Rugged and breathable forms of stretchable electronics with adherent composite substrates for transcutaneous monitoring.
Research in stretchable electronics involves fundamental scientific topics relevant to applications with importance in human healthcare. Despite significant progress in active components, routes to mechanically robust construction are lacking. Here, we introduce materials and composite designs for thin, breathable, soft electronics that can adhere strongly to the skin, with the ability to be applied and removed hundreds of times without damaging the devices or the skin, even in regions with substantial topography and coverage of hair. The approach combines thin, ultralow modulus, cellular silicone materials with elastic, strain-limiting fabrics, to yield a compliant but rugged platform for stretchable electronics. Theoretical and experimental studies highlight the mechanics of adhesion and elastic deformation. Demonstrations include cutaneous optical, electrical and radio frequency sensors for measuring hydration state, electrophysiological activity, pulse and cerebral oximetry. Multipoint monitoring of a subject in an advanced driving simulator provides a practical example.


Association between neurodevelopmental impairments and motor function in Duchenne muscular dystrophy.
We explored various prognostic factors of motor outcomes in corticosteroid-naive boys with Duchenne Muscular Dystrophy (DMD). The associations between parent-reported neurodevelopmental concerns (speech delay, speech and language difficulties (SLD), and learning difficulties), DMD mutation location, and motor outcomes (6-minute walk distance (6MWD), North Star Ambulatory Assessment (NSAA) total score, 10-meter walk/run velocity, and rise from floor velocity) were studied in 196 corticosteroid-naive boys from ages 4 to less than 8 years. Participants with SLD walked 25.8 fewer meters in 6 minutes than those without SLD (p = 0.005) but did not demonstrate statistical differences in NSAA total score, 10-meter walk/run velocity, and rise from floor velocity. Participants with distal DMD mutations with learning difficulties walked 51.8 fewer meters in 6 minutes than those without learning difficulties (p = 0.0007). Participants with distal DMD mutations were slower on 10-meter walk/run velocity, and rise from floor velocity (p = 0.02) than those with proximal DMD mutations. Participants with distal DMD mutations, who reported speech delay or learning difficulties, were slower on rise from floor velocity (p = 0.04, p = 0.01) than those with proximal DMD mutations. The mean NSAA total score was lower in participants with learning difficulties than in those without (p = 0.004). Corticosteroid-naive boys with DMD with distal DMD mutations may perform worse on some timed function tests, and that those with learning difficulties may perform worse on the NSAA. Pending confirmatory studies, our data underscore the importance of considering co-existing neurodevelopmental symptoms on motor outcome measures.


Conducting environmental health research in the Arabian Middle East: lessons learned and opportunities.
The Arabian Gulf nations are undergoing rapid economic development, leading to major shifts in both the traditional lifestyle and the environment. Although the pace of change is brisk, there is a dearth of environmental health research in this region. We describe challenges and successes of conducting an environmental epidemiologic study in the United Arab Emirates (UAE), a Gulf nation in the Middle East, with an inter-disciplinary team that includes in-country academic and government collaborators as well as U.S. academic collaborators. We present several issues, including study and data collection design, exposure assessment, scheduling and time coordination, quality assurance and quality control, and institutional review board protocols. These topics are considered in a cultural context. Benefits of this research included building linkages among multinational, interdisciplinary team members, generating data for local environmental decision making, and developing local epidemiologic research capacity. The Middle Eastern culture of hospitality greatly benefited the project team. Cultural differences impact multiple aspects of epidemiologic research and should be respectfully addressed. Conducting international population-based environmental research poses many challenges; these challenges can be met successfully with careful planning, cultural knowledge, and flexibility. Lessons learned are applicable to interdisciplinary research all over the world. The research conducted will benefit the environmental and public health agencies of the UAE and provide the nation's leadership with country-specific environmental health data that can be used to protect the public's health in a rapidly changing environment.


Assessing liver injury associated with antimycotics: Concise literature review and clues from data mining of the FAERS database.
To inform clinicians on the level of hepatotoxic risk among antimycotics in the post-marketing setting, following the marketing suspension of oral ketoconazole for drug-induced liver injury (DILI). The publicly available international FAERS database (2004-2011) was used to extract DILI cases (including acute liver failure events), where antimycotics with systemic use or potential systemic absorption were reported as suspect or interacting agents. The reporting pattern was analyzed by calculating the reporting odds ratio and corresponding 95%CI, a measure of disproportionality, with time-trend analysis where appropriate. From 1687284 reports submitted over the 8-year period, 68115 regarded liver injury. Of these, 2.9% are related to antimycotics (1964 cases, of which 112 of acute liver failure). Eleven systemic antimycotics (including ketoconazole and the newer triazole derivatives voriconazole and posaconazole) and terbinafine (used systemically to treat onychomicosis) generated a significant disproportionality, indicating a post-marketing signal of risk. Virtually all antimycotics with systemic action or absorption are commonly reported in clinically significant cases of DILI. Clinicians must be aware of this aspect and monitor patients in case switch is considered, especially in critical poly-treated patients under chronic treatment.


Personal and social norms for food portion sizes in lean and obese adults.
Portion size is an important component of dietary advice for weight control, but little is known about what portion sizes people consider 'normal'. This study determined the effect of body mass index (BMI), gender, dietary restraint and liking of the food on personal and social portion size norms for a range of foods and the degree of certainty over the norms. Thirty lean (BMI 20-25 kg m(-)(2)) and 30 obese (BMI 30-35 kg m(-)(2)) men and women (aged 18-60 years) viewed 17 different portion sizes of 12 foods on a computer screen on two occasions a week apart. Participants responded 'more' or 'less' to each photograph reflecting personal portion size preference or perceived portion sizes of others. Personal and social norms for portion sizes of each food were determined using the method of constant stimuli giving a sigmoidal curve of the probability of answering 'less' over a range of portion sizes. The slope of the sigmoid at the norm gave a measure of certainty about the norm. Regression models were used to examine the effect of BMI, gender, dietary restraint and liking of the food on personal norms, social norms, the relationship between norms, and the slopes. Personal norms were significantly larger in the obese (P=0.026), men (P<0.001), those with lower dietary restraint (P<0.001), and those with higher liking for the food (P<0.001). Social norms were larger for women (P=0.012). The slopes at the norms were 30% shallower in the obese and in men (P<0.001). Larger personal norms for portion size among the obese, men, those with lower dietary restraint and those with higher liking for a food imply greater consumption, which may undermine weight control. Shallower slopes for norms in the obese and in men may imply less clearly defined habitual portion sizes.


Involvement of ergosterol in tolerance to vanillin, a potential inhibitor of bioethanol fermentation, in Saccharomyces cerevisiae.
A vanillin-tolerant strain of Saccharomyces cerevisiae was screened and its intracellular ergosterol levels were compared with several laboratory yeast strains to study the potential relationship between ergosterol content and vanillin tolerance. Saccharomyces cerevisiae NBRC1950 was selected as a vanillin-tolerant strain. Its ergosterol content was higher than those of the laboratory strains. The results of DNA microarray and quantitative reverse transcriptase-polymerase chain reaction analysis showed that five genes involved in ergosterol biosynthesis (ERG28, HMG1, MCR1, ERG5, and ERG7) were upregulated in NBRC 1950 compared with strain X2180, suggesting that high expression of genes involved in ergosterol biosynthesis may cause high ergosterol content in strain NBRC 1950. The S. cerevisiae HX strain, which was a high-ergosterol-containing strain derived from X2180, was more tolerant to vanillin than the parental strain, suggesting that high ergosterol content may, in part, be responsible for vanillin tolerance. These findings provide a biotechnological basis for the molecular engineering of S. cerevisiae with increased tolerance to vanillin.


Participants' experiences of facilitated physical activity for the management of depression in primary care.
A qualitative study was conducted within a randomised trial of facilitated physical activity for depression based on Self-Determination Theory and motivational interviewing. Interviews were held with 19 participants at 4 months, and 12 participants were re-interviewed 8 months later. The interviews were analysed in accordance with Grounded Theory using framework. Themes consisted of the following: relationship with the physical activity facilitators, mode of facilitation, impact of contact with physical activity facilitator/assimilation and future plans, change in activity, and effectiveness of physical activity facilitator techniques. Engagement in physical activity was enhanced within an autonomy-supportive environment.


5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential.
In vitro, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 exhibited high-affinity binding to the serotonin2C (5HT2C) receptors and stimulated turnover of inositol 1,4,5-triphosphate. Affinity to several of the other 5-HT receptor subtypes and to numerous nonserotonergic receptors was much lower. In rats, both compounds elicited behavioral signs of 5-HT2C receptor agonism but not 5-HT2A receptor agonism. Hypomotility induced in rats by high doses of these compounds was reversed by the 5-HT2C receptor antagonist N-(2-naphthyl)-N'-(3-pyridyl)-urea 1:1 HCI. In addition, these compounds were active in tests used to demonstrate anticompulsive effects: reducing schedule-induced polydipsia in rats (prevented by the 5-HT2C/2B receptor antagonist N-(1-methyl-5'-indolyl)-(3-pyridyl)urea 1:1 HCl, reversing increased scratching induced with 8-hydroxy-dipropylaminotetralin 1:1 HCl in squirrel monkeys (no tolerance developed), decreasing responding in the marble-burying task in mice, and decreasing excessive eating of palatable food in rats. In contrast to these compounds, fluoxetine was much less potent, and in some tasks less efficacious, in reducing excessive behavior in these models. These two 5-HT2C receptor agonists do not show anxiogenic effects in the plus-maze in rats. (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 reduced the olfactory bulbectomy-induced passive avoidance impairment in rats, a result that indicates antidepressant potential. Similarly, in the differential-reinforcement-of-low rate 72-s operant schedule task in rats, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 increased (and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 showed a tendency to increase) total reinforcements received, which is suggestive of antidepressant activity. The electroencephalography defined sleep-waking pattern in rats produced by these two 5-HT2C agonists, as well as fluoxetine, included increased quiet-waking and decreased rapid-eye-movement sleep, which is characteristic of antidepressant drugs. These results suggest that 5-HT2C receptor agonism is associated with therapeutic potential in obsessive compulsive disorder and depression.


Robotic assisted laparoscopic prostatectomy versus radical retropubic prostatectomy for clinically localized prostate cancer: comparison of short-term biochemical recurrence-free survival.
We compared biochemical recurrence-free survival of patients who underwent radical retropubic prostatectomy vs robot assisted laparoscopic prostatectomy in concurrent series at a single institution. A total of 2,132 patients were treated between June 2003 and January 2008. We excluded from study patients with prior treatment (115), missing data (83) and lymph node involvement (30). The remaining cohort (1,904) was compared based on clinical, surgical and pathological factors. Kaplan-Meier analysis was performed comparing biochemical recurrence after robot assisted laparoscopic prostatectomy and radical retropubic prostatectomy. A Cox proportional hazards model was generated to determine whether surgical approach is an independent predictor of biochemical recurrence. There were 491 radical retropubic prostatectomies (25.9%) and 1,413 robot assisted laparoscopic prostatectomies (74.1%) performed, and median followup was 10 months (IQR 2 to 23). On univariate analysis the robot assisted laparoscopic prostatectomy group was slightly lower risk with lower median prostate specific antigen (5.4 vs 5.8, p <0.01), a lower proportion of pathological grade 7-10 (48.5% vs 54.7%, p <0.01) and lower pathological stage (80.5% pT2 vs 69.6% pT2, p <0.01). The 3-year biochemical recurrence-free survival rate was similar between the robot assisted laparoscopic prostatectomy and radical retropubic prostatectomy groups on the whole as well as when stratified by pathological stage, grade and margin status. On multivariate analysis extracapsular extension (p <0.01), pathological grade 7 or greater (p <0.01) and positive surgical margin (p <0.01) were independent predictors of biochemical recurrence while surgical approach was not. The likelihood of biochemical recurrence was similar between groups when stratified by known risk factors of recurrence. Surgical approach was not a significant predictor of biochemical recurrence in the multivariate model. Our analysis is suggestive of comparable effectiveness for robot assisted laparoscopic prostatectomy, although longer term studies are needed.


[The research of decoded compression arithmetic for medical high-frequency ultrasound coded excitation imaging].
This paper combined the coded excitation with the technique of ophthalmic high-frequency ultrasonic imaging, and raised a new high-velocity data detection and signal processing method. 16 bit Golay complementarity sequences were produced by FPGA, which excited the probe to produce ultrasonic waves. Data detection circuit achieved the digitalized of the 15 MHz high-frequency ultrasonic echo signals in real time. Sampling rate was 120MHz, and sampling bit was 14 bit. Decoded compression arithmetic was realized by FPGA in real time, in which A code compression was alternated with B code compression. The return echo was correlated with the corresponding decode filter A and filter B respectively, and then the echo was delayed and summed to complete the decoding process. The experiment indicated that coded excitation can effectively increase the range of mainlobe and decrease the range of sidelobe. This technique can effectively raise the signal-to-noise ratio, and has significant research value in advancing the ophthalmic ultrasonic image quality and raising the safety of the equipment.


A cancer specific oxaliplatin-releasing Pt(iv)-prodrug.
We prepared a Pt(iv)-prodrug, which under cancer specific conditions (elevated concentration of reactive oxygen species, ROS) releases a DNA-binding drug oxaliplatin as well as ROS-amplifying drugs p-quinone methide and N-alkylferrocenium. Due to the concerted action of these components, an excellent anticancer effect was achieved: IC50 = 0.4 ± 0.1 μM for human ovarian carcinoma A2780 cells. Importantly, the prodrug was found to be 45-fold less toxic to normal cells (HDFa).


Rectified random cell motility as a mechanism for embryo elongation.
The body of vertebrate embryos forms by posterior elongation from a terminal growth zone called the tail bud. The tail bud is a source of highly motile cells that eventually constitute the presomitic mesoderm (PSM), a tissue that plays an important role in elongation movements. PSM cells establish an anterior-posterior cell motility gradient that parallels a gradient associated with the degradation of a specific cellular signal (FGF) known to be implicated in cell motility. Here, we combine the electroporation of fluorescent reporters in the PSM with time-lapse imaging in the chicken embryo to quantify cell diffusive movements along the motility gradient. We show that a simple microscopic model for random cell motility induced by FGF activity along with geometric confinement leads to rectified tissue elongation consistent with our observations. A continuum analog of the microscopic model leads to a macroscopic mechano-chemical model for tissue extension that couples FGF activity-induced cell motility and tissue rheology, and is consistent with the experimentally observed speed and extent of elongation. Together, our experimental observations and theoretical models explain how the continuous addition of cells at the tail bud combined with lateral confinement can be converted into oriented movement and drive body elongation.


IMP production and energy metabolism during exercise in rats in relation to age.
IMP production in and force exerted by rat quadriceps muscle in situ during various types of exercise were examined in relation to age. During continuous isometric exercise with constant stimulation time, the amount of IMP was linearly and inversely related to the age of the animals; a higher IMP concentration was found in intermittent isometric and dynamic exercise. No relationship was found between the total AMP deaminase activity and age. Exercise influenced neither the total activity nor the activity in the soluble fraction. From the results it is concluded that: the IMP concentration is linearly related to the free intracellular ATP4-/ADP3- ratio and the free AMP2- concentration; older animals are better able to maintain a high intramuscular ATP4-/ADP3- ratio and a low AMP2- concentration; IMP is produced in particular under conditions when the muscle has to work under extreme stress. IMP possibly exerts a feed-back control on the contraction system.


Genomics and Pharmacogenomics Knowledge, Attitude and Practice of Pharmacists Working in United Arab Emirates: Findings from Focus Group Discussions-A Qualitative Study.
(1) Background: Genomics and pharmacogenomics are relatively new fields in medicine in the United Arab Emirates (UAE). Understanding the knowledge, attitudes and current practices among pharmacists is an important pillar to establish the roadmap for implementing genomic medicine and pharmacogenomics; (2) Methods: A qualitative method was used, with focus group discussions (FGDs) being conducted among pharmacists working in public and private hospitals in Abu Dhabi Emirate. Snowball sampling was used. Thematic inductive analysis was performed by two researchers independently. NVIVO software was used to establish the themes; (3) Results: Lack of knowledge of genomics and pharmacogenomics among pharmacists was one of the most prominent findings. Therefore, the role of pharmacist in making the right decisions was highlighted to be a barrier for pharmacogenomics implementation in the UAE. Pharmacists have a positive attitude toward pharmacogenomics, but they are preoccupied with concern of confidentiality. In addition, religion and culture shadowed their attitudes toward genetic testing; (4) Conclusions: It is highly recommended to introduce new courses and training workshops for healthcare providers to improve the opportunities for genomics and pharmacogenomics application in the UAE. Pharmacists agreed that the health authorities should take the lead for improving trust and confidence in the system for a better future in the era of genomics and pharmacogenomics.


Study on the interaction between ligustrazine and 12-tungstophosphoric acid using resonance Rayleigh scattering and resonance nonlinear scattering spectra, and its analytical applications.
In an HCl medium (pH 1.5), ligustrazine (2,3,5,6-tetramethylpyrazine, TMP) reacted with 12-tungstophosphoric acid (TP) to form a 3 : 1 ion-association complex. As a result, the intensities of resonance Rayleigh scattering (RRS), second-order scattering (SOS) and frequency doubling scattering (FDS) were greatly enhanced and new scattering spectra appeared. The maximum RRS, SOS and FDS wavelengths of the ion-association complexes were located at 379, 738 and 395 nm, respectively. The scattering intensity increments (ΔIRRS , ΔISOS and ΔIFDS ) were directly proportional to the concentration of ligustrazine within certain ranges. The detection limits (3σ) of RRS, SOS and FDS were 1.6, 3.2 and 2.8 ng/mL. Optimal conditions for the RRS method and factors influencing the method were discussed, and the structure of the ion-association complex and the reaction mechanism were investigated. Transmission electron microscopy (TEM) was used to characterize the structures of the ion-association complex. Based on the ion-association reaction and its spectral response, a rapid, simple and sensitive RRS method for the determination of TMP was developed. It was applied to the determination of TMP in tablet and urine samples with satisfactory results.


Postdischarge survival and functional status following in-hospital cardiopulmonary resuscitation.
Outcome from cardiopulmonary resuscitation (CPR) at community hospitals is seldom reported in the literature. Data regarding long-term functional status of CPR survivors are virtually nonexistent. We retrospectively reviewed the medical records of all patients receiving CPR during 1989 at a community teaching hospital to determine survival to hospital discharge from CPR. Long-term functional status was determined by contacting primary care physicians in January 1992. We found 24 of 83 (29 percent) patients survived in-hospital CPR and were discharged. Follow-up of these 24 patients showed 13 (54 percent) were alive a mean of 31 months postdischarge with 10 of the 13 (77 percent) reported to be living independently. We believe survival from CPR at community teaching hospitals is comparable to university hospitals. Additionally, patients who survive in-hospital CPR to hospital discharge have a 54 percent chance of being alive a mean of 31 months postdischarge with most being able to live independently. Further work is needed to validate these long-term functional status results.


Reinforced sternal closures for prevention of sternal dehiscence in high risk patients.
Sternal dehiscence is still a frequent complication after cardiac surgery procedures, performed through midline sternotomy. Its cumulative incidence has been reported to be around 2.5%, but several risk factors for increased incidence have also been identified. In past years several techniques have been proposed to achieve reinforced sternal approximation, mainly considered for the treatment of sternal dehiscence, more than for its prevention. The objective of this paper is the evaluation of the results, in terms of prevention of sternal dehiscence in high-risk patients, using reinforced closure techniques compared to standard technique. Our study population included 212 patients who underwent cardiac surgery procedure and presented at least one of the increased risk factor for sternal dehiscence. Fifty-six patients (26.4%) received a reinforced sternal closure technique (RC group), 156 patients (73.6%) received a conventional sternal closure (CC group). The cumulative incidence of sternal refixation, in this selected population, was 5.6% with a statistically significant difference in favour of the RC group. The results of this study clearly show that the appropriate utilisation and selection of one of the several techniques of reinforced sternal closures can be effective in the reduction of sternal dehiscence in high risk patients. A reinforced technique should therefore be utilised in all patients undergoing cardiac surgery, presenting one or more risk factors for increased incidence of sternal dehiscence.


Highly accurate reconstruction algorithm for bandwidth-limited signals and application to fringe signal recovery.
We present a bandwidth-limited signal reconstruction algorithm with high accuracy as a generalization of the conventional "self-truncating" method by using samples taken at a rate higher than the Nyquist rate. The extra sampling rate enables us to lower the truncation error by applying an appropriate window function that tapers the signal to be approximately limited in both the space and frequency domains up to exponentially small errors. The sampling theorem is used in the frequency domain for a space-limited signal to parameterize the tapered signal in terms of discrete samples in the frequency domain, which are determined by a least-squares fitting to handle both irregularly and regularly sampled data. Error analysis for the Gaussian and Kaiser window functions shows that the upper bounds of the errors for reconstructing the signal near the center of sampling decay exponentially in parameter qN faster than the error upper bound of the conventional "self-truncating" method, where q is the extra sampling rate relative to the Nyquist rate and 2N+1 is the number of samples used. We use simulation data to demonstrate the efficacy of this algorithm in reconstructing the fringe signals, which is crucial for the SIM (Space Interferometry Mission) PlanetQuest instrument calibration.


Diverse genetic origin of Indian Muslims: evidence from autosomal STR loci.
The origin and relationships of Indian Muslims is still dubious and are not yet genetically well studied. In the light of historically attested movements into Indian subcontinent during the demic expansion of Islam, the present study aims to substantiate whether it had been accompanied by any gene flow or only a cultural transformation phenomenon. An array of 13 autosomal STR markers that are common in the worldwide data sets was used to explore the genetic diversity of Indian Muslims. The austere endogamy being practiced for several generations was confirmed by the genetic demarcation of each of the six Indian Muslim communities in the phylogenetic assessments for the markers examined. The analyses were further refined by comparison with geographically closest neighboring Hindu religious groups (including several caste and tribal populations) and the populations from Middle East, East Asia and Europe. We found that some of the Muslim populations displayed high level of regional genetic affinity rather than religious affinity. Interestingly, in Dawoodi Bohras (TN and GUJ) and Iranian Shia significant genetic contribution from West Asia, especially Iran (49, 47 and 46%, respectively) was observed. This divulges the existence of Middle Eastern genetic signatures in some of the contemporary Indian Muslim populations. Our study reveals that the spread of Islamic faith in the Indian subcontinent was predominantly cultural transformation associated with minor gene flow from West Asia.


Molecular mechanism involved in the transport of a prodrug dopamine glycosyl conjugate.
We have previously demonstrated that dopamine conjugation to glucose allows it to induce therapeutic effects against Parkinson's disease after intravenous administration. In this paper we demonstrate that, unlike dopamine, the prodrug glu-dopamine is a transportable substrate of glucose transporters. Towards this, the effect of glucose-conjugation on the affinity and uptake of dopamine have been assessed in vitro, using human retinal pigment epithelium (HRPE) cells. Glucose transporter-mediated uptake was measured using [(3)H]3-O-methylglucose ([(3)H]3-O-MG) as the tracer. The uptake was found to be rapid and hyperbolically related to its concentrations (K(t)=7.8+/-1.2mM and V(max)=54+/-2 nmol/min mg protein). Inhibition experiments showed that dopamine was able to interact with glucose carriers only when conjugated to glucose (IC(50)=2.6+/-0.6mM). HPLC analysis of HRPE cell extracts showed that both dopamine and the prodrug permeate the cell, but only the uptake of the prodrug is inhibitable by glucose. This confirms that glucose transporters mediate the transport of the prodrug glu-dopamine, but not of dopamine. HRPE cells is therefore proposed as a promising model for in vitro studies involving the glucose transporter-mediated transport of drugs and their conjugates.


Cervical Colposcopy: Indications and Risk Assessment.
The practice of colposcopy, a diagnostic procedure to evaluate for vaginal, vulvar, and cervical dysplasia, has evolved to incorporate patient risk factors for high-grade cervical intraepithelial neoplasia (CIN) and cancer. Changes in cervical cancer screening and guidelines, human papillomavirus (HPV) vaccination recommendations, and colposcopy standards from the American Society for Colposcopy and Cervical Pathology (ASCCP) have implications for all primary care clinicians, not only those who perform colposcopies. Primary care clinicians should offer HPV vaccination to all patients between the ages of nine and 26, in addition to cervical cancer screening and follow-up guidance. Primary care clinicians should recognize the degrees of risk of high-grade CIN and cancer conferred by cytology, HPV subtype, and persistence of HPV infection. Clinicians should address modifiable risk factors such as tobacco use, and provide counseling to patients about colposcopy based on their individual risks. Clinicians should conduct shared decision-making about immediate loop electrosurgical excision procedure vs. colposcopy with multiple biopsies and endocervical sampling for patients with the highest risk of cervical cancer, and for patients who are older than 25 years with at least two of the following: HPV-16, HPV-18, and high-grade squamous intraepithelial lesion cytology. Primary care clinicians should be familiar with the 2019 ASCCP guidelines and develop clinic-based systems to ensure appropriate follow-up of abnormal cytology, positive high-risk HPV testing, diagnosed CIN, and cervical cancer. Patients with an abnormal cervical cancer screening history require surveillance, which differs from routine screening for patients with normal prior screening results. Long-term surveillance is recommended for patients with CIN 2 or worse.


Correlation between hypertrophy and risk of hypertension in congenital solitary functioning kidney.
Solitary functioning kidney (SFK) may be associated to hypertrophy, hypertension and chronic kidney disease. We evaluated blood pressure (BP) of children with congenital SFK comparing agenesis to multicystic dysplastic kidney (MCDK) and correlated BP profiles with renal dimensions of affected and contralateral kidney. We compared 40 patients with MCDK, grouped for either treatment options (A: conservative vs B: nephrectomy) or involution time (A1: before 4 years-of-age vs A2: persistence-of-MCDK), to 10 unilateral agenesis (C). Patients were evaluated with ultrasound, scintigraphy, office-ambulatory BP monitoring. Compensatory hypertrophy was demonstrated in most of the subjects, without differences between subgroups, with an increase over time (p < 0.001). A1-C showed an overall percentage of hypertrophy significantly higher than A2-B (83%-88% vs 70%-73%, respectively; p = 0.03); moreover, cumulative risk to develop hypertension in A1-C is significantly higher compared to A2-B in office and ambulatory BP monitoring (p = 0.03). Insufficient dipping in systolic and/or diastolic BP was found in 82% children, without differences between subtypes. Patients with a small/absent dysplastic kidney have an increased risk to develop hypertrophy and hypertension compared to patients with a large residual, regardless of nephrectomy. ABPM revealed absent dipping in most patients with SFK, warning further investigations in apparently not symptomatic patients.


A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages.
Numerous strains of mice with defined mutations display pronounced abnormalities of hair follicle cycling, even in the absence of overt alterations of the skin and hair phenotype; however, in order to recognize even subtle, hair cycle-related abnormalities, it is critically important to be able to determine accurately and classify the major stages of the normal murine hair cycle. In this comprehensive guide, we present pragmatic basic and auxiliary criteria for recognizing key stages of hair follicle growth (anagen), regression (catagen) and quiescence (telogen) in C57BL/6NCrlBR mice, which are largely based on previous work from other authors. For each stage, a schematic drawing and representative micrographs are provided in order to illustrate these criteria. The basic criteria can be employed for all mouse strains and require only routine histochemical techniques. The auxiliary criteria depend on the immunohistochemical analysis of three markers (interleukin-1 receptor type I, transforming growth factor-beta receptor type II, and neural cell-adhesion molecule), which allow a refined analysis of anatomical hair follicle compartments during all hair cycle stages. In contrast to prior staging systems, we suggest dividing anagen III into three distinct substages, based on morphologic differences, onset and progression of melanogenesis, and the position of the dermal papilla in the subcutis. The computer-generated schematic representations of each stage are presented with the aim of standardizing reports on follicular gene and protein expression patterns. This guide should become a useful tool when screening new mouse mutants or mice treated with pharmaceuticals for discrete morphologic abnormalities of hair follicle cycling in a highly reproducible, easily applicable, and quantifiable manner.


Anaerobic arsenite oxidation by novel denitrifying isolates.
Autotrophic microorganisms have been isolated that are able to derive energy from the oxidation of arsenite [As(III)] to arsenate [As(V)] under aerobic conditions. Based on chemical energetics, microbial oxidation of As(III) can occur in the absence of oxygen, and may be relevant in some environments. Enrichment cultures were established from an arsenic contaminated industrial soil amended with As(III) as the electron donor, inorganic C as the carbon source and nitrate as the electron acceptor. In the active enrichment cultures, oxidation of As(III) was stoichiometrically coupled to the reduction of NO(3) (-). Two autotrophic As(III)-oxidizing strains were isolated that completely oxidized 5 mM As(III) within 7 days under denitrifying conditions. Based on 16S rRNA gene sequencing results, strain DAO1 was 99% related to Azoarcus and strain DAO10 was most closely related to a Sinorhizobium. The nitrous oxide reductase (nosZ) and the RuBisCO Type II (cbbM) genes were successfully amplified from both isolates underscoring their ability to denitrify and fix CO(2) while coupled to As(III) oxidation. Although limited work has been done to examine the diversity of anaerobic autotrophic oxidizers of As(III), this process may be an important component in the biological cycling of arsenic within the environment.


Human leukocyte antigen variants B*44 and B*57 are consistently favorable during two distinct phases of primary HIV-1 infection in sub-Saharan Africans with several viral subtypes.
As part of an ongoing study of early human immunodeficiency virus type 1 (HIV-1) infection in sub-Saharan African countries, we have identified 134 seroconverters (SCs) with distinct acute-phase (peak) and early chronic-phase (set-point) viremias. SCs with class I human leukocyte antigen (HLA) variants B*44 and B*57 had much lower peak viral loads (VLs) than SCs without these variants (adjusted linear regression beta values of -1.08 ± 0.26 log(10) [mean ± standard error] and -0.83 ± 0.27 log(10), respectively; P < 0.005 for both), after accounting for several nongenetic factors, including gender, age at estimated date of infection, duration of infection, and country of origin. These findings were confirmed by alternative models in which major viral subtypes (A1, C, and others) in the same SCs replaced country of origin as a covariate (P ≤ 0.03). Both B*44 and B*57 were also highly favorable (P ≤ 0.03) in analyses of set-point VLs. Moreover, B*44 was associated with relatively high CD4(+) T-cell counts during early chronic infection (P = 0.02). Thus, at least two common HLA-B variants showed strong influences on acute-phase as well as early chronic-phase VL, regardless of the infecting viral subtype. If confirmed, the identification of B*44 as another favorable marker in primary HIV-1 infection should help dissect mechanisms of early immune protection against HIV-1 infection.


Alcohol intake, consumption pattern and beverage type, and the risk of Type 2 diabetes.
To examine associations between amount and frequency of alcohol consumption, and Type 2 diabetes. A prospective study of 36 527 adults aged 40-69 at baseline. Incident cases of Type 2 diabetes were identified by questionnaire 4 years later. Sex-specific logistic regression models, adjusting for country of birth, dietary glycaemic index, energy intake and age, and in a second model body mass index (BMI) and waist-hip ratio (WHR), were used. Diabetes status was ascertained for 31 422 (86%) participants, and 362 cases identified. Former drinkers had higher risks than lifetime abstainers. Female drinkers had lower risk than lifetime abstainers (ORs < 10 g/day 0.54, 95% CI 0.36-0.82; 10-19.9 g/day 0.57, 0.34-0.94; > or = 20 g/day 0.46, 0.24-0.88, P trend = 0.005). There was no relationship after adjustment for body size. For men, a weak inverse association was observed after adjustment for body size (ORs relative to lifetime abstainers: < 10 g/day 1.56, 0.95-2.55; 10-19.9 g/day 1.21, 0.69-2.10; 20-29.9 g/day 0.80, 0.40-1.60; = 30 g/day 0.86, 0.50-1.58, P trend = 0.036). Wine was the only beverage for which an inverse association was observed. Compared with men who did not drink in the week before baseline, men who drank > or = 210 g over 1-3 days had an increased risk of diabetes (OR 5.21, 1.79-15.19), while the same amount over more days did not increase risk. Total alcohol intake was associated with reduced risk only in women. Alcohol from wine was associated with reduced risk of Type 2 diabetes. A high daily intake of alcohol, even on only 1-3 days a week, may increase the risk of diabetes in men.


Redefining "Critical" Bone Loss in Shoulder Instability: Functional Outcomes Worsen With "Subcritical" Bone Loss.
Glenoid bone loss is a common finding in association with anterior shoulder instability. This loss has been identified as a predictor of failure after operative stabilization procedures. Historically, 20% to 25% has been accepted as the "critical" cutoff where glenoid bone loss should be addressed in a primary procedure. Few data are available, however, on lesser, "subcritical" amounts of bone loss (below the 20%-25% range) on functional outcomes and failure rates after primary arthroscopic stabilization for shoulder instability. To evaluate the effect of glenoid bone loss, especially in subcritical bone loss (below the 20%-25% range), on outcomes assessments and redislocation rates after an isolated arthroscopic Bankart repair for anterior shoulder instability. Cohort study; Level of evidence, 3. Subjects were 72 consecutive anterior instability patients (73 shoulders) who underwent isolated anterior arthroscopic labral repair at a single military institution by 1 of 3 sports medicine fellowship-trained orthopaedic surgeons. Data were collected on demographics, the Western Ontario Shoulder Instability (WOSI) score, Single Assessment Numeric Evaluation (SANE) score, and failure rates. Failure was defined as recurrent dislocation. Glenoid bone loss was calculated via a standardized technique on preoperative imaging. The average bone loss across the group was calculated, and patients were divided into quartiles based on the percentage of glenoid bone loss. Outcomes were analyzed for the entire cohort, between the quartiles, and within each quartile. Outcomes were then further stratified between those sustaining a recurrence versus those who remained stable. The mean age at surgery was 26.3 years (range, 20-42 years), and the mean follow-up was 48.3 months (range, 23-58 months). The cohort was divided into quartiles based on bone loss. Quartile 1 (n = 18) had a mean bone loss of 2.8% (range, 0%-7.1%), quartile 2 (n = 19) had 10.4% (range, 7.3%-13.5%), quartile 3 (n = 18) had 16.1% (range, 13.5%-19.8%), and quartile 4 (n = 18) had 24.5% (range, 20.0%-35.5%). The overall mean WOSI score was 756.8 (range, 0-2097). The mean WOSI score correlated with SANE scores and worsened as bone loss increased in each quartile. There were significant differences (P < .05) between quartile 1 (mean WOSI/SANE, 383.3/62.1) and quartile 2 (mean, 594.0/65.2), between quartile 2 and quartile 3 (mean, 839.5/52.0), and between quartile 3 and quartile 4 (mean, 1187.6/46.1). Additionally, between quartiles 2 and 3 (bone loss, 13.5%), the WOSI score increased to rates consistent with a poor clinical outcome. There was an overall failure rate of 12.3%. The percentage of glenoid bone loss was significantly higher among those repairs that failed versus those that remained stable (24.7% vs 12.8%, P < .01). There was no significant difference in failure rate between quartiles 1, 2, and 3, but there was a significant increase in failure (P < .05) between quartiles 1, 2, and 3 (7.3%) when compared with quartile 4 (27.8%). Notably, even when only those patients who did not sustain a recurrent dislocation were compared, bone loss was predictive of outcome as assessed by the WOSI score, with each quartile's increasing bone loss predictive of a worse functional outcome. While critical bone loss has yet to be defined for arthroscopic Bankart reconstruction, our data indicate that "critical" bone loss should be lower than the 20% to 25% threshold often cited. In our population with a high level of mandatory activity, bone loss above 13.5% led to a clinically significant decrease in WOSI scores consistent with an unacceptable outcome, even in patients who did not sustain a recurrence of their instability.


In vivo imaging indicates muscle fiber dedifferentiation is a major contributor to the regenerating tail blastema.
During tail regeneration in urodele amphibians such as axolotls, all of the tissue types, including muscle, dermis, spinal cord, and cartilage, are regenerated. It is not known how this diversity of cell types is reformed with such precision. In particular, the number and variety of mature cell types in the remaining stump that contribute to the blastema is unclear. Using Nomarski imaging, we followed the process of regeneration in the larval axolotl tail. Combining this with in vivo fluorescent labeling of single muscle fibers, we show that mature muscle dedifferentiates. Muscle dedifferentiation occurs by the synchronous fragmentation of the multinucleate muscle fiber into mononucleate cells followed by rapid cell proliferation and the extension of cell processes. We further show that direct clipping of the muscle fiber and severe tissue damage around the fiber are both required to initiate dedifferentiation. Our observations also make it possible to estimate for the first time how many of the blastema cells arise specifically from muscle dedifferentiation. Calculations based on our data suggest that up to 29% of nondermal-derived cells in the blastema come from dedifferentiation of mature muscle fibers. Overall, these results show that endogenous multinucleate muscle fibers can dedifferentiate into mononucleate cells and contribute significantly to the blastema.


Optically directed molecular transport and 3D isoelectric positioning of amphoteric biomolecules.
We demonstrate the formation of charged molecular packets and their transport within optically created electrical force-field traps in a pH-buffered electrolyte. We call this process photoelectrophoretic localization and transport (PELT). The electrolyte is in contact with a photoconductive semiconductor electrode and a counterelectrode that are connected through an external circuit. A light beam directed to coordinates on the photoconductive electrode surface produces a photocurrent within the circuit and electrolyte. Within the electrolyte, the photocurrent creates localized force-field traps centered at the illuminated coordinates. Charged molecules, including polypeptides and proteins, electrophoretically accumulate into the traps and subsequently can be transported in the electrolyte by moving the traps over the photoconductive electrode in response to movement of the light beam. The molecules in a single trap can be divided into aliquots, and the aliquots can be directed along multiple routes simultaneously by using multiple light beams. This photoelectrophoretic transport of charged molecules by PELT resembles the electrostatic transport of electrons within force-field wells of solid-state charge-coupled devices. The molecules, however, travel in a liquid electrolyte rather than a solid. Furthermore, we have used PELT to position amphoteric biomolecules in three dimensions. A 3D pH gradient was created in an electrolyte medium by controlling the illumination position on a photoconductive anode where protons were generated electrolytically. Photoelectrophoretic transport of amphoteric molecules through the pH gradient resulted in accumulation of the molecules at their apparent 3D isoelectric coordinates in the medium.


Molecular cloning, functional expression and pharmacological characterization of a mouse melanocortin receptor gene.
We describe the cloning of the mouse HGMP01A gene that encodes a melanocortin receptor functionally distinct from the adrenal cortex corticotropin (adrenocorticotrophic hormone; ACTH) receptor and the melanocyte-stimulating hormone (MSH) receptor expressed in melanoma. The gene encodes a protein of 323 amino acids with a calculated molecular mass of 35,800 Da, displaying potential sites for N-linked glycosylation and phosphorylation by protein kinase C. An RNAase protection assay detected weak expression in the brain, but not in adrenal gland, skin, or any of the other tissues tested. Stable CHO cell lines expressing over 100,000 receptors per cell were generated. The recombinant receptor binds iodinated [Nle4,D-Phe7]alpha-MSH (NDP-MSH) with an apparent Kd of 700 pM. Displacement of the ligand by a variety of pro-opiomelanocortin-derived peptides revealed a pharmacological profile distinct from that of the classical ACTH and MSH receptors. NDP-MSH was the most powerful competitor (IC50 1.4 nM), followed by gamma-MSH (IC50 7 nM). alpha-MSH, beta-MSH and ACTH-(1-39) were significantly less potent, with IC50 values of 30, 19 and 21 nM respectively. ACTH-(4-10) was poorly active (IC50 2.4 microM), while corticotropin-like intermediate lobe peptide (CLIP) and beta-endorphin were totally ineffective. The recombinant receptor was found to stimulate adenylate cyclase. The potency order of the agonists in this assay was consistent with that of the binding displacement assays. This receptor represents the orthologue of the human melanocortin 3 receptor reported recently. The growing family of melanocortin receptors constitute the molecular basis for the variety of actions of melanocortins that have been described over the years. The availability of functionally expressed receptors from the melanocortin family will allow the development of a specific pharmacology, and a better understanding of the function of the pro-opiomelanocortin-derived peptides.


Effect of Huperzine A on Cognitive Function and Perception of Effort during Exercise: A Randomized Double-Blind Crossover Trial.
Huperzine A has shown the ability to acutely improve cognitive function in certain populations, and therefore is commonly added to pre-workout supplements. However, its effects have not been studied in exercise-trained individuals. We hypothesized that acute consumption of huperzine A would improve cognitive function during exercise, which may be beneficial for exercise performance. From January to April, 2018, 15 exercise-trained individuals (11 women [height 166 ± 2 cm, weight 60.5 ± 3.0 kg] and 4 men [height 173 ± 4 cm, weight 82.0 ± 11.0 kg], BMI 23.5 ± 1.4 kg/m2, age 30.4 ± 3.6 years) were studied in a double blind randomized-sequence cross-over study, in which they underwent tests for cognitive function (digit span, verbal/word fluency, and Stroop), neuromuscular performance (sharpened Romberg and dart throwing), and exercise performance (estimated aerobic capacity, hand-grip strength, vertical jump, and push-up) after acute ingestion of huperzine A (200 mcg) or placebo. One week separated the two trials. No measures of cognitive function differed between placebo and huperzine A trials (all p ≥ 0.296). Heart rates (157 ± 4 vs. 158 ± 4 bpm; p = 0.518) and ratings of perceived exertion (13.7 ± 0.56 vs. 13.9 ± 0.61; p = 0.582) did not differ between placebo and huperzine A trials, respectively. Ratings of subjective difficulty post-exercise (0-10 scale) were significantly higher (5.7 ± 0.38 vs. 6.8 ± 0.38; p = 0.002) in the huperzine A trial than the placebo trial. No differences were observed for neuromuscular or exercise performance measures between groups (all p ≥ 0.497). Huperzine A does not enhance cognitive function during exercise despite it being marketed as a cognitive enhancer. Because of its inability to enhance cognitive function, its inclusion in pre-workout supplements warrants reconsideration. Other more practical and effective strategies should be considered.


Probability density methods for smooth function approximation and learning in populations of tuned spiking neurons.
This article proposes a new method for interpreting computations performed by populations of spiking neurons. Neural firing is modeled as a rate-modulated random process for which the behavior of a neuron in response to external input can be completely described by its tuning function. I show that under certain conditions, cells with any desired tuning functions can be approximated using only spike coincidence detectors and linear operations on the spike output of existing cells. I show examples of adaptive algorithms based on only spike data that cause the underlying cell-tuning curves to converge according to standard supervised and unsupervised learning algorithms. Unsupervised learning based on principal components analysis leads to independent cell spike trains. These results suggest a duality relationship between the random discrete behavior of spiking cells and the deterministic smooth behavior of their tuning functions. Classical neural network approximation methods and learning algorithms based on continuous variables can thus be implemented within networks of spiking neurons without the need to make numerical estimates of the intermediate cell firing rates.


Calcium imaging analysis - how far have we come?
Techniques for calcium imaging were first achieved in the mid-1970s, whilst tools to analyse these markers of cellular activity are still being developed and improved. For image analysis, custom tools were developed within labs and until relatively recently, software packages were not widely available between researchers. We will discuss some of the most popular, alongside our preferred, methods for calcium imaging analysis that are now widely available and describe why these protocols are so effective. We will also describe some of the newest innovations in the field that are likely to benefit researchers, particularly as calcium imaging is often an inherently low signal-to-noise method. Although calcium imaging analysis has seen recent advances, particularly following the rise of machine learning, we will end by highlighting the outstanding requirements and questions that hinder further progress, and pose the question of how far we have come in the past sixty years and what can be expected for future development in the field.


Drosophila PS2 integrin mediates RGD-dependent cell-matrix interactions.
Integrins are a family of transmembrane glycoproteins that mediate cell-matrix and cell-cell interactions. We have transfected cultured Drosophila cells with genes that express the Drosophila PS2 integrin. We demonstrate that this integrin is expressed on the surface of the cells and can mediate cell spreading on an undefined component of fetal calf serum or on the purified vertebrate matrix molecules vitronectin and fibronectin. Additionally, PS2 integrin can cause cell spreading on RGD peptide. The spreading on matrix components or RGD peptide can be inhibited by soluble RGD peptide and is dependent on divalent cations.


Lost in the shuffle: culture of homeless adolescents.
Estimates indicate that approximately 1.7 million youth are homeless in the United States. Many associated risk factors have been identified for adolescent homelessness, including family conflict, leaving foster care, running away or being thrown away, physical or sexual abuse, and coming out to parents as gay, lesbian, bisexual, transgender, or questioning one's sexual identity (GLBTQ). The purpose of this ethnographic study was to explore the culture of homelessness for adolescents. Nineteen homeless adolescents from a major urban area in the northeast U.S. were observed and interviewed over an 18-month period. The elements of the street culture of homeless adolescents were identified by study participants' stories. For many study participants, the decision to live on the streets was a logical and rational alternative to remaining in possibly dangerous and unstable home environments. It provided a means to their generating social capital. Nevertheless, it can be concluded that existing programs and policies relative to adolescents who are at risk for homelessness or already living on the streets should be re-examined and redesigned to meet the unique needs of vulnerable youth so they do not get lost in the shuffle.


[Causes for the underreporting of adverse drug events by health professionals: a systematic review].
Identifying the main causes for underreporting of Adverse Drug Reaction (ADR) by health professionals. A systematic review carried out in the following databases: LILACS, PAHO, SciELO, EMBASE and PubMed in the period between 1992 and 2012. Descriptors were used in the search for articles, and the identified causes of underreporting were analyzed according to the classification of Inman. In total, were identified 149 articles, among which 29 were selected. Most studies were carried out in hospitals (24/29) for physicians (22/29), and pharmacists (10/29). The main causes related to underreporting were ignorance (24/29), insecurity (24/29) and indifference (23/29). The data show the eighth sin in underreporting, which is the lack of training in pharmacovigilance. Therefore, continuing education can increase adherence of professionals to the service and improve knowledge and communication of risks due to drug use.


Anorectal function in patients with complete supraconal spinal cord lesions.
Anorectal manometry and sphincter electromyography were performed in 23 patients with complete supraconal traumatic spinal injuries and 30 age and sex matched control subjects. Basal pressures in the spinal group were similar to those in normal subjects but conscious control of sphincter activity was abolished in all spinal patients. Discriminant rectal sensation was also abolished during rectal distension, but 40% of patients experienced a dull pelvic ache at maximum levels of distension. Phasic rectal contraction and anal relaxation were present but exaggerated and induced at lower distending volumes than in normal subjects. The configuration of the rectal pressure/volume relationship was linear in patients compared with a reversed 'S' shape in normal subjects. The external anal sphincter response to rectal distension was noticeably attenuated, reinforcing the view that this spinal reflex is heavily modulated by supraspinal centres under normal circumstances. The external anal sphincter response to increases in abdominal pressure was also attenuated, and the anal pressures were strongly correlated with the level of the lesion and the abdominal pressure the patient could generate. No spinal patient showed a decrease in external anal sphincter activity during straining 'as if to defecate.' The exaggerated anorectal smooth muscle responses to rectal distension and the attenuated external sphincter response explain why patients with complete supraconal spinal lesions experience uncontrollable reflex defecation, while the persistance of external and sphincter contraction and the absence of any external anal sphincter relaxation during straining 'as if to defecate' might explain the difficulty that these patients have in consciously expelling rectal contents.


Serological Assays Estimate Highly Variable SARS-CoV-2 Neutralizing Antibody Activity in Recovered COVID-19 Patients.
The development of neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following infection or vaccination is likely to be critical for the development of sufficient population immunity to drive cessation of the coronavirus disease of 2019 (COVID-19) pandemic. A large number of serologic tests, platforms, and methodologies are being employed to determine seroprevalence in populations to select convalescent plasma samples for therapeutic trials and to guide policies about reopening. However, the tests have substantial variations in sensitivity and specificity, and their ability to quantitatively predict levels of NAbs is unknown. We collected 370 unique donors enrolled in the New York Blood Center Convalescent Plasma Program between April and May of 2020. We measured levels of antibodies in convalescent plasma samples using commercially available SARS-CoV-2 detection tests and in-house enzyme-linked immunosorbent assays (ELISAs) and correlated serological measurements with NAb activity measured using pseudotyped virus particles, which offer the most informative assessment of antiviral activity of patient sera against viral infection. Our data show that a large proportion of convalescent plasma samples have modest antibody levels and that commercially available tests have various degrees of accuracy in predicting NAb activity. We found that the Ortho anti-SARS-CoV-2 total Ig and IgG high-throughput serological assays (HTSAs) and the Abbott SARS-CoV-2 IgG assay quantify levels of antibodies that strongly correlate with the results of NAb assays and are consistent with gold standard ELISA results. These findings provide immediate clinical relevance to serology results that can be equated to NAb activity and could serve as a valuable roadmap to guide the choice and interpretation of serological tests for SARS-CoV-2.


Direct muscarinic cholinergic inhibition of hepatic glucose production in humans.
To explore the potential role of the parasympathetic nervous system in human glucoregulatory physiology, responses to the muscarinic cholinergic agonist bethanechol (5.0 mg s.c.) and antagonist atropine (1.0 mg i.v.) were measured in normal humans. There were no changes in the plasma glucose concentration or rates of glucose production or utilization following atropine administration. After bethanechol administration there were no changes in the plasma glucose concentration or fluxes despite increments in plasma glucagon (75 +/- 7 to 103 +/- 10 pg/ml, P less than 0.02). There were no changes in insulin or C-peptide levels. To test the hypothesis that direct muscarinic inhibition of glucose production was offset by an indirect action of the agonist, specifically increased glucagon secretion with consequent stimulation of glucose production, bethanechol was administered while glucagon levels were held constant with the islet clamp technique (somatostatin infusion with insulin, glucagon and growth hormone replacement at fixed rates). Under that condition the muscarinic agonist induced a 25% decrement in the plasma glucose concentration (101 +/- 8 to 75 +/- 8 mg/dl, P less than 0.05). When compared with separate clamp control studies (with placebo rather than bethanechol injection) both the rate of glucose production and the glucose concentration were reduced (P less than 0.05) following bethanechol injection; the rate of glucose utilization was unaltered. Thus, we conclude: Withdrawal of parasympathetic tone does not appear to be an important glucoregulatory process in humans. Direct muscarinic cholinergic inhibition of hepatic glucose production occurs in humans but during generalized muscarinic activation this is offset by an indirect muscarinic action, increased glucagon secretion with consequent stimulation of glucose production. Thus, particularly if regional neuronal firing occurs, the parasympathetic nervous system may play an important role in human glucoregulatory physiology.


Influence of absorption and scattering on the quantification of fluorescence diffuse optical tomography using normalized data.
Reconstruction algorithms for imaging fluorescence in near infrared ranges usually normalize fluorescence light with respect to excitation light. Using this approach, we investigated the influence of absorption and scattering heterogeneities on quantification accuracy when assuming a homogeneous model and explored possible reconstruction improvements by using a heterogeneous model. To do so, we created several computer-simulated phantoms: a homogeneous slab phantom (P1), slab phantoms including a region with a two- to six-fold increase in scattering (P2) and in absorption (P3), and an atlas-based mouse phantom that modeled different liver and lung scattering (P4). For P1, reconstruction with the wrong optical properties yielded quantification errors that increased almost linearly with the scattering coefficient while they were mostly negligible regarding the absorption coefficient. This observation agreed with the theoretical results. Taking the quantification of a homogeneous phantom as a reference, relative quantification errors obtained when wrongly assuming homogeneous media were in the range +41 to +94% (P2), 0.1 to -7% (P3), and -39 to +44% (P4). Using a heterogeneous model, the overall error ranged from -7 to 7%. In conclusion, this work demonstrates that assuming homogeneous media leads to noticeable quantification errors that can be improved by adopting heterogeneous models.


Platelets interact with fibrin only after activation.
Interactions between platelets and fibrin have been visualized by phase contrast, epifluorescence, and scanning electron microscope examination of clots formed with dansylcadaverine-labeled fibrin and gel-filtered platelets. After thrombin activation, the platelets appeared as fluorescent aggregates with bridging strands of fibrin; formaldehyde-fixed platelets were not fluorescent under the same experimental conditions. Scanning electron micrographs demonstrated that thrombin-activated cells had numerous pseudopods to which the fibrin strands adhered; fixed platelets exhibited a smooth discoid appearance and did not interact with the clot. Platelets trapped in clots formed with Batroxobin (Pentapharm) (platelets are not activated by Batroxobin as confirmed by light-scattering aggregometry measurements) remained as nonfluorescent, discoid cells, whereas platelets first activated by adenosine diphosphate formed brightly fluorescent aggregates. Light-scattering data of thrombin activation (0.2 U/mL) indicated that preincubation of platelets with 0.1 mmol/L prostaglandin E1 (PGE1) prior to addition of thrombin decreased the extent and rate of platelet shape change and resulted in 100-fold slower aggregation. Clots formed in the presence of PGE1 revealed decreased fluorescence intensity and fewer platelet-fibrin contacts. Gly-Pro-Arg-Pro, which blocks fibrinogen binding and fibrin assembly, was also effective in blocking platelet-fibrin interactions. These results indicate that platelet activation is a prerequisite for attachment of platelets to fibrin.


Comparison of hospitalization costs and Medicare payments for carotid endarterectomy and carotid stenting in asymptomatic patients.
Hospitals struggle to provide care for elderly patients based on Medicare payments. Amid concerns of inadequate reimbursement, we sought to evaluate the hospitalization costs for recipients of CEA and CAS placement, identify variables associated with increased costs, and compare these costs with Medicare reimbursements. All CEA and CAS procedures were extracted from the 2001-2008 NIS. Average CMS reimbursement rates for CEA and CAS were obtained from www.CMS.gov. Annual trends in hospital costs were analyzed by Sen slope analysis. Associations between LOS and hospital costs with respect to sex, age, discharge status, complication type, and comorbidity were analyzed by using the Wilcoxon rank sum test. Least-squares regression models were used to predict which variables had the greatest impact on LOS and hospital costs. The 2001-2008 NIS contained 181,200 CEA and 12,485 CAS procedures. Age and sex were not predictive of costs for either procedure. Among favorable outcomes, CAS was associated with significantly higher costs compared with CEA (P < .0001). Average Medicare payments were $1,318 less than costs for CEA and $3,241 less than costs for CAS among favorable outcomes. Greater payment-to-cost disparities were noted for both CEA and CAS in patients who had unfavorable outcomes. The 2008 Medicare hospitalization payments were substantially less than median hospital costs for both CAS and CEA. Efforts to decrease hospitalization costs and/or increase payments will be necessary to make these carotid revascularization procedures economically viable for hospitals in the long term.


[Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency].
One hundred and eighty-seven patients with different stages of cerebrovascular insufficiency (CI) have been examined. A diagnosis of CI was based on the results of neurological and neuropsychological study, ultrasonic dopplerography, rheo- and encephalography, electrocardiography, brain MRI and eyegrounds examination. Neurological scales were used for neurological status assessment and further data processing. The study aimed at evaluation of tolerability and clinical efficacy of the medication and complications in CI course. Semax treatment resulted in significant clinical improvement, stabilization of the disease progress and reduced a risk of stroke and transitory ischemic attacks in the disease course. The drug is featured by minor percent of side-effects and is well tolerated by patients, including those of older age groups.


[Are inpatient rehabilitation or ambulatory physical therapy of patients with musculoskeletal problems effective and are patients referred to proper treatment?].
The aim of the present study was to investigate the effectiveness of an inpatient rehabilitation program and outpatient physiotherapy, respectively. Moreover, we wanted to know whether the referral to these two treatment paths was appropriate with regard to the patient's initial health status. According to the referring physician's indication patients with health problems in the cervical, lumbar spine, arm or leg were treated by an inpatient rehabilitation program or by outpatient physiotherapy. These two consecutively recruited patient cohorts were then compared. Those patients treated by the inpatient rehabilitation program differed from the outpatient group with regard to the initial health status and to age. Patients with musculoskeletal problems, who underwent an inpatient rehabilitation program, showed a significantly worse health and functional status than the outpatient group. Therefore, it can be concluded that the indication towards inpatient rehabilitation or outpatient physiotherapy was correctly given by the referring physicians. Patients treated by outpatient physiotherapy did also show a reduced health and functional status in comparison to the average population. Both types of treatment led to statistically significant and clinically relevant improvement of both the health and functional status in all patient groups.


Glycyrrhiza uralensis root extract ameliorates high glucose-induced renal proximal tubular fibrosis by attenuating tubular epithelial-myofibroblast transdifferentiation by targeting TGF-β1/Smad/Stat3 pathway.
Growing evidences indicate that high glucose toxicity-associated fibrotic effects play a pivotal role in diabetic nephropathy (DN). Tubular epithelial-myofibroblast transdifferentiation is a major hallmark of renal fibrosis event under diabetic stress. Roots of Glycyrrhiza uralensis (Radix glycyrrhizae) used as a sweetener and traditional Chinese medicine possess high potential for renal protection. In this study, a cell model for high glucose (HG) injury with HK-2 renal proximal tubular epithelial cell line and a type-II-diabetes model with Apoeem1/Narl /Narl mice was established and the beneficial effects of aqueous R. glycyrrhizae extract (RGE) was investigated. RGE-induced regulation on the high glucose-induced excessive production of TGF-β1 and the Smad/Stat3 mechanisms of renal fibrosis were determined. HK-2 cells were challenged with 45 mM of high glucose for 48 hr. Following high glucose challenge, the cells were treated with 0.5, 1, and 1.5 mg/ml concentrations of RGE. The effect of RGE on DN was determined using high fructose diet-induced type-II-diabetes in Apoeem1/Narl /Narl mice models. Our results showed that RGE suppressed the expression of HG-induced TGFβ signaling and associated fibrosis mechanism better than the pharmacological drug acarbose. These data suggest that RGE as a potential herbal supplement in attenuating fibrosis-associated diabetic nephropathy and a potential agent in diabetes treatments.


A Chinese traditional medicine, juzentaihoto, inhibits the O2- generation by macrophages.
Guinea pig peritoneal macrophages generate superoxide anion (O2-), when stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), phorbol-myristate acetate (PMA) or ovalbumin complex of guinea pig IgG2 antibody (OA gamma 2). These responses were found to be inhibited by a Chinese traditional medicine, Juzentaihoto (JT). When the inhibition was assayed by the use of fMLP as a stimulant, at least one of the substances responsible for the inhibitory activity of JT was identified to be cinnamic acid. An authentic sample of cinnamic acid also inhibited the O2- generation by fMLP-stimulated macrophages. Cinnamic acid, however, did not inhibit the O2- generation, when macrophages were stimulated with PMA and OA gamma 2. These results indicate that a certain cinnamic acid-inhibitable factor may be involved in the intracellular triggering event(s) initiated by fMLP, leading to activation of the respiratory burst reduced nicotinamide adenine dinucleotide phosphate oxidase, but not in those by PMA and OA gamma 2.


Microfixation techniques in pediatric craniomaxillofacial surgery.
Microfixation represents a technical advance that has been developed for the specific needs of the infantile and pediatric craniomaxillofacial skeleton. The microplates provide significant skeletal stability despite their size and are relatively easy to apply and adjust after placement. The advantages and the technical aspects of microfixation use versus those of minifixation in smaller skeletal structures are presented. The range of applications in pediatric craniofacial surgery is demonstrated and reviewed in our series of 65 children, with a greater than 1-year follow-up.


Aberrant Current Source-Density and Lagged Phase Synchronization of Neural Oscillations as Markers for Emerging Psychosis.
Converging evidence indicates that neural oscillations coordinate activity across brain areas, a process which is seemingly perturbed in schizophrenia. In particular, beta (13-30 Hz) and gamma (30-50 Hz) oscillations were repeatedly found to be disturbed in schizophrenia and linked to clinical symptoms. However, it remains unknown whether abnormalities in current source density (CSD) and lagged phase synchronization of oscillations across distributed regions of the brain already occur in patients with an at-risk mental state (ARMS) for psychosis. To further elucidate this issue, we assessed resting-state EEG data of 63 ARMS patients and 29 healthy controls (HC). Twenty-three ARMS patients later made a transition to psychosis (ARMS-T) and 40 did not (ARMS-NT). CSD and lagged phase synchronization of neural oscillations across brain areas were assessed using eLORETA and their relationships to neurocognitive deficits and clinical symptoms were analyzed using linear mixed-effects models. ARMS-T patients showed higher gamma activity in the medial prefrontal cortex compared to HC, which was associated with abstract reasoning abilities in ARMS-T. Furthermore, in ARMS-T patients lagged phase synchronization of beta oscillations decreased more over Euclidian distance compared to ARMS-NT and HC. Finally, this steep spatial decrease of phase synchronicity was most pronounced in ARMS-T patients with high positive and negative symptoms scores. These results indicate that patients who will later make the transition to psychosis are characterized by impairments in localized and synchronized neural oscillations providing new insights into the pathophysiological mechanisms of schizophrenic psychoses and may be used to improve the prediction of psychosis.


Surgical closure of atrial septal defect in patients older than 50 years of age.
Between 1962 and 1986, 51 patients 50 years of age or older (mean, 59.7 years; range, 50 to 77 years) underwent operative closure of atrial septal defect. The mean pulmonary vascular resistance was 1.7 +/- 0.79 wood units and the mean pulmonary blood flow-systemic blood flow ratio was 2.8 +/- 1.4. Patch closure with pericardium or Dacron was performed in 36 patients (70%), while 15 patients (30%) underwent primary closure. There were no operative deaths, and one patient was not available for follow-up. The remaining 50 patients (98%) have been followed up for 0.5 to 25 years (mean, 9.6 years). Mean preoperative New York Heart Association classification was 2.40 +/- 0.70. This improved significantly to 1.21 +/- 0.42 at follow-up, with all patients improving by at least one category. No patient received long-term anticoagulation treatment, and no pulmonary or systemic emboli were identified. Two (13%) of 15 patients who underwent primary closure developed septal dehiscence. Actuarial survival was 93%, 86%, and 79% at 5, 10, and 15 years, respectively. Atrial septal defect closure can be safely performed in older patients with excellent results, provided the ratio of systemic to pulmonary blood flow is greater than or equal to 1.5 to 1.0, the pulmonary vascular resistance is low, and the shunt remains left to right. Primary closure should be discouraged, and postoperative anticoagulation therapy appears unwarranted.


Looking backwards to move forward: Using a social mission lens in nursing education.
The ideals of health equity continue to be constrained by the conditions in which people live, learn and work. But to what extents are nursing schools strengthening the preparedness of nurses to extend their reach and help individuals and communities achieve their highest level of health? A culture of health and health equity is built on a framework of social mission. The authors believe that social mission is not new to the nursing profession. However, a clear understanding of the historical evolution of social mission as it relates to nursing education could provide a solid foundation for understanding the extent to which nursing curricula aligns with a commitment to advancing healthcare outcomes. This manuscript is a commentary that outlines the foundational understanding of the history of social mission in nursing education through the present time and amplifies that educators should consider how adopting a social mission lens could help schools more effectively align their curricula, policies and practices with health equity. Social mission refers to the school's commitment to advance health equity in everything it does from admissions and faculty hiring policies, to curriculum development, the extent of community based experiential learning, and, ultimately measured in their graduates' outcomes (Mullan, 2017). It is the authors' view that the rich history, the magnitude of the sector, and the current transformational conversations occurring in the nursing profession, all call for a deeper analysis and engagement of nursing leaders in this topic.


A New Fusion Peptide Targeting Pancreatic Cancer and Inhibiting Tumor Growth.
Pancreatic cancer is a highly malignant tumor of the digestive system. Early pancreatic cancer is often difficult to diagnosis due to its atypical clinical symptoms. Patients with pancreatic cancer have a very poor prognosis because they have lost the opportunity for radical surgical tumor resection and they are less sensitive to the clinically used radiotherapy and chemotherapy. In this study, a peptide targeting pancreatic cancer cells was screened by phage display technology, and its targeting property was evaluated in vitro using PANC1 cells by fluorescence imaging and flow cytometry. Furthermore, the targeting peptide was conjugated to the pro-apoptotic KLAKLAKKLAKLAK (KLA), the fusion peptide and its targeting ability that allowing KLA to specifically enter pancreatic tumor cells in vitro and in vivo was confirmed by fluorescence imaging and in vivo imaging system (IVIS). Its mechanism was determined using flow cytometry, mitochondrial membrane potential evaluation and Western blot. The inhibitory effect on pancreatic tumor growth and toxic effects were evaluated by animal experiment. Due to the internalization facilitated by the targeting mechanism of the targeting peptide, KLA specifically entered pancreatic cancer cells, destroyed mitochondria and induced apoptosis. The fusion peptide and its targeting ability that allowing KLA to specifically enter pancreatic tumor cells and exert a significant inhibitory effect on pancreatic tumor growth with reduced toxic effects. This approach possesses potential advantages in the clinical diagnosis and treatment of pancreatic cancer.


Plasma monoamine oxidase levels in mammals.
Plasma monoamine oxidase (MAO) levels in ruminants and non-ruminants including man are reported. The mean MAO levels in units are, goat 6699.7+/-367.4; cattle 6272.9+/-9.257.4; camel 5166.0+/-666.8; sheep 4831.4+/-543.8; buffaloe 4045.8+/-387.3; rabbit 837.0+/-19.3; dog 441.8+/-55.5 and man 20.0+/-2.8 respectively.


First Report of Cherry mottle leaf virus Infecting Cherry in China.
Cherry mottle leaf virus (CMLV) is a member of the genus Trichovirus (family Betaflexiviridae). CMLV infects several species of the genus Prunus including cherry (Prunus avium) and peach (P. persica) (2,3). It is spread via budding and grafting with infected wood and can be transmitted from infected bitter cherry (P. emarginata), or infected but symptomless peach trees to healthy sweet cherry trees by the bud mite (Eriophyes inaequalis) (1). On susceptible sweet cherry cultivars, CMLV causes symptoms such as chlorotic mottle-leaf pattern, distortion, puckering of younger leaves, and small fruits that ripen late (1), which may lead to severe economic losses in some cultivars. Cherry is one of the most important fruit tree species in North China, and Shandong Province is one of the major cherry production areas. In June 2013, a survey of possible CMLV presence was conducted in a cherry orchard planted in 1996 in Zoucheng city, Shandong. The sweet cherry cultivars in this orchard included Black Tartarian, Bing, Hongdeng (a hybrid between cvs. Napoleon and Huangyu), and others; the rootstock cultivar utilized to graft these cultivars was mountain cherry (P. tomentosa). During the survey, characteristic symptoms on leaves such as leaf mottling, distortion, and puckering similar to those caused by CMLV were observed on some trees of the cv. Hongdeng, and the symptomatic trees accounted for ~10% of the total trees of this cultivar. Five symptomatic cherry leaf samples and three healthy-looking cherry leaf samples of cv. Hongdeng were collected. Total RNA extracted from the leaf samples using RNeasy plant mini kit (Qiagen Inc., Valencia, CA) was subjected to first strand cDNA synthesis with the reverse primer CMLV-3R (5'-CTCGAGAACACAGAGATTTGTCGAGAC-3', sequence in italics indicates restriction site XhoI) and M-MLV reverse transcriptase (Promega, Madison, WI) according to the manufacturer's instruction. The cDNA was then used as template in the PCR assay using primers CMLV-5F (5'-GGATCCATGTCGGCGCGATTGAATC-3', sequence in italics indicates restriction site BamHI) and CMLV-3R, which amplify the genome fragment including the capsid protein gene of CMLV. The expected PCR product ~590 bp was amplified from all five symptomatic samples, while no such PCR product was amplified from the symptomless samples. The PCR products were cloned into pMD18-T vector (TaKaRa, Dalian, China). Three positive clones for each of the five amplicons were sequenced in both directions. Sequence alignment and nucleotide BLAST analysis of the sequences revealed that they were 99% to 100% identical to the corresponding capsid protein gene sequence of a cherry isolate of CMLV (GenBank Accession No. AF170028) and 85% identical with that of the peach wart strain of CMLV (KC207480). Our results confirm the infection of cherry trees by CMLV in Shandong. To our knowledge, this is the first report of CMLV on cherry in China. As the spread of CMLV by mite vector in the field is rare (1), and no bud mite outbreak had occurred in this orchard in the past years, so it is possible that virus-infected propagation materials are largely responsible for the spread of this virus. Considering the importance of cherry cultivation in China, this report prompts the need to survey the occurrence of this virus in Shandong and other provinces, and the need to develop more effective management strategies such as the use of certified virus-free nursery stocks to reduce the impact of CMLV. References: (1) J. E. Adaskaveg et al. Diseases. Page 61 in: UC IPM Pest Management Guidelines: Cherry. University of California ANR Publication 3444, 2014. (2) D. James et al. Arch. Virol. 145:995, 2000. (3) T. A. Mekuria et al. Arch. Virol. 158:2201, 2013.


Functional correlates of positional and gender-specific renal asymmetry in Drosophila.
In humans and other animals, the internal organs are positioned asymmetrically in the body cavity, and disruption of this body plan can be fatal in humans. The mechanisms by which internal asymmetry are established are presently the subject of intense study; however, the functional significance of internal asymmetry (outside the brain) is largely unexplored. Is internal asymmetry functionally significant, or merely an expedient way of packing organs into a cavity? Like humans, Drosophila shows internal asymmetry, with the gut thrown into stereotyped folds. There is also renal asymmetry, with the rightmost pair of renal (Malpighian) tubules always ramifying anteriorly, and the leftmost pair always sitting posteriorly in the body cavity. Accordingly, transcriptomes of anterior-directed (right-side) and posterior-directed (left-side) Malpighian (renal) tubules were compared in both adult male and female Drosophila. Although genes encoding the basic functions of the tubules (transport, signalling) were uniformly expressed, some functions (like innate immunity) showed positional or gender differences in emphasis; others, like calcium handling or the generation of potentially toxic ammonia, were reserved for just the right-side or left-side tubules, respectively. These findings correlated with the distinct locations of each tubule pair within the body cavity. Well known developmental genes (like dorsocross, dachshund and doublesex) showed continuing, patterned expression in adult tubules, implying that somatic tissues maintain both left-right and gender identities throughout life. Gender asymmetry was also noted, both in defence and in male-specific expression of receptors for neuropeptide F and sex-peptide: NPF elevated calcium only in male tubules. Accordingly, the physical asymmetry of the tubules in the body cavity is directly adaptive. Now that the detailed machinery underlying internal asymmetry is starting to be delineated, our work invites the investigation, not just of tissues in isolation, but in the context of their unique physical locations and milieux.


Influence of an Organic Salt-Based Stabilizing Additive on Charge Carrier Dynamics in Triple Cation Perovskite Solar Cells.
Besides further improvement in the power conversion efficiency (PCE) of perovskite solar cells (PSC), their long-term stability must also be ensured. Additives such as organic cations with halide counter anions are considered promising candidates to address this challenge, conferring both higher performance and increased stability to perovskite-based devices. Here, a stabilizing additive (N,N-dimethylmethyleneiminium chloride, [Dmmim]Cl) is identified, and its effect on charge carrier mobility and lifetime under thermal stress in triple cation perovskite (Cs0.05 MA0.05 FA0.90 PbI3 ) thin films is investigated. To explore the fundamental mechanisms limiting charge carrier mobility, temperature-dependent microwave conductivity measurements are performed. Different mobility behaviors across two temperature regions are revealed, following the power law Tm , indicating two different dominant scattering mechanisms. The low-temperature region is assigned to charge carrier scattering with polar optical phonons, while a strong decrease in mobility at high temperatures is due to dynamic disorder. The results obtained rationalize the improved stability of the [Dmmim]Cl-doped films and devices compared to the undoped reference samples, by limiting temperature-activated mobile ions and retarding degradation of the perovskite film.


[Transference interpretations and how they work: a systematic review].
In clinical theory transference interpretations represent a central therapeutic technique and a specific mechanism of change in psychodynamic psychotherapies. However, the empirical basis lags behind the theoretical considerations. This article reviews both the results of empirical research on transference interpretations and their definitions of the measures employed (systematic database search for the timespan 1970-2011). The empirical results are rather heterogeneous and in part contradictory. As it turns out, specific patient characteristics (e.g., the quality of object relations), the amount and quality of transference interpretations as well as the patients' immediate reaction all decisively influence the potency of the change of transference interpretations. Currently, it is not possible to develop clear therapeutic strategies based on previous findings. Careful use of transference interpretations is generally recommended. Various methods for measuring transference interpretations exist, but the definitions do not correspond completely. A standardization of definitions would increase the comparability and interpretability of findings and greatly improve concordance with theory.


IL-33 is an unconventional Alarmin that stimulates IL-2 secretion by dendritic cells to selectively expand IL-33R/ST2+ regulatory T cells.
IL-33 is a recently characterized IL-1 family member that is proposed to function as an alarmin, or endogenous signal of cellular damage, as well as act as a pleiotropic cytokine. The ability of IL-33 to potentiate both Th1 and Th2 immunity supports its role in pathogen clearance and disease immunopathology. Yet, IL-33 restrains experimental colitis and transplant rejection by expanding regulatory T cells (Treg) via an undefined mechanism. We sought to determine the influence of IL-33 on hematopoietic cells that drives Treg expansion and underlies the therapeutic benefit of IL-33 administration. In this study, we identify a feedback loop in which conventional mouse CD11c(+) dendritic cells (DC) stimulated by IL-33 secrete IL-2 to selectively expand IL-33R(ST2(+))- suppressive CD4(+)Foxp3(+) Treg. Interestingly, this occurs in the absence of classical DC maturation, and DC-derived (innate) IL-2 increases ST2 expression on both DC and interacting Treg. ST2(+) Treg represent an activated subset of Foxp3(+) cells, demonstrated to be ICOS(high)CD44(high) compared with their ST2(-) counterparts. Furthermore, although studies have shown that IL-33-exposed DC promote Th2 responses, we reveal that ST2(+) DC are required for IL-33-mediated in vitro and in vivo Treg expansion. Thus, we have uncovered a relationship between IL-33 and innate IL-2 that promotes the selective expansion of ST2(+) Treg over non-Treg. These findings identify a novel regulatory pathway driven by IL-33 in immune cells that may be harnessed for therapeutic benefit or for robust expansion of Treg in vitro and in vivo.


[Extramedullary haematopoiesis as a cause of a paravertebral mass in the thorax (author's transl)].
The radiological due to extensive extramedullary haematopoiesis taking place in the posterior mediastinum in two patients are described, and the literature is reviewed. Characteristic features are a polycyclic or spindle-shaped configuration of the mass, with bilateral paravertebral localisation in the caudal and middle third of the thorax. There is absence of inflammatory or neoplastic changes in the neighbouring skeleton, but in thalassaemia there may be changes in the paravertebral portion of the ribs. Computer tomographically, the combination of a solid paravertebral tumour, with adjacent rib changes, is characteristic of thalassaemia with extramedullary haematopoiesis. In the absence of other skeletal changes, computed tomography is valuable for differential diagnosis. Lymphomas occur considerably more often and may appear identical but, because of the well know fat content of myolipoma, the scan shows contrast values between -15 and + 40 HU. Because of their high vascularity, there is a marked increase in density following intravenous contrast medium.


Non-medical prescription stimulant use to improve academic performance among Australian university students: prevalence and correlates of use.
Some university students consume pharmaceutical stimulants without a medical prescription with the goal of improving their academic performance. The prevalence of this practice has been well documented in the US, but less so in other countries. The potential harms of using prescription stimulants require a better understanding of the prevalence of this practice within Australian universities. An internet survey of 1136 Australian students was conducted in 2015 in three large Australian universities. Students were asked about their personal use of prescription stimulants, attitudes and experiences with prescription stimulants. They were also asked about their use of caffeine, energy drinks and illicit drugs to enhance their academic performance. Lifetime self-reported use of stimulant medication to improve academic performance was 6.5, and 4.4% in the past year. Students were far more likely to report using coffee and energy drinks (41.4 and 23.6% respectively, lifetime use) than prescription stimulants to help them study and complete university assessments. Non-medical use of prescription stimulants was strongly associated with a history of illicit drug use. The prevalence of nonmedical prescription stimulant use to improve academic performance is low among university students in Australia, especially when compared with their use of coffee and energy drinks.


Growth suppressing effect of garlic compound diallyl disulfide on prostate cancer cell line (PC-3) in vitro.
Prostate cancer is the most predominant cancer in men and prostate cancer related death increases every year. Till date, there is no effective therapy other than androgen ablation therapy. At this stage, induction of apoptosis is considered as a better strategy to control cancer. Previous studies reported that aged garlic extract suppresses cancer growth and enhances immune system against cancer. In the present study, diallyl disulfide, oil soluble organosulfur compound of garlic, was studied for its antiproliferative effect on prostate cancer cells in vitro. The suppression of cell growth was demonstrated by [(3)H]thymidine incorporation assay. Induction of DNA damage was assessed by agarose gel electrophoresis. The results showed that diallyl disulfide inhibited the growth of prostate cancer cells in a dose dependent manner, compared to the control. At 50 microM and 100 microM concentrations, diallyl disulfide induced DNA damage in PC-3 cells. It is concluded that diallyl disulfide, component of aged garlic extract, inhibits proliferation of prostate cancer cells through the induction of apoptosis.


[Development of a questionnaire for assessing motivational conditions for prediction of therapy cooperation of LVA insured patients during inpatient medical rehabilitation--initial results of scale development].
Medical staff working in rehabilitation often criticize their in-patients' lack of motivation to cooperate in therapy. Consequently, very often the aims of the therapy would not be reached. That, again, causes expenses that could be avoided and it also causes frustration on both sides. On the basis of Schwarzer's Health Action Process Approach (HAPA) we designed a questionnaire on motivation to predict the degree of the in-patients' cooperation in therapy during rehabilitation. The results presented here are based on an interim analysis of 508 questionnaires answered by LVA insurees (Landesversicherungsanstalten, wage earners' pension insurance funds) who had applied for rehabilitation in a clinic. The applicants suffered from illness of the back and spine as well as degenerative illness of the joints. A first examination of the scales Specific Outcome Expectancies, Specific Self-efficacy and Intention of the questionnaire showed very good statistical results as well as correlations between these variables that correspond to HAPA. It also turned out that there is a direct connection between the scores of the motivation variables (e.g. Specific Self-efficacy) and that of cooperation in therapy. These initial test results indicate a generic character of the instruments used in this research project. They also point out starting points for interventions to increase motivation that are to be developed.


Signature amyloid β profiles are produced by different γ-secretase complexes.
γ-Secretase complexes are involved in the generation of amyloid-β (Aβ) in the brain. Therefore, γ-secretase has been proposed as a potential therapeutic target in Alzheimer disease (AD). Targeting γ-secretase activity in AD requires the pharmacological dissociation of the processing of physiological relevant substrates and the generation of "toxic" Aβ. Previous reports suggest the differential targeting of γ-secretase complexes, based on their subunit composition, as a valid strategy. However, little is known about the biochemical properties of the different complexes, and key questions regarding their Aβ product profiles should be first addressed. Here, we expressed, purified, and analyzed, under the same conditions, the endopeptidase and carboxypeptidase-like activities of the four γ-secretase complexes present in humans. We find that the nature of the catalytic subunit in the complex affects both activities. Interestingly, PSEN2 complexes discriminate between the Aβ40 and Aβ38 production lines, indicating that Aβ generation in one or the other pathway can be dissociated. In contrast, the APH1 subunit mainly affects the carboxypeptidase-like activity, with APH1B complexes favoring the generation of longer Aβ peptides. In addition, we determined that expression of a single human γ-secretase complex in cell lines retains the intrinsic attributes of the protease while present in the membrane, providing validation for the in vitro studies. In conclusion, our data show that each γ-secretase complex produces a characteristic Aβ signature. The qualitative and quantitative differences between different γ-secretase complexes could be used to advance drug development in AD and other disorders.


In silico Approach for Validating and Unveiling New Applications for Prognostic Biomarkers of Endometrial Cancer.
Endometrial cancer (EC) mortality is directly associated with the presence of prognostic factors. Current stratification systems are not accurate enough to predict the outcome of patients. Therefore, identifying more accurate prognostic EC biomarkers is crucial. We aimed to validate 255 prognostic biomarkers identified in multiple studies and explore their prognostic application by analyzing them in TCGA and CPTAC datasets. We analyzed the mRNA and proteomic expression data to assess the statistical prognostic performance of the 255 proteins. Significant biomarkers related to overall survival (OS) and recurrence-free survival (RFS) were combined and signatures generated. A total of 30 biomarkers were associated either to one or more of the following prognostic factors: histological type (n = 15), histological grade (n = 6), FIGO stage (n = 1), molecular classification (n = 16), or they were associated to OS (n = 11), and RFS (n = 5). A prognostic signature composed of 11 proteins increased the accuracy to predict OS (AUC = 0.827). The study validates and identifies new potential applications of 30 proteins as prognostic biomarkers and suggests to further study under-studied biomarkers such as TPX2, and confirms already used biomarkers such as MSH6, MSH2, or L1CAM. These results are expected to advance the quest for biomarkers to accurately assess the risk of EC patients.