the objectives, frequency, scope, data collection methodology, resources required, definitions/metrics used, and process for reporting outcomes. All eleven ODOs participated in both phases of the ES (July and October 2019). The primary purposes for conducting DAs were to estimate the following: 1) donor potential (5/11, 45%); 2) system performance at the provincial level (3/11, 27%); and 3) system performance at the hospital level (3/11, 27%). Frequency of DAs varied from weekly to annually, depending on the availability of death reports, urban vs rural setting, and staffing. High variability was observed in DA methodology, donor definitions, and metrics across jurisdictions. There is significant variability across Canadian ODOs in the methodology, definitions, timeliness, data collection, and reporting of DAs. This underscores the need for a national donor audit strategy to reduce preventable harm from MDOs to patients/families at end of life and those on transplant waitlists.


Factors that modify the effect of excess calcium on skeletal development in puppies.
Developmental skeletal problems are often connected to mistakes in feeding, i.e. a deficiency or excess supply of nutrients, especially minerals. The energy consumption, the resulting growth intensity and the breed of animals are also known as factors that influence developmental orthopaedic diseases. In most clinical trials, excess Ca was connected to alterations in normal, healthy skeletal development, which led to severe clinical symptoms in some dogs, subclinical changes in the radiographic or histological examinations in other animals, or even no observable symptoms. These results correspond to practical experience in the field of clinical nutrition consultation, since excess Ca has been shown to have various impacts in growing dogs. The present review of results published in the literature and from my own trials led to the hypothesis that P is an important co-factor that can alleviate or aggravate the development of skeletal problems in growing dogs.


Tartrazine (FD & C yellow #5) anaphylaxis: a case report.
Tartrazine dye has been implicated in a variety of adverse reactions. There is a high correlation between aspirin sensitivity and tartrazine sensitivity but the reverse is exceedingly rare. Herewith is presented a case where repeated occult exposures to tartrazine yellow dye in a patient who could take aspirin with impunity was uncovered by a deduction. The ubiquitous nature and protean manifestations of dye sensitivity are discussed.


[State of cardiac activity in patients with varicose disease of the lower extremity veins].
The intracardiac characteristics were studied in 100 patients prior to a removal of varicose veins by surgical or screrotherapeutic methods using US methods. An analysis of these characteristics has shown that investigation of the diastolic function of the heart ventricles is the most demonstrative one. The function of one or two ventricles was shown to worsen with age having negative influence on the venous system of lower extremities which can cause the appearance of varicose veins or their progression thus increasing the stage of chronic venous insufficiency, the appearance of recurrent varicosity after its removal.


Gender-dependent associations between occupational status and untreated caries in Japanese adults.
The aim of this study was to examine whether the presence of untreated caries is different across occupational status among Japanese adults. This was a cross-sectional survey of 1,342 individuals (990 males and 352 females) aged 40-64 yr who underwent medical and dental checkups at a healthcare center in 2011. Oral examination was performed by a dentist and the presence of untreated caries was defined as having at least one untreated decayed tooth. Data regarding current occupational status were obtained using a self-administered questionnaire; the participants were classified into five groups: professionals and managers, clerical and related workers, service and salespersons, agricultural, forestry, and fishery workers, and homemakers and unemployed. Gender-specific odds ratios (ORs) and 95% confidence intervals (CIs) of occupational status for the presence of untreated caries were estimated using logistic regression. After adjusting for potential confounders, female professionals and managers (OR=3.51, 95% CI=1.04-11.87) and service and salespersons (OR=5.29, 95% CI=1.39-20.11) had greater risks of the presence of untreated caries than female homemakers and unemployed. However, this tendency was not observed among males. In conclusion, there was a significant difference in risk of the presence of untreated caries by occupational status among females.


Daily spiritual experiences in a biracial, community-based population of older adults.
The objectives of this study were to describe the levels of daily spiritual experiences (DSEs) in community-dwelling older adults, to compare the levels of spiritual experiences with the levels of prayer and religious service attendance, and to examine the demographic and psychosocial correlates of spiritual experiences. The data came from 6534 participants in the Chicago Health and Aging Project, an ongoing population-based, biracial (65% African American) study of the risk factors for incident Alzheimer's disease among older adults. A 5-item version of the Daily Spiritual Experiences Scale (DSES) was used in the study. Multivariable linear regression models were used to examine the relationship between sociodemographic and psychosocial factors and DSES scores. The majority of the participants reported having spiritual experiences at least daily. In the bivariate analyses, African Americans and women had higher DSES scores than Whites and men, respectively (p's < 0.001). Prayer and worship were moderately associated with DSES scores. In the multivariable analyses, African American race, older age, female gender, better self-rated health, and greater social networks were associated with higher DSES scores, while higher levels of education and depressive symptoms were associated with lower DSES scores. We observed high levels of spiritual experiences and found that the DSES is related to, but distinct from the traditional measures of religiosity. We found associations between DSES, demographic, and psychosocial factors that are consistent with the findings for other religiosity and spirituality (R/S) measures. Future research should test whether DSES contributes to our understanding of the relationship between R/S and health in older adults.


Seeing Complexity: Cultural Historical Activity Theory (CHAT) As a Lens for Shared Decision Making.
Shared decision making, a collaborative approach between patient and provider that considers the patient's values and preferences in addition to the scientific evidence, is a complex clinical activity that has not realized its full potential. Gaps in education and training have been cited as barriers to shared decision making, and evidence is inconsistent on effective educational interventions. Because individual agents with their own social and behavioral contexts co-construct a shared decision, the educational approach may need to consider the role of patient agency and sociocultural influences. To address the inherent complexity in shared decision making, the authors identified cultural historical activity theory (CHAT) as a framework for analysis. Although certainly not the only relevant theory, CHAT offers an appropriate lens through which the multivoiced nature of shared decision making can be more clearly appreciated. In this article, the authors demonstrate the application of CHAT as a lens for researchers and educators to examine the complexity of shared decision making. The fictitious case presented in this article describes the use of CHAT with a patient who experiences 2 clinical encounters; during the second, shared decision making takes place. Elements of the case are threaded through the article, demonstrating a sample analysis of the interacting activity systems of the patient and physician and highlighting inherent tensions and contradictions. The authors propose CHAT as a tool for future research around the role of agency in shared decision making and other complex topics and as a framework for design of novel instructional strategies. Although not applicable to all topics and settings, CHAT has significant potential within health professions education.


Analysis of total aerobic viable counts in raw fish by high-throughput optical oxygen respirometry.
A simple, miniaturized, and automated screening assay for the determination of total aerobic viable counts in fish samples is presented here. Fish tissue homogenates were prepared in peptone buffered water medium, according to standard method, and aliquots were dispensed into wells of a 96-well plate with the phosphorescent, oxygen-sensing probe GreenLight. Sample wells were covered with mineral oil (barrier for ambient oxygen), and the plate was monitored on a standard fluorescent reader at 30°C. The samples produced characteristic profiles, with a sharp increase in fluorescence above the baseline level at a certain threshold time, which could be correlated with initial microbial load. Five different fish species were analyzed: salmon, cod, plaice, mackerel, and whiting. Using a conventional agar plating method, the relationship between the threshold time and total aerobic viable counts load (in CFU per gram) was established, calibration curve generated, and the test was validated with 169 unknown fish samples. It showed a dynamic range of 10(4) to 10(7) CFU/g, accuracy of ± 1 log(CFU/g), assay time of 2 to 12 h (depending on the level of contamination), ruggedness with respect to the key assay parameters, simplicity (three pipetting steps, no serial dilutions), real-time data output, high sample throughput, and automation. With this test, quality of fish samples, CFU-per-gram levels, and their respective time profiles were determined.


Updated mortality analysis of radiation workers at Rocketdyne (Atomics International), 1948-2008.
Updated analyses of mortality data are presented on 46,970 workers employed 1948-1999 at Rocketdyne (Atomics International). Overall, 5,801 workers were involved in radiation activities, including 2,232 who were monitored for intakes of radionuclides, and 41,169 workers were engaged in rocket testing or other non-radiation activities. The worker population is unique in that lifetime occupational doses from all places of employment were sought, updated and incorporated into the analyses. Further, radiation doses from intakes of 14 different radionuclides were calculated for 16 organs or tissues using biokinetic models of the International Commission on Radiation Protection (ICRP). Because only negligible exposures were received by the 247 workers monitored for radiation activities after 1999, the mean dose from external radiation remained essentially the same at 13.5 mSv (maximum 1 Sv) as reported previously, as did the mean lung dose from external and internal radiation combined at 19.0 mSv (maximum 3.6 Sv). An additional 9 years of follow-up, from December 31,1999 through 2008, increased the person-years of observation for the radiation workers by 21.7% to 196,674 (mean 33.9 years) and the number of cancer deaths by 50% to 684. Analyses included external comparisons with the general population and the computation of standardized mortality ratios (SMRs) and internal comparisons using proportional hazards models and the computation of relative risks (RRs). A low SMR for all causes of death (SMR 0.82; 95% CI 0.78-0.85) continued to indicate that the Rocketdyne radiation workers were healthier than the general population and were less likely to die. The SMRs for all cancers taken together (SMR 0.88; 95% CI 0.81-0.95), lung cancer (SMR 0.87; 95% CI 0.76-1.00) and leukemia other than chronic lymphocytic leukemia (CLL) (SMR 1.04; 95% 0.67-1.53) were not significantly elevated. Cox regression analyses revealed no significant dose-response trends for any cancer. For all cancers excluding leukemia, the RR at 100 mSv was estimated as 0.98 (95% CI 0.82-1.17), and for all leukemia other than CLL it was 1.06 (95% CI 0.50-2.23). Uranium was the primary radionuclide contributing to internal exposures, but no significant increases in lung and kidney disease were seen. The extended follow-up reinforces the findings in the previous study in failing to observe a detectable increase in cancer deaths associated with radiation, but strong conclusions still cannot be drawn because of small numbers and relatively low career doses. Larger combined studies of early workers in the United States using similar methodologies are warranted to refine and clarify radiation risks after protracted exposures.


The orientation of the three haems of the 'in situ' ubiquinol oxidase, cytochrome bd, of Escherichia coli.
The Escherichia coli cytochrome bd complex incorporates three haems as prosthetic groups. In the ferric form these are a predominantly high-spin chlorin (haem d), a high-spin haem b (b595) and a low-spin haem b (b558). The orientations of these three haems have been determined by e.p.r. studies on oriented multilayer preparations of cytoplasmic membrane fragments. The low-spin haem b (b558) and the high-spin haem d are oriented with their haem planes perpendicular to the membrane plane. The high-spin haem b595 is oriented with its haem plane at approx. 55 degrees to the membrane plane. A minor low-spin component, attributable to a low-spin subpopulation of the haem d, is also oriented with its haem plane perpendicular to the membrane plane.


Trainees' use of supervision for therapy with sexual minority clients: A qualitative study.
In the supervision literature, research on sexual orientation considerations often focuses on sexual minority supervisees and less often on their work with sexual minority clients. Yet both heterosexual and sexual minority supervisees serve sexual minority clients and may have different supervision needs. Twelve predoctoral interns from 12 APA-accredited counseling center internships were interviewed about how they made use of supervision for their work with a sexual minority client. The sample consisted of 6 heterosexual-identified supervisees and 6 supervisees who identified as lesbian, gay, or queer (LGQ). Data were analyzed using consensual qualitative research. All participants reported positive gains from supervision that carried over to their work with heterosexual and sexual minority clients, even when not all supervisors disclosed or discussed their own sexual orientation. Heterosexual supervisees used supervision to ensure that their heterosexuality does not interfere with an affirmative experience for their sexual minority client, whereas LGQ supervisees used supervision to explore differences in sexual identity development between themselves and their client to minimize the negative impact of overidentification. Thus, affirmative supervision may unfold with different foci depending on supervisees' sexual identity. Implications for training and supervision are discussed. (PsycINFO Database Record


Impaired Light Adaptation of ON-Sustained Ganglion Cells in Early Diabetes Is Attributable to Diminished Response to Dopamine D4 Receptor Activation.
Retinal neuronal signaling is disrupted early in diabetes, before the onset of the vascular pathologies associated with diabetic retinopathy. There is also growing evidence that retinal dopamine, a neuromodulator that mediates light adaptation, is reduced in early diabetes. Previously, we have shown that after 6 weeks of diabetes, light adaptation is impaired in ON-sustained (ON-s) ganglion cells in the mouse retina. The purpose of this study was to determine whether changes in the response to dopamine receptor activation contribute to this dysfunction. Single-cell retinal patch-clamp recordings from the mouse retina were used to determine how activating dopamine type D4 receptors (D4Rs) changes the light-evoked and spontaneous excitatory inputs to ON-s ganglion cells, in both control and 6-week diabetic (STZ-injected) animals. Fluorescence in situ hybridization was also used to assess whether D4R expression was affected by diabetes. D4R activation decreased light-evoked and spontaneous inputs to ON-s ganglion cells in control and diabetic retinas. However, D4R activation caused a smaller reduction in light-evoked excitatory inputs to ON-s ganglion cells in diabetic retinas compared to controls. This impaired D4R signaling is not attributable to a decline in D4R expression, as there was no change in D4R mRNA density in the diabetic retinas. These results suggest that the cellular response to dopamine signaling is disrupted in early diabetes and may be amenable to chronic dopamine supplementation therapy.


Not all sounds sound the same: Parkinson's disease affects differently emotion processing in music and in speech prosody.
Does emotion processing in music and speech prosody recruit common neurocognitive mechanisms? To examine this question, we implemented a cross-domain comparative design in Parkinson's disease (PD). Twenty-four patients and 25 controls performed emotion recognition tasks for music and spoken sentences. In music, patients had impaired recognition of happiness and peacefulness, and intact recognition of sadness and fear; this pattern was independent of general cognitive and perceptual abilities. In speech, patients had a small global impairment, which was significantly mediated by executive dysfunction. Hence, PD affected differently musical and prosodic emotions. This dissociation indicates that the mechanisms underlying the two domains are partly independent.


DNA-protein interactions as the source of large-length-scale chirality evident in the liquid crystal behavior of filamentous bacteriophages.
Although all filamentous phages are constructed of chiral components, this study of eight of these phages (fd, IKe, I(2)2, X-2, Pf1, Pf3, tf-1, and X) shows that some form nematic liquid crystals, which are apparently oblivious to the chirality of the components, while others form cholesteric liquid crystals revealing a type of structural chirality not normally encountered. Additions of dopants that interact with the DNA or protein components of the viruses change the liquid crystal properties of seven of the phages. In these seven, DNA-capsid symmetry differences do not allow strict structural equivalency among the protein subunits. The polymorphism arising from this nonequivalency is proposed here to give rise to coiling of the filaments, a large-length-scale chirality that is responsible for forming cholesteric liquid crystal phases. Only one phage of those studied here, Pf1, which is distinguished from the others in its DNA-capsid interactions, forms nematic phases under all conditions tried. The formation of liquid crystals has been developed as a method to detect subtle overall shape effects arising from DNA-subunit-derived polymorphism, an unusual role for the mesogenic state and a new tool for the study of filamentous phage structure.


Safety and effectiveness of long-acting versus intermediate-acting insulin for patients with type 1 diabetes: protocol for a systematic review and individual patient data network meta-analysis.
The choice of a basal insulin regimen to manage type 1 diabetes mellitus (T1DM) may have different risks of adverse events and effectiveness, due to the difference in the effectiveness of these agents across patient characteristics (eg, baseline glycosylated haemoglobin; A1C). Currently, there is a lack of high quality evidence to support the tailoring of insulin regimens according to an individual's needs. The aim of this study is to update our previous systematic review and perform an individual patient data network meta-analysis (IPD-NMA) to evaluate the comparative safety and effectiveness of long-acting versus intermediate-acting insulin in different subgroups of patients with T1DM. We will update our previous literature search from January 2013 onwards searching relevant electronic databases (eg, MEDLINE), as well as perform grey literature search through relevant society/association websites, and conference abstracts, and scan reference lists of the eligible studies. We will include randomised clinical trials of any duration examining long-acting versus intermediate-acting insulin preparations for adult patients with T1DM. We will focus on A1C and severe hypoglycaemia outcomes. For each pairwise treatment comparison, we will combine all IPD from all studies in a single multilevel model, where each study is a different cluster. For a connected network of trials, we will perform an IPD-NMA to identify potential effect modifiers, and estimate the most effective and safe treatments for patients with different characteristics. If we are not successful in obtaining IPD for at least one study, we will include aggregated data (AD) abstracted from the included RCTs in our analysis, combining IPD and AD into a single model. We will report our results using the PRISMA-IPD statement. The results of this systematic review and IPD-NMA will be of interest to stakeholders and will help in improving existing guideline recommendations. CRD42015023511.


Risk and climate change: perceptions of key policy actors in Canada.
This article examines factors that predict perceptions of risk associated with global climate change. The research focuses on the perceptions of those associated with climate change policy making in the prairie region of Canada. The data are from an online survey (n=851) of those policy actors. The analysis integrates several dominant approaches to the study of risk perception: psychometric approaches that examine the effects of cognitive structure; demographic assessments that examine, for example, differences in perception based on gender or family status; and political approaches that suggest that one's position in the policy process may affect his or her perceived risk. Attitudes toward climate change are to a degree predicted by all of these factors, but only when indirect effects are observed. Sociodemographic characteristics have little direct effect on perceived risk, but do affect general beliefs that affect risk perceptions. Perceived risk is related more strongly to these general beliefs or world views than to more specific beliefs about the effects of climate change on weather patterns. Position within the policy process also contributes to our understanding of perceptions, with industry and governmental actors demonstrating similar attitudes, which contrast with environmental groups and university researchers.


Stereoselective [3+2] cycloaddition of N-tert-butanesulfinyl imines to arynes facilitated by a removable PhSO₂CF₂ group: synthesis and transformation of cyclic sulfoximines.
An unprecedented [3+2] cycloaddition between N-tert-butanesulfinyl imines and arynes provides a stereoselective method for the synthesis of cyclic sulfoximines. Not only does the difluoro(phenylsulfonyl)methyl group play an important role in facilitating the cycloaddition reaction, it can also be removed or substituted through the transformation of the difluorinated cyclic sulfoximines to cyclic sulfinamides.


Adaptive social strategies in a solitary carnivore.
Cost-benefit trade-offs for individuals participating in social behaviors are the basis for current theories on the evolution of social behaviors and societies. However, research on social strategies has largely ignored solitary animals, in which we assume that rare interactions are explained by courtship or territoriality or, in special circumstances, resource distributions or kinship. We used directed network analysis of conspecific tolerance at food sources to provide evidence that a solitary carnivore, the puma (Puma concolor), exhibited adaptive social strategies similar to more social animals. Every puma in our analysis participated in the network, which featured densely connected communities delineated by territorial males. Territorial males also structured social interactions among pumas. Contrary to expectations, conspecific tolerance was best characterized by direct reciprocity, establishing a fitness benefit to individuals that participated in social behaviors. However, reciprocity operated on a longer time scale than in gregarious species. Tolerance was also explained by hierarchical reciprocity, which we defined as network triangles in which one puma (generally male) received tolerance from two others (generally females) that also tolerated each other. Hierarchical reciprocity suggested that males might be cheating females; nevertheless, we suspect that males and females used different fitness currencies. For example, females may have benefited from tolerating males through the maintenance of social niches that support breeding opportunities. Our work contributes evidence of adaptive social strategies in a solitary carnivore and support for the applicability of theories of social behavior across taxa, including solitary species in which they are rarely tested.


Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.
Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.


Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): multicentre, randomised controlled, endpoint blinded trial.
To determine the safety and efficacy of aerobic exercise on activities of daily living in the subacute phase after stroke. Multicentre, randomised controlled, endpoint blinded trial. Seven inpatient rehabilitation sites in Germany (2013-17). 200 adults with subacute stroke (days 5-45 after stroke) with a median National Institutes of Health stroke scale (NIHSS, range 0-42 points, higher values indicating more severe strokes) score of 8 (interquartile range 5-12) were randomly assigned (1:1) to aerobic physical fitness training (n=105) or relaxation sessions (n=95, control group) in addition to standard care. Participants received either aerobic, bodyweight supported, treadmill based physical fitness training or relaxation sessions, each for 25 minutes, five times weekly for four weeks, in addition to standard rehabilitation therapy. Investigators and endpoint assessors were masked to treatment assignment. The primary outcomes were change in maximal walking speed (m/s) in the 10 m walking test and change in Barthel index scores (range 0-100 points, higher scores indicating less disability) three months after stroke compared with baseline. Safety outcomes were recurrent cardiovascular events, including stroke, hospital readmissions, and death within three months after stroke. Efficacy was tested with analysis of covariance for each primary outcome in the full analysis set. Multiple imputation was used to account for missing values. Compared with relaxation, aerobic physical fitness training did not result in a significantly higher mean change in maximal walking speed (adjusted treatment effect 0.1 m/s (95% confidence interval 0.0 to 0.2 m/s), P=0.23) or mean change in Barthel index score (0 (-5 to 5), P=0.99) at three months after stroke. A higher rate of serious adverse events was observed in the aerobic group compared with relaxation group (incidence rate ratio 1.81, 95% confidence interval 0.97 to 3.36). Among moderately to severely affected adults with subacute stroke, aerobic bodyweight supported, treadmill based physical fitness training was not superior to relaxation sessions for maximal walking speed and Barthel index score but did suggest higher rates of adverse events. These results do not appear to support the use of aerobic bodyweight supported fitness training in people with subacute stroke to improve activities of daily living or maximal walking speed and should be considered in future guidelines. ClinicalTrials.gov NCT01953549.


Bovine herpesvirus-1 (BHV-1) - a re-emerging concern in livestock: a revisit to its biology, epidemiology, diagnosis, and prophylaxis.
Bovine herpesvirus-1 (BHV-1) is known to cause several diseases worldwide. It is a double-stranded DNA virus consisting of 33 structural proteins out of which 13 are associated with the envelope. Based on genomic analysis and viral peptide patterns, BHV-1 virus can be divided into several subtypes like BHV-1.1, BHV-1.2, and BHV-1.3. However, all subtypes are antigenically similar. The symptoms of the related diseases are mainly non-life-threatening but have a rather wide host range that limits animal trade. The different modes of transmission as unique feature of this virus and the tendency to cause infection in the early age with latency development in trigeminal and sacral ganglion cause huge economic losses around the world. The virus also affects endangered bovine species like mithun (Bos frontalis) and yak (Poephagus grunniens). The disease can be diagnosed by using conventional procedures (like cell culture, immune-histopathology, and enzyme-linked immunosorbent assay (ELISA)) as well as highly sensitive modern techniques (like nested PCR and southern hybridization) with the virus neutralization test regarded as gold standard. With the currently available diagnostic tests it is not possible to identify animals which have a latent BHV-1 infection. Different types of modern and conventional vaccines are available for immunoprophylaxis. Inactivated vaccines are not as efficacious as modified live virus (MLV) vaccines. Marker vaccines allow the distinction between vaccinated and naturally infected animals. In this review the present status of BHV-1 around the world will be addressed besides the current knowledge with regard to its biology, epidemiology, diagnosis, and prophylaxis.